Current experimental and early investigational agents for cardiac fibrosis: where are we at?

INTRODUCTION: Myocardial fibrosis (MF) is induced by factors activating pro-fibrotic pathways such as acute and prolonged inflammation, myocardial ischemic events, hypertension, aging process, and genetically-linked cardiomyopathies. Dynamics and characteristics of myocardial fibrosis development are very different. The broad range of myocardial fibrosis presentations suggests the presence of multiple potential targets. AREA COVERED: Heart failure treatment involves medications primarily aimed at counteracting neurohormonal activation. While these drugs have demonstrated efficacy against MF, not all specifically target inflammation or fibrosis progression with some exceptions such as RAAS inhibitors. Consequently, new therapies are being developed to address this issue. This article is aimed to describe anti-fibrotic drugs currently employed in clinical practice and emerging agents that target specific pathways, supported by evidence from both preclinical and clinical studies. EXPERT OPINION: Despite various preclinical findings suggesting the potential utility of new drugs and molecules for treating cardiac fibrosis in animal models, there is a notable scarcity of clinical trials investigating these effects. However, the pathology of damage and repair in the heart muscle involves a complex network of interconnected inflammatory pathways and various types of immune cells. Our comprehension of the positive and negative roles played by specific immune cells and cytokines is an emerging area of research.

Direct anchoring technique for pacing and defibrillation leads inserted through cephalic vein: insight for a single high-volume center.

BACKGROUND: Direct anchoring of PM and ICD leads over cephalic vein body is officially discouraged by manufactures due to a supposed risk of conductor fracture or insulation failure, however careful tightening of anchoring knots can probably prevent lead damage. Direct anchoring (DA) technique is routinely used in our center for all leads inserted by cephalic vein while standard anchoring sleeves are used to secure subclavian leads only. Aim of the study is to assess short- and long-term safety of cephalic direct anchoring technique. METHODS: All patients undergoing PM and ICD implantation in our center from November 2014 to March 2016 were consecutively enrolled. Primary endpoints were acute lead fracture, lead dislodgement and chronic lead failure. Secondary endpoint was a composite of short-term surgical complications (pocket hematoma, pneumothorax, and pericardial effusion) plus device infections. Subclavian leads secured with sleeve anchoring (SA) were used as control. RESULTS: A total of 550 leads were implanted in 310 consecutive patients. DA involved 323 leads (59%) while SA was used for 227 (41%). Median follow-up was 50 months (IQR 24-62 months). 17 lead malfunctions (3.1%) were observed during follow-up. No difference was observed between groups (10 DA vs. 7 SP, P=ns). Survival analysis found no difference between groups. Secondary endpoints were not statistically different between groups (5 vs. 1, P=0.08). CONCLUSIONS: Direct anchoring technique of PM and ICD leads is a safe technique and does not increase lead malfunction risk.