andrea ungar, md, phd, fesc - tigullio · pdf fileandrea ungar, md, phd, fesc syncope unit,...

Andrea Ungar, MD, PhD, FESC

Syncope Unit, Hypertension CentreGeriatric Cardiology and Medicine

University of Florence, Italy

L’evoluzione negli anni

ILFUTUROPROSSIMOILFUTUROPROSSIMO

ILFUTUROPROSSIMOILFUTUROPROSSIMO

Connessione wireless

La sincope

Situations in which ILR is proved to be useful (1):Situations in which ILR is proved to be useful (1):§ Patients with bundle branch block in whom a paroxysmal AV block is likely

despite a negative electrophysiological evaluation;

§ Patients with definite structural heart disease in whom an arrhythmia is likely despite a negative cardiological work-up;

§ Patients with cardioinhibitory carotid sinus hypersensitivity when the understanding of the exact mechanism of spontaneous syncope is needed to guide a specific therapy;

§ In pediatric patients in whom a cardiac cause of syncope is suspected due to structural heart disease or electrocardiographical abnormalities.

Situations in which ILR is proved to be useful (2):Situations in which ILR is proved to be useful (2):§ Patients in whom epilepsy was suspected but the treatment has proved

ineffective and in patients with established epilepsy in order to detect periictal cardiac arrhythmias that require treatment;

§ Patients with major depressive diseases and frequent recurrent unexplained episodes of LOC in order to exclude an arrhythmic cause of syncope;

§ In older patients with non-accidental falls to establish the syncopal nature of the event.

Recommendations: Electrocardiograhic monitoringRecommendations: Electrocardiograhic monitoring

• Il monitoraggio è diagnostico se vi è una correlazione tra sintomo e aritmia

• In assenza di correlazione sono diagnostici un blocco atrioventricolare avanzato, una pausa ventricolare > 3 secondi, o una tachicardia atriale ad elevata frequenza

• Le altre aritmie asintomatiche non hanno rilievo diagnostico

• La bradicardia sinusale in assenza di sintomi non è indicativa della causa di sincope

• La presincope non è diagnostica

ISSUE 3

SYNCOPE

ISSUE3International Study on Syncope of Uncertain Etiology 3

Background

ISSUE3International Study on Syncope of Uncertain Etiology 3

ISSUE 3

SYNCOPE

Total51centers,504patients

ISSUE 3

SYNCOPEIssue3Registry

Ptsaffectedbysevere,recurrentreflexsyncopes,aged>40yrs

ILRimplantation(RevealDX/XT)

ILRfollow-up(max2yrs)

ILRscreeningphase

ISSUE3therapyphase Diagnosis&ILR-guidedspecifictherapy

Follow-up

0

.1

.2

.3

.4

.5

.6

.7

.8

.9

1

Free

dom

from

dia

gnos

is

0 6 12 18 24 30 36Months

504 343 278 238 151 37 15 Number at risk

31%40%

47%

ISSUE 3

SYNCOPEDiagnosis

NND:2.1

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

Free

dom

from

syn

copa

l rec

urre

nce

62 42 35 29 23 19 16 14PM86 63 57 46 44 35 30 22NO PM

Number at risk

0 3 6 9 12 15 18 21Months

27%vs54%at21monthslogrank:p=0.01

RRR(hazardratio):57%NNT:3.7

PM(n=62)

NoPM(n=86)

ISSUE 3

SYNCOPE

PacemakertherapyvsnopacemakertherapyinestablishedNMSpatients

Recurrenceofsyncope

To compare the diagnosis of NMS madeat initial evaluation and with TT withthat obtained with the documentation ofa spontaneous event made byimplantable loop recorder (ILR)

Aimofthestudy

UngarA.etal,heart2013

NMSatinitialevaluation ILRimplantation504

DiagnosisafterECGdocumentation

Follow-up:15±11months

187(37%)

HypotensiveNMS

63(34%)

AsystolicNMS

99(53%)

Intrinsiccardiac

arrhythmias21(11%)

Non-arrhythmic

T-LOC4(2%)

NMSlikely162(87%)

NMSexcluded25(13%)

ISSUE 3

SYNCOPEDiagnosis


ISSUE 3

SYNCOPEDiagnosis

Intrinsiccardiacarrhythmias21(11%)

Non-arrhythmicT-LOC4(2%)

NMSexcluded25(13%)

• longpausepost-tachyarrhythmia[#8]• paroxatrialfibrillation [#3]• AVNRT[#3]• persistentbradycardia[#3]• ventriculartachycardia[#4]

• non-syncopalT-LOC[#3],• orthostatichypotension [#1]


Characteristics NMS n=162

Cardiacn=21

P value

Age, mean 64 68 nsMen 46% 62% nsSyncope events:

- Total events, median 8 5 ns- Events last 2 years, median 4 4 ns- Events last 2 years without prodrome, median 3 3 ns- Age at first syncope, mean 48 53 ns- Interval between first and last episode, median 9 5 ns- History of presyncope 55% 48% ns- Hospitalization for syncope 42% 57% ns- Injuries related to fainting:

- Major (fractures, concussion) 11% 5% ns- Minor (bruises, contusion, hematoma) 44% 43% ns

- Typical vasovagal/situational presentation 49% 43% ns- No prodromes 54% 67% ns

ISSUE 3

SYNCOPE

Factors predicting intrinsic cardiac syncope (I)Ungar A. et al, heart 2013

Characteristics NMS n=162

Cardiacn=21

P value

Tilt testing: performed 84% 81% ns- Positive of those performed 56% 47% ns

Medical history- Structural heart disease 12% 10% ns- Atrial tachyarrhythmias 5% 38% 0.001- Hypertension 50% 49% ns- Diabetes 11% 10% ns- Neurologiacal/psychiatric 4% 0% ns

Echocardiogram- Any abnormality 8% 10% ns

Concomitant medications- Anti-hypertensive 48% 29% ns- Psychiatric 12% 0% ns- Any other drugs 27% 33% ns

ISSUE 3

SYNCOPE

Factors predicting intrinsic cardiac syncope (II)Ungar A. et al, heart 2013

Tilttest+ ILR+

28

48

Asystole(Vasis2B)

MorVD(Vasis1,2A,3)

Asystole47

29 Slightrhythmvariations

24(86%)

4(14%)

23(48%)

25(52%)

Total76pts

Positivepredictivevalueofasystolictilt:0.86(95%CI0.70-0.95)

ISSUE 3

SYNCOPE

CorrelationbetweentilttestresponsesandILR-documentedmechanism


M.M. female, 74 years old

Hypertension, Hypercholesterolemia; Depressive syndrome. May 2009, an episode of transient global amnesia;Since 2009 epileptic absences, EEG confirmed; the patient start therapy with levetiracetam;Since 2009 several recurrent falls, sometimes traumatic.March 2012: Syncope Unit: Orthostatic Hypotension.June/July 2012: two falls with consequent mild trauma and some suspected presyncopal episodes. We decided to implant a Loop recorder08-19-2012: dizziness episode with fall after a

prolonged orthostatic period, without prodromal symptoms, with consequent fall and occipital trauma……..

M.M. female, 74 years old

• The Insertable Cardiac Monitor

supraventricular tachycardia, 200 bpm, lasting 39 seconds, during the loss of consciousness

La diagnosi differenzialecon alter TPdC

Additional diagnostic value of implantable loop recorder in patients with initial diagnosis of non-syncopal transient loss of consciousness

Maggi R, Rafanelli M, Ceccofiglio A, Solari D, Brignole M, Ungar A

Europace 2014

Patients’ characteristicsPatients’ characteristicsTotalptsn=58

Suspectedepilepsy(*)

n=28

Unexplainedfallsn=29

Meanage,yrs 71± 17 64±18 78±8

Males 25(43%) 17(63%) 7(25%)

Mediannumber ofT-LOCbeforeimplantation 4.6±2.3 3.7±2.1 5.5±3.3

Competingabnormalities/diagnoses: 29(50%) 14(50%) 15(52%)

- Structuralheartdisease 16(28%) 5(18%) 11(38%)

- Bundlebranchblock 10(17%) 4(14%) 6(20%)

- Positivetilttesting 10/41(17%) 8(29%) 2(7%)

- Carotidsinushypersensitivity 6/49(10%) 2(7%) 4(14%)

Europace 2014

Results:ILRdiagnosisResults:ILRdiagnosis58

15 (26%)

Total pts with ILR

Spontaneous episode documented by ILR

Follow-up 20±13 months

33 (57%)

Arrhythmic syncopeNND: 4

Asystole of 6 s (IQR 4-10)

-sinus arrest, 11 pts- AV block, 1 pt

Tachyarrhythmia

-ectopic atrial tachycardia, 1 pt-atrial fibrillation, 1 pt- ventricular tachycardia, 1 pt

12 3

Europace 2014

Diagnosis after ILRClinical evalution andconventional tests

SuspectedEPILEPSYn=28

UnexplainedFALLn=29

No arrhythmia(epilepsy or non-

arrhythmic syncope)n=9 (16%)

Arrhythmicsyncope

n=15 (26%)

No arrhythmia(fall or non-arrhythmic

syncope)n=9 (16%)

ILR-undocumentedn=25 (43%)

9

7

11

9

13

8

Pseudo-syncopen=1

1

Follow-up 20±13 months

Europace 2014

ConclusionConclusion

ILR provides an additional diagnostic value in “difficult”patients with initial diagnosis of non syncopal T-LOC:• 57% of patients with an initial diagnosis of either likelyepilepsy or unexplained fall had ILR documentation of arelapse of their index attack;• in 26% patients, the final diagnosis was of arrhythmicsyncope;• in the other 31% of patients, in whom no arrhythmia wasdocumented at the time of a spontaneous attack, ILRmonitoring definitely excluded an arrhythmic cause..

Europace 2014

La fibrillazione atriale

INdicationS fordiaGnosis,ArrhytHmia andMoniToring ofRevealXT

INSIGHT-XT

Observational multicentre study thatenrolled patients inserted with an insertable cardiac monitor (ICM) for arrhythmia diagnosis or monitoring in real life

Totalrecruitedn=1003

Dataavailablen=997

Availableforanalysesn=975

• Noimplant/Baseline data n=6

• In-/Exclusion criterianotmet n=22

Atleast1follow-up availablen=968

• Losttofollow-up n=7

Fullpo

pulatio

n

12months* follow-up availablen=779

• PatientreceivesanICD,PMorCRT-devicen=103• RevealXTexplanted n=36• Losttofollow-up n=30• Patientdeath n=8• Patientrequestedwithdrawalfromthestudy n=8• Investigatorwithdrewpatientfromthestudy n=1• Otherreasons n=3

*Morethan300days

Patient Disposition

INdicationS fordiaGnosis,ArrhytHmia andMoniToring ofRevealXTINSIGHT-XT

INSIGHT-XTEnrollmentTotal Enrollments per Country

214

141

115

53

27 26 20 19 19 13 11 11 9 5 2 00

50

100

150

200

250

German

y

Netherlan

ds

Russia

Austria

Switzerl

and

Italy

Spain

Czech

Rep

ublic

Finlan

d

Portug

al

Slovac R

epub

lic

United Arab E

mirates

Belarus

Slovenia

Sweden

Belgium

968INSIGHT-XTpatientsforindication

391

172

284

121

0

50

100

150

200

250

300

350

400

450

Syncope/ Presyncope

AF ablation management

Other indication Cryptogenic stroke (incl. Palpitations)

Primary Indication

PatientCharacteristicsSyncopeorPre-

syncope(N=391)

AFpatients

(N=327)

CryptogenicStroke

(N=121)

Other(N=129)

Total(N=968)

Demographics

Male %, n/Pts 50.1%(196/391) 65.7%(220/335) 52.9%(64/121) 47.9%(58/121) 55.6%(538/968)Age at first implant (years) 63.0± 16.6 59.9± 11.0 62.4± 13.2 57.5± 16.5 61.1± 14.5Medical historyAT/AF history %, n/Pts 18.4%(72/391) 87.5%(293/335) 0.0%(0/121) 18.2%(22/121) 40.0%(387/968)Coronary artery disease %, n/Pts 6.4%(25/391) 7.8%(26/335) 71.9%(87/121) 4.1%(5/121) 14.8%(143/968)Prior Myocardial Infarction %, n/Pts 7.2%(28/391) 5.7%(19/335) 5.0%(6/121) 7.4%(9/121) 6.4%(62/968)Prior Transient Ischemic Attack %,n/Pts

4.6%(18/391) 6.0%(20/335) 35.5%(43/121) 3.3%(4/121) 8.8%(85/968)

Prior CVA/Stroke%, n/Pts 4.6%(18/391) 6.3%(21/335) 71.1%(86/121) 3.3%(4/121) 13.3%(129/968)Hypertension %, n/Pts 60.9%(238/391) 68.1%(228/335) 62.0%(75/121) 54.5%(66/121) 62.7%(607/968)Diabetes %, n/Pts 15.3%(60/391) 12.5%(42/335) 11.6%(14/121) 10.7%(13/121) 13.3%(129/968)Hypercholesterolemia%, n/Pts 33.5%(131/391) 33.4%(112/335) 52.9%(64/121) 38.0%(46/121) 36.5%(353/968)CHADS ≥ 3 %, n/Pts 16.4%(64/391) 16.8%(55/327) 67.8%(82/121) 14.0%(18/129) 22.6%(219/968)CHADSVASC ≥ 4 %, n/Pts 31.5%(123/391) 26.6%(87/327) 60.3%(73/121) 24.8%(32/129) 32.5%(315/968)

Patientscharacteristics


MedicationsSyncopeorPre-

syncope(N=391)

AFpatients

(N=327)

CryptogenicStroke(N=121)

Other(N=129)

Total(N=968)

Antiarrhytmicdrugs

Antiarrhythmics (overall),n/Pts 41.9%(164/391) 87.5%(286/327) 31.4%(38/121) 57.4%(74/129) 58.1%(562/968)

AAClassI,n/Pts 4.1%(16/391) 21.7%(71/327) 1.7%(2/121) 11.6%(15/129) 10.7%(104/968)

Beta-blockers,n/Pts 34.5%(135/391) 54.7%(179/327) 29.8%(36/121) 48.8%(63/129) 42.7%(413/968)

Sotalol,n/Pts 2.0%(8/391) 11.3%(37/327) 0.8%(1/121) 2.3%(3/129) 5.1%(49/968)

AAClassIII,n/Pts 4.1%(16/391) 28.4%(93/327) 0.8%(1/121) 0.8%(1/129) 11.5%(111/968)

Amiodaron,n/Pts 3.6%(14/391) 22.9%(75/327) 0.8%(1/121) 0.8%(1/129) 9.4%(91/968)

OtherAAClassIII,n/Pts 0.5%(2/391) 5.8%(19/327) 0.0%(0/121) 0.0%(0/129) 2.2%(21/968)

OACorAntiplatelets

OACorAntiplatelets,n/Pts 51.2%(200/391) 85.6%(280/327) 97.5%(118/121) 54.3%(70/129) 69.0%(668/968)

OAC,n/Pts 12.0%(47/391) 64.2%(210/327) 5.0%(6/121) 13.2%(17/129) 28.9%(280/968)

Antiplatelets,n/Pts 40.2%(157/391) 27.5%(90/327) 93.4%(113/121) 42.6%(55/129) 42.9%(415/968)


SymptomsatbaselineSyncopeorPre-

syncope(N=391)

AFpatients

(N=327)


Other(N=129)

Total(N=968)

Any symptom*, n/Pts 97.2%(380/391) 91.1%(298/327) 33.9%(41/121) 93.8%(121/129) 86.8%(840/968)Palpitations, n/Pts 20.7%(81/391) 63.6%(208/327) 12.4%(15/121) 69.0%(89/129) 40.6%(393/968)Dizziness/Lightheaded/Pre-syncope,n/Pts

33.0%(129/391) 17.7%(58/327) 13.2%(16/121) 38.0%(49/129) 26.0%(252/968)

Syncope, n/Pts 84.4%(330/391) 5.8%(19/327) 6.6%(8/121) 27.9%(36/129) 40.6%(393/968)Dyspnea, n/Pts 10.2%(40/391) 42.2%(138/327) 5.8%(7/121) 27.1%(35/129) 22.7%(220/968)Fatigue, n/Pts 8.4%(33/391) 41.6%(136/327) 2.5%(3/121) 18.6%(24/129) 20.2%(196/968)Chest pain, n/Pts 9.5%(37/391) 16.8%(55/327) 3.3%(4/121) 17.8%(23/129) 12.3%(119/968)

FU durationSyncopeorPre-syncope(N=391)

AFpatients

(N=327)


Other(N=129)

Total(N=968)

Follow-upduration[months,Median(QI-

QIII)]15(10- 23) 16(12- 26) 13(12- 13)

15(12-24)

14(11- 23)


391

172

284

121

0

50

100

150

200

250

300

350

400

450

Syncope/ Presyncope



Primary Indication

AtrialfibrillationinpatientsimplantedwithReveal-XTforSyncope

INdicationS fordiaGnosis,ArrhytHmia andMoniToring ofRevealXT

INSIGHT-XT

Results– AFprevalence

Resultsonsyncopepatientswithatleast30daysoffollowupavailable

Insight-XTSyncope andAF,preliminary data

Results– AFprevalence

• 18%ofthesyncopepatients hadahistoryofAFatstudyenrollmentand57%(n=28)ofthesehadAFduringthestudy

• 82% ofthesyncopepatientshadnopriorhistoryofAFatenrollmentand16%(n=34) ofthesehadnewlydiagnosedAFduringthestudy

Insight-XTSyncope andAF,preliminary data

391

172

284

121

0

50

100

150

200

250

300

350

400

450

Syncope/ Presyncope



Primary Indication


The median time to diagnosis of AF was 100 days after ICM insertion

AF was observed in 19.8% (1Q-3Q: 11.7% -13.4%) of patients (n=24) during a median follow-up time of 12.5 months

Managing cryptogenic stroke patients using insertable cardiac monitors:Results of the INSIGHT XT study

Anti-thrombotic medication at last follow-up in patients diagnosed with AF

OAC therapy was started in 62.5% of the patients who were diagnosed with AF during the study and allpatients with AF received some type of anti-thrombotic medication

Preliminary data on diagnosis in total population

DIAGNOSIS1. VT

2. AF/AFlutter (incl.AF,AFlutter,Brady-Tachy)

3. AT(incl.ATandAVNRT)

4. SinusTachycardia

5. SinusArrest/Bradycardia

6. HighergradeAVblock(incl.2ndand3rddegreeAVblock)

In 63.1% of patients enrolled Reveal-XT obtain clinical useful data for the management of the patients

Patientswith diagnosis by reveal-xt

Overall% (n)N=968

Syncope orPre-syncope

% (n)N=391

AF patients% (n)N=327

CryptogenicStroke% (n)N=121

Other% (n)N=129

No diagnosis during FU 36.9%(357) 36.6%(143) 27.5%(90) 62.8%(76) 37.2%(48)

At least 1 diagnosis during FU 63.1%(611) 63.4%(248) 72.5%(237) 37.2%(45) 62.8%(81)

Preliminary data on total population

Grazie per l’attenzione

Atrial fibrillation was asymptomatic in 23 of 29 first episodes in the ICM group(79%) and in 2 of 4 first episodes in the control group (50%).

97.0% of patients in whom atrial fibrillation had been detected were receiving oral anticoagulants

andrea ungar, md, phd, fesc - tigullio · pdf fileandrea ungar, md, phd, fesc syncope unit,...

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