Background Structural remodeling and atrial fibrosis are hallmarks of atrial fibrillation (AF), yet molecular alterations associated with atrial remodeling remain incompletely characterized, particularly their spatial distribution within human atrial tissue. Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI) enables spatially resolved metabolic profiling of tissue sections and may provide insight into metabolic alterations associated with atrial remodeling in AF. This study investigated whether DESI-MSI could identify distinct metabolic signatures in atrial tissue from patients with AF. Methods In this exploratory pilot study, atrial tissue samples from 10 patients undergoing cardiac surgery (4 with AF and 6 controls) underwent DESI-MSI analysis across an m/z range of 50–1200, followed by histologic assessment with hematoxylin–eosin staining. Metabolic profiles were analyzed using principal component analysis (PCA) and linear discriminant analysis (LDA) to explore group-specific metabolic patterns. Results Histologic evaluation demonstrated minimal fibrosis without significant differences between AF and control samples. In contrast, DESI-MSI identified distinct metabolic features associated with AF. Arachidonic acid (m/z 303.2) and phosphatidylinositol species (m/z 885.5) demonstrated spatial correspondence with myocardial architecture and contributed to metabolic separation between groups. Exploratory supervised multivariate analysis showed partial separation between AF and control spectra, while LD loading plots identified differential lipid-related ion patterns associated with AF samples. Conclusions In this exploratory pilot cohort, DESI-MSI demonstrated preliminary metabolic differences between AF and control atrial tissues despite limited histologic remodeling. These findings should be considered hypothesis-generating and will require validation in larger, adequately matched cohorts integrating metabolic, histologic, and clinical phenotypes. Although they do not establish that metabolic remodeling precedes fibrosis, they raise the possibility that DESI-MSI may detect metabolic differences in atrial tissue exhibiting minimal histologic remodeling.
Rheumatic heart disease (RHD) remains a major cause of maternal cardiovascular morbidity and mortality in low-resource settings, particularly among women of reproductive age. Physiological changes during pregnancy can unmask previously undiagnosed disease or precipitate decompensation in those with established valvular lesions. We present a case series of three women with RHD during pregnancy and the early postpartum period, highlighting the burden, clinical presentation, and management challenge in a resource-limited setting. All patients presented with advanced disease, including severe mitral stenosis, atrial fibrillation, and heart failure, with one case complicated by multivalvular involvement and reduced left ventricular function. Management focused on hemodynamic stabilization using diuretics, rate control, anticoagulation, and multidisciplinary care. Definitive interventions such as percutaneous balloon mitral valvotomy or valve replacement were indicated but deferred due to limited availability and financial constraints. All three mothers were clinically stabilized and remained alive at short-term follow-up, although one preterm neonate died from respiratory distress syndrome and Case 3 required readmission because of medication nonadherence. This series underscores the persistent burden of RHD in pregnancy in sub-Saharan Africa and highlights critical gaps in access to definitive cardiac interventions and anticoagulation monitoring. Strengthening health systems, improving access to specialized cardiac care, and implementing preventive strategies are essential to reduce morbidity and mortality associated with RHD in pregnancy in resource-limited settings.
Cardiovascular disease remains the leading cause of line-of-duty mortality among firefighters. Sudden cardiac death occurs disproportionately during emergency operations, particularly fire suppression, suggesting an interaction between occupational stressors and underlying cardiovascular vulnerability. This narrative review integrates epidemiologic, mechanistic, and clinical data from observational studies, systematic reviews, and contemporary cardiovascular guidelines. A structured literature search of PubMed and Google Scholar identified studies addressing cardiovascular disease, sudden cardiac death, occupational stress, and autonomic regulation in firefighters. Autopsy and case–control data indicate that most duty-related sudden cardiac deaths occur in the presence of underlying coronary atherosclerosis. Firefighters exhibit a high prevalence of cardiovascular risk factors, including hypertension (10%–44%), obesity (14%–60%), dyslipidemia (20%–56%), and metabolic syndrome (∼22%); these rates exceed those reported in age-matched general-population samples. Emergency operations are associated with marked sympathetic activation, hemodynamic stress, and circadian perturbation, which may promote plaque destabilization, myocardial ischemia, and ventricular arrhythmia. Additionally, occupational stress and sleep disturbance are linked to autonomic imbalance, potentially increasing arrhythmic susceptibility. Sudden cardiac death in firefighters reflects the interaction between baseline cardiometabolic risk and intermittent high-intensity physiologic stress rather than a distinct occupational disease entity. Early risk identification, guideline-directed therapy, and recognition of occupational stressors are central to cardiovascular risk reduction in this population.
Background Depression and frailty are prevalent geriatric syndromes. Their co-occurrence may define a phenotype of heightened cardiovascular disease (CVD). In Latin America the joint association of these syndromes with CVD has not been previously characterised. Objective To evaluate the association between the overlap of depression and frailty and the prevalence of CVD in older adults. Methods A cross-sectional analysis was conducted using data from the 2015 SABE Colombia study. Adults aged ≥60 years with complete information on depression, frailty, and history of acute myocardial infarction or stroke defined as CVD were included. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using bivariate and multivariate log-binomial regression models. Results 18,973 participants were analysed (mean age 69.3 ± 7.1 years; 56% women). The prevalence of depression, frailty, and CVD was 57.3%, 3.5%, and 15.4%, respectively. In bivariate analyses, depression (PR 1.83, 95% CI 1.51–2.23), prefrailty (PR 1.61, 95% CI 1.50–1.73), and frailty (PR 2.91, 95% CI 2.57–3.28) were associated with CVD. In multivariate model, the overlap of depression and frailty demonstrated the strongest association with CVD (PR 4.86; 95% CI 3.37–7.01), exceeding that of depression with prefrailty and each condition individually. This association persisted after adjustment for traditional cardiovascular risk factors (PR 2.05, 95% CI 1.05–3.97). Conclusion In older adults, the overlap of depression and frailty remained associated with a higher prevalence of CVD after adjustment for traditional cardiovascular risk factors. Although the association was attenuated after adjustment, the coexistence of both conditions remained associated with increased cardiovascular burden.
Objective:This study investigates gender disparities in clinical outcomes among patients with systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH), focusing on cardiovascular events, right ventricular function, and survival. Introduction:PAH is a severe and life-threatening complication of SSc, with male patients often experiencing worse outcomes despite its higher prevalence in women. Comparative data on gender differences in this population remain limited. Methods:We conducted a retrospective, single-center study including 61 patients with SSc-associated PAH (52 women, 9 men), confirmed by right heart catheterization. Clinical, serological, pulmonary, and echocardiographic data were analyzed. Differences between sexes in cardiovascular events, right ventricular dilation, and survival were evaluated using appropriate statistical methods. Results:Male patients had a significantly higher incidence of cardiovascular events (median: 2.00 vs 1.00 in women; P = .031) and a greater prevalence of right ventricular dilation (100.00% vs 44.23%; P = .002). Kaplan-Meier analysis demonstrated reduced cardiovascular event-free survival (P = .001) and overall survival (P = .014) in men. Although mortality was higher in men (88.89%) than in women (57.69%), the difference was not statistically significant (P = .134). Conclusion:Men with SSc-associated PAH experience worse clinical outcomes, including more frequent cardiovascular events and reduced survival. The absence of estrogen's protective effects and the adverse influence of testosterone on cardiac remodeling may contribute to these disparities. These findings highlight the importance of early gender-specific risk stratification and the need for tailored therapeutic strategies to improve outcomes in this high-risk group.
Background Sodium-glucose transporter 2 (SGLT2) inhibitors have shown significant cardiovascular benefits in heart failure (HF) patients with diabetes mellitus or chronic kidney disease. However, their safety and efficacy in non-diabetic patients without HF presenting with acute myocardial infarction (AMI) remain understudied. Methods Databases including MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.gov were queried through August 2025 to identify randomized controlled trials (RCTs). Data were pooled using a random-effects model using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). Results Five RCTs involving 9,135 patients (SGLT2i: 4,581 and placebo: 4,554) were included. On pooled analysis, SGLT2 inhibitors were associated with significantly reduced first HF hospitalization (RR: 0.74, p=0.02), improved LVEF (MD: 2.08; p=0.002), and reduced NT-proBNP levels (MD: 12.81; p < 0.0001). No significant differences were noted in all-cause mortality and the composite of first HF hospitalization with all-cause mortality. Conclusion In non-diabetic patients without HF, SGLT2 inhibitors significantly reduce the first HF hospitalization and improve LVEF following AMI. The findings of this meta-analysis suggest that future research should evaluate the cardiovascular benefits of SGLT2 inhibitors in this patient population.
Aim: To evaluate the efficacy and safety of the HeartMate 3 (HM3) left ventricular assist device (LVAD) as a destination therapy (DT) for patients with end-stage heart failure (HF) ineligible for transplantation, from a Peruvian healthcare perspective. Methods: A health technology assessment (HTA) was conducted, which included a systematic review of clinical effectiveness and safety, complemented by a critical appraisal of relevant evidence. Searches were performed in 3 databases, complemented by manual searches in HTA organizations and clinical practice guidelines (CPGs) repositories. The search included CPGs, HTAs, randomized clinical trials (RCTs), and high-quality observational studies evaluating LVADs for DT. Cost-effectiveness analyses and device costs specific to the Peruvian context were also reviewed. Results: All the CPGs supported the use of the HM3 LVAD, emphasizing its significant survival benefits demonstrated in primary studies. The HM3 showed a 5-year survival rate exceeding 50%, compared to 25% at 1 year and 8% at 2 years with optimal medical therapy (OMT). Functional and quality of life outcomes also improved significantly. However, common adverse events included bleeding and infections. Cost-effectiveness analyses from high-income settings indicated that the HM3 exceeded conventional willingness-to-pay thresholds but highlighted its critical clinical benefits for high-risk patients with no alternative therapies. Conclusion: The HM3 LVAD offers significant survival and quality of life improvements for patients with end-stage HF ineligible for transplantation. Despite challenges in cost-effectiveness, the adoption of the HM3 as DT in Peru is justified to address a critical unmet clinical need, provided robust medical device surveillance is implemented.
Background Obstructive hypertrophic cardiomyopathy (HCM) is defined by left ventricular hypertrophy with outflow tract obstruction. Despite clear guideline-directed medical therapy recommendations from the European Society of Cardiology (ESC), it remains unclear whether real-world treatment aligns with these guidelines. This study evaluates adherence to ESC guidance in Germany, focusing on pharmacological and invasive therapies and identifying gaps in real-world care for patients with obstructive HCM. Methods A retrospective cohort analysis was conducted using the WIG2 Benchmark database, containing administrative claims data from German statutory health insurers. Patients aged ≥18 years who received an International Classification of Diseases (ICD)-coded diagnosis of HCM between 2012 and 2018 were included. Treatment alignment was assessed against ESC guidelines on HCM. Results Of 6793 patients with an HCM diagnosis, 1141 had obstructive HCM. Mean age was 59.7 years and 62% were male. Following initial HCM consultation, 18% received beta-blocker (BB) monotherapy and 12% received calcium channel blocker (CCB) monotherapy, in accordance with ESC guidelines. However, 43% of treatment combinations were not aligned with the ESC guidelines, including use of contraindicated dihydropyridine CCBs and vasodilating BBs, and 22% of patients did not receive any HCM-related pharmacological treatment. Overall, only 57% of the prescribed treatments were consistent with ESC guidelines for obstructive HCM management. Conclusions This study reveals substantial gaps in alignment with the ESC guidelines for obstructive HCM management in Germany, underscoring the need for enhanced clinician education on existing therapies. Greater uptake of guideline-directed medical therapy is critical to improving patient well-being, functional status and outcomes.
Coronary computed tomography angiography (CCTA) is widely used for noninvasive evaluation of coronary artery disease (CAD) and is highly sensitive for detecting anatomic coronary stenosis with a high negative predictive value. However, CCTA is limited in its ability to determine the physiological significance of lesions, resulting in reduced specificity and disagreement with invasive coronary angiography in a substantial proportion of cases. Fractional Flow Reserve derived from CCTA (FFR-CT) was developed to address this anatomic–physiologic discordance by providing noninvasive, lesion-specific functional assessment of ischemia. This narrative review summarizes the current state of FFR-CT technology, its diagnostic performance relative to CCTA alone and invasive FFR, and its evolving role in contemporary CAD evaluation. Across prospective trials and meta-analyses, FFR-CT consistently improves diagnostic accuracy for ischemia-producing lesions, driven primarily by gains in specificity, with favorable agreement to invasive FFR at clinically relevant thresholds. Advances in computational modeling and machine learning have substantially reduced processing times, improving feasibility and workflow integration. Clinical studies demonstrate that incorporation of FFR-CT following CCTA improves selection for invasive coronary angiography, reduces unnecessary diagnostic catheterization, and provides prognostic information beyond anatomic disease burden alone. Important limitations remain, including dependence on CCTA image quality, reduced reliability in heavily calcified or complex coronary anatomy, and uncertainty near ischemic thresholds, necessitating careful interpretation within the clinical context. When applied selectively after high-quality CCTA, FFR-CT offers a robust noninvasive surrogate for invasive coronary physiology and supports a more targeted, physiology-guided diagnostic pathway for patients with suspected CAD.
Tirzepatide is a first-in-class, once-weekly dual GIP and GLP-1 receptor agonist approved for type 2 diabetes and obesity. Given the tight link between hyperglycemia, adiposity, and cardiovascular disease, tirzepatide has rapidly gained interest as a broader cardiometabolic intervention. This narrative review summarizes mechanistic rationale and clinical evidence on cardiovascular risk-factor modification, cardiorenal signals, and outcome data. Across the SURPASS program in type 2 diabetes, tirzepatide produces large, dose-dependent reductions in HbA1c and substantial weight loss, with consistent benefits versus active comparators. In obesity, the SURMOUNT trials showed marked and durable weight reduction over long follow-up, with clinically relevant improvements in waist circumference, blood pressure, triglycerides, and inflammatory biomarkers. Beyond weight and glycaemia, available data suggest favorable effects on lipids, ambulatory blood pressure, inflammatory markers, and kidney-related endpoints in exploratory analyses. Tirzepatide also improves obstructive sleep apnea severity in adults with obesity. Regarding cardiovascular outcomes, SURPASS-CVOT supports cardiovascular safety by demonstrating noninferiority versus dulaglutide for 3-point major adverse cardiovascular events in patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD). In obesity-related HFpEF, SUMMIT shows reductions in worsening heart failure (HF) events and improvements in health status, supporting a phenotype-specific role in HF. Overall, tirzepatide is emerging as a key therapeutic option for integrated cardiometabolic risk reduction, with ongoing research needed to define its incremental benefit versus established GLP-1 receptor agonists, long-term effectiveness in routine care, and optimal positioning across HF phenotypes.
Pulmonary atresia with ventricular septal defect and systemic-to-pulmonary collateral supply is a severe conotruncal malformation characterized by complete right ventricular outflow tract obstruction, a large ventricular septal defect, and absence of a main pulmonary artery. Without surgical repair, survival into adulthood is rare and depends on the adequacy of collateral pulmonary blood flow. Pregnancy in women with unrepaired cyanotic congenital heart disease carries extreme maternal and fetal risk and is classified as modified World Health Organization class IV when resting oxygen saturation is below 85%. We report a 22-year-old woman at 32 weeks’ gestation who presented with progressive dyspnoea, severe hypoxaemia (oxygen saturation 74%), and heart failure. Echocardiography demonstrated a large perimembranous ventricular septal defect and pulmonary atresia. Cardiac computed tomography confirmed an overriding aorta, non-confluent pulmonary arteries arising from the descending thoracic aorta and aortic arch, and absence of a main pulmonary trunk, establishing the diagnosis of pulmonary atresia with ventricular septal defect and systemic-to-pulmonary collateral supply. She underwent caesarean delivery for maternal decompensation, complicated by postpartum haemorrhage requiring hysterectomy. Ten days postpartum, she developed an acute ischaemic stroke. Telemetry excluded atrial fibrillation, and imaging showed no intracardiac thrombus. She improved with antiplatelet therapy and supportive care and remained clinically stable at six-month follow-up. This case highlights the rare survival of unrepaired complex cyanotic congenital heart disease into adulthood, the extreme risks of pregnancy in this setting, and the need for preconception counselling, multidisciplinary management, and vigilant postpartum thromboembolic risk assessment, particularly in resource-limited settings.
Cardiovascular diseases remain the leading cause of global mortality, necessitating precise strategies for diagnosing and managing myocardial injury. This review critically synthesizes the current biomarker landscape and proposes an integrative framework to address the significant translational gaps between biomarker science and clinical practice. We conducted a comprehensive critical review, analyzing established and emerging biomarkers, including cardiac troponins, natriuretic peptides, and inflammatory and fibrotic markers, within the context of biological confounders, etiology-specific challenges, and clinical implementation barriers. Through thematic synthesis, we developed the novel C.A.L.I.B.R.A.T.E. framework to structure biomarker integration. While high-sensitivity assays have improved detection, they reveal chronic elevations in conditions like renal dysfunction, aging, and heart failure, reducing specificity and complicating acute diagnosis. Emerging biomarkers (eg, sST2, galectin-3) offer prognostic insight but lack therapeutic guidance and specificity. Etiology-specific puzzles (eg, myocarditis, COVID-19, MINOCA) highlight the limitations of isolated biomarker interpretation. The C.A.L.I.B.R.A.T.E. framework addresses these gaps by integrating Clinical context, Assay characteristics, Likelihood, Injury mechanism, Biomarker profiles, Rule-out/in thresholds, Adjunctive tests, Time kinetics, and Etiologies & comorbidities. The future of myocardial injury management depends on shifting from isolated biomarker measurement to integrated, algorithm-driven interpretation. The C.A.L.I.B.R.A.T.E. framework provides a structured pathway for personalized diagnostic reasoning, bridging the translational chasm and advancing precision cardiology through context-dependent, multi-modal data synthesis.
Cardioembolic stroke primarily results from thromboembolism caused by cardiac conditions such as atrial fibrillation, characterised by high recurrence rates, high rates of disability, and high mortality. Anticoagulation therapy is a key measure for the prevention of stroke recurrence, though the timing of its initiation remains debated, requiring a balance between the risk of thromboembolic recurrence and the risk of bleeding. The widely adopted “1-3-6-12-day rule” is based on expert consensus but lacks support from high-level evidence. In recent years, multiple randomized controlled trials (such as TIMING, ELAN, OPTIMAS, and START) have demonstrated that for patients with mild-to-moderate cardioembolic stroke, early initiation (within 2–4 days after stroke) of direct oral anticoagulants (DOACs) is not only safe but also significantly reduces the risk of early recurrence, without increasing the incidence of symptomatic intracranial hemorrhage. In particular, the recently completed individual participant data meta-analysis (CATALYST) has provided robust evidence for early anticoagulation. Unlike previous reviews that have focused solely on the timing of anticoagulation in non-valvular atrial fibrillation, this review provides a critical appraisal of the evidence gaps for severe stroke and post-reperfusion populations, a practical comparison of individual DOACs to guide drug selection, and a summary of management principles for other cardioembolic sources (mechanical valves, infective endocarditis, patent foramen ovale, left ventricular thrombus, and atrial flutter). This review summarises the pathophysiological mechanisms of cardioembolic stroke, clinical strategies for anticoagulation timing, characteristics of different anticoagulant agents and their indications for use. It emphasises the importance of individualised treatment and indicates that future research should further clarify the optimal timing of anticoagulation in patients with severe stroke and those undergoing reperfusion therapy.
Objective:Long COVID is associated with persistent symptoms including cardiovascular complications; however, the epidemiology and directionality of this association remain unclear. Methods:Utilizing a retrospective cohort study design with cross-sectional analyses, 8,332 respondents aged 18 and older from the 2022 Medical Expenditure Panel Survey (MEPS) who had a prior COVID-19 infection, were analyzed to determine the temporal association between long COVID and cardiovascular disease (CVD), modeling each as both outcome and exposure in separate analyses. Results:Long COVID was associated with any CVD diagnosis (OR 1.37; 95% CI: 1.05-1.80), specifically angina (OR 1.81; 95% CI: 1.18-2.77) and myocardial infarction (OR 1.50; 95% CI: 1.01-2.23). Temporally, long COVID was associated with higher odds of CVD diagnoses in the same year or following year after COVID-19 (OR 2.62; 95% CI: 1.05-6.51) and in subsequent years only (OR 8.60; 95% CI: 1.53-48.3). Respondents with pre-existing CVD did not have statistically significant greater odds of reporting new long COVID symptoms. Conclusion:Our findings demonstrate that long COVID is associated with the subsequent development of CVD, underscoring the need for further research in this patient population to improve health interventions.
Objectives: Amyloidosis is a group of rare diseases that often manifest in multi-organ symptoms requiring an effective multidisciplinary team of care providers to manage. This study aimed to identify the best practices and key barriers to patient-centric care at US specialized amyloidosis centers (SACs) which have emerged as central hubs for multidisciplinary amyloidosis care.Methods: We conducted and analyzed interviews with 77 stakeholders of amyloidosis diseases, including specialist physicians from 17 SACs across the US, patients, patient advocacy group representatives, and referring physicians.Results: The most commonly mentioned best practices were patient-centric multidisciplinary care, timely intake of new high-risk patients, and responsiveness to patient questions. Expanding local physician education was noted as critical to earlier diagnosis. Fifteen out of 17 SACs are actively involved in clinical trials for amyloidosis treatments. Key barriers to care identified were patient distance to SACs, limited medical records and data sharing, and insurance hurdles. Most SACs keep track of metrics, such as patient volume, patient demographics, time to first appointment, as part of internal or in external registries to measure progress.Conclusion: These findings offer practical insights for optimizing amyloidosis care and highlight the structural and informational gaps that must be addressed to improve access and outcomes.
Background: Hypertension affects over 1.3 billion globally, many remain uncontrolled, and aldosterone synthase inhibitors (ASIs) are emerging as a treatment. This network meta-analysis compared the effectiveness and safety of ASI regimens in hypertensive patients. Methods: PubMed, Cochrane Central, and ScienceDirect were searched till December 2025. We conducted a frequentist network meta-analysis using RStudio version 4.3.3 with the “meta” and “netmeta” packages. P -scores were used for treatment ranking. Results: Ten randomized controlled trials were included in the analysis. Baxdrostat 1 mg, 2 mg, lorundrostat 100 mg once daily, 12.5 mg twice daily, 25 mg twice daily, 50 mg once daily, 50 mg and escalation to 100 mg, osilodrostat 0.25, 0.5, and 1.0 mg once daily, vicadrostat 10, 20, and 3 mg plus empagliflozin, and 20 mg significantly reduced the systolic blood pressure (SBP), where the baxdrostat 2 mg ( P -score = 0.89) was ranked best. Lorundrostat 50 mg once daily, Baxdrostat 1 and 2 mg significantly reduced the diastolic blood pressure (DBP) with Lorundrostat 50 mg once daily ranked best ( P -score = 0.84). Adverse events were increased with lorundrostat regimens, but serious adverse events were similar across regimens. Hyperkalemia was more frequent with Baxdrostat 1 and 2 mg and all lorundrostat regimens. Symptomatic hypotension occurred mainly with lorundrostat 50 mg daily. Conclusion: The SBP and DBP were significantly reduced with the baxdrostat and lorundrostat regimens, although the risk of hyperkalemia increased. Adverse events were also higher in the lorundrostat regimens, whereas serious adverse events were comparable.
Background: Coronary artery disease (CAD) is the leading cause of death worldwide. After percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is recommended to reduce thrombotic events. This meta-analysis assesses the effectiveness of clopidogrel compared to aspirin monotherapy following DAPT post-PCI. Methods: From inception to April 2025, an exhaustive literature search was conducted across electronic databases, including PubMed, Cochrane Library, ScienceDirect, EMBASE, and Web of Science. Risk ratios (RRs) along with 95% confidence intervals (CIs) were pooled using the random-effects model in Review Manager. Leave-one-out sensitivity analysis and funnel plots were used to evaluate heterogeneity and publication bias, respectively. Results: Six studies, including 3 RCTs and 3 observational studies, spanning over 19 494 patients, were included in our analysis. Clopidogrel significantly reduced major adverse cardiovascular events (MACE) (RR = 0.78; 95% CI: [0.69, 0.89]; P = .0002; I 2 = 0%) and myocardial infarction (MI) (RR = 0.73; 95% CI: [0.56, 0.94]; P = .02; I 2 = 21%) compared to aspirin. Likewise, the clopidogrel group demonstrated a substantial advantage in reducing the incidence of any stroke (RR = 0.66; 95% CI: [0.49, 0.89]; P = .006; I 2 = 14%), including ischemic stroke (RR = 0.69; 95% CI: [0.49, 0.97]; P = .04; I 2 = 0%). All other endpoints, including hemorrhagic stroke, all-cause mortality, cardiac death, major bleeding, stent thrombosis, repeat, and target vessel revascularization, were comparable between the 2 arms. Conclusion: Clopidogrel significantly reduced the incidence of MACE, MI, and stroke after DAPT following PCI compared to aspirin, indicating greater effectiveness. However, the main conclusion of this meta-analysis depends primarily on the estimates from RCTs. Additional randomized studies are necessary to confirm these results and support clinical decision-making.
Sudden cardiac death (SCD) remains one of the most devastating manifestations of cardiovascular disease. While traditional risk stratification has focused on structural heart disease and electrophysiological markers, growing evidence suggests that modifiable lifestyle factors—particularly physical activity (PA) and cardiorespiratory fitness (CRF)—play a critical role in mitigating the risk of SCD. This narrative review synthesizes evidence on the associations between PA, CRF, and SCD risk. It explores potential biological mechanisms underlying these relationships, identifies key gaps in the literature, and discusses the clinical and public health implications. A substantial body of prospective cohort studies and meta-analyses demonstrates a strong, inverse, and dose-dependent association between both PA and CRF and the risk of SCD. Engaging in ⩾4 hours/week of moderate-to-vigorous PA or achieving CRF levels of ⩾8 to 10 METs is associated with 40% to 50% reductions in SCD risk. CRF also modifies the risk conferred by traditional cardiovascular risk factors such as hypertension, diabetes, and systemic inflammation. Proposed mechanisms include favorable modulation of cardiovascular risk profiles, improved autonomic regulation, anti-arrhythmic and anti-ischemic effects, and enhanced myocardial function. However, evidence gaps persist regarding causal inference (absence of Mendelian randomization studies), optimal PA and CRF thresholds, sex- and age-specific effects, and interactions with other risk factors. PA and CRF are powerful, modifiable predictors of SCD and should be integrated into preventive strategies and routine clinical assessments. Targeted interventions to increase PA and improve CRF, especially among underrepresented and high-risk groups, offer an important opportunity to reduce the burden of SCD globally.
We present the clinical case of a 20-year-old male patient who presented recurrent pneumothorax on 5 occasions; in addition, he revealed a history of skeletal malformations in the hands and joint hypermobility. A genetic panel for connective tissue disorders was performed, in which a heterozygous variant in the gene was detected ABL1 : (NM_007313.2): c.199T>C (p.Trp67Arg), which was classified as probably pathogenic, which is why the diagnosis of Heart Defects and Skeletal Malformations Syndrome was confirmed (CHDSKM).
