Asymptomatic heart failure patients are likely to benefit from prophylactic implantable cardioverter defibrillator (ICD) treatment, irrespective of cardiomyopathy aetiology, according to the findings from a study that assessed appropriate device therapy and mortality in New York Heart Association (NYHA) class I patients with reduced left ventricular ejection fraction (LVEF).
Writing in the American Journal of Cardiology, Anne-Lotte CJ van der Lingen, Cornelis P Allaart (Amsterdam UMC, Amsterdam, the Netherlands) et al say: “Primary prevention NYHA I patients with a LVEF ≤35% are likely to benefit from ICD therapy and should not be excluded from a potentially life-saving therapy.”
Prophylactic ICD implantation is recommended in heart failure patients with reduced LVEF and NYHA functional class II–III, and is currently advocated in guidelines for sudden cardiac death (SCD) from the European Society of Cardiology (ESC), American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS), and the National Institute for Health and Care Excellence (NICE). But there are discrepancies between guidelines for asymptomatic heart failure patients. NICE recommends prophylactic ICD implantation in NYHA I patients, whereas the ESC advises against it, and the AHA/ACC/HRS guidelines differentiate between patients with ischaemic and non-ischemic cardiomyopathy (CMP). The authors point out that the majority of trials were conducted almost two decades ago, and say: “Since then, advancements in medical therapy have led to a decrease in risks of mortality and SCD in heart failure patients. The present study set out to evaluate the occurrence of appropriate device therapy and death in a contemporary NYHA I patient cohort with systolic heart failure who received an ICD for primary prevention of SCD.”
A retrospective cohort was studied between 2009 and 2016, with 1098 patients eligible for ICD implantation. Of these, 572 patients with a LVEF ≤35% who received a prophylactic ICD with or without resynchronisation therapy (CRT-D) were included. At baseline, 106 (19%) were in NYHA I, 277 (48%) were in NYHA II and 189 (33%) were in NYHA III.
To evaluate the incidence of appropriate device therapy and mortality, NYHA I was compared to NYHA II–III using Cox regression analysis. During follow-up of four years, 33% of the NYHA I patients received appropriate device therapy compared to 20% of the NYHA II–III patients (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.04–2.31, p=0.03). No differences in mortality were observed between the three different NYHA classes (HR 0.70, 95% CI 0.49–1.07, p=0.10). Additional analyses showed no difference in time to appropriate device therapy excluding CRT patients (ICD NYHA I patients versus ICD NYHA II–III patients, p=0.17) and comparing ischaemic and non-ischaemic cardiomyopathy NYHA I patients (p=0.13). Multivariable Cox regression analyses showed that NYHA class was the strongest independent predictor of appropriate device therapy.
The observation of more appropriate device therapy in NYHA I than NYHA II–III was an unexpected finding, say the investigators, hypothesising that NYHA class I patients, who are without limitation of physical activity, are physically more active, thereby exposing themselves to a greater risk of exercise-induced ventricular tachyarrhythmias. Alternatively, they say, it could be due to multiple types of bias, such as healthy candidate bias, referral bias and survivor bias.
Van der Lingen, Allaart et al add: “Our results suggest that NYHA I patients with non-ischaemic CMP have a similar risk of developing ventricular tachyarrhythmias as compared to patients with ischaemic CMP. Prophylactic ICD implantation in ischaemic CMP has been studied extensively, and survival benefit in this subgroup is undisputable. There is less agreement on the effectiveness of prophylactic ICD implantation in non-ischemic CMP. It is often suggested that an increase in heart failure severity is associated with a higher risk of death due to pump failure and a lower risk of SCD. It is therefore possible that the non-ischaemic NYHA I patients benefit significantly from ICD therapy, because they are less likely to die from other causes.”
They conclude: “With the differences in recommendations, the eligibility of NYHA I patients for prophylactic ICD implantation remains ambiguous and at the physician’s discretion. Obviously, selecting patients for ICD implantation must be done carefully and the decision should not solely be based on NYHA class. Nevertheless, the current data, in line with previous studies, imply that asymptomatic heart failure patients with LVEF ≤35% are at substantial risk of developing ventricular tachyarrhythmias and it therefore seems only reasonable that prophylactic ICD implantation should be considered.”
They call for future randomised controlled trials focusing on prophylactic ICD implantation in asymptomatic heart failure patients. Van der Lingen and Allaart told Cardiac Rhythm News: “Risk stratification for SCD solely based on LVEF and NYHA class alone is probably insufficient, we propose future studies focusing on a multifactorial prediction model for SCD, including imaging parameters, electrophysiological parameters and functional status of the patient. We should work towards an ICD-Risk-SCD prediction model, such as the well-known HCM Risk-SCD Calculator.”