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Background: Experimental data suggest ryanodine receptor-mediated intracellular calcium leak is a mechanism for atrial fibrillation (AF), but evidence in humans is still needed. Propafenone is composed of two enantiomers that are equally potent sodium-channel blockers; however, (R )-propafenone is an ryanodine receptor inhibitor whereas (S )-propafenone is not. This study tested the hypothesis that ryanodine receptor inhibition with (R )-propafenone prevents induction of AF compared to (S )-propafenone or placebo in patients referred for AF ablation. Methods: Participants were randomized 4:4:1 to a one-time intravenous dose of (R )-propafenone, (S )-propafenone, or placebo. The study drug was given at the start of the procedure and an AF induction protocol using rapid atrial pacing was performed before ablation. The primary endpoint was 30 s of AF or atrial flutter. Results: A total of 193 participants were enrolled and 165 (85%) completed the study protocol (median age: 63 years, 58% male, 95% paroxysmal AF). Sustained AF and/or atrial flutter was induced in 60 participants (84.5%) receiving (R )-propafenone, 60 (80.0%) receiving (S )-propafenone group, and 12 (63.2%) receiving placebo. Atrial flutter occurred significantly more often in the (R )-propafenone (N=23, 32.4%) and (S )-propafenone (N=26, 34.7%) groups compared to placebo (N=1, 5.3%, P =0.029). There was no significant difference between (R )-propafenone and (S )-propafenone for the primary outcome of AF and/or atrial flutter induction in univariable ( P =0.522) or multivariable analysis ( P =0.199, adjusted for age and serum drug level). Conclusions: There is no difference in AF inducibility between (R )-propafenone and (S )-propafenone at clinically relevant concentrations. These results are confounded by a high rate of inducible atrial flutter due to sodium-channel blockade. Registration: https://clinicaltrials.gov ; Unique Identifier: NCT02710669.

Background: Pacing-induced cardiomyopathy (PICM) has been increasingly recognized as a cause of heart failure in patients with pacemakers. Thus far, clinical trials and observational studies of PICM have largely included elderly patients with mean age > 70 years. The prevalence and predictors of PICM in younger patients (age ≤ 59 years) after pacemaker implantation are not known. Methods: We retrospectively studied the prevalence and predictors of PICM in younger adults (18-59 years) who received single ventricular chamber or dual chamber pacemakers at Vanderbilt University Medical Center from 1986-2015. Patients without documented ventricular pacing burden, and patients with baseline left ventricular ejection fraction (LVEF) < 30% were excluded. PICM was defined as LVEF drop of ≥ 10% and LVEF < 50% during follow up in the setting of significant right ventricular pacing (≥ 20%), without alternative explanations for cardiomyopathy. Univariate and multivariable Cox proportional hazards regression models were utilized to study the factors associated with hazard of developing PICM. Results: A total of 325 patients were included in the study. 182 patients had high ventricular pacing (≥ 20%), which was associated with pre-existing atrial fibrillation (AF) and reduced baseline LVEF in addition to atrioventricular block (AVB) in the multivariate analysis. During the median follow up duration of 11.5 (Interquartile range 7 - 17) years, 38 patients (11.7%) developed PICM (1.3 per 100 patient-year). The median time to the development of PICM was 5 (Interquartile range 2 - 10) years. Older age (HR 2.5 for age ≥ 50 years, P = 0.013), reduced baseline LVEF (HR 2.4, P = 0.022), and AVB (HR 2.7, P = 0.007) were associated with an increased risk of PICM in the multivariate analysis. Furthermore, pre-existing AF was associated with an increased risk of PICM in patients without pre-implant AVB (HR 8.8 compared to the absence of both AF and AVB, P = 0.039). Conclusion: The incidence of PICM in young patients was low in this cohort of younger patients. Older age, baseline reduced LVEF, and AVB were associated with an increased risk of PICM in the young patient cohort. AF was associated with an increased risk of PICM in a subset of patients without pre-existing AVB at implant.

Background: Return of incidental genetic findings is recommended for pathogenic/likely pathogenic (P/LP) variants in Mendelian arrhythmia genes. The extent to which these variants are associated with arrhythmia phenotypes in unselected populations is unknown. Objective: Assess the impact of return of results (RoR) of P/LP variants in 4 arrhythmia genes in research participants not selected for cardiovascular disease. Methods: The cohort included 24,410 participants from the Electronic Medical Records and Genomics Network. Rare variants (minor allele frequency KCNE1 , KCNH2 , KCNQ1 , and SCN5A were identified and classified according to ACMG guidelines. Arrhythmia phenotypes extracted from electronic health records (EHRs) included atrial fibrillation/flutter (AF/AFL), conduction system disease, long QT syndrome (LQTS), ventricular tachycardia/fibrillation (VT/VF), and premature ventricular contractions (PVCs). P/LP carriers’ phenotypes were compared to non-carriers using logistic regression adjusted for demographic covariates and site. Participants with P/LP variants were informed of their results and the impact of this RoR was assessed after 1 year of follow-up clinical care. Results: The participants included 53.7% females and 72.5% white individuals, with a median age of 57 years. 71 participants had a heterozygous P/LP variant in one of the 4 genes. LQTS diagnoses were associated with P/LP carrier status for all 4 genes ( KCNE1 OR 22.8, p=1.0e-4; KCNH2 OR 35.1, p=1.8e-7; KCNQ1 OR 27.3, p=3.6e-18; SCN5A OR 5.6, p=0.02). Carriers of SCN5A P/LP variants were also more likely to have PVCs (OR 4.3, p=0.003). Sensitivity analyses showed the associations predated the RoR. EHRs included a diagnosis of LQTS or Brugada Syndrome in 11/71 (16%) pre-RoR, and 16 more were diagnosed after RoR (27/71, 38%). A total of 47/71 (66%) participants had a documented arrhythmia phenotype 1 year after RoR, although 20 of these participants were not diagnosed with an inherited arrhythmia syndrome. Conclusion: Inherited arrhythmia diagnoses could be established in nearly half of participants with P/LP variants. These data indicate that return of incidental P/LP variants in these genes may facilitate the early diagnosis of arrhythmias.

To investigate what factors contribute to increased length of stay (LOS) and increased costs in treatment of elderly patients with hip fractures.Retrospective chart review.All patients who presented to a large tertiary care center between January 2000 and December 31, 2009.Charts for all patients older than 60 years who presented with isolated low-energy hip fractures were reviewed. Of the 719 patients identified, 660 were included.Patients who underwent operative fixation or hemiarthroplasty secondary to hip fracture were identified using a search of Current Procedural Terminology (CPT) codes search.Gender, height, weight, body mass index, length of procedure, American Society of Anesthesiologists (ASA) classification, and medical comorbidities were gathered and compared with LOS and direct daily inpatient hospital cost.No correlation existed between body mass index or specific comorbidities and LOS, but ASA classification was a predictor. For each ASA increase of 1, average LOS increased 2.053 days (P0.001). Given total daily cost to the hospital for these patients was $4530, each increase in ASA classification translated to an increase of $9300.ASA classification proved useful in estimating LOS and cost for patients undergoing operative fixation of hip fractures. Because ASA classification and cost are universally collected, this method can be employed in almost any hospital. This highlights a role for ASA classification in preoperative estimation of the elderly patient's cost and a potential advantage for incorporating patient factors in the development of tiered reimbursement models.Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.