In the context of multi-organ involvement in sepsis, cardiac toxicity is manifested as sepsis-induced cardiomyopathy (SICM). To date, no unified SICM definition exists, though a left ventricular ejection fraction ≤ 50% and/or an absolute drop ≥ 10% from baseline are the most widely accepted components. Several molecular pathways have been associated with SICM, including (i) pro-inflammatory mediator-induced cardiac depression; (ii) sarcolemmal membrane dysfunction; (iii) autonomic nervous system (ANS) imbalance; (iv) blunted cardiovascular response to catecholamines; (v) dysfunctional intracellular calcium handling; (vi) mitochondrial dysfunction; (vii) metabolic reprogramming; and (viii) disturbed endothelial and microcirculatory function. Atrial and ventricular arrhythmias—particularly atrial fibrillation—commonly complicate disease management and are associated with adverse outcomes. Key mechanisms outlining sepsis-induced arrhythmogenesis are (i) inflammation; (ii) electrolyte imbalances; (iii) myocardial ischemia; (iv) QT prolongation/dispersion; (v) adrenergic overactivation; (vi) calcium mishandling; and (vii) fever-induced arrhythmogenesis in Brugada. Established therapeutic approaches include prompt treatment with antibiotics, hemodynamic optimization, and/or selective use of beta-blockers. Furthermore, several molecules are currently being investigated targeting numerous pathways activated in sepsis. Vitamin C, ginsenoside Rc, Schistosoma Japonicum cystatin, and gasmerdin-D inhibitor Y2 exert anti-inflammatory actions, while melatonin and α-ketoglutarate regulate mitochondrial homeostasis. Triiodothyronine targets microcirculatory optimization and regulates protective pathways against stress-related cell death. Engineered exosomes may facilitate targeted drug delivery, inflammatory response modulation, and activation of pathways related to cell survival, while sodium octanoate exhibits anti-inflammatory actions coupled with improved energy metabolism. Finally, gene-regulating therapies aiming at inflammatory response optimization have also been proposed and are currently under development. Future research should aim to standardize the SICM definition, translate emerging therapeutics into clinical practice, identify novel molecular targets, and implement personalized treatment strategies for SICM.

Background/Objectives: Patients with atrial fibrillation and mitral regurgitation (MR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER) often have concomitant indications for left atrial appendage occlusion (LAAO), mandating a more personalized treatment approach. This study aimed to examine the effectiveness and safety of combining M-TEER/LAAO in one procedure. Methods: MEDLINE (PubMed), Scopus, and Cochrane were searched through 21 March 2025 for studies examining M-TEER/LAAO with or without control (M-TEER only). Double-independent study selection, extraction, and quality assessments were performed. Frequentist random-effects models were used to calculate mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). Results: Seven studies (223 participants) were included. For M-TEER/LAAO, the mean procedural time was 101.6 min (95% CI = [85.06, 118.13]), the mean radiation time was 29.97 min (95% CI = [23.85, 36.09]), the mean length of stay was 5.21 days (95% CI = [3.31, 7.12]), procedural success was achieved in 89.5% of cases (95% CI = [73.4, 96.3], and post-procedure MR > 2+ occurred in 14.8% of cases (95% CI = [3.6, 44.5]). Compared to M-TEER only, patients with M-TEER/LAAO had similar procedural (RR = 0.91, 95% CI = [0.71, 1.17]) and technical success (RR = 1, 95% CI = [0.94, 1.06]) with a similar risk of acute kidney injury (RR = 1, 95% CI = [0.07, 15.12]), bleeding (RR = 0.40, 95% CI = [0.01, 18.06]), and all-cause death (RR = 0.59, 95% CI = [0.22, 1.54]). M-TEER/LAAO was non-significantly associated with in-hospital death (RR = 3, 95% CI = [0.13, 70.23]), stroke (RR = 3, 95% CI = [0.13, 70.23]), and vascular complications (RR = 1.55, 95% CI = [0.43, 5.59]) compared to M-TEER only. Most patients (34.2%, 95% CI = [2.8, 90.4]) received dual antiplatelet therapy at discharge, followed by anticoagulation only (20.2%, 95% CI = [7.5, 44.3]). Conclusions: M-TEER/LAAO can be combined into a single procedure with good peri-procedural outcomes. Safety was also satisfactory; however, some concerns may arise regarding in-hospital death, stroke, and vascular complications. Further research is needed to explore the effectiveness and safety of this combined strategy and elucidate the risk–benefit profile of this personalized treatment approach.