Search Results (434)

Ventricular tachycardia (VT) remains a major cause of morbidity and mortality in patients with structural heart disease. While catheter ablation has become a cornerstone in VT management, recurrence rates remain substantial due to limitations in electroanatomic mapping (EAM), particularly in cases of deep or heterogeneous arrhythmogenic substrates. Cardiac imaging, especially when multimodal and integrated with mapping systems, has emerged as a critical adjunct to enhance procedural efficacy, safety, and individualized strategy. This comprehensive review explores the evolving role of various imaging modalities, including echocardiography, cardiac magnetic resonance (CMR), computed tomography (CT), positron emission tomography (PET), and intracardiac echocardiography (ICE), in the preprocedural and intraprocedural phases of VT ablation. We highlight their respective strengths in substrate identification, anatomical delineation, and real-time guidance. While limitations persist, including costs, availability, artifacts in device carriers, and lack of standardization, future advances are likely to redefine procedural workflows. 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

Cardiac fibrosis following myocardial infarction plays a critical role in the formation of scar tissue and contributes to ventricular arrhythmias, including ventricular tachycardia and sudden cardiac death. Current clinical diagnostics use electrical and structural markers, but lack precision due to low spatial resolution and absence of molecular information. In this paper, we employed line scan Raman microspectroscopy to classify sheep myocardial tissue into muscle, necrotic, granulated, and fibrotic tissue types, using collagen as a molecular biomarker. Three spectral regions were evaluated: region A (600–2960 cm⁻¹), region B (600–1399 cm⁻¹ and 1751–2960 cm⁻¹), and region C (1400–1750 cm⁻¹), which includes the prominent collagen-associated peaks at 1448 cm⁻¹ and 1652 cm⁻¹. Linear and nonlinear principal component analysis (PCA) and support vector machines (SVMs) were applied for dimensionality reduction and classification, with nonlinear models specifically addressing the nonlinearity of collagen formation during fibrogenesis. Histological validation was performed using Masson’s trichrome staining. Raman bands associated with collagen in region C consistently outperformed regions A and B, achieving the highest explained variance and best class separation in both binary and multiclass PCA models for both linear and nonlinear approaches. The ratio of collagen-related peaks enabled stage-dependent tissue characterization, confirming the nonlinear nature of fibrotic remodeling. Our findings highlight the diagnostic potential of collagen-associated Raman bands for characterizing myocardial fibrosis. The proposed PCA-SVM framework demonstrates robust performance even with limited sample size and has the potential to lay the foundation for real-time intraoperative diagnostics. Full article

Background: The onset of cardiomyopathy in Duchenne muscular dystrophy (DMD) is insidious and poorly defined. We proposed integrated wall stress (iWS) as a marker of total left ventricular (LV) workload and tested whether the increased iWS represents early DMD cardiomyopathy. Methods: Peak systolic wall stress (PS-WS) was calculated in M-mode echocardiography with simultaneous blood pressure measurement. iWS was defined as a product of PS-WS and heart rate (HR) divided by 60 (=PS-WS/RR interval). We measured iWS in normal controls (CTRL), DMD with normal LV shortening fraction (%LVSF ≥ 30%) (DMD-A), and DMD with decreased %LVSF (<30%) (DMD-B). Results: 40 CTRL and 79 DMD patients were studied. Despite comparable %LVSF, both HR and iWS were significantly higher in DMD-A (n = 50) than in CTRL (p < 0.0001). iWS was significantly higher in DMD-B (n = 29) than in DMD-A (p < 0.0001) despite comparable HR. PS-WS was significantly higher in DMD-A than in CTRL and higher in DMD-B than in DMD-A, suggesting high HR is not a sole determinant of increased iWS in DMD-A compared with CTRL. In a longitudinal study in 35 DMD patients over 4.0 ± 2.0 years, iWS showed significant increase (p = 0.0062) alongside a significant decline in %LVSF (p < 0.0001). Conclusions: iWS significantly increased in DMD before %LVSF declined. The progressive increase of iWS in DMD is initially associated with increased HR and then with increased PS-WS. iWS may serve as a useful echocardiographic marker in identifying preclinical DMD cardiomyopathy. 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

Background: Left ventricular non-compaction cardiomyopathy (LVNC) is a congenital heart disease characterized by abnormal prenatal development of the left ventricle that has an aberrantly thick trabecular layer and a thinner compacted myocardial layer. However, the underlying molecular mechanisms of LVNC regulated by mitochondrial phosphatase genes remain largely unresolved. Methods: We generated a mouse model with cardiac-specific deletion (CKO) of Ptpmt1, a type of mitochondrial phosphatase gene, using the αMHC-Cre, and investigated the effects of cardiac-specific Ptpmt1 deficiency on cardiac development. Morphological, histological, and immunofluorescent analyses were conducted in Ptpmt1 CKO and littermate controls. A transcriptional atlas was identified by RNA sequencing (RNA-seq) analysis. Results: We found that CKO mice were born at the Mendelian ratio with normal body weights. However, most of the CKO mice died within 24 h after birth, developing spontaneous ventricular tachycardia. Morphological and histological analysis further revealed that newborn CKO mice developed an LVNC phenotype, evidenced by a thicker trabecular layer and a thinner myocardium layer, when compared with the littermate control. We then examined the embryonic hearts and found that such an LVNC phenotype could also be observed in CKO hearts at E15.5 but not at E13.5. We also performed the EdU incorporation assay and demonstrated that cardiac cell proliferation in both myocardium and trabecular layers was significantly reduced in CKO hearts at E15.5, which is also consistent with the dysregulation of genes associated with heart development and cardiomyocyte proliferation in CKO hearts at the same stage, as revealed by both the transcriptome analysis and the quantitative real-time PCR. Deletion of Ptpmt1 in mouse cardiomyocytes also induced an increase in phosphorylated eIF2α and ATF4 levels, indicating a mitochondrial stress response in CKO hearts. Conclusions: Our results demonstrated that Ptpmt1 may play an essential role in regulating left ventricular compaction during mouse heart development. Full article

Background and Clinical Significance: Evaluating wide complex rhythms in patients with permanent pacemakers can be a diagnostic challenge, particularly when the rhythm is irregular. While pacemaker-mediated rhythms are typically regular and predictable, the appearance of wide complex irregular rhythms raises concerns ranging from lead malfunction to life-threatening arrhythmias, such as ventricular tachycardia. Understanding the interplay between intrinsic cardiac activity and device function is crucial for timely and accurate diagnosis in this increasingly common clinical scenario. Case presentation: We report on a 74-year-old female with a VVI pacemaker implanted for binodal disease, who presented with intermittent palpitations and an irregular rhythm. The patient has a recent history of falling on her right shoulder, which is also the site of the device implantation. We used a clinical step-by-step approach to rule out pacemaker malfunction and to establish the need for an unscheduled device interrogation. Conclusions: This case presentation highlights the important role of clinical reasoning and the approach to such a patient, especially when a key method of pacemaker evaluation, such as device interrogation, is not readily available. Full article

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder primarily affecting motor neurons. Emerging evidence suggests it also involves multiple organs, including potential cardiac manifestations. This study aimed to evaluate cardiac abnormalities in pediatric SMA patients compared to age-matched healthy controls, providing insight into underlying cardiomyopathy in this population. A total of 126 children were included in the study, with 63 SMA patients and 63 age-matched controls. We conducted clinical examinations, standard electrocardiography (ECG), and cardiac ultrasound (CUS) in all patients. Electrocardiographic analysis revealed a higher prevalence of sinus tachycardia in the SMA group and significantly deeper Q waves, indicating possible myocardial involvement. Echocardiographic findings demonstrated a significant reduction in left ventricular mass and left ventricular mass index in SMA patients compared to controls, despite normal systolic function. Statistical analysis confirmed that SMA diagnosis was an independent predictor of reduced myocardial mass, suggesting a distinct cardiac phenotype in SMA patients. This study provides new evidence of subclinical cardiac involvement in SMA, characterized by reduced myocardial mass, altered electrocardiographic parameters, and increased sinus tachycardia. These findings suggest a previously unrecognized form of cardiomyopathy in SMA that differs from cardiac manifestations typically seen in other neuromuscular disorders. Full article

Background/Objectives: Left atrial function can be a tool for risk stratification for hypertrophic cardiomyopathy (HCM). Over the past decade, there has been growing interest in the application of strain analysis for earlier and more accurate prediction of cardiovascular disease prognosis. This study aimed to investigate the performance of left atrial strain analysis compared to conventional left atrial measures in predicting clinical outcomes in Asian patients with HCM. Methods and Results: This was a retrospective study involving 291 patients diagnosed with HCM between 2010 and 2017. Left atrial volumes were assessed using the method of discs in orthogonal plans at both end diastole and end systole. Left atrial (LA) strain was obtained using a post-hoc analysis with TOMTEC software. We tested the various left atrial parameters against outcomes of (1) heart failure hospitalization and (2) event-free survival from a composite of adverse events, including all-cause mortality, ventricular tachycardia (VT)/ventricular fibrillation (VF) events, appropriate device therapy if an implantable cardioverter defibrillator (ICD) was implanted, stroke, and heart failure hospitalization. The patients had a mean age of 59.0 ± 16.7 years with a male preponderance (71.2%). The cumulative event-free survival over a follow-up of 3.9 ± 2.7 years was 55.2% for patients with an abnormal LA strain versus 82.4% for patients without one (p < 0.001). Multivariable Cox regression analyses were performed separately for each LA parameter, adjusting for age, sex, LV mass index, LV ejection fraction (EF), E/e’, the presence of LV outflow tract (LVOT) obstruction at rest, and atrial fibrillation. An analysis showed that all parameters except for LAEF demonstrated an independent association with heart failure hospitalization. Left atrial strain outperformed the rest of the parameters by demonstrating an association with a composite of adverse events. Conclusions: In Asian patients with HCM, measures of left atrial strain were independently associated with heart failure hospitalization and a composite of adverse outcomes. Left atrial strain may be used as a tool to predict adverse outcomes in patients with HCM. Full article

Sudden cardiac death represents an unexpected death for which a strong underlying genetic background has been described. The primary causes are identified in cardiomyopathies and channelopathies, which are heart diseases of the muscle and electrical system, respectively, without coronary artery disease, hypertension, valvular disease, and congenital heart malformations. Genetic variants, especially single nucleotide variants and short insertions/deletions impacting essential myocardial functions, have shown that cardiomyopathies display high heritability. However, genetic heterogeneity, incomplete penetrance, and variable expression may complicate the interpretation of genetic findings, thus delaying the management of seriously at-risk patients. Moreover, recent studies show that the diagnostic yield related to genetic cardiomyopathies ranges from 28 to 40%, raising the need for further research. In this regard, investigating the occurrence of structural variants, especially copy number variants, may be crucial. Based on these considerations, this review aims to provide an overview of copy number variants identified in cardiomyopathies and discuss them, considering diagnostic yield. This review will ultimately address the necessity of incorporating copy number variants into routine genetic testing for cardiomyopathies and channelopathies, a process increasingly enabled by advances in next-generation sequencing technologies. Full article

The anatomical arrangement of the atrioventricular node has been likened to a riddle wrapped up in an enigma. There are several reasons for this alleged mystery, not least the marked variability in structure between different species. Lack of detailed knowledge of the location of the node relative to the atrial and ventricular septal structures has also contributed to previous misunderstandings. Recent studies comparing the findings of gross dissection with virtual dissection of living datasets, combined with access to a large number of serially sectioned human and animal hearts, have served to provide the evidence to solve the riddle. We summarise these findings in this review. We explain how the node is located within the atrial walls of the inferior pyramidal space. It becomes the non-branching component of the atrioventricular conduction axis as the axis extends through the plane of atrioventricular insulation to enter the infero-septal recess of the left ventricular outflow tract. The node itself is formed by contributions from the tricuspid and mitral vestibules, with extensive additional inputs from the base of the atrial septum. We show how knowledge of development enhances the appreciation of the arrangements and offers an explanation as to why, on occasion, there can be persisting nodoventricular connections. We discuss the findings relative to the circuits producing atrioventricular re-entry tachycardia. We conclude by emphasising the significance of the variation of the anatomical arrangements within different mammalian species. Full article

The macrolide class of antibiotics are widely utilized in clinical settings for a broad range of bacterial infections and have additional roles as immunomodulatory agents. Although efficacious with a good safety profile overall, they have been associated with prolongation of the QT interval and development of the polymorphic ventricular tachycardia, Torsades de pointes (TdP). In a 2020 scientific statement, the American Heart Association (AHA) classified azithromycin, clarithromycin and erythromycin as QT-prolonging drugs known to cause TdP and the online database, CredibleMeds, that maintains a list of drugs known to cause QT prolongation classifies these drugs as having an increased risk of QT prolongation. The mechanism of this risk has been delineated to involve macrolide binding to and a blockade of delayed rectifier potassium channels that conduct rapid potassium current, I_kr, during repolarization, leading to prolonged repolarization and subsequent QT prolongation. Studies investigating this association have revealed variable results, with several suggesting that the risk of QT prolongation and TdP with macrolide use may be highly dependent on underlying patient risk factors and comorbidities. In the present investigation, we summarize current evidence on association of macrolide antibiotics, azithromycin, clarithromycin and erythromycin, with the development of QT prolongation and TdP, pathophysiology of and risk factors predisposing to development of these events, the role of implementation of strategies to reduce this risk and highlight emerging research. Full article

Enterovirus (EV) infections in neonates can be transmitted vertically or horizontally, with symptoms ranging from mild to severe, including myocarditis, meningoencephalitis, and hepatitis. Neonates with EV-induced myocarditis may present severe cardiovascular disease with sudden onset of arrhythmia. Neonatal arrhythmias, particularly in low birth weight or critically ill infants, can impair cardiac function and worsen outcomes. EV targets cardiomyocyte receptors, inducing apoptosis pathways and triggering cardiac conduction disturbances. We present an extremely low-birth-weight preterm infant (GW 27 + 6) who developed EV-induced myocarditis, complicated with a sudden onset of supraventricular tachycardia (SVT), pericardial effusion and bi-atrial enlargement. Despite multi-agent regimen, including propranolol, flecainide, and amiodarone, the infant showed persistent junctional rhythm until seven months of age, later transitioning to atrial rhythm with stable cardiac function. A review of previously published rhythm disturbances due to EV-induced myocarditis is presented. Newborns with EV-induced arrhythmia may require a multi-modal treatment such as a multi-agent medical regimen or, in severe non-responsive cases, an electrophysiological approach. EV infections may cause long-term cardiovascular comorbidities (such as left ventricular dysfunction or mitral valve regurgitation), necessitating continuous monitoring through echocardiography and ECG. Collaboration between neonatologists and pediatric cardiologists is crucial for effective treatment and follow-up. Full article

Background: Estrogens play a protective role during the early stages of life. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression. Aim: The purpose of this study was to test for the significance of the sex-specific associations of gonadal hormones with the extent of the inflammatory response, myocardial damage, and ventricular arrhythmia risk in acute myocardial infarction (MI). Materials and Methods: Study design: single-center cohort study. Blood samples for the assessment of sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitivity C-reactive protein (CRP), white blood cell (WBC) counts, and cardiac enzymes were collected 48 h after the onset of symptoms (and within 6 h after PCI) from 111 patients (37% women) with acute MI. Coronary disease severity, left ventricular systolic function (LV), and indices of ventricular repolarization were assessed using coronary angiography, echocardiography, and a conventional electrocardiogram, respectively. Results: In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels, peak WBC count, and peak CRP plasma levels. T levels and the E2/T ratio were associated with post-PCI CRP in these men. For women, peak WBC count was a marker of highest testosterone, and only WBC count was a significant indicator of myocardial injury extent. The incidence of acute ventricular tachycardia detected in AMI was significantly associated with left ventricular ejection fraction and with peak WBC count (as a tendency) regardless of sex. A longer duration of cardiac repolarization prior to PCI was predicted by lower ejection fractions in men and by age, CRP, and testosterone levels in female patients. Conclusions: During acute MI, elevated endogenous estradiol levels in men and increased leukocytes in women indicate acute myocardial damage. Post-PCI plasma inflammatory markers are sex-specific confounding factors for acute endogenous E2 levels, T levels, and the E2/T ratio. LV systolic function in men and, characteristically, the acute inflammatory response and testosterone levels in women are predictors of longer ventricular repolarization and arrhythmia risk. Full article