2. Device Therapy In tachyarrhythmia and prevention of sudden cardiac death MAHDY HASANZADEH, MD Interventional Electrophysiologist MUMS-CRC OCT.2011

3. 3 Cardiac Devices Designed to: –Restore or maintain a rhythm and rate sufficient to meet metabolic needs –Provide diagnostic information about Device operation The patient

4. 4 Cardiac Devices Pacemakers or Implantable Pulse Generators (IPG) –Provide a rate to support metabolic needs –Provide various diagnostics –Single and dual chamber –About 8-10 years longevity –Some of the newer pacemakers include therapies which pace-terminate AT/AF

5. 5 Cardiac Devices Implantable Cardioverter Defibrillators (ICDs) –Restore sinus rhythm in the presence of tachycardia Defibrillate Cardiovert Anti-Tachy Pace (ATP) –Provide a rate to support metabolic needs Includes single or dual chamber pacing –Provide various diagnostics –About 6-9 years longevity –There are also devices designed to terminate AF via cardioversion/ATP in addition to standard ICD therapies

6. 6 Cardiac Devices Cardiac Resynchronization Therapy (CRT) –IPG with CRT, or an IPG + ICD with CRT –Restore ventricular synchrony Uses a specially designed lead placed usually on the posterior-lateral wall of the LV via the Coronary Sinus circulation LV epicardial lead placement is an option Provides RV and LV synchronous pacing –May restore rhythms in presence of lethal tachycardia CRT pacing +ICD (High-Power CRT) –Provides a rate to support metabolic needs CRT pacing only (Low-Power CRT) –Provides various diagnostics

7. 7 Cardiac Devices Implantable Loop Recorders (ILR) –Provides rate-based monitoring Fast rates Slow rates –Provides EGM during patient triggered events

8. 8 Indications Pacemakers The AHA and ACC have defined the indications for pacing by the underlying arrhythmia Very detailed, but to simplify: –Symptomatic bradycardia refractory to any treatment –Typical diagnoses: Sinus Node Disease (SND), or Sick Sinus Syndrome Complete Heart Block Chronotropic Incompetence Vaso-vagal syncope Carotid sinus hypersensitivity –Usually excludes “low grade” blocks (Mobitz I and 1 st degree)

9. 9 Indications Defibrillators Primary vs. Secondary Prevention for SCA –Secondary Patients who have experienced a previous SCA or ventricular arrhythmia Studies such as AVID 1, CIDS 2, CASH 3 support the use of ICDs in this population –Primary Patients who have not previously experienced SCA/VA, but are at risk Studies, such as MADIT II 4 and SCD-HeFT 5, have demonstrated the use of ICDs in these patients

10. 10 Indications Defibrillators (cont.) Well defined by Heart Rhythm Society (HRS) and include: Cardiac Arrest –Due to VT or VF, not transient or reversible –Spontaneous sustained VT with structural heart disease Syncope of undetermined origin with: –Sustained VT or VF induced during EP Nonsustained VT with: –Coronary disease or prior MI and LV Dysfunction –Inducible VF or sustained VT (non-suppressible by antiarrhythmic drugs) Spontaneous sustained VT –Not amenable to other treatments

11. 11 Indications Defibrillators (cont.) ICD Class I Recommendation Patients at least 40 days post-MI LVEF ≤ 30 – 40% NYHA class II or III Non-ischemic patients LVEF ≤ 30 – 35% NYHA class II or III Patients at risk of SCA due to genetic disorders Long QT syndrome Brugada syndrome Hypertrophic cardiomyopathy (HCM) Arrhythmogenic right ventricular dysplasia (ARVD) Note: This list includes the current major indications for an ICD

12. 12 Indications Cardiac Resynchronization Therapy NYHA Class III or IV heart failure On optimal medical therapy QRS > 120 ms wide –Or Echo evidence of ventricular dyssynchrony Ejection Fraction of < 35% Who are candidates for an ICD with CRT, and who for an IPG with CRT? –Most get an ICD with CRT (also called “High-Power CRT”) because of the risk of SCD in patients with LV dysfunction

13. Sudden cardiac death(SCD) Introduction Sudden cardiac death (SCD) is used to describe cardiac arrest with cessation of cardiac function, whether or not resuscitation or spontaneous reversion occurs Patients who do not die after cardiac arrest should be said to have experienced aborted SCD

14. Sudden cardiac death(SCD) Definition by WHO Sudden collapse of cardiac function occurring within one hour of symptoms

15. Sudden cardiac death(SCD) Pathophysiology The vast majority of cases of SCD are due to ventricular arrhythmias Ventricular tachycardia (VT) or ventricular fibrillation (VF) account for the majority of episodes This almost always occurs in the setting of underlying myocardial disease More than 80% of SCD events occur in individuals with coronary artery disease (CAD)

16. SCD & ischemic heart disease 65 to 70 % of SCDs are attributable to CAD SCD accounts for 30 to 50 % of coronary deaths A peak incidence of VT and VF within the first 48 hours after acute MI has also been noted in other reports

17. SCD & ischemic heart disease(2) Incidence of VT and VF after ST- elevation MI VF:4.2 % VT:3.5 % Both VF and VT:2.7 % 80 to 85 % of these arrhythmias occurred in the first 48 hours.

18. Treatments to Reduce Sudden Cardiac Death Correcting Ischemia –Revascularization –Beta-blocker Preventing Plaque Rupture –Statin –ACE inhibitor –Aspirin Stabilizing Autonomic Balance –Beta-blocker –ACE inhibitor Improving Pump Function –ACE inhibitor –Beta-blocker Prevention of Arrhythmias –Beta-blocker –Amiodarone Terminating Arrhythmias –ICDs –AEDs Prevent Ventricular Remodeling and Collagen Formation –Aldosteron e receptor blockade

19. Small devices, pectoral implant site Transvenous, single incision Local anesthesia; conscious sedation Short hospital stays Few acute complications Perioperative mortality < 1% Programmable therapy options Single- or dual-chamber therapy Battery longevity up to 9 years Implantable Cardioverter Defibrillator First-line therapy for patients at risk for VT/VF

20. 1 Moss AJ. N Engl J Med. 1996;335:1933-40. 2 Buxton AE. N Engl J Med. 1999;341:1882-90. 3 Moss AF. N Engl J Med. 2002;346:877-83. 4 Moss AJ. Presented before ACC 51st Annual Scientific Sessions, Late Breaking Clinical Trials, March 19, 2002. 123, 4 54% 75% 55% 73% 31% 61% ICD Mortality Benefits in Primary Prevention Trials 27 Months 39 Months 20 Months % Mortality Reduction w/ ICD Rx

21. Secondary Prevention of SCD-- Conclusions from Three RCT’s The ICD is first-line therapy for patients with hemodynamically-compromising primary ventricular tachyarrhythmias (relative mortality reduction of 27% compared to medication). Benefit of ICD mainly with EF<35%, and is independent of beta blocker use. Further study is required to assess the cost- efficacy of the ICD in other patient subsets (EF>35%, well-tolerated VT, secondary VT/VF).

22. 1 Moss AJ. N Engl J Med. 1996;335:1933-40. 2 Buxton AE. N Engl J Med. 1999;341:1882-90. 3 Moss AJ. N Engl J Med. 2002;346:877-83 4 Moss AJ. Presented before ACC 51st Annual Scientific Sessions, Late Breaking Clinical Trials, March 19, 2002. 5 The AVID Investigators. N Engl J Med. 1997;337:1576-83. 6 Kuck K. Circ. 2000;102:748-54. 7 Connolly S. Circ. 2000:101:1297-1302. ICD mortality reductions in primary prevention trials are equal to or greater than those in secondary prevention trials. 13, 42 5 7 6 Mortality Benefits with ICD Therapy 54% 75% 55% 76% 31% 61% 27 months39 months20 months 31% 56% 28% 59% 20% 33% % Mortality Reduction w/ ICD Rx 3 Years

23. Major Implantable Cardioverter-Defibrillator Trials for Prevention of Sudden Cardiac Death TrialYearPatients (n) LVEFAdditional Study Features Hazard Ratio* 95% CIp MADIT I1996196< 35%NSVT and EP+0.46(0.26-0.82)p=0.009 MADIT II20021232< 30%Prior MI0.69(0.51-0.93)p=0.016 CABG-Patch1997900< 36%+SAECG and CABG1.07(0.81-1.42)p=0.63 DEFINITE2004485< 35%NICM, PVCs or NSVT0.65(0.40-1.06)p=0.08 DINAMIT2004674< 35%6-40 days post-MI and Impaired HRV 1.08(0.76-1.55)p=0.66 SCD-HeFT20061676< 35%Prior MI of NICM0.77(0.62-0.96)p=0.007 AVID19971016Prior cardiac arrest NA0.62(0.43-0.82)NS CASH†2000191Prior cardiac arrest NA0.766‡1-sided p=0.081 CIDS2000659Prior cardiac arrest, syncope NA0.82(0.60-1.1)NS * Hazard ratios for death from any cause in the ICD group compared with the non-ICD group. Includes only ICD and amiodarone patients from CASH. ‡CI Upper Bound 1.112 CI indicates Confidence Interval, NS = Not statistically significant, NSVT = nonsustained ventricular tachycardia, SAECG = signal-averaged electrocardiogram. Epstein A, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities. J Am Coll Cardiol 2008; 51:e1–62. Table 5.

24. SCD Prevention Trials Antiarrhythmic Vs. Implantable Defibrillator (AVID) [N Engl J Med 1997;337:1576-1583.] Multicenter Unsustained Tachycardia (MUSTT) Trial [N Engl J Med 1996; 1747S-51S] Multicenter Automatic Debrillator Implantation (MADIT II) Trial [N Engl J Med 2002; 346: 877-83.] Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) [NEJM 2005;352:225] Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure Trial (COMPANION) [N Engl J Med. 2004;350:2140-2150]

25. AVID (Antiarrhythmic Vs. Implantable Defibrillator) Purpose: to compare the efficacy of ICD versus antiarrhythmics in patients who survive life-threatening ventricular arrhythmias. Inclusion: –Patient rescustitated from near fatal VF –Patients who have undergone CV from sustained VT with syncope –Or Patients who have undergone CV from sustained VT with severe cardiac symptoms with EF of ≤.40. Primary endpoint: overall mortality.

26. AVID Adapted from: Exner DV, et al. J Am Coll Cardiol 1999; 34:325-333. Screened for participation = 5,989 excluded = 1,368 Registry = 4,621 Randomized = 1,016Not Randomized = 2,101 Discharged with amiodarone or an ICD = 970 Discharged with amiodarone, an ICD, or neither = 1,931 Amiodarone (484) ICD (486) Amiodarone (658) Neither (412) ICD (861)

27. AVID Results YearICD survival (%) AAD survival (%) Reduction in mortality 189.382.339±20 281.674.727 ±21 375.464.131 ±21 N Engl J Med 1997;337:1576-1583

28. Multicenter Unsustained Tachycardia (MUSTT) Trial Hypothesis: Antiarrhythmic therapy guided by EP testing can reduce risk of arrhythmic death and cardiac arrest in patients with: CAD, EF  0.40, and asymptomatic NSVT Primary endpoint: arrhythmic death or cardiac arrest. Secondary endpoint: Total mortality, cardiac mortality, sustained VT.

29. Multicenter Unsustained Tachycardia (MUSTT) Trial N Engl J Med 1996; 1747S-51S

30. MUSTT Results N Engl J Med 1996; 1747S-51S

31. MUSTT Conclusion For CAD patients with EF <.40, asymptomatic NSVT and inducible VT: ICD therapy significantly reduces the incidence of: –Arrhythmic death or cardiac arrest (73% – 76% reduction) –Total mortality (55% – 60% reduction) EP-guided pharmacologic antiarrhythmic therapy provides no survival benefit

32. MULTICENTER AUTOMATIC DEFIBRILLATOR IMPLANTATION TRIAL-II (MADIT-II) 1997-2001 A trial designed to evaluate the effect of prophylactic ICD therapy on survival in patients with prior MI and LV dysfunction. Supported by a research grant from Guidant Corp.

33. MADIT -II: Eligibility Chronic CAD with prior MI EF<0.30 No requirement for NSVT or EPS No upper age limitation

34. Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) 1232 patients ≥ 1 month post-MI and LVEF ≤ 30% Randomized to ICD (n=742) or medical therapy (n=490) No spontaneous or induced arrhythmia required for enrollment 6% absolute and 31% relative risk ↓ in all-cause mortality with ICD therapy (p=0.016) Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-83.

35. MADIT-II: CONCLUSION In coronary patients with LVEF <0.30, prophylactic ICD therapy is associated with 31% reduction in mortality. This improved survival is on top of optimal medical Rx.

36. SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) DCM + CAD and CHF Placebo N = 847 ICD Implant N = 829 Minimum of 2.5 years follow-up required 45 months average follow-up Optimized  B, ACE-I, Diuretics Amiodarone N = 845 EF < 35% NYHA Class II or III 6-Minute Walk, Holter R 2521 Patients Bardy GH. N Engl J Med. 2005;352:225-237.

37. SCD-HeFT Endpoints Primary: Overall Mortality Secondary: Mortality: ischemic vs. non-ischemic Mortality: NYHA Class II vs. III Mortality by Sub Groups: age, gender, LVEF, MI Hx, time of MI, QRS width Cause-Specific Death HF Morbidity and Mortality Quality of Life Cost of Care and Cost-Effectiveness Bardy GH. N Engl J Med. 2005;352:225-237.

38. SCD-HeFT Mortality Rate Overall Results Months of Follow-Up Mortality Rate 483624120 Amiodarone Placebo ICD 0.4 0.3 0.2 0.1 0.0 60 No. at Risk Amiodarone84577271548428097 Placebo84779772450530489 ICD 829778733501304103 Hazard Ratio (97.5% Cl)P-Value Amiodarone vs. Placebo1.06 (0.86 - 1.30)0.53 ICD vs. Placebo0.77 (0.62 - 0.96)0.007 Bardy GH. N Engl J Med. 2005;352:225-237.

39. Sudden Death in Heart Failure (SCD-HeFT) Trial 2521 patients with NYHA Class II or III HF, ICM, or NICM and LVEF ≤ 35% Randomized to 1) conventional rx for HF + placebo; 2) conventional rx + amiodarone; or 3) conventional rx + conservatively programmed shock- only single lead ICD No survival benefit for amiodarone 23% ↓ in overall mortality with ICD therapy Absolute ↓ in mortality of 7.2% after 5 y in the overall population Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-37.

41. COMPANION Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure Trial Bristow M. N Engl J Med. 2004;350:2140-2150.

42. COMPANION Objective: Evaluate the effectiveness of CRT with or without an ICD in reducing the risk of death and hospitalizations in patients with advanced heart failure and intraventricular conduction delays Primary Endpoint: Composite of death from any cause or hospitalization for any cause Secondary Endpoint: Death from any cause Bristow M. N Engl J Med. 2004;350:2140-2150.

43. COMPANION Inclusion Criteria NYHA Class III or IV (ischemic or non-ischemic) LVEF ≤ 35%, LVEDD ≥ 60 mm QRS ≥ 120 ms, PR interval > 150 ms Hx of HF hospitalization 1 month prior to enrollment Bristow M. N Engl J Med. 2004;350:2140-2150.

44. Prospective randomized study 1520 patients randomized 1:2:2 to three arms: –308 Optimal Pharmacological Therapy (OPT) alone –617 OPT + CRT –595 OPT + CRT-D Median follow-up: 11.9 - 16.2 months COMPANION Study Design Bristow M. N Engl J Med. 2004;350:2140-2150.

45. COMPANION All-Cause Death Results Days from Randomization Event-Free Survival (%) 100 90 80 70 60 50 OPT CRT CRT-D (CRT vs. OPT) P = 0.059 (CRT-D vs. OPT) P = 0.003 Bristow M. N Engl J Med. 2004;350:2140-2150. No. at Risk OPT3082842552171861419457452542 CRT61757952048843935525116410460255 CRT-D 5955555174704203312191489547211 9090081072063054036027018009901080450

46. COMPANION Conclusions In patients with advanced heart failure and prolonged QRS: –CRT and CRT-D reduce all-cause death and all cause hospitalizations by 19-20% –CRT reduces all-cause mortality by 24% –CRT-D reduces all-cause mortality by 36% Bristow M. N Engl J Med. 2004;350:2140-2150.

47. Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Trial 1520 patients with NYHA Class III or IV HF, ischemic cardiomyopathy (ICM) or nonischemic cardiomyopathy (NICM) and QRS ≥ 120 ms Randomized 1:2:2 to optimal pharmacological therapy (OPT) alone or in combination with cardiac resynchronization therapy with either a pacemaker (CRT-P) or pacemaker-defibrillator (CRT-D) Both device arms significantly ↓ combined risk of all-cause hospitalization and all-cause mortality by ~20% compared with OPT CRT-D ↓ mortality by 36% compared with OPT (p=0.003) Insufficient evidence to conclude that CRT-P inferior to CRT-D Bristow MR, Saxon LA, Boehmer J, et al. Cardiac- resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-50.

48. Defibrillator in Acute Myocardial Infarction (DINAMIT) Trial 674 patients 6 to 40 days post-MI with LVEF ≤ 35% and impaired cardiac autonomic function Randomized to ICD therapy (n=332) or no ICD therapy (n=342) Arrhythmic death ↓ in ICD group, but ↑ in nonarrhythmic death (6.1% per year vs. 3.5% per year, HR 1.75 (95% CI 1.11 to 2.76; p=0.016) No difference in total mortality Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481-8.

49. Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Trial 458 patients with NYHA Class I to III, NICM, LVEF ≤ 35% and premature ventricular contractions (> 10/h) or NSVT Randomized to standard medical rx alone or in combination with single-chamber ICD Strong trend toward ↓ all-cause mortality with ICD therapy, although not statistically significant (p=0.08) Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004;350:2151-8.

50. 1 The AVID Investigators. N Engl J Med. 1997;337:1576- 1583. 2 Connolly SJ. Circulation. 2000; 101; 1297-1302. 3 Moss AJ. N Engl J Med. 1996;335;1933-1940. 4 Buxton AE. N Engl J Med. 1999; 341:1882-90. 5 Moss AJ. N Engl J Med. 2002 ; 346:877-83. 31% 20% NS 54% 60% AVID 1 3 years CIDS 2 3 years MADIT 3 2 years MUSTT 4 2 years MADIT II 5 2 years 31% ICD Trials Summary

51. Atrial ICD shock for AF Recent implantable cardiac resynchronization (CRT) devices allow electrical therapies to treat AF automatically. TRADE-HF (trial registration: NCT00345592 ; http://www.clinicaltrials.gov webcite http://www.clinicaltrials.govwebcite

52. CRT pacemaker with the additional ability to convert AF as well as ventricular arrhythmias may play a simultaneous role in rhythm control and HF treatment. The value of the systematic implantation of CRT ICDs with the capacity to deliver atrial therapy in HF patients at risk of AF has not yet been explored.

53. Predictors of implantable cardioverter- defibrillator use in patients with ischemic cardiomyopathy.

54. “Reduced left ventricular ejection fraction (LVEF) remains the single most important risk factor for overall mortality and sudden cardiac death.” 1

55. EF and ventricular events Impact of left ventricular ejection fraction on occurrence of ventricular events in defibrillator patients with coronary artery disease. Schaer BSchaer B, Sticherling C, Szili-Torok T, Osswald S, Jordaens L, Theuns DA.Sticherling CSzili-Torok TOsswald S Jordaens LTheuns DA

56. More ICD-therapies occurred in patients with poorer LVEF, but the difference was significant only with the cut-off value of ≤/>20%. Only 2 of 12 parameters were predictors of appropriate ICD therapy

57. Prediction of life-threatening arrhythmias-- still an unresolved problem. Haugaa KHHaugaa KH, Edvardsen T, Amlie JP.Edvardsen TAmlie JP

58. Left ventricular ejection fraction (EF) is currently the main risk stratification tool used to select patients for ICD therapy. However, EF is insufficient in predicting arrhythmic risk. A number of techniques have been presented to improve arrhythmic risk stratification without having reached clinical utility. Conduction abnormalities and dispersion of action potential duration forms the substrate for malignant ventricular arrhythmias in infarcted tissue as in several cardiomyopathies.

59. The ability to assess electrical dispersion in patients noninvasively has been limited. Myocardial strain by echocardiography has been presented as an accurate tool for assessing myocardial function and timing. Inhomogeneous and dispersed myocardial contraction has been related to the occurrence of ventricular arrhythmias and seems to be a promising tool in risk stratification. This review focuses on arrhythmia mechanisms and novel echocardiographic tools for assessing risk of ventricular arrhythmias.

60. Predicting Ventricular Arrhythmias in Patients With Ischemic Heart Disease Clinical Application of the ECG-Derived QRS-T Angle C. Jan Willem BorleffsC. Jan Willem Borleffs, MD, Roderick W.C. ScherptongRoderick W.C. Scherptong, MD, Sum-Che ManSum-Che Man, MD, Guido H. van WelsenesGuido H. van Welsenes, MS, Jeroen J. BaxJeroen J. Bax, MD, PhD, Lieselot van ErvenLieselot van Erven, MD, PhD, Cees A. SwenneCees A. Swenne, PhD and Martin J. SchalijMartin J. Schalij, MD, PhD

61. A wide QRS-T angle is a strong predictor of appropriate device therapy in primary prevention ICD recipients with ischemic heart disease. Furthermore, a spatial QRS-T angle ≤100° might be of value in the identification of patients in whom, although currently indicated, ICD treatment should be reconsidered.

62. Findings suggest that CABG patients with ischemic cardiomyopathy have low rates of ICD utilization. This is particularly evident among females and elderly patients. Furthermore our data suggests that few patients post- revascularization undergo follow-up EF assessment despite current guidelines likely contributing to the low rates of ICD utilization

63. Effect of implantable cardioverter- defibrillator on left ventricular ejection fraction in patients with idiopathic dilated cardiomyopathy.

64. In patients with idiopathic dilated cardiomyopathy, the potential for LVEF improvement is considerable and that the rate of ICD interventions strongly depends on the prevention mode and LVEF. These findings could be the basis for additional risk stratification tools.

65. The results of meta-analysis provide strong evidence for the beneficial effect of ICD-only therapy on the survival of patients with ischaemic or non-ischaemic heart disease, with a left ventricular ejection fraction ≤ 35%, if they are 40 days from myocardial infarction and ≥ 3 months from a coronary revascularization procedure.

67. Indications for ICD Therapy

68. Implantable Cardioverter-Defibrillators ICD therapy is indicated in patients who are survivors of cardiac arrest due to ventricular fibrillation or hemodynamically unstable sustained VT after evaluation to define the cause of the event and to exclude any completely reversible causes. ICD therapy is indicated in patients with structural heart disease and spontaneous sustained VT, whether hemodynamically stable or unstable. ICD therapy is indicated in patients with syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at electrophysiological study. All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.

69. ICD therapy is indicated in patients with LVEF less than or equal to 35% due to prior MI who are at least 40 days post-MI and are in NYHA functional Class II or III. ICD therapy is indicated in patients with nonischemic DCM who have an LVEF less than or equal to 35% and who are in NYHA functional Class II or III. ICD therapy is indicated in patients with LV dysfunction due to prior MI who are at least 40 days post-MI, have an LVEF less than or equal to 30%, and are in NYHA functional Class I. ICD therapy is indicated in patients with nonsustained VT due to prior MI, LVEF less than or equal to 40%, and inducible VF or sustained VT at electrophysiological study. All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable Cardioverter-Defibrillators

70. ICD implantation is reasonable for patients with unexplained syncope, significant LV dysfunction, and nonischemic DCM. ICD implantation is reasonable for patients with sustained VT and normal or near-normal ventricular function. ICD implantation is reasonable for patients with HCM who have 1 or more major † risk factors for SCD. ICD implantation is reasonable for the prevention of SCD in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) who have 1 or more risk factors for SCD. ICD implantation is reasonable to reduce SCD in patients with long-QT syndrome who are experiencing syncope and/or VT while receiving beta blockers. I IIaIIbIII All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. † See Section 3.2.4, “Hypertrophic Cardiomyopathy,” in the full-text guidelines for definition of major risk factors. I IIaIIbIII I IIaIIbIII I IIaIIbIII I IIaIIbIII Implantable Cardioverter-Defibrillators

71. ICD implantation is reasonable for nonhospitalized patients awaiting transplantation. ICD implantation is reasonable for patients with Brugada syndrome who have had syncope. ICD implantation is reasonable for patients with Brugada syndrome who have documented VT that has not resulted in cardiac arrest. ICD implantation is reasonable for patients with catecholaminergic polymorphic VT who have syncope and/or documented sustained VT while receiving beta blockers. ICD implantation is reasonable for patients with cardiac sarcoidosis, giant cell myocarditis, or Chagas disease. I IIaIIbIII I IIaIIbIII I IIaIIbIII I IIaIIbIII I IIaIIbIII All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable Cardioverter-Defibrillators

72. ICD therapy may be considered in patients with nonischemic heart disease who have an LVEF of less than or equal to 35% and who are in NYHA functional Class I. ICD therapy may be considered for patients with long-QT syndrome and risk factors for SCD. ICD therapy may be considered in patients with syncope and advanced structural heart disease in whom thorough invasive and noninvasive investigations have failed to define a cause. ICD therapy may be considered in patients with a familial cardiomyopathy associated with sudden death. ICD therapy may be considered in patients with LV noncompaction. I IIaIIbIII I IIaIIbIII I IIaIIbIII I IIaIIbIII All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable Cardioverter-Defibrillators

73. ICD therapy is not indicated for patients who do not have a reasonable expectation of survival with an acceptable functional status for at least 1 year, even if they meet ICD implantation criteria specified in the Class I, IIa, and IIb recommendations above. ICD therapy is not indicated for patients with incessant VT or VF. ICD therapy is not indicated in patients with significant psychiatric illnesses that may be aggravated by device implantation or that may preclude systematic follow-up. ICD therapy is not indicated for NYHA Class IV patients with drug-refractory congestive heart failure who are not candidates for cardiac transplantation or cardiac resynchronization therapy defibrillators (CRT-D). All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable Cardioverter-Defibrillators

74. ICD therapy is not indicated for syncope of undetermined cause in a patient without inducible ventricular tachyarrhythmias and without structural heart disease. ICD therapy is not indicated when VF or VT is amenable to surgical or catheter ablation (e.g., atrial arrhythmias associated with the Wolff-Parkinson-White syndrome, RV or LV outflow tract VT, idiopathic VT, or fascicular VT in the absence of structural heart disease). ICD therapy is not indicated for patients with ventricular tachyarrhythmias due to a completely reversible disorder in the absence of structural heart disease (e.g., electrolyte imbalance, drugs, or trauma). All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable Cardioverter-Defibrillators

75. ICDs in Pediatric Patients and Patients With Congenital Heart Disease ICD implantation is indicated in the survivor of cardiac arrest after evaluation to define the cause of the event and exclusion of any reversible causes. ICD implantation is indicated for patients with symptomatic sustained VT in association with congenital heart disease who have undergone hemodynamic and electrophysiological evaluation. Catheter ablation or surgical repair may offer possible alternatives in carefully selected patients. All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.

76. ICDs in Pediatric Patients and Patients With Congenital Heart Disease ICD implantation is reasonable for patients with congenital heart disease with recurrent syncope of undetermined origin in the presence of either ventricular dysfunction or inducible ventricular arrhythmias at electrophysiological study. ICD implantation may be considered for patients with recurrent syncope associated with complex congenital heart disease and advanced systemic ventricular dysfunction when thorough invasive and noninvasive investigations have failed to define a cause. All Class III recommendations found in Section 3 of the full-text guidelines, “Indications for Implantable Cardioverter-Defibrillator Therapy,” apply to pediatric patients and patients with congenital heart disease, and ICD implantation is not indicated in these patient populations. All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.

77. Summary Primary Prevention: –ICMP: EF ≤ 35% at least 1 month post MI or 3 months post revascularization. EF ≤ 40% with NSVT and inducible VT. –NICMP: EF ≤ 35% for at least 3 months. Must have NYHA class II or III.

78. Summary Secondary Prevention: –SCD due to VF or VT (not reversible cause) –Sustained VT/VF with structural heart disease –Recurrent syncope with inducible VT/VF. Special situations: –Recurrent unexplained syncope (for EPS) –Familial disease with symptoms.

79. Take home message The vast majority of cases of SCD are due to ventricular arrhythmias The causes of SCD is different in different age groups The most effective strategy for prevention of SCD is implantable cardioverter defibrillator (ICD) Strictly speaking, most victims of SCD can not be the donor of heart transplantation

80. Delayed lateral wall contraction Disorganized ventricular contraction Decreased pumping efficiency Sinus node AV node Conduction block Cardiac Resynchronization

81. Courtesy of C. Stellbrink, MD. Dysynchrony Healthy Abnormal wall motion

82. Intraventricular Activation Organized ventricular activation sequence Coordinated septal and free-wall contraction Improved pumping efficiency Ventricular resynchronization Sinus node AV node Stimulation therapy Conduction block

83. Baseline DCM with CRT Courtesy of C. Stellbrink, MD. Cardiac resynchronization therapy (CRT)

84. ACC/AHA Classification of Recommendations Class I: –Conditions for which there is evidence and/or general agreement that a given procedure or treatment is beneficial, useful, and effective Class II: –Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment –Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy –Class IIb: Usefulness/efficacy is less well established by evidence/opinion Class III: –Conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/effective and in some cases may be harmful

85. Class I Cardiac arrest due to VF or VT not due to a transient or reversible cause. Spontaneous sustained VT in association with structural heart disease. Spontaneous sustained VT in patients without structural heart disease not amenable to other treatments Syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at electrophysiologic study when drug therapy is ineffective, not tolerated, or not preferred.

86. ICD therapy is indicated in patients with LVEF less than 35% due to prior MI who are at least 40 days post-MI and are in NYHA functional Class II or III. ICD therapy is indicated in patients with LV dysfunction due to prior MI who are at least 40 days post-MI, have an LVEF less than or equal to 30%, and are in NYHA functional Class I. ICD therapy is indicated in patients with nonischemic DCM who have an LVEF less than or equal to 35% and who are in NYHA functional Class II or III. ICD therapy is indicated in patients with nonsustained VT due to prior MI, LVEF less than 40%, and inducible VF or sustained VT at electrophysiological study. All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable Cardioverter-Defibrillators

87. CRT Guideline LVEF less than or equal to 35%, NYHA functional class III or ambulatory class IV symptoms despite recommended, optimal medical therapy cardiac dyssynchrony: QRS duration greater than 120 ms, Supporting Clinical Trials 1.MIRACLE: Abraham WT. N Engl J Med 2002;346:1845-1853. 2.COMPANION: 2 Bristow M. N Engl J Med 2004;350:1140-1150. 3.CARE-HF: Cleland JGF. N Engl J Med 2005;352:1539-1549.

88. MADIT-CRT Ischemic heart disease (NYHA Class I or II) or non-ischemic heart disease (NYHA Class II) for at least three months prior to entry Optimal pharmacologic therapy Left ventricular ejection fraction ≤ 30% QRS duration ≥ 130 ms, sinus rhythm Primary endpoint: of all-cause mortality or heart failure events. Secondary endpoint: Risk of recurrent heart failure events Moss AJ, et al. N Engl J Med. 2009;361:1329-1338.

89. 89 MADIT-CRT: Methods Enrollment –1820 patients, 110 centers, 14 countries Average follow-up –34.3 months Moss AJ, et al. N Engl J Med. 2009;361:1329-1338. Baseline Evaluation To document inclusion/exclusion criteria and establish baseline heart status Randomization (3:2 CRT-D:ICD) Stratified by center and ischemic status Clinic Follow-up Visits 1 month post-enrollment/randomization, 3 months post- randomization, and quarterly thereafter to a common study closure date CRT-D + OPT (1089 patients) ICD + OPT (731 patients) a Baseline evaluation includes history and physical exam, electrocardiogram, and echocardiogram. Patients are randomized and then baseline testing is completed including BNP (US only), quality-of-life assessment, 6-minute walk test, and Holter monitor recording (CRT-D patients only). b The 12-month follow-up visit includes echocardiogram, BNP (US only), 6-minute walk test, Holter monitor recording (CRT-D patients only), and device interrogation. Other follow-up visits include history and physical exam, clinical events, and device interrogation. Quality-of-life assessments were conducted at 6-month intervals. 89

90. Previously Published and Updated Results Results showed that CRT-D was associated with a 34% reduction in the relative risk of the primary endpoint Additional 6 months of data analyzed It was subsequently discovered and validated that in the LBBB subgroup, patients received substantial benefit from CRT-D. Non-LBBB patients did not show evidence of benefit. The LBBB sub-group made up approximately 70% of the total MADIT-CRT population. 34% 57% Moss AJ, et al. N Engl J Med. 2009;361:1329-1338.