A" förutsäga och förebygga plötslig hjärtdöd. Mårten Rosenqvist Karolinska InsBtutet Kardiologen DS

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1 A" förutsäga och förebygga plötslig hjärtdöd. Mårten Rosenqvist Karolinska InsBtutet Kardiologen DS

2 Disclosures Konsult/föreläsningar/forskningsanslag Bayer Boehringer- Ingelheim Pfizer Sanofi- AvenBs St Jude Medical Medtronic Zenicor

3 PubMed oktober 2014 Sudden cardiac death PredicBon SCD PredicBon & prevenbon SCD arbklar

4 Översiktsli"eratur Sudden Cardiac Death, Predic1on and Preven1on Report from NIH & HRS Fishman et al, CirculaBon 2010 Preven1ng and Predic1ng Sudden Cardiac Death Estes M, CirculaBon 2011

5 Hur vill man dö? 200 kända personer intervjuade i Veckojournalen. 2/3 av män plötsligt 1/3 av kvinnor - - I en swimmingpool berusad av champagne ( How to die?, Biörck G. Arch. Internal Med 1973)

6 Fallbeskrivning 52 årig kollega Fader dog plötsligt i (sannolik) AMI vid 55 års ålder Gör allt rä"(röker inte, mobonerar regelbundet, dricker må"ligt och äter klokt, ingen övervikt) Tidigare helt frisk Inga aktuella symtom

7 Fortsä"ning I samband med skidsemester påträffas han på morgonen av sin son, nybliven läkare, livlös. HLR utan resultat ObdukBon ( omfa"ande) visar inga patologiska fynd som förklaring. Hade de"a kunna förebyggas?

8 Plötslig hjärtdöd / per år Ca 1/ <35 år per år i SE 5000 Startas HLR utanför sjukhus 60% bevi"nade 50% Inga varningssymtom 55% män 68% kvinnor ingen känd hjärtsjukdom Fishman et al CirculaBon 2010)

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10 Mass Screening Värnpliktsverket- finns ej Idro"smän- elitklass HälsodeklaraBon före tävlingar ( Vasaloppet, Stockholm Maraton etc) Skolläkare- finns ej

11 Hjärtstopp utanför sjukhus % i hemmet Äldreboende, VC men även idro"sanläggningar och gym ( 17-20%). Hög befolkningstäthet Ffa män ca 65 år Överlevnad (Sthlm) % (17 personer) Överlevnad 2013 > 12% ( > 100)

12 Public Access AED Stockholm ca AED Under åren , 80 fall där AED använts och givit shock Överlevnad > 60% Bevi"nade Utanför hemmet De flesta används ej (Ringh et al 2014)

13 KriBska faktorer InsatsBden Tidig HLR Snabb defibrillering Ambulans, polis, brandkår Frivilliga ( SMS livräddare) Strategisk utplacering AED

14 Plötslig död vid idro" 80 % av tävlingsidro"are som avlidit under fysisk akbvitet uppvisar strukturell hjärtpatologi

15 Sudden cardiac death in athletes C. Schmied1 & M. Borjesson2 Journal of Internal Medicine 2014 Incidence of sudden cardiac death US male Joggers (age 30 64) Thompson 1 : 7620 CompeBBve Italian athletes Corrado. 1 : US military Eckart et al. 1 : 9000 (SCD) 11.8 US athletes Maron 1 : (SCD) 8.4 US college athletes Harmon 1 : US marathon racers (age 29 55) Kim 1: ggr vanligare hos män

16 Screening av elit idro"are Young, compebbve athlete (age<35 years) Cardiac screening: Personal/Family history, physical examinabon, 12- lead resbng ECG Pathology? Screening recommendabons for young compebbve athletes (<30 35 years). C. Schmied & M. Borjesson Review: Sudden cardiac death in sports Journal of Internal Medici 2014

17 Vad är patologiskt? T wave inversion (excl. III, avr, V1) - ST segment depression ( 0.5 mm) - Q waves (excl. III and avr) - Complete lew bundle branch block - QRS durabon 140 ms - Lew axis deviabon - Lew atrial enlargement - Right ventricular hypertrophy pa"ern - Ventricular arrhythmias - Wolff- Parkinson- White pa"ern - Long- or short- QT interval - Brugada- like ECG pa"ern - Profound sinus bradycardia <30 bpm - Atrial tachyarrhythmias - Ventricular arrhythmias

18 From: Trends in Sudden Cardiovascular Death in Young Competitive Athletes After Implementation of a Preparticipation Screening Program! JAMA. 2006;296(13): doi: /jama " Figure Legend:! During the study period, the annual incidence of sudden cardiovascular death decreased by 89% in screened athletes (P for trend <.001). In contrast, the incidence rate of sudden cardiovascular death did not demonstrate consistent changes over time in unscreened nonathletes." Date of download: 10/11/2014" Copyright 2014 American Medical Association. All rights reserved."

19 Conclusion ( Schmiedt and Börjesson) - The risk of SCD doubles during physical acbvity and is 2- to 3- fold higher in athletes compared to nonathletes. - The incidence in young athletes is low, at around 1 3 per , but a"racts much public a"enbon. - The incidence of SCD in older ( 35 years) athletes is higher and may be expected to rise, as more and older take part in organized sports. - SCD first clinical manifestabon underlying cardiovascular disorder in previously asymptomabc athletes. Young (<35 years), SCD is mainly due to congenital whilst CAD most common in older. - Screening) may idenbfy individuals at risk and has the potenbal to decrease the risk of SCD in young athletes. - Screening including the ECG has a high sensibvity for underlying disease in young athletes, but the specificity needs to be improved, the sensibvity without ECG is very low. - The screening modality recommended for young athletes is of limited value in older with underlying CAD. - Screening will never be able to idenbfy all at risk, preparedness at the sporbng arena.

20 Riskfaktorer för plötslig död vid HCM

21 Rate of sudden death or cardiac arrest with resuscitation according to time after myocardial infarction. IHD, 70% av alla plötsliga dödsfall EF vikbgaste prediktorn Zaman S, and Kovoor P Circulation. 2014;129: Copyright American Heart Association, Inc. All rights reserved.

22 Förebyggande åtgärder hos de med symtom eller patologi Lägre fysisk akbvitet Hypertrof cardiomyopab ARVD

23 Trial yr n EF Add HR 95%CI p Madit I NSVT and EP positiv e 0.46 ( ) Primary prevenbon trials MADIT II MUSTT Prior MI 0.69 Prior MI, NSVT, 0.77 induci ble VT ( ) ( ) Prior SCD- HeFT MI or NICM 0.77 ( ) DEFINI TE NICM, PVCs, or NSVT 0.65 ( ) 0.08

24 PrimärprevenBon Bdigt ewer AMI DINA MIT d post- MI and impair ed HRV 1.08 ( IRIS <30 d post- MI, HR >90, or NSVT 1.04 ( ) 0.78

25 MADITT II Risk score NYHA > II AF QRS durabon >0.12 Ålder > 75 Nedsa" jurfunkton Figure 3 Probability of Survival in Patients With Risk Scores 1, 2, and 3 Kaplan-Meier estimates of the probability of survival, by treatment group, in (A) patients with risk score = 1; (B) patients with risk score = 2; and (C) patients with risk score > 3... Ilan Goldenberg, Anant K. Vyas, W. Jackson Hall, Arthur J. Moss, Hongyue Wang, Hua He, Wojciech Zareba, Sc... Risk Stratification for Primary Implantation of a Cardioverter-Defibrillator in Patients With Ischemic Left Ventricular Dysfunction Journal of the American College of Cardiology, Volume 51, Issue 3, 2008,

26 Non- invasiva test för at förutsäga SCD Vänster kammares funkbon ( EF) VES Autonom modulering HRV, turbulens, baroreflex Impulsledning SAEKG, QRS frakbonering Repolarisering T vågs alternans, QT Myokardfibros (MR)

27 Figure 3 Combined Effect of MTWA and EPS Risk Stratification on 1-Year Actuarial Event Rates Patients having both normal MTWA tests and negative EPS (MTWA Nml/EPS ) exhibited lowest event rate, whereas patients having both positive EPS and abnormal MTWA t... Otto Costantini, Stefan H. Hohnloser, Malcolm M. Kirk, Bruce B. Lerman, James H. Baker II, Barathi Sethuraman... The ABCD (Alternans Before Cardioverter Defibrillator) Trial : Strategies Using T-Wave Alternans to Improve Efficiency of Sudden Cardiac Death Prevention Journal of the American College of Cardiology, Volume 53, Issue 6, 2009,

28 To date no randomized studie have been conducted that demonstrate benefit of non- invasive risk strabficabonin in reducing SCD events. (Fisher et al CirculaBon 2010)

29 Hypertrofisk kardiomyopab (HCM) Autosomalt dominant, uppvisar nedsa" penetrans och variabel expressivitet, 1/ GeneBsk test AsymptomaBsk, effort dyspné, yrsel, svimning, angina God prognos om diagnos ewer 50 års ålder

30 h"p:// Riskkalkyl för a" bedöma ICD behov vid HOCM Ålder Familjehistoria Oförklarlig syncope Max LV tjocklek Max gradient Förmaksdiameter NSVT Kalkylerad 5 års överlevnad: Hög risk > 6% ICD Intermediär 4-6% ICD övervägs Låg risk <4 % ej indikabon

31

32 Figure 2 Kaplan-Meier event-free survival for (A) the endpoint of cardiac mortality in patients with NYHA class I/II and II/IV at implantation, (B) the endpoint of appropriate ICD intervention in patients who received an ICD for primary or secondary preven... Pieter A. Vriesendorp, Arend F.L. Schinkel, Johan Van Cleemput, Rik Willems, Luc J.L.M. Jordaens, Dominic A.M... Implantable cardioverter-defibrillators in hypertrophic cardiomyopathy: Patient outcomes, rate of appropriate and inappropriate interventions, and complications American Heart Journal, Volume 166, Issue 3, 2013,

33 Arytmogen högerkammarkardiomyopa2 (ARVC) Autosomalt dominant med varierande pentrans 1/5000 InfiltraBon av fibrös vävnad/fe" I höger kammare Tidigt VT ger hög risk för SD Senare i livet främst ökad risk för hjärtsvikt Finns inga mediciner som förebygger sjukdomen el risk för SD Behandla högersvikt I vissa fall ICD GeneBsk test kan vara av värde

34 ICD behandling Two major criteria or One major plus two minor criteria or Four minor criteria

35 A, Kaplan-Meier analysis of cumulative survival from any appropriate ICD interventions in the 106 ARVC/D patients. Corrado D et al. Circulation. 2010;122: Copyright American Heart Association, Inc. All rights reserved.

36 Incidence rate of appropriate shocks versus serious harm. Olde Nordkamp L R et al. Circ Arrhythm Electrophysiol. 2013;6: Copyright American Heart Association, Inc. All rights reserved.

37 Percentage of patients with complications per number of implantable cardioverterdefibrillators (ICD) implantations. Olde Nordkamp L R et al. Circ Arrhythm Electrophysiol. 2013;6: Copyright American Heart Association, Inc. All rights reserved.

38 Primär preven1on plötslig hjärtdöd - Livss2l (IHD) - Screening av popula2on? (Allmän värnplikt) (Skolläkare) - Screening riskgrupper IdroEare Familjehistoria - Spridning av externa defibrillatorer

39 SekundärprevenBon plötslig död LivssBl (ffa IHD) Fysisk akbvitet (minskad) HOCM, ARVD ICD - allvarliga symtom, VT, EF <35%, riskscore AED

40 Jussi Björling

41 Figure 2 Kaplan-Meier event-free survival for (A) the endpoint of cardiac mortality in patients with NYHA class I/II and II/IV at implantation, (B) the endpoint of appropriate ICD intervention in patients who received an ICD for primary or secondary preven... Pieter A. Vriesendorp, Arend F.L. Schinkel, Johan Van Cleemput, Rik Willems, Luc J.L.M. Jordaens, Dominic A.M... Implantable cardioverter-defibrillators in hypertrophic cardiomyopathy: Patient outcomes, rate of appropriate and inappropriate interventions, and complications American Heart Journal, Volume 166, Issue 3, 2013,

42 Distribution of clinical status of individuals suffering sudden cardiac death (SCD). Estes N M Circulation. 2011;124: Copyright American Heart Association, Inc. All rights reserved.

43 Incidence rate of appropriate shocks versus serious harm. Olde Nordkamp L R et al. Circ Arrhythm Electrophysiol. 2013;6: Copyright American Heart Association, Inc. All rights reserved.

44 Primär prevenbv ICD LVEF < 35% HCM > 6% 5- year risk ARVD

45 Mild segmental dilatabon of the right ventricle Regional right ventricular hypokinesia II Tissue characterisabon ofwalls MAJOR Fibrofa"y replacement of myocardium on endomyocardial biopsy m RepolarisaBon abnormalibes MINOR Inverted T waves in right precordial leads (V2 and V3) (people aged more than 12 yr; in absence of right bundle branch block) IV DepolarisaBon/conducBon abnormalibes MAJOR Epsilon waves or localised prolongabon (> 1 10 ms) of the QRS complex in right precordial leads (V1- V3) MINOR Late potenbals (signal averaged ECG) V Arrhythmias MINOR Lew bundle branch block type ventricular tachycardia

46 Fortsä"ning Inga Bdigare besvär Inga varningssymtom Defibrillator hemma?? Brandsläckare ca 1000 kronor AED ca koronor De flesta används inte

47 h"p:// Riskkalkyl för a" bedöma ICD behov vid HOCM Ålder Familjehistoria Oförklarlig syncope Max LV tjocklek Max gradient Förmaksdiameter NSVT Kalkylerad 5 års överlevnad: Hög risk > 6% ICD Intermediär 4-6% ICD övervägs Låg risk <4 % ej indikabon