Cardiovascular-kidney-metabolic (CKM) syndrome is a multifaceted, systemic disorder characterized by the interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and obesity. This review synthesizes current and emerging therapeutic strategies aimed at addressing the shared pathophysiologic mechanisms driving CKM progression, such as insulin resistance, inflammation, oxidative stress, and neurohormonal activation. Established pharmacotherapies that include sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and nonsteroidal mineralocorticoid receptor antagonists like finerenone have demonstrated robust efficacy in reducing cardiovascular events, slowing renal decline, and improving metabolic outcomes. Additionally, novel agents targeting lipoprotein(a), interleukin-6, and hepatic fat accumulation are expanding the therapeutic landscape. RNA-based therapies, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), are designed to modulate lipoprotein(a) and PCSK9 expression. Artificial intelligence (AI) is also emerging as a transformative tool for personalized CKM management, enhancing risk prediction and clinical decision-making. The review highlights the relevance of metabolic dysfunction-associated steatotic liver disease (MASLD) as a CKM modifier and discusses the approval of resmetirom, a selective thyroid hormone receptor β agonist, for noncirrhotic MASH. By integrating evidence from clinical trials, mechanistic studies, and emerging technologies, this review provides a comprehensive resource for clinicians and researchers navigating the evolving field of CKM syndrome.

Background: Melatonin has antioxidant and anti-inflammatory properties that may attenuate ischemia-reperfusion injury, but randomized cardiovascular trial data remain inconsistent. Objectives: This study sought to evaluate the association of melatonin supplementation with cardiovascular outcomes across randomized trials. Methods: We performed a systematic review and meta-analysis of randomized trials comparing melatonin with placebo, usual care, or no melatonin in patients with cardiovascular disease. PubMed, Embase, and CENTRAL were searched from inception to 1 January 2026. Random-effects models with Hartung–Knapp–Sidik–Jonkman confidence intervals were used. Prespecified outcomes included left ventricular ejection fraction (LVEF), change in LVEF, troponin, infarct size by cardiac magnetic resonance, heart failure outcomes, inflammatory and oxidative stress biomarkers, and adverse events. Results: A total of 14 randomized controlled trials involving 1027 participants were included. Melatonin significantly improved change in LVEF from baseline to follow-up (mean difference: 3.95 percentage points; 95% CI: 1.70–6.20; p < 0.001), with the most consistent signal in coronary artery bypass grafting studies (mean difference: 4.65 percentage points; 95% CI: 2.56–6.74). Final LVEF was numerically higher with melatonin but not statistically significant. Troponin reduction was not significant. Narrative synthesis suggested lower inflammatory and oxidative stress markers after coronary artery bypass grafting and improvement in heart failure symptoms and quality of life, whereas infarct size findings in ST-segment elevation myocardial infarction were mixed and timing-dependent. Conclusions: Melatonin was associated with improved LVEF change, particularly in coronary artery bypass grafting settings, but benefit was not consistently demonstrated across final LVEF, troponin, or infarct size outcomes.

Cardiovascular-kidney-metabolic (CKM) syndrome is a multifaceted, systemic disorder characterized by the interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and obesity. This review synthesizes current and emerging therapeutic strategies aimed at addressing the shared pathophysiologic mechanisms driving CKM progression, such as insulin resistance, inflammation, oxidative stress, and neurohormonal activation. Established pharmacotherapies that include sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and nonsteroidal mineralocorticoid receptor antagonists like finerenone have demonstrated robust efficacy in reducing cardiovascular events, slowing renal decline, and improving metabolic outcomes. Additionally, novel agents targeting lipoprotein(a), interleukin-6, and hepatic fat accumulation are expanding the therapeutic landscape. RNA-based therapies, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), are designed to modulate lipoprotein(a) and PCSK9 expression. Artificial intelligence (AI) is also emerging as a transformative tool for personalized CKM management, enhancing risk prediction and clinical decision-making. The review highlights the relevance of metabolic dysfunction-associated steatotic liver disease (MASLD) as a CKM modifier and discusses the approval of resmetirom, a selective thyroid hormone receptor β agonist, for noncirrhotic MASH. By integrating evidence from clinical trials, mechanistic studies, and emerging technologies, this review provides a comprehensive resource for clinicians and researchers navigating the evolving field of CKM syndrome.

Background and Clinical Significance: Mycotic aortic aneurysm is a rare but life-threatening vascular condition characterized by infection-induced dilation or pseudoaneurysm formation in the aorta. The condition carries a high risk of rupture and mortality, especially in individuals with underlying cardiovascular disease, who have undergone recent vascular procedures, or with immunocompromising comorbidities such as diabetes. Its diagnosis is challenging due to its non-specific symptoms and often requires a high index of suspicion, especially in patients presenting with persistent fever and negative initial imaging. Early recognition and intervention are critical, as delayed treatment significantly worsens outcomes. Case Presentation: A 68-year-old male with a history of coronary artery disease, recent stent placement, and hypertension presented with two days of fever, chills, rigors, and a mild nonproductive cough. The laboratory findings were only significant for leukocytosis. The initial chest X-ray and non-contrast CT scans were unremarkable. He was admitted for presumed pneumonia and started on intravenous antibiotics. Persistent fever prompted further investigation with contrast-enhanced CT, which revealed a distal-aortic-arch pseudoaneurysm and mild mediastinal stranding. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA). Transthoracic echocardiogram was negative for endocarditis. The patient was transferred to a tertiary center, where repeat imaging confirmed a 1.5 cm pseudoaneurysm and a 4 mm penetrating atherosclerotic ulcer. After multidisciplinary assessment, he underwent thoracic endovascular aortic repair (TEVAR) and completed four weeks of intravenous cefazolin. Follow-up imaging showed successful aneurysm repair with no complications. Conclusions: Thoracic mycotic aneurysm is a rapidly fatal entity despite intervention. High clinical suspicion is necessary given its non-specific presentation. It is diagnosed most practically using CTA. In addition to antibiotics, TEVAR is gaining traction as a feasible and a safe alternative to open surgical repair (OSR).