Arrhythmia Burden Research Articles

Morbidity Burden in Patients With Ebstein Anomaly: The Natural History.

The lifetime morbidity burden of patients with Ebstein anomaly (EA) has not been well described. Through an extensive 2-country register-based collaboration, patients diagnosed with EA who were born between 1930 and 2017 were identified in Danish and Swedish nationwide medical registries. Each patient was matched by age and sex with 10 control subjects from the general population. Cox proportional-hazards regression, Fine-Gray competing risk regression, and Kaplan-Meier failure function were used to estimate the morbidity burden. The study included 794 patients diagnosed with EA and 7940 controls, with a median follow-up period of 33 years. Among patients with EA, approximately half (n=442) had isolated EA, and 28% (n=218) had concomitant atrial septal defect. Patients with complex anatomy demonstrated the highest cardiovascular morbidity burden, followed by those with concomitant atrial septal defect and isolated EA. The lifetime cumulative incidence of supraventricular arrhythmia and ventricular preexcitation in patients with EA, with or without atrial septal defect, was approximately 70% and 19%, respectively. Supraventricular arrhythmia substantially increased the risk of ischemic stroke (hazard ratio [HR] 22.6 [95% CI, 11.1-45.9]). Presence of atrial septal defect significantly affected arrhythmia and heart failure burden compared with isolated EA. In the total cohort of patients with EA, supraventricular arrhythmia onset led to an immediate high incidence of heart failure, with a 10-year cumulative incidence of 18%. The natural history of EA, whether isolated or not, involves a substantial burden of cardiovascular morbidity and thus a highly vulnerable long-term prognosis.

Arrhythmia burden in patients with congenital heart disease

Abstract Background The prevalence of congenital heart defects (CHD) is rising. Many patients experience arrhythmias either due to the defect itself or necessary intervention. Sudden onset of arrhythmia poses grave risks such as heart failure, stroke, or cardiac death. Research gaps exist regarding high-risk defects, age susceptibility, and prognostic implications of arrhythmia. Purpose Delineate the burden of arrhythmias in patients with CHD. Methods Patients born in the period 1970-2017 and diagnosed with CHD were identified in Swedish nationwide medical registries. Each patient was matched by birthyear and sex with ten controls from the general population. Cox proportional hazard regression model and Fine-Gray regression model with death as competing risk were used to compute risk (hazard ratio [HR]) and cumulative incidence of arrhythmias (supraventricular and ventricular arrhythmias). Estimates were compared with the matched controls. Follow-up started at time of birth. Results We included 63,559 patients and 583,205 matched controls with median follow-up of 12.8 years. Almost two-thirds of the total CHD population were born after year 2000 and 89% (n=56,564) had a simple lesion (defined as atrial or ventricular septal defect, coarctation of the aorta or malformation of the heart valves). During follow-up, 1,632 events of arrhythmia (90% of supraventricular origin) were registered in the population of patients with CHD, yielding an incidence rate of 16.4 per 10,000 person-years (versus 1.6 in the control population). The cumulative incidence of arrhythmias in the total CHD population was slightly increased during childhood compared with the control population, but rose significantly hereafter, illustrated in Figure 1, yielding an overall risk of 10.5 (CI 95%: 9.8-11.2). Stratified by lesion severity, the risk for arrhythmias was 8.7 (CI 95%: 7.6-8.7) and 30.4 (CI 95%: 26.2-35.2) in patients with simple and complex lesions, respectively. Patients with simple CHD lesions displayed a risk of 7.7 (95% CI: 7.1-8.4) for supraventricular arrhythmias and 11.5 (95% CI: 9.2-14.5) for ventricular arrhythmias. Correspondingly, patients with complex CHD lesions displayed risks of 66.7 (95% CI: 42.7-104.2) and 28.9 (95% CI: 24.8-33.6). Conclusion Arrhythmias, irrespective of origin, are common in patients with CHD and correlate with lesion severity. The overall burden of arrhythmias increased significantly after childhood. Meticulous follow-up is vital in order to prevent, detect and treat arrhythmias as it might trigger clinical deterioration and even sudden cardiac death in patients with CHD.

Ventricular and supraventricular ectopic beats burden is correlated with bone mineral density and osteoporotic fracture risk in postmenopausal females

Abstract Introduction Patients (pts) with osteoporosis (OP) have an increased 10-year cardiovascular death risk. Low bone mineral density (BMD) observed in OP may be associated with arrhythmic presentation of cardiovascular diseases (CVD). Few studies assessed the relationship between OP and arrhythmia. Aim Arrhythmias assessment in pts with OP. Methods A total of 103 postmenopausal female pts (mean age 69 +/- 7), consulted by endocrinologist, were divided into 2 groups according to BMD (assessed by dual energy X-ray absorptiometry). BMD measurements, expressed as T-score (T-sc), were taken from the femoral neck (T-sc Neck), entire total hip (T-sc TH) and/or spine (T-sc L2-L4, L1-L4). Arrhythmia was evaluated using 24-hour Holter-ECG monitoring (HM). Major osteoporotic and total hip fracture risks (MOFR and THFR, respectively) were assessed by the FRAX scale. We compared 51 pts with OP (T-sc ≤ -2.5), with 52 matched controls without OP, including 44 pts with osteopenia (T-sc > -2.5). There were no significant differences between the groups regarding the history of stroke, myocardial infarction, coronary artery disease or arterial hypertension. Exclusion criteria included heart failure NYHA >II and/or LVEF <36%, acute coronary syndrome within the last 6 months, severe valvular disease, cardiac implantable electronic device. Results There was a trend towards a greater number of supraventricular and ventricular arrhythmias in the OP group compared to the controls. Arrhythmic burden was significantly correlated with BMD measures: correlations were observed between 24-hour ventricular ectopic beats (VEB) count with T-sc Neck (r=-0.20, p=0.04), with T-sc TH (r=-0.22, p=0.03). The number of supraventricular ectopic beats (SVEB) in HM was also correlated with BMD parameters: T-sc Neck (r=-0.21, p=0.03), T-sc TH (r=-0.23, p=0.02). Multivariate analysis (linear regression model) revealed that age and T-sc TH were independently related with ectopy: age (0.07; CI: 0.01 - 0.13, p=0.03) and T-sc TH (-0.58; CI: -1.07 - -0.08, p=0.02) were predictors for VEB, and SVEB were related to age (0.07; CI: 0.03 - 0.12, p<0.01) and, with borderline significance with T-sc TH (-0.34; CI: -0.699 - 0.012, p=0.058). Ectopic beats count was also positively correlated with osteoporotic fracture risk: VEB with THFR (r=0.206, p=0.04) and SVEB with MOFR (r=0.21, p=0.04). Conclusions The study showed an increased arrhythmia burden as detected in HM in pts with OP. Beside the T-sc TH, age was identified as an independent factor of increased SVEB / VEB. The main significant negative correlations were observed between the number of VEB / SVEB and BMD in femur (T-sc Neck, T-sc TH). Ectopic beats count was also positively correlated with osteoporotic fracture risk: VEB with THFR and SVEB with MOFR.

CRT should be recommended for all heart failure patients with mechanical dyssynchrony and a ventricular conduction delay regardless of the QRS morphology

Abstract Introduction Two recent meta-analyses displayed the heterogeneous effect of cardiac resynchronization therapy (CRT) in patients with a non-left bundle branch block (non-LBBB) and found an increased burden of ventricular arrhythmias after CRT (1,2). Careful patient selection is therefore paramount. Evidence suggests the assessment of mechanical dyssynchrony may guide decision-making to CRT in this challenging population. Purpose To assess the effect of CRT in patients with and without mechanical dyssynchrony compared to medication only, and in particular in patients with a non-LBBB morphology. Methods We retrospectively screened for symptomatic heart failure patients who presented between 2012 and 2018 at our clinic with a QRS duration ≥130ms and a left ventricular ejection fraction (LVEF) ≤35%. We identified 361 patients who received CRT and 1107 patients who could have been considered for CRT. Patients were excluded if echocardiographic data was unavailable, they received CRT after 2018, were 80 years or older, or had other significant co-morbidities. We enrolled the remaining 220 CRT patients ("CRT") and 124 patients treated with medication only ("Control") for analysis. Patients were categorized for the presence of mechanical dyssynchrony on echocardiography, defined as the presence of either septal flash, apical rocking, or both. Multivariable-adjusted Cox regression analyses, including stratification by the presence of dyssynchrony, was performed to compare the effect of CRT to medication only. Hazard ratios (aHR) were obtained after adjustment for age, sex, atrial rhythm, QRS duration, QRS morphology, ischemic disease, kidney function, medication and presence of a defibrillator. Sensitivity analysis was performed in patients with a non-LBBB morphology. Results The CRT and Control group were comparable except for the QRS duration (163±22ms vs 152±16ms, p<0.001), the proportion of patients on optimal medical therapy (64% vs 47%, p=0.001), patients with a defibrillator (81% vs 19%, p<0.001), and patients with a LBBB morphology (75% vs 47%, p<0.001). During an average follow-up of 6.0(±3.2) years, 162 patients (47%) died. In the overall cohort, CRT did not significantly improve survival (aHR: 0.66, p=0.065). There was, however, a marked survival benefit for CRT over medication only in patients with mechanical dyssynchrony (aHR: 0.37, p=0.001). In patients without dyssynchrony there was a trend towards harm due to CRT (aHR: 2.05, p=0.062). These results were consistent in the sub-cohort of patients with a non-LBBB morphology. Conclusion CRT significantly improves the life expectancy of patients with mechanical dyssynchrony, including patients with a non-LBBB morphology. These results add to the evidence that all heart failure patients with LVEF≤35%, QRS≥130ms and mechanical dyssynchrony should be recommended (Class I) for CRT regardless of QRS morphology, while awaiting the results of ongoing randomized controlled trials.

Impact of dapagliflozin on supraventricular and ventricular arrhythmias, assessed by Holter ECG, in patients with heart failure with reduced ejection fraction

Abstract Background & Introduction Dapagliflozin has significantly reduced morbidity & mortality in patients with heart failure with reduced ejection fraction (HFrEF) (1). Some studies reported supraventricular & ventricular arrhythmia suppression, but Holter ECG was underused, hindering precise assessment of arrhythmia burden. Purpose We aim to assess the impact of dapagliflozin on reduction of arrhythmia in HFrEF at 1 year follow-up (FU) by Holter ECG. Methods This is a single center, prospective study. We have screened 219 HFrEF patients, but only 156 patients were enrolled with LVEF <40% in sinus rhythm from December 2021 to July 2023. All patients had dapagliflozin 10 mg once/day tablet with the standard HF therapy. Clinical evaluation, NYHA evaluation, 6-minute walking test (6MWT), echocardiogram, 24-hours Holter ECG and laboratory work-up were done at baseline, and FU at 6 months and 12 months. Results Males constituted 61.5% of study population; mean± SD participants’ age was 56.8 ± 8.6 years. The most common comorbidities were: ischemic etiology (63.3%), dilated cardiomyopathy (28.1%), hypertension (27.3%), smokers (14.7%), and type II diabetes (31.4%). LVEF was ≤ 35% in 85.9% of patients. We have reported (7.69%) deaths during 1-year FU, and 4 patients (2.56%) didn't complete 1-year FU. Main clinical and echocardiographic findings (baseline vs. 1-year FU): NYHA FC III& ambulant IV dropped from (42.9 to 32.9%), P value<0.05. Distance walked in 6MWT improved from 191.52 ± 75.37 to 219.35 ± 71.51 mean± SD meters, P value<0.05. E/e improved (9.4 to 8.3 cm/s, P value <0.01), LVEF improved (31.3 to 36.4%, P value<0.05). HF emergency: [HF visits dropped (23.7 to 19.2%) and HF hospitalization dropped (11.1 to 7.8%)], P value<0.05. Holter ECG (baseline vs. 1-year FU): Supraventricular Arrhythmia: [Paroxysmal AF reduced (56.2 to 47.6%), frequent PACs (≥ 10%) dropped (3.8 to 1.4%) & Intermittent 1st degree heart block dropped (12.5 to 7.3%)] P value <0.01. Ventricular Arrhythmia: [PVCs >5%-<10% dropped (16% to 9.3%), Frequent PVCs >10% dropped (3.2 to 1.4%), and NSVT dropped (7.8 to 3.1%)], P value <0.01. Stepwise logistic regression multivariable model aiming to predict the occurrence of ventricular and supraventricular arrhythmias has indicated a direct linear correlation with male gender, smoking, body mass index, left atrial volume, and a history of myocardial infarction. Conversely, there is an inverse relationship with systolic blood pressure, 6MWT distance, LVEF, and the administration of dapagliflozin (OR 0.72 [0.61 - 1.07], P value <0.01) concerning the likelihood of supraventricular and ventricular arrhythmias. Conclusions Dapagliflozin has demonstrated significant improvement in functional and echocardiographic parameters in HFrEF patients. Furthermore, it has effectively decreased the incidence of supraventricular and ventricular arrhythmias, identified through 24-hour Holter ECG monitoring during 1-year follow-up.

Phase I gene therapy clinical trial design of RP-A601 in adult patients with PKP2-arrhythmogenic cardiomyopathy (PKP2-ACM)

Abstract Background Arrhythmogenic cardiomyopathy (ACM) is a rare, progressive, autosomal dominant disorder characterized by increased risk of ventricular arrhythmias and sudden cardiac death. Up to 45% of all ACM cases are caused by pathogenic variants in the PKP2 gene, which encodes for the desmosomal protein Plakophilin-2. This genetic cardiomyopathy is referred to as PKP2-ACM. AAVrh.74-PKP2a is a recombinant adeno-associated viral (AAV) vector containing the coding sequence of human PKP2 isoform A (PKP2a) and delivers the functional PKP2 gene to cardiomyocytes. Preclinical testing conducted in a clinically relevant mouse model of PKP2-ACM (with survival ≤50 days post disease onset) demonstrated that administration of a single AAVrh.74-PKP2a dose after disease onset extended survival through 5 months with improved right ventricular (RV) function, and decreased cardiac dilation, myocardial fibrosis, and arrhythmias. Additional studies in rodents and nonhuman primates demonstrated AAVrh.74-PKP2a safety. These preclinical findings support clinical initiation. Purpose We describe the design of a phase I trial to assess safety and preliminary efficacy of AAVrh.74-PKP2a (RP-A601) in high-risk adult patients with PKP2-ACM. Methods This study (NCT05885412) is a multi-center, open-label, dose escalation trial evaluating the safety and preliminary efficacy of a single intravenous infusion of RP-A601 in adult patients (age ≥18 yrs) with clinical and genetic PKP2-ACM diagnosis and an implanted ICD. Patients with severe right ventricular dysfunction, LV ejection fraction ≤50% (echocardiogram or cardiac MRI) and/or NYHA Class IV heart failure are excluded. Preliminary efficacy will be assessed at 12 months after RP-A601 infusion and includes evaluation of change in PKP2 myocardial tissue expression and clinical markers of arrhythmia burden. Conclusions PKP2-ACM is a devastating disease associated with high morbidity and mortality. This Phase I trial will evaluate the safety and preliminary efficacy of RP-A601 and was initiated based on robust preclinical efficacy and safety data.

Risk Factors Associated With Ventricular Dysfunction in Wolff-Parkinson-White Syndrome

BackgroundWolff-Parkinson-White (WPW) syndrome is associated with ventricular dysfunction in the absence of sustained tachyarrhythmias. Our aim was to determine the prevalence of ventricular dysfunction and to assess risk factors associated with this condition. MethodsA single-centre retrospective analysis of all patients <18 years of age with WPW syndrome and normal cardiac anatomy who underwent an electrophysiology study ablation over a 14-year period was performed. Patients with an ejection fraction <55% were defined as having ventricular dysfunction. ResultsAmong 305 patients, 14 cases (4.5%) with ventricular dysfunction were identified. In 4 of 14 cases (28%), the presenting symptom was heart failure, and only 6 of 14 (43%) had symptoms of palpitations or documented supraventricular tachycardia. The vast majority of patients with dysfunction had right-sided pathways, and only 2 patients had a left-sided pathway locations. Right anteroseptal, anterior, and anterolateral accessory pathway locations were more common in the dysfunction group. The presence of multiple pathways and pathway characteristics assessed during electrophysiology study were comparable between the 2 groups. ConclusionsThe prevalence of ventricular dysfunction in WPW syndrome in children was 4.5%, and this is seen more frequently with right anteroseptal, anterior, and anterolateral pathway locations. Risk analysis identified these pathway locations to be associated with a 4-fold risk of developing ventricular dysfunction (odds ratio: 4.32 [confidence interval: 1.38-14.18], P = 0.012). Because of this rare complication, serial assessment of ventricular function is recommended regardless of arrhythmia burden and an ablation should be considered in the presence of dysfunction.

A Comprehensive Review on Stereotactic Arrhythmia Radioablation (STAR): Pioneering a New Era in Arrhythmia Management.

Stereotactic arrhythmia radioablation (STAR) is an innovative treatment modality that leverages advanced imaging techniques and focused radiation to target arrhythmogenic foci within the heart, offering a non-invasive alternative to traditional catheter ablation methods. Arrhythmias, characterized by irregular heartbeats, pose significant health risks, including heart failure and stroke, particularly among older adults. Traditional management approaches, such as pharmacological therapies and catheter ablation, often face efficacy, safety, and recurrence limitations. STAR addresses these challenges by utilizing high-precision stereotactic technology to deliver targeted radiation, minimizing damage to surrounding tissues while maximizing therapeutic effects. This review explores the mechanisms, clinical indications, procedural techniques, and outcomes associated with STAR. Recent clinical studies demonstrate that STAR provides comparable efficacy to catheter ablation, with a favorable safety profile, making it a promising option for patients who have not responded to conventional treatments. Integrating STAR into arrhythmia management protocols may enhance patient outcomes and reduce the burden of recurrent arrhythmias. As research in this field advances, STAR holds the potential to reshape the landscape of arrhythmia treatment, providing new hope for patients suffering from these complex conditions. This review aims to elucidate the significance of STAR in modern arrhythmia management and to encourage further exploration and clinical application of this pioneering technique.

Magnetic Resonance-Guided StereotacticRadioablation for SeptalVentricular Tachycardias.

Stereotactic arrhythmia radioablation (STAR) was introduced to treat ventricular tachycardia (VT) refractory to catheter ablation. No data are now available in the septal VT substrate setting, representing a challenge when using conventional techniques. This study sought to evaluate the arrhythmic burden in patients with septal VT treated with magnetic resonance-guided STAR (MRgSTAR). We enrolled consecutive patients with septal VT substrate. The therapy target was achieved by combining anatomic/functional and electrophysiologic information. Patients were treated with a single fraction of 25Gy adopting MRgSTAR. All patients were clinically followed up, and all implantable cardiac devices were remotely monitored. The efficacy outcome included recurrences of any sustained VT beyond the 6-week blanking period after MRgSTAR. The safety outcome was the incidence of adverse events and atrioventricular block. We included 11 patients with septal substrate VT (median age: 68 years; Q1-Q3: 64.5-78 years; 100% male). Clinical presentation was an electrical storm in 81.8% of patients. No complications occurred after MRgSTAR, and 6(54.5%) patients were discharged on the same day of treatment. During a mean follow-up of 12 ± 6months, the efficacy outcome occurred in 3 (27.3%) cases. A significative reduction of implantable cardioverter-defibrillator (ICD) therapy (23.6 before MRgSTAR vs 1.7 after MRgSTAR; P< 0.001) was observed. Left ventricular ejection fraction increased significantly after treatment (38% [Q1-Q3: 33.5%-42.0%] before MRgSTAR vs 43.8% [Q1-Q3: 35%-47%] after MRgSTAR; P=0.04). No adverse effects were observed in the implantable cardioverter-defibrillator and lead system; in the 7 patients with preserved atrioventricular conduction, no atrioventricular block was reported. MRgSTAR represents a safe and effective strategy for treating septal VT.

Ertugliflozin to Reduce Arrhythmic Burden in Patients with ICDs/CRT-Ds

BackgroundSodium–glucose cotransporter 2 inhibitors (SGLT2is) have beneficial pleiotropic effects, contributing to improved cardiovascular and renal outcomes for patients with and without diabetes. The impact of SGLT2is on arrhythmic burden remains largely unexplored through randomized trials.MethodsIn this multicenter, double-blind, randomized, placebo-controlled trial, we investigated the effects of ertugliflozin on arrhythmic burden among patients with heart failure with an ejection fraction less than 50%. All patients had an implantable cardioverter–defibrillator (ICD) with or without a cardiac resynchronization therapy device (CRT-D) and were randomized (1:1) to receive either ertugliflozin 5 mg once daily or placebo. The primary end point was the number of incident sustained (>30 seconds) ventricular tachycardia or ventricular fibrillation events from baseline to week 52. Secondary end points included the total number of non-sustained ventricular tachycardias, appropriate ICD therapies, changes in N-terminal pro-brain–type natriuretic peptide (NTproBNP) levels, and the number of heart failure hospitalizations.ResultsRandomization was prematurely terminated, after class IA guideline recommendations were published for SGLT2is in patients with heart failure regardless of the ejection fraction. The final analysis included 46 patients (11% of the originally planned sample size). The yearly rate of the primary end point was 3.5 (95% confidence interval [CI] 2.8 to 4.4) with ertugliflozin compared with 13.3 with placebo (95% CI 11.8 to 14.8; rate ratio 0.16, 95% CI 0.04 to 0.61; P<0.001). There were no apparent differences in appropriate ICD therapies, hospitalizations, NTproBNP levels, or predefined adverse and serious adverse events.ConclusionsErtugliflozin reduced sustained ventricular tachycardia or ventricular fibrillation events in adults with heart failure and an ICD compared with placebo; however, our trial ended early and thus results should be interpreted with caution. (Funded by Investigator-initiated Studies Program of Merck Sharp & Dohme Corp and Pfizer; EudraCT number, 2020-002581-14; ClinicalTrials.gov number NCT04600921.)

Efficacy and safety of early postoperative ablation in patients with congenital heart disease

BackgroundPostoperative arrhythmias are most often transient and medically treated, but some patients may require electrophysiology study (EPS) and ablation. ObjectiveThe purpose of this study was to describe the efficacy and safety of early postoperative ablation. MethodsThis study presents a retrospective series of patients who underwent EPS within 12 months of surgery for congenital heart disease between 2000 and 2021. The procedural outcome included complete or partial success, empirical ablation or failure, and complications. The long-term outcome included arrhythmia recurrence and burden according to a 12-point clinical arrhythmia severity score (documented arrhythmia, arrhythmia severity, cardioversion, and antiarrhythmic medication). ResultsAmong 28,902 operations during the study period, 24 patients (0.1%) underwent EPS within 3 months of surgery and 26 (0.1%) 3–12 months after surgery. Most patients had great (n = 27 [50%]) or moderate (n = 21 [42%]) congenital heart disease complexity. Mechanisms of arrhythmias included intra-atrial reentrant tachycardia (n = 23 [46%]), ectopic atrial tachycardia (n = 13 [26%]), accessory pathway (n = 6 [12%]), atrioventricular nodal reentrant tachycardia (n = 7 [14%]), twin atrioventricular node (n = 1 [2%]), atrial fibrillation (n = 1 [2%]), junctional ectopic tachycardia (n = 1 [2%]), and ventricular tachycardia (n = 2 [4%]). The procedure was acutely successful in 41 patients (82%), empirical in 5 (10%), and unsuccessful in 4 (8%). Complications occurred in 4 (8%) patients (major in 1, moderate in 1, and minor in 2). The recurrence of arrhythmia was documented in 27 patients (54%), although the burden of arrhythmia was significantly reduced. ConclusionA minority of patients require early postoperative EPS and ablation. For those, the procedure can be performed with reasonable acute success and manageable morbidity even in critically ill patients with complex surgical anatomy.

Impact on ventricular arrhythmic burden of SGLT2 inhibitors in patients with chronic heart failure evaluated with cardiac implantable electronic device monitoring

BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors have revolutionized the therapeutic scenario of heart failure, demonstrating favorable effects on mortality and quality of life. Previous studies have yielded conflicting data regarding the effects on ventricular arrhythmias. MethodsA prospective observational study was conducted to investigate the anti-arrhythmic properties of SGLT2 inhibitors evaluating the intra-patient difference in major adverse arrhythmic cardiac events (MAACE) over a six-month period in patients with chronic heart failure who were undergoing continuous monitoring using a cardiac implantable electronic device. ResultsFrom January 2022 to January 2023, 82 patients [median age 63 years (IQR 15), male 87 %] were enrolled in the study, with a median follow-up of 28 weeks (IQR 5). The rate of MAACE at baseline was 11 %, without relevant differences in the follow up in terms of major and minor arrhythmic events. In patients with an arrhythmic phenotype at baseline, a mild but non statistically significant reduction of MAACE (from 36 % to 28 %, p = 0.727) was observed and a significant decrease of non-sustained ventricular tachycardia (from 68 % to 32 %, p = 0.022). ConclusionsOur findings suggest potential anti-arrhythmic properties of SGLT2 inhibitors, evident in patients with arrhythmic events before the initiation of the drug.

Emergence of Atrial Fibrillation and Flutter in COVID-19 Patients: A Retrospective Cohort Study.

COVID-19 is associated with various cardiovascular complications, including arrhythmias. This study investigated the incidence of new-onset atrial fibrillation (AFB) and atrial flutter (AFL) in COVID-19 patients and identified potential risk factors. We conducted a retrospective cohort study at a tertiary-care safety-net community hospital including 647 patients diagnosed with COVID-19 from March 2020 to March 2021. Patients with a prior history of AFB or AFL were excluded. Data on demographics, clinical characteristics, and outcomes were collected and analyzed using chi-square tests, t-tests, and binary logistic regression. We found that 69 patients (10.66%) developed AFB or AFL, with 41 patients (6.34%) experiencing new-onset arrhythmias. The incidence rates for new-onset AFB and AFL were 5.4% and 0.9%, respectively. Older age (≥65 years) was significantly associated with new-onset AFB/AFL (OR: 5.43; 95% CI: 2.31-12.77; p < 0.001), as was the development of sepsis (OR: 2.73; 95% CI: 1.31-5.70; p = 0.008). No significant association was found with patient sex. Our findings indicate that new-onset atrial arrhythmias are a significant complication in COVID-19 patients, particularly among the elderly and those with sepsis. This highlights the need for targeted monitoring and management strategies to mitigate the burden of atrial arrhythmias in high-risk populations during COVID-19 infection.

Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation

Bruton’s tyrosine kinase inhibitors (BTKi) have dramatic efficacy against B-cell malignancies, but link with cardiotoxicity, including atrial fibrillation (AF). Burden, severity, and implications of BTKi-related AF are unknown. Leveraging a large-cohort of consecutive B-cell malignancy patients initiated on BTKi from 2009–2020, we identified patients with extended ambulatory rhythm monitoring. The primary outcome was AF burden after BTKi-initiation. Secondary outcomes included ventricular arrhythmia burden and other arrhythmias. Observed incident-AF rates and burden with next-generation BTKi’s were compared to ibrutinib. Multivariable regression defined association between rhythm measures and major adverse cardiac events (MACE), and mortality. There were 98 BTKi-treated patients [38.8% next-generation BTKi’s, 14.3% prior-AF], with 28,224 h of monitoring. Median duration BTKi-use was 34 months. Over mean duration 12 days monitoring, 72.4% developed arrhythmias (16.3% incident-AF, 31.6% other SVTs, 14.3% ventricular tachycardia). 14.3% had high AF-burden. AF-burden was similar between ibrutinib and next-generation BTKi’s. No single antiarrhythmic-therapy prevented BTKi-related AF. However, antiarrhythmic initiation associated with reduction in arrhythmic burden (P = 0.009). In a multivariable model accounting for traditional cardiovascular risk factors, prior-AF associated with increased post-BTKi AF-burden. In follow-up, high AF burden associated with MACE (HR 3.12, P = 0.005) and mortality (HR 2.97, P = 0.007). Among BTKi-treated patients, high AF burden prognosticates future MACE and mortality risk.

Clinical utility of ambulatory ECG monitoring and 2D-ventricular strain for evaluation of post-COVID-19 ventricular arrhythmia

BackgroundA relatively common complication of COVID -19 infection is arrhythmia. There is limited information about myocardial deformation and heart rate variability (HRV) in symptomatic post COVID patients presented by ventricular arrhythmia.Aim of the studyOur goal was to assess 2D-ventricular strain and heart rate variability indices (evaluated by ambulatory ECG monitoring) in post-COVID-19 patients suffering from ventricular arrhythmia.MethodsThe current observational case–control study performed on 60 patients one month after they had recovered from the COVID-19 infection. Thirty healthy volunteers served as the control group. Each participant had a full medical history review, blood tests, a 12-lead surface electrocardiogram (ECG), 24-h ambulatory ECG monitoring, and an echo-Doppler examination to evaluate the left ventricular (LV) dimensions, tissue Doppler velocities, and 2D-speckle tracking echocardiography (2D-STE) for both the LV and right ventricular (RV) strain.ResultsSymptomatic post-COVID patients with monomorphic premature ventricular contractions (PVCs) showed a substantial impairment of LV/RV systolic and diastolic functions, LV/RV myocardial performance (MPI) with reduced indices of HRV. Patients with higher versus lower ventricular burden had poorer functional status, higher levels of inflammatory biomarkers and reduced parameters of HRV (New York Heart Association (NYHA) class: 2.1 ± 0.9 vs. 1.5 ± 0.6, p < 0.001, C-reactive protein (CRP): 13.3 ± 4.1 vs. 8.3 ± 5.9 mg/L, p < 0.0001, low frequency/high frequency (LF/HF): 3.6 ± 2.4 vs. 2.2 ± 1.2, p < 0.002, the root mean square of the difference between successive normal intervals (rMSSD): 21.8 ± 4.7 vs. 29.3 ± 14.9 ms, p < 0.039 and the standard deviation of the RR interval (SDNN): 69.8 ± 19.1 vs.108.8 ± 37.4 ms, p < 0.0001). The ventricular burden positively correlated with neutrophil/lymphocyte ratio (NLR) (r = 0.33, p < 0.001), CRP (r = 0.60, p < 0.0001), while it negatively correlated with LV-global longitudinal strain (GLS) (r = -0.38, p < 0.0001), and RV-GLS (r = -0.37, p < 0.0001).ConclusionsPatients with post-COVID symptoms presented by ventricular arrhythmia had poor functional status. Patients with post-COVID symptoms and ventricular arrhythmia had subclinical myocardial damage, evidenced by speckle tracking echocardiography while having apparently preserved LV systolic function. The burden of ventricular arrhythmia in post-COVID patients significantly correlated with increased inflammatory biomarkers and reduced biventricular strain.

Innovative approaches to atrial fibrillation prediction: should polygenic scores and machine learning be implemented in clinical practice?

Atrial fibrillation (AF) prediction and screening are of important clinical interest because of the potential to prevent serious adverse events. Devices capable of detecting short episodes of arrhythmia are now widely available. Although it has recently been suggested that some high-risk patients with AF detected on implantable devices may benefit from anticoagulation, long-term management remains challenging in lower-risk patients and in those with AF detected on monitors or wearable devices as the development of clinically meaningful arrhythmia burden in this group remains unknown. Identification and prediction of clinically relevant AF is therefore of unprecedented importance to the cardiologic community. Family history and underlying genetic markers are important risk factors for AF. Recent studies suggest a good predictive ability of polygenic risk scores, with a possible additive value to clinical AF prediction scores. Artificial intelligence, enabled by the exponentially increasing computing power and digital data sets, has gained traction in the past decade and is of increasing interest in AF prediction using a single or multiple lead sinus rhythm electrocardiogram. Integrating these novel approaches could help predict AF substrate severity, thereby potentially improving the effectiveness of AF screening and personalizing the management of patients presenting with conditions such as embolic stroke of undetermined source or subclinical AF. This review presents current evidence surrounding deep learning and polygenic risk scores in the prediction of incident AF and provides a futuristic outlook on possible ways of implementing these modalities into clinical practice, while considering current limitations and required areas of improvement.

Exploring suitability to electrical storm ablation in patients in waiting list for heart transplantation: A single center experience.

Electrical storm (ES) is among the most fearsome events in patients in waiting list for heart transplantation (HT) and catheter ablation (CA) demonstrated to be effective in reduce the arrhythmic burden. However, selection criteria for CA suitability in this specific population have never been addressed before. We retrospectively enrolled 36 patients (mean age 51±8 years; 83% men) waiting HT referred to our department for ES resistant to antiarrhythmic drugs and percutaneous stellate ganglion blockade. Twenty patients were judged suitable for VT ablation according to specific criteria including absence of increased arrhythmic burden secondary to volume overload and hemodynamic decompensation; expected CA outcome favorable due to etiology of the cardiomyopathy, no need for coronary revascularization and technical feasibility of the procedure. The pre-emptive use of mechanical circulatory supports (MCS) were discussed integrating the PAINESD score with additional clinical and hemodynamic parameters. Acute procedural success was accounted in 85% of cases with only two major complications. The CA group reported lower length of in-hospital stay after CA suitability evaluation (56±17vs. 131±64 days, p=.004). Furthermore, at a mean follow-up of 703±145 days, this group showed reduction of ventricular arrhythmia (VA) recurrence leading to implantable cardioverter defibrillator shock (4vs. 8, p=.051) and underwent HT with a lower level of urgency (0vs. 6 patients needed for UNOS1 status upgrade). Respectively, one patient of the CA group and two patients of the conservative group died (p=.839). At the end of follow-up, eight patients underwent heart transplantation (p=.964) while four patients underwent Left Ventricular Assist device (LVAD) implantation (p=.440). This pilot study should be a proof for further studies exploring CA of VAs as a possible bridge therapy to HT.

Catheter ablation for focal atrial tachycardias during pregnancy: A systematic review

ObjectivePregnancy can trigger maternal tachycardias, and the onset of recurrent or incessant focal atrial tachycardia (AT) can lead to tachycardia-induced cardiomyopathy. Medical interventions are commonly employed, but they carry potential fetal and maternal risks. Catheter ablation (CA), particularly with non-fluoroscopic navigation systems, may be considered as an alternative. This systematic review aims to explore the feasibility and outcomes of CA for focal AT during pregnancy. MethodsA thorough literature search was conducted until September 30th, 2023, on PubMed, Embase, and Cochrane databases. Included articles described maternal focal ATs diagnosed through electrophysiological studies and treated with CA. Data derived from these studies were organized into tables and subsequently analyzed. ResultsOut of 278 papers reviewed, 15 articles involving 24 patients were retrieved. CA, utilizing radiofrequency energy achieved acute success in 95.8% of cases. Sixteen patients (66.7%) underwent complete fluoroless procedures, with two adverse events directly related to the procedure reported. Long-term follow-up revealed minimal AT recurrences, with a 0.06% arrhythmia burden in one case. ConclusionFocal ATs during pregnancy can be incessant and refractory to medical intervention, precipitating an acute decline in left ventricular ejection fraction. In this setting, CA emerges as an efficacious treatment modality, particularly in cases of tachycardia-induced cardiomyopathies. Whenever feasible, it is advisable to perform these procedures with minimal or no fluoroscopy guidance. Larger studies are needed to establish the safety and the efficacy of CA for focal ATs during pregnancy, as current research consists of case reports or small case series.

Long-Term Changes in Atrial Arrhythmia Burden After Renal Denervation Combined With Pulmonary Vein Isolation: SYMPLICITY-AF

BackgroundThe autonomic nervous system plays an important role in atrial fibrillation (AF) and hypertension. Renal denervation (RDN) lowers blood pressure (BP), but its role in AF is poorly understood. ObjectivesThe purpose of this study was to investigate whether RDN reduces AF recurrence after pulmonary vein isolation (PVI). MethodsThis study randomized patients from 8 centers (United States, Germany) with drug-refractory AF for treatment with PVI+RDN vs PVI alone. A multielectrode radiofrequency Spyral catheter system was used for RDN. Insertable cardiac monitors were used for continuous rhythm monitoring. The primary efficacy endpoint was ≥2 minutes of AF recurrence or repeat ablation during all follow-up. The secondary endpoints included atrial arrhythmia (AA) burden, discontinuation of class I/III antiarrhythmic drugs, and BP changes from baseline. ResultsA total of 70 patients with AF (52 paroxysmal, 18 persistent) and uncontrolled hypertension were randomized (RDN+PVI, n = 34; PVI, n = 36). At 3.5 years, 26.2% and 21.4% of patients in RDN+PVI and PVI groups, respectively, were free from the primary efficacy endpoint (log rank P = 0.73). Patients with mean ≥1 h/d AA had less daily AA burden after RDN+PVI vs PVI (4.1 hours vs 9.2 hours; P = 0.016). More patients discontinued class I/III antiarrhythmic drugs after RDN+PVI vs PVI (45% vs 14%; P = 0.040). At 1 year, systolic BP changed by −17.8 ± 12.8 mm Hg and −13.7 ± 18.8 mm Hg after RDN+PVI and PVI, respectively (P = 0.43). The composite safety endpoint was not significantly different between groups. ConclusionsIn patients with AF and uncontrolled BP, RDN+PVI did not prevent AF recurrence more than PVI alone. However, RDN+PVI may reduce AF burden and antiarrhythmic drug usage, but this needs further prospective validation.

Mid-term outcomes after stereotactic arrhythmia radioablation for refractory ventricular tachycardia

Abstract Introduction stereotactic arrhythmia radioablation (STAR) is used as a rescue treatment for refractory ventricular tachycardia (VT) originating from unreachable myocardial substrate following unsuccessful radiofrequency catheter ablation (RFCA). The mid-term outcomes of STAR, however, remain poorly known. Objective to report the mid-term efficacy and safety outcomes in our series of 21 patients (pts) treated by STAR over 6 years. Methods Inclusion of consecutive pts treated by STAR with a Cyberknife system between 2017 and 2023. 3D-electroanatomical maps (EAM) of the VT substrate during unsuccessful RFCA were used to delineate the planned target volumes (PTV) on a 4D CT scan. Patients were followed up at least every 6 months by echocardiography and ICD interrogation at the outpatient clinic. Results 21 pts [16 (76 %) male, age 66±8 years] with a mean LVEF of 40±15% were included. The underlying substrate was ischemic in 7 (33 %); non-ischemic dilated in 7 (33 %); inflammatory in 4 (19%); hypertrophic in 1 (5%); neoplasic in 1 (5%); and malignant mitral valve prolapse in 1 (5%). A dose of 21±2 Gray was delivered to the PTV (26 ml, IQR 18-43 ml). After a median follow-up of 39 [IQR, 14-48] months, 12 pts (57%) remained in stable condition, 1 (5%) underwent a heart transplantation, 1 (5%) a left ventricular assistance device, 1 (5%) was in an incessant slow VT and 6 (29%) pts died (3 from end stage heart failure). 15 (71%) pts presented VT recurrences [7 (33%) ATPs; 3 (14%) shocks; 4 (19%) VT storm and 1 (5%) with a well-tolerated slow VT (100 bpm) with an LVAD till transplantation, of whom 9 (43%) required redo RFCA. The median value of total ventricular arrhythmic burden (defined as any arrhythmia requiring ICD therapies) decreased significantly from 31 (IQR, 4-100) to 7 (IQR, 1-23) (p&amp;lt;0.05); for nsVT from 57 (IQR, 1.5- 1196) to 41 (IQR, 0.5-584) (p ns); or ICD shocks from 1.5 (IQR, 0-5.5) to 0 (IQR, 0-2) (p&amp;lt;0.05); for ATPs from 21 (IQR, 2.5-94) to 4 (IQR, 0.5-13) (p&amp;lt;0.05). Figure 1 shows a graphic representation of arrhythmic burden before and after STAR. Conclusion in this cohort of highly selected pts with refractory VT, STAR significantly reduced the arrhythmic burden by a factor of 4 over a 3-year follow-up. Death rate remained high (29%), mostly by terminal heart failure. Nevertheless, a high proportion of pts had VT recurrences that were successfully managed by redo RFCA.VT burden before and after STAR