Search Results (369)

Background and Clinical Significance: Brugada syndrome (BrS) is a rare inherited cardiac channelopathy, often associated with SCN5A loss-of-function mutations. Clinical presentations range from asymptomatic to malignant arrhythmias and sudden cardiac death. Physiological and pharmacological stressors affecting sodium channel function—such as pyrexia, certain medications, and possibly pregnancy—may unmask or exacerbate arrhythmic risk. However, there is limited information regarding pregnancy and obstetric outcomes. Obstetric management remains largely informed by isolated case reports and small case series. A literature review was conducted using OVID Medline and Embase, identifying case reports, case series, and one retrospective cohort study reporting clinical presentation, obstetric management, and outcomes in maternal BrS. A case is presented detailing coordinated multidisciplinary input, antenatal surveillance, and intrapartum and postpartum care to contribute to the growing evidence base guiding obstetric care in this complex setting. Case Presentation: A 30-year-old G2P0 woman with asymptomatic BrS (SCN5A-positive) was referred at 31 + 5 weeks’ gestation for multidisciplinary antenatal care. Regular review and collaborative planning involving cardiology, anaesthetics, maternal–fetal medicine, and obstetrics guided a plan for vaginal delivery with continuous cardiac and fetal monitoring. At 38 + 0 weeks, the woman presented with spontaneous rupture of membranes and underwent induction of labour. A normal vaginal delivery was achieved without arrhythmic events. Epidural block with ropivacaine and local anaesthesia with lignocaine were well tolerated, and 24 h postpartum monitoring revealed no abnormalities. Conclusions: This case adds to the limited but growing literature suggesting that with individualised planning and multidisciplinary care, pregnancies in women with BrS can proceed safely and without complication. Ongoing case reporting is essential to inform future guidelines and optimise maternal and fetal outcomes. Full article

Cardiac arrhythmias remain a major source of morbidity and mortality, often stemming from molecular and structural abnormalities that are insufficiently addressed by current pharmacologic and interventional therapies. Gene therapy has emerged as a transformative approach, offering precise and durable interventions that directly target the arrhythmogenic substrate. Across the spectrum of inherited and acquired arrhythmias—including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation, and post-infarction ventricular tachycardia—gene-based strategies such as allele-specific silencing, gene replacement, CRISPR-mediated editing, and suppression-and-replacement constructs are showing growing translational potential. Advances in delivery platforms, including cardiotropic viral vectors, lipid nanoparticle-encapsulated mRNA, and non-viral reprogramming tools, have further enhanced the specificity and safety of these approaches. Additionally, innovative applications such as biological pacemaker development and mutation-agnostic therapies underscore the versatility of genetic modulation. Nonetheless, significant challenges remain, including vector tropism, immune responses, payload limitations, and the translational gap between preclinical models and human electrophysiology. Integration of patient-derived cardiomyocytes, computational simulations, and large-animal studies is expected to accelerate clinical translation. This review provides a comprehensive synthesis of the mechanistic rationale, therapeutic strategies, delivery platforms, and translational frontiers of gene therapy for cardiac arrhythmias. Full article

The electrical ventricular storm (VES) is defined as multiple sustained ventricular arrhythmias arising in a short time, often refractory to standard antiarrhythmic treatment. The three pillars of the physiopathogenesis of the VES are autonomic dysfunction, triggers, and an altered ventricular substrate. Incessant or highly recurrent ventricular arrhythmia impacts the hemodynamic status by worsening heart failure and increasing mortality. A stepwise, team-based, and tailored therapeutic approach is required to stop ventricular arrhythmia and regain the hemodynamic and electric stability of the patient. The authors focused on describing all currently available therapeutic approaches for VES, intending to establish the best VES therapeutic approaches. This process involves considering the patient’s specific condition, responses to previous treatments, and the potential risks and benefits of each approach. The options range from adjusting antiarrhythmic therapy to reprogramming of the ICD, sedation, epidural anaesthesia, stellate ganglia anaesthetic block, and the use of ECMO or left ventricular assist devices and radiofrequency catheter ablation. Particular attention is paid to the detailed management of genetic primary arrhythmia syndromes like long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome and Wolff–Parkinson–White syndrome, early repolarisation syndrome, right ventricular arrhythmogenic dysplasia, and idiopathic ventricular fibrillation. After overcoming the acute events of VES and obtaining hemodynamic stability, the treatment should shift toward an optimal balance of heart failure therapy, controlling the substrate by revascularisation procedures and resolving other pathology-generating ventricular arrhythmias. This article provides a comprehensive overview of ESV’s current management options using the most efficient strategies known to date. Full article

Background and Objectives: The perioperative use of beta-blockers remains controversial due to conflicting evidence of their risks and benefits. The aim of this study was to evaluate the association between chronic beta-blocker (bb) therapy and perioperative cardiac events in non-cardiac surgeries using 24 h continuous Holter monitoring. Materials and Methods: A prospective observational study was conducted on patients undergoing elective or emergency non-cardiac surgery at a Romanian tertiary care hospital. The patients were divided into two groups: G1 (not receiving Bb) and G2 (on chronic Bb). The incidences of perioperative cardiac events, such as severe bradycardia (<40 b/min), new-onset atrial fibrillation (AF), extrasystolic arrhythmia (Ex), and sustained ventricular tachycardia (sVT) and arterial hypotension, were compared between the two groups using clinical, electrocardiography (ECG), and Holter ECG data. Beta-blocker indications, complications, and outcomes were analyzed using chi-squared tests and logistic regression. Results: A total of 100 consecutive patients (63% men, mean age of 53.7 years) were enrolled in the study. G2 included 30% (n = 30) of patients on chronic beta-blocker therapy. The indications included atrial fibrillation (46.7%, n = 14), arterial hypertension (36.7%, n = 11), extrasystolic arrhythmias (10%, n = 3), and chronic coronary syndrome (6.6%, n = 2). Beta-blocker use was significantly associated with severe bradycardia (n = 6; p < 0.001) in G2, whereas one patient in G1 had bradycardia, and 15 and 1 patients had hypotension (p < 0.001) in G1 and G2, respectively. The bradycardia and arterial hypotension cases were promptly treated and did not influence the patients’ prognoses. The 14 patients with AF in G2 had a 15-fold higher odds of requiring beta-blockers (p < 0.001, odds ratio (OR) = 15.145). No significant associations were found between beta-blocker use and the surgery duration (p = 0.155) or sustained ventricular tachycardia (p = 0.857). Ten patients developed paroxysmal postoperative atrial fibrillation (AF), which was related to longer surgery durations (165 (150–180) vs. 120 (90–150) minutes; p = 0.002) and postoperative anemia [hemoglobin (Hg): 10.4 (9.37–12.6) vs. 12.1 (11–13.2) g/dL; p = 0.041]. Conclusions: Patients under chronic beta-blocker therapy undergoing non-cardiac surgery have a higher risk of perioperative bradycardia and hypotension. Continuous Holter monitoring proved effective in detecting transient arrhythmic events, emphasizing the need for careful perioperative surveillance of these patients, especially the elderly, in order to prevent cardiovascular complications These findings emphasize the necessity of tailored perioperative beta-blocker strategies and support further large-scale investigations to optimize risk stratification and management protocols. Full article

Brugada syndrome is a rare inherited heart disease characterized by ventricular arrhythmias and characteristic ST segment elevation, which increases the risk of sudden death. Studies have shown that the pathogenesis of this disease involves a variety of gene mutations, including abnormal functions of sodium, calcium, and potassium ion channels, resulting in cardiac electrophysiological disorders. These variants affect excitability and conduction of cardiomyocytes, thereby increasing the susceptibility to ventricular arrhythmias and sudden death. However, many genetic variants remain of uncertain significance or are insufficiently characterized, necessitating further investigation. This review summarizes the genetic variants associated with Brugada syndrome and discusses their potential implications for improving diagnosis and therapeutic approaches. Full article

Introduction: Methadone, a synthetic opioid used for opioid substitution therapy (OST), is typically associated with arrhythmias rather than direct myocardial depression. Neurological complications, especially with concurrent antipsychotic use, have also been reported. Acute left ventricular failure in young adults is uncommon and often linked to genetic or infectious causes. We present a rare case of reversible cardiogenic shock and cerebellar insult due to methadone toxicity. Case Presentation: A 37-year-old man with a history of drug abuse on OST with methadone (130 mg/day) was admitted to the ICU with hemodynamic instability, seizures, and focal neurological deficits. Diagnostic workup revealed low cardiac output syndrome and a right cerebellar insult, attributed to methadone toxicity. The patient received individualized catecholamine support. After 10 days in the ICU, he was transferred to a general ward for ongoing cardiac and neurological rehabilitation and discharged in stable condition seven days later. Conclusions: Methadone-induced reversible left ventricular failure, particularly when accompanied by cerebellar insult, is rare but potentially life-threatening. Early recognition and multidisciplinary management are essential for full recovery in such complex toxicological presentations. Full article

Objectives: With the growing importance of mobile technology and artificial intelligence (AI) in healthcare, the development of automated cardiac diagnostic systems has gained strategic significance. This review aims to summarize the current state of knowledge on the use of AI in the analysis of electrocardiographic (ECG) signals obtained from wearable devices, particularly smartwatches, and to outline perspectives for future clinical applications. Methods: A narrative literature review was conducted using PubMed, Web of Science, and Scopus databases. The search focused on combinations of keywords related to AI, ECG, and wearable technologies. After screening and applying inclusion criteria, 152 publications were selected for final analysis. Conclusions: Modern AI algorithms—especially deep neural networks—show promise in detecting arrhythmias, heart failure, prolonged QT syndrome, and other cardiovascular conditions. Smartwatches without ECG sensors, using photoplethysmography (PPG) and machine learning, show potential as supportive tools for preliminary atrial fibrillation (AF) screening at the population level, although further validation in diverse real-world settings is needed. This article explores innovation trends such as genetic data integration, digital twins, federated learning, and local signal processing. Regulatory, technical, and ethical challenges are also discussed, along with the issue of limited clinical evidence. Artificial intelligence enables a significant enhancement of personalized, mobile, and preventive cardiology. Its integration into smartwatch ECG analysis opens a path toward early detection of cardiac disorders and the implementation of population-scale screening approaches. Full article

Background/Objectives: Long QT Syndrome type 2 (LQT2) is a cardiac channelopathy linked to pathogenic variants in the KCNH2 gene, which encodes the Kv11.1 potassium channel, essential for cardiac repolarization. Variants affecting splice sites disrupt potassium ion flow, prolong QT interval, and increase the risk of arrhythmias and sudden cardiac death (SCD). Understanding genotype–phenotype correlations is key, given the variability of clinical manifestations even within families sharing the same variant. We aimed to evaluate new pathogenic variants by analyzing genotype–phenotype correlations in informative families. Methods: Genetic and clinical assessments were performed on index cases and family members carrying KCNH2 pathogenic variants, referred for genetic testing between 2010 and June 2023. The next-generation sequencing (NGS) of 210 cardiovascular-related genes was conducted. Clinical data, including demographic details, family history, arrhythmic events, electrocardiographic parameters, and treatments, were collected. Results: Among 390 patients (152 probands) tested for LQTS, only 2 KCNH2 variants had over 5 carriers. The detailed clinical information of 22 carriers of this KCNH2 p.Ser261fs. has already been reported by our research group. Moreover, we identified 12 carriers of the KCNH2 c.77-2del variant, predicted to disrupt a splice site and not previously reported. Segregation analysis showed its high penetrance, supporting its classification as pathogenic. Conclusions: The newly identified KCNH2 c.77-2del variant is a pathogenic, as strongly supported by the segregation analysis. Our findings underscore the importance of further research into splice site variants to enhance clinical management and genetic counseling for affected families. Full article

Background/Objectives: Patients with chronic kidney disease (CKD) are associated with a significantly elevated cardiovascular risk. The incidence and prevalence of mediated cardiac disorders and major adverse cardiac events (MACEs), such as heart failure, arrhythmias, acute coronary syndrome (ACS) based on coronary artery disease (CAD), stroke, venous thromboembolism, and peripheral artery disease, are significantly higher in CKD patients as compared with the general population. Methods: This narrative review summarizes the current clinical understanding, the pathophysiological mechanisms, and the clinical consequences in the context of cardiovascular risk and disease in CKD. Results: The impact of CKD on mediated cardiovascular disorders and elevated MACE prevalence is complex and multifactorial. The underlying mechanisms involve various traditional cardiovascular risk factors, such as arterial hypertension, smoking, dyslipidemia, and diabetes. Furthermore, CKD-specific molecular and pathophysiological factors, such as chronic inflammation and associated oxidative stress and endothelial cell dysfunction, pro-coagulatory status, uremic toxins and uremic lipids, progressive vascular calcification, and alterations in the regulation of the renin–angiotensin–aldosterone system (RAAS) and sympathetic activation cause an increased cardiovascular risk. Conclusions: Understanding the complex disease mechanisms between CKD and elevated cardiovascular risk might contribute to optimizing individual patients’ risk stratification and result in individualized diagnostic and treatment strategies via appropriate clinical biomarker application and individualized anti-inflammatory approaches. Full article

Objective: Sudden infant death syndrome (SIDS), sudden neonatal unexpected death (SNUD), and sudden intrauterine unexpected death (SIUD) are major unsolved, shocking forms of death that occur frequently and without warning. The body of literature on the anatomo-pathological substrates in the cardiac conduction system of SIDS-SIUD and their possible relationship with risk factors and triggers is fragmentary and scarce. The work aims is to analyze the cardiac conduction system findings collected at the national referral center for SIDS-SIUD. Methods: A total of 123 autopsied cases of SIDS (59.35% males, 40.65% females, mean age ± SD: 103.49 ± 67.17 days), 36 cases of SNUD (61.11% males, 38.89% females, mean age ± SD: 8.4 ± 9.17 days), and 127 cases of SIUD (45.67% males, 54.33% females, mean age ± SD: 36 ± 4.59 gestational weeks) were analyzed. In-depth pathological examinations of the cardiac conduction system were performed on serial sections according to the Lino Rossi Research Center’s protocol. Results: Among the studied cases, the following findings were observed: resorptive degeneration (SIDS: 88.7%, SNUD: 88.88%, SIUD: 56.69%), fetal dispersion (SIDS: 73.17%, SNUD: 91.66%, SIUD: 78.74%), Mahaim fibers (SIDS: 40.65%, SNUD: 44.44%, SIUD: 32.28%), cartilaginous meta-hyperplasia (SIDS: 56.91%, SNUD: 25%, SIUD: 33.07%), septated atrio-ventricular junction (AVJ) (SIDS: 21.14%, SNUD: 33.33%, SIUD: 38.58%), AVJ duplicity (SIDS: 6.5%, SNUD: 11.11%, SIUD: 2.36%), intramural bifurcation (SIDS: 3.25%, SNUD: 2.77%, SIUD: 4.72%). Conclusions: The prevalence of cardiac conduction findings was consistent across the SIDS, SNUD and SIUD groups. These findings provide valuable insights into the pathological characteristics of the cardiac conduction system in SIDS-SIUD that are potential morphological substrates for the development of cardiac arrhythmias. Further investigation and study of the conduction system are needed to understand the underlying mechanisms of these forms of death. Full article

Introduction: In the past decade, chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of relapsed refractory multiple myeloma (RRMM) and lymphoma, but it is associated with significant cardiovascular adverse effects. We aim to analyze the incidence, patterns, and outcomes of cardiac events in RRMM and lymphoma patients undergoing CAR-T therapy utilizing the FDA Adverse Event Reporting System (FAERS) database, paving the way for future research and being more vigilant in treating high-risk populations. Methods: We conducted a retrospective post-marketing pharmacovigilance inquiry using the FDA Adverse Event Reporting System (FAERS) database and the Medical Dictionary for Regulatory Activities (MEDRA). We examined the adverse effects associated with CAR-T and TCE since their FDA approval in US and non-US populations (accessed 5 January 2024), and we analyzed the incidence of cardiac events related to six CAR-T products: Idecabtagene vicleucel, Ciltacabtagene autoleucel, Axicabtagene ciloleucel, Tisagenlecleucel, Lisocabtagene maraleucel, and Brexucabtagene autoleucel since FDA approval. Cardiotoxicities were assessed, including coronary artery disease (CAD), myocardial infarction (MI), arrhythmia, heart failure, and hypotension. Results: Out of 12,949 adverse events, we identified 675 (5.2%) cardiac events irrespective of severity. Almost 440 (65%) cardiac events were associated with cytokine release syndrome (CRS). The most common cardiotoxic event was atrial fibrillation (122), followed by the development of heart failure (113), ventricular arrhythmia (108), hypotension (87), and bradyarrhythmia (41). The mortality rate was highest among Brexucabtagene autoleucel recipients (n = 26, 2.3%), followed by Tisagenlecleucel (n = 71, 2.1%) and Lisocabtagene maraleucel (n = 10, 2.1%). Conclusions: CAR-T therapy can result in fatal adverse events due to its cardiotoxic properties. Timely monitoring, such as screening echocardiography and electrocardiograms, can help identify the at-risk population and allow for early intervention—particularly in patients with high baseline cardiovascular risk or previous exposure to cardiotoxic agents—thereby improving outcomes by enabling risk stratification and supportive management. Full article

Thyroid hormones (THs) play a central role in cardiovascular and metabolic regulation, influencing lipid metabolism, insulin sensitivity and resting energy expenditure. Inherited disorders of impaired sensitivity to THs—including resistance to thyroid hormone alpha (RTHα) and beta (RTHβ), monocarboxylate transporter 8 (MCT8) deficiency and selenoprotein deficiency—lead to complex, multisystemic clinical features. Although these conditions are rare, with RTHβ being the most common and affecting about 1 in 20,000 newborns, they share clinical features with more prevalent thyroid disorders, such as hypothyroidism and hyperthyroidism, as well as neurological manifestations including muscle wasting and spasticity. These conditions present abnormal patterns of thyroid function and are associated with tissue-specific comorbidities such as arrhythmias, heart failure, dyslipidemia, hepatic steatosis, insulin resistance, and metabolic syndrome. To date, no targeted or controlled studies have evaluated the impact of lifestyle modifications in these patient populations. Therefore, this narrative review proposes plausible management strategies based on pathophysiological insights into the effects of thyroid hormones on target organs, combined with clinical reasoning and evidence extrapolated from related disorders. Physical exercise and diet may complement pharmacological treatments (e.g., levothyroxine or TRIAC) to improve cardiovascular and metabolic outcomes. In RTHβ, aerobic exercise enhances cardiovascular health, while a Mediterranean diet supports lipid control and glycemic parameters. In RTHα, physical exercise may aid neuromotor development, and a fluid-rich, fiber-moderated diet can alleviate constipation. In MCT8 deficiency, physiotherapy may improve mobility and relieve contractures, while nutritional support (e.g., feeding tube, gastrostomy) can be necessary to tackle feeding difficulties and reduce pulmonary complications. In selenoprotein deficiency, low-to-moderate physical exercise and an antioxidant-rich diet may protect against oxidative stress at several tissue levels. Although quantitative evidence is limited, this narrative review synthesizes current insights, providing a meaningful basis for future validation and research. Full article

Background/Objectives: Obesity is increasingly common among patients with acute ST-segment elevation myocardial infarction (STEMI), potentially influencing both clinical evaluation and outcomes. Traditional echocardiographic metrics may be suboptimal for prognosis estimation in this population. Left ventricular myocardial work (LVMW) represents an emerging, load-adjusted marker of myocardial performance. This study aimed to assess the prognostic relevance of LVMW in obese STEMI patients. Methods: A total of 143 patients presenting with STEMI were prospectively enrolled and categorized based on their obesity status (body mass index ≥30 kg/m²). LVMW parameters were measured using echocardiography within 72 ± 24 h of hospital admission. The patients were monitored for major adverse cardiovascular events (MACE), defined as cardiovascular death, malignant ventricular arrhythmias, or unplanned hospitalizations due to heart failure or acute coronary syndrome. Results: During a median follow-up of 13 months (interquartile range: 6–28 months), MACE occurred in 30 patients (21%). Among obese individuals, left ventricular global work efficiency (LVGWE) emerged as the most robust predictor of adverse events, with an area under the receiver operating characteristic curve of 0.736 (95% confidence interval [CI]: 0.559–0.914; p = 0.009). A threshold value of 79% for LVGWE was identified as optimal for predicting MACE. Kaplan–Meier analysis revealed significantly lower event rates in obese patients with LVGWE ≥79% (log-rank p = 0.006). In univariate Cox regression analysis, LVGWE <79% was associated with a markedly elevated risk of MACE in obese patients (hazard ratio [HR] = 5.59; 95% CI: 1.33–23.50; p = 0.019), and remained a significant predictor in the overall cohort (HR = 2.73; 95% CI: 1.26–5.90; p = 0.010). Conclusions: LVGWE demonstrates strong prognostic utility in STEMI, particularly among obese patients. The incorporation of myocardial work indices into routine evaluation may enhance risk stratification and guide management in this high-risk subgroup. Full article

Background: Among patients with congenital heart disease, particularly those with a history of undergoing the Fontan operation, pregnancy presents a significant maternal–fetal risk, especially when complicated by severe valvular dysfunction. Lung reperfusion syndrome (LRS) is a rare but life-threatening complication occurring following valve intervention. Multidisciplinary management, including by Cardio-Obstetrics teams, is essential for optimizing outcomes in such high-risk cases. Methods: We present the case of a 37-year-old pregnant patient with previously repaired tetralogy of Fallot (via the Fontan procedure) who presented at 24 weeks gestation with worsening severe pulmonary stenosis and right-ventricular dysfunction. The patient had been lost to cardiac follow-up for over a decade. She experienced recurrent arrhythmias, including supraventricular and non-sustained ventricular tachycardia, prompting hospital admission. A multidisciplinary team recommended transcatheter pulmonic valve replacement (TPVR), performed at 28 weeks’ gestation. Results: Post-TPVR, the patient developed acute hypoxia and hypotension, consistent with Lung Reperfusion Syndrome, necessitating intensive cardiopulmonary support. Despite initial stabilization, progressive maternal respiratory failure and fetal compromise led to an emergent cesarean delivery. The neonate’s neonatal intensive care unit (NICU) course was complicated by spontaneous intestinal perforation, while the mother required intensive care unit (ICU)-level care and a bronchoscopy due to new pulmonary findings. She was extubated and discharged in stable condition on postoperative day five. Conclusions: This case underscores the complexity of managing severe congenital heart disease and valve pathology during pregnancy. Lung reperfusion syndrome should be recognized as a potential complication following TPVR, particularly in pregnant patients with Fontan physiology. Early involvement of a multidisciplinary Cardio-Obstetrics team and structured peripartum planning are critical to improving both maternal and neonatal outcomes. Full article

Background: Uniparental disomy (UPD) refers to the condition in which both chromosomes (or part of chromosome) of a pair are inherited from the same parent. There are two types of UPD: uniparental isodisomy (both chromosomes inherited from one parent are identical copies) and uniparental heterodisomy (two different chromosomes are inherited from one parent). UPD presents two primary developmental risks: recessive trait inheritance or an imprinting disorder. These risks may coexist, leading to an ultra-rare comorbidity. Managing the comorbidities associated with rare diseases presents unique clinical challenges. Results: The existence of such phenomena is evidenced by our case report of a boy who was ultimately diagnosed with two rare diseases: Prader–Willi syndrome (PWS), due to the maternal uniparental disomy of chromosome 15 (UPD), and autosomal recessive Lodder–Merla type 1 syndrome, linked to a novel pathogenic variant in the G protein subunit β 5 (GNB5) gene, as detailed in this paper. Conclusions: An unusual or severe phenotype in a patient diagnosed with PWS should invariably prompt the consideration of a comorbid genetic disease attributable to genes located in the PWS critical region of chromosome 15q, or elsewhere on chromosome 15. In cases of epileptic encephalopathy with cardiac arrhythmia, prompt consultation with a cardiologist and comprehensive genetic testing are essential to reduce the risks associated with untreated arrhythmia and ensure the provision of appropriate and safe anti-epileptic therapy. The presented case provides further support for the hypothesis that uniparental disomy may serve as an underlying cause of Lodder–Merla syndrome. This underscores the significance of comprehensive genetic testing, encompassing parental testing and familial cascade testing (in selected cases where there is consanguinity, or the likelihood of close common ancestral background between partners) to establish the recurrence risk. Full article