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2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology Foundation/American ...

BJ Gersh, BJ Maron, RO Bonow... - Journal of the ..., 2011 - Am Coll Cardio Found 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 Society of Thoracic Surgeons, ...

2. Prevalence/Nomenclature/Differential Diagnosis Top

ACCF/AHA Task Force Members

Table of Contents

Preamble

1. Introduction

2....

3. Clinical Course and...

4. Pathophysiology

5. Diagnosis

6. Management of HCM

7. Other Issues

8. Future Research Needs

Staff

References 2.1 Prevalence. HCM is a common genetic cardiovascular disease. In addition, HCM is a global disease (4), with epidemiological studies from several parts of the world (5) reporting a similar prevalence of left ventricular (LV) hypertrophy, the quintessential phenotype of HCM, to be about 0.2% (i.e., 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 Nomenclature. 2.2.1 Historical Context Although 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 (7).

2.2.2 Clinical Definition and Differential Diagnosis The 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 (e.g., 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 (i.e., 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 (9,10).

Differential 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 (i.e., HCM) and physiologic LV hypertrophy (i.e., 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 enlargement (26) 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 26).

Notably, 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 -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 [R At Sarcoma] pathway [14,15]), or distinct cardiomyopathies such as Pompe disease (also a glycogen storage disease II, with skeletal muscle weakness and cardiomyopathy because of deficiency of 1,4 glycosidase [acid maltase]) (34 38) (Figure 1). In addition, differential diagnosis of HCM may require distinction from systemic hypertension or physiologic athlete's heart (23) or from dilated cardiomyopathy when HCM presents in the end stage (39).

Figure 1 Summary of the nomenclature that distinguishes HCM from other genetic diseases associated with LV hypertrophy. *At this time the overwhelming evidence links the clinical diagnosis of HCM with a variety of genes encoding protein components of the cardiac sarcomere. However, it is possible that in the future other nonsarcomeric (but also nonmetabolic) genes may prove to cause HCM. An example is Noonan syndrome with cardiomyopathy. Modified with permission from Maron et al. (12).