Nonischemic cardiomyopathies

The results of MADIT II were met with some skepticism, but later confirmed by the recent Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) [24]. This study evaluated the benefit of ICD therapy versus amiodarone or placebo as primary prevention in over 2,500 patients with stable NYHA class II or III heart failure and EF < 35%, without the requirement for NSVT or EPS. Patients with both ischemic and nonischemic etiologies for cardiomyopathy were included. Over a follow-up of 4 years, there was no benefit of amiodarone over placebo for overall mortality, but ICD therapy resulted in a significant 23% reduction in overall mortality [p = 0.007] (Fig. 3.5). The benefit of ICD therapy was comparable for ischemic and nonischemic cardiomyopathy. 

The DEFINITE (The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation)... 

Patients with nonischemic cardiomyopathy who have an LVEF less than or equal to 35% and who are in NYHA functional Class II or II B Class I... 

Fig. 4.4 Morbidity and mortality effects of CRT in ischemic and nonischemic cardiomyopathy. Panel A shows the effects of CRT and CRT-D on the primary endpoint of all-cause hospitalization and all-cause mortality, along with the effect of CRT-D on mortality for all patient, and patients with...

Kittleson MM, Minhas KM, Irizarry RA, et al. Gene expression analysis of ischemic and nonischemic cardiomyopathy shared and distinct genes in the development of heart failure, Physiol Genomics 2005 21 299-307. 

Risk stratification of patients with nonischemic cardiomyopathy has proven to be more challenging than in their counterparts with CAD. The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation... 

FIGURE 1.5 Summary of evidence supporting defibrillator implantation as stratified by ejection fraction and heart failure class in patients with ischemic cardiomyopathy (A) and nonischemic cardiomyopathy (B). For details of COMPANION trial, see Chapter 5. (CRT, cardiac resynchronization therapy EPS, electrophysiology study NYHA,New York Heart Association.)... 

SCD-HeFT enrolled 252T patients with ischemic or nonischemic cardiomyopathy with class II or III HF and an LVEF <35% (29). Patients were randomized to... 

The results of these primary prevention trials in nonischemic cardiomyopathy patients led to an indication for ICD implantation in patients with a nonischemic cardiomyopathy, LVEF <35%, and class II or III HF (Figure 1.5b) (9). Importantly in SCD-HeFT, patients had to have a diagnosis of HF for at least three months and be on appropriate medical therapy. 

FIGURE 1.6 Kaplan-Meier estimates of death from any cause in patients with both ischemic and nonischemic cardiomyopathy randomized to amiodarone, placebo, or implantable cardioverter-defibrillator therapy in SCD-HeFT. (From Ref. 29, with permission.)... 

TWA for Risk Stratification in Patients With Nonischemic Cardiomyopathy... 

The ALPHA results contrast results of a SCD-HeFT substudy which investigated TWA in 490 patients with LVEF <35% and class II-III HF (51). In SCD-HeFT, TWA was unable to predict SCD or sustained ventricular arrhythmias. However, in SCD-HeFT the patients had a lower LVEF, a mix of ischemic and nonischemic cardiomyopathy, and a 41% indeterminate rate compared to a 20.6% rate in ALPHA, potentially lowering the predictive value of TWA. 

In patients with nonischemic cardiomyopathy, SAECG has not been shown to be predictive of sustained VT, VF, or SCD (63). 

In conclusion, the high NPV of SAECG in patients with ischemic LV dysfunction may help decide which patients do not need an ICD, but the results need to be reliably reproduced. Although the data are limited, there appears to be less of a role for SAECG in patients with nonischemic cardiomyopathy. 

Baroreflex sensitivity (BRS) is a measure of the reflex bradycardia that follows an increase in systemic blood pressure. This reflex is mediated by arterial baroreceptors and may be measured after injection of phenylephrine or after spontaneous rises in blood pressure (64). Correlation between the two different tests is poor (69) and measures of baroreflex sensitivity are only moderately reproducible (70). Data on the ability of BRS to predict sudden death are conflicting. In the ATRAMI study in 1284 patients post-MI, HRV, and BRS were assessed at discharge (71). Depressed HRV and BRS carried a significant risk of cardiac mortality when both parameters were depressed the risk increased further. Thus, ATRAMI demonstrated that since BRS adds to the prognostic value of HRV, the two measures are complimentary rather than redundant. However, in another study of 700 post-MI patients, HRV or BRS was not predictive of SCD (60). BRS also does not appear useful for risk stratification in patients with nonischemic cardiomyopathy (63). 

In patients with nonischemic cardiomyopathy, NSVT does not seem to be predictive of SCD. In DEFINITE (28), which used NSVT as part of the selection process, the absolute mortality reduction was 6.2%. In SCD-HeFT (29) where NSVT was not an inclusion criterion, there was a similar reduction in mortality of 7.2%, implying that NSVT does not provide additional risk stratification beyond LVEF and HF class. In the... 

Therefore, in patients post-MI with ischemic cardiomyopathy, NSVT may predict SCD and total mortality however, the incremental risk stratification in patients with LVEF <35% is unclear. The utility of obtaining routine Holter monitors for screening in this population is unclear and not currently recommended (77). NSVT may be more useful in patients post-MI with LVEF over the range of 35% to 40% however, it is difficult to separate the predictive ability of NSVT versus EP study in this population. In patients with nonischemic cardiomyopathy, NSVT has not been demonstrated to reliably predict SCD. 

In patients with nonischemic cardiomyopathy, the DEFINITE trial did not show a relationship between QRS duration and all-cause mortality (28). In the Marburg Cardiomyopathy Study, neither left nor right bundle branch block predicted SCD (63). While SCD-HeFT reported a greater benefit of ICD therapy in mortality reduction in patients with a QRS >120 msec, the data include patients with both ischemic and... 

Thus, while QRS duration is an appealing measure for risk stratification due to its ease of use and availability, there are conflicting data that prolonged QRS duration identifies patients at higher risk for SCD with ischemic cardiomopathy, and a paucity of data to support its use in patients with nonischemic cardiomyopathy. 

Salerno-Uriarte JA, De Ferrari GM, Klersy C, et al. Prognostic value of T-wave alternans in patients with heart failure due to nonischemic cardiomyopathy. ALPHA Study Group Investigators. J Am Coll Cardiol 2007 50(19) 1896-904. 

In a broader unselected population referred for nuclear stress testing, Sharir et al. (6) found that the extent of reversible perfusion defect (as expressed by the summed difference score) was the best predictor of subsequent nonfatal myocardial infarction, and was best fit by an exponential curve. Among these patients, 26% had a history of myocardial infarction, and patients with nonischemic cardiomyopathies, valvular disease, or who underwent revascularization within 60 days were excluded. Importantly, even though ejection fraction most powerfully stratified the risk of cardiac death, in patients with an ejection fraction >30% the amount of perfusion defect provided incremental prognostic information. In patients with an ejection fraction of <30%, the rates of cardiac death were high (>4% per year) regardless of the amount of ischemia. 

ICD as a primary prevention therapy in patients with nonischemic cardiomyopathy (NICM) and nonsus-tained VT... 

SCD-HeFT targeted the entire population of heart failure patients with ischemic and nonischemic cardiomyopathy with less bias than previous primary prevention trials. SCD-HeFT study raised the standard of care for many heart failure patients. 

CAT and AMIOVERT, smaller studies that examined use of prophylactic ICDs in nonischemic cardiomyopathy patients, failed to show benefit from ICDs. CAT was terminated early due to low 1-year mortality rates (5.6% as opposed to the anticipated rate of 30%). After 2-year follow-up, mortality rate was 26% in ICD group, 50% in controls (p = 0.554). Final conclusions cannot be derived from these small studies (148,176) and, in a meta-analysis, ICDs benefit patient with nonischemic cardiomyopathy(177). 

Class lib indications for an ICD (1) Patients optimally managed with New York Heart Association Functional Class I heart failure and nonischemic cardiomyopathy who have a left ventricular ejection fraction <0.35. (2) Syncope of unclear etiology and ECG evidence of Brugada syndrome. (3) Patients with congenital long QT interval syndrome who have reasonable expectation of survival. 

CMS found that ICDs for primary prevention purposes are reasonable and necessary for (1) Patients with ischemic cardiomyopathy, myocardial infarction at least 40 days before. New York Heart Association Functional Class 11 and III heart failure, and left ventricular ejection fraction <0.35. (2) Patients with nonischemic cardiomyopathy treated for at least 9 months (although as short as 3 months is considered reasonable). Functional Class II or III heart failure and a left ventricular ejection fraction <0.35. (3). Patients with New York Heart Association Functional Class 1 heart failure, and a left ventricular ejection fraction <0.30. (4) Patients who have a QRS > 0.120, have New York Heart Association Functional Class IV heart failure, may benefit from cardiac resynchronization therapy and have a left ventricular ejection fraction <0.30. 

Desai, A.S., et al., Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy a meta-analysis of randomized controlled trials. JAMA, 2004. 292(23) p. 2874-9. 

Inappropriate therapy is the most common adverse event associated with ICDs (53). With the first generation of ICDs (Ventak 1500,1550, inappropriate shocks ranged from 15-25%. Unfortunately, the frequency of inappropriate therapy with the latest generation of devices is probably similar (5). In the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Trial, that evaluated the use of ICDs in patients with nonischemic cardiomyopathy, inappropriate therapy was more likely than appropriate therapy (22 versus 18%) (78). A case of an inappropriate shock due to noise oversensing inducing ventricular fibrillation and subsequent death in a patient has been reported (79). Finally it is important to confirm from the device that therapies were in fact delivered phantom shocks are not uncommon, occurring in approximately 6-7% of people (80). 

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