Melatonin: A potential protective multifaceted force for sepsis-induced cardiomyopathy.

Sepsis is a life-threatening condition manifested by organ dysfunction caused by a dysregulated host response to infection. Lung, brain, liver, kidney, and heart are among the affected organs. Sepsis-induced cardiomyopathy is a common cause of death among septic patients. Sepsis-induced cardiomyopathy is characterized by an acute and reversible significant decline in biventricular both systolic and diastolic function. This is accompanied by left ventricular dilatation. The pathogenesis underlying sepsis-induced cardiomyopathy is multifactorial. Hence, targeting an individual pathway may not be effective in halting the extensive dysregulated immune response. Despite major advances in sepsis management strategies, no effective pharmacological strategies have been shown to treat or even reverse sepsis-induced cardiomyopathy. Melatonin, namely, N-acetyl-5-methoxytryptamine, is synthesized in the pineal gland of mammals and can also be produced in many cells and tissues. Melatonin has cardioprotective, neuroprotective, and anti-tumor activity. Several literature reviews have explored the role of melatonin in preventing sepsis-induced organ failure. Melatonin was found to act on different pathways that are involved in the pathogenesis of sepsis-induced cardiomyopathy. Through its antimicrobial, anti-inflammatory, and antioxidant activity, it offers a potential role in sepsis-induced cardiomyopathy. Its antioxidant activity is through free radical scavenging against reactive oxygen and nitrogen species and modulating the expression and activity of antioxidant enzymes. Melatonin anti-inflammatory activities control the overactive immune system and mitigate cytokine storm. Also, it mitigates mitochondrial dysfunction, a major mechanism involved in sepsis-induced cardiomyopathy, and thus controls apoptosis. Therefore, this review discusses melatonin as a promising drug for the management of sepsis-induced cardiomyopathy.

Effect of Clinical and Genetic Factors on the Development of Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting (CABG) in Egyptian Patients Receiving Beta-Blockers.

PURPOSE: Prophylactic beta-blockers are recommended to prevent postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). Polymorphisms in the beta-1 adrenergic receptor (ADRB1) and G protein-coupled receptor kinase 5 (GRK5) genes are associated with variable responses to beta-blockers. The aim of this study was to determine the clinical and genetic factors that influence the response to beta-blockers for POAF prophylaxis after CABG. METHODS: Patients undergoing isolated CABG and receiving prophylactic beta-blockers (n = 249) were prospectively recruited and followed up for 6 postoperative days. Genotyping of ADRB1 rs1801253, and 3 GRK5 SNPs (rs3740563, rs10787959, and rs17098707) was performed. RESULTS: Of the 249 patients, 52 patients (20.8%) experienced POAF. Age, hypertension, vasopressor use, calculated POAF risk score, GRK5 rs2230345 T-allele, and GRK5 rs3740563 A-allele were associated with POAF despite beta-blocker prophylaxis. The multivariate analysis revealed that age [odds ratio (OR) 1.06, 95% CI 1.02-1.11, p = 0.003] and GRK5 rs2230345 T-allele [OR 2.81, 95% CI 1.39-5.67, p = 0.004] were independent predictors of POAF after CABG despite beta-blocker prophylaxis. CONCLUSION: GRK5 rs2230345 T-allele carriers were less responsive than AA genotype carriers to prophylactic beta-blockers for the prevention of POAF after CABG. The study was registered on http://clinicaltrials.gov in March 2019, with trial registration number (TRN): NCT03871647.

Validation of Cardiac Surgery-Associated Neutrophil Gelatinase-Associated Lipocalin Score for Prediction of Cardiac Surgery-Associated Acute Kidney Injury.

BACKGROUND: The Cardiac Surgery-Associated Neutrophil Gelatinase-Associated Lipocalin (CSA-NGAL) score has been developed to stratify patients with cardiac surgery-associated acute kidney injury (CSA-AKI). Its predictive power needs to be validated to guide clinical decision for such high-risk patients. METHODS: A prospective study was conducted on 637 consecutive adult patients who developed postoperative AKI after cardiac surgery with cardiopulmonary bypass. AKI was defined according to Kidney Disease: Improving Global Outcomes criteria (KDIGO). The CSA-NGAL score was calculated. Assessment of the diagnostic performance of the scoring model was performed by area under the receiver operating curve analysis. RESULTS: The area under the curve for the postoperative Urinary NGAL showed an area under the curve ([standard error (SE)] 0.80 (0.38); p<0.001; 95% CI 0.72-0.87). Its sensitivity for CSA-AKI in the first 24 hours was 66% and specificity was 80% (cut-off value 300.1 ng/mL). There was a positive correlation between NGAL score and KDIGO criteria, with a significant increase in postoperative mean Urinary NGAL values as the KDIGO stage increased. CONCLUSION: The CSA-NGAL score has a high sensitivity, specificity and positive predictive value that can translate into improved outcomes and resource allocation. It is believed that adding it to the existing clinical scoring systems for AKI prediction will be productive.

On-X versus St Jude Medical Mechanical Prosthesis in mitral position: are we moving forward in design technology?

BACKGROUND: Continuous effort is still provided in designing optimal artificial heart valves with better hemodynamic function and reduced thromboembolic potential. The question is do we have moved forward toward this goal or not. METHODS: A prospective, randomized comparative study was done on 360 patients scheduled for elective mitral valve replacement. Patients were grouped into an On-X group (N.=180), who received On-X mechanical valve, and a SJM group (N.=180), who received St Jude mechanical valve. Echocardiographic and clinical assessments were performed for all patients at 6 and 12 months follow-up period. RESULTS: Rheumatic heart disease was the most common cause of valve affection (94.2%). Early mortality was 6.4%. The mean follow-up time was 3.11±2.44 years. No structural or non-structural valvular dysfunction and no thromboembolism cases were encountered. Late valve thrombosis was1.9%/patient-year in On-X group and 2.1%/patient-year in SJM group. The mean EOA was higher in On-X group (2.0±0.3 cm2) than in SJM group (1.9±0.2 cm2), (P≥0.05). The mean EOAI was higher in On-X group (1.1±0.1 cm2/m2) than in SJM group (1.0±0.1 cm2/m2), (P=0.034), especially significant in small valve size (25 mm) where it was 1.09±021 cm2/m2 in On-X group and 0.93±0.12 cm2/m2 in SJM group (P=0.02). CONCLUSIONS: On-X and St Jude prosthetic valves have a comparable hemodynamic performance in mitral position. However, On-X prosthesis might have a forward step on the way of design technology that may allow better function in terms of EOA and EOAI especially in smaller valve size.