2013 asia-pacific cardiology symposium from hypertension ... · serono symposia international...

FINAL PROGRAMME AND ABSTRACT BOOK

2013 Asia-Pacific Cardiology SymposiumFrom hypertension to heart failure - Interruption of the cardiovascular continuumHanoi, Vietnam - 6-7 April 2013

General information

VenueThe symposium takes place at the:

INTERCONTINENTAL HANOI WESTLAKE1A Nghi TamTay Ho DistrictHanoi, Vietnam

LanguageThe official language of the symposium is English.

Scientific secretariatSerono Symposia International FoundationSalita di San Nicola da Tolentino, 1/b00187 Rome, Italy

Senior Project Manager: Dorina Monaco

Specialist Medical Advisor: Davide Mineo

Tel.: +39 (0)6 420 413 314Fax: +39 (0)6 420 413 677E-mail: [email protected]

Serono Symposia International Foundation is a Swiss Foundation with headquarters in 14, rue du Rhône, 1204 Geneva, Switzerland

Organizing secretariatConnex Asia Consulting37A Hong Kong Street Singapore 059676Congress Coordinator: Suzanna TehT +65 9 776 4243 - F +65 6 5333 239E-mail: [email protected]

1

2013 Asia-Pacific Cardiology SymposiumFrom hypertension to heart failure - Interruption of the cardiovascular continuum

Serono Symposia International Foundation symposium on:

2013 Asia-Pacific Cardiology SymposiumFrom hypertension to heart failure - Interruption of the cardiovascular continuumHanoi, Vietnam - 6-7 April 2013

Aims of the symposiumCardiovascular diseases, the continuum of events from exposure to risk factors to occurrence of pathologic conditions, continue toincrease in the Asia-Pacific region, along with the diffusion of a western life-style and its related metabolic disorders. As a result,hypertension, cardiac ischemic disease and heart failure, the world’s main cause of premature or sudden deaths and disabilitiesrepresent an increasing burden for its healthcare systems and professionals. A continuous upgrading of scientific knowledge andskills, derived from evidence-based medicine and approved guidelines, is necessary to manage this emergency at every stage of itsprogression, especially when using different therapeutic approaches for different conditions.

Serono Symposia International Foundation is proud to organize the 2013 Asia-Pacific Cardiology Symposium “From hypertensionto heart failure - Interruption of the cardiovascular continuum”.

This symposium aims to re-examine recent achievements in the management of hypertension, coronary cardiac disease and chronicheart failure, also discussing prevention strategies for their complications, such as cardiac arrhythmias and cerebrovascular events,and it will also provide participants with solutions for optimizing patient care in daily clinical practice.

Learning objectivesAfter attending this symposium, participants will receive updated knowledge on the management of hypertension, coronary arterydisease and chronic heart failure, and so they will be able to:• Utilize the international guidelines for hypertension treatment and heart failure management• Evaluate the impact of beta-blockers and the other anti-hypertensive agents on mortality and morbidity of hypertension, coronaryartery disease and chronic heart failure

• Appreciate the role of sympathetic hyperactivity in hypertension, cardiac ischemic disease and heart failure• Manage the current anti-thrombotic therapies for the primary and/or secondary prevention of cerebrocardiovascular events

Target audienceCardiologists, internists and all the other healthcare professionals managing hypertension, cardiac ischemic disease and heartfailure, including general practitioners (GPs).

AccreditationThe educational event «2013 Asia-Pacific Cardiology Symposium “From hypertension to heart failure - Interruption of thecardiovascular continuum” Hanoi, Vietnam on 6-7 April 2013» is accredited by the European Board for Accreditation in Cardiology(EBAC) for 9 (nine) hours of External CME credits.

Each participant should claim only those hours of credit that have actually been spent in the educational activity. EBAC worksaccording to the quality standards of the European Accreditation Council for Continuing Medical Education (EACCME®), which is aninstitution of the European Union of Medical Specialists (UEMS).

2

3

We value your opinion!

We are continually trying to develop and improve our educational initiative to provide you with cutting-edge learning activities.

During this symposium you will be asked to answer a real time survey and after this educational event you will be receivingan online survey to help us to better tailor our future educational initiatives.

We thank you for participating!

All Serono Symposia International Foundation programmes are organized solely to promote the exchange and dissemination of scientific and medical information. Noforms of promotional activities are permitted. This programme is made possible thanks to an educational grant received from Merck Pte.

Scientific organizerPham Gia KhaiVietnam Heart InstituteVietnam Heart Association Hanoi, Vietnam

Serono Symposia International Foundation designed this programme in partnership with the Vietnam National Heart Association.

4

List of speakers and chairmenPham Gia KhaiVietnam Heart InstituteVietnam Heart Association Hanoi, Vietnam

Pham Nguyen VinhCardiology DepartmentTam Duc Heart HospitalHo chi Minh City, Vietnam

Brian TomlinsonDepartment of Medicine and TherapeuticsThe Chinese University of Hong KongHong Kong, China

Omar S. AwwadDepartment of CardiologyAin Shams UniversityCairo, Egypt

Stefano TaddeiDepartment of Internal MedicineUniversity of PisaPisa, Italy

H.A.J. Struijker BoudierDepartment of PharmacologyMaastricht UniversityMaastricht, The Netherlands

Peter YanCardiology ClinicGleneagles Medical Centre SingaporeParkway Heart and Vascular CenterSingapore, Republic of Singapore

Eugenio B. ReyesUniversity of the Philippines College of MedicineInternal MedicineSection of CardiologyManila,The Philippines

Dang Van PhuocHo Chi Minh City University Medical CenterCardiology DepartmentHo Chi Minh City, Vietnam

Nguyen Lan VietVietnam Heart InstituteBachmai HospitalHanoi, Vietnam

Pham Manh HungVietnam National Heart InstituteHanoi, Vietnam

Ravi Kishore Amancharla GangaNarayana Hrudayalaya Institute of Cardiac SciencesBangalore, India

Ho Huynh Quang TriHeart Institute - Ho Chi Minh CityIntensive Care UnitHo Chi Minh City, Vietnam

Abdul Rashid Abdul RahmanCenter of Graduate StudiesResearch and CommercialisationCyberjaya University College of Medical SciencesCyberjaya, Selanger, Malaysia

Shirish M.S. HiremathCardiology DepartmentRuby Hall ClinicPune, India

C. Sreenivas GopalVijaya Heart FoundationDepartment of CardiologyChennai, India

Piyamitr SritaraDepartment of MedicineRamathiboi Hospital Mahidol UniversityBangkok, Thailand

5

Chair: H.A.J. Struijker Boudier (The Netherlands)

Real time survey

14.00 L6: High heart rate in hypertension and coronaryartery disease: is there clinical evidence for abenefit of heart rate reduction?Pham Gia Khai (Vietnam)

14.30 L7: Are beta-blockers ineffective in coronaryartery disease? Critical assessment of therecent longitudinal, observational study ofpatients in the REACH registryPeter Yan (Republic of Singapore)

15.00 L8: Long term use of aspirin for primary andsecondary prevention: evidence and guidelinesEugenio B. Reyes (The Philippines)

Real time survey

15.30 Coffee break

Real time survey

16.00 L9: Sympathetic hyperactivity: sharing ofpathophysiology for hypertension, CAD andCHF and their pharmacological approachDang Van Phuoc (Vietnam)

16.30 L10: Novel non-pharmacological approaches forsuppressing sympathetic activity: renaldenervation and baroflex stimulatorsPham Manh Hung (Vietnam)

17.00 Case studiesPeter Yan (Republic of Singapore)

Real time survey

17.30 End of the day

Scientific programme6-7 April 2013

6

Chair: Pham Gia Khai (Vietnam)

09.00 Introduction Pham Gia Khai (Vietnam)

Real time survey

09.15 L1: Tackling hypertension year 2012: effectiveblood pressure reduction according to currentguidelinesPham Nguyen Vinh (Vietnam)

09.45 L2: The cardiovascular continuum -cardioprotective interventions by β-blockade Brian Tomlinson (China)

10.15 L3: Beta Blockers are still considered the first lineof therapy in essential hypertension?Omar S. Awwad (Egypt)

Real time survey

Saturday - 6 April 2013

Improving cardiovascular risk reduction in the management of hypertensionSession I

10.45 Coffee break

Real time survey

11.15 L4: Renin-angiotensin-aldosterone system (RAAS)inhibitors for mortality reduction inhypertension: a recent meta-analysiscomparing ACEIs and ARBsStefano Taddei (Italy)

11.45 L5: BP control with fixed-dose combinationtherapy: where are we now? H.A.J. Struijker Boudier (The Netherlands)

12.15 Case studiesBrian Tomlinson (China)

Real time survey

12.45 Lunch

Discussions on CAD treatments just emerged and role of sympathetic overactivitySession II

7

Chair: Pham Gia Khai (Vietnam) and Ravi Kishore Amancharla Ganga (India)

Real time survey

08.30 L11: The coming of atrial fibrillation from hypertensionand CAD to CHF: placing beta- blockers in itsprevention and managementHo Huynh Quang Tri (Vietnam)

09.00 L12: Benefits of β-blockade across patient types inCHFAbdul Rashid Abdul Rahman (Malaysia)

09.30 Case studiesAbdul Rashid Abdul Rahman (Malaysia)

Real time survey

10.00 Coffee break

Real time survey

10.30 L13: Traditional and new anti- thrombotic therapy inatrial fibrillationShirish M.S. Hiremath (India)

11.00 L14: Update 2012 of the ESC heart failure guidelines:any new perspectives?C. Sreenivas Gopal (India)

11.30 L15: Diuretics in heart failure. Practical guidance forusePiyamitr Sritara (Thailand)

Real time survey and needs assessment

12.00 Closing remarksPham Gia Khai (Vietnam)

12.15 End of the symposium

Closing lunch

Sunday - 7 April 2013

Update and practical guidance for heart failure and atrial fibrillation managementSession III

Disclosure of faculty relationships

Serono Symposia International Foundation adheres to guidelines of the European Accreditation Council for Continuing MedicalEducation (EACCME) and all other professional organizations, as applicable, which state that programmes awarding continuingeducation credits must be balanced, independent, objective, and scientifically rigorous. Investigative and other uses for pharmaceuticalagents, medical devices, and other products (other than those uses indicated in approved product labeling/package insert for theproduct) may be presented in the programme (which may reflect clinical experience, the professional literature or other clinical sourcesknown to the presenter). We ask all presenters to provide participants with information about relationships with pharmaceutical ormedical equipment companies that may have relevance to their lectures. This policy is not intended to exclude faculty who haverelationships with such companies; it is only intended to inform participants of any potential conflicts so that participants may form theirown judgements, based on full disclosure of the facts. Further, all opinions and recommendations presented during the programmeand all programme-related materials neither imply an endorsement nor a recommendation on the part of Serono SymposiaInternational Foundation. All presentations represent solely the independent views of the presenters/authors.

The following faculty provided information regarding significant commercial relationships and/or discussions of investigational ornon-EMEA/FDA approved (off-label) uses of drugs:

Pham Gia Khai Declared no potential conflict of interest.

Pham Nguyen Vinh Declared receipts of honoraria and consultation fees from: MSD, Astra-Zeneca, Servier, Abbott,Sanofi Aventis. Declared to be member of company advisory board, board of director, or othersimilar groups of: Astra-Zeneca. Declared to be stakeholder of Tam Duc Heart Hospital.

Brian Tomlinson Declared declared receipts of grants and contracts from: Bristol-Myers Squibb, Merck Serono,GlaxoSmithKline, Merck Sharp and Dohme, Novartis. Declared receipts of honoraria andconsultation fees from: Amgen, Genzyme, Jannsen, Merck Serono. Declared to be member ofcompany advisory board, board of directors or other similar groups of: Amgen, Genzyme,Jannsen, Merck Serono. Declared his participation in company sponsored speaker’s bureau of:Boehringer Ingelheim, Merck Serono, Merck Sharp and Dohme, Ranbaxy.

Omar S. Awwad Declared no potential conflict of interest.

Stefano Taddei Declared declared receipts of grants and contracts from: Boehringer Ingelheim, Servier,Novartis, Menarini. Declared his participation in company sponsored speaker’s bureau of:Servier, Pfizer, Recordati International, Novartis.

H.A.J. Struijker Boudier Declared receipts of grants and contracts form Servier. Declared receipts of honoraria andconsultation fees from: Servier, Merck Serono, Durect. Declared to be member of companyadvisory board, board of director, or other similar groups of: Merck Serono, Serono SymposiaInternational Foundation, Durect.

Peter Yan Declared no potential conflict of interest.

Eugenio B. Reyes Declared declared receipts of grant and contracts from Merck Serono. Declared receipt ofhonoraria from E. Merck, Merck Sharpe and Dohme, Astra-Zeneca, Novartis, Servier. Declared to be member of a company advisory board: Merck Serono and Novartis.

Dang Van Phuoc Declared no potential conflict of interest.

Nguyen Lan Viet Declared receipts of honoraria or consultation fees from: Astra-Zeneca, Servier, MSD.

Pham Manh Hung Declared receipts of honoraria or consultation fees from: Astra-Zeneca, Servier, MSD.

Ravi Kishore Amancharla Ganga Declared no potential conflict of interest.

Ho Huynh Quang Tri Declared receipts of honoraria or consultation fees from: Novartis, Boehringer Ingelheim,Merck Serono, Astra-Zeneca.

Abdul Rashid Abdul Rahman Declared receipts research Grant from Merck Serono. Declared receipt of honoraria orconsultation fees: from Merck Serono and Bayer. Declared participation in a companysponsored speaker’s bureau: MercK Serono, Servier, Sanofi Aventis, Bayer, MSD. Declared thathis presentation include discussion of any off-labeled or otherwise non-approved uses of anyproduct.

8

Shirish M.S. Hiremath Declared no potential conflict of interest.

Piyamitr Sritara Declared receipt of honoraria or consultation fees from: Astra Zeneca, Pfizer, Sanofi, MSD,Novartis, Takeda, Daiichi Sankyo, Berlinger INgelheim, Servier, Otsuka, Bayer, Sandoz,Medtronic. He declared his participation in: Astra Zeneca, Pfizer, Sanofi, MSD; novartis, Takeda,Daiichi Sankyo, Berlinger Ingelheim, Servier, Otsuka, Bayer, Sandoz, Medtronic sponsoredspeaker's bureau.

The following faculty have provided no information regarding significant relationship with commercial supporters and/or discussionof investigational or non-EMEA/FDA approved (off-label) uses of drugs as of 22 March 2013.

C. Sreenivas Gopal

9

Abstracts

L1 - Tackling hypertension year 2012: effective blood pressurereduction according to current guidelines

Systemic arterial hypertension (HTN) gets high prevalence in developed countries and also in developing countries. Up to 2025, thepredicted prevalence of hypertensive patients will be over 500 millions people in only China and India alone.

Up to now, there are many guidelines for management of HTN: JNC VII (2003), ESC-ESH 2007 and update 2009, NICE guidelines inhypertension of 2011, ACC/AHA guidelines for management of hypertension in the elderly 2011, and Canadian HypertensionEducation Programme recommendation (CHEP) 2012, 2013.

Some important points for management of HTN from these guidelines are:

Out of office blood pressure measurements are important in both diagnosis and management of hypertension.

For patients with nondiabetic chronic kidney disease, target blood pressure should be < 140/90 mmHg.

Lifestyle changes are a critical component of hypertension management and prevention.

The management of hypertension is all about global cardiovascular risk management and vascular protection.

Single pill combination-based treatment improves blood pressure control rates and treatment adherence.

The most important step in prescription of antihypertensive therapy is achieving patient “buy-in”.

According to NICE 2011 guidelines of hypertension management (UK), the first step drug is only A (ACE inhibitors or ARBs) or C(Calcium antagonists); only in step 4 can the, drug combination may be A + C + D and beta-blockers or alpha-blockers.

The ACC/AHA 2011 guidelines for management of hypertension in the elderly suggests that favors target blood pressure for thoseaged ≥ 80 years old can be 140 or 145 mmHg if tolerated.

Beta-blockers are still the first drug in non-complicated hypertension according to JNC VII, ESC/ESH 2007, 2009 and CanadianHypertension Education Programme (CHEP) 2012, 2013. Beta-blocker may be first choice in HTN patients with concomitant medicalillness: chronic coronary artery disease, post acute myocardial infarction, chronic heart failure, aortic dissection, tachyarrhythmia,glaucoma, and also for pregnant women.

11

Pham Nguyen VinhCardiology Department, Tam Duc Heart Hospital, Ho chi Minh City, Vietnam

L2 - The cardiovascular continuum - cardioprotectiveinterventions by β-blockade

Beta-blockers were originally developed for the treatment of angina pectoris and soon after their introduction it was demonstratedthat they were also effective in the treatment of hypertension. Some recent hypertension guidelines no longer recommend beta-blockers as first-line therapy for hypertension, but these guidelines still endorse beta-blockers as appropriate initial therapy inpatients with increased sympathetic activity. Increased resting heart rate may be one manifestation of excessive sympathetic driveand a high resting heart rate has been associated with increased cardiovascular and all cause mortality in patients with hypertensionas well as the general population. Early studies of beta-blockade in acute myocardial infarction showed significant reductions inmortality and morbidity with oral or intravenous administration of these drugs, particularly those without intrinsic sympathomimeticactivity. With the more recent introduction of new antiplatelet and thrombolytic medications and interventional procedures, beta-blockade still has an essential role in reducing the risk of reinfarction and ventricular fibrillation, but it has been recognized that itis important to start beta-blocker therapy when the haemodynamic condition has stabilised.

Current guidelines from Europe and the United States recommend the use of beta-blockers in chronic stable coronary artery diseaseand they have an important role in secondary prevention for patients with coronary and other atherosclerotic vascular diseases.Likewise, evidence has accrued that certain beta-blockers have an essential role in the treatment of patients with chronic systolicheart failure and their use is recommended by current guidelines. The benefits of beta-blockers in these conditions appear to bemainly due to inhibition of beta1-receptors and in coronary artery disease the drugs which are more beta1-selective arerecommended including atenolol, bisoprolol and metoprolol and in heart failure, bisoprolol and specifically metoprolol succinate andthe vasodilating beta-blockers carvedilol and nebivolol are also endorsed.

As reduction of heart rate is an important goal of therapy in coronary artery disease, heart failure and probably throughout thecardiovascular continuum, choosing a beta-blocker which produces consistent and effective reduction of heart rate throughout 24hours is an important consideration. There are few direct comparisons of different beta-blockers in this respect but the recent CIBIS-ELD trial which compared bisoprolol and carvedilol in elderly heart failure patients with reduced or preserved left ventricular ejectionfraction showed similar overall tolerability but the use of bisoprolol resulted in greater heart rate reduction with more dose limitingbradycardia, whereas carvedilol was associated with more adverse pulmonary events. In the pharmacogenetic substudy of this trial,patients with atrial fibrillation who had the Arg389Arg homozygous form of the beta1-adrenoceptor Arg389Gly polymorphism, whichis more responsive to beta1-agonists and antagonists, showed insufficient reduction in heart rate with carvedilol but not withbisoprolol. This finding may herald the exciting possibility that pharmacogenetic testing may one day help to identify the mosteffective form of therapy for individual patients with beta-blockers and with other pharmacotherapy. However, for the time beingbeta-blockers remain a cornerstone of treatment throughout the cardiovascular continuum.

12

Brian TomlinsonDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China

L3 - Beta Blockers are still considered the first line of therapy inessential hypertension?

The Cardiovascular Continuum starts with risk factors like hypertension and diabetes, reaching Myocardial Infarction, Chronic HeartFailure and Death.

The β-blockers are effective in each step of the Cardiovascular Continuum.

β-blockers have been widely prescribed to treat hypertension over years and their benefits in reducing Cardiovascular events inpatients with pre existing heart disease are clear, while their benefits in patients with uncomplicated hypertension are less clear.

β-blockers have many clinical indications beside their action as antihypertensives like treatment of ischemia, heart failure andarrhythmia.

There are many Pharmacological Characteristics of β-blockers, which produce different clinical effects depending on selectivity,solubility and vasodilator ability.

Many studies like the MRC, MAPHY and HEP proved that β-blockers are effective in Primary Protection. Newer studies like LIFE &ASCOT started to doubt this fact. While there is no doubt about the role of β-blockers in Secondary Protection as proved by BHATand UKPDS.

The Heart Rate slowing effect of the β-blockers has its role in reducing Cardiovascular Mortality and Sudden Cardiac Death.

Recent studies disapproved the concept that β-blockers are contraindicated in patients with Peripheral Arterial Disease, because β-blockers are not the same.

The European Hypertension Guidelines stated that all major antihypertensive groups can be considered suitable for the initiation andmaintenance of antihypertensive treatment.

To conclude, β-blockers are the Cornerstone in the management of many Cardiovascular Diseases.

The most recent guidelines recommended β-blockers as first line option in the management of hypertension.

Not all β-blockers are the same, newer β-blockers avoid points of weaknesses of older β-blockers like effect on Central AorticPressure and Glucose Tolerance.

13

Omar S. AwwadDepartment of Cardiology, Ain Shams University, Cairo, Egypt

L4 - Renin-angiotensin-aldosterone system for mortalityreduction in hypertension: a recent meta-analysis comparingACE-Inhibitors and Angiotensin Receptor Blockers

Blockade of the renin-angiotensin-aldosterone system (RAAS) by ACE-inhibitors (ACE-Is) or Angiotensin Receptors Blockers (ARBs)is considered a corner stone in cardiovascular medicine for the treatment not only of essential hypertension but also otherpathological conditions, including post myocardial infarction, heart failure or kidney disease.

A common opinion exists that ACE-Is and ARBs might be considered equivalent in terms of clinical efficacy, despite availablescientific evidence which does not support this statement.

First of all, ACE-Is and ARBs have a different mechanism of action. The inhibition of bradykinin degradation exerted by ACE-Is isoften considered an “adjunctive” mechanism with a limited clinical significance. This view should be partially corrected, since formost ACE-Is the ability to block the ACE site responsible for bradykinin degradation is almost the same as the activity on the siteresponsible for the conversion of angiotensin I into angiotensin II. If we consider the potential effect of bradykinin on cardiovascularsystem it is conceivable that this pathway might be at least partially responsible of many effects of ACE-Is usually tributed to RAASblockade. In contrast, ARBs greatly increase Angiotensin II plasma concentrations and no clear evidence demonstrates whether thisphenomen has to be considered positive or negative.

In line with this difference in the mechanism of action, consolidated evidence demonstrates that only ACE-Is can prevent coronaryartery disease while the results of different meta-analysis indicate that ARBs show no protective activity .

However, a definite demonstration of the superiority of ACE-Is in respect to ARBs derives from two recently published meta-analysis.

Van Vark et al. (Eur Heart J 2012;33:2088-97) analyzed findings obtained in clinical studies performed in hypertensive patients andevaluated whether ACE-I or ARBs can reduce all-cause mortality, the most important hard end-point in clinical trials. The analysishas considered only recently performed studies (from 2.000 to 2011), including a very large number of patients (n=158.998). Theresults demonstrate that ACE-I are able to significantly reduce all-cause mortality while ARBs are totally non effective.

Another important point derives from the paper of Savarese et al. (JACC 2013;61:131-142). The aim of this meta-analysis was toassess the effects of ACE-Is and ARBs as compared to placebo (standard treatment not including a RAAS blocker) on composite ofCV death, myocardial infarction (MI) and stroke, and on all-cause death, new onset HF and new onset diabetes mellitus (DM) in108.212 high-risk patients without HF.

The results demonstrate that ACE-Is and ARBs reduce the risk of the composite outcome of CV death, MI and stroke. However onlyACE-Is, but not ARBs, reduce the risk of all-cause death, new onset HF and new onset DM. Thus, this meta-analysis confirms asuperiority of ACE-Is as compared to ARBs.

In conclusion, the present results provide crucial information for choosing the best treatment in patients with hypertension or highcardiovascular risk and suggest the need to continue to explore mechanisms of action and clinical effectiveness of drug classeswhich, although introduced many years ago, still have much to demonstrate.

14

Stefano TaddeiDepartment of Internal Medicine, University of Pisa, Pisa, Italy

References:1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction

6 1206-1212. 2 - Filicori M, Cognigni GE, Pocognoli P et al. 2003 Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and

Metabolism 14, 267-273.

L5 - BP control with fixed-dose combination therapy: where arewe now?

Hypertension is the primary cause of premature death on a world-wide scale. Over 1 billion people have hypertension with an 80%increase in hypertension in economically developing regions. The level of protection against cardiovascular diseases is related to thedegree of blood pressure reduction. However, only about one quarter of treated patients achieve and maintain internationallyrecognized targets of normal blood pressure. Major causes of inadequate blood pressure control include:1. poor patient compliance to therapy; 2. improper diagnosis of hypertension; 3. physician inertia to treat hypertension.

In recent years there has been an increasing awareness that combination therapy can give major improvement in treatment ofhypertension. More than 75% of patients require multiple therapies to achieve target. Combination therapy improves the degree ofblood pressure control, but it also enhances patient compliance and reduces the number of side-effects. Combination therapy ismore effective than increasing the dose of monotherapy of each major class of antihypertensives. Thus, all major hypertensionguidelines recommend that for the vast majority of hypertensive patients, effective blood pressure control can only be achieved bycombinations of at least two antihypertensive drugs.

Several different combinations of antihypertensives are effective in the treatment of hypertension. Fixed-dose combinations give ahigher degree of compliance and a better degree of blood pressure control than free combinations. Criteria for an optimal fixed-dosecombination include that:1. the drugs should act via different and complimentary mechanisms; 2. the blood pressure decreasing effect of the combination should be greater than that of the components alone;3. the incidence of side-effects should be reduced or at least not increased.

15

H.A.J. Struijker BoudierDepartment of Pharmacology, Maastricht University, Maastricht, The Netherlands




L6 - High heart rate in cardiovascular diseases: is there clinicalevidence for a benefit of heart rate reduction?

Increased heart rate is directly harmful to for the heart: it causes decreased diastolic duration, decreased perfusion of coronaryarteries, hence, decreased oxygen supply, meanwhile: Increased heart rate develops increased cardiac work leading to increasedOxygen needs. All this contribute to the imbalance of Oxygen supply and Oxygen consumption.

Heart rate is involved in the whole Cardiovascular Continuum: Risk factors such as: Dyslipidemia, Hypertension, Diabetes, Smoking,Obesity, are closely linked to Atherosclerosis of coronary arteries, their narrowing due to atherosclerotic plaques that induce angina.Later on, coronary thrombosis can lead to myocardial infarction, structural changes of the myocardium as seen in remodeling,frequent episodes of cardiac arrhythmias, and finally, ventricular dilation in end-stage heart disease: heart failure, and death.

Several studies have shown the harmful effect of increased heart rate in all-cause mortality for both sexes, and in CVD:Hypertension, ischemic heart disease, that may trigger ischemia in stable angina, and predict the outcome of ACS, of heart failure.Therefore, reduction of heart rate is consistent with prevention of cardiac ischemia and improvement of CV prognosis: Heart ratereduction is an important therapeutic goal in CVD.

16

Pham Gia KhaiVietnam Heart Institute, Vietnam Heart Association, Hanoi, Vietnam

L7 - Are beta-blockers ineffective in coronary artery disease?Critical assessment of the recent longitudinal, observationalstudy of patients in the REACH registry

The benefit of long-term treatment with beta-blockers in coronary artery disease (CAD) (especially after post-myocardial infarction)is well-established and has remain the standard of care based on trials predating the advent of modern perfusion therapies(thrombolysis and acute MI-PCI) as well as modern pharmacotherapies for CHD (statins, anti-platelet therapies, ACE inhibitors, etc)and modern heart failure therapy. The mechanisms for this are well established. Beta-blockers reduce myocardial oxygenconsumption by reducing heart rate, myocardial contractility and afterload, with attenuation of cardiovascular remodelling anddecreasing LV wall tension. In addition the reduction of heart rate also shift the cardiac cycle, permitting more diastolic time andgreater coronary perfusion thereby improving myocardial oxygen supply. However the benefits of beta-blockers in chronic stable CADpatients in the post era of modern reperfusion therapies as well as modern pharmacological therapies have challenged the benefitsof beta-blockers especially in those with no history of MI, those with remote history of MI as well as patients without CAD but withsignificant coronary risk factors.

A recent analysis of the REACH Registry data by Bangalore suggest that there was no significant benefit of beta-blockers use in thereduction of CV events including CV deaths and non-fatal myocardial infarction in patients with known CAD without myocardialinfarction or remote history of MI and in patients with CAD risk factors only. In fact beta-blockers may be associated with a worseningoutcome in some patients. However in the subgroup of CAD patients with a recent MI (less than 1 year) beta-blocker used wasassociated with a lower incidence of secondary outcome which includes the primary composite endpoint of cardiovascular deaths,non-fatal MI and non-fatal stroke plus hospitalisation for atherothrombotic event or revascularisation procedure.

In addition the use of beta-blockers in acute coronary syndrome – unstable angina/non-STEMI and STEMI is now well-establishedin several international guidelines :

(1) 2013 ACCF/AHA Guideline for management of ST elevation Myocardial Infarction

(2) 2011 ACCF/AHA Focus update incorporated into the ACC/AHA 2007 guidelines for management of patients with unstableangina/non-ST elevation myocardial infarction and

(3) 2012 ESC Guidelines of the management of acute myocardial infarction in patients presenting with ST elevation.

The guidelines specified beta-blockers usage in the early acute phase of AMI versus delayed post-MI, the route of administration i.e.intravenous versus oral and also the different types of beta-blockers, i.e. beta- blockers with or without ISA, selective beta-adrenergic blockers, mixed beta/alpha adrenergic blockers and those beta-blockers with vasodilating properties.

Finally the 2012 AHA/ACCF Secondary Prevention and risk reduction therapy for patients with coronary and other atheroscleroticvascular disease: 2011 update has recommended the following:

1) Class I (level A) evidence that beta-blockers should be used in all patients with left ventricular systolic dysfunction (ejectionfraction ≤ 40%) with heart failure or prior myocardial infarction unless contraindicated. It also clearly specifies that the use ofbeta-blockers should be limited to carvedilol, metoprolol succinate or bisoprolol which has been shown to reduce mortality.

2) Class I (level B) evidence was also recommended for the use of beta-blockers in all patients with normal left ventricular functionwho have had a myocardial infarction or acute coronary syndrome, to be started as soon as possible and continued for 3 years.

3) Class IIb (level C) evidence for use of beta-blockers as a chronic therapy for all other patients with coronary or other vasculardisease - clearly agreeing with the recent REACH registry analysis on the use of beta blockers in stable CAD outpatients with andwithout CAD.

The 2012 AACF/AHA/ACP/AATS/PCNA/SCAI/STS guidelines for the diagnosis and management of patients with stable ischemicheart disease has added a class I (Level B) evidence of beta-blockers use as an initial therapy for relief of symptoms in patients withstable ischemic heart disease.

Therefore are beta-blockers ineffective in CAD? The answer is clearly NO. There are subsets of CAD patients that will benefit fromthe use of beta-blockers. Physicians need to know and understand - whom, when, and how to use beta-blockers.

17

Peter YanGleneagles and Mt Elizabeth Hospital, Singapore Parkway Heart & Vascular Centre @ Mt E Novena Hospital, Singapore

L8 - Long term use of aspirin for primary and secondaryprevention: evidence and guidelines

Platelets are cell fragments that have the central role in primary hemostasis and repair. Their average lifespan is about 5-9 days.Abnormalities in their agonists, receptors and effectors can lead to their uncontrolled activation and aggregation, and promotethrombus formation. They participate in forming and extending atherosclerosis.

Aspirin, a COX-1 inhibitor, irreversibly inhibit platelet function by blocking thromboxane A2 formation and has been the cornerstoneof CVD prevention. Its use has been documented since the 5th century BC as an extract, in 1763 as a tincture, in 1828-1899 as apowder and in the 1900 as tablet for pain and fever. In 1982, it was introduced as an antiplatelet agent and has been recommendedin the guidelines in 1989 to be used in patients with CHD and with risk factors for CHD to prevent MI.

Current evidence of aspirin on the primary prevention of cardiovascular events comes from 9 randomized controlled trials involvingmore than 100,000 patients without prior CHD or stroke with duration of exposures ranging from 43 to 120 months. The results ofthe different trials showed a significant reduction in the number of non-fatal MI. The number of vascular events was also reduced,a combination of stroke and MI. But death was not reduced. The incidence of death was very small to show significant difference andit doesn’t mean that because an intervention did not reduce mortality, it is useless. Since these trials are dealing with low riskindividuals, it is prudent to look into total CV events. The absolute increase in GI bleeding and hemorrhagic stroke however, weresignificantly higher statistically but may not be clinically significant.

The evidence of aspirin for the secondary prevention of CV events among patients who had a stroke, TIA or MI comes from 16randomized controlled studies which involved 17,000 patients with cumulative exposure of 43,000 person years. Aspirin reduced therisk of major coronary event by 20% (absolute 0.6%), stroke by 19% with significant increase in hemorrhagic stroke and major extra-cranial bleeding.

Since aspirin therapy is not without harm, it is imperative that we should be able to weigh the benefit/risk ratio before initiatingaspirin for individual patients. Guidelines were created to address these issues. The ESC and ACC recommended using aspirin forprimary prevention of MI/stroke among high risk individuals (>2% risk). For lower risk patients, the benefit/risk ratio becomes 1. Forthe secondary prevention of MI/stroke, guidelines recommend aspirin to be the based antiplatelet therapy for patients with chronicCAD, previous stroke or TIA, PAD, in all acute coronary syndrome patients as first antiplatelet together with other antiplatelet agentswhether the patient has been considered for revascularization procedure or pure medical therapy and for elective PCI patients.

18

Eugenio B. ReyesUniversity of the Philippines, College of Medicine, Internal Medicine, Section of Cardiology, Manila,The Philippines

L9 - Sympathetic hyperactivity: sharing of pathophysiology forhypertension, CAD and CHF and their pharmacologicalapproach

Many different hormone and neurohormonal systems are involved in maintaining normal cardiovascular homeostasis, including: (1)Sympathetic nervous system (SNS), (2) Renin - Angiotensin - Aldosterone system (RASS) and (3) Vasopressin.

Sympathetic hyperactivity produces a lot of consequences such as vascocontriction, tachycardia, cardiac electrical instability, cardiacremodelling, large artery stiffening and remodelling, increased RASS, decreased renal blood flow, also Insulin resistance,dyslipidaemia and increased coagulation. There are the interactions between the Sympathic Nervous System (SNS) and the RAAS.High levels of Plasma Renin Activity (PRA) have been linked to metabolic imbalances such as hyperlipidemia and hyperinsulinemia,both of which are a risk factor for CVD. When sympathetic activity is blocked, it has been shown to inhibit RASS activity. Theheightened secretion of Norepinephine (NE) by the SNS has also shown a link to CVD. A large scale clinical trial demonstrated thatNE levels of > 900 pg/ml were correlated with shortened life expectancy in patients with hypertension or severe congestive heartfailure (CHF). In hypertension, sympathetic outflow is increased to the heart and the peripheral circulation, which causes andincreases heart rate and contractility. In addition, vasocontriction occurs which increases the peripheral vascular resistance. Strokevolume is subsequently increased which inturn increases mean arterial pressure. Heart rate is a major determinant of ischemia andan independent risk factor for cardiovascular prognosis. The association between heart rate and overall and cardiovascular mortalityhold true. Increased heart rate is directly harmful for the heart. Heart rate reduction is beneficial for patients with stable angina. Byreducing heart rate, the oxygen consumption is decrease and also oxygen supply increased. Because the sympathetic nervoussystem plays a key role for the development of hypertension, especially in younger patients, beta blockers have an important part toplay. However there is the controversy about the using of Beta-Blockers as first line therapy in hypertension (NICE UK guidelines2006), Beta blocker is one of 5 main classes of BP-lowering drugs, which were similarly effective in reducing BP and preventing CHDevents and strokes. Beta blockers were shown to exert effects beyond BP lowering secondary prevention of CAD and protectiveeffects when administered after myocardial infarction. Sympathetic activation is dangerous in CAD. It can lead to increased heartrate, increased contractility, increased peripheral resistance, further ischemia, increased arrhythmias and sudden death. Longterm sympathetic activation can include induced RASS activation, cytokine activation, electrolyte abnormalities, myocyteabnormalities, vasoconstriction, progressive remodeling and heart failure. Therefore, Beta Blockers have a particular role in thespectrum of ischemic heart disease: (1) Stable Angina Pectoris and (2) Acute Coronary Syndromes.

Chronic Heart Failure (CHF) is associated with neurohumoral activation and also with alterations in autonomic control. Thesecompensatory neurohumoral mechanisms offer valuable support for the heart under normal physiological circumstances. However,they also play a fundamental role in development and progress of CHF. The neurohumoral response includes sympathetic systemactivation and RASS activation. The historical time courses of the landmark ACE inhibitor trials and Beta-Blocker trials show that,ACE inhibitors were shown to be effective in CHF before the efficacy of Beta-Blockers was proven. The effect on mortality in threetrials (MERIT-HF with Metoprolol, CIBIS II with Bisoprolol and COPENICUS with carvedilol) was very similar with a reduction in totalmortality of 34% and 35%. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: Pharmacologicaltreatment indicated in potentially all patients with symptomatic (NYHA functional class II- IV) systolic heart failure recommend thatan ACE inhibitor in addition to a Beta-Blocker (Class I, level A) or Beta Blocker in addition to an ACE inhibiter (Class I, level A) for allpatients with an EF <40% to reduce the risk of HF hospitalization and the risk of premature death.

19

Dang Van PhuocHo Chi Minh City University Medical Center, Cardiology Department, Ho Chi Minh City, Vietnam

L10 - Novel non-pharmacological approaches for suppressingsympathetic activity: renal denervation and baroflexstimulators

Resistant hypertension is defined as blood pressure that remains above goal in spite of the concurrent use of three antihypertensiveagents of different classes, including one diuretic, prescribed at optimal dose. Estimates suggest 20% to 30% of patients with highblood pressure have resistant hypertension. Resistant hypertension (RH) is a powerful risk factor for cardiovascular morbidity andmortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering agreat area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS) activity is present in all these underlyingconditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical andexperimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines,endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, andbaroreceptors dysregulation... The further investigation and understanding of the mechanisms leading to SNS activation could revealnovel therapeutic targets and expand our treatment options in the challenging management of RH.

Managing refractory hypertension involves addressing the issues identified in the initial assessment, intensifying dietary sodiumrestriction and diuretic therapy, considering sympathetic nervous system activation and the need to add appropriate drugs, usingmineralocorticoid anta¬gonists, investigating for secondary causes of hypertension, and considering the use of newer/investigationaldrugs and devices if necessary.

Transcatheter renal sympathetic denervation (RDN) and the carotid baroreflex stimulation are the most promissing methods of novelnon-pharmacological appoaches for the treatment of RH. Current results from the use of renal denervation suggest stable efficiencyof the method, the results becoming significant 6 months after the procedure is applied and sustained for two years in the follow-up. As much as 90% of the treated patients respond to the procedure. The transcatheter renal denervation is associated with only2.61% of procedural complications. The baroreflex carotid stimulation, too, is known to produce a stable effect on blood pressure:the effect become obvious at 12 months in 88% of the treated subjects. The neurologic complications associated with the procedureare reported to occur in 4.4% of cases.

Non-pharmacological methods for suppressing sympathetic activity: renal denervation and baroflex stimulators in the treatment ofresistant hypertension show great promise despite some open questions concerning their long term effects and procedural safety.

20

Nguyen Lan Viet and Pham Manh HungVietnam National Heart Institute, Hanoi, Vietnam

L11 - The coming of atrial fibrillation from hypertension and CADto CHF: placing beta-blockers in its prevention andmanagement

Hypertension, CAD, and CHF represent different stages of the cardiovascular continuum. Epidemiological data showed that atrialfibrillation (AF) may occur in all of these three conditions. In the Framingham Heart Study, AF along with hypertension, CAD, andCHF were risk factors for stroke (Wolf 1991). According to the CHA2DS2-VASc score, hypertension, CHF, and prior myocardialinfarction are all contributors to the risk of stroke/systemic thromboembolism in patients with nonvalvular AF.

Hypertension is the most prevalent, independent, and modifiable risk factor for AF. The incidence of AF among hypertensive patientsis approximately 94 of 1,000 patient-years (Ciaroni 2000). Antihypertensive therapy, especially with blockers of the renin-angiotensin-aldosterone system, can prevent the development of AF (Pedersen 1999, Madrid 2002). A study based on the UK General PracticeResearch Database showed that beta-blockers could also reduce the risk for incident AF in hypertensive patients (Schaer 2010).According to the 2007 ESH/ESC guidelines for the management of arterial hypertension, tachyarrhythmias (including AF) wereamong the conditions favouring the use of beta-blockers as antihypertensive drugs.

In a contemporary study in patients with acute ST elevation myocardial infarction, the incidence of new-onset AF duringhospitalization was 6,3% (Lopes 2009). New-onset AF was significantly associated with shock, CHF, stroke, and 90-day mortality.Beta-blockers are indicated for acute rate control if there are no clinical signs of acute HF.

AF is common in patients with CHF, with a prevalence ranging from 10% in patients with NYHA class I to 50% in patients with NYHAclass IV (Morady & Zipes. Braunwald’s Heart Disease, 9th edition, 2012). In patients with structural heart disease and preexistingleft ventricular dysfunction, AF may be responsible for worsening of CHF. The most appropriate rate-control drugs in patients withCHF are digitalis and beta-blockers.

There are two options for the long-term management of AF: rhythm control or rate control. The mortality-morbidity outcomes ofthese two strategies are similar. Beta-blockers are frequently used for rate control in patients with AF. The advantages of beta-blockers are: high rate-control efficacy at rest and during exercise, and positive effect on outcomes in patients with prior myocardialinfarction or concomitant CHF.

21

Ho Huynh Quang TriHeart Institute - Ho Chi Minh City, Intensive Care Unit, Ho Chi Minh City, Vietnam

L12 - Benefits of β-blockade across patient types in congestiveheart failure

The therapeutic use of beta blockade in heart failure is one of the most remarkable “U turn” stories in all of medicine. From a drugwhich is almost absolutely contraindicated it has become one of the most used drugs in heart failure. Key to this is the ability ofclinician- scientists to translate pathophysiological concepts into “proof of concept” studies followed by major outcome trials whichdemonstrated unequivocally the benefits of beta blockade in heart failure. While the bulk of evidence was generated from studies inpatients with systolic heart failure, extrapolation of data of other patient category with heart failure suggest that its benefits will beseen across the spectrum of patients. In the hypertensive patients with coronary disease and heart failure, the INVEST trial showedthat the primary endpoint is reduced more with beta blocker based therapy than with calcium antagonist based therapy 1. Althoughtrials on diastolic heart failure have so far not shown conclusive results with the RAAS blockade, both retrospective 2 and fairly largeprospective observation study3 suggest that the benefits of beta blockers are seen both in patients systolic dysfunction and preservedsystolic function. A prospective randomised trial is in the pipeline to address this.

There are also those patients who are typically excluded from major heart failure trials including those with renal impairment,chronic obstructive airways disease ( COAD) and the very elderly. Will beta blockers also work in them? In newly diagnosed patientswith systolic heart failure and chronic kidney disease, beta blocker therapy is associated significant reduction in risk of death andhospitalisation4. Despite apprehension on its used in patients with COAD, retrospective analysis of patients with heart failure on betablockers showed that outcome benefits is equally seen in patients with or without COAD5 . Systematic review of the very elderly heartfailure patients meanwhile showed that the efficacy of beta blockers appears to extend to this population 6.

The benefits of beta blockade in heart failure appears to be across the board for the various beta blockers. As a class they are alsovery well tolerated with patients adherence rate in the “real world” as good as that of the RAAS blockade (both close to 90%) 7. Assuch beta blockade remains an integral armamentarium in the management of patients across the spectrum of heart failure.Although patients recruited in outcome studies do not necessarily match the characteristics of patients in the real world 8, thebenefits of beta blockers as seen under the controlled environment of randomised trials should be transferable to daily clinicalpractice.

22

Abdul Rashid Abdul RahmanCenter of Graduate Studies, Research and Commercialisation, Cyberjaya University College of Medical Sciences, Cyberjaya, Selanger, Malaysia

References:1. Pepine et al. JAMA 2003; 290:2805-28162. El Refai M et al. J Card Fail 2013; 19:73-793. Mori Y et al. Int Heart J 2013; 54:15-224. Tang et al. J Card Fail 2013; 19:176-825. Mentz RJ et al. Am J Cardiol 2013; 111:582-76. Sztramko R et al. Can Geriatr J 2011; 14:79-927. Gjesing A et al. Eur J Heart Fail 2013; Feb 8 (E pub)8. Niederseer D et al. Int J Cardiol 2013 Jan 24 (E pub)

L13 - Traditional and new anti- thrombotic therapy in atrialfibrillation

Atrial fibrillation is the most common sustained arrhythmia. Thromoembolic stroke is the most serious potential complication ofatrial fibrillation (AF). Patients with AF have 5-fold higher risk of stroke than those without AF. The ESC recently recommended theapplication of the CHA2DS2-VASc score when further risk stratification is indicated, particularly for patients with low and mediumstroke risk, with a CHADS2 score of 0 or 1.

Traditional recommendation is antiplatelet with parenteral and oral anticoagulant therapy such as Aspirin and Clopidogrel. Aspirinmonotherapy reduces risk of stroke in AF by 22 % but GI effects, bleeding, hypersensitivity Limitations of aspirin and clopidogrelinclude Bleeding, drug interactions, unpredictable inhibition of platelet aggregation leading to resistance, and prolonged durationof action requiring early cessation before surgical procedures. LMW heparin (enoxaparin, reviparin, nadroparin) have got betterbioavailability, longer t1/2. Heparin needs be administered 3 weeks prior to cardio-version with INR 1.8 on two separate occasionsbefore attempts of cardio version. Warfarin reduced the risk of stroke in non-valvular AF by 68 %. However only 50-60% patientsachieve INR in therapeutic range, there are problems of patient compliance, lack of knowledge of warfarin use and sudden warfarindiscontinuation. Triple therapy of aspirin, clopidogrel and warfarin: has increased risk of bleeding. Broad spectrum antibiotics, newercephalosporins, aspirin, phenytoin, indomethacin, metronidazole, erythromycin, chloramphenicol enhance anticoagulant action ofwarfarin and rifampicin, barbiturates, griseofulvin, oral contraceptives reduces its effectiveness.

Newer anti-thrombotics include e.g. rivaroxaban and apixaban, are well tolerated in patients with liver and renal diseases.Advantages of newer anti-thrombotics include: more specific action; enhanced efficacy with reduced intracranial bleeding; noroutine coagulation monitoring or dose adjustments; administration at fixed doses and simple therapeutic regimen; predictablepharmacokinetics and pharmacodynamics; minimal drug-food and drug-drug interactions; no need of bridging heparin therapy;overall improved patient compliance. Disadvantages include: cross comparative studies difficult due to differences in study designs,patients, pharmacokinetics and mechanism of action; expensive molecules; bleeding episodes that can pose a challenge; no specificantidotes available in bleeding emergency.

23

Shirish M.S. HiremathCardiology Department, Ruby Hall Clinic, Pune, India

L14 - Update 2012 of the ESC heart failure guidelines: any newperspectives?

The ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 were developed by the EuropeanSociety of Cardiology (ESC) in collaboration with the Heart Failure Association (HFA) of the ESC. The guidelines included various newadditions in all areas such as diagnosis, pharmacological approach, imaging, surgical etc. It also changed the level ofrecommendation to uniformly suit outcome variables. The principal changes from the 2008 guidelines are:i. an expansion of the indication for mineralocorticoid (aldosterone) receptor antagonists (MRAs);ii. a new indication for the sinus node inhibitor ivabradine;iii. an expanded indication for cardiac resynchronization therapy (CRT);iv. new information on the role of coronary revascularization in HF; v. recognition of the growing use of ventricular assist devices; vi. the emergence of transcatheter valve interventions.

Other recent papers have mentioned these changes as significant and relevant. Pharmacotherapy is the backbone of treatment andis based on neurohormonal inhibition and reversal of ventricular remodelling, after the first description of ACE-I, Beta-blockers,MRA-s now have expanded indications in the new guidelines meaning more patients are benefiting. For many patients, standardtherapy should include three neurohumoral antagonists-an angiotensin-converting enzyme (ACE) inhibitor [or angiotensin receptorblocker (ARB)], a beta-blocker and, if symptoms persist, now a mineralocorticoid receptor antagonist as well. In the area ofdiagnostics, there is a new biomarker called mid-regional pro-A-type natriuretic peptide. This has led to an explosion of knowledgewhich has led to further understanding of heart failure and research into newer bio-markers both for diagnosis as well asoptimisation of therapy. In device therapy, there are expanded indications for CRT, and an exploration of role of this treatment inpatients with dysynchrony and normal QRS. A new class of continuous flow left ventricular assist devices (L-VDAs) have emergedwhich are increasingly being applied as destination therapy.

24

C. Sreenivas GopalVijaya Heart Foundation, Department of Cardiology, Chennai, India

References:1. John J.V. McMurray (Chairperson) (UK)*,Stamatis Adamopoulos (Greece) et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaborationwith the Heart Failure Association (HFA) of the ESC. European Heart Journal (2012) 33, 1787–1847

2. Cowie MR. Recent developments in the management of heart failure.Practitioner. 2012 Jun;256(1752):25-9, 3.3. Taylor J The 2012 ESC Guidelines on Heart Failure. The latest Guidelines feature new evidence on diagnosis, drugs, and devices. Eur Heart J (2012) 33 (14):

1703-1711. 4. Sandek A, von Haehling S, Anker SD.Muscle in heart disease: highlights from the European Society of Cardiology's annual meeting 2012. Int J Cardiol. 2012

Nov 29;161(3):126-9.

L15 - Diuretics in heart failure. Practical guidance for use

Heart failure occurs when the left ventricle is unable to perform sufficient pump action to circulate blood flow to meet the needs ofthe body. Reduction of cardiac output to organs will stimulate the neurohormonal system e.g. sympathetic nervous system, renin-angiotensin-addosterone. Arteriole constriction will lead to high systemic vascular resistance and high afterload. Reduction of renalblood flow will initiate high aldosterone level and reduction of urinary levels. A high aldosterone level will preserve salt and waterresulting in high venous pressure, the preload. High intravascular volume and venous pressure will facilitate leakage of fluid to theinterstitial tissue both in systemic vein and lungs. Systemic edema and pulmonary congestion will cause symptoms and signs ofcongestive heart failure include: orthopnea, paroxysmal nocturnal dyspnea, dyspnea on exertion, ascites and leg edema. Leakageof fluid in the lungs interferes with oxygen exchanges in the alveoli causing hypoxemia and worsening of left ventricular function.The ongoing processes of fluid leakages, hypoxemia and worsening of left ventricular pumping function are a vicious cycle ofdeterioration which will lead to death.

Treatment of congestive heart failure by preload reduction started in the eleventh century by using leeches to suck blood fromcongested patients. Bloodletting by the barber in England was another treatment for heart failure in the past by similar rational.There are many kinds of treatment to reduce the preload such as turniquet, nitrate administration, morphine and the most importantone, diuretics.

In clinical practice, assessment of fluid status is quite crucial in management of congestive heart failure. Clinical symptoms, suchas bodyweight, jugular venous pressure, apical gallop S3, fine crepitation at basal lung’s fields and pitting edema of the legs areimportant in the assessment. Patients have to understand how to control salt in diet and the necessity of daily bodyweightmonitoring, checking leg edema in order to adjust diuretics by themselves.

Patients with evidence of fluid overload must be treated with diuretics. Intravenous loop diuretic is drug of choice for decompensatedheart failure patient. High potency drug like furosemide will effectively reduce preload and left ventricular end diastolic pressurewithin hours. Loop diuretics resistant might occurs in patients with impaired renal function and low cardiac output. If negative fluidbalance is inadequate, a second diuretic, thiazide or spironolactone, could be added to improve diuretic responsiveness. Diureticsshould be given at optimum doses, sufficient to produce diuresis that will reduce volume status and relieve signs and symptoms ofcongestion without bringing an unreasonably reduction in intravascular volume. Overuse of diuretics will decrease the cardiac outputleads to hypotension, decline in glomerular filtration rate and acute kidney injury.

Since loop diuretics have a short half-life, sodium reabsorption in the renal tubules will arise when the tubular concentration of thediuretics declines. Therefore, strictly restrictive sodium intake, multiple dosing of diuretic during the day, avoid non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors will enhance the efficacy. Loop diuretics may cause hypokalemia and increasechance for digitalis intoxication in concomitant uses.

25

Piyamitr SritaraDepartment of Medicine, Ramathiboi Hospital, Mahidol University, Bangkok, Thailand




Copyright © Serono Symposia International Foundation, 2013. All rights reserved.

Serono Symposia International Foundation Headquarters14, Rue du Rhône - 1204 Geneva, SwitzerlandRepresentative OfficeSalita di San Nicola da Tolentino 1/b - 00187 Rome, ItalyT +39.(0)6.420.413.1 - F +39.(0)6.420.413.677

Improving the patient's life through medical educationwww.seronosymposia.org

2013 asia-pacific cardiology symposium from hypertension ... · serono symposia international...

Documents