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New Paradigms in the Prevention of Sudden Cardiac Arrest and Heart Failure Treatment

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Abstract

Congestive heart failure is a very real public health issue not only in the United States, but worldwide. Mortality in patients with congestive heart failure is typically either sudden cardiac death or pump failure. Paradoxically, patients with less severe heart failure are at higher relative risk of sudden cardiac death. Defining which patients are best treated with implantable defibrillators and resynchronization is the purpose of this review.

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Abbreviations

ADVANCE CRT-D:

Antitachycardia Pacing (ATP) Delivery for Painless Implantable Cardioverter Defibrillator (ICD) Therapy

BEST:

Beta-Blocker Evaluation in Survival Trial

CARE-HF:

Cardiac Resynchronization in Heart Failure

COMPANION:

Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure

DINAMIT:

Defibrillators in Acute Myocardial Infarction Trial

EMPHASIS-HF:

A Comparison of Outcomes in Patients in New York Heart Association (NYHA) Class II Heart Failure When Treated with Eplerenone or Placebo in Addition to Standard Heart Failure Medicines

IRIS:

Immediate Risk Stratification Improves Survival

MADIT-CRT:

Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy

MADIT-II:

Multicenter Automatic Defibrillator Implantation Trial 2

MIRACLE:

Multicenter InSync Randomized Clinical Evaluation

MUSIC:

Muerte Subita en Insuficiencia Cardiaca

RAFT:

Resynchronization/Defibrillation for Ambulatory Heart Failure Trial

REVERSE:

Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction

SCD-HeFT:

Sudden Cardiac Death in Heart Failure

VALIANT:

Valsartan in Acute Myocardial Infarction Trial.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2011 update: a report from the American heart association. Circulation. 2011;123(4):e18–209. This is the latest update from the AHA highlighting heart disease and stroke statistics.

    Article  PubMed  Google Scholar 

  2. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics—2009 update: a report from the American heart association statistics committee and stroke statistics subcommittee. Circulation. 2009;119(3):e21–e181.

    Article  PubMed  Google Scholar 

  3. Zafrir B, Paz H, Wolff R, et al. Mortality rates and modes of death in heart failure patients with reduced versus preserved systolic function. Eur J Intern Med. 2011;22(1):53–6.

    Article  PubMed  Google Scholar 

  4. Stevenson WG, Stevenson LW, Middlekauff HR, Saxon LA. Sudden death prevention in patients with advanced ventricular dysfunction. Circulation. 1993;88(6):2953–61.

    PubMed  CAS  Google Scholar 

  5. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352(3):225–37.

    Article  PubMed  CAS  Google Scholar 

  6. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004;350(21):2151–8.

    Article  PubMed  CAS  Google Scholar 

  7. •• Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361(14):1329–38. In this randomized prospective trial, patients with mildly symptomatic heart failure with depressed EF and prolonged QRS duration had a decrement in heart failure and overall mortality when CRT-D was placed rather than ICD alone.

    Article  PubMed  Google Scholar 

  8. Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Woo MA, Tillisch JH. The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol. 2001;38(3):789–95.

    Article  PubMed  CAS  Google Scholar 

  9. • Choy B, Hansen E, Moss AJ, et al. Relation of body mass index to sudden cardiac death and the benefit of implantable cardioverter-defibrillator in patients with left ventricular dysfunction after healing of myocardial infarction. Am J Cardiol. 2010;105(5):581–6. In the MADIT-II population, this analysis demonstrated that with every 5-unit BMI decrement, all-cause mortality increased by 23% (P = 0.009) and SCD increased by 41% (P = 0.04).

    Article  PubMed  Google Scholar 

  10. • Gastelurrutia P, Pascual-Figal D, Vazquez R, et al. Obesity paradox and risk of sudden death in heart failure results from the MUerte subita en insuficiencia cardiaca (MUSIC) study. Am Heart J. 2011;161(1):158–64. In mild-moderate chronic heart failure, every unit BMI increase led to a decrement in heart failure and overall mortality. There was no significant correlation with SCD.

    Article  PubMed  Google Scholar 

  11. • Patton KK, Sotoodehnia N, DeFilippi C, Siscovick DS, Gottdiener JS, Kronmal RA. N-terminal pro-B-type natriuretic peptide is associated with sudden cardiac death risk: The cardiovascular health study. Heart Rhythm. 2011;8(2):228–33. In this analysis of the Cardiovascular Health Study, NT-BNP was predictive of SCD when adjusting for numerous clinical characteristics and risk factors, with an adjusted HR for the fifth versus the first quintile of 2.5 (P < 0.001).

    Article  PubMed  Google Scholar 

  12. • Kanoupakis EM, Manios EG, Kallergis EM, et al. Serum markers of collagen turnover predict future shocks in implantable cardioverter-defibrillator recipients with dilated cardiomyopathy on optimal treatment. J Am Coll Cardiol. 2010;55(24):2753–9. In 70 patients with mild to moderate symptomatic heart failure with LVEF less than 35% who received ICD, serum concentrations of C-terminal telopeptide of collagen type I levels, MMP-1, and tissue inhibitor of MMP-1 were higher in patients who received appropriate ICD therapy than in those who did not require any therapy.

    Article  PubMed  CAS  Google Scholar 

  13. • Chan PS, Gold MR, Nallamothu BK. Do beta-blockers impact microvolt T-wave alternans testing in patients at risk for ventricular arrhythmias? A meta-analysis. J Cardiovasc Electrophysiol. 2010;21(9):1009–14. This is a meta-analysis of nine prospective studies that evaluated MTWA. In the four studies in which β blockers were continued for MTWA, there was a fivefold increased risk of arrhythmic events (pooled RR, 5.39; P < 0.001). Conversely, when β blockers were held the association between MTWA and arrhythmic events was much less robust.

    Article  PubMed  Google Scholar 

  14. • Strauss DG, Poole JE, Wagner GS, et al. An ECG index of myocardial scar enhances prediction of defibrillator shocks: an analysis of the sudden cardiac death in heart failure trial. Heart Rhythm. 2011;8(1):38–45. A novel 12-lead electrocardiographic Selvester QRS scoring was applied to 797 patients enrolled in the ICD arm of the SCD-HeFT trial. Over a median 45.5 months of follow-up, patients with absence of scar (QRS score = 0) had 48% fewer VT/VF events than the rest of the population (95% CI, 0.31–0.88). The predictive value of the QRS score remained after controlling for clinical variables.

    Article  PubMed  Google Scholar 

  15. •• Iles L, Pfluger H, Lefkovits L, et al. Myocardial fibrosis predicts appropriate device therapy in patients with implantable cardioverter-defibrillators for primary prevention of sudden cardiac death. J Am Coll Cardiol. 2011;57(7):821–8. In this prospective trial of 103 patients meeting criteria for ICD therapy, cardiac MRI pre-ICD implantation was performed. In patients with ICMP, all of whom had late enhancement, 14% of patients had ICD discharges. In NICMP patients with late enhancement, 29% of patients had ICD discharges, whereas in those without late enhancement no ICD discharges occurred.

    Article  PubMed  Google Scholar 

  16. • Boogers MJ, Borleffs CJ, Henneman MM, et al. Cardiac sympathetic denervation assessed with 123-iodine metaiodobenzylguanidine imaging predicts ventricular arrhythmias in implantable cardioverter-defibrillator patients. J Am Coll Cardiol. 2010;55(24):2769–77. In this trial of 116 heart failure patients referred for ICD therapy, those with large 123-I MIBG defects corresponding to sympathetic denervation had significantly more appropriate ICD therapy that those with small defects at 3-year follow-up.

    Article  PubMed  Google Scholar 

  17. Makikallio TH, Barthel P, Schneider R, et al. Frequency of sudden cardiac death among acute myocardial infarction survivors with optimized medical and revascularization therapy. Am J Cardiol. 2006;97(4):480–4.

    Article  PubMed  Google Scholar 

  18. • Gheorghiade M, Flaherty JD, Fonarow GC, et al. Coronary artery disease, coronary revascularization, and outcomes in chronic advanced systolic heart failure. Int J Cardiol. 2010. In this analysis of the BEST population, which included adults greater than 18 years of age with chronic heart failure (NYHA class III–IV) and LVEF less than 35%, propensity score matching was performed. The investigators found that when ICMP patients were treated with CABG, all-cause mortality was decreased (HR, 0.77; P = 0.015) and there was a trend toward decrease in SCD (HR, 0.80; P = 0.147).

  19. • Barsheshet A, Goldenberg I, Narins CR, et al. Time dependence of life-threatening ventricular tachyarrhythmias after coronary revascularization in MADIT-CRT. Heart Rhythm. 2010;7(10):1421–7. In this post hoc analysis of the MADIT-CRT population, there was a significant decrement in 3-year cumulative rate of VT/VF when coronary revascularization was performed (42% vs 32%; P = 0.02). With multivariate analysis, the relationship was preserved and as time elapsed after revascularization, the benefit of revascularization appeared to be of greater magnitude.

    Article  PubMed  Google Scholar 

  20. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. randomized aldactone evaluation study investigators. N Engl J Med. 1999;341(10):709–17.

    Article  PubMed  CAS  Google Scholar 

  21. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348(14):1309–21.

    Article  PubMed  CAS  Google Scholar 

  22. • Wei J, Ni J, Huang D, Chen M, Yan S, Peng Y. The effect of aldosterone antagonists for ventricular arrhythmia: a meta-analysis. Clin Cardiol. 2010;33(9):572–7. In a meta-analysis of seven randomized trials, containing a total of heart failure 8635 patients, aldosterone antagonists when compared with placebo led to a 21% decrement in SCD (RR, 0.79; 95% CI, 0.67–0.93) and reduced VT by 72% (RR, 0.28; 95% CI, 0.10–0.77). Moreover, over 24 hours, the number of ventricular premature complexes was decreased by an average of 95%.

    Article  PubMed  Google Scholar 

  23. • Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011; 364(1):11–21. In this placebo-controlled, prospective, randomized trial of NYHA class II, chronic systolic heart failure, eplerenone reduced a composite end point of death from cardiovascular causes and hospitalizations from heart failure. Although not significantly reduced, there was a trend toward reduction in SCD (HR, 0.76; P = 0.12).

    Article  PubMed  CAS  Google Scholar 

  24. •• Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American college of Cardiology/American heart association task force on practice guidelines (writing committee to revise the ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices) developed in collaboration with the American Association for thoracic surgery and society of thoracic surgeons. J Am Coll Cardiol. 2008;51(21):e1–62. These are the latest guidelines published jointly by ACC, AHA, and HRS for device-based therapy.

    Article  PubMed  Google Scholar 

  25. • Al-Khatib SM, Hellkamp A, Curtis J, et al. Non-evidence-based ICD implantations in the united states. JAMA. 2011;305(1):43–9. In this analysis of the National Cardiovascular Data Registry–ICD Registry, 22.5% of patients underwent ICD implantation outside of published guidelines. Patients who underwent non-evidenced-based ICD therapy had more comorbidities and suffered a greater number of complications. Moreover, patients who underwent ICD therapy outside of guidelines were more likely to have had implantation by a noncardiac electrophysiologist.

    Article  PubMed  CAS  Google Scholar 

  26. 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(24):2481–8.

    Article  PubMed  CAS  Google Scholar 

  27. Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med. 2009;361(15):1427–36.

    Article  PubMed  CAS  Google Scholar 

  28. • Pouleur AC, Barkoudah E, Uno H, et al. Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. Circulation. 2010;122(6):597–602. In this retrospective analysis of autopsy records from patients enrolled in the VALIANT trial, 105 patients had SCD. In the first month post-MI, 24 of 30 deaths were nonarrhythmic, providing an explanation for why ICD implantation early post-MI proved unhelpful in the IRIS and DINAMIT trials.

    Article  PubMed  Google Scholar 

  29. Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002;346(24):1845–53.

    Article  PubMed  Google Scholar 

  30. 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(21):2140–50.

    Article  PubMed  CAS  Google Scholar 

  31. Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539–49.

    Article  PubMed  CAS  Google Scholar 

  32. • Linde C, Abraham WT, Gold MR, et al. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol. 2008;52(23):1834–43. In this prospective, randomized trial, 600 patients with class I or II heart failure, LVEF less than 40%, and QRS greater than 120 msec were randomized to CRT-ON or CRT-OFF in a 2:1 fashion. In a primary end point that was a composite heart failure response there was a trend for benefit with biventricular pacing. Patients assigned to CRT-ON experienced a greater improvement in LVESV index and other measures of LV remodeling.

    Article  PubMed  Google Scholar 

  33. •• Tang AS, Wells GA, Talajic M, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med. 2010; 363(25):2385–95. In this randomized trial, patients with NYHA class II (the vast majority) and III heart failure, widened QRS, and depressed EF who were receiving ICD implantation for primary or secondary prevention of SCD were randomized to ICD only or CRT-D. When the class II patients were analyzed, there was a decrease in the primary outcome of death or hospitalization (34.7% vs 27.3%; P < 0.05). Moreover, this is the first trial demonstrating significant decrease in death from any cause when CRT-D was placed rather than ICD alone in mildly symptomatic heart failure (21.1% vs 15.5%; P < 0.05).

    Article  PubMed  CAS  Google Scholar 

  34. • Al-Majed NS, McAlister FA, Bakal JA, Ezekowitz JA. Meta-analysis: cardiac resynchronization therapy for patients with less symptomatic heart failure. Ann Intern Med. 2011;154(6):401–12. This recent meta-analysis including the REVERSE, MADIT-CRT, RAFT, and three smaller trials evaluated CRT in class I and II heart failure. The analysis showed improvement in all-cause mortality and heart failure hospitalizations when CRT was utilized. There was no improvement in functional outcomes or quality of life.

    PubMed  Google Scholar 

  35. • Gold MR, Linde C, Abraham WT, Gardiwal A, Daubert JC. The impact of cardiac resynchronization therapy on the incidence of ventricular arrhythmias in mild heart failure. Heart Rhythm. 2010. In this analysis of the REVERSE trial, patients with mild heart failure who had CRT-D placement were evaluated for ventricular arrhythmias. Over the course of 2 years, there was no difference in VT/VF episodes between the group that had CRT turned “ON” versus those that had CRT turned “OFF.” However, in the CRT-ON patients, those with reverse remodeling had significantly reduced incidence of VT/VF compared to those without remodeling (5.6% vs 16.3%; P = 0.001).

  36. • Foley PW, Chalil S, Khadjooi K, Irwin N, Smith RE, Leyva F. Left ventricular reverse remodelling, long-term clinical outcome, and mode of death after cardiac resynchronization therapy. Eur J Heart Fail. 2011;13(1):43–51. In this study, 322 patients with CRT had echocardiography before and after implantation. Those who had LV reverse remodeling (≥ 15% reduction in LVESV) had improved survival (HR, 0.57; P = 0.0066) and death from pump failure (HR, 0.45; P = 0.0024). However, in this population, remodeling did not predict SCD.

    Article  PubMed  Google Scholar 

  37. • Solomon SD, Foster E, Bourgoun M, et al. Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: Multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy. Circulation. 2010;122(10):985–92. In the MADIT-CRT population, improvement in LVEDV index at 1 year after CRT predicted subsequent heart failure and death.

    Article  PubMed  Google Scholar 

  38. • Kleemann T, Becker T, Strauss M, et al. Impact of left ventricular lead position on the incidence of ventricular arrhythmia and clinical outcome in patients with cardiac resynchronization therapy. J Interv Card Electrophysiol. 2010;28(2):109–16. One-hundred eighty-seven consecutive patients enrolled in a registry who received CRT were assessed for frequency of malignant arrhythmias depending on LV lead placement site. Over the course of 2 years, ventricular arrhythmias occurred in 35% of patients with anterior lead versus 30% of patients with posterior LV lead (P = 0.53), and the incidence of VT storm and number of episodes were not different between the two groups. However, the 2-year mortality in the anterior LV lead group was 22% compared with 3.2% in the posterior group (P < 0.001).

    Article  PubMed  Google Scholar 

  39. • Delgado V, van Bommel RJ, Bertini M, et al. Relative merits of left ventricular dyssynchrony, left ventricular lead position, and myocardial scar to predict long-term survival of ischemic heart failure patients undergoing cardiac resynchronization therapy. Circulation. 2011;123(1):70–8. In this study of 397 ICMP patients, placement of the LV lead in the area of latest mechanical activation (termed concordant LV lead position) led to a higher 3-year survival rate (80% vs 54%; P < 0.001). When the LV lead was placed in an area free of myocardial scar, 3-year survival rate was also higher (87% vs 58%; P < 0.001).

    Article  PubMed  Google Scholar 

  40. • Singh JP, Klein HU, Huang DT, et al. Left ventricular lead position and clinical outcome in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) trial. Circulation. 2011; 123(11):1159–66. In an analysis of the MADIT-CRT trial, the clinical benefit of CRT was similar for leads in the anterior, lateral, or posterior position. However, apical lead position was associated with an increased risk for heart failure and death.

    Article  PubMed  Google Scholar 

  41. • Gasparini M, Anselme F, Clementy J, et al. Biventricular versus right ventricular antitachycardia pacing to terminate ventricular tachyarrhythmias in patients receiving cardiac resynchronization therapy: The ADVANCE CRT-D trial. Am Heart J. 2010; 159(6):1116–23.e2. In the ADVANCE trial, 526 patients with CRT-D were prospectively randomized to RV or biventricular pacing. Over 12 months follow-up, there were no syncopal or presyncopal episodes with biventricular pacing while there were four events in the RV pacing group (P = 0.016). In addition, in subgroup analysis, biventricular pacing was more effective in ICMP (P = 0.032).

    Article  Google Scholar 

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  1. Division of Electrophysiology, Department of Cardiology, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA

    Mustafa Dohadwala, N. A. Mark Estes III & Mark S. Link

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  1. Mustafa Dohadwala
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Dohadwala, M., Estes, N.A.M. & Link, M.S. New Paradigms in the Prevention of Sudden Cardiac Arrest and Heart Failure Treatment. Curr Cardiol Rep 13, 377–386 (2011). https://doi.org/10.1007/s11886-011-0204-3

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