1887
Volume 2015, Issue 1
  • ISSN: 2305-7823
  • EISSN:

Abstract

Early pharmacological interventions on transgenic models of hypertrophic cardiomyopathy (HCM) using angiotensin receptor blockers (ARBs) may be effective in preventing development of clinical phenotype or causing phenotype regression in early stages of disease. In the clinical setting, however, the effects of ARBs on HCM phenotype have been less consistent. INHERIT (INHibition of the renin angiotensin system in hypertrophic cardiomyopathy and the Effect on hypertrophy—a Randomised Intervention Trial with losartan) was designed to assess the effect of 100 mg of losartan in promoting the regression of LV hypertrophy in HCM. The primary end-point of the study was the reduction in LV mass assessed by MRI or computed tomography. After 12 months, no reduction in LV mass was observed in the losartan arm, and there was no difference in LV mass change with the placebo arm. The same was true for all secondary endpoints. The implications of these findings are discussed in the light of further, ongoing study targeting the HCM phenotype.

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2015-03-01
2024-11-07
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References

  1. Maron BJ, Ommen SR, Semsarian C, Spirito P, Olivotto I, Maron MS. Hypertrophic cardiomyopathy: Present and future, with translation into contemporary cardiovascular medicine. J Am Coll Cardiol. 2014; 64::8399.
    [Google Scholar]
  2. Watkins H, Ashrafian H, Redwood C. Inherited cardiomyopathies. N Engl J Med. 2011; 364::16431656.
    [Google Scholar]
  3. van der Velden J, Ho CY, Tardiff J, Olivotto I, Knollmann BC, Carrier L. Research priorities in sarcomeric cardiomyopathies. Cardiovasc Res. 2015 Jan 28;, pii: cvv019. [Epub ahead of print].
    [Google Scholar]
  4. Spoladore R, Maron MS, D'Amato R, Camici PG, Olivotto I. Pharmacological treatment options for hypertrophic cardiomyopathy: High time for evidence. Eur Heart J. 2012; 33::17241733.
    [Google Scholar]
  5. Abozguia K, Elliott P, McKenna W, Phan TT, Nallur-Shivu G, Ahmed I, Maher AR, Kaur K, Taylor J, Henning A, Ashrafian H, Watkins H, Frenneaux M. Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation. 2010; 122::15621569.
    [Google Scholar]
  6. Ho CY, Lakdawala NK, Cirino AL, Lipshultz SE, Sparks E, Abbasi SA, Kwong RY, Antman EM, Semsarian C, González A, López B, Diez J, Orav EJ, Colan SD, Seidman CE. Diltiazem treatment for pre-clinical hypertrophic cardiomyopathy sarcomere mutation carriers: A pilot randomized trial to modify disease expression. JACC Heart Fail. 2014 Oct 31;, pii: S2213-1779(14)00445-4. doi: 10.1016/j.jchf.2014.08.003. [Epub ahead of print].
    [Google Scholar]
  7. Axelsson A, Iversen K, Vejlstrup N, Ho C, Norsk J, Langhoff L, Ahtarovski K, Corell P, Havndrup O, Jensen M, Bundgaard H. Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy: The INHERIT randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014;, published online Dec 19. DOI: http://dx.doi.org/10.1016/S2213-8587(14)70241-4 .
    [Google Scholar]
  8. Marian AJ. Experimental therapies in hypertrophic cardiomyopathy. J Cardiovasc Transl Res. 2009; 2::483492.
    [Google Scholar]
  9. Teekakirikul P, Eminaga S, Toka O, Alcalai R, Wang L, Wakimoto H, Nayor M, Konno T, Gorham JM, Wolf CM, Kim JB, Schmitt JP, Molkentin JD, Norris RA, Tager AM, Hoffman SR, Markwald RR, Seidman CE, Seidman JG. Cardiac fibrosis in mice with hypertrophic cardiomyopathy is mediated by non-myocyte proliferation and requires Tgf-β. J Clin Invest. 2010; 120::35203529.
    [Google Scholar]
  10. Penicka M, Gregor P, Kerekes R, Marek D, Curila K, Krupicka J. The effects of candesartan on left ventricular hypertrophy and function in nonobstructive hypertrophic cardiomyopathy: A pilot, randomized study. J Mol Diagn. 2009; 11::3541.
    [Google Scholar]
  11. Yamazaki T, Suzuki J, Shimamoto R, Tsuji T, Ohmoto-Sekine Y, Ohtomo K, Nagai R. A new therapeutic strategy for hypertrophic nonobstructive cardiomyopathy in humans. A randomized and prospective study with an angiotensin II receptor blocker. Int Heart J. 2007; 48::715724.
    [Google Scholar]
  12. Araujo AQ, Arteaga E, Ianni BM, Buck PC, Rabello R, Mady C. Effect of losartan on left ventricular diastolic function in patients with nonobstructive hypertrophic cardiomyopathy. Am J Cardiol. 2005; 96::15631567.
    [Google Scholar]
  13. Shimada YJ, Passeri JJ, Baggish AL, O'Callaghan C, Lowry PA, Yannekis G, Abbara S, Ghoshhajra BB, Rothman RD, Ho CY, Januzzi JL, Seidman CE, Fifer MA. Effects of losartan on left ventricular hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy. JACC Heart Fail. 2013; 1::480487.
    [Google Scholar]
  14. van Dockum WG, Beek AM, ten Cate FJ, ten Berg JM, Bondarenko O, Götte MJ, Twisk JW, Hofman MB, Visser CA, van Rossum AC. Early onset and progression of left ventricular remodeling after alcohol septal ablation in hypertrophic obstructive cardiomyopathy. Circulation. 2005; 111::25032508.
    [Google Scholar]
  15. El-Hamamsy I, Lekadir K, Olivotto I, El Guindy A, Merrifield R, Rega L, Yang G, Cecchi F, Yacoub MH. Pattern and degree of left ventricular remodeling following a tailored surgical approach for hypertrophic obstructive cardiomyopathy. Glob Cardiol Sci Pract. 2012 Jul 3; 2012:1:9. doi:10.5339/gcsp.2012.9.
    [Google Scholar]
  16. Todiere G, Aquaro GD, Piaggi P, Formisano F, Barison A, Masci PG, Strata E, Bacigalupo L, Marzilli M, Pingitore A, Lombardi M. Progression of myocardial fibrosis assessed with cardiac magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2012; 60::922929.
    [Google Scholar]
  17. Force T, Bonow RO, Houser SR, Solaro RJ, Hershberger RE, Adhikari B, Anderson ME, Boineau R, Byrne BJ, Cappola TP, Kalluri R, LeWinter MM, Maron MS, Molkentin JD, Ommen SR, Regnier M, Tang WH, Tian R, Konstam MA, Maron BJ, Seidman CE. Research priorities in hypertrophic cardiomyopathy: Report of a Working Group of the National Heart, Lung, and Blood Institute. Circulation. 2010; 122::11301133.
    [Google Scholar]
  18. Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, Watkins H, Authors/Task Force Members . 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::27332779.
    [Google Scholar]
  19. Schmieder RE, Martus P, Klingbeil A. Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies. JAMA. 1996; 275::15071513.
    [Google Scholar]
  20. Olivotto I, Ommen SR, Maron MS, Cecchi F, Maron BJ. Surgical myectomy versus alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Will there ever be a randomized trial? J Am Coll Cardiol. 2007; 50::831834.
    [Google Scholar]
  21. Jiang J, Wakimoto H, Seidman JG, Seidman CE. Allele-specific silencing of mutant Myh6 transcripts in mice suppresses hypertrophic cardiomyopathy. Science. 2013; 342::111114.
    [Google Scholar]
  22. Gedicke-Hornung C, Behrens-Gawlik V, Reischmann S, Geertz B, Stimpel D, Weinberger F, Schlossarek S, Précigout G, Braren I, Eschenhagen T, Mearini G, Lorain S, Voit T, Dreyfus PA, Garcia L, Carrier L. Rescue of cardiomyopathy through U7snRNA-mediated exon skipping in Mybpc3-targeted knock-in mice. EMBO Mol Med. 2013 Jul; 5:7:10601077.
    [Google Scholar]
  23. Olivotto I, Tomberli B, Spoladore R, Mugelli A, Cecchi F, Camici PG. Hypertrophic cardiomyopathy: The need for randomized trials. Glob Cardiol Sci Pract. 2013; 2013::243248, doi: 10.5339/gcsp.2013.31.
    [Google Scholar]
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