Simple mental and verbal activities markedly affect HRV through changes in respiratory frequency. This possibility should be taken into account when analyzing HRV without simultaneous acquisition and analysis of respiration.

Our data first show that ED is a powerful predictor of cardiovascular morbidity and mortality in diabetic patients with silent CAD and that the treatment with statins and 5-PDE inhibitors might reduce the occurrence of MACE among CAD diabetic patients with ED.

Parasympathetic reinnervation depends on the surgical technique: because bicaval surgery cuts all sympathetic and parasympathetic nerves, regeneration might be stimulated similarly in both branches. Standard surgery cuts only approximately 50% of sympathetic fibers; most recipient parasympathetic axons remain intact, hence their regeneration might not be stimulated.

Background and aims Despite anticoagulation, usually with heparin, mortality for thromboembolic events in COVID-19 remains high. Clinical efficacy of heparin is due to its interaction with antithrombin (AT) that may be decreased in COVID-19. Therefore, we correlated AT levels with outcomes of COVID-19. Methods and results We recruited 49 consecutive patients hospitalized for COVID-19. AT levels were significantly lower in 16 non-survivors than in 33 survivors (72.2 ± 23.4 versus 94.6 ± 19.5%; p = 0.0010). A multivariate Cox regression analysis showed that low AT (levels below 80%) was a predictor of mortality (HR:3.97; 95%CI:1.38 to 11.43; p = 0.0103). BMI was the only variable that showed a significant difference between patients with low and those with normal AT levels (32.9 ± 7.9 versus 27.5 ± 5.9%; p = 0.0104). AT levels were significantly lower in obese patients than in subjects with normal weight or overweight (77.9 ± 26.9 versus 91.4 ± 26.9 versus 91.4 ± 17.1%; p = 0.025). An inverse correlation between AT levels and BMI was documented (r:-0.33; p = 0.0179). Conclusions Our data first suggest that AT is strongly associated with mortality in COVID-19. In addition, AT may be the link between obesity and a poorer prognosis in patients with COVID-19. Other studies should confirm whether AT may become a prognostic marker and a therapeutic target in COVID-19.

BackgroundThe independent prognostic impact of diabetes mellitus (DM) and prediabetes mellitus (pre‐DM) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐DM on survival outcomes in the GISSI‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial.Methods and ResultsWe assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI‐HF trial, who were stratified by presence of DM (n=2852), pre‐DM (n=2013), and non‐DM (n=2070) at baseline. Compared with non‐DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐DM patients and those with pre‐DM. Cox regression analysis showed that DM, but not pre‐DM, was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI, 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI, 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI, 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI, 1.01–1.29, respectively).ConclusionsPresence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.

Aims To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM‐HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes. Methods and results Outpatients with HFrEF in the ESC‐EORP‐HFA Long‐Term Heart Failure (HF‐LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM‐HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM‐HF and guideline criteria, respectively. Absent PARADIGM‐HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub‐optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub‐optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM‐HF and guidelines. One‐year heart failure hospitalization was higher (12% and 17% vs. 12%) and all‐cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM‐HF. Conclusions Among outpatients with HFrEF in the ESC‐EORP‐HFA HF‐LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM‐HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM‐HF enalapril group.

The impact of the screening for asymptomatic coronary artery disease (CAD) on the cardiovascular prognosis in diabetes is controversial. The aim of the study was to investigate whether screening for asymptomatic CAD can have an impact on cardiovascular morbidity and mortality in diabetes. In this nonrandomized longitudinal study, 1,189 consecutive type 2 diabetic patients without a history of CAD were evaluated. They were subdivided into two groups according to whether they were screened (screening group, n = 921) or not (no-screening group, n = 268) for asymptomatic CAD. Among the screened patients, 386 had angiographically proven CAD (CAD group) and 535 did not have silent CAD (no-CAD group). During a mean follow-up period of 4.3 ± 1.9 years, 130 patients experienced major adverse cardiac events (MACE). The incidence of MACE was significantly greater in the no-screening than in the screening group (22.0 vs. 7.7%; p = 0.001). The Kaplan-Meier method showed that: (1) the screening was associated with a lower rate of MACE (log-rank test, 3-95; p = 0.047); (2) the no-screening group had a risk profile similar to that of CAD group (log-rank test, 2.02; p = 0.154); and (3) cardiovascular prognosis was significantly better in no-CAD than in no-screening group (log-rank test, 4.27; p = 0.039). Multivariate Cox regression analysis showed that screening for CAD (HR 0.2; 95% CI 0.2-0.3; p = 0.000) was significantly protective against the occurrence of MACE. Our data suggest that screening for asymptomatic CAD can significantly reduce cardiovascular morbidity and mortality in type 2 diabetic patients. This may be due to specific diagnostic and therapeutic interventions in diabetic patients with proven CAD at screening.

About 40% of diabetic patients with asymptomatic coronary artery disease (CAD) are missed on the basis of the current screening guidelines. Erectile Dysfunction (ED) is a powerful marker of asymptomatic CAD. Aim of the study is to evaluate whether ED can improve the effectiveness of the current guidelines for the screening of CAD in diabetes. From among 299 consecutive men with newly diagnosed type 2 diabetes without any apparent vascular complication, 293 (mean age 56.6±5.9 years) were enrolled. Among them, 219 did not have myocardial ischemia (NO CAD group) and 74 men had a coronary stenosis angiographically proven (CAD group). Five risk factors (RFs) of the current screening guidelines (hypertension, dyslipidemia, family history for CAD, smoking e micro/macroalbuminuria) and ED were assessed. ED was significantly more prevalent in the CAD than in the NO CAD group (37.8 versus 15.1%; P<0.001) and was a predictor of asymptomatic CAD (OR: 4.4; 95%CI: 2.1-9.0; P<0.001). If ED is added to the list of RFs, it can increase the sensitivity of the current guidelines from 62 to 89%, without a significant variation in specificity (from 60 to 57%). The negative predictive value can increase from 82 to 94%. ED can reduce from 37.84 to 10.81% the percentage of patients with silent CAD missed at the screening. This study first shows that ED can improve the effectiveness in discriminating diabetic men to screen for asymptomatic CAD, when it is added to the list of RFs of the current screening guidelines.