Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a cornerstone of adult heart failure (HF) therapy and are increasingly prescribed off-label to children, yet pediatric outcomes have never been pooled. We searched PubMed/MEDLINE, Embase, Scopus, and Web of Science to 14 August 2026 for studies of any SGLT2 inhibitor in children or adolescents with HF and performed a single-arm meta-analysis of all exposed patients and a pairwise meta-analysis of the comparative studies with random-effects models. Nine studies contributed 599 exposed patients and 97 controls. Pooled rates were 3.8% (95% confidence interval [CI] 1.6-8.4) for mortality, 8.5% (6.2-11.5) for transplantation, 11.2% (8.2-15.1) for worsening HF, 0.2% (0.03-1.6) for ketoacidosis, 4.5% (1.2-14.9) for acute kidney injury, 3.7% (1.1-11.7) for urinary tract infection, and 4.1% (1.4-11.2) for discontinuation because of an adverse event. After initiation, left ventricular ejection fraction rose by 7.7 percentage points (3.6-11.8) and natriuretic peptide fell by 0.42 standard deviations (0.34-0.49). In the comparative synthesis (63 exposed, 97 unexposed), risk ratios were 0.80 (0.11-6.07) for mortality and 0.21 (0.03-1.68) for worsening HF; ejection fraction improved 3.34 percentage points more with SGLT2 inhibitors (0.22-6.46) whereas natriuretic peptide did not differ (standardized mean difference -0.09, -0.50 to 0.33).

Postinfarction ventricular septal rupture is a rare, frequently lethal mechanical complication of acute myocardial infarction, and the optimal timing of repair remains controversial. Early surgery is often unavoidable in refractory shock but is technically hazardous because necrotic, friable myocardium provides poor suture support. Delayed repair after tissue maturation is associated with lower operative mortality, although this apparent benefit is substantially inflated by survivorship and immortal time bias. Mechanical circulatory support, including intra-aortic balloon counterpulsation, venoarterial extracorporeal membrane oxygenation, and microaxial flow pumps, may stabilize selected patients, permit end-organ recovery, and bridge them to later repair. However, available evidence is almost entirely observational, and the certainty supporting major timing and device selection recommendations is low or very low. This narrative review synthesizes the biological basis of timing, diagnostic and anatomic considerations, surgical and transcatheter options, mechanical support strategies, and transplantation. We propose a practical Heart Team framework based on hemodynamic status, tissue maturation, rupture anatomy, and daily reassessment, with explicit clinical triggers for abandoning delay. Surgical timing should therefore be individualized according to physiology rather than dictated by a fixed chronological threshold, pending prospective multicenter validation.

Mental health disorders are linked with increased cardiovascular disease and mortality risk, yet national trends in cardiovascular mortality among US adults with mental health disorders remain incompletely characterized. We performed a nationwide multiple cause of death analysis using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death database to evaluate long-term trends and demographic patterns in cardiovascular mortality among US adults aged 25 years or older with mental health disorders between 1999 and 2024. Adults with mental health disorders were identified using International Classification of Diseases, Tenth Revision codes F00-F99, and cardiovascular deaths were reported using circulatory system codes (I00-I99). Age-adjusted mortality rates and crude mortality rates were calculated, and Joinpoint regression was used to derive annual percentage change and average annual percent change (AAPC). Between 1999 and 2024, more than 7.2 million cardiovascular deaths occurred among US adults with mental health disorders. Cardiovascular mortality rose steadily through the study period, and across sex, race/ethnicity, age group, geographic region, and urbanization levels. The greatest increases were noted among adults ages 55-64 years (AAPC: 6.90%, P < 0.001), males (AAPC: 5.40%, P < 0.001), and individuals residing in rural counties and the Northeast. Cardiovascular mortality among US adults with mental health disorders increased significantly between 1999 and 2024, highlighting the persistent disparities in this vulnerable population. These findings reinforce the need for integrated cardiovascular and psychiatric care, targeted prevention strategies, and equitable access to healthcare.

Cyanotic congenital heart defects are malformations of the heart that affect its structure and function. The etiology of most of these defects is multifactorial, but some common causes include maternal conditions, genetic defects, and genetic mutations. Six of the most common cyanotic congenital heart defects include Tetralogy of Fallot, transposition of the great arteries, persistent truncus arteriosus, total anomalous pulmonary venous return, tricuspid atresia, and Ebstein's anomaly. These defects share several common features, however, each is distinguished by key cardiac abnormalities and effects on systemic circulation. Tetralogy of Fallot is the most common cause of early cyanosis in infants due to a ventricular septal defect, overriding aorta, right ventricular outflow tract obstruction, and right ventricular hypertrophy. In transposition of the great arteries, the aorta arises from the right ventricle, and the pulmonary artery arises from the left ventricle. Persistent truncus arteriosus presents with failure of truncus arteriosus separation, resulting in a single arterial trunk. In total anomalous pulmonary venous return, all pulmonary veins drain into systemic circulation rather than the left atrium, and tricuspid atresia patients lack a tricuspid valve and possess a hypoplastic right ventricle. Lastly, Ebstein's anomaly is a defect associated with apical displacement of a malformed tricuspid valve into the right ventricle.

Despite significant breakthroughs in preventative medicine, atherosclerotic cardiovascular disease (ASCVD) is still the primary cause of morbidity and death worldwide. In this context, 2 apoB-containing particles-LDL and lipoprotein(a) [Lp(a)] have emerged as important but mechanistically separate causes of atherothrombotic illness. This review synthesizes current knowledge in lipid biology, epidemiology, measurement, and therapeutics to address 3 key questions: (1) how LDL-C/apoB and Lp(a) differ in structure, pathophysiology, and clinical risk; (2) what the evidence shows about the safety and efficacy of driving LDL-C to very low or near-zero levels; and (3) where PCSK9-based therapies and soon, dedicated Lp(a) -lowering agents-fit into modern prevention strategies. Randomized trials, MR studies, and population-level cohort data all contribute to a clear and convincing picture: LDL-C/apoB and Lp(a) are separate causative drivers of cardiovascular risk, with Lp(a) introducing an orthogonal risk axis determined by genetics rather than lifestyle. By combining both viewpoints, we propose a feasible, dual-axis strategy to ASCVD prevention that addresses both cumulative apoB load and genetically driven Lp(a) risk.

Preexisting atrial fibrillation (AF) or atrial flutter may impair cardiovascular reserve during septic shock, potentially leading to worse clinical outcomes; however, its independent association with short-term outcomes remains uncertain. Using the TriNetX U.S. Collaborative Network, we identified adults with septic shock and compared patients with preexisting AF/flutter, documented at least 1 month before the index event, with those without prior AF/flutter. Clinical outcomes were compared after 1:1 propensity score matching for demographic characteristics, comorbidities, and baseline cardiovascular medication use. Outcomes included 30-day all-cause mortality, cerebral infarction, renal replacement therapy, invasive mechanical ventilation, acute-care utilization, and vasopressor/inotrope use. Effect estimates were reported as relative risks (RRs) with 95% confidence intervals. After propensity score matching, 76,295 patients were included in each cohort. Preexisting AF/flutter was associated with significantly higher risks of all-cause mortality (RR 1.07, 95% CI, 1.06-1.09; P<0.001), renal replacement therapy (RR 1.30, 95% CI, 1.25-1.35; P<0.001), invasive mechanical ventilation (RR 1.14, 95% CI, 1.12-1.16; P<0.001), acute-care utilization (RR 1.06, 95% CI, 1.05-1.06; P<0.001), and vasopressor/inotrope use (RR 1.09, 95% CI, 1.08-1.10; P<0.001). There was no significant difference in cerebral infarction (RR 1.11, 95% CI, 1.00-1.24; P=0.054). Among patients with septic shock, preexisting AF/flutter was associated with higher mortality and greater use of organ-supportive therapies, including renal replacement therapy, invasive mechanical ventilation, and vasopressor/inotrope use, but not with a significant increase in cerebral infarction. Preexisting AF/flutter may serve as an important prognostic marker for early risk stratification in septic shock.

Transcatheter aortic valve replacement (TAVR) has transformed the treatment of severe aortic stenosis across all surgical risk profiles. However, as TAVR expands into younger, lower-risk populations with longer life expectancies, the management of late bioprosthetic failure has emerged as a critical clinical challenge. While valve-in-valve TAVR offers a less-invasive reintervention strategy, absolute anatomical contraindications frequently render it infeasible, necessitating surgical explantation. Driven primarily by structural valve deterioration, acute device failure, and prosthetic valve infective endocarditis, TAVR explantation presents a uniquely hostile operative field. Unlike traditional redo-surgical aortic valve replacement, the endothelialized and fibrotic integration of transcatheter stent frames into the aortic root and subvalvular apparatus significantly complicates extraction. These procedures often require complex, unplanned concomitant reconstructive procedures. Consequently, explantation carries a substantial morbidity and mortality burden that significantly eclipses native redo-surgical aortic valve replacement, with a stark volume-outcome relationship highlighting the necessity of institutional expertise. This review synthesizes contemporary data from high-volume international registries to evaluate the evolving landscape of TAVR explantation, detailing the primary indications, anatomical hurdles, and clinical outcomes. Ultimately, we emphasize the necessity of rigorous, computed tomography-based lifetime management protocols at the time of the index procedure and the regionalization of explant operations to specialized multidisciplinary structural heart centers to mitigate the severe surgical risks of transcatheter valve failure.

Sedentary behavior and physical inactivity are distinct but interrelated risk factors that independently influence cardiovascular health. This narrative review synthesizes current evidence on the association between sedentary behavior and early cardiovascular markers in young adults, particularly university students. Epidemiological data indicate high levels of sedentary time (7-10 hours/day) alongside low adherence to physical activity guidelines in this population. Mechanistic evidence suggests that prolonged sitting impairs endothelial function, reduces nitric oxide bioavailability, alters autonomic balance by decreasing heart rate variability, and promotes arterial stiffness and metabolic dysfunction. Evidence from randomized and controlled trials demonstrates that uninterrupted sitting can induce acute adverse changes in glucose metabolism and autonomic regulation, while frequent light-intensity activity breaks may mitigate these effects. However, findings remain heterogeneous, with limited long-term improvements in structural cardiovascular outcomes. Observational studies further support associations between sedentary time and elevated blood pressure, arterial stiffness, and impaired heart rate recovery. Despite growing evidence, limitations include small sample sizes, short intervention durations, and lack of diverse populations. Overall, reducing sedentary time through feasible behavioral and institutional strategies may represent an effective early intervention to prevent future cardiovascular disease in young adults.

Vascular calcification complicates endovascular intervention by reducing vessel compliance, impairing device delivery and expansion, and increasing the risk of suboptimal procedural outcomes. Intravascular lithotripsy (IVL) has emerged as a calcium-modification strategy that uses acoustic pressure waves to fracture vascular calcium while minimizing injury to surrounding tissue. This paper reviews the mechanisms, procedural applications, clinical evidence, and evolving role of IVL in calcified coronary and peripheral arterial disease. We summarize evidence from pivotal prospective trials, randomized studies, registries, observational cohorts, imaging studies, and expert consensus, with particular emphasis on complex coronary and peripheral applications. IVL has demonstrated high procedural success and a favorable acute safety profile in severely calcified coronary lesions, with randomized evidence also supporting its use in calcified femoropopliteal disease. Expanding observational evidence supports its feasibility in complex coronary subsets, including left main and bifurcation lesions, as well as iliac and common femoral disease. Evidence remains more limited for chronic total occlusions, calcified nodules, stent underexpansion, and infrapopliteal disease. Emerging technologies and applications may further broaden the role of lithotripsy, but randomized comparative studies and longer-term outcome data are needed to define its optimal use.

Drug-coated balloons (DCBs) represent an accepted approach for in-stent restenosis (ISR); however, post-procedural predictors for risk stratification remain limited. Angiography-based physiological parameters, including quantitative flow ratio (QFR), microvascular QFR (μQFR), and coronary angiography-derived fractional flow reserve (caFFR), enable noninvasive functional assessment, but their clinical implications after DCB intervention for ISR are not well established. A comprehensive literature search of PubMed, Embase, and the Cochrane Library from inception to May 2026 was conducted to identify studies evaluating post-procedural angiography-based physiological parameters in ISR patients treated with DCB. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models, and heterogeneity was assessed using the I2 statistic. Five studies comprising 1702 patients were included. Mean age ranged from 59 to 75 years, with 75-78% males. Patients with lower post-procedural physiological index values had a significantly higher risk of vessel-oriented composite outcomes (a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization) compared with those with higher values (28.0% vs 10.3%; RR 4.65, 95% CI 1.67-12.91; P = 0.014; 5 studies). Similarly, target vessel revascularization was more frequent in the lower-value group (28.8% vs 7.5%; RR 4.88, 95% CI 1.26-18.91; P = 0.034; 4 studies). No significant associations were observed for myocardial infarction, target lesion revascularization, or cardiovascular death. Post-procedural angiography-derived physiological indices provide important prognostic information after DCB treatment for ISR. Lower values are associated with an increased risk of adverse clinical outcomes, supporting their role in risk stratification.

Obesity remains a major modifiable driver of cardiovascular disease. Emerging antiobesity pharmacotherapies demonstrate substantial weight loss alongside improvements in multiple cardiometabolic parameters. This literature review summarizes the early clinical studies of eloralintide, a selective long-acting amylin receptor agonist, and evaluates whether its weight loss and cardiometabolic effects may be relevant to cardiovascular risk reduction. Early clinical studies suggest a potentially distinct and favorable cardiometabolic profile for eloralintide, including reductions in body weight, pulse rate, blood pressure, inflammatory markers, lipid parameters, and preferential fat mass loss. The reduction in pulse rate stands out as it contrasts with the increase in heart rate that is associated with glucagon-like peptide-1 receptor agonists. The favorable profile may be further supported by eloralintide's preferential fat mass loss and improvements in both the high-sensitivity C-reactive protein and lipid markers. While these findings are promising, current evidence is limited as it is based on preclinical, phase 1, and phase 2 studies with relatively small sample sizes and short durations. No amylin receptor agonist, including eloralintide, has been evaluated in a dedicated cardiovascular outcomes trial, and their ability to reduce major adverse cardiovascular events remain to be studied. Therefore, epidemiological benchmarks should be viewed as contextual rather than predictive. Future clinical studies and dedicated cardiovascular outcomes trials will be essential to determine whether these early cardiometabolic improvements translate to clinically meaningful cardiovascular risk reduction.

Percutaneous coronary intervention relieves angina in chronic coronary syndromes, yet contemporary randomized trials have not shown that relieving ischemia reduces death or myocardial infarction when added to optimal medical therapy. This discordance requires a mechanistic reevaluation. Inducible ischemia identifies obstructive coronary disease and the likelihood of angina but does not reliably identify plaques that will rupture. Fractional flow reserve-guided percutaneous intervention reduces urgent revascularization without reducing death or infarction. Most spontaneous infarctions arise from lesions that were not severely obstructive before rupture. Coronary artery bypass grafting reduces spontaneous infarction in complex multivessel and left main disease, plausibly through more complete revascularization and through placement of grafts distal to long diseased segments that preserve perfusion if proximal plaque rupture occurs. Advances in intracoronary imaging and coronary computed tomography angiography can identify high-risk plaque features, but trials of focal treatment of non-flow-limiting vulnerable plaques have not shown benefit. Modern medical therapy with high-intensity lipid lowering, icosapent ethyl in selected patients, anti-inflammatory approaches, and therapies for diabetes and chronic kidney disease has lowered overall event rates. Chronic coronary syndromes comprise 2 overlapping but distinct pathophysiological mechanisms. Flow-limiting stenoses cause angina and are effectively treated by percutaneous coronary intervention. Plaque instability causes infarction and is modified by systemic therapy. Bypass surgery in selected patients with complex coronary anatomy addresses both mechanisms by relieving flow limitation and protecting myocardium against future plaque events.

Anxiety is common among patients undergoing coronary angiography and may adversely affect physiological stability and procedural outcomes. Although pharmacological anxiolytics are commonly used, they may be associated with undesirable adverse effects. Aromatherapy has been proposed as a complementary intervention with potential anxiolytic benefits. This systematic review and meta-analysis evaluated the effectiveness of inhalational aromatherapy in reducing anxiety and improving physiological parameters in patients undergoing coronary angiography. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and registered in the International Prospective Register of Systematic Reviews (CRD420261329600). A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Cochrane CENTRAL was performed from database inception to October 2025. Randomized controlled trials comparing inhalational aromatherapy with standard care or placebo before coronary angiography were included. Outcomes of interest were anxiety scores, systolic and diastolic blood pressure, heart rate, and respiratory rate. Data were pooled using a random-effects model and reported as standardized mean differences (SMDs) or mean differences with 95% confidence intervals (CIs). Three randomized controlled trials involving 274 participants met the inclusion criteria. Baseline anxiety levels were comparable between the aromatherapy and control groups (SMD 0.06, 95% CI -0.18 to 0.30; I2 = 3%). Aromatherapy significantly reduced postprocedural anxiety (SMD -0.66, 95% CI -1.20 to -0.13; I2 = 79%). No statistically significant differences were observed between groups in systolic blood pressure, diastolic blood pressure, heart rate, or respiratory rate. These findings suggest that aromatherapy may be an effective complementary intervention for reducing anxiety in patients undergoing coronary angiography, although its effects on physiological parameters remain uncertain. Larger, high-quality randomized controlled trials are needed to confirm these findings.

Subclinical cardiovascular disease (SCVD) encompasses a spectrum of vascular abnormalities that emerge well before the onset of overt cardiovascular events. Although a wide range of metabolic, inflammatory, and vascular markers have been associated with SCVD, current assessment strategies remain largely dependent on individual indicators, limiting their ability to capture the multidimensional and dynamic nature of disease progression. Increasing evidence suggests that SCVD develops through a continuum of interconnected biological processes, beginning with metabolic dysregulation, progressing through chronic low-grade inflammation, and ultimately leading to vascular remodeling and calcification. Notably, many of these processes can be partially reflected by routinely available health examination data, providing an opportunity to move beyond traditional risk factor assessment toward a more integrated evaluation of vascular health. In this review, we summarize the pathophysiological basis of SCVD and discuss the stage-specific significance of commonly available examination indicators across metabolic, inflammatory, structural, and functional domains. We further examine emerging strategies for multi-indicator integration, including conventional risk models, expanded assessment frameworks, and machine learning-based approaches. Collectively, these observations support a shift from isolated marker interpretation toward dynamic and stage-oriented assessment frameworks that better reflect the biological complexity of SCVD progression.

Dyslipidemia is a major modifiable risk factor for atherosclerotic cardiovascular disease, and many high-risk patients do not reach target low-density lipoprotein cholesterol (LDL-C) levels despite conventional therapy. Ongericimab is a humanized monoclonal antibody against proprotein convertase subtilisin/kexin type 9. We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL from inception to April 4, 2026 for randomized controlled trials comparing ongericimab with placebo in dyslipidemia, pooled data using random-effects models, and rated certainty with GRADE. Five double- blind trials (10 intervention-placebo comparisons; 1415 participants), all conducted in China, were included. Ongericimab reduced LDL-C at 12 weeks by 69.39 percentage points relative to placebo (95% confidence interval, -73.67 to -65.11), with sustained reductions at 24 weeks (-68.19; -73.67 to -62.71) and 52 weeks (-68.99; -78.33 to -59.65). At 12 weeks, it also reduced apolipoprotein B (-60.68), non-high-density lipoprotein cholesterol (-66.30), total cholesterol (-46.49), lipoprotein(a) (-45.74), and triglycerides (-25.89), and increased apolipoprotein A1 (8.15) and high-density lipoprotein cholesterol (10.33) (all P < 0.0001). Treatment-emergent adverse events (risk ratio 1.01; 0.90-1.14), serious adverse events (1.52; 0.30-7.58), injection-related adverse events (1.31; 0.45-3.78), and laboratory abnormalities did not differ from placebo.