Search Results (728)

Sudden cardiac death (SCD) prevention in cardiomyopathies such as hypertrophic (HCM), dilated (DCM), non-dilated left ventricular (NDLCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) remains a crucial but complex clinical challenge, especially among younger populations. Accurate risk stratification is hampered by the variability in phenotypic expression and genetic heterogeneity inherent in these conditions. This article explores the multifaceted strategies for preventing SCD across a spectrum of cardiomyopathies and emphasizes the integration of clinical evaluations, genetic insights, and advanced imaging techniques such as cardiac magnetic resonance (CMR) in assessing SCD risks. Advanced imaging, particularly CMR, not only enhances our understanding of myocardial architecture but also serves as a cornerstone for identifying at-risk patients. The integration of new research findings with current practices is essential for advancing patient care and improving survival rates among those at the highest risk of SCD. This review calls for ongoing research to refine risk stratification models and enhance the predictive accuracy of both clinical and imaging techniques in the management of cardiomyopathies. Full article

Obesity is a major risk factor for the development of life-threatening malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Risks may be highest for patients with high levels of the proinflammatory cytokine interleukin (IL)-6. We used our guinea pig model of high-fat diet (HFD)-induced arrhythmias that exhibit a heightened proinflammatory-like pathology, which is also observed in human obesity arrhythmias, as well as immunofluorescence and confocal microscopy approaches to evaluate the pathological IL-6 trans-signaling function and explore the underlying mechanisms. Using blind-stick and electrocardiogram (ECG) techniques, we tested the hypothesis that heightened IL-6 trans-signaling would exhibit increased ventricular arrhythmia/SCD incidence and underlying arrhythmia substrates. Remarkably, compared to low-fat diet (LFD)-fed controls, HFD promoted phosphorylation of the IL-6 signal transducer and activator of transcription 4 (STAT4), leading to its activation and enhanced nuclear translocation of pSTAT4/STAT4 compared to LFD controls and pSTAT3/STAT3 nuclear expression. Overactivation of IL-6 trans-signaling in guinea pigs prolonged the QT interval, which resulted in greater susceptibility to arrhythmias/SCD with isoproterenol challenge, as also observed with the downstream Janus kinase (JAK) 2 activator. These findings may have potentially profound implications for more effective arrhythmia therapy in the vulnerable obese patient population. Full article

Cardiac amyloidosis is the most frequent infiltrative disease caused by the deposition of misfolded proteins in the cardiac tissue, leading to heart failure, brady- and tachyarrhythmia and death. Conduction disorders, atrial fibrillation (AF) and ventricular arrhythmia (VA) significantly impact patient outcomes and demand recognition. However, several issues remain unresolved regarding early diagnosis and optimal management. Extreme bradycardia is the most common cause of arrhythmic death, while fast and sustained VAs can be found even in the early phases of the disease. Risk stratification and the prevention of sudden cardiac death are therefore to be considered in these patients, although the time for defibrillator implantation is still a subject of debate. Moreover, atrial impairment due to amyloid fibrils is associated with an increased risk of AF resistant to antiarrhythmic therapy, as well as recurrent thromboembolic events despite adequate anticoagulation. In the last few years, the aging of the population and progressive improvements in imaging methods have led to increases in the diagnosis of cardiac amyloidosis. Novel therapies have been developed to improve patients’ functional status, quality of life and mortality, without data regarding their effect on arrhythmia prevention. In this review, we consider the latest evidence regarding the arrhythmic risk stratification of cardiac amyloidosis, as well as the available therapeutic strategies. Full article

The diagnosis of early acute myocardial infarction is of particular importance in forensic practice considering the frequency of sudden cardiac death and the difficulty of positively identifying it through classical histological methods if survival is less than 6 h. This article aims to analyze potential immunohistochemical markers that could be useful in diagnosing acute myocardial infarction within the first 6 h of its onset. We conducted an extensive evaluation of the literature according to the PRISMA guidelines for reporting systematic literature reviews. We searched the Web of Science and PubMed databases from their inception to 2023 using the following keywords: “myocardial infarction” and “immunohistochemistry”. Fifteen studies met the inclusion criteria. Immunohistochemical markers as complement factors and CD59, myoglobin, fibrinogen, desmin, tumor necrosis factor alpha (TNF-α), P-38, JNK (Jun N Terminal Kinase), transforming growth factor β1 (TGF-β1), cardiac troponins, fibronectin, H-FABP (heart fatty acid binding protein), dityrosine, fibronectin, CD15, IL-1β, IL-6, IL-15, IL-8, MCP-1, ICAM-1, CD18, and tryptase can be used to identify the first six hours of acute myocardial infarction. These markers are mostly studied in experimental animal models. It is necessary to conduct extensive studies on human myocardial tissue fragments, which will involve the analysis of several immunohistochemical markers and careful analysis of the available data on perimortem events, resuscitation, and postmortem intervals in the context of a uniform laboratory methodology. Full article

Mitral valve prolapse (MVP) affects 2–3% of the general population, and despite its benign prognosis overall, it is associated with sudden death in a small subset of patients. The term “arrhythmic MVP syndrome” (AMVPS) refers to the presence of frequent or complex ventricular arrhythmias, commonly reported in female patients with a stereotypical phenotype including bileaflet myxomatous disease, ECG repolarisation abnormalities in inferior leads, mitral annular disjunction, and significant fibrosis in the inferolateral LV and papillary muscles. Modern imaging technologies have led to the identification of new risk factors that have been implemented in recent risk stratification guidelines; however, screening for patients with MVP who are at risk of sudden cardiac death (SCD) remains challenging. In addition, there is a limited amount of data on the outcomes of different treatment approaches in AMVP and no specific indication for targeted or disease-modifying therapies within current guidelines. Potential arrhythmic substrates in patients with AMVP syndrome have been the subject of interest in previous studies, with areas consisting of fibrosis at the papillary muscle level and the Purkinje system. Premature ventricular contractions (PVCs) originating from these areas have been shown to play an important role as triggers for ventricular fibrillation and SCD in patients with AMVP. Catheter ablation has emerged as a potential treatment modality in patients with MVP and ventricular arrhythmias (VAs), targeting arrhythmic substrates and triggering PVC foci. The aim of this review is to explore the role of catheter ablation in treating patients with AMVP. Full article

In systemic sclerosis (SSc), fibrosis of the myocardium along with ongoing autoimmune inflammation can alter the electric function of the cardiac myocytes, which may increase the risk for ventricular arrhythmias and sudden cardiac death. We analyzed the electrocardiographic (ECG) variables describing ventricular repolarization such as QT interval, QT dispersion (QTd), T wave peak-to-end interval (Tpe), and arrhythmogeneity index (AIX) of 26 patients with SSc and 36 healthy controls. Furthermore, echocardiographic and laboratory parameters were examined, with a focus on inflammatory proteins like C-reactive ptotein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), and progranulin (PGRN). The CRP, sICAM-1, and sVCAM-1 levels were positively correlated with the length of the QT interval. Although the serum PGRN levels were not increased in the SSc group compared to the controls, in SSc patients, the PGRN levels were positively correlated with the QT interval and the AIX. According to our results, we conclude that there may be a potential association between autoimmune inflammation and the risk for ventricular arrhythmias in patients with SSc. We emphasize that the measurement of laboratory parameters of inflammatory activity including CRP, PGRN, sVCAM-1, and sICAM-1 could be helpful in the prediction of sudden cardiac death in patients with SSc. Full article

Coronary arteries have a wide range of anatomical variability, and their spectrum ranges from asymptomatic cases to those predisposed to hemodynamic compromise or even sudden cardiac death. This paper aims to review the classification of coronary artery anomalies (CAAs) and illustrate their imaging characteristics by highlighting the important role of CT coronary angiography. Some of the coronary anomalies usually met in current practice are the high origin coronary artery, multiple ostia, aberrant origin from the opposite/non-coronary Valsalva sinus, single coronary artery, ALCAPA syndrome, duplications of the left anterior descending artery, coronary fistulas, and extracardiac terminations. CT coronary angiography is a non-invasive diagnostic modality for CAAs. The complex anatomy of these anomalies can be accurately described by employing 3D reconstructions and post-processing techniques. Knowledge of the imaging characteristics and potential functional impact of these anomalies is essential for accurate diagnosis and therapeutic planning of patients. Full article

Cardiovascular disease (CVD) constitutes the most common cause of death worldwide. In Europe alone, approximately 4 million people die annually due to CVD. The leading component of CVD leading to mortality is myocardial infarction (MI). MI is classified into several types. Type 1 is associated with atherosclerosis, type 2 results from inadequate oxygen supply to cardiomyocytes, type 3 is defined as sudden cardiac death, while types 4 and 5 are associated with procedures such as percutaneous coronary intervention and coronary artery bypass grafting, respectively. Of particular note is type 1, which is also the most frequently occurring form of MI. Factors predisposing to its occurrence include, among others, high levels of low-density lipoprotein cholesterol (LDL-C) in the blood, cigarette smoking, chronic kidney disease (CKD), diabetes mellitus (DM), hypertension, and familial hypercholesterolaemia (FH). The primary objective of this review is to elucidate the issues with regard to type 1 MI. Our paper delves into, amidst other aspects, its pathogenesis, risk assessment, diagnosis, pharmacotherapy, and interventional treatment options in both acute and long-term conditions. Full article

Background: The number of young patients receiving ICDs or CRT-Ds has been increasing in recent decades and understanding the key characteristics of this special population is paramount to optimized patient care. Methods: The DEVICE I+II registry prospectively enrolled patients undergoing ICD/CRT-D implantation or revision from 50 German centers between 2007 and 2014 Data on patient characteristics, procedural outcome, adverse events, and mortality during the initial stay and 1-year follow-up were collected. All patients under the age of 45 years were identified and included in a comparative analysis with the remaining population. Results: A total number of 5313 patients were enrolled into the registry, of which 339 patients (6.4%) were under the age of 45 years. Mean age was 35.0 ± 8.2 vs. 67.5 ± 9.7 years, compared to older patients (≥45 years). Young patients were more likely to receive an ICD (90.9 vs. 69.9%, p < 0.001) than a CRT-D device (9.1 vs. 30.1%). Coronary artery disease was less common in younger patients (13.6 vs. 63.9%, p < 0.001), whereas hypertrophic cardiomyopathy (10.9 vs. 2.7%, p < 0.001) and primary cardiac electrical diseases (11.2 vs. 1.5%, p < 0.001) were encountered more often. Secondary preventive ICD was more common in younger patients (51.6 vs. 39.9%, p < 0.001). Among those patients, survival of sudden cardiac death (66.7 vs. 45.4%, p < 0.001) due to ventricular fibrillation (60.6 vs. 37.9%, p < 0.001) was the leading cause for admission. There were no detectable differences in postoperative complications requiring intervention (1.5 vs. 1.9%, p = 0.68) or in-hospital mortality (0.0 vs. 0.3%, p = 0.62). Median follow-up duration was 17.9 [13.4–22.9] vs. 16.9 [13.1–23.1] months (p = 0.13). In younger patients, device-associated complications requiring revision were more common (14.1 vs. 8.3%, p < 0.001) and all-cause 1-year-mortality after implantation was lower (2.9 vs. 7.3%, p = 0.003; HR 0.39, 95%CI: 0.2–0.75) than in older patients. Conclusions: Young patients < 45 years of age received defibrillator therapy more often for secondary prevention. Rates for periprocedural complications and in-hospital mortality were very low and without differences between groups. Young patients have lower mortality during follow-up but experienced a higher rate of postoperative complications requiring revision, potentially due to a more active lifestyle. Full article

Objective: To assess the frequency and types of genetic mutations in patients with arrhythmias who underwent cardiac device implantation. Methods: Retrospective observational study, including 38 patients with different arrhythmias and cardiac arrest as a first cardiac event. Treatment modalities encompass pacemakers, transvenous defibrillators, loop recorders, subcutaneous defibrillators, and cardiac resynchronization therapy. All patients underwent genetic testing, using commercially available panels (106–174 genes). Outcome measures include mortality, arrhythmia recurrence, and device-related complications. Results: Clinical parameters revealed a family history of sudden cardiac death in 19 patients (50%), who were predominantly male (58%) and had a mean age of 44.5 years and a mean left ventricle ejection fraction of 40.3%. Genetic testing identified mutations in various genes, predominantly TMEM43 (11%). In two patients (3%) with arrhythmogenic cardiomyopathy, complete subcutaneous defibrillator extraction with de novo transvenous implantable cardioverter-defibrillator implantation was needed. The absence of multiple associations among severe gene mutations was crucial for cardiac resynchronization therapy response. Mortality in this group was around 3% in titin dilated cardiomyopathy patients. Conclusions: Integration of genetic testing into the decision-making process for patients with electronic devices represents a paradigm shift in personalized medicine. By identifying genetic markers associated with arrhythmia susceptibility, heart failure etiology, and cardiac resynchronization therapy response, clinicians can tailor device choices to optimize patient outcomes. Full article

A three-dimensional (3D) cell culture can more precisely mimic tissues architecture and functionality, being a promising alternative model to study disease pathophysiology and drug screening. Chagas disease (CD) is a neglected parasitosis that affects 7 million people worldwide. Trypanosoma cruzi’s (T. cruzi) mechanisms of invasion/persistence continue to be elucidated. Benznidazole (BZ) and Nifurtimox (NF) are trypanocidal drugs with few effects on the clinical manifestations of the chronic disease. Chronic Chagas cardiomyopathy (CCC) is the main manifestation of CD due to its frequency and severity. The development of fibrosis and hypertrophy in cardiac tissue can lead to heart failure and sudden death. Thus, there is an urgent need for novel therapeutic options. Our group has more than fifteen years of expertise using 3D primary cardiac cell cultures, being the first to reproduce fibrosis and hypertrophy induced by T. cruzi infection in vitro. These primary cardiac spheroids exhibit morphological and functional characteristics that are similar to heart tissue, making them an interesting model for studying CD cardiac fibrosis. Here, we aim to demonstrate that our primary cardiac spheroids are great preclinical models which can be used to develop new insights into CD cardiac fibrosis, presenting advances already achieved in the field, including disease modeling and drug screening. Full article

Background: In arrhythmogenic right ventricular cardiomyopathy (ARVC) non-invasive scar evaluation is not included among the diagnostic criteria or the predictors of ventricular arrhythmias (VA) and sudden death (SD). Computed tomography (CT) has excellent spatial resolution and allows a clear distinction between myocardium and fat; thus, it has great potential for the evaluation of myocardial scar in ARVC. Objective: The objective of this study is to evaluate the feasibility, and the diagnostic and prognostic value of semi-automated quantification of right ventricular (RV) fat replacement from CT images. Methods: An observational case–control study was carried out including 23 patients with a definite (19) or borderline (4) ARVC diagnosis and 23 age- and sex-matched controls without structural heart disease. All patients underwent contrast-enhanced cardiac CT. RV images were semi-automatically reconstructed with the ADAS-3D software (ADAS3D Medical, Barcelona, Spain). A fibrofatty scar was defined as values of Hounsfield Units (HU) <−10. Within the scar, a border zone (between −10 HU and −50 HU) and dense scar (<−50 HU) were distinguished. Results: All ARVC patients had an RV scar and all scar-related measurements were significantly higher in ARVC cases than in controls (p < 0.001). The total scar area and dense scar area showed no overlapping values between cases and controls, achieving perfect diagnostic performance (sensitivity and specificity of 100%). Among ARVC patients, 16 (70%) had experienced sustained VA or aborted SD. Among all clinical, ECG and imaging parameters, the dense scar area was the only one with a statistically significant association with VA and SD (p = 0.003). Conclusions: In ARVC, RV myocardial fat quantification from CT is feasible and may have considerable diagnostic and prognostic value. Full article

Background: Brugada syndrome (BrS) is an inherited primary channelopathy syndrome associated with the risk of ventricular fibrillation (VF) and sudden cardiac death in a structurally normal heart. Aim of the Study: The aim of this study was to clinically and genetically evaluate a large family with severe autosomal dominant Brugada syndrome. Methods: Clinical and genetic studies were performed. Genetic analysis was conducted with NGS technologies (WES) using the Illumina instrument. According to the standard procedure, variants found by WES were confirmed in all available families by Sanger sequencing. The effect of the variants was studied by using in silico prediction of pathogenicity. Results: The proband was a 52-year-old man who was admitted to the emergency department for syncope at rest. WES of the index case identified a heterozygous VUS CASQ2, c.532T>C, p.(Tyr178His). We studied the segregation of the variation in all pedigree members. All the patients were heterozygous for the variation CASQ2 p.(Tyr178His), whereas the remaining healthy individuals in the family were homozygous for the normal allele. Structural analysis of CASQ2 p.(Tyr178His) was performed and revealed an important effect of the missense variation on monomer stability. The CASQ2 Tyr180 residue is located inside the sarcoplasmic reticulum (SR) junctional face membrane interaction domain and is predicted to disrupt filamentation. Conclusions: Our data suggest that the p.Tyr178His substitution is associated with BrS in the family investigated, affecting the stability of the protein, disrupting filamentation at the interdimer interface, and affecting the subsequent formation of tetramers and polymers that contain calcium-binding sites. Full article

The fire service suffers from high rates of cardiovascular disease and poor overall health, and firefighters often suffer fatal and non-fatal injuries while on the job. Most fatal injuries result from sudden cardiac death, while non-fatal injuries are to the musculoskeletal system. Previous works suggest a mechanistic link between several health and performance variables and injury risk. In addition, studies have suggested physical activity and nutrition can improve overall health and occupational performance. This review offers practical applications for exercise via feasible training modalities as well as nutritional recommendations that can positively impact performance on the job. Time-efficient training modalities like high-intensity interval training and feasible modalities such as resistance training offer numerous benefits for firefighters. Also, modifying and supplementing the diet and can be advantageous for health and body composition in the fire service. Firefighters have various schedules, making it difficult for planned exercise and eating while on shift. The practical training and nutritional aspects discussed in this review can be implemented on-shift to improve the overall health and performance in firefighters. Full article

Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths associated with ibogaine use have been reported, and it has been hypothesized that the adverse effects are related to ibogaine’s tendency to induce cardiac arrhythmias. Considering that the bioavailability of ibogaine and its primary metabolite noribogaine is two to three times higher in female rats than in male rats, we here investigated the effect of a single oral dose (1 or 20 mg/kg) of ibogaine on cardiac histopathology and oxidative/antioxidant balance. Our results show that ibogaine induced dose-dependent cardiotoxic necrosis 6 and 24 h after treatment and that this necrosis was not a consequence of inflammation. In addition, no consistent dose- and time-dependent changes in antioxidant defense or indicators of oxidative damage were observed. The results of this study may contribute to a better understanding of ibogaine-induced cardiotoxicity, which is one of the main side effects of ibogaine use in humans and is often fatal. Nevertheless, based on this experiment, it is not possible to draw a definitive conclusion regarding the role of redox processes or oxidative stress in the occurrence of cardiotoxic necrosis after ibogaine administration. Full article