Prognostic importance of left ventricular mechanical dyssynchrony in heart failure with preserved ejection fraction

Abstract

Aims: Left ventricular mechanical dyssynchrony has been described in heart failure with preserved ejection fraction (HFpEF), but its prognostic significance is not known.

Methods and results: Of 3445 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, dyssynchrony analysis was performed on 424 patients (12%) by multiple speckle tracking echocardiography strain-based criteria. The primary dyssynchrony analysis was the standard deviation of the time to peak longitudinal strain (SD T2P LS). Cox proportional hazards models assessed the association of dyssynchrony with the composite outcome of cardiovascular death or heart failure hospitalization. Mean age was 70 ± 10 years, LVEF was 60 ± 8%, and QRS duration was 101 ± 27 ms. Worse dyssynchrony, reflected in SD T2P LS, was associated with wider QRS, prior myocardial infarction, larger LV volume and mass, and worse systolic (lower LVEF and global longitudinal strain) and diastolic (lower e' and higher E/e') function. During a median follow-up of 2.6 (interquartile range 1.5-3.8) years, 107 patients experienced the composite outcome. Worse dyssynchrony was associated with the composite outcome in unadjusted analysis [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01-1.07; P = 0.021, per 10 ms increase], but not after adjusting for clinical characteristics, or after further adjustment for LVEF, AF, NYHA class, stroke, heart rate, creatinine, haematocrit, and QRS duration (HR 1.03, 95% CI 0.99-1.06; P = 0.16, per 10 ms increase).

Conclusion: Worse LV mechanical dyssynchrony, assessed by speckle tracking echocardiography, is not an independent predictor of adverse outcomes in HFpEF, suggesting that mechanical dyssynchrony is unlikely to be an important mechanism underlying this syndrome. These findings warrant validation in an independent study specifically designed to assess the prognostic utility of mechanical dyssynchrony in HFpEF.

Trial registration: NCT00094302.

Keywords: Clinical trial; Dyssynchrony; Heart failure; Heart ventricles; Preserved left ventricular function; Spironolactone.

Conflict of interest statement

Conflict of interest

Dr A. Shah reports receiving research support from Novartis, Gilead, and Myocaria Inc. Dr Pitt reports serving as a consultant for Bayer, Astra Zeneca, Merck, Boehringer Ingelheim, KBP biosciences and Relypsa; and has a patent pending on site-specific delivery of Eplerenone to the myocardium. Dr Sweitzer reports consulting for Medtronic. Dr Pfeffer reports receiving research grants from Amgen, Celladon, Novartis and Sanofi Avantis and serving as a consultant for Amgen, AstraZeneca, Bayer, DalCor Pharma UK, Genzyme, Lilly, Medicines Company, MedImmune, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Salix, Sanderling, Sanofi, Takeda, Teva, Thrasos and Vericel. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in selected survivors of MI with Novartis. Dr Pfeffer is a coinventor. His share of the licensing agreement is irrevocably transferred to charity. The other authors report no conflicts.

© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Figures

Figure 1. Association between the myocardial dyssynchrony and LS, E/e′ and QRS duration

Cubic splines regression models with 95% confidence intervals for the association between mechanical dyssynchrony as assessed by SD T2P LS and LS (A), E/e′ (B) and QRS duration (C), respectively. LS – Global Longitudinal Strain; SD T2P LS – Standard Deviation Time To Peak LS.

Figure 2. Association of LV mechanical dyssynchrony and incident HF hospitalization or CV death

Unadjusted incidence with 95% confidence intervals of composite endpoint per 100 patient years based on LV mechanical dyssynchrony as assessed by SD T2P. A Poisson model was used to estimate the incidence rate. P for overall relationship = 0.021; p for non-linearity = 0.082. Histograms shows the population distribution of LV mechanical dyssynchrony. SD T2P LS – Standard Deviation Time To Peak LS.