title: The effects of candesartan on left ventricular hypertrophy and function in nonobstructive hypertrophic cardiomyopathy: a pilot, randomized study.
abstract: Hypertrophic cardiomyopathy is caused by mutations in the genes that encode sarcomeric proteins and is primarily characterized by unexplained left ventricular hypertrophy, impaired cardiac function, reduced exercise tolerance, and a relatively high incidence of sudden cardiac death, especially in the young. The extent of left ventricular hypertrophy is one of the major determinants of disease prognosis. Angiotensin II has trophic effects on the heart and plays an important role in the development of myocardial hypertrophy. Here in a double-blind, placebo-controlled, randomized study, we show that the long-term administration of the angiotensin II type 1 receptor antagonist candesartan in patients with hypertrophic cardiomyopathy was associated with the significant regression of left ventricular hypertrophy, improvement of left ventricular function, and exercise tolerance. The magnitude of the treatment effect was dependent on specific sarcomeric protein gene mutations that had the greatest responses on the carriers of ss-myosin heavy chain and cardiac myosin binding protein C gene mutations. These data indicate that modulating the role of angiotensin II in the development of hypertrophy is specific with respect to both the affected sarcomeric protein gene and the affected codon within that gene. Thus, angiotensin II type 1 receptor blockade has the potential to attenuate myocardial hypertrophy and may, therefore, provide a new treatment option to prevent sudden cardiac death in patients with hypertrophic cardiomyopathy.
authors.affiliation: Cardiocenter, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic. Electronic address: penicka@fnkv.cz.
authors.forename: Martin
authors.initials: M
authors.lastname: Penicka
authors.affiliation: Cardiocenter, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Gregor
authors.affiliation: Department of Internal Medicine, Associated Medical Institution, Krnov, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Kerekes
authors.affiliation: First Department of Medicine-Cardiology, University Hospital Olomouc, Prague, Czech Republic.
authors.forename: Dan
authors.initials: D
authors.lastname: Marek
authors.affiliation: Cardiocenter, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Karol
authors.initials: K
authors.lastname: Curila
authors.affiliation: Department of Cardiosurgery, Na Homolce Hospital, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Krupicka
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D024722:Cardiac Myosins / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D010865:Pilot Projects; D013777:Tetrazoles / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*; D000099163:Myosin Binding Protein C
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D013777:Tetrazoles; D000099163:Myosin Binding Protein C; C081643:candesartan