Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register.

Aims: This sub-study deriving from a multicentre Italian register [Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry (DISCOVER)-ARNI] investigated whether sacubitril/valsartan in addition to optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator (ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors. Methods and results: In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical, and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had no indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV) ejection fraction (EF) ≤ 35% and New York Heart Association (NYHA) class = II-III, 69 (60%) did not show ICD indications; 44 (40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation > moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With receiver operating characteristic curves, age ≥ 75 years, LAVi ≥ 42 mL/m2 and LV GLS ≥-8.3% were associated with ICD indications persistence (area under the curve = 0.65, 0.68, 0.68, respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models. Conclusions: Sacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.

77 Routine outpatients visits during SARS-CoV2 global pandemic.

Aims: The inability to carry office visits was collateral damage caused by the Coronavirus (COVID-19) pandemic. Tele-health is a relatively new, and yet fundamental amid the current crisis, resource to bridge the gap between phisicians and patients. Methods and results: We report our experience with telemedicine and describe the major events occured in our patients. 121 consecutive adult patients with arterial hypertension (F/M: 56/65; mean age: 66.8 years) were enrolled. 33 patients (27%) had also diabetes, 94 (78%) were also affected from dyslipidemia and 11 (9%) had CAD. They all referred to our ambulatory of hypertension, in most of case for several years. Given the impossibility to continue routine outpatient visits during lockdown, they were all phone called by three residents in order to detect their state of health or any events they could have experienced over this period. They were all asked about their own blood pressure values, the occurrence of new symptoms and of new-onset both cardiovascular and non cardiovascular events. We also followed a self-made preset form. 31 of them (26%) experienced cardiovascular symptoms/events during this period: 11 had hypertensive peaks, in one case associated with nausea and vomiting while 2 of them had hypotensive episodes; 10 had typical angina and/or dyspnoea while 4 had atypical angina; 6 had palpitations; 1 of them developed new onset atrial fibrillation resolved with pharmacologic cardioversion during hospitalization; 1 had syncope; 1 patient reported new onset peripheral oedema; 2 patients died during lockdown for non cardiovascular causes. 17 of them also developed non cardiovascular symptoms, 7 of whom were severe anxiety and/or panic attacks. Almost all patients had important lifestyle changes, in 15 cases (12.3%) associated with weight increase. Conclusion: The impossibility to access to routine outpatient visits during lockdown due to global pandemic of SARS-CoV2, has brought out the risk of underestimating consequences of chronic disease, in absence of appropriate Follow-up. Nevertheless, the two deaths we report were not related to cardiovascular disease. The risk is that both the missing of cardiovascular control visit and the extension of the waiting list, could provoke serious complications in patients suffering from chronic cardiovascular disease.

Strain-oriented strategy for guiding cardioprotection initiation of breast cancer patients experiencing cardiac dysfunction.

AIMS: This study assessed the impact of the strain-guided therapeutic approach on cancer therapy-related cardiac dysfunction (CTRCD) and rate of cancer therapy (CT) interruption in breast cancer. METHODS AND RESULTS: We enrolled 116 consecutive female patients with HER2-positive breast cancer undergoing a standard protocol by EC (epirubicine + cyclophosphamide) followed by paclitaxel + trastuzumab (TRZ). Coronary artery, valvular and congenital heart disease, heart failure, primary cardiomyopathies, permanent or persistent atrial fibrillation, and inadequate echo-imaging were exclusion criteria. Patients underwent an echo-Doppler exam with determination of ejection fraction (EF) and global longitudinal strain (GLS) at baseline and every 3 months during CT. All patients developing subclinical (GLS drop >15%) or overt CTRCD (EF reduction <50%) initiated cardiac treatment (ramipril+ carvedilol). In the 99.1% (115/116) of patients successfully completing CT, GLS and EF were significantly reduced and E/e' ratio increased at therapy completion. Combined subclinical and overt CTRCD was diagnosed in 27 patients (23.3%), 8 at the end of EC and 19 during TRZ courses. Of these, 4 (3.4%) developed subsequent overt CTRCD and interrupted CT. By cardiac treatment, complete EF recovery was observed in two of these patients and partial recovery in one. These patients with EF recovery re-started and successfully completed CT. The remaining patient, not showing EF increase, permanently stopped CT. The other 23 patients with subclinical CTRCD continued and completed CT. CONCLUSION: These findings highlight the usefulness of 'strain oriented' approach in reducing the rate of overt CTRCD and CT interruption by a timely cardioprotective treatment initiation.

Gender-differences in glycemic control and diabetes related factors in young adults with type 1 diabetes: results from the METRO study.

PURPOSE: To describe gender differences concerning glycemic control, cardiovascular risk factors, diabetic complications, concomitant pathologies, and circulating endothelial progenitor cells (EPCs), in a population of young adults with type 1 diabetes. METHODS: We collected data from 300 consecutively patients (168 males and 132 females), aged 18-30 years, among those admitted at Diabetes Unit of University of Campania "Luigi Vanvitelli" (Naples, Italy) from March 2012 to January 2017. Circulating levels of seven EPCs phenotypes were determined by flow cytometry. RESULTS: As compared to men, women with type 1 diabetes had a significantly higher HbA1c levels (%, 8.4 ± 1.3 vs. 8.1 ± 1.3, P = 0.020), body mass index (Kg/m2, 24.8 ± 4.2 vs. 23.9 ± 3.9, P = 0.034), HDL-cholesterol (mg/dL, 61.7 ± 13.7 vs. 54.7 ± 13.9, P < 0.001), and a lower count of both CD133+KDR+ and CD34+KDR+CD133+ EPCs (P = 0.022, P < 0.001, respectively). A higher proportion of women had overweight/obesity, and thyroiditis; smoking and sexual dysfunctions were more prevalent in men than in women. CONCLUSIONS: Young adults with type 1 diabetes present gender differences with regard to glycemic control, prevalence of some cardiovascular risk factors, sexual dysfunctions and circulating levels of EPCs, most often to the detriment of women.

The Effects of Subcutaneous Insulin Infusion Versus Multiple Insulin Injections on Glucose Variability in Young Adults with Type 1 Diabetes: The 2-Year Follow-Up of the Observational METRO Study.

BACKGROUND: Type 1 diabetic patients have high instability of daily glucose levels. The aim of this study was to evaluate the long-term effects of continuous subcutaneous insulin infusion (CSII) therapy, compared with multiple daily injections of insulin (MDI), on glucose variability, in young type 1 diabetic patients transitioned to the adult diabetes care. METHODS: Patients aged 18-30 years and considered eligible for insulin pump therapy were included in the study. Ninety-eight patients who started CSII therapy and 125 who remained in MDI completed a 2-year follow-up. Glucose variability was assessed with continuous glucose monitoring using blood glucose standard deviation (BGSD), mean amplitude of glycemic excursion (MAGE), continuous overall net glycemic action (CONGA-2 h), low blood glucose index, high blood glucose index, and average daily risk range. RESULTS: MAGE and BGSD decreased in both groups, with adjusted differences at 2 years of -0.74 mM (95% confidence interval [CI] -1.22 to -0.26, P = 0.003) and -0.3 (CI -0.52 to -0.1, P = 0.005) favoring the pump-therapy group. No significant differences between groups in the other variability indexes were observed. HbA1c decreased in both groups without significant difference (0.05%, -0.26, 0.35, P = 0.77); fasting glucose, insulin dose, and overall hypoglycemia (daily, nocturnal, and severe) decreased more in patients with CSII, compared with those with MDI. CONCLUSIONS: Among young adults with type 1 diabetes transitioning from the pediatric care, the use of CSII is associated with lower glucose variability, fasting glycemia, and overall hypoglycemic events than MDI during a 2-year period of follow-up.

Reducing glucose variability with continuous subcutaneous insulin infusion increases endothelial progenitor cells in type 1 diabetes: an observational study.

Circulating endothelial progenitor cells (EPCs) are involved in the repairing mechanisms of vascular damage. Glucose variability may contribute to the development of chronic vascular complications of diabetes. We evaluated whether reducing glucose variability with continuous subcutaneous insulin infusion (CSII) would increase circulating levels of EPCs in type 1 diabetes. The study population consisted of 106 type 1 diabetic patients: 41 subjects considered eligible for CSII completed a 6-month follow-up. Sixty-five patients on intensified insulin therapy with multiple daily injections served as control group. Seven EPCs phenotypes were assessed by flow cytometry, and glucose variability by mean amplitude of glycemic excursions (MAGE). Both CD34+KDR+ [difference between groups 32.0, 95 % CI (19.6-44.4) number/10(6) cells, P < 0.001] and CD34+KDR+CD133+ [12.5 (5.5-19.5), P < 0.001)] cell count increased at endpoint in the CSII group, associated with a reduction of MAGE [-1.1 (-2.1 to -0.1), P = 0.026]. No changes occurred in the control group. In multivariate analyses, changes in MAGE were independently associated with changes in both CD34+KDR+ (P = 0.019) and CD34+KDR+CD133+ (P = 0.022) cell count. Reducing glucose variability with CSII in type 1 diabetes increases circulating EPCs levels, suggesting a novel mechanism of vascular damage by oscillating glucose.