This letter challenges the prevailing assumption that residual shunt following patent foramen ovale (PFO) closure is a primary driver of recurrent stroke risk. While residual shunt has been associated with higher rates of neurologic events in observational studies, the author argues that this relationship is not supported by randomized data and may be confounded by diagnostic ambiguity, particularly the inclusion of transient ischemic attack alongside stroke outcomes. The complex pathophysiology of PFO-related stroke, requiring thrombus formation, transient right-to-left shunting, and specific anatomic factors, is often substantially mitigated by the closure procedure itself. Emerging evidence suggests that device-related factors, including incomplete endothelialization and altered atrial hemodynamics, may independently contribute to thromboembolic risk after closure, irrespective of residual shunting. The letter proposes that residual shunt may be an inadequate surrogate endpoint and that clinical focus should instead remain on true stroke recurrence. It further cautions against routine re-intervention to eliminate residual shunt, advocating instead for consideration of prolonged antithrombotic therapy and alternative closure strategies, such as suture-based approaches, which may avoid device-related complications. Overall, this perspective calls for a reassessment of current paradigms in post-PFO closure management and outcome evaluation.
Background:Sudden cardiac arrest (SCA) in young adults (18-40 years) is rare but devastating, often occurring without prior symptoms. It often occurs in the absence of preceding symptoms or known structural heart disease. A comprehensive and systematic evaluation of its multifactorial aetiology, diagnostic challenges and preventive strategies is fundamental to reducing morbidity and mortality in this population. Objective:This systematic review aims to comprehensively evaluate the epidemiology, underlying aetiologies, associated risk factors, diagnostic approaches and preventive strategies for SCA in adults aged 18-40 years. Methods:PubMed, Scopus, Embase, Web of Science and Google Scholar were searched from January 2015 to June 2025. Eligible studies examined aetiologic mechanisms, screening strategies, clinical outcomes or public health interventions targeting the prevention, detection or management of SCA in individuals aged 18-40 years. Study quality was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist, the Risk of Bias in Nonrandomized Studies of Exposures (ROBINS-E), A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and the Newcastle-Ottawa Scale (NOS). Results:Of 3,000 records identified through the literature search, 55 studies met the inclusion criteria. The reported incidence of SCA among young adults ranged from 1 to 2 per 100,000 person-years in Western countries, with higher incidence rates observed in Asian populations. Structural cardiomyopathies were the predominant aetiologies, most notably hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. These were followed by inherited channelopathies, including long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia, as well as acquired conditions such as myocarditis and substance-related cardiac toxicity involving cocaine, amphetamines and anabolic steroids. Additional risk factors included systemic comorbidities, particularly sarcoidosis, chronic kidney disease and autonomic dysfunction. Diagnostic evaluation most frequently incorporated electrocardiography, transthoracic echocardiography, cardiac magnetic resonance imaging and genetic testing. Survival following out-of-hospital cardiac arrest was significantly improved in settings with prompt bystander cardiopulmonary resuscitation, widespread availability of automated external defibrillators and the implementation of community-based education initiatives. Conclusion:Targeted screening strategies, improved access to advanced diagnostic modalities and population-level community interventions are essential for reducing the burden of SCA among young adult individuals. Further prospective research is warranted to enhance risk stratification and optimize prevention strategies in this high-impact population.
Ventricular fibrillation (VF) is a malignant tachyarrhythmia underlying cardiac arrest, yet the mechanisms maintaining VF remain incompletely understood. Ethical constraints and technical limitations have largely precluded systematic investigation of sustained VF in humans, resulting in a body of evidence derived predominantly from animal models and ex vivo human preparations, often yielding apparently conflicting mechanistic interpretations. This article summarizes the experimental studies and conceptual frameworks that underpin the contemporary understanding of VF maintenance. We discuss evidence derived from frequency-and phase-based mapping approaches in short-and long-duration VF studies across species, highlighting how methodological constraints, animal models, spatial scale and VF duration critically influence mechanistic interpretation. Despite the heterogeneity across studies, overall, the data indicate that VF is not inherently chaotic but exhibits transient spatiotemporal organization that evolves dynamically over time. The underlying drivers sustaining VF throughout its progression are not uniform: multiple at times co-existing mechanisms, including reentrant activity, self-perpetuating wavelets and rapid focal activation, have been implicated. The predominance and temporal evolution of these mechanisms are shaped by progressive global ischaemia with metabolic deterioration, pre-existing structural remodelling and the involvement as well as architecture of the Purkinje network. Collectively, these observations support the concept of duration-dependent and likely also substrate-specific electrophysiological phenotypes of VF, while also exposing a paucity of studies that have explicitly and systematically evaluated the effect of pre-existing structural and electrical substrate characteristics to examine their reciprocal interaction with VF dynamics. We conclude by outlining future directions, emphasizing the need for true 3D transmural mapping technologies and multimodal integration of structural and functional substrate features to enable mechanistic phenotyping and inform more personalized and effective strategies for VF management and prevention.
Resistant hypertension (rHTN), defined as uncontrolled blood pressure despite adherence to three antihypertensive agents, presents a major clinical and economic burden that disproportionately affects certain minority populations. Current therapeutic options do not target the endothelin-1 pathway, a potent mediator of vasoconstriction, inflammation and sodium retention, which has been increasingly recognized as a key contributor to the pathophysiology of rHTN. However, aprocitentan, a novel dual endothelin receptor antagonist, directly targets this mechanism. In the Parallel-group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension (PRECISION) trial (Multi-center, Blinded, Randomized, Parallel-group, Phase 3 Study With Aprocitentan in Subjects With Resistant Hypertension [RHT]; ClinicalTrials.gov identifier: NCT03541174), aprocitentan demonstrated durable blood pressure-lowering effects in patients with rHTN. This study reported significant and sustained reductions in both office and ambulatory systolic and diastolic blood pressure among patients with rHTN, along with a favourable safety profile at the subsequently approved 12.5 mg dose. Pharmacokinetic studies support once-daily oral administration with low potential for drug-drug interactions. This article will discuss the significant potential benefits in the evolving landscape of hypertension management, how aprocitentan is a promising fourth-line agent for rHTN and recommendations for its use in the 2025 American Heart Association/American College of Cardiology (AHA/ACC) High Blood Pressure Guideline.
Resistant hypertension (RH), defined as uncontrolled blood pressure on three or more antihypertensive agents (including a diuretic) or controlled blood pressure on four or more, poses a major clinical challenge. It disproportionately drives adverse cardiovascular outcomes, including stroke, heart failure and chronic kidney disease. Accurate diagnosis first requires distinguishing true RH from pseudo-resistance, which stems from inaccurate measurement, poor medication adherence and clinical inertia. The pathophysiology is multifactorial, driven by mechanisms such as sympathetic nervous system overactivity, renin-angiotensin-aldosterone system dysregulation, obesity and obstructive sleep apnoea. Consequently, effective management extends beyond mere drug intensification. It demands a comprehensive strategy that addresses lifestyle factors, ensures therapeutic adherence and treats secondary causes. For eligible patients, device-based therapies, such as renal denervation, are emerging as valuable adjuncts to pharmacological treatment. This article synthesizes the current understanding of RH's epidemiology, pathophysiology and diagnostic workup. It also critically examines the evolving landscape of integrated therapeutic strategies, discussing on-going controversies and future research directions to improve patient outcomes.
Background: Hypertension is the leading modifiable risk factor for cardiovascular disease, yet awareness and control remain low, particularly in low-and middle-income countries (LMICs). In India, caregivers playa central role in patient support, but their comparative knowledge has been underexplored. This study assessed hypertension-related knowledge among patients and caregivers in a tertiary care setting in Northern India. Methods: A cross-sectional study was conducted over 7 months (October 2024-April 2025) in the cardiology out-patient department of a tertiary hospital in Punjab, India. Adults living with hypertension and their accompanying caregivers were consecutively enrolled. A structured questionnaire assessed sociodemographic factors and blood pressure (BP) monitoring practices, and the knowledge scores were compared between patients and caregivers, and associations with sociodemographic variables were examined. Results: Of 3,501 participants, 2,032 (58%) were patients, and 1,469 (42%) were caregivers. The cohort was predominantly male (56.6%), urban (69%) and educated up to the 12th grade (69%). Only 22.5% reported regular BP monitoring. Awareness of the hypertension definition (50.2%), the normal BP range (67%) and key risk factors, such as alcohol (41.2%), obesity (37%) and smoking (34.2%), was limited. Caregivers consistently demonstrated higher knowledge than patients (mean score: 8.7 versus 8.5/15; p=0.004), with better performance associated with higher education, urban residence and skilled occupations. Conclusions: Caregivers demonstrated greater knowledge of hypertension than patients, underscoring their potential as partners in disease management. Persistent gaps in awareness of risk factors, complications and follow-up emphasize the need for family-centred education, caregiver-focused counselling and accessible self-monitoring to strengthen hypertension control in LMICs.
Despite strides in cardiovascular disease (CVD) management, dyslipidaemia remains a significant yet underdiagnosed and undertreated risk factor, particularly among women. Sex-based disparities persist in screening, diagnosis and treatment, leading to suboptimal management and increased CVD risk in female populations. This article explores the current literature on sex disparities in dyslipidaemia, analysing screening guidelines, diagnosis trends and treatment gaps. It examines factors influencing lipid metabolism across a woman's lifespan, including hormonal fluctuations, pregnancy, menopause and their impact on CVD risk. The article also highlights barriers to effective lipid management in women, including clinician biases, inadequate screening and lower prescription rates of statin and non-statin therapies. Women are less likely to undergo lipid screening despite having significant CVD risk factors. Even when diagnosed, they receive statin therapy at lower rates than men, and treatment intensification is less frequent. Additionally, clinical trials assessing lipid-lowering therapies often underrepresent women, limiting the applicability of evidence-based recommendations. The lack of sex-specific risk assessment tools further contributes to missed opportunities for prevention and treatment. Addressing disparities in dyslipidaemia management is crucial to reducing the burden of CVD in women. Enhancing awareness among clinicians, improving screening strategies, incorporating sex-specific risk factors into predictive models and increasing female representation in clinical trials are essential steps towards equitable cardiovascular care.
Introduction:Guidelines widely recommend exercise training as a complementary therapy for individuals with heart failure. While research highlights the potential of both high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), a systematic review is required to solidify their effects on improving patients' oxygen uptake, functional capacity, cardiac function and quality of life (QoL). Objective:This meta-analysis aimed to compare the efficacy of HIIT and MICT on cardiopulmonary fitness, functional capacity, cardiac function and QoL among individuals with heart failure. Method:This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42024602309). We searched PubMed, Cochrane Controlled Register of Trials (CENTRAL), Scopus, Web of Science, ProQuest, Embase, Google Scholar, PubMed Central (PMC), Elton B. Stephens Company (EBSCO) and Wiley. Risk of bias was assessed with the Revised Cochrane for Risk-Of-Bias Tool for Randomized Trials (RoB 2), and analyses were conducted in RStudio version 4.4.1. (Posit PBC, Massachusetts, USA) using the 'meta' package. Result:A total of 21 randomized controlled trials were included in the analysis. The overall quality assessment showed a low risk of bias. We found that the HIIT group is favourable in terms of cardiac function improvement, represented by left ventricular ejection fraction (LVEF; mean difference [MD]=2.69 [95% confidence interval (CI): 0.01, 5.38; p=0.0495]), peak oxygen uptake (peak VO2; MD=1.19 [95% CI: 0.43, 1.95; p=0.0021]) and functional capacity, assessed with the six-minute walk test (6MWT; MD=24.87 [95% CI: 11.19, 37.75; p=0.0002]). Furthermore, HIIT showed non-significant trends towards improvement in QoL (MD=1.11 [95% CI: -1.02, 3.24; p=0.31]) and oxygen pulse (MD=1.03 [95% CI: -0.18, 2.24; p=0.095]). Conclusion:HIIT appears to be more effective than MICT in improving functional capacity, such as LVEF, peak VO2 and 6MWT, as well as cardiac functional outcome.
The Evolut Low Risk trial (Transcatheter Aortic Valve Replacement With the Medtronic Transcatheter Aortic Valve Replacement System In Patients at Low Risk for Surgical Aortic Valve Replacement; ClinicalTrials.gov identifier: NCT02701283) provides reassuring evidence that transcatheter aortic valve replacement remains non-inferior to surgery at 5-year follow-up with regard to mortality and disabling stroke in low-risk patients. Valve performance, durability and quality-of-life improvements were excellent in both groups.
Drug-coated balloon (DCB)-only angioplasty is a 'leave nothing behind' approach, necessitating a modified percutaneous coronary intervention strategy and mindset to accept coronary dissection during lesion preparation while simultaneously achieving an optimal angiographic outcome. Drawing from the lessons learned during the plain old balloon angioplasty era, it is imperative to re-familiarize ourselves with the strategies of dissection avoidance, recognition and management. With our increasing clinical and research experience in DCB angioplasty, we present our approach to managing dissections, emphasizing the distinction between safe and unsafe dissections, techniques for modifying unsafe or indeterminate dissections into a safe category and the appropriate consideration of bailout stenting (BOS). We provide examples of each dissection category, including those that can be safely left, those requiring BOS and those that necessitate modification through techniques such as further dilatation with specialized balloons (such as non-compliant, scoring and cutting balloons) and prolonged balloon inflation.
Epicardial adipose tissue (EAT), located between the myocardium and visceral pericardium, plays an active role in coronary artery disease (CAD) through local inflammatory and metabolic signalling. This review explores the prognostic significance of EAT volume and attenuation (density) as measured by cardiac computed tomography. While increased EAT volume has been linked to higher plaque burden, coronary artery calcium (CAC) and incident CAD - even in low-CAC populations - attenuation offers additional value by reflecting tissue inflammation and remodelling. Lower EAT density has been independently associated with major adverse cardiac events and vulnerable plaque features, outperforming both volume and CAC score in several cohorts. We also highlight the clinical relevance of these metrics in early disease detection and risk stratification, and their potential for therapeutic modulation. As evidence builds, EAT volume and density may soon serve as practical, imaging-based biomarkers to guide personalized prevention in CAD.
Background:The gut microbiome has a crucial role in host metabolism and immune regulation, and there is growing evidence that dysbiosis may be associated with the pathogenesis of cardiovascular disease (CVD). This narrative review provides an overview of the recent literature on mechanistic connections between the gut and heart, as well as on the therapeutic strategies and research gaps in the gut-heart axis. Methods:We conducted a systematic literature search on PubMed and Embase databases with MeSH and keyword terms: 'gut microbiome', 'cardiovascular disease', 'TMAO', 'short-chain fatty acids', 'probiotics' and 'faecal microbiota transplantation'. We considered human and relevant animal studies focusing on mechanistic pathways or microbiome treatments and excluded editorials, small (less than 10 subjects) case series and articles not published in the English language. Results:Key microbiota-derived metabolites, trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), contribute to atherogenesis, blood pressure and myocardial inflammation. Dysbiosis-induced barrier dysfunction and disturbed bile acid signalling also serve as the mediators of cardiac remodelling. Dietary fibre, probiotics/prebiotics, postbiotics and faecal microbiota transplantation are emerging interventions for the modulation of CVD risk. Nevertheless, most result from observational studies, whilst such are heterogeneous in sequencing platforms and too small to draw any definitive conclusions. Conclusion:The modulation of gut microbiome might be a new target for CVD prevention and treatment. Large-scale, standardized randomized trials with hard cardiovascular endpoints, as well as integrated multi-omics profiling, will be required to validate microbial biomarkers and to optimize microbiome-based interventions.
Background:The development of eHealth has offered a solution to the challenge of effective self-management for patients with heart failure (HF) by facilitating health information exchange, enabling frequent home monitoring, enhancing self-management and promoting patient empowerment. This study aimed to evaluate the effectiveness of eHealth interventions in improving self-management for patients with HF. Methods:Systematic review and meta-analysis were performed adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines, by first selecting the relevant publications from the Cochrane Library, EBSCOhost, Epistemonikos, ProQuest, PubMed and Scopus as of 25 February 2025. The quality of the included studies was appraised using Cochrane Risk of Bias 2.0 tool. A meta-analysis of randomized controlled trials was performed using Review Manager software to estimate odds ratios (ORs) and standardized mean differences (SMDs). Results:We included 37 trials with 13,366 participants. eHealth reduced HF-related admissions (OR: 0.73 [95% confidence interval (CI): 0.62, 0.86; p=0.0002]). All-cause mortality did not differ (OR: 0.93 [95% CI: 0.85, 1.03; p=0.16]). Cardiovascular mortality was not reduced (OR: 0.85 [95% CI: 0.71, 1.01; p=0.07]). Quality of life showed borderline improvement on the Minnesota total score (mean difference: -7.25 [95% CI: -14.81, 0.31; p=0.06]; I²=91%). HF-related knowledge did not differ (SMD: 0.53 [95% CI: -0.12, 1.19; p=0.11]). Conclusion:This meta-analysis demonstrates that incorporating eHealth interventions, particularly telemedicine, into standard HF care substantially decreases hospital admissions. While broader impacts on mortality, quality of life and knowledge remain inconclusive, the findings underscore the value of standardized eHealth integration as a pragmatic strategy to strengthen HF management and optimize patient outcomes.
Background:The use of an implantable closure device with medical therapy to prevent recurrent stroke in patent foramen ovale (PFO)-associated stroke has been shown to be superior to medical therapy alone. Recently, an alternative, suture-based method also has shown promise for effective PFO closure. There has been little published data comparing the outcomes of these two technologies. Methods:This retrospective study explores the safety and efficacy outcomes of device-based versus suture-based percutaneous PFO intervention. The occurrence of post-procedural atrial fibrillation was of primary interest. Data from 55 single-institution, single-operator PFO closure cases between 1 January 2021 and 8 April 2022 were analyzed. Closure occurred via one of two Food and Drug Administration (FDA)-approved occluders or the NobleStitch™ EL suture-based approach. Data were transcribed into a registered REDCap database for descriptive analysis. Demographics, medical history, imaging, procedural and post-procedural outcomes were the variables collected for each participant. Results:All patients had successful PFO closure without major adverse outcomes. Overall efficacy was similar between the two groups. No patient had a residual shunt greater than grade 1. Several suture-group patients required multiple sutures for satisfactory closure. Those who had multiple sutures had no anomalous anatomic PFO features. Three patients (5%), all from the device group, developed atrial fibrillation after PFO closure. Conclusions:This study supports the safety and efficacy of device- and suture-based approaches in PFO closure. Suture-based closure would seem a reasonable option where device-based closure raises concerns. Future studies could further explore the observed disparity of atrial fibrillation occurrence between the two PFO closure strategies.
Introduction:Functional status is a predictor of rehospitalization and mortality in patients with heart failure (HF). The purpose of this study was to test the variables in the Multidimensional Model of Functional Status (MMFS) as determinants of functional status. Methods:Using structural equation modelling, we analysed data from 520 patients with HF to determine the best multivariate model of functional status. In the MMFS, the potential determinants of functional status include demographic, clinical, psychosocial, behavioural and symptom burden variables. We measured functional status using the Duke Activity Status Index. Other variables were collected by standardized questionnaires and patient interviews. Results:Patients who were older, less educated, or had greater comorbidity burden or greater symptom burden had worse functional status. Sex, body mass index, depression, anxiety and social support were indirectly associated with functional status mediated by symptom burden. Being married was indirectly associated with better functional status via the pathways of more social support and fewer depressive symptoms through lower symptom burden. Conclusion:Multidimensional variables proposed in the MMFS were directly and indirectly associated with functional status. Among these variables, symptom burden is the most important mediator. Targeting these variables, especially symptom burden, may improve patients' functional status.
Transthyretin amyloid cardiomyopathy is a progressive and fatal cardiomyopathy caused by the deposition of misfolded transthyretin in the form of amyloid fibrils in the myocardium. The advent of various highly efficacious transthyretin amyloid-specific disease-modifying therapies has sparked a growing interest in identifying the clinical indicators of disease progression that will be crucial in guiding treatment decisions. Markers of disease progression include changes in commonly measured biomarkers such as the N-terminal pro-B-type natriuretic peptide and the estimated glomerular filtration rate, a decline in the 6-m inute walk test distance, outpatient diuretic intensification, changes in heart failure symptom burden and also changes in various cardiac-imaging parameters. Considering the wide array of markers that can detect disease progression, it is likely that a comprehensive clinical assessment will involve monitoring multiple markers simultaneously. Integrating multiple markers of disease progression offers additional insights beyond individual markers, enabling a refined assessment of disease trajectory and mortality risk. Many of these markers are readily available, simple to measure and universally applicable, making them easy to implement in clinical practice for identifying patients with advancing disease and a heightened risk of mortality.
Background:This meta-analysis article aimed to investigate the efficacy of magnesium in preventing new-onset postoperative atrial fibrillation (POAF). Methods:We searched Medline, Embase, Web of Science and Cochrane Library without any language or publication date restriction up to August 2023. We included randomized controlled trials (RCTs) that enrolled adults undergoing cardiac surgery without a history of atrial fibrillation, exploring the effect of magnesium supplementation in preventing new-onset POAF. We assessed the risk of bias using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool. We conducted a random-effects meta-analysis using R and assessed the certainty of the evidence. Results:A total of 24 RCTs with 3,373 participants were included. We found that magnesium may reduce the risk of POAF compared to the control group (relative risk [RR]: 0.55; 95% confidence interval [CI]: 0.41, 0.74; low certainty). The subgroup analysis for trials with low/some concerns risk of bias showed that magnesium reduces the risk of new-onset POAF compared to control (RR: 0.70 [95% CI: 0.58, 0.84]; high certainty). Magnesium consumption had no significant effect on all-cause mortality (RR: 1.00 [95% CI: 0.34, 2.90]) or days of hospitalization (mean difference: -0.34 [95% CI: -0.94, 0.26]). Conclusion:The evidence indicates that magnesium administration reduces the incidence of new-onset POAF.
Left bundle branch area pacing has been a breakthrough in pacing therapy and is being increasingly adopted. It delivers a more physiological form of pacing compared with right ventricular and biventricular pacing and also avoids the risk of perforation of the ventricular free wall. However, the therapy comes at the price of new complications related to the transseptal route for placing the lead. This article provides an update on these complications and discusses how to avoid and manage these adverse events.
