Blue Zones are geographically distinct populations characterized by exceptional longevity and remarkably low rates of cardiovascular disease. Although these regions differ culturally and environmentally, they share common lifestyle patterns, including habitual natural physical activity, predominantly plant-based diets, caloric moderation, strong social integration, stress reduction, and purpose-driven living. In this review, we examine the cardiovascular phenotype of Blue Zone populations and discuss the biologic mechanisms through which these lifestyle patterns may influence vascular aging, metabolic health, and longevity. We summarize emerging evidence linking Blue Zone-associated behaviors to improved endothelial function, reduced arterial stiffness, mitochondrial quality control, attenuation of chronic inflammation, and preservation of metabolic flexibility. Focus is placed on nutrient-sensing pathways involving adenosine monophosphate-activated protein kinase, Sirtuin 1, Forkhead box O signaling, and mTOR, as well as mechanisms related to autophagy, oxidative stress, inflammation, endothelial homeostasis, and cellular aging. We further review evidence regarding immune regulation, epigenetic aging, telomere stability, and longevity-associated biomarkers observed in centenarian populations. Finally, we discuss the translational implications of the Blue Zones framework for preventive cardiology and public health, including the development of culturally adaptable lifestyle interventions to extend health span and reduce the burden of cardiovascular and age-related disease.

Aim: This study aimed to develop and validate a multitask deep learning model, termed the information fusion model for single-photon emission computed tomography (SPECT)-based prognosis (IF-SPECT), for predicting all-cause mortality in patients with ischemic heart failure (IHF).

Methods: We retrospectively enrolled 356 patients with IHF who underwent resting-state SPECT myocardial perfusion imaging at Beijing Anzhen Hospital between 2017 and 2022. The cohort was divided into a training set (n = 213) and a validation set (n = 143). IF-SPECT uses a 3D U-Net backbone with a structure-aware module to simultaneously perform left ventricular segmentation (auxiliary task) and survival prediction (main task). A deep learning-derived risk score was generated from 3D SPECT images and then integrated with clinical variables (age, sex, body mass index, and NYHA_3_4) in the final prognostic model.

Results: IF-SPECT achieved the highest C-index in the validation cohort (0.724; 95%CI: 0.621-0.814), outperforming both the clinical and radiomics models in paired bootstrap testing. In the validation cohort, patients classified as high-risk by IF-SPECT had a significantly higher risk of all-cause mortality than those in the low-risk group (HR: 5.01; 95%CI: 2.17-11.59; P < 0.001). Exploratory subgroup analyses suggested that IF-SPECT further restratified patients within the low HM_TPD subgroup into distinct prognostic categories.

Conclusion: IF-SPECT provides a promising approach for prognostic risk stratification in IHF by combining a deep learning-derived imaging risk score with routine clinical variables.

Aim: The early initiation of guideline-directed medical therapy (GDMT) in patients with acute heart failure (AHF) is significantly associated with clinical prognosis. However, the optimal timing for initiating GDMT in AHF patients requiring Intensive Care Unit (ICU) admission remains unclear. This study aims to investigate the association between the timing of GDMT initiation and prognosis in ICU patients with acute heart failure.

Methods: This study identified ICU-admitted AHF patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and determined GDMT initiation timing based on clinical treatment context. Patients were categorized into three groups according to the timing of GDMT initiation. Primary endpoints were 1-year all-cause mortality and the composite endpoint of 1-year all-cause mortality and heart failure rehospitalization. Cox proportional hazards regression and restricted cubic splines were utilized to elucidate the association between GDMT initiation timing and long-term adverse outcomes in patients with acute heart failure.

Results: A total of 7,002 patients were included in this study, of whom 4,260 (60.7%) received GDMT within one day after AHF onset. Compared to patients who initiated GDMT between one and four days, those who received GDMT within one day and those who received GDMT after four days had a higher composite risk of one-year all-cause mortality and heart failure rehospitalization. The restricted cubic spline analysis demonstrated a U-shaped relationship between GDMT initiation timing and the primary outcome. The composite risk of one-year all-cause mortality and heart failure rehospitalization decreased as GDMT initiation was delayed, reaching its lowest point around two days, after which the risk began to rise and eventually stabilized.

Conclusion: In critically ill acute heart failure patients, a nonlinear U-curve relationship emerged between GDMT initiation timing and all-cause mortality. The optimal therapeutic window diverges across patient subgroups defined by clinical characteristics, notably warranting individualized timing strategies - particularly in geriatric populations.

Heart failure with preserved ejection fraction (HFpEF) represents a predominant heart failure phenotype characterized by intricate pathophysiology and an escalating global prevalence. Beyond classical hemodynamic disturbances, emerging evidence identifies mitochondrial dysfunction as a central mechanism in HFpEF pathogenesis. This review synthesizes the pivotal mitochondrial aberrations driving HFpEF, including impaired bioenergetics, disrupted mitochondrial quality control, oxidative stress, and Ca²⁺ dyshomeostasis, particularly under the burden of cardiometabolic stressors. Importantly, we highlight that HFpEF represents a multisystem disorder wherein the mitochondria of adipose tissue, the vasculature, the immune system, and skeletal muscle actively contribute to the pathological process. By reclassifying HFpEF as a bioenergetic failure, we hope to provide a conceptual framework for the development of integrated, mitochondria-targeted therapeutic strategies.

Aim: To examine the association between intravenous immunoglobulin (IVIG) use and in-hospital outcomes in adults with fulminant myocarditis (FM).

Methods: This two-center retrospective cohort study included 316 adults hospitalized with FM between January 2020 and January 2025; 184 received IVIG, and 132 did not. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were a composite of acute liver injury (ALI) or Kidney Disease: Improving Global Outcomes-defined acute kidney injury (AKI) and successful extracorporeal membrane oxygenation (ECMO) weaning with survival to discharge. We evaluated associations using multivariable and time-dependent Cox models, an analysis restricted to methylprednisolone-treated patients, propensity-score overlap weighting, Aalen-Johansen cumulative-incidence analyses, and Fine-Gray competing-risk models. Dose- and timing-related analyses were exploratory.

Results: In-hospital death occurred in 17 of 184 IVIG-treated patients (9.2%) and 51 of 132 non-IVIG-treated patients (38.6%). IVIG use was associated with lower mortality across multiple models, including the multivariable Cox model (hazard ratio [HR], 0.23; 95% confidence interval [95%CI]: 0.14-0.40; P < 0.001), the time-dependent model (HR, 0.15; 95%CI: 0.08-0.29), the methylprednisolone-treated cohort (HR, 0.15; 95%CI: 0.08-0.27), and the overlap-weighted analysis (HR, 0.24; 95%CI: 0.07-0.87). ALI/AKI occurred in 53 of 184 IVIG-treated patients (28.8%) and 72 of 132 non-IVIG-treated patients (54.5%; adjusted HR, 0.43; 95%CI: 0.30-0.61; P < 0.001). Among ECMO-supported patients, successful weaning with survival to discharge occurred in 50 of 61 IVIG-treated patients and 6 of 18 non-IVIG-treated patients (subdistribution HR, 5.89; 95%CI: 2.96-11.73; P < 0.001). Exploratory dose- and timing-related estimates did not establish an optimal IVIG regimen.

Conclusions: In this two-center retrospective cohort, IVIG use within a corticosteroid-containing care pathway was associated with lower in-hospital mortality, less ALI/AKI, and a greater likelihood of successful ECMO weaning with survival. Residual and unmeasured confounding preclude causal inference; prospective multicenter validation is required.

Aim: Deep learning has advanced medical artificial intelligence, but many electrocardiogram (ECG) records remain available only as paper-based documents. Scanned paper ECG images often contain grid lines, background artifacts, and unstructured waveform information, which limits their direct use for quantitative ECG analysis. This study aimed to develop an improved ECG image segmentation method for extracting clean ECG traces from scanned paper-based ECG records and supporting subsequent ECG signal digitization.

Methods: We proposed CU²-NeXt, an ECG image segmentation framework that extends U²-Net with ConvNeXt modules and incorporates convolutional block attention module (CBAM) to emphasize waveform-related features while suppressing background artifacts. Viterbi dynamic programming was subsequently applied to reconstruct continuous signal trajectories from the segmented waveform pixels.

Results: On the evaluated dataset, CU²-NeXt achieved a macro-F1 score of 88.9% and a Dice coefficient of 78.7%, with higher overlap-based performance than the evaluated baseline segmentation models.

Conclusion: These findings demonstrate the feasibility of using CU²-NeXt for ECG trace extraction and digitization from scanned paper ECG images. The proposed framework may provide a useful preprocessing approach for converting paper ECG records into analyzable digital signals and supporting downstream quantitative ECG analysis.

Aim: Aging is an irreversible primary risk factor for arteriosclerosis, causing high cardiovascular morbidity-mortality in the elderly via vascular remodeling and cellular senescence. Gut microbiota-derived short-chain fatty acids (SCFAs) exert cardiovascular protective effects, yet cross-species functional SCFAs counteracting age-related arteriosclerosis remain unclear. This study aimed to identify conserved SCFAs linked to vascular aging and validate caproic acid’s protective function against AngII-induced arteriosclerosis.

Methods: We assessed vascular aging phenotypes in young (8-week) and aged (24-month) mice and a human cohort (97 young < 65 years, 30 old ≥ 65 years). Serum SCFAs were quantified by targeted GC-MS. Correlation and mediation analyses evaluated relationships between caproic acid, pulse pressure (PP), and pulse wave velocity (PWV). Caproic acid protection was validated in AngII-induced arteriosclerosis mice and MOVAS cells.

Results: Circulating SCFAs declined with aging in humans and mice. Caproic acid and butyric acid were the two shared significantly down-regulated SCFAs. Serum caproic acid negatively correlated with human PP, and with both PP and aortic PWV in mice. Mediation analysis showed caproic acid directly ameliorated age-related vascular dysfunction. In AngII-treated mice, caproic acid reduced systolic blood pressure, PP and aortic PWV, mitigated aortic remodeling and elastic fiber damage, and suppressed vascular senescence protein upregulation. Gpr41 knockdown in MOVAS cells eliminated caproic acid’s anti-senescence effect, confirming GPR41-dependent protection.

Conclusion: Caproic acid acts as a conserved metabolite against age-related arteriosclerosis by inhibiting vascular cell senescence and improving hemodynamics, representing a promising therapeutic target for arteriosclerosis.

Aim: Persistent loss of cardiomyocyte contractile function is a major driver of cardiac dysfunction following myocardial infarction (MI). Long noncoding RNAs (lncRNAs) have emerged as important regulators of cardiac biology, yet their contribution to maintenance of myocardial contractility remains incompletely understood. To address this question, we investigated the role of the muscle-enriched lncRNA lnc-mg in cardiomyocyte contractility and its underlying molecular basis.

Methods: Ardiomyocyte-specific lnc-mg knockout mice were generated to investigate the physiological function of lnc-mg in the heart. Cardiac function, exercise capacity, myocardial tissue contractility, and single-cardiomyocyte contractility were assessed by echocardiography, treadmill testing, the Myostation-intact system, and the IonOptix platform, respectively. RNA-seq of myocardial tissue, bioinformatic prediction, RNA immunoprecipitation, molecular docking, immunofluorescence, and analysis of published cardiac MBNL1 CLIP-seq data were used to investigate the underlying molecular mechanism. Finally, Adeno-associated virus 9 (AAV9)-mediated overexpression of lnc-mg in cardiomyocytes was evaluated in a mouse model of MI.

Results:Lnc-mg was highly enriched in cardiomyocytes and progressively increased during postnatal cardiac development. Cardiomyocyte-specific deletion of lnc-mg impaired left ventricular systolic function, exercise capacity, and contractility at both the myocardial tissue and single-cardiomyocyte levels. Consistent with these functional abnormalities, lnc-mg deficiency was accompanied by coordinated suppression of gene programs governing sarcomere organization, myofibril assembly, actomyosin organization, and muscle contraction. MBNL1 was identified as an lnc-mg-associated RNA-binding protein. The nuclear localization of MBNL1 was reduced following lnc-mg deficiency, and MBNL1-bound cardiac transcripts are enriched for cardiomyocyte contractile gene programs. Importantly, AAV9-mediated lnc-mg overexpression in cardiomyocytes preserved cardiac systolic function, attenuated chronic fibrotic remodeling, and improved myocardial tissue contractility after MI.

Conclusion: Our study identifies lnc-mg as a previously unrecognized regulator of cardiomyocyte contractile function and suggests that an lnc-mg-MBNL1-associated mechanism may contribute to the maintenance of cardiac contractile gene programs. These observations provide a rationale for further investigation of lnc-mg as a potential therapeutic target for preserving myocardial contractility after ischemic injury.

Fulminant myocarditis (FM) is a rapidly progressive, life-threatening inflammatory cardiomyopathy requiring early recognition, mechanical circulatory support, and immunomodulation. We report a 41-year-old man with a 20-day prodrome of cough and fever who presented with severe dyspnea and biventricular dysfunction (ejection fraction 12%) with multiple left ventricular apical thrombi. Coronary angiography excluded obstructive disease, and influenza B IgM was positive. Intra-aortic balloon pump (IABP), methylprednisolone (200 mg/day), intravenous immunoglobulin (10 g/day), and anticoagulation were initiated. IABP was weaned on day 11, and cardiac magnetic resonance on day 13 confirmed left ventricular excessive trabeculation with persistent thrombi. Follow-up echocardiography on day 17 demonstrated complete thrombus resolution. The patient was discharged on day 19, and at 3-month follow-up, ejection fraction normalized to 51%. This case underscores that even severe FM with multiple left ventricular thrombi remains potentially reversible with aggressive multidisciplinary management.