Preclinical systolic dysfunction relating to ankle-brachial index among high-risk PAD population with preserved left ventricular ejection fraction.

Peripheral artery disease (PAD) shares common clinical risk factors, for example, endothelial dysfunction, with preserved ejection fraction (LVEF) heart failure (HFpEF). Whether PAD is associated with preclinical systolic dysfunction and higher HF risk among individuals presenting preserved LVEF remains uncertain. We retrospectively included outpatients with at least one known or established cardiovascular (CV) risk factor with LVEF ≥ 50%. Patients were categorized into high risk and low risk of developing PAD (PAD vs Non-PAD) by ankle-brachial index (ABI) (≤ 0.90 or > 1.4) and further stratified based on their history of HFpEF (HFpEF vs. Non-HFpEF), resulting in the formation of four distinct strata. Preclinical systolic dysfunction was defined using dedicated speckle-tracking algorithm. A total of 2130 consecutive patients were enrolled in the study, with a median follow-up of 4.4 years. The analysis revealed a higher prevalence of high risk of developing PAD in patients with HFpEF compared to those without HFpEF (25.1% vs. 9.4%). Both high risk of developing PAD and HFpEF were independently associated with preclinical systolic dysfunction (global longitudinal strain, GLS ≥ - 18%) (odds ratio, OR: 1.38; 95% confidence interval, CI: 1.03-1.86). In comparison to patients at low risk of developing PAD without HFpEF (Non-PAD/Non-HFpEF group), those categorized as having a high risk of developing PAD with HFpEF (PAD/HFpEF group) exhibited the most impaired GLS and a heightened susceptibility to heart failure hospitalization (hazard ratio, HR: 6.51; 95% CI: 4.43-9.55), a twofold increased risk of all-cause mortality (HR: 2.01; 95% CI: 1.17-3.38), cardiovascular mortality (HR: 2.44; 95% CI: 1.08-5.51), and non-cardiovascular mortality (HR: 1.78; 95% CI: 0.82-3.84). A high risk of developing PAD was strongly linked to impaired preclinical systolic function and an increased likelihood for subsequent hospitalization for HF, all-cause mortality, CV mortality and non-CV mortality. There is a clear need for preventive strategies aimed at reducing hospitalizations for HF and mortality in this high-risk population.

Discriminative Ability of Left Ventricular Strain in Mildly Reduced Ejection Fraction Heart Failure.

Background: Left ventricular (LV) systolic strain is presumably a more sensitive myocardial indicator than LV ejection fraction (LVEF). Data regarding the use of LV strain in clinical risk stratification and in identifying angiotensin receptor-neprilysin inhibitor (ARNi) responders remain scarce in heart failure with mildly reduced ejection fraction (HFmrEF). Objectives: The authors aimed to examine whether assessing LV strain may provide prognostic insight beyond LVEF and help discriminate the therapeutic efficacy of ARNi in HFmrEF patients. Methods: LVEF and LV strain were quantified among 1,075 first-time hospitalized HFmrEF patients (mean age: 68.1 ± 15.1 years, 40% female). The MAGGIC (Meta-analysis Global Group in Chronic Heart Failure) risk score and its components were calculated. A Cox proportional hazard model was constructed for time-to-event analysis. Restrictive cubic spline curves were used to model the therapeutic effects of ARNi against renin-angiotensin system inhibitor according to baseline LVEF or LV strain. Results: LV strain showed a statistically significant inverse association with MAGGIC cardiac risk (coefficient: -0.14, P < 0.001). LV strain was independently associated with clinical outcomes after accounting for LVEF. MAGGIC-LV strain strata outperformed MAGGIC-LVEF strata in overall survival (Harrell's C-index: 0.71 and 0.56, P for difference <0.001; category-free net reclassification index: 0.44, P < 0.001). Lower LV strain but not LVEF consistently showed the beneficial therapeutic effects of ARNi against renin-angiotensin system inhibitor by Cox models and restrictive cubic spline (all P interaction <0.05). Conclusions: Among HFmrEF patients, LV strain may serve as an attractive systolic marker and provide a better prognostic and therapeutic discriminative measure for ARNi treatment than conventional LVEF.