Dual Medical Therapy for Treatment of Arrhythmias in Cardiac Sarcoidosis.

Anti-arrhythmics can be useful for ventricular arrhythmias in cardiac sarcoidosis (CS) that are refractory to immunosuppression. However, there is conflicting evidence on the efficacy of immunosuppression for treating arrhythmias in CS patients and a lack of data to support using immunosuppression alone as an initial strategy. The objective of this study was to assess for differences in arrhythmia burden over time with currently used immunosuppression and anti-arrhythmic regimens. Patients with CS and implanted cardiac devices were identified from a single-center registry. Study participants were retrospectively classified based on the medication regimen as follows: control (no therapy), immunosuppression, anti-arrhythmics, or dual therapy. Device interrogations were reviewed for premature ventricular contractions (PVCs), non-sustained ventricular tachycardia (NSVT), and device firings over time. Interrogations for 42 patients were reviewed over a mean period of 31 months. Regression analysis showed a significant decrease in the frequencies of PVCs (slope, -1.47; P = .04) and NSVT (slope, -0.05; P = .01) for patients on dual therapy compared to an increase or no change in the other groups. Across all patients, there was no difference between groups in the percentage of patients experiencing device firings. In a subset analysis of patients with implantable cardioverter-defibrillators for primary prevention, 6% on dual therapy required device firings compared to 43% and 40% on single or no therapy, respectively (P = .049, χ2 = 6.02). In conclusion, patients on both immunosuppression and anti-arrhythmics had a reduction in PVCs and NSVT over time. Overall, there were no differences between groups in terms of device firings, except in a subset analysis of patients with no history of ventricular tachycardia.

Etiology of gastrointestinal bleeding in patients on dual antiplatelet therapy.

OBJECTIVE: Dual antiplatelet therapy (DAPT) is associated with an increased risk of gastrointestinal (GI) bleeding and is thought to cause upper gastrointestinal bleeding (UGIB). However, recent reports indicate that the incidence of lower gastrointestinal bleeding (LGIB) in patients on DAPT may be increasing. We aimed to compare the endoscopic findings and etiology of GI bleeding between patients on DAPT compared with those not on DAPT. METHODS: This was a retrospective, single-center, case-control study. Cases were 114 consecutive patients admitted with a first episode of GI bleeding while on DAPT who underwent detailed GI evaluation. We chose 114 controls who had GIB but were not on DAPT. RESULTS: There was no significant difference in the incidence of UGIB or LGIB between the two groups (UGIB: 53.5% vs 51.3% and LGIB: 46.5% vs 48.7%, P = 0.10) or within groups (DAPT: 53.5% vs 46.5%, P = 0.30 and controls: 51.3% vs 48.7%, P = 0.80). Although the DAPT group had a lower prevalence of the usual UGIB risk factors, it had a higher likelihood of bleeding from varices or upper GI inflammation [odds ratio (OR) 3.54, 95% confidence interval (CI) 0.14-92.3; OR 13.98, 95% CI 1.40-140.36]. No etiology of bleeding was identified in a higher percentage of patients on DAPT than those who were not (22.8% vs 5.3%). CONCLUSION: In patients with GI bleeding, the incidences of UGIB and LGIB are similar irrespective of their DAPT use.

The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis.

Discovering the genetic and cellular mechanisms that drive cardiac morphogenesis remains a fundamental goal, as three-dimensional architecture greatly impacts functional capacity. During development, accurately contoured chambers balloon from a primitive tube in a process characterized by regional changes in myocardial cell size and shape. How these localized changes are achieved remains elusive. Here, we show in zebrafish that microRNA-143 (miR-143) is required for chamber morphogenesis through direct repression of adducin3 (add3), which encodes an F-actin capping protein. Knockdown of miR-143 or disruption of the miR-143-add3 interaction inhibits ventricular cardiomyocyte F-actin remodeling, which blocks their normal growth and elongation and leads to ventricular collapse and decreased contractility. Using mosaic analyses, we find that miR-143 and add3 act cell-autonomously to control F-actin dynamics and cell morphology. As proper chamber emergence relies on precise control of cytoskeletal polymerization, Add3 represents an attractive target to be fine-tuned by both uniform signals, such as miR-143, and undiscovered localized signals. Together, our data uncover the miR-143-add3 genetic pathway as essential for cardiac chamber formation and function through active adjustment of myocardial cell morphology.

VEGF improves survival of mesenchymal stem cells in infarcted hearts.

Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infarcted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16(INK), p21 and p19(ARF). VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI.