Clinical Outcomes of Early Rhythm or Rate Control for New Onset Atrial Fibrillation Following Transcatheter Aortic Valve Replacement.

BACKGROUND: New onset atrial fibrillation (NOAF) is a common occurrence after transcatheter aortic valve replacement (TAVR) and portends a poorer prognosis. The optimal strategy for managing NOAF in this population is uncertain. METHODS: This retrospective cohort study utilized deidentified patient data from the TriNetX Research Network. Patients with TAVR and NOAF were stratified into a rhythm control cohort if they were treated with antiarrhythmics, received AF ablation, or underwent cardioversion within 1 year of AF diagnosis. A rate control cohort was similarly defined by the absence of rhythm control strategies and treatment with a beta blocker, calcium channel blocker, or digoxin. After 1:1 propensity score matching, the Kaplan-Meier survival analysis and Cox proportional hazard ratios (HRs) were used to compare outcomes at 7 years of follow-up. RESULTS: We identified 569 patients in each cohort following propensity matching. At 7 years, the primary composite outcome of all-cause death, myocardial infarction, cerebrovascular accident, and heart failure hospitalization was not significantly different between the rhythm and rate control cohorts (HR 0.99, 95% CI 0.83-1.18). The individual components of the primary outcome in addition to all-cause hospitalization were also similar between the groups. CONCLUSIONS: Similar outcomes were seen among patients receiving an early rhythm or rate control strategy to manage NOAF after TAVR. The attenuated benefits of an early rhythm control strategy observed in this setting may be due to the overall high burden of comorbidities and advanced age of these patients.

Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.

INTRODUCTION: The cardiac conduction system (CCS) is crucial for maintaining adequate cardiac frequency at rest and modulation during exercise. Furthermore, the atrioventricular node and His-Purkinje system are essential for maintaining atrioventricular and interventricular synchrony and consequently maintaining an adequate cardiac output. AREAS COVERED: In this review article, we examine the anatomy, physiology, and pathophysiology of the CCS. We then discuss in detail the most common genetic mutations and the molecular mechanisms of cardiac conduction disease (CCD) and provide our perspectives on future research and therapeutic opportunities in this field. EXPERT OPINION: Significant advancement has been made in understanding the molecular mechanisms of CCD, including the recognition of the heterogeneous signaling at the subcellular levels of sinoatrial node, the involvement of inflammatory and autoimmune mechanisms, and the potential impact of epigenetic regulations on CCD. However, the current treatment of CCD manifested as bradycardia still relies primarily on cardiovascular implantable electronic devices (CIEDs). On the other hand, an If specific inhibitor was developed to treat inappropriate sinus tachycardia and sinus tachycardia in heart failure patients with reduced ejection fraction. More work is needed to translate current knowledge into pharmacologic or genetic interventions for the management of CCDs.

Comprehensive atrial fibrillation burden and symptom reduction post-ablation: insights from DECAAF II.

AIMS: Traditional atrial fibrillation (AF) recurrence after catheter ablation is reported as a binary outcome. However, a paradigm shift towards a more granular definition, considering arrhythmic or symptomatic burden, is emerging. We hypothesize that ablation reduces AF burden independently of conventional recurrence status in patients with persistent AF, correlating with symptom burden reduction. METHODS AND RESULTS: Ninety-eight patients with persistent AF from the DECAAF II trial with pre-ablation follow-up were included. Patients recorded daily single-lead electrocardiogram (ECG) strips, defining AF burden as the proportion of AF days among total submitted ECG days. The primary outcome was atrial arrhythmia recurrence. The AF severity scale was administered pre-ablation and at 12 months post-ablation. At follow-up, 69 patients had atrial arrhythmia recurrence and 29 remained in sinus rhythm. These patients were categorized into a recurrence (n = 69) and a no-recurrence group (n = 29). Both groups had similar baseline characteristics, but recurrence patients were older (P = 0.005), had a higher prevalence of hyperlipidaemia (P = 0.007), and had a larger left atrial (LA) volume (P = 0.01). There was a reduction in AF burden in the recurrence group when compared with their pre-ablation burden (65 vs. 15%, P < 0.0001). Utah Stage 4 fibrosis and diabetes predicted less improvement in AF burden. The symptom severity score at 12 months post-ablation was significantly reduced compared with the pre-ablation score in the recurrence group, and there was a significant correlation between the reduction in symptom severity score and the reduction in AF burden (R = 0.39, P = 0.001). CONCLUSION: Catheter ablation reduces AF burden, irrespective of arrhythmia recurrence post-procedure. There is a strong correlation between AF burden reduction and symptom improvement post-ablation. Notably, elevated LA fibrosis impedes AF burden decrease following catheter ablation.

Electronic ventricular pacing at the end of the QRS complex: Is it abnormal?

An 82-year-old man with ischemic cardiomyopathy, heart failure with reduced ejection fraction and Medtronic biventricular ICD presented with shortness of breath. His ECG is presented with shortness of breath. ECG shows atrial sensed, electronic ventricular pacing. At the end of each QRS complex there is another pacemaker stimulus. This represents typical case of cardiac contractility modulation therapy and not pacemaker malfunction.

Association between neighborhood household income and inpatient atrial fibrillation outcomes.

BACKGROUND: The impact of socioeconomic status on the clinical outcomes of patients admitted to the hospital for atrial fibrillation (AF) is not well described. OBJECTIVE: The purpose of this study was to determine the association between median neighborhood household income (mNHI) and clinical outcomes among patients admitted to the hospital for AF. METHODS: We retrospectively analyzed primary AF hospitalizations from the United States National Inpatient Sample between 2016 and 2020. The analyzed sample was divided into quartiles based on the mNHI in the zip code of the patient's residence. The lowest quartile was used as the reference category. Study outcomes included inpatient procedure utilization (ablation, cardioversion, percutaneous left atrial appendage closure), length of stay, cost, mortality, and disposition. Weighted multivariable logistic and linear regression, adjusting for multiple patient and hospital-level characteristics, was performed. RESULTS: Patients in the highest mNHI quartile had lower comorbidity burden, lower in-hospital mortality (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.7-0.87; P <.001), lower discharges to care facility (OR 0.86; 95% CI 0.83-0.9; P <.001), shorter length of stay (adjusted mean difference -0.26; 95% CI -0.30 to -0.22; P <.001), higher procedure utilization, and higher health care costs ($12,124 vs $10,018) compared to the lowest mNHI quartile patients. CONCLUSION: We identified significantly higher in-hospital mortality and lower procedural/resource utilization in patients living in lower-income neighborhoods compared to higher-income neighborhoods. Further research is needed to better understand the drivers of these disparities and the strategies to improve health care disparities between socioeconomic groups.

Arrhythmic Risk in Biventricular Pacing Compared With Left Bundle Branch Area Pacing: Results From the I-CLAS Study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy. We sought to compare the occurrence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP. METHODS: The I-CLAS study (International Collaborative LBBAP Study) included patients with left ventricular ejection fraction ≤35% who underwent BVP or LBBAP for cardiac resynchronization therapy between January 2018 and June 2022 at 15 centers. We performed propensity score-matched analysis of LBBAP and BVP in a 1:1 ratio. We assessed the incidence of VT/VF and new-onset AF among patients with no history of AF. Time to sustained VT/VF and time to new-onset AF was analyzed using the Cox proportional hazards survival model. RESULTS: Among 1778 patients undergoing cardiac resynchronization therapy (BVP, 981; LBBAP, 797), there were 1414 propensity score-matched patients (propensity score-matched BVP, 707; propensity score-matched LBBAP, 707). The occurrence of VT/VF was significantly lower with LBBAP compared with BVP (4.2% versus 9.3%; hazard ratio, 0.46 [95% CI, 0.29-0.74]; P<0.001). The incidence of VT storm (>3 episodes in 24 hours) was also significantly lower with LBBAP compared with BVP (0.8% versus 2.5%; P=0.013). Among 299 patients with cardiac resynchronization therapy pacemakers (BVP, 111; LBBAP, 188), VT/VF occurred in 8 patients in the BVP group versus none in the LBBAP group (7.2% versus 0%; P<0.001). In 1194 patients with no history of VT/VF or antiarrhythmic therapy (BVP, 591; LBBAP, 603), the occurrence of VT/VF was significantly lower with LBBAP than with BVP (3.2% versus 7.3%; hazard ratio, 0.46 [95% CI, 0.26-0.81]; P=0.007). Among patients with no history of AF (n=890), the occurrence of new-onset AF >30 s was significantly lower with LBBAP than with BVP (2.8% versus 6.6%; hazard ratio, 0.34 [95% CI, 0.16-0.73]; P=0.008). The incidence of AF lasting >24 hours was also significantly lower with LBBAP than with BVP (0.7% versus 2.9%; P=0.015). CONCLUSIONS: LBBAP was associated with a lower incidence of sustained VT/VF and new-onset AF compared with BVP. This difference remained significant after adjustment for differences in baseline characteristics between patients with BVP and LBBAP. Physiological resynchronization by LBBAP may be associated with lower risk of arrhythmias compared with BVP.

Sex-Specific Outcomes of LBBAP Versus Biventricular Pacing: Results From I-CLAS.

BACKGROUND: Cardiac resynchronization therapy (CRT) using biventricular pacing (BVP) has been associated with greater clinical improvement in women than men. Recently, left bundle branch area pacing (LBBAP) has been shown to be an alternative form of CRT. OBJECTIVES: The purpose of this study was to investigate sex-specific outcomes for death and heart failure events in a large, international, multicenter, cohort of patients undergoing CRT with BVP or LBBAP. METHODS: In this international study of 1,778 patients (575 female and 1203 male), sex-specific survival analysis was performed to compare the effect of LBBAP-CRT relative to BVP-CRT on the combined endpoint of death or heart failure hospitalization (HFH), and secondary endpoints of HFH only, and death alone. RESULTS: Female patients were more likely to have nonischemic cardiomyopathy and left bundle branch block (LBBB) and less likely to have hypertension, diabetes, or coronary artery disease than were male patients. Overall, female patients had a better result with LBBAP compared with BVP than did male patients, with a significant 36% reduction in death or HFH (HR: 0.64; 95% CI: 0.43 to 0.97; P = 0.03) and a significant 60% reduction in HFH alone (HR: 0.4; 95% CI: 0.24 to 0.69, P < 0.01). Women had a greater reduction in death or HFH among those with nonischemic cardiomyopathy (HR: 0.45 95% CI: 0.26 to 0.79; P < 0.01) and LBBB (HR: 0.49; 95% CI: 0.27 to 0.87; P < 0.01). Sex-specific echocardiographic outcomes were better in women than in men. CONCLUSIONS: Women obtained significantly greater reductions in the combined endpoint of death or HFH (primarily driven by reduction in HFH) with LBBAP compared with BVP among patients requiring CRT than did men.

Smartphone AF Burden During the Blanking Period Predicts Catheter Ablation Outcomes: Insights From DECAAF II.

BACKGROUND: Atrial fibrillation (AF) recurrence during the blanking period is under investigated. With the rise of smartphone-based electrocardiogram (ECG) monitoring, there's potential for better prediction and understanding of AF recurrence trends. OBJECTIVES: In this study the authors hypothesize that AF burden derived from a single-lead Smartphone ECG during the blanking period predicts recurrence of atrial arrhythmias after ablation. METHODS: 630 patients with persistent AF undergoing ablation were included from the DECAAF II (Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation) trial. Patients recorded daily ECG strips using a smartphone device. AF burden was defined as the ratio of ECG strips with AF to the total number of strips submitted. The primary outcome was the recurrence of atrial arrhythmia. RESULTS: Recurrence occurred in 301 patients during the 18-month follow-up period. In patients who developed recurrent arrhythmia after 90 days of follow-up, AF burden during the blanking period was significantly higher when compared with patients who remained in sinus rhythm (31.3% vs 7.5%; P < 0.001). AF burden during the blanking period was an independent predictor of arrhythmia recurrence (HR: 1.41; 95% CI: 1.36-1.47; P < 0.001). Through grid searching, an AF burden of 18% best discriminates between recurrence and no-recurrence groups, yielding a C-index of 0.748. After a follow-up period of 18 months, recurrence occurred in 33.7% of patients (147 of 436) with an AF burden <18% and in 79.4% of patients (154 of 194) with an AF burden >18% (HR: 4.57; 95% CI: 3.63-5.75; P < 0.001). CONCLUSIONS: A high AF burden derived from a smartphone ECG during the blanking period is a strong predictor of atrial arrhythmia recurrences after ablation.

Detection of atrial fibrillation in real world setting in patients with cryptogenic stroke and an implantable loop recorder.

INTRODUCTION: Implantable loop recorders (ILR) are used to screen for atrial fibrillation (AF) in patients with cryptogenic stroke (CS). However, there is limited real-world data regarding the long-term rate of AF detection using ILR and management consequences in patients with CS. The objective is to assess the rate of AF detection in patients with CS in a real-world study over 36 months of follow-up and its consequences on stroke prevention. METHODS: This retrospective study included patients with an ILR placed for CS at Baylor College of Medicine and Baylor St. Luke's Medical Center between January 2014 and July 2021. The primary outcome was AF detection in patients with ILR. The secondary outcome was the rate of subsequent strokes after ILR placement in patients with or without diagnosed AF. The AF detection rate in our cohort was compared to the rate in CRYSTAL-AF Trial at 36-month follow-up. The impact of AF detection on clinical management was examined. RESULTS: We identified 225 patients. 51.1% were women and 38.2% African American. Among 85 patients with ILR labeled AF, 43 patients had true AF, and 42 had incorrectly labeled AF (48.3% false positive). The estimated AF detection rate at 36 months follow-up was 28.6% (95% CI, 26.6%-30.6%). 58.1% of patients with AF were initiated on oral anticoagulation, 80.0% of whom were started on a direct oral anticoagulant. 13.8% of patients had recurrent strokes after ILR implantation; 4 of whom were diagnosed with AF. CONCLUSION: Compared to CRYSTAL-AF, the AF detection rate in our cohort is similar, but this cohort includes a higher proportion of female and African American patients. Most patients with recurrent strokes after ILR implant did not have AF during 36 months of monitoring.

Clinical outcomes of conduction system pacing versus biventricular pacing for cardiac resynchronization therapy: A systematic review and meta-analysis.

INTRODUCTION: Conduction system pacing (CSP) is observed to produce greater improvements in echocardiographic and hemodynamic parameters as compared to conventional biventricular pacing (BiVP). However, whether these surrogate endpoints directly translate to improvements in hard clinical outcomes such as death and heart failure hospitalization (HFH) with CSP remains uncertain as studies reporting these outcomes are scarce. The aim of this meta-analysis was to analyze the existing data to compare the clinical outcomes of CSP versus BiVP. METHODS: A systematic search of the Embase and PubMed database was performed for studies comparing CSP and BiVP for patients indicated to receive a CRT device. The coprimary endpoints were all-cause mortality and HFH. Other secondary outcomes included change in left ventricular ejection fraction (LVEF), change in NYHA class, and increase in NYHA class ≥1. A random-effects model was chosen a priori to analyze the composite effects given the anticipated heterogeneity of included trials. RESULTS: Twenty-one studies (4 randomized and 17 observational) were identified reporting either primary outcome and were included in the meta-analysis. In total 1960 patients were assigned to CSP and 2367 to BiVP. Median follow-up time was 10.1 months (ranging 2-33 months). CSP was associated with a significant reduction in all-cause mortality (odds ratio [OR] 0.68, 95% confidence interval [CI]: 0.56-0.83) and HFH (OR 0.52, 95% CI: 0.44-0.63). Mean improvement in LVEF was also greater with CSP (mean difference 4.26, 95% CI: 3.19-5.33). Reduction in NYHA class was significantly greater with CSP (mean difference -0.36, 95% CI: -0.49 to -0.22) and the number of patients with an increase in NYHA class ≥1 was significantly greater with CSP (OR 2.02, 95% CI: 1.70-2.40). CONCLUSIONS: CSP was associated with a significant reduction in all-cause mortality and HFH when compared to conventional BiVP for CRT. Further large-scale randomized trials are needed to verify these observations.

Comparison of Left Bundle Branch Area Pacing and Biventricular Pacing in Candidates for Resynchronization Therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS or expected frequent ventricular pacing. Left bundle branch area pacing (LBBAP) has recently been shown to be a safe alternative to BVP. OBJECTIVES: The aim of this study was to compare the clinical outcomes between BVP and LBBAP among patients undergoing CRT. METHODS: This observational study included patients with LVEF ≤35% who underwent BVP or LBBAP for the first time for Class I or II indications for CRT from January 2018 to June 2022 at 15 international centers. The primary outcome was the composite endpoint of time to death or heart failure hospitalization (HFH). Secondary outcomes included endpoints of death, HFH, and echocardiographic changes. RESULTS: A total of 1,778 patients met inclusion criteria: 981 BVP, 797 LBBAP. The mean age was 69 ± 12 years, 32% were female, 48% had coronary artery disease, and mean LVEF was 27% ± 6%. Paced QRS duration in LBBAP was significantly narrower than baseline (128 ± 19 ms vs 161 ± 28 ms; P < 0.001) and significantly narrower compared to BVP (144 ± 23 ms; P < 0.001). Following CRT, LVEF improved from 27% ± 6% to 41% ± 13% (P < 0.001) with LBBAP compared with an increase from 27% ± 7% to 37% ± 12% (P < 0.001) with BVP, with significantly greater change from baseline with LBBAP (13% ± 12% vs 10% ± 12%; P < 0.001). On multivariable regression analysis, the primary outcome was significantly reduced with LBBAP compared with BVP (20.8% vs 28%; HR: 1.495; 95% CI: 1.213-1.842; P < 0.001). CONCLUSIONS: LBBAP improved clinical outcomes compared with BVP in patients with CRT indications and may be a reasonable alternative to BVP.

Catheter ablation improved ejection fraction in persistent AF patients: a DECAAF-II sub analysis.

AIMS: The aim of our study was to assess differences in post-ablation atrial fibrillation (AF) recurrence and burden and to quantify the change in LVEF across different congestive heart failure (CHF) subcategories of the DECAAF-II population. METHODS AND RESULTS: Differences in the primary outcome of AF recurrence between CHF and non-CHF groups was calculated. The same analysis was performed for the three subgroups of CHF and the non-CHF group. Differences in AF burden after the 3-month blanking period between CHF and non-CHF groups was calculated. Improvement in LVEF was calculated and compared across the three CHF groups. Improvement was also calculated across different fibrosis stages. There was no significant differences in AF recurrence and AF burden after catheter ablation between CHF and non-CHF patients and between different CHF subcategories. Patients with heart failure with reduced ejection fraction (HFrEF) experienced the greatest improvement in EF following catheter ablation (CA, 16.66% ± 11.98, P < 0.001) compared to heart failure with moderately reduced LVEF, and heart failure with preserved EF (10.74% ± 8.34 and 2.00 ± 8.34 respectively, P-value < 0.001). Moreover, improvement in LVEF was independent of the four stages of atrial fibrosis (7.71 vs. 9.53 vs. 5.72 vs. 15.88, from Stage I to Stage IV respectively, P = 0.115). CONCLUSION: Atrial fibrillation burden and recurrence after CA is similar between non-CHF and CHF patients, independent of the type of CHF. Of all CHF groups, those with HFrEF had the largest improvement in LVEF after CA. Moreover, the improvement in ventricular function seems to be independent of atrial fibrosis in patients with persistent AF.

Innovations in atrial fibrillation ablation.

BACKGROUND: Catheter-based ablation to perform pulmonary vein isolation (PVI) has established itself as a mainstay in the rhythm control strategy of atrial fibrillation. This review article aims to provide an overview of recent advances in atrial fibrillation ablation technology. METHODS: We reviewed the available literature and clinical trials of innovations in atrial fibrillation ablation technologies including ablation catheter designs, alternative energy sources, esophageal protection methods, electroanatomical mapping, and novel ablation targets. RESULTS: Innovative radiofrequency (RF) catheter designs maximize energy delivery while avoiding overheating associated with conventional catheters. Single-shot balloon catheters in the form of cryoballoons, radiofrequency, and laser balloons have proven effective at producing pulmonary vein isolation and improving procedural efficiency and reproducibility. Pulsed field ablation (PFA) is a highly anticipated novel nonthermal energy source under development, which demonstrates selective ablation of the myocardium, producing durable lesions while also minimizing collateral damage. Innovative devices for esophageal protection including esophageal deviation and cooling devices have been developed to reduce esophageal complications. Improved electroanatomical mapping systems are being developed to help identify additional non-pulmonary triggers, which may benefit from ablation, especially with persistent atrial fibrillation. Lastly, the vein of Marshall alcohol ablation has been recently studied as an adjunct therapy for improving outcomes with catheter ablation for persistent atrial fibrillation. CONCLUSIONS: Numerous advances have been made in the field of atrial fibrillation ablation in the past decade. While further long-term data is still needed for these novel technologies, they show potential to improve procedural efficacy and safety.

Sinus node dysfunction: current understanding and future directions.

The sinoatrial node (SAN) is the primary pacemaker of the heart. Normal SAN function is crucial in maintaining proper cardiac rhythm and contraction. Sinus node dysfunction (SND) is due to abnormalities within the SAN, which can affect the heartbeat frequency, regularity, and the propagation of electrical pulses through the cardiac conduction system. As a result, SND often increases the risk of cardiac arrhythmias. SND is most commonly seen as a disease of the elderly given the role of degenerative fibrosis as well as other age-dependent changes in its pathogenesis. Despite the prevalence of SND, current treatment is limited to pacemaker implantation, which is associated with substantial medical costs and complications. Emerging evidence has identified various genetic abnormalities that can cause SND, shedding light on the molecular underpinnings of SND. Identification of these molecular mechanisms and pathways implicated in the pathogenesis of SND is hoped to identify novel therapeutic targets for the development of more effective therapies for this disease. In this review article, we examine the anatomy of the SAN and the pathophysiology and epidemiology of SND. We then discuss in detail the most common genetic mutations correlated with SND and provide our perspectives on future research and therapeutic opportunities in this field.

Comparison of cryoballoon and radiofrequency ablation for persistent atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: There is limited data comparing radiofrequency (RF) and cryoballoon (CB) ablation for persistent atrial fibrillation (AF), which tends to have higher recurrence rates following ablation compared to paroxysmal AF. METHODS: A systematic search of the Embase, PubMed, and Cochrane database was performed for studies comparing RF vs CB ablation for persistent AF. An inverse-variance random-effects model was used to calculate the composite effects. RESULTS: One randomized and 9 observational studies were identified, with 1650 patients receiving CB and 1706 patients receiving RF ablation. Mean follow-up time ranged from 12 to 48 months. Freedom from recurrent atrial tachyarrhythmia was similar with the two modalities (HR 0.93, 95% CI 0.80 to 1.08, I2 0%). Total complications were similar in both groups (RR 1.05, 95% CI 0.73 to 1.53, I2 0%) although rates of phrenic nerve palsy (PNP) were greater with CB (RR 4.13, 95% CI 1.49 to 11.46, I2 0%). Shorter procedure times were observed with CB (mean reduction 43.77 min, 95% CI 66.45 to 21.09 min, I2 96%) with no difference in fluoroscopy time (mean difference 0.82 min, 95% CI - 11.92 to 13.55 min, I2 100%). CONCLUSIONS: In persistent AF patients, CB ablation has similar efficacy and overall safety as compared to RF ablation. While CB is associated with significantly shorter procedure times, the improved procedural efficiency with CB is offset by increased rates of PNP and the potential need for touch-up RF ablation.