Prevalence of Hypertrophic Cardiomyopathy and Limitations of Screening Methods
1995; Lippincott Williams & Wilkins; Volume: 92; Issue: 4 Linguagem: Inglês
10.1161/01.cir.92.4.700
ISSN1524-4539
AutoresLameh Fananapazir, Neal D. Epstein,
Tópico(s)Cardiovascular Function and Risk Factors
ResumoHomeCirculationVol. 92, No. 4Prevalence of Hypertrophic Cardiomyopathy and Limitations of Screening Methods Free AccessResearch ArticleDownload EPUBAboutView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticleDownload EPUBPrevalence of Hypertrophic Cardiomyopathy and Limitations of Screening Methods Lameh Fananapazir and Neal D. Epstein Lameh FananapazirLameh Fananapazir From the Inherited Cardiac Diseases Section, Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. and Neal D. EpsteinNeal D. Epstein From the Inherited Cardiac Diseases Section, Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. Originally published15 Aug 1995https://doi.org/10.1161/01.CIR.92.4.700Circulation. 1995;92:700–704Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease with an autosomal dominant pattern of inheritance that has traditionally been characterized by left ventricular hypertrophy (LVH) in the absence of another cause for the increased cardiac mass.1 It may be associated with severe symptoms and occasionally masquerades as "heart attacks," valvular heart disease, or arrhythmias of uncertain origin. HCM is the most common cause of sudden cardiac death in otherwise healthy young individuals, such as athletes. Since the diagnosis is frequently made postmortem, there is a pressing need to investigate the prevalence of HCM and the methods by which it is detected. Recent advances in the molecular genetics of HCM have increased our understanding of its pathophysiology and heightened our awareness of the variable expression of the disease. The use of molecular markers (the genetic defects) has demonstrated the marked phenotypic variability of HCM even within the same family. Features associated with HCM, such as arrhythmias, myocardial ischemia, and/or diastolic dysfunction, may be present in patients in the absence of LVH as determined by echocardiography.234 Hence, epidemiological studies that rely solely on echocardiographic parameters provide a restricted view of the prevalence and impact of HCM in the general population. Limitations of Epidemiological Studies of HCM Several echocardiographic studies have estimated the prevalence of HCM in the general population to be 0.2%.56 The Coronary Artery Risk Development in Adults (CARDIA) study investigators report an almost identical prevalence of HCM.7 The CARDIA study was initially designed to investigate the longitudinal influence of lifestyle and other factors on the risk of coronary heart disease in a biracial cohort population of adults 18 to 30 years old.8 Recruitment to the study was from four urban areas. In a subset of this population, the CARDIA investigators identified 7 patients with HCM out of 4111 study subjects. HCM was estimated to be 2.9 times more common in men than women and 2.4 times more common in blacks than whites. HCM was mild in almost every case. Only 1 patient had significant LV outflow tract obstruction. Two of the 7 patients had normal 12-lead ECGs. An additional 5 subjects with LV wall thickness of 15 to 21 mm were not thought to have HCM because of coexisting hypertension. Although the CARDIA population undoubtedly provides valuable information about the risks of coronary artery disease in young adults, it is questionable whether it or similar epidemiological populations are appropriate for the determination of the prevalence and characteristics of a relatively uncommon genetic cardiac disease such as HCM. In particular, the number of patients who were diagnosed with HCM in the CARDIA study is too small to be certain about the precision of the calculated prevalence of HCM or the apparent sex and racial predispositions to HCM. We estimate that equal sample sizes of approximately 9470 men and 9470 women may be needed to detect the difference reported in the CARDIA study of 0.17% (0.26% in men versus 0.09% in women) between the two groups with an 80% statistical power at a P=.05 (two-sided) significance level. Although no claims of statistical significance are made, the findings of the CARDIA study suggest that HCM is almost three times more frequent in men than women. However, a population recruited for epidemiological study may be deemed to be sufficiently large only if the identified patients reflect what is known about the genetics of the disease. The genetics of HCM (autosomal dominant) dictate an equal inheritance of the disease gene in men and women, and although it is possible that men with an HCM gene more frequently express LVH, the use of molecular markers allows a definitive comparison of LV wall thickness in men and women with HCM caused by a β-myosin heavy chain (β-MHC) disease gene. Fig 1 depicts the maximum LV wall thickness in adult men and women who have inherited distinct β-MHC gene mutations and demonstrates that the LV wall dimensions are not significantly different in men and women with the identical disease genes. Hence, a valid population should have an equal prevalence of men and women with HCM as detected by echocardiography. The CARDIA study also suggests more than two times greater frequency of HCM in blacks versus whites. However, we estimate that equal sample sizes of ≈13 750 blacks and 13 750 whites would be needed to detect a difference of 0.14% (0.24% in blacks versus 0.1% in whites) between the two groups with an 80% statistical power at a P=.05 (two-sided) significance level. Thus, there is a danger that the echocardiographic findings in the CARDIA population will reinforce a mistaken impression that HCM is more common in black than white athletes. This impression has arisen because far more black than white athletes participate in certain competitive sports. For example, at present, a large percentage of the NBA basketball players are black. At the NIH, the racial mix of ≈600 HCM families that are followed is similar to that of the general population. A far greater sample size than the one available to the CARDIA investigators would also have been necessary to determine the prevalence of the diverse clinical presentations and morphologies characteristic of HCM. Individuals with many of these morphologies may not have been recruited because the study specifically excluded subjects with long-term disease or disability. It is also possible to either underestimate or overestimate the prevalence of HCM through the choice of the locality from which subjects are recruited. For example, we have observed from our family/genetic studies that it is not uncommon for many members of an extended HCM family to reside in rural areas around a small town.34 It is therefore possible that the disease is underrepresented in the four urban areas that were part of the CARDIA study. Conversely, if by chance an epidemiological study includes one of these large local families, a false impression would be created that HCM is very prevalent among young and otherwise healthy adults. Insights From Genetic Studies Limitations of Echocardiographic Definitions Echocardiography has played an indispensable role in describing the diverse morphological features of HCM and in defining the mechanisms of LV outflow tract obstruction in patients with the obstructive form of the disease. The many names that the disease has acquired, such as idiopathic hypertrophic subaortic stenosis, asymmetrical septal hypertrophy, midcavity obstructive HCM, and apical or Japanese HCM, attest to its phenotypic heterogeneity. In recognition of this, and to differentiate the disease from other causes of LVH, it has become customary to use a broad echocardiographic definition of HCM: LV wall thickness of ≥15 mm without LV dilatation in the absence of another cardiac or systemic cause for the increased LV mass.1 This definition, however, has serious limitations: (1) It fails, even in adults, to identify many patients with HCM who have inherited a disease gene but who have not developed LVH; (2) it excludes patients who do have HCM but who have another coexisting disease that may contribute to the LVH, such as hypertension or valvular heart disease; and (3) the clinical outcome of HCM patients correlates poorly with the severity of the LVH. Notably, it is now recognized that arrhythmias and sudden cardiac death can occur in the absence of significant LVH (Fig 2).910 Furthermore, an LV wall thickness of 16 mm in a patient who has inherited a genetic defect that is associated with a high incidence of sudden death may be a more significant prognostic finding than an LV wall thickness of 32 mm in an HCM patient in whom the disease is caused by a mutation associated with a benign prognosis.34The same concerns also apply to population studies that use echocardiography to differentiate between LVH due to athletic training and the milder forms of HCM.11 Since many patients who have mild LVH may carry an HCM disease gene, exclusion of the disease in these subjects may not be possible until genetic testing becomes feasible for all patients in question. Genetic Heterogeneity It is now clear that HCM is not a single genetic disease. To date, three genes, β-MHC on chromosome 14q, an α-tropomyosin on chromosome 15, and cardiac troponin-T on chromosome 1, and two loci on chromosomes 11 and 7 have been linked to HCM.12131415 HCM also displays allelic heterogeneity; ie, one of multiple distinct mutations of a particular gene can cause the disease. For example, more than 30 missense mutations of the β-MHC gene have been described.3416 Hence, it is likely that eventually >100 genetically distinct diseases may be shown to cause LVH and similar echocardiographic appearances. The natural histories of the various genetic abnormalities, however, may be significantly different.3417 Increasingly, therefore, the starting point of diagnosis and management of the disease in an HCM family will be the definition of the particular genetic abnormality, followed by the description of its specific features and clinical course. Although the initial identification of a genetic defect may be laborious, once the genetic abnormality has been detected in a patient, determination of which of his or her relatives has inherited the disease gene is straightforward. For example, to date, at the NIH we have identified 26 distinct β-MHC gene mutations in 48 unrelated kindreds with HCM. The natural history and clinical features of each mutation are being characterized in extended kindreds. Sporadic Versus Inherited HCM and Disease Penetrance HCM occurs sporadically or is inherited. A problem that has arisen from the echocardiographic definition of HCM is that previously ≈40% of the cases of HCM were believed to be sporadic.1819 This estimation of sporadic cases was probably because of the small size of families that were studied and the lack of appreciation that the LVH associated with HCM can skip one or more generations.3420 True instances of sporadic HCM, ie, those in which a genetic mutation demonstrated in an offspring is not present in either biological parent, are probably rare.21 Even in such de novo examples of HCM, the pattern of inheritance of the disease in the progeny of the sporadic case is autosomal dominant (Fig 3). The echocardiographic definition of HCM requires that all subjects who inherit the disease gene express the classic cardiac phenotype. However, the disease penetrance, ie, the percentage of individuals with the genetic mutation who manifest the LVH phenotype, varies significantly in HCM. For example, the 403Arg→Gln β-MHC gene mutation is associated with a 100% disease penetrance in adults,3 but the 908Leu→Val and the 256Gly→Glu β-MHC gene mutations are associated with a markedly reduced disease penetrance.34 As shown in Fig 1, if a maximum LV wall thickness of 15 mm is taken to be the cutoff point between normal and LVH due to HCM, the calculated disease penetrances of the 908Leu→Val and the 256Gly→Glu β-MHC gene mutations are only 47% and 57%, respectively. The determination of the genotype also provides an opportunity for reevaluation of the definition of LVH. An important finding of our genetic studies in large HCM families is that LVH needs to be assessed not by reference to an arbitrary value of LV wall thickness but in the context of cardiac dimensions of family members who do not have the disease allele. The upper limit of normal wall thickness in the family with the 908Leu→Val β-MHC gene mutations was 12 mm,3 but the normal LV wall thickness in the family with the 256Gly→Glu β-MHC gene mutation was 14 mm4. Genotyping also confirms that within a kindred, clinical features of family members with the mutant allele may vary considerably (Fig 3). Conversely, it is possible that the similar morphological appearances of the seven patients with HCM identified by the CARDIA study were due to inheritance of seven distinct genetic abnormalities. The prevalence and spectrum of these distinct genetic abnormalities can only be known by study of all the blood relatives of each patient. A further consideration is that LVH may be only one of several phenotypic characteristics of the disease. Because the myocardium can only respond to disease in a limited number of ways, it is not surprising that examples of dilated and restrictive cardiomyopathy are also occasionally noted in large HCM families. Some children and adult patients may have an abnormal 12-lead ECG or be prone to arrhythmias in the absence of LVH (Fig 2).34 Conversely, the ECG may be normal despite significant LVH.4 A more recent finding is that although in most cases the disease predominantly affects the heart, other organs may be involved. For example, we have demonstrated that β-MHC gene–associated HCM is a generalized disease of striated muscle: the β-MHC gene mutation is expressed in slow skeletal muscle,22 isolated skinned slow skeletal muscle fibers from patients with β-MHC gene mutations have abnormal mechanics,23 soleus muscle from these patients shows abnormal energetics during exercise as demonstrated by magnetic resonance spectroscopy,24 and many patients with β-MHC gene mutations show a muscle histology similar to that of central core disease—a nonprogressive myopathy characterized by loss of mitochondria from the center of many of the slow fibers.25 Consistent with the pleiotropy of HCM, central cores can be present in skeletal muscle in some of the children and adults in the absence of LVH.24Genetic Screening Genetic studies in HCM (1) lead to better definition and diagnosis of the disease; (2) increase our understanding of its pathophysiology and are critical for the elucidation of the molecular basis of the disease and of LVH in general; (3) permit preclinical diagnosis and genetic counseling; (4) improve risk stratification; and (5) may lead to development of therapies that may prevent progression of the disease in children or cause regression of the disease in adults. However, before there is a rush to commercialize this new development, it is worth considering that genetic testing also presents certain problems: (1) Genetic defects identified to date probably account for less than one third of the cases of HCM. (2) The clinical presentation of the disease varies significantly in affected patients within the same kindred. For example, the risk of sudden cardiac death differs within the family on the basis of whether individuals have one or a number of the following: ventricular arrhythmias, atrial tachycardia, bradyarrhythmias, myocardial ischemia, or severe LV outflow tract obstruction.2 (3) Genetic testing may increase the psychological burden in patients who have inherited a disease gene with incomplete penetrance who will never develop the clinical disease. (4) It may have other social consequences, such as adversely affecting employment or the ability to obtain medical insurance. In conclusion, the molecular biology of HCM has considerably expanded the spectrum of the disease beyond its original morphological definitions, illustrating the limitations of traditional epidemiological studies. The knowledge that will accrue from the joining of molecular studies to the careful clinical and physiological evaluation of affected families will benefit many patients with diverse cardiac disease. However, in our effort to hasten these benefits, we should also be aware of the pitfalls of genetic testing and try to anticipate the problems that may undermine its promise. Download figureDownload PowerPoint Figure 1. Graph illustrating maximum left ventricular (LV) wall thickness, determined by two-dimensional echocardiography, in men and women ≥20 years of age who inherited two distinct β-myosin heavy chain (βMHC) gene mutations. The solid circles represent family members of a kindred in which hypertrophic cardiomyopathy (HCM) is caused by a 908Leu→Val mutation. The open circles represent family members with a 256Gly→Glu mutation. Both mutations have been associated with a low incidence of sudden cardiac death in the two HCM kindreds.34 Sixteen of the 30 adult family members, or 53%, with the 908Leu→Val mutation have a maximum left ventricular wall thickness of <15 mm. Similarly, 15 of the 35 adult family members with the 256Gly→Glu mutation, or 43%, do not fit this echocardiographic definition of HCM. These two β-myosin heavy chain mutations were selected for this evaluation because of their benign prognosis.34Download figureDownload PowerPointDownload figureDownload figureDownload PowerPoint Figure 2. A, Pedigree of an adult patient (patient 17) who presented several years ago with light-headedness related to episodes of nonsustained ventricular tachycardia.20 The echocardiogram and 12-lead ECG were normal.20 Hypertrophic cardiomyopathy (HCM) in this kindred has been associated with a high incidence of premature sudden death. At electrophysiological study, a sustained ventricular tachycardia was induced with two premature extrastimuli, for which she received an implantable defibrillator. This has discharged appropriately once. Subsequently, the patient has had a child (patient 21) who at 5 years of age has an abnormal 12-lead ECG (B) and left ventricular hypertrophy (LVH) on the echocardiogram (C).Download figureDownload PowerPoint Figure 3. Pedigree illustrating a de novo (sporadic) occurrence of hypertrophic cardiomyopathy (HCM) and the phenotypic heterogeneity in a kindred in which the disease is caused by the 741Gly→Arg β-myosin heavy chain gene mutation. Four siblings have inherited the mutation from their father (patient II-1), who had a history of syncope related to obstructive HCM. The mutation was absent in both of his parents (patients I-1 and I-2). Haplotype analysis using five informative intragenic alleles flanking the mutation established that the mutant allele occurred on the background of a paternal haplotype. The first sibling (patient III-3) has nonobstructive HCM and has had a cardiac arrest precipitated by myocardial ischemia induced by an atrioventricular nodal reentrant tachycardia. She has a 6-year-old child (patient IV-12) who has inherited the mutation but has a normal 12-lead ECG and echocardiogram. The second sibling (patient III-5) also has nonobstructive HCM but is asymptomatic. The third sibling (patient III-7), 26 years old, also has a normal echocardiogram and 12-lead ECG. The fourth affected sibling (patient III-11) presented with severe drug-refractory symptoms related to obstructive HCM, which has been treated effectively with permanent dual-chamber (DDD) pacing. LVH indicates left ventricular hypertrophy.FootnotesCorrespondence to Lameh Fananapazir, MD, FRCP, Co-Chief, Inherited Cardiac Diseases Section, Director, Clinical Electrophysiology Laboratory, Building 10, Room 7B-14, Cardiology Branch, NHLBI, National Institutes of Health, 10 Center Dr MSC 1650, Bethesda, MD 20892-1650. References 1 Maron BJ, Epstein SE. Hypertrophic cardiomyopathy: a discussion of nomenclature. Am J Cardiol.1979; 43:1242-1244. CrossrefMedlineGoogle Scholar2 Fananapazir L, McAreavey D, Epstein ND. Hypertrophic cardiomyopathy. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1995:769-779. Google Scholar3 Epstein ND, Cohn GM, Cyran F, Fananapazir L. Differences in clinical expression of hypertrophic cardiomyopathy associated with two distinct mutations in the β-myosin heavy chain gene: a 908Leu→Val mutation and a 403Arg→Gln mutation. Circulation.1992; 86:345-352. CrossrefMedlineGoogle Scholar4 Fananapazir L, Epstein ND. Genotype-phenotype correlations in hypertrophic cardiomyopathy: insights provided by comparisons of kindreds with distinct and identical β-myosin heavy chain gene mutations. Circulation.1994; 89:22-32. CrossrefMedlineGoogle Scholar5 Hada Y, Sakamoto T, Amano K, Yamguchi T, Takahasi H, Takikawa R, Hasegawa T, Takahashi T, Suzuki J-I, Sugimoto T, Saito K-I. Prevalence of hypertrophic cardiomyopathy in a population of adult Japanese workers as detected by echocardiographic screening. Am J Cardiol.1987; 59:183-184. CrossrefMedlineGoogle Scholar6 Savage DD, Castelli WP, Abbott RD, Garrison RJ, Anderson SJ, Kanell WB, Feinlieb M. Hypertrophic cardiomyopathy and its markers in the general population: the great masquerader revisited: the Framingham study. J Cardiovasc Ultrason.1983; 2:41-47.Google Scholar7 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. Circulation.1995; 92:785-789. CrossrefMedlineGoogle Scholar8 Freidman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR, Liu K, Savage PJ. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol.1988; 41:1105-1116. CrossrefMedlineGoogle Scholar9 McKenna WJ, Stewart JT, Nihoyannopoulos P, McGinty F, Davies MJ. Hypertrophic cardiomyopathy without hypertrophy: two families with myocardial disarray in the absence of increased myocardial mass. Br Heart J.1990; 63:287-290. CrossrefMedlineGoogle Scholar10 Maron BJ, Kragel AH, Roberts WC. Sudden death due to hypertrophic cardiomyopathy in the absence of increased left ventricular mass. Br Heart J.1990; 63:308-310. CrossrefMedlineGoogle Scholar11 Pelliccia A, Maron BJ, Spataro A, Caselli G. Determination of maximum limits of physiologically induced left ventricular cavity enlargement due to training: echocardiographic assessment in 1000 elite athletes. Circulation. 1994;90(suppl I):I-165. Abstract. Google Scholar12 Geister-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CF, Seidman JG. A molecular basis for familial hypertrophic cardiomyopathy: a β-cardiac myosin heavy chain gene missense mutation. Cell.1990; 62:999-1006. CrossrefMedlineGoogle Scholar13 Thierfelder L, Watkins H, MacRae C, Lama R, McKenna W, Vosberg HP, Seidman JG, Seidman CE. α-Tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell.1994; 77:701-712. CrossrefMedlineGoogle Scholar14 Carrier L, Hengstenberg C, Beckman JS, Guicheny P, Dufour C, Bercovici J, Dausse E, Berebbi-Bertrand I, Wisnewsky C, Pulvenis D, Fetler L, Vignal A, Weissenbach J, Hilaire D, Feingold J, Bouhour J-B, Hagege A, Desnos M, Isnard R, Duborg O, Komajda M, Schwartz K. Mapping of a novel gene for familial hypertrophic cardiomyopathy to chromosome 11. Nature Genet.1993; 4:311-313. CrossrefMedlineGoogle Scholar15 MacRae C, Ghaisa N, McGarry K, McKenna W, Seidman JG, Seidman CE. Familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. Circulation. 1994;90(suppl I):I-25. Abstract. Google Scholar16 Rayment I, Holden HM, Sellers J, Fananapazir L, Epstein ND. Structural interpretation of the mutations in the β-cardiac myosin that have been implicated in familial hypertrophic cardiomyopathy. Proc Natl Acad Sci U S A.1995; 92:3864-3868. CrossrefMedlineGoogle Scholar17 Watkins H, Rosenzweig A, Hwang D-S, Levi T, McKenna W, Seidman CE, Seidman JG. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med.1992; 326:1108-1114. CrossrefMedlineGoogle Scholar18 Maron BJ, Nichols PF, Pickle LW, Wesley YE, Mulvihill JJ. Patterns of inheritance in hypertrophic cardiomyopathy: assessment by M-mode and two dimensional echocardiography. Am J Cardiol.1984; 53:1087-1094. CrossrefMedlineGoogle Scholar19 Maron BJ. Patterns of inheritance and progression of left ventricular hypertrophy. In: Toshima H, Maron BJ, eds. Cardiomyopathy Update 2: Hypertrophic Cardiomyopathy. Tokyo, Japan: University of Tokyo Press; 1988:171-188. Google Scholar20 Epstein ND, Lin HJ, Fananapazir L. Generational skips in families with hypertrophic cardiomyopathy: genetic evidence of dissociation of electrical from morphological forms of the disease. Am J Cardiol.1990; 66:627-631. CrossrefMedlineGoogle Scholar21 Watkins H, Thierfelder L, McKenna W, Seidman JG, Seidman CE. Sporadic hypertrophic cardiomyopathy due to de novo myosin mutations. Circulation. 1992;86(suppl I):I-228. Abstract. Google Scholar22 Cuda G, Fananapazir L, Zhu W-S, Sellers J, Epstein ND. Skeletal muscle expression and abnormal function of β-myosin in hypertrophic cardiomyopathy. J Clin Invest.1993; 91:2861-2865. CrossrefMedlineGoogle Scholar23 Lankford EB, Sweeney HL, Epstein ND, Fananapazir L. Abnormal contractile properties of muscle fibers expressing mutations in β-myosin in patients with hypertrophic cardiomyopathy. J Clin Invest.1995; 95:1409-1414. CrossrefMedlineGoogle Scholar24 Ryschon TW, Fowler MD, Arai AE, Wysong RE, McAreavey D, Epstein ND, Fananapazir L, Balaban RS. Muscle energetics during dynamic exercise in hypertrophic cardiomyopathy. Circulation. 1994;90(suppl I):I-442. Abstract. Google Scholar25 Fananapazir L, Dalakas MC, Cyran F, Cohn G, Epstein ND. Missense mutations in the β-myosin heavy chain gene cause central core disease in hypertrophic cardiomyopathy. Proc Natl Acad Sci U S A.1993; 90:3993-3997.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Hong Y, Su W and Li X (2021) Risk factors of sudden cardiac death in hypertrophic cardiomyopathy, Current Opinion in Cardiology, 10.1097/HCO.0000000000000939, 37:1, (15-21), Online publication date: 1-Jan-2022. Efthimiadis G, Zegkos T, Parcharidou D, Ntelios D, Panagiotidis T, Gossios T and Karvounis H (2021) A simple algorithm for a clinical step-by-step approach in the management of hypertrophic cardiomyopathy, Future Cardiology, 10.2217/fca-2020-0230, 17:8, (1395-1405), Online publication date: 1-Nov-2021. Hindieh W, Weissler-Snir A, Hammer H, Adler A, Rakowski H and Chan R (2017) Discrepant Measurements of Maximal Left Ventricular Wall Thickness Between Cardiac Magnetic Resonance Imaging and Echocardiography in Patients With Hypertrophic Cardiomyopathy, Circulation: Cardiovascular Imaging, 10:8, Online publication date: 1-Aug-2017. Corona-Villalobos C, Sorensen L, Pozios I, Chu L, Eng J, Abraham M, Abraham T, Kamel I and Zimmerman S (2016) Left ventricular wall thickness in patients with hypertrophic cardiomyopathy: a comparison between cardiac magnetic resonance imaging and echocardiography, The International Journal of Cardiovascular Imaging, 10.1007/s10554-016-0858-4, 32:6, (945-954), Online publication date: 1-Jun-2016. LIU L, TUO S, ZHANG J, ZUO L, LIU F, HAO L, SUN Y, YANG L, SHAO H, QI W, ZHOU X and GE S (2014)(2014) Reduction of left ventricular longitudinal global and segmental systolic functions in patients with hypertrophic cardiomyopathy: Study of two-dimensional tissue motion annular displacement, Experimental and Therapeutic Medicine, 10.3892/etm.2014.1617, 7:6, (1457-1464), Online publication date: 1-Jun-2014. Mohiddin S and Knight C (2011) Interventional Treatments for Hypertrophic Cardiomyopathy, Cardiovascular Therapeutics, 10.1111/j.1755-5922.2010.00229.x, 30:3, (e107-e114), Online publication date: 1-Jun-2012. Östman-Smith I, Wisten A, Nylander E, Bratt E, Granelli A, Oulhaj A and Ljungström E (2009) Electrocardiographic amplitudes: a new risk factor for sudden death in hypertrophic cardiomyopathy, European Heart Journal, 10.1093/eurheartj/ehp443, 31:4, (439-449), Online publication date: 1-Feb-2010., Online publication date: 1-Feb-2010. Kim Y, Choi B, Hur J, Lee H, Seo J, Kim T, Choe K and Ha J (2008) Delayed enhancement in hypertrophic cardiomyopathy: Comparison with myocardial tagging MRI, Journal of Magnetic Resonance Imaging, 10.1002/jmri.21366, 27:5, (1054-1060), Online publication date: 1-May-2008. Mohiddin S and McKenna W Hypertrophic Cardiomyopathy Diastolic Heart Failure, 10.1007/978-1-84628-891-3_20, (285-310) Östman-Smith I, Wettrell G, Keeton B, Riesenfeld T, Holmgren D and Ergander U (2005) Echocardiographic and electrocardiographic identification of those children with hypertrophic cardiomyopathy who should be considered at high-risk of dying suddenly, Cardiology in the Young, 10.1017/S1047951105001824, 15:06, (632) Sanders A, Boggess B, Koenig S and Toth A (2005) Medicolegal Issues in Sports Medicine, Clinical Orthopaedics and Related Research, 10.1097/01.blo.0000159764.03919.33, &NA;:433, (38-49), Online publication date: 1-Apr-2005. Restrepo C, Largoza A, Lemos D, Diethelm L, Koshy P, Castillo P, Gomez R, Moncada R and Pandit M (2005) CT and MR imaging findings of benign cardiac tumors, Current Problems in Diagnostic Radiology, 10.1067/j.cpradiol.2004.10.002, 34:1, (12-21), Online publication date: 1-Jan-2005. Graham‐Cryan M, Rowe G, Hathaway L, Biddle S, Tripodi D and Fananapazir L (2008) Obstructive Hypertrophic Cardiomyopathy, Progress in Cardiovascular Nursing, 10.1111/j.0889-7204.2003.03400.x, 19:4, (133-140), Online publication date: 1-Sep-2004. Mohiddin S and Fananapazir L Cardiac Involvement in the Neuroacanthocytosis Syndromes Neuroacanthocytosis Syndromes, 10.1007/1-4020-2898-9_16, (139-152) Evans C and Cassady S Sudden Cardiac Death in Athletes: What Sport-Rehabilitation Specialists Need to Know, Journal of Sport Rehabilitation, 10.1123/jsr.12.3.259, 12:3, (259-271) Earing M, Ackerman M and O'Leary P (2003) Diastolic ventricular dysfunction as a marker for hypertrophic cardiomyopathy in a family with a novel alpha-tropomyosin mutation, Journal of the American Society of Echocardiography, 10.1016/S0894-7317(03)00285-2, 16:6, (698-702), Online publication date: 1-Jun-2003. Hwang J, Allen P, Tseng G, Lam C, Fananapazir L, Dzau V and Liew C (2002) Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure, Physiological Genomics, 10.1152/physiolgenomics.00122.2001, 10:1, (31-44), Online publication date: 12-Jul-2002. Freedman R (2001) Use of implantable pacemakers and implantable defibrillators in hypertrophic cardiomyopathy, Current Opinion in Cardiology, 10.1097/00001573-200101000-00009, 16:1, (58-65), Online publication date: 1-Jan-2001. Olson T, Doan T, Kishimoto N, Whitby F, Ackerman M and Fananapazir L (2000) Inherited and de novo Mutations in the Cardiac Actin Gene Cause Hypertrophic Cardiomyopathy, Journal of Molecular and Cellular Cardiology, 10.1006/jmcc.2000.1204, 32:9, (1687-1694), Online publication date: 1-Sep-2000. Bevilacqua L and Berul C (2000) Familial Hypertrophic Cardiomyopathy Genetics Molecular Genetics of Cardiac Electrophysiology, 10.1007/978-1-4615-4517-0_12, (181-194), . Devlin A, Moore N and Ostman-Smith I (1999) A comparison of MRI and echocardiography in hypertrophic cardiomyopathy., The British Journal of Radiology, 10.1259/bjr.72.855.10396215, 72:855, (258-264), Online publication date: 1-Mar-1999. Zieman S and Fortuin N (1999) HYPERTROPHIC AND RESTRICTIVE CARDIOMYOPATHIES THE ELDERLY, Cardiology Clinics, 10.1016/S0733-8651(05)70062-X, 17:1, (159-172), Online publication date: 1-Feb-1999. ALDAY L, BRUNO E, MOREYRA E, AMUCHASTEGUI L, JUANEDA E and MAISULS H (1998) Mid-Term Results of Dual-Chamber Pacing in Children with Hypertrophic Obstructive Cardiomyopathy, Echocardiography, 10.1111/j.1540-8175.1998.tb00609.x, 15:3, (289-295), Online publication date: 1-Apr-1998. Palmiter K and Solaro R (1998) Molecular mechanisms regulating the myofilament response to Ca2+: Implications of mutations causal for familial hypertrophic cardiomyopathy Alterations of Excitation-Contraction Coupling in the Failing Human Heart, 10.1007/978-3-642-48670-8_10, (105-121), . Runge M, Stouffer G, Sheahan R, Lerakis S, Sheahan R and Stouffer G (1997) Hypertrophic Cardiomyopathy: Presentation and Pathophysiology, The American Journal of the Medical Sciences, 10.1097/00000441-199711000-00009, 314:5, (324-329), Online publication date: 1-Nov-1997. Runge M, Stouffer G, Sheahan R and Lerakis S (1997) Hypertrophic Cardiomyopathy: Presentation and Pathophysiology, The American Journal of the Medical Sciences, 10.1016/S0002-9629(15)40230-7, 314:5, (324-329), Online publication date: 1-Nov-1997. FANANAPAZIR L and McAREAVEY D (1997) Hypertrophic Cardiomyopathy: valuation and Treatment of Patients at High Risk for Sudden Death, Pacing and Clinical Electrophysiology, 10.1111/j.1540-8159.1997.tb06206.x, 20:2, (478-501), Online publication date: 1-Feb-1997. Palmiter K and Solaro R (1997) Molecular mechanisms regulating the myofilament response to Ca2+: Implications of mutations causal for familial hypertrophic cardiomyopathy, Basic Research in Cardiology, 10.1007/BF00794070, 92:S1, (63-74), . Posma J, van der Wall E, Blanksma P, van der Wall E and Lie K (1996) New diagnostic options in hypertrophic cardiomyopathy, American Heart Journal, 10.1016/S0002-8703(96)90018-6, 132:5, (1031-1041), Online publication date: 1-Nov-1996. Vikstrom K and Leinwand L (1996) Contractile protein mutations and heart disease, Current Opinion in Cell Biology, 10.1016/S0955-0674(96)80053-6, 8:1, (97-105), Online publication date: 1-Feb-1996. August 15, 1995Vol 92, Issue 4 Advertisement Article InformationMetrics Copyright © 1995 by American Heart Associationhttps://doi.org/10.1161/01.CIR.92.4.700 Originally publishedAugust 15, 1995 KeywordscardiomyopathyhypertrophyEditorials Advertisement
Referência(s)