Lack of efficacy of aprotinin over tranexamic acid in type A aortic dissection repair.

BACKGROUND: The role of aprotinin in modern cardiac surgery is not well defined. While licensed for use in isolated coronary artery bypass grafting it is more commonly used for cases deemed to be at an increased risk of bleeding. The relative efficacy, and safety profile, of aprotinin as compared to other antifibrinolytics in these high-risk cases is uncertain. STUDY DESIGN AND METHODS: A retrospective observational study with propensity matching to determine whether aprotinin versus tranexamic acid reduced bleeding or transfusion requirements in patients presenting for surgical repair of type A aortic dissection (TAD). RESULTS: Between 2016 and 2022, 250 patients presented for repair of TAD. A total of 231 patients were included in the final analysis. Bleeding and transfusion were similar between both groups in both propensity matched and unmatched cohorts. Compared to tranexamic acid, aprotinin use did not reduce transfusion requirements for any product. Rates of bleeding in the first 12 h, return to theater and return to intensive care unit with an open packed chest were similar between groups. There was no difference in rates of renal failure, stroke, or death. CONCLUSION: Aprotinin did not reduce the risk of bleeding or transfusion requirements in patients undergoing repair of type A aortic dissections. Efficacy of aprotinin may vary depending on the type of surgery performed and the underlying pathology.

Prosthesis-Patient Mismatch and Aortic Root Enlargement: Indications, Techniques and Outcomes.

Prosthesis-patient mismatch (PPM) is defined as implanting a prosthetic that is insufficiently sized for the patient receiving it. PPM leads to high residual transvalvular gradients post-aortic valve replacement and consequently results in left ventricular dysfunction, morbidity and mortality in both the short and long term. Younger patients and patients with poor preoperative left ventricular function are more vulnerable to increased mortality secondary to PPM. There is debate over the measurement of valvular effective orifice area (EOA) and variation exists in how manufacturers report the EOA. The most reliable technique is using in vivo echocardiographic measurements to create tables of predicted EOAs for different valve sizes. PPM can be prevented surgically in patients at risk through aortic root enlargement (ARE). Established techniques include the posterior enlargement through Nicks and Manouguian procedures, and aortico-ventriculoplasty with the Konno-Rastan procedure, which allows for a greater enlargement but carries increased surgical risk. A contemporary development is the Yang procedure, which uses a Y-shaped incision created through the non- and left-coronary cusp commissure, undermining the nadirs of the non- and left-coronary cusps. Early results are promising and demonstrate an ability to safely increase the aortic root by up to two to three sizes. Aortic root enlargement thus remains a valuable and safe tool in addressing PPM, and should be considered during surgical planning.

Anti-malarial drugs: Mechanisms underlying their proarrhythmic effects.

Malaria remains the leading cause of parasitic death in the world. Artemisinin resistance is an emerging threat indicating an imminent need for novel combination therapy. Given the key role of mass drug administration, it is pivotal that the safety of anti-malarial drugs is investigated thoroughly prior to widespread use. Cardiotoxicity, most prominently arrhythmic risk, has been a concern for anti-malarial drugs. We clarify the likely underlying mechanisms by which anti-malarial drugs predispose to arrhythmias. These relate to disruption of (1) action potential upstroke due to effects on the sodium currents, (2) action potential repolarisation due to effects on the potassium currents, (3) cellular calcium homeostasis, (4) mitochondrial function and reactive oxygen species production and (5) cardiac fibrosis. Together, these alterations promote arrhythmic triggers and substrates. Understanding these mechanisms is essential to assess the safety of these drugs, stratify patients based on arrhythmic risk and guide future anti-malarial drug development.

Mitochondrial Dysfunction Increases Arrhythmic Triggers and Substrates; Potential Anti-arrhythmic Pharmacological Targets.

Incidence of cardiac arrhythmias increases significantly with age. In order to effectively stratify arrhythmic risk in the aging population it is crucial to elucidate the relevant underlying molecular mechanisms. The changes underlying age-related electrophysiological disruption appear to be closely associated with mitochondrial dysfunction. Thus, the present review examines the mechanisms by which age-related mitochondrial dysfunction promotes arrhythmic triggers and substrate. Namely, via alterations in plasmalemmal ionic currents (both sodium and potassium), gap junctions, cellular Ca2+ homeostasis, and cardiac fibrosis. Stratification of patients' mitochondrial function status permits application of appropriate anti-arrhythmic therapies. Here, we discuss novel potential anti-arrhythmic pharmacological interventions that specifically target upstream mitochondrial function and hence ameliorates the need for therapies targeting downstream changes which have constituted traditional antiarrhythmic therapy.