Impaired left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction: insights from the RELAX trial

Abstract

Background: While abnormal left ventricular (LV) global longitudinal strain (GLS) has been described in patients with heart failure with preserved ejection fraction (HFpEF), its prevalence and clinical significance are poorly understood.

Methods and results: Patients enrolled in the RELAX trial of sildenafil in HFpEF (LV ejection fraction ≥50%) in whom two-dimensional, speckle-tracking LV GLS was possible (n = 187) were analysed. The distribution of LV GLS and its associations with clinical characteristics, LV structure and function, biomarkers, exercise capacity and quality of life were assessed. Baseline median LV GLS was -14.6% (25th and 75th percentile, -17.0% and -11.9%, respectively) and abnormal (≥ - 16%) in 122/187 (65%) patients. Patients in the tertile with the best LV GLS had lower N-terminal pro-brain natriuretic peptide (NT-proBNP) [median 505 pg/mL (161, 1065) vs. 875 pg/mL (488, 1802), P = 0.008) and lower collagen III N-terminal propeptide (PIIINP) levels [median 6.7 µg/L (5.1, 8.1) vs. 8.1 µg/L (6.5, 10.5), P = 0.001] compared with the tertile with the worst LV GLS. There was also a modest linear relationship with LV GLS and log-transformed NT-proBNP and PIIINP (r = 0.29, P < 0.001 and r = 0.19, P = 0.009, respectively). We observed no linear association of LV GLS with Minnesota Living with Heart Failure scores, 6-min walk distance, peak oxygen consumption, or expiratory minute ventilation/carbon dioxide excretion slope.

Conclusions: Impaired LV GLS is common among HFpEF patients, indicating the presence of covert systolic dysfunction despite normal LV ejection fraction. Impaired LV GLS was associated with biomarkers of wall stress and collagen synthesis and diastolic dysfunction but not with quality of life or exercise capacity, suggesting other processes may be more responsible for these aspects of the HFpEF syndrome.

Trial registration: ClinicalTrials.gov NCT00763867.

Keywords: Echocardiography; Heart failure; Strain.

Conflict of interest statement

Conflict of Interest Disclosures

The authors report no relevant disclosures.

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

Figures

Figure 1. Study Flow Diagram

This figure displays the initial study population, through exclusions, to the final study population. HFpEF indicates heart failure with preserved ejection fraction; RELAX trial, PhosphodiesterRasE-5 Inhibition to Improve CLinical Status And EXercise Capacity in Diastolic Heart Failure; US, United States; LV GLS, left ventricular global longitudinal strain.

Figure 2. Relationships between Left Ventricular Global Longitudinal Strain and Baseline Patient Characteristics

A, Relationship between left ventricular global longitudinal strain (LV GLS) and peak oxygen consumption (peak VO2). B, Relationship between LV GLS and N-terminal pro-B-type natriuretic peptide (NT-proBNP). C, Relationship between LV GLS and collagen III N-terminal propeptide (PIIINP). D, Relationship between LV GLS and Minnesota Living with Heart Failure score. By convention, better systolic performance as assessed by LV GLS is noted by numbers of greater magnitude with a negative sign to indicate myocardial longitudinal shortening.