Clinical Diagnosis of Hypertrophic Cardiomyopathy Over Time in the United States (A Population-Based Claims Analysis)

Abstract

Hypertrophic cardiomyopathy (HC) is a common genetic heart disease. However, the number of gene mutation carriers who develop HC and manifest clinical symptoms is not well established. Our objective was to estimate annual prevalence and incidence rates of clinically diagnosed HC in the United States. Data from the HealthCore Integrated Research Database (HIRD) were interrogated for years 2013–2019 to identify patients with ≥1 claim of HC International Classification of Diseases, Clinical Modification Ninth and Tenth Revision diagnosis codes. In 2013, among 16,243,109 patients, 8,526 were identified with HC, yielding an estimated prevalence of clinically diagnosed HC of 0.052% (0.035% for obstructive [oHC], 0.017% for nonobstructive [nHC]). This prevalence yielded an estimated 164,403 patients with clinical diagnosis of HC. For the same year, the incidence of new HC diagnoses was 0.030% (0.020% for oHC, 0.010% for nHC). Over the following 6 years, prevalence and incidence of HC increased by 0.005%/year (p <0.01) and 0.001%/year (p <0.01), respectively, with an estimated 262,591 patients with a clinical diagnosis of HC in 2019. Over this period, incidence of nHC increased (0.012% vs 0.026%, p <0.01), whereas incidence of oHC decreased (0.020% versus 0.015%, p <0.01). In conclusion, over 6 years, the number of patients with clinically diagnosed HC in the United States increased 1.5-fold to ∼262,591, primarily because of a rise in nHC diagnoses. These prevalence data support further investigation to better understand factors accounting for increasing clinical recognition of HC. Hypertrophic cardiomyopathy (HC) is a common genetic heart disease. However, the number of gene mutation carriers who develop HC and manifest clinical symptoms is not well established. Our objective was to estimate annual prevalence and incidence rates of clinically diagnosed HC in the United States. Data from the HealthCore Integrated Research Database (HIRD) were interrogated for years 2013–2019 to identify patients with ≥1 claim of HC International Classification of Diseases, Clinical Modification Ninth and Tenth Revision diagnosis codes. In 2013, among 16,243,109 patients, 8,526 were identified with HC, yielding an estimated prevalence of clinically diagnosed HC of 0.052% (0.035% for obstructive [oHC], 0.017% for nonobstructive [nHC]). This prevalence yielded an estimated 164,403 patients with clinical diagnosis of HC. For the same year, the incidence of new HC diagnoses was 0.030% (0.020% for oHC, 0.010% for nHC). Over the following 6 years, prevalence and incidence of HC increased by 0.005%/year (p <0.01) and 0.001%/year (p <0.01), respectively, with an estimated 262,591 patients with a clinical diagnosis of HC in 2019. Over this period, incidence of nHC increased (0.012% vs 0.026%, p <0.01), whereas incidence of oHC decreased (0.020% versus 0.015%, p <0.01). In conclusion, over 6 years, the number of patients with clinically diagnosed HC in the United States increased 1.5-fold to ∼262,591, primarily because of a rise in nHC diagnoses. These prevalence data support further investigation to better understand factors accounting for increasing clinical recognition of HC. Hypertrophic cardiomyopathy (HC) is a common cardiac genetic heart disease,1Ommen SR Mital S Burke MA Day SM Deswal A Elliott P Evanovich LL Hung J Joglar JA Kantor P Kimmelstiel C Kittleson M Link MS Maron MS Martinez MW Miyake CY Schaff HV Semsarian C Sorajja P. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Circulation. 2020; 142: e558-e631PubMed Google Scholar with a prevalence as high as 1 in 2002Maron BJ Peterson EE Maron MS Peterson JE. Prevalence of hypertrophic cardiomyopathy in an outpatient population referred for echocardiographic study.Am J Cardiol. 1994; 73: 577-580Abstract Full Text PDF PubMed Scopus (98) Google Scholar and a low mortality rate (0.5% per year3Semsarian C Ingles J Maron MS Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy.J Am Coll Cardiol. 2015; 65: 1249-1254Crossref PubMed Scopus (632) Google Scholar) as a result of contemporary cardiovascular treatments.3Semsarian C Ingles J Maron MS Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy.J Am Coll Cardiol. 2015; 65: 1249-1254Crossref PubMed Scopus (632) Google Scholar, 4Maron BJ Rowin EJ Casey SA Link MS Lesser JR Chan RH Garberich RF Udelson JE Maron MS. Hypertrophic cardiomyopathy in adulthood associated with low cardiovascular mortality with contemporary management strategies.J Am Coll Cardiol. 2015; 65: 1915-1928Crossref PubMed Scopus (203) Google Scholar, 5Marian AJ van Rooij E Roberts R. Genetics and genomics of single-gene cardiovascular diseases: common hereditary cardiomyopathies as prototypes of single-gene disorders.J Am Coll Cardiol. 2016; 68: 2831-2849Crossref PubMed Scopus (36) Google Scholar, 6Maron BJ Maron MS Rowin EJ. Perspectives on the overall risks of living with hypertrophic cardiomyopathy.Circulation. 2017; 135: 2317-2319Crossref PubMed Scopus (23) Google Scholar, 7Maron BJ Rowin EJ Casey SA Haas TS Chan RH Udelson JE Garberich RF Lesser JR Appelbaum E Manning WJ Maron MS. Risk stratification and outcome of patients with hypertrophic cardiomyopathy ≥60 years of age.Circulation. 2013; 127: 585-593Crossref PubMed Scopus (155) Google Scholar, 8Spirito P. The dawn of a better day for patients with hypertrophic cardiomyopathy.J Am Coll Cardiol. 2015; 65: 1929-1930Crossref PubMed Scopus (9) Google Scholar Echocardiographic and population-based studies estimate prevalence of clinically evident HC in the general population of 1 in 5009Maron BJ Gardin JM Flack JM Gidding SS Kurosaki TT Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults.Circulation. 1995; 92: 785-789Crossref PubMed Scopus (1635) Google Scholar to 1 in 3,000 persons.10Maron MS Hellawell JL Lucove JC Farzaneh-Far R Olivotto I. Occurrence of clinically diagnosed hypertrophic cardiomyopathy in the United States.Am J Cardiol. 2016; 117: 1651-1654Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar However, the number of patients clinically diagnosed with HC is considered to be substantially lower than the true prevalence in the general population.9Maron BJ Gardin JM Flack JM Gidding SS Kurosaki TT Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults.Circulation. 1995; 92: 785-789Crossref PubMed Scopus (1635) Google Scholar,10Maron MS Hellawell JL Lucove JC Farzaneh-Far R Olivotto I. Occurrence of clinically diagnosed hypertrophic cardiomyopathy in the United States.Am J Cardiol. 2016; 117: 1651-1654Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar This is because previous prevalence studies largely used older diagnostic testing methods, and therefore, did not take into account contemporary diagnostic testing strategies that have emerged over the past 2 decades,11Maron 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: 83-99Crossref PubMed Scopus (453) Google Scholar,12Maron MS Maron BJ. Clinical impact of contemporary cardiovascular magnetic resonance imaging in hypertrophic cardiomyopathy.Circulation. 2015; 132: 292-298Crossref PubMed Scopus (49) Google Scholar including advanced cardiovascular imaging and genetic testing of family members, as well as increased recognition of HC in the general practicing cardiology community. In addition, it remains unknown if HC prevalence and incidence have changed over time. Therefore, it is timely to reassess the prevalence and incidence rates of clinically diagnosed HC, including obstructive (oHC) and nonobstructive (nHC), in the current diagnostic era, by leveraging a large, contemporary United States insurance claims database13Wasser T We B Ycas J Tunceli O. Applying weighting methodologies to a commercial database to project US census demographic data.Am J Accountable Care. 2015; 3: 33-38Google Scholar from the years 2013 to 2019. This was a retrospective observational study utilizing claims data from the HealthCore Integrated Research Database (HIRD)13Wasser T We B Ycas J Tunceli O. Applying weighting methodologies to a commercial database to project US census demographic data.Am J Accountable Care. 2015; 3: 33-38Google Scholar submitted during the study period of January 1, 2013 through November 30, 2019. The HIRD is a large, clinically rich, and geographically diverse administrative healthcare database of longitudinal medical and pharmacy claims data from health plan members across the United States, representing over 75 million lives of commercially insured and Medicare Advantage members.13Wasser T We B Ycas J Tunceli O. Applying weighting methodologies to a commercial database to project US census demographic data.Am J Accountable Care. 2015; 3: 33-38Google Scholar The HIRD13Wasser T We B Ycas J Tunceli O. Applying weighting methodologies to a commercial database to project US census demographic data.Am J Accountable Care. 2015; 3: 33-38Google Scholar was interrogated from years 2013 to 2019 to identify patients with ≥1 claim of HC International Classification of Diseases, Clinical Modification Ninth and Tenth (ICD-914World Health Organization. International Classification of Diseases: [9th] ninth revision, basic tabulation list with alphabetic index. World Health Organization. 1978 [Accessed July 1, 2021]; Available at: https://apps.who.int/iris/handle/10665/39473Google Scholar; ICD-1015World Health Organization. ICD-10: International Statistical Classification of Diseases and related health problems: tenth revision, 2nd ed World Health Organization. 2004 [Accessed July 1, 2021]; Available at: https://apps.who.int/iris/handle/10665/42980Google Scholar) diagnosis codes: HC: 425.1x, I42.1, I42.2; oHC: 425.11, I42.1; nHC: 425.18, I42.2. A clinical diagnosis of HC was defined as ≥1 medical claim of HC in a given calendar year and only patients continuously enrolled in a medical health plan for the given calendar year were included. The method for capturing patients with specific ICD codes for a clinical diagnosis of HC is based on the inherent structure of claims data, although the American Heart Association/American College of Cardiology (AHA/ACC) recommendation for first-line test for diagnosis of HC is echocardiogram and cardiac magnetic resonance imaging.1Ommen SR Mital S Burke MA Day SM Deswal A Elliott P Evanovich LL Hung J Joglar JA Kantor P Kimmelstiel C Kittleson M Link MS Maron MS Martinez MW Miyake CY Schaff HV Semsarian C Sorajja P. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Circulation. 2020; 142: e558-e631PubMed Google Scholar The AHA/ACC recommended diagnostic method used to confirm HC diagnosis13Wasser T We B Ycas J Tunceli O. Applying weighting methodologies to a commercial database to project US census demographic data.Am J Accountable Care. 2015; 3: 33-38Google Scholar was not provided in the database. Statistical analyses were undertaken with SAS, version 9.3 (SAS Institute Inc., Cary, NC). Two sample t tests addressed statistical significance and were 2-sided; p <0.01 was considered statistically significant. The annual prevalence rate was defined as the number of patients diagnosed with the disease divided by the total population with a full year of health plan enrollment in the given calendar year (Figure 1). Prevalence of HC was then multiplied by the United States population to estimate the projected number of patients with clinically diagnosed HC nationally. The incidence rate was calculated as the number of incident (new) cases of a disease divided by the total population with 2 full years of health plan enrollment (Figure 2). The immediate previous year was used to define incident cases: without any previous diagnosis of HC to define HC incidence rate, without any previous diagnosis of nHC to define nHC incidence rate and without any previous diagnosis of oHC to define oHC incidence rate.Figure 2Flow diagram for 2019 United States claims incidence in the HIRD population. HC = hypertrophic cardiomyopathy; HIRD = HealthCore Integrated Research Database; ICD-9,10 = International Classification of Diseases, Clinical Modification Ninth and Tenth; nHC = nonobstructive hypertrophic cardiomyopathy; oHC = obstructive hypertrophic cardiomyopathy. *Incidence was calculated for all years from 2013 to 2019.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In 2013, among 16,243,109 unique patients in HIRD,13Wasser T We B Ycas J Tunceli O. Applying weighting methodologies to a commercial database to project US census demographic data.Am J Accountable Care. 2015; 3: 33-38Google Scholar 8,526 were identified with an HC diagnostic code, yielding an estimated prevalence of clinically diagnosed HC of 0.052% (1:1,905): 0.035% for oHC and 0.017% for nHC. Based on a United States census population of 316,159,818,16United States Census Bureau. Annual estimates of the resident population for the United States, Regions, States, and Puerto Rico: April 1, 2010 to July 1, 2019. 2019 [Accessed February 24, 2021]; Available at:https://www.census.gov/data/tables/time-series/demo/popest/2010s-state-total.htmlGoogle Scholar this prevalence suggests an estimated 164,403 patients with a clinical diagnosis of HC in the United States in 2013. Over the subsequent 6 years, HC prevalence increased by 0.005% each year (p <0.01; Figure 3), to a prevalence of 0.080% (1:1,250) in 2019 (1.5-fold increase compared with 2013, p <0.01): 0.033% for oHC and 0.047% for nHC. This represents an estimated 262,591patients with a clinical diagnosis of HC in 2019 (United States census population of 328,239,52316United States Census Bureau. Annual estimates of the resident population for the United States, Regions, States, and Puerto Rico: April 1, 2010 to July 1, 2019. 2019 [Accessed February 24, 2021]; Available at:https://www.census.gov/data/tables/time-series/demo/popest/2010s-state-total.htmlGoogle Scholar). All occurrence rates of HC between 2013 and 2019 are presented in Table 1. The incidence of HC increased by 0.001% each year (p <0.01) over the 6-year study period (Figure 4). The increase in prevalence of HC over this time period predominantly reflects a significant increase in new cases of nHC (0.012% vs 0.026%, p <0.01), whereas new cases of oHC decreased (0.020% vs 0.015%, p <0.01).Table 1Occurrence of clinically diagnosed hypertrophic cardiomyopathy over timeYearPrevalence (%)Incidence (%)HC95% CIoHC95% CInHC95% CIHC95% CIoHC95% CInHC95% CI20130.0525(0.0514, 0.0536)0.0353(0.0344, 0.0362)0.0172(0.0166, 0.0179)0.0302(0.0293, 0.0312)0.0205(0.0197, 0.0212)0.0120(0.0114, 0.0126)20140.0539(0.0528, 0.0550)0.0341(0.0332, 0.0349)0.0199(0.0192, 0.0205)0.0297(0.0288, 0.0306)0.0192(0.0184, 0.0199)0.0127(0.0121, 0.0133)20150.0604(0.0592, 0.0615)0.0344(0.0335, 0.0352)0.0260(0.0252, 0.0267)0.0340(0.0330, 0.0350)0.0190(0.0182, 0.0197)0.0175(0.0168, 0.0182)20160.0690(0.0678, 0.0702)0.0327(0.0319, 0.0336)0.0363(0.0354, 0.0371)0.0392(0.0381, 0.0402)0.0174(0.0167, 0.0181)0.0246(0.0238, 0.0254)20170.0703(0.0691, 0.0715)0.0317(0.0309, 0.0325)0.0386(0.0377, 0.0395)0.0351(0.0341, 0.0361)0.0152(0.0145, 0.0158)0.0230(0.0222, 0.0238)20180.0759(0.0746, 0.0771)0.0319(0.0310, 0.0327)0.0440(0.0430, 0.0450)0.0380(0.0370, 0.0390)0.0150(0.0144, 0.0156)0.0263(0.0255, 0.0271)20190.0800(0.0787, 0.0813)0.0333(0.0325, 0.0342)0.0467(0.0457, 0.0477)0.0375(0.0365, 0.0385)0.0150(0.0143, 0.0156)0.0257(0.0248, 0.0265)CI = confidence interval; HC = hypertrophic cardiomyopathy; nHC = nonobstructive hypertrophic cardiomyopathy; oHC = obstructive hypertrophic cardiomyopathy. Open table in a new tab Figure 4United States HC incidence trends. HC = hypertrophic cardiomyopathy; nHC = nonobstructive hypertrophic cardiomyopathy; oHC = obstructive hypertrophic cardiomyopathy.View Large Image Figure ViewerDownload Hi-res image Download (PPT) CI = confidence interval; HC = hypertrophic cardiomyopathy; nHC = nonobstructive hypertrophic cardiomyopathy; oHC = obstructive hypertrophic cardiomyopathy. Leveraging a large, diverse, and clinically rich set of medical and pharmacy claims from a health insurance claims database with longitudinality,13Wasser T We B Ycas J Tunceli O. Applying weighting methodologies to a commercial database to project US census demographic data.Am J Accountable Care. 2015; 3: 33-38Google Scholar our results demonstrate a noteworthy increase in the prevalence and incidence of clinically diagnosed HC over a recent 6-year period in the United States. During this time, the number of patients with clinically diagnosed HC significantly increased by 1.5-fold, to an estimated 262,591 in 2019. The increase predominantly reflected a significant increase in new cases of nHC. Notably, this contemporary estimate of patients with clinically diagnosed HC exceeds previous estimates of HC prevalence,10Maron MS Hellawell JL Lucove JC Farzaneh-Far R Olivotto I. Occurrence of clinically diagnosed hypertrophic cardiomyopathy in the United States.Am J Cardiol. 2016; 117: 1651-1654Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar likely reflecting several relevant advances that have occurred over the study's observation period, which have helped to enhance HC diagnosis. Most prominent of recent advances in the general cardiology practicing community is the increased use of advanced cardiovascular imaging over the last 10 years. Advanced cardiac magnetic resonance imaging techniques permit a more comprehensive evaluation of the HC phenotype than echocardiography and may be primarily responsible for the increase in recognition of nHC reported here. Cardiac magnetic resonance imaging provides higher spatial resolution imaging and can identify mild focal areas of increased wall thickness not identified by echocardiography, providing a more accurate and reliable measurement of left ventricular wall thickness.17Maron MS. Clinical utility of cardiovascular magnetic resonance in hypertrophic cardiomyopathy.J Cardiovasc Magn Reson. 2012; 14 (Published 2012 Feb 1): 13https://doi.org/10.1186/1532-429X-14-13Crossref PubMed Scopus (203) Google Scholar,18Amano Y Kitamura M Takano H Yanagisawa F Tachi M Suzuki Y Kumita S Takayama M Cardiac MR imaging of hypertrophic cardiomyopathy: techniques, findings, and clinical relevance.Magn Reson Med Sci. 2018; 17: 120-131https://doi.org/10.2463/mrms.rev.2017-0145Crossref PubMed Scopus (23) Google Scholar Therefore, it is likely that the increase in HC diagnosis observed here is driven by an increase in patients identified by cardiac magnetic resonance imaging with mild left ventricular hypertrophy and who are also more likely to be nonobstructed. In addition, greater access to affordable commercial genetic testing has provided the opportunity for cascade family testing resulting in HC identification. Additionally, the visibility of patient advocacy organizations and other educational campaigns may have greatly increased recognition of HC in the general community. The prevalence of HC has been estimated at 1 in 500, based on numerous echocardiographic studies worldwide.9Maron BJ Gardin JM Flack JM Gidding SS Kurosaki TT Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults.Circulation. 1995; 92: 785-789Crossref PubMed Scopus (1635) Google Scholar The first estimate of clinically diagnosed HC prevalence using healthcare insurance claims data was 0.03% in the United States in 2013,10Maron MS Hellawell JL Lucove JC Farzaneh-Far R Olivotto I. Occurrence of clinically diagnosed hypertrophic cardiomyopathy in the United States.Am J Cardiol. 2016; 117: 1651-1654Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar compared with our HC prevalence of 0.05% in 2013. The discrepancy is a little surprising as the methodology between the 2 studies was similar – a large proprietary integrated claims database (Symphony Health Solutions) was interrogated to identify patients with diagnosed HC based on ≥1 HC claim for the ICD-9 diagnosis codes for HC. However, although the Symphony Health Solutions database had a much larger sample size for the estimation, the analysis only captured claims made over a single year. In contrast, our analysis is not only more current but also more precise, as we also included ICD-10 diagnosis codes and patients with ≥12 months of baseline continuous medical and pharmacy health plan enrollment to capture patients with longitudinal follow-up. The source database, although smaller, was still 1 of the commercially insured including Medicare Advantage members, from of 14 health T We B Ycas J Tunceli O. Applying weighting methodologies to a commercial database to project US census demographic data.Am J Accountable Care. 2015; 3: 33-38Google Scholar These prevalence data that the between the estimated BJ Gardin JM Flack JM Gidding SS Kurosaki TT Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults.Circulation. 1995; 92: 785-789Crossref PubMed Scopus (1635) Google Scholar,10Maron MS Hellawell JL Lucove JC Farzaneh-Far R Olivotto I. Occurrence of clinically diagnosed hypertrophic cardiomyopathy in the United States.Am J Cardiol. 2016; 117: 1651-1654Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar by HC in the United States and who are clinically identified may not be as large as a number of and may be at for including and cardiac diagnostic and disease for the general and are to clinical of HC, patients to from recognition and MS Hellawell JL Lucove JC Farzaneh-Far R Olivotto I. Occurrence of clinically diagnosed hypertrophic cardiomyopathy in the United States.Am J Cardiol. 2016; 117: 1651-1654Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar have been in recent years that have helped to the between the estimated prevalence and the number clinically but is an opportunity to this further with and diagnostic Additionally, the for the observed in prevalence of obstructive HC over time in our results is but in HC disease compared with previous studies be considered to in more the for this in prevalence of in HC. are several to this study that are common using medical claims All patients included in the study were enrolled in commercial Medicare Advantage health insurance in the United States. The results may not be to patients with other of health who are to the United States. Additionally, the prevalence rate for oHC and nHC may be because HC is and in clinical for patients who are have nHC. data not specific R B I of heart in in with in patients heart 2015; PubMed Scopus Google B R P B I ventricular cardiomyopathy in heart patients heart 2016; PubMed Scopus Google Scholar genetic diagnostic methods, used to at the ICD for However, leveraging a large commercially insured claims database for and provides estimates of clinically diagnosed HC in the United States. In conclusion, over a recent 6-year period, the number of patients with clinically diagnosed HC in the United States has significantly increased by 1.5-fold to an estimated This increase has been primarily because of a rise in new nHC whereas new cases of oHC The increasing prevalence of HC suggests that several advances have likely clinical including use of advanced cardiovascular imaging techniques, increased of genetic greater and HC in the general population. Rowin has relevant to Maron is a of the at and are of and are of was an of at the time the was The and for which was by

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