Supraventricular Tachycardia Research Articles

Holter monitoring in neuromuscular disorders: frequency and importance in clinical management

Abstract Introduction Cardiac involvement is a common manifestation in a variety of neuromuscular disorders (NMD) and initial cardiac manifestations in these patients are often asymptomatic. Hence, regular 24h-Holter monitoring is recommended to identify conduction disturbances and rhythm disturbances. Purpose In this study, we aimed to assess abnormal findings in 24h-Holter monitoring to screen for conduction disturbances and arrhythmias in patients with NMD and evaluate its impact in patients’ treatment. Methods A retrospective single-centre study was conducted including all adult patients with NMD who received a 24h-Holter from January 2013 to September 2023. Results A total of 76 patients with NMD were included, 39 (51.3%) were male, and mean age was 46,3 ± 11,5 years. Most patients were asymptomatic. A total of 220 Holter recording was analysed. An average of 2,9 ± 1,6 Holter recordings per patient was performed. Abnormal Holter results were found in 47 (61,8%) patients, and mainly consisted of conduction disorders such as atrioventricular block in 31 (65,9%) patients. Other abnormalities included atrial fibrillation/flutter in 6 (12,8%) patients, supraventricular tachycardia in 4 (8,5%) patients, and non-sustained ventricular tachycardia in 6 (12,8) patients. Out of the group of the patients with abnormal Holter findings, ten patients had direct clinical treatment consequences, namely implantation of cardiac electronic devices or initiation of anticoagulation therapy. Conclusion In this study, holter findings resulted in relevant clinical treatment consequences in 10 out of 76 patients (13,2%). These results suggest that 24h-Holter monitoring may improve routine cardiac screening in patients with NMD.

Pregnancy and inherited cardiomyopathies: insights from specialized care

Abstract Background Pregnancy and postpartum represent periods of increased risk of cardiovascular complications. Management of women with modified World Health Organization (mWHO) class II–III, III, and IV during pregnancy and around delivery should be conducted at an expert centre by a multidisciplinary team. Purpose Our objective was to analyze the impact of pregnancy on cardiomyopathy outcomes in a centre specialized in inherited cardiovascular conditions in the United Kingdom. Methods All women with cardiomyopathy referred due to pregnancy to our centre between 2016 and 2023 were retrospectively analyzed. Demographic, clinical, obstetric, genetic, electrocardiographic, and multimodal imaging variables were collected. Results Between 2016 and 2023, follow-up and delivery planning were initiated for 86 pregnancies in women with cardiomyopathies referred to our centre, resulting in 81 live births and 5 miscarriages, all in the first trimester. Among the full-term pregnancies, 17 (21%) were in patients in mWHO class I or II, 22 (27.2%) in II-III, 34 (42%) in III, and 8 (9.8%) in IV. The distribution of cardiomyopathy types among different mWHO classification is represented in Table 1. Women in mWHO class ≥ II-III had more pregnancy-related events than patients in mWHO I or II [28 (34.6%) vs 1 (1.2%); p = 0.004]. The most common complication in the first group was supraventricular tachycardia in 11 pregnancies (13.6%), followed by gestational diabetes in 9 (11.1%), left ventricular ejection fraction impairment in 4 (4.9%), preeclampsia in 3 (3.7%), and 1 (1.2%) ventricular tachycardia. One patient in the second group developed gestational diabetes. The distribution of the type of delivery among different mWHO classification is represented in Table 2. Only one patient with hypertrophic cardiomyopathy in mWHO II-III who underwent a caesarean section presented a post-delivery complication related to retroperitoneal haematoma, with no statistical significative differences between the groups (p = 0.604). 100% of the patients survived pregnancy and postpartum period. Conclusions Pregnant women with cardiomyopathy face an increased risk of adverse events. Despite the presence of cardiovascular and obstetric complications, careful monitoring at a specialized centre leads to favourable outcomes particularly concerning mortality rates for both the mother and fetus. This highlights the importance of a comprehensive risk assessment and meticulous pregnancy and delivery planning to ensure optimal maternal and fetal health.Table 1.Cardiomyopathy and mWHOTable 2.Type of delivery and mWHO

Comparison of angiography-derived index of microcirculatory resistance measurements between low and high frame-rate acquisitions: the prospective ADMIRAL-study

Abstract Background Angiography-derived index of microcirculatory resistance (angio-IMR) is a novel, wire-free, angiography-based method (QFR-IMR®) to assess coronary microvascular dysfunction. If a frame-rate of 15 frames per second (fps) is recommended, there is an interest in decreasing this frame-rate to reduce X-ray exposure. However, the impact of frame-rate reduction on angio-IMR quantification has not been investigated. Purpose To compare angio-IMR at 7.5 fps (angio-IMRlow) to angio-IMR at 15 fps (angio-IMRhigh) in a multicentric study. Methods From October 2023 to February 2024, we conducted a multicentre prospective study including consecutive patients referred for an invasive coronary angiogram with a final diagnosis of ischemia with no obstructive coronaries arteries (INOCA) (positive stress test with normal coronary angiogram) or acute coronary syndrome (ACS). Main exclusion criteria were creatinine clearance<45ml/kg/1.73m2, factors that might substantially impact the coronary angiograms quality (e.g: aortic stenosis, supraventricular tachycardia), and TIMI flow <3. In ACS patients, angio-IMR was measured after revascularisation. The same two acquisitions with different angles (≥25°) were recorded at a rate of 7.5 fps and a rate of 15 fps to measure angio-IMR in the selected vessel (culprit coronary vessel in ACS patients or left anterior descending artery in patients with INOCA). Angio-IMR was measured with dedicated software (QFR-IMR® RE, Medis Medical Imaging). Correlation between angio-IMRlow and angio-IMRhigh was assessed by linear regression and Bland-Altman test. The diagnostic accuracy of angio-IMRlow to predict microcirculatory dysfunction (defined as angio-IMRhigh≥ 25 for INOCA and ≥ 40 for ACS) was also assessed. Statistical significance was awarded by p≤0.05. Results Of 87 consecutive eligible patients, 75 were included in the study, comprising 57 with ACS and 18 with INOCA (mean age 61±12 years, 72% male). Angio-IMRlow (median=35; [IQR:28-48]) was slightly but significantly higher (p=0.04) than angio-IMRhigh (median=34; [IQR:25-45]). Angio-IMRlow and angio-IMRhigh were significantly correlated (r=0.90; p<0.0001) (Figure 1). Using Bland-Altman analysis, mean difference between the two measurements was 2.2 (95% CI 0.1-4.4) with a significant higher value with angio-IMRlow (p=0.04). Moreover, as value of Angio-IMRhigh increases, the difference between angio-IMRlow and angio-IMRhigh becomes more significant (Figure 2). Using angio-IMRhigh to diagnose microcirculatory dysfunction as reference, angio-IMRlow achieved positive and negative predictive values of 83% and 85% respectively with 6 false positives, and 6 false negatives. Conclusion Correlation between angio-IMRhigh and angio-IMRlow is acceptable. Lowering frame acquisition rate reduces radiation exposure without relevantly impact on the diagnostic accuracy of angio-IMR, which can contribute to a widespread use of angio-IMR.Correlation between angioIMRlow and highBland-Altman plot

Clinical characteristic and zero-fluoroscopy ablation outcomes of tachyarrhythmias in pregnant: a single center study

Abstract Background Although recommended avoid any intervention during gestation in cases of drug refractory of arrhythmias catheter ablation may be necessary in pregnant women. Purpose To present clinical characteristics and outcomes of zero-fluoroscopy catheter ablation during gestation. Methods This prospective, single center study included 84 cases of tachyarrhythmias during gestation. In 44 cases of drug refractory was performed catheter ablation without fluoroscopy (main group). We evaluated the further course of gestation and obstetric outcomes after ablation in comparison with pregnant with antiarrhythmic therapy of tachyarrhythmias (n=40, control group). Results Both groups were comparable by mean age of pregnant (28.2±4.2 vs. 27.3±3.9 years, p=0.093) and mean duration of gestation (24 ±3.4 vs. 23.8 ±3.2 weeks, p=0.123). New onset arrhythmia prevailed in both groups (64% vs. 55%, p=0,280). Supraventricular tachycardia was the most common arrhythmia during gestation (81,8% vs. 52,5%, p=0,005), which was followed by premature contraction (13,6% vs. 40%, p=0,007). Cases of ventricular tachycardia were rare (4,6% vs. 7,5%, p=0,665). Ablation was performed under the guidance of CARTO (45%) and Ensite Precision systems (55%) without using fluoroscopy in all cases. Acute procedural success of zero-fluoroscopy ablation was in 100% with mean procedural time 71±17 minutes without any complication. Outcomes: further course of gestation characterized by increased incidence of uterine contractile activity and placental abruption only in main group (4,54%, p=0.464 and 2.3%, p=642 respectively). There were no differences in the rate of other complication: uterine blood flow violation (15.9% vs 12.9%, p=0.234) and preeclampsia (4.55% vs 5%, p=0.237). Vaginal type of delivery was in the majority of cases in both groups (82% vs 83%, p=0.242). Neonatal outcomes characterized with normal range of fetal birth weight (median 3207,39±485,61 vs. 3312,3±234,1 grams, p=0.709) and 5 minute Apgar score (median 8,4±1,6 vs. 8,7±1,2, p=0.921). There was no incidence of maternal and fetal mortality. In 12 month, follow-up all there was no arrhythmia recurrence. Conclusions Zero-fluoroscopy ablation of tachyarrhythmias in pregnant is feasible and can be safety performed during gestation in cases of drug refractory with benign outcomes.

Significant reduction of complications applying an optimized vascular access and post-interventional groin-site management during electrophysiology procedures

Abstract Background Catheter ablation of cardiac arrhythmias is an established treatment strategy. However, the optimal femoral vascular access strategy and post-interventional management in the electrophysiology (EP) setting is still under debate. Purpose To assess the impact of ultrasound-guided versus conventional femoral vascular puncture and of a modified post-interventional groin-site management strategy on complication rates. Method Patients undergoing EP procedures at the our university heart and vascular center are included in an institutional prospective registry. Conventional vascular access as well as post-interventional groin site pressure-bandage and bed rest of 6 hours (group I) was compared to a new strategy including ultrasound-guided vascular access, venous closure by a Z-suture and groin site pressure-bandage for only 2 hours plus additional 4 hours bed rest (group II). Incidences of minor and major groin site complications for both groups were compared. Hematoma, bleeding, arteriovenous fistula or pseudoaneurysm of the femoral artery without need for intervention (e.g. transfusion, thrombin injection, surgery) were classified as minor complications. Complications requiring intervention or retroperitoneal hematoma were defined as major complications. Results A total of 1535 procedures in 1381 patients (779 (51 %) procedures in 705 (51%) patients in group I and 756 (49%) procedures in 676 (49%) patients in group II) were analyzed. In group I and group II, respectively, 39%/44% procedures were index pulmonary vein isolations, 30%/29% repeat atrial fibrillation, 16 %/15% supraventricular tachycardia, 12%/11% PVC or VT ablations, and 4%/2% left atrial appendage occlusions. The total groin site complication rate was 9% (70/779 procedures) for group I, and 5% (38/756 procedures) for group II (OR 0.54 [95%-CI 0.35-0.82], p=0.003). Major groin site complications occurred in 2% (19/779 procedures) in group I and were reduced to 1% (10/756 procedures) in group II (OR 0.53 [95%-CI 0.22-1.22], p=0.156). Conclusion The overall groin site complication rate in EP-procedures was significantly reduced by implementing a novel institutional standard for vascular access management including ultrasound-guided puncture and a modified post-interventional groin site management.

A systematic assessment of myocardial involvement and cardiovascular events up to six months in patients hospitalised with COVID-19

Abstract Background Retrospective cohort studies indicate that myocardial injury occurs in approximately 25% of patients hospitalised with COVID-19. However, prospective studies with a systematic assessment of myocardial involvement and major adverse cardiovascular events (MACE) after COVID-19 are scarce. Purpose The primary objective was to determine the incidence of MACE within six months of hospitalisation. MACE was defined as a composite of cardiac death, sudden death, life-threatening ventricular arrhythmia's, heart failure, non-fatal myocardial infarction, and/or non-fatal stroke. The main secondary objective was to determine the frequency of other cardiac complications not covered by this definition. Methods We conducted a prospective multicenter cohort study in 13 Dutch medical centers. Adult patients hospitalised with COVID-19 were consecutively recruited (May 2021-April 2023). Exclusion criteria were age ≥70 years, a history of new cardiac disease in the past six months, or dependency in the activities of daily living. Cardiac involvement was evaluated by a standardised healthcare pathway that was implemented in participating hospitals. All patients received an electrocardiogram, transthoracic echocardiogram, and troponin measurement at admission and at six months follow-up. Furthermore, a questionnaire was distributed at three and six months after admission to collect information on post-COVID symptomatology. Results In total 190 patients were included, median age of 57 years [IQR 48; 64], mostly male (n=110, 60%) and white (n=136, 72%). Cardiovascular risk factors were present in 116 (61.1%) patients and 33 (17.4%) had a history of cardiac disease. At admission, troponin was above the upper limit of normal in 68 (35.8%) patients. Seven (3.7%) patients died during follow-up. The cumulative incidence of MACE was 2.6% at discharge with no additional events during follow-up. Other cardiac complications were detected in 18 (9.5%) patients during admission with 3 (1.6%) additional events at six months follow-up. Supraventricular tachycardias (n=8, 4.2%) were the most common cardiac complication. Other complications were myocarditis (n=2, 1.1%), pericarditis (n=1, 0.5%), non-sustained ventricular tachycardia (n=1, 0.5%), and other arrhythmias or conduction disorders (n=5, 2.6%). At six months follow-up, three (2.3%) patients reported chest pain, with one requiring a percutaneous coronary intervention. Palpitations and dizziness were experienced by 88.9% and 83.3% of patients three months after admission but the prevalence of these symptoms decreased to 9.8% and 11.8% at six months. Conclusion With a systematic assessment, one in three patients hospitalized with COVID-19 have elevated troponin levels at admission. However, the overall incidence of MACE within six months is low. Palpitations and dizziness are commonly reported after discharge but these symptoms disappeared for most participants within six months.

Long-term outcome after Mustard procedure at young age: longitudinal follow-up of 40 to 48 years after surgery

Abstract Objectives To evaluate the long-term clinical outcome and quality of life up to 48 years of patients with Transposition of the Great Arteries (TGA) after Mustard procedure at young age. Primary outcome was defined as a composite endpoint of death, re-intervention, clinically relevant heart failure or arrhythmia, ischemic stroke and endocarditis. Methods Single center, longitudinal cohort study evaluating consecutive patients with TGA who underwent Mustard procedure before the age of 15 between 1973 and 1980 at our medical center, the Netherlands. Survival of all eligible patients was obtained. All eligible patients were invited for in hospital evaluation and underwent extensive cardiac and psychological evaluation every 10 years. The latest evaluation took place in 2021 and 2022. Results The original study cohort consisted of 91 consecutive patients. Cumulative survival at 48 years (95% complete) was 62% and significantly decreased compared to the general Dutch population (p<0.001). Cumulative survival at 48 years in hospital survivors was 66%. Mortality rate was 0.19 per 100 patient-years. Thirty-four patients (77%) of the eligible 44 survivors (71% male, median age at study 46 years) were included in the present study. Median follow-up since initial surgical correction was 46 (range 40-48) years. Event-free survival at 48 years was 14%. Overall, 34 patients underwent re-intervention of which 3 in the last 10 years (predominantly Baffle revision). In total, 29 patients had supraventricular tachycardia and 11 patients had ventricular tachycardia of which 8 and 4 respectively occurred in the last 10 years. Alltogether, 22 patients had symptomatic heart failure of which 9 occurred in the last 10 years. Cardiac magnetic resonance imaging (n=11) showed a median systemic right ventricular ejection fraction (sRVEF) of 35% [32-40%]. In 73% of the patients, sRVEF fraction was below 40%. Echocardiography showed a diminished sRVEF in all patients. VO2max was reduced in 95% of all patients. Self-perceived quality of life (SF-36) generally was comparable to the general Dutch population with the exception of domain general health (p<0.001). Conclusion Late mortality, and especially morbidity of hospital survivors after Mustard procedure was substantial, with an event free survival of only 14% at 48 years. Re-intervention and symptomatic arrhythmia were often reported. The function of the systemic right ventricle was diminished and VO2max was also reduced. The burden of heart failure increased drastically in the last decade. Therefore, intensive follow-up of these patients is warranted.

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.

Potential use of pharmacogenetics in cardiology: genome-wide association studies of amiodarone-induced thyroid disorders

Abstract Background Amiodarone is a commonly prescribed antiarrhythmic drug used to manage supraventricular and ventricular arrhythmias. The use of amiodarone is associated with a broad range of adverse effects, including amiodarone-induced hypothyroidism (AIH) or amiodarone-induced thyrotoxicosis (AIT) (1). Both conditions are linked with increased mortality and have no known reliable risk predictors (2). Purpose We investigated the genetic underpinnings of amiodarone-induced thyroid disorders, and the clinical validity and utility of screening for genetic variants. Methods We conducted the first genome-wide association studies (GWAS) of AIH and AIT using data from three large biobanks. We compared the AUCs for SNPs identified through the above GWAS with polygenic risk scores for both hypo- and hyperthyroidism. Finally, we tested the clinical validity and utility of screening for risk variants. Results We found two risk loci for AIH. The lead variant at the first locus, rs1443438, was intronic to FOXE1 (OR 0.39, MAF = 35%, P = 1.59 × 10-42). The other lead variant, rs2209796, was located 93 kb upstream to FOXA2 (OR 0.56, MAF = 29%, P = 2.64 × 10-15: Figure 1). For AIT, we found one risk locus. The lead variant, rs2268803, was intronic to CAPZB (OR 1.81, MAF = 42%, P = 2.43 × 10-8: Figure 1). Next, we added GWAS SNPs or polygenic risk scores to risk prediction models consisting of age, sex and 4 principal components (PCs), and compared AUC estimates between risk models. Using GWAS SNPs, we found that the AIT variant increased the AUC with 6% (95%CI 1.1 – 10.3, AUC: 0.72) and 9% (95%CI 6.2 – 11.2, AUC: 0.75) for AIH, compared to the benchmark model. Both GWAS SNP models were superior to polygenic risk scores in terms of AUC (P for difference <0.05). The positive and negative predictive value (PPV and NPV) for the AIT-variant was 14.6% and 95.7%, respectively. For the AIH-variants combined, we found a PPV of 17% and a NPV of 95%. Conclusions Common genetic variants are associated with both amiodarone-induced hypo- and hyperthyroidism and are at this point, superior to polygenic risk scores in predicting amiodarone-induced thyroid disorders. These findings add to the potentials of pharmacogenetics in cardiology. Figure 1. Double Manhattan plot of amiodarone induced thyroid disorders. The Y-axis is the negative log10 of the P-value for each single nucleotide polymorphism. The X-axis is the chromosome, with positions on each chromosome ranging from lower to higher (left to right). The dotted line marks the threshold for genome-wide significance. Amiodoarone-induced hypothyroidism at the top, and amiodarone-induced thyrotoxicosis at the bottom.Figure 1

A prospective analysis of the efficacy and safety of ethacizine during premature atrial contractions and premature ventricular contractions

Abstract Background Ethacizine, a class Ic antiarrhythmic agent, is prescribed for managing severe or refractory supraventricular and ventricular arrhythmias, including premature atrial (PACs) and ventricular contractions (PVCs). Despite its use, there is a lack of substantial research exploring the therapeutic effects of ethacizine at present. Purpose The study evaluated the efficacy and safety of ethacizine in addressing PACs and PVCs, in cases where other antiarrhythmic medications proved ineffective. Methods We performed a prospective analysis of ethacizine treatment (50 mg. b.i.d.) for early (30-45 days) and late periods (150-210 days), in male (n=58; 59.2%) and female (n=40; 40.8%) patients aged ≥ 18 years (18-72 y.o; mean age 45 years), with 46 cases of PACs and 52 cases of PVCs, who had previously been treated with another antiarrhythmic medication (bisoprolol, metoprolol, sotalol, verapamil, amiodarone, or propafenone) and had not achieved the target rate of extrasystoles (≤1000/24h). Results The findings reveal a substantial decrease in the mean parameters of PACs during both, the early period (initial 6877 ± 2432, following 761 ± 341); (88,9%); t([45]) = [13,336], p = [< .001) and the late period (initial 6877 ± 2432, following 574 ± 294); (91,7%); t([45]) = [15,124], p = [< .001). The quantitative reduction in PACs reached a maximum of 93.8% in the early period (19406 PACs □ 1211 PACs) and 94.3% in the late period (19406 PACs □ 1105 PACs). The mean parameters of PVCs in the early period experienced a significant reduction (initial 3205 ± 1145, following 550 ± 194); (82,8%); t([51]) = [8,284], p = [< .001). Similarly, the mean PVC values in the late period exhibited a noteworthy decrease (initial 3205 ± 1145, following 490 ± 181); (84,8%); t([51]) = [8,553], p = [< .001). For PVCs, the maximum effect observed in the early period was 94.8% (18929 PVCs □ 989 PVCs), and in the late period, it reached 95% (18929 PVCs □ 950 PVCs). The target rate in the late period (≤1000/24h.) for PACs reached 89%, and for PVCs - 86% (Figure 1). Adverse effects were noted in a mere four subjects (4%). These events manifested as 2nd-degree AV block (Mobitz 1), sustained ventricular tachycardia, asymptomatic nonsustained polytopic ventricular tachycardia, and asymptomatic transient ST-segment elevation observed through 24-hour ECG holter monitoring. Conclusion A prospective study on ethacizine treatment (50 mg. b.i.d.) confirmed its effectiveness and safety in reducing PACs and PVCs. It demonstrated a sustained reduction in extrasystole occurrences for an extended period, achieving the target rate with minimal side effects. Ethacizine merits consideration for addressing extrasystolic arrhythmia, particularly in cases where other antiarrhythmic medications prove ineffective.Results of the study

Quality of life measures with etripamil self-administration for acute episodes of paroxysmal supraventricular tachycardia in a medically unsupervised setting: patient-reported outcomes from NODE-303

Abstract Background Etripamil nasal spray (NS) is a fast-acting, self-administered calcium-channel blocker in development for the conversion of AV-nodal dependent paroxysmal supraventricular tachycardia (PSVT) in a medically unsupervised setting. Prior studies show favorable safety and efficacy in converting single episodes of PSVT to sinus rhythm (SR). Purpose In NODE-303, patient-reported outcome (PRO) instruments assessed quality of life (QoL) over multiple etripamil-treated episodes of PSVT. Methods NODE-303 was an event-driven, multi-center, open-label Phase 3 study in North and South American patients with documented PSVT that evaluated the safety and efficacy of etripamil in PSVT termination, over multiple episodes and without the need for prior test dosing. Enrolled patients who perceived PSVT symptoms applied an ambulatory ECG cardiac monitoring system (CMS), performed a pre-trained vagal maneuver and, if symptoms persisted, self-administered etripamil NS 70 mg. A study amendment allowed a repeat dose (etripamil NS, 70 mg) if symptoms persisted 10 min after the first dose. Each patient could self-treat up to 4 episodes. Safety was assessed through adverse events, clinical data, and ECG CMS recordings. The Treatment Satisfaction Questionnaire for Medication (TSQM; validated for acute episodic assessments) and other PROs were administered, and healthcare utilization data were acquired. Patients completed PROs at baseline (BL), monthly, and per PSVT episode, which collected information on symptoms, episode characteristics, rescue medications, and emergency room visits. Additional PROs were the Brief Illness Perception Questionnaire (BIPQ), Cardiac Anxiety Questionnaire (CAQ), and 36-Item Short Form Health Survey (SF-36). Results There were higher proportions of patients reporting mild, minimal or no disease severity, every 6 months, than at BL; extremely severe, severe, and moderate disease severity was reported by smaller proportions of patients than at BL, though incomplete surveys at later visits may limit this analysis. Anxiety and stress about future PSVT episodes were consistently reduced from BL. Measures of treatment satisfaction, effectiveness, and convenience were consistent across multiple episodes, and were at levels considered favorable for the TSQM instrument (Table 1). Rates of emergency-room visits and hospital admissions across multiple, treated PSVT episodes were similar to those observed in trials assessing single episodes (Table 2). The BIPQ, CAQ or SF-36 had no notable changes from BL. Conclusions Etripamil self-administration was associated with patient-reported improvements in degree of disease severity, decreased anxiety and stress over future PSVT episodes, and levels of treatment satisfaction, effectiveness, and convenience considered favorable for respective PRO instrument. Using a symptom-prompted, self-administered treatment for PSVT could potentially improve QoL measures and reduce healthcare resource utilization.

A multilabel deep learning model for the detection of conduction and rhythm disorders from PDF outputs of a widely available portable ECG Device

Abstract Background Wearable and portable devices with ECG capabilities can provide broad access to screening for cardiovascular disorders. However, most are approved for the detection of only atrial fibrillation. Most algorithms for detecting rhythm and conduction disorders are trained and tested on 12-lead ECGs or the lead I of clinical ECGs, with an unclear role for extending the diagnostic range of wearable and portable devices. Moreover, no current algorithms enable cardiovascular diagnosis on data available to end users, who largely have access to the PDF outputs of their data. Purpose To validate a novel artificial intelligence (AI) model trained to identify conduction disorders and arrhythmias on synthetic ECG outputs from lead I data of clinical ECGs, to detect the same disorders on cardiologist-annotated PDF outputs from the Alivecor KardiaMobile single-lead ECGs (Kardia ECGs). Methods We extracted lead I data from 3,076,352 clinical ECGs across 5 hospitals of a large U.S.-based hospital system from 2000-2024 and simulated wearable PDF outputs from commercial devices using a novel plotting approach that replicated the variations in plotted formats. Gold-standard cardiologist written diagnosis statements were processed to generate 8 clinical labels spanning conduction and rhythm disorders, and we developed a multilabel model to predict these labels using an EfficientNet-B3 convolutional neural network. We examined the performance of the model on 24,808 Kardia ECGs annotated by cardiologists. Results The model achieved a high performance on clinical ECGs in a held-out subset of the synthetic lead I ECG printouts resembling wearable outputs (AUC > 0.9 for all 8 labels). In the independent 24,808 Kardia ECGs, annotated by experts, the model achieved high performance across all labels. For the rhythm disorders atrial fibrillation or atrial flutter, premature atrial contraction, and premature ventricular contraction, the model had AUROCs of 0.99, 0.91, and 0.95, respectively. For the conduction disorders 1st-degree AV block and 2nd or 3rd-degree AV blocks, the model had AUROCs of 0.94 and 0.99, respectively. Finally, for supraventricular tachycardias, wide QRS, and paced ECGs, the model had AUROCs of 0.998, 0.98, and 0.98, respectively. Conclusions We demonstrate that a deep learning model trained to identify rhythm and conduction disorders based on synthetic ECGs where lead I data from clinical 12 lead ECGs are used to replicate real-world PDF outputs of wearable ECGs, generalizes to real-world wearable and handheld single-lead devices.

Digital health in the EP lab: routine implementation of remote access and technical support for complex ablation procedures

Abstract Background Complex electrophysiological procedures are performed using three-dimensional (3D) electroanatomical mapping (EAM) systems, which are usually operated on site, by field technical engineers (FTE). Due to a lack of skilled personnel, the engineers usually must travel between different hospitals and the procedures have to be planed in advance. Remote access (RA) technologies were recently implemented in clinical practice, aiming to increase the flexibility in the EP lab and maximise healthcare resources use. Methods Electroanatomical mapping was performed remotely by means of an integrated audio-visual solution for RA. The operator and the FTE communicated exclusively using the RA system, while the latter worked only in home office. Consecutive procedures were prospectively enrolled and analysed in terms of indication, procedural characteristics, feasibility and saved travelled time by the FTA. Results Between September 2022 and July 2023, a total of 133 EP procedures were performed in a high volume, tertiary electrophysiological centre in Germany. The mean age was 67 (57.5, 75.5) years. Women represented 39.8% of the population. The median BMI was 26.2 (23.1, 30.3) Kg/m2. A total of 56 (42.1%) patients underwent an atrial fibrillation ablation procedure (37.5% paroxysmal), 22 (16.5%) an atrial tachycardia ablation, 13 (9.8%) cavotricuspid isthmus ablation, 15 (11.3%) supraventricular tachycardia ablation, 14 (10.5%) a premature ventricular contraction ablation, 12 (9%) ventricular tachycardia ablations and 1 patient an electrophysiological diagnostic study. The median time length of procedure was 130 (96.5, 168) minutes. The median number of radiofrequency applications was 63.5 (22.3, 109.5), while the median RF time was 14.2 (6.9, 25.1) minutes. The fluoroscopy time was 9.2 (6.5, 12.6) minutes, with a median radiation dose of 408.5 (233.0, 631.8) cGy x cm2. The median amount of contrast media was 40 (8.75, 50.0) ml and the median amount of heparin administered was 12000 (8000, 16000) UI. Protamine was used in 9 cases, with a median of 7000 (5000, 7000) UI. Except for one supraventricular procedure, where no arrhythmia induction was possible, all procedures were successful. One major complication was observed. In one case, the internet-based headphone connection was not stable. Therefore, the communication was established via a conventional smartphone. No change to on-site support was needed. The travel time reduction was available in 130 cases. In total, 290 travel hours could be saved. Conclusion The routine implementation of RA for complex EP procedures proved to be safe and efficient. This approach has the potential to increase the feasibility in case of emergency procedures, reduce travel times for FTE and streamline healthcare resources allocation.

Artificial intelligence in cardiology: a machine learning model for supraventricular tachycardia discrimination

Abstract Background Distinguishing atrioventricular nodal reentrant tachycardia (AVNRT) from orthodromic atrioventricular reentrant tachycardia (AVRT) presents a diagnostic challenge, with clinical and electrocardiogram (ECG) features playing a crucial role in differential diagnosis. Purpose The aim of this study was to devise and validate a predictive algorithm that utilises basic clinical and ECG parameters to accurately classify AVNRT versus AVRT. Furthermore, this algorithm was integrated into a user-friendly, web-based tool to support clinical decision-making. Methods We conducted a prospective analysis of 704 patients (median age: 53.6 years; 59.7% female) with electrophysiologically confirmed AVNRT (n=535) or AVRT (n=169). A comprehensive evaluation was performed using a structured questionnaire tailored to arrhythmia-specific symptoms. The study utilised advanced machine learning techniques for classification, employing feature selection methods to enhance predictive accuracy. The analysis included 19 demographic, clinical, and ECG variables, adopting an 80-20% split for training and internal validation. The algorithm's performance was evaluated against a model comprising all variables (Full Model), expert ECG interpretations (ExpertECG), objective ECG criteria (ECG model), and a baseline dummy classifier, with efficacy assessed by the Area Under the Receiver Operating Characteristic curve (AUC) and the Area Under the Precision-Recall Curve (AUPRC). Results The optimised model, utilising the XGBoost algorithm with six critical variables (initial age at first episode, biological sex, presence of neck palpitations, pseudoR wave in lead V1/pseudoS wave in inferior leads, visibility of retrograde P-waves, and tachycardia cycle length), exhibited superior performance, achieving an AUC of 0.916 and an AUPRC of 0.823. This model significantly outperformed other comparative models in terms of predictive accuracy (Figure 1). Implementation of the model into a web-based interface was accomplished using Shiny, enhancing its accessibility for clinical application (Figure 2). Conclusions This study illustrates the efficacy of employing machine learning algorithms to utilise bedside clinical and ECG variables for accurately differentiating between AVNRT and AVRT. The creation of a web-based calculator marks a significant advancement, empowering clinicians, especially non-specialists, with a potent tool for providing personalised diagnostic insights. Future research should focus on external validation to ascertain the model's generalisability and its applicability in broader clinical settings.Figure 1Figure 2

Outcome of pregnancy in women with unrepaired atrial septal defect - study of a single tertiary centre

Abstract Background Patients with unrepaired atrial septal defect (ASD) are prone to develop arrhythmia, right heart failure and to suffer paradoxical embolism. The risk might be even bigger during pregnancy due to the hemodynamic changes combined with the hypercoagulable state. Purpose To evaluate maternal, foetal, and neonatal outcome of pregnancy in women with unrepaired ASD. Methods A retrospective study of 43 pregnancies in 24 women with unrepaired ASD was performed in our tertiary centre from 2004. Previous maternal cardiovascular events and events during pregnancy (maternal, neonatal, and obstetric) were documented. Results 24 women with unrepaired ASD (median age: 27.5 ± 6.2) had 43 pregnancies resulting in one termination, 4 miscarriages and 38 live births. 55% were primigravida and 2 twin pregnancies were documented. At baseline 2 women (10.5%) were in NYHA functional class II and signs of right ventricle (RV) volume overload were detected on echocardiography in 18 cases (47%). 2 women had a history of supraventricular tachycardia. Median gestation at delivery was 39 ± 2.6 weeks. No thromboembolic events, pulmonary hypertension, or desaturation occurred during pregnancy. However maternal cardiovascular complications all affected women with RV volume overload: 2 cases (5.2%) of supraventricular tachycardia, 2 (5.2%) cases with NYHA functional class deterioration and 1 case (2.6%) of syncope were documented. Only one obstetric event; preeclampsia occured. Neonatal complications were as follows: premature delivery in 3 cases (7.9%) and recurrence of congenital heart disease (CHD) in 4 pregnancies (10.5%). After the pregnancy device or surgical closure of the ASD was indicated for 11 women (45.8%). Since then, five already underwent device closure, one had surgical repair, while five women are still waiting for intervention. Conclusions Our results align with the mWHO classification. Pregnancy with an unrepaired ASD is well tolerated and has a low risk of neonatal and maternal cardiovascular events. However, women with right ventricle volume overload are prone to develop arrhythmia or right heart failure during pregnancy. Therefore, cardiology follow-up during pregnancy should be decided on an individual basis. In our cohort no thromboembolic events were documented during pregnancy, however the prevalence of congenital heart disease in the foetus was higher compared to the literature.

Identification and Functional Investigation of SOX4 as a Novel Gene Underpinning Familial Atrial Fibrillation.

Background: Atrial fibrillation (AF) signifies the most prevalent supraventricular arrhythmia in humans and may lead to cerebral stroke, cardiac failure, and even premature demise. Aggregating strong evidence points to genetic components as a cornerstone in the etiopathogenesis of familial AF. However, the genetic determinants for AF in most patients remain elusive. Methods: A 4-generation pedigree with idiopathic AF and another cohort of 196 unrelated patients with idiopathic AF as well as 278 unrelated healthy volunteers were recruited from the Chinese population of Han ethnicity. A family-based whole-exome sequencing examination followed by a Sanger sequencing assay in all research subjects was implemented. The functional impacts of the identified SOX4 mutations were explored via a dual-reporter assay. Results: Two new heterozygous SOX4 mutations, NM_003107.3: c.211C>T; p.(Gln71*) and NM_003107.3: c.290G>A; p.(Trp97*), were observed in the family and 1 of 196 patients with idiopathic AF, respectively. The two mutations were absent in the 278 control individuals. The biochemical measurements revealed that both Gln71*- and Trp97*-mutant SOX4 failed to transactivate GJA1 (Cx43). Moreover, the two mutations nullified the synergistic activation of SCN5A by SOX4 and TBX5. Conclusions: The findings first indicate SOX4 as a gene predisposing to AF, providing a novel target for antenatal genetic screening, individualized prophylaxis, and precision treatment of AF.

National Costs for Cardiovascular-Related Hospitalizations and Inpatient Procedures in the United States, 2016 to 2021

The current economic burden of cardiovascular-related hospitalizations grouped by diagnoses and procedures in the U.S. has not been well characterized. The objective was to identify current trends in cardiovascular-related hospitalizations, procedural utilization, and health care costs, using the most recent 6 years of hospitalization data. A retrospective analysis of discharge data from the National Inpatient Sample (NIS) database was conducted to determine trends in cardiovascular-related hospitalizations, costs, and procedures for each year from 2016 to the most recent available dataset, 2021. Total cardiovascular-related costs were adjusted to and reported in 2023 dollars. In 2021, there were 4,687,370 cardiovascular-related hospitalizations at a cost of $108 billion. Heart failure hospitalizations accounted for the highest costs at $18.5 billion, followed by Non-ST-Elevation Myocardial Infarction at $11.2 billion, and stroke at $10.9 billion. Significant upward trends in costs from 2016 to 2021 were observed for heart failure, stroke, atrial fibrillation, ST-elevation myocardial infarction, chest pain, hypertensive emergency, ventricular tachycardia, aortic dissection, sudden cardiac death, pericarditis, supraventricular tachycardia, and pulmonary heart disease. Over the 6 observational years, total costs increased by over $10 billion, representing a 10 percent increase. However, the increases were not linear, as there was a significant increase of 6.5% from 2018 to 2019, then a dip of over 7% from 2019 to 2020, followed by a rise of about 6% from 2020 to 2021. By 2030, total CV-related costs are projected to reach $131.3 billion. For all years, coronary procedures were the most performed, followed by ECMO, non-bypass peripheral vascular surgery, pacemaker placement, and CABG. Both TAVR and MitraClip procedures demonstrated significant upward trends from 2016 to 2021. Overall, from the years 2016 to 2021, cardiovascular-related hospitalizations, costs, and procedures demonstrated upward trends. In conclusion, cardiovascular disease remains a high burden in the hospital setting with tremendous health care costs.

Left Atrial Low-Voltage Extent Predicts the Recurrence of Supraventricular Arrhythmias.

The incidence of left atrial (LA) supraventricular arrhythmias is increasing. Even after LA ablation, recurrence of these tachycardias is common. MRI studies show that LA cardiomyopathy is a significant risk factor for recurrence and correlates with low voltage areas detected via 3D electroanatomic mapping (EAM). There are limited data on the impact of low voltage extent detected by EAM on recurrence-free survival. Voltage thresholds defining low voltage vary across different studies. This study aims to investigate the impact of the extent of low voltage areas in the LA on recurrence-free survival and to assess whether defining low voltage areas using thresholds of 0.5, 0.4, or 0.3 mV offers better predictive performance. Patients with atrial arrhythmia who underwent LA EAM at Ulm University Heart Center between September 2018 and September 2022 were included from the ATRIUM registry. ROC analysis determined the voltage threshold for predicting recurrence-free survival. Kaplan-Meier and logistic regression models adjusted for patient variables were used to analyze recurrence-free survival. Of 1089 screened patients, 108 met the inclusion criteria. ROC analysis indicated that a 0.4 mV threshold for low voltage provided the best predictive performance. Logistic regression showed a 1.039-fold increase in recurrence risk per percent increase in LA low voltage area (odds ratio = 1.039, 95% CI 1.014-1.064). Low voltage extent in EAM correlates with 1-year recurrence rate after ablation of left atrial supraventricular arrhythmias. The threshold of 0.4 mV is the most suitable for predicting recurrences of those examined.

Physicochemical and microbiological stability of 40mg/mL amiodarone hydrochloride oral suspension.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Amiodarone hydrochloride is an antiarrhythmic drug used to treat supraventricular tachycardia. However, there are currently no commercial pediatric forms available to treat young patients. Various oral formulations were previously reported in the literature, but the concentration was lower than the doses prescribed in clinical practice (a loading dose of 500mg/m2/day for 7-10 days followed by a maintenance dose of 250mg/m2/day). The objective of this study was to develop an oral liquid formulation of amiodarone hydrochloride at an optimal concentration for use in children and to evaluate its physicochemical and microbiological stability. No commercial suspension vehicle was used, allowing the choice of excipients. Compounding was performed using hydroxypropylmethylcellulose as thickener, potassium sorbate preservative, citric acid/sodium citrate buffer, sodium saccharin as a , and a strawberry flavoring agent. A concentration of 40mg/mL was selected based on a 5-year compilation of prescribed doses. Analyses performed were the following: visual and microscopic inspection, testing for antimicrobial preservation, osmolality and pH measurements, quantification of amiodarone hydrochloride by a stability-indicating liquid chromatography method, and a microbiological count. At least 95% of the initial amiodarone hydrochloride remained stable during the 60-day study period under refrigeration. All other tested parameters remained stable at 5 °C. A targeted log reduction of the microorganism inoculum by day 14 and no microbial growth by day 28 were demonstrated in the test for antimicrobial preservation. The stability of 40mg/mL amiodarone hydrochloride oral suspension was maintained under refrigeration for 60 days before opening bottles and for 1 month after opening bottles.