Response by Ho et al to Letter Regarding Article, “Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights From the Sarcomeric Human Cardiomyopathy Registry (SHaRe)”
Authors: Carolyn Y. Ho, Sharlene M. Day, Euan A. Ashley, Michelle Michels, Alexandre C. Pereira, Daniel Jacoby, Neal K. Lakdawala, James S. Ware, Adam S. Helms, Steven D. Colan, Christine E. Seidman, Iacopo Olivotto
Journal: Circulation (2019)

In Response:The Sarcomeric Human Cardiomyopathy Registry (SHaRe) originates from international centers deeply invested in clinical investigation and state-of-theart management of hypertrophic cardiomyopathy (HCM).Unlike single-center studies with relatively small patient cohorts and limited follow-up, the value of SHaRe lies in amassing the scale and diversity of patient experience needed to address fundamental questions regarding the natural history of this complex disease.Our recent article 1 describes the lifetime burden of HCM from nearly 5000 patients, spanning ≈25 000 patient-years.No other study has done this.We found that patients with early-onset HCM have more adverse outcomes in the ensuing decades than patients with late-onset HCM.All SHaRe sites have expert surgical programs that provide excellent myectomy outcomes.However, it is important to recognize that, although myectomy provides highly effective symptomatic relief, it has never been proven to improve mortality, and as Dr Maron and colleagues have reported, 2 not all patients benefit.That the real burden of disease takes longer than previously appreciated to emerge, and emerges despite good treatment, is a novel finding from our study.SHaRe provides an important step forward: a platform to address unresolved questions and unmet needs, both of which remain substantial.Through multicenter collaboration, we demonstrated that genotype is informative of adverse natural history.Therefore, it is imperative to understand how sarcomere gene mutations cause profound abnormalities in myocardial energetics, contractile function, and cellular architecture.In addition, the SHaRe study highlights that some HCM, in particular, nonfamilial HCM, carries a more favorable prognosis and may not require as aggressive management as sarcomeric HCM.Thus, it is critical to refine the identification of clinically important and distinct subcohorts of HCM.Finally, we are puzzled by the suggestion that our data might "adversely affect attitudes of clinicians."We share Drs Maron and Rowin's optimism that HCM can be treated well with careful management.But equally so, we caution against underestimating the lifelong risks of HCM, in particular, in younger patients.Overemphasizing midterm therapeutic successes will not prevent the emergence of chronic arrhythmias and heart failure.Indeed, progressive heart failure both in nonobstructive and obstructive HCM (despite myectomy) has been well reported by Dr Maron and colleagues, including that subsets of patients (notably, younger patients with sarcomere mutations) experience greater morbidity and mortality despite their contemporary management. 2-5Moreover, only a minority of patients with HCM benefit from the major advances in management championed by Dr Maron and colleagues, specifically myectomy,