5Case VignetteA 74-year-old man with a history of hypertension and myocardial infarction that occurred 5 years previously presents with breathlessness on exertion.His current medications include a statin and aspirin.On examination, his pulse is 76 beats per minute and regular, and his blood pressure is 121/74 mm Hg.There is jugular venous distention, lateral displacement of the apex beat, and edema in his lower limbs.The lung examination is normal.An echocardiogram shows left ventricular dilatation, globally reduced contractility, and an ejection fraction of 33%.How should his case be managed?
6Pathophysiology of Systolic Heart Failure McMurray J. N Engl J Med 2010;362:
7Clinical Classifications of Heart Failure Severity McMurray J. N Engl J Med 2010;362:
8Treatment Algorithm for Systolic Heart Failure McMurray J. N Engl J Med 2010;362:
9Telemetry Strip Showing Pause-Independent Polymorphic Ventricular Tachycardia. Figure 1. Telemetry Strip Showing Pause-Independent Polymorphic Ventricular Tachycardia.Britton KA et al. N Engl J Med 2010;362:
10Sudden Cardiac Death (SCD) Death from unexpected circulatory arrest, usually due to cardiac arrhythmia occurring within an hour of the onset of symptoms.Sudden Cardiac Arrest (SCA)- Episode of resuscitated SCD
11Sudden Cardiac DeathEstimates range 200, , 000 SCD’s annually depending on the definition used.13% of all natural deaths are SCD using the 1 hour definition.50% of all CHD deaths are sudden.Overall incidence of SCD 1 to 2/1000 population.
14Implantable Cardioverter Defibrillator (ICD) Secondary Prevention- Multiple studies have shown a 50% relative-risk reduction in arrhythmic death and a 25% relative- risk reduction in all-cause mortality. Patients who die once are more likely to die again.
15Primary Prevention of SCD Patients with a history of myocardial infarction and a reduced ejection fraction are at increased risk for life-threatening ventricular arrhythmias.Which of these patients are the most appropriate candidates for implantable cardioverter–defibrillator (ICD) therapy is unclear.
16Summary of Major Randomized Trials of ICD Therapy for Primary Prevention of Sudden Death after Myocardial InfarctionMyerburg R. N Engl J Med 2008;359:
17Amiodarone or an Implantable Cardioverter-Defibrillator for Congestive Heart Failure Gust H. Bardy, M.D., Kerry L. Lee, Ph.D., Daniel B. Mark, M.D., Jeanne E. Poole, M.D., Douglas L. Packer, M.D., Robin Boineau, M.D., Michael Domanski, M.D., Charles Troutman, R.N., Jill Anderson, R.N., George Johnson, B.S.E.E., Steven E. McNulty, M.S., Nancy Clapp-Channing, R.N., M.P.H., Linda D. Davidson-Ray, M.A., Elizabeth S. Fraulo, R.N., Daniel P. Fishbein, M.D., Richard M. Luceri, M.D., John H. Ip, M.D. and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) InvestigatorsN Engl J MedVolume 352;3:January 20, 2005
18Study OverviewThis placebo-controlled study compared the effect of amiodarone and an implantable cardioverter-defibrillator (ICD) on mortality in patients with New York Heart Association class II or III congestive heart failure (CHF)Amiodarone had no benefit overall and slightly increased mortality among patients with class III CHFICD therapy reduced mortality overall, but the benefit appeared to be restricted to patients with class II CHFThese important results will broaden the use of ICD therapy
19Minimum of 2.5 years follow-up required 45 months average follow-up SCD-HeFT ProtocolDCM + CAD and CHFEF < 35%NYHA Class II or III6-Minute Walk, HolterR2521 PatientsPlacebo N = 847Amiodarone N = 845ICD Implant N = 829Minimum of 2.5 years follow-up required45 months average follow-upOptimized B, ACE-I, DiureticsBardy GH. N Engl J Med. 2005;352:
20Kaplan-Meier Estimates of Death from Any Cause Bardy, G. et al. N Engl J Med 2005;352:
21Kaplan-Meier Estimates of Death from Any Cause for the Prespecified Subgroups of Ischemic CHF (Panel A) and Nonischemic CHF (Panel B)Bardy, G. et al. N Engl J Med 2005;352:
22Kaplan-Meier Estimates of Death from Any Cause for the Prespecified Subgroups of NYHA Class II (Panel A) and Class III (Panel B)Bardy, G. et al. N Engl J Med 2005;352:
23Hazard Ratios for the Comparison of Amiodarone and ICD Therapy with Placebo in Various Subgroups of InterestBardy, G. et al. N Engl J Med 2005;352:
24ConclusionsIn patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent
25Incremental Cost-Effectiveness Cardiovascular Interventions $200,000EconomicallyUnattractive$150,000$135,000$120,000Incremental Cost per Life-Year SavedExpensive$67,000BorderlineCost-Effective$40,750Cost-Effective$17,701Highly Cost-Effective$8,461PTCA(chronic CAD, severe angina 1 VD)CABG(chronic CAD mild angina, 3 VD)Hypertension Therapy (diastolic mmHg)End Stage Renal Disease TreatmentExercise SPECT (atypical angina who can walk on treadmill)Lovastatin (chol. = 290 mg/dL, 50 yrs old,male, no risk factors)Carotid Disease Screening(65 yrs old,male, no symptoms)Routine Coronary Angiography( yrs old,low risk MI, has CHF)
26Incremental Cost-Effectiveness ICD, CRT, and CRT-D Therapies EconomicallyUnattractiveIncremental Cost per Life-Year SavedExpensive$67,000$50,000BorderlineCost-Effective$28,000$33,000$38,200Cost-EffectiveHighly Cost-EffectiveCOMPANION CRT1SCD-HeFT ICD2COMPANION CRT-D1MADIT-II ICD3AVID ICD41 Feldman AM. ACC News. March 16, 2005.2 Mark DB. AHA News. November 11, 2004.3 Ak-Khatib S. Ann Intern Med. 2005;142:4 Larsen G. Circulation. 2002;105:
27Original Article Defibrillator Implantation Early after Myocardial Infarction Gerhard Steinbeck, M.D., Dietrich Andresen, M.D., Karlheinz Seidl, M.D., Johannes Brachmann, M.D., Ellen Hoffmann, M.D., Dariusz Wojciechowski, M.D., Zdzisława Kornacewicz-Jach, M.D., Beata Sredniawa, M.D., Géza Lupkovics, M.D., Franz Hofgärtner, M.D., Andrzej Lubinski, M.D., Mårten Rosenqvist, M.D., Alphonsus Habets, Ph.D., Karl Wegscheider, Ph.D., Jochen Senges, M.D., for the IRIS InvestigatorsN Engl J MedVolume 361(15):October 8, 2009
28Study OverviewImplantation of a defibrillator early after myocardial infarction (MI) in high-risk patients reduced the risk of sudden cardiac death, but there was a reciprocal increase in the risk of nonsudden cardiac deathOverall mortality was not affected by early defibrillator implantation, and therefore this intervention cannot be recommended after MI in high-risk patients
29Baseline Demographic and Clinical Characteristics of the Patients, According to Study Group Table 1. Baseline Demographic and Clinical Characteristics of the Patients, According to Study Group.Steinbeck G et al. N Engl J Med 2009;361:
30Cumulative Risk of Death from Any Cause According to Study Group Figure 1. Cumulative Risk of Death from Any Cause According to Study Group. At the close of the study, definitive information about vital status was available for 897 patients. One patient was lost to follow-up. For patients who withdrew their consent, data were censored at the time of withdrawal. ICD denotes implantable cardioverter-defibrillator.Steinbeck G et al. N Engl J Med 2009;361:
31Cumulative Risk of Cardiac Death, According to Study Group Figure 3. Cumulative Risk of Cardiac Death, According to Study Group. The cumulative risk of sudden cardiac death is shown in Panel A, and the cumulative risk of nonsudden cardiac death is shown in Panel B. ICD denotes implantable cardioverter-defibrillator.Steinbeck G et al. N Engl J Med 2009;361:
32ConclusionProphylactic ICD therapy did not reduce overall mortality among patients with acute myocardial infarction and clinical features that placed them at increased risk
33ICD implantation Post Acute MI Acute MI-Sudden Cardiac Death paradox firmly establishedSCD post-MI may not be due to arrhythmia alonePotential deleterious effect of ICD implantation and testing?
34Volume 7, Issue 10, Pages 1396-1403 (October 2010) Sudden cardiac death after myocardial infarction in patients with type 2 diabetesM. Juhani Junttila, MD, Petra Barthel, MD, Robert J. Myerburg, MD, Timo H. Mäkikallio, MD, Axel Bauer, MD, Kurt Ulm, PhD, Antti Kiviniemi, PhD, Mikko Tulppo, PhD, Juha S. Perkiömäki, MD, Georg Schmidt, MD and Heikki V. Huikuri, MDHeart RhythmVolume 7, Issue 10, Pages (October 2010)DOI: /j.hrthm
35Sudden cardiac death after myocardial infarction in patients with type 2 diabetes Study population included enrollees in two prospective post-MI studies: Multiple Risk Factor Analysis Trial and Improved Stratification of Autonomic Regulation for Risk Prediction postinfarction survey program.3276 acute MI patientsDiabetic vs Non Diabetic patients: Mean Age 64 vs 59 years, 32 vs 22% females, LVEF 49% vs 52, 3 vs CAD 42 vs 30%
36Figure 1Incidence of non–sudden cardiac death (non-SCD) and sudden cardiac death (SCD) in type 2 diabetic and nondiabetic patients after acute myocardial infarction. A: Kaplan-Meier curve for non-SCD shows the significant difference between diabetic and nondiabetic patients. The difference becomes evident early after myocardial infarction. B: Curve for SCD illustrates the significant difference of SCD incidence between diabetic and nondiabetic patients. The slope of the accelerated portion of the delayed SCD risk curve is much steeper for diabetic patients than for nondiabetic patients.
37Figure 2Kaplan-Meier curves illustrate the difference in incidence of non–sudden cardiac death (Non-SCD; A) and sudden cardiac death (SCD; B) for diabetic patients with left ventricular ejection fraction (EF) >35% and nondiabetic patients in the same EF group. The curves also illustrate the identical incidence of SCD between diabetic patients with EF >35% and nondiabetic patients with EF ≤35% and the significantly higher incidence of non-SCD in the latter group compared to diabetic patients with EF >35%. Diabetic patients with EF ≤35% have an extraordinary high incidence of sudden cardiac death after myocardial infarction. DM = type 2 diabetes mellitus.
38Aggregate National Experience With the Wearable Cardioverter-Defibrillator: Event Rates, Compliance, and Survival Chung et al. JACC. 2010;56;1943,569 patientsIndications: ICD explants (23.4%), VT/VF (16.1%), LVEF ≤ 35% with Recent MI (12.5%), Post-CABG (8.9%), Nonischemic CM (20.0%), and LVEF> 35% with recent MI (3.8%)
42Original Article An Entirely Subcutaneous Implantable Cardioverter-Defibrillator Gust H. Bardy, M.D., Warren M. Smith, M.B., Margaret A. Hood, M.B., Ian G. Crozier, M.B., Iain C. Melton, M.B., Luc Jordaens, M.D., Ph.D., Dominic Theuns, Ph.D., Robert E. Park, M.B., David J. Wright, M.D., Derek T. Connelly, M.D., Simon P. Fynn, M.D., Francis D. Murgatroyd, M.D., Johannes Sperzel, M.D., Jörg Neuzner, M.D., Stefan G. Spitzer, M.D., Andrey V. Ardashev, M.D., Ph.D., Amo Oduro, M.B., B.S., Lucas Boersma, M.D., Ph.D., Alexander H. Maass, M.D., Isabelle C. Van Gelder, M.D., Ph.D., Arthur A. Wilde, M.D., Ph.D., Pascal F. van Dessel, M.D., Reinoud E. Knops, M.D., Craig S. Barr, M.B., Pierpaolo Lupo, M.D., Riccardo Cappato, M.D., and Andrew A. Grace, M.B., Ph.D.N Engl J MedVolume 363(1):36-44July 1, 2010
43Locations of the Components of a Subcutaneous Implantable Cardioverter-Defibrillator In Situ Figure 2. Locations of the Components of a Subcutaneous Implantable Cardioverter-Defibrillator In Situ. The distal and proximal sensing electrodes (D and P, respectively) of the LGen-S8 device are shown, with the left lateral pulse generator and an 8-cm parasternal coil electrode (C).Bardy GH et al. N Engl J Med 2010;363:36-44
44Chest Radiographs and an Electrocardiogram in a Patient Who Underwent Placement and Testing of a Subcutaneous Implantable Cardioverter-Defibrillator (ICD)Figure 4. Chest Radiographs and an Electrocardiogram in a Patient Who Underwent Placement and Testing of a Subcutaneous Implantable Cardioverter-Defibrillator (ICD). The radiographs in Panels A and B show the locations of the electrode and pulse generator of a subcutaneous ICD in a 54-year-old man who was evaluated in the pilot study. Panel C shows an electrocardiogram of an episode of induced ventricular fibrillation and its termination in the patient. The subcutaneous ICD was being evaluated for primary prevention in the patient, who had coronary disease, New York Heart Association class II heart failure with an ejection fraction of 15%, and obstructive lung disease; the patient's weight was 92 kg (203 lb).Bardy GH et al. N Engl J Med 2010;363:36-44
46Case VignetteA 55-year-old man who had had an anterior-wall myocardial infarction six months previously is admitted with an exacerbation of congestive heart failure.An electrocardiogram shows sinus rhythm with a left bundle-branch block; an echocardiogram demonstrates a left ventricular ejection fraction of 25 percent.He is treated with furosemide, lisinopril, and carvedilol.However, during an office visit three months later, he reports persistent shortness of breath with mild exertion.He is referred to a cardiologist, who recommends implantation of a biventricular pacemaker.
47The Cardiac Conduction System and Biventricular Pacing Jarcho J. N Engl J Med 2006;355:
48The Cardiac Conduction System and Biventricular Pacing In patients with a LBBB, conduction of the wave of depolarization in the left ventricle is markedly altered, proceeding from the anterior septum through the left ventricular myocardium to the inferior and lateral left ventricular walls- left ventricular contraction is dyssynchronous, mechanically inefficient with decreases in left ventricular ejection farction and cardiac output.
53CRT IndicationsClass I- EF ≤ 35%, QRS ≥ 0.12 sec, SR, NYHA III/ Ambulatory Class IV + OMT- CRT±ICDClass IIA- EF ≤ 35%, QRS ≥ 0.12 sec, AF, NYHA III/ Ambulatory Class IV + OMT- CRT±ICD
54Original Article Cardiac-Resynchronization Therapy for the Prevention of Heart-Failure Events Arthur J. Moss, M.D., W. Jackson Hall, Ph.D., David S. Cannom, M.D., Helmut Klein, M.D., Mary W. Brown, M.S., James P. Daubert, M.D., N.A. Mark Estes, III, M.D., Elyse Foster, M.D., Henry Greenberg, M.D., Steven L. Higgins, M.D., Marc A. Pfeffer, M.D., Ph.D., Scott D. Solomon, M.D., David Wilber, M.D., Wojciech Zareba, M.D., Ph.D., for the MADIT-CRT Trial InvestigatorsN Engl J MedVolume 361(14):October 1, 2009
55Kaplan-Meier Estimates of the Probability of Survival Free of Heart Failure Figure 2. Kaplan-Meier Estimates of the Probability of Survival Free of Heart Failure. There was a significant difference in the estimate of survival free of heart failure between the group that received cardiac-resynchronization therapy plus an implantable cardioverter-defibrillator (CRT-ICD) and the group that received an ICD only (unadjusted P<0.001 by the log-rank test).Moss AJ et al. N Engl J Med 2009;361:
56ConclusionCRT combined with ICD decreased the risk of heart- failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex
57MADIT-CRT Editorial- Mariell Jessup, MD CRT benefit solely driven by a 41% reduction in risk of first heart failure event, since mortality not influenced.In CRT trials with symptomatic patients, 29 patients need to be treated for 6 months, 13 patients for 2 years and 9 patients for 3 years to prevent 1 death.MADIT CRT enrolled patients with stage C and NOT stage B (truly asymptomatic).MADIT CRT- treat 12 patients to prevent 1 heart failure hospitalization
58Cardiac Resynchronization- Effect of Bundle Branch Block Analyzed the results of MADIT-CRT1820 patients, NYHA I/II, LVEF≤ 30%, QRS ≥130 ms, on optimal medical therapy1281 LBBB, 228 RBBB, 308 IVCDHazard ratios for the primary end-point of death or heart failure event were significantly lower in the LBBB patients than in the non- LBBB patient.Zareba et al. JACC 2011
59Cardiac Resynchronization In Hypertrophic Obstructive Cardiomyopathy Biventricular pacing was attempted in 12 severely symptomatic HOCM patients and was successful in 9 patients.Functional capacity and QOL improvedNYHA class decreased from 3.2±0.4 at baseline to 1.4±0.5 at 1 year with a reduction in the LV gradient from 74±23 mmHg at baseline to 28±17 mmHg at 1 year.Berruezo et al. Heart Rhythm 2011
60US Registry of Sudden Death in Athletes Healthy young competitive athletes assembled over 27 years, 1,866 died suddenly (or survived cardiac arrest).Sudden death were due to cardiovascular disease in 56% and 82% occurred with physical exertion.HCM – 36% and congenital coronary anomalies- 17%Pre-participation screening with history, PE and EKG did not impact the rate of sudden death.Maron et al. Circ. 2009;119:1085
70Original Article Lenient versus Strict Rate Control in Patients with Atrial Fibrillation Isabelle C. Van Gelder, M.D., Hessel F. Groenveld, M.D., Harry J.G.M. Crijns, M.D., Ype S. Tuininga, M.D., Jan G.P. Tijssen, Ph.D., A. Marco Alings, M.D., Hans L. Hillege, M.D., Johanna A. Bergsma-Kadijk, M.Sc., Jan H. Cornel, M.D., Otto Kamp, M.D., Raymond Tukkie, M.D., Hans A. Bosker, M.D., Dirk J. Van Veldhuisen, M.D., Maarten P. Van den Berg, M.D., for the RACE II InvestigatorsN Engl J MedVolume 362(15):April 15, 2010
71Study OverviewThis clinical trial of outcomes in patients with atrial fibrillation showed that lenient rate control (resting heart rate, <110 beats per minute) was not inferior to strict rate control (resting heart rate, <80 beats per minute)On the basis of the results, strict rate control may be abandoned as a therapeutic strategy in many patients with permanent atrial fibrillation
72Cumulative Incidence of the Composite Primary Outcome and Its Components during the 3-Year Follow-up Period, According to Treatment GroupTable 3. Cumulative Incidence of the Composite Primary Outcome and Its Components during the 3-Year Follow-up Period, According to Treatment Group.Van Gelder IC et al. N Engl J Med 2010;362:
73Kaplan-Meier Estimates of the Cumulative Incidence of the Primary Outcome, According to Treatment GroupFigure 2. Kaplan-Meier Estimates of the Cumulative Incidence of the Primary Outcome, According to Treatment Group. The numbers at the end of the Kaplan-Meier curves are the estimated cumulative incidence of the primary outcome at 3 years.Van Gelder IC et al. N Engl J Med 2010;362:
74ConclusionIn patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve
81AF guidelines update 2011-Dabigatran Class IDabigatran is useful as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with paroxysmal to persistent AF and risk factors for stroke or systemic embolization who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (creatinine clearance < 15 ml/min) or advanced liver disease (impaired baseline clotting function). Level of evidence B
83Catheter ABlation versus ANtiarrhythmic Drug Therapy in Atrial Fibrillation (CABANA) Trial Mayo Clinic RochesterDuke Clinical Research InstituteNational Heart Lung and Blood InstituteCP Packer, DL maCP Packer, DL MC
84Future of AF--ATRIA Study Projected Number of Adults with AF in the U Future of AF--ATRIA Study Projected Number of Adults with AF in the U.S.Upper scenarios based on sensitivity analysesLower scenarios based on sensitivity analysesMillionsYearGo et al: JAMA 285:2370, 2001CP Packer, DL maCP Packer, DL MC
85Impact of Atrial Fibrillation on Mortality in Framingham Study 55-74 Years Old75-94 Years OldMen AFWomen AFMen no AFWomen no AFDead (%)Follow-up (yr)Follow-up (yr)Benjamin et al: Circ 98:946, 1998CP Packer, DL maCP Packer, DL MC
86CABANA Trial Inclusion Criteria Subjects must meet all of the following criteriaHave documented AF episodes 1 hour in duration; with 2 episodes over 4 months with ECG documentation of 1 episode or at least 1 episode of AF lasting >1 weekWarrant active therapy beyond simple ongoing observationBe eligible for catheter ablation and 2 sequential rhythm control and/or 3 rate control drugsBe 65 yr of age, or <65 yr with 1 of the following risk factors for strokeHypertensionDiabetesCongestive heart failure (including systolic or diastolic heart failure)Prior stroke or TIALA size >5.0 cm (or volume index 40 cc/m2)EF 35
87Primary Objective and Hypothesis CABANA TrialPrimary Objective and HypothesisThe treatment strategy of percutaneous left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) is superior to current state-of-the-art medical therapy with either rate control or rhythm control drugs for reducing total mortality (primary endpoint) and decreasing the composite endpoint of total mortality, disabling stroke, serious bleeding, or cardiac arrest (key secondary endpoint) in patients with untreated or incompletely treated AF warranting therapy
88Design of the CABANA Study Atrial fibrillationEligible for ablation and/or drug therapy65 yr of age<65 yr w/ 1 CVA risk factorRDrug Rx & ACRate controlRhythm Rx1° ablation & ACPV isolationAdjunctiveDescriptive analysisNSR vs AF impactw/ w/o heart diseaseAF type – (paroxysmal; persistent; long-standing persistent)CT/MR image analysisECG/EGM analysisFollow-up60 months
89CABANA Sites International Approach Canada 10UK 10Europe 30U.S. 90Asia 5South Am 5Australia NZ 5