SGLT-2 Inhibitors on Top of Current Pharmacological Treatments for Heart Failure: A Comparative Review on Outcomes and Cost Effectiveness.

Heart failure (HF) represents a major global health and economic burden with still unacceptably high morbidity and mortality rates. In recent decades, novel therapeutic opportunities with a significant impact on HF outcomes have been introduced in addition to angiotensin-converting enzyme (ACE) inhibitors, ß-blockers, and mineralocorticoid receptor antagonists. These include drugs such as ivabradine, sacubitril-valsartan, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. The availability of an extremely large pharmacological armamentarium to face this chronic global disease highlights the importance of assessing cost effectiveness to promote sustainable healthcare. In light of the recent approval of SGLT-2 inhibitors for the treatment of HF with reduced ejection fraction, including in individuals without type 2 diabetes mellitus, the aim of this review was to provide an updated comparative evaluation of the efficacy and cost effectiveness of different pharmacological treatments for the prevention (stage A) and treatment of asymptomatic (stage B) and symptomatic (stages C-D) left ventricular dysfunction.

The Pivotal Role of Invasive Functional Assessment in Patients With Myocardial Infarction With Non-Obstructive Coronary Arteries (MINOCA).

Myocardial infarction with non-obstructive coronary arteries (MINOCA) encompasses several pathophysiological mechanisms not yet fully understood. Among the latter, vasomotion abnormalities and coronary microvascular dysfunction (CMD) play a major role for both epidemiological and prognostic reasons. Despite current guidelines do not recommend routine physiological assessment of both epicardial and microvascular coronary compartments within the context of an acute myocardial infarction, several recent evidence support the critical role of a comprehensive invasive functional assessment in order to identify the underlying pathophysiological mechanism and consequently to select an appropriate therapeutic strategy. Unfortunately, optimal medical therapy for these patients is not currently established due to the lack of dedicated trials evaluating clinical outcomes of commonly used medications for secondary prevention in MINOCA patients. For this reason, additional research is warranted to provide personalized treatments for patients affected by this puzzling clinical entity.

Invasive Assessment of Coronary Microvascular Function.

The critical role of the coronary microvascular compartment and its invasive functional assessment has become apparent in light of the significant proportion of patients presenting signs and symptoms of myocardial ischemia, despite the absence of epicardial disease, or after the adequate treatment of it. However, coronary microvascular dysfunction (CMD) represents a diagnostic challenge because of the small dimensions of the coronary microvasculature, which prevents direct angiographic visualization. Several diagnostic tools are now available for the invasive assessment of the coronary microvascular function, which, in association with the physiological indices used to investigate the epicardial department, may provide a comprehensive evaluation of the coronary circulation as a whole. Recent evidence suggests that the physiology-guided management of CMD, although apparently costly and time-consuming, may offer a net clinical benefit in terms of symptom improvement among patients with angina and ischemic heart disease. However, despite the results of several observational studies, the prognostic effect of the physiology-driven management of CMD within this population is currently a matter of debate, and therefore represents an unmet clinical need that urgently deserves further investigation.

Early prediction of contrast-induced acute kidney injury by a "bedside" assessment of Neutrophil Gelatinase-Associated Lipocalin during elective percutaneous coronary interventions.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication during percutaneous coronary interventions (PCI). Currently, the diagnosis of CI-AKI relies on serum creatinine (SCr) that is however affected by several limitations potentially leading to delayed or missed diagnoses. In this study we examined the diagnostic accuracy of a "bedside" measurement of plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL) in the early detection of CI-AKI in 97 patients undergoing elective PCI. The overall incidence of CI-AKI was 3%. A significant positive correlation was observed between 6-hours NGAL and post-PCI SCr (r = 0.339, p = 0.004) and a significant negative correlation between 6-hours NGAL and post-PCI CrCl (r = -0.303, p = 0.010). In patients with post-PCI SCr increase > 0.24 mg/dl (median SCr absolute increase), delta NGAL 0-6 hours and 6-hours NGAL values were higher compared with patients with SCr elevation below the defined threshold (p = 0.049 and p = 0.056). The ROC analysis showed that a 6 hours NGAL value > 96 ng/ml significantly predicted an absolute SCr increase > 0.24 mg/dl after contrast exposure with sensitivity of 53% and specificity of 74% (AUC 0.819, 95% CI: 0.656 to 0.983, p = 0.005). The use of bedside NGAL assessment may significantly hasten diagnosis and treatment of CI-AKI, with remarkable clinical prognostic consequences.

Platelet function and long-term antiplatelet therapy in women: is there a gender-specificity? A 'state-of-the-art' paper.

Although the female gender is generally less represented in cardiovascular studies, observational and randomized investigations suggest that-compared with men-women may obtain different benefits from antiplatelet therapy. Multiple factors, including hormonal mechanisms and differences in platelet biology, might contribute to such apparent gender peculiarities. The thrombotic and bleeding risks, as well as outcomes after a cardiovascular event, appear to differ between genders, partly in relation to differences in age, comorbidities and body size. Equally, the benefits of antiplatelet therapy may differ in women compared with men in different vascular beds, during primary or secondary prevention and according to the type of an antiplatelet agent used. This document is an attempt to bring together current evidence, clinical practices and gaps of knowledge on gender-specific platelet function and antiplatelet therapy. On the basis of the available data, we provide suggestions on current indications of antiplatelet therapy for cardiovascular prevention in women with different clinical features; no strong recommendation may be given because the available data derive from observational studies or post hoc/subgroup analyses of randomized studies without systematic adjustments for baseline risk profiles.

Safety of drug-eluting stents in patients with left ventricular dysfunction undergoing percutaneous coronary intervention.

Recent studies have reported a higher incidence of late stent thrombosis in patients undergoing drug-eluting stent (DES). Reduced left ventricular (LV) ejection fraction (EF) is considered a risk factor for this complication after both bare-metal stent (BMS) and DES implantation. Therefore, the aim of this study was to evaluate the safety of DES on long-term follow-up in patients with LV dysfunction undergoing percutaneous coronary intervention. We retrospectively selected all patients with an EF <45% undergoing percutaneous coronary intervention with implantation of > or =1 sirolimus- or paclitaxel-eluting stent at our institution. The primary endpoint of the study was all-cause mortality, retrieved using both Social Security Database and hospital records. We also compared the results of this group with a historical cohort of patients with LV dysfunction undergoing BMS implantation; 121 patients who received > or =1 DES were enrolled. The mean LVEF was 36 +/- 8%, with 20 patients (16%) with a LVEF < or =25%; 36 patients (30%) had diabetes mellitus, and DES implantation was considered off-label in 100 patients (83%). Survival at 1-, 2-, and 3-year follow-up was 94% (95% confidence interval [CI] 88 to 100), 90% (95% CI 82 to 98) and 88% (95% CI 80 to 96), respectively. In conclusion, the favorable results of this study demonstrate the safety of DES in patients with LV dysfunction.