Takotsubo syndrome (TTS) represents a form of acute heart failure featured by reversible left ventricular systolic dysfunction. The management during the acute phase is mainly performed with supportive pharmacological (diuretics, ACE-inhibitors/angiotensin-receptor blockers (ARBs), anticoagulants, antiarrhythmics, non-catecholamine inotropics (levosimendan), and non-pharmacological (mechanical circulatory and respiratory support) therapy, due to the wide clinical presentation and course of the disease. However, there is a gap in evidence and there are no randomized and adequately powered studies on clinical effectiveness of therapeutic approaches. Some evidence supports the use ACE-inhibitors/ARBs at long-term. A tailored approach based on cardiovascular and non-cardiovascular risk factors is strongly suggested for long-term management. The urgent need for evidence-based treatment approaches is also reflected by the prognosis following TTS. The acute phase of the disease can be accompanied by various cardiovascular complications. In addition, long term outcome of TTS patients is also related to non-cardiovascular comorbidities. Physical triggers such as hypoxia and acute neurological disorders in TTS are associated with a poor outcome.

Purpose: The use of sodium-glucose-cotransporter-type-2 inhibitors (SGLT2i) was associated in previous studies with an improved vascular function in non-human experimental models. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with chronic heart failure (CHF) and type-2 diabetes mellitus (T2DM), switching from other oral hypoglycemic agents to SGLT2i in an observational study. Methods: Twenty-two consecutive outpatients with CHF and T2DM were enrolled after switching to SGLT2i therapy, and compared with 23 consecutive controls from the same registry comparable for principal clinical characteristics. In all patients, endothelial function was assessed by FMD at baseline and after 3 months of follow-up. Results: Three months of therapy with SGLT2i were associated with a statistically significant improvement in endothelial function (19.0 ± 5.7% vs 8.5 ± 4.1%, p < 0.0001); baseline levels of FMD were comparable between groups (p n.s.). Therapy with SGLT2i was significantly associated to improved FMD levels even at multivariable stepwise regression analysis (p < 0.001). Conclusions: Switch to SGLT2i in patients with CHF and T2DM was associated in an observational non-randomized study with an improved endothelial function.

Background Several hematological indices including subtypes of leukocytes populations have been associated with cardiovascular outcome. Takotsubo syndrome (TTS) is a form of acute heart failure syndrome featured by several in-hospital complications (IHCs). Hypothesis Hematological indices at admission may predict IHCs in TTS patients. Methods One hundred and sixty consecutive patients with TTS were enrolled in a multicenter prospective registry. Clinical data, admission hemogram, and IHCs were recorded. Results Incidence of IHCs was 37%, including pulmonary edema 9%, cardiogenic shock 9%, need of invasive ventilation 10%, death 8%, stroke 2.5%, and left ventricular thrombi 6%. Patients with IHCs were older, more frequently male, with physical stressor-induced TTS, lower left ventricular ejection fraction at admission. Neutrophil/lymphocyte ratio (NLr) (12 +/- 12 vs 7 +/- 8,P= .002) and white blood cells/mean platelet volume ratio (1.2 +/- 0.5 vs 1.0 +/- 0.5,P= .03) at admission were significantly higher in patients with IHCs. NLr values were predictor of IHCs (Odds ratios [OR] 1.07, 95% CI 1.03-1.11,P < .01). When stratified according to NLr into tertiles, the rate of IHCs was from first to third tertile was, respectively, 22%, 31%, and 58%. NLr values in the higher tertile were independent predictors of IHCs even at multivariate analysis (OR 3.7, 95% CI 1.5-9.4,P < .01). NLr values higher than 5 were able to predict IHCs with a sensitivity of 82% and specificity of 58%; negative predictive power was 84% (area under the ROC curve 0.73). Conclusions NLr is an independent predictor of IHCs in patients admitted with TTS. Admission hemogram may represent a potential tool for prediction of IHCs in TTS.

(1) Background: Previous studies showed left ventricular (LV) and left atrial (LA) improvement and reverse remodeling after therapy with Sacubitril/Valsartan (S/V) in patients affected by heart failure with reduced ejection fraction (HFrEF). Therefore, we sought to investigate predictors of LA structural and functional reverse remodeling (LARR) in this setting of patients after therapy with S/V, focusing on left atrial strain parameters, such as peak atrial longitudinal strain (PALS). (2) Methods: Patients with HFrEF underwent clinical and echocardiographic evaluation at baseline and after six months of therapy with S/V. Measures of LA structure (LA volume index, LAVi) and function (LA emptying fraction (LAEF), PALS, LA conduit strain and peak atrial contraction strain (PACS) were also analyzed. Patients were divided in two groups, those with a LARR (relative reduction in LAVi > 15%, LARR+) and those without (LARR−). (3) Results: A total of 47 consecutive patients (66 ± 8 years, 85% male, mean LVEF 28 ± 6%) were enrolled in the study and followed up. A significant increase of LAEF (46 ± 13 vs. 37 ± 11%, p < 0.001) and a significant reduction of LAVi (42 ± 15 vs. 45 ± 15 mL/m², p = 0.008) were found after 6 months of S/V therapy; 47% of the population showed LA reverse remodeling. LA strain parameters, PALS (19 ± 8 vs. 15 ± 7 %, p < 0.001) and LA conduit (−9.7 ± 5.2% vs. −7.6 ± 4.1%, p = 0.007) significantly improved after 6 months of S/V therapy. At multivariable stepwise regression analysis, changes in LV End Diastolic Volume (LVEDV) and PALS were significantly proportional to changes in LAVi values. (4) Conclusions: Six months of treatment with S/V in patients with HFrEF was associated with an improvement in LA functional reverse remodeling in a real-world scenario. LARR was not significantly correlated to baseline echocardiographic variables, but was proportional to changes in LV volumes and LA strain parameters. Finally, after S/V therapy, a strict connection between LA and LV reverse remodeling and between LA anatomical and functional reverse remodeling seems to be outlined.