Abstract
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.
Résumé
Introduction
La durée du QRS est considérée comme un indicateur de résultats défavorables chez
les patients ayant une insuffisance cardiaque (IC) et les polymorphismes génétiques
peuvent être impliqués dans cette altération de la conductivité. Nous avons étudié
les conséquences pronostiques du taux d’élargissement du QRS (TE-QRS) sur les patients
ayant une IC et l’influence des polymorphismes des gènes des métalloprotéinases matricielles
(MMP : matrix metalloproteinases) sur le TE-QRS.
Méthodes
Cette étude de cohorte prospective incluait 184 patients ayant une dysfonction systolique
ventriculaire gauche (VG; fraction d’éjection VG < 45 %). Le TE-QRS a été calculé
comme étant la différence entre 2 évaluations d’électrocardiogramme (en millisecondes
[ms]) divisée par le temps écoulé entre chaque évaluation (mois). Les polymorphismes
MMP-1 -1607 1G/2G, MMP-2 -790G/T et -1575G/A, MMP-3 -1171 5A/6A, MMP-9 -1562 C/T et R279Q, et MMP-12 -82A/G ont été génotypés par le polymorphisme de longueur des fragments de restriction
et la réaction en chaîne de la polymérase.
Résultats
Les patients étaient en majorité des hommes (67 %) caucasiens (68 %) répondant à la
classification fonctionnelle I et II de la New York Heart Association (77 %). Les
patients ayant une insuffisance cardiaque qui avaient un TE-QRS ≥ 0,5 ms/mois subissaient
plus de décès liés à l’IC et plus d’événements cliniques combinés que ceux qui avaient
un TE-QRS < 0,5 ms/mois (P = 0,03 et P = 0,01, respectivement). Après l’ajustement des autres covariables, le TE-QRS demeurait
un prédicteur indépendant des événements cliniques combinés (rapport de risque 1,6;
intervalles de confiance à 95 % de 1,1–2,5; P = 0,02). Le génotype MMP-1 2G2G a été associé à une augmentation de près de 2 fois du TE-QRS (P = 0,03). Inversement, les patients ayant un génotype MMP-3 5A5A et une étiologie non ischémique étaient protégés contre l’élargissement du QRS
(P = 0,03).
Conclusion
Le TE-QRS conserve sa valeur pronostique chez les patients ayant une IC chronique
recevant le traitement pharmacologique selon les recommandations. Les polymorphismes
des gènes MMP peuvent influencer le taux d’élargissement du QRS avec le temps.
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Article info
Publication history
Published online: November 21, 2013
Accepted:
November 15,
2013
Received:
September 18,
2013
Footnotes
See page 350 for disclosure information.
Identification
Copyright
© 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
