How common is hypertrophic cardiomyopathy… really?: Disease prevalence revisited 27 years after CARDIA

doi:10.1016/j.ijcard.2023.04.005

International Journal of Cardiology

Volume 382, 1 July 2023, Pages 64-67

https://doi.org/10.1016/j.ijcard.2023.04.005 Get rights and content

Highlights

•
The estimated prevalence of HCM based on the disease phenotype by imaging is 1:500.
•
HCM prevalence is relevant to clinical practice, funding and public awareness.
•
HCM is not rare but clinically underdiagnosed by a factor of almost 3×.

Abstract

Hypertrophic cardiomyopathy (HCM) is a heterogeneous albeit treatable cardiac disease of variable severity, with the potential for heart failure, atrial fibrillation and arrhythmic sudden death, characterized by otherwise unexplained left ventricular (LV) hypertrophy and affecting all ages and races. Over the last 30 years, several studies have estimated the prevalence of HCM in the general population, employing echocardiography and cardiac magnetic resonance imaging (CMR), as well electronic health records and billing databases for clinical diagnosis. The estimated prevalence in the general population based on the disease phenotype of LV hypertrophy by imaging is 1:500 (0.2%). This prevalence was initially proposed in 1995 in the population-based CARDIA study employing echocardiography, and more recently confirmed by automated CMR analysis in the large UK Biobank cohort. The 1:500 prevalence appears most relevant to clinical assessment and management of HCM. These available data suggest that HCM is not a rare condition but likely underdiagnosed clinically and by extrapolation potentially affects about 700,000 Americans and possibly 15 million people worldwide.

Graphical abstract

Central Illustration. Spectrum of reported population prevalence estimates for HCM. The predominant and most clinically relevant (1:500) is based on the disease phenotype and documented by both echocardiography and CMR.

EHR = electronic health records; MRI = magnetic resonance imaging.

Section snippets

Historical context

For much of its 60-year history, hypertrophic cardiomyopathy (HCM) has been considered a distinctly uncommon and largely untreatable disease with unfavorable prognosis [1]. Consequently, the clinical importance of HCM has at times been marginalized, particularly compared to more common conditions in cardiology such as ischemic heart disease. However, with time HCM has come to be regarded as a disease with worldwide geographic distribution identified in at least 125 countries on all continents,

Strategies to estimate population prevalence

However, assessing prevalence of HCM can be associated with several obstacles including the heterogeneous nature of the disease and its well-recognized incomplete phenotypic penetrance. A definitive answer to the prevalence question would require a large population-based study encompassing multiple modalities (ideally including echocardiography, CMR and advanced genomics), and would likely be logistically difficult if not unrealistic at this time.

Over >25 years a number of clinical

Confounding role of systemic hypertension

A major issue in assessing prevalence data among HCM studies concerns the potential influence of associated systemic hypertension. Not uncommonly, HCM patients have systemic hypertension as an independent second disease. Because both HCM and hypertension are characterized by LV hypertrophy and are often difficult to distinguish clinically, particularly in the absence of outflow obstruction, associated hypertension often obscures a definitive diagnosis of HCM [26].

An additional concern is the

Conclusions

The frequency with which HCM occurs in the general population is of substantial importance to all aspects of this disease, including the introduction of novel drugs [27]. In this regard, a broad range of studies and methodologies have reported various estimates of disease and diagnostic prevalence over 27 years since publication of the first such study (i.e., CARDIA in 1995). While billing and electronic health record data can suggest rates of clinical recognition of the disease and genomic

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Statement of authorship

All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Disclosures

Dr. Massera has served as a consultant for Bristol Myers Squibb Co, Tenaya Therapeutics and Sanofi. Dr. Sherrid has served as a consultant for Pfizer Inc. Dr. Martin S. Maron has served as a consultant for Cytokinetics Inc. and Imbria Pharmaceuticals. Dr. Rowin has a research grant from Pfizer Inc. Dr. Barry J. Maron has no conflicts of interest to declare.

References (27)

B.J. Maron et al.
Diagnosis and evaluation of hypertrophic cardiomyopathy: JACC state-of-the-art review
J. Am. Coll. Cardiol.
(2022)
B.J. Maron et al.
Global burden of hypertrophic cardiomyopathy
JACC Heart Fail.
(2018)
B.J. Maron et al.
Personalized treatment strategies effective in hypertrophic cardiomyopathy do not rely on genomics in 2022: a different tale of precision medicine
Am. J. Cardiol.
(2022)
Y. Hada et al.
Prevalence of hypertrophic cardiomyopathy in a population of adult Japanese workers as detected by echocardiographic screening
Am. J. Cardiol.
(1987)
B.J. Maron et al.
Clinical profile of hypertrophic cardiomyopathy identified de novo in rural communities
J. Am. Coll. Cardiol.
(1999)
B.J. Maron et al.
Prevalence of hypertrophic cardiomyopathy in a population-based sample of American Indians aged 51 to 77 years (the strong heart study)
Am. J. Cardiol.
(2004)
Y. Zou et al.
Prevalence of idiopathic hypertrophic cardiomyopathy in China: a population-based echocardiographic analysis of 8080 adults
Am. J. Med.
(2004)
J. Rodriguez-Capitan et al.
Prevalence of hypertrophic cardiomyopathy in a large sample of the Spanish working population
Rev. Clin. Esp (Barc)
(2021)
A. de Marvao et al.
Phenotypic expression and outcomes in individuals with rare genetic variants of hypertrophic cardiomyopathy
J. Am. Coll. Cardiol.
(2021)
M.S. Maron et al.
Occurrence of clinically diagnosed hypertrophic cardiomyopathy in the United States
Am. J. Cardiol.
(2016)

M. Butzner et al.

Clinical diagnosis of hypertrophic cardiomyopathy over time in the United States (a population-based claims analysis)

Am. J. Cardiol.

(2021)

A.G. Bick et al.

Burden of rare sarcomere gene variants in the Framingham and Jackson heart study cohorts

Am. J. Hum. Genet.

(2012)

C. Semsarian et al.

New perspectives on the prevalence of hypertrophic cardiomyopathy

J. Am. Coll. Cardiol.

(2015)

Cited by (6)

Hypertrophic cardiomyopathy as a high-risk feature on perioperative care: How to deal with this self-fulfilling prophecy?
2024, International Journal of Cardiology
Clinical course of adults with co-occurring hypertrophic cardiomyopathy and hypertension: A scoping review
2024, American Heart Journal Plus: Cardiology Research and Practice
Hypertension affects approximately 50 % of patients with hypertrophic cardiomyopathy (HCM) but clinical course in adults with co-occurring HCM and hypertension is underexplored. Management may be challenging as routine anti-hypertensive medications may worsen obstructive HCM, the most common HCM phenotype. In this scoping review, we sought to synthesize the available literature related to clinical course and outcomes in adults with both conditions and to highlight knowledge gaps to inform future research directions.
We searched 5 electronic databases (PubMed, CINAHL, Scopus, Embase, Web of Science) to identify peer-reviewed articles, 2011–2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review (PRISMA-ScR) guideline.
Eleven articles met eligibility. Adults with both conditions were older and had higher rates of obesity and diabetes than adults with HCM alone. Results related to functional class and arrhythmia were equivocal in cross-sectional studies. Only 1 article investigated changes in medical therapy among adults with both conditions. Hypertension was a predictor of worse functional class, but was not associated with all-cause mortality, heart failure-related mortality, or sudden-death. No data was found that related to common hypertension-related outcomes, including renal disease progression, nor patient-reported outcomes, including quality of life.
Our results highlight areas for future research to improve understanding of co-occurring HCM and hypertension. These include a need for tailored approaches to medical management to optimize outcomes, evaluation of symptom burden and quality of life, and investigation of hypertension-related outcomes, like renal disease and ischemic stroke, to inform cardiovascular risk mitigation strategies.
Clinical to Population Prevalence of Hypertrophic Cardiomyopathy Phenotype: Insights From the National Echo Database Australia
2024, Heart Lung and Circulation
There is a paucity of data describing the underlying prevalence of hypertrophic cardiomyopathy (HCM), a primary genetic disorder characterised by progressive left ventricular (LV) hypertrophy and sudden death, from both a clinical and a population perspective.
We screened the echocardiographic reports of 155,668 men and 147,880 women within the multicentre National Echo Database Australia (NEDA) (2001–2019). End-diastolic wall thickness ≥15 mm anywhere in the left ventricle was identified as a characteristic of an HCM phenotype according to current guideline recommendations. Applying a septal-to-posterior wall thickness ratio >1.3 and LV outflow tract obstruction ≥30 mmHg (when documented), we further identified asymmetric septal hypertrophy and obstructive HCM (oHCM), respectively. The observed pattern of phenotypical HCM within the overall NEDA cohort (>650,000 cases) was then extrapolated to the ∼539,000 (5.7% of adult population) and ∼474,000 (4.8%) Australian men and women, respectively, who were investigated with echocardiography in 2021 on an age-specific basis.
Overall, 15,380 cases (mean age 71.1±14.6 years, 10,138 men [65.9%]) with the characteristic HCM phenotype within the NEDA cohort were identified. Of these 15,380 cases, 5,552 (36.1%) had asymmetric septal hypertrophy, and 2,276 of the 10,290 cases with LV outflow tract obstruction profiling data (22.1%) had obstructive HCM. A further 3,389 of 13,715 cases (24.7%) had evidence of LV systolic dysfunction (LV ejection fraction <55%). Within the entire NEDA cohort (including those without LV profiling), HCM was found in 10,138 of 342,161 men (2.96%; 95% confidence interval [CI] 2.91%–3.02%) and 5,242 of 308,539 women (1.70%; 95% CI 1.65%–1.75%). When extrapolated to the Australian population, we estimate that a minimum of 15,971 men and 8,057 women presented with echocardiographic features of phenotypical HCM in 2021. This translates into a minimum caseload/prevalence of ∼17 adult men (∼2.5 in those aged ≤50 years) and eight adult women (∼1 in those aged ≤50 years) per 10,000 population meeting phenotypical HCM criteria.
Using contemporary Australian echocardiographic and population data, we estimate that a minimum of 15,971 (17.5 cases/10,000) men and 8,057 women (8.2 cases/10,000) had echocardiographic evidence of phenotypical HCM in 2021. These disease burden data are particularly relevant as new treatment options are emerging.
Recent highlights on myocarditis and cardiomyopathies from the International Journal of Cardiology and International Journal of Cardiology: Heart & Vasculature
2023, IJC Heart and Vasculature
Imaging cardiac hypertrophy in hypertrophic cardiomyopathy and its differential diagnosis
2023, Current Opinion in Cardiology
Mouse Models of Cardiomyopathies Caused by Mutations in Troponin C
2023, International Journal of Molecular Sciences

View full text

ReviewHow common is hypertrophic cardiomyopathy… really?: Disease prevalence revisited 27 years after CARDIA

Highlights

Abstract

Graphical abstract

Section snippets

Historical context

Strategies to estimate population prevalence

Confounding role of systemic hypertension

Conclusions

Funding

Statement of authorship

Disclosures

J. Am. Coll. Cardiol.

JACC Heart Fail.

Am. J. Cardiol.

Am. J. Cardiol.

J. Am. Coll. Cardiol.

Am. J. Cardiol.

Am. J. Med.

Rev. Clin. Esp (Barc)

J. Am. Coll. Cardiol.

Am. J. Cardiol.

Am. J. Cardiol.

Am. J. Hum. Genet.

J. Am. Coll. Cardiol.

Review
How common is hypertrophic cardiomyopathy… really?: Disease prevalence revisited 27 years after CARDIA