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BackgroundAging is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction.ObjectiveThe aim of this study was to investigate the structural and functional remodeling in the atrioventricular junction (AVJ) with aging.MethodsElectrophysiology, histology, and immunohistochemistry experiments on male Wistar Hannover rats aged 3 months (n = 24) and 2 years (n = 15) were performed. Atrio-His (AH) interval, Wenkebach cycle length (WBCL), and AVN effective refractory period (AVNERP) were measured. Cesium (2 mM) was used to block hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, while ryanodine (2 μM) was used to block ryanodine 2 (RyR2) channels. Protein expression from different regions of the AVJ was studied using immunofluorescence. The expression of connexins (connexin 43 and connexin 40), ion channels (Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), voltage sensitive sodium channel (Nav1.5), and L-Type calcium channel (Cav1.3)), and calcium handling proteins (RyR2 and sarco/endoplasmic reticulum calcium ATPaset type 2a (SERCA2a)) were measured. Morphological characteristics were studied with histology.ResultsWithout drugs to block HCN and RyR2 channels, there was prolongation of the AH interval, WBCL, and AVNERP (P < .05) with aging. In young rats only, cesium prolonged the AH interval, WBCL, and AVNERP (P < .01). Ryanodine prolonged the AH interval and WBCL (P < .01) in both young and old rats. Immunofluorescence revealed that with aging, connexin 43, HCN4, Nav1.5, and RyR2 downregulate in the regions of the AVJ and connexin 40, SERCA2a, and Cav1.3 upregulate (P < .05). Aging results in cellular hypertrophy, loosely packed cells, a decrease in the number of nuclei, and an increase in collagen content.ConclusionHeterogeneous ion channel expression changes were observed in the AVJ with aging. For the first time, we have shown that HCN and RyR2 play an important role in AVN dysfunction with aging.

The atrioventricular node (AVN), the molecular basis has been studied in animal models; however, the human AVN remains poorly explored at the molecular level in heart failure patients. We studied ex vivo donor human hearts rejected for transplantation (n=6) and end-stage failing hearts with cardiomyopathy of various etiologies (n=6). Microdissection and quantitative PCR (qPCR) were used to anatomically map mRNA expression in both failing and non-failing hearts from tissue sections through the AVN, atrial and ventricular muscle. In the failing ventricle significant (P<0.05) downregulation is apparent for vimentin, hERG and Kir3.4 and trend to downregulation for Nav1.5, Cav1.2, Tbx3, Kir2.1, NCX1, Cx43 and Cx45. In the failing atrium, there is non-significant trend in upregulation for Nav1.5, HCN2, Cav3.1, Kv1.5, Kir3.1, RYR2 and significant upregulation for Cx40 and trend in downregulation for hERG, Kir2.1 and NCX1, and significant downregulation for HCN4 and Kir3.4. In the failing AVN there is significant (P<0.05) downregulation for vimentin, collagen, Tbx3, Kir3.1, Kir3.4, Cx45 and HCN4; there is also trend toward downregulation for HCN2, Kv1.5, Kir2.1 and RYR2. In the failing AVN there is significant (P<0.05) upregulation for Cx40, HCN1 and Cav3.1; and trend in upregulation for Nav1.5 and Cx43. For several transcripts, we also analysed corresponding protein expression via immunofluorescence. The protein expression data on the AVN for HCN1, Cav3.1 and Cx40 support qPCR data. Remodelling of AVN in heart failure might contribute to prolonged AV conduction time and could explain the prolonged PR interval that occurs in heart failure patients.

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ObjectiveAtrial fibrillation (AF) ablation services were significantly affected by the COVID-19 pandemic. We aimed to evaluate a symptom-based clinician prioritisation scheme for waiting list management compared with patient-completed quality of life (QoL) scores. We also sought to understand factors influencing QoL, particularly the impact of COVID-19, on patients awaiting AF ablation, via a bespoke questionnaire.MethodsPatients awaiting AF ablation were sent two QoL questionnaires (Atrial Fibrillation Effect on QualiTy of Life (AFEQT) and EuroQol 5D (EQ5D-5L)) and the bespoke questionnaire. At a separate time point, patients were categorised as C1—urgent, C2—priority or C3—routine by their cardiologist based on review of clinic letters.ResultsThere were 118 patients included with priority categorisation available for 86 patients. Median AFEQT scores were lower in C2 (30.4; 17.2–51.9) vs C3 patients (56.5; 32.1–74.1; p<0.01). Unplanned admission occurred in 3 patients in C3 with AFEQT scores of <40. Although 65 patients had AF symptoms during the pandemic, 43.1% did not seek help where they ordinarily would have. An exercise frequency of ≥3–4 times a week was associated with higher AFEQT (56.5; 41.2–74.1; p<0.001) and EQ5D (0.84; 0.74–0.88; p<0.0001) scores.ConclusionThe QoL of patients awaiting AF ablation is impaired and AFEQT helps to identify patients at risk of admission, over and above physician assessment. COVID-19 influenced patients seeking medical attention with symptomatic AF when they normally would. Regular exercise is associated with better QoL in patients awaiting AF ablation.