Association of active and passive components of LV diastolic filling with exercise intolerance in heart failure with preserved ejection fraction. Mechanistic insights from spironolactone response

Objectives: This study sought to investigate the association of left ventricular (LV) untwisting rate (UT) and E/e' ratio with the response of exercise capacity to spironolactone in heart failure with preserved ejection fraction (HFpEF).Background: In most patients with HFpEF, LV filling abnormalities represent a central component in the development of dyspnea. LV diastolic filling is determined by the interplay of passive (LV stiffness and myocardial collagen content, reflected by E/e' ratio) and active myocardial properties (UT, a precursor to isovolumic pressure decay and contributor to diastolic suction).Methods: In 194 patients with HFpEF (64 ± 8 years), a complete echocardiogram (including assessment of myocardial deformation and rotational mechanics) was performed. Echocardiography following maximal exercise was undertaken to assess LV systolic and diastolic responses to stress. A subset of 105 patients with an exercise-induced increase in estimated LV filling pressure were randomly assigned to spironolactone 25 mg (n = 51) or placebo (n = 54) for 6 months.Results: Baseline peak Vo2 was associated with UT (β = 0.19; p = 0.01) and E/e' (β = -0.16; p = 0.03), independent of clinical data and exercise reserve in longitudinal deformation and ventricular-arterial coupling. An increase in peak Vo2 with treatment was independently associated with changes in UT (β = 0.28; p = 0.003) and exertional increase in E/e' (β = -0.23; p = 0.01) from baseline to follow-up. A significant interaction with the use of spironolactone on peak Vo2 was found for E/e' (p = 0.02) but not for UT (p = 0.62).Conclusions: Both active and passive determinants of LV filling, as reflected by UT and E/e', contribute to reduced exercise capacity in HFpEF. Improvement in functional capacity with a 6-month therapy with spironolactone is associated with improvements in both indices. However, the possible mediating effect of this medication is observed only on E/e'

Prognostic Value of the MAGGIC Score, H(2)FPEF Score, and HFA-PEFF Algorithm in Patients with Exertional Dyspnea and the Incremental Value of Exercise Echocardiography

International audienceBACKGROUND: The strategies for improving outcomes in heart failure with preserved ejection fraction (HFpEF) are insufficiently defined, which affects optimal patient management. The aim of the study was to compare the prognostic value of the previously validated Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score with 2 approaches primarily dedicated to diagnosing HFpEF: the H(2)FPEF score (heavy, 2 or more hypertensive drugs, atrial fibrillation, pulmonary hypertension [pulmonary artery systolic pressure >35 mm Hg], elder age >60, elevated filling pressures [E/e’ > 9]) and the HFA-PEFF algorithm (Heart Failure Association diagnostic algorithm-pretest assessment; echocardiography and natriuretic peptide score; functional testing; final etiology) in patients with exertional dyspnea categorized as HFpEF. METHODS: Clinical and biochemical variables and echocardiographic resting and exercise data from 201 enrollees were retrospectively analyzed. Participants were followed for 48 (24-60) months for HF hospitalization and cardiovascular death. RESULTS: Seventy-four patients (36.8%) met the study outcome. In sequential Cox analysis, the addition of MAGGIC risk score, H(2)FPEF score, and HFA-PEFF step 2 (including only resting echocardiographic evaluation) and step 3 (including also exercise diastolic data) algorithms to the base model comprising brain natriuretic peptide and peak oxygen uptake improved the predictive power for the study endpoint. Harrell’s c statistic showed a greater predictive ability for the HFA-PEFF step 3 algorithm than for each of the other scores (c index 0.715 vs 0.637, 0.644, and 0.638 for MAGGIC, H(2)FPEF, and HFA-PEFF step 2, respectively; all P < .05). No significant differences were found for other between-score comparisons. CONCLUSION: In patients with exertional dyspnea and a possible HFpEF, the H(2)FPEF score and HFA-PEFF algorithm limited to resting echocardiography provide prognostic value comparable to the MAGGIC risk score. Extending the HFA-PEFF algorithm with exercise diastolic data is associated with a significant improvement in risk stratification