https://doi.org/10.4081/monaldi.2021.2147
A complex unit for a complex disease: the HCM-Family Unit
Submitted: November 14, 2021
Accepted: November 30, 2021
Published: December 29, 2021
Accepted: November 30, 2021
Abstract Views: 1599
PDF: 514
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Hypertrophic cardiomyopathy (HCM) is a group of heterogeneous disorders that are most commonly passed on in a heritable manner. It is a relatively rare disease around the globe, but due to increased rates of consanguinity within the Kingdom of Saudi Arabia, we speculate a high incidence of undiagnosed cases. The aim of this paper is to elucidate a systematic approach in dealing with HCM patients and since HCM has variable presentation, we have summarized differentials for diagnosis and how different subtypes and genes can have an impact on the clinical picture, management and prognosis. Moreover, we propose a referral multi-disciplinary team HCM-Family Unit in Saudi Arabia and an integrated role in a network between King Faisal Hospital and Inherited and Rare Cardiovascular Disease Unit-Monaldi Hospital, Italy (among the 24 excellence centers of the European Reference Network (ERN) GUARD-Heart).
Graphical Abstract
Teekakirikul P, Padera RF, Seidman JG, Seidman CE. Hypertrophic cardiomyopathy: translating cellular cross talk into therapeutics. J Cell Biol 2012;199:417–21.
DOI: https://doi.org/10.1083/jcb.201207033
Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC Guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: Executive Summary: A report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. Circulation 2020;142:e533–57.
DOI: https://doi.org/10.1161/CIR.0000000000000945
Maron BJ, Gardin JM, Flack JM, et al. Prevalence of hypertrophic cardiomyopathy in a general population of young adults: Echocardiographic analysis of 4111 subjects in the CARDIA study. Circulation 1995;92:785–9.
DOI: https://doi.org/10.1161/01.CIR.92.4.785
Semsarian C, Ingles J, Maron MS, Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol 2015;65:1249–54.
DOI: https://doi.org/10.1016/j.jacc.2015.01.019
Maron BJ, Rowin EJ, Maron MS. Global burden of hypertrophic cardiomyopathy. JACC Heart Fail 2018;6:376–8.
DOI: https://doi.org/10.1016/j.jchf.2018.03.004
Ahmed W, Akhtar N, Bech-Hanssen O, et al. Hypertrophic cardiomyopathy in the Saudi Arabian population: Clinical and echocardiographic characteristics and outcome analysis. J Saudi Heart Assoc 2014;26:7–13.
DOI: https://doi.org/10.1016/j.jsha.2013.08.003
Authors/Task Force members, Elliott PM, Anastasakis A, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014;35:2733–79.
DOI: https://doi.org/10.1093/eurheartj/ehu284
Ingles J, Burns C, Bagnall RD, et al. Nonfamilial hypertrophic cardiomyopathy. Circ Cardiovasc Genet 2017;10:e001620.
DOI: https://doi.org/10.1161/CIRCGENETICS.116.001620
Verdecchia P, Carini G, Circo A, et al. Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study. J Am Coll Cardiol 2001;38:1829–35.
DOI: https://doi.org/10.1016/S0735-1097(01)01663-1
Koren MJ, Devereux RB, Casale PN, et al. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 1991;114:345–52.
DOI: https://doi.org/10.7326/0003-4819-114-5-345
Casale PN, Devereux RB, Milner M, et al. Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med 1986;105:173–8.
DOI: https://doi.org/10.7326/0003-4819-105-2-173
Pelliccia F, Alfieri O, Calabrò P, et al. Multidisciplinary evaluation and management of obstructive hypertrophic cardiomyopathy in 2020: Towards the HCM Heart Team. Int J Cardiol 2020;304:86–92.
DOI: https://doi.org/10.1016/j.ijcard.2020.01.021
Marston NA, Han L, Olivotto I, et al. Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy. Eur Heart J 2021;42:1988–96.
DOI: https://doi.org/10.1093/eurheartj/ehab148
Monda E, Rubino M, Lioncino M, et al. Hypertrophic cardiomyopathy in children: pathophysiology, diagnosis, and treatment of non-sarcomeric causes. Front Pediatr 2021;9:632293.
DOI: https://doi.org/10.3389/fped.2021.632293
Barriales-Villa R, Gimeno-Blanes JR, Zorio-Grima E, et al. Plan of action for inherited cardiovascular diseases: Synthesis of recommendations and action algorithms. Rev Esp Cardiol (Engl Ed) 2016;69:300–9.
DOI: https://doi.org/10.1016/j.rec.2015.11.029
Biagini E, Spirito P, Rocchi G, et al. Prognostic implications of the Doppler restrictive filling pattern in hypertrophic cardiomyopathy. Am J Cardiol 2009;104:1727–31.
DOI: https://doi.org/10.1016/j.amjcard.2009.07.057
Sen-Chowdhry S, Jacoby D, Moon JC, McKenna WJ. Update on hypertrophic cardiomyopathy and a guide to the guidelines. Nat Rev Cardiol 2016;13:651–75.
DOI: https://doi.org/10.1038/nrcardio.2016.140
Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation 2006;114:2232-9.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.106.644682
Yang K, Song Y-Y, Chen X-Y, et al. Apical hypertrophic cardiomyopathy with left ventricular apical aneurysm: prevalence, cardiac magnetic resonance characteristics, and prognosis. Eur Heart J Cardiovasc Imaging 2020;21:1341–50.
DOI: https://doi.org/10.1093/ehjci/jeaa246
Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic cardiomyopathy with left ventricular apical aneurysm: Implications for risk stratification and management. J Am Coll Cardiol 2017;69:761-73.
DOI: https://doi.org/10.1016/j.jacc.2016.11.063
Basso C, Thiene G, Mackey-Bojack S, et al. Myocardial bridging, a frequent component of the hypertrophic cardiomyopathy phenotype, lacks systematic association with sudden cardiac death. Eur Heart J 2009;30:1627-34.
DOI: https://doi.org/10.1093/eurheartj/ehp121
Abuarqoub A, Naranjo M, Shamoon F. Myocardial bridging with left ventricular hypertrophy presenting as Wellens pattern. Ann Transl Med 2017;5:401.
DOI: https://doi.org/10.21037/atm.2017.07.25
Díez-López C, Salazar-Mendiguchía J. Clinical presentations of hypertrophic cardiomyopathy and implications for therapy. Glob Cardiol Sci Pract 2018;2018:19.
DOI: https://doi.org/10.21542/gcsp.2018.19
Olivotto I, Girolami F, Sciagr R, et al. Microvascular function is selectively impaired in patients with hypertrophic cardiomyopathy and sarcomere myofilament gene mutations. J Am Coll Cardiol 2011;58:839–48.
DOI: https://doi.org/10.1016/j.jacc.2011.05.018
Schulze-Bahr E, Klaassen S, Abdul-Khaliq H, Schunkert H. [Molecular diagnosis for cardiovascular diseases].[Article in German]. Dtsch Med Wochenschr 2015;140:1538.
DOI: https://doi.org/10.1055/s-0041-106132
McLeod CJ, Ackerman MJ, Nishimura RA, et al. Outcome of patients with hypertrophic cardiomyopathy and a normal electrocardiogram. J Am Coll Cardiol 2009;54:229–33.
DOI: https://doi.org/10.1016/j.jacc.2009.02.071
Finocchiaro G, Sheikh N, Biagini E, et al. The electrocardiogram in the diagnosis and management of patients with hypertrophic cardiomyopathy. Hear Rhythm 2020;17:142–51.
DOI: https://doi.org/10.1016/j.hrthm.2019.07.019
Maron BJ, Ackerman MJ, Nishimura RA, et al. Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol 2005;45:1340–5.
DOI: https://doi.org/10.1016/j.jacc.2005.02.011
Patten M, Pecha S, Aydin A. Atrial fibrillation in hypertrophic cardiomyopathy: Diagnosis and considerations for management. J Atr Fibrillation 2018;10:1556.
DOI: https://doi.org/10.4022/jafib.1556
Maron MS, Rowin EJ, Maron BJ. How to image hypertrophic cardiomyopathy. Circ Cardiovasc Imaging 2017;10:e005372.
DOI: https://doi.org/10.1161/CIRCIMAGING.116.005372
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;26:1699–708.
DOI: https://doi.org/10.1016/0735-1097(95)00390-8
Haland TF, Edvardsen T. The role of echocardiography in management of hypertrophic cardiomyopathy. J Echocardiogr 2020;18:77–85.
DOI: https://doi.org/10.1007/s12574-019-00454-9
Schroeder S, Achenbach S, Bengel F, et al. Cardiac computed tomography: indications, applications, limitations, and training requirements: report of a Writing Group deployed by the Working Group Nuclear Cardiology and Cardiac CT of the European Society of Cardiology and the European Council of Nuc. Eur Heart J 2008;29:531–56.
DOI: https://doi.org/10.1093/eurheartj/ehm544
Alegria JR, Herrmann J, Holmes DR, et al. Myocardial bridging. Eur Heart J 2005;26:1159–68.
DOI: https://doi.org/10.1093/eurheartj/ehi203
Maron BJ, Doerer JJ, Haas TS, et al.Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006. Circulation 2009;119:1085–92.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.108.804617
Lairez O. [Hypertrophic cardiomyopathies].[Article in French]. Rev Med Interne 2019;40:380-8.
DOI: https://doi.org/10.1016/j.revmed.2019.01.001
Mogensen J, Kubo T, Duque M, et al. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J Clin Invest 2003;111:209–16.
DOI: https://doi.org/10.1172/JCI200316336
Olivotto I, Cecchi F, Poggesi C, Yacoub MH. Patterns of disease progression in hypertrophic cardiomyopathy: an individualized approach to clinical staging. Circ Heart Fail 2012;5:535–46.
DOI: https://doi.org/10.1161/CIRCHEARTFAILURE.112.967026
Kubo T, Gimeno JR, Bahl A, et al. Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype. J Am Coll Cardiol 2007;49:2419–26.
DOI: https://doi.org/10.1016/j.jacc.2007.02.061
De Bortoli M, Vio R, Basso C, et al. Novel missense variant in MYL2 gene associated with hypertrophic cardiomyopathy showing high incidence of restrictive physiology. Circ Genomic Precis Med 2020;13:e002824.
DOI: https://doi.org/10.1161/CIRCGEN.119.002824
Rapezzi C, Arbustini E, Caforio ALP, et al. Diagnostic work-up in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013;34:1448–58.
DOI: https://doi.org/10.1093/eurheartj/ehs397
Charron P, Arad M, Arbustini E, et al. Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2010;31:2715–26.
DOI: https://doi.org/10.1093/eurheartj/ehq271
Teekakirikul P, Kelly MA, Rehm HL, et al. Inherited cardiomyopathies: molecular genetics and clinical genetic testing in the postgenomic era. J Mol Diagn 2013;15:158–70.
DOI: https://doi.org/10.1016/j.jmoldx.2012.09.002
Teekakirikul P, Zhu W, Huang HC, Fung E. Hypertrophic cardiomyopathy: An overview of genetics and management. Biomolecules 2019;9:878.
DOI: https://doi.org/10.3390/biom9120878
Richard P, Charron P, Carrier L, et al. Hypertrophic cardiomyopathy: Distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation 2003;107:2227–32.
DOI: https://doi.org/10.1161/01.CIR.0000066323.15244.54
Walsh R, Thomson KL, Ware JS, et al. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med 2017;19:192–203.
DOI: https://doi.org/10.1038/gim.2016.90
Shinwari ZMA, Almesned A, Alakhfash A, et al. The phenotype and outcome of infantile cardiomyopathy caused by a homozygous ELAC2 mutation. Cardiology 2017;137:188-92.
DOI: https://doi.org/10.1159/000465516
Charron P, Dubourg O, Desnos M, et al. Clinical features and prognostic implications of familial hypertrophic cardiomyopathy related to the cardiac myosin-binding protein C gene. Circulation 1998;97:2230–6.
DOI: https://doi.org/10.1161/01.CIR.97.22.2230
Fiorillo C, Astrea G, Savarese M, et al. MYH7-related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients. Orphanet J Rare Dis 2016;11:91.
DOI: https://doi.org/10.1186/s13023-016-0476-1
Watkins H, Rosenzweig A, Hwang DS, et al. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med 1992;326:1108–14.
DOI: https://doi.org/10.1056/NEJM199204233261703
Pasquale F, Syrris P, Kaski JP, et al. Long-term outcomes in hypertrophic cardiomyopathy caused by mutations in the cardiac troponin T gene. Circ Cardiovasc Genet 2012;5:10–7.
DOI: https://doi.org/10.1161/CIRCGENETICS.111.959973
van den Wijngaard A, Volders P, Van Tintelen JP, et al. Recurrent and founder mutations in the Netherlands: cardiac Troponin I (TNNI3) gene mutations as a cause of severe forms of hypertrophic and restrictive cardiomyopathy. Neth Heart J 2011;19:344–51.
DOI: https://doi.org/10.1007/s12471-011-0135-z
Coppini R, Ho CY, Ashley E, et al. Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations. J Am Coll Cardiol 2014;64:2589–600.
DOI: https://doi.org/10.1016/j.jacc.2014.09.059
Karibe A, Tobacman LS, Strand J, et al. Hypertrophic cardiomyopathy caused by a novel alpha-tropomyosin mutation (V95A) is associated with mild cardiac phenotype, abnormal calcium binding to troponin, abnormal myosin cycling, and poor prognosis. Circulation 2001;103:65–71.
DOI: https://doi.org/10.1161/01.CIR.103.1.65
Flavigny J, Richard P, Isnard R, C et al. Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy. J Mol Med (Berl) 1998;76:208-14.
DOI: https://doi.org/10.1007/s001090050210
Andersen PS, Havndrup O, Bundgaard H, et al. Myosin light chain mutations in familial hypertrophic cardiomyopathy: phenotypic presentation and frequency in Danish and South African populations. J Med Genet 2001;38:E43.
DOI: https://doi.org/10.1136/jmg.38.12.e43
Yadav S, Sitbon YH, Kazmierczak K, Szczesna-Cordary D. Hereditary heart disease: pathophysiology, clinical presentation, and animal models of HCM, RCM, and DCM associated with mutations in cardiac myosin light chains. Pflugers Arch 2019;471:683–99.
DOI: https://doi.org/10.1007/s00424-019-02257-4
Gurr MI. Lipid metabolism in man. Proc Nutr Soc 1988;47:277–85.
DOI: https://doi.org/10.1079/PNS19880045
Matsson H, Eason J, Bookwalter CS, et al. Alpha-cardiac actin mutations produce atrial septal defects. Hum Mol Genet 2008;17:256–65.
DOI: https://doi.org/10.1093/hmg/ddm302
Cicerchia M, Ochoa J, Cardenas-Reyes I, et al. Genotype/phenotype correlation and prognosis for undescribed ACTC1 missense variants. Eur Heart J 2020;41:ehaa946.2075.
DOI: https://doi.org/10.1093/ehjci/ehaa946.2075
Zhang C, Zhang H, Wu G, et al. Titin-truncating variants increase the risk of cardiovascular death in patients with hypertrophic cardiomyopathy. Can J Cardiol 2017;33:1292–7.
DOI: https://doi.org/10.1016/j.cjca.2017.05.020
Chiu C, Bagnall RD, Ingles J, et al. Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-wide analysis. J Am Coll Cardiol 2010;55:1127–35.
DOI: https://doi.org/10.1016/j.jacc.2009.11.016
Girolami F, Iascone M, Tomberli B, et al. Novel α-actinin 2 variant associated with familial hypertrophic cardiomyopathy and juvenile atrial arrhythmias: a massively parallel sequencing study. Circ Cardiovasc Genet 2014;7:741-50.
DOI: https://doi.org/10.1161/CIRCGENETICS.113.000486
Niimura H, Patton KK, McKenna WJ, et al. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation 2002;105:446–51.
DOI: https://doi.org/10.1161/hc0402.102990
Ching Y-H, Ghosh TK, Cross SJ, et al. Mutation in myosin heavy chain 6 causes atrial septal defect. Nat Genet 2005;37:423–8.
DOI: https://doi.org/10.1038/ng1526
Carniel E, Taylor MRG, Sinagra G, et al. Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy. Circulation 2005;112:54–9.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.104.507699
Ishikawa T, Jou CJ, Nogami A, et al. Novel mutation in the α-myosin heavy chain gene is associated with sick sinus syndrome. Circ Arrhythm Electrophysiol 2015;8:400–8.
DOI: https://doi.org/10.1161/CIRCEP.114.002534
Geier C, Gehmlich K, Ehler E, et al. Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy. Hum Mol Genet 2008;17:2753–65.
DOI: https://doi.org/10.1093/hmg/ddn160
Salazar-Mendiguchía J, Barriales-Villa R, Lopes LR, et al. The p.(Cys150Tyr) variant in CSRP3 is associated with late-onset hypertrophic cardiomyopathy in heterozygous individuals. Eur J Med Genet 2020;63:104079.
DOI: https://doi.org/10.1016/j.ejmg.2020.104079
Bos JM, Poley RN, Ny M, et al. Genotype-phenotype relationships involving hypertrophic cardiomyopathy-associated mutations in titin, muscle LIM protein, and telethonin. Mol Genet Metab 2006;88:78–85.
DOI: https://doi.org/10.1016/j.ymgme.2005.10.008
Cirino AL, Ho C. Hypertrophic cardiomyopathy overview. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle: University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1768/
Jhang WK, Choi J-H, Lee BH, et al. Cardiac Manifestations and associations with gene mutations in patients diagnosed with RASopathies. Pediatr Cardiol 2016;37:1539–47.
DOI: https://doi.org/10.1007/s00246-016-1468-6
Digilio MC, Conti E, Sarkozy A, et al. Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene. Am J Hum Genet 2002;71:389–94.
DOI: https://doi.org/10.1086/341528
Caiazza M, Rubino M, Monda E, et al. Combined PTPN11 and MYBPC3 gene mutations in an adult patient with Noonan syndrome and hypertrophic cardiomyopathy. Genes (Basel) 2020;11:947.
DOI: https://doi.org/10.3390/genes11080947
Aoki Y, Niihori T, Kawame H, et al. Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nat Genet 2005;37:1038–40.
DOI: https://doi.org/10.1038/ng1641
Pandit B, Sarkozy A, Pennacchio LA, et al. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet 2007;39:1007–12.
DOI: https://doi.org/10.1038/ng2073
Tartaglia M, Pennacchio LA, Zhao C, et al. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet 2007;39:75–9.
DOI: https://doi.org/10.1038/ng1939
Roberts AE, Araki T, Swanson KD, et al. Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet 2007;39:70–4.
DOI: https://doi.org/10.1038/ng1926
Rodriguez-Viciana P, Tetsu O, Tidyman WE, et al. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science 2006;311:1287–90.
DOI: https://doi.org/10.1126/science.1124642
Niihori T, Aoki Y, Narumi Y, et al. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet 2006;38:294–6.
DOI: https://doi.org/10.1038/ng1749
Legius E, Schrander-Stumpel C, Schollen E, et al. PTPN11 mutations in LEOPARD syndrome. J Med Genet 2002;39:571–4.
DOI: https://doi.org/10.1136/jmg.39.8.571
Martiniuk F, Mehler M, Pellicer A, et al. Isolation of a cDNA for human acid alpha-glucosidase and detection of genetic heterogeneity for mRNA in three alpha-glucosidase-deficient patients. Proc Natl Acad Sci USA 1986;83:9641–4.
DOI: https://doi.org/10.1073/pnas.83.24.9641
Van der Ploeg AT, Hoefsloot LH, Hoogeveen-Westerveld M, et al. Glycogenosis type II: protein and DNA analysis in five South African families from various ethnic origins. Am J Hum Genet 1989;44:787–93.
Bernstein HS, Bishop DF, Astrin KH, et al. Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene. J Clin Invest 1989;83:1390–9.
DOI: https://doi.org/10.1172/JCI114027
Davies JP, Winchester BG, Malcolm S. Mutation analysis in patients with the typical form of Anderson-Fabry disease. Hum Mol Genet 1993;2:1051–3.
DOI: https://doi.org/10.1093/hmg/2.7.1051
Eng CM, Desnick RJ. Molecular basis of Fabry disease: mutations and polymorphisms in the human alpha-galactosidase A gene. Hum Mutat 1994;3:103–11.
DOI: https://doi.org/10.1002/humu.1380030204
Arad M, Maron BJ, Gorham JM, et al. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N Engl J Med 2005;352:362–72.
DOI: https://doi.org/10.1056/NEJMoa033349
Charron P, Villard E, Sébillon P, et al. Danon’s disease as a cause of hypertrophic cardiomyopathy: a systematic survey. Heart 2004;90:842–6.
DOI: https://doi.org/10.1136/hrt.2003.029504
Benson MD. Inherited amyloidosis. J Med Genet 1991;28:73–8.
DOI: https://doi.org/10.1136/jmg.28.2.73
Saraiva MJ. Transthyretin mutations in health and disease. Hum Mutat 1995;5:191–6.
DOI: https://doi.org/10.1002/humu.1380050302
Saraiva MJ. Transthyretin mutations in hyperthyroxinemia and amyloid diseases. Hum Mutat 2001;17:493–503.
DOI: https://doi.org/10.1002/humu.1132
Lachmann HJ, Booth DR, Booth SE, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med 2002;346:1786–91.
DOI: https://doi.org/10.1056/NEJMoa013354
Blair E, Price SJ, Baty CJ, et al. Mutations in cis can confound genotype-phenotype correlations in hypertrophic cardiomyopathy. J Med Genet 2001;38:385–8.
DOI: https://doi.org/10.1136/jmg.38.6.385
Maron BJ, Maron MS, Semsarian C. Double or compound sarcomere mutations in hypertrophic cardiomyopathy: a potential link to sudden death in the absence of conventional risk factors. Heart Rhythm 2012;9:57–63.
DOI: https://doi.org/10.1016/j.hrthm.2011.08.009
Girolami F, Ho CY, Semsarian C, et al. Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations. J Am Coll Cardiol 2010;55:1444–53.
DOI: https://doi.org/10.1016/j.jacc.2009.11.062
European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart [Internet]. Target Groups. 2021. Accessed: 10 October 2021. Available from: https://guardheart.ern-net.eu/ern-guard-heart/target-groups/
Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med 2003;349:583–96.
DOI: https://doi.org/10.1056/NEJMra023144
Tanaka H. Efficacy of echocardiography for differential diagnosis of left ventricular hypertrophy: special focus on speckle-tracking longitudinal strain. J Echocardiogr 2021;19:71-9.
DOI: https://doi.org/10.1007/s12574-020-00508-3
Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2020;396:759–69.
DOI: https://doi.org/10.1016/S0140-6736(20)31792-X
Nguyen A, Schaff H V. Surgical myectomy: Subaortic, midventricular, and apical. Cardiol Clin 2019;37:95–104.
DOI: https://doi.org/10.1016/j.ccl.2018.08.006
Said SM, Schaff HV, Abel MD, Dearani JA. Transapical approach for apical myectomy and relief of midventricular obstruction in hypertrophic cardiomyopathy. J Card Surg 2012;27:443–8.
DOI: https://doi.org/10.1111/j.1540-8191.2012.01475.x
Maron BJ, Spirito P, Shen W-K, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 2007;298:405–12.
DOI: https://doi.org/10.1001/jama.298.4.405
Maron BJ, Spirito P, Ackerman MJ, et al. Prevention of sudden cardiac death with implantable cardioverter-defibrillators in children and adolescents with hypertrophic cardiomyopathy. J Am Coll Cardiol 2013;61:1527–35.
DOI: https://doi.org/10.1016/j.jacc.2013.01.037
Monda E, Lioncino M, Pacileo R, et al. Advanced heart failure in special population—Pediatric age. Heart Fail Clin 2021;17:673–83.
DOI: https://doi.org/10.1016/j.hfc.2021.05.011
Adelman AG, Shah PM, Gramiak R, Wigle ED. Long-term propranolol therapy in muscular subaortic stenosis. Br Heart J 1970;32:804–11.
DOI: https://doi.org/10.1136/hrt.32.6.804
Stenson RE, Flamm MD, Harrison DC, Hancock EW. Hypertrophic subaortic stenosis. Clinical and hemodynamic effects of long-term propranolol therapy. Am J Cardiol 1973;31:763–73.
DOI: https://doi.org/10.1016/0002-9149(73)90012-X
Flamm MD, Harrison DC, Hancock EW. Muscular subaortic stenosis. Prevention of outflow obstruction with propranolol. Circulation 1968;38:846–58.
DOI: https://doi.org/10.1161/01.CIR.38.5.846
Sherrid MV, Barac I, McKenna WJ, et al. Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005;45:1251–8.
DOI: https://doi.org/10.1016/j.jacc.2005.01.012
Sherrid MV, Shetty A, Winson G, et al. Treatment of obstructive hypertrophic cardiomyopathy symptoms and gradient resistant to first-line therapy with β-blockade or verapamil. Circ Heart Fail 2013;6:694–702.
DOI: https://doi.org/10.1161/CIRCHEARTFAILURE.112.000122
Rosing DR, Kent KM, Borer JS, et al. Verapamil therapy: a new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. I. Hemodynamic effects. Circulation 1979;60:1201–7.
DOI: https://doi.org/10.1161/01.CIR.60.6.1201
Bonow RO, Rosing DR, Epstein SE. The acute and chronic effects of verapamil on left ventricular function in patients with hypertrophic cardiomyopathy. Eur Heart J 1983;4:S57–65.
DOI: https://doi.org/10.1093/eurheartj/4.suppl_F.57
Spicer RL, Rocchini AP, Crowley DC, et al. Hemodynamic effects of verapamil in children and adolescents with hypertrophic cardiomyopathy. Circulation 1983;67:413–20.
DOI: https://doi.org/10.1161/01.CIR.67.2.413
Rosing DR, Idänpään-Heikkilä U, Maron BJ, Bonow RO, Epstein SE. Use of calcium-channel blocking drugs in hypertrophic cardiomyopathy. Am J Cardiol 1985;55:185B-95.
DOI: https://doi.org/10.1016/0002-9149(85)90630-7
Epstein SE, Rosing DR. Verapamil: its potential for causing serious complications in patients with hypertrophic cardiomyopathy. Circulation 1981;64:437–41.
DOI: https://doi.org/10.1161/01.CIR.64.3.437
Robbins RC, Stinson EB. Long-term results of left ventricular myotomy and myectomy for obstructive hypertrophic cardiomyopathy. J Thorac Cardiovasc Surg 1996;111:586–94.
DOI: https://doi.org/10.1016/S0022-5223(96)70310-0
Schönbeck MH, Brunner-La Rocca HP, Vogt PR, et al. Long-term follow-up in hypertrophic obstructive cardiomyopathy after septal myectomy. Ann Thorac Surg 1998;65:1207–14.
DOI: https://doi.org/10.1016/S0003-4975(98)00187-8
Desai MY, Bhonsale A, Smedira NG, et al. Predictors of long-term outcomes in symptomatic hypertrophic obstructive cardiomyopathy patients undergoing surgical relief of left ventricular outflow tract obstruction. Circulation 2013;128:209–16.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.112.000849
Faber L, Welge D, Fassbender D, et al. One-year follow-up of percutaneous septal ablation for symptomatic hypertrophic obstructive cardiomyopathy in 312 patients: predictors of hemodynamic and clinical response. Clin Res Cardiol 2007;96:864–73.
DOI: https://doi.org/10.1007/s00392-007-0578-9
Sorajja P, Valeti U, Nishimura RA, et al. Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation 2008;118:131–9.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.107.738740
Maron BJ, Nishimura RA, McKenna WJ, et al. Assessment of permanent dual-chamber pacing as a treatment for drug-refractory symptomatic patients with obstructive hypertrophic cardiomyopathy. A randomized, double-blind, crossover study (M-PATHY). Circulation 1999;99:2927–33.
DOI: https://doi.org/10.1161/01.CIR.99.22.2927
Mickelsen S, Bathina M, Hsu P, et al. Doppler evaluation of the descending aorta in patients with hypertrophic cardiomyopathy: potential for assessing the functional significance of outflow tract gradients and for optimizing pacemaker function. J Interv Card Electrophysiol 2004;11:47–53.
DOI: https://doi.org/10.1023/B:JICE.0000035929.84238.2f
Glikson M, Gurevitz O, Yaacobi E, et al. Multiple adverse events with a dual chamber pacemaker. Pacing Clin Electrophysiol 2000;23:1010–3.
DOI: https://doi.org/10.1111/j.1540-8159.2000.tb00889.x
Thomas F, Rader F, Siegel RJ. The use of MitraClip for symptomatic patients with hypertrophic obstructive cardiomyopathy. Cardiology 137:58–61.
DOI: https://doi.org/10.1159/000454800
Long A, Mahoney P. Use of MitraClip to target obstructive SAM in severe diffuse-type hypertrophic cardiomyopathy: Case report and review of literature. J Invasive Cardiol 2020;32:E228–32.
Rowin EJ, Maron BJ, Abt P, et al. Impact of advanced therapies for improving survival to heart transplant in patients with hypertrophic cardiomyopathy. Am J Cardiol 2018;121:986–96.
DOI: https://doi.org/10.1016/j.amjcard.2017.12.044
Maron BJ, Rowin EJ, Casey SA, et al. Hypertrophic cardiomyopathy in adulthood associated with low cardiovascular mortality with contemporary management strategies. J Am Coll Cardiol 2015;65:1915–28.
DOI: https://doi.org/10.1016/j.jacc.2015.02.061
Syed IS, Ommen SR, Breen JF, Tajik AJ. Hypertrophic cardiomyopathy: identification of morphological subtypes by echocardiography and cardiac magnetic resonance imaging. JACC Cardiovasc Imaging 2008;1:377–9.
DOI: https://doi.org/10.1016/j.jcmg.2008.02.008
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;81:459–67.
DOI: https://doi.org/10.4065/81.4.459
Gardin JM, Palabrica T, Dubria S, et al. Localized basal ventricular septal hypertrophy: Prevalence, functional and clinical correlates in a population referred for echocardiography. Am J Noninvasive Cardiol 1992;6:5–8.
DOI: https://doi.org/10.1159/000470319
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;28:1–83.
DOI: https://doi.org/10.1016/0033-0620(85)90024-6
Rajtar-Salwa R, Tokarek T, Dimitrow PP. Reversed septal curvature is associated with elevated troponin level in hypertrophic cardiomyopathy. Dis Markers 2020;2020:8821961.
DOI: https://doi.org/10.1155/2020/8821961
Sakamoto T, Tei C, Murayama M, et al. Giant T wave inversion as a manifestation of asymmetrical apical hypertrophy (AAH) of the left ventricle. Echocardiographic and ultrasono-cardiotomographic study. Jpn Heart J 1976;17:611–29.
DOI: https://doi.org/10.1536/ihj.17.611
Eriksson MJ, Sonnenberg B, Woo A, et al. Long-term outcome in patients with apical hypertrophic cardiomyopathy. J Am Coll Cardiol 2002;39:638–45.
DOI: https://doi.org/10.1016/S0735-1097(01)01778-8
Towe EC, Bos JM, Ommen SR, Gersh BJ, Ackerman MJ. Genotype-phenotype correlations in apical variant hypertrophic cardiomyopathy. Congenit Heart Dis 10:E139-45.
DOI: https://doi.org/10.1111/chd.12242
Cooke JC, Cotton JM, Monaghan MJ. Mid-ventricular HOCM with apical asynergy. Heart 2000;83:517.
DOI: https://doi.org/10.1136/heart.83.5.517
Minami Y, Kajimoto K, Terajima Y, et al. Clinical implications of midventricular obstruction in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2011;57:2346–55.
DOI: https://doi.org/10.1016/j.jacc.2011.02.033
Inagaki N, Hayashi T, Takei Y, et al. Clinical and genetic backgrounds of hypertrophic cardiomyopathy with mid-ventricular obstruction. J Hum Genet 2018;63:1273–6.
DOI: https://doi.org/10.1038/s10038-018-0509-9
Baxi AJ, Restrepo CS, Vargas D, et al. Hypertrophic cardiomyopathy from A to Z: Genetics, pathophysiology, imaging, and management. Radiographics 2016;36:335–54.
DOI: https://doi.org/10.1148/rg.2016150137
Hughes SE. The pathology of hypertrophic cardiomyopathy. Histopathology 2004;44:412–27.
DOI: https://doi.org/10.1111/j.1365-2559.2004.01835.x
Kansal S, Roitman D, Sheffield LT. Interventricular septal thickness and left ventricular hypertrophy. An echocardiographic study. Circulation 1979;60:1058–65.
DOI: https://doi.org/10.1161/01.CIR.60.5.1058
Elliott P, McKenna WJ. Hypertrophic cardiomyopathy. Lancet 2004;363:1881–91.
DOI: https://doi.org/10.1016/S0140-6736(04)16358-7
Kim S-H, Kim S-O, Han S, et al. Long-term comparison of apical versus asymmetric hypertrophic cardiomyopathy. Int Heart J 2013;54:207–11.
DOI: https://doi.org/10.1536/ihj.54.207
Hansen MW, Merchant N. MRI of hypertrophic cardiomyopathy: part I, MRI appearances. AJR Am J Roentgenol 2007;189:1335–43.
DOI: https://doi.org/10.2214/AJR.07.2286
Maron MS, Maron BJ, Harrigan C, et al. Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance. J Am Coll Cardiol 2009;54:220–8.
DOI: https://doi.org/10.1016/j.jacc.2009.05.006
Agarwal A, Khandheria BK, Paterick TE, et al. Myocardial mechanics in noncontiguous HCM. JACC Cardiovasc Imaging 2013;6:1216–8.
DOI: https://doi.org/10.1016/j.jcmg.2013.04.016
Jordà P, García-Álvarez A. Hypertrophic cardiomyopathy: Sudden cardiac death risk stratification in adults. Glob Cardiol Sci Pract 2018;2018:25.
DOI: https://doi.org/10.21542/gcsp.2018.25
Frey N, Luedde M, Katus HA. Mechanisms of disease: hypertrophic cardiomyopathy. Nat Rev Cardiol 2011;9:91–100.
DOI: https://doi.org/10.1038/nrcardio.2011.159
Saumarez RC, Camm AJ, Panagos A, et al. Ventricular fibrillation in hypertrophic cardiomyopathy is associated with increased fractionation of paced right ventricular electrograms. Circulation 1992;86:467–74.
DOI: https://doi.org/10.1161/01.CIR.86.2.467
Olivotto I, Maron MS, Adabag AS, et al. Gender-related differences in the clinical presentation and outcome of hypertrophic cardiomyopathy. J Am Coll Cardiol 2005;46:480–7.
DOI: https://doi.org/10.1016/j.jacc.2005.04.043
Frenneaux MP, Counihan PJ, Caforio AL, et al. Abnormal blood pressure response during exercise in hypertrophic cardiomyopathy. Circulation 1990;82:1995–2002.
DOI: https://doi.org/10.1161/01.CIR.82.6.1995
Gollob MH, Blier L, Brugada R, et al. Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can J Cardiol 27:232–45.
DOI: https://doi.org/10.1016/j.cjca.2010.12.078
Stătescu C, Enachi Ș, Ureche C, et al. Pushing the limits of medical management in HCM: A review of current pharmacological therapy options. Int J Mol Sci 2021;22:7218.
DOI: https://doi.org/10.3390/ijms22137218
Ammirati E, Contri R, Coppini R, et al. Pharmacological treatment of hypertrophic cardiomyopathy: current practice and novel perspectives. Eur J Heart Fail 2016;18:1106–18.
DOI: https://doi.org/10.1002/ejhf.541
Marstrand P, Han L, Day SM, et al. Hypertrophic cardiomyopathy with left ventricular systolic dysfunction: Insights from the SHaRe Registry. Circulation 2020;141:1371-83.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.119.044366
Ho CY, Day SM, Ashley EA, et al. Genotype and lifetime burden of disease in hypertrophic cardiomyopathy: Insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Circulation 2018;138:1387-98.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.117.033200
How to Cite
Vriz, Olga, Hani AlSergani, Ahmed Nahid Elshaer, Abdullah Shaik, Ali Hassan Mushtaq, Michele Lioncino, Bandar Alamro, et al. 2021. “A Complex Unit for a Complex Disease: The HCM-Family Unit”. Monaldi Archives for Chest Disease 92 (3). https://doi.org/10.4081/monaldi.2021.2147.
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Luigi Pinto, Pietro Schino, Michele Bitetto, Ersilia Tedeschi, Michele Maiellari, Giancarlo De Leo, Elena Ludovico, Giovanni Larizza, Franco Mastroianni, Fibrotic outcomes from SARS-CoV-2 virus interstitial pneumonia , Monaldi Archives for Chest Disease: Early Access
- Carmine Guarino, Cristiano Cesaro, Giuseppe Fiorentino, Francesco Rossi, Benedetto Maria Polverino, Fiorentino Fragranza, Luca Monastra, Patrizia Murino, Enzo Zamparelli, Giuseppe La Cerra, Bronchoscopy in COVID-19 patients: When, how and why. Experience in clinical practice , Monaldi Archives for Chest Disease: Vol. 91 No. 2 (2021)
- Silvia Faverzani, Filippo Nocera, Ernesto Crisafulli, Maurizio Marvisi, Andrea Becciolini, Federica Mosetti, Eleonora Di Donato, Flavio Mozzani, Daniele Santilli, Giuseppe Scopelliti, Alarico Ariani, Home-based unsupervised pulmonary rehabilitation program improves the respiratory disability in systemic sclerosis patients with dyspnea: an observational prospective study , Monaldi Archives for Chest Disease: Vol. 92 No. 3 (2022)
- Fortuna Lubrano, Ilaria Fucile, Maurizio Conte, Ciro Santoro, Francesco Rozza, Nicola De Luca, Costantino Mancusi, Adherence to Mediterranean diet among patients with acute cardiovascular events admitted in Cardiac Rehabilitation unit , Monaldi Archives for Chest Disease: Vol. 93 No. 3 (2023)
- Marzia Testa, Enrico Lombardo, Enrico Avogadri, Marco Agostini, Giuseppe Forte, Salvatore Piccolo, Mauro Feola, Infective endocarditis or myxoma? Description of a patient with new diagnosis of congestive heart failure , Monaldi Archives for Chest Disease: Vol. 78 No. 2 (2012): Cardiac series
- Cristiano Cesaro, Umberto Caterino, Fabio Perrotta, Umberto Masi, Alessandra Cotroneo, Roberta Cianci, Enzo Zamparelli, Flavio Cesaro, Dario Amore, Danilo Rocco, Alectinib rescue therapy in advanced ALK rearranged lung adenocarcinoma: a case report , Monaldi Archives for Chest Disease: Vol. 93 No. 3 (2023)
- Carmine Guarino, Cristiano Cesaro, Giuseppe La Cerra, Raffaella Lucci, Flavio Cesaro, Enzo Zamparelli, Gianfranco Gaglione, Agostina Pontarelli, Annunziata De Rosa, Roberto Parrella, Endobronchial hamartoma in a young COVID-19 symptomatic woman. Radical endoscopic treatment with a disposable bronchoscope. Case Report , Monaldi Archives for Chest Disease: Vol. 92 No. 3 (2022)
- Gianfranco Beghi, Antonio De Tanti, Paolo Serafini, Chiara Bertolino, Antonietta Celentano, Graziella Taormina, Monitoring of hospital acquired pneumonia in patients with severe brain injury on first access to intensive neurological rehabilitation: First year of observation , Monaldi Archives for Chest Disease: Vol. 88 No. 1 (2018)
- Massimiliano Polastri, Lara Pisani, Andrea Dell'Amore, Stefano Nava, Revolving door respiratory patients: A rehabilitative perspective , Monaldi Archives for Chest Disease: Vol. 87 No. 3 (2017)
- Agata Buonacera, Benedetta Stancanelli, Lorenzo Malatino, Management of hypertension in the elderly: Looking for a trade-off between cardiovascular prevention and serious adverse events , Monaldi Archives for Chest Disease: Vol. 88 No. 2 (2018)
<< < 3 4 5 6 7 8 9 10 11 12 > >>
You may also start an advanced similarity search for this article.
