journal.iha.org.irjournal.iha.org.ir/files/journal/issue_30.pdf · 1 heart journal i a n ihj...

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Heart Jo

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IHJ

According to the ruling of the Medical Sciences Publications Commission No.

14313-80/10/1 and 36914-85/2/10 signed by the Minister of Health and

Medical Education and the Head of the Medical Sciences Publications

Commission of the Islamic Republic of Iran, this journal has been granted

accreditation as a scientific-research journal.

This Journal is indexed in the Scientific Information Database (WWW.SID.IR) and IMEMR

and Index COPERNICUS, SCOPUS, CINAHL and Google Scholar.

ISSN: 1735-7306

http://www.sid.ir/

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OFFICIAL QUARTERLY PUBLICATION OF THE IRANIAN HEART ASSOCIATION

2

Executive Board:

Chairman: Editor-in-Chief: Executive Manager: Feridoun Noohi, MD A. Hussein Tabatabaei, MD Majid Maleki, MD

Technical Editors: Associate Editors: Assistant Manager: Farshad Amouzadeh, MA Rasoul Azarfarin, MD Shahin Shrani, MD

Hooman Bakhshandeh, MD Shabnam Madadi, MD Reza Golpira, MD

Local Editorial Board: Abdi S. Firouzabadi H. Javidi D. Mostafavi A. Radpour M.

Ahmadi H. Firouzi A. Jebbeli M Motamedi M. R. Sadeghi M. Alizadeh Ghavidel A. R. Firouzi I. Kalantar Motamedi M. H. Nabavizadeh Rafsanjani F. Sadeghpour Tabaee A.

Alizadeh Sani, Z Ghaffari Nejad M. H. Karimi A. Navabi M. A. Sadr Ameli M. A.

Almassi N. Ghasemi M. Kazemi Saleh D. Nazeri I. Sadeghpour A. Aminian B. Gholampour Dehaki M. Kamal hedayat D. Nematipour E. Sattarzadeh R.

Arefi H. Hagh Azali M. Kiavar M. Nikdoost F. Shahmohammadi A.

Azarfarin R. Haghjoo M. Madadi Sh. Nozari Y. Shakibi J. Azarnik H. Haj Sheikholeslami F. Maleki M. Ojaghi Haghigi S. Z. Shirani SH.

Bagherzadeh A. Haji Zeinali AM. Mandegar M. H. Noohi F. Tabatabaei A. H.

Baharestani B. Hakim H. Mehranpour M. Omrani G. Tabatabaei M. B. Bakhshankdeh H. Hashemi J. Mohagheghi A. Oraii S. Yousefi A.A.

Bassiri H. Hashemian M. Mohebbi A. Peighambari M. M. Youssefnia M. A.

Bolourian A. Heidarpour A. Mojtahedzadeh S. Pezeshkian M. Vahedian J. Eslami M. Hosseini K. Momtahen M. Poorhosseini HR Zavarehee A.

Farasatkish R. Hosseini S. Mortezaeian H. Pourmoghaddas M Zand parsa A.F.

International Editorial Consultants:

Alipour M. USA Khaghani A. UK

Anderson D. UK Koolen J. Netherlands Qureshi S. A. UK Bagir R. USA Kranig W. Germany Razavi M. USA

Bellosillo A. Phillipines Kusmana D. Indonesia Robin J. France Davis W. UK M Samuel. India Sadeghi A. USA

Deutsch M. Austria Malek J. USA Samad A. Pakistan

Djavan S. Austria Marco J. France Sheikh S. Pakistan Dorosti K. USA Mee R. USA Sheikhzadeh A. Germany

Elliott M. UK Mirhoseini M. USA Shenasa M. USA

Estafanous F.G. USA Monga M. S. Pakistan Siddiqui H. India Foale R. UK Moosivand T. Canada Sloman G. Australia

Gandjbakhch I. France Moten M. USA Smith W. M. New Zealand

Jahangiri M. UK Nagamia H. USA Tajik A. J. USA Jazayeri M.R. USA Otto A. Turkey Tynan M. UK

Karim S. Indonesia Pavie A. France Wolner E. Austria

Contributing Editors of This Issue:

Abdi S. Jebbeli M Mandegar M. H. Peighambari M. M.

Azarfarin, R. Kamal hedayat D. Mohebbi A. Sadr Ameli M. A.

Bassiri H.A. Madadi, Sh. Noohi F. Shirani, Sh.

Hosseini S. Maleki M. Omrani G.R. Tabatabaei A. H.

Technical Typist: F. Ghomi

Secretary: A. Beheshti

Address: Iranian Heart Association: P.O. Box: 15745-1341, Tehran, IR. Iran. Tel: (009821) 22048174,

Fax: (009821) 22048174

Email: [email protected]

mailto:[email protected]

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EDITORIAL

In the Name of God, the Most Beneficent, the Most Merciful

Dear colleagues and friends,

It is with immense pleasure that we present Volume 21, Number 1 (2020) issue of Iranian

Heart Journal, which features some new scintillating studies and case reports in the domains

of cardiovascular medicine and surgery from our Iranian colleagues.

Iranian Heart Journal is indexed in the Web of Science (ISI), the Scientific Information

Database (WWW.SID.IR), IMEMR, Index Copernicus, Scopus, and CINAHL, thereby

facilitating access to published literature. Indubitably, however, our journal is reliant upon

your opinions, ideas, and constructive criticism so as to accomplish its main objective of

disseminating cutting-edge medical knowledge.

As ever before, we look forward to receiving your latest studies and cases.

Yours truly,

A. Hussein Tabatabaei, MD F. Noohi, MD

Editor-in-Chief, Chairman,

Iranian Heart Journal Iranian Heart Journal

http://www.google.com/url?q=http%3A%2F%2Fwww.sid.ir%2F&sa=D&sntz=1&usg=AFQjCNHRnJsC9DZFqkWALefGHlBJVA9QNg

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Volume 21, Number 1

2020

CCOONNTTEENNTTSS:: PPaaggee

ORIGINAL ARTICLES: CLINICAL SCIENCE

Efficacy and Safety of Dual Antiplatelet Therapy on Graft Patency After Coronary Artery Bypass Graft Surgery: A Randomized Controlled Trial Seifollah Abdi; Mahmood Momtahen; Hossein-Ali Bassiri; Ali Shafiei ; Parham Sadeghipour; Mohsen Madani; Hooman Bakhshandeh

6-16

Clinical and Echocardiographic Characteristics of Patients With Cardiac Tamponade and its Survival Prognostic Factors Behnam Askari; Kamal Khademvatani; Mir-hosein Seyed mohammadzad; Alireza Rostamzadeh; Nuaman Mohammadzaie; Mitra Golmohammadi

17-26

Role of Left Atrial Structure and Function in the Early Prediction of Cardiac Iron Overload in

Transfusion-Dependent β-Thalassemia Patients Mozhgan Parsaee; Nakisa Khansari; Azita Azarkeivan; Mitra Chitsazan; Behshid Ghadrdoost; Hoda Mombeini

27-33

Hospital Facilities at Home for Heart Failure Patients Shiva Khaleghparast; Alireza Maleki; Sepideh Taghavi; Ahmad Amin; Majid Maleki; Mehrdad Oveisi; Behrooz Ghanbari; Zahra Hanifi; Nasim Naderi

34-44

Predictive Power of N-terminal Prohormone of Brain Natriuretic Peptide on Admission and on Discharge for Short- and Long-term Clinical and Echocardiographic Outcomes in Patients With Pulmonary Thromboembolism Abdolvahhab Baradaran; Davood Kazemi Saleh; Yaser Jenab; Susan Hashemi; Arash Jalali; Elham Feizabad

45-54

Chest Pain is Associated With Decreased Irisin Serum Levels in Type 2 Diabetic Patients With Coronary Artery Disease Taybeh Zyaddini; Gholamreza Asadikaram; Mohammad Masoumi

55-66

Association Between Blunted Heart Rate Response to Dipyridamole and Myocardial Ischemia in Diabetic Patients as Compared With Nondiabetic Patients Hadi Malek; Raheleh Hedayati; Nahid Yaghoobi; Hassan Firoozabadi; Fereydoon Rastgou; Ahmad Bitarafan Rajabi

67-74

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CCOONNTTEENNTTSS:: PPaaggee

ORIGINAL ARTICLES: CLINICAL SCIENCE

Fine Particle Air Pollution (PM 2.5) and Cardiovascular Hospitalization in Isfahan in 2012: CAPACITY Study Ehsan Shirvani; Masoumeh Sadeghi; Sayed Mohsen Hosseini; Alireza Khosravi; Katayoun Rabiei; Mojtaba Rahimi; Tohid Jafari-Koshki; Mansour Shishehforoush; Ahmadreza Lahijanzadeh; Elham Moazam; Mohammad Bagher Mohebi; Nizal Sarrafzadegan

75-81

Correlation Between Type II Diabetes Mellitus and Left Atrial Function as Assessed by 2D Speckle-Tracking Echocardiography in Patients Without Coronary Artery Disease Fariba Bayat; Mohammad Khani; Fatemeh Saffarian; Mohammad Amin Shahrbaf

82-93

Prevalence of Anemia in Patients Undergoing Cardiac Surgery and Need for Transfusion During Surgery Regarding Hemoglobin Levels in Rajaie Heart Center

Ali Sadeghi; Rasool Ferasatkish; Avaz Heydarpour; Rasoul Azarfarin; Mohsen Ziyaeifard; Zahra Faritous; Fatemehshima Hadipourzadeh

94-102

Assessment of Global Longitudinal Strain via Speckle-Tracking Echocardiography in Patients With Rheumatoid Arthritis Farahnaz Nikdoust; Samira Safiarian; Atoosa Mostafavi; Farhad Gharibdoust; Seyed Abdol Hussein Tabatabaei

103-109

CASE REPORT

Coronary and Cerebral Artery Air Embolism Complicating Trans-septal Accessory Pathway Ablation Hamid Farzamnia; Farzad Kamali; Mohsen Neshati Pirborji; Ala Keykhavani; Azadeh Meibodi Ardekani; Shabnam Madadi

110-114

Successful Surgical Management of a Retained Guide-Wire Fragment in the Left Main Coronary Artery Masoud Tarbiat; Amir Shams; Farnaz Fariba

115-118

Hiccups Are a Rare Symptom of Supraventricular Tachycardia: Case Report Amir Hosein Khandan; Asghar Mohamadi

119-121

INSTRUCTIONS FOR AUTHORS 122-124

FORTHCOMING MEETINGS 125-128

SUBSCRIPTION FORM 129-130

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DAPI in CABG Abdi et al

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Original Article DAPI in CABG Abdi et al

Efficacy and Safety of Dual Antiplatelet Therapy on Graft Patency

After Coronary Artery Bypass Graft Surgery:

A Randomized Controlled Trial

Seifollah Abdi1, MD; Mahmood Momtahen

1, MD; Hossein-Ali Bassiri

1, MD;

Ali Shafiei1, MD; Parham Sadeghipour

*1, MD; Mohsen Madani

1, MD;

Hooman Bakhshandeh2, MD, PhD

ABSTRACT

Background: Early vein graft occlusion after coronary artery bypass grafting (CABG) is one of

the major problems after the surgery which directly impacts its short- and long-term

outcomes. One of the potential explanations is aspirin resistance. The aim of this study

was to evaluate the efficacy and safety of dual antiplatelet therapy (DAPT) with

clopidogrel and aspirin compared with aspirin alone on the reduction of early graft occ

usion.

Methods: In a multicenter randomized controlled trial with a parallel design, from 2012 to 2015

among 1165 patients, we compared 140 candidates for CABG: 71 in the DAPT group

(300 mg c of clopidogrel and 80–325 mg of aspirin) and 69 in the aspirin group. The

primary outcome was graft patency assessed by coronary computed tomography

angiography performed at 6 months’ follow-up. Bleeding complications were considered

the secondary outcome.

Results: Saphenous vein grafts were occluded in 10 (14.1%) patients in the DAPT and 11

(15.9%) in the control group (P = 0.758). After adjustments for study centers, the

associations remained unchanged (OR [95% CI]: 1.49 [0.59–3.74]). Bleeding endpoints

were also similar in the 2 groups (P > 0.05).

Conclusions: Our study did not demonstrate the superiority of the DAPT regimen over aspirin

monotherapy in patients undergoing elective CABG. Larger multicenter studies may

provide more evidence. (Iranian Heart Journal 2020; 21(1): 6-16)

KEYWORDS: Coronary artery bypass, Platelet aggregation inhibitors, Aspirin, Clopidogrel

1 Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences,

Tehran, IR Iran. 2 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

* Corresponding Author: Parham Sadeghipour, MD; Vali-e-Asr St, Niayesh Blvd, Rajaie Cardiovascular, Medical, and Research Center,

Tehran, IR Iran. Email: [email protected] Tel: 02123922092

Received: February 6, 2019 Accepted: March 25, 2019


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arly vein graft failure is still one of

the important caveats of coronary

artery bypass grafting (CABG),

which might translate to major

cardiovascular events. Thrombosis, intimal

hyperplasia, smooth muscle cell

proliferation, and de novo atherosclerosis

plaques have been suggested as a possible

candidate for graft failure, among which

thrombosis plays a crucial role in the early

phase. By blocking cyclooxygenase-1, ASA

inhibits platelet activity and decreases the

rate of graft thrombosis. 1 Despite this

protective approach, around 30% of venous

grafts will become occluded in the first year

after surgery, which may be considered

aspirin resistant. 2,

3 This may be due to the

inability of aspirin to inhibit all aspects of

the platelet activation process and also the

aspirin resistance phenomena. 4 To

overcome these problems, it was suggested

to add clopidogrel in order to lower the rate

of early graft occlusion. To date, there is no

clear consensus regarding the use of dual

antiplatelet therapy (DAPT) after elective

CABG. Several studies have investigated the

clinical use of clopidogrel in the matter, but

they have reached mixed results.

Considering the abovementioned

controversy, this study aimed primarily to

evaluate the effects of a combination of

clopidogrel and aspirin therapy on the

reduction of early graft occlusion evaluated

by coronary computed tomography (CT)

angiography in patients with recent CABG.

METHODS

The study was an open-label multicenter

randomized controlled trial with a parallel

design. It was aimed to evaluate the

superiority of DAPT of clopidogrel and

aspirin compared with aspirin alone on the

reduction of early graft occlusion in patients

with recent CABG.

Study Participants and Settings

The study was conducted from May 2012 to

December 2015 in 3 professional centers for

cardiovascular diseases (Day General

Hospital, Pars General Hospital, and Rajaie

Cardiovascular, Medical, and Research

Center) in Tehran, Iran. All the selected

centers were referral private or teaching

hospitals.

The study protocol was approved by the

ethics committee of Karaj Islamic Azad

University (Code: 030- 8/9/1390).

Inclusion Criteria:

1. Patients’ age ≥ 18 y

2. Candidates for CABG

Exclusion Criteria:

1. Concomitant valve surgeries

2. Concomitant aortic surgery

3. Redo-CABG

4. Patients who did not take aspirin at

least 48 hours before surgery

5. Clopidogrel use within 5 days before

CABG

6. Any condition with increased

bleeding risk, precluding DAPT

7. Significant bleeding in the first 4

hours after surgery, defined as

continuous chest tube drainage > 100

cm3 per hour on average in this time

interval

Totally, 1165 patients who were candidated

to undergo CABG were assessed for the

eligibility criteria by a cardiologist. Every

eligible patient was given a written informed

consent form by the main investigator; and

after signing the form, he/she was registered

in the study.

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Study Groups and Randomization

The participants in this study underwent

randomization (on a 1: 1 basis) via the

permuted block method to either the DAPT

group (clopidogrel and aspirin) or the aspirin

monotherapy group within 24 hours after

surgery. The process of random assignment

was conducted in our data management

center, located in one of the collaborating

hospitals (Rajaie Cardiovascular, Medical,

and Research Center) by the team members

not involved in the conduction of the trial

performed. Random sequence was generated

using the permuted block randomization

method (blocks of 4). After the registration

of each patient in the trial, the nurse in

charge called the center’s data management

center and asked for the assigned study

group. According to the random sequence,

the staff in the center announced the

assigned group as Group A (DAPT) or

Group B (control) to the nurse. The trial was

open-label, and no masking was applied.

The patients who were randomized in the

DAPT group received a loading dose of 300

mg (4 tablets) of clopidogrel (Plavix ®,

Sanofi-Aventis Co) within 24 hours after

surgery and a maintenance dose of 75 mg/d

was continued for 30 days in combination

with 80–325 mg of aspirin. The patients who

were assigned to the control group received

aspirin (80 mg/d). For both groups, aspirin

was recommended for lifelong treatment.

Study Endpoints

The primary endpoint was graft patency

evaluated by CT angiography 6 months after

surgery. A graft was considered patent if no

significant stenosis (≥ 70%) was detected by

CT angiogram; otherwise, it was regarded as

occluded.

The secondary endpoints were:

1) The amount of chest tube output in the

early postoperative period, defined as the

amount of the bloody fluid drained. The

chest tube drainage was considered

significant when its amount exceeded 100

cm3 per hour on average for a 4-hour

interval in the intensive care unit (ICU) after

surgery.

2) The need for blood transfusions with

either of the following criteria:

a. ≥ 2 units of packed red blood cells

b. ≥ 2 units of fresh frozen plasma

c. ≥ 5 units of platelets

3) In-hospital mortality, defined as cardiac

death in the postoperative period and during

hospitalization as a secondary endpoint of

the study.

After undergoing surgery, the patients were

discharged to the ICU, where they were

visited every day by the principal

investigator or eligible cardiologists and

assessed for the study endpoints.

Data Collection and Follow-up

All the data related to the patients’

characteristics, intervention, and bleeding

complications from the index event until

discharge were recorded in a CRF by a

trained and qualified study coordinator (SC).

During the time of hospitalization, all the

participants were monitored in terms of the

amount of chest tube drainage and blood

product transfusion.

Afterward, the patients were asked by the

study coordinator to refer for a visit at 1

month’s follow-up. Treatment adherence

was evaluated, along with any complication,

by the principal investigator.

Six months after surgery, CT-angiography

was performed to evaluate graft patency.

During the recruitment for imaging follow-

up, the patients who refused to attend this

examination were asked to give the reason

for not attending and cases of death were

reported when available.

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After CT angiography for the participant, all

data about the number and type of involved

graft vessel(s) were saved in the CRF.

All the CT angiographic examinations were

double-checked by the radiologist involved

in the study.

Statistical Analysis

The data were analyzed via the intention-to-

treat approach. The data were described as

the mean (± the standard deviation) for the

interval variables with normal distributions,

the median (interquartile ranges) for the

interval variables without normal

distributions, and count (%) for the

categorical variables. Fitness of the

distribution of the interval variables to

normal distribution was assessed using the

one-sample Kolmogorov–Smirnov test.

Associations between DAPT and other

variables were determined using the Student

t-test for the interval variables with normal

distributions, the Mann–Whitney U test for

the interval variables without normal

distributions and the ordinal variables, and

the Pearson χ2

test (or the Fisher exact test,

as needed) for the nominal variables. A P

value ≤ 0.05 was considered statistically

significant.

Adjusted associations between the primary

endpoint (graft occlusion) and DAPT were

investigated using a multivariate binary

logistic model. The study center was

considered a covariate, and other covariates

in the model were chosen if a significant P

value was detected in the bivariate statistical

analysis.

The statistical analyses were performed via

IBM SPSS Statistics 19 for Windows (IBM

Inc, Armonk, NY) and Stata 11 (Stata Inc,

Texas, USA).

RESULTS

Baseline and Background Data

The study was conducted from May 2012 to

December 2015 in 3 centers for

cardiovascular diseases in Tehran, Iran. In

total, 1165 patients were assessed primarily

for the inclusion criteria. Among them, 740

did not satisfy the inclusion criteria and 209

did not participate and sign the informed

consent form. The remaining 216 patients

were randomly assigned to the 2 study arms

(108 in each group). Nonetheless, due to a

nurse’s error, 3 patients were misclassified

and, therefore, 111 participants received

DAPT and 105 received aspirin only.

Finally, 140 (65%) participants (71 in the

intervention group and 69 in the control

group) remained until the end of the study

and their relevant data were used in the

statistical analysis. Seventy-six (35%)

patients quit the study as they chose not to

undergo CT angiography or could not

complete the follow-up course. The study

participants’ flow diagram is presented in

Figure 1.

Table 1 depicts a comparison of the

background characteristics between the 2

groups: the patients who agreed to undergo

CT angiography (ie, those who were entered

in the final analysis) and the patients who

did not. The results showed that the 2 groups

were similar in several aspects; thus, it can

be concluded that the acceptance of CT

angiography was random in the study

participants. The participants’ characteristics

were compared between the study groups,

and the results are presented in Table 2. The

findings suggested that the patients were

roughly similar in the 2 study groups.

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ALLOCATION

ANALYSIS

FOLLOW -UP

Analyzed (n= 69 ) Excluded from analysis (n= 0 )

Figure 1. CONSORT Flow Diagram

Table 1. Comparison of the patients’characteristics between the group that underwent CTA and the group that did not

CTA Performed (n=140) CTA NOT Performed (n=76) P value

Study Group a 0.714

Intervention 71 (50.7%) 40 (52.6%)

Control 69 (49.3%) 35 (46.1%)

Gender a 0.144

Male 113 (80.7%) 54 (71.1%)

Female 27 (19.3%) 21 (27.6%) 0.198

Age (y) b 62 (±9.4) 61 (±9.7)

Center a 0.428

1 28 (20%) 11 (14.5%)

2 33 (23.6%) 15 (19.7%)

3 79 (56.4%) 49 (64.5%)

History of MI a 72 (51.4%) 40 (52.6%) 0.790

Family history a 58 (46.4%) 29 (38.2%) 0.503

Hypertension a 82 (58.6%) 52 (68.4%) 0.121

Dyslipidemia a 95 (67.9%) 48 (63.2%) 0.568

Diabetes a 57 (40.7%) 28 (36.8%) 0.629

Smoking a 77 (55%) 44 (57.9%) 0.730

Coronary Vessel Stenosis a 0.583

Single vessel 13 (9.3%) 4 (5.3%)

Two vessels 29 (20.7%) 17 (22.4%)

Three vessels 98 (70%) 54 (71.1%)

LVEF (%)b 47 (±10.8) 46 (±10.3) 0.882

Results are presented as: a: count (%), b: mean (±standard deviation). CTA, Computed tomography angiography; MI, Myocardial infarction; LVEF, Left ventricular ejection fraction

Assessed for eligibility (n= 1165)

Excluded (n= 949 )

Not meeting inclusion criteria (n= 740)

Declined to participate (n= 209)

Analyzed (n= 71 ) Excluded from analysis (n= 0 )

Allocated to Plavix + aspirin (according to study protocol) (n=108 )

Received allocated intervention (n= 111)

Lost to follow-up (30 patients chose not to undergo CT angiography, 2 patients had chronic kidney disease, 1 patient had hypersensitivity to contrast media, and 3 cases of irrelevant death; total n=36)

Discontinued intervention (n=0)

Allocated to aspirin (according to study protocol) (n= 108)

Received allocated intervention (n= 105)

Did not receive allocated intervention (The nurse in charge

made a mistake about the prescription of Plavix.) (n=3)

Randomized (n= 216)

ENROLLMENT

Lost to follow-up (33 patients chose not to undergo CT angiography, 2 patients had chronic kidney disease, 1 patient had hypersensitivity to contrast media, 1 case of irrelevant death, and 1 patient continued Plavix > 30 days because of carotid stenting: total n=38)

Discontinued intervention (1 occurrence of thoracic surgery due to mediastinitis, 1 because of patient’s willing, total n=2)

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Table 2. Comparison of characteristics between the patients who were entered in the analysis (ITT) (N=140)

Plavix-Aspirin (n=71)

Aspirin (n=69)

P value

Gender a

Male 57 (80.3%) 56 (81.2%) 0.895

Female 14 (19.7%) 13 (18.8%)

Age (y) b 62 (±8.4) 61 (±10.4) 0.423

History of MI a 31 (43.7%) 41 (59.4%) 0.062

Family history a 33 (52.4%) 25 (40.3%) 0.176

Hypertension a 44 (62%) 38 (55.1%) 0.407

Dyslipidemia a 50 (70.4%) 45 (65.2%) 0.501

Diabetes a 24 (33.8%) 33 (47.8%) 0.121

Smoking a 40 (56.3%) 37 (53.6%) 0.884

Coronary Vessel Stenosis a

Single vessel 5 (7%) 8 (11.6%)

0.317 Two vessels 18 (25.4%) 11 (15.9%)

Three vessels 47 (67.6%) 50 (72.5%)

LVEF (%) c 50 (45-55) 50 (35-55) 0.172

Emergent operation a 3 (4.2%) 1 (1.4%) 0.324

Number of grafts c 2 (2-3) 2 (2-3) 0.399

Hemoglobin (g/dL) b 13.4 (2.8) 13.7 (2.4) 0.171

Results are presented as: a: count (%), b: mean (standard deviation), c: median(Q1-Q3). MI, Myocardial infarction; LVEF, Left ventricular ejection fraction

In-Hospital Events

The patients were assessed in terms of

bleeding, transfusion, and other outcomes

and the comparative results are presented in

Table 3. There was no statistical difference

in the chest tube drainage between the 2

groups (P > 0.05). The incidence of

significant bleeding leading to blood product

transfusion was similar between the 2

groups. However, the amount of RBC

transfused to the intervention group was less

than that transfused to the control group (P <

0.05). No death was reported during this

period.

Table 3. Comparison of the findings during hospitalization between the study treatment groups (ITT)

Plavix-Aspirin

(n=71) Aspirin (n=69)

P value

Chest tube drainage (cm3)

First day after surgery b 400 (250 - 500) 400 (250 - 541.5) 0.541

ICU period b 500 (350 - 700) 500 (325 - 725) 0.828

Ward b 0 (0 - 0) 0 (0 - 0) 0.555

Total b 600 (350 - 750) 500 (350 - 875) 0.602

Need for transfusion a 42 (59.2%) 47 (68.1%) 0.271

Hemoglobin before transfusion c (g/dL) 10.6 (2.4) 10.9 (2.7) 0.169

In Transfused Patients:

Units of packed RBCs b 1 (1 - 2) 2 (1 - 3) 0.004

Volume of packed RBCs (cm3)

b 250 (250 - 500) 500 (250 - 775) 0.005

Units of FFP b 3 (1.5 - 3) 3 (1.75 - 3) 0.894

Volume of FFP (cm3)

b 450 (300 - 450) 450 (275 - 450) 0.789

Units of platelet b 3 (2 - 4) 3 (2 - 4) 0.515

Volume of platelet (cm3)

b 150 (100 - 200) 150 (100 - 200) 0.515

Units of whole blood b 1 (1 - 1) 3 (3 - 3) 0.317

Volume of whole blood (cm3)

b 350 (350 - 350) 900 (900 - 900) 0.317

Re-operation because of bleeding a 0 (0%) 1 (1.4%) 0.493

Hospitalization (days after surgery) 6 (6 - 7) 7 (6 - 8) 0.223

Mortality a 0 0 -

Results are presented as: a: count (%), b: median (Q1-Q3), c: mean (standard deviation). FFP, Fresh frozen plasma; RBC, Red blood cells

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Six Months After Surgery

After discharge, there were no records of

bleeding, ischemic events, or mortality.

Graft Occlusion

As the primary endpoint of the study, the

occlusions of venous (and arterial) grafts

were measured via coronary CT

angiography. Saphenous vein grafts were

occluded in 10 (14.1%) patients in the

DAPT group and 11 (15.9%) patients in the

control group (P = 0.758). Arterial graft

occlusion was observed in 5 (7%) patients in

the DAPT group and 3 (4.3%) patients in the

control group (P = 0.492). To adjust the

association between the study intervention

and graft occlusion for each of our 3 centers,

we performed a multivariable logistic

regression analysis (Table 4). The analysis

showed that the study center did not

influence the study outcomes (P > 0.05).

Table 4. Multivariable analysis for adjusting the findings for the centers

Crude OR (95% CI) Adjusted OR (95% CI) P value

Dual antiplatelet therapy 0.86 (0.34 – 2.19) 1.49 (0.59 – 3.74) 0.397

Center of study

1 (reference)

2 0.51 (0.11 – 2.40) 0.392

3 1.66 (0.54 – 5.10) 0.378

Adverse Events

The frequencies of adverse events according

to the study groups are presented in Table 5

(in the study treatment group, n=140) and in

Table 6 (in the randomized patients, n=216).

Additionally, the frequencies of serious

adverse events, compared between the study

groups, are mentioned in Table 7.

Table 5. Frequency of adverse events in the study population until the end of 6 months after follow-up in the study

treatment groups (N=140)

Plavix-Aspirin

(n=71) Aspirin (n=69)

Transient Mild Thrombocytopnia 3 4

Transient Mild Azotemia 1 1

Transient Microscopic Hematuria 1 0

Subcutaneous Emphysema 0 1

Vasovagal Syndrome 1 1

Ventricular Tachycardia 0 1

Fever 1 0

Pneumonia 0 0

Mediastinitis 0 0

Tamponade 0 1

Pericardial Effusion 1 1

Pleural Effusion 4 3

Hematoma at the Site of Saphenectomy 0 1

Wound Infection 2 1

Pressure Ulcer 0 0

Retroperitoneal abscess 0 0

Exsessive Bleeding 0 1

LV Clot 0 1

Death Due to CVA (Out of Hospital) 0 0

Death Due to Cirrhosis (Out of Hospital) 0 0

Death Due to Mediastinitis ( in Hospital) 0 0

Total AEs 14 17

Total Patients with AEs 11 14

Total Patients with AEs Leading to Discontinuation 1 0

Total Patients with SAEs 5 8

LV, Left ventricle; CVA, Cerebrovascular accident; SAE, Serious adverse event

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Table 6. Frequency of adverse events in the study population until the end of 6 months after follow-up in the

randomized patients (n=216)

Plavix-Aspirin

(n=111) Aspirin (n=105)

Transient Mild Thrombocytopnia 3 4

Transient Mild Azotemia 1 1

Transient Microscopic Hematuria 1 0

Subcutaneous Emphysema 0 1

Vasovagal Syndrome 1 1

Ventricular Tachycardia 0 1

Fever 1 0

Pneumonia 0 1

Mediastinitis 1 0

Tamponade 0 1

Pericardial Effusion 2 2

Pleural Effusion 6 4

Hematoma at the Site of Saphenectomy 0 1

Wound Infection 2 1

Pressure Ulcer 2 1

Retroperitoneal abscess 1 0

Exsessive Bleeding 0 1

LV Clot 0 1

Death Due to CVA (Out of Hospital) 0 1

Death Due to Cirrhosis (Out of Hospital) 0 1

Death Due to Mediastinitis ( in Hospital) 1 1

Total AEs 22 24

Total Patients with AEs 21 19

Total Patients with SAEs 7 15

LV, Left ventricle; CVA, Cerebrovascular accident; SAE, Serious adverse event Table 7. Frequency of serious adverse events (SAEs) according to the study groups

Serious Adverse Events

Randomized (n=216)

Analyzed (n=140)

Total DAPT (n=111)

Aspirin (n=105)

Total DAPT (n=71)

Aspirin (n=69)

Death 4 1 3 0 0 0

Requiring/Prolonging Hospitalization 16 5 11 11 4 7

Congenital Anomaly/ Birth Defect 0 0 0 0 0 0

Life-threatening 3 1 2 2 1 1

Persistent/Significant Disability/ Incapacity 0 0 0 0 0 0

Other Medically Important Events 0 0 0 0 0 0

DAPT, Dual antiplatelet therapy

DISCUSSION

In the present study, we compared the effect

of DAPT (ie, aspirin and clopidogrel) with

that of aspirin alone in patients having

undergone elective CABG. Our study was

an open-label multicenter controlled

randomized trial with a parallel design, and

our analysis showed no significant

differences in terms of the primary outcome

(ie, graft patency 6 months after surgery)

between the 2 groups of study. Additionally,

the 2 groups were similar according to

bleeding complications.

Different investigations have shown the

important rate of graft (especially venous

graft) failure early after CABG. Although

different mechanisms including intimal

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hyperplasia, smooth muscle cell

proliferation, and de novo atherosclerosis

plaques have been suggested for the

complication, thrombosis appears to play an

important role in the early phase.

Considering these mechanisms, it seems

logical that potent platelet inhibition with

DAPT may improve graft patency. This

benefit should be weighed against the

potential bleeding complication of the

combined regimen. 6 The mentioned

hypothesis was firstly tested in an acute

coronary syndrome population. The CREDO 7 and CURE

8 trials analyzed the effect of

DAPT vs aspirin alone in an acute coronary

syndrome setting in which DAPT showed

promising results toward decreasing the all-

cause mortality without a significant

increase in major bleeding.

Various studies have evaluated the value of

DAPT in elective CABG patients. Graft

patency, evaluated within 3 to 12 months

following CABG, was their main outcome.

In all of them, ASA and/or clopidogrel were

re-administrated when chest tube drainage

was no longer active. In our study, we chose

to show the effect of DAPT on 6 months’

graft patency.

Goa et al, 9

in their randomized controlled

trial, investigated the value of the DAPT

regimen vs aspirin monotherapy in elective

CABG. Their primary outcome was graft

failure 3 months after surgery. Graft failure

was significantly lower in the DAPT group,

in which a trend toward a decrease in all

grafts failure was also detected. It should,

however, be mentioned that bleeding

complications were not elaborated

separately in their analysis.

Mannacio et al, 10

in their CRYSSA trial,

also studied the effect of DAPT on post-

CABG graft patency and its relation with

single or dual antiplatelet resistance. The

study showed that the DAPT regimen had a

beneficial effect compared with

monotherapy. Their results also revealed

that the combination of ASA and

clopidogrel might overcome the single

antiplatelet drug resistance and the

synergistic activity of combined aspirin and

clopidogrel was a strong predictor of

saphenous vein graft (SVG) patency (RR:

5.1, 95% CI: 1.4 to 16.3; P < 0.01).

Likewise, Gasparovic et al 11

compared

specifically the 2 regimens on an aspirin-

resistance population. There were no

significant differences between the 2 groups

regarding graft patency or bleeding

complications. However, the subgroup

analysis showed a benefit for the DAPT

regimen in the obese population.

The CASCADE trial was also a randomized

study with a genuine design. Their primary

endpoint was the effect of clopidogrel on

intimal hyperplasia 1 year after surgery.

With the help of intravascular ultrasound,

the SVGs were analyzed regarding intimal

hyperplasia. Interestingly, clopidogrel had

no impact on the primary outcome. 12

Recently, van Diepen et al, 13

in their post

hoc secondary analysis of the FREEDOM

trial, showed that the DAPT regimen was

not superior to ASA monotherapy in the

post-CABG population. Their results were

consistent in regard to primary graft patency,

bleeding complications, and subgroup

analysis in which important subgroups such

as the ACS population and higher syntax

scores were evaluated. Verma et al, 14

in

their meta-analysis of studies investigating

the role of the DAPT regimen compared

with aspirin monotherapy in both ACS and

elective populations, showed no additional

benefit from adding clopidogrel to ASA in

the post-CABG population.

Our study did not evaluate the possible

effect of the DAPT regimen on the native

coronary arteries. Previous research has

shown that native coronary vessels are at

risk of plaque rupture and other

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complications in which added clopidogrel

might be beneficial. In a substudy of the

CASCADE trial, Une et al 15

proved the

efficacy of DAPT in reducing native

coronary events compared with ASA

monotherapy. The matter still needs further

investigation.

A limitation of the current study was the

considerable number of registered patients

who chose not to undergo CT angiography

(76 out of 216). As was shown in Table 3,

this might not affect the internal validity of

the study. However, from a sociological

point of view, it may affect the

generalizability of the results and may, thus,

need to be considered in future studies.

In conclusion, there is still no consensus on

the efficacy of the DAPT regimen in patients

candidated for elective CABG. Our results

showed a neutral effect of the DAPT

regimen. Large multicenter randomized

clinical trials are needed to definitely

investigate the role of DAPT in patients with

acute coronary syndrome after CABG and to

clearly identify which patients will benefit

the more.

Acknowledgments

This project was sponsored by Sanofi-Iran.

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Reichart B, Seidel D. [Prevention of early

graft occlusion after coronary bypass

grafting by post-operative reduction of

plasma fibrinogen by H.E.L.P. apheresis.

First evaluation of 12 patients treated during

our study (44 bypasses)]. Zeitschrift fur

Kardiologie. 2003;92(Suppl 3):III42-7. Epub

2003/12/10. Verhinderung von

Fruhverschlussen nach koronarer

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H.E.L.P.-Apherese. Erste Auswertung von

12 im Rahmen dieser Studie behandelten

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2. Cambria-Kiely JA, Gandhi PJ. Possible

mechanisms of aspirin resistance. Journal of

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3. Gluckman TJ, McLean RC, Schulman SP,

Kickler TS, Shapiro EP, Conte JV, et al.

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Cardiology. 2011;57(9):1069-77. Epub

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4. Kayacioglu I, Gunay R, Saskin H, Idiz M,

Sensoz Y, Ates M, et al. The role of

clopidogrel and acetylsalicylic acid in the

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due to reactive thrombocytosis after

coronary artery bypass operation. The heart

surgery forum. 2008;11(3):E152-7. Epub

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5. Ibrahim K, Tjomsland O, Halvorsen D,

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revascularization surgery. The heart surgery

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2006/10/25.

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pathophysiology to clinical outcomes.

Nature Reviews Cardiology, 2016.

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of clopidogrel therapy after the first

percutaneous coronary intervention or

coronary artery bypass grafting versus that

after the second or repeat intervention. The

American journal of cardiology, 2004. 94(5):

p. 623-625.

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Combination of Clopidogrel and Aspirin in

Patients Undergoing Surgical

Revascularization for Non–ST-Elevation

Acute Coronary Syndrome The Clopidogrel

in Unstable angina to prevent Recurrent

ischemic Events (CURE) Trial. Circulation,

2004. 110(10): p. 1202-1208.

9. Gao G, Zheng Z, Pi Y, Lu B, Lu J, Hu S. et

al. Aspirin plus clopidogrel therapy

increases early venous graft patency after

coronary artery bypass surgery a single-

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2010;56(20):1639-43. Epub 2010/11/06.

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optimal platelet inhibition following off-

pump coronary artery bypass surgery: results

from the CRYSSA (prevention of Coronary

arteRY bypaSS occlusion After off-pump

procedures) randomised study. Heart, 2012.

98(23): p. 1710-1715.

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patients following coronary artery bypass

grafting. The American journal of

cardiology, 2014. 113(10): p. 1660-1667.

12. Kulik, A., The clopidogrel after surgery for

coronary artery disease (CASCADE)

randomized controlled trial: clopidogrel and

aspirin versus aspirin alone after coronary

bypass surgery [NCT00228423]. Trials,

2005. 6(1): p. 1.

13. Van Diepen S, Fuster V, Verma S, Hamza

TH, Siami FS, Goodman SG, et al. Dual

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Monotherapy in Diabetics With Multivessel

Disease Undergoing CABG: FREEDOM

Insights. J Am Coll Cardiol. 2017 Jan

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randomized controlled trials. BMC surgery,

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May M, et al. Ruel M. Impact of clopidogrel

plus aspirin versus aspirin alone on the

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Characteristics of Patients With Cardiac Tamponade and Their Survival Askari et al

17

Original Article Characteristics of Patients With Cardiac Tamponade and Their Survival Askari et al Clinical and Echocardiographic Characteristics of Patients With

Cardiac Tamponade and its Survival Prognostic Factors

Behnam Askari1, MD; Kamal Khademvatani

2, MD;

Mir-hosein Seyed mohammadzad2, MD; Alireza Rostamzadeh

2, MD;

Nuaman Mohammadzaie3, MD; Mitra Golmohammadi, MD*

4

ABSTRACT

Background: Cardiac tamponade nearly always requires urgent intervention, but the optimal

management of pericardial effusion is still controversial. The aim of our study was to

introduce the profile and treatment results of patients with tamponade in our referral heart

center.

Methods: From November 2010 to November 2014, our retrospective study was performed on

220 patients with tamponade. All the clinical and echocardiographic findings of the

patients, as well as their operative and follow-up data, were recorded and analyzed.

Results: The overall prevalence of tamponade relative to the entire study population undergoing

heart surgery was 8.5%. There were 106 men and 114 women at a mean age of 55.5 years

(range = 5–99). The most common causes of tamponade were cardiac diseases (21%),

malignancy (20.4%), unknown (20.4%), chronic renal failure (15%), and post-cardiac

surgery complications (10.5%). The approaches for pericardial effusion drainage were the

subxiphoid approach (97.7%), mini-thoracotomy (1.4%), and percutaneous

pericardiocentesis (0.9%). The intraprocedural mortality rate was zero, the mortality rate

during hospital stay was 4.5%, and the recurrence rate was 9.1%. Patients with primary

sanguineous pericardial effusion, malignant etiologies of tamponade, and malignant

pericardial effusion had significantly poor survival. The survival rates at 1 month, 1 year,

2 years, and 3 years were 87.1%, 67.7%, 64.5%, and57.2%, respectively.

Conclusions: We found an association between left pleural effusion and small amounts of

pericardial effusion, hence the necessity of more attention in the echocardiographic

evaluation of these patients. The subxiphoid approach for pericardial effusion drainage is

a safe and simple procedure associated with relatively lower postoperative complications,

mortality, and recurrence rate. Sanguineous pericardial effusion is concomitant with poor

prognoses. (Iranian Heart Journal 2020; 21(1): 17-26)

KEYWORDS: Cardiac tamponade, Subxiphoid pericardial window, Pericardial effusion, Pericardial drainage 1

Department of Cardiovascular Surgery, Seyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, IR Iran. 2

Department of Cardiology, Seyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, IR Iran. 3

General Physician, Urmia University of Medical Sciences, Urmia, IR Iran. 4

Department of Cardiac Anesthesiology, Seyyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, IR Iran.

*Corresponding Author: Mitra Golmohammadi, MD

Email: [email protected] Tel: 09123953220

Received: February 6, 2019 Accepted: March 28, 2019


Tel:+984432375911

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ericardial effusion is pathological

fluid accumulation in the pericardial

cavity. It is usually due to an

imbalance in fluid formation and absorption.

If this accumulation occurs quickly or

gradually, it can lead to the collapse of the

heart chambers and tamponade, which is a

life-threatening condition. 1

The clinical presentations of pericardial

effusion at the time of diagnosis vary, 2 with

the most common causes of large pericardial

effusion being malignancies, uremia,

infections, collagen vascular disease, and

chest radiation. 1, 3

Cardiac tamponade nearly always requires

urgent intervention, but the optimal

management of pericardial effusion is still

controversial. There are several pericardial

drainage approaches: the percutaneous

approach or pericardiocentesis and the

surgical approach such as the subxiphoid

pericardial window, left mini-thoracotomy,

and the left paraxiphoidian approach, each

of which has its own advantages and

disadvantages. 4- 6

Pericardiocentesis is a less invasive

procedure than surgical procedures; it,

however, has a higher recurrence rate and is

sometimes associated with such

complications as severe bleeding. 6 The

subxiphoid approach is a more invasive

technique but has lower recurrence rates. 1

Optimal urgent decompression targets are

sufficient fluid drainage and sampling,

resection of the pericardial sample for

pathological evaluation, and prevention of

recurrence with minimal morbidity and

mortality. Given that the existing literature

contains conflicting data about various

intervention options, we sought to introduce

the profile and treatment results of patients

with tamponade in our referral heart center.

METHODS

From November 2010 to November 2014,

our retrospective study was performed on

261 patients who were admitted and treated

at Seyed-al-Shohada Heart Center in

Urmia, Iran, for pericardial effusion with

cardiac tamponade. Our study protocol was

approved by the Ethics Committee of Urmia

University of Medical Sciences. Cardiac

tamponade diagnosis and decision for

surgery consultation in all cases were made

by a cardiology specialist based on clinical

evaluations and echocardiography.

Postoperative patients requiring re-

sternotomy and chest re-exploration during

several days after open-heart surgery were

excluded from the study.

All the clinical findings of the patients at the

time of admission such as age, gender,

dyspnea, hypotension, pulse paradox,

elevation of jugular pressure, heartbeat

mutations, and tachycardia were recorded.

Echocardiographic findings such as right

and left atrial collapse, right ventricular

collapse, the ejection fraction, and findings

compatible with fluid accumulation in the

pericardial space were also recorded.

Local anesthesia and intravenous sedation or

general anesthesia were used. The surgical

procedure for most of the patients was the

subxiphoid pericardial window. A 4 to 6-cm

incision was made in the midline and the

upper abdominal region approximately over

the xiphoid process. In the thoracotomy

approach, anterior mini-thoracotomy was

done with a 4 to 6-cm incision beneath the

left nipple and through the fifth intercostal

interspace. After the identification and

incision of the pericardium, pericardial fluid

suction was performed. A chest tube (28 or

32 F) was placed into the pericardial space

through a separate stab wound. Percutaneous

drainage was performed with an 8-cm

P

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18-gauge angiocatheter, guide wire, dilator,

and a pigtail catheter.

The pericardial fluid was sent for culture and

cytological, bacteriological, and histological

analyses. A biopsy specimen (a piece of

pericardium 1 to 2 cm in diameter) was

resected for pathological evaluation. The

fluid volume and its appearance were also

recorded.

When the amount of the mediastinal

drainage was less than 100 cc in 24 hours

and control echocardiography showed no

significant residual effusion, the tube drain

was withdrawn.

Echocardiography was done after 1 month

and 1 year for asymptomatic patients in the

follow-up period and for all symptomatic

patients.

Operative and follow-up data of the patients

such as the drainage technique, the

anesthesia technique, the amount of fluid

drained, the nature of the pericardial fluid,

cytological and pathological findings,

hospital mortality, mortality in the follow-up

period, and the mean survival rate were

recorded.

The data analyses were conducted with

version 20 of SPSS software. The

quantitative data were shown as the mean ±

the standard deviation (SD), and the

qualitative data were presented as

frequencies and percentages. The overall

survival was calculated from the date of

surgery until death or the last follow-up. For

the univariate analysis, both the independent

t-test and the ANOVA test were used to

report any difference in the survival rates

during the follow-up period. Differences

were considered significant if the P value

was < 0.05.

RESULTS

Within a study period of 48 months, 261

patients were diagnosed with tamponade.

Forty-one patients were excluded due to

incomplete medical records. The evaluations

were performed on 106 men and 114 women

at a mean age of 55.57 ± 18.28 years (range

= 5–99). Two patients did not accept

surgical or percutaneous intervention. Two

patients underwent percutaneous drainage

with echocardiography-guided

pericardiocentesis. In the 4-year period, the

overall prevalence of tamponade relative to

the entire study population undergoing heart

surgery was 8.5% (257/3010). The patients’

demographics and clinical characteristics are

described in Table 1. The most prevalent

clinical problem was dyspnea (91.8%).

Table 1. demographic and clinical characteristics of the patients with tamponade (N=220)

Characteristic No %

Age(y) 55.57±18.28 (5-99)

Gender: male female

114(51.8%) 106(48.2%)

BMI(kg/m2) 25.92±4.82 (14.7-38.6)

Diabetes 39(17.7%)

Hypertension 86(39.1%)

Smoking 42(19.1%)

Familial history of tamponade 3(1.4%)

History of any previous surgery 75(34.1%)

History of tamponade drainage 20(9.1%)

Habitation location: urban rural

155(70.5%) 65(29.5%)

Signs: Dyspnea Elevated jugular venous pressure Pulse paradox Hypotension (SBP < 90 mm Hg) Muffled heart sounds

202(91.8%) 64(29.1%) 22(10%) 29(13.2%) 62(28.2%)

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Common ECG findings were sinus

tachycardia 154 (70%), low voltage 78

(35.5%), and electrical alternans 35 (15.9%).

Radiographic evidence of pleural effusion

was present in 38 (17.3%) patients. The

echocardiographic and laboratory findings

are depicted in Table 2.

Table 2. Echocardiographic characteristics of the patients with tamponade (N=220)

Characteristic No %

EF (%): < 30 30-45 45-55 > 55

34(15.5%) 47(21.4%) 59(26.8%) 80(36.4%)

RV collapse 99(45%)

LA collapse 2(0.9%)

RA collapse 85(38.6%)

Respiratory variation: Mitral valve Tricuspid valve

32(14.5%) 17(7.7%)

IVC dilation 54(24.5%)

Swimming heart 10(4.5%)

Fluid amount: Mild(< 5mm) Moderate( 5-15mm) Sever( > 15mm)

5(2.3%) 40(18.2%) 175(79.5%)

Fluid type: Localized Generalized

23(10.5%) 197(89.5%)

Hb(gr/dL) 11.54±2.08 (5-19)

ESR(mm/h) 29.67±28 (1-125)

CRP(mg/lit) 29.1±27.57 ( 0.1-97)

WBC 9356±4429 (4900-30300 )

PLT 137067±24169(35000-1654000)

Cr(mg/dL) 1.46±1.3 (0.5-8.5)

EF, Ejection fraction; RV, Right ventricle; LA, Left atrium; IVC, Inferior vena cava; Hb, Hemoglobin; ESR, Erythrocyte sedimentation rate; CRP, C-reactive protein; PLT, Platelet; Cr, Creatinine

The most common causes of effusion were

cardiac diseases, malignancy, renal failure,

and post-cardiac surgery complications. The

etiology was malignant in 45 (20.5%)

patients and benign in 175 (79.5%) patients.

Unknown etiology accounted for 45

patients. The causes of tamponade are

presented in Table 3.

Table 3. Causes of tamponade (N=220)

Cause No %

Cardiac 46(21%)

Malignancy: Lung cancer Hematological malignancy Gastrointestinal Breast cancer Ovarian Squamous cell carcinoma (neck) Osteosarcoma

45(20.4%) 13(29%) 12(26.7%) 9(19.9%) 8(17.8%) 1(2.2%) 1(2.2%) 1(2.2%)

Chronic renal failure 33(15%)

Post cardiac surgery 23(10.5%)

Autoimmune disease 7(3.2%)

TB 6(2.7%)

Pericarditis 6(2.7%)

Myxedema 5(2.3%)

Liver disease 4(1.8%)

Unknown 45(20.4%)

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Pericardial effusion drainage was performed

on 218 patients. Two patients underwent

percutaneous drainage with

echocardiography-guided pericardiocentesis.

The most common drainage procedure was

surgery via the subxiphoid approach and

general anesthesia. The appearance of

effusion was serous and yellowish in most

patients. The operative and postoperative

data of the patients are shown in Table 4.

Table 4. Operative and postoperative data of the patients (N=218)

Characteristic No %

Operative procedure n (%): Subxiphoid approach Mini-thoracotomy Percutaneous

213(97.7%) 3(1.4%) 2(0.9%)

Anesthesia: General Local

202(92.7%) 16(7.3%)

Volume of drainage fluid, mL 600±391 (10-3000)

Nature of pericardial fluid: Serous Sanguineous Purulent

128(58.2%) 85(38.6%) 5(2.3%)

Operative complication: Renal Pulmonary Arrhythmia None

3(1.4%) 1(0.5%) 2(0.9%) 212(97.2%)

Hospital mortality 10(4.5%)

Follow-up (mon) 0-78

There was no intraprocedural mortality. The

mortality rate during hospital stay was

10(4.5%). The fluid samples and pericardial

biopsy samples were sent for evaluation for

81(36.8%) patients. The cytological findings

included malignancy in 20 (24.7%), normal

in 21 (25.9%), inflammatory in 28 (34.6%),

and bloody in 12 (14.8%) patients.

Additionally, the pericardial biopsy reports

of 81 patients included malignancy in 16

(19.8%), normal in 28 (34.5%), acute

pericardial inflammation in 22 (27.2%),

chronic fibrotic inflammation in 12 (14.8%),

tuberculosis (TB) presentation in 2 (2.5%),

and non-pericardial tissue in 1 (1.2%).

The median follow-up period for all the

study participants was 35.5 (range = 0–78

mon). The survival rates at 1 month

(108/124), 1 year (84/124), 2 years (80/124),

and 3 years (71/124) were 87.1%, 67.7%,

64.5%, and 57.2%, respectively.

The mean survival rate of the patients was

not different significantly in terms of age (P

= 0.15), sex (P = 0.258), smoking (P = 0.6),

diabetes (P = 0.594), hypertension (P = 0.5),

the body mass index (P = 0.71), dyspnea (P

= 0.3), elevated jugular venous pressure (P =

0.293), hypotension (P = 0.45), the ejection

fraction (P = 0.998), fluid amounts (P =

0.549), right atrial collapse (P = 0.068),

respiratory variation (P = 0.356), and

anesthesia type (P = 0.256). Nonetheless,

the etiology of tamponade and cytological

and pathological findings significantly

affected the mean survival rate. The risk

factors affecting survival are presented in

Table 5.

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Table 5. Risk factors affecting survival (N=124) (follow-up of 0–78 months and mean survival of 35.5 months)

Characteristic Mean survival (months)

P value

Demographic Findings 32.67-42.28 >0.05

Clinical findings: Pulse paradox Others

48.58 versus 34.10 31.26-43.1

0.05

>0.05

Echocardiographic Findings 27.3-50.33 >0.05

Operative procedure n (%): Subxiphoid approach Mini-thoracotomy Percutaneous

36.15 11 6

0.614

Etiology of Tamponade: Cardiac Malignancy Chronic renal failure Post cardiac surgery Autoimmune disease TB Pericarditis Myxedema Liver disease Unknown

41.81±24.73 14.93±17.92 33.54±28.37 37.15±17.89 55.40±11.33 47±4.64 35±30.51 58.50±2.12 63.66±9.29 41.46±20.13

0.001

Cytological Findings: Malignancy Normal Inflammatory Bloody

15.55±19.51 45.93±28.88 45.75±27.35 20.50±21.61

0.002

Pathological Evaluation of Pericardium Biopsy: Malignancy Normal Acute inflammation Chronic inflammation TB Non-pericardial tissue

15.45±19.49 44.85±25.85 44.14±30.02 18.28±25.99 47±4.64 11

0.009

DISCUSSION

Pericardial effusion is rarely symptomatic,

and often it is an incidental finding.

However, with rapid or massive fluid

accumulation, signs and consequences of a

dangerous status of life may be created. 7

The diagnosis of significant pericardial

effusion based on clinical signs alone is

usually difficult. One study revealed that the

prevalence rates of hypotension, pulse

paradox, and elevated jugular venous

pressure in patients with echocardiography-

based tamponade were 70%, 60%, and 50%,

correspondingly. Puls paradox (> 10 mm

Hg drop in systolic blood pressure during

normal breathing) underscores the diagnosis

of cardiac tamponade, but it has a low

specificity. 2 In our study, most of the

patients were symptomatic and dyspnea was

the most common symptom (in 91.8%);

nevertheless, the prevalence of hypotension,

puls paradox, and elevated jugular venous

pressure was lower than that reported by

other studies.

Wang et al 8 showed sinus tachycardia in

72%, low voltage in 35% and electrical

alternans in 15.9% of their patients with

tamponade, which is similar to our common

ECG findings.

Transthoracic echocardiography is a reliable,

simple, and noninvasive method for the

diagnosis of tamponade. It diagnoses as

small as 20–50 mL of pericardial fluid.

Hamid et al 9 showed atrial collapse in all

their patients with large pericardial effusion

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and 50% of their patients with moderate

effusion presenting with tamponade. The

increased respiratory variation in the

tricuspid and mitral inflow velocities in

patients with pericardial effusion reveals

tamponade regardless of the amount of

effusion. 2 In our study, cardiac chambers

collapse, respiratory variation, and other

echocardiographic parameters were close to

similar studies, but the number of patients

with low left ventricular ejection fractions

was high because our hospital is the only

referral heart center in West Azerbaijan

province and most heart failure patients are

admitted to this center.

Ekim et al 10

showed left pleural effusion in

26.7% of their patients with purulent

pericarditis. We found radiographical

evidence of left pleural effusion in 38

(17.3%) patients. Considering the

association between left pleural effusion and

small amounts of pericardial effusion and

the possibility of the misdiagnosis of

pericardial effusion, we recommend more

attention in the echocardiographic

evaluation of these patients and re-

evaluation after left pleural effusion

drainage.

Multiple diseases such as malignancies,

uremia, hypothyroidism, infections, chest

trauma, collagen vascular disease, and

unknown causes may lead to pericardial

effusion and tamponade.

The most common malignant tumors

associated with tamponade are carcinoma of

the breast, melanoma, and lymphoma. 11

Jeon et al 6 reported lung cancer, followed

by breast cancer, in 65.5% and 10.9% of

their cases, respectively. A study reported

that 15%–20% of the autopsy specimens of

patients with malignancy exhibited

pericardial or cardiac metastasis. 12

We

detected malignancy etiologies in 20.5% of

all the cases, with the most common

malignant tumors being lung cancer,

hematological malignancy, gastrointestinal

cancer, and breast cancer, respectively. This

distribution of malignant tumors was also

reported in other studies. 1

The rate of pericardial effusion due to

benign diseases in our study was 79.5%,

which is higher than that reported by

previous studies. 1, 2

The prevalence of

patients with heart failure in our study was

high, so that the prevalence of patients with

left ventricular ejection fractions < 55% was

63.6%. Quraishi et al 2 showed normal left

ventricular function in 86.4% of their

patients.

We showed a history of pericardial effusion

drainage in 20 (9.1%) patients, which is

lower than the figure reported by Petcu et al 5 (32%–40% of the patients). A previous

study reported that the recurrence of

pericardial effusion after surgery in patients

with cancer-related pericardial effusion was

27.3%. 6 The reason for the low incidence of

recurrence in our study may be due to the

low prevalence of malignant causes.

Unlike developed countries, TB is the most

common cause of significant pericardial

effusion in developing countries. 13, 14

In our

study, TB was uncommon in that it was

responsible for 2.7% (6 patients) of all the

cases. In another study from Iran by

Mirhosseini et al, 1 the prevalence of TB in

symptomatic pericardial effusion was 6%–

8.6%. In the study by Quraishi et al 2 from

Pakistan, TB was detected in 27% of the

patients with massive pericardial effusion.

Cardiac tamponade is a rare manifestation of

hypothyroidism, 15

and its prevalence in our

patients was 2.3%. We had no traumatic

cases because our patients were treated in a

trauma referral center.

Treatment approaches for patients with

tamponade are different in many centers,

and there is controversy about the standard

procedure. The subxiphoid pericardial

drainage technique was first done by Larrey

in 1829. 17

The advantages of the subxiphoid

technique include simplicity and safety, 3

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inexpensiveness, 1 less postoperative pain,

and earlier postoperative extubation 7 and its

disadvantage is that it is associated with a

high recurrence rate in comparison with the

thoracotomy approach.7

The thoracotomy approach is more effective

at preventing effusion recurrence. 7

However, it is a more invasive operation that

is associated with greater potential for

morbidity, higher ventilation time, more

postoperative pain, 7 higher risk of sudden

hypotension during the induction of general

anesthesia, and difficulty in obese patients

and women with large breasts. 16

Pericardiocentesis is associated with

advantages inasmuch as it is less invasive

and it obviates the need for general

anesthesia; nonetheless, its disadvantages

include great risk of recurrence (as high as

60%) in comparison with window

operations, 6, 7

no direct visualization for

pericardial biopsy taking, 3 and active

bleeding after pericardiocentesis. 6 In our

center, in order to avoid cardiac penetrating

trauma and subsequent sternotomy and

exploration, we usually avoid

pericardiocentesis.

At our center, the subxiphoid technique is

the preferred option for the majority of

patients with tamponade. The recurrence

rate in our study was 9.1% (in 20 patients).

Celik et al 16

reported a recurrence rate of

2.08% for the left mini-thoracotomy

approach for tamponade. In all the recurrent

cases, we chose the subxiphoid technique for

the second drainage; however, for the third

drainage, we opted for the thoracotomy

approach. All 3 recurrent patients, who

underwent the left mini-thoracotomy

approach drainage, had malignancy.

Becit et al 18

reported a recurrence rate of

10% within 1 month following subxiphoid

surgical pericardiostomy in 368 patients.

Celik et al 16

reported that the nature of the

pericardial fluid was hemorrhagic in 37.5%,

serous in 60.4%, and purulent in 2.1% of

their patients, 16

which is similar to our

study.

Our surgical subxiphoid pericardiotomy was

done under local anesthesia in 16 (7.3%)

patients, which is less than the figure

reported by other studies. Celik et al 16

reported surgery under local anesthesia in

77% of their 57 patients. In order to avoid

severe hypotension and cardiac arrest in our

hypotensive patients, we performed the

surgical operations under local anesthesia.

Our postoperative complications were

reported in 2.8% of the cases. Jeon et al 6

reported operative morbidity in 12.7% of

their study patients, which included atrial

fibrillation, prolonged mechanical

ventilation, refractory hypotension,

constrictive pericarditis, and acute renal

failure.

In a study by Petcu et al, 5 hospital mortality

was reported in 13.04% of the patients in the

subxiphoid technique group and 20.37% in

the pericardiocentesis group. In another

study, the rate of hospital mortality in

patients treated with left mini-thoracotomy

was 8.33%. 16

In our study, there was no

surgery-related mortality and the hospital

mortality rate was 4.5%.

In most studies, the mean volume of the

drainage fluid was 600–800 cc. 1, 8

In

contrast to our results, Wagner et al 19

showed that the volume of the drained fluid

was one of the predictors of poor survival

after pericardial effusion drainage. Chiming

in with our results, Celik et al 16

showed that

there was no correlation between the

survival time and the amount of effusion

drained.

In our study, the mean survival rate of the

patients was not significantly different in

terms of demographic and clinical

characteristics such as age, sex, and

hypotension or echocardiographic

characteristics such as the ejection fraction,

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the fluid amount, and cardiac chamber

collapse. Pulse paradox affected the mean

survival rate of our patients (48.58 vs 34.10

mon) with unknown reasons. We found a

significant difference between the mean

survival rates of sanguineous (no

postoperative cases) and serous pericardial

effusions (20.5 vs 45 mon).

The underlying disease of patients with

tamponade is an established risk factor for

survival. 20

Patients with underlying

malignancy and malignant pericardial

effusion have poor survival in comparison

with patients with benign pericardial

effusion. 1, 16

Wagner et al, 19

in a review of

179 patients with pericardial window

surgery, reported poor overall survival for

the lung cancer group (median survival of 5

months). Nonetheless, in a study by Dosios

et al, 21

in contrast to our study, there was no

significant difference in the mean survival

rate between patients with positive and

negative cytological or histological results

for malignant invasion to the pericardium.

Whereas Wang et al 22

reported no

significant difference in the survival rates

between malignant and benign pericardial

effusion cases, we found a significant

difference between these groups in our

study. The etiology of tamponade and

cytological and pathological findings

significantly affected the mean survival rate

(15.5 vs 45 mon).

In a review of patients with cancer-related

pericardial effusion, the mean survival rate

was 4 months (range = 0–39 mon) and the 1-

year survival rate was 21.8%. 6 In another

study, the overall mean survival rate was

10.41 ± 1.79 months and the 1- and 2-year

survival rates were 45 ± 7% and 18 ± 5%,

respectively. 16

The mean survival time in

hematological malignancies was reported to

be 29.20 ± 7.59 months in a previous study. 21

In our study, the mean survival time in

malignant etiologies was 15.5 months. The

survival rates at 1 month (108/124), 1 year

(84/124), 2 years (80/124), and 3 years

(71/124) were 87.1%, 67.7%, 64.5%,

and57.2%, respectively.

CONCLUSIONS

The most common cause of tamponade in

our study was cardiac diseases (21%).

Malignancy etiologies were responsible for

20.5% of the cases. The most common

approach for pericardial effusion drainage

was the subxiphoid approach (> 97%),

which proved to be a safe and simple

procedure. In the current study, the rate of

intraoperative mortality was zero and the

rates of postoperative complications,

hospital mortality, and recurrence were

relatively low. Our results revealed an

association between left pleural effusion and

small amounts of pericardial effusion, which

underscores the significance of due attention

in the echocardiographic evaluation of these

patients. According to our results, patients

with primary sanguineous pericardial

effusion, malignant etiologies of tamponade,

and malignant pericardial effusion had

significantly poor survival.

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Choi SY, Suh JH , et al. Prognostic factors

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12. Laham RJ, Cohen DJ, Kuntz RE, Baim DS,

Lorell BH, Simons M. Pericardial effusion

in patients with cancer: outcome with

contemporary management strategies. Heart

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13. Imazio M and Adler Y. Management of

pericardial effusion. European Heart Journal

2013; 34, 16, 1186–1197.

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diagnosis and management of pericardial

disease to the epidemiological setting. Mayo

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Tamponade: The First Manifestation of

Myxedema. RJMS. 2007; 14 (54):139-142.

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Okay T , Tanrikulu N. Surgical properties

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CU, Koc¸ak H, Gu¨rlertop Y. Subxiphoid

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Asimacopoulos P: Risk factors affecting the

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submitted to subxiphoid pericardiostomy.

Chest 2003, 124:242–246

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Left Atrial Function in Transfusion-Dependent Thalassemia Parsaee et al

27

Original Article Left Atrial Function in Transfusion-Dependent Thalassemia Parsaee et al

Role of Left Atrial Structure and Function in the Early Prediction

of Cardiac Iron Overload in Transfusion-Dependent

β-Thalassemia Patients

Mozhgan Parsaee1, MD; Nakisa Khansari

*2, MD; Azita Azarkeivan

3, MD;

Mitra Chitsazan3, MD; Behshid Ghadrdoost

4, PhD; Hoda Mombeini

5, MD

ABSTRACT

Background: β-thalassemia is the most common monogenic disease caused by abnormalities in

the synthesis of the β-chain of hemoglobin.

Methods: From January 2018 to September 2018, 90 patients (age >18 y) with β-thalassemia

major or intermedia who referred to Rajaei Cardiovascular, Medical, and Research

Center, Tehran, Iran, for the assessment of myocardial iron overload were enrolled. All

the patients were receiving regular blood transfusions and chelating therapy.

Comprehensive transthoracic echocardiographic studies consisting of 2D

echocardiography, tissue Doppler imaging, and real-time 3D echocardiography were

performed.

Results: A total of 90 patients were enrolled in the study. Cardiac iron toxicity (ie, T2* < 20 ms)

was seen in 28 (31%) patients; whereas in 62 (69%) patients, the cardiac iron level was

undetectable (ie, T2* > 20 ms). Patients with T2* < 20 ms had significantly higher serum

ferritin levels than those with T2* > 20 ms (P = 0.02). No significant correlation was

found between the serum ferritin level and T2* (r = −0.08, P = 0.41). The left ventricular

ejection fraction was statistically similar in the 2D and 3D examinations. Left atrial end-

systolic and end-diastolic volumes were greater in the patients with iron cardiotoxicity

than in those with no detectable cardiac iron deposition (P = 0.01 and P <0.001,

respectively). Left atrial strain was also significantly lower in the patients with critical

iron overload. The patients with T2* < 20 ms also had lower left atrial ejection fractions

than those with T2* >20 ms, both in 2D and 3D examinations (both Ps <0.001).

Conclusions: Our study showed that changes in the left atrial structure and function precede

impairment in the left ventricular systolic function in thalassemia patients with critical

myocardial iron loading. (Iranian Heart Journal 2020; 21(1): 27-33)

KEYWORDS: Left atrium, Iron overload, -thalassemia

1 Echocardiography Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran. 2 Departement of Cardiology, Farshchian Heart Center, Hamadan University of Medical Sciences, Hamadan, IR Iran.

3 Department of Thalassemia Clinic, Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IR Iran. 4 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Department of Thalassemia Clinic, 5 Department of Cardiology, Khomeini Hospital, Jundishapour University of Medical Sciences, Ahvaz, IR Iran.

*Corresponding Author: Nakisa Khansary, MD; Echocardiography Research Center, Rajaie Cardiovascular, Medical, and Research Center,

Iran University of Medical Sciences, Tehran, IR Iran. Email: [email protected] Tel: 09188123413

Received: February 12, 2019 Accepted: April 15, 2019


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-thalassemia is the most common

monogenic disease caused by

abnormalities in the synthesis of the β-

chain of hemoglobin. 1, 2

Recent advances in

available therapies have improved long-term

prognosis in the affected individuals, with

approximately 80% of patients surviving

beyond 40 years. 3 Chronic hemolysis,

enhanced iron absorption by the intestine,

and frequent blood transfusions lead to iron

overload in these patients, ultimately

infiltrating various body organs including

the heart, liver, glands, and skin. 4, 5

Excessive cardiac iron accumulation results

in heart failure and cardiac arrhythmias,

which constitute the major etiologies of

death in patients with transfusion-dependent

thalassemia. 6-8

The gold standard technique to assess

cardiac iron deposition is cardiac magnetic

resonance imaging, 9 although its use is

limited by high costs involved and less

availability. Recently, echocardiographic

modalities including conventional 2D

echocardiography, Doppler

echocardiography, tissue Doppler

echocardiography, and 3D echocardiography

have provided promising results in the

diagnosis of iron overload in patients with

transfusion-dependent thalassemia.

Although most of these modalities have

assessed left ventricular diastolic and

systolic dysfunction as a surrogate marker of

cardiac involvement in thalassemia patients,

there is increasing evidence that ventricular

dysfunction occurs late in the disease course.

On the other hand, the data regarding the

predictive role of the assessment of the left

atrium in the early recognition of cardiac

iron toxicity are still scarce.

Accordingly, in the present study, we aimed

to investigate the association between the

left atrial structure and function and critical

cardiac iron deposition using conventional

2D echocardiography and real-time 3D

echocardiography in patients with β-

thalassemia receiving regular blood

transfusions.

METHODS

Study Population

From January 2018 to September 2018, 90

consecutive adult patients (age >18 y) with

β-thalassemia major or intermedia who were

referred to Rajaei Cardiovascular, Medical,

and Research Center, Tehran, Iran, for the

assessment of myocardial iron overload

were enrolled. All the patients were

receiving regular blood transfusions and

were on chelating therapy (deferoxamine

mesylate).

All the patients provided written informed

consent, and the Institutional Board Review

at Rajaei Cardiovascular, Medical, and

Research Center approved the study

protocol.

Echocardiographic Examination

Comprehensive transthoracic

echocardiographic studies comprised of 2D

echocardiography, tissue Doppler imaging,

and real-time 3D echocardiography were

performed in all the patients by a single

echocardiography specialist using a Philips

EPIQ 7 ultrasound system for cardiology

(Philips Ultrasound, Bothell, WA, USA)

equipped with xMATRIX ultrasound

transducer technology. All the

echocardiographic examinations were

performed in the left decubitus position and

at least 4 days after a recent blood

transfusion.

Magnetic Resonance Imaging

Cardiac magnetic resonance imaging (CMR)

scan was used to quantify myocardial tissue

iron loading by Heart T2* measurements.

All the scans were performed using a torso

β

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coil on a 1.5 T General Electric CVi scanner

via a single breath-hold multi-echo gradient

technique. As described by Anderson et al, 7

critical iron loading was defined as a T2*

value < 20 ms and values ≥ 20 ms were

considered to be uncritical (no detectable

cardiac iron).


All the analyses were conducted using IBM

SPSS Statistics 22 for Windows (IBM Inc,

Armonk, NY, USA). The data were initially

assessed for normality using the

Kolmogorov–Smirnov test. The categorical

variables were presented as numbers and

percentages and were compared using

the χ2 test. The continuous variables were

presented as the mean ± the standard

deviation or the median and the interquartile

range (IQR) and analyzed using the Student

t-test, the Mann–Whitney test, and the

Kruskal–Wallis test, depending on the data

distribution. The relationships were assessed

using the Pearson correlation coefficient (r)

and the Spearman rank correlation

coefficient (ρ), as appropriate. All the P

values were 2-tailed and a P value < 0.05

was considered statistically significant.

RESULTS

A total of 90 patients, including 42 females

(46.6%), at a mean age of 29 ± 6 years were

enrolled in the study. The median serum

ferritin level was 693.50 μg/L (IQR, 309.00

to 1205.25) and mean cardiac T2* was 24.46

± 7.91 ms. Cardiac iron toxicity (ie, T2* <

20 ms) was seen in 28 (31%) patients;

whereas in 62 (69%) patients, the cardiac

iron level was undetectable (ie, T2* > 20

ms). The baseline characteristics of the

patients are summarized in Table 1.

Table 1. Baseline characteristics of the study population

Characteristic P value

Age 29±6

Gender male female

48 (53.4) 42 (46.6)

Dyspnea No Yes

52 (57.8)

NYHA Function Class I II III IV

31 (34.5) 7 (7. 4) 0 (0) 0 (0)

Electrocardiographic Findings Normal PAC PVC

75 (83.3) 14 (15.6) 1 (1.1)

Laboratory Measurements

Hemoglobin 10.4 (9.5-11.5)

Ferritin 693.5 (309-1205.25)

CMR data

T2* 24 918-30.25)

Data are presented as the mean ± the standard deviation or the median (interquartile ranges) and numbers (percentage). CMR, Cardiac magnetic resonance imaging; NYHA, New York Heart Association; PAC, Premature atrial contraction; PVC, Premature ventricular contraction

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The patients with T2* < 20 ms had

significantly higher serum ferritin levels

than those with T2* > 20 ms (1150 [340–

1750] vs 567 [300.75–886.50]; P = 0.02).

However, no significant correlation was

found between the serum ferritin level and

T2* (r = −0.08, P = 0.41).

The left ventricular ejection fraction was

statistically similar between the 2 study

groups, both in 2D and 3D examinations (P

= 0.29 and P = 0.20, respectively)

Left atrial end-systolic and end-diastolic

volumes were greater in the patients with

iron cardiotoxicity than in those with no

detectable cardiac iron deposition (P = 0.01

and P < 0.001, respectively). Left atrial

strain was also significantly lower in the

patients with critical iron overload than in

those without detectable cardiac iron

deposition (P = 0.001). The patients with

T2* < 20 ms also had lower left atrial

ejection fractions than those with T2*>20

ms, both in 2D and 3D examinations (both

Ps < 0.001). All the echocardiographic

variables are compared between the 2 study

groups in Table 2.

The correlations between serum ferritin,

cardiac T2*, and echocardiographic indices

are shown in Table 3.

Table 2. Echocardiographic indices in the patients with T2*< 20 ms and >20 ms

Variable T2*<20 ms (Critical Iron Overload)

(n=28)

T2*>20 ms (No Detectable Iron Overload)

(n=62)

P value

LVEF (2D) (%) 55 (50-55) 55 (53.75-55) 0.29

LVEF (3D) (%) 50.5 (44.25-60.25) 53 (50-60) 0.20

RVEF (3D) (%) 43.5 (38.5-48.75) 48.5 (43.25-52.75) 0.01

LAESV (mL) 42.5 (33.5-53.75) 33 (28-43.25) 0.01

LAEDV (mL) 30 (22-38) 18 (14-22.12) <0.001

LA Stroke volume (mL) 16 (12-22.5) 17.4 (14-23) 0.53

LA volume Normal Enlarged Mild Moderate Severe

10 (35.7) 11 (39.3) 3 (10.7) 4 (14.3)

48 (77.4) 11 (17.8) 2 (3.2) 1 (1.6)

0.001

LA strain 32 (25-38) 40 (33-44) 0.001

LAEF (2D) (%) 35.22±10.40 46.20±12.72 <0.001

LAEF (3D) (%) 35.89±12.25 45.40±13.48 0.002

SPAP (mm Hg) 35 (30-40) 30 (30-35) 0.11

RAEF (2D) (%) 29.88±10.71 40.57±10.92 <0.001

RAEF (3D) (%) 30±2.88 33.75±14.64 0.51

Data are presented as the mean ± the standard deviation or the median (interquartile ranges) and numbers (percentages). LA, Left atrial; LAEF, Left atrial ejection fraction; LAEDV, Left atrial end-diastolic volume; LAESV, Left atrial end-systolic volume; LVEF, Left ventricular ejection fraction; RAEF, Right atrial ejection fraction; RVEF, Right ventricular ejection fraction; SPAP, Systolic pulmonary artery pressure

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Table 3. Correlations between echocardiography-

derived indices and serum ferritin levels and cardiac T2*

ENB’ Serum Ferritin

T2* ms

LVEF (2D) R 0.04 0.19

P 0.66 0.06

LVEF3D R 0.25 0.22

P 0.01 0.03

RV3DEF R 0.20 0.20

P 0.05 0.05

LAESV R 0.18 -0.34

P 0.07 0.001

LAEDV R 0.12 -0.44

P .23 <0.001

SV R 0.03 -0.03

P 0.74 0.77

LA strain R -0.07 0.40

P 0.51 <0.001

LAEF2D R -0.02 0.36

P 0.79 .001

LAEF3D R -0.01 0.33

P 0.91 0.001

SPAP R 0.08 -0.19

P 0.40 0.06

RA_EF2D R 0.07 0.48

P 0.48 <0.001

RAEF3D R 0.62 0.69

P 0.05 0.02

LA, Left atrial; LAEF, Left atrial ejection fraction; LAEDV, Left atrial end-diastolic volume; LAESV, Left atrial end-systolic volume; LVEF, Left ventricular ejection fraction; RAEF, Right atrial ejection fraction; RVEF, Right ventricular ejection fraction; SPAP, Systolic pulmonary artery pressure

DISCUSSION

Iron toxicity greatly affects the long-term

prognosis in patients with β-thalassemia and

is a major cause of morbidity and mortality

in these patients. 3, 6-8

CMR is considered the

gold standard method in the early

recognition of iron deposition in the

myocardium. However, its use is limited due

to high cost and less availability, particularly

in developing countries. As a result,

echocardiography has been introduced as a

less expensive, widely available, and

reproducible method for this purpose,

although its sensitivity and specificity in

assessing cardiac iron accumulation are

limited.

Assessments of the left ventricular function

(ie, the ejection fraction) have been drawn

upon as a marker of iron toxicity, even

though an iron deposition level sufficient

enough to affect the left ventricular function

occurs late in the disease course. Moreover,

high cardiac output due to chronic anemia

masks proper detection of ventricular

dysfunction. As a result, other

echocardiographic indices have been

investigated for the early recognition of iron

accumulation in susceptible patients. A

study by Rodrigues et al 11

showed that the

left atrial volume index, the mitral septal

E/Em ratio, the duration of reverse

pulmonary vein flow, and the mitral E/A

ratio were higher in patients with

asymptomatic thalassemia major than in

healthy individuals and patients with iron

deficiency anemia. However, they found no

significant differences in the left ventricular

structures and systolic function indices

among their 3 study groups. In contrast to

our study, Rodrigues and colleagues did not

evaluate cardiac iron accumulation CMR.

In the present study, to determine the

predictive role of the left atrial structure and

function in the early recognition of cardiac

iron overload in patients with thalassemia,

we employed conventional 2D

echocardiography and real-time 3D

echocardiography with a view to comparing

relevant indices in patients suffering from

thalassemia with and without critical iron

deposition. All the patients were on chronic

blood transfusion and were receiving iron

chelation therapy (deferoxamine mesylate).

Of note, all the participants had preserved

left ventricular functions (ie, ejection

fraction > 40%) and normal left and right

ventricular sizes.

We found that the patients with and without

critical myocardial iron deposition had

statistically comparable left ventricular

ejection fractions, reinforcing the limited

role of the left ventricular function in the

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early identification of myocardial iron

loading, as previously described.

Cardiac involvement in infiltrating diseases

primarily begins with diastolic dysfunction,

causing gradual dilatation in atrial size and

impairment in atrial contraction. 12-15

The

progression of cardiac infiltration would

eventually lead to the deterioration of the

ventricular systolic function. Thus, changes

in the left atrial structure and function might

precede the development of overt pump

failure. In accordance with this hypothesis,

our results demonstrated that patients with

iron cardiotoxicity had significantly lower

left atrial ejection fractions than those

without critical iron deposition, highlighting

the predictive role of the left atrial function

in the early prediction of iron toxicity in

patients with thalassemia receiving chronic

blood transfusions. In a case-control study,

Aggeli et al 16

compared the left atrial

performance in 28 patients with

asymptomatic β-thalassemia who were on

chelating therapy with 20 age- and sex-

matched healthy controls using transthoracic

real-time 3D echo. The thalassemia group

had normal echocardiographic systolic and

diastolic functions; however, unlike the

patients in our study, there was no

myocardial iron disposition according to

MRI. They found that the left atrial active

emptying fraction was reduced in the

thalassemia group compared with the

healthy controls.

We also found a significant correlation

between T2* and the left atrial ejection

fraction (both in 2D and 3D

echocardiography, r = 0. 36, P < 0.001 and r

= 0.33, P < 0.001; respectively). Moreover,

our results showed that the patients with

critical iron loading had higher left atrial

volumes (end-systolic and end-diastolic

volumes) and lower left atrial strain than

those with non-critical iron loading.

However, in the study by Aggeli et al, 16

no

significant differences were seen in the left

atrial volumes (the left atrial maximum

volume at end-systole, the left atrial volume

just before the mitral valve opening, and the

left atrial volume before atrial active

contraction) between patients with

thalassemia and healthy individuals. It

should be noted, however, that the patients

with thalassemia in the aforementioned

study did have cardiac iron deposition,

which might explain discrepancies seen in

their results with our study.

CONCLUSIONS

In conclusion, our study showed that

changes in the left atrial structure and

function precede impairment in the left

ventricular systolic function in patients

suffering from thalassemia with critical

myocardial iron loading. Larger left atrial

systolic and diastolic volumes and poorer

left atrial performance in these patients

might be used as echocardiographic markers

for the early identification of iron

deposition, which, in turn, could affect

management strategies such as the

employment of more aggressive chelating

therapies.

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DT, Zoumbos NC. Heart failure in β-

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V. Cardiac failure in β-thalassemia:

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JC, Rodrigues CS, Waib P, Fabron-Junior

A, Tan DM, França AC, Okoshi MP, Okoshi

K. Echocardiography in thalassemic patients

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Torres P, Zhang R, et al. Effect of aging and

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Brandts B, Trappe HJ. Assessment of left

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Rentoukas EI, Vretou HP, Toutouzas PK.

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Prescott E, Walker JM, Porter JB, et al. Left

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16. Aggeli A, Felekos I, Poulidakis E, Aggelis

A, Tousoulis D. Quantitative analysis of left

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https://www.ncbi.nlm.nih.gov/pubmed/?term=Rodrigues%20A%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

https://www.ncbi.nlm.nih.gov/pubmed/?term=Guimar%C3%A3es-Filho%20FV%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

https://www.ncbi.nlm.nih.gov/pubmed/?term=Braga%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

https://www.ncbi.nlm.nih.gov/pubmed/?term=Braga%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

https://www.ncbi.nlm.nih.gov/pubmed/?term=Rodrigues%20CS%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

https://www.ncbi.nlm.nih.gov/pubmed/?term=Waib%20P%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

https://www.ncbi.nlm.nih.gov/pubmed/?term=Fabron-Junior%20A%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

https://www.ncbi.nlm.nih.gov/pubmed/?term=Fabron-Junior%20A%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

https://www.ncbi.nlm.nih.gov/pubmed/?term=Tan%20DM%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

https://www.ncbi.nlm.nih.gov/pubmed/?term=Fran%C3%A7a%20AC%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

https://www.ncbi.nlm.nih.gov/pubmed/?term=Okoshi%20MP%5BAuthor%5D&cauthor=true&cauthor_uid=23295250

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https://www.ncbi.nlm.nih.gov/pubmed/23295250


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Hospital at Home Khaleghparast et al

34

Original Article Hospital at Home Khaleghparast et al

Hospital Facilities at Home for Heart Failure Patients

Shiva Khaleghparast, PhD1; Alireza Maleki, MD

2*; Sepideh Taghavi, MD

1;

Ahmad Amin, MD1; Majid Maleki, MD

3; Mehrdad Oveisi, PhD

1;

Behrooz Ghanbari, PhD4; Zahra Hanifi, BS

1; Nasim Naderi, MD

1

ABSTRACT

Background: Heart failure is a complex syndrome and also one of the common reasons for

readmission following discharge. This condition imposes an enormous economic burden

on healthcare sectors. The present research aimed to study the establishment of a home

care system for patients with heart failure in order to evaluate the cost-effectiveness of

this system and patient satisfaction.

Methods: The present health system research selected 40 patients as the sample with eligible

criteria. Care was provided by nurses based on physicians’ instructions. In the first visit at

home, a questionnaire on the quality of life was filled out by the patients or the nurses.

The financial data of the medical records of the patients constituted the reference for the

analysis of cost. After the intervention, the questionnaire on the quality of life was filled

out by the patients once again and their satisfaction was measured. The data were

statistically analyzed using the Python programming language and SPSS-16 at the 0.05

level of significance.

Results: The length of stay in the hospital for each patient decreased from 2.1 days to 0.9 days

per month. The number of annual hospitalizations also decreased from 5 to 3, and the

number of annual outpatient visits showed a reduction from 46 to 38 for each patient. The

results of the patient satisfaction assessment also indicated that most of the patients were

satisfied with the services provided to them.

Conclusions: The results showed that our study was cost-effective. We suggest that

interventions be performed on larger scales so that the results can be used in the future as

services available to patients with heart failure. (Iranian Heart Journal 2020; 21(1): 34-44)

KEYWORDS: Home care, Heart failure, Hospital facilities

1 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

2 Department of Anesthesiology, Hazrat Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, IR Iran.

3 Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences,

Tehran, IR Iran. 4 Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

*Corresponding Author: Alireza Maleki, MD; Hazrat Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, IR Iran. Email: [email protected] Tel: 02123922192

Received: February 12, 2019 Accepted: April 26, 2019


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eart failure (HF) is a complex,

chronic, and debilitating clinical

syndrome and also one of the

common reasons for readmission following

discharge.1-5

This condition not only

increases complications and mortality while

reducing the quality of life in the process 6

but also imposes an enormous economic

burden on the healthcare sector. The

insufficient attention of patients to the

recommendations made by the treatment

team is a contributing factor for a 50% rate

of readmission in patients with HF. 7, 8

The

statistics show that approximately 5.1 to 5.8

million individuals in the United States and

26 million worldwide suffer from HF,

accounting for 1%–3% of the general

population. 9

In Iran, 3.3% of adults are

afflicted with HF. 10

The prevalence of HF

increases with age, reaching 8.4% and

17.4% among people aged 75 and 85 years,

respectively. This disease is the most

common reason for hospitalization of

individuals aged over 65 years in the United

States and Europe. In addition, it is the cause

of 18%–27% of readmissions within the first

month and 50% of readmissions during the

first 6 months following discharge. 9

Although the mortality rate of this disease

has decreased overall, its 5-year mortality

rate is still equal to that of most cancers, 11

accounting for its description as a

malignancy and its very difficult prognosis.

The signs and symptoms increase as the

disease progresses, and patients exhibit

symptoms such as pain, dyspnea, and

fatigue. Moreover, this disease negatively

affects the quality of life and the

psychosocial status of patients. 2 The high

complications and mortality of this disease

can lead to an increase in treatment costs.

Approximately 1%–2% of national health

costs in the United States and Britain are

spent on patients with HF, 80% of which is

related to hospitalization costs. 9

These

patients do not adhere to their medical

treatment plan according to the guidelines.

Therefore, they need a complex and

multidisciplinary care program. Without

periodic interventions and follow-ups, they

will need emergency hospitalization or

readmission. This indicates the importance

of continuous care and the expansion of

professional services at home. Home care,

remote monitoring, outpatient clinics,

communications, and follow-ups by

professional team members can increase the

safety, satisfaction, and quality of life of

these patients after discharge. 1-3, 12, 13

Quality of life, as a quality index for health

systems, decreases in chronic patients after

discharge. 14

Hence, these patients need an

emotional system that not only saves

medical costs but also improves their

clinical outcomes and quality of life. 2, 15, 16

Recent studies have shown that home care

interventions reduce mortality up to 34%

and readmission by 30%–56% in patients

with HF. 8

However, there are still doubts

with regard to the cost-effectiveness of this

system 15

and there is a need for the

development of evidence to back this

approach. 2

To the best of our knowledge, no

study has been conducted in Iran about the

establishment of this system for patients

with HF. Hence, the present research aimed

to study the establishment of a home care

system for patients with advanced HF

referred to the Heart Failure Department of

Rajaie Cardiovascular, Medical, and

Research Center (RCMRC), tertiary center

for HF programs in Iran, in order to evaluate

the cost-effectiveness of this system and

patient satisfaction.

METHODS

Design

The present research was aimed at studying

satisfaction with regard to the cost-

effectiveness of a health system. To begin, a

home care center was established for

patients with HF at RCMRC. Manpower,

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equipment, and appropriate physical space

were provided in accordance with the

instructions set out by Iran’s Ministry of

Health and Medical Education (139/d/672-

2016 July 25).

Data Collection

The statistical population comprised all

patients with HF hospitalized at RCMRC

from August 2017 to March 2018. Based on

the convenience sampling method, 40

patients were selected as the sample group

consecutively. The inclusion criteria were

those with advanced HF 17

aged over 18,

residing in Tehran, an ejection fracture <

30%, a history of frequent hospitalization, at

least on rehospitalization within 6 months,

no history of surgery in the last 2 months,

and willingness to obtain home care

services. Patients with severe cognitive

impairment or those who needed dialysis

during the intervention were excluded from

the study.

Ethical Considerations

First, a workshop consisting of a briefing

session was scheduled for the staff where

they were provided with necessary

explanations on communication with

patients/families; professional code of

conducts and dress codes; ethical principles;

and principles of HF management including

guideline-directed medical therapies, self-

care measures, and HF nursing roles and

strategies. The study protocol was approved

by the ethics committee of RCMRC

(IR.RHC.REC.1397.001).

Investigation

When patients with advanced HF were being

discharged, their medical records were

reviewed by an HF specialist for the

eligibility of enrollment. Finally, 40 patients

were enrolled in this study. An informed

consent form was obtained, and the patients’

basic information was recorded. Care was

provided by a nurse holding at minimum a

bachelor’s degree and based on the

instructions made by the physician. In the

first visit at home, a questionnaire on the

quality of life was filled out by the patients

themselves or with help from the nurses.

The care provided at home included control

of vital signs; physical examination; diet and

medication training; weight control;

absorption and excretion control through

training and documentation; the

administration of necessary medications

such as diuretics; and blood sampling for

blood chemistry, electrolytes, and

coagulation status based on the patients’

condition and physician’s preference. Self-

care was taught to the patients and

monitored. In addition, phone follow-ups

involved answering the patients’ questions,

clearing any ambiguities, and emphasizing

compliance with the instructions.

The financial data of the medical records of

the patients constituted the reference for the

analysis of hospitalization and outpatient

service cost. The visitation costs consisted of

staff costs, supplies and equipment, and

personnel transfer and phone follow-up costs

included the cost of phone calls and the

wage of experts calling the patients.

Patients’ quality of life was the criteria for

measuring the effectiveness of the study.

Moreover, the number of readmissions, the

length of stay at the hospital, man-hour (the

amount of work performed by the average

worker in 1 hour), and patient satisfaction

with both the system and the provided care

were also determined.

Analysis

Cost-effectiveness analysis was performed

in 3 stages. In the first stage, all costs

consisting of nursing care, telephone follow-

ups, referrals to the clinic, hospital

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admissions, laboratory and pharmaceutical

services, and personnel costs during the 6

months before and after the implementation

of the study were calculated and compared

with each other. In the second stage, the

number of readmissions, the length of stay at

the hospital, and the patients’ quality of life

were compared before and after the

intervention. The required data were

collected using a 3-part questionnaire,

consisting of the personal information of the

patients (14 items), disease-related factors

(15 items), and quality of life 18

(13 items:

physical dimension, 14 items: psychological

dimension, 9 items: socioeconomic

dimension, and 4 items: general health

dimension). The items were scored based on

a 5-point Likert scale from “very much” 5 to

“not at all”. 1 Higher scores indicate a higher

quality of life. The minimum and maximum

scores on this questionnaire were 40 and

200, respectively. The quality of life scores

of 200 and 40 were determined as the

highest level of effectiveness (with a mean

of 5) and a lack of effectiveness (a mean of

1), respectively. This questionnaire was used

by Rezaei in 2006, and its validity has been

confirmed by experts. In addition, the

reliability of this questionnaire has been

reported to be 91%. 18

In the third stage, a

cost-effectiveness analysis was done in 3

steps consisting of the comparison of cost-

effectiveness before and after the

intervention, the determination of the

incremental cost-effectiveness ratio (ICER),

and a sensitivity analysis. The sensitivity

analysis itself was performed in 3 stages as

follows: the identification of non-

deterministic parameters, including the cost

of treatment and patient recovery; the

determination of the acceptable range for

changing the non-deterministic parameters

by making a change of 5% in treatment

costs; and the calculation for the ratio of

incremental cost-effectiveness using new

values of the parameters.

The quality of life questionnaire was refilled

out by all the study population after

completing the home care course, and their

satisfaction was measured. The satisfaction

form measured the patients’ satisfaction in 4

areas of admission, physician, nurse, and

equipment and facilities based on a 3-point

Likert scale from “Yes” (2) to “No” (0). The

data were statistically analyzed using the

Python programming language and SPSS-16

at the 0.05 level of significance.

RESULTS

Out of 40 patients participating in the study,

21 (52%) patients were male and the

educational attainment of half of these

individuals was at an elementary school

level. The demographic information of the

participants is shown in Table 1. Since the

patients were added to the home care project

on different days, the mean and standard

deviation of the number of study days before

and after the implementation of the plan was

96.25 ± 35.80 and 97.75 ± 35.80,

respectively.

During the implementation of this plan, a

total of 138 home visits and 473 phone

consultation sessions were provided to the

patients. The total number of patients’

referrals for admission before and after the

implementation of the study was 54 and 34,

respectively. Table 2 shows all the treatment

costs by services before and after the

implementation of the home care (for 40

patients for 6 months).

The results of the cost analysis also

indicated that the mean total finished cost

per patient was reduced by 50% after the

study. In addition, the total monthly cost

paid by the patients showed a reduction of

about 61%. The finished cost for the

implementation of home care in our study

was considered by adjusting the number of

service providers from 2 to 1 while

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considering one-tenth of the equipment cost

as wear and tear.

Figure 1 shows the finished costs for each

patient per month in payment systems.

Table 1. Demographic characteristics of the patients participating in the study

Frequency Percentage

Sex Male 21 52.5

Female 19 47.5

Age >=51 36 90

41-50 2 5

31-40 2 5

Marital status

Married 29 72.5

Single 11 27.5

Education Elementary 20 50

Diploma 10 25

High school 7 17.5

Bachelor’s degree 2 5

Postgraduate 1 2.5

Jobs Housewife 14 35

Retired 9 22.5

Unemployed 9 22.5

Worker 5 12.5

Freelance 2 5

Employee 1 2.5

Table 2. Treatment costs by services before and after the implementation of the home care

Type Inpatient Outpatient Visits Calls Total

Stage

Pt_Fee Before 15,411 7,717 0 0 23,127

After 3,055 5,914 0 0 8,969

Ins_Fee Before 203,997 13,675 0 0 217,672

After 78,040 10,006 0 0 88,047

Other_Fee Before 20,506 3,092 0 0 23,598

After 19,930 2,426 0 0 22,356

Home care_Fee Before 0 0 0 0 0

After 0 0 11,532 2,659 14,192

Total

Before 239,913 24,484 0 0 264,398

After 101,026 18,346 11,532 2,659 133,563

All 340,939 42,830 11,532 2,659 397,961

*All fees are in 10,000 Rials.

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Figure 1. Finished costs for each patient per month in payment systems

* All fees are in 10,000 Rials.

By adding the cost spent on the

implementation of the home care to the costs

paid by insurance companies, we observed a

32% reduction in the insurance costs. In

addition, reducing the number of service

providers and equipment led to a 54%

reduction in costs (Fig. 2).

Figure 2. Comparison of the finished cost of insurance companies

before and after the implementation of the study

The mean quality of life score among the

studied patients before and after the

implementation of the home care was 2.4 ±

0.39 and 2.9 ± 0.39, respectively.

Accordingly, there was a significant

difference between the quality of life before

and after the intervention (P < 0.001) (Table

3).

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Table 3. Comparison of the mean quality of life before and after the home care intervention

Index Variable

Mean

Standard deviation

Paired

t-statistic

Degree of freedom

Probability

value

95% confidence interval

Lower limit

Upper limit

Quality of life

Before the intervention

2.4 0.39

-17.44

62

<0.001

-0.52

-0.41 After the intervention

2.9 0.39

Based on the study results, the length of stay

at the hospital for each patient decreased

from 2.1 days to 0.9 days per month. The

number of annual hospitalization also

decreased from 5 to 3, and the number of

annual outpatient visits showed a reduction

from 46 to 38 for each patient. The results of

the patient satisfaction assessment also

indicated that 94% of the patients were

satisfied with the services provided. Figure 3

shows the outcomes of the home care

intervention.

Considering the cost-effectiveness ratio data,

the cost for each unit of increase in the

quality of life score after the intervention

was less than that before the intervention.

Given that medical prices varied during the

6 months before and after the intervention,

the incremental cost-effectiveness ratio

determined a total reduction in medical costs

with 1 unit of increase in the mean quality of

life after the home care intervention.

After the completion of the sensitivity

analysis with a 5% change in medical costs

and the recalculation of incremental cost-

effectiveness, this ratio was not significantly

different from the main findings without any

change in medical costs. Therefore, it can be

stated that the study findings are of

acceptable strength. In addition, the man-

hour for physician and nurse was equal to

half an hour and 4 hours for each patient

during a day, respectively.

Figure 3. Outcomes of the home care intervention

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DISCUSSION

The study results showed that the home care

intervention significantly reduced the mean

monthly cost of home care for each patient.

In addition, the length of stay at the hospital

and the annual number of admissions

showed a reduction after the intervention.

The results also indicated that the quality of

life significantly increased after the home

care intervention and the patients were

greatly satisfied with the services provided

to them.

In a study conducted by Maru et al 1

(2015),

home care intervention led to a higher

quality of life and lower medical costs for

patients with chronic HF in a 3.2-year

follow-up period. They also illustrated that

home care interventions significantly

reduced the length of stay at the hospital.

Finally, their findings suggested that home

care interventions were more cost-effective

than hospital interventions for old patients

with HF.

Alina et al 2 (2018) reported a significant

difference in the mean score of quality of

life between 2 groups of patients with HF

who received home care intervention and

conventional treatment. However, they

observed no significant difference between

the 2 groups in terms of distress symptoms

or performance status during a 12-week

follow-up period. Patient satisfaction was

higher and the working pressure of nurses

was lower in the intervention. In addition,

the home care intervention reduced some of

the disease symptoms.

Cowie et al 3 (2010) reported a study

conducted by Tibaldi in Italy, in which 2

interventions consisting of home care

without a cardiologist and hospital

intervention (physicians and nurses) were

compared with each other. The home care

and hospital interventions lasted 21 and 12

days, respectively. The home care services

included the establishment of the venous

route, blood pressure check, and the

administration of intravenous drugs. In the

present study, the home care services also

consisted of vital signs control, training, and

intravenous injections of necessary drugs.

The readmission rate was reported the same

in both groups by Cowie and colleagues,

while the readmission rate showed a

reduction after the home care intervention in

the present study. This difference may be

due to the shorter duration and lower

number of visits at home in the study by

Cowie and coworkers. By contrast, the cost

of home care was lower than hospitalization,

which is consistent with the findings of the

present study. It is noteworthy that part of

the home care intervention in the present

study was related to training and telephone

follow-ups.

Hugylund et al 8 (2015) emphasized the

significance of training patients with HF and

its impact on the improvement of their

quality of life. Additionally, training reduced

the hospitalization days of the patients, 19-21

which is consistent with the findings of the

present study. Baglimeyhem et al 10

(2013)

showed that training was effective in

promoting the health behavior of their

patients with HF. In this regard, Chen et al 15

(2010) stated that telephone counseling by

trained nurses significantly reduced the

hospitalization rate (all-cause admission). In

addition, it reduced the hospitalization days

by 8 days and the 6-month medical expenses

by 2682 dollars for each patient.

In the present study, the quality of life score

presented a significant increase after the

home care intervention. This is consistent

with the results of many previous studies. 1,

8, 16 The reduced length of stay and

readmission rate after the home care

intervention in the present study are also

consistent with many previous studies. 3, 7-9,

12, 15, 22

Overall, the study findings indicated the

cost-effectiveness of home care intervention

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for patients with HF. Ottawa 23

(2015)

reported that the use of telehealth services

such as telephone support or telemonitoring

reduced the rate of hospitalization and

mortality and improved the quality of life

and lifestyle of patients. Telemonitoring

reduces hospitalization and death due to HF

and all other causes. However, the use of

telemonitoring in the hospitals of the

Netherlands made no significant difference

in the annual medical costs of patients Cost-

effectiveness indicated the high level of

uncertainty in decision-making. Another

study conducted in the Netherlands also

showed that telemonitoring failed to cause a

significant difference in patients’ quality of

life and their annual costs. The results of a

study conducted in Canada in 2013 showed

no significant difference between 3 groups

of conventional care, telephone intervention,

and telemonitoring intervention in terms of

medical costs. 13

Kendall Ho 12

(2016) showed that the

telemonitoring of patients with HF at home

was a cost-effective strategy to reduce the

rate of revisits and readmissions and it was

able to improve their comfort and quality of

life in a 90-day period. This difference can

be due to the non-provision of home care

services by expert personnel and the mere

provision of telemonitoring and telephone

follow-ups for patients in previous studies.

CONCLUSIONS

In summary, the present study suggested the

cost-effectiveness of the home care

intervention for patients with HF. Sahlen et

al 11

(2016) also indicated that home care

was a cost-effective strategy for patients

insofar as it saved resources. Reduced

medical costs through home visitations have

been also reported in many other studies. 2, 3,

7, 9, 11, 12, 15, 24

Undoubtedly, modern home care systems for

patients with HF require multidisciplinary

services so that patients and their families

can have access to various specialties at the

required time. Many patients may need to be

hospitalized for these reasons, but many of

these cases can be potentially prevented

through the proper management of chronic

diseases, effective communication, and the

correct monitoring of conditions by patients

and medical teams. If such an intervention is

performed on larger scales, the results can

be used in the future as services available to

patients suffering from HF.

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Malakouti K, SeyedAlinaghi S, Sudhinaraset

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A, Rahgozar M. The Effect of Self Care

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23. Naderi N, Bakhshandeh H, Amin A,

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N-terminal Prohormone of Brain Natriuretic Peptide in Patients With Pulmonary Thromboembolism Baradaran et al

45

Original Article N-terminal Prohormone of Brain Natriuretic Peptide in Patients With Pulmonary Thromboembolism Baradaran et al Predictive Power of N-terminal Prohormone of Brain Natriuretic

Peptide on Admission and on Discharge for Short- and Long-term

Clinical and Echocardiographic Outcomes in Patients With

Pulmonary Thromboembolism

Abdolvahhab Baradaran 1, MD; Davood Kazemi Saleh

*1, MD; Yaser Jenab

2, MD;

Susan Hashemi 2, MD; Arash Jalali

3, PhD; Elham Feizabad

3, MD

ABSTRACT

Background: This prospective case-series study was conducted to determine the predictive

power of the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) on short-

and long-term outcomes in patients with pulmonary thromboembolism (PTE).

Methods: Ninety-two patients (age = 60 ± 1.97 y, 54.7% male) diagnosed with PTE were

recruited. NT-proBNP levels and echocardiographic indices were measured and recorded.

The primary endpoint was considered to be 3-month PTE-related deaths and long-term

adverse outcomes including 1-year all-cause mortality, rehospitalization due to the

recurrence of PTE, right ventricular dysfunction, and pulmonary hypertension.

Results: The serum NT-proBNP level and the right ventricular diameter were significantly

higher in the patients with adverse outcomes than in the outcome-free patients. Several

significant correlations were found between NT-proBNP levels and echocardiographic

indices. During a mean follow-up time of 12 months, 1 patient suffered PTE relapse, 15

patients had right ventricular dysfunction and pulmonary hypertension, and 2 patients

expired. Age was an independent value in the prediction of the adverse outcome (OR:

1.064, 95% CI: 1.01 to 1.11). Discharge NT-proBNP levels, calculated according to a

multiple cutoff point strategy for heart failure, in the PTE patients with adverse outcomes

was 2.36 fold that in the outcome-free patients. The optimal value for discharge NT-

proBNP according to the receiver operating characteristic analysis was 327 pg/mL, with a

sensitivity of 80% and a specificity of 43%.

Conclusions: NT-proBNP measurement during the course of PTE, especially on discharge, may

have a role as an easy-to-use diagnostic tool for determining patients with poor

prognoses. (Iranian Heart Journal 2020; 21(1): 45-54)

KEYWORDS: N-terminal prohormone, Brain natriuretic peptide, Biomarkers, Pulmonary embolism

1 Atherosclerosis Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran. 2 Department of Cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, IR Iran..

3 Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, IR Iran.

*Corresponding Author: Davud Kazemi Saleh, Atherosclerosis Research Center, Baqiyatallah University of Medical Sciences, Mollasadra St,

Vanak Sq, Tehran, IR Iran.. Zip code: 1435915371 Email: [email protected] Tel: 09121191169

Received: April 7, 2019 Accepted: July 10, 2019


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ulmonary thromboembolism (PTE) is

a potentially fatal disorder, and its

severity ranges from asymptomatic to

multi-organ manifestations. 1-3

Hence, rapid

and accurate diagnosis of patients,

particularly to distinguish high-risk patients

from low-risk ones, presents a challenge to

emergency physicians. The most notable

prognostic modalities currently available are

imaging tools such as echocardiography and

computed tomography angiography (CTA)

and serum biomarkers such as troponins,

plasma leptin concentrations, and heart-type

fatty acid-binding proteins. 4-8

N-terminal prohormone of brain natriuretic

peptide (NT-proBNP) has been proposed as

an additional tool for risk stratification. 9

NT-proBNP, released from myocytes in the

ventricles of the heart, is frequently used in

the diagnosis of congestive heart failure and

in distinguishing between patients with

dyspnea of cardiac or pulmonary origin. It

has also been evaluated for the assessment

and management of several other diseases

such as sepsis, cirrhosis of the liver, and

renal failure. 10

Elevated NT-proBNP levels can identify

patients with acute PTE at high risk of short-

term death and adverse outcome events.

Although evidence has shown that the NT-

proBNP measurement in the primary phase

has excellent power to predict the 30-day

(short) outcome like pulmonary

hypertension and right ventricular

dysfunction in patients with PTE, 11 12

it has

a low positive predictive value; accordingly,

serial measurements in the hospital

admission phase appear to be helpful. 13

Currently, there is a paucity of data on the

sequential measurement of NT-proBNP

from admission to discharge and there are no

known predictive models capable of

forecasting poor long-term outcomes in

patients suffering from PTE. 14

We,

therefore, sought to determine the predictive

power of the sequential measurement of NT-

proBNP on admission and on discharge for

short- and long-term clinical and echo-

cardiographic outcomes in patients with

PTE.

METHODS

This prospective case-series study was

conducted on 92 consecutive patients with a

diagnosis of acute PTE registered in the

Pulmonary Embolism Database of Tehran

Heart Center, affiliated with Tehran

University of Medical Sciences, Tehran,

Iran, between 2013 and 2016. The

definitions of the diagnosis and management

of PTE in our center have been published

previously. 15

The exclusion criteria were comprised of a

history of previous PTE, PTE occurrence

during patient admission due to another

medical condition, and death during the first

hospitalization due to PTE. Also excluded

were patients with hemodynamic instability

at presentation and delayed pulmonary

computed tomography angiography (CTA)

(48 hours after diagnosis).

In all the patients, PTE was defined as the

illustration of partial or complete filling

defects in the pulmonary circulation by

pulmonary spiral CTA scan. According to

pulmonary spiral CTA scans, PTE was

classified as saddle PTE (if the thrombus

was lodged at the level of the bifurcation of

the pulmonary trunk and extended into both

main pulmonary arteries), central PTE (if the

thrombus involved the main branches

through the segmental branches), and

peripheral PTE (if the thrombus involved the

segmental and sub-segmental branches).

Doppler and 2D echocardiographic

examinations were conducted by

experienced operators within 48 hours of

admission, on discharge, and in each follow-

up visit. All the quantifications were

performed in accordance with the

P

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recommendations of the American Society

of Echocardiography Committee. Right

ventricular dysfunction was defined as a

right ventricular diameter > 34 mm or a

right-to-left ventricular ratio > 0.9, or the

presence of wall motion abnormalities in the

right ventricular free wall. Right ventricular

systolic dysfunction was defined as a

tricuspid annular plane systolic excursion

< 16 mm or a pulsed Doppler peak velocity

at the tricuspid annulus < 10 cm/s.

All the patients were cured in the acute

phase with conventional therapeutic doses of

unfractionated or low molecular-weight

heparin. Thrombolytic therapy was used at

the discretion of the treating cardiologist.

The patients were discharged with warfarin

and control of their international normalized

ratio. Complete data on the study

population’s baseline demographic

characteristics as well as clinical, laboratory,

and imaging findings were acquired through

face-to-face interviews and medical files.

Upon admission, the levels of systolic blood

pressure, heart rate, respiratory rate, O2

saturation, and high-sensitivity cardiac

troponin T (hs-cTnT) were measured.

Hemodynamic instability was defined as the

presence of the following in the patients

upon admission: need for cardiopulmonary

resuscitation, systolic blood pressure < 90

mm Hg or a drop in systolic blood pressure

> 40 mm Hg for 15 minutes with signs of

end-organ hypoperfusion or need for

catecholamine prescription to protect

adequate organ perfusion, and systolic blood

pressure < 90 mm Hg.

Within 48 hours of PTE diagnosis and on

discharge, blood samples (2 cc) were taken

from the patients. The samples were

centrifuged at 5 °C at 3000 rpm for 10

minutes. The separated serum was thereafter

stored at −20 °C until the NT-proBNP

measurement. The levels of NT-proBNP

were determined using an ELISA kit (USA).

After discharge, the patients were contacted

and asked to refer to our center for follow-

up evaluations based on their availability

time. In the case of death, the outcome data

were obtained by contacting the deceased

patient’s relatives.

Follow-up was done by clinical

examinations in outpatient clinics or

telephone contacts with the patients or their

relatives. The primary endpoint was

considered to be 3-month PTE-related

deaths; and because of our small sample

size, in addition to 1-year all-cause

mortality, other related outcomes such as

rehospitalization due to the recurrence of

PTE and echocardiographic indices

including right ventricular dysfunction and

pulmonary hypertension were considered to

be long-term adverse outcomes.

This study was approved by our institutional

review board, and all the patients gave

informed consent for the use of their data for

research purposes.

The continuous variables were expressed as

the mean and the standard deviation and

were compared between the patients with

and without outcomes using the independent

samples t-test. When the continuous data

were nonparametric, they were expressed as

the mean and the standard error and were

compared between the groups via the

nonparametric 2-independent samples

(Mann–Whitney U) test. The categorical

variables were displayed as frequencies and

percentages and were compared between the

patients with and without outcomes using

the χ2 or Fisher exact test, as appropriate.

Variables with a P value < 0.2 in the

univariate analysis were chosen as

candidates to enter the multivariable model.

The multiple predictors of long-term

outcomes were found through the

application of a backward logistic regression

model, with the removal and entry

probabilities of 0.1 and 0.05. The effect of

the covariates on the adverse outcomes was

reported as an odds ratio (OR) with a 95%

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48

confidence interval (CI). The discrimination

power of the model was determined by

applying the area under the receiver

operating characteristics (ROC) curve. IBM

SPSS Statistics for Windows, version 22.0,

was used to conduct the analyses.

RESULTS

Totally, 92 patients diagnosed with acute

PTE were evaluated. During the first

admission, 6 patients died and were, as a

result, excluded. During a mean follow-up

time of 12 months from the diagnosis of

PTE, 13 patients were lost to follow-up

(failure to return for the follow-up visits), 1

patient suffered PTE relapse, 15 (23%)

patients sustained right ventricular

dysfunction and pulmonary hypertension,

and 2 patients expired due to PTE (1 patient

immediately after discharge and the other

after 14 months). Finally, 73 patients were

analyzed in our study. The mean age of the

study population, including 33 (40%)

women, was 60 ± 1.97 years. All the patients

were diagnosed by means of CTA. Only 1

patient needed fibrinolytic therapy. A

previous history of diabetes was reported in

10 (13.7%) patients, hypertension in 26

(35.6%), and dyslipidemia in 13 (17.8%).

Additionally, a previous history of HF was

reported in only a single patient. All the

baseline medical information of the study

population is depicted in Table 1.

Upon admission, 5 (6.2%) patients had

cancer (breast, gallbladder, ovary, prostate,

and testis cancer 1 each). Immobility for

more than 3 days was reported in 17 (21%)

patients and previous deep vein thrombosis

in 4 (4.9%).

On admission, the mean value of NT-

proBNP was 4064.7 ± 577.3 pg/mL, the

mean value of hs-cTnT was 68.2±8.8

ng/mL, the mean value of hemoglobin was

14.3±0.2 g/dL, and the mean value of

creatinine was 1.01 ± 0.04 mg/dL.

Additionally, the mean values of systolic

blood pressure, heart rate, and O2 saturation

were 130.8 ± 2.1 mm Hg, 103.4 ± 2.1, and

92.6%, respectively. On discharge, NT-

proBNP had a mean value of 1876.5 ± 358.1

pg/mL.

The change in the NT-proBNP level over

time was evaluated: There was a decreasing

trend of serum NT-proBNP during

hospitalization, from admission to discharge,

in the 2 study groups and there was a

significant difference in the admission and

discharge NT-proBNP levels between the 2

groups (P < 0.05) (Fig. 1).

Figure 1. Comparison of the trend of

serum NT-proBNP on admission and on discharge between the 2 study groups NT-proBNP, N-terminal prohormone of brain natriuretic peptide

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Table 1. Demographic and clinical characteristics of the study patients

Variable Total

(N=73) Without

Outcomes, n=48 With Outcomes,

n=25 P

value OR (95% CI)

Male 40(54.7) 26(54.1) 14(56) 0.881 1.077(0.407-2.848)

Age (y) 73 54.38±2.39 71.32±2.67 ‹0.001 -

Comorbid Conditions

Diabetes mellitus 10(13.6) 7(14.5) 3(12) 0.761 0.799 (0.188-3.399)

Hypertension 26(35.6) 16(33.3) 10(40) 0.572 1.333 (0.490-3.625)

Dyslipidemia 13(17.8) 7(14.5) 6(24) 0.318 1.850 (0.547-6.256)

Heart failure 1(1.3) 0(0) 1(4) 0.342 0.333 (0.240-0.462)

Risk Factors

Immobility ≥3d 15(20.5) 7(14.5) 8(32) 0.801 2.756 (0.863-8.804)

Previous DVT 4(5.4) 3(6.2) 1(4) 0.689 0.625 (0.062-6.339)

Obesity 29(39.7) 18(37.5) 11(44) 0.590 1.310 (0.490-3.497)

Recent surgery 6(8.2) 4(8.3) 2(8) 0.961 0.957 (0.163-5.620)

Cancer 5(6.8) 4(8.3) 1(4) 0.487 0.458 (0.048-4.336)

Estrogen use 8(10.9) 8(16.6) 0(0) 0.031 0.615 (0.508-0.746)

Recent air travels 6(8.2) 4(8.3) 2(8) 0.961 0.957 (0.163-5.620)

Physical Examination

Heart rate (b/min) 73 105.06±2.81 97.88±4.07 0.135 -

SBP (mm Hg) 73 132.17±3.32 127.56±2.57 0.613 -

RR (min) 73 21.93±0.93 25.25±1.43 0.020 -

O2 saturation (%) 73 93.38±0.55 91.33±1.29 0.249 -

Sign of DVT 12(16.4) 7(14..5) 5(20) 0.371 1.813 (0.487-6.753)

High risk in simplified PESI score 44(60.2) 30(62.5) 14(56) 0.590 0.764 (0.286-2.040)

ECG Findings

RBBB 14(19.1) 8(16.6) 6(24) 0.450 1.579 (0.480-5.196)

S1Q3T3 40(54.7) 26(54.1) 14(56) 0.881 1.077 (0.407-2.848)

Precordial T inversion in V1 42(57.5) 24(50) 18(72) 0.071 2.571 (0.909-7.278)

Echocardiographic Findings

RV dysfunction 629(84.9) 39(81.2) 23(92) 0.223 2.654 (0.527-13.363)

RV diameter 61(83.5) 37(77) 24(96) 0.039 7.135 (0.865-58.887)

Lab Findings

Hemoglobin (g/dL) 73 14.45±0.33 14.16±0.49 0.577 -

White blood cell (mL) 73 11750.65±622.25 11248.33±517.99 0.897 -

Serum creatinine (mg/dL) 73 0.95±0.04 1.10±0.07 0.058 -

High sensitivity cardiac troponin T (ng/L)

73 78.47±12.12 46.02±6.27 0.374 -

D-Dimer (g/L) 73 7.92±0.96 8.681.47 0.964 -

NT-proBNP (admission) (pg/mL) 73 2952.12±569.26 4906.72±1071.07 0.037 -

NT-proBNP (discharge) (pg/mL) 73 1032.69±247.39 3017.46±922.55 0.004 -

Spiral CTA Findings

Pulmonary infarction 18(24.6) 10(20.8) 8(32) 0.294 1.788 (0.600-5.327)

Saddle embolism 15(20.5) 11(22.9) 4(16) 0.708 0.779 (0.211-2.8883)

Segmental artery embolism 5(6.8) 4(8.3) 1(4) 0.487 0.458 (0.048-4.336)

Pleural effusion 10(13.6) 6(12.5) 4(160 0.680 1.333 (0.339-5.243)

Continuous variables are displayed as the mean ± the standard errors and the categorical variables are presented as numbers (%). DVT, Deep vein thrombosis; SBP, Systolic blood pressure; RR, Respiratory rate; RV, Right ventricle; RBBB, Right bundle branch block; NT-proBNP, N-terminal prohormone of brain natriuretic peptide

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As can be seen in Table 1, of all the

variables in the baseline paraclinical

assessment, the serum NT-proBNP level,

especially on discharge, and the right

ventricular diameter were significantly

higher in the patients with adverse outcomes

than in the outcome-free patients.

Furthermore, there were several significant

correlations between the NT-proBNP level

and echocardiographic indices (Table 2).

Table 2. Correlation between plasma NT-proBN at different time points and echocardiographic indices

Parameter RV Diameter RV Function RV:LV Ratio

r P value r P value r P value

NT-proBNP (admission) 0.293 0.009 -0.363 0.001 0.477 ‹0.001

NT-proBNP (discharge) 0.273 0.015 -0.298 0.008 0.567 ‹0.001

NT-proBNP (admission-discharge) 0.138 0.226 -0.198 0.085 0.140 0.237

RV, Right ventricle; LV, Left ventricle; NT-proBNP, N-terminal prohormone of brain natriuretic peptide

The existing literature lacks a cutoff point

for NT-proBNP in patients with PTE; we

were, therefore, obliged to use the cutoff

point of NT-proBNP in patients with heart

failure in order to calculate the diagnostic

markers. Table 3 shows the univariant

comparisons between several parameters. As

is depicted in Table 3, NT-proBNP on

discharge, NT-proBNP–based heart failure,

and age had significant differences between

the patients with and without outcomes (P <

0.05) (Table 3).

NT-proBNP exhibited no predictive effect in

the logistic regression equation, prompting

us to enter the NT-proBNP calculated based

on the multiple cutoff point strategy for

heart failure in our logistic regression

analysis. The results showed that age was an

independent value in the prediction of the

adverse outcome (OR: 1.064, 95% CI: 1.01

to 1.11) and discharge NT-proBNP

calculated based on the multiple cutoff point

strategy for heart failure in the PTE patients

with adverse outcomes was 2.36 fold that in

the outcome-free patients (Table 3).

Moreover, the area under the ROC curve

analysis was used to identify the optimal

plasma level of the discharge NT-proBNP

cutoff value so as to distinguish patients

with and without poor outcomes throughout

the period of the study: The optimal value

was 327 pg/mL. The value of the area under

the ROC curve for the patients throughout

the study was 0.707 (95% CI: 0.583 to

0.831), with a sensitivity of 80% and a

specificity of 43% (Fig. 2).

Table 3. Prediction of the adverse outcomes in the patients with pulmonary thromboembolism

Variables Entered in the Model

Univariate Analysis Multivariable

Analysis

OR (95% CI) P value

OR (95% CI) P value

NT-proBNP (admission) 1.009 0.095

NT-proBNP (discharge) 1.026 0.027

NT-proBNP difference (admission-discharge) 1.000 0.977

NT-proBNP– based HF (discharge) 3.250 0.024 2.360 0.168

Age 1.078 ‹0.001 1.064 0.007

Serum creatinine 3.379 0.095 1.684 0.566

Immobility ≥ 3 d 2.756 0.087 2.614 0.176

HF, Heart failure; NT-proBNP, N-terminal prohormone of brain natriuretic peptide

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Figure 2. Area under the receiver operating characteristics (ROC) curve for serum NT-proBNP

on discharge NT-proBNP, N-terminal prohormone of brain natriuretic peptide

DISCUSSION

Our study showed that in patients with

adverse outcomes, the serum NT-proBNP

level and the right ventricular diameter were

significantly higher than those in outcome-

free patients. There were several significant

correlations between NT-proBNP levels and

echocardiographic indices. We found that

age was an independent value in the

prediction of adverse outcomes and that

discharge NT-proBNP calculated based on a

multiple cutoff point strategy for heart

failure in PTE patients with adverse

outcomes was 2.36 fold that in outcome-free

patients.

PTE is potentially an acute and fatal disease

and requires emergency interventions if the

patient’s life is to be saved. Nonetheless,

usually due to nonspecific symptoms,

diagnosis is delayed and the golden time for

treatment is lost. 16

Recent years have

witnessed the emergence of several

diagnostic modalities for the determination

of patients with poor prognoses. Of course,

it is not feasible to draw upon all these tools

in practice, but NT-proBNP measurement

during the course of PTE appears to be

simple. 17-21

Aside from patients with PTE, the level of

NT-proBNP rises in other groups of patients

with morbid conditions, including heart

failure. 22-24

Similarly, our study showed that

in patients with PTE, higher levels of NT-

proBNP were significantly correlated with

future adverse outcomes such as heart

failure. 25, 26

Interestingly, in our study, the mortality rate

was low by comparison with previous

studies. This variation may be due to a lack

of significant difference in the baseline risk

factors of PTE and the existing underlying

disease between our 2 study groups. Another

possible explanation is that we reported the

death rate after the discharge time in our

study, while previous studies have merely

explained this rate within their patients’

hospitalization period. 14, 27, 28

In our univariate analysis, age and discharge

NT-proBNP had significant correlations

with the adverse outcomes (OR: 1.064, 95%

CI: 1.01 to 1.11 and OR: 1.026 95% CI:

1.003 to 1.049, respectively). Whereas age is

an unchangeable predictor, patients’

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discharge NT-proBNP is a suitable guide for

appropriate follow-up interventions.

In our study, the discharge NT-proBNP

cutoff point according to the ROC curve

analysis was lower than the figures

previously reported. This discrepancy may

be because those investigations assessed

NT-proBNP on admission, while we

assessed it on discharge. In addition, NT-

proBNP has a decreasing trend during the

course of PTE. However, our study supports

this notion that a low level of NT-proBNP is

associated with having a good prognosis in

the course of PTE. 10, 29

We found a significant correlation between

NT-proBNP levels and echocardiographic

indices such as right ventricular dysfunction

and the right-to-left ventricular ratio. It is

worthy of note, however, that

echocardiographic indices—in comparison

with NT-proBNP levels—have low

sensitivity for detecting poor prognoses in

patients with PTE. Echocardiography

should, therefore, be considered a suitable

supplementary paraclinical tool in patients

with PTE. 30-32

First and foremost among the limitations of

the present study is its small sample size.

Another weakness of note is that we

recruited only patients who were diagnosed

with PTE in the emergency department and

not those in whom PTE diagnosis was

missed or those who expired before PTE

diagnosis. That our study population was

selected from a single-center PTE registry

may limit the generalization of our results.

Indeed, had we assessed a larger sample

volume, some results that were significant in

the univariate analysis might have been

statistically significant in the logistic

regression analysis.

CONCLUSIONS

Our study showed that higher serum NT-

proBNP levels and abnormalities in

echocardiographic indices were associated

with adverse outcomes in patients with PTE.

Although natriuretic peptides rise in several

morbidity conditions such as heart failure,

an increase in NT-proBNP should be

deemed an alarm for all-cause mortality in

patients with PTE. Thus, the NT-proBNP

measurement during the course of PTE,

especially on discharge, may have a role as

an easy-to-use diagnostic tool for

determining patients with poor prognoses.

Acknowledgments

Not applicable.

Conflict of Interest

The authors have no conflicts of interest.

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Irisin and Type 2 Diabetes Complications Zyaddini et al

55

Original Article Irisin and Type 2 Diabetes Complications Zyaddini et al

Chest Pain is Associated With Decreased Irisin Serum Levels in

Type 2 Diabetic Patients With Coronary Artery Disease

Taybeh Zyaddini1, MD; Gholamreza Asadikaram

2, PhD;

Mohammad Masoumi3*

, MD

ABSTRACT

Background: This study aimed to determine irisin serum levels in type 2 diabetic patients with

and without coronary artery disease (CAD).

Methods: This study was performed on 56 type 2 diabetic patients with and without CAD and 28

normal controls. The serum levels of irisin, HbA1c, and fasting blood sugar of all the

participants and the severity of CAD in the diabetic patients were determined.

Results: The irisin serum level was significantly decreased in the CAD diabetic patients who

were symptomatic. HbA1c had a moderate positive correlation with the SYNTAX score

in the diabetic patients with CAD. The serum level of irisin was not significantly

different between the evaluated groups.

Conclusions: Based on the results, decreased irisin may be considered a risk factor for type 2

diabetic patients with CAD. Accordingly, the evaluation of patients with decreased irisin

serum levels regarding the prediction of heart infarcts may be valuable. (Iranian Heart

Journal 2020; 21(1): 55-66)

KEYWORDS: Irisin, Type 2 diabetes, Cardiovascular diseases, Angiography

1 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, IR Iran. 2 Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Biochemistry,

Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, IR Iran. 3 Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, IR Iran.

*Corresponding Author: Mohammad Masoumi, MD; Cardiovascular Research Center and Department of Cardiology, Afzalipur Faculty of Medicine Kerman University of Medical Science, Kerman, IR Iran.

Email: [email protected] Tel:09131409938

Received: February 23, 2019 Accepted: May 26, 2019

iabetes is the most common chronic

disease and affects human life world

wide. 1 It has been estimated that

diabetes will be raised to more than 328

million cases in the near future. 2 It is the

fourth cause of morbidity and mortality in

developed countries. 3 Diabetes can be

associated with several complications

including retinopathy, nephropathy, and

cardiovascular diseases 4, 5

It has been

reported that diabetic patients suffer from

cardiovascular diseases 2 to 5 times more

than nondiabetic individuals. 6 Diabetes can

be associated with the incidence of heart

D


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56

ischemia and cardiovascular disease-related

complications. Therefore, the identification

of new markers for the prediction of heart

ischemia in diabetic patients who suffer

from cardiovascular diseases is a new aim of

investigators.

Recent investigations have proposed that

irisin, a novel defined myokine, may be

considered a potential marker for the

induction of cardiovascular diseases and

then heart ischemia in diabetic patients. 7

Irisin is a novel glycoprotein produced by

the proteolysis of membrane fibronectin

type ΙΙΙ domain-containing, which happens

in response to the activation of PPAR-γ co-

activator-1α (PGC-1α). 8 It has been

proposed that irisin is an important molecule

that participates in the conversion of white

to brown adipose tissues and, thus, decreases

the risk of obesity, a critical risk factor for

the induction of type 2 diabetes and

cardiovascular diseases. 9 There is some

controversy regarding the serum levels of

irisin in type 2 diabetic patients with and

without coronary artery disease (CAD). 9, 10

However, some investigations have reported

that the serum level of irisin is associated

with decreased risks of insulin resistance

and glucose tolerance. 11, 12

It has also been

hypothesized that the altered expression of

irisin during cardiovascular diseases may be

a mechanism to manipulate the ATP levels

of myocardial cells, which are under

ischemic conditions, to protect them from

further damage. 10

It appears that the altered

expression of irisin may be associated with

either physiological or pathological

responses to heart ischemia. Due to the

recent defined roles played by irisin, it has

been hypothesized that the molecule may

participate in the pathogenesis of type 2

diabetes and its complications. Thus, the

main aim of the present study was to

identify the irisin serum level in type 2

diabetic patients suffering from CAD in

comparison with type 2 diabetic patients

without CAD and healthy controls. Another

aim of the current study was to determine

the relationship between the irisin serum

level and other risk factors such as the

SYNTAX score, HbA1C, and ethnic factors

in the evaluated groups.

METHODS

Subjects

This cross-sectional study was performed

between 2016 and 2017 on type 2 diabetic

patients who referred to Shafa Hospital,

Kerman University of Medical Sciences,

Kerman, Iran. Fifty-six type 2 diabetic

patients with angiography criteria, based on

clinical presentations and paraclinical

indications, and 28 healthy controls without

diabetes and CAD were introduced to the

study. Blood samples were collected in both

groups pre-treated and without anticoagulant

agents to evaluate HbA1C and irisin serum

levels, respectively. Healthy controls were

comprised of individuals who had

angiography criteria but who did not suffer

from diabetes and CAD. The type 2 diabetic

patients were divided into 2 groups

consisting of patients with and without

CAD. The demographic data including age

and sex, as well as other information

regarding the history of familial CAD,

smoking, blood hypertension, drug

consumption, dyslipidemia, and obesity,

were collected from the participants.

Angiography was performed by an expert

cardiologist via the Judkins method and

interpreted by another cardiologist blinded

to the study aims. The severity of CAD was

determined using the SYNTAX scoring

method. 13

The exclusion criteria were as

follows: type 2 diabetes of less than 1 year’s

duration, age < 30 years and > 60 years, and

regular exercise in the recent 12 months (due

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57

to the effects of exercise on the irisin serum

level).

Determination of the Irisin Serum Level

The irisin serum level was determined using

commercial kits from BioCompare

Company (New York, USA).

Evaluation of HbA1C

The status of HbA1C was evaluated using a

commercial kit according to the

manufacturer’s guidelines.


SPSS software, version 18, was used to

analyze raw data. Based on the normality in

the data distribution, one-way ANOVA was

employed to analyze the differences in irisin,

HbA1C, fasting blood glucose (FBG), age,

and weight between the groups. The χ2 test

was applied to analyze the differences

between the groups regarding gender;

smoking; opium consumption; regular

exercise; chest pain; chronic diarrhea; a

history of diabetes; elevated triglyceride and

cholesterol; heart diseases; familial heart

diseases; hospitalization; and liver, kidney,

and infectious diseases. The independent t-

test was also used to analyze the differences

in the variables within each group between

the male and female patients, between the

participants residing in urban and rural

areas, between the smokers and nonsmokers,

between the opium users and non-users, and

finally between the patients with and

without chest pain. The Pearson correlation

test was also utilized to calculate the

correlation between irisin, FBG, weight, age,

HbA1C, and the SYNTAX score.

RESULTS

The results showed that the serum level of

irisin was not significantly altered (P =

0.097) in the type 2 diabetic patients with

(3.16 ± 0.44 ng/mL) and without (3.35 ±

0.38 ng/mL) CAD and the normal controls

(2.25 ± 0.27 ng/mL) (Fig. 1).

The data analysis revealed that there were no

significant differences between the groups

regarding age (P = 0.08); sex (P = 0.168);

smoking (P = 0.210); opium addiction (P =

0.199); a history of kidney (P = 0.350), liver

(P = 0.376), and familial heart (P = 0.103)

diseases; weight (P = 0.370); regular

exercise (P = 0.304), and chronic diarrhea

(P = 0.583). However, the levels of FBG

and HbA1C were significantly higher in the

type 2 diabetic patients (with and without

CAD) than in the normal controls, while

there were no significant differences

between the 2 diabetic groups regarding

FBG (P = 0.938) and HbA1C (P = 0.202)

(Fig. 1).

The diabetic patients (with and without

CAD) had significantly higher scores of a

history of increased triglyceride (P = 0.012)

and cholesterol (P = 0.027) levels as well as

chest pain (P < 0.001).

The results also showed that the serum

levels of irisin, FBG, and HbA1c were not

changed between the male and female (Fig.

2), between the smoking and nonsmoking

(Fig. 3), and between opium-addicted and

nonaddicted (Fig. 4) type 2 diabetic patients

with and without CAD.

The statistical analysis also revealed that the

serum level of irisin significantly decreased

in the type 2 diabetic patients with CAD

who suffered from chest pain in comparison

with the patients without chest pain (P =

0.039) (Fig. 5). Nonetheless, there were no

significant associations regarding FBG and

HbA1c between the type 2 diabetic patients

with and without CAD who were suffering

from chest pain in comparison with those

without chest pain. The irisin serum level

also was not changed between the type 2

diabetic patients without CAD with chest

pain in comparison with those without chest

pain (P = 0.342).

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The Pearson test demonstrated that HbA1c

had a moderate positive correlation with the

SYNTAX score and a significant correlation

with FBG in the type 2 diabetic patients with

CAD (Table 1 Section A). The evaluation of

the type 2 diabetic patients with CAD (Table

1 Section A) showed that there was a poor

negative correlation between the SYNTAX

score and weight in the patients. HbA1c also

had a significant correlation with FBG in the

type 2 diabetic patients without CAD (Table

1 Section B). Table 1 Section C reveales no

correlation between the variables in the

normal controls.

Table 1. Correlation analysis regarding irisin, FBG, age, HbA1c, the SYNTAX score, and weight

in the type 2 diabetic patients with CAD (A), without CAD (B), and normal controls (C)

FBG Weight Age SYNTAX score HbAIC Irisin A

-0.081 -0.190 -0.085 -0.113 0.017 1 Pearson Correlation Irisin

0.682 0.332 0.667 0.567 0.933 P value

0.885** -0.239 0.176 0.646* 1 0.017 Pearson Correlation HbAIC

0.000 0.220 0.371 >0.001 0.933 P value

0.521 -0.375*** 0.268 1 0.646* -0.113 Pearson Correlation SYNTAX score 0.004 0.050 0.168 >0.001 0.567 P value

FBG Weight Age HbAIC Irisin B

0.267 0.044 0.082 0.361 1 Pearson Correlation Irisin

0.162 0.820 0.674 0.054 P value

HbAIC 0.816***** -0.116 0.125 1 0.361**** Pearson Correlation

>0.001 0.549 0.518 0.054 P value

FBG Weight Age HbAIC Irisin C

-0.05 .081 -0.328 0.161 1 Pearson Correlation Irisin

.980 .687 .095 0.254 P value

HbAIC 0.416 -0.216 0.225 1 0.161 Pearson Correlation

0.095 0.849 0.438 0.254 P value

Data analysis revealed that HbA1c had a moderate positive correlation with the SYNTAX score (*) and a significant correlation with FBG (**) in the type 2 diabetic patients with CAD (A). Evaluation of the type 2 diabetic patients with CAD (A) revealed that there was a poor negative correlation between the SYNTAX score and weight in the patients (***). HbA1c also had a poor and significant correlation with irisin (****) and FBG (*****) in the type 2 diabetic patients without CAD (B). The variables had no significant correlation with each other in the normal controls. CAD, Coronary artery disease; FBG, Fasting blood glucose

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Figure 1. Serum levels of irisin and fasting blood glucose (FBG) as well as the HbA1c percentage, age, and weight

values in the type 2 diabetic patients with and without coronary artery disease (CAD) as well as the healthy controls. The figure demonstrates that there were no significant differences between the groups regarding irisin, age, and weight. However, the serum level of FBG and the HbA1c percentage were significantly higher in the diabetic patients than in the normal controls.

343 x 412 mm (96 x 96 DPI)

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Figure 2. Serum levels of irisin and fasting blood glucose (FBG) as well as the HbA1c percentage in the male and

female type 2 diabetic patients with and without coronary artery disease (CAD). The figure demonstrates that there were no significant differences between the male and female patients in both groups regarding irisin, FBG, and the HbA1c percentage.

405 x 293 mm (96 x 96 DPI)

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Figure 3. Serum levels of irisin and fasting blood glucose (FBG) as well as the HbA1c percentage in the smoking and

nonsmoking type2 diabetic patients with and without coronary artery disease (CAD). The figure demonstrates that there were no significant differences between the smoking and nonsmoking patients in both groups regarding irisin, FBG, and the HbA1c percentage.

264 x 205 mm (96 x 96 DPI)

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Figure 4. Serum levels of irisin and fasting blood glucose (FBG) as well as the HbA1c percentage in the opium-

addicted and nonaddicted type 2 diabetic patients with and without coronary artery disease (CAD). The figure demonstrates that there were no significant differences among the opium-addicted and nonaddicted patients in both groups regarding irisin, FBG, and the HbA1c percentage.

411 x 350 mm (96 x 96 DPI)

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Figure 5. Serum levels of irisin and FBG as well as HbA1c percent in the type 2 diabetic patients with and

without CAD who were suffered from chest pain in comparison to without chest pain. The figure shows that irisin significantly decreased in the type 2 diabetic patients with CAD who were suffered from chest pain in comparison to the patients without chest pain (*P = 0.049). There were no significant differences among the type 2 diabetic patients with and without CAD who were suffered from chest pain in comparison to without chest pain.

405 x 341 mm (96 x 96 DPI)

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DISCUSSION

In the present study, the results revealed no

significant differences between the 2 groups

regarding the serum level of irisin;

nevertheless, the statistical analysis

demonstrated that the irisin serum level in

the type 2 diabetic patients with CAD

suffering from chest pain was significantly

decreased when compared with the type 2

diabetic patients with CAD but without

chest pain. Given that chest pain in patients

with CAD is a major criterion in the

induction of heart ischemia, it may be

hypothesized that decreased serum levels of

irisin in patients with chest pain may be

considered a predicting factor for the onset

of heart ischemia. Chiming in with this

notion, Wang et al 14

reported that irisin

played a key role in protecting the

mitochondria function, the myocardial

infarct size, and finally the heart against

ischemia and reperfusion injuries in their

study population. The role played by irisin

in the protection of the mitochondria

function during ischemia was also

documented by Chen and colleagues. 15

Thus, decreased irisin levels following chest

pain in type 2 diabetic patients with CAD

may be a risk factor for susceptibility to

cardiac infarction. Additionally, Aydin et al 16

demonstrated that using iloprost and

sildenafil, 2 pharmaceutical factors to

mediate the resumption of reperfusion,

played a significant role in increasing the

expression of irisin in the heart, liver, and

kidney blood tissues and that it was

associated with improved cardiovascular

diseases. The significant roles played by

irisin in the protection of the cell system

following ischemia via the downregulation

of the ROS-NLRP3 inflammatory signaling

pathway 17

and the induction of the Akt and

ERK1/2 signaling pathways have also been

demonstrated previously.

We also found that the serum level of irisin

had a poor positive correlation with the

HbA1c percentage in our type 2 diabetic

patients without CAD. It has been

documented that obesity is a risk factor for

the development of type 2 diabetes.

Bonfante et al 18

reported that obesity had a

positive association with increased serum

levels of irisin. Rana and colleagues 19

also

showed that increased irisin serum levels

was a major marker for type 2 diabetes,

associated with the increased expression of

pro-inflammatory molecules such as E-

selectins. It has also been reported that irisin

induces glucose metabolism in the p38

MAPK signaling dependent manner. 20

Another investigation reported that, although

the serum level of irisin increased in type 2

diabetic patients, its serum levels decreased

in type 2 diabetic patients who suffered from

nephropathy. 21

Moreover, Shelbaya et al 21

demonstrated that the serum level of irisin

had a negative correlation with advanced

glycation end-products, a factor for the

worsening of type 2 diabetic patients.

Collectively, it appears that irisin is a normal

body response to increased FBG to

minimize the side effects of diabetes. Our

results also showed that the irisin serum

level significantly increased in parallel with

the increased percentage of HbA1c in our

type 2 diabetic patients without CAD. Thus,

it may be hypothesized that irisin is a

response to increased HbA1c to protect the

human cell system from type 2 diabetes

complications.

Our results also showed that the SYNTAX

score had a moderate correlation with

HbA1c, which is a risk factor for the

induction of cardiovascular diseases in type

2 diabetic patients.

We also found no significant differences

between the male and female, smoking and

nonsmoking, and opium-addicted and

nonaddicted type 2 diabetic patients. Thus, it

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65

appears that although the factors were the

risk factors for the development of type 2

diabetes, they were unable to alter irisin

expression. Further research can elucidate in

more detail the roles played by these

variables in the expression and function of

irisin.

Acknowledgments

We would like to express our thanks to our

type 2 diabetic patients and healthy

volunteers for their cooperation. The study

was supported by Kerman University of

Medical Sciences.


The authors have no conflict of interest to

declare.

REFERENCES

1. Arababadi, M.K., et al., Nephropathic

complication of type-2 diabetes is following

pattern of autoimmune diseases? Diabetes

research and clinical practice, 2010. 87(1):

p. 33-37.

2. Olafsdottir, E., et al., The prevalence of

retinopathy in subjects with and without type

2 diabetes mellitus. Acta Ophthalmol, 2014.

92(2): p. 133-7.

3. Khan, A.R., et al., Knowledge, attitude and

practice of ministry of health primary health

care physicians in the management of type 2

diabetes mellitus: a cross-sectional study in

the Al Hasa District of Saudi Arabia, 2010.

Niger J Clin Pract, 2011. 14(1): p. 52-9.

4. Masoomi, M., S. Samadi, and M.

Sheikhvatan, Thrombolytic effect of

streptokinase infusion assessed by ST-

segment resolution between diabetic and

non-diabetic myocardial infarction patients.

Cardiol J, 2012. 19(2): p. 168-73.

5. Arababadi, M.K., et al., Nephropathic

complication of type-2 diabetes is following

pattern of autoimmune diseases? Diabetes

Res Clin Pract, 2010. 87(1): p. 33-7.

6. Franks, P.W. and J. Merino, Gene-lifestyle

interplay in type 2 diabetes. Curr Opin Genet

Dev, 2018. 50: p. 35-40.

7. Kuloglu, T., et al., Irisin: a potentially

candidate marker for myocardial infarction.

Peptides, 2014. 55: p. 85-91.

8. Roca-Rivada, A., et al., FNDC5/irisin is not

only a myokine but also an adipokine. PLoS

One, 2013. 8(4): p. e60563.

9. Moreno-Navarrete, J.M., et al., Irisin is

expressed and produced by human muscle

and adipose tissue in association with

obesity and insulin resistance. J Clin

Endocrinol Metab, 2013. 98(4): p. E769-78.

10. Fatahian, A., H. Nayeri, and M. Sadeghi,

Irisin, a new biomarker in diagnosis of

atherosclerosis and myocardial infarction. J

Isfahan Med Sch, 2015. 33(350): p. 1-11.

11. Choi, Y.K., et al., Serum irisin levels in

new-onset type 2 diabetes. Diabetes Res

Clin Pract, 2013. 100(1): p. 96-101.

12. Liu, J.J., et al., Lower circulating irisin is

associated with type 2 diabetes mellitus. J

Diabetes Complications, 2013. 27(4): p.

365-9.

13. Farooq, V., et al., Combined anatomical and

clinical factors for the long-term risk

stratification of patients undergoing

percutaneous coronary intervention: the

Logistic Clinical SYNTAX score. Eur Heart

J, 2012. 33(24): p. 3098-104.

14. Wang, H., et al., Irisin plays a pivotal role to

protect the heart against ischemia and

reperfusion injury. J Cell Physiol, 2017.

232(12): p. 3775-3785.

15. Chen, K., et al., Irisin protects mitochondria

function during pulmonary

ischemia/reperfusion injury. Sci Transl Med,

2017. 9(418).

16. Aydin, S., et al., The effect of iloprost and

sildenafil, alone and in combination, on

myocardial ischaemia and nitric oxide and

irisin levels. Cardiovasc J Afr, 2017. 28(6):

p. 389-396.

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17. Peng, J., et al., Irisin protects against

neuronal injury induced by oxygen-glucose

deprivation in part depends on the inhibition

of ROS-NLRP3 inflammatory signaling

pathway. Mol Immunol, 2017. 91: p. 185-

194.

18. Bonfante, I.L.P., et al., Obese with higher

FNDC5/Irisin levels have a better metabolic

profile, lower lipopolysaccharide levels and

type 2 diabetes risk. Arch Endocrinol Metab,

2017. 61(6): p. 524-533.

19. Rana, K.S., et al., Plasma irisin is elevated in

type 2 diabetes and is associated with

increased E-selectin levels. Cardiovasc

Diabetol, 2017. 16(1): p. 147.

20. Pang, Y., et al., beta-arrestin-2 is involved in

irisin induced glucose metabolism in type 2

diabetes via p38 MAPK signaling. Exp Cell

Res, 2017. 360(2): p. 199-204.

21. Shelbaya, S., et al., Study of Irisin Hormone

Level in Type 2 Diabetic Patients and

Patients with Diabetic Nephropathy. Curr

Diabetes Rev, 2017. 29(85535): p.

1573399813666170829163442.

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Blunted Heart Rate Response to Dipyridamol Stress Testing Malek et al

67

Original Article Blunted Heart Rate Response to Dipyridamol Stress Testing Malek et al

Association Between Blunted Heart Rate Response to

Dipyridamole and Myocardial Ischemia in Diabetic Patients as

Compared With Nondiabetic Patients

Hadi Malek1, MD; Raheleh Hedayati

2*, MD; Nahid Yaghoobi

1, MD;

Hassan Firoozabadi1, MD; Fereydoon Rastgou

1, MD;

Ahmad Bitarafan Rajabi1, PhD

ABSTRACT

Background: Blunted heart rate response (BHR) during dipyridamole stress testing has been

reported to be related to higher cardiac death. This study was performed to assess the

association between BHR and perfusion abnormalities in diabetic patients undergoing

dipyridamole stress ECG-gated myocardial perfusion imaging (MPI) as compared with

nondiabetic patients.

Methods: A total of 2172 subjects (1602 women and 570 men) at a mean age of 61 ± 11 years

who were referred for MPI to our department were studied. The subjects were divided

into 2 groups on the basis of the presence or absence of diabetes mellitus (849 diabetic vs

1323 nondiabetic subjects).

Results: Dipyridamole-related BHR was noted in 471 (67.7%) patients, demonstrating a

significantly higher incidence in the diabetic patients than in the nondiabetic subjects

(P < 0.05). Both basal systolic and peak systolic blood pressures were significantly

higher in the patients with diabetes mellitus (P < 0.05). However, no significant

difference was noted in the number of segments with perfusion abnormalities in patients

with BHR as compared with the subjects with a normal hemodynamic response, neither

in the diabetic nor in the nondiabetic subjects.

Conclusions: The results of our study suggest that the presence of myocardial perfusion

abnormalities and left ventricular dysfunction is not related to abnormal heart rate

response during dipyridamole stress testing, neither in diabetic nor in nondiabetic

subjects. The incidence of BHR to dipyridamole is significantly higher in diabetic

patients, however. (Iranian Heart Journal 2020; 21(1): 67-74)

KEYWORDS: Diabetes mellitus, Hemodynamic response, Ischemic heart disease, Myocardial perfusion imaging,

Dipyridamole stress testing


2 Rasule Akram General Hospital, Iran University of Medical Sciences, Tehran, IR Iran.

* Corresponding Author: Raheleh Hedayati, MD; Department of Nuclear Medicine, Rasoule Akram General Hospital, Satarkhan St, Tehran, IR Iran.

Email: [email protected] Tel : 00982166509312

Received: February 23, 2019 Accepted: May 11, 2019


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n individual’s heart rate is a

physiological response to

autonomic, central, and peripheral

reflexes as well as intrinsic cardiac control

mechanisms. Different abnormalities could

be responsible for an abnormal heart rate

response to physiological stress including

renal failure, diabetes, and intrinsic cardiac

conditions such as coronary artery disease

(CAD) and cardiomyopathy. 1 Dipyridamole

is routinely employed for pharmacological

stress testing in myocardial perfusion

imaging (MPI). This vasodilator agent has

also been used for the assessment of heart

rate response variability. 2,3,4

Dipyridamole

may cause a modest decrease in blood

pressure, whereas there is a modest increase

in heart rate, which have been believed to be

a normal hemodynamic response to this

vasodilator agent. 5 Chronotropic

incompetence, which is defined as an

attenuated chronotropic response to exercise,

has been considered to be a predictor of

increased mortality. 6,7

Likewise, it has been

shown recently that blunted heart rate

response (BHR) during dipyridamole stress

testing is related to cardiac death. 1,6,7,8

Myocardial ischemia and left ventricular

dysfunction have been shown to be in

association with chronotropic incompetence

during exercise, 8,3

and the same association

might be present in dipyridamole-related

abnormal heart rate response, despite the

fact that the underlying mechanisms are not

yet understood. 9 Furthermore, BHR to

dipyridamole has been associated with a

higher mortality risk, even in the presence of

normal myocardial perfusion, 7 which could

partly be explained by sudden cardiac death

and ventricular arrhythmias related to an

abnormal cardiac autonomic nervous

system, 10,11

Diabetes mellitus is known as

the most common metabolic disease in the

world. 12

It is estimated that 20%–40% of

diabetic patients suffer from cardiac

autonomic neuropathy, which can be

assessed by heart rate variability during the

vasodilator stress test, 13,14

resulting in an

increased risk of cardiovascular-related

mortality. 2,15

Hence, we performed the present study to

assess the association between BHR and

perfusion abnormalities in diabetic patients

undergoing dipyridamole stress ECG-gated

MPI as compared with nondiabetic patients,

using single-photon emission computed

tomography (SPECT).

METHODS

Study Population

Consecutive patients (N = 2172) who

underwent dipyridamole stress ECG-gated

SPECT MPI in Rajaie Cardiovascular,

Medical, and Research Center were enrolled

in this study. The exclusion criteria were

pregnancy, severe obstructive lung disease,

second- or third-degree atrioventricular

block without a functioning pacemaker,

acute myocardial infarction or unstable

coronary syndrome (< 24 h), systolic blood

pressure < 90 mm Hg, hypersensitivity to

dipyridamole, or atrial fibrillation.

Dipyridamole Stress Protocol All the patients were instructed to interrupt

xanthine-containing compounds and

dipyridamole for 24 hours and to be in a

fasting state for 8 hours before testing.

When possible, they were also instructed to

discontinue β-blocking medications for 48

hours and calcium channel blockers as well

as long-acting nitrates for 24 hours. All the

patients underwent a structured interview for

recording demographic data, clinical history,

prior cardiac events, cardiac risk factors,

therapeutic procedures, and prior diagnostic

tests before the study. A 12-lead ECG was

obtained before and during stress testing at

2-minute intervals. The patients underwent

dipyridamole stress SPECT MPI according

A

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69

to the standard protocol. 16

Dipyridamole in

a dose of 0.56 mg/kg of body weight was

infused intravenously over a 4-minute

period.

Heart rate and blood pressure were

measured at resting state in the supine

position and then every 1 minute after the

commencement of dipyridamole infusion for

a total period of 10 minutes. Next, 99mTc-

Sestamibi was injected 3 to 5 minutes after

the termination of dipyridamole infusion.

The peak stress heart rate was defined as the

maximum recorded heart rate during a 6-

minute period after the completion of

dipyridamole infusion. The peak stress to

baseline heart rate ratios were calculated and

the results were categorized as normal

(ratios ≥ 1.2) or BHR groups (ratios < 1.2),

according to the previously published data. 6,8

Acquisition Protocol

All the patients underwent a 2-day stress-

rest protocol, using 99mTc-Sestamibi with

an injection dose of 10 to 15 mCi in each

phase of the study. A series of 2

acquisitions, composed of a 60- to 90-

minute post-stress as well as a resting-state

acquisition, was carried out for all the

patients. The SPECT acquisitions were

conducted in the step-and-shoot mode with

32 thirty-second or 64 twenty-second

projections, a zoom factor of 1.46, and in a

non-circular 180° arc (45° RAO-to-LPO),

using a PHILIPS BrightView dual-head

gamma camera (USA), an Infinia Hawkeye

dual-head SPECT/CT hybrid camera (GE

Healthcare, USA), or a Symbia T2 dual-

head SPECT/CT hybrid camera (Symbia T2

System; Siemens Medical Solutions, USA),

equipped with low-energy, high resolution

(LEHR) collimators and an automated body

contour detection system.

Post-stress gated MPI with an acceptance

window of 30% was carried out for all the

subjects. All the data were stored in a

64×64×16 computer matrix and

reconstructed with 3D ordered subset

expectation maximization (3D-OSEM),

using 2 iterations and 8 subsets. 17

The

rotating raw images of all the participants

were seen visually, and the studies with

motion artifacts or low-count density were

excluded.

Image Interpretation

The reconstructed and reoriented images

were quality controlled and interpreted by

experienced nuclear physicians, using

AutoQUANT® software for cardiac

quantification and functional analysis. 18

A

semi-quantitative visual analysis of images

was performed on the basis of standard 17-

segment scoring. Each segment was

considered to be normal (with no perfusion

abnormality), ischemic (with reversible

perfusion abnormality), or infarcted (with

persistent perfusion abnormality and after

the exclusion of attenuation artifacts, using

the planar lateral view in the lateral

decubitus portion or CT-based attenuation

correction if available). 19

Gated short-axis images were processed, and

the left ventricular ejection fraction was

automatically calculated. Patients with a

post-stress ejection fraction < 50% were

considered to have left ventricular

dysfunction.


The χ2

test was used for the categorical and

the Student t-test and the Mann–Whitney U

test for the numerical variables. Multivariate

logistic regression models were also

performed to investigate adjusted

associations between the variables.

The data were described as the mean ± the

standard deviation (SD) and as counts (%)

for the interval and the categorical variables,

respectively. A P value < 0.05 was

considered a statistically significant result.

The data were handled and analyzed with

Statistical Program for Social Sciences

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(SPSS 15.0 for Windows, SPSS Inc,

Chicago, Illinois).

RESULTS

A total of 3021 patients, who were referred

to Rajaie Cardiovascular, Medical, and

Research Center for MPI study, were

included in the study. A total of 849 patients

were also excluded from the analysis due to

recent intakes of beta-blockers, calcium

channel blockers, known chronic renal

failure, or incomplete data. Therefore, 2172

patients (1602 women and 570 men) at a

mean age of 61 ± 11 years were enrolled in

this study. Of this total, 520 (23.9%) patients

had diabetes mellitus. The background and

demographic descriptive data are shown in

Table 1 and the comparisons of the

demographic differences, hemodynamic

response, and MPI parameters according to

the presence or absence of diabetes mellitus

are depicted in Table 2.

Dipyridamole-related BHR was noted in

1476 (68%) patients, demonstrating a

significantly higher incidence in the diabetic

patients than in the nondiabetic subjects (P =

0.008). Both basal systolic and peak systolic

blood pressures were significantly higher in

the patients with diabetes mellitus (P =

0.002), whereas no significant difference

was noted in the peak to basal blood

pressure changes. Furthermore, no

significant difference was noted in the

number of either ischemic or infarcted

myocardial segments in the patients with

BHR as compared with the subjects with a

normal hemodynamic response, neither in

the diabetic nor in the nondiabetic subjects

(Table 3).

The adjusted association analysis by logistic

regression models (Table 4) revealed no

significant association between the

incidence of myocardial ischemia and BHR,

whereas there was a statistically significant

association between ischemia and diabetes

mellitus (OR = 1.574; P < 0.001) as well as

hypertension (OR = 1.283; P = 0.010).

DISCUSSION

Normal hemodynamic response to

dipyridamole is reflected by systemic

vasodilatation, with a modest decrease in

blood pressure and a modest increase in

heart rate. 5,20

Despite the fact that CAD has

been introduced as an intrinsic cardiac

condition, responsible for BHR, 5,2,21,22

we

found no association between the incidence

of abnormal perfusion in patients with

dipyridamole-related BHR as compared with

patients with a normal response, neither in

diabetic nor in nondiabetic subjects.

Furthermore, BHR was not related to left

ventricular dysfunction in our study as well.

However, the incidence of BHR was

significantly higher in diabetic patients than

in nondiabetic subjects. One of the

explanations for this finding could be related

to the higher incidence of cardiac autonomic

neuropathy in diabetes mellitus. 1314

In a large cohort of patients undergoing

adenosine stress MPI, Abidov et al 8

demonstrated that several hemodynamic

variables could provide independent

information in the risk assessment of

patients. They found that patients with high

resting heart rates were at a higher risk of

cardiac death and that the peak to basal HR

ratio provided incremental prognostic

information over MPI results, enhancing the

risk stratification of patients regarding

cardiac death, particularly among those with

normal perfusion. Although the authors

showed that this fact might be related to

heart failure, the ventricular function was

not assessed in that study. Furthermore,

diabetes mellitus was not regarded as a

separate entity.

Bhatheja et al 6 also reached the same

conclusion by showing that BHR to

dipyridamole was a predictor of cardiac

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death even in the setting of normal perfusion

scan and normal ECG.

In a recent study by Mathur et al, 1 BHR was

an independent predictor of cardiac

mortality after adjustments for perfusion and

function-related gated SPECT variables.

Our study is in accordance with the

previously published data that found no

association between myocardial ischemia or

infarction and BHR, using MPI. Previous

research has linked BHR to dipyridamole to

higher mortality as a result of an abnormal

cardiac nervous system, predisposing

patients to ventricular arrhythmias and

sudden death. 7,10,11

The findings of our study are also in

accordance with previous epidemiological

studies, which have demonstrated that

diabetic patients have a higher probability of

BHR. 2,9,18

Limitations

Our results are based on a population of

patients who were referred to our

department for gated SPECT MPI study;

therefore, there might be a question on the

implication of the results to a broader

population. Moreover, the current study is

retrospective, in spite of the prospective

collection of all the data. Chronic renal

failure and diabetic neuropathy have been

concluded to cause BHR in previous studies. 2,9,18,20

However, the data concerning these

conditions were unavailable and were not

included in our study. Finally, this study was

carried out in a single nuclear cardiology

center.

Table 1. Background and demographic descriptive data (N = 2172)

Age (y) 61 ± 11

Gender (F/M) 1602/570 (73.8/26.2)

Symptoms:

Atypical chest pain 1151 (53.0)

Typical chest pain 234 (10.8)

DOE 1068(49.2)

Palpitation 579 (26.7)

Arrhythmia 22 (1.0)

None 225 (10.4)

Risk Factors:

Diabetes mellitus 520 (23.9)

Hypertension 1132 (52.1)

Hypercholesterolemia 885 (40.7)

Family history 286 (13.2)

Hemodynamic Variables:

Basal HR (beat per minute) 69.6 ± 17.9

Peak HR (beat per minute) 60.6 ± 34.5

Peak HR/Basal HR <1.2 >1.2

1471(67.7) 693 (31.9)

Basal systolic BP (mm Hg) 138.0 ± 18.0

Basal diastolic BP (mm Hg) 74.1 ± 23.5

Peak systolic BP (mm Hg) 142.0 ± 31.0

Peak diastolic BP (mm Hg) 73.8 ± 23.8

EF 66.2 ± 7.6

Statistics are numbers (%) or the mean ± the standard deviation. HR, Heart rate; BP, Blood pressure

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Table 2. Comparison of the demographic differences, hemodynamic, and MPI parameters in the patients with

diabetes mellitus as compared with the nondiabetic subjects

Characteristic/ Variable

Diabetes Mellitus

P value Yes n = 520

No n = 1652

Age (y) 62 ± 9.8 61 ± 11.3 0.015

Gender (F/M) 385/135 1217/435 0.867

Hemodynamic Variables:

Peak HR/Basal HR ≤1.2 >1.2

378 (72.7) 142 (27.3)

1098 (66.5) 554 (33.5)

0.008

Peak HR (beat per minute) 61.2 ± 35.1 60.4 ± 34.4 0.199

Basal HR (beat per minute) 70.1 ± 20.4 69.5 ± 17.1 0.001

Basal systolic BP (mm Hg) 14.1 ± 1.9 13.8 ± 1.8 0.002

Basal diastolic BP (mm Hg) 73.1 ± 24.6 74.4 ± 23.1 0.586

Peak systolic BP (mm Hg) 14.6 ± 4.1 14.1 ± 2.8 0.002

Peak diastolic BP (mm Hg) 72.8 ± 24.9 74.1 ± 23.4 0.560

Basal/peak systolic BP (mm Hg) 0.9 ± 0.1 0.9 ± 0.1 0.664

Basal/peak diastolic BP (mm Hg) 1.1 ± 1.1 1.1 ± 1.01 0.795

Number of ischemic infarcted segments 348 (66.9) 856 (51.8) <0.001

Number of ischemic segments 341 (65.6) 827 (50.1) <0.001

Number of infracted segments 55 (10.6) 104 (6.3) 0.001

EF 66.8 ± 6.6 66.1 ± 7.8 0.298

Statistics are numbers (%) or the mean ± the standard deviation. Significant P values in bold MPI, Myocardial perfusion imaging; HR, Heart rate; BP, Blood pressure; EF, Ejection fraction Table 3. Comparison of the number of ischemic, infarcted, or ischemic infarcted segments according to the peak to

baseline heart rates in the diabetic patients


Peak-to-Baseline Heart Rate P

value ≤1.2 n = 378

>1.2 n = 142

Number of ischemic infarcted segments 256 (67.7) 92 (64.8) 0.526

Number of ischemic segments 252 (66.7) 89 (62.7) 0.393

Number of infracted segments 43 (11.4) 12 (6.5) 0.296

Statistics are numbers (%). Table 4. Multivariate logistic regression analysis for the association between ischemia and HR variability, adjusted for

the EF, diabetes mellitus, hypertension, and hypercholesterolemia


B

OR

95% CI for EXP(B) P value Lower Upper

Diabetes mellitus 0.454 1.574 0.000 1.978 0.001

Hypertension 0.249 1.283 0.010 1.551 0.010

Hypercholesterolemia 0.172 1.188 0.083 1.443 0.083

EF 0.001 1.001 0.892 1.013 0.892

Peak to basal HR 0.032 0.969 0.753 1.182 0.753

Significant P values in bold HR, Heart rate; EF, Ejection fraction

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CONCLUSIONS

The incidence of BHR to dipyridamole was

significantly higher in the diabetic patients

in the present study; nonetheless, the results

presented herein suggest that myocardial

perfusion abnormalities and left ventricular

dysfunction are not related to an abnormal

heart rate response during dipyridamole

stress testing, neither in diabetic nor in

nondiabetic subjects. As previously

published data indicate, given an increased

risk of cardiac-related mortality in patients

with BHR during dipyridamole stress

testing, more attention should be paid to the

risk stratification of patients with normal

gated SPECT MPI but with BHR to

dipyridamole stress testing.

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WR, Kim BT. Dipyridamole myocardial

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CK, Cohen I, Friedman JD, et al. Prognostic

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R Hedayati, H Amouzadeh, Sh Hosseini, H

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Air Pollution and CVD Shirvani et al

75

Original Article Air Pollution and CVD Shirvani et al

Fine Particle Air Pollution (PM 2.5) and Cardiovascular

Hospitalization in Isfahan in 2012: CAPACITY Study

Ehsan Shirvani1, MD;

Masoumeh Sadeghi

2, MD; Sayed Mohsen Hosseini*

3, PhD;

Alireza Khosravi4, MD

; Katayoun Rabiei

1, MD, PhD

; Mojtaba Rahimi

5, MD

;

Tohid Jafari-Koshki6, PhD

; Mansour Shishehforoush

7, MS;

Ahmadreza Lahijanzadeh8, PhD; Elham Moazam

9, MD;

Mohammad Bagher Mohebi10

, PhD; Nizal Sarrafzadegan1, MD

ABSTRACT

Background: This study aimed to evaluate the relationship between exposure to PM2.5 and the

number of hospital admissions due to cardiovascular diseases.

Methods: The present time-series, case-crossover study is a part of the CAPACITY study on

patients admitted to 15 hospitals in the Iranian city of Isfahan because of cardiovascular

diseases in 2012. PM2.5 concentrations were calculated in air pollution monitoring

stations and divided into 3 groups of good or moderate, unhealthy for sensitive people,

and unhealthy or hazardous. The relationship between the number of admissions and fine

particle concentrations was assessed.

Results: This study evaluated 15752 participants at a mean age of 59 ± 19.4 years. Men

accounted for 52.6% (n = 8282) of the study population. The mean concentration of fine

particles was 53.77 ± 29.65 micrometers. In most days of the year, the concentration of

PM2.5 was at an unhealthy level for sensitive people. Poisson regression analysis showed

a significant correlation between the number of hospital admissions due to cardiovascular

diseases and ischemic heart diseases and fine particle concentrations in the unhealthy

level for sensitive people (P = 0.001, P = 0.001, and P = 0.002). There was a significant

correlation between PM2.5 concentrations and the number of admissions due to

conductive heart diseases and heart blocks in unhealthy or hazardous levels (P = 0.02 and

P = 0.04).

Conclusions: The number of hospital admissions due to cardiovascular diseases can increase

during air pollution, especially when the concentrations of PM2.5 are elevated. (Iranian

Heart Journal 2020; 21(1): 75-81)

KEYWORDS: Fine particle, Cardiovascular diseases, Air pollution

1 Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, IR Iran. 2 Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, IR Iran. 3 Department of Biostatistics and Epidemiology, School of Public Health, Isfahan University of Medical Sciences, Isfahan, IR Iran. 4 Hypertension Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, IR Iran. 5 Department of Anesthesiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, IR Iran. 6 Road Traffic Injury Research Center and Department of Statistics and Epidemiology, School of Health, Tabriz University of Medical Sciences, Tabriz, IR Iran. 7 Isfahan Disaster Management Office, Isfahan Governer’s Office, Isfahan, IR Iran. 8 Khouzestan Department of Environment, Ahvaz, IR Iran. 9 Cancer Prevention Research Center, Isfahan University of Medical Sciences, Isfahan, IR Iran. 10 Information Technology Offices, Isfahan University of Medical Sciences, Isfahan, IR Iran.

*Corresponding Author: Sayed Mohsen Hosseini, PhD; School of Public Health, Isfahan University of Medical Sciences, Isfahan, IR Iran. Email: [email protected] Tel: 09133056890

Received: March, 2, 2019 Accepted: June 10, 2019


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76

ir pollution in cities is one of the

main health problems worldwide

and is defined as the presence of

harmful or excessive quantities of

substances in the earth’s atmosphere. 1 Air

pollution substances include coarse particles

(PM10: 2.5–10 micrometers), fine particles

(PM2.5: < 2.5 micrometers), and ultraPM2.5

(PM0.1: < 0.1 micrometers). 2

There is evidence indicating a remarkable

correlation between air pollution and

adverse cardiovascular events. 3-6

Epidemiological investigations have

revealed an increase in the level of the

incidence of arrhythmias, the duration of

hospitalization, and mortality and morbidity

after long-term exposure to polluted air. 7

Previous research has also demonstrated that

the inhalation of air pollutants may increase

platelet counts and activity, systemic

inflammation, and the level of oxidative

stress, which can lead to vascular damage,

atherosclerosis, and autonomic dysfunction. 8 In a case-crossover study, an increased

level of PM2.5 for 2 hours increased the risk

of myocardial infarction in 48% of cases. 9

Inhalation of air polluted substances can

decrease heart rates and increase blood

pressure. 10

Studies on the effects of air pollution on

cardiovascular diseases are divided into 2

groups: short-term investigations evaluating

the effects of acute exposure with polluted

air on health and long-term investigation

(eg, cohort studies) assessing the correlation

between air pollution and its chronic effects

on increasing cardiovascular disease risks.

Both of these studies have revealed the

significant relationship between excessive

exposure to polluted air and increased

mortality rates due to cardiovascular

diseases. 10,11

Cardiovascular diseases are prevalent in

Iran, and there is a well-known relationship

between air pollution and cardiovascular

diseases. 6,12

Isfahan is the third most

populated province of Iran with a population

of 2 240 249 in 2016. Isfahan is a great

industrial city featuring several different

industrial factories. 13

Indeed, the city is

surrounded by thermal power plants, steel

companies, cement plants, and oil refineries. 14

To assess air pollution in Isfahan, we

sought to evaluate patients in the majority of

hospitals in Isfahan. PM2.5 is an aqueous

ionic composition in the air that is used for

estimating organic masses in meteorology. 15

Previous studies that have evaluated the


cardiovascular diseases had small sample

sizes or evaluated the effects of specific

particles on cardiovascular diseases. In the

present study, we aimed to evaluate the

relationship between exposure to PM2.5 and

the number of hospital admissions due to

cardiovascular diseases.

METHODS

The present retrospective time-series case-

crossover study was conducted on the


cardiovascular and respiratory diseases (air

pollution and cardiovascular and respiratory

diseases: rationale and methodology of the

CAPACITY study). The CAPASITY study

is a comprehensive study on the correlation

between the presence of air pollutants and

hospitalization rates due to cardiovascular

and pulmonary diseases from 2010 to 2012. 16

The current study evaluated the findings

of the year 2012 because PM2.5 was

evaluated only during this year. The study

population consisted of patients admitted to

15 hospitals of the Iranian city of Isfahan

(Sina, Shariati, Sepahan, Askarieh, Amin,

Chamran, Sadoughi, Gharazi, Khanevadeh,

A

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77

Noor, Alzahra, Kashani, Amiralmomenin,

Isabne Maryam, and Feiz) because of

cardiovascular diseases in 2012. Participants

were selected via nonrandom convenience

sampling methods according to hospital

records. The inclusion criteria were as

follows 1) patients with the diagnosis of

cardiovascular diseases based on the

International Classification of Diseases -10

(ICD-10) criteria (International

Classification of Diseases, I00-I99 for

cardiovascular diseases) and 2) residence in

Isfahan city based on addresses in the

patients’ medical records. Patients with

incomplete clinical and paraclinical data

were excluded from this study. The study

protocol was approved by the Regional

Bioethics Committee of Isfahan University

of Medical Sciences (IUMS).

The medical records of patients with

cardiovascular disease diagnoses were taken

from hospital archives. Cardiovascular

diseases were comprised of hypertension,

ischemic heart diseases, conductive heart

diseases and heart blocks, heart failure, and

cerebrovascular disease with ICD-10 (I10-

I15), (I20-I25), (I44-I46), (I50), and (I60-

I69), respectively. The data extracted from

each medical record included demographic

data, as well as diagnostic and therapeutic

data. These data were extracted from paper

medical records or the Hospital Information

System (HIS). About 8 hospitals had HIS

and 7 hospitals had paper medical records.

About 10% of the medical records were

evaluated by cardiologists to assess the

diagnosis of the patients for the quality

control of the study.

Data regarding air pollution with PM2.5, air

temperature, and air humidity were extracted

from the archives of the weather and

pollution monitoring stations in Isfahan

from 2011 to 2012. Hourly records of air

pollutants were extracted from the air

pollution monitoring station archives and

managed in Microsoft Excel files by the lab

experts of Isfahan’s Department of

Environment. The data on PM2.5 were

recorded only in the year 2010. First, the

average 24-hour level of each station and

then the mean level of the PM2.5

concentration in Isfahan were calculated. All

the files related to 24-hour levels of different

stations and the whole Isfahan city were

finally used to evaluate the PM2.5

concentrations. The PM2.5 concentrations

were divided into 3 groups of good or

moderate, unhealthy for sensitive people,

and unhealthy or hazardous. 17

Time-series and case-crossover methods

were simultaneously applied for the data

analysis of all the objectives of the

CAPACITY study. The data analyses were

conducted using R version 3.2.3. A

confidence interval (CI) of 95% was

considered in both Poisson and conditional

regression methods. The Poisson regression

analysis was used to investigate the effect of

the PM2.5 concentration on per day

admission due to cardiovascular diseases,

and the first level of concentration

classification (good or moderate) was

considered the reference level. A 2-sided α

level of 0.05 was used to assess statistical

significance.

RESULTS

The current study evaluated 15752 hospital

patients at a mean age of 59 ± 19.4 years.

Men represented 52.6% (n = 8282) of the

study population. The mean wind speed,

temperature, and humidity were 5.46 ± 2.63

m/s, 60 ± 19.06 °F, and 25.56 ± 8.87%,

respectively. The distributions of the

cardiovascular diseases were as follows:

ischemic heart diseases (60.5%, n = 7580),

hypertension (15.8%, n = 1982),

cerebrovascular disease (12.3%, n = 1535),

heart failure (7.8%, n = 982), and conductive

heart diseases and heart blocks (3.6%,

n = 447).

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The mean concentration of PM2.5 was 53.77

± 29.65 micrometers. The concentration of

PM2.5 in the 1-year period was in the

classification of good or moderate,

unhealthy for sensitive people, and

unhealthy or hazardous in 102 (28%), 187

(51.4%), and 75 (20.6%) days in the year,

respectively.

The one-way ANOVA analysis did not show

any significant correlation between the

concentrations of PM2.5 and the number of

hospital admissions due to different

cardiovascular diseases (P = 0.68) (Table 1).

Table 1. Number of hospital admissions due to cardiovascular diseases in the different concentrations of PM2.5

P value

PM2.5 concentration

Cardiovascular disease Unhealthy or Hazardous Number (%)

Unhealthy for Sensitive People

Number (%)

Good or Moderate Number (%)

0.683

408(20.6) 1047(53.0) 522(26.4) Hypertension

1491(19.7) 4058(53.7) 2010(26.6) Ischemic heart diseases

97(21.7) 227(50.9) 122(27.4) Conductive heart diseases and heart blocks

188(19.2) 522(53.2) 271(27.6) Heart failure

306(20.0) 788(51.4) 438(28.6) Cerebrovascular diseases

The Poisson regression analysis had 3

models, as follows: a primary model without

considering confounding variables; an

analysis considering age and gender; and an

analysis considering age, gender, and

weather variables (wind speed, humidity,

etc). This analysis showed a significant

correlation between the number of per day

admissions due to all cardiovascular diseases

and PM2.5 concentrations in the level of

unhealthy for sensitive people in the 3

models (P = 0.001, P = 0.001, and P =

0.002). There was a statistically remarkable

correlation between the PM2.5 concentrations

and the number of per day admissions due to

ischemic heart diseases in the level of

unhealthy for sensitive people in the 3

models of analysis (P < 0.001, P < 0.001,

and P < 0.01). There was a nonsignificant

correlation between the PM2.5 concentrations

and the number of admissions due to

conductive heart diseases and heart blocks in

the first model (P > 0.05), but this

correlation was significant in the level of

unhealthy or hazardous in the other 2 models

(P = 0.02 and P = 0.04). There was no

significant correlation between the PM2.5

concentrations and the number of per day

admissions due to hypertension,

cerebrovascular diseases, and heart failure

(P > 0.05) (Table 2).

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Table 2. Poisson regression analysis for evaluating the correlation between the number of admissions and the type of

cardiovascular diseases

Cardiovascular Disease

PM2.5 concentration Primary Model Second Model Third Model

IRR(95%CI) P value IRR(95%CI) P value IRR(95%CI) P value

Hypertension

good or moderate 1 1 1

unhealthy for sensitive people

1.09 (0.98,1.22)

0.09 (0.95,1.22)

1.07 0.24

1.08 (0.94,1.24)

0.26

unhealthy or hazardous 1.06

(0.93,1.21) 0.35

1.00 (0.85,1.17)

0.98 0.98

(0.83,1.16) 0.80

Ischemic heart diseases



1.10 (1.04,1.16)

<0.001 1.11

(1.05,1.17) <0.001

1.08 (1.02,1.14)

0.01


(0.94,1.08) 0.82

1.00 (0.94,1.07)

0.93 0.99

(0.93,1.07) 0.95

Conductive heart diseases

and heart blocks



1.01 (0.81,1.26)

0.89 1.31

(0.76,2.26) 0.33

1.29 (0.73,2.33)

0.38


(0.83,1.41) 0.57

2.03 (1.13,3.66)

0.02 1.94

(1.03,3.63) 0.04

Heart failure



1.05 (0.91,1.22)

0.51 1.15

(0.91,1.44) 0.25

1.23 (0.96,1.57)

0.10


(0.78,1.14) 0.54

1.06 (0.79,1.43)

0.68 1.15

(0.84,1.56) 0.39

Cerebrovascular diseases



0.98 (0.87,1.10)

0.75 1.03

(0.89,1.19) 0.71

1.03 (0.87,1.20)

0.76


(0.82,1.10) 0.49

1.03 (0.86,1.25)

0.72 1.04

(0.85,1.26) 0.73

All types of cardiovascular

diseases



1.07 (1.03,1.12)

<0.001 1.07

(1.03,1.12) 0.001

1.06 (1.02,1.11)

0.005


(0.96,1.06) 0.79

1.00 (0.95,1.05)

0.94 1.00

(0.94,1.06) 0.94

DISCUSSION

The present study evaluated the correlation

between PM2.5 concentrations and the

number of per day admissions due to

different cardiovascular diseases in the year

2012. We found a significant correlation

between PM2.5 concentrations and the

number of hospital admissions due to all

cardiovascular diseases, especially ischemic

heart diseases, in the level of unhealthy for

sensitive people. There was also a

significant correlation between the number

of hospital admissions due to conductive

heart diseases and heart blocks in the level

of unhealthy or hazardous PM2.5

concentrations.

Studies have demonstrated that more

exposure to air pollution can increase acute

cardiovascular events and exacerbate

chronic cardiovascular diseases. 8

Researchers have also evaluated the

relationship between air pollution and

cardiovascular diseases. Dominici et al 18

evaluated the relationship between air PM2.5

concentrations and the number of

hospitalization due to cardiovascular and

pulmonary diseases and revealed that an

increase of 10 μg/m3 in PM2.5 daily

concentrations could cause a 1.3% increase

in the number of hospitalization because of

heart failure. Another study on 7 cities in the

United States of America reported that a rise

of 10 μg/m3 in air pollution in a day could

cause a 0.7% increase in the number of

hospitalization due to congestive heart

diseases. 19

Another investigation showed a

significant increase in coronary artery

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80

disease complications after short-term

exposure to PM2.5 air pollution. 20

A study

on a sample of the Iranian population

revealed an annual mortality rate of 4.64%

owing to air pollutants. 21

Air pollution can increase the release of pro-

oxidative and pro-inflammatory mediators

from the lungs to the circulation and also

cause autonomic nerve systemic imbalances.

It has direct effects on the heart and triggers

the entrance of fine and ultraPM2.5 to the

systemic circulation. Oxidative stress

induction by these particles can lead to

impairment in coagulation and thrombosis. 22

Air pollution also increases heart rate,

decreases heart rate variability, and causes

endothelial dysfunction, arterial

vasoconstriction, apoptosis, and

hypertension. Acute exposure to air

pollution can cause plaque instability,

affecting the risk factors of cardiovascular

events, and chronic exposure to air pollution

causes atherosclerosis and hypertension. 8

In the current study, the relationship

between the number of hospital admissions

due to cardiovascular diseases and PM2.5 in

the level of unhealthy for sensitive people is

likely due to the fact that the number of days

with this level of air pollution was more than

that of other situations in the year 2012. The

CAPACITY study showed that the mean

annual pollutants in the years 2010 and 2011

were higher than the standard levels and the

mean concentrations of ozone, carbon

monoxide, and PM10 were lower in the year

2011 than in the year 2010, while the mean

levels of sulfur dioxide and nitrogen dioxide

were higher. 16

Our study had strengths and limitations. One

of the strengths of this study is its large

sample size, allowing the generalization of

the results to the general population.

Another strong point of this study is that we

evaluated each type of cardiovascular

diseases separately. Nonetheless, one of the

limitations of this study is that we

considered only PM2.5 as air pollution; if we

had taken into account all 3 types of

particles (coarse, fine, and ultrafine) and

evaluated the relationship between all these

particles and the number of hospital

admissions due to cardiovascular diseases,

we might have obtained more reliable results

concerning this relationship. In this study,

we did not distinguish between new cases of

cardiovascular diseases and the exacerbation

of previous cardiovascular diseases. Future

studies should take into consideration this

situation and evaluate the past medical

history of patients admitted during air

pollution because of cardiovascular diseases.

In conclusion, the number of hospital

admissions due to cardiovascular diseases

can increase during air pollution, especially

when the concentrations of PM2.5 have risen.

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Correlation Between Type II Diabetes and Left Heart Function Bayat et al

82

Original Article Correlation Between Type II Diabetes and Left Heart Function Bayat et al

Correlation Between Type II Diabetes Mellitus and Left Atrial

Function as Assessed by 2D Speckle-Tracking Echocardiography

in Patients Without Coronary Artery Disease

Fariba Bayat1, MD; Mohammad Khani

1, MD;

Fatemeh Saffarian*1

, MD; Mohammad Amin Shahrbaf2, MD

ABSTRACT

Background: Diabetes mellitus (DM) is associated with several comorbidities and complications

such as hypertension, obesity, hyperlipidemia, nephropathy, and cardiovascular diseases.

This study aimed to investigate the correlation between the left atrial (LA) function and

DM via conventional and speckle-tracking echocardiography (STE).

Methods: In this prospective study, from 198 patients with sinus rhythms, 174 patients were

included based on inclusion and exclusion criteria. Conventional and STE examinations

were done for all the patients. The patients’ demographics, comorbidities, and family

history, as well as the results of their angiography or computed tomography angiography,

electrocardiography, and echocardiography, were recorded. The variables were compared

between the groups with and without DM, and the association between the LA function

and DM was studied in the patients.

Results: Totally, 45.2% of the diabetic patients (n = 28) and 38.4% of the nondiabetic patients

(n = 30) had diastolic dysfunction (P = 0.384). The diabetic patients had a lower mean of

the left ventricular end-diastolic diameter, the LA peak strain during the reservoir phase,

the LA pump, and the LA peak positive strain rate during ventricular systole

(all Ps < 0.001) and a higher mean of the left ventricular mass index, the A-wave, the

E/A, the LA peak negative strain rate during early diastole (all Ps <0.001), the left

ventricular end-systolic volume (P = 0.001), the Ea (P = 0.008), the LA ejection fraction

(P = 0.011), and the passive emptying volume (P = 0.026).

Conclusions: The results of the present study indicated LA and left ventricular dysfunction in

diabetic patients. However, the LA function may be affected by several factors, and our

nonrandomized patient selection could also have affected the results. Thus, it is suggested

that future randomized clinical trials compare the LA echocardiographic parameters in

matched groups. (Iranian Heart Journal 2020; 21(1): 82-93)

KEYWORDS: Diabetes mellitus, Left atrium, Atrial function, Echocardiography, STE 1 Department of Cardiology, Modarres Hospital Research and Development Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran. 2 Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

*Corresponding Author: Fatemeh Saffarian, MD; Fellow of Echocardiography, Echo Lab, Shahid Modarres Hospital and Cardiovascular Research Center, Yadegare-Emam Highway, Tehran, IR Iran.


Received: March 15, 2019 Accepted: June 26, 2019


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83

iabetes mellitus (DM) is one of the

world’s most common chronic

noncommunicable diseases with a

high prevalence in most developing

countries. 1 The prevalence of DM is

estimated to be on the rise because of the

increasing trend of diabetes risk factors,

obesity, and the aging of the populations. 2

In Iran, although the general prevalence of

DM is close to that of the global prevalence

(8%–9%), its prevalence surges in the

elderly and illiterate urban dwellers,

approaching nearly 20%. 3,4

In addition to

the high prevalence of DM, about one-third

of patients are not aware of their disease and

may be, thus, affected by the silent

complications; this issue is associated with a

great mortality rate. 5 The chronicity of

hyperglycemia in diabetic patients

predisposes them to numerous micro- and

macrovascular complications such as

nephropathy, retinopathy, neuropathy,

cardiomyopathy, and vasculopathy. 6,7

Furthermore, DM is associated with several

comorbidities including hypertension,

obesity, and hyperlipidemia, which increase

the risk of complications and mortality rates. 8

The cardiac complications of DM are the

most important diabetes-related

complications and the first cause of

mortality in diabetic patients, 9,10

with the

evidence suggesting a 5-fold increase in the

risk of myocardial infarction and ischemic

stroke and a 2- to 4-fold increase in the risk

of peripheral artery disease in diabetic

patients compared with nondiabetics. 11,12

Several pathophysiologies are suggested for

the etiology of cardiac complications in DM

like inflammation, reactive oxygen, and

endothelial dysfunction. 13-15

In addition to

the complexity of DM, a wide range of

changes is observed in diabetic hearts

including left ventricular (LV) systolic and

diastolic dysfunction (leading to heart

failure), cardiomyocyte hypertrophy,

myocardial interstitial fibrosis, and the

apoptosis of cardiomyocytes. 16,17

The effect of DM on the LV has been

studied and the role of LV dysfunction has

been confirmed in diabetic cardiomyopathy. 18,19

Nevertheless, there is insufficient

evidence on the importance of changes in

the left atrium (LA) in diabetic

cardiomyopathy. 20

Some studies have

shown no influence on the LA diameter, 21

while a significant increase in the LA index

has been observed in other studies. 22,23

Considering the lack of knowledge related to

the LV function in diabetic patients and the

predictive value of the LA in cardiovascular

events, we aimed to study the association

between LA dysfunction and DM in patients

with stable cardiac function by conventional

and speckle-tracking echocardiography

(STE) methods.

METHODS

Study Design

In this prospective study, patients who

referred to Modarres Hospital from March

2018 to July 2018 were considered the study

population. The study sample size was

calculated at 198. The inclusion criteria for

this study were as follows: patients with

sinus rhythms (determined according to the

electrocardiogram [ECG] taken at baseline),

an ejection fraction (EF) > 50% (determined

based on echocardiography taken at baseline

by the echocardiologist), and normal

coronary arteries over the past month

(determined based on angiographic or

computed tomography [CT] angiographic

assessments by the cardiologist). The

exclusion criteria for this study were as

follows: patients with atrial fibrillation or

flutter (based on the initial ECG), EF < 50%,

regional wall motion abnormalities, a left

ventricular end-diastolic diameter (LVEDD)

> 53 mm in women or > 58 in men,

moderate-to-severe valvular regurgitation

D

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and any degree of valvular stenosis,

myocardial hypertrophy with a septal

diameter > 12 mm or poor echo windows

(based on the initial echocardiography), a

history of ischemic heart disease

(myocardial infarction, stent implantation,

and coronary artery bypass graft surgery), a

history of stroke, peripheral artery disease,

uncontrolled blood pressure (> 160/110 mm

Hg), chronic renal or liver or lung disease,

and pregnancy. Accordingly, 24 patients

were excluded from the study: 14 had a poor

echocardiographic view, 6 had moderate-to-

severe valvular disease, and 4 had moderate-

to-severe hypertrophy. Finally, a total of 174

patients were investigated.

Primary Assessment

An ECG was recorded from all the patients

at the baseline of the study. Furthermore, the

height and weight of all the samples were

recorded for calculating the body surface

area (BSA). In addition, the researcher

recorded the patients’ demographics (age

and sex), comorbidities (hyperlipidemia,

hypertension, smoking, DM, and obesity),

drug history, familial history of

cardiovascular diseases, and the duration of

DM in diabetic patients from the patients’

medical records. Systolic pressure > 140

mm Hg and diastolic pressure > 90 mm Hg

were considered high blood pressure. 24

Moreover, the diagnosis of DM was made in

accordance with the American Diabetes

Association criteria. 25

Echocardiographic Assessment

Echocardiography was performed by

conventional and STE methods (Siemens®,

Health Care Acuson SC2000). STE was

performed using eSie VVI software. All the

patients had sinus rhythms during

echocardiography, and an ECG lead

constantly recorded the patients’ ECG.

Echocardiography was done in the left

lateral position based on the American

Society of Echocardiography protocol. 26

In

addition, the LV and LA volumes were

measured and interpreted based on the BSA.

Conventional Echocardiography

The ventricular details recorded in the

conventional method were comprised of

systolic parameters: the LVEDD, the LV

end-systolic diameter, the LV end-diastolic

volume, the left ventricular end-systolic

volume (LVESV), the interventricular septal

end-diastole, the diastolic posterior wall

thickness diameter (PWTd), the left

ventricular mass index (LVMI), and the left

ventricular ejection fraction (LVEF). The

LVMI was measured as , and the

LVM was calculated based on the following

equation 26-28

:

0.8×1.04 [(LVIDd + LVPWTd + IVSTd)3− (LVIDd)

3]+0.6.

The ventricular diastolic parameters

consisted of diastolic dysfunction (DD), the

deceleration time (DT), the S wave, and E

and A waves and their ratio (E/A, Ea, and

E/Ea).

The atrial details recorded encompassed the

LA diameter, which is the maximum

diameter of the LA in the parasternal long-

axis view, the LA volume index or LAVmax,

the left atrial minimum volume (LAVmin),

the left atrial stroke volume (LASV) or the

total emptying volume (TEV) (which is

calculated based on the following formula:

LAVmax- LAVmin and represents the LA

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reservoir function), the left atrial volume

before atrial contraction (LAVpreA), the left

atrial ejection fraction (LAEF) or the active

ejection fraction (AEF) (which is calculated

based on the following algorithm:

and describes the pump

function of the LA at the end of diastole),

the left atrial emptying fraction or total

ejection fraction (TEF) (which is estimated

as LASV/LAVmax and indicates the reservoir

function of the LA during systole), the

active emptying volume (AEV) (which is

calculated based on the following formula:

LAVpreA- LAVmin and describes the pump

function of the LA), the passive emptying

volume (PEV) (which indicates the conduit

role of the LA in early diastole and is

calculated according to the following

formula: LAVmax-LAVpreA), and the passive

ejection fraction (PEF) (which describes the

conduit role of the LA in early diastole and

is calculated according to the following

formula: ). 26

STE

STE was done by using eSie VVI software.

The STE images were recorded in 3 cardiac

cycles at a frame rate (FR) of 40–60. For the

assessment of the strain (S) and strain rate

(SR) of the LA, the endocardium and

epicardium were traced manually and

automatically, respectively. The assessment

of the S and SR of the LA was performed

after the LA was automatically divided into

6 segments. The parameters that were

evaluated by STE were as follows: the left

atrial peak positive strain rate during

ventricular systole (LASRS), the left atrial

peak negative strain rate during early

diastole (LASRE), the left atrial peak

negative strain rate during late systole

(LASRA), the left atrial peak strain during

the reservoir phase (LARES) (before mitral

opening), and the left atrial peak strain

during the pump phase (LA-pump).


The results were presented as the mean ± the

standard deviation (SD) for the quantitative

variables and were summarized as

frequencies (percentages) for the categorical

variables. The patients were categorized into

2 groups of diabetic and nondiabetic, and the

categorical variables were compared

between these 2 groups using the χ2

or Fisher

exact test. Additionally, according to the

one-sample Kolmogorov–Smirnov test, the

data were not normally distributed (P <

0.05); therefore, for the comparison of the

numeric variables between the 2 groups with

and without DM, the Mann–Whitney U test

was used. The correlation between the

variables was tested using the Spearman

correlation coefficient. For the statistical

analyses, the statistical software IBM SPSS

Statistics for Windows, version 21.0, (IBM

Corp 2012. Armonk, NY: IBM Corp) was

used. A P value ≤ 0.05 was considered

statistically significant.

Ethical Considerations

Before the enrollment of the patients into the

study, the design and objectives of the study

were explained to all the participants and

written informed consent was obtained from

those who were willing to participate in the

study. The patients were reassured that they

were free to leave the study whenever they

wished to and that their participation would

not affect their routine care at the medical

center. All the ethical principles of

Helsinki’s declaration on human studies

were met throughout the study. The protocol

of the study was approved by the Ethics

Committee of Shahid Beheshti University of

Medical Sciences.

RESULTS

Among 174 patients, whose details were

analyzed, 96 (55.2%) patients were male and

78 (44.8%) patients were female. The mean

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age of the patients was 53.71 ± 9.21 years

(range = 29–75 y). DM was reported in 62

(35.6%) patients. The results of the Mann–

Whitney U test indicated that the mean age

of the patients was not significantly different

between the groups with and without DM

(54.40 ± 8.23 vs 53.32 ± 9.72 y,

respectively; P = 0.345). Similarly, the

frequency of male and female patients was

not different between the groups with and

without DM (P = 0.374). Table 1

demonstrates the frequency of

comorbidities. The comparison of the

demographics and the frequency of

comorbidities between the patients with and

without DM showed no statistically

significant difference between the groups

(Table 1).

Table 1. Frequency of the patients’ sex and history of underlying diseases

Variable Total, No.

(%) Diabetic Patients

Nondiabetic Patients

P value

Sex Male 96 (55.2%) 37 (59.7%) 59 (52.7%)

0.374 Female 78 (44.8%) 25 (40.3%) 53 (47.3%)

Comorbidities

Hypertension 63 (36.2%) 23 (37.1%) 40 (35.7%) 0.856

Hyperlipidemia 35 (20.1%) 10 (16.1%) 25 (22.3%) 0.329

Smoking 31 (17.8%) 7 (4.02%) 24 (13.79%) 0.094

Family history 18 (10.3%) 1 (1.6%) 17 (15.2%) 0.005

Obesity 23 (13.2%) 5 (8.1%) 18 (16.1%) 0.135

At the baseline of the study, 45% (n=28) of

the diabetic patients received insulin and

81% (n=50) received oral antidiabetic

agents. The mean BSA was 1.88 ± 1.54 m2

(mean ± SD); the results of the Mann–

Whitney U test indicated that the mean BSA

of the patients was not significantly different

between the groups with and without DM

(2.09 ± 2.57 vs 1.77 ± 0.13 m2, respectively;

P = 0.968).

A total of 70 (40.8%) patients had diastolic

dysfunction, and the results of the χ2

test

showed that the frequency of diastolic

dysfunction in the studied patients was not

significantly different between the groups

with and without DM (45.2% vs 38.4%,

respectively; P = 0.384).

The echocardiographic parameters of the LV

compared between the groups with and

without DM are demonstrated in Table 2. As

is shown in Table 2, the mean values of the

LVEDD (P < 0.001) and the Ea (P = 0.008)

were higher in the nondiabetic patients and

the mean values of the LVMI, the A wave,

the E/A (all Ps < 0.001), and the LVESV (P

= 0.001) were higher in the diabetic patients,

while the other echocardiographic

parameters including the deceleration time

(DT), the E/Ea, and the S wave were not


(P > 0.05).

The echocardiographic parameters of the LA

compared between the groups with and

without DM are demonstrated in Table 3.

The LARES, the LA-pump, the LASRS, and

the LASRE (all Ps < 0.001) were higher in

the nondiabetic patients. In addition, the

LAEF (P = 0.011) and the PEV (P = 0.026)

were higher in the diabetic patients. The

other parameters of the LA were not


(P > 0.05).

The correlations between DM and the LA

echocardiographic parameters are presented

in Table 4. As is depicted, the Spearman

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correlation coefficient showed that DM had

a significant association with the LASRE,

the LA-pump, the LARES, and the LASRS

(all Ps < 0.001) (Table 4).

Table 2. Comparison of the values of the LV echocardiographic measures between the patients with and without

diabetes

Variable Total Diabetic Patients


P value**

LVEDD (mm) 48.28±6.08 45.24±7.96 49.96±3.85 <0.001

LVESD (mm) 29.48±3.94 29.69±5.19 29.37±3.04 0.573

IVSD (mm) 10.00±1.78 10.21±1.91 9.88±1.79 0.322

PWI (mm) 8.3678±1.73 8.71±1.82 8.17±1.65 0.074

LVMI 80.27±7.29 83.98±8.83 78.22±5.29 <0.001

LVEDV (cc) 72.05±6.32 73.34±7.80 71.33±5.23 0.237

LVESV(cc) 25.86±3.78 27.45±4.31 24.99±3.15 0.001

LVEF % 59.45±3.05 59.98±2.03 59.15±3.46 0.069

Peak E wave velocity (cm/s) 69.85±15.48 69.50±15.67 70.04±15.45 0.957

Peak A wave velocity (cm/s) 68.76±18.12 75.38±17.85 65.06±17.26 <0.001

Septal e' wave (Ea) (cm/s) 7.91±1.78 7.42±1.74 8.18±1.75 0.008

E/A 1.65±7.70 2.53±12.84 1.16±0.80 <0.001

E/Ea 8.49±2.27 8.89±2.45 8.26±2.13 0.065

D.T (ms) 147.33±26.40 152.14±31.74 144.63±22.60 0.208

Septal S' wave (cm/s) 7.42±1.00 7.24±1.09 7.52±0.93 0.278

LVEDD, Left ventricular end-diastolic diameter; LVESD, Left ventricular end-systolic diameter; IVSD, Interventricular septal end-diastole; LVEDV, Left ventricular end-diastolic volume; LVESV, Left ventricular end-systolic volume; LVIDd, Left ventricular diastolic internal diameter; PWI, Diastolic posterior wall thickness; LVMI, Left ventricular mass index; LVEF, Left ventricular ejection fraction; DT, Deceleration time ** The results of the Mann–Whitney U test

Table 3. Comparison of the values of the LA echocardiographic measures between the patients with and without

diabetes

Variable Total Diabetic Patients


P value**

LA diameter 3.87±4.61 4.94±7.62 3.27±0.38 0.912

LAVI 26.77±5.91 27.05±6.18 26.62±5.77 0.751

LAVmin 11.93±3.83 11.50±4.23 12.16±3.59 0.147

LAVpreA 17.96±4.74 17.72±5.13 18.09±4.53 0.556

LAEF (AEF) 36.66±5.66 38.16±7.62 35.83±4.01 0.011

LAS.V 15.12±2.50 15.53±3.15 14.89±2.05 0.106

LATEF (TEF) 58.01±4.99 58.24±6.87 57.89±3.58 0.195

AEV 5.97±1.45 6.24±1.71 5.82±1.26 0.154

PEV 8.57±2.46 9.21±3.83 8.22±1.01 0.026

PEF 33.23±4.37 33.48±5.90 33.09±3.25 0.386

LARES 46.54±4.03 44.35±4.65 47.75±3.04 <0.001

LA-pump 18.70±2.64 17.22±3.16 19.52±1.86 <0.001

LASRS 2.53±9.64 1.29±0.58 3.22±11.98 <0.001

LASRE -1.32±0.71 -0.96±0.58 -1.51±0.72 <0.001

LASRA -1.48±0.69 -1.51±0.75 -1.46±0.66 0.586

LAVI, Left atrial volume index; LAVmin, Left atrial minimum volume; LAVpreA, Left atrial volume pre-atrial contraction; LAEF, Left atrial ejection fraction; AEV, Active emptying volume; PEV, Passive emptying volume; PEF, Passive ejection fraction; LASV, Left atrial stroke volume; LARES, Left atrial peak strain during the reservoir phase; LA-pump, Left atrial peak strain in the late diastolic pump; LASRS, Left atrial peak strain during systole; LASRE, Left atrial peak strain during diastole; LASRA, Left atrial peak strain during atrial systole ** The results of the Mann–Whitney U test

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Table 4. Correlations between diabetes mellitus and

echocardiographic parameters

Variable Spearman Coefficient

P value

LARES 0.348 <0.001

LA-pump 0.416 <0.001

LASRS 0.277 <0.001

LASRE -0.397 <0.001

LASRA -0.41 0.587

LARES, Left atrial peak strain during the reservoir phase; LA-pump, Left atrial peak strain in the late diastolic pump; LASRS, Left atrial peak strain during systole; LASR-D, Left atrial peak strain during diastole; LASR-A, Left atrial peak strain during atrial systole

DISCUSSION

The results of the present study showed that

among patients with a stable cardiac

condition (sinus rhythms, LVEFs > 50%,

and normal coronary arteries), the mean

values of the LVEDD, the LARES, the LA-

pump, and the LASRS were higher in the

nondiabetic patients and the mean values of

the LVMI, the A wave, the E/A, the

LASRE, the LVESV, the Ea, the LAEF, and

the PEV were higher in the diabetic patients.

These results indicated that diabetic patients

have several alterations in their LV

including higher LV hypertrophy and LV

dysfunction and several alterations in their

LA, as discussed further.

Several roles have been established for the

LA. It acts as a reservoir for the pulmonary

venous return during the LV contraction and

isovolumetric relaxation, transfers blood

passively into the LV, and contributes to

15%–30% of the LV stroke volume by its

contraction during the final phase of

diastole; therefore its size and function

imply LV compliance. 29

According to the

evidence, the LA volume (size) is an

appropriate predictor of adverse

cardiovascular outcomes 30,31

and the LA

function (indexed to the BSA) is associated

with LV dysfunction, especially diastolic

heart failure. 23,32

However, only a few

studies have evaluated LA changes in

diabetic patients.

A study by Gulmez et al 33

compared the

echocardiographic parameters of 56 diabetic

patients with 56 controls. The results

showed higher LA diameter, indexed Vmax,

LAVpreA, LAVmin, AEV, and TEV in the

diabetic patients, while the A and E waves

and their ratio were not different between

the groups. Furthermore, Gulmez and

colleagues 34

reported high LA diameter,

indexed Vmax, LAVpreA, LAVmin, AEV, and

TEV in their patients with prediabetes (n =

114) compared with their 70 controls. These

results are regarding several LA changes in

diabetic patients and no difference in the LA

function between patients with and without

(pre)diabetes. However, these are not

associated with the current study, as we

found significant differences between the

groups in the A and E waves and their ratio

(A wave, E/A, and Ea), without significant

differences in the LAVpreA, the LAVmin, and

the AEV. Nevertheless, the differences

between our results and those of Gulmez et

al 33,34

could be associated with several

factors such as the duration of diabetes 35

and differences in the patients’ body mass

index and age, which can affect the LA

function. 36

In addition, the results of a study

by Kadappu et al, 37

in line with the present

study, indicated significant differences in the

E and A waves and their ratio between

diabetic patients and controls.

According to the previous studies, the

duration of DM has a significant role in LA

enlargement 35

and patients who show no

change in the LA diameter after 5 years’

follow-up have significant changes after 20

years. 22

Therefore, no difference in the LA

function between the groups in our study

could be attributed to several factors

affecting the LA diameter and function in

diabetic patients.

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Significant changes in the LA of diabetic

patients in the present study included lower

LARES, LA-pump (indicating the LA pump

function), and LASRS (indicating the LA

reservoir function), but higher LASRE

(indicating the conduit function), LAEF, and

PEV. Particularly, all the significant

differences between the groups were in the

STE parameters. Similar to these results,

Mondillo et al 38

reported reduced LASRS,

LARES, LA-pump, and LASRD in patients

with hypertension and DM with normal LA

volumes (< 28 mL/m2). Kadappu et al

37 also

indicated lower strain parameters in all 6

parameters and a higher LA volume index in

diabetic patients. These results are consistent

with those of ours, indicating several LA

strain reductions in diabetic patients.

Nevertheless, patients with DM had higher

LASRE, LAEF, and PEV than the control

group. A study by Liu et al 39

demonstrated

lower LASRS and LARES in diabetic

patients without significant differences in

the LA-pump. These differences in the LA

STE parameters between the studies on

diabetic patients may be related to the

accuracy of different imaging methods. 20

Studies have suggested that the accuracy of

LA mechanics measurement by 2D and 3D

echocardiography is comparable to that of

CT imaging. 40,41

Furthermore, the

measurement of strain rates by STE is

considered a simple, feasible, sensitive, and

reliable method for the evaluation of LA

deformation 42

and the prediction of

cardiovascular adverse events, 43

atrial

fibrillation, and stroke. 44, 45

Additionally,

LA strain is associated with LV diastolic

dysfunction. 46

Thus, impaired LA

deformation, as indicated by LA strain in the

present study, is considered to be the most

important finding, indicating LV diastolic

dysfunction in diabetic patients.

Considering LV measurements, the results

of our study showed a greater LVEDD in the

nondiabetic patients and greater LVESV and

LVMI in the diabetic patients. The results of

a cohort study by Inoue et al 47

indicated the

LVEDD as an independent predictor of all-

cause mortality, better than other

echocardiographic parameters. The LVESV,

indicating LV dysfunction, is also

recommended as a more accurate parameter,

considering the shortcomings in the

measurement of the LV end-systolic

diameter. 48

The LVMI, indicating LV

hypertrophy, is associated with a greater LA

dimension and lower systolic and diastolic

functions and is, thus, regarded as a

predictor of heart failure. 49

The results

obtained in the present study regarding LV

changes also indicate significant LV

dysfunction in diabetic patients, which is

consistent with the results of previous

studies. 18,19,50

While the present study successfully

compared 2 groups of diabetic and

nondiabetic patients with similar baseline

characteristics, this study, like any other,

may have several limitations. One of the

important limitations of the study is

nonrandomized patient selection and

grouping, which could have affected the

results. Moreover, the LA appendix was not

evaluated in the current study. It is,

therefore, recommended that future studies

take this factor into account. The positive

point of the current study is that we

considered any factors that could influence

the results as the exclusion criteria to reduce

the effect of confounding variables.

CONCLUSIONS

The results of the present study showed that

the diabetic patients had a lower mean

LVEDD and a higher mean LVESV and

LVMI, indicating LV dysfunction in the

diabetic patients. Studying LA parameters

showed that the LA volume and function

were not impaired in the diabetic patients.

Additionally, the LAEF and the PEV were

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higher in the diabetic than in the nondiabetic

patients. Meanwhile, strain LA

measurements showed lower LARES, LA-

pump, and LASRS, but a higher LASRE.

These results indicate several LA and LV

dysfunction in diabetic patients. However,

the LA function may be affected by several

factors and our nonrandomized patient

selection could also have affected the

results. Thus, it is suggested that future

randomized clinical trials compare LA

echocardiographic parameters in matched

groups.

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Prevalence of Anemia in Cardiac Surgery Sadeghi et al

94

Original Article Prevalence of Anemia in Cardiac Surgery Sadeghi et al

Prevalence of Anemia in Patients Undergoing Cardiac Surgery

and Need for Transfusion During Surgery Regarding Hemoglobin

Levels in Rajaie Heart Center

Ali Sadeghi1, MD; Rasool Ferasatkish

1, MD; Avaz Heydarpour

1, MD;

Rasoul Azarfarin2, MD; Mohsen Ziyaeifard

1, MD; Zahra Faritous

1, MD;

Fatemehshima Hadipourzadeh*1, MD

ABSTRACT

Background: Bleeding occurs during and after cardiac surgery, resulting in postoperative

anemia. If patients have preoperative anemia, the need for blood transfusion increases.

Transfusion is associated with several complications.

Methods: In this study, severe anemia was defined as hemoglobin (Hb) < 8 g/dL, moderate

anemia was defined as Hb = 8–10 g/dL, and mild anemia was defined as Hb = 10–12

g/dL for women and Hb = 10–13 g/dL for men. In the entire study population, the need

for transfusion according to the Hb level and the amount of blood transfusion were

evaluated. The study aimed to determine the association between anemia and the

patients’ age, sex, type of surgery, and weight.

Results: In this study, 306 patients were evaluated in a 3-month period. The mean Hb level of

the patients was 13.1 g/dL (12.08–14.2), and the mean hematocrit level was 39.5%

(36.17–42.15). Anemia was reported in 32.4% of the patients (Hb < 12 g/dL for women

and Hb < 13 g/dL for men). According to the anemia classification, 90.9% of the anemic

patients had mild anemia, 8.1% moderate anemia, and 1% severe anemia. Of the 306

patients, 68.6% did not need to receive packed red blood cells. Additionally, of the 207

patients who were not included in the anemia group, 44 (21.2%) cases received packed

red blood cells due to surgical bleeding. However, of the 99 patients who were anemic,

52 (52.52%) cases needed packed red blood cells.

Conclusions: In the present investigation, about one-third of the study population had anemia

before surgery and these patients required blood transfusion 2.5 times more than those

without anemia. (Iranian Heart Journal 2020; 21(1): 94-102)

KEYWORDS: Anemia, Transfusion, Cardiac surgery


2 Echocardiography Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR

Iran.

*Corresponding Author: Fatemehshima Hadipourzadeh , MD; Fellows of Cardiac Anesthesia, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Vali-Asr Ave, Tehran, IR Iran.




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According to the World Health

Organization, anemia is defined as

hemoglobin (Hb) < 12 g/dL in women and

< 13 g/dL in men. Preoperative anemia can

be due to several reasons such as iron

deficiency or gastrointestinal bleeding. The

incidence of preoperative anemia in cardiac

surgery ranges between 25% and 32%. 1

Various observational studies have reported

that preoperative anemia is related to

increased neurological and renal

complications. 2,3

Anemic patients have

higher early and late mortality rates than

non-anemic patients undergoing cardiac

surgery. 4 During cardiac surgery, because

of hemostatic abnormalities, intra- and

postoperative bleeding is usually seen,

which can result in postoperative anemia. In

a previous study, up to 44% of the patients

had anemia in the postoperative period. 5

Another investigation reported that every 1

mg/dL decrease in the Hb concentration was

associated with a 13% increase in

cardiovascular events and a 22% increase in

all-cause mortality. 6

Although blood transfusion is necessary in

cardiac surgery, various studies have found

that it also has side effects. In these studies,

the transfusion of red blood cells (RBCs)

was dose-dependently related to

postoperative infections such as

mediastinitis, respiratory infection, and

sepsis and higher mortality. 7,8

Moreover, the

transfusion of packed RBCs is reported to

increase the length of hospital stay. 9

Some authors have described the importance

of a careful preoperative assessment because

it can reduce the risk of bleeding and the

requirement for blood transfusion during the

postoperative period. The evaluation of

serum iron and iron administration and

preoperative erythropoietin may reduce the requirement for transfusion.

10

The aim of the present study was to

determine the prevalence of anemia in

patients undergoing cardiac surgery in

Rajaie Cardiovascular, Medical, and

Research Center, Tehran, Iran, in 2018 to

prevent anemia in preoperative protocols

and treatments for anemia and to reduce the

need for transfusion.

METHODS

In this study, patients after the admission,

blood sample were sent to the laboratory and

the hemoglobin level In this study, severe

anemia was defined as hemoglobin (Hb) < 8

g/dL, moderate anemia was defined as Hb =

8–10 g/dL, and mild anemia was defined as

Hb = 10–12 g/dL for women and Hb = 10–

13 g/dL for men. In this study, the

demographic and clinical variables and the

type of operation of the patients were also

considered and anemia relationship with the

mentioned cases was considered. During the

surgery, the duration of CPB and patient's

need for blood transfusion were recorded

during surgery, and with this, the need for

transfusion was evaluated.

The criteria for entering the plan were all

patients 18 years of age and older who were

referred for coronary surgery and valve

operation or together at the same time

(coronary artery bypass graft surgery and

valve surgery) for elective surgery.

Exit criteria for this study included patients

with congenital heart disease, emergency

patients, Patients who have received blood

transfusion before surgery, patients treated

for anemia, and patients undergoing dialysis.

RESULTS

This research project evaluated 306 patients,

comprised of 197 (64.4%) male and 109

(35.6%) female patients, over a period of 3

months. The average age of the patients was

60 (52–67) years, the mean height was 167

(160–173) cm, the mean weight was 74

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(65–83) kg, and the mean body mass index

was 26 (24–29).

Diabetes mellitus was reported in 5.9% of

the patients and hypertension in 5.2%. Of

the 306 patients, coronary artery bypass

graft surgery (CABG) was performed on

246 (80.4%) patients, 35.9% of whom had 1

graft, 2.9% had 2 grafts, 28.1% had 3 grafts,

12.4% had 4 grafts, and 1% had 5 grafts.

Mitral valve replacement was performed on

51 (16.7%) patients, aortic valve

replacement on 31 (10.1%), tricuspid valve

replacement on 12 (3.9%), and the Bental

surgery on 8 (2.6%). The mean duration of

surgery was 6 hours, the mean duration of

the pump was 83 (110–160) minutes, and

the mean cross-clamping time was 45 (32–

61) minutes.

The study population had a mean Hb level

of 13.1 (12.08–14.2) g/dL and a mean

hematocrit level of 39.5 (36.17–42.15).

Anemia was reported in 32.4% of the study

population. According to the classification

of anemia based on Hb levels (See

Methods), 90.9% of the patients had mild

anemia, 8.1% had moderate anemia, and 1%

had severe anemia.

No significant relationships existed between

anemia and the variables of age, the body

mass index, the duration of surgery, the

duration of bypass, and the duration of

cross-clamping.

In terms of gender, in the anemia group,

58.6% of the patients were male and 41.1%

female; there was no significant relationship

between sex and anemia (P = 0.143).

Additionally, 9.1% of the patients had

anemia and diabetes, and there was no

significant relationship between diabetes and

anemia in this study (P = 0.099). Anemia

and hypertension were reported in 10.1% of

the patients; the relationship between

hypertension and anemia was significant

(P = 0.08). No significant association was,

however, found between the type of surgery

and anemia, nor was there any significant

association between the number of grafts

and anemia in the post-CABG patients

(P = 0.878).

Table 1. Demographic and clinical characteristics of the patients

P value Non-anemic Group (n=207)

Anemic Group (n=99)

0.105 59(52-66) 61(54-69) Age (y) Median (range)

0.143 67.1 % 58.6 % Sex(male)

32.9% 41.1% Sex(female)

0.283 27(24.4-29.4) 26(24.3-29.4) BMI Median (range)

0.671 6(5-6) 6(5-6) Operation time(h) Median (range)

0.741 85(60-110) 80(60-110) CPB time(min) Median (range)

0.882 45(31-63) 44(32-60) Aortic cross-clamp time (min) Median (range)

0.099 4.3% 9.1% DM

0.008 2.9% 10,1% HTN

0.096 77.8% 85.9% CABG

0.870 16.4% 17.2% MVR

0.990 10.1% 10.1% AVR

0.242 4.8% 2% TVR

0.652 2.9% 2% Bental procedure

BMI, Body mass index; CPB, Cardiopulmonary bypass; DM, Diabetes mellitus; HTN, Hypertension; CABG, Coronary artery bypass; MVR, Mitral valve replacement, AVR, Aortic valve replacement; TVR, Tricuspid valve replacement

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Of the 207 patients who were not in the

anemia group, 44 (21.2%) cases received

packed RBCs. Of the 99 patients in the

anemia group, 47 (47.47%) patients did not

need to receive packed RBCs: 97.9% were

in the mild anemia group, 2.1% in the

moderate anemia group, and 0.0% in the

severe anemia group. Fifty-two (52.52%) of

the 99 patients in the anemia group needed

blood transfusion. The patients who needed

1 blood unit comprised 82.5% of the mild

anemia group, 15% of the moderate anemia

group, and 2.5% of the severe anemia group.

The patients who needed 2 blood units

comprised 90.9% of the mild anemia group,

9.1% of the moderate anemia group, and

0.0% of the severe anemia group. The

patients who needed to receive 4 blood units

comprised 100% of the mild group. In this

study, there was no significant relationship

between the severity of anemia and the need

for more blood units (P = 0.362).

The results revealed that about one-third of

the study population had anemia before

surgery and those with anemia were in need

of blood transfusion 2.5 times more than

those without anemia.

DISCUSSION

In this research project, 306 patients were

studied over a period of 3 months. Anemia

was reported 32.4% of the study population.

According to the anemia classification based

on the Hb level (severe anemia: Hb < 8

g/dL, moderate anemia: Hb = 8–10 g/dL,

and mild anemia: Hb = 10–12 g/dL for

women and Hb = 10–13 g/dL for men), of

the patients with anemia, 90.9% had mild

anemia, 8.1% had moderate anemia, and 1%

had severe anemia. Our results demonstrated

no relationship between anemia and the

variables of gender, the body mass index,

the type of surgery, the duration of surgery,

the duration of bypass, and the duration of

cross-clamping. Our results showed no

relationship between anemia and the

underlying disease of diabetes; nonetheless,

we found a significant correlation between

anemia and hypertension (P = 0.08). Our

patients with anemia were also more likely

to require blood transfusion during the

operation, although there was no significant

relationship between the severity of anemia

and blood intake. The transfusion of blood is

commonly performed in heart surgery, but

many studies have associated it with such

side effects as an increased risk of infectious

occurrences (eg, mediastinitis, respiratory

infection, and sepsis), atrial fibrillation,

acute renal failure, cerebrovascular accident,

and acute respiratory distress syndrome, as

well as with an increased length of hospital

stay. 9

A study on 502 patients who underwent

elective cardiac surgery reported that 60% of

the patients had received blood during the

first 72 hours of surgery. 11

In that study,

those who received blood were more likely

to be old, to be female, to need re-surgery, to

have complicated surgery, to have elevated

EuroSCOREs, to have lower levels of Hb

and hematocrit, and to suffer the incidence

of renal disease. In addition, the patients

who received packed RBCs in the first 72

hours after surgery had a higher incidence of

complications such as renal failure,

cardiogenic shock, acute respiratory distress

syndrome, infections, and neurological and

inflammatory complications. Also in that

study, the length of hospital stay was

increased in the patients who received more

than 3 units of packed RBCs (nearly 6 days)

and in the patients who received fewer or up

to 3 units of packed RBCs (up to 1 day)

compared with the patients not on packed

RBCs.

A recent research on 798 hospitals in the

United States for the evaluation of blood and

blood products reported that in the hospitals

performing at least 100 CABGs on

cardiopulmonary bypass (n = 82 446 cases),

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the rates of packed RBC transfusion ranged

from 7.8% to 92.8% for RBCs, from 0% to

97.5% for fresh frozen plasma, and from

0.4% to 90.4% for platelets. 12

In that study,

after adjustments for the patients’ risk

factors, the amount of transfusion in the

hospital varied because of the patients’

geographic locations (P = 0.007) and

academic status (P = 0.03), as well as the

hospital volume (P < 0.001). Also in that

investigation, a higher number of packed

RBCs was associated with female gender,

older age, need for re-surgery or complex

operations, elevated EuroSCOREs, renal

disease, and previous anemia. This finding

highlights the need for further efforts to

improve perioperative care in these

subgroups of patients to avoid blood

transfusion, which leads to complications

such as increased lengths of stay in the

hospital. 13

Guidelines from the Society of Thoracic

Surgeons and the Society of Cardiovascular

Anesthesiologists emphasize the deficiency

of evidence on transfusion triggers after

cardiac surgery. 14

Most transfusion

indications occur in the first 72 hours

postoperatively, starting in the operating

room, where usually the transfusion

indication is due to hemodilution and based

on triggers. 15

The principle for

implementing a restrictive transfusion

strategy is based on the analysis of studies

reporting a deficiency of benefits and, at the

same time, considerably increased costs and

side effects allied to the transfusion of

packed RBCs. These side effects include

acute hemolytic and non-hemolytic

reactions, the transmission of viral and

bacterial diseases, transfusion-associated

acute lung injury, and transfusion with

circulatory overload. 16

Immunosuppression

has also been related to transfusion and may

explain the higher risk of infection and the

recurrence of neoplastic diseases in

transfused patients. 17

In a study on 11 963

patients who underwent isolated CABG,

Koch et al 18

explained that the perioperative

transfusion of packed RBCs was associated

with a dose-dependent increased risk of

cardiac complications after surgery, critical

infections, renal failure, neurological

complications, overall morbidity, prolonged

mechanical ventilation, and in-hospital

mortality. In a retrospective study, Murphy

et al 19

showed that the transfusion of packed

RBCs was strongly associated with

infections, postoperative ischemic

morbidity, hospital stay, early and late

mortality, and hospital charges. De Cocker

et al 20

performed a retrospective analysis on

1566 patients undergoing cardiac surgery

and demonstrated that age > 75 years,

female gender, New York Heart Association

functional class > II, arrhythmias, mitral

regurgitation, requirement for inotropic

support or intra-aortic balloon pumps, non-

elective procedures, and aortic surgery were

the predictive factors for a prolonged stay in

the intensive care unit. Although blood

transfusion was not a potential predictor of

increased lengths of stay in the hospital in

the current study, a prolonged hospital

length of stay merits evaluation because of

its correlation with increased costs and

clinical complications such as exposure to

infectious agents. 21

Previous research has underscored the

significance of meticulous preoperative

assessments with a view to reducing the risk

of bleeding and the need for blood

transfusion during the postoperative period.

22,23 Indeed, an evaluation of serum iron and

iron administration and preoperative

erythropoietin may lessen the need for

transfusion. 10

Recombinant human erythropoietin

(rHuEPO) is used for the treatment of

anemia related to reduced erythropoiesis

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caused by chronic renal disease and some

hematological diseases. 24,25

Various studies have shown the efficacy of

the preoperative administration of rHuEPO

for cardiac surgery to lower erythrocyte

transfusion in patients having autologous

blood donations. 26,27

Furthermore, rHuEPO

has been shown to be safe and effective in

correcting preoperative anemia, and it can be

used in association with iron therapy in

patients with Hb concentrations < 13 g/dL.

28,29 A typical preoperative regimen of

rHuEPO is, however, costly and requires at

least 4 days of hospitalization before

surgery, limiting a more extensive use of

this strategy. 30

Outpatient-based repeated

subcutaneous injections of rHuEPO may be

practical, 28

although it may be associated

with the increased occurrence of therapy-

related complications such as hypertension

and thromboembolism. 31

Moreover, the

absorption of subcutaneously administered

rHuEPO may not be firm and reliable

compared with the intravenous way because

of decreased microcirculation in patients

with cardiac diseases. 32

In a prospective study, patients with

preoperative anemia were randomly

allocated to either the erythropoietin group

or the control group. The erythropoietin

group was given 500 IU/kg of erythropoietin

and 200 mg of iron sucrose intravenously 1

day before cardiac surgery, while the control

group was given the same volume of normal

saline. The initial result was the need for

transfusion during surgery and 4 days after

surgery. The reticulocyte count and the iron

profile were investigated serially and

compared preoperatively and on

postoperative days 1, 2, 4, and 7.

The results of that study showed that single

doses of erythropoietin and supplemental

iron injections 1 day prior to cardiac surgery

clearly reduced the need for the transfusion

of blood after surgery in anemic patients

undergoing valvular cardiac surgery. The

complications of erythropoietin injections

include hypertension, headaches,

tachycardia, nausea, vomiting,

hypercalcemia, diarrhea, and

thromboembolism; nonetheless, these

complications are usually shown in patients

receiving chronic erythropoietin treatment. 28,30

The chronic use in patients with cancer

is associated with an increased risk of

thrombotic disease, but the short-term use

for acute indications even in critical patients

can be safe. 34,35

Limitations

We conducted a retrospective cohort study

using data from the Cardiovascular Surgery

Department of Rajaie Cardiovascular,

Medical, and Research Center, Tehran, Iran.

CONCLUSIONS

The results of the present study revealed that

about one-third of the patients had anemia

before surgery and the anemic patients

required blood transfusion 2.5 times more

than their non-anemic counterparts. Blood

transfusion is associated with side effects

and increases the length of hospital stay and

hospital costs; therefore, diagnostic

evaluations before elective surgery may

reduce the need for transfusion and

complications and, thus, shorten the length

of hospital stay.


The authors declare no conflict of interest in

this work. This research received no

financial support.

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Ventricular Functional Status in Patients With Rheumatoid Arthritis Nikdoust et al

103

Original Article Ventricular Functional Status in Patients With Rheumatoid Arthritis Nikdoust et al

Assessment of Global Longitudinal Strain via Speckle-Tracking

Echocardiography in Patients With Rheumatoid Arthritis

Farahnaz Nikdoust1, MD; Samira Safiarian

1, MD; Atoosa Mostafavi

1, MD;

Farhad Gharibdoust2, MD; Seyed Abdol Hussein Tabatabaei

1*, MD

ABSTRACT

Background: The inflammatory nature of rheumatoid arthritis presents a hypothesis on the

increase in the likelihood of cardiovascular diseases in patients with rheumatoid arthritis.

Recently, the use of speckle-tracking echocardiography to evaluate ventricular strain,

especially the global longitudinal strain (GLS), has provided more comprehensive

information on ventricular dysfunction in these patients. In the present study, we

evaluated changes in the GLS index along with other left and right ventricular parameters

in patients with rheumatoid arthritis compared with healthy controls.

Methods: The study population was comprised of a case group (patients with rheumatoid

arthritis in the active phase during the first 5 years of diagnosis referred to Shariati

Hospital without a history of any other diseases) and a control group (individuals without

a history of rheumatoid arthritis or cardiac abnormalities referred for clinical check-ups).

In both groups, 2D and 3D echocardiographic examinations were performed by a single

cardiologist to assess cardiac functional parameters.

Results: Comparisons of the echocardiographic indices between the 2 groups showed

significantly lower LA (Left Atrium), AO (Aorta), interventricular septal end-diastole

(IVSD), Posterior wall diastolic diameter (PWD), and RVsm (Right Ventricular systolic

celocity) in the group suffering from rheumatoid arthritis than in the control group. The

GLS parameter was significantly lower in the rheumatoid arthritis group than in the

healthy group (-19.5 ± 2.34 vs -20.42 ± 3.07; P = 0.042); however, there was no

difference in the global circumferential strain parameter between the 2 groups

(-19.69 ± 3.55 vs -20.49 ± 1.79; P = 0.566). In contrast, the mean right ventricular GLS

was -18.77 ± 5.34 in the case group versus -21.87 ± 13.99 in the control group, indicating

a significant difference (P = 0.008).

Conclusions: In the echocardiographic assessment of patients with rheumatoid arthritis, a

decrease in the ventricular function parameters, especially the GLS, is expected, which

may be due to the effect of inflammatory factors on the cardiac ventricular strain. (Iranian

Heart Journal 2020; 21(1): 103-109)

KEYWORDS: Rheumatoid arthritis, Global longitudinal strain, Speckle-tracking echocardiography

1Department of Cardiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IR Iran. 2Department of Rheumatology, Faculty of medicine, Tehran University of Medical Sciences, Tehran, IR Iran.

*Corresponding Author: Seyed Abdol Hussein Tabatabaei, MD; Shariati Hospital, Tehran University of Medical Sciences, Tehran, IR Iran.




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104

atients with rheumatoid arthritis are

about 1.5 to 2 times more likely to be

at risk of coronary heart disease. 1,2

This is almost identical to the risk of heart

disease among patients with diabetes

mellitus. 3 This increase in the risk of heart

disease occurs even before the onset of

rheumatoid arthritis manifestations. 4 In the

Framingham Heart Study, a 1.5-fold

increase in the risk of heart disease among

patients with rheumatoid arthritis was noted. 4 Patients with rheumatoid arthritis also have

a high risk of heart failure. 5 This increase in

risk is mainly seen in patients with positive

rheumatoid factors. 6 Most importantly,

patients with heart failure and simultaneous

rheumatoid arthritis also experience a

progressive reduction in the left ventricular

(LV) systolic function manifested by a drop

in the left ventricular ejection fraction

(LVEF). 7 The set of these statements

reflects the fact that patients with

rheumatoid arthritis encounter heart failure

with systolic and diastolic dysfunction of the

LV, the underlying cause of which is

systemic inflammation associated with the

disease. Patients with rheumatoid arthritis

face an increased risk of LV systolic and

diastolic dysfunction; therefore,

echocardiographic evaluations in these

patients are of utmost importance. Because

rheumatoid arthritis is a type of connective

tissue inflammatory disease, this

involvement in the connective and muscular

components of the heart is also contagious;

thus, myocardial and endocardial

disturbances can also be expected in such

patients. Nonetheless, in some patients, and

with regard to the severity of the disease,

heart disease is sometimes asymptomatic

and because patients are not physically

active, changes in the cardiac function may

not be detected until the end stages of the

disease. Echocardiography is very useful in

evaluating and detecting cardiac

disturbances in patients with rheumatoid

arthritis, especially in the early stages of the

disease. Various studies have been

conducted on echocardiographic impairment

in rheumatoid arthritis. Overall, it appears

that the prevalence of valvular involvement

in patients with rheumatoid arthritis, not

least mitral valve regurgitation, followed by

pericardial effusion, is a common and

prevalent finding. 8,9

In addition to

pericardial and valve involvement, what is

revealed in patients with rheumatoid arthritis

is systolic and diastolic dysfunction and

what is predictable in rheumatoid arthritis is

systolic dysfunction (with a reduction in the

LVEF), diastolic dysfunction (accompanied

by changes in the E (E velocity in mitral

inflow), E/A (E velocity/A velocity), IVRT

(Isuvolomic Relaxation time), and

myocardial performance indices), valve

involvement, mitral insufficiency, and mild

pericardial effusion, especially in nodular

types.

Myocardial strain imaging is one of the

advanced echocardiographic methods aimed

at evaluating myocardial deformities during

ventricular contraction and relaxation. 10

The

evaluation of the strain index is reported as

the percentage change in myocardial

dystonia at a point from another point and

can be analyzed and reported through

speckle-tracking echocardiography (STE). 11-13

Accordingly, strain abnormalities for a

wide range of cardiovascular diseases 14

and

strain imaging are accurate and sensitive in

the diagnosis and prediction of systolic

dysfunction. 15-17

The disruption of

myocardial strain can be a symptom of

coronary heart disease, even in the early and

subclinical stages. Given the importance of

identifying cardiovascular and myocardial

infarction in patients with rheumatoid

arthritis, the imaging of myocardial strain in

the early stages of the disease is very

beneficial. 18

In this regard, some studies

P

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have identified the sensitivity and specificity

of the global longitudinal strain (GLS) index

in assessing the infarct size and the severity

of myocardial involvement in coronary heart

disease. 19-21

The GLS index is valuable for

the evaluation of systolic dysfunction

compared with other indicators such as the

LVEF. Indeed, the GLS index can be drawn

upon to assess the severity of myocardial

dysfunction in patients with rheumatoid

arthritis. The present study aimed to assess

and compare the GLS along with other

parameters for cardiac systolic dysfunction

in patients with rheumatoid arthritis.

METHODS

This is a descriptive-analytical case-control

study conducted in Shariati Hospital in

Tehran in 2018. The study population was

comprised of a case group (patients with

rheumatoid arthritis in the active phase

during the first 5 years of diagnosis referred

to Shariati Hospital without a history of any

other diseases except rheumatoid arthritis)

and a control group (individuals without a

history of rheumatoid arthritis or cardiac

abnormalities referred for clinical check-

ups). The American College of

Rheumatology (ACR) diagnostic criteria for

rheumatoid arthritis include 1) morning

stiffness more than an hour, 2) arthritis in 3

or more joints, 3) arthritis in the hand joints

(≥ 1 swollen joint), 4) symmetric arthritis, 5)

the presence of rheumatoid nodules, 6)

positive serum rheumatic factor, and 7)

radiographic X-ray changes of the hands as

the erosion. In both groups, 2D and 3D

echocardiographic examinations were

performed by a single cardiologist to assess

the cardiac functional parameters including

the Left Atrium (LA), the Aorta (AO), the

interventricular septal end-diastole (IVSD),

the Posterior Wall Diastolic Diameter

(PWD), the Posterior Wall Diastolic

Diameter (RVD), the Right Ventricular

systolic velocity (RVsm), the tricuspid

annular plane systolic excursion (TAPSE),

and the 2 strain-related indices of the GLS

and the global circumferential strain (GCS).

For the description of the data, descriptive

analysis was used, including the mean ± the

standard deviation (SD) for the quantitative

variables and frequencies (percentages) for

the categorical variables. The χ2

test, the t-

test, or the Mann–Whitney U test was used

for the comparison of the variables. The

correlations between the quantitative

variables were assessed using the Pearson or

Spearman correlation test. For the statistical

analyses, the statistical software IBM SPSS

Statistics for Windows, version 23.0 (IBM

Corp, released 2013, Armonk, NY) was

used. A P value < 0.05 was considered

statistically significant.

RESULTS

In this study, 35 patients with active

rheumatoid arthritis (mean age = 43.33 ±

22.9 y) and 35 healthy controls (mean age =

34.27 ± 9.10 y) were evaluated for

echocardiographic parameters.

Comparisons of the echocardiographic

indices between the 2 groups (Table 1)

showed significantly lower LA, AO, IVSD,

PWD, and RVSm in the group suffering

from rheumatoid arthritis than in the control

group. The GLS parameter was significantly

lower in the rheumatoid arthritis group than

in the healthy group (-19.5 ± 2.34 vs -20.42

± 3.07; P = 0.042); however, there was no

difference in the GCS parameter between

the 2 groups (-19.69 ± 3.55 vs -20.49 ± 1.79;

P = 0.566). In contrast, the mean RV-GLS

was -18.77 ± 5.34 in the case group versus -

21.87 ± 13.99 in the control group, indicating

a significant difference (P = 0.008). With

respect to the association between age and

the echocardiographic parameters (Table 2),

the patients’ age was adversely correlated

with the RVSm (r = -0.616, P = 0.001) and

with the TAPSE (r = -0.496, P = 0.005), but

not with the other cardiac parameters.

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Table 1. Values of echocardiographic parameters in both case and control groups

Parameter RA Group Healthy Group P value

LA 30.83 ± 4.02 34.07 ± 3.31 0.001

AO 26.53 ± 4.84 29.64 ± 3.87 0.003

IVSD 8.57 ± 1.25 7.64 ± 1.00 0.001

PWD 8.40 ± 1.00 7.42 ± 0.94 0.001

RVD 26.21 ± 3.56 26.89 ± 3.02 0.380

RVSm 11.61 ± 1.23 13.96 ± 1.45 0.001

TAPSE 22.73 ± 3.32 22.60 ± 1.84 0.824

GLS -19.5 ± 2.34 -20.42 ± 3.07 0.042

GCS -19.69 ± 3.55 -20.49 ± 1.79 0.566

RV-GLS -18.77 ± 5.34 -21.87 ± 13.99 0.008

RA, Rheumatoid arthritis; LA, Left Atrium; AO, Aorta; IVSD, Interventricular septal diastolic diameter; PWD, Posterior wall diastolic diameter; RVD, Right ventricular diastolic diameter; RVsm, Right ventricular systolic velocity ;TAPSE, Tricuspid annular plane systolic excursion; GLS, Global longitudinal strain; GCS, Global circumferential strain; RV-GLS, Right ventricular global longitudinal strain

Table 2. Correlations between the patients’ age and the echocardiographic parameters in the affected group

Parameter R Coefficient P value

LA 0.299 0.108

AO 0.298 0.109

IVSD 0.139 0.465

PWD 0.201 0.286

RVD 0.293 0.123

RVSM -0.616 0.001

TAPSE -0.496 0.005

GLS 0.182 0.336

GCS 0.355 0.098

RV-GLS 0.122 0.884

LA, Left Atrium; AO, Aorta ; IVSD, Interventricular septal diastolic diameter; PWD, Posterior wall diastolic diameter ; RVD, Right ventricular diastolic diameter; RVsm, Right ventricular systolic velocity ;TAPSE, Tricuspid annular plane systolic excursion; GLS, Global longitudinal strain; GCS, Global circumferential strain; RV-GLS, Right ventricular global longitudinal strain

DISCUSSION

The inflammatory nature of rheumatoid

arthritis and the role of inflammatory factors

in the development and progression of

coronary artery atherosclerosis and also the

valve defects present a new hypothesis on

the increase in the likelihood of

cardiovascular diseases in patients with

rheumatoid arthritis. This has been

confirmed in clinical observations as well as

heart imaging studies. Recently, the use of

STE to evaluate the ventricular strain,

especially the GLS, has provided more

comprehensive information on ventricular

dysfunction in these patients. In the current

study, we aimed to assess changes in the

GLS index along with other LV and RV

parameters in patients with rheumatoid

arthritis compared with healthy controls. We

found that whereas the decrease in the GLS

index in patients with rheumatoid arthritis

was significant compared with the healthy

controls, these changes were not significant

concerning the GCS index. Additionally,

among the other parameters of the

ventricular function, reductions in the LA,

the AO, the IVSD, the PWD, and the RVSm

in these patients were evident in comparison

with the healthy controls. In other words, the

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consequence of rheumatoid arthritis in the

first 5 years of the active phase of the

disease is the involvement of the LV and the

RV. In this regard, 2 important issues should

also be considered. Firstly, ventricular

echocardiographic changes in patients with

rheumatoid arthritis may not appear in the

early stages of the disease or they may be

asymptomatic; consequently, after years of

active disease and with the progression of

inflammatory processes, changes in the

ventricular function become evident. In

contrast, these changes may begin to appear

subclinically at the very beginning of the

active period of the disease. An

echocardiographic evaluation with the aim

of examining the course of changes in the

parameters of the heart within 5 years of the

active period of the disease is necessary.

The results of the previous studies chime in

with our findings concerning changes in the

ventricular function parameters in

rheumatoid arthritis. In a study by Naseem

et al, 22

the values of the GLS in both LV

and RV for patients with active rheumatoid

arthritis were significantly lower than those

in healthy controls. In addition, the severity

of rheumatoid arthritis activity was

significantly correlated with a further

reduction in the GLS. Cioffi et al 23

reported

reduced GLS values in 24% of their patients.

In a study by Benacka et al, 24

patients with

rheumatoid arthritis had a greater LV mass,

a lower LVEF, and a more prolonged IVCT

(Isovolumic Contraction time). Moreover,

the prolongation of the IVRT and a higher

E/E' ratio showed a much higher degree of

diastolic ventricular dysfunction in the

patients. In the STE evaluation, a significant

reduction in the GLS was also reported.

Benacka et al 25

reported that the active

status of the disease was significantly

correlated with the decrease in the GLS. In

an investigation by Fine et al, 26

the mean

GLS in both RV and LV showed a

significant decrease compared with healthy

controls. Therefore, with the development

and progression of rheumatoid arthritis, the

risk of developing heart disease, in particular

of ventricular dysfunction, is predictable. In

this regard, the efficiency of the GLS

evaluation can be very important and

diagnostic in predicting adverse cardiac

outcomes in patients with rheumatoid

arthritis, which, of course, needs to be

further evaluated.

CONCLUSIONS

In the echocardiographic assessment of

patients with rheumatoid arthritis, a decrease

in the ventricular function parameters,

especially the GLS, is expected, which may

be due to the inflammatory nature of the

disease and the effect of inflammatory

factors on the cardiac ventricular strain.

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https://www.ncbi.nlm.nih.gov/pubmed/?term=Naseem%20M%5BAuthor%5D&cauthor=true&cauthor_uid=30559579

https://www.ncbi.nlm.nih.gov/pubmed/?term=Samir%20S%5BAuthor%5D&cauthor=true&cauthor_uid=30559579

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ibrahim%20IK%5BAuthor%5D&cauthor=true&cauthor_uid=30559579

https://www.ncbi.nlm.nih.gov/pubmed/?term=Khedr%20L%5BAuthor%5D&cauthor=true&cauthor_uid=30559579

https://www.ncbi.nlm.nih.gov/pubmed/?term=Khedr%20L%5BAuthor%5D&cauthor=true&cauthor_uid=30559579

https://www.ncbi.nlm.nih.gov/pubmed/?term=Shahba%20AAE%5BAuthor%5D&cauthor=true&cauthor_uid=30559579



https://www.ncbi.nlm.nih.gov/pubmed/?term=Cioffi%20G%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Viapiana%20O%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ognibeni%20F%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ognibeni%20F%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Dalbeni%20A%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Giollo%20A%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gatti%20D%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Idolazzi%20L%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Idolazzi%20L%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Faganello%20G%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Di%20Lenarda%20A%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Rossini%20M%5BAuthor%5D&cauthor=true&cauthor_uid=28391000

https://www.ncbi.nlm.nih.gov/pubmed/?term=Rossini%20M%5BAuthor%5D&cauthor=true&cauthor_uid=28391000



https://www.ncbi.nlm.nih.gov/pubmed/?term=Benacka%20O%5BAuthor%5D&cauthor=true&cauthor_uid=28127980

https://www.ncbi.nlm.nih.gov/pubmed/?term=Benacka%20J%5BAuthor%5D&cauthor=true&cauthor_uid=28127980

https://www.ncbi.nlm.nih.gov/pubmed/?term=Blazicek%20P%5BAuthor%5D&cauthor=true&cauthor_uid=28127980

https://www.ncbi.nlm.nih.gov/pubmed/?term=Belansky%20M%5BAuthor%5D&cauthor=true&cauthor_uid=28127980

https://www.ncbi.nlm.nih.gov/pubmed/?term=Belansky%20M%5BAuthor%5D&cauthor=true&cauthor_uid=28127980

https://www.ncbi.nlm.nih.gov/pubmed/?term=Payer%20J%5BAuthor%5D&cauthor=true&cauthor_uid=28127980

https://www.ncbi.nlm.nih.gov/pubmed/?term=Killinger%20Z%5BAuthor%5D&cauthor=true&cauthor_uid=28127980

https://www.ncbi.nlm.nih.gov/pubmed/?term=Lietava%20J%5BAuthor%5D&cauthor=true&cauthor_uid=28127980


https://www.ncbi.nlm.nih.gov/pubmed/?term=Midtb%C3%B8%20H%5BAuthor%5D&cauthor=true&cauthor_uid=27269296

https://www.ncbi.nlm.nih.gov/pubmed/?term=Semb%20AG%5BAuthor%5D&cauthor=true&cauthor_uid=27269296

https://www.ncbi.nlm.nih.gov/pubmed/?term=Matre%20K%5BAuthor%5D&cauthor=true&cauthor_uid=27269296

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kvien%20TK%5BAuthor%5D&cauthor=true&cauthor_uid=27269296

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kvien%20TK%5BAuthor%5D&cauthor=true&cauthor_uid=27269296

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gerdts%20E%5BAuthor%5D&cauthor=true&cauthor_uid=27269296


https://www.ncbi.nlm.nih.gov/pubmed/?term=Fine%20NM%5BAuthor%5D&cauthor=true&cauthor_uid=23873875

https://www.ncbi.nlm.nih.gov/pubmed/?term=Crowson%20CS%5BAuthor%5D&cauthor=true&cauthor_uid=23873875

https://www.ncbi.nlm.nih.gov/pubmed/?term=Lin%20G%5BAuthor%5D&cauthor=true&cauthor_uid=23873875

https://www.ncbi.nlm.nih.gov/pubmed/?term=Oh%20JK%5BAuthor%5D&cauthor=true&cauthor_uid=23873875

https://www.ncbi.nlm.nih.gov/pubmed/?term=Oh%20JK%5BAuthor%5D&cauthor=true&cauthor_uid=23873875

https://www.ncbi.nlm.nih.gov/pubmed/?term=Villarraga%20HR%5BAuthor%5D&cauthor=true&cauthor_uid=23873875

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gabriel%20SE%5BAuthor%5D&cauthor=true&cauthor_uid=23873875



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Coronary and Cerebral Artery Air Embolism Complicating Trans-septal Accessory Pathway Ablation Farzamnia et al

110

Case Report Coronary and Cerebral Artery Air Embolism Complicating Trans-septal Accessory Pathway Ablation Farzamnia et al

Coronary and Cerebral Artery Air Embolism Complicating

Trans-septal Accessory Pathway Ablation

Hamid Farzamnia1, MD; Farzad Kamali MD

1, MD;

Mohsen Neshati Pirborji1, MD, MD; Ala Keykhavani

1, MD;

Azadeh Meibodi Ardekani1, MD; Shabnam Madadi

2, MD

ABSTRACT

A 30-year-old woman presented with frequent episodes of paroxysmal palpitation and

electrocardiographic evidence of minimal pre-excitation of the left lateral accessory pathway.

The patient underwent septostomy, which revealed air bubbles in the left ventricular cavity.

Aspiration was done with a pigtail catheter via the retrograde aortic approach. Transient ST-

elevation in the inferior leads was demonstrated. Left-sided hemiplegia was present after

consciousness, which was completely resolved after 24 hours. (Iranian Heart Journal 2020; 21(1):

110-114)

KEYWORDS: Accessory pathway, Trans-septal catheterization, Air embolism


2 Cardiac Electrophysiology Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences,

Tehran, IR Iran.

*Corresponding Author: Shabnam Madadi, MD; Rajaie Cardiovascular, Medical, and Research Center, Vali-E-Asr Ave, Ayatolah Rafsanjani

Blvd, Tehran 1995614331, IR Iran.

Email:[email protected] Tel: 02123922019

Received: April 6, 2019 Accepted: July 11, 2019

bout 0.1%–0.3% of the general

population have ECG findings in

favour of accessory atrioventricular

pathways, which ise called Wolff–

Parkinson–White (WPW) syndrome in the

presence of arrhythmias. 1

The most common arrhythmias in these

patients are reentrant tachycardia and atrial

fibrillation (AF). The catheter ablation of the

accessory pathway is the treatment of

choice, and it can be done via the retrograde

or trans-septal approach.

We herein describe a patient with WPW

syndrome who suffered coronary and

cerebral air embolism as a complication of

septostomy for trans-septal radiofrequency

catheter ablation.

Case

A 30-year-old woman with a history of

frequent episodes of supraventricular

tachycardia presented with the ECG

manifestations of a minimal left-sided

accessory pathway and WPW syndrome.

A

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An electrophysiological study was

performed in conscious sedation status, and

diagnostic catheters were introduced via the

left and right femoral veins.

Intracardiac ECGs were recorded using the

Bard (Boston Scientific) electrophysiology

system.

The evaluation of the conduction system

revealed the most fused atrioventricular

(AV) signal in the left lateral side of the

coronary sinus (CS) (Fig. 1).

Figure 1. Most fused atrioventricular signal in the left lateral side of the coronary sinus

The retrograde conduction pattern was also

eccentric, and the earliest retrograde atrial

signal was recorded in the distal part of the

CS during right ventricular pacing. A narrow

QRS tachycardia was reproducibly inducible

with programmed atrial and ventricular

stimulation.

Septostomy was attempted with the use of

an Agilis long sheet (Agilis NxT™

Steerable Introducer, St Jude Medical). A

needle was inserted and advanced into the

left atrium without the need for the puncture

of the interatrial septum. Immediately after

the septostomy, air bubbles were observed in

the left ventricular apex (Fig. 2).

Figure 2. Air bubbles in the left ventricular

apex

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112

Immediately, 100% oxygen was

administrated. The right femoral artery was

cannulated, and a pigtail catheter (Dawson–

Mueller Drainage Catheter) was introduced

via the femoral artery via the retrograde

approach into the left ventricular cavity.

Next, suction was done, during which ST-

elevation in the inferior leads appeared with

sinus bradycardia and manifest accessory

pathway conduction, in favor of AV block

(Fig. 3).

Figure 3. ST-elevation in the inferior leads with sinus bradycardia and accessory pathway conduction, in favor of

atrioventricular block

Rapid right ventricular pacing was done,

100% oxygen was administrated, and an

inotrope was injected. ST-elevation was

resolved in about 1–2 minutes.

The procedure was terminated without any

attempt for ablation. A decision was made

against propofol injection.

After regaining consciousness, the patient

was alert and awake and obeyed orders.

However, she had left-sided hemiparesis

without left central hemifacial weakness.

Brain computed tomography scan was done,

and the results were normal. The distal force

of the left upper extremity was resolved in

about 1 hour, but the proximal force of the

left arm as well as the total force of the left

leg was still compromised. Neurological

consultation was done, and heparin drips and

dexamethasone were recommended by the

neurologist.

Twenty-four hours after the procedure, all

the forces returned to the normal status and

after 72 hours, the patient was discharged in

a good general condition without any

problems.

The follow-up of the patient showed no

problems. Fourteen days later, she

underwent a redo procedure, during which

the accessory pathway was successfully

ablated via the retrograde approach.

Transesophageal echocardiography in the

second admission revealed a patent foramen

ovale, about 2 × 5 mm in size, and a right-

to-left shunt.

DISCUSSION

Radiofrequency ablation for WPW

syndrome can be done via the retrograde or

trans-septal approach. The retrograde

approach may be associated with the risk of

prolonged catheter manipulation and

potential arrhythmogenic ventricular lesions

created during ablation. 2-4

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Potential risks can be avoided using trans-

septal atrial insertion. The approach was

developed in the 1950s and nowadays is one

of the most useful approaches for the

ablation of left-sided targets in

electrophysiology studies. 5,10

Lesh et al 9 reported a case of coronary air

embolism complicating the trans-septal

radiofrequency ablation of the left lateral

accessory pathway during catheter exchange

and recommended continuous flushing with

heparinized saline during the catheter

exchange.

Khurram et al 4 in 2016 reported a case of

catastrophic coronary air embolism during

AF ablation with massive air embolism into

the right coronary artery, leading to the

hemodynamic collapse, and its subsequent

successful management with catheter-based

coronary aspiration.

Murat Tulmac et al 9 reported a case of

massive systemic air embolism during the

aortic root angiography in 2012, with the

collapse of the patient and pulseless

electrical activity. The patient became

electrically stable shortly after

cardiopulmonary resuscitation, but she had

garbled speech and left hemiplegia with

partial weakness and paresthesia in the right

leg and arm. 6-8

The brain computed

tomography of the patient was normal, as

was the case in our patient, and she was

transferred to a center with facilities for

hyperbaric oxygen chamber treatment

(HBOT), and all of her neurological

functions became normal after 1 day.

Our center lacks HBOT facilities. We

administered 100% O2 and after 24 hours,

everything was normal and our patient was

discharged after 72 hours without any

residual defect.

CONCLUSIONS

Air embolism is almost always iatrogenic

during cardiac procedures, and the

administration of 100% O2 or the catheter-

based aspiration of the air may reduce the

risk of sequels.

REFERENCES

1. Luh Oliva Saraswati Suastika and Yudi Her

Oktaviono Multiple Air Embolism During

Coronary Angiography: How Do We Deal

With It? Clin Med Insights Cardiol. 2016;

10: 67–70.

2. CHANG-BUM PARK, HUI-JEONG

HWANG, JIN-MAN CHO, BYUNG-

HYUN JO, and CHONG-JIN KIM Massive

right coronary air embolism in the right

coronary artery during left coronary

angiography: A case report Exp Ther Med.

2013 Apr; 5(4): 1073–1074

3. Voci, P., Yang, Y., Greco, C., Nigri, A., and

Critelli, G. Coronary air embolism

complicating accessory pathway catheter

ablation: detection by echocardiography. J

Am Soc Echocardiogr. 1994; 7: 312–314

4. 4.Khurram Ahmad,MD,* Samuel

Asirvatham,MD,† Sreenivas Kamath,MD,*

Stephen Peck,MD,* Xiaoke

Liu,MD,PhDSuccessful interventional

management of catastrophic coronary

arterial air embolism during atrial fibrillation

ablation,Heart rhythm case reports,March

2016, Volume 2, Issue 2, Pages 153–156

5. Khan, M., Schmidt, D.H., Bajwa, T., and

Shalev, Y. Coronary air embolism:

incidence, severity, and suggested

approaches to treatment. Cathet Cardiovasc

Diagn. 1995; 36: 313–318

6. Rawlins, R.1, Momin, A., Platts, D., and El-

Gamel, A. Traumatic cardiogenic shock due

to massive air embolism. A possible role for

cardiopulmonary bypass. Eur J Cardiothorac

Surg. 2002; 22: 845–846

7. Sinha, S.K., Madaan, A., Thakur, R.,

Pandey, U., Bhagat, K., and Punia, S.

Massive coronary air embolism treated

successfully by simple aspiration by guiding

catheter. Cardiol Res. 2015; 6: 236–238

https://www.ncbi.nlm.nih.gov/pubmed/?term=Suastika%20LO%5BAuthor%5D&cauthor=true&cauthor_uid=27226738

https://www.ncbi.nlm.nih.gov/pubmed/?term=Oktaviono%20YH%5BAuthor%5D&cauthor=true&cauthor_uid=27226738

https://www.ncbi.nlm.nih.gov/pubmed/?term=Oktaviono%20YH%5BAuthor%5D&cauthor=true&cauthor_uid=27226738

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874743/

https://www.ncbi.nlm.nih.gov/pubmed/?term=PARK%20CB%5BAuthor%5D&cauthor=true&cauthor_uid=23596473

https://www.ncbi.nlm.nih.gov/pubmed/?term=HWANG%20HJ%5BAuthor%5D&cauthor=true&cauthor_uid=23596473

https://www.ncbi.nlm.nih.gov/pubmed/?term=HWANG%20HJ%5BAuthor%5D&cauthor=true&cauthor_uid=23596473

https://www.ncbi.nlm.nih.gov/pubmed/?term=CHO%20JM%5BAuthor%5D&cauthor=true&cauthor_uid=23596473

https://www.ncbi.nlm.nih.gov/pubmed/?term=JO%20BH%5BAuthor%5D&cauthor=true&cauthor_uid=23596473

https://www.ncbi.nlm.nih.gov/pubmed/?term=JO%20BH%5BAuthor%5D&cauthor=true&cauthor_uid=23596473

https://www.ncbi.nlm.nih.gov/pubmed/?term=KIM%20CJ%5BAuthor%5D&cauthor=true&cauthor_uid=23596473

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627689/

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8. French, K.F., Garcia, C., Wold, J.J., Hoesch,

R.I., and Ledyard, H.K. Cerebral air emboli

with atrial-esophageal fistula following

atrial fibrillation ablation a case report and

review. Neurohospitalist. 2011

9. Lesh, M.D., Coggins, D.L., and Ports, T.A.

Coronary air embolism complicating

transseptal radiofrequency ablation of left

free-wall accessory pathways. Pacing Clin

Electrophysiol. 1992; 15: 1105–1108

10. S Madadi, Z Emkanjoo, M Sharifi, H

AhmadpourAn unusual location of the

accessory pathway on the anteromedial side

of the mitral annulusIranian Heart Journal

19 (2), 75-78.

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Surgical Management of Retained Guide-Wire Fragment Tarbiat et al

115

Case Report Surgical Management of Retained Guide-Wire Fragment Tarbiat et al

Successful Surgical Management of a Retained

Guide-Wire Fragment in the Left Main Coronary Artery

Masoud Tarbiat1, MD; Amir Shams

2, MD; Farnaz Fariba

3*, MD

ABSTRACT

Guide-wire fracture during percutaneous coronary interventions is a rare and potentially serious

complication. Herein, we report a case of guide-wire fracture inside the left main coronary

artery following percutaneous coronary intervention in a 58-year-old man. The patient had

severe chest pain, and the extraction of the retained guide-wire fragment was thwarted via

percutaneous retrieval approaches. Ultimately, he had a successful emergency surgical

extraction of THE retained guide-wire fragment and coronary artery bypass graft surgery. This

report indicates that the surgical extraction of a retained guide-wire fragment is still safe and

the only option for its treatment after the failure of retrieval approaches. (Iranian Heart Journal

2020; 21(1): 115-118)

KEYWORDS: Percutaneous coronary intervention, Coronary artery bypass, Coronary vessels

1 Clinical Research Development Unit of Farshchian Hospital, Department of Anesthesiology, School of Medicine, Hamadan University of

Medical Sciences, Hamadan, IR Iran. 2

Clinical Research Development Unit of Farshchian Hospital, Department of Cardiac Surgery, School of Medicine, Hamadan University of

Medical Sciences, Hamadan, IR Iran. 3

Clinical Research Development Unit of Farshchian Hospital, Department of Cardiology, School of Medicine, Hamadan University of Medical

Sciences, Hamadan, IR Iran.

*Corresponding Author: Farnaz Fariba, MD; Department of Cardiology, School of Medicine, Hamadan University of Medical Sciences,

Hamadan, IR Iran.



uide-wire fracture during

percutaneous coronary intervention

(PCI) is a rare and potentially

serious complication, with a reported

incidence of around 0.08%. The first case of

this complication was reported in the late

1980s. 1

The main causes of fracture

mechanisms are wire cutting by directional

or rotational coronary atherectomy catheter,

wire wedging into the distal or winding

vessels, and structural failure. This rare and

dangerous complication may be life-

threatening and sometimes require

emergency cardiac surgery if percutaneous

retrieval fails. 2,3

Herein, we report a case of

guide-wire fracture during an elective PCI,

requiring emergent surgical removal and

coronary artery bypass graft surgery

(CABG).

Case Report

A 58-year-old male smoker with

hypertension was admitted to the emergency

department for the sudden onset of typical

cardiac chest pain and sweating. The patient

had suffered from occlusive coronary artery

disease for about 12 years. Due to the

history of occlusive coronary artery disease,

as well as strong clinical and

electrocardiographic evidence of unstable

G


Tel:09188118143

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angina, he was referred for cardiac

catheterization. Cardiac catheterization,

performed through the right radial artery,

revealed a significant lesion in the

proximal part of the left anterior

descending artery with good retrograde

filling via the ipsilateral collaterals and a

good run-off. The obtuse marginal artery 2

had a 50%–60% lesion in the mid-part

with a good runoff. No other significant

lesion was observed.

The physician decided to treat the artery

percutaneously. He used a guide wire with

hydrophilic coating (PILOT 200) to cross

the total occlusion of the left anterior

descending artery and a BMW guide wire

as an anchoring wire. Unfortunately,

however, the PILOT 200 guide wire was

detached during the procedure. He used

ANDROSNARE MICRO ASM 4 set 3F and

ENSNARE 6F but failed to remove the

detached fragment of the guide wire from

inside the left main coronary artery (Fig. 1 &

2).

Figure 1. Coronary artery angiography,

showing a retained guide-wire fragment within the left main coronary artery (arrow) in the right anterior oblique caudal view

Figure 2. Coronary artery angiography,

showing the retained guide-wire fragment within the left main coronary artery (arrow) in the left anterior oblique caudal view

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Therefore, the patient was referred for

emergent CABG. On admission in the

operating room, the patient was agitated and

suffered severe chest pain. He was in a

stable hemodynamic state with an

epinephrine infusion. Without delay, he was

prepared for the induction of anesthesia. He

was monitored with a pulse oximeter and

standard electrocardiography. The veins on

both arms were immediately cannulated with

16-G catheters after a subcutaneous

lidocaine (1%) injection. The blood pressure

was monitored via the left radial artery. The

patient was induced with sufentanil (50 μg),

etomidate (16 mg), and cisatracurium (16

mg). Anesthesia was maintained using an

infusion of sufentanil (2 μg/kg/h),

propofol (50–75 μg/ kg/min), and

cisatracurium (2 μg/kg/ min). Subsequently,

a catheter was inserted in the right

subclavian vein for central vein pressure

(CVP) monitoring. Under general

anesthesia, median sternotomy was

performed, followed by aortic and right

atrial cannulations (unicaval approach).

Cardiopulmonary bypass (CPB) was

initiated through systemic cooling to 33 °C.

After aortic cross-clamping, an infusion of

antegrade and retrograde cold blood

cardioplegic solutions was done. Following

transverse aortotomy, the remanent of the

guide wire was removed from the left main

coronary artery ostium. Subsequently, the

left internal mammary artery was

anastomosed to the left anterior descending

artery and the obtuse marginal artery 2 was

grafted with the saphenous vein. The grafts

were positioned and checked successfully.

Following rewarming, normal sinus rhythms

occurred. The patient had uneventful

weaning from CPB. The operation course

was uneventful, and he was finally extubated

in the Open Heart Intensive Care Unit after

6 hours. He was in a complete alertness state

without any hemodynamic complications.

Finally, he was discharged home in a good

overall condition 7 days later.

DISCUSSION

Although PCI has been a progressive

technological improvement of devices and

techniques, its accidental complications

remain technically challenging. A fracture

or retained guide wire during PCI is a well-

known rare but feared complication

(estimated incidence of 0.1%–0.2%). The

complications of guide-wire remnants

following guide-wire fracture are

perforation, thrombosis, embolic events, and

vessel occlusion. 2,3

Several risk factors,

sometimes in combination, have been

suggested for guide-wire entrapment. These

suggested risk factors for guide-wire

entrapment are type of procedure (“jailing”

of the wire between overlapping stents or

between stent and vessel wall), type of

lesion (bifurcation lesions, chronic total

occlusions, and lesions in very tortuous and

calcified vessels), type of material used

(hydrophilic wires), and excessive rotation

of the guide wire. In our case, it appears

that the use of a “hydrophilic” wire

facilitated the occurrence of this event. 1,3

The optimal management of guide-wire

entrapment depends on the site and extent

of the guide-wire remnant and is

controversial. Therefore, it should be

managed on an individual basis. The

therapeutic options of guide-wire fracture

are percutaneous retrieval, surgical

removal, or leaving the guide-wire

remnants in-situ. The first preferable option

is the removal of the retained guide-wire

remnants from the coronary circulation. 3

The percutaneous retrieval methods for the

extraction of a retained guide-wire fragment

are the double- or triple-wire rotation

technique, the deep wedging of the guiding

catheter and the traction of the system,

retrieval using the balloon inflation

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technique, retrieval by snare loops, retrieval

using microcatheters (Tornus catheters),

extraction with Bioptome, and stenting over

the retained wire. 3,4

When percutaneous

retrieval techniques fail, some physicians

believe that if the guide-wire remnant is

jailed in a distal portion of a small vessel

without inducing ischemia, conservative

therapy may be safe. Nevertheless, others

believe that leaving guide-wire remnants in

situ is not advisable due to thrombotic risks,

and surgical removal should be performed.

Eventually, the other preferable approach is

surgical extraction. 1,3

Emergent cardiac

surgery is sometimes associated with

significant morbidity and mortality. The

surgical removal of a retained guide-wire

fragment is direct coronary arteriotomy or

aortotomy. The surgical extraction of

proximal wire entrapment is sometimes the

left main coronary arteriotomy and patch

repair. 3,5

In our case, the percutaneous

retrieval of the retained guide-wire fragment

failed. Since the guide-wire fragment was in

the left main coronary artery and the patient

suffered severe chest pain, emergent cardiac

surgery for the removal of the retained

guide-wire fragment and CABG was

performed.

In conclusion, guide-wire fracture during

PCI is a rare complication with favorable

early and long-term outcomes when

recognized timely and managed properly.

Physicians should be aware of this rare

complication and prepared to manage it.

Furthermore, the surgical extraction of A

retained guide-wire fragment is still safe

and the only option for its treatment after

the failure of retrieval approaches.


The authors have no conflict of interest.

Funding/Support

We wish to thank Hamadan University of

Medical Sciences for its support in the

conduct of the present study.

REFERENCES

1. Koulouris S, Saad M. An unusual case of an

angioplasty wire entrapped and fractured

within the struts of a recently implanted

coronary stent: Treatment with the

implantation of a "jailing" stent. Hellenic J

Cardiol 2017;58:236-8.

2. Balbi M, Bezante GP, Brunelli C, Rollando

D. Guide wire fracture during percutaneous

transluminal coronary angioplasty: possible

causes and management. Interactive

CardioVascular and Thoracic Surgery

2010;10: 992-4.

3. Abdulrahman M. Al-Moghairi, Al-Amri H.

Management of retained intervention guide-

wire: A literature review. Current

Cardiology Reviews 2013;9:260-6.

4. Hong YM, M, Lee SR. A case of guide wire

fracture with remnant filaments in the left

anterior descending coronary artery and

aorta. Korean Circ J 2010; 40:475-7.

5. Assar O. Emergency CABG and surgical

retrieval of entrapped coronary stent

balloon: A case report. The Iranian Journal

of Cardiac Surgery 2012;4:41-2.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Koulouris%20S%5BAuthor%5D&cauthor=true&cauthor_uid=28455008

https://www.ncbi.nlm.nih.gov/pubmed/?term=Saad%20M%5BAuthor%5D&cauthor=true&cauthor_uid=28455008



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Hiccups Are a Rare Symptom of Supraventricular Tachycardia: Case Report Khandan et al

119

Case Report Hiccups Are a Rare Symptom of Supraventricular Tachycardia: Case Report Khandan et al

Hiccups Are a Rare Symptom of Supraventricular Tachycardia:

Case Report

Amir Hosein Khandan1, MD; Asghar Mohamadi*

2, MS

ABSTRACT

Paroxysmal supraventricular tachycardia (PSVT) is one of the most common arrhythmias, and it

occurs in the general population with a good prognosis. PSVT occurs in all age groups, with an

incidence rate of approximately 1–3 cases per 1000 persons. We describe a patient presenting

with PSVT and a complaint of hiccups. (Iranian Heart Journal 2020; 21(1): 119-121)

KEYWORDS: Paroxysmal supraventricular tachycardia, Hiccup

1 Lorestan University of Medical Sciences.Khorramabad, IR Iran.

2 Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, IR Iran.

*Corresponding Author: Asghar Mohamadi, MS; Lorestan University of Medical Sciences, Khorramabad, IR Iran. Email: [email protected] Tel: 09106042707


aroxysmal supraventricular

tachycardia (PSVT) is defined as a

sudden increase in heart rate that ends

suddenly. PSVT has different types of

electrophysiologic patterns such as atrial

tachycardia, atrioventricular (AV) nodal

reentry, and atrioventricular reentrant

tachycardia (AVRT). 1

The most common

symptom of this arrhythmia is palpitation

and other symptoms include shortness of

breath, chest discomfort, weakness and

fatigue, lightheadedness, dizziness, and

syncope. 2 We herein describe a 45-year-old

man with PSVT who presented to the

emergency department with a complaint of

hiccups.

Case Report

A 45-year-old man who had a history of

hypertension and cigarette smoking

presented to the emergency department with

a complaint of hiccups. On physical

examinations, the patient had blood pressure

of 120/80 mm Hg, heart rate of 160 bpm,

respiratory rate of 18, and body temperature

of 37 °C. Cardiac examinations were

normal. The patient did not mention a

history of heart disease and did not take any

medication. The reason for his referral to the

hospital was a hiccup of 2 hours’ duration.

He was immediately monitored, and an ECG

was taken. The ECG revealed a regular

narrow complex tachycardia (Fig. 1). Given

a retrograde P-wave just after the QRS, an

AVNRT rhythm was suggested as the first

differential diagnosis. However, other

diagnoses such as an orthodromic AVRT

rhythm could not be ruled out definitively

and a definitive diagnosis required

electrophysiology study. The patient refused

to undergo an electrophysiology study,

forcing the treating physician to interpret the

rhythm based on the surface ECG.

Adenosine (6 mg intravenously) was rapidly

P


https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahUKEwikvbDFyPvVAhXpJMAKHcdKA6QQFgguMAE&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FAtrioventricular_reentrant_tachycardia&usg=AFQjCNGvrCndqw1nZQw885mOHu4_6Y5F4A

https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahUKEwikvbDFyPvVAhXpJMAKHcdKA6QQFgguMAE&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FAtrioventricular_reentrant_tachycardia&usg=AFQjCNGvrCndqw1nZQw885mOHu4_6Y5F4A

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injected, after which the patient suffered

dyspnea. The dyspnea was resolved after 1

hour, and the arrhythmia was converted into

the sinus rhythm. Moreover, the hiccup

disappeared after the termination of the

tachyarrhythmia.

Figure 1. ECG recorded immediately after the presentation of the patient to the emergency department

Given the retrograde P-wave just after the QRS, an atrioventricular reentrant tachycardia rhythm was proposed as the first differential diagnosis.

DISCUSSION

PSVT has several symptoms that include

palpitations, shortness of breath, chest

discomfort, weakness and fatigue,

lightheadedness, dizziness, and syncope. 2

We herein reported a rare symptom of

arrhythmia that our patient suffered due to a

hiccup. The symptoms lasted for several

hours, thus the patient was forced to seek

treatment. A hiccup is an involuntary

contraction of the diaphragm, followed by

laryngeal closure. 3 Many disorders can

cause hiccups including stroke, tumors,

herpes infection, gastroesophageal reflux

disease, various drugs (eg, anti-

Parkinsonism drugs, anesthetic agents, and

steroids), and chemotherapies. 4 Suh et al

5

reported a case in which hiccups were

associated with bradycardia and suggested

that the Valsalva maneuver had enhanced

the parasympathetic tone and caused the

hiccup. Hiccups can also be a sign of more

serious problems in the heart. For example,

hiccups after cardiac pacemakers or

implantable cardioverter-defibrillator

placement are probably a sign of lead

perforation. 7 Hiccups can also be a sign of

the pathological activation of the arc reflex,

and some disorders in the heart such as

myocardial ischemia and the inflammation

of the pericardium can lead to hiccups. In a

case report, myocardial ischemia generated

hiccups, which were treated with coronary

angioplasty. 6 The existing literature is

devoid of an explanation about the

mechanism of hiccups secondary to PSVT;

nonetheless, a possible mechanism that may

be involved is myocardial ischemia that

occurs during tachyarrhythmias and induces

hiccups. Interestingly, in our patient,

although the hiccup increased the vagal tone,

https://en.wikipedia.org/wiki/Diaphragm_%28anatomy%29

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it could not terminate the PSVT and the

authors did not have a clear explanation for

this phenomenon.

The goal of this case report is to introduce a

sign of arrhythmia to emergency department

physicians and cardiologists in order that

they will be aware of this rare symptom of

arrhythmia and suspect PSVT in patients

who refer to the emergency department with

this complaint.

REFERENCES

1. Kadish A, Passman R. Mechanisms and

management of paroxysmal supraventricular

tachycardia. Cardiology in review.

1999;7(5):254-64.

2. Al-Zaiti SS, Magdic KS. Paroxysmal

Supraventricular Tachycardia. Critical Care

Nursing Clinics. 2016;28(3):309-16.

3. Krysiak W, Szabowski S, Stepien M,

Krzywkowska K, Krzywkowski A,

Marciniak P. Hiccups as a myocardial

ischemia symptom. Polskie Archiwum

Medycyny Wewn trznej. 2008;118(3):148.

4. Chang F-Y, Lu C-L. Hiccup: mystery,

nature and treatment. Journal of

neurogastroenterology and motility.

2012;18(2):123.

5. Suh WM, Krishnan SC. Violent hiccups: an

infrequent cause of bradyarrhythmias.

Western Journal of Emergency Medicine.

2009;10(3):176.

6. Saarel EV, Hinkle K, Etheridge SP. Serious

case of the hiccups. HeartRhythm Case

Reports. 2015;1(4):159.

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name and location of the institutional

affiliation or department (no more than 2),

and address, telephone number, fax number

and Email address for reprint requests at the

bottom of the page. If more than 1 institution

is named, indicate which authors are

affiliated with each.

Titles should be as short as possible

(fewer than 95 letters and spaces). Also

submit a short title of 40 characters to be

used as a running title.

Abstracts should be no longer than

250 words and should contain 4 sections in

the following order: Background, Methods,

Results, and Conclusions. Abstracts for case

reports and correspondences should not be

structured and must be shorter (50 to 75

words). Include keywords at the end of the

abstract.

Text should be organized as follows:

Introduction, Methods, Results, Discussion,

and Conclusion. Methods should include the

statistical analysis. Cite references,

illustrations, and tables in numeric order in

the text. Give all measurements and weights

in standard metric units. Credit suppliers of

drugs, equipment, and other brand-name

material mentioned in the article in

parentheses, giving company name and

location.

Acknowledgments All contributors

who do not meet the criteria for authorship

may be mentioned in the Acknowledgments

section. It should include persons who

provided technical help, writing assistance,

and departmental supervision who only

provided general support. Financial and

material support should also be

acknowledged.

Conflict of interest Authors must

acknowledge and declare any sources of

funding and potential conflicting interest,

such as receiving funds or fees by, or

holding stocks and shares in, an organization

that may profit or lose through the

publication of the paper. Declaring a

competing interest will not lead to the

automatic rejection of the paper.

Ethical guidelines must be

addressed in the Materials and Methods

section. (1) Please state that informed

consent was obtained from all human adult

participants and from the parents or legal

guardians of minors. Include the name of the

appropriate institutional review board that

approved the project. (2) Indicate in the text

that the maintenance and care of

experimental animals complies with

National Institutes of Health guidelines for

the humane use of laboratory animals, or

those of your institute or agency.

References should be identified by

using superscript numbers without changing

the font size (eg,1, 2, 3

). Do not cite personal

communications, manuscripts in preparation,

or unpublished data. Type the references

double spaced on a separate sheet and

number consecutively in the order in which

they are mentioned in the text. List all

authors if 6 or fewer; otherwise list the first

6 and add et al. Style and punctuation of

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references should conform to the Vancouver

style or the Index Medicus format as in the

examples below:

Journal articles:

1. Burt VL, Cutler JA, Higgins M, Horan

MJ, Labarthe D, Whelton P, et al. Trends in

the prevalence, awareness, treatment and

control of hypertension in the adult US

population. Hypertension 1995; 26: 60-69.

Chapters in books:

2. Ross DN, Martelli V, Wain WH:

Allograft and autograft valves used for

aortic valve replacement. In: Ionescu MI,

(ed.). Tissue Heart Valves. London:

Butterworth, 1979: pp. 319-29.

Tables should be typed double

spaced on separate sheets, each with a table

number and title above the table and

explanatory notes and legends below.

Tables should be self-explanatory and the

data should not be duplicated in the text or

figures. If tables provide repetitive

information, they will be deleted.

Legends to illustrations should be

typed double spaced on a separate sheet.

Numbers should correspond to the order in

which they appear in the text. Give the type

of stain and magnification power for

photomicrographs. Patients should not be

recognizable in illustrations unless written

consent is supplied.

Illustrations should be submitted digitally

(preferable), or in 3 sets of glossy prints.

High-quality laser artwork is also

acceptable, but photocopies are not. Write

the first author’s last name, figure number,

and an arrow indicating the top of the figure

on the back of each illustration in pencil.

All illustrations will be published in black

and white unless color prints are specifically

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The author must be prepared to pay a fee for

publication of color photographs.

Reprints: Reprints can be ordered at

an extra charge. Contact the Editorial Office

for details.

Electronic manuscripts

All authors are strongly encouraged to

submit their manuscripts via Email using

Microsoft Office Word (2003 or afterward)

in order to allow more rapid editing and

preparation for publication. The author

should retain copies of all files as backup.

Emails should bear the author’s name, short

title of the article, and operating system

used.

All manuscripts and correspondences

should be submitted to:

Hussein Tabatabaei, M.D.

Editor-in-Chief

Iranian Heart Association Journal

P. O. Box: 15745-1341

Tehran 19974 Iran

Tel: (009821) 22048174

Fax: (009821) 22048174

Email: [email protected]


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Forthcoming Meetings

The 38th Annual International Symposium: Clinical Update in Anesthesiology, Surgery and Perioperative Medicine Sunday, January 19, 2020 to Friday, January 24, 2020 St. Kitts Marriott Resort St. Kitts Saint Kitts and Nevis See map: Google Maps STS 56th Annual Meeting & Tech-Con 2020 Saturday, January 25, 2020 to Tuesday, January 28, 2020 New Orleans Ernest N. Morial Convention Center New Orleans, LA United States See map: Google Maps 30th Annual Meeting in Scandinavian Society for Research in Cardiothoracic Surgery (SSRCTS) Thursday, February 6, 2020 to Saturday, February 8, 2020 Bardøla Høyfjellshotell Geilo Norway See map: Google Maps IACTS2020 - 66th Annual Conference of Indian Association of Cardiovascular-Thoracic Surgery Thursday, February 6, 2020 to Sunday, February 9, 2020 Forum - GrandO7 Convention Center Ahmedabad, GJ India See map: Google Maps Indian Association of Cardiovascular Anaesthesia Conference 2020 Friday, February 7, 2020 to Sunday, February 9, 2020 Hotel Holiday Inn and Resort, GOA Goa, GA India See map: Google Maps

28th Congress of the Asian Society for Cardiovascular & Thoracic Surgeon Friday, February 7, 2020 to Monday, February 10, 2020 Shangri La Hotel, Chiang Mai Chiang Mai Thailand See map: Google Maps AATS Mechanical Support for the Heart and Lung Symposium Friday, February 14, 2020 to Saturday, February 15, 2020 Marriot Marquis Houston Houston, TX United States See map: Google Maps C3 Meeting 2020 - Consensus – Controversy – Compromise Sunday, February 16, 2020 to Tuesday, February 18, 2020 InterContinental Hotel Vienna Austria See map: Google Maps 6th Assiut VATS workshop Thursday, February 20, 2020 to Friday, February 21, 2020 Assiut university Heart Hospital , conference hall Assiut Egypt See map: Google Maps WSCTS RCS International TAVI Congress, The Aortic Valve Meeting Friday, February 28, 2020 to Sunday, March 1, 2020 Royal College of Surgeons of Edinburgh Edinburgh United Kingdom See map: Google Maps The Houston Aortic Symposium: Frontiers in Cardiovascular Diseases, the Thirteenth in the Series

https://www.ctsnet.org/events/38th-annual-international-symposium-clinical-update-anesthesiology-surgery-and-perioperative



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https://www.ctsnet.org/events/sts-56th-annual-meeting-tech-con-2020

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https://www.ctsnet.org/events/30th-annual-meeting-scandinavian-society-research-cardiothoracic-surgery-ssrcts



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https://www.ctsnet.org/events/iacts2020-66th-annual-conference-indian-association-cardiovascular-thoracic-surgery



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https://www.ctsnet.org/events/28th-congress-asian-society-cardiovascular-thoracic-surgeon

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http://maps.google.com/?q=%2C+Chiang+Mai%2C+%2C+%2C+th

https://www.ctsnet.org/events/aats-mechanical-support-heart-and-lung-symposium

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https://www.ctsnet.org/events/c3-meeting-2020-consensus-%E2%80%93-controversy-%E2%80%93-compromise

https://www.ctsnet.org/events/c3-meeting-2020-consensus-%E2%80%93-controversy-%E2%80%93-compromise

http://maps.google.com/?q=%2C+Vienna%2C+%2C+%2C+at

https://www.ctsnet.org/events/6th-assiut-vats-workshop

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https://www.ctsnet.org/events/wscts-rcs-international-tavi-congress-aortic-valve-meeting

https://www.ctsnet.org/events/wscts-rcs-international-tavi-congress-aortic-valve-meeting

http://maps.google.co.uk/?q=%2C+Edinburgh%2C+%2C+gb

https://www.ctsnet.org/events/houston-aortic-symposium-frontiers-cardiovascular-diseases-thirteenth-series



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Thursday, March 5, 2020 to Saturday, March 7, 2020 Westin Oaks Hotel Houston United States See map: Google Maps 4th Vienna-ESTS Laryngotracheal Course Thursday, March 5, 2020 to Saturday, March 7, 2020 Medical University of Vienna Vienna Austria See map: Google Maps 16th International Congress of Update in Cardiology and Cardiovascular Surgery Thursday, March 12, 2020 to Sunday, March 15, 2020 Royal Seginus Convention Center Antalya Turkey See map: Google Maps 2020 General Thoracic Surgical Club 33rd Annual Meeting Thursday, March 12, 2020 to Sunday, March 15, 2020 Hilton Tucson El Conquistador Golf & Tennis Resort Tucson, AZ United States See map: Google Maps ESTS School of Thoracic Surgery: Knowledge Track Course Monday, March 16, 2020 to Saturday, March 21, 2020 Lindner Hotel Prague Castle Prague Czech Republic See map: Google Maps 2020 Techno Practicum College Friday, March 20, 2020 to Sunday, March 22, 2020 InterContinental Sydney Sydney, NSW Australia See map: Google Maps

SCTS Annual Meeting & SCTS Ionescu University 2020 Sunday, March 22, 2020 to Tuesday, March 24, 2020 ICC Wales Newport United Kingdom See map: Google Maps 4th Structural Heart Disease Asia Pacific Symposium Thursday, April 2, 2020 to Saturday, April 4, 2020 Grand Millennium Hotel Auckland New Zealand See map: Google Maps The Fredric G. Levin Lung Cancer Symposium Thursday, April 2, 2020 to Friday, April 3, 2020 Sanders Beach-Corinne Jones Resource Center Pensacola, FL United States See map: Google Maps Toronto Anesthesia Symposium Saturday, April 4, 2020 to Sunday, April 5, 2020 MaRS Discovery District Toronto Canada See map: Google Maps 2nd ESTS-ERS Collaborative Course on Thoracic Oncology: Pleura, Mediastinum, Rare Tumours Monday, April 6, 2020 to Wednesday, April 8, 2020 Johnson & Johnson Institute Hamburg Germany See map: Google Maps MI Esophagectomy and Anastomosis Course Thursday, April 16, 2020 to Friday, April 17, 2020 Istanbul, Turkey Istanbul Turkey

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https://www.ctsnet.org/events/4th-vienna-ests-laryngotracheal-course

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https://www.ctsnet.org/events/16th-international-congress-update-cardiology-and-cardiovascular-surgery

https://www.ctsnet.org/events/16th-international-congress-update-cardiology-and-cardiovascular-surgery

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https://www.ctsnet.org/events/2020-general-thoracic-surgical-club-33rd-annual-meeting

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https://www.ctsnet.org/events/ests-school-thoracic-surgery-knowledge-track-course

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http://maps.google.cz/?q=%2C+Prague%2C+%2C+cz

https://www.ctsnet.org/events/2020-techno-practicum-college

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https://www.ctsnet.org/events/scts-annual-meeting-scts-ionescu-university-2020

https://www.ctsnet.org/events/scts-annual-meeting-scts-ionescu-university-2020

http://maps.google.co.uk/?q=%2C+Newport%2C+%2C+gb

https://www.ctsnet.org/events/4th-structural-heart-disease-asia-pacific-symposium

https://www.ctsnet.org/events/4th-structural-heart-disease-asia-pacific-symposium

http://maps.google.com/?q=%2C+Auckland%2C+%2C+%2C+nz

https://www.ctsnet.org/events/fredric-g-levin-lung-cancer-symposium

https://www.ctsnet.org/events/fredric-g-levin-lung-cancer-symposium

http://maps.google.com/?q=%2C+Pensacola%2C+FL%2C+%2C+us

https://www.ctsnet.org/events/toronto-anesthesia-symposium-2

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See map: Google Maps AATS Aortic Symposium Thursday, April 23, 2020 to Friday, April 24, 2020 New York Marriott Marquis New York United States See map: Google Maps AATS 100th Annual Meeting Saturday, April 25, 2020 to Tuesday, April 28, 2020 New York Hilton Midtown and Sheraton New York Times Square New York United States See map: Google Maps 10th Anniversary London Core Review Cardiothoracic Surgery Course Thursday, May 7, 2020 to Sunday, May 10, 2020 Royal College Of Physicians London United Kingdom See map: Google Maps 3rd International Conference Sublobar Resections for Lung Cancer Thursday, May 21, 2020 to Friday, May 22, 2020 Grand Nikko Tokyo Dabai Tokyo Dabai Japan See map: Google Maps 28th European Conference on General Thoracic Surgery Sunday, May 31, 2020 to Wednesday, June 3, 2020 World Forum, The Hague, The Netherlands The Hague Netherlands See map: Google Maps ASAIO 66th Annual Conference Wednesday, June 10, 2020 to Saturday, June 13, 2020 Chicago Hilton Chicago, IL United States

See map: Google Maps 7th ECC International Congress on Complications during Cardiovascular Interventions: prevention and management Wednesday, June 10, 2020 to Friday, June 12, 2020 InterContinental Hotel Düsseldorf Germany See map: Google Maps WTSA 46th Annual Meeting Wednesday, June 24, 2020 to Saturday, June 27, 2020 Vail Marriott Mountain Vail, CO United States See map: Google Maps 40th Annual Cardiothoracic Surgery Symposium (CREF 2020) Wednesday, September 2, 2020 to Sunday, September 6, 2020 Marriott Marquis San Diego Marina San Diego, CA United States See map: Google Maps AATS Surgical Treatment of Arrhythmias and Rhythm Disorders Friday, October 2, 2020 to Saturday, October 3, 2020 Westin Boston Waterfront Boston, MA United States See map: Google Maps AATS Clinical Trials Methods Course Thursday, October 22, 2020 to Saturday, October 24, 2020 JB Duke Hotel Durham, NC United States See map: Google Maps AATS International Thoracic Surgical Oncology Summit Friday, October 30, 2020 to Saturday, October 31, 2020 Sheraton Times Square New York City: New York New York City, NY

http://maps.google.com/?q=%2C+Istanbul%2C+%2C+%2C+tr

https://www.ctsnet.org/events/aats-aortic-symposium-0

http://maps.google.com/?q=%2C+New+York%2C+%2C+%2C+us

https://www.ctsnet.org/events/aats-100th-annual-meeting

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https://www.ctsnet.org/events/10th-anniversary-london-core-review-cardiothoracic-surgery-course

https://www.ctsnet.org/events/10th-anniversary-london-core-review-cardiothoracic-surgery-course

http://maps.google.co.uk/?q=%2C+London%2C+%2C+gb

https://www.ctsnet.org/events/3rd-international-conference-sublobar-resections-lung-cancer

https://www.ctsnet.org/events/3rd-international-conference-sublobar-resections-lung-cancer

http://maps.google.com/?q=%2C+Tokyo+Dabai%2C+%2C+%2C+jp

https://www.ctsnet.org/events/28th-european-conference-general-thoracic-surgery

https://www.ctsnet.org/events/28th-european-conference-general-thoracic-surgery

http://maps.google.nl/?q=%2C+The+Hague%2C+%2C+nl

https://www.ctsnet.org/events/asaio-66th-annual-conference

http://maps.google.com/?q=Chicago+Hilton%2C+Chicago%2C+IL%2C+%2C+us

https://www.ctsnet.org/events/7th-ecc-international-congress-complications-during-cardiovascular-interventions-prevention-0



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https://www.ctsnet.org/events/wtsa-46th-annual-meeting

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https://www.ctsnet.org/events/40th-annual-cardiothoracic-surgery-symposium-cref-2020

https://www.ctsnet.org/events/40th-annual-cardiothoracic-surgery-symposium-cref-2020

http://maps.google.com/?q=%2C+San+Diego%2C+CA%2C+%2C+us

https://www.ctsnet.org/events/aats-surgical-treatment-arrhythmias-and-rhythm-disorders

https://www.ctsnet.org/events/aats-surgical-treatment-arrhythmias-and-rhythm-disorders

http://maps.google.com/?q=%2C+Boston%2C+MA%2C+%2C+us

https://www.ctsnet.org/events/aats-clinical-trials-methods-course-2

http://maps.google.com/?q=%2C+Durham%2C+NC%2C+%2C+us

https://www.ctsnet.org/events/aats-international-thoracic-surgical-oncology-summit-0

https://www.ctsnet.org/events/aats-international-thoracic-surgical-oncology-summit-0

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United States See map: Google Maps ATCSA 2020 - Annual Congress of the Association of Thoracic and Cardiovascular Surgeons of Asia Thursday, November 5, 2020 to Sunday, November 8, 2020 Hilton Arcadia Phuket Thailand

See map: Google Maps The Aalst Hands-on Cadaveric Endoscopic Mitral Course Tuesday, November 17, 2020 to Friday, November 20, 2020 OLV Clinic Aalst, Belgium Aalst Belgium See map: Google Maps

http://maps.google.com/?q=%2C+New+York+City%2C+NY%2C+%2C+us

https://www.ctsnet.org/events/atcsa-2020-annual-congress-association-thoracic-and-cardiovascular-surgeons-asia



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http://maps.google.be/?q=%2C+Aalst%2C+%2C+be

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SUBSCRIPTION ORDER FORM

Please enter my subscription to Iranian Heart Journal for 500 000 Rials for one year

(Four quarterly issues) beginning (Year)

ADDRESS: Please type or print clearly:

Name:

Address:

Zip Code: City:

PAYMENT

Check enclosed Cheek or money order must be made to:

Iranian Heart Association

Account no: 6166/1, Mellat Bank, Rajaie Cardiovascular, Medical and Research Center Branch, Tehran,

Iran.

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_

SUBSCRIPTION ORDER FORM

Please enter my subscription to Iranian Heart Journal for $ 50 us. for one year

(Four quarterly issues) beginning (Year)

ADDRESS: Please type or print clearly:

Name:

Address:

Zip Code: City:

PAYMENT

Check enclosed Cheek or money order must be made to:


Account no: 116AC252899, Mellat Bank, Mirdamad Branch

Tehran, Iran, Branch code 6507/8

P.O.Box: 15745-1341

Bill me

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تهران :گيرنده مجلة قلب ايران

17537-1431صندوق پستي

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

_

To:


P.O.Box: 15745-1341

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