Author + information
- Alan H. Kadish, MD∗ ( and )
- Jason T. Jacobson, MD
- ↵∗Reprint requests and correspondence:
Dr. Alan H. Kadish, New York Medical College, 500 7th Avenue, New York, New York 10018.
“A tincture of time” is often “prescribed” when faced with a new diagnosis of unclear etiology, with the hope that the process will correct itself or our early interventions will help reverse whatever process we believe we are treating. This therapy is standard of care when faced with the question of implantable cardioverter-defibrillator (ICD) implantation for idiopathic-dilated cardiomyopathy (DCM). Currently, it is recommended that patients with DCM, ejection fraction (EF) ≤35%, and New York Heart Association functional class II to III symptoms are treated for at least 90 days with optimal medical therapy (OMT) before reassessing the need for an ICD (1). This reassessment includes repeat evaluation of left ventricular function and reevaluation of symptom status. Clinicians are faced with many uncertainties when dealing with DCM. What is the true process behind this patient’s diagnosis? What currently constitutes OMT for this patient? What are the short-term risks of sudden cardiac death (SCD) for this patient? How long should I wait before offering an ICD? Should I protect this patient in the meantime?
In this issue of JACC: Clinical Electrophysiology, Losurdo et al. (2) attempt to shed some light on the issue of early SCD in this patient population. In a retrospective analysis of 952 DCM patients enrolled in their Heart Muscle Disease Registry of Trieste, the investigators sought to identify clinical parameters that imparted higher risk of SCD and/or malignant ventricular arrhythmias (MVAs) within 6 months after enrollment in the registry. Patients with significant coronary disease (>50% stenosis on angiography), history of severe hypertension, excessive alcohol use, severe valvular disease, congenital heart disease, severe systemic disease that affected short-term prognosis, and untreated persistent supraventricular tachyarrhythmias were excluded from analysis. Importantly, the time period of enrollment was >25 years (1988 to 2014). A small proportion of patients in this cohort underwent early ICD implantation based on a perception of high risk, which was included in the analysis. The primary endpoint was a composite of SCD and MVA (aborted SCD, sustained ventricular tachycardia [VT], appropriate ICD shocks for syncopal VT or VT >200 beats/min). The investigators evaluated many (34 total) demographic, clinical, electrocardiographic, echocardiographic, and pharmacological variables in univariate and multivariate analyses. Of note, 21% of patients were not treated with beta-blockers due to hemodynamic chronotropic intolerance. The primary endpoint occurred in 2.1% of the overall population in the 6-month follow-up from the time of enrollment.
Despite the large number of variables analyzed, only 3 were significantly associated with early SCD in both univariable and multivariable analyses: QRS duration, left ventricular end-systolic volume index (LVESVI), and the inability to treat with beta-blockers. For every 1-ms increase in QRS duration, the odds ratio (OR) was 1.017 (95% confidence interval [CI]: 1.003 to 1.030; p = 0.015). Likewise, for every 1 ml/m2 increase in LVESVI, the OR was 1.012 (95% CI: 1.000 to 1.024; p = 0.043). A linear association was seen with these 2 parameters; therefore, a definite cutoff could not be identified. Of interest, these 2 parameters also predicted a lack of left ventricular EF improvement in a similar fashion. As expected, beta-blockers were protective (OR: 0.169; 95% CI: 0.048 to 0.593; p = 0.006).
The investigators are to be congratulated for their dedication to maintaining such a registry for >25 years. Their findings do offer some insight into the problem of early risk stratification in the DCM population. However, a number of limitations must be considered. Foremost is the retrospective nature of this study without a control group. In addition, the time span this registry encompasses is of concern. Diagnostic and therapeutic options have changed significantly over the past few decades. Important therapies, such as aldosterone antagonists, were not evaluated in this study. Likewise, the diagnostic modalities available to further characterize the etiology of cardiomyopathies have certainly expanded over the past few decades. The investigators did find that there were no differences when the data were stratified by decade of enrollment. The analysis only included the “tried-and-true” techniques of electrocardiography, echocardiography, and angiography, whereas more contemporary modalities, such as cardiac magnetic resonance imaging, which were conspicuously absent, might not only suggest an etiology (3), but also risk stratify for an SCD and/or MVA (4). In addition, although myocardial biopsy has displayed a low diagnostic yield in the past (and as such was not routinely performed after 1992 in this cohort), current methods of voltage-map guidance do show promise (5). Definitive diagnosis remains important in that some etiologies respond to specific treatments, whereas others may impart a higher risk of SCD and/or MVA.
One other interesting point that may be gleaned by “reading between the lines” of this study: despite a clinician perceiving that a patient was “high risk” and recommending early ICD implantation, there was no difference in implantation rates between those who experienced SCD and/or MVA and those who did not. Furthermore, no patient was known to experience an ICD shock (although post-mortem analysis was not performed, and an accounting of episodes treated with antitachycardia pacing was not performed). This important finding underscores our inability to identify those at high risk of early SCD who should receive an ICD before a trial of OMT is completed. Although the current study does offer additional guidance, the retrospective nature of the study precludes changing clinical practice as yet. It is possible that the data could be useful in patients with borderline indications for ICD implantation (e.g., an EF of 30% to 35%) and in those with modest heart failure symptoms. In addition, the results of the current study suggest the need for further randomized or observational studies on the wearable defibrillator (6). At the very least, it may allow our patients (as well as ourselves) to tolerate the tincture of time.
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Dr. Jacobson is a consultant for St. Jude Medical. Dr. Kadish has reported that he has no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Russo A.M.,
- Stainback R.F.,
- Bailey S.R.,
- et al.
- Losurdo P.,
- Stolfo D.,
- Merlo M.,
- et al.
- Casella M.,
- Pizzamiglio F.,
- Dello Russo A.,
- et al.
- Salehi N.,
- Nasiri M.,
- Bianco N.R.,
- et al.