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J Card Fail. 2025 Sep 28:S1071-9164(25)00428-2. doi: 10.1016/j.cardfail.2025.09.017. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies have suggested that patients with ischemic etiology of heart failure (HF) and iron deficiency may derive greater benefits with intravenous ferric carboxymaltose (FCM). We aim to assess the effects of FCM versus placebo in patients with ischemic versus non-ischemic etiology of HF.

METHODS AND RESULTS: The FAIR-HF2 trial included 1105 patients with HF, with a left-ventricular ejection fraction ≤45%, and concomitant iron deficiency. Patients were randomized 1:1 to either intravenous FCM or placebo. Ischemic etiology was defined as investigator reported or prior coronary revascularization or myocardial infarction. The primary endpoints were time-to-first event of cardiovascular death or HF hospitalization, total HF hospitalizations, and time-to-first event of cardiovascular death or HF hospitalization in patients with transferrin saturation <20% at baseline. Of 1105 patients, 858 (78%) had ischemic etiology of HF. These were more frequently older, men and had more co-morbidities. For the first primary endpoint, FCM was associated with a hazard ratio (HR) of 0.85 (95%CI: 0.66-1.10, p=0.23) for ischemic HF and 0.61 (95% CI: 0.39-0.98, p=0.038) for non-ischemic HF (P-interaction=0.26). The HR for the second primary endpoint was 0.87 (95% CI: 0.63-1.21, p=0.41) for ischemic HF and 0.57 (95% CI: 0.35-0.94, p=0.028) for non-ischemic HF (P-interaction=0.17), while HR for the third primary endpoint was 0.84 (95% CI: 0.62-1.14, p=0.27) for ischemic HF and 0.63 (95% CI: 0.37-1.07, p=0.087) for non-ischemic HF (P-interaction=0.35).

CONCLUSIONS: Effect of intravenous iron supplementation is likely similar in patients with ischemic or non-ischemic etiology of HF, just like other HF guideline-directed medical therapies.

PMID:41027507 | DOI:10.1016/j.cardfail.2025.09.017

JMIR Med Inform. 2025 Sep 30;13:e72237. doi: 10.2196/72237.

ABSTRACT

BACKGROUND: Planning for coronary artery bypass grafting (CABG) necessitates advanced spatial visualization skills and consideration of multiple factors, including the depth of coronary arteries within the subepicardium, calcification levels, and pericardial adhesions.

OBJECTIVE: This study aimed to address these requirements by reconstructing a dynamic cardiovascular model, displaying it as a naked-eye hologram, and evaluating the clinical utility of this innovative visualization tool for preoperative CABG planning.

METHODS: We used preoperative 4D cardiac computed tomography angiography (4D-CCTA) data from 14 patients scheduled for CABG to develop a semiautomated workflow. This workflow enabled time-resolved segmentation of the heart chambers, epicardial adipose tissue (EAT), and coronary arteries, complete with calcium scoring. Methods for segmenting cardiac structures, quantifying coronary calcification, visualizing coronary depth within EAT, and assessing pericardial adhesions via motion analysis were incorporated. These dynamic reconstructions captured spatial relationships, coronary stenosis, calcification, and depth in EAT, as well as pericardial adhesions. Dynamic cardiovascular holograms were then generated and displayed using the Looking Glass platform (Looking Glass Factory Inc). Thirteen cardiac surgeons assessed the utility of the holographic visualization tool on a Likert scale. In addition, a surgeon visually scored pericardial adhesions using the holograms of all 21 patients (including 7 undergoing secondary cardiac surgeries) and compared these scores with actual intraoperative findings.

RESULTS: Cardiac surgeons highly rated the visualization tool for its utility in preoperative planning, with a mean Likert score of 4.57/5.0 (SD 0.5). The hologram-based scoring of pericardial adhesions showed a strong correlation with intraoperative findings (correlation coefficient r=0.786; P<.001).

CONCLUSIONS: This study delineates the structural framework of a visualization tool specifically designed for preoperative CABG planning. It produces high-quality, clinically relevant, dynamic holograms from patient-specific volumetric data, with clinical feedback confirming its practicality and effectiveness for preoperative surgical planning.

PMID:41027031 | PMC:PMC12483336 | DOI:10.2196/72237

Ann Med. 2025 Dec;57(1):2566878. doi: 10.1080/07853890.2025.2566878. Epub 2025 Sep 30.

ABSTRACT

BACKGROUND: Multivessel coronary artery disease (MVD) often requires revascularization. However, the effectiveness of various techniques in reducing stroke and achieving complete revascularization remains uncertain. This study aimed to address this gap by comparing key revascularization strategies in terms of early mortality, stroke, complete revascularization, postoperative atrial fibrillation (POAF), and renal failure.

METHODS: This study is a systematic review and network meta-analysis of 32 studies including 65,861 patients. Five revascularization techniques were compared: on-pump coronary artery bypass (ONCAB), off-pump coronary artery bypass (OPCAB), OPCAB with proximal anastomotic device (OPCAB-PAD), anaortic OPCAB (anOPCAB), and percutaneous coronary intervention (PCI). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random effects model. Risk of bias was assessed using the RoB2 and ROBINS-I tools.

RESULTS: Compared to ONCAB, early mortality was significantly lower with anOPCAB (OR: 0.57, 95% CI: 0.44-0.73), OPCAB-PAD (OR: 0.61, 95% CI: 0.40-0.92), and OPCAB (OR: 0.64, 95% CI: 0.47-0.87). Stroke risk was lowest with anOPCAB (OR: 0.29, 95% CI: 0.21-0.40) and OPCAB-PAD (OR: 0.32, 95% CI: 0.21-0.49). All surgical techniques achieved significantly more complete revascularization than PCI. Both POAF and renal failure were significantly lower with anOPCAB compared to ONCAB (POAF: OR: 0.72, 95% CI: 0.59-0.89; renal failure: OR: 0.63, 95% CI: 0.46-0.86). No significant publication bias was detected for mortality and stroke, though funnel plot asymmetry was noted for revascularization.

CONCLUSION: Off-pump techniques, particularly anOPCAB, significantly reduce stroke risk while achieving comparable revascularization success to ONCAB. PCI remains limited by incomplete revascularization, supporting its use primarily in patients at high surgical risk.

PMID:41026043 | PMC:PMC12486457 | DOI:10.1080/07853890.2025.2566878

Curr Opin Cardiol. 2025 Nov 1;40(6):448-458. doi: 10.1097/HCO.0000000000001259. Epub 2025 Oct 2.

ABSTRACT

PURPOSE OF REVIEW: Stress perfusion cardiac magnetic resonance imaging (CMR) has gained increasing adoption across North America and Europe for the evaluation of symptomatic suspected or established ischemic heart disease (IHD).

RECENT FINDINGS: Over the past decade, stress perfusion CMR has demonstrated excellent diagnostic and prognostic performance, particularly in patients at intermediate or high risk of IHD or with established coronary artery disease (CAD). After the landmark ISCHEMIA trial, stress CMR may play an important role in selecting patients for invasive management strategies and determination of revascularization technique. Artificial intelligence has streamlined CMR scanning techniques and in-line automation of quantitative pixelated perfusion maps. Quantitative stress CMR can evaluate absolute myocardial blood flow and perfusion reserve that improves risk stratification and detection of coronary microvascular disease (CMD). CMD detection may assist clinicians with diagnosis of chest pain in patients without obstructive CAD and improve prognostication and detection of pathophysiological mechanisms in a variety of cardiomyopathies.

SUMMARY: Quantitative stress perfusion CMR will play an important clinical role in evaluating patients at risk of IHD and cardiomyopathy with iterative cost and time efficiency owing to continued integration of artificial intelligence techniques. More widespread adoption will likely improve cost effective cardiac care and reduce adverse clinical outcomes.

PMID:41025335 | DOI:10.1097/HCO.0000000000001259

Curr Opin Cardiol. 2025 Nov 1;40(6):390-394. doi: 10.1097/HCO.0000000000001252. Epub 2025 Sep 24.

ABSTRACT

PURPOSE OF REVIEW: Minimally invasive coronary artery bypass grafting (MICS CABG) offers the benefits of surgical revascularization without sternotomy but remains underutilized due to technical demands and a lack of structured training. This review outlines a stepwise framework for safe adoption.

RECENT FINDINGS: Studies and real-world experience confirm that off-pump CAB (OPCAB) proficiency, systematic technical progression, and mentorship in high-volume centers are essential for safe learning. Recent training innovations and simulator-based techniques improve outcomes and reduce complications during the learning curve.

SUMMARY: Wider adoption of MICS CABG hinges on structured training rooted in OPCAB, technical sequencing, and surgical mentorship. Programs emphasizing patient safety, proper case selection, and skill development can expand access to minimally invasive coronary surgery.

PMID:41025333 | DOI:10.1097/HCO.0000000000001252

Circ Cardiovasc Imaging. 2025 Sep 30:e018368. doi: 10.1161/CIRCIMAGING.125.018368. Online ahead of print.

ABSTRACT

BACKGROUND: Coronary computed tomography angiography (CCTA) could evaluate myocardial fibrosis as well by estimating extracellular volume fraction (ECV). While coronary microvascular dysfunction (CMD) has been increasingly recognized as an important pathophysiological mechanism underlying chest pain, the association between CMD in angina with nonobstructive coronary artery disease (ANOCA) and CCTA-derived ECV remains to be elucidated. We sought to evaluate the association between CCTA-derived ECV and CMD in patients with ANOCA.

METHODS: We retrospectively analyzed 57 patients with ANOCA from a single center who underwent CCTA on ECV protocol with subtraction method (including precontrast and 7-minute delayed postcontrast) and invasive functional testing using pressure-temperature sensor-tipped wire. Patients with significant epicardial stenosis (fractional flow reserve ≤0.80 or stenosis on computed tomography ≥50%), prior history of revascularization, known myocardial infarction, or heart failure were excluded. CMD was defined as a coronary flow reserve of <2.5 in any of the vessels evaluated. Standard transthoracic echocardiography assessed diastolic dysfunction (DD).

RESULTS: Among the 57 patients included, 26 (45.6%) were diagnosed with CMD. CMD was significantly associated with age, NT-proBNP (N-terminal pro-B-type natriuretic peptide) level, calcium score, DD, and higher ECV. In a multivariable logistic regression analysis, a CCTA-derived ECV >31.9% (the optimal cutoff value derived from receiver operating characteristic curve analysis) was independently associated with CMD (odds ratio, 10.50 [95% CI, 2.34-47.40]; P=0.002). DD also emerged as an independent predictor (odds ratio, 17.90 [95% CI, 2.53-127.00]; P=0.004). The addition of elevated ECV to a clinical model including DD significantly enhanced the discrimination efficacy for CMD (area under the receiver operating characteristic curve, 0.742 versus 0.854; P=0.019).

CONCLUSIONS: In patients with ANOCA with CMD, ECV was significantly elevated, alongside a higher prevalence of DD. These findings suggest that ECV and DD may serve as pivotal markers for personalized management strategies in patients with CMD with ANOCA disease.

PMID:41025226 | DOI:10.1161/CIRCIMAGING.125.018368

World J Cardiol. 2025 Sep 26;17(9):110061. doi: 10.4330/wjc.v17.i9.110061.

ABSTRACT

BACKGROUND: Stable angina pectoris, a clinical manifestation of coronary artery disease (CAD), is commonly evaluated using non-invasive diagnostic tools. Traditionally, stress testing modalities such as exercise electrocardiography (ECG), myocardial perfusion imaging (MPI), and stress echocardiography have been the first-line strategies. However, coronary computed tomography angiography (CCTA), an anatomic imaging modality, is increasingly used for its ability to directly visualize coronary artery stenoses and plaque burden. Despite growing adoption, the comparative effectiveness of CCTA and stress testing in terms of diagnostic accuracy, prognostic value, and clinical outcomes in stable angina remains an area of active debate.

AIM: To compare the diagnostic and prognostic performance of CCTA with various forms of stress testing in adult patients presenting with suspected or confirmed stable angina.

METHODS: A comprehensive literature search was performed across PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials in accordance with the PRISMA guidelines. Only randomized controlled trials (RCT) published in English within the last 15 years were included. Studies involving adult patients (≥ 18 years) with stable angina or low-risk chest pain were selected. The intervention was CCTA, and the comparators included ECG, MPI, and stress echocardiography. Data were extracted using a standardized process, and study quality was assessed using the Cochrane Risk of Bias 2.0 tool. Due to heterogeneity in outcome measures and modalities, narrative synthesis was employed.

RESULTS: Five high-quality RCTs encompassing a total of 5551 patients were included. CCTA demonstrated superior diagnostic accuracy and prognostic capability across multiple studies. It was more effective in predicting major adverse cardiac events, including myocardial infarction and cardiac death, and was associated with fewer unnecessary invasive coronary angiographies and better event-free survival. Studies also reported improved revascularization rates in patients evaluated with CCTA, particularly within tiered diagnostic protocols. Stress testing, while useful, showed limitations in sensitivity and downstream clinical decision-making.

CONCLUSION: CCTA offers a diagnostically superior and clinically impactful strategy for the initial evaluation of patients with stable angina, especially those with intermediate pretest probability of CAD. Compared to conventional stress testing, it enhances risk stratification, reduces unnecessary procedures, and may improve long-term outcomes. These findings support its broader integration into diagnostic pathways for stable angina.

PMID:41024970 | PMC:PMC12476583 | DOI:10.4330/wjc.v17.i9.110061

World J Cardiol. 2025 Sep 26;17(9):110220. doi: 10.4330/wjc.v17.i9.110220.

ABSTRACT

BACKGROUND: Peripheral endovascular intervention (PEVI) is performed using radiation. Radiation has deleterious health consequences for patients and operators.

AIM: To investigate the gender radiation disparities and procedural outcomes in PEVI.

METHODS: A prospective observational study was performed in 186 consecutive patients (65 ± 12 years) at an academic medical center from January 2019 to April 2020 (mean follow-up of 3.9 ± 3.6 months) comparing the gender radiation disparity and outcomes of PEVI (n = 147 underwent intervention, 79.0%). Groups were divided into women (n = 99, 53.2%) and men (n = 87, 48.4%). Primary endpoints included air kerma, dose area product (DAP), fluoroscopy time, and contrast use. Secondary endpoints included all-cause mortality, acute myocardial infarction, acute kidney injury, stroke, repeat revascularization, major adverse limb event, and the composite of complications.

RESULTS: Men showed increased DAP compared with women (15221.2 ± 25858.5 µGy × m2 vs 9251.7 ± 9555.3 µGy × m2, P = 0.047), but no significant difference in air kerma or any other primary endpoints. In the secondary endpoints, no significant difference was found between gender.

CONCLUSION: Men had increased DAP indicating more radiation absorption in the exposed area. Gender outcomes showed no difference in complications. Thus, PEVI can be safely performed in men or women.

PMID:41024969 | PMC:PMC12476585 | DOI:10.4330/wjc.v17.i9.110220

World J Cardiol. 2025 Sep 26;17(9):111044. doi: 10.4330/wjc.v17.i9.111044.

ABSTRACT

BACKGROUND: Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are well-established treatments for multivessel coronary artery disease (CAD), a condition where multiple heart arteries are narrowed. A newer approach, fractional flow reserve (FFR)-guided PCI, uses a specialized measurement to select which artery blockages to treat, aiming to enhance patient outcomes. Despite its adoption, the comparative effectiveness of FFR-guided PCI vs CABG remains unclear, particularly regarding key health outcomes such as survival, heart-related complications, and the need for further procedures.

AIM: To evaluate the safety and effectiveness of FFR -guided PCI compared to CABG in patients with multivessel CAD.

METHODS: This meta-analysis followed standard reporting guidelines and included randomized controlled trials (RCTs) comparing FFR-guided PCI with CABG in patients with multivessel CAD. We searched medical databases, including PubMed, EMBASE, ScienceDirect, and ClinicalTrials.gov, from their start to May 2025. We calculated combined risk ratios (RRs) with 95% confidence intervals (95%CIs) to analyze the data.

RESULTS: Three RCTs were analyzed. There was no notable difference in all-cause mortality between FFR-guided PCI and CABG (RR = 1.01, 95%CI: 0.78-1.31, P = 0.93). However, FFR-guided PCI showed higher rates of major adverse cardiac events (MACEs; RR = 1.30, 95%CI: 1.11-1.52, P = 0.001), myocardial infarction (RR = 1.49, 95%CI: 1.11-2.01, P = 0.009), and repeat revascularization (RR = 2.25, 95%CI: 1.78-2.85, P < 0.00001). Stroke rates were comparable between the two treatments (RR = 0.80, 95%CI: 0.54-1.20, P = 0.28).

CONCLUSION: FFR-guided PCI and CABG have similar rates of all-cause mortality and stroke in patients with multivessel CAD. However, CABG results in fewer MACEs, myocardial infarctions, and repeat procedures.

PMID:41024968 | PMC:PMC12476596 | DOI:10.4330/wjc.v17.i9.111044

World J Cardiol. 2025 Sep 26;17(9):110403. doi: 10.4330/wjc.v17.i9.110403.

ABSTRACT

BACKGROUND: Optical coherence tomography (OCT) offers detailed cross-sectional imaging during percutaneous coronary intervention (PCI), aiding in anatomically complex coronary lesions. Despite its advantages, evidence on the clinical effectiveness of OCT-guided PCI remains limited.

AIM: To compare clinical outcomes of OCT-guided vs angiography-guided PCI in patients with complex lesions.

METHODS: Major databases were systematically searched for randomized controlled trials (RCTs) comparing OCT-guided and angiography-guided PCI in complex lesions. Primary outcomes included major adverse cardiovascular events (MACE) and target vessel failure (TVF); secondary outcomes included mortality, myocardial infarction (MI), and other procedural outcomes. A random-effects model was used to pool risk ratio (RR), with 95%CI. Statistical analysis was conducted in R software (v4.4.1), with significance set at P < 0.05.

RESULTS: Five RCTs (5737 patients) showed OCT-guided PCI significantly reduced MACE (RR: 0.63, 95%CI: 0.52-0.77, P < 0.01), TVF (RR: 0.68, 95%CI: 0.56-0.83, P < 0.01), all-cause (RR: 0.58, 95%CI: 0.38-0.87, P < 0.01) and cardiac mortality (RR: 0.43, 95%CI: 0.24-0.76, P < 0.01), target-lesion revascularization (RR: 0.53, 95%CI: 0.33-0.84, P < 0.01), stent thrombosis (RR: 0.52, 95%CI: 0.31-0.86, P = 0.01), and target-vessel MI (RR: 0.64, 95%CI: 0.42-0.97, P = 0.04) vs angiography-guided PCI. Periprocedural MI, any revascularization, target-vessel revascularization, and contrast-associated kidney injury were similar between groups.

CONCLUSION: OCT-guided PCI improves outcomes in complex lesions by reducing MACE, TVF, mortality, stent thrombosis, and target-vessel MI. These findings highlight the need for further large-scale RCTs to confirm its benefits.

PMID:41024966 | PMC:PMC12476618 | DOI:10.4330/wjc.v17.i9.110403

BMC Cardiovasc Disord. 2025 Sep 29;25(1):700. doi: 10.1186/s12872-025-05186-6.

ABSTRACT

BACKGROUND: The European Society of Cardiology (ESC) recently endorsed low-dose colchicine for chronic coronary syndrome. However, its role in acute coronary syndrome (ACS) remains uncertain due to inconsistent trial outcomes. This systematic review and meta-analysis aimed to assess the efficacy and safety of colchicine in patients with ACS.

METHODS: A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted through April 2025 to identify randomized controlled trials (RCTs) evaluating colchicine in adults with ACS. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, stroke, myocardial infarction (MI), major adverse cardiovascular events (MACE), coronary revascularization, and gastrointestinal (GI) adverse events. Data were pooled using a random-effects model to estimate relative risks (RRs) with 95% confidence intervals (CIs), using the longest available follow-up.

RESULTS: Eleven RCTs encompassing 12,730 patients were included. Among them, 6,844 received colchicine for at least one month, while 5,886 received placebo or no additional treatment. Colchicine did not significantly reduce all-cause mortality (RR 0.95, 95% CI: 0.79-1.14) or cardiovascular mortality (RR 1.03, 95% CI: 0.82-1.29). No significant reductions were observed in MACE, MI, stroke, or coronary revascularization. Colchicine was associated with a non-significant trend toward increased GI adverse events, particularly at higher doses.

CONCLUSION: This meta-analysis does not support the routine use of colchicine in ACS management. While generally safe, colchicine did not confer clear cardiovascular benefits in this setting. However, potential subgroup effects, such as in longer-term use or among specific high-risk populations, warrant further investigation in future large-scale, well-designed trials.

PMID:41023831 | PMC:PMC12482528 | DOI:10.1186/s12872-025-05186-6

Nat Commun. 2025 Sep 30;16(1):8680. doi: 10.1038/s41467-025-63749-9.

ABSTRACT

Myocardial ischemia (MI), caused by insufficient blood supply, is a pathological condition where cardiomyocytes lack oxygen and energy supply. Herein, we developed a natural photosynthetic system (HCU) consisting of chlorella pyrenoidosa (C. pyre), hyaluronic acid methacryloyl (HAMA) and degradable upconversion nanoparticles (UCNPs, NaCeF4:Yb,Tm,Zr). Upon near-infrared irradiation, HCU was photo-crosslinked in situ, thereby facilitating C. pyre photosynthetic oxygen generation within the myocardium. Concurrently, cytochrome c oxidase (CCO) in mitochondria was activated to enhance electron transport along the respiratory chain, synergistically boosting cardiac energy metabolism. Consequently, the ATP levels were elevated, and the hypoxic microenvironment was mitigated. In MI mouse models, echocardiography readings returned to normal levels, and the infarct size was significantly reduced following a 7-day treatment with HCU. Based on the photosynthetic system, this study proposes an in situ oxygen and energy metabolic regulation strategy for MI, holding certain inspiration for other ischemia diseases.

PMID:41028003 | PMC:PMC12485038 | DOI:10.1038/s41467-025-63749-9

Neoreviews. 2025 Oct 1;26(10):e660-e678. doi: 10.1542/neo.26-10-060.

ABSTRACT

Congenital diaphragmatic hernia (CDH) presents a complex challenge in neonatal care, requiring tailored pharmacological strategies to manage its distinct cardiorespiratory pathophysiology. CDH is commonly associated with pulmonary hypertension, impaired myocardial function, and adverse cardiorespiratory interactions, contributing to significant morbidity and mortality. Effective pharmacotherapy must address these interconnected factors while minimizing complications or side effects. Despite limited randomized controlled trial data specific to CDH, recent reports highlight the benefits of a precision medicine approach, focusing on individualized treatments based on evolving pathophysiology. Therapeutic interventions primarily involve pulmonary vasodilators, inotropes and vasopressors, prostaglandins, and corticosteroids; each agent has a distinct physiologic effect, and use needs to be tailored to the specific patient pathophysiology. Targeted neonatal echocardiography has emerged as a valuable tool for optimizing treatment decisions by providing real-time insights into ventricular performance and hemodynamic status. In this review, we explore the shift from a generalized pharmacological approach to targeted interventions based on evolving patient physiology. We discuss key therapeutic principles and the role of different drug classes in optimizing the management of infants with CDH throughout their intensive care journey.

PMID:41027625 | DOI:10.1542/neo.26-10-060

Am J Cardiol. 2025 Sep 28:S0002-9149(25)00590-9. doi: 10.1016/j.amjcard.2025.09.035. Online ahead of print.

ABSTRACT

Alcohol's impact on cardiovascular health is biphasic: low-to-moderate intake may appear protective, but excessive or binge drinking causes significant harm. This review examines mechanisms linking overconsumption to cardiovascular disease. Acute heavy drinking can trigger "Holiday Heart Syndrome," a transient atrial arrhythmia from electrophysiological instability, autonomic imbalance, and electrolyte shifts. Chronic excess contributes to alcoholic cardiomyopathy via oxidative stress, mitochondrial dysfunction, and impaired calcium handling. Alcohol also promotes atrial fibrillation and hypertension by inducing atrial fibrosis, neurohormonal dysregulation, and endothelial injury. Excessive intake accelerates coronary artery disease and type 2 diabetes through dyslipidemia, vascular inflammation, and insulin resistance, raising risks of stroke, heart failure, and myocardial infarction. While moderate consumption was once thought cardioprotective, emerging evidence-especially for atrial fibrillation-suggests risks may outweigh benefits. In conclusion, public health guidance increasingly emphasizes moderation, individualized assessment, and avoiding binge patterns, particularly for those with underlying cardiovascular vulnerabilities.

PMID:41027502 | DOI:10.1016/j.amjcard.2025.09.035

Phytomedicine. 2025 Sep 23;148:157317. doi: 10.1016/j.phymed.2025.157317. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperlipidemia significantly exacerbates myocardial ischemia-reperfusion (I/R) injurfy through lipid metabolic dysfunction and lipotoxicity. Current evidence suggests that lipid droplet accumulation and impaired lipophagy represent critical pathological mechanisms underlying cardiac dysfunction in hyperlipidemic conditions. This study investigated the cardioprotective effects of asiaticoside (AS) against myocardial I/R injury in hyperlipidemic mice and elucidated its underlying mechanisms, emphasizing the AMPK/ORP8-mediated lipophagy pathway.

METHODS: Hyperlipidemic C57BL/6 mice were established using high-fat diet feeding and subjected to myocardial I/R injury. Mice received AS (12.5, 25, or 50 mg/kg) treatment for 4 weeks prior to surgery. In vitro experiments involved H9C2 cardiomyocytes treated with palmitic acid followed by hypoxia/reoxygenation. The role of AMPK/ORP8 signaling was evaluated using pharmacological modulators [AMPK activator (A-769662) and AMPK inhibitor (Compound C)] and genetic manipulation (ORP8 siRNA knockdown).

RESULTS: AS dose-dependently improved cardiac function parameters, reduced myocardial infarct size (LVEF and LVFS) and decreased triglyceride and cardiac injury biomarkers (cTnI, LDH, CK-MB) in hyperlipidemic I/R mice. Treatment with AS significantly reduced cardiac lipid accumulation and triglyceride content while enhancing lipophagy markers (LC3B-II and Beclin-1) and reducing p62 levels. Mechanistically, AS activated AMPK phosphorylation and upregulated ORP8 expression, which was accompanied by enhanced lipophagy flux. In H9C2 cells, AS protected against palmitic acid-induced lipotoxicity and H/R injury through AMPK/ORP8-dependent lipophagy activation. AMPK inhibition (Compound C) or ORP8 knockdown significantly attenuated AS's protective effects, while AMPK activation (A-769,662) potentiated these benefits, which were reversed to some extent by ORP8 silencing.

CONCLUSIONS: This study demonstrates that AS mitigates myocardial I/R injury in hyperlipidemic conditions by promoting lipophagy through the AMPK/ORP8 signaling axis. The AMPK/ORP8-lipophagy pathway represents a novel therapeutic target for metabolic cardiovascular diseases, and AS emerges as a promising cardioprotective agent with significant translational potential.

PMID:41027151 | DOI:10.1016/j.phymed.2025.157317

J Trace Elem Med Biol. 2025 Sep 26;92:127769. doi: 10.1016/j.jtemb.2025.127769. Online ahead of print.

ABSTRACT

BACKGROUND: Zinc is an essential nutrient implicated in cardiovascular health. This study investigates whether Zn2+ protects H9c2 cells by regulating mitochondrial biogenesis, dynamics, and calcium homeostasis via the mitochondrial calcium uniporter (MCU).

METHODS: The I/R model were established using simulated ischemia and reoxygenation as previous reported, and cells were then treated with MCU siRNA. Biochemical kits, inductively coupled plasma mass spectrometry (ICP-MS), RT-qPCR, and transmission electron microscopy were used to assess the effects of Zn2+ on cell viability, cytotoxicity, Zn2+ and ATP content, NAD⁺/NADH ratio, mtDNA copy number, and mitochondrial morphological changes following myocardial I/R. Confocal microscopy and fluorescence microscopy were used to observe the fluorescence changes of Zn2+, mitochondrial membrane potential, protein expression, and mitochondrial Ca2+. The effects of Zn2+ on protein expression levels were evaluated using molecular docking and Western blot analysis.

RESULTS: Compared to the Control group, the I/R group exhibited decreased cell viability, and increased cytotoxicity. Intracellular and mitochondrial Zn2+ levels were reduced, accompanied by mitochondrial dysfunction and an increase in mitochondrial Ca2+ content. The expression levels of mitochondrial biosynthesis proteins SIRT1, PGC-1α, NRF1, and TFAM, mitochondrial fusion proteins OPA1, MFN1, and MFN2, as well as MCUb gene and protein expression were downregulated. Conversely, the expression of mitochondrial fission proteins DRP1 and FIS1, along with MCU, MICU1, and MICU2 proteins, was upregulated. Exogenous Zn2+ treatment reversed these alterations. MCU silencing by siRNA further enhanced the protection effects of Zn2+.

CONCLUSIONS: I/R induced damage in H9c2 cells and mitochondrial dysfunction. Zn2+ protected H9c2 cells against I/R injury by regulating mitochondrial biogenesis, mitochondrial dynamics, and Ca2+ homeostasis via the MCU, with this protective effect potentially associated with the entire MCU complex.

PMID:41027049 | DOI:10.1016/j.jtemb.2025.127769

EuroIntervention. 2025 Sep 30:EIJ-D-25-00486. doi: 10.4244/EIJ-D-25-00486. Online ahead of print.

ABSTRACT

Coronary artery disease (CAD) is the leading cause of heart failure with reduced ejection fraction (HFrEF). Coronary artery bypass grafting (CABG) improves long-term mortality in HFrEF. Percutaneous coronary intervention (PCI) is often performed as an alternative to CABG in patients at high surgical risk. However, in patients with HFrEF and limited myocardial reserve, PCI may result in haemodynamic instability, increasing risk and precluding optimal revascularisation. Mechanical circulatory support (MCS) during high-risk PCI may enhance haemodynamic stability during the procedure and enable complete revascularisation. We thus performed the PROTECT IV trial to determine whether PCI with routine use of the Impella CP microaxial flow pump improves early and late outcomes in patients with HFrEF and complex CAD compared with PCI with or without use of an intra-aortic balloon pump (IABP). PROTECT IV is a prospective, multicentre, randomised, parallel-controlled, open-label, superiority trial with an adaptive design. Patients with complex CAD and left ventricular ejection fraction ≤40% (n=1,252) deemed at excessive surgical risk for bypass grafting by the Heart Team will be randomised in a 1:1 ratio to PCI with Impella CP versus PCI with or without an IABP. The primary endpoint is the composite of all-cause death, stroke, myocardial infarction, unplanned clinically driven revascularisation, durable left ventricular assist device implant or heart transplant, or other hospitalisation for cardiovascular causes at 3-year follow-up, with at least 1-year follow-up in all patients. Prespecified substudies will evaluate the impact of MCS on renal function, the procedural role of right heart catheterisation, and the utility of myocardial viability assessment. The PROTECT IV trial will determine whether routine MCS with Impella CP during high-risk PCI improves the prognosis of patients with complex CAD and HFrEF.

PMID:41024656 | DOI:10.4244/EIJ-D-25-00486

Eur J Med Res. 2025 Sep 29;30(1):903. doi: 10.1186/s40001-025-03144-8.

ABSTRACT

Myocardial infarction, a serious cardiovascular disease, is still a major cause of morbidity and mortality worldwide. Growth differentiation factor-15, a stress-responsive cytokine, has been involved in cardiac pathophysiology, but its exact role in myocardial infarction remains controversial. This study aimed to clarify the mechanisms underlying the cardioprotective effects of GDF-15 in myocardial infarction. By using a combination of in vivo and in vitro methods, including immunofluorescence staining, echocardiography, RNA sequencing, and high-resolution respirometry, we showed that GDF-15 expression is significantly upregulated in infarcted myocardium and its deficiency aggravates cardiac injury. Mechanistically, GDF-15 deficiency impairs mitochondrial function and energy metabolism under hypoxic stress, as evidenced by changes in mitochondrial membrane potential and respiratory parameters. Moreover, we identified that GDF-15 suppresses hypoxia-induced reactive oxygen species generation through activation of the AMPK signaling pathway. Therapeutic administration of exogenous GDF-15 reduces myocardial injury, hypoxic stress, and fibrosis after myocardial infarction, suggesting its potential as a therapeutic target. These findings collectively demonstrate that GDF-15 plays a crucial role in cardiac protection during myocardial infarction by regulating mitochondrial function, energy metabolism, and oxidative stress. Our results provide novel insights into the molecular mechanisms of GDF-15-mediated cardioprotection and suggest its potential as a therapeutic intervention for myocardial infarction. Future studies should focus on translational research to evaluate the clinical efficacy of GDF-15-based therapies in myocardial infarction patients.

PMID:41023695 | PMC:PMC12482560 | DOI:10.1186/s40001-025-03144-8

Br J Haematol. 2025 Sep 30. doi: 10.1111/bjh.70167. Online ahead of print.

ABSTRACT

Evolution of acute myeloid leukaemia (AML) treatments and transplantation procedures may affect outcomes after second haematopoietic stem cell transplantation (HSCT2) for relapsed paediatric AML. We analysed 345 paediatric patients reported to the European Society for Bone Marrow Transplantation (EBMT) registry for HSCT2 performed for AML relapse post-HSCT between 2000 and 2022. Multivariable analyses were adjusted for sex, age, transplant period, donor, disease status pre-HSCT2, cytogenetics, conditioning, total body irradiation (TBI) and post-first haematopoietic stem cell transplantation (HSCT1) remission duration. At three years leukaemia-free survival (LFS), overall survival (OS), non-relapse mortality (NRM), relapse incidence (RI) and graft-versus-host disease (GVHD)/relapse-free survival (GRFS) were 30.2%, 37.5%, 19.1%, 50.7% and 20.7% respectively. Compared with the 2000-2013 period, HSCT2 performed in 2014-2022 had better LFS (hazard ration [HR]: 0.66, 95% confidence interval [95% CI]: 0.48-0.90; 3-year: 34.3% vs. 26.3%), OS (HR: 0.60, 95% CI: 0.42-0.84; 3-year: 42.9% vs. 32.8%), RI (HR: 0.66, 95% CI: 0.46-0.98; 3-year: 46.0% vs. 54.7%) and GRFS (HR: 0.65, 95% CI: 0.48-0.90; 3-year: 25.3% vs. 16.1%) while NRM and GVHD incidence were stable. Relapse >6 months post-HSCT1 and remission pre-HSCT2 were associated with better LFS, OS and RI. Conditioning and cytogenetics did not influence outcomes. Mismatched unrelated donor negatively affected OS. These results highlight the improving survival after HSCT2 and support it in selected patients, particularly those relapsing later and in remission at HSCT2.

PMID:41027844 | DOI:10.1111/bjh.70167

J Card Fail. 2025 Sep 28:S1071-9164(25)00435-X. doi: 10.1016/j.cardfail.2025.09.021. Online ahead of print.

NO ABSTRACT

PMID:41027506 | DOI:10.1016/j.cardfail.2025.09.021