Prognostic utility of diastolic dysfunction and speckle tracking echocardiography in heart failure with reduced ejection fraction

Abstract

Aims We hypothesized that grading of diastolic dysfunction (DDF) according to two DDF grading algorithms and strain imaging yields prognostic information on all‐cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). Methods and results We enrolled ambulatory HFrEF (left ventricular ejection fraction < 45%; N = 1 065) patients who underwent echocardiography and speckle tracking assessment of global longitudinal strain (GLS). Patients were stratified according to DDF grades (Grades I–III) according to two contemporary DDF grading algorithms. Prognostic performance was assessed by C‐statistics. Of the originally 1 065 enrolled patients, a total of 645 (61%) patients (age: 67 ± 11 years, male: 72%, ejection fraction: 27 ± 9%) were classified according to both DDF grading algorithms. Concordance between the algorithms was moderate (kappa = 0.48) and the reclassification rate was 33%. During a median follow‐up of 3.3 years (1.9, 4.7 years), 101 (16%) died from all causes. When comparing DDF Grade I vs. Grade III, both algorithms provided prognostic information [Nagueh: (hazard ratio) HR 2.09, 95% confidence interval (CI),1.32–3.31, P = 0.002; Johansen: HR 2.47, 95% CI, 1.57–3.87, P < 0.001]. However, when comparing DDF Grade II vs. Grade III, only the Johansen algorithm yielded prognostic information (Nagueh: HR 1.04, 95% CI, 0.60–1.77, P = 0.90; Johansen: HR 2.26, 95% CI, 1.35–3.77, P = 0.002). We found no difference in prognostic performance between the two algorithms (C‐statistics: 0.604 vs. 0.623, P = 0.24). Assessed by C‐statistics, the most powerful predictors of the endpoint from the two algorithms were E/e'‐ratio (C‐statistics: 0.644), tricuspid regurgitation velocity (C‐statistics: 0.625) and E/A‐ratio (C‐statistics: 0.602). When adding GLS to a combination of these predictors, the prognostic performance increased significantly (C‐statistics: 0.705 vs. C‐statistics: 0.634, P = 0.028). Conclusions Evaluation of DDF in patients with HFrEF yields prognostic information on all‐cause mortality. Furthermore, adding GLS to contemporary algorithms of DDF adds novel prognostic information.

Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial

“…However, E/e ′ and LA volumes did not increase, suggesting that such changes were not associated with an increase in cardiac filling pressures. Moreover contribute to morbidity in HFrEF, 19,20 treatment with a cardiac myosin activator that preserves relaxation may lead to enhanced clinical benefits. Consistent with the pre-clinical ex vivo and in vivo findings of direct atrial activation, danicamtiv had pronounced effects on LA volume and function, with concentration-dependent reductions in LA minimum volume and increases in LAEF and LAFI.…”

“…Moreover, since forward flow (SV) remained enhanced, any effects of the potentially slowed relaxation on diastolic filling may have been offset by improved atrial systolic performance, in the setting of unaltered ventricular stiffness. Since diastolic dysfunction may contribute to morbidity in HFrEF, 19,20 treatment with a cardiac myosin activator that preserves relaxation may lead to enhanced clinical benefits.…”

Prognostic utility of the assessment of diastolic function in patients undergoing cardiac resynchronization therapy

“…Recent studies have shown that diastolic dysfunction (DD) is associated with increased mortality in patients with HF and reduced ejection fraction (3), (4). The best modality to assess diastolic function in CRT-candidates is an object of debate and the relationship between diastolic function, CRTresponse and survival is not definitely understood (5).…”

Diastolic function grading by American Society of Echocardiography guidelines and prediction of heart failure readmission and all‐cause mortality in a community‐based cohort

“…As compared to normal DF, any Ddys grade had significant hazard ratios for the composite outcome. Hansen 34 compared the use of the algorithm by the ASE/EACVI and Johansen's for prediction of ACM over 3 years in a cohort of 546 patients with HFrEF and demonstrated that the hazard ratio = 1.09 for ASE/EACVI for grade 1 versus grade 3 Ddys and 2.236 for Johansen's algorithm for grade 2 versus grade 3 Ddys. The AUC = .604 for ASE/EACVI and .625 for Johansen's algorithm, which are slightly higher than our data.…”