Catheter ablation for atrial fibrillation in elderly patients: an updated meta-analysis of comparative studies.

BACKGROUND: Age is a relevant risk factor for the development of atrial fibrillation (AF) and is associated with increased recurrence rates in the setting of rhythm-control. Catheter ablation is increasingly advocated in elderly despite conflicting data regarding its efficacy and safety in this patient cohort. Therefore, we aimed to analyze currently available evidence regarding catheter ablation for AF in patients ≥75 years compared to younger patients. METHODS: We performed a systematic literature search and meta-analysis on efficacy and safety of catheter ablation in patients ≥75 years with AF. Primary efficacy and safety endpoints were: first recurrence of atrial arrhythmia following first-time ablation and occurrence of death, stroke, or any procedure-related complication. Secondary outcomes included procedure and fluoroscopy time. RESULTS: We identified 301 potentially relevant studies of which 39 underwent detailed analysis. A total of 19 studies (MINORS score ≥13) reporting on 108,419 patients (101,844 <75 years, 6,575 ≥75 years) undergoing first-time catheter ablation for AF were included. Risk of arrhythmia recurrence following catheter ablation (39% vs. 32%; RR [95% CI] 1.24 [1.09-1.41]; P=0.001) and occurrence of safety endpoints (10.8% vs. 8.5%; RR [95% CI] 1.64 [1.53-1.76], P<0.00001) were significantly higher in patients ≥ 75 years compared to younger patients. There was no difference concerning procedure (P=0.33) or fluoroscopy time (P=0.91) between younger and elderly patients. CONCLUSION: In patients ≥75 years of age catheter ablation for AF has higher risk of arrhythmia recurrence and is associated with an increased risk of procedure-related complications and safety endpoint occurrence compared to younger patients.

Angiotensin Receptor-Neprilysin Inhibitor Is Associated With Improved Cardiac Autonomic Function in Heart Failure.

BACKGROUND: Heart failure with reduced ejection fraction is associated with potentially deleterious imbalance of the cardiac autonomic nervous system. Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor [ARNI]) reduces cardiovascular mortality and hospitalization for heart failure with reduced ejection fraction. Whether ARNI affects the cardiac autonomic nervous system has not been studied. METHODS AND RESULTS: This investigator-initiated, prospective, single-center cohort study compared heart rate (HR) variability, HR, deceleration capacity, and periodic repolarization dynamics as noninvasive measures of the cardiac autonomic nervous system before and after initiation of ARNI therapy. Patients underwent standardized 12-lead Holter-ECG, echocardiography and laboratory testing before and 3 months after start of therapy. End points were changes in HR variability (SD of normal-to-normal intervals, mean square of differences between consecutive R-R intervals), HR, deceleration capacity, and periodic repolarization dynamics as well as ventricular function and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Of 63 patients with heart failure with reduced ejection fraction enrolled, 48 (76.2%) patients were still on ARNI at follow-up. SD of normal-to-normal intervals increased from 25 to 36 milliseconds (P<0.001), mean square of differences between consecutive R-R intervals increased from 12 to 19 milliseconds (P<0.001), HR decreased from 73±9 bpm to 67±4 bpm, (P<0.001), and deceleration capacity increased from 2.1 to 4.4 milliseconds (P<0.001). A trend for periodic repolarization dynamics reduction was observed (5.6 deg2 versus 4.7 deg2, P=0.09). Autonomic changes were accompanied by increased left ventricular ejection fraction (29±6% versus 40±8%, P<0.001) and reduced NT-proBNP (3548 versus 685 ng/L, P<0.001). Correlation analysis showed a significant relationship between volume-unloading (as evidenced by NT-proBNP reduction) and autonomic improvement. CONCLUSIONS: Three months of ARNI therapy resulted in a significant increase in cardiac parasympathetic tone. The improvement in autonomic properties may be mediated by "volume unloading" and likely contributes to the beneficial effects of ARNI in heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04587947.

Pulmonary Vein Isolation in Elderly Patients ≥ 75 Years: A Propensity Score-Matched Analysis With Focus on Differences Among Atrial Fibrillation Types.

BACKGROUND: Age is a major risk factor for development of atrial fibrillation (AF) and associated with increased recurrence rates in the setting of rhythm control. Current data tend to support catheter ablation in elderly patients, but uncertainties exist regarding efficacy and safety of ablation in elderly patients. METHODS: This was a prospective single-centre observational study with propensity score matching (PSM) to investigate the influence of age on efficacy and safety of cryoballoon ablation (CBA) stratified by age (< 75 years vs ≥ 75 years) and AF phenotype (paroxysmal vs persistent). Primary efficacy endpoint was recurrence of atrial arrhythmia after a 90-day blanking period. Safety endpoints were death, stroke, or procedure-associated complications. RESULTS: Consecutive patients (n = 953) underwent CBA for first-time AF ablation. Median follow-up was 18 months. By means of PSM, 268 matches were formed. At 1 year, primary efficacy endpoint occurred in 22.4% of young vs 33.2% of elderly patients, including both AF phenotypes (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.47-0.90; P = 0.01). AF relapse occurred in 19.7% of young vs 28.5% of elderly patients with paroxysmal (HR, 0.63; 95% CI, 0.40-0.99; P = 0.046) compared with 25.9% (30 of 116, young) vs 38.8% (45 of 116, elderly) patients with persistent AF (HR, 0.62; 95% CI, 0.39-0.97; P = 0.038). No difference was observed regarding the incidence of safety endpoints between young and elderly patients (P = 0.38). CONCLUSIONS: CBA is associated with higher recurrence rates in elderly (≥ 75 years) than in younger patients, with highest recurrence rates in elderly patients with persistent AF.

Cryoballoon pulmonary vein isolation for atrial fibrillation in obese patients: A non-inferiority analysis.

Background: Patients with obesity are at higher risk of developing atrial fibrillation (AF) and benefit from radiofrequency ablation. Potentially, cryoballoon ablation (CBA) may be equally effective and safe in such patients. Methods: We conducted a prospective, single-center study to investigate whether CBA for pulmonary vein isolation is as effective and safe in obese patients as it is in non-obese controls. Primary efficacy endpoint was recurrence of AF, atrial flutter or atrial tachycardia after a 90-day blanking period. Safety endpoints were death, stroke or procedure-associated complications. Conduction of a subgroup analysis regarding the impact of additional diabetes was predefined in case the primary efficacy endpoint was met. The study was event driven and powered for noninferiority. Results: A total of 949 patients underwent CBA (251 obese with mean body-mass-index 33.5 ± 3 kg/m2 and 698 non-obese with mean body-mass-index 25.3 ± 3 kg/m2) during a 5-year recruitment period. Median follow-up was 15 months. The primary efficacy endpoint occurred in 78/251 obese and 247/698 non-obese patients (12-months Kaplan-Meier event-rate estimates, hazard ratio 0.79; 95% confidence interval [CI], 0.58 to 1.07; log-rank P = 0.0002 for noninferiority). No differences were observed in safety end point occurrence (P = 0.78). The occurrence of primary efficacy end point was found to be unaffected by the presence of diabetes in the prespecified subgroup analysis (log-rank P = 0.57). Conclusion: CBA is effective and safe in obese and DM patients. Weighing the high cardiovascular risk of obese patients against a reduction of cardiovascular events by early rhythm control, CBA should be offered to this patient population.

Testosterone affects type I/type II interferon response of neutrophils during hepatic amebiasis.

Differences in immune response between men and women may influence the outcome of infectious diseases. Intestinal infection with Entamoeba histolytica leads to hepatic amebiasis, which is more common in males. Previously, we reported that innate immune cells contribute to liver damage in males in the murine model for hepatic amebiasis. Here, we focused on the influences of sex and androgens on neutrophils in particular. Infection associated with neutrophil accumulation in the liver was higher in male than in female mice and further increased after testosterone treatment in both sexes. Compared with female neutrophils, male neutrophils exhibit a more immature and less activated status, as evidenced by a lower proinflammatory N1-like phenotype and deconvolution, decreased gene expression of type I and type II interferon stimulated genes (ISGs) as well as downregulation of signaling pathways related to neutrophil activation. Neutrophils from females showed higher protein expression of the type I ISG viperin/RSAD2 during infection, which decreased by testosterone substitution. Moreover, ex vivo stimulation of human neutrophils revealed lower production of RSAD2 in neutrophils from men compared with women. These findings indicate that sex-specific effects on neutrophil physiology associated with maturation and type I IFN responsiveness might be important in the outcome of hepatic amebiasis.

Persistent Atrial Fibrillation in Elderly Patients: Limited Efficacy of Pulmonary Vein Isolation.

(1) Background: Cryoballoon pulmonary vein isolation (cryoPVI) is established for symptomatic paroxysmal atrial fibrillation (AF) treatment, but its value in persistent AF is less clear. In particular, limited data are available on its efficacy in elderly patients (≥75 years) with persistent AF. Age is an important modifier of AF progression and represents a risk-factor for AF recurrence. (2) Methods: Prospective, single-center observational study to evaluate the impact of age on efficacy and safety of cryoPVI in elderly patients. Primary efficacy endpoint was symptomatic AF recurrence after 90-day blanking period. Primary safety endpoints were death from any cause, procedure-associated complications or stroke/transient ischemic attack. Median follow-up was 17 months (range 3−24). (3) Results: We included 268 patients with persistent AF (94 ≥ 75 years of age). Multivariate Cox regression analysis identified age as the only independent factor influencing AF recurrence in the overall cohort (p = 0.006). To minimize confounding bias in efficacy and safety analysis of cryoPVI, we matched younger and elderly patients with respect to baseline characteristics. At 24 months, primary efficacy endpoint occurred in 13/69 patients <75 years and 31/69 patients ≥75 years of age (24 months Kaplan−Meier event-rate estimates, HR 0.34; 95% CI, 0.19 to 0.62; log-rank p = 0.0004). No differences were observed in the occurrence of safety end points. (4) Conclusions: Elderly (≥75 years) patients with persistent AF undergoing cryoPVI had an approximately threefold higher risk of symptomatic AF recurrence than matched younger patients. Accordingly, other treatment modalities may be evaluated in this population.

Process optimization for atrial fibrillation ablation.

AIMS: In the light of an increasing prevalence of atrial fibrillation (AF) and growing evidence for the superiority of early invasive rhythm control, the demand for ablation therapy is rising. Accordingly, ablation centres will have to maximize their capacity by either adding electrophysiology laboratory resources or optimizing process management. In order to optimize process management, we applied "Lean Six Sigma" method to a single ablation center. We compared procedural parameters, acute efficacy and safety of cryoballoon pulmonary vein isolation (cryoPVI) before and after modifications. METHODS AND RESULTS: Patients (n = 713) undergoing cryoPVI (108 before and 605 after process optimization) were analysed. Within 3 years of process optimization, electrophysiology laboratory occupancy time (150.7 ± 44.4 vs. 94 ± 22.1 min, P < 0.001), procedure time (84.5 ± 21-47.4 ± 12 min, P < 0.001), left-atrial dwell time (53.9 ± 18.4-31.9 ± 9.9 min, P < 0.001), and fluoroscopy time (15.8 ± 5.1 vs. 6.2 ± 2.8 min, P < 0.001) decreased. Contrast dye use (116 ± 35 vs. 27 ± 15 mL, P < 0.001) and radiation dose (893 ± 1078 vs. 253 ± 249 cGy cm2, P < 0.001) were reduced by ∼77 and ∼72%, respectively. There was no difference in safety endpoint occurrence (3.7 vs. 1.5%, P = 0.11). CONCLUSION: The process optimization of cryoPVI for AF therapy using the 'Lean Six Sigma' method significantly increases efficiency without compromising patient safety.

[Supraventricular tachycardia - ECG interpretation and clinical management]. / Vorgehen und Behandlungsoptionen bei supraventrikulären Tachykardien.

Supraventricular tachycardia (SVT) is a very common cause of hospital admission and its diagnostic and treatment may be difficult sometimes. While vagal maneuvers or intravenous adenosis administration during 12-lead ECG recording should be performed in hemodynamically stable patients for diagnosis and treatment, hemodynamically unstable patients should be carioverted immediately. The new ESC guideline (2019) on diagnosis and clinical management of SVT significantly upgrades catheter ablation and gives it a new preferential status. For example, in patients with symptomatic recurrence, atrioventricular nodal re-entrant tachycardia should be ablated due to the very low risk of AV block. Furthermore, catheter ablation should also be offered as first-line therapy to patients with reentrant and focal arrhythmias. The diagnosis and therapy of tachycardiomyopathy is of particular importance and treatment should incorporate the ablation of the underlying supraventricular tachycardia. The therapy of supraventricular tachycardia during pregnancy should be free of antiarrhythmic medication, especially in the first trimester. If ablation is necessary during pregnancy, only fluoroscopy-free mapping systems should be used. This review covers aspects of ECG diagnosis and guideline-based treatment of SVT.