000			03446nam a22004817a 4500
003			OSt
005			20230312211513.0
008			211101s20212021 xxu||||| |||| 00| 0 eng d
022			_a1078-8956
040			_aOvid MEDLINE(R) _cwhc
099			_a34556856
245			_aValsartan in early-stage hypertrophic cardiomyopathy: a randomized phase 2 trial.
251			_aNature Medicine. 27(10):1818-1824, 2021 10.
252			_aNat Med. 27(10):1818-1824, 2021 10.
260			_c2021
260			_fFY2022
265			_sppublish
266			_d2021-11-01
520			_aHypertrophic cardiomyopathy (HCM) is often caused by pathogenic variants in sarcomeric genes and characterized by left ventricular (LV) hypertrophy, myocardial fibrosis and increased risk of heart failure and arrhythmias. There are no existing therapies to modify disease progression. In this study, we conducted a multi-center, double-blind, placebo-controlled phase 2 clinical trial to assess the safety and efficacy of the angiotensin II receptor blocker valsartan in attenuating disease evolution in early HCM. In total, 178 participants with early-stage sarcomeric HCM were randomized (1:1) to receive valsartan (320 mg daily in adults; 80-160 mg daily in children) or placebo for 2 years ( NCT01912534 ). Standardized changes from baseline to year 2 in LV wall thickness, mass and volumes; left atrial volume; tissue Doppler diastolic and systolic velocities; and serum levels of high-sensitivity troponin T and N-terminal pro-B-type natriuretic protein were integrated into a single composite z-score as the primary outcome. Valsartan (n = 88) improved cardiac structure and function compared to placebo (n = 90), as reflected by an increase in the composite z-score (between-group difference +0.231, 95% confidence interval (+0.098, +0.364); P = 0.001), which met the primary endpoint of the study. Treatment was well-tolerated. These results indicate a key opportunity to attenuate disease progression in early-stage sarcomeric HCM with an accessible and safe medication. Copyright (c) 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
546			_aEnglish
650			_a*Cardiomyopathy, Hypertrophic/dt [Drug Therapy]
650			_a*Heart Failure/dt [Drug Therapy]
650			_a*Heart/de [Drug Effects]
650			_a*Valsartan/ad [Administration & Dosage]
650			_aAdolescent
650			_aAdult
650			_aCardiomyopathy, Hypertrophic/pp [Physiopathology]
650			_aDouble-Blind Method
650			_aFemale
650			_aHeart Failure/pp [Physiopathology]
650			_aHeart/pp [Physiopathology]
650			_aHumans
650			_aMale
650			_aMiddle Aged
650			_aValsartan/ae [Adverse Effects]
650			_aYoung Adult
656			_aMedStar Heart and Vascular Institute
657			_aJournal Article
700			_aVargas, Jose D _956
790			_aAxelsson A, Bach RG, Becker JR, Benson L, Braunwald , Bundgaard H, Burns KM, Canter C, Cirino AL, Colan SD, Day SM, Ho CY, Lakdawala NK, Lever HM, MacRae CA, Margossian R, McMurray JJV, Mestroni L, Murphy AM, Orav EJ, Owens AT, Patel AR, Pereira AC, Rossano JW, Russell MW, Seidman CE, Solomon SD, Soslow JH, Taylor MRG, Thrush P, VANISH Investigators, Vargas JD, Wheeler MT, Wilmot I, Zahka K
856			_uhttps://dx.doi.org/10.1038/s41591-021-01505-4 _zhttps://dx.doi.org/10.1038/s41591-021-01505-4
942			_cART _2ddc
999			_c990 _d990