Rhythm Control Vs Rate Control in a Contemporary Ambulatory Atrial Fibrillation Cohort: Post Hoc Analysis of the IMPACT-AF Trial.

Background: We examined the characteristics and outcomes in a contemporary ambulatory population of patients with atrial fibrillation (AF), comparing rate control with rhythm control. Methods: This is a post hoc analysis of a cluster-randomized trial (Integrated Management Program Advancing Community Treatment of Atrial Fibrillation [IMPACT-AF]) in ambulatory AF patients from 2016 to 2018, which compared use of a clinical decision support tool for general practitioners to usual care. This analysis compared patients managed with rate vs rhythm control, at entry into the study. Outcomes included AF-related emergency department (ED) visits, unplanned cardiovascular hospitalizations, and bleeding events at 12 months. Results: A total of 870 patients were included in this analysis, 99 (11.4%) in the rhythm-control group, and 40% women. In the rhythm-control group, the mean age was younger (70 ± 11.4 vs 72.7 ± 9.5 years, P = 0.03), a higher number were paroxysmal (80% vs 43%, P < 0.001), and CHADS2 scores were lower. The rate of AF-related ED visits was higher in the rhythm-control group (17.2 vs 7.3%, P = 0.003), and repeat visits (rate ratio 3.03, 95% confidence interval [1.99-4.52], P < 0.001). The number of repeat ED visits was independently associated with female sex and being in the rhythm-control group. Conclusions: Both rate- and rhythm-control patients have recurrent ED visits, with a higher rate in patients treated with rhythm control. These findings are observational, but taken in the context of current guidelines could help develop further therapies aimed at improving symptom burden in both rhythm- and rate-control patients to broadly improve healthcare utilization in the AF population.

Contexte: Nous avons examiné les caractéristiques et le devenir de patients ambulatoires contemporains atteints de fibrillation auriculaire (FA) dans le cadre d'une comparaison entre la maîtrise de la fréquence cardiaque et la maîtrise du rythme cardiaque. Méthodologie: Nous avons effectué une analyse a posteriori d'un essai à répartition aléatoire par grappes ( I ntegrated M anagement P rogram A dvancing C ommunity T reatment of A trial F ibrillation [IMPACT-AF]) mené de 2016 à 2018 chez des patients ambulatoires atteints de FA en vue de comparer un outil d'aide à la décision clinique destiné aux omnipraticiens avec les soins habituels. Notre analyse a permis d'établir une comparaison entre les patients pris en charge par une maîtrise de la fréquence cardiaque et ceux pris en charge par une maîtrise du rythme cardiaque lors de leur inscription à l'essai. Les paramètres d'évaluation comprenaient les consultations aux urgences liées à la FA, les hospitalisations imprévues ayant des causes cardiovasculaires et les épisodes hémorragiques à 12 mois. Résultats: Au total, 870 patients ont été inclus dans cette analyse; 99 (11,4 %) faisaient partie du groupe pris en charge par une maîtrise du rythme cardiaque, et 40 % étaient de femmes. Dans le groupe pris en charge par une maîtrise du rythme cardiaque, l'âge moyen était moindre (70 ± 11,4 ans vs 72,7 ± 9,5 ans, P = 0,03), un plus grand nombre de patients présentaient une FA paroxystique (80 % vs 43 %, P < 0,001) et les scores CHADS2 étaient moins élevés. Le taux de consultations aux urgences liées à la FA était plus élevé dans le groupe pris en charge par une maîtrise du rythme cardiaque (17,2 vs 7,3 %, P = 0,003) tout comme le taux de consultations répétées aux urgences (rapport des taux de 3,03, intervalle de confiance à 95 % de 1,99 à 4,52, P < 0,001). Le nombre de consultations répétées aux urgences était indépendamment associé au sexe féminin et à l'inclusion dans le groupe pris en charge par une maîtrise du rythme cardiaque. Conclusions: Des consultations répétées aux urgences ont été notées tant chez les patients pris en charge par une maîtrise de la fréquence cardiaque que chez ceux pris en charge par une maîtrise du rythme cardiaque quoique plus fréquemment chez ces derniers. Nos constats sont de type observationnel. Néanmoins, dans le contexte des lignes directrices actuelles, ils pourraient contribuer à la mise au point d'autres traitements visant à atténuer le fardeau des symptômes tant chez les patients pris en charge par une maîtrise du rythme cardiaque que chez ceux pris en charge par une maîtrise de la fréquence cardiaque et ainsi permettre globalement une meilleure utilisation des soins de santé chez les patients atteints de FA.

Characterizing the role of atrial natriuretic peptide signaling in the development of embryonic ventricular conduction system.

Patients born with congenital heart defects frequently encounter arrhythmias due to defects in the ventricular conduction system (VCS) development. Although recent studies identified transcriptional networks essential for the heart development, there is scant information on the mechanisms regulating VCS development. Based on the association of atrial natriuretic peptide (ANP) expression with VCS forming regions, it was reasoned that ANP could play a critical role in differentiation of cardiac progenitor cells (CPCs) and cardiomyocytes (CMs) toward a VCS cell lineage. The present study showed that treatment of embryonic ventricular cells with ANP or cell permeable 8-Br-cGMP can induce gene expression of important VCS markers such as hyperpolarization-activated cyclic nucleotide-gated channel-4 (HCN4) and connexin 40 (Cx40). Inhibition of protein kinase G (PKG) via Rp-8-pCPT-cGMPS further confirmed the role of ANP/NPRA/cGMP/PKG pathway in the regulation of HCN4 and Cx40 gene expression. Additional experiments indicated that ANP may regulate VCS marker gene expression by modulating levels of miRNAs that are known to control the stability of transcripts encoding HCN4 and Cx40. Genetic ablation of NPRA revealed significant decreases in VCS marker gene expression and defects in Purkinje fiber arborisation. These results provide mechanistic insights into the role of ANP/NPRA signaling in VCS formation.

Protecting the aged heart during cardiac surgery: single-dose del Nido cardioplegia is superior to multi-dose del Nido cardioplegia in isolated rat hearts.

BACKGROUND: Aged hearts are particularly vulnerable to reperfusion injury. We recently showed that single-dose del Nido cardioplegia was superior to 'standard' multi-dose 4:1 blood cardioplegia in aged rat hearts. This study seeks to determine if multi-dose del Nido cardioplegia offers additional benefits over single-dose del Nido cardioplegia. METHODS: Functional recovery after 60 min of cardioplegic arrest was assessed in isolated, working, senescent rat hearts. Single-dose del Nido cardioplegia (n=14) was compared to multi-dose del Nido cardioplegia (n=12) delivered every 20 min. RESULTS: Troponin release during reperfusion was similar in the single (0.263 ± 0.056 ng/ml) and multi-dose groups (0.261 ± 0.055 ng/ml). Although functional recovery was similar early after reperfusion (stroke work 91 ± 6 ml*mmHg*g(-1) vs. 91 ± 8 ml*mmHg*g(-1) for single- vs. multi-dose), it declined over time in the multi-dose group (71 ± 9 vs. 43 ± 9 ml*mmHg*g(-1) at 60 min, p=0.0175) CONCLUSIONS: In aged rat hearts, a single-dose del Nido cardioplegia strategy results in superior functional recovery compared to a multi-dose del Nido cardioplegia strategy.

Protecting the aged heart during cardiac surgery: use of del Nido cardioplegia provides superior functional recovery in isolated hearts.

OBJECTIVES: Aged hearts are particularly vulnerable to ischemia-reperfusion injury. Our objective was to determine if del Nido cardioplegia, which contains lidocaine, less blood, and less calcium than our standard cardioplegia, provides superior protection for aged hearts. We also sought to determine if the lidocaine in del Nido cardioplegia is adequate to prevent Na(+) influx via the window current. METHODS: Sodium channel kinetics were measured in rat cardiomyocytes with and without lidocaine. Recovery after 60 minutes of cardioplegic arrest was assessed in isolated working senescent rat hearts. Del Nido cardioplegia was delivered as a single dose (n = 8) because it is used clinically, and standard cardioplegia was delivered as an induction dose with re-dosing every 20 minutes (n = 8). After 20 minutes of reperfusion, hearts were switched to working mode for 60 minutes. Flows were indexed to ventricular dry weight. Troponin release was assayed. RESULTS: Sodium channel kinetics indicated that the lidocaine concentration in del Nido cardioplegia minimizes the potential for Na+ influx via the window current. Spontaneous contractions occurred in fewer hearts arrested with del Nido cardioplegia (88% vs 13%; P = .01), and troponin release was reduced (0.24 vs 0.89 ng/mL; P = .017). Cardiac output was approximately 90% of baseline in the del Nido group compared with approximately 50% in the standard group (173 ± 14 vs 86 ± 22 mL · min(-1) · g(-1); P = .0008). Stroke work was higher in the del Nido group (93 ± 6 vs 41 ± 10 mL · mm Hg · g(-1); P = .0002). CONCLUSIONS: Del Nido cardioplegia prevents spontaneous contractions during arrest, reduces troponin release, and results in superior myocardial function in isolated aged hearts. Del Nido cardioplegia has the potential to provide superior myocardial protection for older patients undergoing cardiac surgery.