Cardiovascular outcomes and molecular targets for the cardiac effects of Sodium-Glucose Cotransporter 2 Inhibitors: A systematic review.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new class of glucose-lowering drugs traditionally used to control blood glucose levels in patients with type 2 diabetes mellitus, have been proven to reduce major adverse cardiovascular events, including cardiovascular death, in patients with heart failure irrespective of ejection fraction and independently of the hypoglycemic effect. Because of their favorable effects on the kidney and cardiovascular outcomes, their use has been expanded in all patients with any combination of diabetes mellitus type 2, chronic kidney disease and heart failure. Although mechanisms explaining the effects of these drugs on the cardiovascular system are not well understood, their effectiveness in all these conditions suggests that they act at the intersection of the metabolic, renal and cardiac axes, thus disrupting maladaptive vicious cycles while contrasting direct organ damage. In this systematic review we provide a state of the art of the randomized controlled trials investigating the effect of SGLT2i on cardiovascular outcomes in patients with chronic kidney disease and/or heart failure irrespective of ejection fraction and diabetes. We also discuss the molecular targets and signaling pathways potentially explaining the cardiac effects of these pharmacological agents, from a clinical and experimental perspective.

Chronic thromboembolic pulmonary disease: Association with exercise-induced pulmonary hypertension and right ventricle adaptation over time: Chronic thromboembolic pulmonary disease and exercise pulmonary hypertension.

BACKGROUND AND AIM: Chronic thromboembolic pulmonary disease (CTEPD) is a progressive condition caused by fibrotic thrombi and vascular remodeling in the pulmonary circulation despite prolonged anticoagulation. We evaluated clinical factors associated with CTEPD, as well as its impact on functional capacity, pulmonary haemodynamics at rest and after exercise, and right ventricle (RV) morphology and function. METHODS: We compared 33 consecutive patients with a history of acute pulmonary embolism and either normal pulmonary vascular imaging (negative Q-scan, group 1, n = 16) or persistent defects on lung perfusion scan (positive Q-scan) despite oral anticoagulation at 4 months (group 2, n = 17). Investigations included thrombotic load, the Pulmonary Embolism Severity Index (PESI) score, functional class, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), cardiopulmonary exercise test (CPET) and echocardiographic parameters at rest and after exercise (ESE), at 4 and at 24 months. RESULTS: Compared with group 1, group 2 featured a higher PESI score (p = 0.02) and a higher thrombotic load (p = 0.004) at hospital admission. At 4 months, group 2 developed exercise-induced pulmonary hypertension (Ex-PH) at CPET (p < 0.001) and ESE (p < 0.001). At 24 months group 2 showed higher NT-proBNP (p < 0.001), WHO-FC (p < 0.001), systolic (p<0.001) and diastolic (p = 0.037) RV dysfunction and worse RV-arterial coupling (p < 0.001) despite maintaining a low or intermediate echocardiographic probability of PH. CONCLUSIONS: This is the first "proof of concept" study showing that patients with a positive Q-scan frequently develop Ex-PH and RV functional deterioration as well as reduced functional capacity, generating the hypothesis that Ex-PH could help detect the progression to CTEPD.