Author + information
- Francesco Cappelli, MD∗ (, )
- Sofia Morini, MD,
- Paolo Pieragnoli, MD, PhD,
- Mattia Targetti, MD,
- Pierluigi Stefàno, MD,
- Niccolò Marchionni, MD, PhD and
- Iacopo Olivotto, MD
- ↵∗Intensive Cardiac Care Unit, Cardiothoracovascular Department, Azienda Ospedaliero-Universitaria Careggi [AOUC], Largo Brambilla 3, 50134 Florence, Italy
Cardiac resynchronization therapy (CRT) is a well-established treatment for patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF), whereas its role in patients with preserved LVEF is controversial at best (1). Hypertrophic cardiomyopathy (HCM) is characterized by normal or enhanced LVEF, even in patients with severe congestive symptoms. About 5% to 7% of patients with HCM, however, develop systolic dysfunction with LVEF values <50% and as low as 25% to 30%, subtended by extensive myocardial fibrosis (“end-stage”) (2). In this subset, CRT appears a reasonable option, but the limited data available show conflicting results (1,3), possibly because eligibility criteria are undefined and variably extrapolated from systolic HF. Whether dilated cardiomyopathy (DCM) criteria apply to HCM is unresolved. Therefore, we aimed to evaluate the effects CRT on symptomatic status and outcome in end-stage HCM in a tertiary referral center.
We evaluated patients with HCM consecutively seen from 2000 to 2016; patients with storage or metabolic disease were excluded. We identified 61 patients with end-stage HCM, of whom 13 (21%) received CRT (7 females, age at diagnosis 29 ± 10 years). Patients with CRT were <1% of the total cohort.
At CRT implantation (age 49 ± 12 years), 8 patients were in New York Heart Association (NYHA) functional class II and 5 patients in class III/IV. Cardiopulmonary exercise testing was performed in 8 patients, showing marked Vo2 reduction (average 52% of predicted). Left bundle branch block (LBBB) was present in 12 of 13 patients with average QRS duration of 173 ± 27 ms, and LVEF was 42 ± 12% (2 patients were implanted despite EF >50% due to refractory HF and marked intraventricular dyssynchrony). Nine patients had paroxysmal atrial fibrillation, evolving into permanent in 6; 4 required ablate-and-pace. The CRT group showed a higher proportion of LBBB compared with end-stage patients without CRT (12 of 13 vs. 9 of 48; p < 0.01); no difference was seen in NYHA functional class, age, LVEF, and diuretics dose.
At 1 year, 7 patients (54%) improved ≥1 NYHA functional class, 3 reported no change, and 2 worsened ≥1 class. No differences were observed in LVEF and left ventricular (LV) volumes. At end of follow-up (5.2 ± 3.1 years after implantation), 6 patients died (46%) due to HF (n = 3), cerebral hemorrhage, cardiorenal complications, and heart transplant complications. Two patients were alive after heart transplantation. In the 7 CRT responders, symptomatic improvement lasted 2.7 ± 2.5 years. At final evaluation, however, there was no sustained symptomatic improvement compared with baseline. No difference in survival was evident between CRT and no-CRT end-stage patients during comparable follow-up (p = 0.46). Time from onset of NYHA functional class III/IV symptoms to listing in transplant candidates was also similar (2.1 vs. 1.9 years, respectively; p = 0.73). Two long-term CRT responders (sustained improvement to NYHA functional class II) were observed: a 48-year-old woman with LVEF of 32% and LBBB, and a 32-year-old woman with normal systolic function (LVEF 64%) and marked mitral regurgitation associated with LBBB following extensive surgical myectomy.
Patients vaguely fulfilling DCM criteria for CRT implantation are rare in large HCM cohorts and bear an ominous prognosis with an overall mortality or need for transplantation exceeding 50% at 5 years. CRT provided no significant advantage over pharmacological therapy alone, and failed to induce LV reverse remodeling or improvement in systolic function. We did observe transient symptomatic improvement at 1 year, but this effect was not maintained long term. A likely explanation for lack of CRT efficacy lies in the peculiar pathophysiology of HCM. Imaging and pathology studies (4,5) show that more than one-third of the LV in end-stage patients is replaced by fibrosis, which predominates, but is not confined to, the anteroseptal region and is often diffuse. Such substrate appears hardly amenable to the beneficial effects of CRT. Therefore, DCM criteria combining systolic dysfunction and LBBB are not applicable to HCM patients. The fact that individual responders exist, however, suggests that disease-specific eligibility criteria should be sought, rather than admitting defeat too early over this important therapeutic issue. A case-by-case evaluation of HF symptoms, QRS duration, LV dyssynchrony, and mechanism of mitral regurgitation may help identify patients who will benefit from CRT. Need for permanent pacing should prompt consideration for CRT in order to prevent worsening of diastolic function. Most importantly, exploring earlier stages of HCM progression and assessing the burden of fibrosis by cardiac magnetic resonance may be key in patient selection (5). Unfortunately, too few of our patients had cardiac magnetic resonance before CRT (n = 5) to address this important issue.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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