HomeCirculationVol. 124, No. 242011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUB2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic CardiomyopathyA Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Bernard J. Gersh, MB, ChB, DPhil, FACC, FAHA, Barry J. Maron, MD, FACC, Robert O. Bonow, MD, MACC, FAHA, Joseph A. Dearani, MD, FACC, Michael A. Fifer, MD, FACC, FAHA, Mark S. Link, MD, FACC, FHRS, Srihari S. Naidu, MD, FACC, FSCAI, Rick A. Nishimura, MD, FACC, FAHA, Steve R. Ommen, MD, FACC, FAHA, Harry Rakowski, MD, FACC, FASE, Christine E. Seidman, MD, FAHA, Jeffrey A. Towbin, MD, FACC, FAHA, James E. Udelson, MD, FACC, FASNC and Clyde W. Yancy, MD, FACC, FAHA Bernard J. GershBernard J. Gersh Appendix 1 , Barry J. MaronBarry J. Maron Appendix 1 , Robert O. BonowRobert O. Bonow , Joseph A. DearaniJoseph A. Dearani , Michael A. FiferMichael A. Fifer Appendix 1 , Mark S. LinkMark S. Link Appendix 1 , Srihari S. NaiduSrihari S. Naidu Appendix 1 , Rick A. NishimuraRick A. Nishimura , Steve R. OmmenSteve R. Ommen , Harry RakowskiHarry Rakowski , Christine E. SeidmanChristine E. Seidman , Jeffrey A. TowbinJeffrey A. Towbin , James E. UdelsonJames E. Udelson and Clyde W. YancyClyde W. Yancy Originally published8 Nov 2011https://doi.org/10.1161/CIR.0b013e318223e2bdCirculation. 2011;124:e783–e831Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 Table of ContentsPreamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e785 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e787 1.1. Methodology and Evidence Review . . . . . . . . . .e7871.2. Organization of the Writing Committee . . . . . . .e7871.3. Document Review and Approval. . . . . . . . . . . . .e7871.4. Scope of the Guideline . . . . . . . . . . . . . . . . . . . .e788Prevalence/Nomenclature/Differential Diagnosis . . . .e788 2.1. Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e7882.2. Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . .e788 2.2.1. Historical Context. . . . . . . . . . . . . . . . . . .e7882.2.2. Clinical Definition and Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . .e7882.2.3. Impact of Genetics . . . . . . . . . . . . . . . . . .e7892.2.4. Hypertrophic Cardiomyopathy Centers . .e789Clinical Course and Natural History, Including Absence of Complications . . . . . . . . . . . . . . . . . . . . .e790Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e790 4.1. LVOT Obstruction. . . . . . . . . . . . . . . . . . . . . . . .e7904.2. Diastolic Dysfunction . . . . . . . . . . . . . . . . . . . . .e7914.3. Myocardial Ischemia . . . . . . . . . . . . . . . . . . . . . .e7914.4. Autonomic Dysfunction. . . . . . . . . . . . . . . . . . . .e7914.5. Mitral Regurgitation . . . . . . . . . . . . . . . . . . . . . .e791Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e792 5.1. Genetic Testing Strategies/Family Screening—Recommendations . . . . . . . . . . . . . . . . . . . . . . . .e792 5.1.1. Genotype-Positive/Phenotype-Negative Patients—Recommendation. . . . . . . . . . . .e7935.2. Electrocardiography—Recommendations. . . . . . .e7935.3. Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e794 5.3.1. Echocardiography—Recommendations . . . .e7945.3.2. Stress Testing—Recommendations . . . . . .e7965.3.3. Cardiac Magnetic Resonance—Recommendations . . . . . . . . . . . . . . . . . . .e7965.4. Detection of Concomitant Coronary Disease—Recommendations . . . . . . . . . . . . . . . . . . . . . . . .e797 5.4.1. Choice of Imaging Modality . . . . . . . . . . .e798 5.4.1.1. Invasive Coronary Arteriography . . .e7985.4.1.2. Noninvasive CTA . . . . . . . . . . . .e7985.4.1.3. Single Photon Emission Computed Tomography Myocardial Perfusion Imaging. . . . . . . . . . . . . . . . . . . . .e7995.4.1.4. Positron Emission Tomography . . .e7995.4.1.5. Stress Echocardiography . . . . . . .e799Management of HCM . . . . . . . . . . . . . . . . . . . . . . . .e800 6.1. Asymptomatic Patients—Recommendations . . . .e8006.2. Symptomatic Patients . . . . . . . . . . . . . . . . . . . . .e801 6.2.1. Pharmacologic Management—Recommendations . . . . . . .e8016.2.2. Invasive Therapies—Recommendations . . .e802 6.2.2.1. Selection of Patients . . . . . . . . . .e8036.2.2.2. Results of Invasive Therapy for the Relief of LVOT Obstruction. . .e8046.2.2.3. Operator Experience . . . . . . . . . .e8046.2.2.4. Surgical Therapy . . . . . . . . . . . . .e804 6.2.2.4.1. Selection of Patients . . .e8056.2.2.4.2. Outcomes . . . . . . . . . .e8056.2.2.4.3. Complications . . . . . . .e8056.2.2.4.4. Mitral Valve Abnormalities and Other Anatomic Issues . . . . . . . . . . . . .e8056.2.2.5. Alcohol Septal Ablation . . . . . . .e806 6.2.2.5.1. Selection of Patients . .e8066.2.2.5.2. Results . . . . . . . . . . . .e8066.2.2.5.3. Complications . . . . . . .e8076.2.2.6. Pacing—Recommendations . . . . .e807 6.2.2.6.1. Results of DDD Pacing . . . . . . . . . . . . .e8076.2.2.6.2. DDD Pacing: Caveats. . .e8086.2.2.6.3. Pacing and ICDs . . . . .e8086.2.3. Patients With LV Systolic Dysfunction—Recommendations . . . . . . .e8086.2.4. Selection of Patients for Heart Transplantation—Recommendations . . . . .e8096.3. Prevention of SCD . . . . . . . . . . . . . . . . . . . . . . .e809 6.3.1. SCD Risk Stratification—Recommendations . . . . . . . . . . . . . . . . . . .e809 6.3.1.1. Established Risk Markers . . . . . .e809 6.3.1.1.1. Prior Personal History of Ventricular Fibrillation, SCD, or Sustained VT. . . . . . . .e8096.3.1.1.2. Family History of SCD . . . . . . . . . . . . . .e8096.3.1.1.3. Syncope. . . . . . . . . . . .e8106.3.1.1.4. Nonsustained Ventricular Tachycardia. . . . . . . . . .e8106.3.1.1.5. Maximum LV Wall Thickness . . . . . . . . . .e8106.3.1.1.6. Abnormal Blood Pressure Response During Exercise. . . . . .e8106.3.1.2. Other Potential SCD Risk Modifiers . . . . . . . . . . . . . . . . . . .e810 6.3.1.2.1. LVOT Obstruction . . .e8106.3.1.2.2. LGE on CMR Imaging. .e8106.3.1.2.3. LV Apical Aneurysm . . .e8106.3.1.2.4. Genetic Mutations . . . .e8106.3.1.3. Utility of SCD Risk Markers in Clinical Practice . . . . . . . . . . . . .e8116.3.2. Selection of Patients for ICDs—Recommendations . . . . . . . . . . . . .e811 6.3.2.1. Results of ICD Therapy in HCM. . . . . . . . . . . . . . . . . . . . . .e8126.3.2.2. Complications of ICD Therapy in HCM. . . . . . . . . . . . . . . . . . . .e8126.3.2.3. Overall Risk Assessment and Selection of Patients for ICD Therapy . . . . . . . . . . . . . . . . . . . .e8126.3.2.4. Selection of ICD Device Type—Recommendations . . . . . . . . . . . .e8136.3.3. Participation in Competitive or Recreational Sports and Physical Activity—Recommendations. . .e8136.4. Management of AF—Recommendations . . . . . . .e814Other Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e816 7.1. Pregnancy/Delivery—Recommendations . . . . . . .e8167.2. Occupational Considerations . . . . . . . . . . . . . . . .e816Future Research Needs. . . . . . . . . . . . . . . . . . . . . . . .e816 8.1. Establishing the Cause of HCM . . . . . . . . . . . . .e8168.2. Defining the Link Between Genotype and Phenotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e8168.3. Management and Evaluation of HCM Genotype- Positive/Phenotype-Negative Relatives . . . . . . . .e8178.4. Clinical Significance of Myocardial Fibrosis. . . .e8178.5. Therapies to Directly Modify the HCM Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . .e8178.6. Refining Risk Stratification for SCD. . . . . . . . . .e8178.7. Comparative Assessment of Septal Reduction Strategies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e8178.8. Therapies to Treat and Prevent AF and Its Associated Risks . . . . . . . . . . . . . . . . . . . . . . . . .e817References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e818Appendix 1. Author Relationships With Industry and Other Entities (Relevant) . . . . . . . . . . . . . .e828Appendix 2. Reviewer Relationships With Industry and Other Entities (Relevant) . . . . . . . . . . . . . .e829Appendix 3. Abbreviation List . . . . . . . . . . . . . . . . . . . .e831Jacobs Alice K., MD, FACC, FAHAChair, ACCF/AHA Task Force on Practice GuidelinesPreambleIt is essential that the medical profession play a central role in critically evaluating the evidence related to drugs, devices, and procedures for the detection, management, or prevention of disease. Properly applied, rigorous, expert analysis of the available data documenting absolute and relative benefits and risks of these therapies and procedures can improve the effectiveness of care, optimize patient outcomes, and favorably affect the cost of care by focusing resources on the most effective strategies. One important use of such data is the production of clinical practice guidelines that, in turn, can provide a foundation for a variety of other applications such as performance measures, appropriateness use criteria, clinical decision support tools, and quality improvement tools.The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of guidelines in the area of cardiovascular disease since 1980. The ACCF/AHA Task Force on Practice Guidelines (Task Force) is charged with developing, updating, and revising practice guidelines for cardiovascular diseases and procedures, and the Task Force directs and oversees this effort. Writing committees are charged with assessing the evidence as an independent group of authors to develop, update, or revise recommendations for clinical practice.Experts in the subject under consideration have been selected from both organizations to examine subject-specific data and write guidelines in partnership with representatives from other medical practitioner and specialty groups. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against particular tests, treatments, or procedures, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that may influence the choice of tests or therapies are considered. When available, information from studies on cost is considered, but data on efficacy and clinical outcomes constitute the primary basis for recommendations in these guidelines.In analyzing the data and developing the recommendations and supporting text, the writing committee used evidence-based methodologies developed by the Task Force, which are described elsewhere.1 The committee reviewed and ranked evidence supporting current recommendations with the weight of evidence ranked as Level A if the data were derived from multiple randomized clinical trials (RCTs) or meta-analyses. The committee ranked available evidence as Level B when data were derived from a single RCT or nonrandomized studies. Evidence was ranked as Level C when the primary source of the recommendation was consensus opinion, case studies, or standard of care. In the narrative portions of these guidelines, evidence is generally presented in chronological order of development. Studies are identified as observational, retrospective, prospective, or randomized when appropriate. For certain conditions for which inadequate data are available, recommendations are based on expert consensus and clinical experience and ranked as Level C. An example is the use of penicillin for pneumococcal pneumonia, for which there are no RCTs and treatment is based on clinical experience. When recommendations at Level C are supported by historical clinical data, appropriate references (including clinical reviews) are cited if available. For issues where sparse data are available, a survey of current practice among the clinicians on the writing committee was the basis for Level C recommendations and no references are cited. The schema for Classification of Recommendations and Level of Evidence is summarized in Table 1, which also illustrates how the grading system provides an estimate of the size and the certainty of the treatment effect. A new addition to the ACCF/AHA methodology is separation of the Class III recommendations to delineate whether the recommendation is determined to be of "no benefit" or associated with "harm" to the patient. In addition, in view of the increasing number of comparative effectiveness studies, comparator verbs and suggested phrases for writing recommendations for the comparative effectiveness of one treatment/strategy with respect to another for Class of Recommendation I and IIa, Level of Evidence A or B only have been added.Table 1. Applying Classification of Recommendation and Level of EvidenceTable 1. Applying Classification of Recommendation and Level of EvidenceA recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use.†For comparative effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated.The Task Force makes every effort to avoid actual, potential, or perceived conflicts of interest that may arise as a result of relationships with industry and other entities (RWI) among the writing committee. Specifically, all members of the writing committee, as well as peer reviewers of the document, are required to disclose all relevant relationships and those 12 months prior to initiation of the writing effort. The policies and procedures for RWI for this guideline were those in effect at the initial meeting of this committee (March 28, 2009), which included 50% of the writing committee with no relevant RWI. All guideline recommendations require a confidential vote by the writing committee and must be approved by a consensus of the members voting. Members who were recused from voting are indicated on the title page of this document with detailed information included in Appendix 1. Members must recuse themselves from voting on any recommendations where their RWI apply. If a writing committee member develops a new RWI during his/her tenure, he/she is required to notify guideline staff in writing. These statements are reviewed by the Task Force and all members during each conference call and/or meeting of the writing committee and are updated as changes occur. For detailed information regarding guideline policies and procedures, please refer to the ACCF/AHA methodology and policies manual.1 RWI pertinent to this guideline for authors and peer reviewers are disclosed in Appendixes 1 and 2, respectively. Comprehensive disclosure information for the Task Force is also available online at http://www.cardiosource.org/ACC/About-ACC/Leadership/Guidelines-and-Documents-Task-Forces.aspx. The work of the writing committee was supported exclusively by the ACCF and AHA without commercial support. Writing committee members volunteered their time for this effort.The ACCF/AHA practice guidelines address patient populations (and healthcare providers) residing in North America. As such, drugs that are currently unavailable in North America are discussed in the text without a specific class of recommendation. For studies performed in large numbers of subjects outside of North America, each writing group reviews the potential impact of different practice patterns and patient populations on the treatment effect and on the relevance to the ACCF/AHA target population to determine whether the findings should inform a specific recommendation.The ACCF/AHA practice guidelines are intended to assist healthcare providers in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, and prevention of specific diseases or conditions. These practice guidelines represent a consensus of expert opinion after a thorough review of the available current scientific evidence and are intended to improve patient care. The guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and patient in light of all the circumstances presented by that patient. Thus, there are situations in which deviations from these guidelines may be appropriate. Clinical decision making should consider the quality and availability of expertise in the area where care is provided. When these guidelines are used as the basis for regulatory or payer decisions, the goal should be improvement in quality of care. The Task Force recognizes that situations arise for which additional data are needed to better inform patient care; these areas will be identified within each respective guideline when appropriate.Prescribed courses of treatment in accordance with these recommendations are effective only if they are followed. Because lack of patient understanding and adherence may adversely affect outcomes, physicians and other healthcare providers should make every effort to engage the patient's active participation in prescribed medical regimens and lifestyles.The guideline will be reviewed annually by the Task Force and considered current unless it is updated, revised, or withdrawn from distribution.Guidelines are official policy of both the ACCF and AHA.Alice K. Jacobs, MD, FACC, FAHA Chair, ACCF/AHA Task Force on Practice Guidelines1. Introduction1.1. Methodology and Evidence ReviewThe recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted through January 2011. Searches were limited to studies, reviews, and other evidence conducted in human subjects and published in English. Key search words included, but were not limited to, hypertrophic cardiomyopathy (HCM), surgical myectomy, ablation, exercise, sudden cardiac death (SCD), athletes, dual-chamber pacing, left ventricular outflow tract (LVOT) obstruction, alcohol septal ablation, automobile driving and implantable cardioverter-defibrillators (ICDs), catheter ablation, defibrillators, genetics, genotype, medical management, magnetic resonance imaging, pacing, permanent pacing, phenotype, pregnancy, risk stratification, sudden death in athletes, surgical septal myectomy, and septal reduction. Additionally, the committee reviewed documents related to the subject matter previously published by the ACCF and AHA. References selected and published in this document are representative and not all-inclusive.To provide clinicians with a comprehensive set of data, whenever deemed appropriate or when published, the absolute risk difference and number needed to treat or harm are provided in the guideline, along with confidence intervals and data related to the relative treatment effects, such as odds ratio, relative risk, hazard ratio, or incidence rate ratio.1.2. Organization of the Writing CommitteeThe committee was composed of physicians and cardiac surgeons with expertise in HCM, invasive cardiology, noninvasive testing and imaging, pediatric cardiology, electrophysiology, and genetics. The committee included representatives from the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons.1.3. Document Review and ApprovalThis document was reviewed by 2 outside reviewers nominated by both the ACCF and AHA, as well as 2 reviewers each from the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. Other content reviewers included members from the ACCF Adult Congenital and Pediatric Cardiology Council, ACCF Surgeons' Scientific Council, and ACCF Interventional Scientific Council. All information on reviewers' RWI was distributed to the writing committee and is published in this document (Appendix 2).This document was approved for publication by the governing bodies of the ACCF and the AHA and endorsed by the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.1.4. Scope of the GuidelineAlthough there are reports of this disease dating back to the 1800s, the first modern pathologic description was provided over 50 years ago by Teare2 and the most important early clinical report by Braunwald et al in 1964.3 Since then, there has been a growing understanding of the complexity and diversity of the underlying genetic substrate, the clinical phenotype, natural history, and approaches to treatment.The impetus for the guideline is based on an appreciation of the frequency of this clinical entity and a realization that many aspects of clinical management, including the use of diagnostic modalities and genetic testing, lack consensus. Moreover, the emergence of 2 different approaches to septal reduction therapy (septal myectomy and alcohol septal ablation) in addition to the ICD has created considerable controversy. The discussion and recommendations about the various diagnostic modalities apply to patients with established HCM and to a variable extent to patients with a high index of suspicion of the disease.Although the Task Force was aware of the lack of high levels of evidence regarding HCM provided by clinical trials, it was believed that a guideline document based on expert consensus that outlines the most important diagnostic and management strategies would be helpful.To facilitate ease of use, it was decided that recommendations in the pediatric and adolescent age groups would not appear as a separate section but instead would be integrated into the overall content of the guideline where relevant.2. Prevalence/Nomenclature/Differential Diagnosis2.1. PrevalenceHCM is a common genetic cardiovascular disease. In addition, HCM is a global disease,4 with epidemiological studies from several parts of the world5 reporting a similar prevalence of left ventricular (LV) hypertrophy, the quintessential phenotype of HCM, to be about 0.2% (ie, 1:500) in the general population, which is equivalent to at least 600 000 people affected in the United States.6 This estimated frequency in the general population appears to exceed the relatively uncommon occurrence of HCM in cardiology practices, implying that most affected individuals remain unidentified, probably in most cases without symptoms or shortened life expectancy.2.2. Nomenclature2.2.1. Historical ContextAlthough HCM is the preferred nomenclature to describe this disease,7 confusion over the names used to characterize the entity of HCM has arisen over the years. At last count, >80 individual names, terms, and acronyms have been used (most by early investigators) to describe HCM.7 Furthermore, nomenclature that was popular in the 1960s and 1970s, such as IHSS (idiopathic hypertrophic subaortic stenosis) or HOCM (hypertrophic obstructive cardiomyopathy), is potentially confusing by virtue of the inference that LVOT is an invariable and obligatory component of the disease. In fact, fully one third of patients have no obstruction either at rest or with physiologic provocation.8 Although terms such as IHSS and HOCM persist occasionally in informal usage, they now rarely appear in the literature, whereas HCM, initially used in 1979, allows for both the obstructive and nonobstructive hemodynamic forms and has become the predominant formal term used to designate this disease.72.2.2. Clinical Definition and Differential DiagnosisThe generally accepted definition of HCM, the clinical entity that is the subject of this guideline, is a disease state characterized by unexplained LV hypertrophy associated with nondilated ventricular chambers in the absence of another cardiac or systemic disease that itself would be capable of producing the magnitude of hypertrophy evident in a given patient,6,7,9–12 with the caveat that patients who are genotype positive may be phenotypically negative without overt hypertrophy.13,14 Clinically, HCM is usually recognized by maximal LV wall thickness ≥15 mm, with wall thickness of 13 to 14 mm considered borderline, particularly in the presence of other compelling information (eg, family history of HCM), based on echocardiography. In terms of LV wall-thickness measurements, the literature at this time has been largely focused on echocardiography, although cardiovascular magnetic resonance (CMR) is now used with increasing frequency in HCM,15 and we presume that data with this latter modality will increasingly emerge. In the case of children, increased LV wall thickness is defined as wall thickness ≥2 standard deviations above the mean (z score ≥2) for age, sex, or body size. However, it should be underscored that in principle, any degree of wall thickness is compatible with the presence of the HCM genetic substrate and that an emerging subgroup within the broad clinical spectrum is composed of family members with disease-causing sarcomere mutations but without evidence of the disease phenotype (ie, LV hypertrophy).16–19 These individuals are usually referred to as being "genotype positive/phenotype negative" or as having "subclinical HCM." Furthermore, although a myriad of patterns and distribution of LV hypertrophy (including diffuse and marked) have been reported in HCM,15,20,21 about one third of patients have largely segmental wall thickening involving only a small portion of the left ventricle, and indeed such patients with HCM usually have normal calculated LV mass.15 The clinical diagnosis of HCM may also be buttressed by other typical features, such as family history of the disease, cardiac symptoms, tachyarrhythmias, or electrocardiographic abnormalities.9,10Differential diagnosis of HCM and other cardiac conditions (with LV hypertrophy) may arise, most commonly with hypertensive heart disease and the physiologic remodeling associated with athletic training ("athlete's heart").22–26 These are not uncommon clinical scenarios, and confusion between mild morphologic expressions of HCM and other conditions with LV hypertrophy usually arises when maximum wall thickness is in the modest range of 13 to 15 mm. In older patients with LV hypertrophy and a history of systemic hypertension, coexistence of HCM is often a consideration. The likelihood of HCM can be determined by identification of a diagnostic sarcomere mutation or inferred by marked LV thickness >25 mm and/or LVOT obstruction with systolic anterior motion (SAM) and mitral-septal contact.The important distinction between pathologic LV hypertrophy (ie, HCM) and physiologic LV hypertrophy (ie, athlete's heart) is impacted by the recognition that athletic conditioning can produce LV, right ventricular, and left atrial (LA) chamber enlargement, ventricular septal thickening, and even aortic enlargement26 but is often resolved by noninvasive markers, including sarcomeric mutations or family history of HCM, LV cavity dimension (if enlarged, favoring athlete's heart), diastolic function, pattern of LV hypertrophy (if unusual location or noncontiguous, favoring HCM), or short deconditioning periods in which a decrease in wall thickness would favor athlete's heart.22–26Notably, it is evident that metabolic or infiltrative storage disorders with LV hypertrophy in babies, older children, and young adults can mimic clinically diagnosed HCM (attributable to sarcomeric protein mutations), for example, conditions such as mitochondrial disease,27,28 Fabry disease,29 or storage diseases caused by mutations in the genes encoding the γ-2-regulatory subunit of the adenosine monophosphate (AMP)-activated protein kinase (PRKAG2) or the X-linked lysosome-associated membrane protein gene (LAMP2; Danon disease).30–33 Use of the term HCM is not appropriate to describe these and other patients with LV hypertrophy that occurs in the context of a multisystem disorder such as Noonan syndrome (with craniofacial and congenital heart malformations, as well as LV hypertrophy from mutations in genes of the RAS [RAt Sarcoma] pathway14,15), or distinct cardiomyopathies such as Pompe disease (also a glycogen storage disease II, with skeletal muscle weakness and cardiomyopathy because of deficiency of α1,4 glycosidase [acid maltase])34–38 (Figure 1). In addition, differential diagnosis of HCM may require distinction from systemic hypertension or physiologic athlete's heart23 or from dilated cardiomyopathy whe
