Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that affects patients of all ages, from infants to the elderly, with a prevalence of at least 1:500.¹ HCM has been considered the most common cause of non-traumatic sudden death in the young, with an understandably disproportionate attention on HCM in young patients. HCM patients of more advanced age beyond mid-life are being increasingly recognized due to heightened index of suspicion for this disease² and increased penetration of advanced cardiac imaging into practice.^3,4 Such older patients will present for evaluation and management to general cardiology practices, with questions related to life expectancy, progression of heart failure, risk of sudden cardiac death, and for implantable defibrillator (ICD) therapy.

Is HCM Really a Progressive Disease?

HCM can cause significant disability, morbidity, and even mortality in middle-aged and young patients due to the risks of heart failure, sudden death, and the consequences of atrial fibrillation. However, it is now evident that many (if not most) affected HCM patients probably experience relatively benign clinical course and even normal (if not extended) life expectancy.⁵

Notably, age is an important determinant in the natural history of HCM, but there is a historic, prevalent, and persistent misunderstanding that HCM is not only grim and unrelenting but, in fact, increasingly progressive throughout life. However, recent data change perceptions of the natural course of HCM. HCM-related death/event rates owing to progressive heart failure, embolic stroke, or sudden death in patients of more advanced age (>60 years) are less than rates reported at other ages, and the estimated annual mortality risk is less than that in the general population matched for age and sex.^2,6 Non-HCM-related comorbidities more likely impact the longevity of HCM patients in their seventh decade and beyond than HCM specifically. The natural course of HCM demonstrates stability in this advanced age group with almost 80% of surviving patients reporting no or mild HCM-related heart failure symptoms.² In a study of 428 consecutive HCM patients between ages of 60 to 91 years at study entry, survival at five and 10 years (accounting for all-cause mortality) was 77% and 54%, respectively, with 125 patients achieving age ≥80 years.² Mortality events attributable to HCM (Figure 1) occurred in 16 patients (0.64% per year) at 72 ± eight years of age, due to atrial fibrillation-related embolic stroke (n = 6; with 2 on warfarin), progressive heart failure (n = 2), heart transplantation for end-stage disease (n = 1), postoperative complications (n = 2), and arrhythmic sudden death events (n = 5).²

Figure 1

What Is the Risk of Sudden Death in HCM Patients of More Advanced Age?

SD in HCM predominantly manifests itself in young adults and is the most common cause of death in competitive athletes.⁷ Reaching the seventh or eight decades (>60 years) in a genetic disease like HCM is a negative risk marker, conveying relative protection from ongoing sudden death risk. The common perception among patients and many cardiologists that the course of HCM is one of unwavering progression throughout a lifetime is not accurate. The relatively low HCM-related sudden death event rate of 0.20% per year (in the absence of coronary artery disease in patients >60 years at study design) underscores this principle.² Clinical markers that convey predictive power for SD in younger HCM patients <50 years of age do not necessarily assume the same significance in patients who have achieved more advanced ages. For example, massive left ventricular (LV) hypertrophy (wall thickness ≥30 mm), a sudden death risk marker in younger patients,⁸ is rare in HCM patients ≥60 years of age and compatible with advanced age.² Similarly, about 40% of patients in the Maron et al. study achieved advanced age despite LV outflow gradients (average, 70 mm Hg), which underscores that many patients tolerate these gradients for extensive periods of time.² Late gadolinium enhancement (LGE) on contrast cardiac magnetic resonance imaging, a potential predictor of sudden death events and progressive heart failure,⁹ is common in older patients, raising skepticism concerning LGE as a risk marker in this age group.² Among survivors in the Maron et al. study, about 50% had one or more major conventional risk markers used to stratify sudden death risk in HCM patients,^2,10 most commonly unexplained syncope, and nonsustained ventricular tachycardia. The five sudden death events (1.2%; 0.20% per year) included three survivors: two with appropriate primary prevention defibrillator (ICD) therapy at 60 and 61 years of age, respectively, and one with aborted out-of-hospital cardiac arrest with therapeutic hypothermia at 72 years of age.²

Conclusions

Patient age importantly dictates the clinical course for many patients with HCM. Aging in HCM, in effect, represents a negative risk marker for sudden death to many patients. HCM patients of advanced age are more likely to die of non-cardiac competing morbidities than of HCM. Recommendations for primary prevention ICDs in older HCM patients should be made on a case-by-case basis with prudent restraint.

References

1. Maron BJ, Ommen SR, Semsarian C, Spirito P, Olivotto I, Maron MS. Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine. J Am Coll Cardiol 2014;64:83-99.
2. Maron BJ, Rowin EJ, Casey SA, et al. Risk stratification and outcome of patients with hypertrophic cardiomyopathy >=60 years of age. Circulation 2013;127:585-93.
3. Maron MS, Maron BJ, Harrigan C, et al. Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance. J Am Coll Cardiol 2009;54:220-8.
4. Knickelbine T, Lesser JR, Haas TS, et al. Identification of unexpected nonatherosclerotic cardiovascular disease with coronary CT angiography. JACC Cardiovasc Imaging 2009;2:1085-92.
5. Maron BJ, Rowin EJ, Casey SA, et al. Hypertrophic cardiomyopathy in adulthood associated with low cardiovascular mortality with contemporary management strategies. J Am Coll Cardiol 2015;65:1915-28.
6. Maron BJ, Olivotto I, Spirito P, et al. Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large non-referral-based patient population. Circulation 2000;102:858-64.
7. Maron BJ. Sudden death in young athletes. N Engl J Med 2003;349:1064-75.
8. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342:1778-85.
9. Chan RH, Maron BJ, Olivotto I, et al. Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation 2014;130:484-95.
10. Maron BJ. Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation 2010;121:445-56.

Keywords: Aged, Atrial Fibrillation, Biomarkers, Cause of Death, Cardiomyopathy, Hypertrophic, Comorbidity, Coronary Artery Disease, Death, Sudden, Cardiac, Defibrillators, Implantable, Gadolinium, Heart Failure, Heart Transplantation, Hypertrophy, Hypothermia, Induced, Life Expectancy, Magnetic Resonance Imaging, Out-of-Hospital Cardiac Arrest, Postoperative Complications, Prevalence, Primary Prevention, Stroke, Syncope, Tachycardia, Ventricular, Ventricular Fibrillation, Warfarin, Geriatrics

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