BACKGROUND: Plant-based diets have been consistently associated with a lower risk of several individual cardiometabolic diseases (CMDs). However, whether such dietary patterns differentially influence the progression from health to first-occurrence cardiometabolic disease (FCMD), cardiometabolic multimorbidity (CMM), and ultimately mortality remains unclear. METHODS: The present study analyzed data from 83,610 participants in the UK Biobank cohort who were not diagnosed with diabetes, ischaemic heart disease (IHD), or stroke at baseline. Multi-state models were employed to examine the impact of plant-based diets on trajectories of cardiometabolic multimorbidity. RESULTS: During a median follow-up period of 15.61 years, the median age of the participants at baseline was 57 years (IQR: 50 years-62 years), 42.72% were male. 9298 participants developed at least one CMD, 1,045 participants progressed to CMM, and 4169 participants ultimately died. The finding of the multi-state model suggest that, compared with Q1, both the overall plant-based diet index (PDI)[HR (95%CI): 0.88 (0.83, 0.94) for baseline to FCMD, 0.85 (0.83, 0.94) for baseline to CMM] and the healthy plant-based diet index (hPDI) [HR (95%CI): 0.60 (0.41, 0.89) for baseline to FCMD, 0.79 (0.53, 1.17) for baseline to CMM] were negatively associated with the risk of transitioning from health to FCMD and CMM. When grouping FCMD into disease-specific analyses, it was found that the three plant-based indices also exerted differential effects on the transition from health to diabetes. CONCLUSION: In the progression of CMM, high adherence of PDI and hPDI has been demonstrated to reduce the risk of transitioning from CMD-free to FCMD, particularly in diabetes, and lowers the risk of CMM with a much lower incidence risk from CMD-free to CMM compared to CMD-free to FCMD. The present study hypothesizes that both hPDI and unhealthy plant-based index (uPDI) are associated with the risk from baseline to death.

Atherectomy devices have become a widely used tool to treat peripheral vessels in a variety of clinical situations. This trial assesses the efficacy, safety and clinical success of the Rotarex Catheter, a rotational athero-thrombectomy system, for the treatment of acute, subacute and chronic occlusions in peripheral arteries including native arteries, bypasses and in-stent restenosis, used alone or as an adjunctive tool. 220 patients were enrolled in this prospective, multicentre, single-arm study in Europe. Procedural success was measured after the index procedure. Freedom from major adverse events (MAEs), was collected through 30 days. Primary patency was collected at 1, 6, 12, and 24 months. Secondary outcomes included safety events, freedom from target lesion and vessel revascularization (TLR and TVR) and quality of life improvement. Procedural success of Rotarex with an adjunctive treatment was 94.1%. Primary patency was 87.2%, 68.1%, 57.8% and 49.1% at 1, 6, 12 and 24 months, respectively. Freedom from MAEs through 30 days was 96.3%. The MAE rate was 21.0%, 31.0% and 41.1% at 6, 12 and 24 months. Freedom from TLR was 97.7%, 81.0%, 72.0% and 64.3% at 1, 6, 12 and 24 months. Freedom from TVR was 95.8%, 79.0%, 69.9% and 62.3% at 1, 6, 12 and 24 months. Most subjects showed improvement in Rutherford Class and in the quality-of-life measures. These results show that Rotarex performs effectively and safely when it is being used as an adjunctive treatment in acute, subacute and chronic occlusions of native arteries, ISR and bypass.

Viral myocarditis (VM) is a cardiac inflammatory condition caused by viral infection and serves as a critical precursor to life-threatening complications, such as dilated cardiomyopathy and heart failure. Coxsackievirus B3 (CVB3), a predominant etiological agent of VM, lacks targeted therapeutic interventions despite ongoing antiviral development. Mitophagy is a selective mitochondrial quality control mechanism mediated by PINK1. It has two key roles: maintaining mitochondrial homeostasis and regulating innate antiviral immunity. Here, we employed single-cell RNA sequencing to reveal a significant correlation between impaired mitophagy and cardiomyocyte pathology in CVB3-induced myocarditis. We demonstrated that CVB3 infection suppresses PINK1-dependent mitophagy, while the attenuation of PINK1 reciprocally enhances CVB3 replication. Mechanistically, CVB3 non-structural protein 3C promotes the degradation of mitochondrial antiviral signaling protein (MAVS). MAVS interacts with PINK1 to form a regulatory loop: PINK1 deficiency boosts MAVS reduction, which further promotes viral replication and worsens myocardial injury. Furthermore, we identify the transcription factor FOSL1 as a novel negative regulator of PINK1 transcription through direct promoter binding. Collectively, these findings show that the 3C/FOSL1/PINK1/MAVS signaling axis is a key mechanism in CVB3 pathogenesis. We propose innovative therapeutic targets for viral myocarditis through restoration of mitochondrial homeostasis and modulation of host-virus interactions.

OBJECTIVES: Accurate mortality data for American Indian and Alaska Native (AI/AN) people are critical for describing health disparities and program planning needs. We describe the rates of leading causes of death among non-Hispanic AI/AN as compared with non-Hispanic White populations living in the same area, by sex and Indian Health Service (IHS) Area in 2020. METHODS: We used the 2020 US Cancer Statistics AI/AN Mortality Database and SEER*Stat software to calculate sex-specific age-adjusted death rates (per 100 000 population) for the 15 leading causes of death among non-Hispanic AI/AN and non-Hispanic White people in the United States overall (all areas combined), by IHS Area, and by age group. We restricted analyses to non-Hispanic AI/AN and non-Hispanic White people living in Purchased/Referred Care Delivery Area counties. RESULTS: Death rates were higher among non-Hispanic AI/AN people than among non-Hispanic White people in the United States overall (rate ratio = 1.90) and in every IHS Area (rate ratio range = 1.11-2.78). Death rates also varied by sex and age. Death rates were nearly 4 times higher among non-Hispanic AI/AN people than among non-Hispanic White people in the 25- to 44-year age group. Leading causes of death among non-Hispanic AI/AN males and females included COVID-19, heart disease, unintentional injury, cancer, and chronic liver disease. CONCLUSIONS: Death rates differed between non-Hispanic AI/AN and non-Hispanic White people by IHS Area, sex, and age when data corrected for racial misclassification were used. Our findings have important implications for guiding future public health practice to address disparities in mortality, particularly in the context of public health emergencies.

BACKGROUND: Left ventricular hypertrophy (LVH) is a serious complication of hypertension. However, the association between the nondipper heart rate (NDHR) and the risk of LVH remains unclear. METHODS: A cross-sectional analysis was conducted involving 991 patients with essential hypertension. NDHR was defined as a <10% reduction in nocturnal heart rate assessed by 24-h ambulatory blood pressure monitoring. Propensity score matching (PSM) was used to balance baseline characteristics. The independent association was assessed using multivariable logistic regression, and interactions were evaluated on multiplicative and additive scales. RESULTS: After exclusions, 991 eligible hypertensive patients were included, with 234 PSM pairs of nondipper and dipper participants achieving balanced baseline characteristics. The NDHR was independently associated with LVH after multivariable adjustment (OR = 1.588 [95%CI: 1.062-2.373];  = 0.024). A significant synergistic interaction was observed between NDHR and nondipper blood pressure, with the dual nondipper phenotype conferring the highest odds of LVH (OR = 2.52 [95%CI: 1.68-3.78]). Additive interaction measures confirmed biological synergy (RERI = 0.98; AP, 0.39). A nomogram incorporating NDHR demonstrated acceptable discrimination for LVH (AUC = 0.66 [95%CI: 0.61-0.71]) and provided superior net benefit across a wide threshold probability range (20%-80%). Subgroup analyses indicated stronger associations in younger patients and those not using ACEI/ARBs. CONCLUSION: NDHR is an independent risk factor for LVH and exhibits significant synergy with NDBP. Assessment of nocturnal heart rate decline, despite its behavioral confounders, may enhance cardiovascular risk stratification in hypertension.

OBJECTIVE: Phase II of MVP-CHAMPION, a federal collaboration between the Veterans Affairs Healthcare System (VA) and the Department of Energy (DoE), leveraged large-scale clinical, geo-spatial, and genetic data with state-of-the-art artificial intelligence (AI), and high-performance computing (HPC) to improve value in healthcare. MATERIALS AND METHODS: Eight clinical priority projects for which AI was a critical missing capability were initiated to address: lung cancer screening (MVP 061), suicide risk screening (MVP 062), cardiovascular risk in obstructive sleep apnea (MVP 063), checkpoint inhibitor toxicity (MVP 064), heart failure (MVP 065), renal complications in diabetes (MVP 066), post COVID-19 sequelae (MVP 067), and antipsychotic medication toxicity (MVP 068). RESULTS: Building on a strong regulatory and administrative foundation, we developed multimorbidity-aware analytic frameworks, reusable computational tools, and analytic pipelines. These greatly facilitated identification of novel risk factors including genetic variants and specification of more discriminating prediction models. Novel genetic risk factors are informing development and repurposing of medications and discriminating prediction models promise to improve healthcare value. DISCUSSION: The research foundation developed in Phase I and extended in Phase II of MVP CHAMPION has supported an unprecedented federal collaboration and yielded significant scientific advances. Our clinical findings are poised for near-term application, while advances in machine learning and high-performance computing may accelerate the broader adoption of artificial intelligence in healthcare. CONCLUSION: This maturing VA-DoE federal collaboration is poised to transform the future of Veterans' healthcare and the broader national landscape of precision health.

OBJECTIVE: To determine the proportion of patients with a persistent left superior vena cava (PLSVC) and structurally normal heart who have associated extra cardiac anomalies and/or genetic variations and to review their clinical outcomes. METHODS: A retrospective cohort study of foetuses with a prenatal diagnosis of PLSVC and structurally normal heart seen at Saint Mary's Hospital Foetal Medicine Unit Manchester, UK between January 2017 and December 2024. Outcome of the pregnancy and for the infants up to one year follow-up data was collected from Electronic Patient Records (EPR). RESULTS: Eighty cases of foetal persistent PLSVC were detected during the study period. Six were excluded from the study because of a postnatal diagnosis of congenital heart disease. 19 out of the 74 foetuses (25%) had associated extra-cardiac structural anomalies, with 5 of these diagnosed postnatally. Seven of the 74 patients (9.5%) had genetic abnormalities. CONCLUSIONS: This study shows that PLSVC detected in foetus with an otherwise structurally normal heart is associated with an increased risk of extracardiac and genetic abnormalities. Therefore, we would recommend a detailed anatomy scan by an FMU specialist in all cases. There is a notable incidence of genetic and chromosomal abnormalities, which suggests that genetic testing is warranted in this patient population.

AIMS: The natural history and response to tafamidis treatment in women with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) remain insufficiently characterised. Current study aimed to explore sex-differences in clinical presentation, natural course and tafamidis treatment efficacy, focusing on women with ATTRwt-CM. METHODS AND RESULTS: An international, multicentric cohort of ATTRwt-CM subjects was evaluated, including for all-cause mortality. In total 1454 patients were studied (mean age 81±7y), including 307 (21.1%) females. At presentation, females were ∼3 years older than males with slightly worse phenotype, including higher indexed left ventricular wall thickness and National Amyloidosis Centre (NAC) disease stage (p<0.050). Heart failure with preserved ejection fraction and hypertension coincided more often in women (p=0.001). Natural disease course was poor without sex-difference, even when age-corrected (p=0.210). Tafamidis was initiated in 1055 patients, 12% less in females (p<0.001), although reasons for non-initiation and discontinuation did not show heterogeneity by sex (p=0.116 and p=0.304, respectively), indicating structural undertreatment. After 1.9 (0.9-3.3) years of median follow-up, 409 (28.1%) patients died. Tafamidis related to lower mortality in the overall and propensity score-matched cohort (n=742, HR 0.44, 95%CI 0.32-0.61, p<0.001), without sex-difference (female HR 0.76, 95%CI 0.52-1.11, p=0.150) nor sex-based treatment efficacy interaction (p=0.381). NAC disease stages strongly related to mortality under tafamidis treatment (HR 2.13%, 95%, 1.81-2.50, p<0.001), but female sex did not (HR 0.82, 95%CI 0.53-1.27, p=0.365). CONCLUSIONS: Women with ATTRwt-CM are prone to underdiagnosis and undertreatment, despite similar poor natural course and tafamidis treatment efficacy. Initiatives to increase diagnostic awareness and disease modifying treatment initiation in women are urgently needed.

AIMS: Pressure overload-induced heart failure is a major cause of fatality in patients with heart diseases. At present, there exists no highly effective treatment for this incapacitating condition. Cardiolipin (CL) is a mitochondrial specific phospholipid that plays an essential role in cardiac health. Depletion of tetralinoleoyl CL (TLCL), the signature CL species, is implicated in human and animal models of heart failure. We investigated whether pathological CL remodeling by lysocardiolipin acyltransferase-1 (ALCAT1) promotes the progression of left ventricular (LV) hypertrophy induced by pressure overload by depleting TLCL in the heart and underlying molecular mechanisms. METHODS AND RESULTS: We identified a remarkable causative role of ALCAT1 in promoting the development of pressure overload hypertrophy in a mouse model of heart failure by transverse aortic constriction (TAC). We show that ALCAT1 expression in the heart is dramatically upregulated by TAC. Consequently, deletion or inhibition of ALCAT1 through targeted genetic manipulation or pharmacological intervention with Dafaglitapin (Dafa), a highly potent and specific small molecular inhibitor, effectively mitigates pressure overload hypertrophy and its related pathogenesis, including cardiomyopathy, cardiac dysfunction, inflammation, and fibrosis by preventing mitochondrial dysfunction in the heart. Furthermore, ablation or inhibition of ALCAT1 not only restores TLCL level, but also mitochondrial function and the related signal transduction pathways underlying these disorders, including mTORC1 signaling, oxidative stress, inflammation, and apoptosis in the heart of TAC mice. CONCLUSIONS: In summary, these findings identified ALCAT1 not only as a key mediator of mitochondrial etiology of pressure overload-induced heart failure, but also a novel drug target for hypertensive heart failure and Dafa as a potential treatment for the disorder.

Leptin is a hormone secreted by white adipose tissue that regulates food intake. However, leptin also modulates cardiovascular health. Obesity is characterized by elevated circulating leptin concentrations, which can cause leptin resistance, and increased risk of cardiovascular disease. However, the role of leptin sensitivity or leptin resistance in the pathogenesis of cardiovascular disease is unclear in humans. Overall, in vivo rodent studies indicate that factors to consider regarding the relationship between leptin and cardiovascular health are: 1) selective leptin resistance, where the effects of leptin are only impaired for certain outcomes, and 2) mosaic leptin resistance, where within a certain outcome, leptin signalling may only be impaired in certain tissues/cells. This is further complicated by sex-specific differences. In the current mini-review, the effects of leptin on the cardiovascular system, directly and via the central nervous system, are discussed.

BACKGROUND: Rheumatic mitral stenosis is commonly associated with left atrial enlargement and impaired flow, predisposing to thrombus formation. Left atrial thrombi increase the risk of systemic embolization and cerebrovascular ischemia. Antithrombotic therapy is essential to reduce embolic risk and to bridge patients to surgical valve intervention. CASE PRESENTATION: A 36-year-old woman with rheumatic mitral stenosis complicated by left atrial thrombi presented with multi-vessel occlusion within the cervicocephalic circulation, resulting in cerebellar infarction. Dual antithrombotic therapy was followed by partial recanalization, enabling successful mitral valve replacement. Postoperative anticoagulation was maintained and effectively prevented recurrence. CONCLUSIONS: This case highlights rheumatic mitral stenosis complicated by extensive cervicocephalic thromboembolism. The findings underscore the high embolic risk of left atrial appendage thrombosis in young patients. Dual antithrombotic therapy with rivaroxaban (anticoagulant) and aspirin (antiplatelet) was followed by partial recanalization and neurological stabilization, serving as a bridge to surgery. Delayed valve replacement after cerebral infarction minimized perioperative bleeding risk and ensured a favorable outcome. These findings emphasize the importance of individualized antithrombotic therapy and careful surgical planning in complex valvular disease.

BACKGROUND: Pw1, a maternally imprinted gene, is expressed in various stem cell populations, underscoring its crucial roles in tissue development, maintenance, and regeneration. While our recent work has revealed its regulatory function in cardiac fibrosis following ischemic injury, whether PW1 cells exhibit stem cell properties in the heart remains unclear. METHODS: We utilized genetic lineage tracing with Pw1;R26-tdT and Pw1;R26-tdT mouse models. The adipogenic and fibrogenic potential of PW1 cells was assessed in vitro using sorted tdTomato cells subjected to differentiation assays. In vivo fate mapping was performed during postnatal development and after myocardial infarction (MI) induced by permanent coronary artery ligation. Single-cell RNA sequencing data from adult mouse hearts were reanalyzed to characterize Pw1 expression across cardiac cell types. RESULTS: PW1 was expressed in multiple cardiac cell types-such as mesenchymal cells, epicardial cells, and endothelial cells-during early postnatal development. Isolated PW1 cells from infant hearts differentiated into adipocytes in vitro, and lineage tracing experiments confirmed their significant contribution to cardiac adipocyte formation throughout postnatal development. Single-cell transcriptomic analysis further revealed predominant Pw1 expression in adult cardiac fibroblasts. In vitro, adult PW1 cells differentiated into myofibroblasts upon TGFb1 stimulation and showed upregulated expression of extracellular matrix genes and TGFb receptors. After MI, PW1 cells preferentially expanded and contributed to the myofibroblast population within the infarcted region. CONCLUSION: This study reveals that PW1 cells serve as a progenitor population capable of generating cardiac adipocytes during postnatal development and contributing to myofibroblast formation after MI. These findings offer new insights into cardiac adipogenesis and fibrogenesis, providing a potential foundation for future therapies aimed at mitigating pathological adipose accumulation and fibrosis in the heart.

The decade from 2016 to 2026 has witnessed an extraordinary transformation in cardiometabolic medicine, propelled by the maturation of cardiovascular outcome trials (CVOTs). What began as regulatory requirements to establish cardiovascular safety for novel glucose-lowering agents has evolved into a robust body of evidence demonstrating profound cardiorenal protective effects-often extending beyond diabetes itself. Landmark trials such as EMPA-REG OUTCOME, LEADER, SELECT, SURPASS-CVOT, and VESALIUS-CV have not only redefined therapeutic priorities but have also catalyzed a conceptual shift from glucocentric management to an integrated cardiorenal metabolic (CRM) framework. This narrative review traces the epidemiological imperatives driving this evolution, chronicles the historical trajectory of CVOTs, synthesizes key findings across major pharmacological classes, and reflects on emerging therapies and risk markers that are shaping the precision-medicine paradigm of 2026.

OBJECTIVE: To evaluate the predictive utility of the initial lactate-to-albumin ratio (LAR) measured within 24 h of admission for in-hospital all-cause mortality in critically ill patients with congestive heart failure (CHF) and diabetes mellitus (DM). METHODS: A retrospective cohort study was performed using the Medical Information Mart for Intensive Care IV (MIMIC-IV; n = 960) and the eICU Collaborative Research Database (eICU-CRD; n = 1,850). Kaplan-Meier curves, Cox regression, restricted cubic splines (RCS), subgroup analyses, and five machine learning models were applied, with predictive performance assessed via receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA). RESULTS: The highest LAR quartile (Q4) was associated with higher in-hospital mortality (MIMIC-IV: 50.83%; eICU-CRD: 29.71%) than lower quartiles (all P < 0.001). LAR was identified as an independent predictor of in-hospital mortality (MIMIC-IV: HR = 1.878, P = 0.009; eICU-CRD: HR = 3.141, P < 0.001). A nonlinear positive association between LAR and in-hospital mortality was demonstrated by RCS (P < 0.001), with inflection points at 2.73 in MIMIC-IV and 2.50 in eICU-CRD. For both outcomes, higher discriminative performance was observed for LAR than for lactate alone in both cohorts. Model performance was further improved when incorporating into machine learning models. CONCLUSION: Initial LAR is a reliable predictor of in-hospital mortality in critically ill CHF-DM patients.

BACKGROUND: Frailty is common among patients undergoing maintenance haemodialysis (MHD) and is linked to multiple adverse outcomes, including increased mortality. However, large-scale cohort studies in China on the associations between frailty and major adverse cardiovascular events (MACE) as well as all-cause mortality in patients undergoing haemodialysis are lacking. This study aimed to investigate the associations between frailty and MACE and all-cause mortality in this population. METHODS: This single-centre retrospective cohort study enrolled patients on haemodialysis at the First Affiliated Hospital, Zhejiang University School of Medicine, from August 2020 to December 2021, with follow-up until August 31, 2025. Frailty status was assessed using the Fried Frailty Scale. Endpoints included the occurrence of all-cause mortality and MACE. A competing risk model was used to examine the associations between frailty and both MACE and all-cause mortality. Additionally, multidimensional sensitivity analyses were performed to assess the robustness of the findings. RESULTS: This study encompassed a cohort of 810 patients undergoing maintenance haemodialysis (MHD). The cumulative incidence of major adverse cardiovascular events (MACE) over five years was 33.0% (95% CI: 26.1-39.8%), while the cumulative incidence of all-cause mortality was 61.0% (95% CI: 53.4-68.7%). Both incidences were significantly elevated in the frail patient group compared to their non-frail counterparts (P < 0.001). Following multivariable adjustment, the Fine-Gray competing risk model revealed that frail patients exhibited a 4.96-fold increased risk of MACE (95% CI: 2.50-9.85; P < 0.001) and a 3.35-fold increased risk of all-cause mortality (95% CI: 2.10-5.35; P < 0.001), underscoring a significant positive association. Sensitivity analyses corroborated that frailty remained significantly associated with both MACE and all-cause mortality. CONCLUSION: Frailty demonstrated a significant correlation with an increased risk of MACE and all-cause mortality in patients undergoing MHD, with the risk escalating in a linear manner in accordance with the severity of frailty.