Skip to main content
SpringerLink
Log in

Emerging pharmacologic and structural therapies for hypertrophic cardiomyopathy

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Hypertrophic cardiomyopathy is the most common inherited heart disease. Although it was first described over 50 years ago, there has been little in the way of novel disease-specific therapeutic development for these patients. Current treatment practice largely aims at symptomatic control using old drugs made for other diseases and does little to modify the disease course. Septal reduction by surgical myectomy or percutaneous alcohol septal ablation are well-established treatments for pharmacologic-refractory left ventricular outflow tract obstruction in hypertrophic cardiomyopathy patients. In recent years, there has been a relative surge in the development of innovative therapeutics, which aim to target the complex molecular pathophysiology and resulting hemodynamics that underlie hypertrophic cardiomyopathy. Herein, we review the new and emerging therapeutics for hypertrophic cardiomyopathy, which include pharmacologic attenuation of sarcomeric calcium sensitivity, allosteric inhibition of cardiac myosin, myocardial metabolic modulation, and renin-angiotensin-aldosterone system inhibition, as well as structural intervention by percutaneous mitral valve plication and endocardial radiofrequency ablation of septal hypertrophy. In conclusion, while further development of these therapeutic strategies is ongoing, they each mark a significant and promising advancement in treatment for hypertrophic cardiomyopathy patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Maron BJ, Gardin JM, Flack JM et al (1995) Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Circulation 92:785–789. https://doi.org/10.1161/01.CIR.92.4.785

    Article  CAS  PubMed  Google Scholar 

  2. Maron BJ, Olivotto I, Spirito P et al (2000) Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large non-referral-based patient population. Circulation 102:858–864. https://doi.org/10.1161/01.CIR.102.8.858

    Article  CAS  PubMed  Google Scholar 

  3. Maron BJ, McKenna WJ, Danielson GK et al (2003) American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on hypertrophic cardiomyopathy. J Am Coll Cardiol 42:1687–1713. https://doi.org/10.1016/S0735-1097(03)00941-0

    Article  PubMed  Google Scholar 

  4. Sen-Chowdhry S, Jacoby D, Moon JC, McKenna WJ (2016) Update on hypertrophic cardiomyopathy and a guide to the guidelines. Nat Rev Cardiol 13:651–675. https://doi.org/10.1038/nrcardio.2016.140

    Article  CAS  PubMed  Google Scholar 

  5. Maron MS, Olivotto I, Zenovich AG et al (2006) Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation 114:2232–2239. https://doi.org/10.1161/CIRCULATIONAHA.106.644682

    Article  PubMed  Google Scholar 

  6. Spoladore R, Maron MS, D’Amato R et al (2012) Pharmacological treatment options for hypertrophic cardiomyopathy: high time for evidence. Eur Heart J 33:1724–1733. https://doi.org/10.1093/eurheartj/ehs150

    Article  CAS  PubMed  Google Scholar 

  7. Ammirati E, Contri R, Coppini R et al (2016) Pharmacological treatment of hypertrophic cardiomyopathy: current practice and novel perspectives. Eur J Heart Fail 18:1106–1118. https://doi.org/10.1002/ejhf.541

    Article  PubMed  Google Scholar 

  8. Agarwal S, Tuzcu EM, Desai MY et al (2010) Updated meta-analysis of septal alcohol ablation versus myectomy for hypertrophic cardiomyopathy. J Am Coll Cardiol 55:823–834. https://doi.org/10.1016/j.jacc.2009.09.047

    Article  PubMed  Google Scholar 

  9. Valeti US, Nishimura RA, Holmes DR et al (2007) Comparison of surgical septal myectomy and alcohol septal ablation with cardiac magnetic resonance imaging in patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 49:350–357. https://doi.org/10.1016/j.jacc.2006.08.055

    Article  PubMed  Google Scholar 

  10. Liebregts M, Vriesendorp PA, Mahmoodi BK et al (2015) A systematic review and meta-analysis of long-term outcomes after septal reduction therapy in patients with hypertrophic cardiomyopathy. JACC Hear Fail 3:896–905. https://doi.org/10.1016/j.jchf.2015.06.011

    Article  Google Scholar 

  11. Semsarian C, Ahmad I, Giewat M et al (2002) The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. J Clin Invest 109:1013–1020. https://doi.org/10.1172/JCI200214677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ho CY, Lakdawala NK, Cirino AL et al (2015) Diltiazem treatment for pre-clinical hypertrophic cardiomyopathy sarcomere mutation carriers: a pilot randomized trial to modify disease expression. JACC Hear Fail 3:180–188. https://doi.org/10.1016/j.jchf.2014.08.003

    Article  Google Scholar 

  13. Coppini R, Ferrantini C, Yao L et al (2013) Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy. Circulation 127:575–584. https://doi.org/10.1161/CIRCULATIONAHA.112.134932

    Article  CAS  PubMed  Google Scholar 

  14. Gentry JL, Mentz RJ, Hurdle M, Wang A (2016) Ranolazine for treatment of angina or dyspnea in hypertrophic cardiomyopathy patients (RHYME). J Am Coll Cardiol 68:1815–1817. https://doi.org/10.1016/j.jacc.2016.07.758

    Article  PubMed  Google Scholar 

  15. Bemporad D (2016) Ranolazine in patients with symptomatic hypertrophic cardiomyopathy: a pilot study assessing the effects on exercise capacity, diastolic function and symptomatic status. EU Clin Trials Regist. https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-004507-20/DE. Accessed August 1, 2016

  16. Gilead Sciences (2017) Effect of eleclazine (GS-6615) on exercise capacity in subjects with symptomatic hypertrophic cardiomyopathy (LIBERTY-HCM). US National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT02291237. Accessed February 17, 2017

  17. Gilead Sciences (2017) Effect of eleclazine on shortening of the QT interval, safety, and tolerability in adults with long QT syndrome type 3. US National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT02300558?te. Accessed February 17, 2017

  18. Nag S, Sommese RF, Ujfalusi Z et al (2015) Contractility parameters of human beta-cardiac myosin with the hypertrophic cardiomyopathy mutation R403Q show loss of motor function. Sci Adv 1:1–16. https://doi.org/10.1126/sciadv.1500511

    Article  CAS  Google Scholar 

  19. Kamdar F, Klaassen Kamdar A, Koyano-Nakagawa N et al (2015) Cardiomyopathy in a dish: using human inducible pluripotent stem cells to model inherited cardiomyopathies. J Card Fail 21:761–770. https://doi.org/10.1016/j.cardfail.2015.04.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Maslov MY, Chacko VP, Stuber M et al (2007) Altered high-energy phosphate metabolism predicts contractile dysfunction and subsequent ventricular remodeling in pressure-overload hypertrophy mice. Am J Physiol Heart Circ Physiol 292:H387–H391. https://doi.org/10.1152/ajpheart.00737.2006

    Article  CAS  PubMed  Google Scholar 

  21. Ferrantini C, Belus A, Piroddi N et al (2009) Mechanical and energetic consequences of HCM-causing mutations. J Cardiovasc Transl Res 2:441–451. https://doi.org/10.1007/s12265-009-9131-8

    Article  PubMed  Google Scholar 

  22. Wilder T, Ryba DM, Wieczorek DF et al (2015) N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy. Am J Physiol Heart Circ Physiol. doi:https://doi.org/10.1152/ajpheart.00339.2015

  23. Lee L, Campbell R, Scheuermann-Freestone M et al (2005) Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation 112:3280–3288. https://doi.org/10.1161/CIRCULATIONAHA.105.551457

    Article  CAS  PubMed  Google Scholar 

  24. Horowitz JD, Sia STB, Macdonald PS et al (1986) Perhexiline maleate treatment for severe angina pectoris—correlations with pharmacokinetics. Int J Cardiol 13:219–229. https://doi.org/10.1016/0167-5273(86)90146-4

    Article  CAS  PubMed  Google Scholar 

  25. Olivotto I, Gistri R, Petrone P et al (2003) Maximum left ventricular thickness and risk of sudden death in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 41:315–321. https://doi.org/10.1016/S0735-1097(02)02713-4

    Article  PubMed  Google Scholar 

  26. Shimada YJ, Passeri JJ, Baggish AL et al (2013) Effects of losartan on left ventricular hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy. JACC Hear Fail 1:480–487. https://doi.org/10.1016/j.jchf.2013.09.001

    Article  Google Scholar 

  27. Axelsson A, Iversen K, Vejlstrup N et al (2015) Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy: the INHERIT randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 3:123–131. https://doi.org/10.1016/S2213-8587(14)70241-4

    Article  CAS  PubMed  Google Scholar 

  28. Lim DS, Reynolds MR, Feldman T et al (2014) Improved functional status and quality of life in prohibitive surgical risk patients with degenerative mitral regurgitation after transcatheter mitral valve repair. J Am Coll Cardiol 64:182–192. https://doi.org/10.1016/j.jacc.2013.10.021

    Article  PubMed  Google Scholar 

  29. Maron BJ, Dearani JA, Ommen SR et al (2004) The case for surgery in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 44:2044–2053. https://doi.org/10.1016/j.jacc.2004.04.063

    Article  PubMed  Google Scholar 

  30. Lawrenz T, Kuhn HJ (2004) Endocardial radiofrequency ablation of septal hypertrophy: a new catheter-based modality of gradient reduction in hypertrophic obstructive cardiomyopathy. Z Kardiol 93:493–499

    Article  CAS  PubMed  Google Scholar 

  31. Pohlmann L, Kröger I, Vignier N et al (2007) Cardiac myosin-binding protein C is required for complete relaxation in intact myocytes. Circ Res 101:928–938. https://doi.org/10.1161/CIRCRESAHA.107.158774

    Article  CAS  PubMed  Google Scholar 

  32. Iorga B, Blaudeck N, Solzin J et al (2008) Lys184 deletion in troponin I impairs relaxation kinetics and induces hypercontractility in murine cardiac myofibrils. Cardiovasc Res 77:676–686. https://doi.org/10.1093/cvr/cvm113

    Article  CAS  PubMed  Google Scholar 

  33. Huke S, Knollmann BC (2010) Increased myofilament Ca2+ sensitivity and arrhythmia susceptibility. J Mol Cell Cardiol 48:824–833. https://doi.org/10.1016/j.yjmcc.2010.01.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Baudenbacher F, Schober T, Pinto JR et al (2008) Myofilament Ca sensitization causes susceptibility to cardiac arrhythmia in mice. J Clin Invest 118:3845–3903. https://doi.org/10.1172/JCI36642

    Google Scholar 

  35. Ho CY, Sweitzer NK, McDonough B et al (2002) Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation 105:2992–2997. https://doi.org/10.1161/01.CIR.0000019070.70491.6D

    Article  PubMed  Google Scholar 

  36. Nagueh SF, Bachinski LL, Meyer D 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. https://doi.org/10.1161/01.CIR.104.2.128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Michele D, Albayya FP, Metzger JM (1999) Direct, convergent hypersensitivity of calcium-activated force generation produced by hypertrophic cardiomyopathy mutant alpha-tropomyosins in adult cardiac myocytes. Nat Med 5:1413–1417. https://doi.org/10.1038/70990

    Article  CAS  PubMed  Google Scholar 

  38. Frey N, McKinsey TA, Olson EN (2000) Decoding calcium signals involved in cardiac growth and function. Nat Med 6:1221–1227. https://doi.org/10.1038/81321

    Article  CAS  PubMed  Google Scholar 

  39. Tardiff JC, Carrier L, Bers DM et al (2015) Targets for therapy in sarcomeric cardiomyopathies. Cardiovasc Res 105:457–470. https://doi.org/10.1093/cvr/cvv023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Robinson P, Griffiths PJ, Watkins H, Redwood CS (2007) Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments. Circ Res 101:1266–1273. https://doi.org/10.1161/CIRCRESAHA.107.156380

    Article  CAS  PubMed  Google Scholar 

  41. Fatkin D, Mcconnell BK, Mudd JO et al (2000) An abnormal Ca2+ response in mutant sarcomere protein-mediated familial hypertrophic cardiomyopathy. J Clin Invest 106:1351–1359. https://doi.org/10.1172/JCI11093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lovelock JD, Monasky MM, Jeong EM et al (2012) Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity. Circ Res 110:841–850. https://doi.org/10.1161/CIRCRESAHA.111.258251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Flenner F, Friedrich FW, Ungeheuer N et al (2016) Ranolazine antagonizes catecholamine-induced dysfunction in isolated cardiomyocytes, but lacks long-term therapeutic effects in vivo in a mouse model of hypertrophic cardiomyopathy. Cardiovasc Res 109:90–102. https://doi.org/10.1093/cvr/cvv247

    Article  CAS  PubMed  Google Scholar 

  44. Buvoli M, Hamady M, Leinwand LA, Knight R (2008) Bioinformatics assessment of β-myosin mutations reveals myosin’s high sensitivity to mutations. Trends Cardiovasc Med 18:141–149. https://doi.org/10.1016/j.tcm.2008.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kirschner SE, Becker E, Antognozzi M et al (2004) Hypertrophic cardiomyopathy-related-myosin mutations cause highly variable calcium sensitivity with functional imbalances among individual muscle cells. AJP Hear Circ Physiol 288:H1242–H1251. https://doi.org/10.1152/ajpheart.00686.2004

    Article  CAS  Google Scholar 

  46. Spudich JA (2014) Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases. Biophys J 106:1236–1249. https://doi.org/10.1016/j.bpj.2014.02.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Walsh R, Rutland C, Thomas R, Loughna S (2009) Cardiomyopathy: a systematic review of disease-causing mutations in myosin heavy chain 7 and their phenotypic manifestations. Cardiology 115:49–60. https://doi.org/10.1159/000252808

    Article  PubMed  CAS  Google Scholar 

  48. Green EM, Wakimoto H, Anderson RL et al (2016) A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science 351(80):617–621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. MyoKardia Inc (2015) MyoKardia provides update on two phase 1 trials of MYK-461 for the treatment of hypertrophic cardiomyopathy. In: http://investors.myokardia.com/phoenix.zhtml?c=254211&p=irol-newsArticle&ID=2097088

  50. Witjas-Paalberends ER, Güclü A, Germans T et al (2014) Gene-specific increase in the energetic cost of contraction in hypertrophic cardiomyopathy caused by thick filament mutations. Cardiovasc Res 103:248–257. https://doi.org/10.1093/cvr/cvu127

    Article  CAS  PubMed  Google Scholar 

  51. Witjas-Paalberends ER, Ferrara C, Scellini B et al (2014) Faster cross-bridge detachment and increased tension cost in human hypertrophic cardiomyopathy with the R403Q MYH7 mutation. J Physiol 592:3257–3272. https://doi.org/10.1113/jphysiol.2014.274571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ashrafian H, Redwood C, Blair E, Watkins H (2003) Hypertrophic cardiomyopathy: a paradigm for myocardial energy depletion. Trends Genet 19:263–268. https://doi.org/10.1016/S0168-9525(03)00081-7

    Article  CAS  PubMed  Google Scholar 

  53. Frey N, Olson EN (2003) Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol 65:45–79. https://doi.org/10.1146/annurev.physiol.65.092101.142243

    Article  CAS  PubMed  Google Scholar 

  54. Blair E, Redwood C, Ashrafian H et al (2001) Mutations in the γ 2 subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. Hum Mol Genet 10:1215–1220. https://doi.org/10.1093/hmg/10.11.1215

    Article  CAS  PubMed  Google Scholar 

  55. Crilley JG, Boehm EA, Blair E et al (2003) Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. J Am Coll Cardiol 41:1776–1782. https://doi.org/10.1016/S0735-1097(02)03009-7

    Article  CAS  PubMed  Google Scholar 

  56. Unno K, Isobe S, Izawa H et al (2009) Relation of functional and morphological changes in mitochondria to myocardial contractile and relaxation reserves in asymptomatic to mildly symptomatic patients with hypertrophic cardiomyopathy. Eur Heart J 30:1853–1862. https://doi.org/10.1093/eurheartj/ehp184

    Article  CAS  PubMed  Google Scholar 

  57. Camici P, 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. J Am Coll Cardiol 17:879–886. https://doi.org/10.1016/0735-1097(91)90869-B

    Article  CAS  PubMed  Google Scholar 

  58. Cecchi F, Olivotto I, Gistri R et al (2003) Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy. N Engl J Med 349:1027–1035

    Article  CAS  PubMed  Google Scholar 

  59. Petersen SE, Jerosch-Herold M, Hudsmith LE et al (2007) Evidence for microvascular dysfunction in hypertrophic cardiomyopathy: new insights from multiparametric magnetic resonance imaging. Circulation 115:2418–2425. https://doi.org/10.1161/CIRCULATIONAHA.106.657023

    Article  PubMed  Google Scholar 

  60. Lombardi R, Rodriguez G, Chen SN et al (2009) Resolution of established cardiac hypertrophy and fibrosis and prevention of systolic dysfunction in a transgenic rabbit model of human cardiomyopathy through thiol-sensitive mechanisms. Circulation 119:1398–1407. https://doi.org/10.1161/CIRCULATIONAHA.108.790501.Resolution

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Marian AJ (2015) Hypertrophic regression with N-Acetylcysteine in HCM (HALT). US National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT01537926?. Accessed February 17, 2017

  62. Lele SS, Thomson HL, Seo H et al (1995) Exercise capacity in hypertrophic cardiomyopathy. Circulation 92:2886–2894

    Article  CAS  PubMed  Google Scholar 

  63. Phan TT, Shivu GN, Abozguia K et al (2010) Impaired heart rate recovery and chronotropic incompetence in patients with heart failure with preserved ejection fraction. Circ Hear Fail 3:29–34. https://doi.org/10.1161/CIRCHEARTFAILURE.109.877720

    Article  Google Scholar 

  64. Jeffrey FMH, Alvarez L, Diczku V et al (1995) Direct evidence that perhexiline modifies myocardial substrate utilization from fatty acids to lactate. J Cardiovasc Pharmacol 25:469–472

    Article  CAS  PubMed  Google Scholar 

  65. Abozguia K, Elliott P, McKenna W et al (2010) Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation 122:1562–1569. https://doi.org/10.1161/CIRCULATIONAHA.109.934059

    Article  CAS  PubMed  Google Scholar 

  66. Cole PL, Beamer AD, Mcgowan N et al (1990) Efficacy and safet of perhexiline maleate refractory angina a double-blind placebo-controlled clinical trial of a novel. Circulation 81:1260–1270

    Article  CAS  PubMed  Google Scholar 

  67. Heart Metabolics Limited (2015) Efficacy, safety, and tolerability of perhexiline in subjects with hypertrophic cardiomyopathy and heart failure. US National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT02431221. Accessed February 17, 2017

  68. Varnava AM, Elliott PM, Sharma S et al (2000) Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Heart 84:476–482. https://doi.org/10.1136/heart.84.5.476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Marian AJ (2000) Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy. Lancet 355:58–60. https://doi.org/10.1016/S0140-6736(99)06187-5

    Article  CAS  PubMed  Google Scholar 

  70. Spirito P, Chiarella F, Carratino L et al (1989) Clinical course and prognosis of hypertrophic cardiomyopathy in an outpatient population. N Engl J Med 320:749–755. https://doi.org/10.1056/NEJM198603273141302

    Article  CAS  PubMed  Google Scholar 

  71. Elliott PM, Gimeno Blanes JR, Mahon NG et al (2001) Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet 357:420–424. https://doi.org/10.1016/S0140-6736(00)04005-8

    Article  CAS  PubMed  Google Scholar 

  72. Maron BJ, Casey SA, Hauser RG, Aeppli DM (2003) Clinical course of hypertrophic cardiomyopathy with survival to advanced age. J Am Coll Cardiol 42:882–888. https://doi.org/10.1016/S0735-1097(03)00855-6

    Article  PubMed  Google Scholar 

  73. Teekakirikul P, Eminaga S, Toka O et al (2010) Cardiac fibrosis in mice with hypertrophic cardiomyopathy is mediated by non-myocyte proliferation and requires TGF-β. J Clin Invest 120:3520–3529. https://doi.org/10.1172/JCI42028DS1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lim D, Lutucuta S, Bachireddy P et al (2001) Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation 103:789–792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kawano H, Toda G, Nakamizo R et al (2005) Valsartan decreases type I collagen synthesis in patients with hypertrophic cardiomyopathy. Circ J 69:1244–1248

    Article  CAS  PubMed  Google Scholar 

  76. Araujo AQ, Arteaga E, Ianni BM et al (2005) Effect of losartan on left ventricular diastolic function in patients with nonobstructive hypertrophic cardiomyopathy. Am J Cardiol 96:1563–1567. https://doi.org/10.1016/j.amjcard.2005.07.065

    Article  CAS  PubMed  Google Scholar 

  77. Yamazaki T, Suzuki J-I, Shimamoto R et al (2007) A new therapeutic strategy for hypertrophic nonobstructive cardiomyopathy in humans. A randomized and prospective study with an angiotensin II receptor blocker. Int Heart J 48:715–724. https://doi.org/10.1536/ihj.48.715

    Article  PubMed  Google Scholar 

  78. Penicka M, Gregor P, Kerekes R et al (2009) The effects of candesartan on left ventricular hypertrophy and function in nonobstructive hypertrophic cardiomyopathy. J Mol Diagnostics 11:35–41. https://doi.org/10.2353/jmoldx.2009.080082

    Article  CAS  Google Scholar 

  79. US National Library of Medicine (2016) clinicaltrials.gov https://clinicaltrials.gov/ct2/show/NCT01912534

  80. Maron MS, Olivotto I, Betocchi S et al (2003) Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 348:295–303. https://doi.org/10.1056/NEJMoa021332\r348/4/295

    Article  PubMed  Google Scholar 

  81. Wigle ED, Marquis Y, Auger P (1967) Muscular subaortic stenosis: initial left ventricular inflow tract pressure in the assessment of intraventricular pressures differences in man. Circulation 36:1100–1117

    Article  Google Scholar 

  82. Ross J, Braunwald E, Gault JH et al (1966) The mechanism of the intraventricular pressure gradient in idiopathic hypertrophic subaortic stenosis. Circulation 34:558–578

    Article  PubMed  Google Scholar 

  83. Shah PM, Gramiak R, Kramer D (1969) Ultrasound localization of left ventricular outflow obstruction in hypertrophic obstructive cardiomyopathy. Circulation 40:3–11. https://doi.org/10.1161/01.CIR.40.1.3

    Article  CAS  PubMed  Google Scholar 

  84. Cape EG, Simons D, Jimoh A et al (1989) Chordal geometry determines the shape and extent of systolic anterior mitral motion: in vitro studies. J Am Coll Cardiol 13:1438–1448. https://doi.org/10.1016/0735-1097(89)90326-4

    Article  CAS  PubMed  Google Scholar 

  85. Sherrid MV, Balaram S, Kim B et al (2016) The mitral valve in obstructive hypertrophic cardiomyopathy: a test in context. J Am Coll Cardiol 67:1846–1858. https://doi.org/10.1016/j.jacc.2016.01.071

    Article  PubMed  Google Scholar 

  86. Spirito P, Maron BJ (1984) Patterns of systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy: assessment by two-dimensional echocardiography. Am J Cardiol 54:1039–1046. https://doi.org/10.1016/S0002-9149(84)80141-1

    Article  CAS  PubMed  Google Scholar 

  87. Grigg LE, Wigle ED, Williams WG et al (1992) Transesophageal Doppler echocardiography in obstructive hypertrophic cardiomyopathy: clarification of pathophysiology and importance in intraoperative decision making. J Am Coll Cardiol 20:42–52. https://doi.org/10.1016/0735-1097(92)90135-A

    Article  CAS  PubMed  Google Scholar 

  88. Schwammenthal E, Nakatani S, He S et al (1998) Mechanism of mitral regurgitation in hypertrophic cardiomyopathy: mismatch of posterior to anterior leaflet length and mobility. Circulation 98:856–865

    Article  CAS  PubMed  Google Scholar 

  89. Yu EHC, Omran AS, Wigle ED et al (2000) Mitral regurgitation in hypertrophic obstructive cardiomyopathy: relationship to obstruction and relief with myectomy. J Am Coll Cardiol 36:2219–2225. https://doi.org/10.1016/S0735-1097(00)01019-6

    Article  CAS  PubMed  Google Scholar 

  90. Smedira NG, Lytle BW, Lever HM et al (2008) Current effectiveness and risks of isolated septal myectomy for hypertrophic obstructive cardiomyopathy. Ann Thorac Surg 85:127–133. https://doi.org/10.1016/j.athoracsur.2007.07.063

    Article  PubMed  Google Scholar 

  91. Balaram SK, Tyrie L, Sherrid MV et al (2008) Resection-plication-release for hypertrophic cardiomyopathy: clinical and echocardiographic follow-up. Ann Thorac Surg 86:1539–1545. https://doi.org/10.1016/j.athoracsur.2008.07.048

    Article  PubMed  Google Scholar 

  92. Balaram SK, Ross RE, Sherrid MV et al (2012) Role of mitral valve plication in the surgical management of hypertrophic cardiomyopathy. Ann Thorac Surg 94:1990–1998. https://doi.org/10.1016/j.athoracsur.2012.06.008

    Article  PubMed  Google Scholar 

  93. Shah AA, Glower DD, Gaca JG (2016) Trans-aortic Alfieri stitch at the time of septal myectomy for hypertrophic obstructive cardiomyopathy. J Card Surg 31:503–506. https://doi.org/10.1111/jocs.12804

    Article  PubMed  Google Scholar 

  94. Ferrazzi P, Spirito P, Iacovoni A et al (2015) Transaortic chordal cutting mitral valve repair for obstructive hypertrophic cardiomyopathy with mild septal hypertrophy. J Am Coll Cardiol 66:1687–1696. https://doi.org/10.1016/j.jacc.2015.07.069

    Article  PubMed  Google Scholar 

  95. Maron BJ, Dearani JA, Maron MS, et al (2017) Why we need more septal myectomy surgeons: an emerging recognition. J Thorac Cardiovasc Surg 1–6. doi:https://doi.org/10.1016/j.jtcvs.2016.12.038

  96. Feldman T, Foster E, Glower DD et al (2011) Percutaneous repair or surgery for mitral regurgitation. N Engl J Med 364:1395–1406

    Article  CAS  PubMed  Google Scholar 

  97. Mauri L, Foster E, Glower DD et al (2013) 4-year results of a randomized controlled trial of percutaneous repair versus surgery for mitral regurgitation. J Am Coll Cardiol 62:317–328. https://doi.org/10.1016/j.jacc.2013.04.030

    Article  PubMed  Google Scholar 

  98. Sorajja P, Pedersen W, Bae R et al (2016) First experience with percutaneous mitral valve plication as primary therapy for symptomatic obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 67:1516. https://doi.org/10.1016/S0735-1097(16)31517-0

    Article  Google Scholar 

  99. Jaber WA, Nishimura RA, Ommen SR (2007) Not all systolic velocities indicate obstruction in hypertrophic cardiomyopathy: a simultaneous Doppler catheterization study. J Am Soc Echocardiogr 20:5–7. https://doi.org/10.1016/j.echo.2007.01.015

    Article  Google Scholar 

  100. Criley JM, Siegel RJ (1986) Obstruction is unimportant in the pathophysiology of hypertrophic cardiomyopathy. Postgrad Med J 62:515–529. https://doi.org/10.1136/pgmj.62.728.515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Murgo JP, Alter BR, Dorethy JF et al (1980) Dynamics of left ventricular ejection in obstructive and nonobstructive hypertrophic cardiomyopathy. J Clin Invest 66:1369–1382. https://doi.org/10.1172/JCI109990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Criley JM (1997) Unobstructed thinking (and terminology) is called for in the understanding and management of hypertrophic cardiomyopathy. J Am Coll Cardiol 29:741–743. https://doi.org/10.1016/S0735-1097(96)00590-6

    Article  CAS  PubMed  Google Scholar 

  103. Sahn DJ, Yoganathan AP, Editors G et al (1989) Pressure recovery distal to a stenosis: potential cause of a gradient “overestimation” by Doppler echocardiography. J Am Coll Cardiol 13:706–715

    Article  Google Scholar 

  104. Braunwald E, Lambrew CT, Rockoff SD et al (1964) Idiopathic hypertrophic subaortic stenosis: I. A description of the disease based upon an analysis of 64 patients. Circulation 29:IV-3–IV-119. https://doi.org/10.1161/01.CIR.29.5S4.IV-3

    Google Scholar 

  105. Geske JB, Sorajja P, Ommen SR, Nishimura RA (2009) Left ventricular outflow tract gradient variability in hypertrophic cardiomyopathy. Clin Cardiol 32:397–402. https://doi.org/10.1002/clc.20594

    Article  PubMed  Google Scholar 

  106. Geske JB, Sorajja P, Ommen SR, Nishimura RA (2011) Variability of left ventricular outflow tract gradient during cardiac catheterization in patients with hypertrophic cardiomyopathy. JACC Cardiovasc Interv 4:704–709. https://doi.org/10.1016/j.jcin.2011.02.014

    Article  PubMed  Google Scholar 

  107. Veselka J, Jensen MK, Liebregts M et al (2016) Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: results from the Euro-ASA registry. Eur Heart J 37:1517–1523. https://doi.org/10.1093/eurheartj/ehv693

    Article  PubMed  Google Scholar 

  108. Veselka J, Anavekar NS, Charron P (2017) Hypertrophic obstructive cardiomyopathy. Lancet 389:1253–1267. https://doi.org/10.1016/S0140-6736(16)31321-6

    Article  PubMed  Google Scholar 

  109. Lawrenz T, Borchert B, Leuner C et al (2011) Endocardial radiofrequency ablation for hypertrophic obstructive cardiomyopathy: acute results and 6 months’ follow-up in 19 patients. J Am Coll Cardiol 57:572–576. https://doi.org/10.1016/j.jacc.2010.07.055

    Article  PubMed  Google Scholar 

  110. Sreeram N, Emmel M, De Giovanni JV (2011) Percutaneous radiofrequency septal reduction for hypertrophic obstructive cardiomyopathy in children. J Am Coll Cardiol 58:2501–2510. https://doi.org/10.1016/j.jacc.2011.09.020

    Article  PubMed  Google Scholar 

  111. Cooper RM, Shahzad A, Hasleton J et al (2015) Radiofrequency ablation of the interventricular septum to treat outflow tract gradients in hypertrophic obstructive cardiomyopathy: a novel use of CARTOSound® technology to guide ablation. Eur Eur pacing, arrhythmias, Card Electrophysiol J Work groups Card pacing, arrhythmias, Card Cell Electrophysiol Eur Soc Cardiol 18:113–120. https://doi.org/10.1093/europace/euv302

    Google Scholar 

  112. Crossen K, Jones M, Erikson C (2016) Radiofrequency septal reduction in symptomatic hypertrophic obstructive cardiomyopathy. Hear Rhythm 13:1885–1890. https://doi.org/10.1016/j.hrthm.2016.04.018

    Article  Google Scholar 

  113. Shelke AB, Menon R, Kapadiya A et al (2016) A novel approach in the use of radiofrequency catheter ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy. Indian Heart J 68:618–623. https://doi.org/10.1016/j.ihj.2016.02.007

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, UCLA, 200 UCLA Medical Plaza Suite 420, Los Angeles, CA, 90095, USA

    Daniel J. Philipson

  2. Ahmanson-UCLA Cardiomyopathy Center, Division of Cardiology, Department of Medicine, UCLA, Los Angeles, CA, USA

    Eugene C. DePasquale & Arnold S. Baas

  3. Division of Cardiology, Department of Medicine, UCLA, Los Angeles, CA, USA

    Eric H. Yang

Authors
  1. Daniel J. Philipson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eugene C. DePasquale
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eric H. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arnold S. Baas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel J. Philipson.

Ethics declarations

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Philipson, D.J., DePasquale, E.C., Yang, E.H. et al. Emerging pharmacologic and structural therapies for hypertrophic cardiomyopathy. Heart Fail Rev 22, 879–888 (2017). https://doi.org/10.1007/s10741-017-9648-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-017-9648-x

Keywords

Search

Navigation