History Of Atrial Fibrillation Research Articles

Oxidative stress and mitochondrial function among various types of atrial fibrillation

Abstract Introduction Mitochondrial dysfunction has been shown to be associated with atrial fibrillation (AF) in previous studies. Purpose We aimed to determine mitochondrial function in various AF types and AF burden to further delineate whether mitochondrial function has graded or quantal response relationship with AF. Methods This is a cross-sectional study in patients with atrial high-rate episode (AHRE) or AF who have dual-chamber cardiovascular implantable electronic device (CIED). Patients were categorized into clinical AF and subclinical AF. AF burden was measured as AHRE via CIED interrogations. Oxidative stress and mitochondrial function were determined in peripheral blood mononuclear cells (PBMCs). Results There was a total of 54 CIED patients. Mean age was 69.9+12.8 years. There were 9 (16.7%) patients with diabetes mellitus and 36 (66.7%) patients with history of clinical AF. After adjusting with multiple linear regression for age, left ventricular ejection fraction, glomerular filtration rate, history of AF, and diabetes mellitus, we found that clinical AF, as compared to subclinical AF, was independently associated with lower non-mitochondrial respiration (20.8, 6.5-35.6 vs. 48.0, 14.0-60.9 pMol/min, p=0.021) (median, IQR); lower basal respiration (72.1, 47.4-94.4 vs.97.2, 52.1-152.6 pMol/min, p=0.020); and lower ATP production (57.3, 24.7-73.2 vs. 78.6, 45.7-112.0 pMol/min, p=0.014) (Table 1). However, AF burden was not associated with alterations in oxidative stress and mitochondrial function. Conclusions Mitochondrial function from PBMC was significantly lower in patients with clinical AF compared to those with subclinical AF. However, there was no association between AF burden and the change in mitochondrial function. The study revealed a quantal response relationship between PBMC’s mitochondrial function and AF.

Circadian occurence patterns of atrial fibrillation after cardiac surgery during 2.5 years of continuous rhythm monitoring

Abstract Background Atrial fibrillation (AF) is a common complication after cardiac surgery, and current theories suggest that the autonomic nervous system plays a major role in the development of early postoperative AF (early-POAF).(1) However, its role in late recurrences is still unknown. Previous studies in non-surgical patients have revealed distinct preferential patterns of AF occurrence, such as adrenergic/daytime AF or nocturnal AF.(2, 3) Nevertheless, circadian onset patterns for POAF have never been studied before. Purpose To establish the circadian occurrence patterns of POAF after cardiac surgery during 2.5 years of continuous rhythm monitoring. Methods Patients with and without a history of AF undergoing cardiac surgery were included. Continuous rhythm monitoring was performed over a period of 2.5 years. POAF was defined as an AF episode lasting 2 minutes or longer, detected by the ILR algorithm, and all episodes were manually checked by the investigators. Circadian distribution of AF episode onset was presented in circadian plots for the early postoperative phase (first 90 days) and late postoperative phase (after the first 90 days). Additionally, comparisons for circadian occurrence patterns were made between early and late POAF, after dividing the daytime period into four equal time intervals (night = 12 a.m. to 5.59 a.m., morning = 6 a.m. to 11.59 a.m., afternoon = 12 p.m. to 5.59 p.m., evening = 6 p.m. to 11.59 p.m.), both in patients with and without a preoperative AF history. Results The study population consisted of 98 patients (71 without a preoperative AF history and 27 with a preoperative AF history), of which 53 developed POAF (29 without a preoperative AF history and 24 with a preoperative AF history), resulting in a total of 3607 confirmed AF episodes (Figure 1). Early-POAF occurred in 46 patients, while late-POAF occurred in 36 patients. In both patients with and without AF history, the majority of early-POAF episodes occurred between 12 a.m. and 12 p.m. (59.2% and 55.9%, respectively) (Figure 2). In patients without AF history, late-POAF occurred predominantly in the evening (26.7%), particularly episodes lasting between 10 and 360 minutes, and in the afternoon (32.3%), with a greater number of episodes lasting <10 minutes (Figure 2). Patients with AF history experienced most late-POAF episodes at night (26.4%) and during the morning (33.1%), with a peak of short episodes (<10 minutes) in the morning (Figure 2). The circadian distribution was significantly different between early- and late-POAF for both patients with and without AF history (p<0.001 and p<0.001, respectively). Conclusion In patients without a preoperative AF history, early-POAF showed a more heterogeneous circadian occurrence pattern compared to late-POAF, which occurred mostly in the evening and afternoon. In patients with a preoperative AF history, POAF initiated mostly during the night and in the morning.Figure 1Figure 2

Increased circulating BMP10 levels are associated with late postoperative atrial fibrillation after cardiac surgery and left atrial endomysial fibrosis

Abstract Background Serum bone morphogenetic protein 10 (BMP10) levels are a marker for history of atrial fibrillation (AF) and for major adverse cardiovascular events in AF-patients, including stroke, recurrence after catheter ablation, and mortality. The predictive value of BMP10 in patients undergoing cardiac surgery and association with morphological properties of atrial tissue are unknown. Objective To study the correlation between BMP10 levels and pre-operative clinical traits, occurrence of early and late postoperative atrial fibrillation (POAF), and atrial fibrosis in patients undergoing cardiac surgery. Methods Patients with and without preoperative AF history undergoing first cardiac surgery were included (RACE V, n=147). Pre-operative blood biomarkers were analyzed, left (n=114) and right (n=125) atrial appendage biopsies were histologically assessed following WGA-staining, and post-operative rhythm was monitored continuously with implantable loop recorders (n=134, 2.5yrs). Results Multiple logistic regression indicated that BMP10 accurately predicts a history of persistent AF (OR=1.24, 95%CI: 1.10-1.40, p=4.32e-4), similar to NT-pro-BNP. BMP10 levels were associated with increased late-POAF90 occurrence after adjusting for age, sex, AF history, and early-POAF occurrence (HR=1.07 [per 0.1ng/ml increase], 95%CI: 1.00-1.14, p=0.04). Left atrial endomysial fibrosis (St.β=0.22, p=0.04), but not overall fibrosis (St. β= , p=), was associated with circulating BMP10, after adjusting for age, sex, AF history, reduced LVF, and valvular surgery indication. Conclusion Increased BMP10 levels were associated with persistent AF-history, increased late-POAF incidence, and LAA endomysial fibrosis in a diverse population of patients undergoing cardiac surgery.

Right atrial endomysial fibrosis is associated with higher POAF-burden

Abstract Background Atrial endomysial fibrosis, rather than overall connective tissue content, determines the complexity of conduction in human atrial fibrillation (AF). Moreover, the AF-specific blood biomarker BMP10 is associated with atrial endomysial fibrosis, but not overall connective tissue content. It is unclear whether pre-operative atrial endomysial fibrosis predicts post-operative AF (POAF) incidence and burden. Objective To determine the predictive value of atrial fibrosis for early and late POAF burden. Methods Patients with and without AF history were included in the RACE V tissue bank study (n=134). Post-operative rhythm was monitored continuously for 2.5 years with implantable loop recorders. Late POAF-burden was investigated following a 90-day blanking period. Left (n=89) and/or right (n=92) atrial appendage biopsies (LAA/RAA) were snap-frozen and histologically investigated following WGA-staining. Results Logistic regression, corrected for age, sex and AF history, showed that left (st.β = 0.54 [0.23-0.85], p=0.001) and right (st.β=0.35 [0.07-0.64], p=0.017) atrial endomysial fibrosis were associated with early POAF burden in the blanking period. Only right atrial endomysial fibrosis, however, predicted late POAF-burden (st.β=0.44 [-], p=0.009). Adjusted Cox proportional hazards analyses indicated that patients in the highest tertile of right atrial endomysial fibrosis, in particular, are at risk for late POAF (HR T3 vs T1: 2.47 [1.18-5.17], p=0.016, Fig 1). Overall connective tissue content in both atria was not associated with POAF-burden. Conclusion Patients with higher levels of right atrial endomysial fibrosis are at risk for developing late POAF with a higher POAF-burden.Figure 1

Effects of sodium glucose co-transporter-2 inhibitor on atrial tachyarrhythmia burden in patients with cardiovascular implantable electronic device

Abstract Introduction Previous studies showed that sodium glucose co-transporter-2 inhibitors (SGLT2i) were associated with a lower atrial fibrillation (AF) incidence. Purpose Since mitochondrial dysfunction has been linked with AF, we aimed to examine the effects of SGLT2i on AF burden and mitochondrial function in patients with cardiovascular implantable electronic device (CIED). Methods Patients with CIED were randomly assigned to receive either dapagliflozin 10 mg daily or placebo for 3 months. The AF burden was measured as atrial high-rate episodes (AHRE) via CIED interrogations, and data were collected at baseline and 3-months post-treatment. Oxidative stress and mitochondrial function were determined in peripheral blood mononuclear cells (PBMCs). Results The study enrolled 54 CIED patients. There were 9 (16.7%) patients with diabetes mellitus and 36 (66.7%) patients with history of clinical AF. The changes of AHRE burden after 3-month treatments did not differ between dapagliflozin and placebo groups. However, in those with clinical AF, dapagliflozin significantly decreased the number of AHRE per month as compared to placebo (-2.2 vs. +0.6 episodes per month, p=0.048) (Table 1). Mitochondrial spare respiratory capacity (SRC) percentage was significantly increased after treatment with dapagliflozin (162.1% to 203.2%, p=0.003), whereas this was not found in the placebo group (Figure 1). In the subgroup analysis of patients with clinical AF, dapagliflozin showed significant improvement in both the SRC percentage (165.7 to 201.7%, p=0.016) and a reduction in cellular oxidative stress (26,840.5 to 18,164.0 arbitrary unit, p=0.049). Conclusions Dapagliflozin significantly reduced the number of AHRE per month in patients with history of clinical AF. The improvement in PBMC’s mitochondrial function and reduced cellular oxidative stress among dapagliflozin users could be the mechanisms responsible for its anti-atrial arrhythmic effect.Table 1Figure 1

Predicting atrial fibrillation recurrence after catheter ablation using an artificial intelligence-enabled electrocardiogram algorithm

Abstract Introduction Predicting atrial fibrillation (AF) recurrence post catheter ablation may help to assess procedural eligibility and determine AF management. While several predictors of AF recurrence post ablation have been established and numerous clinical risk scores have been proposed, their performance remained underwhelming and clinical utility was limited. Hence, new predictors are needed. Artificial intelligence (AI) algorithms using deep neural networks (DNN) to analyze biometrical data might generate such predictors. DNN algorithms have been developed to identify patients with AF based on a 12-lead electrocardiogram (ECG) in sinus rhythm. Whether these algorithms can function as a predictor of AF recurrence after AF ablation remains unknown. Purpose To evaluate the prediction of AF recurrence after ablation using an AI-enabled ECG algorithm trained to predict AF on an ECG in sinus rhythm. Methods This study retrospectively analyzed observational data from the DIGITOTAL study, that monitored AF recurrence with a PPG-based smartphone application in 96 subjects after AF ablation. Patients with a 12-lead ECG in SR available within a timeframe of 3 months before the ablation procedure were included in the analysis. Although all patients had a history of AF, an AF-risk score was calculated by the DNN described elsewhere.1 Results An ECG in sinus rhythm was available in 53 patients (14 women [26.4%]; mean [SD] age, 62.0 [9.7] years) out of the 96 patients followed-up in the DIGITOTAL study. Testing the DNN on the last ECG before the ablation procedure resulted in an area under the receiver operating curve (AUC) of 0.65 (95% CI, 0.49 - 0.80), and an area under the precision recall curve (AUPRC) of 0.56 (95% CI, 0.34 - 0.78). The optimal cutoff score resulted in a sensitivity of 60.0% (95% CI, 36.1% - 80.9%), specificity of 66.7% 66.7% (95% CI, 48.2% - 82.0%), accuracy of 0.64 (95% CI, 0.50 - 0.77), F1-score of 55.8% (95% CI, 38.5% - 74.4%), positive predictive value 52.2% (95% CI, 30.6% - 73.2%) and negative predictive value 73.3% (95% CI, 54.1% - 87.7%). Patients classified in the high-risk group versus low-risk group were more likely to exhibit AF recurrence up to one year after AF ablation (hazard ratio, 2.6; 95% CI, 1.1 - 6.5; P-value = 0.037). Conclusions The AI-enabled ECG algorithm, trained to predict AF on a sinus rhythm ECG, was able to predict AF recurrence after ablation with an accuracy comparable to the existing clinical risk scores. Further studies are needed to determine whether the DNN score can be used as an independent predictor and improve existing risk scores.

Continuous QT interval monitoring using insertable cardiac monitors during antiarrhythmic loading hospitalization: Results from the "LINQ QT" Study

Abstract Background QT interval prolongation is associated with the development of potentially lethal cardiac arrhythmias. An implantable cardiac monitor (ICM) capable of longitudinal QT monitoring may allow for mobile assessment of dynamic changes in QT and assist in predicting long term cardiotoxicity. Objective Determine feasibility of continuous QTc interval monitoring in patients with ICM hospitalized for antiarrhythmic drug loading. Methods The previously described QT detection algorithm for an ICM determines the QT interval for every beat thus providing continuous long-term QT trends. QT intervals detected from continuously collected ICM ECG data from patients enrolled in a prospective clinical study from three sites was analyzed with the primary objective of studying the long-term QT interval trends in patients undergoing antiarrhythmic drug loading in an inpatient setting. The ICM ECG was processed through the QT detection algorithm which calculates the QTc interval for every beat to generate continuous long term QTc trends. Metrics including mean and median QTc, minimum and maximum QTc, and magnitude of QTc change were studied during the hospitalization period. Continuous QTc interval trend is presented from a patient displaying increase in QTc interval following antiarrhythmic drug loading during the hospitalization period. Results 5 out of 17 patients enrolled (avg. age 71±7.3 years, 40% females) in the QT clinical study had continuous telemetered ICM ECG data available during the index antiarrhythmic loading hospitalization period. All patients were loaded with Sotalol during the hospitalization. All 5 patients had hypertension and atrial fibrillation (AF). 3 patients (60%) had a history of myocardial infarction (MI), congestive heart failure (CHF), and coronary artery disease (CAD) while 1 patient (20%) had diabetes. The magnitude of change in QTc over the hospitalization period was 139±42 msec with over 100 msec QTc change noticed in 4 of 5 patients (80%) (figure 1). Figure 2 shows continuous QTc interval trend observed from a patient (Male; Age:75; history of AF, hypertension, CHF, stroke) from this study showing a continuous increase in QTc interval. Overall, there was over 150 msec change in QTc observed for this patient during the hospitalization period. Premature ventricular complexes (PVCs) in a pattern of bigeminy were observed from ICM ECG for a 3-hr period from 12 pm-3 pm following the second antiarrhythmic dose which coupled with QT prolongation could indicate early signs of cardiotoxicity (figure 2). The five static 12-lead ECG measurements taken for this patient during the hospitalization period is also reported with the difference between these 12-lead QTc measurements and algorithm measured QTc being 22±8 msec. Conclusion ICM QT monitoring performed utilizing a QT interval detection algorithm can provide longitudinal and long-term dynamic QT trends in patients implanted with ICM.

Association of the pattern of new-onset post-operative atrial fibrillation with adverse clinical events over 1 year follow-up: insights from the VISION Cardiac Surgery Cohort

Abstract Background New-onset post-operative atrial fibrillation (AF) affects approximately 1 in 3 patients after cardiac surgery and is associated with adverse outcomes. Whether the amount of time spent in AF is associated with outcomes is unknown. Methods VISION Cardiac Surgery was an international, prospective cohort of patients who underwent cardiac surgery in 12 countries. We divided participants according to their pattern of AF: no new-onset AF, duration <24 h, duration 24-48 h, duration 48-72 h, duration >72 h and discharged in AF. We created a separate category for those who received electrical cardioversion. We excluded participants with a history of AF before surgery and participants with unknown duration of AF. We assessed the association of different patterns of AF, as compared to no AF, with clinical events occurring between 30 days post-operatively and 1 year of follow up. For each outcome, we created a Cox proportional hazards model adjusted for CHA2DS2-VASc score, smoking, hemodialysis, prior cardiac surgery, surgery type and antithrombotic use at hospital discharge (oral anticoagulation alone, oral anticoagulation plus antiplatelet, antiplatelet alone, or none). Results Among 12,234 eligible participants, 3,887 (30.3%) had new-onset post-operative AF and 3,711 had a known duration of AF. The proportion of patients with new-onset AF who were discharged from hospital on oral anticoagulation was 39%. Table 1 displays event rates by AF pattern. Compared to participants without AF, we observed a higher risk of a composite of stroke or vascular death at one year in participants with estimated AF duration >72 h (3.9%, adjusted hazard ratio (aHR) 1.72; 95% CI 1.03-2.87) and in those who underwent electrical cardioversion (3.7%, aHR 2.18; 95%CI 1.16-4.11). Only AF duration >72 h was associated with an increased risk of stroke (2.1%; aHR 2.42; 95%CI 1.15-5.09). We observed a higher risk of all-cause mortality in participants who were in AF at hospital discharge (4.1%, aHR 1.83; 95%CI 1.10-3.05) and in participants who received electrical cardioversion (5.8%, aHR 2.81; 95%CI 1.67-4.73). Only being in AF at discharge was associated with an increased risk of heart failure (3.8%; aHR 2.63; 95% CI 1.49-4.63). All patterns of AF were associated with AF detection in follow-up, with the strongest associations observed in participants who were in AF at hospital discharge (31.8%, aHR 73.4; 95%CI 51.4- 105.0) and in those who received electrical cardioversion (12.5%, aHR 17.9; 95%CI 11.1-28.8). Conclusions Among patients with new-onset post-operative AF following cardiac surgery, duration of AF >72 h, electrical cardioversion and being in AF at discharge are all markers of adverse events in the year following surgery. All patterns of AF confer a higher risk of AF detection in follow-up. Duration and treatment of early post-operative AF may have implications regarding the longer-term risk of adverse outcomes and recurrent AF.

Comparison between Novel and Conventional Electrocardiographic Markers of Atrial Cardiomyopathy for identification of Persons at Risk for Ischemic Stroke

Abstract Background Atrial cardiomyopathy is associated with increased risk for future atrial fibrillation (AF) and ischemic stroke. Several ECG-derived parameters have been reported to assess the risk for future ischemic stroke. Purpose To predict risk of future ischemic stroke by comparison of the novel parameter duration of the amplified digital sinus-p-wave (APWD; 80mm/mV; 175mm/sec) vs previously described p-wave indices and clinical risk factors (cerebrovascular disease (CVD), CHADS-VASc-score). Methods P-wave-derived parameters were measured on digital 12-lead-sinus-ECGs (recorded +/- 6 months from the clinical stroke event) using the software "ECG-Precision-Analysis V-1-2023". and clinical CHA2DS2-VASc Score was assessed in 80 patients with ischemic stroke (no history of AF, no oral anticoagulation (OAC)) and compared to 80 control patients (without OAC, AF or ischemic stroke within the next five years). Results Patients with ischemic stroke vs control patients presented a higher CHA2DS2-VASc Score (3.7 vs 3.2, p=0.04), had more frequently heart failure (25% vs 13%, p=0.04) and cerebrovascular atherosclerotic disease with stenosis >40% ((22.5% vs 10%, p=0.032). P-wave indices were as follows in patients who developed ischemic stroke within the next 12 months versus patients without stroke within a follow-up period of five years, respectively: APWD (144 vs 128ms, p<0.0001), non-amplified SPWD (118 vs 116ms, p=0.081), A-PTF-V1 (-4660 vs -3860µV*ms, p=0.005), durations and amplitudes of terminal-p-wave in V1 (A-Duration-V1 (83 vs 79ms, p=0.119), A-Amplitude-V1 (-50µV vs -50µV, p=0.028), and advanced interatrial block (aIAB in 25% vs 3.8% of patients; p<0.0001. The novel ECG-derived parameter (duration of the amplified sinus-P-wave >140ms) was the best predictor for future ischemic stroke (accuracy: 74%, sensitivity and specificity: 61% and 86%, respectively; PPV: 82%; area under ROC: 0.776). Sensitivity and specificity of the SPWD, aPTFV1 and aIAB were significantly lower (SPWD>120ms: sensitivity 35% and specificity 78%, PPV: 61%; aPTFV1 ≤-5000µV*ms, accuracy: 61%, sensitivity 46%% and specificity 75%, PPV: 65%; aIAB: accuracy: 61%, sensitivity 25% and specificity 96%, PPV: 87%). Conclusions Among the currently identified ECG markers of atrial cardiomyopathy, the novel APWD and advanced interatrial block have the best predictive performances for diagnosis of persons at risk for ischemic stroke.Comparison between ECG ParametersPredictive Accuracy of Parameters

Assessing heart rate fragmentation to predict atrial fibrillation in the general population aged 65

Abstract Rationale Screening the general population aged 65 for atrial fibrillation (AF) has been proposed as a preventive measure against potential complications. The dysfunction of the autonomic nervous system (ANS) plays an important role in atrial fibrillation (AF). Short-term HRV is conceptually attributed to physiologic vagal tone modulation. But recent data suggest that a component of short-term HRV, called heart rate fragmentation (HRF), is related to ANS breakdown and may be a predictor of AF occurrence. Metrics derived from heart rate variability (HRV) that depict heart rate fragmentation (HRF) have been suggested to reflect autonomic nervous system (ANS) dysfunction. Objectives To assess the predictive capacity of HRF markers for AF occurrence over an 18-year follow-up in individuals aged 65 at the study’s inspection and to develop a predictive score for AF onset. Methods A cohort study was designed to prospectively assess the predictive value of ANS activity level among general population regarding cardiovascular events and mortality. 1011 subjects aged 65 were enrolled in the study from September 2000 to December 2002. The study population had no history of AF and a low cardiovascular risk. A median follow-up of 17.8 years was managed. HRV data were acquired by 24-h Holter electrcardiogram (ECG) monitoring at baseline and assessed by frequency domain and time domain methods. Heart rate fragmentation using the percentage of inflection points (PIP) and alpha 1-index (using fractal evaluation of NN intervals) were then calculated. The study outcome was the development of AF during follow-up, defined as a standard 12-lead ECG recording or Holter recording with ≥ 30 s of AF. Results AF was diagnosed in 123 patients during the 18-year follow-up, representing a cumulative incidence of 13.4%. Using multivariate analysis, the occurrence of AF was independently predicted by the male gender (HR=1.74, 95%CI:1.16-2.63, p<0.01), a heart rate below 70bpm (HR=1.85, 95%CI:1.18-2.90, p<0.01), an increased percentage of NN intervals that differ by more than 50 ms from the previous interval (pnn50) (HR=1.69, 95%CI:1.06-2.70, p=0.03), an increased percentage of inflection points (HR=2.80, 95%CI:1.66-4.72,p<0.01), and a reduced alpha 1 index (HR=1.61, 95%CI:1.03-2.53, p=0.04). Given these results, a predictive score was built up based on the 4 independent predictors, ranging from 0 to 6 (Graphical Abstract). The high-risk group, defined as having a PROOF-AF score of 4 or higher, exhibited a 3.3-fold higher risk of developing AF (Figure). The PROOF-AF score demonstrated superior predictive performance compared to other available risk scores for incident AF such as CHARGE-AF score, C2HEST score, FHS score, and JMC score. Conclusion HRF parameters, included in the PROOF-AF score, may be used to identify individuals aged 65 without pre-existing health conditions who are at high-risk of developing AF and assist population screening.Graphical abstractFigure

Factors influencing inappropriate device therapy in implantable cardioverter defibrillators: a predictive analysis

Abstract Background Implantable cardioverter defibrillator (ICD) implantation and subsequent ICD therapy have shown to be efficacious in the prevention of sudden cardiac death. However, patients with an ICD are at risk of inappropriate device therapy (IDT), which is associated with worse outcomes, reduced quality of life (QoL), and may influence psychosocial and mental wellbeing. Purpose This study aimed to predict which patients are at risk of IDT by investigating the influence of pre-implant clinical parameters on occurrence of IDT. Methods From January 2010 to December 2019, patients who received an ICD in our medical center, were included in a prospective registry. Only patients with ICD (including ICDs used for cardiac resynchronization therapy, i.e. CRT-D) with an atrial lead were included in the current analysis, to better distinguish between appropriate and inappropriate device therapy. After implant, the device was interrogated at least every 6 months and clinical symptoms related to the device, recorded events, and relevant technical setting changes were recorded. IDT was defined as antitachycardia pacing (ATP) or shock delivered for any reason other than ventricular arrhythmia. Follow-up ended after IDT, death, or loss-to-follow-up. Results 428 patients underwent an implantation of a dual chamber ICD or CRT-D of various manufacturers. 14 patients were lost to follow-up within the first year and one patient was excluded because of a dislocated atrial lead, leaving 413 patients (76% male, mean age 67±9.7 years, 39% CRT-D) with a minimum of 1-year follow-up. During a mean of 5.3 (±3.0) years, 136 (32.9%) patients received appropriate therapy and 36 (8.7%) patients received IDT. Of those 36 patients, 18 patients received only ATP, 12 received ATP followed by a shock, and 6 patients received a shock without prior ATP. The median time from implantation to IDT was 2.8 [0.3-5.8] years. Univariate logistic regression on 40 clinical parameters followed by a forward multivariate logistic regression was performed. The area under the ROC curve of the resulting multivariate model was 0.724 (95%CI 0.622-0.826). Cox regression analysis resulted in device type (CRT-D) (HR=0.533, 95%CI 0.234-1.211, p=0.133), use of mineralocorticoid receptor-antagonists (MRA) (HR=0.280, 95%CI 0.104-0.754, p=0.012), use of diuretics (HR=3.378, 95%CI 1.479-7.714, p=0.004), and eGFR (HR=1.217, 95%CI 0.972-1.523, p=0.087) as predictors of IDT. A history of atrial fibrillation was not a significant predictor of IDT. Conclusion This study identified CRT-D and use of MRAs to be protective against IDT, and use of diuretics and lower eGFR as risk factors of IDT. To inform patients optimally, pre-implant assessment of those factors could help identify patients at higher risk of IDT. Furthermore, it could dictate more cautious device programming and consequently reduce rates of IDT, reducing the negative influence of IDT on QoL and wellbeing in the ICD population.

Not too old to be treated: electrophysiological study and catheter ablation in eldery patients

Abstract Background The number of elderly patients referred for electrophysiological study (EPS) and catheter ablation (CA) is increasing. These patients are thought to have more complications due to age and comorbidity. Purpose The aim of our study was to evaluate the safety (EPS and CA) and acute success (CA) in a group of elderly patients (age ≥75 years old). Methods Between August 2020 and September 2023, consecutive elderly patients (32.7% older than 80 years) underwent EPS alone or EPS and CA at our center. Left atrial thrombus was ruled out performing transesophageal echocardiography when indicated. Anticoagulation (ACO) was not interrupted. Femoral veins, arteries and transeptal punctures were performed under ultrasound guidance. A navigation system was used for all CA procedures, except for pulmonary vein isolation, which was performed with a cryoballoon. We analysed procedural complications related to EPS and CA and the acute success of CA procedures. Results A total of 104 patients undergoing EPS±CA (79.9±4.6 years, 41.3% female, 75% HTA, 67.3% diabetes type 2, 19.4% COPD, 20.2% chronic renal disease, 25% structural heart disease, CHA2DS2VasC score 3.6±0.8, IMC 27.3±4.5 kg/m2, weight 72.3±13.6 kg, LVEF 52.7±10.8%, 31% history of atrial fibrillation (AF), 47.1% on ACO, 38.5% bundle-branch block, 34.6% first-degree atrioventricular block, 4.8% implanted pacemaker or ICD) were included. Indications for referral (Figure 1) were typical atrial flutter (TAF, 34.6%), atrioventricular nodal reentrant tachycardia (AVNRT, 26.9%), study of syncope (11.5%) atypical atrial flutter or atrial tachycardia (AAF/AT, 10.6%), AF (8.6%, 6 patients for AV node ablation, 3 for pulmonary vein isolation), ventricular tachycardia or ectopy (VT or VE, 5.7%), orthodromic reentrant tachycardia (ORT, 1.9%). 2 patients had TAF and AVNRT, treated in the same procedure. Acute success was achieved in 100% of AF, 94.6% of TAF, 89.6% of AVNRT, 66% of VT/VE, 50% of ORT, 45% of AAF/AT. There were 4 complications (2.9%) in 3 patients, all during the CA procedure: an AV block during an AVNRT ablation, another AV block during an ischaemic septal VT ablation, a femoral artery pseudoaneurism in the same patient (femoral artery approach), and a dislocation of the electrodes from a previous pacemaker during an AT ablation. None of the patients undergoing EPS alone had complications. Weight was the only variable associated with the development of complications (mean difference= -19.8, 95% CI(-38.9-0.7); p=0.04), being higher in those with than in those without complications (91.5±2.2 vs 71.6±13 Kg),(Table 1). Conclusions EPS and CA procedures in elderly patients with multiple comorbidities are safe and effective. Acute success and complication rates of CA procedures are substrate-dependent and similar to those reported in the literature for younger patients. We conclude that age is not a barrier to the study and treatment of arrhythmias.

Incidence and predictors of heart failure events following cardiac surgery in patients with atrial fibrillation - insights from the LAAOS-III trial

Abstract Background Atrial fibrillation (AF) is a common comorbidity in patients undergoing cardiac surgery and further increases the risk of incident heart failure (HF). However, only limited data exist on HF events following surgery in patients with AF. Methods The Left Atrial Appendage Occlusion Study (LAAOS) III was a randomized trial evaluating concomitant left atrial appendage occlusion in patients with AF undergoing cardiac surgery. In this secondary analysis, we aimed to identify independent predictors of the composite outcome of HF hospitalization or HF-related death following discharge, using a multivariable Cox model – incorporating sex, age (≥65 vs <65 years), systolic blood pressure (≤140 vs >140 mmHg), body mass index (BMI; <25 vs 25-29.9 vs ≥30 kg/m2), diabetes mellitus (DM), prior HF diagnosis, prior stroke, ischemic heart disease (IHD), heart valve surgery, AF history duration, rhythm on discharge electrocardiogram, and trial allocation. Supplementary analyses were undertaken to further assess the continuous variables using cubic spline regression. Results Of 4770 patients enrolled, in-hospital death occurred in 201 (4.2%) and complete discharge data were available for 4564 (95.7%). During a median follow up of 3.9 years, 533 (11.7%) of 4564 patients were hospitalized for HF. In total, 873 (19.1%) died after discharge, including 95 HF-related deaths. The composite outcome of HF hospitalization or HF-related death occurred at an annualized event rate of 3.31%/year [95% confidence interval: 3.04-3.60]. The independent risk factors included age (event rate of 3.64%/year vs 2.03%/year for ≥65 vs <65 years; hazard ratio (HR) 1.71 [1.32-2.21]), DM (4.71%/year vs 2.71%/year for with vs without DM; HR 1.59 [1.34-1.90]), prior HF diagnosis (4.27%/year vs 2.17%/year for with vs without HF; HR 2.00 [1.66-2.41]), IHD (3.63%/year vs 2.85%/year for with vs without IHD; HR 1.26 [1.03-1.54]), AF history duration (3.81%/year vs 2.89%/year for >2 vs <0.5 years; HR 1.23 [1.01-1.50]), and AF rhythm at discharge (3.87%/year vs 2.68%/year for AF vs non-AF rhythm; HR 1.31 [1.09-1.58]). The supplementary spline analyses further revealed a positive correlation between BMI and the risk of the composite outcome (p-value 0.042). Conclusions In patients with AF undergoing cardiac surgery, post-discharge HF hospitalization and HF-related death occurred at a rate of 3.31% per year. Our study identified several significant risk factors including advanced age, higher BMI, DM, prior HF diagnosis, IHD, AF history >2 years, and AF rhythm at discharge.The associations of HF with age and BMI

Ten-year follow-up results of patients with persistent atrial fibrillation treated by combined pulmonary vein isolation and complex fractionated atrial electrocardiogram ablation

Abstract Background For persistent atrial fibrillation (AF), pulmonary vein isolation (PVI) alone is associated with lower success rate compared to paroxysmal AF and additional strategies are needed. Ablation targeting on complex fractionated atrial electrograms (CFAE) is an alternative method. Although clinical benefits of the strategy combined PVI and CFAE ablation have not been shown by large trials, clinical situations and consequences of this approach have not been clearly demonstrated during very long term follow-up. Purpose This study aimed to retrospectively investigate clinical outcomes of patients with persistent AF treated by the approach combined PVI and CFAE ablation during a follow-up period of 10 years. Methods 73 patients (59.4±8.1 years, 64 male, AF history 5.5 years) with persistent (23, 31.5%) and long-standing persistent AF (50, 68.5%) who underwent combined PVI and CFAE ablation in the first procedure were included. Structural heart disease was found in 9 patients, and a history of ablation for typical atrial flutter (AFL) in 4. A complete CFAE mapping in the left atrium and coronary sinus was performed with a 3-D mapping system (EnSite NavX). All CFAEs defined as electrograms with continuous activities or mean cycle length detected by the system <80 ms were eliminated. All patients were controlled regularly during the first year with 12-lead ECG and Holter monitoring and followed by annual control. The electronic health records for all patients were extensively investigated and the patients were interviewed in 2020-2022. Any documented atrial tachyarrhythmia (ATA) after 3-month blanking period was regarded as recurrence. Results Mean 2.2±1.2 (1-5) ablation procedures were performed in each patient. After index ablation, 18 (24.7%) were free of ATAs during 10-year follow-up. 26 (35.6%) had recurrence of only AF, 6 (8.2%) of only AFL and 23 (31.5%) had both AF and AFL. The proportion of AFL was 39.7% with 6 typical AFL. After multiple ablation procedures, 33 (45.2%) patients were free of ATA during the follow-up. 23 (31.5%) had recurrence of only AF, 5 (6.8%) of only AFL and 12 (16.4%) of both AF and AFL. The proportion of AFL was 23.2% with no typical AFL. At 1-year follow-up, freedom of ATAs in persistent AF was higher than that in long-standing AF (65.2 vs. 40.0%, p=0.033) and no significant difference was found after 2 years (47.8 vs. 34.0%, p=0.129) until 10 years (30.4 vs. 22.0%, p=0.167, Figure 1). No difference was observed between these subgroups after multiple procedures at 10-year follow-up (47.8 vs. 44.0%, p=0.708, Figure 2). Conclusions PVI plus CAFE ablation in patients with persistent AF led to a high recurrence of ATA after index ablation. Difference of ATA-freedom between persistent and long-standing persistent AF groups was found only 1 year after the index procedure, but not during further follow-up. Incidence of post-ablation AFL was particularly high, even after multiple ablation procedures.Figure 1Figure 2

Different predictors of AF recurrence after pulmonary vein isolation with cryoballoon and radiofrequency ablation: insights from clinical and electroanatomical mapping data of the NO-PERSAF study

Abstract Background Pulmonary vein isolation (PVI) with cryobaloon ablation (CBA) and radiofrequency ablation (RFA) lead to a similar outcome of freedom from atrial tachyarrhythmia (ATA) during follow-up as showed by the NO-PERSAF study. Analyses of ATA recurrence for these two techniques based on data of electroanatomical mapping (EAM) are scarce from randomized clinical trials. Purpose This study aimed to evaluate and compare clinical outcomes and EAM data recorded in the left atrium (LA) during CBA and RFA procedures in patients with persistent atrial fibrillation (AF). Methods For the NO-PERSAF study, 101 patients (mean 63.2±8.6 years, 80 male, 21 female) with persistent AF (77 persistent AF, 24 long-standing persistent AF) referred to PVI were randomized (1:1) to CBA or RFA and followed for 12 months. A prolonged 3-year follow-up was carried out. EAM was performed by a circular mapping catheter with a 3-dimensional mapping system in all patients. EAM data were recorded and analyzed off-line. The areas of the LA, posterior wall, low-voltage (<0.5mV) and complex fractionated electrogram (cycle length <120 ms) were measured and corrected by body surface area (BSA). EAM data from 90 patients were qualified for further analysis and the others (5 in CBA and 6 in RFA) excluded because of disqualification or technical failure of recording. Correlation between clinical results of 3-year follow-up and the EAM data were analyzed using univariate cox regression. Results After 3-year follow-up, freedom from ATA was achieved in 51 (50.5%) of the 101 patients, 28 (54.9%) out of 51 patients in the CBA group and 23 (46.0%) out of 50 patients in the RFA group and no difference was found (p=0.327). RFA compared with CBA resulted in larger ablation lesions in the LA (23.9% vs. 21.3%; p=0.037) and particularly in the posterior wall (44.2% vs 31.8%; p<0.001). Compared between the patients with and without recurrence, there was no difference with respect to age, gender, AF history, body mass index, heart disease and CHA2DS2-vasc score. For EAM data, the area of the LA and low voltage were significantly higher in ATA recurrent patients in CBA group, but not in RFA group (Table 1). Univariate cox regression analyses suggested that 3-year follow-up outcomes were associated with the size of the LA and the amount of low voltage corrected by BSA. The criteria of the LA area >55 cm2/m2 or low voltage area <19 cm2/m2 could predict ATA recurrence after CBA, but not after RFA procedure (Figure 1). Conclusions The size of the LA and the amount of low voltage corrected by BSA was associated with the outcomes of PVI during follow-up and could be employed as predictors of ATA recurrence for CBA, but not for RFA procedure.Table 1Figure 1K-M curves after CBA and RFA

Multielectrode catheter-based pulsed field ablation of persistent and long-standing persistent atrial fibrillation

Abstract Background Rhythm control of non-paroxysmal atrial fibrillation (AF) is significantly more challenging, as a result of arrhythmia perpetuation promoting atrial substrate changes and AF maintenance. Purpose We describe a tailored ablation strategy targeting multiple left atrial (LA) sites via the multielectrode FarawaveTM pulsed field ablation (PFA) catheter in patients with persistent AF sustained beyond 6 months (PerAF>6m) and long-standing persistent AF (LSPAF). Methods The ablation protocol included the following stages: pulmonary vein antral and posterior wall isolation plus anterior roof line ablation (Stage 1); electrogram-guided substrate ablation (Stage 2); atrial tachyarrhythmia (AT) regionalization and ablation (Stage 3). Results Seventy-two [age:68±10y, 61.1%males; AF history: 25 (18-45) months] patients with PerAF>6m (52.8%) and LSPAF (47.2%) underwent their first PFA via the FarapulseTM system. LA substrate ablation (Stage 1 and 2) led to AF termination in 95.8% of patients. AF termination occurred while ablating the mitral edge of the postero-lateral ridge (40.3%), the inferior left atrium above the proximal coronary sinus (27.4%), the interatrial septum (22.6%), the superior aspect of the postero-lateral ridge (6.5%), the base of the appendage (3.2%). AF organized into a left-sided atrial flutter (AFlu) in 46 (74.2%) patients. The FarawaveTM catheter was used to identify LA sites showing diastolic, low-voltage electrograms and entrainment from its splines was performed to confirm the pacing site was inside the AFlu circuit (Figure 1). Left AFlu termination was achieved in all cases via PFA delivery. Total procedural and LA dwell times were 112±25min and 59±22 min, respectively. Major complications occurred in 2 (2.8%) patients with pre-existing left ventricular systolic dysfunction (EF<35%) who required inotropic therapy due to acute heart failure. Hemodynamics normalized within 24h and both patients were discharged after 2 and 3 additional hospital days. Transient ST-segment elevation was documented in 4 patients after peri-mitral PFA; timely nitrate administration led to ECG normalization within 10 minutes. Single-procedure success rate was 81.8% after 13.3±1.9 months of follow-up; AF-free survival was 93.1% (Figure 2). A subgroup of 36 patients completed a follow-up transthoracic echocardiography study to assess left atrial mechanical contraction changes after ablation. Median A-wave velocity was 30 (IQR: 20-35) cm/s post-ablation and 50 (IQR: 41-70) cm/s after a mean of 7.3±1.8 months post-ablation. Conclusions In our cohort, PFA-based AF substrate ablation led to AF termination in 95.8% of cases. Very favorable clinical outcomes were observed at one year of follow-up.Entrainment from the PFA Catheter.Kaplan-Meier Analysis.

Long-term follow-up of pulmonary vein cryoballoon isolation using a double 120s vs single 240s standard freeze protocol

Abstract Background Recently, pulmonary vein isolation (PVI) using a double 120s freeze protocol has demonstrated to be non-inferior to a single 240s protocol despite a potentially increased procedural safety. Main advantages of a double 120s protocol are a reduction of phrenic nerve injury and an increase of the mean minimal esophageal temperature during the procedure. Methods We performed a long-term follow-up comparison between groups of patients with history of symptomatic atrial fibrillation undergoing PVI with second generation cryoballoon (CB) between 2019 and 2020. Our usual energy dosing protocol was modified including 2 times 120 seconds applications instead of a single 240 seconds application. Of A total of 160 consecutive patients, 80 were treated with double 120s (CB120) and 80 with single 240s (CB240) freeze protocol. 107 patients were, successfully, followed-up. The primary end-point was freedom from atrial tachyarrhythmia. Results Before PVI a total of 11/52 patients (21%) had persistent AF and 41/52 (79%) had paroxysmal AF in the CB120 group; a total of 20/55 patients (36%) had persistent AF and 35/55 (64%) had paroxysmal AF in the CB240 group. On a mean follow-up time of 17 months, freedom from atrial tachyarrhythmia was 63% in those patients undergoing CB240 and 74% with CB120 (log-rank P=0.255). Conclusions The double 120s freeze protocol is not-inferior as compared to the standard 240s in terms of freedom from recurrences on a long term follow-up, but with a more favorable procedural safety profile.

Assessment of mild cognitive dysfunction in patients with atrial fibrillation utilizing the R4Alz assessment test

Abstract Background/Introduction The association between atrial fibrillation and cognitive dysfunction has accumulated a growing body of evidence in recent years. However, establishing such a diagnosis remains challenging, especially in mild oligosymptomatic patients. REMEDES for Alzheimer (R4Alz) is a novel test, designed to assess cognitive control decline at an early stage. Purpose We sought to evaluate the prevalence of early, mild cognitive dysfunction in patients with paroxysmal atrial fibrillation with the use of established and novel diagnostic tools. Methods This is a prospective cross-sectional study that enrolled consecutive patients with history of paroxysmal atrial fibrillation and matched healthy controls, from a tertiary cardiology department. Patients with history of stroke or known cognitive dysfunction of any type were excluded from the study. Demographic and clinical data were collected. All study participants were subjected to Montreal Cognitive Assessment (MoCA) and to R4Alz within the same day. Cognitive function and attention ability is assessed at three stages with R4Alz: working memory updating (R1), supervisory attention system (R2) and task/rule switching and control of inhibition (R3). The primary endpoint was the difference in cognitive function between patients with atrial fibrillation and controls. Secondary endpoints included the correlation between the two assessment tests in both groups. Statistical analysis was performed with R version 4.1.0 and a p-value<0.05 was considered statistically significant. Results Fifty-five patients with atrial fibrillation and thirty-four controls were enrolled in the study (Mean age: 62.6 y, Female gender: 62.9%). MoCA scores (25.4 ± 4.11 for patients with atrial fibrillation vs 22.3 ± 3.72 for healthy controls, p-value <0.001) (Figure 1) as well as scores of all stages of R4ALz {working memory (R1a, R1b, R1c), supervisory attention system (R2) and task/rule switching – inhibition control (R3a1, R3a2, R3b)} were indicative of mild cognitive dysfunction in patients with atrial fibrillation. The control group exhibited significantly better cognitive performance on all assessment tools (Table 1).Figure 1Table 1

Preliminary real-world experience on mitral isthmus ablation with a novel catheter that toggles between radiofrequency and pulsed field ablation

Abstract Background The mitral isthmus (MI) is frequently targeted during the ablation of persistent atrial fibrillation (AF). Nevertheless, achieving a complete bidirectional MI block using radiofrequency (RF) is often technically challenging and time-consuming1,2. Previously, we described a fluoroscopy-guided technique to achieve MI block using a penta-spline pulsed field ablation (PFA) catheter3. Recently, a new catheter was introduced, which toggles between RF and PFA and is integrated into a 3D mapping system, thus supposedly facilitating its use for the ablation of extra-pulmonary vein structures4. Purpose To describe the acute efficacy and procedural features of the first cases of posterior MI ablation performed with the toggling catheter at two centers. Methods We collected and reviewed demographic, clinical and procedural features of all patients who underwent ablation of the posterior MI at our centers between September and October 2023. Ablation of the MI was performed with either RF or PFA according to operator’s discretion. Bidirectional MI block was validated through activation mapping and differential pacing. Results During the study period, 44 patients were treated with the toggling catheter. Out of them, 16 patients (aged 68.3±10.1 years; 29% females) underwent posterior MI ablation for persistent AF, in addition to PVI and posterior wall isolation. Mean history of AF was 29.8±34.5 months and mean LA volume 135.6±54.9 ml. Skin-to-skin procedural time (93 minutes, IQR 64-112), LA mapping time (9.0 min, IQR 7.3-12.1) and time required for MI ablation (4.0 min, IQR 3.3-6.5) were remarkably short. In PFA-treated patients (10 cases), first-pass MI block was achieved in 8 (80%), with 16 (IQR 12-22) applications; none of these patients required RF touch-up. In the remaining 6 RF-treated patients, first-pass MI block was achieved in 3 (50%) patients with 8 (IQR 6-13) applications. Additional PFA applications (median 3, IQR 2-5) on the most venous portion of the MI were required in all RF-treated patients. In the 5 patients in whom bidirectional block could not be achieved at first-pass, remapping and touch-up application time were 2.6 (IQR 2.6- 6.3) and 2.0 (IQR 0.8-5.2) minutes, respectively. Eventually, bidirectional MI block was achieved in 16/16 (100%) patients by the end of the procedure. Importantly, no patients in the entire cohort experienced complications such as coronary artery spasm or clinically significant pericardial effusion. Conclusions Several observations can be made on this first real-world experience on posterior MI ablation with the toggling catheter: first, acute safety and efficacy in achieving a bidirectional MI block are high with both PFA and RF; secondly, patients undergoing RF ablation often require additional PFA applications on the venous segment of the MI; lastly, the time required to achieve MI block is remarkably short even when remapping and touch-up applications are needed.Figure 1Figure 2

Polygenic risk score for Atrial Fibrillation as a predictor for the incidence of Sick Sinus Syndrome: A comprehensive analysis from the UK biobank

Abstract Background Sick sinus syndrome (SSS) and atrial fibrillation (AF) often coexist, demonstrating a bidirectional relationship. The polygenic risk score (PRS) represents the cumulative risk of disease onset based on variations at multiple genetic loci and is known as a predictor for disease incidence. However, the PRS for SSS remains under-investigated. This study aims to evaluate whether the PRS for AF can predict the incidence of SSS in the general population. Methods The UK biobank, comprising of about 500,000 participants aged 40 to 70, was established across 22 centres in the UK between 2006 and 2010. After excluding missing values, prior AF history, and valvular heart disease, a total of 101,654 participants without AF (median age, 56.0 [interquartile range (IQR), 49.0–63.0] years; 44,851 [44.1%] male) were analyzed. Participants were divided into quartiles according to a validated PRS for AF. Throughout the observation period, the incidence of SSS event was documented. Results During a follow-up period of 11.7 (IQR 11.0-12.5) years, a total of 157 cases of Sick sinus syndrome were identified. In the new-onset SSS group, age, PRS for AF, BMI, and waist measurements were significantly higher. Additionally, there was a statistically significant increase in the proportions of male sex, hypertension, previous MI, hypothyroidism, dyslipidemia, and ESRD/CKD. The Kaplan-Meier analysis demonstrated an association between the highest quartile and an increased incidence of SSS compared to the other quartiles. (Log-rank P < 0.001) The Cox regression model revealed that a PRS for AF was associated with an increased risk of incidence of sick sinus syndrome (aHR 1.29, 95% CI 1.10-1.51, p-value 0.002). Notably, the discriminative power of our model was substantial, yielding a C-index of 0.746. Conclusion In our study, the PRS for AF effectively predicted the incidence of SSS. In the absence of a dedicated PRS for SSS, the AF PRS may offer insights into developing one for SSS.