Myocardial Protection and Current Cancer Therapy: Two Opposite Targets with Inevitable Cost.

Myocardial protection against ischemia/reperfusion injury (IRI) is mediated by various ligands, activating different cellular signaling cascades. These include classical cytosolic mediators such as cyclic-GMP (c-GMP), various kinases such as Phosphatydilinositol-3- (PI3K), Protein Kinase B (Akt), Mitogen-Activated-Protein- (MAPK) and AMP-activated (AMPK) kinases, transcription factors such as signal transducer and activator of transcription 3 (STAT3) and bioactive molecules such as vascular endothelial growth factor (VEGF). Most of the aforementioned signaling molecules constitute targets of anticancer therapy; as they are also involved in carcinogenesis, most of the current anti-neoplastic drugs lead to concomitant weakening or even complete abrogation of myocardial cell tolerance to ischemic or oxidative stress. Furthermore, many anti-neoplastic drugs may directly induce cardiotoxicity via their pharmacological effects, or indirectly via their cardiovascular side effects. The combination of direct drug cardiotoxicity, indirect cardiovascular side effects and neutralization of the cardioprotective defense mechanisms of the heart by prolonged cancer treatment may induce long-term ventricular dysfunction, or even clinically manifested heart failure. We present a narrative review of three therapeutic interventions, namely VEGF, proteasome and Immune Checkpoint inhibitors, having opposing effects on the same intracellular signal cascades thereby affecting the heart. Moreover, we herein comment on the current guidelines for managing cardiotoxicity in the clinical setting and on the role of cardiovascular confounders in cardiotoxicity.

Molecular Insights in Atrial Fibrillation Pathogenesis and Therapeutics: A Narrative Review.

The prevalence of atrial fibrillation (AF) is bound to increase globally in the following years, affecting the quality of life of millions of people, increasing mortality and morbidity, and beleaguering health care systems. Increasingly effective therapeutic options against AF are the constantly evolving electroanatomic substrate mapping systems of the left atrium (LA) and ablation catheter technologies. Yet, a prerequisite for better long-term success rates is the understanding of AF pathogenesis and maintenance. LA electrical and anatomical remodeling remains in the epicenter of current research for novel diagnostic and treatment modalities. On a molecular level, electrical remodeling lies on impaired calcium handling, enhanced inwardly rectifying potassium currents, and gap junction perturbations. In addition, a wide array of profibrotic stimuli activates fibroblast to an increased extracellular matrix turnover via various intermediaries. Concomitant dysregulation of the autonomic nervous system and the humoral function of increased epicardial adipose tissue (EAT) are established mediators in the pathophysiology of AF. Local atrial lymphomononuclear cells infiltrate and increased inflammasome activity accelerate and perpetuate arrhythmia substrate. Finally, impaired intracellular protein metabolism, excessive oxidative stress, and mitochondrial dysfunction deplete atrial cardiomyocyte ATP and promote arrhythmogenesis. These overlapping cellular and molecular alterations hinder us from distinguishing the cause from the effect in AF pathogenesis. Yet, a plethora of therapeutic modalities target these molecular perturbations and hold promise in combating the AF burden. Namely, atrial selective ion channel inhibitors, AF gene therapy, anti-fibrotic agents, AF drug repurposing, immunomodulators, and indirect cardiac neuromodulation are discussed here.

Direct Implantation of a Left Atrial Appendage Occluder During Cardiothoracic Surgery.

Surgical suture or exclusion of the left atrial appendage (LAA) is a commonly performed technique in patients undergoing cardiothoracic revascularization or valve repair, or both. However, incomplete surgical sealing of the LAA is not a rare phenomenon and strongly increases the risk for future cerebrovascular embolic events. We report the implantation of a Watchman LAA occluder (Boston Scientific, Natick, MA) during redo minimally invasive open heart surgery. This approach offers a new alternative for LAA occlusion in patients for whom a surgical procedure is scheduled.

Feasibility of single position endoscopic laser balloon ablation for atrial fibrillation: The open 8 approach.

INTRODUCTION: Ablation without shaft repositioning may make the endoscopic laser ablation system (EAS) more like a single shot approach. We tested the feasibility of wide circumferential ablation (WCA; no carina ablation and no shaft repositioning) in an "open 8" pattern for pulmonary vein isolation (PVI). METHODS AND RESULTS: Forty-eight patients (n = 48, age 64.6 ± 12 years) with paroxysmal and persistent atrial fibrillation (AF) were referred to our center for PVI with the EAS. WCA for the lateral and septal pulmonary veins was attempted in all patients. If not feasible, individual full circular isolation of each pulmonary vein (iPVI) was performed. Additional lesions were applied if acute complete electrical isolation was not achieved on the first encirclement. Any documented episode of AF after a 1-month blanking period was registered as a recurrence. Bilateral WCA was feasible in 21 out of 48 patients (43.8%). Additional lesions for complete electrical isolation after the first-pass ablation were less in WCA compared with iPVI (P = 0.02). WCA was accomplished faster, with less applied energy at both lateral (P < 0.01) and septal side (P < 0.01). The mean follow-up of the patient population was 232 ± 150 days. AF recurrence occurred later in patients treated with WCA (315 ± 124 vs 110 ± 88 days, P = 0.008). CONCLUSIONS: WCA with the EAS is safe, at least moderately feasible and highly effective, if achieved. Compared with iPVI it may be less time consuming, results in less energy application, and suppresses AF more effectively.