Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction
- Martin S Maron, MD
Martin S Maron, MD
- Assistant Professor of Medicine
- Tufts University School of Medicine
Hypertrophic cardiomyopathy (HCM) is a genetically determined heart muscle disease most often (60 to 70 percent) caused by mutations in one of several sarcomere genes which encode components of the contractile apparatus. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".)
HCM is characterized by left ventricular hypertrophy of various morphologies, with a wide array of clinical manifestations and hemodynamic abnormalities (figure 1). Depending in part upon the site and extent of cardiac hypertrophy, HCM patients can develop one or more of the following abnormalities:
●Left ventricular outflow obstruction (LVOT)
- Pollick C, Morgan CD, Gilbert BW, et al. Muscular subaortic stenosis: the temporal relationship between systolic anterior motion of the anterior mitral leaflet and the pressure gradient. Circulation 1982; 66:1087.
- Maron BJ, Gottdiener JS, Arce J, et al. Dynamic subaortic obstruction in hypertrophic cardiomyopathy: analysis by pulsed Doppler echocardiography. J Am Coll Cardiol 1985; 6:1.
- Wigle ED, Sasson Z, Henderson MA, et al. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis 1985; 28:1.
- Maron BJ, Epstein SE. Clinical significance and therapeutic implications of the left ventricular outflow tract pressure gradient in hypertrophic cardiomyopathy. Am J Cardiol 1986; 58:1093.
- Maron BJ, Bonow RO, Cannon RO 3rd, et al. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (1). N Engl J Med 1987; 316:780.
- Wigle ED. Hypertrophic cardiomyopathy: a 1987 viewpoint. Circulation 1987; 75:311.
- Panza JA, Petrone RK, Fananapazir L, Maron BJ. Utility of continuous wave Doppler echocardiography in the noninvasive assessment of left ventricular outflow tract pressure gradient in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1992; 19:91.
- Panza JA, Maris TJ, Maron BJ. Development and determinants of dynamic obstruction to left ventricular outflow in young patients with hypertrophic cardiomyopathy. Circulation 1992; 85:1398.
- Maron BJ, Epstein SE, Roberts WC. Hypertrophic cardiomyopathy and transmural myocardial infarction without significant atherosclerosis of the extramural coronary arteries. Am J Cardiol 1979; 43:1086.
- Schwammenthal E, Nakatani S, He S, et al. Mechanism of mitral regurgitation in hypertrophic cardiomyopathy: mismatch of posterior to anterior leaflet length and mobility. Circulation 1998; 98:856.
- Yu EH, Omran AS, Wigle ED, et al. Mitral regurgitation in hypertrophic obstructive cardiomyopathy: relationship to obstruction and relief with myectomy. J Am Coll Cardiol 2000; 36:2219.
- WIGLE ED, HEIMBECKER RO, GUNTON RW. Idiopathic ventricular septal hypertrophy causing muscular subaortic stenosis. Circulation 1962; 26:325.
- Pierce GE, Morrow AG, Braunwald E. Idiopathic hypertrophic subaortic stenosis. 3. Intraoperative studies of the mechanism of obstruction and its hemodynamic consequences. Circulation 1964; 30:Suppl.
- Braunwald E, Lambrew CT, Rockoff SD, et al. Idiopathic hypertrophic subaortic stenosis. I. A description of the disease based upon an analysis of 64 patients. Circulation 1964; 30:Suppl.
- Kizilbash AM, Heinle SK, Grayburn PA. Spontaneous variability of left ventricular outflow tract gradient in hypertrophic obstructive cardiomyopathy. Circulation 1998; 97:461.
- Geske JB, Sorajja P, Ommen SR, Nishimura RA. Variability of left ventricular outflow tract gradient during cardiac catheterization in patients with hypertrophic cardiomyopathy. JACC Cardiovasc Interv 2011; 4:704.
- Feiner E, Arabadjian M, Winson G, et al. Post-prandial upright exercise echocardiography in hypertrophic cardiomyopathy. J Am Coll Cardiol 2013; 61:2487.
- Maron BJ. Evolution of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy. In: Advances in Cardiomyopathies, Baroldi G, Camerini F, Goodwin JF (Eds), Springer-Verlag, Berlin, Heidelberg 1990. p.7.
- Thaman R, Gimeno JR, Reith S, et al. Progressive left ventricular remodeling in patients with hypertrophic cardiomyopathy and severe left ventricular hypertrophy. J Am Coll Cardiol 2004; 44:398.
- Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical profile, and significance of left ventricular remodeling in the end-stage phase of hypertrophic cardiomyopathy. Circulation 2006; 114:216.
- Fighali S, Krajcer Z, Edelman S, Leachman RD. Progression of hypertrophic cardiomyopathy into a hypokinetic left ventricle: higher incidence in patients with midventricular obstruction. J Am Coll Cardiol 1987; 9:288.
- Silbiger JJ. Abnormalities of the Mitral Apparatus in Hypertrophic Cardiomyopathy: Echocardiographic, Pathophysiologic, and Surgical Insights. J Am Soc Echocardiogr 2016; 29:622.
- Rowin EJ, Maron BJ, Lesser JR, et al. Papillary muscle insertion directly into the anterior mitral leaflet in hypertrophic cardiomyopathy, its identification and cause of outflow obstruction by cardiac magnetic resonance imaging, and its surgical management. Am J Cardiol 2013; 111:1677.
- Klues HG, Roberts WC, Maron BJ. Anomalous insertion of papillary muscle directly into anterior mitral leaflet in hypertrophic cardiomyopathy. Significance in producing left ventricular outflow obstruction. Circulation 1991; 84:1188.
- Maron MS, Finley JJ, Bos JM, et al. Prevalence, clinical significance, and natural history of left ventricular apical aneurysms in hypertrophic cardiomyopathy. Circulation 2008; 118:1541.
- Sakamoto T. Apical hypertrophic cardiomyopathy (apical hypertrophy): an overview. J Cardiol 2001; 37 Suppl 1:161.
- Eriksson MJ, Sonnenberg B, Woo A, et al. Long-term outcome in patients with apical hypertrophic cardiomyopathy. J Am Coll Cardiol 2002; 39:638.
- Ho HH, Lee KL, Lau CP, Tse HF. Clinical characteristics of and long-term outcome in Chinese patients with hypertrophic cardiomyopathy. Am J Med 2004; 116:19.
- Kitaoka H, Doi Y, Casey SA, et al. Comparison of prevalence of apical hypertrophic cardiomyopathy in Japan and the United States. Am J Cardiol 2003; 92:1183.
- Klues HG, Schiffers A, Maron BJ. Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients. J Am Coll Cardiol 1995; 26:1699.
- Chikamori T, Doi YL, Akizawa M, et al. Comparison of clinical, morphological, and prognostic features in hypertrophic cardiomyopathy between Japanese and western patients. Clin Cardiol 1992; 15:833.
- Pons-Lladó G, Carreras F, Borrás X, et al. Comparison of morphologic assessment of hypertrophic cardiomyopathy by magnetic resonance versus echocardiographic imaging. Am J Cardiol 1997; 79:1651.
- Moon JC, Fisher NG, McKenna WJ, Pennell DJ. Detection of apical hypertrophic cardiomyopathy by cardiovascular magnetic resonance in patients with non-diagnostic echocardiography. Heart 2004; 90:645.
- Malik R, Maron MS, Rastegar H, Pandian NG. Hypertrophic cardiomyopathy with right ventricular outflow tract and left ventricular intracavitary obstruction. Echocardiography 2014; 31:682.
- Mozaffarian D, Caldwell JH. Right ventricular involvement in hypertrophic cardiomyopathy: a case report and literature review. Clin Cardiol 2001; 24:2.
- Morita H, Larson MG, Barr SC, et al. Single-gene mutations and increased left ventricular wall thickness in the community: the Framingham Heart Study. Circulation 2006; 113:2697.
- Niimura H, Patton KK, McKenna WJ, et al. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation 2002; 105:446.
- Van Driest SL, Ommen SR, Tajik AJ, et al. Yield of genetic testing in hypertrophic cardiomyopathy. Mayo Clin Proc 2005; 80:739.
- Binder J, Ommen SR, Gersh BJ, et al. Echocardiography-guided genetic testing in hypertrophic cardiomyopathy: septal morphological features predict the presence of myofilament mutations. Mayo Clin Proc 2006; 81:459.
- Lewis JF, Maron BJ. Elderly patients with hypertrophic cardiomyopathy: a subset with distinctive left ventricular morphology and progressive clinical course late in life. J Am Coll Cardiol 1989; 13:36.
- Fay WP, Taliercio CP, Ilstrup DM, et al. Natural history of hypertrophic cardiomyopathy in the elderly. J Am Coll Cardiol 1990; 16:821.
- Chikamori T, Doi YL, Yonezawa Y, et al. Comparison of clinical features in patients greater than or equal to 60 years of age to those less than or equal to 40 years of age with hypertrophic cardiomyopathy. Am J Cardiol 1990; 66:875.
- Lever HM, Karam RF, Currie PJ, Healy BP. Hypertrophic cardiomyopathy in the elderly. Distinctions from the young based on cardiac shape. Circulation 1989; 79:580.
- Maron BJ, Rowin EJ, Casey SA, et al. Risk stratification and outcome of patients with hypertrophic cardiomyopathy >=60 years of age. Circulation 2013; 127:585.
- Canepa M, Pozios I, Vianello PF, et al. Distinguishing ventricular septal bulge versus hypertrophic cardiomyopathy in the elderly. Heart 2016; 102:1087.
- PATHOPHYSIOLOGY AND EVOLUTION OF LVOT OBSTRUCTION
- Mechanism of LVOT obstruction
- Development of mitral regurgitation
- DYNAMIC NATURE OF LVOT OBSTRUCTION
- Factors which affect LVOT obstruction
- Evolution of LVOT obstruction
- Transition to end-stage HCM
- HCM VARIANTS
- Mid-cavity obstructive HCM
- Mid-cavity obstruction with LV apical aneurysm
- Apical HCM
- Right ventricular obstruction
- Obstructive HCM in elderly adults
- - Sigmoid septal morphology
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS