Leadless pacemaker implementation at the right atrial appendage apex: An initial preclinical assessment.

OBJECTIVE: This study evaluates the feasibility and efficacy of implanting a leadless pacemaker at the right atrial appendage (RAA) in a preclinical minipig model, aiming to address the limitations of atrial pacing with current leadless devices like the Medtronic Micra, which is typically used for right ventricular implantation. METHODS: Four minipigs, each with a median body weight of 45.8 ± 10.0 kg, underwent placement of the Micra transcatheter pacing system (TPS) via the right femoral vein into the RAA apex. The pacing performance was assessed over 1-week (short-term) and 3-month (long-term) periods. OUTCOMES: The initial findings indicated successful implantation, with satisfactory intrinsic R-wave amplitudes and pacing threshold. In the following period, the sensitivity, threshold, and impedance were stable with time. Notably, upon explanation at 3 months, a deep myocardial penetration by the device was observed, necessitating a redesign for safe long-term use in a growing subject's heart. CONCLUSION: While initial results suggest that RAA apex placement of the Micra TPS is promising for potential inclusion in a dual-chamber pacing system, the issue of myocardial penetration highlights the need for device redesign to ensure safety and effectiveness in long-term applications.

Effectiveness and Safety of Direct Oral Anticoagulants in an Asian Population with Atrial Fibrillation Undergoing Dialysis: A Population-Based Cohort Study and Meta-Analysis.

PURPOSE: Whether direct oral anticoagulants (DOACs) are more effective and safer than warfarin among Asian patients with non-valvular atrial fibrillation (NVAF) undergoing dialysis remains unclear. METHODS: We first compared the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding associated with DOACs compared with warfarin, in NVAF Asians undergoing dialysis using the Taiwan National Health Insurance Research Database (NHIRD) (Aim 1). Next, we searched PubMed and Medline from January 1, 2010 until January 31, 2020, to perform a systematic review and meta-analysis of all observational real-world studies comparing DOACs with warfarin specifically focused on NVAF patients with stage 4 or 5 chronic kidney disease undergoing dialysis (Aim 2). Finally, we tested the hypothesis whether AF patients undergoing dialysis treated with OACs (warfarin and DOACs) would be associated with lower risk of adverse clinical outcomes as compared to those without OACs using the Taiwan NHIRD (Aim 3). RESULTS: From June 1, 2012, to December 31, 2017, a total of 3237 and 9263 NVAF patients comorbid with ESRD receiving oral anticoagulant (OACs) (490 on DOAC, 2747 on warfarin) or no OACs, respectively, were enrolled. Propensity score matching was used to balance covariates across the study groups. For the comparison of DOAC vs. warfarin (Aim 1), DOACs had comparable risks of IS/SE and major bleeding to warfarin in our present cohort. From the original 85 results retrieved, nine studies (including our study) with a total of 6490 and 22,494 patients treated with DOACs and warfarin were included in the meta-analysis, respectively. There were 5343 (82%) and 20,337 (90%) patients treated with DOACs and warfarin undergoing dialysis, respectively. The pooled meta-analysis also indicated no difference of the effectiveness (HR:0.90; [95%CI:0.74-1.10]; P = 0.32) and safety outcomes (HR:0.75; [95%CI:0.54-1.05]; P = 0.09) between DOACs and warfarin (Aim 2). For the comparison of OAC (+) vs. OAC (-) (Aim 3), OAC-treatment was associated with a higher risk of IS/SE (hazard ratio (HR):1.54; [95% confidential interval (CI):1.29-1.84];P < 0.0001) and comparable risk of major bleeding compared to those without OAC treatment. CONCLUSIONS: DOACs did not provide benefit over warfarin regarding effectiveness and safety in AF patients undergoing dialysis. The use of OAC was not associated with a lower risk of IS/SE in ESRD AF patients when compared to those without OAC use.

Fixed-Dose Combinations of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in the Treatment of Hypertension: A Comparison of Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors.

Fixed-dose combinations (FDCs) of different regimens are recommended in guidelines for the treatment of hypertension. However, clinical studies comparing FDCs of angiotensin receptor blocker (ARB)/calcium channel blocker (CCB) and angiotensin-converting enzyme inhibitor (ACE inhibitor)/CCB in hypertensive patients are lacking.Using a propensity score matching of 4:1 ratio, this retrospective claims database study compared 2 FDC regimens, ARB/CCB and ACE inhibitor/CCB, in treating hypertensive patients with no known atherosclerotic cardiovascular disease. All patients were followed for at least 3 years or until the development of major adverse cardiovascular events (MACEs) during the study period. In addition, the effect of medication adherence on clinical outcomes was evaluated in subgroup analysis based on different portions of days covered.There was no significant difference in MACE-free survival (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.98-1.50; P = 0.08) and survival free from hospitalization for heart failure (HR: 1.15; 95% CI: 082-1.61; P = 0.431), new diagnosis of chronic kidney disease (HR: 0.98; 95% CI: 071-1.36; P = 0.906), and initiation of dialysis (HR: 0.99; 95% CI: 050-1.92; P = 0.965) between the 2 study groups. The results remained the same within each subgroup of patients with different adherence statuses.ARBs in FDC regimens with CCBs in the present study were shown to be as effective as ACE inhibitors at reducing the risks of MACEs, hospitalization for heart failure, new diagnosis of chronic kidney disease, and new initiation of dialysis in hypertensive patients, regardless of the medication adherence status.

Newly diagnosed atrial fibrillation is an independent factor for future major adverse cardiovascular events.

OBJECTIVES: This study aims to investigate the impact of newly diagnosed atrial fibrillation (AF) on future major adverse cardiac events (MACE). AF is the most common form of cardiac arrhythmia and is associated with several other cardiovascular (CV) events. Little is known about whether newly diagnosed AF is an independent factor for future MACE, especially in patients without such a history. METHODS AND RESULTS: We evaluated data from the National Health Insurance Research Database, which represented a retrospective cohort of 713,288 adults in Taiwan from 2006 to 2010. Individuals with previous MACE were excluded. Newly diagnosed AF patients were identified by assigning International Classification of Diseases codes. Propensity score matching adjusted for gender, age, hypertension, diabetes mellitus and dyslipidemia. Cox proportional hazard models estimated future MACE ratios. We compared a total of 3,737 patients with newly diagnosed AF and 704,225 patients without. After matching, there was no difference in baseline demographic characteristics in patients across newly diagnosed AF and non-AF groups. The result showed that newly diagnosed AF in multivariate analysis were associated with increased incidents of MACE (hazard ratio: 3.11-3.51 in different models) and mortality. Newly diagnosed AF without other CV risk factors had 8.45 times the risk of developing future MACE than healthy adults. The more associated CV risk factors in addition to AF, the increased rate of future CV events. CONCLUSIONS: Newly diagnosed AF is an independent factor that leads to future CV events after gender, age, hypertension, diabetes mellitus and dyslipidemia matching. AF is associated with a higher mortality rate.

Clinical outcomes and healthcare costs in hypertensive patients treated with a fixed-dose combination of amlodipine/valsartan.

This retrospective claims database analysis compared two strategies of hypertension treatment in outpatient, emergency, and inpatient departments: a fixed-dose combination (FDC) of amlodipine/valsartan vs free combinations of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) (ARB+CCB group). After a mean follow-up of 15.2 months, the FDC group had significantly lower total healthcare costs (US $1844 vs US $2158; P<.001) and hospitalization rates (14.57% vs 18.43%; P<.001), a higher proportion of days covered (80.35% vs 72.57%; P<.001), and better persistence (266 vs 225 days; P<.001) compared with the ARB+CCB group. The FDC group also had a better major adverse cardiovascular event (MACE)-free survival (hazard ratio, 0.83; 95% confidence interval, 0.73-0.94; P=.003) and decreased rates of heart failure (2.12% vs 3.26%; P<.001), malignant dysrhythmia (0.18% vs 0.42%; P=.021), and percutaneous coronary intervention (0.76% vs 1.26%; P=.015). Compared with free combinations of ARB+CCB, an FDC of amlodipine/valsartan improved MACE-free survival and medication compliance and decreased total healthcare costs and hospitalization rates in hypertensive patients.

Clinical Assessment and Implication of Left Ventricular Mechanical Dyssynchrony in Patients with Heart Failure.

UNLABELLED: There have been numerous studies focusing on the assessment of left ventricular mechanical dyssynchrony. These studies are diverse in their purposes, which include more effectively predicting the response to cardiac resynchronization therapy, improving the guidance of the left ventricular lead position, and better prediction of outcome in patients with heart failure. This article reviews the current assessment methods, clinical applications and limitations of left ventricular dyssynchrony indices derived from echocardiography, magnetic resonance imaging and radionuclide imaging in patients with heart failure. KEY WORDS: Cardiac resynchronization therapy; Dyssynchrony; Echocardiography; Heart failure.