Occurrence of Clinically Diagnosed Hypertrophic
`Cardiomyopathy in the United States
`
`®Dunkirk
`
`Martin S. Maron, MDa’*, Jennifer L. Hellawcll, MDb, Jaimc C. Lucovc, MSPHC,
`Ramin Farzanch—Far, MD”, and Iacopo Olivotto, MDd
`
`
`Hypertrophic cardiomyopathy (HC) is the most common genetic heart disease and an
`important cause of sudden death and heart failure symptoms. The current prevalence for
`BC (1:500) is based on echocardiographic population studies in which a substantial pro-
`portion of affected subjects have not come to clinical recognition. Therefore, we sought to
`define the subset of patients with HC who are diagnosed in the US. A proprietary integrated
`claims database including medical condiu'on International Clasification ofDiseases, Ninth
`Revision diagnostic codes for over 160 million individual patients in the US was interro-
`gated for 2013 to identify the prevalence of clinically recognized HC. Patients with 21 claim
`for any of the HC International Classification of Diseases, Ninth Revision diagnosis codes
`from January to December 2013 were identified. The combined occurrence rate of HC was
`stratified by age and gender and multiplied by the 2013 United States populan'on in the
`same age/gender categories to produce the final projected prevalence. The analysis was
`performed on 169,089,614 patients, of whom 59,009 unique patients were identified with 21
`claim for BC. The projected estimated occurrence of diagnosed HC in the US in 2013 was
`13,195 for a total of 98,958 subjects. Average age at BC diagnosis was in the fifth decade of
`life, with 43% of the cohort composed of women. In conclusion, leveraging a claims-based
`data analytic technique, about 100,000 pan'ents are diagnosed clinically with HC in the US,
`an occurrence which is le$ than the prevalence reported in systematic population studies
`based on echocardiographic diagnosis. This observation supports the view that many pa-
`tients with BC are undiagnosed throughout life and enhances our understanding of the
`burden of this genetic heart disease on the health care system. © 2016 Elsevier Inc. All
`rights reserved. (Am J Cardiol 2016;117:1651 1654)
`
`a common
`is
`eardiomyopathy (HC)
`Hyperlrophic
`genetieally inherited heart disease and represents an
`important cause of cardiovascular morbidity and mortality
`in patients of all ages.1 The prevalence of HC in the general
`population has been estimated at 1:500, based on numerous
`epidemiologic studies in the United States (US) and glob-
`ally, in which unrelated subjects were randomly selected
`from the general population to undergo echocardiographic
`evaluation.2 However,
`these estimated figures
`largely
`represent clinieally unrecognized disease in the general
`population because most patients in these studies were not
`known to be affected. In addition, most patients with BC
`never develop (or recognize) cardiovascular symptoms,
`experience an adverse disease-related event or are identified
`with another clinical marker (e.g., abnormal electrocardio-
`gram and family history) which could lead to clinical
`recognition.3 Thus, we sought to define the subset of pa-
`tients with RC who are clinically diagnosed (and treated) in
`
`'Hypertrophic Cardianycpathy Center. Department of Medicine. 'hrfts
`Medical Center. Boston. Massachusetts; ”Gilead Sciences. Inc, Foster City,
`California; ”Symphony Health Solutions, Phoarix, Arizona; and “Referral
`Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy.
`Manuscript received November 15, 2015; revised manuscript received and
`accepted February 18, 2016.
`See page 1653 for disclosure information.
`*Corresponding atlhor. Tel: (617) 636 8066; fax: (617) 651 3261.
`E mail addras: mmaron@tuftsmedicalcenter.org (M.S. Maren).
`
`0002 9149/16/5 see front matter © 2016 Elsevier Inc. All rights reserved.
`han/dx.doi.org110.10166.amjcard.2016.02.044
`
`Page 1 of 4
`
`the US, with important implications to our understanding of
`the burden of this disease on the health eare system.
`
`Methods
`
`We queried a large proprietary integrated claims database
`(Symphony Health Solutions [SHS], Phoenix, Arizona),
`which includes medieal condition diagnostic codes (Inter-
`national Classification ofDiseases, Ninth Revision [ICD-9])
`for over 160 million individual patients (> 1/2 census popu-
`lation of 316,159,818 in 20134) in the United States. These
`claims are captured in each of the US states and include all
`insurance types,
`including Medicare and Medicaid. The
`database is composed of electronically submitted private
`practitioner (Centers for Medicare and Medicaid Services
`1500) claims and hospital and facility (uniform bill 04) claims
`within a given year. The private practitioner claims include
`diagnostic, therapeutic, and procedure information from over
`860,000 practitioners of all medical and surgical specialties,
`and practices of all sizes. The institutional claims encompass
`diagnostic, therapeutic, and procedure information, including
`administered medications, from hospitals and clinics and are
`inclusive of inpatient and outpatient encounters, including
`emergency department care.
`To identify patients with diagnosed HC, subjects with 21
`claim for the [CD-9 diagnosis codes for BC (i.e., 4%.],
`425.11, 425.18) from January 1, 2013 to December 31, 2013
`were searched. To avoid double counting of individual
`patients, patient-level records from each data source were
`
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`1652
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`The American Journal of Cardiology (www.ajconline.org)
`
`represents sum of the 2013 US census population stratified by gender and age, multiplied by crude
`Figure 1. Flow diagram of 2013 claims data analysis.
`prevalence of HC in respective gender and age matched strata, to generate the final estimated prevalence of diagnosed HC in the US. CMS
`Centers for
`Medicare and Medicaid services; UB
`uniform billing.
`
`P
`
`linked longitudinally across settings of care through a Health
`Insurance Portability and Accountability Act-compliant, dei-
`dentified unique patient identifier that matched patients using a
`hash generated from the patient’s first name, last name, gender,
`and date of birth. Because HC is a lifelong condition, period
`prevalence, which reflects both the incidence and duration of
`disease, was selected as the most appropriate measure of dis-
`ease frequency in this analysis. In light of recently published
`clinical guidelines for HC recommending annual surveillance
`visits, the period prevalence was defined as the number of
`individual patients with HC identified during 2013 divided by
`the total United States population alive at the end of this year
`(reported as cases per 100,000 subjects).1,5 Crude prevalence
`of HC was then stratified by dividing the number of patients
`with 1 HC claim in each age and gender category by the total
`number of patients in that stratum and then multiplied by the
`2013 United States population to produce the final projected
`estimated prevalence of diagnosed HC.
`
`Results
`Over the study period, 169,089,614 unique patients were
`identified, of which 59,009 had 1 HC diagnostic claim
`(Figure 1). The final occurrence of diagnosed HC in the
`United States for 2013 was estimated to be 1:3,195. This
`prevalence estimate yielded a total of 98,958 patients with
`HC, approximately half of whom are presumed to be
`symptomatic based on previous large HC cohort studies.3,6
`The average age of HC diagnosis was in the fifth decade
`of life, with 43% of the HC cohort comprised women. There
`were no age differences seen across the 3 diagnostic codes,
`which appeared to be internally consistent (Figure 2).
`
`Discussion
`
`Leveraging a claims-based analytic technique, the num-
`ber of clinically diagnosed patients with HC in the US is
`
`Figure 2. Differences in HC ICD codes by age. ICD 9 code 425.1eHC,
`425.11ehypertrophic obstructive cardiomyopathy, 425.18eother HC.
`
`about 100,000 patients. This figure represents the first
`reasonable estimate on which nationwide resource alloca-
`tion and health care burden related to HC can be evaluated.
`Of note, although considerable in absolute terms, the fre-
`quency with which patients are diagnosed with HC and seek
`medical care contrasts sharply with the much higher esti-
`mated occurrence of unrecognized disease identified in the
`general population. Overall, the number of patients with 1
`HC diagnostic claim represents a fraction of the global
`estimated HC population based on large population studies
`and can be considered to represent the “tip of the iceberg” of
`the disease spectrum (Figure 3).
`These observations support the view that many patients
`with HC are undiagnosed throughout
`life, potentially
`missing the opportunity for appropriate therapies and man-
`agement. What fraction of these undiagnosed patients with
`HC may be candidates for major therapeutic interventions
`remains unresolved. However, the observation that HC can
`
`Page 2 of 4
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`Cardiomyopathy/The Tip of the HC Iceberg
`
`1653
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`largely as a result of increased clinical recognition, wider
`distribution of centers of excellence and improved diag-
`nostic imaging methods.7 The upward shift in average age
`of our analysis might also be explained by the inverse
`relation between advanced age and disease-related risk in
`HC, whereby achieving older age in HC is associated with
`low risk for adverse disease-related complications, including
`sudden cardiac death.8
`limitations of the present analysis
`There are several
`which reflect the inherent constraints in accessing claims
`data. For example, the SHS database does not fully represent
`certain segments of the population, such as the uninsured,
`prisoners, or
`the Veterans’ Administration population.
`Likewise, out of network care and cash payments for private
`practitioner and institutional care are not captured, as claims
`are not generated for reimbursement purposes. Although the
`3 ICD-9 diagnostic codes used in our study are unambigu-
`ous and exhaustive for HC, it is not possible to verify
`diagnosis in each patient. However, the unique strengths of
`accessing a large national claims database, which includes
`over 50% of the US population, provide a large measure of
`compensation for these issues and for this reason, we
`consider our estimates for the number of clinically diag-
`nosed HC in the US to be robust and relevant.
`In conclusion, the occurrence of clinically identified pa-
`tients with HC in the US (w100,000) contrasts with the
`higher prevalence based on echocardiographic-based popu-
`lation studies. These data support the concept that many
`patients with HC remain undiagnosed and emphasize the
`need for concentrated efforts to increase awareness among
`the general public and the clinical practicing community
`regarding symptoms and clinical presentation of HC, as well
`as future efforts to develop rapid noninvasive diagnostic
`markers, which could potentially lead to enhanced recog-
`nition in the population.
`
`Disclosures
`
`Dr. Maron had full access to all the data in the study and
`takes responsibility for the integrity of the data and the ac-
`curacy of the data analysis. The study was funded by Gilead
`Sciences, Inc. The sponsor was involved in design and
`conduct of the study; interpretation of the data; preparation,
`review, and approval of the manuscript; and decision to
`submit the manuscript for publication. Drs. Maron, Olivotto,
`and Lucove report receiving consulting fees from Gilead
`Sciences, Inc. Drs. Hellawell and Farzaneh-Far are employees
`of Gilead Sciences, Inc and hold equity in the company.
`
`1. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS,
`Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE,
`Towbin JA, Udelson JE, Yancy CW. 2011 ACCF/AHA guideline for
`the diagnosis and treatment of hypertrophic cardiomyopathy: a report of
`the American College of Cardiology Foundation/American Heart As
`sociation task force on practice guidelines. Circulation 2011;124:
`e783ee831.
`2. Maron 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;92:785e789.
`3. Adabag AS, Kuskowski MA, Maron BJ. Determinants for clinical
`diagnosis of hypertrophic cardiomyopathy. Am J Cardiol 2006;98:
`1507e1511.
`
`Figure 3. Prevalence of HC in the United States. Overall estimated preva
`lence of HC in US is 1:500 yielding w700,000 cases (left).2 The prevalence
`of clinically diagnosed HC is 1:3,195 (above right), yielding w100,000
`patients with the remaining w600,000 patients likely remaining undiag
`nosed (below right).
`
`cause sudden death in asymptomatic patients as the initial
`manifestation of disease,7 and that 10% of clinically iden-
`tified patients with HC are considered at high arrhythmic
`risk,8 together suggest that a significant proportion of these
`unrecognized patients may be at risk and benefit from early
`recognition and treatment strategies.
`A major advantage of claims data analysis is the inclu-
`sion of much larger and more diverse sample sizes across a
`wider geographic region than is possible with single-center
`referral studies or epidemiologic cohort studies, and to our
`knowledge, this is the first time this type of analysis has
`been performed in a genetic heart disease such as HC.
`Indeed, our analysis comprised more than 169 million
`unique patients, which represents over 50% of the US
`census population in 2013.4 The claims used in this analysis
`leverage data from all 50 states and encompass a wide payer
`mix. Furthermore,
`these data are contemporaneous and
`reflect current clinical practice, with 95% of claims available
`for analysis within 6 weeks of the medical encounter. As
`compared with a closed payer database, patients in the SHS
`database are generally tracked for a longer period of time
`and are not lost to follow-up when their health plan changes.
`In addition, despite different sampling techniques and
`methods, the results of our analysis validate the findings of
`the seminal The Coronary Artery Risk Development
`in
`Young Adults Study.2 The established prevalence of 1:500
`(0.2%) in that study projects a total of 700,000 subjects with
`HC in the United States. When this number is then multi-
`plied by the proportion of symptomatic patients in The
`Coronary Artery Risk Development in Young Adults Study
`of 1 of 7, this also yields approximately 100,000 patients
`with symptomatic, or clinically evident, HC.
`We note that the average age in our analysis was in the
`fifth decade life, which is older than that described in pub-
`lished studies of the fourth decade of life.3 This likely re-
`flects the historical referral bias of tertiary referral centers
`whereby younger and more symptomatic patients were
`referred for expert care. However, more recently HC has
`been identified with increasing frequency in older adults
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`1654
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`The American Journal of Cardiology (www.ajconline.org)
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