Hypertrophic Cardiomyopathy in Elderly Individuals: Is It a Rose by Another Name?

Hypertrophic cardiomyopathy (HCM) is a familial heart muscle disease characterized by a diverse clinical and phenotypic spectrum that is usually identified in the second through fifth decades of life. ¹ , ² Since its early descriptions in 1957, ³ , ⁴ HCM has been increasingly recognized in older patients. However, studies suggest that the condition takes a different form when first diagnosed in this age group and may ultimately represent a disease entity that is distinct from that which predominates in the young. ² , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰

In this issue of the Journal of the American Heart Association (JAHA), Alashi et al ¹¹ describe the clinical characteristics and outcomes of 1100 consecutively studied elderly (aged >75 years) patients with HCM at the Cleveland Clinic over a 16.5‐year period. They found a higher prevalence of traditional cardiovascular risk factors, such as hypertension, hyperlipidemia, and atrial arrhythmia, as opposed to HCM‐related sudden cardiac death risk factors. Half of the study cohort had obstructive physiological features, of which a third underwent symptom‐guided septal reduction therapy with myectomy (79%) or alcohol septal ablation (21%) with low in‐hospital mortality and similar longer‐term outcomes to that of a normal age‐sex matched US population. This study provides an insight into the clinical profile and outcomes of a large elderly population with “HCM,” managed in a specialist tertiary referral center.

The biggest limitation of this study relates to the fundamental issue of whether HCM in elderly individuals, and thus the cohort studied by the authors, truly represents the same disease as that in young and middle‐aged individuals or in most, is a phenocopy related to aging and hypertension. It is recognized that many elderly patients with HCM have distinct echocardiographic features and clinical characteristics, including a higher prevalence of hypertension, exaggerated basal septal hypertrophy, small left ventricular (LV) cavity size, and marked distortion of LV outflow tract morphological features. ⁶ , ⁹ , ¹⁰ , ¹² In addition, unlike HCM in younger patients, most are women and only ≈10% have a recognized pathogenic mutation. There is often dynamic LV outflow tract obstruction, with only a modest increase in LV wall thickness and a different septal shape compared with the younger patients with the more typical phenotypic expression. ⁶ , ⁹ Although dynamic LV outflow obstruction is common, the mechanism may differ, with an angulated aorta and mitral annular calcification contributing to narrowing the LV outflow tract. Furthermore, there appears to be a later onset of symptoms in elderly patients and an inverse relationship between advanced age and disease‐related risk, which further supports the theory that a different disease process may be involved. ⁵ , ⁶

The authors importantly demonstrate that in an HCM surgical center of excellence, myectomy can be performed at a relatively low risk and well below the predicted Society of Thoracic Surgeons' risk score. The overall hospital mortality with septal reduction therapy was only 2.5%. It is surprising that so many patients were offered myectomy rather than alcohol septal ablation, the therapy more commonly used in an elderly cohort. Such a distinction is important because their surgical data cannot be extrapolated to most centers, ¹³ and as they indicate, low‐volume centers can have an alarming mortality, even in younger patients. It is likely that in most experienced centers, alcohol septal ablation will be the more common intervention. However, alcohol septal ablation, as noted, should also be performed in experienced centers shown to have low rates of mortality and morbidity. Ultimately, an adequately powered prospective study would be needed to truly understand outcomes in septal reduction therapy and to avoid “cherry‐picking” of lower‐risk patients, but the inherent challenges of undertaking a randomized control trial in this setting are significant, as previously highlighted. ¹⁴

The authors focused on all‐cause mortality rather than cardiovascular mortality. Most of the mortality documented was attributable to patient age and comorbidity rather than that seen in traditional HCM, with sudden death and progression to systolic or diastolic heart failure. This again highlights the distinction of this cohort with younger patients. Traditional HCM risk factors for sudden cardiac death were also not prevalent, as would be expected. Quantitative contrast‐enhanced cardiovascular magnetic resonance imaging with late gadolinium enhancement is recognized as an important imaging marker for myocardial fibrosis and has a linear relationship to increased risk of sudden cardiac death. ¹⁵ Cardiovascular magnetic resonance imaging was performed in just 10% of the study cohort of Alashi et al, reporting only presence or absence of late gadolinium enhancement without formal late gadolinium enhancement quantification. The 52% who had evidence of late gadolinium enhancement could potentially include patients with enhancement isolated to right ventricular insertion areas, which has been shown to represent gadolinium pooling rather than replacement scarring. ¹⁶ Cardiovascular magnetic resonance imaging and genetic testing have significantly advanced our understanding and evaluation of HCM over time. Both are powerful strategies for diagnosis and differentiation of this complex inherited condition from its phenocopies. ¹⁷ Only 3% of the study population underwent genetic testing, again raising the question as to whether this group represents a genuine cohort with HCM who would frequently have a familial pattern of inheritance.

Another important limitation is the unavoidable degree of selection bias that inherently exists in many studies undertaken in dedicated HCM units. ¹⁸ It is likely that such institutions represent the most symptomatic patients or those with the most significant morphological characteristics and may not necessarily capture undiagnosed HCM or the milder spectrum of disease managed in the community.

Applying information from this study and other HCM studies of elderly patients to clinical practice requires awareness of the potential ambiguities surrounding the diagnosis of this condition in elderly patients and difficulties of generalizing outcome data from a single center. Does this cohort really have what we would traditionally consider true sarcomeric HCM, or rather do most have an acquired form of septal hypertrophy, often associated with dynamic LV outflow tract obstruction and potentially mixed or perhaps even alternative causes, such as hypertension and amyloidosis? It is likely that patients diagnosed earlier in life who progress to older age are different than patients first diagnosed when aged >65 years.

This distinction is important as these patients have a different phenotype, different clinical characteristics, different risk, and, ultimately what some might argue, a different disease process. As William Shakespeare has Juliette tell Romeo, “What's in a name? That which we call a rose by any other name would smell as sweet.” Although the strength of their relationship does not depend on their names, she is a Capulet and he is a Montague, and this distinction makes them different. ¹⁹ In patients with HCM, it is important to correctly separate true HCM from phenocopies. Although HCM in elderly patients may be a misnomer, the authors provide important insights into the characteristics, management, and outcomes of this large, unique population.

Disclosures

None.

(J Am Heart Assoc. 2021;10:e020204. DOI: 10.1161/JAHA.120.020204.)