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Phys Ther Res. 2025;28(2):150-155. doi: 10.1298/ptr.25-E10341. Epub 2025 May 30.

ABSTRACT

OBJECTIVES: The need for early postoperative rehabilitation in patients with congenital heart disease (CHD) is increasing. However, rehabilitation settings in the pediatric intensive care unit (PICU) are usually determined subjectively by therapists. To address the lack of objective measurements, we sought to determine the effectiveness of near-infrared spectroscopy (NIRS) in evaluating skeletal muscles during rehabilitation of patients in the PICU. This case series aimed to clarify the characteristics of skeletal muscle oxygenation during exercise in 2 postoperative patients with CHD.

METHODS: The participants were two 6-month-female infant: one had undergone the Yasui operation (Case 1), and the other had undergone a bidirectional Glenn anastomosis (Case 2). Vital signs and tissue oxygen saturation (StO2) were measured during each exercise task, and the muscle oxygen extraction ratio (MOER), an index of the intramuscular oxygen extraction rate, was calculated. The results were compared between the two cases.

RESULTS: Case 1 showed no significant changes in vital signs, StO2, or MOER, whereas Case 2 had low oxygen saturation at rest and low StO2 during the exercise tasks. MOER increased during the exercise tasks.

CONCLUSIONS: The results showed that sitting did not impose a strong cardiopulmonary load on postoperative patients. However, in children with cyanotic cardiac disease, such as in Case 2, skeletal muscle oxygenation should be considered, and NIRS monitoring may be useful for safely performing rehabilitation.

PMID:40980345 | PMC:PMC12445354 | DOI:10.1298/ptr.25-E10341

Front Pediatr. 2025 Sep 4;13:1622729. doi: 10.3389/fped.2025.1622729. eCollection 2025.

ABSTRACT

Kawasaki disease (KD), or mucocutaneous lymph node syndrome, is a rare systemic inflammatory condition predominantly affecting children under 5 years of age. Complications such as giant coronary artery aneurysms, although rare due to advancements in treatment, remain life-threatening. Coronary artery bypass grafting (CABG) has been a well-established treatment for severe coronary lesions caused by KD. In rare cases of ischemic cardiomyopathy in pediatric patients, heart transplantation may be the only option. We report a case of a 15-year-old male with a history of KD diagnosed at 9 months of age, complicated by giant coronary aneurysms of the left anterior descending and right coronary arteries, who underwent a successful double CABG using the left internal mammary artery) and a saphenous vein graft.

PMID:40980138 | PMC:PMC12443707 | DOI:10.3389/fped.2025.1622729

Cureus. 2025 Aug 19;17(8):e90463. doi: 10.7759/cureus.90463. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: Esophageal atresia (EA) is a rare congenital anomaly frequently associated with congenital heart disease (CHD). This study aimed to evaluate the incidence and characteristics of cardiac anomalies in EA patients treated at a tertiary center in Saudi Arabia.

METHODS: A retrospective review was conducted at National Guard Health Affairs-Riyadh. Medical records of 87 patients diagnosed with EA between 2000 and 2023 were analyzed for EA type, syndromic associations, cardiac anomalies, and the need for cardiac interventions. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York).

RESULTS: Of the 87 patients, 75.9% had cardiac anomalies, which decreased to 42.5% when excluding patent ductus arteriosus (PDA) and patent foramen ovale (PFO). The most common EA type was Type C (80.5%). Syndromic diagnoses were identified in 17.3% of patients, with trisomy 21 being the most common. Cardiac anomalies were significantly associated with female gender (p = 0.013) and syndromic status (p = 0.007). Ventricular septal defect (VSD) and coarctation of the aorta were significantly more frequent in syndromic patients. Nine patients required cardiac intervention during the same admission. The need for cardiac intervention was significantly associated with syndromic status, suggesting that these patients may have more severe cardiac anomalies.

CONCLUSION: Cardiac anomalies excluding PDA and PFO occurred in 42.5% of EA patients. ASD and VSD were the most common findings. Syndromic and female patients had higher rates of cardiac anomalies and cardiac interventions. These results emphasize the need for thorough preoperative cardiac evaluation and multidisciplinary management in EA patients.

PMID:40978987 | PMC:PMC12444801 | DOI:10.7759/cureus.90463

J Cardiovasc Med (Hagerstown). 2025 Sep 1;26(9):477-486. doi: 10.2459/JCM.0000000000001757. Epub 2025 Aug 20.

ABSTRACT

AIMS: Bicuspid aortic valve (BAV) is a common congenital heart disease. However, pivotal randomized trials of transcatheter aortic valve replacement (TAVR) have excluded this population. There remains a lack of consensus on the optimal choice between balloon-expandible valves (BEVs) and self-expanding valves (SEVs) in this setting. This study aimed to compare the efficacy and safety of BEVs vs. SEVs in patients with BAV stenosis.

METHODS: A systematic search using four databases, including PubMed, Embase, Web of Science, and Cochrane CENTRAL, was conducted from inception to 26 November, 2024. Studies comparing the outcome of BEVs and SEVs in patients with BAV stenosis were included.

RESULTS: Nineteen studies comprising 3794 participants were included in this meta-analysis. Procedural mortality did not differ significantly between BEVs and SEVs [odds ratio (OR), 1.06; 95% confidence interval (95% CI) 0.42-2.69, P = 0.91]. Similarly, no differences were observed in all-cause mortality at 1 year or 3 years. BEVs were associated with a lower risk of permanent pacemaker implantation (OR, 0.60; 95% CI 0.48-0.76, P < 0.01) and moderate to severe paravalvular leakage (OR, 0.44; 95% CI 0.23-0.85, P = 0.01) compared with SEVs. However, BEVs were associated with a higher risk of annular rupture (OR, 2.80; 95% CI 1.05-7.49, P = 0.04).

CONCLUSION: BEVs and SEVs demonstrate similar survival outcomes from the procedural period up to 3 years of follow-up. However, the risk profiles for specific complications differ between the valve types. Valve selection for TAVR in patients with BAV stenosis should be considered based on individual anatomical characteristics and the associated risk of specific complications.

PMID:40977467 | DOI:10.2459/JCM.0000000000001757

Cardiol Young. 2025 Sep 22:1-5. doi: 10.1017/S104795112510958X. Online ahead of print.

ABSTRACT

OBJECTIVE: Contemporary management of aortic coarctation in adults is primarily by percutaneous intervention; however, this is not always possible. Intrapericardial ascending-to-descending aortic grafting is an alternative approach in adults with complex aortic coarctation. It can be performed off-pump and allows for a simultaneous treatment of concomitant cardiac lesions. Our aim was to examine the indications and the clinical long-term outcomes of intrapericardial ascending-to-descending aortic grafting in adults with aortic coarctation.

METHODS: We retrospectively reviewed demographic, clinical, surgical, and follow-up data of patients who underwent intrapericardial ascending-to-descending aortic grafting at a single tertiary centre between September 1994 and November 2016.

RESULTS: Ten patients were identified. Indications were primary intervention (n = 4), re-coarctation (n = 5), and iatrogenic coarctation of aorta after stent grafting (n = 1). There were no peri-operative deaths. During a mean follow-up of 13.6 ± 9.4 years, one patient died 11 years after surgery, unrelated to intrapericardial ascending-to-descending aortic grafting. All grafts remained patent with no anastomotic pseudoaneurysms at latest follow-up.The mean systolic blood pressure decreased from 154 ± 24 mmHg at baseline to 134 ± 20 mmHg at latest follow-up (p = 0.05), with the mean number of prescribed antihypertensive medications decreasing from 2.8 ± 1.5 preoperatively to 1.6 ± 0.5 (p = 0.11).

CONCLUSION: Intrapericardial ascending-to-descending aortic grafting is a safe and effective approach for adults with complex coarctation of aorta or re-coarctation not suitable for a percutaneous or conventional surgical approach. Improved blood pressure control and reduced anti-hypertensive use were observed long-term.

PMID:40977163 | DOI:10.1017/S104795112510958X

Cardiol Young. 2025 Sep 22:1-3. doi: 10.1017/S1047951125109566. Online ahead of print.

ABSTRACT

Coronary anomalies are a rare but potentially fatal congenital defect. Among high-risk anatomic features, totally anomalous origin of the coronary arteries from the pulmonary trunk is extremely rare, with only 57 cases reported in the literature as to our knowledge. We report a case of such a congenital anomaly with a successful surgical repair and good cardiac function recovery. We emphasise the need for awareness, since this anatomic presentation precludes collateral development and has, therefore, a higher mortality rate.

PMID:40977144 | DOI:10.1017/S1047951125109566

Med Sci (Basel). 2025 Sep 10;13(3):185. doi: 10.3390/medsci13030185.

ABSTRACT

Background: Mitral valve prolapse is a common valvular heart disorder, usually associated with a benign prognosis in the absence of significant mitral regurgitation. However, a subset of patients is at increased risk for complex ventricular arrhythmias and sudden cardiac death. Identifying these high-risk individuals remains a major clinical challenge. Case Summary: We present the case of a 71-year-old female patient with recurrent syncopal episodes, a strong family history of sudden cardiac death, and complex ventricular ectopy. Multimodality imaging revealed bileaflet mitral valve prolapse, severe mitral regurgitation, mitral annular disjunction, and the Pickelhaube sign, with no evidence of myocardial fibrosis on cardiac magnetic resonance imaging. The patient underwent minimally invasive mitral valve repair and received an implantable cardioverter-defibrillator for primary prevention of sudden cardiac death. Follow-up revealed significant reverse cardiac remodeling, marked reduction in arrhythmic burden, and restoration of mitral valve function. Family screening identified mitral annular disjunction in both of her daughters, who were asymptomatic and without arrhythmias. Discussion: Mitral annular disjunction has emerged as a potentially arrhythmogenic substrate, especially in patients with familial clustering, raising the possibility of a genetic predisposition. Risk stratification remains difficult, as no individual clinical, electrocardiographic, or imaging marker has demonstrated consistent predictive value. Surgical correction of mitral valve prolapse with associated mitral annular disjunction may lead to a reduction in arrhythmic risk and promote favorable structural remodeling. Conclusions: This case-based review emphasizes the importance of advanced imaging techniques in the identification and management of high-risk mitral valve prolapse phenotypes. Early surgical intervention and close arrhythmic surveillance may improve outcomes, although further research is necessary to define risk assessment tools and explore the genetic background of arrhythmogenic mitral valve disease.

PMID:40981183 | PMC:PMC12452400 | DOI:10.3390/medsci13030185

Eur Heart J Case Rep. 2025 Sep 6;9(9):ytaf441. doi: 10.1093/ehjcr/ytaf441. eCollection 2025 Sep.

ABSTRACT

BACKGROUND: Frequent premature ventricular contractions (PVCs) and valvular dysfunction are established contributors to worsening heart failure.

CASE SUMMARY: We present a 67-year-old male with dilated cardiomyopathy, severe aortic regurgitation, and unifocal left ventricle-originated PVCs (37.8% burden) refractory to guideline-directed medical therapy and cardiac devices. Due to high surgical risk, a combined transapical transcatheter aortic valve implantation and PVC ablation was performed. Postoperatively, PVCs were eliminated, left ventricular ejection fraction improved from 35% to 55%, and cardiac dimensions normalized significantly.

DISCUSSION: This case highlights the feasibility of a single apical approach for addressing both valvular and arrhythmic pathologies in high-risk patients, offering a novel strategy to mitigate heart failure progression.

PMID:40977933 | PMC:PMC12448879 | DOI:10.1093/ehjcr/ytaf441

Physiol Rep. 2025 Sep;13(18):e70544. doi: 10.14814/phy2.70544.

ABSTRACT

Chronic kidney disease (CKD) and valvular heart disease (VHD) frequently coexist and are associated with a significant increase in morbidity and mortality. Their interplay is complex and multifactorial, involving shared pathophysiological mechanisms such as chronic inflammation, mineral and bone disorder, vascular and valvular calcification, and neurohormonal activation. These factors contribute to a bidirectional relationship in which each condition can exacerbate the progression and clinical consequences of the other. This review provides a comprehensive synthesis of the current evidence on the epidemiology, pathogenesis, and clinical impact of the CKD-VHD association. Special attention is given to the mechanisms underlying valvular calcification in the uremic milieu, the diagnostic challenges posed by overlapping symptoms, and the prognostic implications of valvular disease in patients with impaired renal function. Furthermore, this paper critically examines the available therapeutic options, including medical management, surgical and transcatheter interventions, and their outcomes in CKD patients. Given the limited evidence from randomized controlled trials in this population, our work also identifies key knowledge gaps and highlights future research directions, advocating for multidisciplinary approaches and tailored strategies. A better understanding of this cardio-renal interaction is crucial to optimize clinical decision-making and improve patient outcomes.

PMID:40976977 | PMC:PMC12451019 | DOI:10.14814/phy2.70544

Intensive Care Med. 2025 Sep 22. doi: 10.1007/s00134-025-08111-9. Online ahead of print.

ABSTRACT

Mechanical ventilation is a life-sustaining treatment needed in patients with acute brain injury to maintain airway permeability, optimize gas exchange, and prevent secondary brain damage. Positive end-expiratory pressure (PEEP), a key component of mechanical ventilation, helps prevent atelectasis, improve oxygenation, and stabilize alveolar recruitment, offering potential benefits in terms of lung protection. However, neurological tolerance of PEEP can be poor in brain-injured patients. The variability in lung and chest-wall elastance, lung recruitability, cardiac function, and fluid status, as well as the integrity of cerebral autoregulation, further complicates the recommendations for the safe range of PEEP in this patient population. This review aims to explore the physiological effects of PEEP on the brain-heart-lung interplay, focusing on the direct and indirect influences of PEEP on intracranial and cerebral perfusion pressures, as well as cerebral perfusion. We also discuss the need for individualized mechanical ventilation settings to balance the respiratory benefits of PEEP against its potential adverse effects on cerebral perfusion.

PMID:40982016 | DOI:10.1007/s00134-025-08111-9

Circ J. 2025 Sep 20. doi: 10.1253/circj.CJ-25-0130. Online ahead of print.

ABSTRACT

BACKGROUND: Current guidelines recommend early revascularization in patients with cardiogenic shock (CS) following acute myocardial infarction (AMI). However, guideline-recommended first medical contact-to-device times is reportedly achieved in only 40% of patients.

METHODS AND RESULTS: We retrospectively analyzed 369 patients with AMI complicated by CS from the Kanagawa-Acute Cardiovascular Registry to evaluate factors influencing delays in treatment and their effect on in-hospital mortality. Patients were stratified into 2 groups based on the median door-to-cardiac catheterization laboratory (D2C) time (≤39 or >39 min). In the group with D2C time ≤39 min, the first-contact physician was more frequently a cardiologist (71.9% vs. 47.0%; P<0.001) and significantly more patients had chest pain as the chief complaint (70.3% vs. 47.4%; P<0.001). Although pre- and post-percutaneous coronary intervention Thrombolysis in Myocardial Infarction flow was similar between the 2 groups, in-hospital mortality was significantly lower in the D2C time ≤39 min group (18.8% vs. 37.6%; P<0.001). Multivariate logistic regression analysis revealed that D2C time >39 min was independently associated with a non-cardiologist being the first-contact physician, the absence of chest pain, a higher heart rate, and elevated creatinine levels.

CONCLUSIONS: D2C time ≤39 min is correlated with reduced mortality in AMI patients with CS. Implementing systems to ensure cardiologists are the initial responders and optimizing in-hospital workflows could reduce the D2C time and improve outcomes.

PMID:40976693 | DOI:10.1253/circj.CJ-25-0130

J Vasc Surg. 2025 Sep 19:S0741-5214(25)01765-3. doi: 10.1016/j.jvs.2025.09.033. Online ahead of print.

ABSTRACT

BACKGROUND: Frailty is increasingly recognized as a key driver of postoperative risk in vascular surgery. Yet the relative accuracy of the major frailty indices in a purely vascular cohort remains unclear.

OBJECTIVE: To compare the predictive accuracy of the Modified Frailty Index (mFI), Risk Analysis Index (RAI), Vascular Quality Initiative Frailty Index (VQI-FI), and VQI Procedure-Based Index (VQI-PBI) in predicting adverse postoperative outcomes in patients undergoing lower extremity revascularization.

METHODS: In this retrospective single-center cohort study, 193 patients who underwent open or endovascular lower extremity revascularization between January 1 and December 31, 2023, were included. Frailty scores were retrospectively calculated based on data available at the time of the preoperative evaluation. Primary outcomes were 30-day and one-year mortality and 30- and 60-day hospital readmission. Secondary outcomes included new dialysis within 30 days, and myocardial infarction. Statistical associations were evaluated using logistic regression models.

RESULTS: The cohort's mean age was 69.4 years, 32 % were female, and 74 % presented with critical limb ischemia. All four indices predicted 1-year mortality and initiation of dialysis within 30 days. The mFI, VQI-FI, and VQI-PBI also predicted 30-day readmission, but only the VQI scores were associated with 60-day readmission. The RAI was the only score associated with in-hospital mortality. The VQI-FI demonstrated the greatest number of statistical associations with good discriminatory ability.

CONCLUSIONS: Vascular specific frailty indices (VQI-FI and VQI-PBI) provide superior risk stratification compared to generic measures. Incorporating these tools into preoperative evaluation may improve patient selection and shared decision-making.

PMID:40976447 | DOI:10.1016/j.jvs.2025.09.033

Biol Pharm Bull. 2025;48(9):1412-1418. doi: 10.1248/bpb.b25-00185.

ABSTRACT

Adriamycin (ADR)-induced cardiotoxicity was previously shown to be attenuated by the preadministration of docetaxel (DOC-ADR), with DOC given 12 h before ADR, and may involve the inhibition of ADR-induced increases in free radical production in myocardial tissue. However, the mechanisms by which DOC suppresses the production of free radicals remain unclear. Therefore, we herein investigated the mechanisms responsible in more detail. The direct effects of DOC on free radical scavenging were examined using a primary cardiomyocyte culture system and the organic radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). To assess the indirect effects of DOC, in vivo components with radical-scavenging activities were measured after the administration of DOC. Cell viability did not improve in the DOC-ADR group, and was lower than that in the ADR group. Furthermore, DOC did not scavenge DPPH. The radical-scavenging activities of antioxidant enzymes did not significantly differ between the DOC-ADR and ADR groups. On the other hand, ceruloplasmin (CP) oxidase activity, which acts on iron ions and suppresses reactive oxygen species (ROS) production, showed a marked transient change that peaked at 12 h after DOC was given (just before the administration of ADR). Therefore, ADR-induced ROS production may have been suppressed by CP activity, which was increased by the preadministration of DOC.

PMID:40976695 | DOI:10.1248/bpb.b25-00185

J Card Fail. 2025 Sep 19:S1071-9164(25)00437-3. doi: 10.1016/j.cardfail.2025.08.021. Online ahead of print.

ABSTRACT

BACKGROUND: Microvascular inflammation (MVI) following heart transplantation can occur with or without circulating anti-HLA donor-specific antibodies (DSAs). We sought to characterize the relationship between MVI, with or without accompanying DSA, and post-transplant outcomes.

METHODS: We analyzed 8,305 endomyocardial biopsies (EMB) from 832 adult and pediatric HT recipients between July 1, 2013 and October 31, 2023. EMBs were graded by consensus guidelines, with MVI defined as pAMR grade ≥1. Rejection phenotypes were classified as no rejection, isolated cellular rejection (ACR), DSA-negative MVI, and DSA-positive MVI. Cox models with time-varying covariates were constructed to evaluate associations with incident CAV and mortality, adjusting for donor and recipient age.

RESULTS: Among 832 HT recipients, 238 developed CAV and 121 died over a median follow-up of 4 years (IQR 2.3-6.4 years). Compared with individuals who never experienced biopsy-proven rejection, DSA-negative MVI was independently associated with CAV (HR, 1.47; 95% CI 1.00-2.16; P-value = 0.047). DSA-positive MVI was associated with mortality (HR 1.97; 95% CI 1.07-3.64) with DSA-negative MVI demonstrating directional-concordance (HR 1.50, 95% CI 0.87-2.57), independent of CAV (HR 1.71, 95% CI 1.13-2.58). These associations remained consistent when stratified by adult and pediatric subgroups and in a six-month landmark sensitivity analysis.

CONCLUSIONS: MVI, with or without DSA, may be harmful in HT, extending recent renal findings to thoracic transplantation. Understanding the mechanistic basis for these results will be essential for identifying novel targets for therapeutic modulation and prolonging graft survival.

PMID:40976551 | DOI:10.1016/j.cardfail.2025.08.021

Can J Cardiol. 2025 Sep 19:S0828-282X(25)01171-7. doi: 10.1016/j.cjca.2025.09.019. Online ahead of print.

ABSTRACT

Just as sex differences have been well-described across the spectrum of heart failure care, there are important sex-specific considerations for heart transplantation (HT) candidates and recipients. Data persistently show that 25-30% of HT recipients are women, highlighting barriers in referral and waitlist selection. Furthermore, women are more likely to be allo-sensitized which may limit potential donors and increase their risk for antibody-mediated rejection in the post-transplant period. Data suggest differential risk by sex for long-term complications including rejection, cardiac allograft vasculopathy (CAV), post-transplant malignancy, and renal disease post-HT. Additionally, reproductive health for female transplant recipients including contraception, pregnancy, and breastfeeding requires complex multidisciplinary planning and considerations. The purpose of the current review is to summarize existing evidence and sex-specific considerations in post-HT management and clinical outcomes, highlight ongoing gaps in the literature and propose strategies for improving equity in access and post-HT outcomes.

PMID:40976383 | DOI:10.1016/j.cjca.2025.09.019

J Cardiovasc Magn Reson. 2025 Sep 19:101962. doi: 10.1016/j.jocmr.2025.101962. Online ahead of print.

ABSTRACT

BACKGROUND: Impaired right atrial (RA) function is strongly predictive of adverse outcomes in adults with pulmonary arterial hypertension (PAH) but remains incompletely understood in pediatric PAH. In this pediatric multicenter retrospective cohort study using cardiac magnetic resonance imaging (CMR), we analyzed RA size and phasic function and its associations with PAH severity.

METHODS: PAH and control pediatric patients from two centers who underwent CMR from 2010-2023 were identified. RA volumes were measured throughout the cardiac cycle using the single-plane, area-length method on a standard 4-chamber cine sequence. Total, conduit phase, and active phase stroke volume (SVi; indexed to BSA) and ejection fraction (EF) were calculated. A novel marker, the A/C ratio, was calculated as active/conduit SVi. RA size and phasic function measurements were correlated with clinical, hemodynamic, and non-RA CMR metrics of PAH severity and were associated with adverse events (Potts shunt, lung transplant listing/surgery, and/or death) using univariate and bivariate Cox proportional hazards regression analyses. Intra- and interrater reliability was analyzed using intra-class correlation coefficients (ICC).

RESULTS: Compared to controls (n=36), children with PAH (n=72) had higher RA volumes, lower conduit phasic function, and higher active phasic function. In PAH patients, minimum RA volume, active SVi, and A/C ratio directly correlated with NT-proBNP and right ventricular (RV) size, filling pressures, and afterload, while they were inversely correlated with exercise capacity and RVEF. RA conduit EF (cEF) correlations were reversed. During median follow-up of 3.2 years [IQR 1.0, 5.9], RA cEF and A/C ratio remained independent predictors of adverse events after adjustment for common metrics of PAH severity on bivariate analysis, including RVEF (RA cEF aHR 0.91 [95% CI: 0.83-0.99]; A/C ratio aHR 1.58 [95% CI: 1.09-2.29]) and indexed pulmonary vascular resistance (RA cEF aHR 0.83 [95% CI: 0.74-0.93]; A/C ratio aHR 1.79 [95% CI: 1.34-2.41]). RA volume measurements had excellent reliability (ICC >0.97).

CONCLUSION: Correlating with disease severity, impaired RA physiology in pediatric PAH is characterized by RA dilation, reduced conduit phasic function and compensatory augmentation of active phasic function. Assessment of RA size and phasic function is feasible and highly reproducible using standard CMR sequences.

PMID:40976452 | DOI:10.1016/j.jocmr.2025.101962

Clin Transl Sci. 2025 Sep;18(9):e70357. doi: 10.1111/cts.70357.

ABSTRACT

This study investigated the relationship between trimethylamine N-oxide (TMAO) levels and plaque instability in Chinese patients with ST-elevation myocardial infarction (STEMI) using optical coherence tomography (OCT), with a 7 -year follow-up. Between January 1, 2017, and December 31, 2018, 188 Chinese patients with STEMI who underwent OCT at the Second Affiliated Hospital of Harbin Medical University were enrolled. Patients were stratified into low TMAO (≤ 2.54 μM) and high TMAO (> 2.54 μM) groups. The primary endpoint was major adverse cardiovascular events (MACE: all-cause mortality, reinfarction, target vessel revascularization, and stroke). Compared with the low TMAO group, the high TMAO group showed a higher incidence of plaque rupture and a lower incidence of plaque erosion. Laboratory findings revealed significantly elevated NT-proBNP levels in the high TMAO group. OCT analyzes demonstrated greater plaque length and more frequent microchannels in the high TMAO group. During follow-up, both TMAO and NT-proBNP were independently associated with 7-year MACE. Receiver operating characteristic analysis identified TMAO as a predictor of MACE, with a sensitivity of 59.5% and a specificity of 65.8%. In conclusion, elevated TMAO levels were associated with adverse plaque characteristics and independently predicted long-term cardiovascular events in Chinese STEMI patients. These findings suggest that TMAO may serve as a valuable biomarker for assessing plaque instability and improving risk stratification in this population.

PMID:40973984 | PMC:PMC12449236 | DOI:10.1111/cts.70357

Int J Stroke. 2025 Sep 19:17474930251383626. doi: 10.1177/17474930251383626. Online ahead of print.

ABSTRACT

BACKGROUND: An in-hospital double-dose influenza vaccination strategy's effect on preventing major cardiovascular events (MACE) in patients with previous stroke is still uncertain. This study is a prespecified analysis of the vaccine against influenza to avoid cardiovascular events after the Acute Coronary Syndrome (VIP-ACS) trial.

METHODS: The VIP-ACS trial was a randomized, pragmatic, multicenter, open-label trial with blinded-adjudication endpoints. Adult patients with acute coronary syndrome (ACS) ≤ seven days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine or a standard-dose vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of all-cause death, myocardial infarction (MI), stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analyzed by the win ratio (WR) method. The secondary endpoint was a hierarchical composite consisting of CV death, MI and stroke (MACE). Patients were followed for 12 months each influenza season.

RESULTS: The trial enrolled 1,801 patients (31% female). A total of 67 patients had a history of stroke. There were no significant differences between groups on the primary hierarchical endpoint: 11.4% wins in the double-dose vaccine group vs 12.1% wins in the standard-dose vaccination group (WR:0.97; 95% CI:0.72-1.24; P=0.69) without a history of stroke. However, in-hospital double-dose vaccination favored individuals with previous stroke (WR:2.62; 95% CI:1.10-6.25; P=0.03; 43.9% wins vs. 16.8% wins). Results were consistent for hierarchical MACE (WR:3.01; 95%CI:1.15-7.88; P=0.02; 41.3% wins vs 13.7% wins) in favor of in-hospital double-dose vaccination.

CONCLUSIONS: After an ACS, in-hospital double-dose influenza vaccination prevents hospitalizations and death compared with standard-dose vaccination at 12 months in individuals with previous strokes.

PMID:40973981 | DOI:10.1177/17474930251383626

Cell Signal. 2025 Sep 18;136:112144. doi: 10.1016/j.cellsig.2025.112144. Online ahead of print.

ABSTRACT

When coronary reperfusion is delayed in myocardial infarction (MI), persistent ischemic injury induces progressive loss of cardiomyocytes, ultimately resulting in pathological ventricular remodeling and heart failure. Secreted proteins may play a critical role in modulating cardiomyocyte death following MI, offering potential therapeutic targets. This study elucidated the biological function of fibroblast-secreted ADAMTSL2 in cardiomyocyte apoptosis post-MI. Elevated ADAMTSL2 levels were detected by ELISA in the serum of acute myocardial infarction patients and by immunoblotting in the infarcted myocardium of mice. Hypoxia treatment significantly upregulated ADAMTSL2 expression in neonatal rat cardiac fibroblasts (NRCFs), whereas no such hypoxic response was observed in neonatal rat cardiomyocytes (NRCMs). In vitro, overexpression of ADAMTSL2 in NRCFs attenuated oxygen-glucose deprivation (OGD)-induced apoptosis in NRCMs, whereas knockdown of ADAMTSL2 in NRCFs exacerbated cardiomyocyte apoptosis. In vivo, fibroblast-targeted overexpression of ADAMTSL2 by adenovirus 5 significantly reduced cardiomyocyte apoptosis and ameliorated adverse left ventricular remodeling post-MI. Conversely, ADAMTSL2 knockdown exacerbated infarct size and accelerated pathological remodeling. Mechanistically, ADAMTSL2 overexpression increased the expression of β-catenin in cardiomyocytes. Co-immunoprecipitation (Co-IP) assay showed that ADAMTSL2 could directly bind to LRP6 and promote its phosphorylation, leading to β-catenin stabilization and subsequent nuclear translocation. In summary, our study indicates that ADAMTSL2 protects against cardiomyocyte apoptosis and promotes cardiac repair by activating LRP6/β-catenin signaling.

PMID:40975504 | DOI:10.1016/j.cellsig.2025.112144

Bioorg Med Chem. 2025 Sep 17;131:118395. doi: 10.1016/j.bmc.2025.118395. Online ahead of print.

ABSTRACT

Cardiac troponin I-interacting kinase (TNNI3K) is a cardiac-specific protein kinase, whose overexpression is closely linked to heart failure and ventricular remodeling. TNNI3K inhibitors regulate the phosphorylation of serine residues in downstream cardiac troponin I (cTnI) and affect the p38 pathway to prevent ventricular remodeling and myocardial cell damage. This study designed 120 compounds based on the reported quantitative structure-activity relationships (QSAR) of TNNI3K inhibitors. Following virtual screening, 4-azaindole was identified as the optimal scaffold. Subsequent synthesis of derivatives SK1-SK5 demonstrated their protective effects on damaged cardiomyocytes. Importantly, molecular dynamics (MD) simulations confirmed that compound SK5 forms a stable complex with TNNI3K and elucidated key binding residues and their interaction modes. These findings collectively validate the rational design of TNNI3K-targeted compounds and support SK5's potential as an anti-heart failure lead candidate.

PMID:40974855 | DOI:10.1016/j.bmc.2025.118395