By Cara Pellegrini, MD

Assistant Professor of Medicine, University of California, San Francisco; Cardiology Division, Electrophysiology Section, San Francisco VA Medical Center

Dr. Pellegrini reports no financial relationships relevant to this field of study.

SYNOPSIS: Patients with recently diagnosed idiopathic dilated cardiomyopathy are at marked risk of major arrhythmia events that are neither well-predicted by traditional methods nor protected against by defibrillator implantation more than three months after diagnosis.

SOURCE: Losurdo P, Stolfo D, Merlo M, et al. Early arrhythmic events in idiopathic dilated cardiomyopathy. JACC Clinical Electrophysiology 2016; 2:535-543.

Idiopathic dilated cardiomyopathy (DCM) often affects the young. Although many experience significant left ventricular function recovery, a sizable percentage do not, and all are at risk for major cardiovascular events during their period of cardiac dysfunction. Guidelines specifically recommend that implantable cardioverter-defibrillators (ICDs) not be placed during a three-month period of optimization of medical therapy, in part to allow for assessment of recovery of left ventricular systolic function. However, the incidence of sudden cardiac death (SCD) and malignant ventricular arrhythmias (MVAs) occurring in the early time period following diagnosis of DCM has not been well studied.

Losurdo et al performed a retrospective analysis of 952 DCM patients consecutively enrolled in the Heart Muscle Disease Registry of Trieste (Italy) over 26 years, ending in 2014. They excluded patients with any discernable etiology of their DCM, such as significant coronary artery disease (every patient had a coronary angiogram), severe systemic hypertension, heavy alcohol intake, severe valvular disease, congenital heart disease, active myocarditis, or high supraventricular tachycardia burden. Following enrollment, efforts were made to ensure that all patients were on the maximum tolerated dosages of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). ICDs could be implanted for primary prevention of SCD at physician discretion following standard guidelines. Patients underwent baseline and periodic follow-up studies, including blood tests, electrocardiograms, and echocardiograms. The primary endpoint was a composite of SCD and MVAs within the first six months after enrollment, which generally was about one month after diagnosis. Multivariable regression was utilized to identify independent predictors of the primary outcome.

Of the 952 enrollees, one-third were asymptomatic, 21% had a familial form of DCM, and the mean LVEF was 33%. After enrollment, the vast majority of patients were receiving ACE inhibitors or ARBs and 79% were on beta-blockers. The primary outcome occurred in 20 patients (2.1% of the overall population), with 70% of the early SCD and MVAs occurring within the first 90 days. Increasing QRS duration and left ventricular end systolic volume index (LVESVI) were independently associated with increased incidence of SCD and MVAs in a linear fashion. Additionally, successful beta-blocker therapy was inversely related to the primary outcome. Interestingly, none of the patients with an ICD received a shock or were observed to suffer SCD or MVAs. The authors concluded that patients with DCM have a non-negligible risk of major arrhythmic events in the early disease period that potentially can be predicted with easily accessible, inexpensive tools.

COMMENTARY

Although this study was a retrospective analysis with only 20 patients reaching the primary endpoint, I thought it made an interesting counterpoint to DANISH, a recent randomized, controlled trial discussed in this publication two months ago, found no all-cause mortality benefit of primary prevention ICDs in patients with nonischemic cardiomyopathy (NICM), although there was a significant interaction with age. The current study concerned a subset of the NICM population, those with an idiopathic cardiomyopathy. These patients typically are younger and more likely to recover left ventricular function. They also may differ in other ways, including their propensity for SCD and MVAs, and the time period during which they are at the highest risk.

In the current study, 1.4% of patients, with a mean age of 46 years, suffered SCD and 0.7% MVAs in six months. The fact that there was no overlap with the patients who received a primary prevention ICD after being deemed to be at highest risk by conventional prediction techniques, primarily the left ventricular ejection fraction and severity of heart failure symptoms, also is notable. It would have been preferable for the study to have included other tests that now are relatively common, such as cardiac MRI and electrophysiology study with voltage mapping. Nonetheless, there is biologic plausibility for both QRS duration and LVESVI as markers for more advanced structural disease. Further, an electrocardiogram and echocardiogram generally are rapidly available, easily accessible, and relatively inexpensive. Beta-blocker therapy truly is protective and should be even more aggressively pursued.

The authors suggest that patients with idiopathic DCM with longer QRS durations and higher LVESVI (although a specific cutpoint was not given), particularly those who cannot tolerate beta-blockers, should be considered for a wearable cardioverter-defibrillator while waiting to assess left ventricle functional recovery. Although a firm recommendation for such a device cannot be given on the basis of this data, it certainly begs for further study, and is something to at least consider and discuss with appropriate patients.