Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension.

While essential hypertension (HTN) is very prevalent, pulmonary arterial hypertension (PAH) is very rare in the general population. However, due to progressive heart failure, prognoses and survival rates are much worse in PAH. Patients with PAH are at a higher risk of developing supraventricular arrhythmias and malignant ventricular arrhythmias. The latter underlie sudden cardiac death regardless of the mechanical cardiac dysfunction. Systemic chronic inflammation and oxidative stress are causal factors that increase the risk of the occurrence of cardiac arrhythmias in hypertension. These stressful factors contribute to endothelial dysfunction and arterial pressure overload, resulting in the development of cardiac pro-arrhythmic conditions, including myocardial structural, ion channel and connexin43 (Cx43) channel remodeling and their dysfunction. Myocardial fibrosis appears to be a crucial proarrhythmic substrate linked with myocardial electrical instability due to the downregulation and abnormal topology of electrical coupling protein Cx43. Furthermore, these conditions promote ventricular mechanical dysfunction and heart failure. The treatment algorithm in HTN is superior to PAH, likely due to the paucity of comprehensive pathomechanisms and causal factors for a multitargeted approach in PAH. The intention of this review is to provide information regarding the role of Cx43 in the development of cardiac arrhythmias in hypertensive heart disease. Furthermore, information on the progress of therapy in terms of its cardioprotective and potentially antiarrhythmic effects is included. Specifically, the benefits of sodium glucose co-transporter inhibitors (SGLT2i), as well as sotatercept, pirfenidone, ranolazine, nintedanib, mirabegron and melatonin are discussed. Discovering novel therapeutic and antiarrhythmic strategies may be challenging for further research. Undoubtedly, such research should include protection of the heart from inflammation and oxidative stress, as these are primary pro-arrhythmic factors that jeopardize cardiac Cx43 homeostasis, the integrity of intercalated disk and extracellular matrix, and, thereby, heart function.

POPDC1 Variants Cause Atrioventricular Node Dysfunction and Arrhythmogenic Changes in Cardiac Electrophysiology and Intracellular Calcium Handling in Zebrafish.

Popeye domain-containing (POPDC) proteins selectively bind cAMP and mediate cellular responses to sympathetic nervous system (SNS) stimulation. The first discovered human genetic variant (POPDC1S201F) is associated with atrioventricular (AV) block, which is exacerbated by increased SNS activity. Zebrafish carrying the homologous mutation (popdc1S191F) display a similar phenotype to humans. To investigate the impact of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling, homozygous popdc1S191F and popdc1 knock-out (popdc1KO) zebrafish larvae and adult isolated popdc1S191F hearts were studied by functional fluorescent analysis. It was found that in popdc1S191F and popdc1KO larvae, heart rate (HR), AV delay, action potential (AP) and calcium transient (CaT) upstroke speed, and AP duration were less than in wild-type larvae, whereas CaT duration was greater. SNS stress by ß-adrenergic receptor stimulation with isoproterenol increased HR, lengthened AV delay, slowed AP and CaT upstroke speed, and shortened AP and CaT duration, yet did not result in arrhythmias. In adult popdc1S191F zebrafish hearts, there was a higher incidence of AV block, slower AP upstroke speed, and longer AP duration compared to wild-type hearts, with no differences in CaT. SNS stress increased AV delay and led to further AV block in popdc1S191F hearts while decreasing AP and CaT duration. Overall, we have revealed that arrhythmogenic effects of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling in zebrafish are varied, but already present in early development, and that AV node dysfunction may underlie SNS-induced arrhythmogenesis associated with popdc1 mutation in adults.

Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

BACKGROUND: Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS: We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS: Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS: The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.

Investigate the relationship between obstructive sleep apnea and cardiac arrhythmia after CABG surgery.

BACKGROUND AND OBJECTIVE: Heart rhythm disorder is one of the most common problems after coronary artery bypass graft surgery. Various factors, such as the history of sleep apnoea before the operation, may aggravate the occurrence of this disorder. The present study was conducted to determine the relationship between sleep apnoea before surgery and heart rhythm disorder after surgery in patients undergoing coronary Artery Bypass Grafting in 2019. METHODS: This analytical cross-sectional study was conducted on 192 patients who were selected by sequential sampling. The research tool included demographic information, a checklist of heart rhythm disorders, and the Berlin sleep apnoea questionnaire. Descriptive statistics and the Chi-square test, Fisher's exact test, Mann-Whitney's U-test, and logistic regression were used to analyze the data. RESULTS: A total of 71.35% of the samples were male, and the mean age of the participants was 57.8 ± 7.5 years. Also, 46.0% of the samples had sleep pane and 21.35% had rhythm disorder. The most frequent heart rhythm disorder in patients with obstructive sleep apnoea was atrial fibrillation. There was a significant relationship between the occurrence of rhythm disorder and a history of smoking (P = 0.021), and the regression model showed that a history of smoking is the only variable related to the occurrence of rhythm disorder after coronary Artery Bypass Grafting (P = 0.005, CI 95%: 6.566-1.386, OR = 3.017). CONCLUSIONS: The results showed that there is no statistically significant relationship between sleep apnea and rhythm disorder after coronary artery bypass surgery.

Novel NKX2.5 variant associated with congenital heart disease and increased risk of malignant arrhythmia and sudden cardiac death.

INTRODUCTION: The NKX2.5 gene is an important cardiac developmental transcription factor, and variants in this gene are most commonly associated with CHD. However, there is an increased need to recognise associations with conduction disease and potentially dangerous ventricular arrhythmias. There is an increased risk of arrhythmia and sudden cardiac death in patients with NKX2.5 variants, an association with relatively less attention in the literature. METHODS: We created a family pedigree and reconstructed familial relationships involving numerous relatives with CHD, conduction disease, and ventricular non-compaction following the sudden death of one family member. Two informative but distantly related family members had genetic testing to determine the cause of arrhythmias via arrhythmia/cardiomyopathy gene testing, and we identified obligate genetic-positive relatives based on family relationships and Mendelian inheritance pattern. RESULTS: We identified a novel pathogenic variant in the NKX2.5 gene (c.437C > A; p. Ser146*), and segregation analysis allowed us to link family cardiac phenotypes including CHD, conduction disease, left ventricular non-compaction, and ventricular arrhythmias/sudden cardiac death. CONCLUSIONS: We report a novel NKX2.5 gene variant linking a spectrum of familial heart disease, and we also encourage recognition of the association between NKX2.5 gene and potentially dangerous ventricular arrhythmias, which will inform clinical risk stratification, screening, and management.

In Vivo Base Editing of Scn5a Rescues Type 3 Long QT Syndrome in Mice.

BACKGROUND: Pathogenic variants in SCN5A can result in long QT syndrome type 3, a life-threatening genetic disease. Adenine base editors can convert targeted A T base pairs to G C base pairs, offering a promising tool to correct pathogenic variants. METHODS: We generated a long QT syndrome type 3 mouse model by introducing the T1307M pathogenic variant into the Scn5a gene. The adenine base editor was split into 2 smaller parts and delivered into the heart by adeno-associated virus serotype 9 (AAV9-ABEmax) to correct the T1307M pathogenic variant. RESULTS: Both homozygous and heterozygous T1307M mice showed significant QT prolongation. Carbachol administration induced Torsades de Pointes or ventricular tachycardia for homozygous T1307M mice (20%) but not for heterozygous or wild-type mice. A single intraperitoneal injection of AAV9-ABEmax at postnatal day 14 resulted in up to 99.20% Scn5a transcripts corrected in T1307M mice. Scn5a mRNA correction rate >60% eliminated QT prolongation; Scn5a mRNA correction rate <60% alleviated QT prolongation. Partial Scn5a correction resulted in cardiomyocytes heterogeneity, which did not induce severe arrhythmias. We did not detect off-target DNA or RNA editing events in ABEmax-treated mouse hearts. CONCLUSIONS: These findings show that in vivo AAV9-ABEmax editing can correct the variant Scn5a allele, effectively ameliorating arrhythmia phenotypes. Our results offer a proof of concept for the treatment of hereditary arrhythmias.

Left bundle branch pacing lead for sensing ventricular arrhythmias in implantable cardioverter-defibrillator: A pilot study (LBBP-ICD study).

BACKGROUND: Left bundle branch pacing (LBBP) has been suggested as an alternative modality for biventricular pacing in cardiac resynchronization therapy (CRT)-eligible patients. As it provides stable R-wave sensing, LBBP has been recently used to provide sensing of ventricular arrhythmia in patients receiving implantable cardioverter-defibrillator (ICD) with CRT. OBJECTIVE: The aim of this study was to analyze the long-term safety and efficacy of the LBBP lead for appropriate detection of ventricular arrhythmia and delivery of antitachycardia pacing (ATP) in patients requiring defibrillator therapy with CRT. METHODS: CRT-eligible patients who underwent successful LBBP-optimized ICD and LBBP-optimized CRT with defibrillator were enrolled. The LBBP lead was connected to the right ventricular-P/S port after capping the IS-1 connector plug of the DF-1-ICD lead. LBBP-optimized ICD or LBBP-optimized CRT with defibrillator was decided on the basis of correction of conduction system disease. Documented arrhythmic episodes and therapy delivered were analyzed. RESULTS: Thirty patients were enrolled. The mean age was 59.7 ± 10.5 years. LBBP resulted in an increase in left ventricular ejection fraction from 29.9% ± 4.6% to 43.9% ± 11.2% (P < .0001). During a mean follow-up of 22.9 ± 12.5 months, 254 ventricular arrhythmic events were documented. Appropriate events (n = 225 [89%]) included nonsustained ventricular tachycardia (VT) (n = 212 episodes [94%]), VT (n = 8 [3.5%]), and ventricular fibrillation (n = 5 [2.5%]). ATP efficacy in terminating VT was 75%. Eleven percent of episodes (n = 29) were inappropriately detected because of T-wave oversensing. Inappropriate therapy (ATP) was delivered for 14 episodes (5.5%). Three patients (10%) had worsening of tricuspid regurgitation. CONCLUSION: Sensing from the LBBP lead for arrhythmia detection is safe as ∼90% of the episodes were detected appropriately. Future studies with a dedicated LBBP-defibrillator lead along with algorithms to avoid oversensing can help in combining defibrillation with conduction system pacing.

Spontaneous Sinus Rhythm Restoration in Patients With Refractory, Permanent Atrial Fibrillation Who Underwent Conduction System Pacing and Atrioventricular Junction Ablation.

Ablate and pace (A&P) with conduction system pacing (CSP) improves outcomes in patients with symptomatic permanent atrial fibrillation (AF). Data on spontaneous sinus rhythm restoration (SSRR) in this setting are lacking. This study aimed to assess the incidence and the predictors of SSRR in a population of patients with permanent AF who underwent A&P with CSP. Prospective, observational study, enrolling consecutive patients with symptomatic permanent AF (of documented duration >6 months) and uncontrolled, drug-refractory high ventricular rate, who underwent A&P with CSP. The incidence and predictors of SSRR were prospectively assessed. A total of 107 patients (79.0 ± 9.1 years, 33.6% male, 74.8% with New York Heart Association class ≥III, 56.1% with ejection fraction <40%) were enrolled: 40 received His' bundle pacing, 67 left bundle branch area pacing. During a median follow-up of 12 months SSRR was observed in 14 patients (13.1%), occurring a median of 3 months after A&P (interquartile range 1 to 6; range 0 to 17). Multivariable analysis identified a duration of permanent AF <12 months (hazard ratio 7.7, p = 0.040) and a left atrial volume index <49 ml/m2 (hazard ratio 14.8, p = 0.008) as independent predictors of SSRR. In patients with coexistence of both predictors the incidence of SSRR was of 41.4%. In a population of patients with symptomatic, permanent AF, treated with A&P with CSP, SSRR was observed in 13% of patients during follow-up. A duration of permanent AF <12 months and a left atrial volume index <49 ml/m2 were independent predictors of this phenomenon.

Identification of non-ischaemic fibrosis in male veteran endurance athletes, mechanisms and association with premature ventricular beats.

Left ventricular fibrosis can be identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in some veteran athletes. We aimed to investigate prevalence of ventricular fibrosis in veteran athletes and associations with cardiac arrhythmia. 50 asymptomatic male endurance athletes were recruited. They underwent CMR imaging including volumetric analysis, bright blood (BB) and dark blood (DB) LGE, motion corrected (MOCO) quantitative stress and rest perfusion and T1/T2/extracellular volume mapping. Athletes underwent 12-lead electrocardiogram (ECG) and 24-h ECG. Myocardial fibrosis was identified in 24/50 (48%) athletes. All fibrosis was mid-myocardial in the basal-lateral left ventricular wall. Blood pressure was reduced in athletes without fibrosis compared to controls, but not athletes with fibrosis. Fibrotic areas had longer T2 time (44 ± 4 vs. 40 ± 2 ms, p < 0.0001) and lower rest myocardial blood flow (MBF, 0.5 ± 0.1 vs. 0.6 ± 0.1 ml/g/min, p < 0.0001). On 24-h ECG, athletes with fibrosis had greater burden of premature ventricular beats (0.3 ± 0.6 vs. 0.05 ± 0.2%, p = 0.03), with higher prevalence of ventricular couplets and triplets (33 vs. 8%, p = 0.02). In veteran endurance athletes, myocardial fibrosis is common and associated with an increased burden of ventricular ectopy. Possible mechanisms include inflammation and blood pressure. Further studies are needed to establish whether fibrosis increases risk of malignant arrhythmic events.

Arrhythmias and laboratory abnormalities after an electrical accident: a single-center, retrospective study of 333 cases.

BACKGROUND: Even though electrical injuries are common in the emergency room, guidelines, consensus, and general recommendations for the management of these patients do not exist in Europe. Documented cases of delayed arrhythmias are rare and their connection with electrical injury has not been fully confirmed. We also use cardio-specific markers for the risk stratification of myocardial injury, but there is no significant study referring to their utility in this clinical situation. These reasons led us to retrospectively analyze all cases of electrical injuries over 23 years to determine the prevalence of cardiac arrhythmias (mainly malignant arrhythmias and delayed arrhythmias). METHODS: We retrospectively searched all patients admitted to the University Hospital in Pilsen, CZ, with a diagnosis of electric injury (ICD diagnostic code T754) from 1997 to 2020. The hospital´s information system was used to research the injury; data were drawn from patient medical records. RESULTS: We identified 333 cases of electrical injury in our hospital. Men accounted for about two-thirds, and women one-third. Children accounted for about one-third of cases. Most were low-voltage injuries (< 1000 V, 91.6%). All participants had an initial ECG, and 77.5% of patients had continuous ECG monitoring, usually lasting 24 h. Cardiac arrhythmias were noticed in 39 patients (11.7%). The most frequent arrhythmias were: ventricular fibrillation, sinus tachycardia, bradycardia and arrhythmia, atrial fibrillation, and supraventricular tachycardia. The ECG showed cardiac conduction abnormalities in 28 patients (8.1%), and ten patients (3%) had supraventricular or ventricular extrasystoles. In ten cases (3%), we found changes in ST segments and T waves on the initial ECG. Thirty-one patients (9.3%) suffered a loss of consciousness and 50 patients (15.02%) reported paresthesia. The most frequent ion disbalances were hypokalemia (18%) and hypocalcemia (3.3%). Patients with an ion disbalance had significantly more arrhythmias and newly diagnosed cardiac conduction abnormalities. Troponin levels (cTnI or hs-cTnT) were measured in 258 cases (77.48%) and found to be elevated above the 99th percentile in 19 cases (5.7%). Almost one-third of patients had burns of various degrees of seriousness, and 41 patients (12.3%) had concomitant traumatic injuries. Eleven patients underwent pre-hospital resuscitation, three died in the hospital, and another died as result of intracranial hemorrhage. CONCLUSION: All malignant arrhythmias occurred immediately after the electrical injury, delayed life-threatening arrhythmias were not observed, and no predictive factors of malignant arrhythmias were found. While elevations of cardiac troponins were observed sporadically, they did not appear helpful for risk stratification. In patients with arrhythmias, ion disbalance may be more critical. We concluded that asymptomatic, uninjured adult and pediatric patients with normal initial ECG findings do not need continuous ECG monitoring and may be discharged home. Recommendations for high-risk patients and patients with mild ECG abnormalities at admission are less obvious.

Novel p.Asp27Glu ACTA1 variant features congenital myopathy with finger flexor weakness, cardiomyopathy, and cardiac conduction defects.

Pathogenic variants in the skeletal muscle α-actin 1 gene (ACTA1) cause a spectrum of myopathies with clinical and myopathological diversity. Clinical presentations occur from the prenatal period to adulthood, commonly with proximal-predominant weakness and rarely preferential distal weakness. Myopathological findings are wide-ranging, with nemaline rods being most frequent. Associated cardiomyopathy is rare and conduction defects are not reported. We describe a family with congenital myopathy with prominent finger flexor weakness and cardiomyopathy with cardiac conduction defects. The proband, a 48-year-old Caucasian male, his 73-year-old mother, 41-year-old sister, and 19-year-old nephew presented with prominent finger flexor weakness on a background of neonatal hypotonia and delayed motor milestones. All had progressive cardiomyopathy with systolic dysfunction and/or left ventricular dilation. The proband and sister had intraventricular conduction delay and left anterior fascicular block, respectively. The mother had atrial fibrillation. Muscle biopsy in the proband and sister demonstrated congenital fiber-type disproportion and rare nemaline rods in the proband. A novel dominant variant in ACTA1 (c.81C>A, p.Asp27Glu) segregated within the family. This family expands the genotypic and phenotypic spectrum of ACTA1-related myopathy, highlighting preferential finger flexor involvement with cardiomyopathy and conduction disease. We emphasize early and ongoing cardiac surveillance in ACTA1-related myopathy.

Long Noncoding RNA UCA1 Correlates With Electropathology in Patients With Atrial Fibrillation.

BACKGROUND: Perpetuation of atrial fibrillation (AF) is rooted in derailment of molecular proteostasis pathways that cause electrical conduction disorders that drive AF. Emerging evidence indicates a role for long noncoding RNAs (lncRNAs) in the pathophysiology of cardiac diseases, including AF. OBJECTIVES: In the present study, the authors explored the association between 3 cardiac lncRNAs and the degree of electropathology. METHODS: Patients had paroxysmal AF (ParAF) (n = 59), persistent AF (PerAF) (n = 56), or normal sinus rhythm without a history of AF (SR) (n = 70). The relative expression levels of urothelial carcinoma-associated 1 (UCA1), OXCT1-AS1 (SARRAH), and the mitochondrial lncRNA uc022bqs.q (LIPCAR) were measured by means of quantitative reverse-transcription polymerase chain reaction in the right atrial appendage (RAA) or serum (or both). A selection of the patients was subjected to high-resolution epicardial mapping to evaluate electrophysiologic features during SR. RESULTS: The expression levels of SARRAH and LIPCAR were decreased in RAAs of all AF patients compared with SR. Also, in RAAs, UCA1 levels significantly correlated with the percentage of conduction block and delay, and inversely with conduction velocity, indicating that UCA1 levels in RAA reflect the degree of electrophysiologic disorders. Moreover, in serum samples, SARRAH and UCA1 levels were increased in the total AF group and ParAF patients compared with SR. CONCLUSIONS: LncRNAs SARRAH and LIPCAR are reduced in RAA of AF patients, and UCA1 levels correlate with electrophysiologic conduction abnormalities. Thus, RAA UCA1 levels may aid staging of electropathology severity and act as a patient-tailored bioelectrical fingerprint.

EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA).

There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research.

Conduction Disturbances and Arrhythmia Risk After Septal Reduction Therapy with Alternative Agents: A Pilot Study with EVOH-DMSO and Systematic Review.

OBJECTIVE: Surgical septal myectomy and alcohol septal ablation are recommended treatment modalities for alleviating Left ventricular outflow tract (LVOT) gradient in obstructive HCM. Alcohol septal ablation offers advantages over surgery in many ways. However, it is associated with some life-threatening complications. For this purpose, our center used alternative agents for septal artery embolization. This study compared and evaluated conduction system defects and arrhythmia risk after EVOH-DMSO septal ablation with other alternative agents and alcohol septal ablation. METHODS: Twenty-five patients who received septal reduction therapy with EVOH-DMSO were analyzed retrospectively, and all non-alcoholic agent's septal ablation studies were systematically reviewed and compared. RESULTS: Twenty-five patients (52% female; mean age: 55.8 ± 17.1) with symptomatic obstructive HCM were enrolled. The Peak LVOT gradient was significantly reduced after the procedure (68 vs. 20 mmHg; P <0.001). During the 12-month follow-up, no mortality occurred. The complete atrioventricular block was noted in 2 (8%) patients. The incidence of right bundle branch block (RBBB) increased after the procedure (pre-procedural 2 patients (8%), post-procedural 9 patients (36%) P = 0.002). On ECG and Holter monitorization, no sustained ventricular tachyarrhythmia occurred during follow-up, and no change was found in the frequency of atrial fibrillation. We systematically compared EVOH-DMSO to other non-alcohol agents, and we found that EVOH-DMSO can cause conduction system problems more commonly than other non-alcohol agents. CONCLUSION: EVOH-DMSO could cause conduction system problems more common than other non-alcohol agents but less than alcohol septal ablation.

Lifestyle habits associated with cardiac conduction disease.

AIMS: Cardiac conduction disease can lead to syncope, heart failure, and death. The only available therapy is pacemaker implantation, with no established prevention strategies. Research to identify modifiable risk factors has been scant. METHODS AND RESULTS: Data from the Cardiovascular Health Study, a population-based cohort study of adults ≥ 65 years with annual 12-lead electrocardiograms obtained over 10 years, were utilized to examine relationships between baseline characteristics, including lifestyle habits, and conduction disease. Of 5050 participants (mean age 73 ± 6 years; 52% women), prevalent conduction disease included 257 with first-degree atrioventricular block, 99 with left anterior fascicular block, 9 with left posterior fascicular block, 193 with right bundle branch block (BBB), 76 with left BBB, and 102 with intraventricular block at baseline. After multivariable adjustment, older age, male sex, a larger body mass index, hypertension, and coronary heart disease were associated with a higher prevalence of conduction disease, whereas White race and more physical activity were associated with a lower prevalence. Over a median follow-up on 7 (interquartile range 1-9) years, 1036 developed incident conduction disease. Older age, male sex, a larger BMI, and diabetes were each associated with incident conduction disease. Of lifestyle habits, more physical activity (hazard ratio 0.91, 95% confidence interval 0.84-0.98, P = 0.017) was associated with a reduced risk, while smoking and alcohol did not exhibit a significant association. CONCLUSION: While some difficult to control comorbidities were associated with conduction disease as expected, a readily modifiable lifestyle factor, physical activity, was associated with a lower risk.

Cysticercosis & Heart: A Systematic Review.

Cysticercosis is a parasitic tissue infection caused by larval cysts of the tapeworm Taenia solium. These larval cysts infect brain, muscle, or other tissue, and are a major cause of adult-onset seizures in most low-income countries with tropical climate. Prevalence it's around 50 million people. Although cardiovascular system is not the most affected, this disease can also be associated with multiple and randomly distributed cysts in the subpericardium, subendocardium and myocardium in up to 25% of infected patients. Most cardiac cysticercosis' cases are asymptomatic, but it can manifest with ventricular arrhythmias and conduction disorders. Area Covered: The "Neglected Tropical Diseases and other Infectious Diseases affecting the Heart" (NET-Heart project) is an initiative by the Emerging Leaders group of the Interamerican Society of Cardiology to systematically review all these endemic conditions affecting the heart. A systematic review was conducted following preferred reporting items for systematic review and meta-analysis guidelines and including articles published in MEDLINE, ScienceDirect, PubMed and LILACS databases. A total of 41 papers were included in this review. Expert Opinion: In the areas of greatest prevalence, unhealthiness and poverty favor the development of this disease, which highlights the need to establish global health policies that reduce morbidity and mortality, economic losses of the affected population, and health costs related to hospitalizations for cardiovascular involvement. Authors provide an algorithm to evaluate the possibility of Cysticercosis' cardiovascular complications.

Conduction System Pacing vs Biventricular Pacing in Heart Failure and Wide QRS Patients: LEVEL-AT Trial.

BACKGROUND: Conduction system pacing (CSP) has emerged as an alternative to biventricular pacing (BiVP). Randomized studies comparing both therapies are scarce and do not include left bundle branch pacing. OBJECTIVES: This study aims to compare ventricular resynchronization achieved by CSP vs BiVP in patients with cardiac resynchronization therapy indication. METHODS: LEVEL-AT (Left Ventricular Activation Time Shortening with Conduction System Pacing vs Biventricular Resynchronization Therapy) was a randomized, parallel, controlled, noninferiority trial. Seventy patients with cardiac resynchronization therapy indication were randomized 1:1 to BiVP or CSP, and followed up for 6 months. Crossover was allowed when primary allocation procedure failed. Primary endpoint was the change in left ventricular activation time, measured using electrocardiographic imaging. Secondary endpoints were left ventricular reverse remodeling and the combined endpoint of heart failure hospitalization or death at 6-month follow-up. RESULTS: Thirty-five patients were allocated to each group. Eight (23%) patients crossed over from CSP to BiVP; 2 patients (6%) crossed over from BiVP to CSP. Electrocardiographic imaging could not be performed in 2 patients in each group. A similar decrease in left ventricular activation time was achieved by CSP and BiVP (-28 ± 26 ms vs -21 ± 20 ms, respectively; mean difference -6.8 ms; 95% CI: -18.3 ms to 4.6 ms; P < 0.001 for noninferiority). Both groups showed a similar change in left ventricular end-systolic volume (-37 ± 59 mL CSP vs -30 ± 41 mL BiVP; mean difference: -8 mL; 95% CI: -33 mL to 17 mL; P = 0.04 for noninferiority) and similar rates of mortality or heart failure hospitalizations (2.9% vs 11.4%, respectively) (P = 0.002 for noninferiority). CONCLUSIONS: Similar degrees of cardiac resynchronization, ventricular reverse remodeling, and clinical outcomes were attained by CSP as compared to BiVP. CSP could be a feasible alternative to BiVP. (LEVEL-AT [Left Ventricular Activation Time Shortening With Conduction System Pacing vs Biventricular Resynchronization Therapy]; NCT04054895).