BACKGROUND:Data on heart failure (HF) phenotypes in India remain limited. We examined clinical characteristics and factors associated with HF phenotype defined according to ejection fraction (EF) in a large multicentre outpatient cohort. METHODS:We performed a retrospective cross-sectional analysis of adult HF outpatients with documented EF at centres across India (April 2021-March 2023). Patients were classified as HFrEF (EF ≤40%), HFmrEF (41-49%), or HFpEF (≥50%); multivariable logistic regression identified factors associated with phenotype. RESULTS:Among 1,207 patients (62 ± 10 years; 73% male), HFrEF was present in 822 (68.1%), HFmrEF in 89 (7.4%), and HFpEF in 296 (24.5%). Patients with HFpEF had higher systolic blood pressure (153 ± 26 vs 122 ± 25 mmHg), higher body mass index (BMI; 27.5 ± 4.9 vs 26.4 ± 4.4 kg/m2), and more chronic kidney disease (45% vs 23%) and stroke (27% vs 6.2%) than those with HFrEF (all p ≤ 0.003). Ischaemic heart disease (66% vs 56%; p = 0.002) and higher NT-proBNP (median 3,705 [481-6,232] vs 140 [121-521] pg/mL; p < 0.001) were more common in HFrEF. In multivariable analysis, higher BMI (OR 1.35 per 5 kg/m2, 95% CI 1.10-1.65), higher systolic blood pressure (OR 1.48 per 10 mmHg, 95% CI 1.37-1.60), and stroke (OR 1.99, 95% CI 1.11-3.54) were associated with higher odds of HFpEF, whereas higher NT-proBNP (OR 0.46, 95% CI 0.40-0.53) and diabetes (OR 0.56, 95% CI 0.38-0.83) were associated with lower odds of HFpEF. CONCLUSIONS:Higher BMI and blood pressure were associated with HFpEF, whereas elevated NT-proBNP and diabetes were associated with HFrEF. These cross-sectional associations may support phenotype-specific management of HF.
AIMS:Anaemia is among the most prevalent comorbidities in heart failure with preserved ejection fraction (HFpEF), but pooled prognostic estimates predate the contemporary left ventricular ejection fraction (LVEF) ≥50% definition and combine legacy with contemporary cohorts. We quantified the association between World Health Organization (WHO)-defined anaemia and all-cause mortality in HFpEF and tested whether it persists under the stricter ejection-fraction threshold. METHODS AND RESULTS:Following PRISMA 2020 (PROSPERO CRD420251361160), we searched five databases from inception to 2026 and included cohort studies reporting an adjusted hazard ratio (aHR) for binary WHO-defined anaemia vs all-cause mortality in an ejection fraction-stratified HFpEF population; every estimate was verified against its primary source and screening was duplicated (κ = 1.00 after adjudication). Of 6123 records, 20 studies were included; 17 (109 909 patients; anaemia prevalence 26%-70%; follow-up 12-72 months) contributed to two pre-specified co-primary pools analysed with Paule-Mandel random-effects models and Hartung-Knapp-Sidik-Jonkman variance correction: a legacy pool (LVEF ≥40%, k = 17) and a contemporary pool (LVEF ≥50%, k = 12). Anaemia was associated with higher all-cause mortality in both: aHR 1.49 (95% CI 1.35-1.66; 95% prediction interval (PI) 1.07-2.09; I2 = 85%) in the ≥40% pool and 1.41 (1.26-1.57; PI 1.06-1.87; I2 = 83%) in the ≥50% pool, both PIs excluding the null. The estimate was stable across 12 pre-specified sensitivity analyses (range 1.45-1.52) with no influential study. Across four Bayesian priors, the posterior median aHR was 1.39-1.49 with posterior probability of harm ≥.999, and a robust Bayesian model-average that entertains null, homogeneity, and publication-bias models returned aHR 1.41 (95% credible interval 1.17-1.58). Although small-study effects were detected (Egger P = .03), the bias-corrected estimate was essentially unchanged (PEESE aHR 1.39). A per-1 g/dL lower-haemoglobin dose-response meta-analysis (k = 6) yielded aHR 1.17 (1.08-1.27). The accrued sample exceeded the diversity-adjusted required information size, and GRADE certainty was moderate under the prognostic-factor framework. CONCLUSIONS:WHO-defined anaemia is independently associated with a ∼40-50% higher all-cause mortality in HFpEF, preserved under the contemporary LVEF ≥50% definition and robust to extensive sensitivity, Bayesian, and bias-correction analyses. These findings support incorporating anaemia into HFpEF risk assessment and motivate mortality-powered trials in rigorously defined HFpEF, while not implying that anaemia correction improves outcomes. REGISTRATION:PROSPERO CRD420251361160.
BACKGROUND:Heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction causes substantial global burden with limited therapies, especially for HFpEF. This pilot study assessed safety and efficacy of a 10-week individualized intermittent hypoxia-hyperoxia exposure (IHHE) program, hypothesizing good tolerability and improvements in exercise capacity and quality of life (QoL). METHODS:In this prospective mechanistic feasibility study, HFpEF and HFrEF patients completed supervised seated IHHE sessions three times weekly for 10 weeks using a medical altitude breathing device (ReOxy, Ai Mediq S.A., Luxembourg). Blood pressure (BP) was monitored before and after sessions. Pre- and post-intervention assessments included echocardiography, cardiopulmonary exercise testing (CPET), 6-minutes walking test (6MWT), isokinetic muscle strength, body composition, biomarkers, patient-reported outcomes, and clinically indicated right heart catheterization (RHC). RESULTS:Nine outpatients (5 HFpEF, 4 HFrEF; age 66.6±10.9 years, 22% female, BMI 27.9±5.4 kg/m2) completed the study. IHHE was safe and well tolerated (adherence 95%), with no adverse events. Across weeks 1-10, post-session reductions in systolic (β =-5.95 mmHg) and diastolic blood pressure (β=-3.74 mmHg), and heart rate (β=-5.18 bpm) were measured (all p< 0.001). A significant decrease of fat mass index 9.32±2.56 vs. 8.92±2.41 kg/m2 (P=0.031), and visceral fat area 127.6±30.6 vs. 121.9±29.7 cm2 (P=0.005), as well as an increase of body mineral content 3.14±0.57 vs. 3.21±0.55 kg (P=0.028), and tissue impedance (RB250: 4.02±0.50 vs. 4.12±0.56 kHz, P=0.041), were measured. There was a numeric improvement (not statistically significant) of peak VO2 1536 [1148; 2064] vs. 1828 [1476; 2175] mL/min (P=0.674, about +300 mL/min), 6MWT 499.66±71.65 vs. 521.12±62.59 m (P=0.260, about +22 m), and right leg peak torque flexion 74±21.77 vs. 81.68±22.67 Nm (P=0.109) and extension 119.89±36.31 vs. 122.69±38.77 Nm (P=0.641). RHC showed no adverse acute hemodynamic effects, while invasively measured left ventricular systolic pressure decreased during hypoxia (151 vs. 120 mmHg). No changes in QoL were observed (P≥0.384). CONCLUSION:Ten-week IHHE was safe and feasible in HF patients and led to improved BP and body composition and showed trends toward better exercise capacity. Larger randomized trials are needed to confirm these results.
BACKGROUND:Right ventricular (RV) dysfunction (RVD) represents a power independent prognostic factor in patients with chronic heart failure (CHF); poor evidence exists about the effect of current guideline directed medical therapy on RVD.We investigated whether dapagliflozin improves right ventricular function, right ventricular-pulmonary arterial coupling and pulmonary artery systolic pressure compared with standard therapy in CHF. METHODS:This is a prospective observational registry with propensity score analysis investigating RV function and right heart failure(RIVED), focused on the effects of Dapagliflozin.Efficacy measures were intra and inter-groups changes from baseline to 6 months in RV end diastolic diameter(RVEDD), tricuspid annular peak systolic excursion(TAPSE), RV global longitudinal strain(RVGLS), fractional area changes(FAC), RV systolic tissue doppler wave(S'), PASP values,TAPSE/PASP,and tricuspid regurgitation(TR).Secondary endpoints were N-terminal pro B-type natriuretic peptide(NTproBNP) levels changes and combined adverse events rate of mortality and hospitalization at 180 days. RESULTS:The final population analysed was of 142 patients,in a balanced dataset consisting of 71 treated with standard HF therapy plus dapagliflozin(Dapa group) and 71 treated with standard therapy without dapagliflozin(control group).Median age was 78 [75-84] years old and 62% of patients were men. Patients in dapa group were younger(76[66-82] vs 82[74-88] years old;p<0.001) and more frequently affected by diabetes mellitus(44% vs 22%; p=0.002) compared to control group. No significant differences were observed between the two groups in terms of gender, renal function, NTproBNP and NYHA class.Over the 6 months follow-up,the Dapa group showed a significant improvement of RV function compared with controls(TAPSE +1.03 mm,p < 0.001 and S' +0.48 cm/s,p = 0.006); whereas no significant differences between-groups were observed for FAC(p = 0.16).RV GLS at follow-up was significantly improved in the Dapagliflozin group compared with controls(adjusted mean difference -1.54%, p < 0.001). as well as of the pulmonary-arterial coupling (TAPSE/PASP adjusted differences ranging from +0.07 to +0.17,p = 0.025).In patients with PH, a significant decrease in PASP(30[25-34] vs 37[31-45] mmHg,p<0.001) associated with a RVGLS significant improvement (-20 [-22 - -19] vs -19 [-20 - -17] p<0.001) in the Dapagliflozin group were observed.TAPSE/PASP ratio was significantly improved in Dapagliflozin group with respect to the control group(0.67[052-0.78] vs 0.51[0.42-0.61], p<0.001).Secondary endpoints analysis revealed that NT-proBNP levels were significantly improved from baseline to follow-up only in dapaglifozin group(from 938 to 726 pg/ml p = 0.013).The rate of 180-days adverse events was significantly higher in control group with respect to Dapaglifozin group(21% vs 8%, p<0.01). CONCLUSIONS:In a real-world HF cohort,dapagliflozin was associated with improved RV morphology and function, lower PASP,and better RV-PA coupling,suggesting a direct haemodynamic and RV-targeted benefit beyond LV remodelling.Trial Registration: (ClinicalTrials.gov Identifier: NCT06002321).
