Primary Care Corner: Decreasing sudden-death in heart failure

by Dr Geoffrey Modest

A recent meta-analysis found that the risk of sudden death in patients with symptomatic heart failure and reduced ejection fraction (HFrEF) has decreased significantly over the past 20 years (see Shen L. N Engl J Med 2017; 377: 41).
— 12 clinical trials from 1999 through 2014, in which patient-level data were available, included 40,195 patients, but excluded those with implantable cardioverter-defibrillators (ICD)
— Mean age 65, 77% men, 95% with NYHA class II or III heart failure, mean ejection fraction 28% (varied from 23% to 32%), 62% with ischemic heart failure, ACE-I/ARB use was >90%.
— sudden death was determined in 3583 patients
–Those with sudden death were more often older (low 60s vs mid 60s​), male (low 80% vs mid 70%), had an ischemic cause of heart failure (70% vs 60%), and had worse cardiac function(LVEF 26% vs 29%). There was also minimally lower systolic blood pressure, minimally higher heart rate, minimally worse heart failure symptoms, minimal difference in renal dysfunction, but there was a somewhat more prominent history of myocardial infarction and diabetes in those with sudden death.​ [These were my rough calculations from the supplementary material, no formal calculations done by them]. Also NT-proBNP was higher in those with sudden death, though this was not checked in many of the studies.
— over time, there was a 44% decline in the rate of sudden death across the trials over the 19 years
— the cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial, and 1.0% in the most recent trial. At 180 days the cumulative incidence of sudden death was approximately double that at 90 days, with these same trend of decrease in the more recent trials.
–My review of the individual trials showed a relatively consistent pattern: those with the same heart failure medications in both the control and experimental groups (as in a trial looking at the role of statins or another medication added on) did not show much difference between these groups in terms of sudden death outcomes. However those in which an additional heart failure medicine, either a beta-blocker or a mineralocorticoid antagonist, was added, there generally was a more impressive benefit: ie, maximizing the standard heart failure regimens seems to be beneficial. Only one study used sacubitril/valsartan, finding some added benefit on top of otherwise maximal therapy
— sudden cardiac death was not higher among patients with a recent diagnosis of heart failure than those with longer standing heart failure
–This study basically reinforces that maximal therapy for HFrEF patients significantly decreases the risk of sudden death, and to levels where automatically implanting an ICD may not be indicated, particularly in the primary prevention of sudden death. It would be important to determine if there is a subset of those patients who might benefit. One leading contender has been ischemic vs nonischemic cardiomyopathy, where the myocardial scar in those with ischemic cardiomyopathy might be the nidus for ventricular arrhythmias (and, indeed, this study confirmed about a 10% increased risk vs non-ischemic cardiomyopathy).
— Another issue is how long to wait to see the degree of myocardial recovery after the presenting symptoms of heart failure or myocardial infarction. There are studies confirming that multiple drugs and maximal doses lead to more reversal of ventricular remodeling and that the LVEF may still improve over 6 to 12 months after starting treatment (which is significantly longer than the 40 days post myocardial infarction highlighted in the ICD guidelines, suggesting that this time interval may still be too short).
–Current recommendations for ICDs include patients with NYHA class II or III symptoms and LVEF< 35%, independent of cause. However, the recent DANISH trial of patients with nonischemic systolic heart failure showed that adding ICD to maximal medical therapy  led to no difference in total mortality, though there was a reduction in sudden death in those with ICDs (4.3% vs 8.2%). It was notable in the above meta-analysis that only 9% of the patients (3180 in total) had had an ICD implanted and were excluded from this study. Given the low LVEF (median 28%) in these symptomatic patients, so that the majority actually met guideline criteria for an ICD, this 9% number suggests that we clinicians have not been pursuing ICDs very vigorously, even though these patients in the meta-analysis were more likely to have been in cardiovascular centers in big academic medical sites, replete with academic cardiologists….
— This study reinforces that we clinicians are doing quite well in preventing sudden cardiac death by putting patients on maximal heart failure medications.  These meds really work
— As with all interventions, in this case ICD placement, there are real risks for the intervention (in this case: infections, ICD failure, documented decreases in quality of life, and in my experience significant PTSD from patients having been shocked either appropriately are not). Therefore, the more targeted we are at selecting patients for this intervention, the better. Further investigation is warranted to determine those subgroups of patients who really benefit from ICD placement (and those who really do not benefit much and ICDs should be a non-issue).
see blog   for a recent review of  the medications for heart failure (including HFpEF), and another which reviewed Medicare patients showing that only 8.1% who qualified for ICDs got them