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The Many Faces of Hypertrophic Cardiomyopathy: From Developmental Biology to Clinical Practice

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Abstract

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterized by complex pathophysiology, heterogeneous morphology, and variable clinical manifestations over time. Besides cardiac hypertrophy, the HCM phenotype is characterized by a host of manifestations, including mitral valve and subvalvar abnormalities, subaortic and mid-ventricular left ventricular (LV) obstruction, microvascular dysfunction, myocardial fibrosis, disarray, atrial remodeling, myocardial bridging of epicardial coronary arteries, LV apical aneurysms, and autonomic nervous system abnormalities. Such heterogeneous phenotype still lacks a comprehensive explanation, which cannot be accounted solely by genetic heterogeneity, despite the large number of genes and mutations involved. It is likely that pre-natal and acquired features deriving from the primary genetic defect interact with the environment to produce the final result evident in each patient. Based on novel insights provided by cardiac developmental biology, a common lineage ancestry of several HCM manifestations might be traced back to the pluripotent epicardium-derived cells, which early during heart development differentiate into interstitial fibroblasts, coronary smooth muscle cells, and atrio-ventricular endocardial cushions as mesenchymal cells. To date, the different faces of HCM have not been sufficiently liked or explained. We here attempt to address these issues by describing the various components of the disease, their origin, interaction, and clinical significance.

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References

  1. Adabag, A. S., Maron, B. J., Appelbaum, E., Harrigan, C. J., Buros, J. L., Gibson, C. M., et al. (2008). Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance. Journal of the American College of Cardiology, 51, 1369–1374.

    PubMed  Google Scholar 

  2. Alcalai, R., Seidman, J. G., & Seidman, C. E. (2008). Genetic basis of hypertrophic cardiomyopathy: From bench to the clinics. Journal of Cardiovascular Electrophysiology, 19, 104–110.

    PubMed  Google Scholar 

  3. Alegria, J. R., Herrmann, J., Holmes, D. R., Jr., Lerman, A., & Rihal, C. S. (2005). Myocardial bridging. European Heart Journal, 26, 1159–1168.

    PubMed  Google Scholar 

  4. Ashrafian, H., & Watkins, H. (2007). Reviews of translational medicine and genomics in cardiovascular disease: New disease taxonomy and therapeutic implications cardiomyopathies: Therapeutics based on molecular phenotype. Journal of the American College of Cardiology, 49, 1251–1264.

    CAS  PubMed  Google Scholar 

  5. Basso, C., Thiene, G., Corrado, D., Buja, G., Melacini, P., & Nava, A. (2000). Hypertrophic cardiomyopathy and sudden death in the young: Pathologic evidence of myocardial ischemia. Human Pathology, 31, 988–998.

    CAS  PubMed  Google Scholar 

  6. Basso, C., Thiene, G., Mackey-Bojack, S., Frigo, A. C., Corrado, D., & Maron, B. J. (2009). Myocardial bridging, a frequent component of the hypertrophic cardiomyopathy phenotype, lacks systematic association with sudden cardiac death. European Heart Journal, 30, 1627–1634.

    PubMed  Google Scholar 

  7. Belus, A., Piroddi, N., Scellini, B., Tesi, C., Amati, G. D., Girolami, F., et al. (2008). The familial hypertrophic cardiomyopathy-associated myosin mutation R403Q accelerates tension generation and relaxation of human cardiac myofibrils. Journal of Physiology, 586, 3639–3644.

    CAS  PubMed  Google Scholar 

  8. Biagini, E., Spirito, P., Leone, O., Picchio, F. M., Coccolo, F., Ragni, L., et al. (2008). Heart transplantation in hypertrophic cardiomyopathy. American Journal of Cardiology, 101, 387–392.

    PubMed  Google Scholar 

  9. Blauwet, L. A., Ackerman, M. J., Edwards, W. D., Riehle, D. L., & Ommen, S. R. (2009). Myocardial fibrosis in patients with symptomatic obstructive hypertrophic cardiomyopathy: Correlation with echocardiographic measurements, sarcomeric genotypes, and pro-left ventricular hypertrophy polymorphisms involving the renin-angiotensin-aldosterone system. Cardiovascular Pathology, 18(5), 262–268.

    CAS  PubMed  Google Scholar 

  10. Bos, J. M., Towbin, J. A., & Ackerman, M. J. (2009). Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 54, 201–211.

    CAS  PubMed  Google Scholar 

  11. Cai, C. L., Martin, J. C., Sun, Y., Cui, L., Wang, L., Ouyang, K., et al. (2008). A myocardial lineage derives from Tbx18 epicardial cells. Nature, 454, 104–108.

    CAS  PubMed  Google Scholar 

  12. Camici, P. G., & Crea, F. (2007). Coronary microvascular dysfunction. New England Journal of Medicine, 356, 830–840.

    CAS  PubMed  Google Scholar 

  13. Camici, P. G., Chiriatti, G., Lorenzoni, R., et al. (1991). Coronary vasodilation is impaired in both hypertrophied and nonhypertrophied myocardium of patients with hypertrophic cardiomyopathy: A study with nitrogen-13 ammonia and positron emission tomography. Journal of the American College of Cardiology, 17, 879–886.

    CAS  PubMed  Google Scholar 

  14. Cannon, R. O., Rosing, D. R., Maron, B. J., et al. (1985). Myocardial ischemia in hypertrophic cardiomyopathy: Contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures. Circulation, 71, 234–243.

    PubMed  Google Scholar 

  15. Cecchi, F., Olivotto, I., et al. (2003). Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy. New England Journal of Medicine, 349, 1027–1035.

    CAS  PubMed  Google Scholar 

  16. Cecchi, F., Olivotto, I., Nistri, S., Antoniucci, D., & Yacoub, M. H. (2006). Midventricular obstruction and clinical decision-making in obstructive hypertrophic cardiomyopathy. Herzl, 31, 871–876.

    Google Scholar 

  17. Charron, P., Carrier, L., Dubourg, O., Tesson, F., Desnos, M., Richard, P., et al. (1997). Penetrance of familial hypertrophic cardiomyopathy. Genetic Counseling, 8, 107–114.

    CAS  PubMed  Google Scholar 

  18. Choudhury, L., Guzzetti, S., Lefroy, D. C., Nihoyannopoulos, P., McKenna, W. J., Oakley, C. M., et al. (1996). Myocardial beta adrenoceptors and left ventricular function in hypertrophic cardiomyopathy. Heart, 75, 50–54.

    CAS  PubMed  Google Scholar 

  19. Choudhury, L., Mahrholdt, H., Wagner, A., Choi, K. M., Elliott, M. D., Klocke, F. J., et al. (2002). Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 40, 2156–2164.

    PubMed  Google Scholar 

  20. Corrado, D., Basso, C., Schiavon, M., & Thiene, G. (1998). Screening for hypertrophic cardiomyopathy in young athletes. New England Journal of Medicine, 339, 364–369.

    CAS  PubMed  Google Scholar 

  21. Cortigiani, L., Rigo, F., Gherardi, S., Galderisi, M., Sicari, R., & Picano, E. (2008). Prognostic implications of coronary flow reserve on left anterior descending coronary artery in hypertrophic cardiomyopathy. American Journal of Cardiology, 102, 1718–1723.

    PubMed  Google Scholar 

  22. Dahl, et al. (2008). Nuclear shape, mechanics and mechanotransduction. Circulation Respiratory, 108, 173–189.

    Google Scholar 

  23. Davies, J. K., Wells, D. J., Liu, K., Whitrow, H. R., Daniel, T. D., Grignani, R., et al. (2006). Characterization of the role of gamma2 R531G mutation in AMP-activated protein kinase in cardiac hypertrophy and Wolff-Parkinson-White syndrome. American Journal of Physiology. Heart and Circulatory Physiology, 290, H1942–H1951.

    CAS  PubMed  Google Scholar 

  24. Deb, S. J., Schaff, H. V., Dearani, J. A., et al. (2004). Septal myectomy results in regression of left ventricular hypertrophy in patients with hypertrophic obstructive. Cardiomyopathy Ann Thorac Surg, 78, 2118–2122.

    Google Scholar 

  25. Douglas, P. S. (2003). The left atrium A biomarker of chronic diastolic dysfunction and cardiovascular disease risk. Journal of the American College of Cardiology, 42, 1206–1207.

    PubMed  Google Scholar 

  26. Elliott, P., & McKenna, W. J. (2004). Hypertrophic cardiomyopathy. Lancet, 363, 1881–1891.

    CAS  PubMed  Google Scholar 

  27. Elliott, P. M., Gimeno, B., Jr., Mahon, N. G., Poloniecki, J. D., & McKenna, W. J. (2001). Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet, 357, 420–424.

    CAS  PubMed  Google Scholar 

  28. Eriksson, M. J., Sonnenberg, B., & Woo, A. (2002). Long-term outcome in patients with apical hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 39, 638–645.

    PubMed  Google Scholar 

  29. Fighali, S., Kracjer, Z., Edelman, S., & Leachman, R. D. (1987). Progression of hypertrophic cardiomyopathy into a hypokinetic left ventricle: Higher incidence in patients with midventricular obstruction. Journal of the American College of Cardiology, 9, 288–294.

    Article  CAS  PubMed  Google Scholar 

  30. Foley, P. W., Frenneaux, M. P., & Leyva, F. (2009). Asystole and scarring of the interventricular septum in hypertrophic cardiomyopathy. Journal of Cardiovascular Medicine (Hagerstown), 10, 349–351.

    Google Scholar 

  31. Germans, T., Wilde, A. A., Dijkmans, P. A., et al. (2006). Structural abnormalities of the inferoseptal left ventricular wall detected by cardiac magnetic resonance imaging in carriers of hypertrophic cardiomyopathy mutations. Journal of the American College of Cardiology, 48, 2518–2523.

    PubMed  Google Scholar 

  32. Hagege, A. A., Dubourg, O., Desnos, M., et al. (1998). Familial hypertrophic cardiomyopathy. Cardiac ultrasonic abnormalities in genetically affected subjects without echocardiographic evidence of left ventricular hypertrophy. European Heart Journal, 19, 490–499.

    CAS  PubMed  Google Scholar 

  33. Harrigan, C. J., Appelbaum, E., Maron, B. J., Buros, J. L., Gibson, C. M., Lesser, J. R., et al. (2008). Significance of papillary muscle abnormalities identified by cardiovascular magnetic resonance in hypertrophic cardiomyopathy. American Journal of Cardiology, 101, 668–673.

    PubMed  Google Scholar 

  34. Harris, K. M., Spirito, P., Maron, M. S., Zenovich, A. G., Formisano, F., Lesser, J. R., et al. (2006). Prevalence, clinical profile, and significance of left ventricular remodeling in the end-stage phase of hypertrophic cardiomyopathy. Circulation, 114, 216–225.

    PubMed  Google Scholar 

  35. Ho, C. Y., & Seidman, C. E. (2006). A contemporary approach to hypertrophic cardiomyopathy. Circulation, 113, e858–e862.

    PubMed  Google Scholar 

  36. Ho, C. Y., Sweitzer, N. K., McDonough, B., Maron, B. J., Casey, S. A., Seidman, J. G., et al. (2002). Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation, 105, 2992–2997.

    PubMed  Google Scholar 

  37. Kaple, R. K., Murphy, R. T., DiPaola, L. M., Houghtaling, P. L., Lever, H. M., Lytle, B. W., et al. (2008). Mitral valve abnormalities in hypertrophic cardiomyopathy: Echocardiographic features and surgical outcomes. Annals of Thoracic Surgery, 85, 1527–1535.

    PubMed  Google Scholar 

  38. Kattman, S. J., Adler, E. D., & Keller, G. M. (2007). Specification of multipotential cardiovascular progenitor cells during embryonic stem cell differentiation and embryonic development. Trends in Cardiovascular Medicine, 17, 240–246.

    CAS  PubMed  Google Scholar 

  39. Kawai, C., Yui, Y., Hoshino, T., Sasayama, S., & Matsumori, A. (1983). Myocardial catecholamines in hypertrophic and dilated (congestive) cardiomyopathy: A biopsy study. Journal of the American College of Cardiology, 2, 834–840.

    CAS  PubMed  Google Scholar 

  40. Kitaoka, H., Doi, Y., Casey, S. A., Hitomi, N., Furuno, T., & Maron, B. J. (2003). Comparison of prevalence of apical hypertrophic cardiomyopathy in Japan and the United States. American Journal of Cardiolog, 92, 1183–1186.

    Google Scholar 

  41. Klaassen, S., Probst, S., Oechslin, E., Gerull, B., Krings, G., Schuler, P., et al. (2008). Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation, 117, 2893–2901.

    CAS  PubMed  Google Scholar 

  42. Klues, H. G., Roberts, W. C., & Maron, B. J. (1993). Morphological determinants of echocardiographic patterns of mitral valve systolic anterior motion in obstructive hypertrophic cardiomyopathy. Circulation, 87, 1570–1579.

    CAS  PubMed  Google Scholar 

  43. Klues, H. G., Schiffers, A., & Maron, B. J. (1995). Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients. Journal of the American College of Cardiology, 26, 1699–1708.

    CAS  PubMed  Google Scholar 

  44. Klues, H. G., Maron, B. J., Dollar, A. L., & Roberts, W. C. (1992). Diversity of structural mitral valve alterations in hypertrophic cardiomyopathy. Circulation, 85, 1651–1660.

    CAS  PubMed  Google Scholar 

  45. Klues, H. G., Proschan, M. A., Dollar, A. L., Spirito, P., Roberts, W. C., & Maron, B. J. (1993). Echocardiographic assessment of mitral valve size in obstructive hypertrophic cardiomyopathy Anatomic validation from mitral valve specimen. Circulation, 88, 548–555.

    CAS  PubMed  Google Scholar 

  46. Krams, R., Kofflard, M. J., Duncker, D. J., et al. (1998). Decreased coronary flow reserve in hypertrophic cardiomyopathy is related to remodeling of the coronary microcirculation. Circulation, 97, 230–233.

    CAS  PubMed  Google Scholar 

  47. Lamke, G. T., Allen, R. D., Edwards, W. D., Tazelaar, H. D., & Danielson, G. K. (2003). Surgical pathology of subaortic septal myectomy associated with hypertrophic cardiomyopathy. A study of 204 cases (1996–2000). Cardiovascular Pathology, 12, 149–158.

    PubMed  Google Scholar 

  48. Lewis, J. F., & Maron, B. J. (1989). Elderly patients with hypertrophic cardiomyopathy: A subset with distinctive left ventricular morphology and progressive clinical course late in life. Journal of the American College of Cardiology, 13, 36–45.

    Article  CAS  PubMed  Google Scholar 

  49. Lie-Venema, H., van den Akker, N. M., Bax, N. A., Winter, E. M., Maas, S., Kekarainen, T., et al. (2007). Origin, fate, and function of epicardium-derived cells (EPDCs) in normal and abnormal cardiac development. Scientific World Journal, 7, 1777–1798.

    CAS  PubMed  Google Scholar 

  50. Lombardi, R., Betocchi, S., Losi, M. A., Tocchetti, C. G., Aversa, M., Miranda, M., et al. (2003). Myocardial collagen turnover in hypertrophic cardiomyopathy. Circulation, 108, 1455–1460.

    CAS  PubMed  Google Scholar 

  51. Losi, M. A., Betocchi, S., Aversa, M., Lombardi, R., Miranda, M., D'Alessandro, G., et al. (2004). Determinants of atrial fibrillation development in patients with hypertrophic cardiomyopathy. American Journal of Cardiology, 94, 895–900.

    PubMed  Google Scholar 

  52. Marian, A. J. (2008). Genetic determinants of cardiac hypertrophy. Current Opinion in Cardiology, 23, 199–205.

    PubMed  Google Scholar 

  53. Markwald, R. R., & Butcher, J. T. (2007). The next frontier in cardiovascular developmental biology—An integrated approach to adult disease? Nature Clinical Practice Cardiovascular Medicine, 4, 60–61.

    PubMed  Google Scholar 

  54. Maron, B. J. (2002). Hypertrophic cardiomyopathy: A systematic review. JAMA, 287, 1308–1320.

    PubMed  Google Scholar 

  55. Maron, B. J. (2004). Hypertrophic cardiomyopathy: An important global disease (editorial). American Journal of Medicine, 116, 63–65.

    PubMed  Google Scholar 

  56. Maron, B. J., Nishimura, R. A., & Danielson, G. K. (1998). Pitfalls in clinical recognition and a novel operative approach for hypertrophic cardiomyopathy with severe outflow obstruction due to anomalous papillary muscle. Circulation, 98, 2505–2508.

    CAS  PubMed  Google Scholar 

  57. Maron, B. J., Wolfson, J. K., Epstein, S. E., & Roberts, W. C. (1986). Intramural (“small vessel”) coronary artery disease in hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 8, 545–557.

    Article  CAS  PubMed  Google Scholar 

  58. Maron, B. J., Maron, M. S., Wigle, E. D., & Braunwald, E. (2009). The 50-year history, controversy, and clinical implications of left ventricular outflow tract obstruction in hypertrophic Cardiomyopathy: From idiopathic hypertrophic subaortic stenosis to hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 54, 191–200.

    PubMed  Google Scholar 

  59. Maron, B. J., McIntosh, C. L., Klues, H. G., Cannon, R. O., III, & Roberts, W. C. (1993). Morphologic basis for obstruction to right ventricular outflow in hypertrophic cardiomyopathy. American Journal of Cardiology, 71, 1089–1094.

    CAS  PubMed  Google Scholar 

  60. Maron, B. J., Spirito, P., Shen, W. K., Haas, T. S., Formisano, F., Link, M. S., et al. (2007). Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA, 298, 405–412.

    CAS  PubMed  Google Scholar 

  61. Maron, B. J., McKenna, W. J., Danielson, G. K., et al. (2003). American college of cardiology/European society of cardiology clinical expert consensus document on hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 42, 1687–1713.

    PubMed  Google Scholar 

  62. Maron, M. S., Olivotto, I., Betocchi, S., Casey, S. A., Lesser, J. R., Losi, M. A., et al. (2003). Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. New England Journal of Medicine, 348, 295–303.

    PubMed  Google Scholar 

  63. Maron, M. S., Olivotto, I., Zenovich, A. G., Link, M. S., Pandian, N. G., Kuvin, J. T., et al. (2006). Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation, 114, 2232–2239.

    PubMed  Google Scholar 

  64. Maron, M. S., Hauser, T. H., Dubrow, E., Horst, T. A., Kissinger, K. V., Udelson, J. E., et al. (2007). Right ventricular involvement in hypertrophic cardiomyopathy. American Journal of Cardiology, 100, 1293–1298.

    PubMed  Google Scholar 

  65. Maron, M. S., Appelbaum, E., Harrigan, C. J., Buros, J., Gibson, C. M., Hanna, C., et al. (2008). Clinical profile and significance of delayed enhancement in hypertrophic cardiomyopathy. Circulation Heart Failure, 1, 184–191.

    PubMed  Google Scholar 

  66. Maron, M. S., Maron, B. J., Harrigan, C., Buros, J., Gibson, C. M., Olivotto, I., et al. (2009). Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance. Journal of the American College of Cardiology, 54, 220–228.

    PubMed  Google Scholar 

  67. Maron, M. S., Finley, J. J., Bos, J. M., et al. (2009). Prevalence, clinical significance and natural history of left ventricular apical aneurysms in hypertrophic cardiomyopathy. Circulation, 118, 1541–1549.

    Google Scholar 

  68. Maron, M. S., Olivotto, I., Maron, B. J., Prasad, S. K., Cecchi, F., Udelson, J. E., et al. (2009). The case for myocardial ischemia in hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 54, 866–875.

    PubMed  Google Scholar 

  69. McLeod, C. J., Ackerman, M. J., Nishimura, R. A., Tajik, A. J., Gersh, B. J., & Ommen, S. R. (2009). Outcome of patients with hypertrophic cardiomyopathy and a normal electrocardiogram. Journal of the American College of Cardiology, 54, 229–233.

    PubMed  Google Scholar 

  70. Miller, M. A., Gomes, J. A., & Fuster, V. (2007). Risk stratification of sudden cardiac death in hypertrophic cardiomyopathy. Nature Clinical Practice Cardiovascular Medicine, 4, 667–676.

    PubMed  Google Scholar 

  71. Möhlenkamp, S., Hort, W., Ge, J., & Erbel, R. (2002). Update on myocardial bridging. Circulation, 106, 2616–2622.

    PubMed  Google Scholar 

  72. Monserrat, L., Hermida-Prieto, M., Fernandez, X., Rodríguez, I., Dumont, C., Cazón, L., et al. (2007). Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects. European Heart Journal, 28, 1953–1961.

    CAS  PubMed  Google Scholar 

  73. Moon, J. C., Fisher, N. G., McKenna, W. J., & Pennell, D. J. (2004). Detection of apical hypertrophic cardiomyopathy by cardiovascular magnetic resonance in patients with non-diagnostic echocardiography. Heart, 90, 645–649.

    CAS  PubMed  Google Scholar 

  74. Moon, J. C., McKenna, W. J., McCrohon, J. A., Elliott, P. M., Smith, G. C., & Pennell, D. J. (2003). Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance. Journal of the American College of Cardiology, 41, 1561–1567.

    PubMed  Google Scholar 

  75. Moon, J. C., Reed, E., Sheppard, M. N., Elkington, A. G., Ho, S. Y., Burke, M., et al. (2004). The histologic basis of late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 43, 2260–2264.

    PubMed  Google Scholar 

  76. Moon, J. C., Mogensen, J., Elliott, P. M., et al. (2005). Myocardial late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy caused by mutations in troponin I. Heart, 91, 1036–1040.

    CAS  PubMed  Google Scholar 

  77. Morita, H., Rehm, H. L., Menesses, A., McDonough, B., Roberts, A. E., Kucherlapati, R., et al. (2008). Shared genetic causes of cardiac hypertrophy in children and adults. New England Journal of Medicine, 358, 1899–1908.

    CAS  PubMed  Google Scholar 

  78. Nagueh, S. F., Bachinski, L. L., Meyer, D., Hill, R., Zoghbi, W. A., Tam, J. W., et al. (2001). Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy. Circulation, 104, 128–130.

    CAS  PubMed  Google Scholar 

  79. Niimura, H., Patton, K. K., McKenna, W. J., Soults, J., Maron, B. J., Seidman, J. G., et al. (2002). Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation, 105, 446–451.

    CAS  PubMed  Google Scholar 

  80. Nistri, S., Olivotto, I., Betocchi, S., Losi, M. A., Valsecchi, G., Pinamonti, B., et al. (2006). Prognostic significance of left atrial size in patients with hypertrophic cardiomyopathy (from the Italian Registry for Hypertrophic Cardiomyopathy). American Journal of Cardiology, 98, 960–965.

    PubMed  Google Scholar 

  81. Olivotto, I., & Cecchi, F. (2003). The epidemiologic evolution and present perception of hypertrophic cardiomyopathy. Italian Heart Journal, 4, 596–601.

    PubMed  Google Scholar 

  82. Olivotto, I., Cecchi, F., & Camici, P. G. (2004). Coronary microvascular dysfunction and ischemia in hypertrophic cardiomyopathy. Mechanisms and clinical consequences. Italian Heart Journal, 5, 572–580.

    PubMed  Google Scholar 

  83. Olivotto, I., Maron, B. J., & Cecchi, F. (2004). Pathophysiology and clinical consequences of atrial fibrillation in hypertrophic cardiomyopathy. In B. J. Maron (Ed.), Diagnosis and management of hypertrophic cardiomyopathy (pp. 105–120). Oxford: Futura-Blackwell.

    Google Scholar 

  84. Olivotto, I., Cecchi, F., & Yacoub, M. H. (2009). Myocardial bridging and sudden death in hypertrophic cardiomyopathy: Salome drops another veil. European Heart Journal, 30, 1549–1550.

    PubMed  Google Scholar 

  85. Olivotto, I., Cecchi, F., Poggesi, C., & Yacoub, M. H. (2009). Developmental origins of hypertrophic cardiomyopathy phenotypes: A unifying hypothesis. Nature Review Cardiology, 6, 317–321.

    CAS  Google Scholar 

  86. Olivotto, I., Cecchi, F., Casey, S. A., Dolara, A., Traverse, J. H., & Maron, B. J. (2001). Impact of atrial fibrillation on the clinical course of hypertrophic cardiomyopathy. Circulation, 104, 2517–2524.

    CAS  PubMed  Google Scholar 

  87. Olivotto, I., Gistri, R., Petrone, P., Pedemonte, E., Vargiu, D., & Cecchi, F. (2003). Maximum left ventricular thickness and risk of sudden death in patients with hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 41, 315–321.

    PubMed  Google Scholar 

  88. Olivotto, I., Cecchi, F., Bini, R., Favilli, S., Murzi, B., El-Hamamsy, I., et al. (2009). Tunneled left anterior descending artery in a child with hypertrophic cardiomyopathy. Nat Clin Pract Cardiovasc Med., 6, 134–139.

    PubMed  Google Scholar 

  89. Olivotto, I., Cecchi, F., Gistri, R., Lorenzoni, R., Chiriatti, G., Girolami, F., et al. (2006). Relevance of coronary microvascular flow impairment to long-term remodeling and systolic dysfunction in hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 47, 1043–1048.

    PubMed  Google Scholar 

  90. Olivotto, I., Maron, M. S., Autore, C., Lesser, J. R., Rega, L., Casolo, G., et al. (2008). Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 52, 559–566.

    PubMed  Google Scholar 

  91. Olivotto, I., Girolami, F., Ackerman, M. J., Nistri, S., Bos, J. M., Zachara, E., et al. (2008). Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy. Mayo Clinic Proceedings, 83, 630–638.

    CAS  PubMed  Google Scholar 

  92. Ommen, S. R., Shah, P. M., & Tajik, A. J. (2008). Left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: Past, present and future. Heart, 94, 1276–1281.

    CAS  PubMed  Google Scholar 

  93. Phadke, R. S., Vaideeswar, P., Mittal, B., & Deshpande, J. (2001). Hypertrophic cardiomyopathy: An autopsy analysis of 14 cases. Journal of Postgraduate Medicine, 47, 165–170.

    CAS  PubMed  Google Scholar 

  94. Pinamonti, B., Di Lenarda, A., Nucifora, G., Gregori, D., Perkan, A., & Sinagra, G. (2008). Incremental prognostic value of restrictive filling pattern in hypertrophic cardiomyopathy: A Doppler echocardiographic study. European Journal of Echocardiography, 9, 466–471.

    PubMed  Google Scholar 

  95. Pope, A. J., Sands, G. B., Smaill, B. H., & LeGrice, I. J. (2008). Three-dimensional transmural organization of perimysial collagen in the heart. American Journal of Physiology. Heart and Circulatory Physiology, 295, H1243–H1252.

    CAS  PubMed  Google Scholar 

  96. Richard, P., Charron, P., Carrier, L., Ledeuil, C., Cheav, T., Pichereau, C., et al. (2003). Hypertrophic cardiomyopathy: Distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation, 107, 2227–2232.

    PubMed  Google Scholar 

  97. Rickers, C., Wilke, N. M., Jerosch-Herold, M., et al. (2005). Utility of cardiac magnetic resonance imaging in the diagnosis of hypertrophic cardiomyopathy. Circulation, 112, 855–861.

    PubMed  Google Scholar 

  98. Ryan, M. P., Cleland, J. G., French, J. A., Joshi, J., Choudhury, L., Chojnowska, L., et al. (1995). The standard electrocardiogram as a screening test for hypertrophic cardiomyopathy. American Journal of Cardiology, 76, 689–694.

    CAS  PubMed  Google Scholar 

  99. Schäfers, M., Dutka, D., Rhodes, C. G., Lammertsma, A. A., Hermansen, F., Schober, O., et al. (1998). Myocardial presynaptic and postsynaptic autonomic dysfunction in hypertrophic cardiomyopathy. Circulation Research, 82, 57–62.

    PubMed  Google Scholar 

  100. Schulz-Menger, J., Abdel-Aty, H., Rudolph, A., Elgeti, T., Messroghli, D., Utz, W., et al. (2008). Gender-specific differences in left ventricular remodelling and fibrosis in hypertrophic cardiomyopathy: Insights from cardiovascular magnetic resonance. European Journal of Heart Failure, 10, 850–854.

    PubMed  Google Scholar 

  101. Schwartzkopff, B., Mundhenke, M., & Strauer, B. E. (1998). Alterations of the architecture of subendocardial arterioles in patients with hypertrophic cardiomyopathy and impaired coronary vasodilator reserve: A possible cause for myocardial ischemia. Journal of the American College of Cardiology, 31, 1089–1096.

    CAS  PubMed  Google Scholar 

  102. Sharkey, S. W., Lesser, J. R., Zenovich, A. G., Maron, M. S., Lindberg, J., Longe, T. F., et al. (2005). Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation, 111, 472–479.

    PubMed  Google Scholar 

  103. Sherrid, M. V., Wever-Pinzon, O., Shah, A., & Chaudhry, F. A. (2009). Reflections of inflections in hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 54, 212–219.

    PubMed  Google Scholar 

  104. Sorajja, P., Ommen, S. R., Nishimura, R. A., Gersh, B. J., Tajik, A. J., & Holmes, D. R. (2003). Myocardial bridging in adult patients with hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 42, 889–894.

    PubMed  Google Scholar 

  105. Sotgia, B., Sciagrà, R., Olivotto, I., Casolo, G., Rega, L., Betti, I., et al. (2008). Spatial relationship between coronary microvascular dysfunction and delayed contrast enhancement in patients with hypertrophic cardiomyopathy. Journal of Nuclear Medicine, 49, 1090–1096.

    PubMed  Google Scholar 

  106. Spirito, P., Bellone, P., Harris, K. M., Bernabo, P., Bruzzi, P., & Maron, B. J. (2000). Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. New England Journal of Medicine, 342, 1778–1785.

    CAS  PubMed  Google Scholar 

  107. St John Sutton, M. G., Lie, J. T., Anderson, K. R., O'Brien, P. C., & Frye, R. L. (1980). Histopathological specificity of hypertrophic obstructive cardiomyopathy. Myocardial fibre disarray and myocardial fibrosis. British Heart Journal, 44, 433–443.

    CAS  PubMed  Google Scholar 

  108. Terai, H., Shimizu, M., & Ino, H. (2003). Changes in cardiac sympathetic nerve innervation and activity in pathophysiologic transition from typical to end-stage hypertrophic cardiomyopathy. Journal of Nuclear Medicine, 44, 1612–1617.

    PubMed  Google Scholar 

  109. van Dockum, W. G., Beek, A. M., ten Cate, F. J., et al. (2005). Early onset and progression of left ventricular remodeling after alcohol septal ablation in hypertrophic obstructive cardiomyopathy. Circulation, 111, 2503–2508.

    PubMed  Google Scholar 

  110. Varnava, A. M., Elliott, P. M., Sharma, S., McKenna, W. J., & Davies, M. J. (2000). Hypertrophic cardiomyopathy: The interrelation of disarray, fibrosis, and small vessel disease. Heart, 84, 476–482.

    CAS  PubMed  Google Scholar 

  111. Varnava, A. M., Elliott, P. M., Mahon, N., Davies, M. J., & McKenna, W. J. (2001). Am Relation between myocyte disarray and outcome in hypertrophic cardiomyopathy. Journal of Cardiology, 88, 275–279.

    CAS  Google Scholar 

  112. Yacoub, M. H., Olivotto, I., & Cecchi, F. (2007). ‘End-stage’ hypertrophic cardiomyopathy: From mystery to model. Nature Clinical Practice Cardiovascular Medicine, 4, 232–233.

    PubMed  Google Scholar 

  113. Yacoub, M., Onuzo, O., Riedel, B., & Radley-Smith, R. (1999). Mobilization of the left and right fibrous trigones for relief of severe left ventricular outflow obstruction. Journal of Thoracic and Cardiovascular Surgery, 117, 126–132.

    CAS  PubMed  Google Scholar 

  114. Yamaguchi, H., Ishimura, T., & Nishiyama, S. (1979). Hypertrophic non-obstructive cardiomyopathy with giant negative T-waves (apical hypertrophy): Ventriculographic and echocardiographic features in 30 patients. American Journal of Cardiology, 44, 404–412.

    Google Scholar 

  115. Yetman, A. T., McCrindle, B. W., MacDonald, C., Freedom, R. M., & Gow, R. (1998). Myocardial bridging in children with hypertrophic cardiomyopathy—A risk factor for sudden death. New England Journal of Medicine, 339, 1201–1209.

    CAS  PubMed  Google Scholar 

  116. Yu, E. H. C., Omran, A. S., Wigle, E. D., Williams, W. G., Siu, S. C., & Rakowski, H. (2000). Mitral regurgitation in hypertrophic obstructive cardiomyopathy: Relationship to obstruction and relief with myectomy. Journal of the American College of Cardiology, 36, 2219–2225.

    CAS  PubMed  Google Scholar 

  117. Zhou, B., Ma, Q., Rajagopal, S., Wu, S. M., Domian, I., Rivera-Feliciano, J., et al. (2008). Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature, 454, 109–113.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, Careggi University Hospital, Florence, Italy

    Iacopo Olivotto, Francesca Girolami, Stefano Nistri, Alessandra Rossi, Francesca Garbini, Camilla Grifoni & Franco Cecchi

  2. Department of Genetic Diagnosis and Pathology, Careggi University Hospital, Florence, Italy

    Francesca Girolami & Francesca Garbini

  3. Department of Radiology, Careggi University Hospital, Florence, Italy

    Luigi Rega

  4. Heart Science Center, Imperial College London, Harefield, UK

    Magdi H. Yacoub

  5. Cardiologia San Luca, Azienda Ospedaliera Universitaria Careggi, Viale Pieraccini 17, 50132, Florence, Italy

    Iacopo Olivotto

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  1. Iacopo Olivotto
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Olivotto, I., Girolami, F., Nistri, S. et al. The Many Faces of Hypertrophic Cardiomyopathy: From Developmental Biology to Clinical Practice. J. of Cardiovasc. Trans. Res. 2, 349–367 (2009). https://doi.org/10.1007/s12265-009-9137-2

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