TY - JOUR
T1 - Clinical Phenotype and Genotype Associations With Improvement in Left Ventricular Function in Dilated Cardiomyopathy
AU - Verdonschot, Job A. J.
AU - Hazebroek, Mark R.
AU - Wang, Ping
AU - Sanders-van Wijk, Sandra
AU - Merken, Jort J.
AU - Adriaansen, Yvonne A.
AU - van den Wijngaard, Arthur
AU - Krapels, Ingrid P. C.
AU - Brunner-La Rocca, Hans-Peter
AU - Brunner, Han G.
AU - Heymans, Stephane R. B.
PY - 2018/11
Y1 - 2018/11
N2 - BACKGROUND: Improvement of left ventricular function (also called left ventricular reverse remodeling [LVRR]) is an important treatment goal in patients with dilated cardiomyopathy (DCM) and hypokinetic non-DCM (HNDC) and is prognostically favorable. We tested whether genetic DCM mutations impact LVRR independent from clinical parameters.METHODS AND RESULTS: Patients with DCM and hypokinetic non-DCM (n=346; mean left ventricular ejection fraction, 30%) underwent genotyping for 47 DCM-associated genes in addition to extensive phenotyping. LVRR was defined as improvement of left ventricular ejection fraction >50% or >= 10% absolute increase, with cardiac dimensions (left ventricular end diastolic diameter) = 10% relative decrease. LVRR occurred in 180 (52%) patients after a median follow-up of 12-month optimal medical treatment. Low baseline left ventricular ejection fraction, a hypokinetic non-DCM phenotype, high systolic blood pressure, absence of a family history of DCM, female sex, absence of atrioventricular block, and treatment with beta-blockers were all independent positive clinical predictors of LVRR. With the exception of TTN, genetic mutations were strongly associated with a lower rate of LVRR (odds ratio, 0.19 [0.09-0.42]; PCONCLUSIONS: The genetic substrate is associated with the clinical course and long-term prognosis of patients with DCM/hypokinetic non-DCM.
AB - BACKGROUND: Improvement of left ventricular function (also called left ventricular reverse remodeling [LVRR]) is an important treatment goal in patients with dilated cardiomyopathy (DCM) and hypokinetic non-DCM (HNDC) and is prognostically favorable. We tested whether genetic DCM mutations impact LVRR independent from clinical parameters.METHODS AND RESULTS: Patients with DCM and hypokinetic non-DCM (n=346; mean left ventricular ejection fraction, 30%) underwent genotyping for 47 DCM-associated genes in addition to extensive phenotyping. LVRR was defined as improvement of left ventricular ejection fraction >50% or >= 10% absolute increase, with cardiac dimensions (left ventricular end diastolic diameter) = 10% relative decrease. LVRR occurred in 180 (52%) patients after a median follow-up of 12-month optimal medical treatment. Low baseline left ventricular ejection fraction, a hypokinetic non-DCM phenotype, high systolic blood pressure, absence of a family history of DCM, female sex, absence of atrioventricular block, and treatment with beta-blockers were all independent positive clinical predictors of LVRR. With the exception of TTN, genetic mutations were strongly associated with a lower rate of LVRR (odds ratio, 0.19 [0.09-0.42]; PCONCLUSIONS: The genetic substrate is associated with the clinical course and long-term prognosis of patients with DCM/hypokinetic non-DCM.
KW - cardiomyopathy, dilated
KW - humans
KW - therapeutics
KW - ventricular remodeling
KW - AMERICAN-COLLEGE
KW - HEART-FAILURE
KW - ARRHYTHMIAS
KW - VARIANTS
KW - MUTATION
KW - INDIVIDUALS
KW - GUIDELINES
KW - GENETICS
KW - RECOVERY
U2 - 10.1161/CIRCHEARTFAILURE.118.005220
DO - 10.1161/CIRCHEARTFAILURE.118.005220
M3 - Article
SN - 1941-3289
VL - 11
JO - Circulation-Heart Failure
JF - Circulation-Heart Failure
IS - 11
M1 - 005220
ER -