Journals
2025 EN
Celik Ahmet · Yesil Emrah · Kılıç Unal
+15 more
Abstract Introduction Early detection of heart failure (HF), particularly in asymptomatic individuals, is essential for timely intervention. This study aimed to determine the prevalence of HF among high‐risk individuals in primary care using N‐terminal probrain natriuretic peptide (NT‐proBNP) screening. Methods A prospective cohort of 874 participants aged ≥40 years with at least one HF risk factor but no prior HF diagnosis was analysed. NT‐proBNP levels were measured, and all participants underwent comprehensive cardiac evaluations, including laboratory tests, electrocardiography and echocardiography. Results The mean age of the cohort was 62.5 ± 9.1 years, and 51.9% were female. Based on ACC/AHA HF staging, 69.1% of participants were classified as Stage A, 21.9% as Stage B and 9.0% as Stage C. Elevated NT‐proBNP levels were detected in 84.8% of Stage B and 100% of Stage C patients. Among Stage C patients, 92.4% had HF with preserved ejection fraction (HFpEF). NT‐proBNP levels correlated positively with left atrial volume index ( r = 0.273, P < 0.001), left ventricular mass index ( r = 0.207, P < 0.001), E/e′ ratio ( r = 0.182, P < 0.001) and estimated systolic pulmonary artery pressure ( r = 0.124, P < 0.001), while showing a negative correlation with estimated glomerular filtration rate ( r = −0.222, P < 0.001). Conclusions A significant proportion of high‐risk individuals in primary care had undiagnosed HF, particularly Stage B (pre‐HF) and early symptomatic Stage C HF. The predominance of HFpEF highlights the need for targeted management. NT‐proBNP screening is a valuable tool for early identification and risk stratification, especially for detecting Stage B HF, where it serves as an effective standalone method in the absence of imaging.
Journals
2025 EN
Sayed Ahmed · Afify Hesham · Munir Malak
+7 more
Abstract Aims We sought to evaluate the prognostic value of different lipid parameters in patients with heart failure (HF). Methods and Results Electronic databases including MEDLINE, Embase, CENTRAL, and Web of Science were searched to identify studies that reported the association of any of the four lipid parameters [total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C) and triglycerides] with mortality among patients with HF. A random‐effects model was used to estimate the association per 10 mg/dL increment. The QUIPS tool was used to assess the risk of bias. Fifty‐two studies enrolling 93 286 patients were included. On univariable analysis, higher levels of the four lipid parameters were associated with lower mortality: TC [hazard ratio/odds ratio (HR/OR): 0.94; 95% confidence interval (CI): 0.93 to 0.96], HDL‐C (HR/OR: 0.89; 95% CI: 0.80 to 0.99), LDL‐C (HR/OR: 0.93; 95% CI: 0.90 to 0.97) and triglycerides (HR/OR: 0.95; 95% CI: 0.92 to 0.99). On multivariable analysis, lower levels of TC (HR/OR: 0.95; 95% CI: 0.93 to 0.97) and LDL‐C (HR/OR: 0.94; 95% CI: 0.89 to 0.99) were associated with lower mortality. Conclusions Higher levels of lipids parameters were associated with lower mortality in patients with HF. Lipid parameters may improve prognostication in predictive models for patients with HF. Because of the observational nature of included studies, no claims about the causal effect of changing lipid parameters can be made.
Journals
2025 EN
Ibrahim Ramzi · Nhat Hoang · Abdelnabi Mahmoud
+10 more
Abstract Aims Left ventricular assist devices (LVADs) are a critical intervention for advanced heart failure (HF), serving as destination therapy or bridge to transplantation. Obesity and diabetes impact outcomes in patients with LVADs. Glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) demonstrate cardiovascular benefits; however, their role in patients with LVADs remains underexplored. We evaluated the association of GLP1‐RA therapy with cardiovascular outcomes in patients with LVADs. Methods This retrospective cohort study used the TriNetX database, a research network database from 98 healthcare organizations. We queried for all adult LVAD recipients (≥18 years) and were stratified into GLP1‐RA users and non‐users. Propensity score matching (PSM) (1:1) balanced demographics, comorbidities, medication use and laboratory data. Outcomes included heart transplantation rates, heart failure hospitalizations, all‐cause mortality, all‐cause hospitalizations and cardiovascular events. Logistic regression models were used to estimate adjusted odds ratios (aOR). Results After PSM, we included a total of 1036 adult LVAD recipients (518 GLP1‐RA users, 518 matched non‐users) with a mean follow‐up time of 311.6 ± 98.4 days for the GLP1‐RA cohort and 304.0 ± 111.5 days for the non‐GLP1‐RAs cohort. Mean age was 56.7 ± 12.2 years in the GLP1‐RA cohort and 58.0 ± 12.5 years in the non‐GLP1‐RA cohort. Females comprised 28.0% of both cohorts while White patients represented 52.1% of the GLP1‐RA group and 53.1% of the non‐GLP1‐RA group. GLP1‐RA users had higher heart transplantation rates [ n = 98 (18.9%) vs. n = 44 (8.5%); aOR 2.514 (95% CI: 1.720–3.673)]. Acute HF events and all‐cause hospitalizations were lower among GLP1‐RA users compared with non‐users [ n = 288 (55.6%) vs. n = 357 (68.9%); aOR 0.565 (95% CI: 0.438–728) and n = 324 (62.5%) vs. n = 390 (75.3%); aOR 0.548 (95% CI: 0.420–0.716)]. No differences were observed when comparing the GLP1‐RA cohort with the non‐GLP1‐RA cohort in regard to all‐cause mortality [ n = 32 (6.2%) vs. n = 44 (8.5%); aOR 0.709 (95% CI: 0.442–1.138)], stroke [ n = 42 (8.1%) vs. n = 58 (11.2%); aOR 0.700 (95% CI: 0.461–1.062)] or cardiac arrest [ n = 18 (3.5%) vs. n = 17 (3.3%); aOR 1.061 (95% CI: 0.541–2.082)]. Conclusions GLP1‐RA therapy in patients with advanced HF and LVADs is potentially associated with improved heart transplantation rates while decreasing hospitalization and acute HF event rates.
Journals
2025 EN
Savage Henry Oluwasefunmi · Dungu Jason N. · Dimarco Anthony
+21 more
Abstract Aims To help avoid therapeutic inertia, we developed a pragmatic treatment score (QUAD Score) for use in daily practice by healthcare professionals managing patients with a left ventricular ejection fraction (LVEF) < 50% and heart failure. We now investigate the association between achieved QUAD scores and 1 year outcomes. Methods This was a multicentre cohort study in consecutive patients with incident heart failure and LVEF <50%, who completed therapy titration between January 2021 and June 2023. The primary outcome was a composite of first hospitalization for heart failure (HHF) and all‐cause mortality at 1 year after final therapy titration, for QUAD scores that were poor (<8), good (8–14) or excellent (15–24). Results Data were analysed from 1691 participants, collected from 10 UK centres, of whom 30% were women and 82% were White. Median age, N terminal pro‐B‐type natriuretic peptide (NTproBNP) and LVEF were 70 (59–78.5) years, 1624 (536–4138) ng/L and 34 (25–38) %, respectively. At the start of therapy titration, only 97 (5%) patients were naïve to any of the four pillars of therapy. After investigator‐declared final titration, QUAD scores were excellent in 806 (48%), good in 382 (22%) and poor in 503 (30%) patients. Patients who failed eventually to achieve a good or excellent QUAD score were more often women, older and had poorer renal function and higher plasma NTproBNP ( P < 0.01). The median number of days to final therapy titration was longer in those who achieved an excellent QUAD score, [174 (99–290) days,133 (80–232) days and 108 (57–193) days P < 0.01, for excellent, good and poor QUAD groups, respectively. There was wide variation in titration schedules across participating centres and overall, 33% of patients completed therapy titration within 90 days, 63% within 6 months and 88% within 1 year. The primary composite outcome at 1 year for those with poor, good and excellent QUAD scores were respectively 16.9%, 9.4% and 5.6%, (log rank P < 0.01), for mortality were 13.1%, 6.5% and 2.4% (log rank P < 0.001) and for first HHF were 7.7%, 3.9% and 3.2% (log rank P < 0.001). Conclusions The QUAD score is a simple tool that can help audit and incentivize uptake of guideline‐recommended therapy for HFrEF and prevent treatment inertia. Excellent QUAD scores are associated with better outcomes.
Journals
2025 EN
Pöss Janine · Jentzer Jacob · Desch Steffen
+11 more
Abstract Aims The Society for Cardiovascular Angiography and Interventions (SCAI) Classification provides risk stratification of patients with acute myocardial infarction complicated by cardiogenic shock (AMI‐CS). This sub‐study of the ECLS‐SHOCK trial investigates the prognostic impact of SCAI stages in AMI‐CS and the influence of SCAI stages on the effect of extracorporeal life support (ECLS) therapy in AMI‐CS patients. Methods Patients with AMI‐CS enrolled in the multicentre, randomized ECLS‐SHOCK trial were included. The outcomes, treatment effect and safety of ECLS were stratified according to SCAI stage at admission using a post‐hoc classification. Results From a total of 417 patients enrolled in the ECLS‐SHOCK trial between June 2019 and November 2022, 51.6% ( n = 215), 13.4% ( n = 56) and 35.0% ( n = 146) presented in SCAI Stages C, D and E, respectively. SCAI stages were associated with the risk of 30 day all‐cause mortality (C vs. D vs. E: 32.6% vs. 67.9% vs. 64.4%, P < 0.001), with rates of renal replacement therapy at 30 days (C vs. D vs. E: 7.0% vs. 19.6% vs. 13.7%, P = 0.03) and with poor neurological outcomes (C vs. D vs. E: 17.2% vs. 44.4% vs. 36.5%, P < 0.001). No interaction was observed between SCAI stage and the treatment effect of ELCS on 30 day all‐cause mortality (ELCS vs. control SCAI C: 32.7% vs. 32.4%; SCAI D: 68.4% vs. 66.7%; SCAI E: 59.7% vs. 68.4%, P for interaction = 0.65). Conclusions In AMI‐CS patients included in the ECLS‐SHOCK trial, SCAI stages at admission were predictive for mortality and for the incidence of safety events. The efficacy of ECLS treatment was not affected by SCAI stage.
Journals
2025 EN
Rosano Giuseppe M.C. · Teerlink John R. · Kinugawa Koichiro
+18 more
Abstract This clinical consensus statement revisits the role of left ventricular ejection fraction (LVEF) as a measurement of cardiac function, a prognostic marker and a major criterion to classify patients with heart failure, and gives new advice for clinical practice. Heart failure is traditionally classified on the basis of LVEF thresholds and this has major implications for treatment recommendations. However, the reproducibility of LVEF measurement is poor and its prognostic and diagnostic value lessens when it is above 45%, with no relationship with the severity of either cardiac dysfunction or outcomes at higher values. These limitations dictate the need for a more comprehensive approach to classify and assess heart failure focusing more on the trajectory of LVEF rather than to its absolute value. Furthermore, the assessment of LVEF is not required for the initiation of treatments like sodium–glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and diuretics in patients with suspected de novo heart failure and elevated N‐terminal pro‐B‐type natriuretic peptide levels. Future research utilizing advanced imaging techniques and biomarkers which can better characterize myocardial structure, metabolism and performance may facilitate the identification of alternative therapeutic targets and better ways to monitor heart failure therapies across the entire spectrum of LVEF.
Journals
2025 EN
Anker Stefan D. · Friede Tim · Butler Javed
+42 more
Aims Prior randomized trials have reported conflicting evidence regarding the efficacy of intravenous (IV) iron in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency (ID). Methods and results FAIR‐HF2 is a double‐blind, randomized, controlled trial evaluating the efficacy of IV ferric carboxymaltose in patients with HFrEF and ID. We report the baseline characteristics of enrolled patients and compare them with other major trials of IV iron in HFrEF (FAIR‐HF, CONFIRM‐HF, AFFIRM‐AHF, IRONMAN, and HEART‐FID). A total of 1105 patients were randomized between March 2017 and November 2023. Most patients were men (67%) and median age was 72 (interquartile range [IQR] 63–79) years. More than one‐third had a heart failure hospitalization within the preceding 12 months (36%), and 53% were hospitalized at randomization. Common comorbidities included hypertension (79%), coronary artery disease (74%), dyslipidaemia (67%), and diabetes (46%). The median left ventricular ejection fraction was 58% (IQR 42–77) and mean estimated glomerular filtration rate was 58 (IQR 42–77) ml/min/1.73 m 2 . A total of 1064 (96%) patients were on renin–angiotensin system inhibitors (angiotensin receptor–neprilysin inhibitors [ARNI] 38%), 1016 (92%) on beta‐blockers, and 779 (71%) on mineralocorticoid receptor antagonists; and 261 (24%) of patients were on sodium–glucose cotransporter 2 (SGLT2) inhibitors, which is much higher than prior trials. A higher proportion of patients had ischaemic HFrEF (78%) compared to preceding trials. The baseline median haemoglobin (g/dl) was 12.7 (IQR 11.8–13.4), median serum ferritin (μg/dl) was 63 (IQR 36–90), and median transferrin saturation (%) was 16.5 (IQR 11.8–22.9), resembling that of other trials. The mean 6‐min walk distance at enrolment was 314 ± 118 m. Conclusion The FAIR‐HF2 trial represents a contemporary cohort of patients with baseline characteristics mostly similar to prior trial populations. Use of SGLT2 inhibitors and ARNI in FAIR‐HF2 was higher than in prior trials. Clinical Trial Registration: ClinicalTrials.gov ID NCT03036462.
Journals
2025 EN
Karakas Mahir · Friede Tim · Butler Javed
+47 more
Abstract Aims Intravenous iron has emerged as a guideline‐recommended therapy in patients with heart failure and iron deficiency, but the potential sex‐related differences in efficacy are unknown. We aimed to assess sex‐specific outcomes in the Intravenous Iron in Patients with Systolic Heart Failure and Iron Deficiency to Improve Morbidity & Mortality (FAIR‐HF2‐DZHK05) trial. Methods and results FAIR‐HF2 included 1105 heart failure patients with a left ventricular ejection fraction ≤45% and iron deficiency. A total of 368 women (mean age 68.7 ± 13.0 years) and 737 men (mean age 70.5 ± 11.0 years) were randomized to intravenous ferric carboxymaltose or placebo. The three primary endpoints were (i) time to cardiovascular death or first heart failure hospitalization, (ii) total heart failure hospitalizations, and (iii) time‐to‐first event of cardiovascular death or heart failure hospitalization only in patients with transferrin saturation <20% at baseline. The hazard ratio (HR) for the first primary outcome was 1.07 (95% confidence interval [CI] 0.63–1.82, p = 0.80) in women and 0.74 (95% CI 0.57–0.95, p = 0.016) in men, while the rate ratios (RRs) for the second primary outcome were 1.06 (95% CI 0.55–2.05, p = 0.86) and 0.79 (95% CI 0.58–1.08, p = 0.136), respectively, and the HRs for the third primary outcome event were 1.21 (95% CI 0.62–2.36, p = 0.58) and 0.73 (95% CI 0.55–0.97, p = 0.028), respectively. Regarding safety outcomes, the HR for all‐cause mortality was 1.46 (95% CI 0.78–2.76, p = 0.24) in women, suggesting increased mortality risk under iron supplementation, in contrast to 0.86 (95% CI 0.64–1.16, p = 0.33) in men ( p for interaction = 0.13). Conclusions This analysis indicates relevant differential efficacy of intravenous iron in heart failure across both sexes. While men receiving ferric carboxymaltose experienced a clinically relevant reduction in cardiovascular death and heart failure hospitalizations, women did not derive similar benefits. The results are clinically relevant and prompt validation in other large outcome trials of intravenous iron supplementation in heart failure. Clinical Trial Registration: ClinicalTrials.gov NCT03036462.
Journals
2025 EN
Dyczko Aleksandra · CôrteReal Beatriz F. · Hamad Ibrahim
+2 more
ABSTRACT Regulatory FOXP3 + T cells (Tregs) have been characterized with unique metabolic demands, preferentially relying on fatty acid β‐oxidation (FAO) and oxidative phosphorylation (OXPHOS). Several studies have indicated that Treg mitochondrial fitness is crucial for maintaining their stability and suppressive activity with an emphasis on complex‐III of the electron transport chain (ETC). Dysfunctional Tregs isolated from patients with autoimmunity like multiple sclerosis (MS) show diminished mitochondrial respiration and the induction of a T helper (Th)1‐like phenotype, characterized by increased production of interferon (IFN)‐γ. Teriflunomide reduces the proliferation of activated T and B lymphocytes by inhibition of de novo pyrimidine synthesis, providing therapy for patients with autoimmune diseases. Recent data demonstrated that teriflunomide further inhibited complex‐III activity in line with hampered mitochondrial respiration in T cells. Considering the essential role of OXPHOS and complex‐III activity for Tregs, we therefore thought to investigate with this study the effects of teriflunomide on immunometabolism and function in human Tregs. Interestingly, teriflunomide impaired the mitochondrial function of human Tregs and further induced a Th1‐like phenotype in line with defective suppressive activity. Our findings suggest that teriflunomide may potentially exert distinct effects on pro‐ versus anti‐inflammatory T cell subsets, indicating the need for further detailed evaluation.
Journals
2025 EN
Joseph Reshma · Baby Haritha · Kaiprampattuparambil Gopi Aswathy
+9 more
Abstract Two‐electron oxidation of water to form hydrogen peroxide is an alternative approach to overcome the photon‐flux density problem as the bottleneck subject in artificial photosynthesis associated with molecular systems for photochemical water splitting. Tin‐porphyrin complexes show promising activity and selectivity for the two‐electron water‐oxidation pathway. A key aspect of the reaction mechanism of these systems is the attack of OH − /H 2 O to the activated axial oxygen atom as the reaction center of the one‐electron oxidized species to form O−O bond, which is feasible when an odd electron is localized on axial oxygen. DFT calculations show that the spin of the odd electron is mostly localized on the axial oxygen atoms when they are in deprotonated states; hence, their pKa determine the applicability of these systems under the pH conditions adopted. The milder pH conditions are most preferable. To explore the conditions the effect of various porphyrin ring substituents on the pKa of the protonation–deprotonation process in A4 and A3B tin‐porphyrin complexes have been studied here by spectrophotometric titration. Tetra‐fluorophenyl (Sn−F4), tetra‐chlorophenyl (Sn−Cl4), and tetra‐methoxycarbonylphenyl (SnTCPPMester)‐substituted Sn−A4 porphyrins have pKa1 values of 10.1 (Sn−F4), 9.8 (Sn−Cl4), and 6.7 (SnTCPPMester), which are in the increasing order of the electron‐withdrawing effect, ‐F (σ p =0.06)<‐Cl (0.23)<‐COOMe (0.45). For A3B (A=fluorophenyl or chlorophenyl, B=methoxycarbonylphenyl) Sn‐porphyrins, pKa1 shifts to the smaller value (Sn−F3Mester: 9.4, Sn−Cl3Mester: 6.6), improving the pH range of the active species from basic to ambient pH. This study shows how the pH range of the active species can be effectively tailored by choosing the meso‐substituents.