Abstract
Background
Data on the contemporary prevalence of hypertrophic cardiomyopathy (HCM) in the United States are limited, and information on the epidemiology by disease characteristics and patient demographics is lacking.
Objectives
This study aimed to estimate the prevalence and incidence of HCM in the United States from 2016 to 2023 overall and stratified by patient subgroups.
Methods
In this observational study, patient-level administrative claims from 2016 to 2023 were collected from the Symphony Integrated Dataverse. Selected patients were those with ≥1 HCM diagnosis code during the study period. Patients were designated as having nonobstructive HCM (nHCM), obstructive HCM (oHCM), and symptomatic HCM using diagnosis codes.
Results
During the period of 2016-2023, there were 431,457 HCM cases in the total population of 141,003,247 patients for a prevalence rate of 1/327 individuals (95% CI: 1/326-328). The incidence of HCM was 50/100,000 (95% CI: 50-51/100,000) in 2017 and was 56/100,000 (95% CI: 56-57/100,000) in 2023. The rates in nHCM and oHCM were 188/100,000 (95% CI: 187-189/100,000) and 117/100,000 (95% CI: 117-118/100,000), respectively. Similarly, the incidence in asymptomatic and symptomatic HCM was 171/100,000 (95% CI: 171-172/100,000) and 135/100,000 (95% CI: 134-135/100,000), respectively. Prevalence generally increased with age and was higher in males than in females (341/100,000 [95% CI: 339-342/100,000] vs 277/100,000 [95% CI: 275-278/100,000], respectively). The regions and locations of individual states with the highest HCM, oHCM, and nHCM rates were in the Northeast and Midwest.
Conclusions
In this administrative claims-based study, the prevalence of HCM from 2016 to 2023 was 1/327 individuals, which translates to an estimated 832,956 HCM cases in the United States.
Key words: incidence, nonobstructive, obstructive, prevalence
Central Illustration
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular condition and is characterized by left ventricular hypertrophy absent other apparent causes.1 HCM is generally classified as obstructive (oHCM) when the hypertrophy impedes left ventricular outflow tract hemodynamics or as nonobstructive (nHCM).2 Although many patients with HCM are asymptomatic, typical signs and symptoms include chest pain, lightheadedness, dyspnea, palpitations, and syncope, which tend to worsen with physical exertion.2,3 Heart failure, atrial fibrillation, sudden cardiac death, and myocardial ischemia are major complications that can occur with HCM.1 With recent advancements in pharmacotherapy and procedural interventions such as septal reduction therapy (SRT) and implantable cardioverter-defibrillators, overall mortality of HCM has been reduced to approximately 0.50% per year.4 Yet, as a progressive disease, inadequate symptom control and enhanced adverse cardiovascular event risk among patients with HCM still poses a substantial clinical and economic health care burden in the United States.5, 6, 7, 8 An American claims analysis found that patients with oHCM experienced an average of 0.42 hospitalizations and a total disease-related cost of over $20,000 within 1 year of diagnosis.5 Furthermore, health care costs for patients with oHCM are significantly higher than that of matched healthy controls and are largely driven by symptomatic disease.7
Data on the contemporary prevalence of HCM in the United States are limited and are often confounded by misdiagnoses, underrecognition, and asymptomatic illness.9,10 A targeted literature review of the epidemiology of HCM concluded that the commonly cited prevalence estimates of 1:200 to 1:500 tend to be based on studies with small sample sizes published in the 1990s.9 As innovations in diagnostic technology and clinical awareness of HCM have improved in recent years, prior prevalence estimates may no longer reflect more modern HCM epidemiology. A longitudinal claims analysis reported that the prevalence of HCM in the United States in 2013 was 1:1,905 and rose to 1:1,250 in 2019.11 However, emerging data on the epidemiology of HCM by disease characteristics and patient demographics in the United States are warranted and timely, as they are applicable to assess the population of patients who may benefit from a novel class of agents, cardiac myosin inhibitors (CMIs).12,13 The objectives of this study were to estimate the prevalence and incidence of HCM in the United States from 2016 to 2023 overall and stratified by patient subgroups.
Methods
Study design and data source
In this retrospective observational study, patient-level administrative claims from 2016 to 2023 were collected from the Symphony Integrated Dataverse (IDV) database. The IDV database is a Health Insurance Portability and Accountability Act compliant platform that contains medical, pharmacy, and hospital claims information from individuals across the country. Uniquely, prescription drug benefits are linked to hospital and physician practice claims with medical procedure (ie, Current Procedural Terminology) and International Classification of Diseases (ICD-10) codes, accounting for all insurance types including commercial plans, Medicare Part D, cash, assistance programs, and Medicaid. The IDV has been used in a previous study evaluating economic burden in patients with HCM14 and was selected due to its longitudinal nature and comprehensive representation of patients across census regions of the United States. In accordance with regulatory rule 45 CFR §46, this retrospective analysis using deidentified patient data was exempt from Institutional Review Board oversight. Reporting of the study is aligned with the Strengthening the Reporting of Observational Studies in Epidemiology checklist.
Patient selection
Selected patients were those with at least one HCM diagnosis code of I42.1 or I42.2, SRT code (ICD-10-Procedure Coding System) of 025M0ZZ, 025M3ZZ, 025M4ZZ, 02BM0ZZ, 02BM3ZZ, 02BM4ZZ, 02BM3ZX, 02BM4ZX, 02BL0ZZ, or 02TM0ZZ or Current Procedural Terminology of 93583, 33542, or 33416, or use of CMIs during the study period. The index diagnosis date was the date of the first HCM diagnosis code during the study period. Patients with only I42.2 diagnosis codes were designated as having nHCM, and patients with at least one I42.1 diagnosis code, SRT code, or CMI use were designated as having oHCM. HCM were considered symptomatic if the patient had an ICD-10 code for chest pain, dyspnea, fatigue, heart failure, palpitations, or syncope in the 365 days before their index diagnosis or underwent SRT at any point in time (Supplemental Table 1). Patients with Fabry disease and/or amyloidosis were excluded from this analysis.
Outcomes and analysis
The primary outcomes were the incidence and prevalence of HCM in the IDV database during the study period of 2016-2023. Secondary outcomes included the incidence and prevalence of HCM in the IDV database stratified by subgroups: sex, age, oHCM, nHCM, symptomatic HCM, asymptomatic HCM, region, and U.S. state. Prevalence was calculated as the number of patients diagnosed with HCM divided by the total number of active patients during the period of interest. Incidence was calculated as the number of patients newly diagnosed with HCM divided by the total number of disease-free patients during the period of interest. A newly diagnosed patient was defined as having no HCM diagnosis code at any point before the index diagnosis. Patients initially with nHCM diagnoses in 1 year with at least one oHCM diagnoses in a following year were retrospectively adjusted to being labeled as having incident oHCM in the initial year.
Another important outcome of interest was the number of prevalent HCM cases in the U.S. population over 2016 to 2023, which was estimated by using the 2016 to 2023 demographic- and state-specific prevalence results and extrapolating to the U.S. population using demographic data obtained in the 5-year American Community Survey (2016-2023 data releases).15 In specific, this computation translates the prevalence rate of every state-age-sex group to group-specific case counts first, and then aggregates the case counts for all groups up to the national level. For example, if the prevalence rate of males aged 65+ in California was 205/100,000 and the average number of males aged 65+ in California over 2016 to 2023 was 2.4 million, then the estimated number of cases for this group was 4,920 (ie, 205/100,000 times 2,400,000). This process is repeated for every state-age-sex group and aggregated appropriately.
Analyses were descriptive only and conducted with R 4.2.1. Prevalence and incidence rates are reported as the number of cases per 100,000 patients, the percentage of all people, and as a ratio (ie, 1:x, in which x represents the number of people there are per case). One set of sensitivity analyses entailed altering the criteria by which prevalence was reported by age group. Various combinations of removing ages 0 to 3 from the <18 age group and using stricter HCM diagnosis criteria—namely, requiring at least 2 HCM diagnoses at least 30 days apart. Further sensitivity analysis used different criteria to classify HCM patients as nHCM over oHCM based on the cumulative number of claims with diagnoses codes of each type. First, absolute differences between the number of nHCM and oHCM diagnoses codes were altered as part of the criteria. In specific, if a patient had at least 10, 3, or 1 more nHCM codes than oHCM codes, they were classified as nHCM. Separately, ratio thresholds were employed as well. For example, if a patient had at least 10 or 3 times as many nHCM codes as oHCM codes, they were classified as nHCM.
Results
Prevalence of HCM (oHCM and nHCM), including symptoms
During the period of 2016-2023, there were 431,457 HCM cases in the total population of 141,003,247 patients, yielding a prevalence rate of 306/100,000 (95% CI: 305/100,000-307/100,000) people (Table 1, Central Illustration). This equates to 0.306% (95% CI: 0.305%-0.307%) of the study population and 1 case per 327 people (95% CI: 1:326-328). The prevalence of nHCM from 2016 to 2023 was 188/100,000 (95% CI: 187-189/100,000) and of oHCM was 117/100,000 (95% CI: 117-118/100,000) (Table 1). The proportion of nHCM patients in the IDV was 61.6% (Table 1), while that of the U.S. population was 63.4% (Table 2). In sensitivity analyses using the most restrictive nHCM criteria, the proportion of nHCM patients increased to 69.3% (Supplemental Table 2).
Table 1.
Number of HCM Cases and the Prevalence Rate (95% CIs) Over 2016-2023
| HCM, n (%) | HCM Rate | oHCM Ratea | nHCM Ratea | |
|---|---|---|---|---|
| Total | 431,457 (100) | 306/100,000 (305-307/100,000); 0.306% (0.305-0.307%); 1:327 (1:326-328) | 117/100,000 (117-118/100,000); 0.117% (0.117-0.118%); 1:851 (1:847-853) | 188/100,000 (187-189/100,000); 0.188% (0.187-0.189%); 1:531 (1:529-533) |
| Presentation | ||||
| Symptomatic | 189,900 (44.0) | 135/100,000 (134-135/100,000); 0.135% (0.134-0.135%); 1:743 (1:739-746) | 53/100,000 (53-53/100,000); 0.053% (0.052-0.053%); 1:1,892 (1:1,878-1,905) | 82/100,000 (81-82/100,000); 0.082% (0.081-0.082%); 1:1,222 (1:1,215-1,229) |
| Asymptomatic | 241,557 (56.0) | 171/100,000 (171-172/100,000); 0.171% (0.171-0.172%); 1:584 (1:581-586) | 65/100,000 (64-65/100,000); 0.065% (0.064-0.065%); 1:1,547 (1:1,537-1,557) | 107/100,000 (106-107/100,000); 0.107% (0.106-107%); 1:937 (1:932-942) |
| Age, yb | ||||
| <18 | 14,928 (3.5) | 246/100,000 (242-250); 0.246% (0.242-0.250%); 1:407 (1:401-414) | 77/100,000 (74-79/100,000); 0.077% (0.074-0.079%); 1:1,305 (1:1,267-1,343) | 169/100,000 (166-172/100,000); 0.169% (0.166-0.172%); 1:591 (1:579-602) |
| 18-34 | 24,325 (5.7) | 167/100,000 (165-169/100,00); 0.167% (0.165-0.169%); 1:598 (1:590-605) | 60/100,000 (58-61/100,000); 0.060% (0.058-0.061%); 1:1,678 (1:1,644-1,714) | 108/100,000 (106-109/100,000); 0.108% (0.106-0.109%); 1:929 (1:916-946) |
| 35-44 | 25,701 (6.0) | 175/100,000 (173-177/100,000); 0.175% (0.173-0.177%); 1:572 (1:565-579) | 64/100,000 (63-65/100,000); 0.064% (0.063-0.065%); 1:1,569 (1:1,528-1,591) | 111/100,000 (109-113); 0.111% (0.109-0.113%); 1:900 (1:886-914) |
| 45-54 | 47,013 (11.0) | 219/100,000 (217-221/100,000); 0.219% (0.217-0.221%); 1:456 (1:452-460) | 83/100,000 (82-84/100,000); 0.083% (0.082-0.084%); 1:1,207 (1:1,190-1,225) | 137/100,000 (135-138/100,000); 0.137% (0.135-0.138%); 1:732 (1:723-740) |
| 55-64 | 87,996 (20.5) | 294/100,000 (293-296/100,000); 0.294% (0.293-296%); 1:340 (1:337-342) | 115/100,000 (114-117/100,000); 0.115% (0.114-0.117%); 1:866 (1:857-875) | 179/100,000 (177-180/100,000); 0.179% (0.177-0.180%); 1:559 (1:554-564) |
| 65+ | 229,364 (53.4) | 422/100,000 (420-424/100,000); 0.422% (0.420-0.424%); 1:237 (1:236-238) | 166/100,000 (165-168/100,000); 0.166% (0.165-0.168%); 1:601 (1:597-605) | 256/100,000 (254-257/100,000); 0.256% (0.254-0.257%); 1:391 (1:389-393) |
| Sexc | ||||
| Male | 220,641 (51.1) | 341/100,000 (339-342/100,000); 0.341% (0.339-0.342%); 1:294 (1:292-295) | 121/100,000 (120-123/100,000); 0.121% (0.120-0.123%); 1:824 (1:818-830) | 219/100,000 (218-220/100,000); 0.219% (0.218-0.220%); 1:456 (1:454-458) |
| Female | 210,793 (48.9) | 277/100,000 (275-278/100,000); 0.277% (0.275-278%); 1:361 (1:360-363) | 114/100,000 (114-115/100,000); 0.114% (0.114-0.115%); 1:876 (1:871-882) | 162/100,000 (161-163/100,000); 0.162% (0.161-0.163%); 1:615 (1:611-618) |
| Regiond | ||||
| Midwest | 103,723 (24.0) | 352/100,000 (350-355/100,000); 0.352% (0.350-0.355%); 1:284 (1:282-285) | 134/100,000 (133-136/100,000); 0.134% (0.133-0.136%); 1:744 (1:737-752) | 218/100,000; (216-219/100,000); 0.218% (0.216-0.219%); 1:459 (1:456-463) |
| Northeast | 105,551 (24.5) | 414/100,000 (411-416/100,000); 0.414% (0.411-0.416%); 1:242 (1:240-243) | 162/100,000 (160-163/100,000); 0.162% (0.160-0.163%); 1:619 (1:613-635) | 252/100,000 (250-254/100,000); 0.252% (0.250-0.254%); 1:396 (1:393-399) |
| South | 154,545 (35.8) | 277/100,000 (275-278/100,000); 0.277% (0.275-0.278%); 1:361 (1:360-363) | 104/100,000 (103-106/100,000); 0.104% (0.103-0.106%); 1:958 (1:951-966) | 172/100,000 (171-173/100,000); 0.172% (0.171-0.173%); 1:581 (1:578-585) |
| West | 62,256 (14.4) | 237/100,000 (236-239/100,000); 0.237% (0.236-0.239%); 1:421 (1:418-424) | 95/100,000 (94-96/100,000); 0.095% (0.094-0.096%); 1:1,057 (1:1,044-1,070) | 143/100,000 (141-144/100,000); 0.143% (0.141-0.144%); 1:700 (1:693-707) |
HCM = hypertrophic cardiomyopathy; nHCM = nonobstructive HCM; oHCM = obstructive HCM.
Data are reported per 100,000 people; % of all people; and 1:x, in which x represents the number of people there are per case.
n (%) for oHCM and nHCM are 165,676 (38.4%) and 265,781 (61.6%), respectively.
Excludes 2,130 HCM (0.5%) cases with unknown age.
Excludes 23 HCM (0.006%) cases with unknown sex.
Excludes 5,382 HCM cases (1.2%) with unknown region.
Central Illustration.
Prevalence of Hypertrophic Cardiomyopathy in the United States From 2016 to 2023
Table 2.
Estimated Number and Percentage of HCM, oHCM, and nHCM Prevalent Cases in the United States in 2016-2023 by Characteristic Based on U.S. Population Demographics
| HCM, n (%) | oHCM, n (%)a | nHCM, n (%)a | |
|---|---|---|---|
| Total | 832,956 | 304,852 | 528,104 |
| Presentation | |||
| Symptomatic | 309,317 (37.1) | 125,021 (41.0) | 184,296 (34.9) |
| Asymptomatic | 523,639 (62.9) | 179,831 (59.0) | 343,808 (65.1) |
| Age, y | |||
| <18 | 180,224 (21.6) | 56,114 (18.4) | 124,110 (23.5) |
| 18-34 | 143,115 (17.2) | 51,369 (16.9) | 91,745 (17.4) |
| 35-44 | 74,934 (9.0) | 27,408 (9.0) | 47,525 (9.0) |
| 45-54 | 92,994 (11.2) | 35,156 (11.5) | 57,838 (11.0) |
| 55-64 | 123,034 (14.8) | 48,404 (15.9) | 74,630 (14.1) |
| 65+ | 218,656 (26.3) | 86,400 (28.3) | 132,256 (25.0) |
| Sex | |||
| Male | 482,703 (58.0) | 169,830 (55.7) | 312,873 (59.2) |
| Female | 350,253 (42.0) | 135,022 (44.3) | 215,231 (40.8) |
| Region | |||
| Midwest | 202,674 (24.3) | 73,851 (24.2) | 128,823 (24.4) |
| Northeast | 192,433 (23.1) | 72,892 (23.9) | 119,541 (22.6) |
| South | 284,389 (34.1) | 101,519 (33.3) | 182,870 (34.6) |
| West | 153,461 (18.4) | 56,590 (18.6) | 96,871 (18.3) |
Abbreviations as in Table 1.
% for oHCM and nHCM are 36.6% and 63.4%, respectively.
There was a higher rate of asymptomatic than symptomatic HCM (171/100,000 [95% CI: 171-172/100,000] vs 135/100,000 [95% CI: 134-135/100,000], respectively), and a higher proportion of asymptomatic patients than symptomatic patients (56.0% vs 44.0%, respectively) (Table 1). The prevalence of symptomatic oHCM was 53/100,000 (95% CI: 52-53/100,000), while that of symptomatic nHCM was 82/100,000 (95% CI: 82-83/100,000) (Table 1). More cases of oHCM were symptomatic (45.0%) than that of nHCM (43.4%) (Table 1). The proportion of HCM cases that were symptomatic by state ranged from 32.4% (Hawaii) to 51.4% (Maine), with 29 states having a proportion between 30% and 45% (Supplemental Figure 1).
Prevalence of HCM by demographic characteristics
Age
Prevalence by age ranged from 175/100,000 (95% CI: 173-177/100,000) in the 35–44-year age group to 422/100,000 (95% CI: 420-424/100,000) in the 65+ year age group. The first- and second-highest prevalence rates of oHCM and nHCM were found in the age 65+ and 55 to 64 groups. Supplemental Table 3 outlines HCM prevalence for the <18 age group when removing people ages 0 to 3 years (220/100,000) and when using stricter HCM diagnosis criteria (30/100,000).
Sex
Prevalence by sex was 341/100,000 (95% CI: 339-342/100,000) in males and 277/100,000 (95% CI: 275-278/100,000) in females. The prevalence rates of oHCM (121/100,000 [95% CI: 120-123/100,000] vs 114/100,000 [95% CI: 114-115/100,000], respectively) and nHCM (219/100,000 [95% CI: 218-220/100,000] vs 162/100,000 [95% CI: 161-163/100,000], respectively) (Table 1) were both higher in males than in females. Relative to sex-specific HCM rates, females were more often diagnosed with oHCM than males (41.3% vs 35.7%, respectively) (Table 1).
Region
The prevalence rate was lowest in the West (237/100,000 [95% CI: 236-239/100,000]) and highest in the Northeast (414/100,000 [95% CI: 411-416/100,000]; Table 1). The states with the top 5 prevalence rates were located in the Northeast and Midwest, while the states with the bottom 5 prevalence rates were located in the South and West (Figure 1). The proportion of HCM cases that were oHCM ranged from 11.5% (North Dakota) to 45.8% (West Virginia), with 43 states having a proportion between 30% and 45% (Supplemental Figure 2).
Figure 1.
Prevalence Rate of Hypertrophic Cardiomyopathy
Data are per 100,000 people over 2016 to 2023 by state. HCM = hypertrophic cardiomyopathy.
Prevalence and incidence over time
The prevalence of HCM underwent a 3.5-fold increase from 78/100,000 (95% CI: 77-79/100,000) in 2016 to 275/100,000 (95% CI: 274-276/100,000) in 2023 (Supplemental Table 6). Increases in the prevalence rate from 2016 to 2023 were 4.1-fold in nHCM (42/100,000 [95% CI: 41-42/100,000)] to 173/100,000 (95% CI: 172-173/100,000), respectively) vs 2.8-fold in oHCM (36/100,000 [95% CI: 35-36/100,000] to 102/100,000 [95% CI: 102-103/100,000], respectively). The increases were 3.7-fold in asymptomatic patients (41/100,000 [95% CI: 41-42/100,000] to 153/100,000 [95% CI: 152-1534/100,000], respectively) vs 3.2-fold in symptomatic patients (38/100,000 [95% CI: 37-38/100,000] to 122/100,000 [95% CI: 121-122/100,000], respectively). The increases in the trajectories of HCM prevalence by diagnosis type and clinical presentation are depicted in Figure 2 and Supplemental Tables 4 and 5. The proportion of all prevalent symptomatic cases that were nonobstructive increased from 50.6% in 2016 to 62.7% in 2023 (Figure 2A). Prevalence rates over time by diagnosis type and clinical presentation, and by age group, region, and sex are presented in Supplemental Figures 3-5.
Figure 2.
Prevalence and Incidence Rate of Hypertrophic Cardiomyopathy Over Time
(A) Prevalence and (B) Incidence Rate of Hypertrophic Cardiomyopathy Over Time. Data are per 100,000 people by clinical presentation and diagnosis type. nHCM = nonobstructive HCM; oHCM = obstructive HCM; other abbreviation as in Figure 1.
The incidence rates generally remained consistent over time from 2017 (50/100,000 [95% CI: 50-51/100,000]) through 2023 (56/100,000 [95% CI: 56-57/100,000]) (Supplemental Table 7). The increase in the incidence rate from 2017 to 2023 was 1.4-fold in nHCM (29/100,000 [95% CI: 29-30/100,000] to 42/100,000 [95% CI: 41-42/100,000], respectively) vs a 1.5-fold decrease in oHCM (21/100,000 [95% CI: 21-22/100,000] to 14/100,000 [95% CI: 14-15/100,000], respectively). The increases were 1.1-fold in asymptomatic patients (30/100,000 [95% CI: 30-31/100,000] to 33/100,000 [95% CI: 33-34/100,000], respectively) vs 1.2-fold in symptomatic patients (20/100,000 [95% CI: 20-21/100,000] to 23/100,000 [95% CI: 23-24/100,000], respectively). The proportion of all incident symptomatic cases that were nonobstructive increased from 58.2% in 2017 to 80.5% in 2023 (Figure 2B). Incidence rates over time by diagnosis type and clinical presentation, and by age group, region, and sex are presented in Supplemental Figures 3 to 5.
Prevalence of HCM in the U.S. population
By extrapolating the 2016-2023 prevalence data from the study population to the U.S. general population, it was estimated that there are 832,956 cases of HCM (304,852 oHCM and 528,104 nHCM) in the United States over this 8-year period (Table 2). An estimated 37.1% of cases were symptomatic. The largest number of cases by group were estimated to be in the 65+ age group (218,656 [26.3%]), males (482,703 [58.0%]), and the South (284,389 [34.1%]).
Discussion
In a contemporary era (2016-2023), the present results of this claims analysis from a large sample of patients in the United States revealed a prevalence of 306/100,000 (0.306%) diagnosed HCM cases. The prevalence more than tripled from 78/100,000 in 2016 to 275/100,000 in 2023, mainly because of an increase in nHCM, particularly in patients over the age of 65 years. This translates to a U.S. prevalence rate of 832,956 HCM cases throughout the study period. There were higher prevalences of nonobstructive than obstructive cases and asymptomatic than symptomatic cases. The percentage of symptomatic patients remained consistent at approximately 44%, and prevalence increased with age, with the <18-year age group being an outlier, and was higher in males than females. HCM was more prevalent in the Midwest and Northeast than the South and West, and annual increases were relatively the same for each region.
Various methods have been employed to estimate the prevalence of HCM, including genetic screening studies, echocardiography screening studies, and population-based studies. Genetic population substudies in the Framingham and Jackson study cohorts concluded that 1 in 200 people carried a pathogenic or likely pathogenic variant in a sarcomeric gene but were not necessarily clinically expressing the HCM phenotype at the time of genetic testing.16,17 Although much progress has been made in exploring the human genome efficiently and comprehensively, much remains to be explored regarding pathogenesis, epigenetics, and environmental factors influencing phenotypic penetrance for patients before genetic testing can be used to predict prognosis, clinical phenotype, or outcomes.
Several diverse studies report a prevalence of unexplained increase in left ventricular thickness in the range of 0.02 to 0.23% in adults.18 The largest of these studies evaluated 8,080 individuals and relied on 7 patients meeting the HCM diagnostic criteria to estimate the prevalence of HCM in the general population.19 An often-cited estimate of disease prevalence (1:500) comes from an echocardiographic substudy of the CARDIA (Coronary Artery Risk Development in [Young] Adults).20 The sample size (n = 4,111) in this study and number of identified individuals (n = 7) was too small to accurately approximate the prevalence in the total U.S. population. Echocardiographic screening studies are significantly underpowered to provide an accurate population estimate of prevalence, as is evident from the 10-fold range of their estimates.
Overall, the prevalence of HCM in the present study falls within the prevalence range of 1:200-1:500 from previously described echocardiography studies.20,21 Compared with 2 recent claims prevalence studies conducted in the United States, the prevalence rate in the current study is almost 2.4- to 10-fold higher, depending on the year. Maron et al22 used the IDV (same database as the present study) to identify patients diagnosed with HCM in the United States using ICD-9 codes, reporting that close to 1 in 3,195 people (approximately 100,000 patients total) in the United States met the clinical diagnostic criteria for HCM in the year 2013. Butzner et al11 used a different claims database (HealthCore claims) from the years 2013 to 2019 (using ICD-9 and -10 codes), reporting a prevalence of 53/100,000 in 2013 and 80/100,000 in 2019. For direct comparison, the prevalence for 2019 in the current study was 190/100,000 (1:526). The current study and the previous claims studies all selected patients with at least one ICD code for HCM, although the database for the current study represented 2- to 3-fold more total individuals.
The prevalence in patients under the age of 18 years was surprisingly high at 246/100,000 individuals (77/100,000 for oHCM). It is unclear if this high prevalence is because of improper age labeling in the claims data, if the sample size for this group is too small, or if the numbers are indicative of a truly concerning prevalence. Our age sensitivity analysis (Supplemental Table 3) indicates that the former explanation likely contributes in part to this observation. Applying stricter inclusion criteria for HCM may offer a more accurate age-specific rate, although this may result in an undercounting of cases when extrapolation to the U.S. population is applied. In a previous analysis of a different claims database (MarketScan), it was reported that the prevalence of oHCM in patients <18 years of age in 2018 was only 3.1/100,000 people.23 Further investigation should be made into pediatric epidemiology for HCM.
Incidence rates in the total study population generally remained consistent over time, perhaps reflecting the proportion of patients with monogenic disease. However, there was an increase in the incidence of nHCM, mainly in the subset of patients over the age of 65 years. Similarly, in a previous claims analysis of HCM prevalence and incidence from 2013 to 2019, the overall rate increase over time was also attributed to an increasing rate of nHCM rather than oHCM.11 The reason for this finding is unknown but is likely related to improved recognition and diagnosis of HCM in the contemporary era, more familiarity with nHCM diagnoses codes, or more familiarity with HCM in general (especially in the Northeast), leading to more diagnoses over time. In addition, the proliferation of work-up for transthyretin amyloidosis as it evolved into a treatable condition has indirectly led to many more patients with left ventricular hypertrophy undergoing evaluation. Current guidelines recognize that more information on the underlying pathophysiology of nHCM is needed to improve care for patients with this subset of disease.1
Sensitivity analyses on the criteria used to classify patients as nHCM and oHCM indicated that this proportion remains roughly the same over time. Although the criteria for HCM patient inclusion were only one diagnosis code of HCM, only one-quarter of patient activity was required in a year to be included for general patient inclusion. If at least 2 HCM diagnoses were required for inclusion, the HCM patient count drops by approximately 40%. However, if more restrictive criteria were used for overall patient inclusion, requiring that a patient is active for every quarter in a year, the overall patient count drops by 33 to 38%, depending on the year. Thus, prevalence and incidence rates would remain roughly the same even in the case that stricter criteria were used for analysis.
Study limitations
This analysis was subject to the inherent limitations of retrospective claims studies, including coding errors and a lack of clinical echocardiogram results to confirm diagnoses. From one point of view, misdiagnosis of HCM with other cardiac disorders and undiagnosed patients likely contribute to an underestimate of the prevalence. On the other hand, one-quarter to one-third of HCM diagnoses are misclassified according to studies analyzing Swedish and Danish medical records.24,25 Similarly, the need to rely on claims data to classify patients as oHCM or nHCM and symptomatic or asymptomatic is a limitation of the analysis. Although the prevalence appeared to be increasing, some of this trend could be driven by the inability to capture all patients at the beginning of the time window, especially when coding for HCM was not as common. Notably, the definitions of prevalence and incidence are equivalent in 2016, and thus, prevalence is likely undercounted while incidence is likely overcounted in this year. Rates for relatively small subgroups, such as the age <18 population (4.3% of the IDV population) and states like North Dakota (0.2%) and Maine (0.4%), may be inflated due to small sample size. Lastly, the analysis could not be conducted by race or ethnicity because this information was not collected in the original claims database. This limitation prevents the ability to develop targeted or tailored diagnostic, screening, and treatment strategies for specific demographic groups. In addition, the inherent nature of claims-based analysis precludes analysis of HCM epidemiology in the uninsured population, and the findings in the current analysis may not be generalizable to this population.
While claims data, such as the present analysis, serve as an important starting point of information for research to their generalizability to the general population of HCM, the quality of data from anonymized sources that cannot be validated, and potential inaccuracy of medical coding proves to be a major limitation for claims-based studies. Despite this, prevalence figures from population-based insurance claims reflect the phenotype-positive HCM population. These individuals may or may not have an identifiable pathogenic variant, but more importantly, have the clinical manifestations that satisfy the diagnostic guidelines for HCM. Moreover, claims data reflect health care information across many geographic regions and hospitals, in contrast to referral cohorts or selected cohorts in imaging and genomics research. Claims data also represent a summary of the opinion of the treating physician, rather than relying only on one modality at a time as is done in prevalence studies using genetics and echocardiography. This is with the caveat that claims data reflect inherent physician behavior and practice patterns. Therefore, the present estimates are likely more reflective of true clinical HCM prevalence than previous genetic screening studies that may not represent clinical disease or previous echocardiography screening studies that were underpowered.
Conclusions
The prevalence of HCM over the study period was 1 in 327 individuals, with a rate of 1 case per 851 individuals for symptomatic disease, and may be increasing over time, driven primarily by an increase in the incidence of nHCM and cases among the age 65+ population. By individual characteristic, HCM is most likely to be nonobstructive, asymptomatic, age 65+, male, and from the South.
Perspectives.
COMPETENCY IN MEDICAL KNOWLEDGE: The prevalence of HCM in the United States appears to be increasing over time, primarily because of increasing cases of nHCM. By individual characteristics, HCM is most likely to be nonobstructive, asymptomatic, age 65+ years, male, and from the South.
TRANSLATIONAL OUTLOOK: This study is the first presentation of HCM epidemiology by an array of sociodemographic characteristics, showing the majority of patients are nonobstructive and asymptomatic. These findings support earlier diagnosing and should be considered when managing patients with HCM, including treatment with novel pharmacotherapies and invasive surgical interventions designed for patients with obstructive physiology. These contemporary epidemiological findings should be considered for addition to the HCM U.S. guidelines for characterizing the HCM population, diagnosis, and management of patients with HCM.
Funding support and author disclosures
This study was funded by Cytokinetics, Inc, South San Francisco, CA, USA. Drs Butzner, Gebrehiwet, and Shreay are employees of Cytokinetics, Inc. Drs ElHabr, Farajkhah, Chhatwal, and Ayer are employees of Value Analytics Labs and report no additional conflicts of interest. Dr Riello reports consultant fees/honoraria: Amgen Inc, AstraZeneca, Aventria, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Incorporated, Jassen Pharmaceuticals, Johnson & Johnson, Roivant, Salix Pharmaceuticals, and Serb Pharmaceuticals. Dr Desai works under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs and reports research grants and consulting for Amgen, Arrowhead, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CSL Vifor, Cytokinetics, Merck, Milestone, Novartis, SC Pharmaceuticals, and Verve Therapeutics. Dr Owens has received consulting/advisor fees from Alexion, Avidity, Bayer, Bristol Myers Squibb, Cytokinetics, Corvista, Edgewise, Imbria, Lexeo, Stealth, Tenaya, Biomarin, and irhythm; and has received research grants to the institution from Bristol Myers Squibb. Dr Abraham has received research grants from Cytokinetics Inc and MyoKardia. Dr Masri has received research grants from Pfizer, Ionis, Attralus, Cytokinetics, and Janssen and personal consulting fees from Cytokinetics, BMS, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Edgewise, Rocket, Lexeo, Prothena, BioMarin, AstraZeneca, Avidity, Neurimmune, and Tenaya.
Acknowledgments
Medical writing and editorial support were provided by Erin P. Scott, PhD, of Scott Medical Communications, LLC. This support was funded by Value Analytics Labs, Boston, MA.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
For supplemental tables and figures, please see the online version of this paper.
Supplementary data
References
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