QRS widening rates and genetic polymorphisms of matrix metalloproteinases in a cohort of patients with chronic heart failure.
BACKGROUND
QRS duration is considered to be an indicator of adverse outcome in patients with heart failure (HF), and genetic polymorphisms may be involved in this conductivity impairment. We studied the prognostic impact of the QRS widening rate (QRS-WR) on patients with HF and the influence of the matrix metalloproteinases gene polymorphisms on the QRS-WR.


METHODS
This prospective cohort study included 184 patients with left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF] < 45%). The QRS-WR was calculated as the difference between 2 electrocardiogram assessments (in ms) divided by the time elapsed between each evaluation (months). The MMP-1 -1607 1G/2G, MMP-2 -790G/T and -1575G/A, MMP-3 -1171 5A/6A, MMP-9 -1562 C/T and R279Q, and MMP-12 -82A/G polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism.


RESULTS
Patients were predominantly white (68%) men (67%) in New York Heart Association functional classes I and II (77%). Patients with HF with a QRS-WR ≥ 0.5 ms/month had more HF-related deaths and more combined clinical events than those with a QRS-WR < 0.5 ms/month (P = 0.03 and P = 0.01, respectively). After adjusting for other covariates, the QRS-WR remained an independent predictor of combined clinical events (hazard ratio, 1.6; 95% confidence interval, 1.1-2.5; P = 0.02). The MMP-1 2G2G genotype was associated with nearly a 2-fold increase in QRS-WR (P = 0.03). Conversely, patients with the MMP-3 5A5A genotype and a nonischemic cause of HF were protected against QRS enlargement (P = 0.03).


CONCLUSIONS
QRS-WR retains prognostic value in patients with chronic HF receiving guideline-based pharmacologic treatment. MMP gene polymorphisms can influence the rate of QRS enlargement over time.
Experimental and Molecular Cardiovascular Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
Virgilio
V
Olsen
Experimental and Molecular Cardiovascular Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Luis E
LE
Rohde
Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Luis
L
Beck-da-Silva
Experimental and Molecular Cardiovascular Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil, Canoas, Rio Grande do Sul, Brazil.
Kátia G
KG
Santos
Experimental and Molecular Cardiovascular Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Andréia
A
Biolo
Experimental and Molecular Cardiovascular Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Nadine
N
Clausell
Experimental and Molecular Cardiovascular Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: michaelandrades@gmail.com.
Michael
M
Andrades
D001938:Brazil / Q000453:epidemiology; D004247:DNA / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006333:Heart Failure / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D016277:Ventricular Function, Left / Q000502:physiology*
D004247:DNA; D020782:Matrix Metalloproteinases