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The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Background: The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Methods and results: We analyzed data from HF patients (958 patients (801 males, 84%, age 67 ± 11 years)) with AF enrolled in the MECKI score database. We evaluated prognosis (composite of cardiovascular death, urgent heart transplant, or left ventricular assist device) of patients receiving β-blockers (n = 777, 81%) vs. those not treated with β-blockers (n = 181, 19%). We also analyzed the role β1-selectivity and the role of daily β-blocker dose. To account for different HF severity, Kaplan-Meier survival curves were normalized for relevant confounding factors and for treatment strategies. Dose was available in 629 patients. Median follow-up was 1312 (577–2304) days in the entire population, 1203 (614–2420) and 1325 (569–2300) days in patients not receiving and receiving β-blockers. 224 (23%, 54/1000 events/year), 163 (21%, 79/1000 events/year), and 61 (34%, 49/1000 events/year) events were recorded, respectively. At 10-year patients treated with β-blockers had a better outcome (HR 0.447, p < 0.01) with no effects as regards β1selective drugs (53%) vs. β1-β2 blockers (47%). Survival improved in parallel with β-blocker dose increase (HR 0.296, 0.496, 0.490 for the high, medium, and low dose vs. no β-blockers, p < 0.0001). Conclusion: HF patients with AF taking a β-blocker have a better outcome (with a survival improvement in parallel with daily dose but no differences as regards β1 selectivity) but this does not mean that β-blockers improve outcomes in these patients as we cannot control for all the potential confounders associated with β-blocker use.

Background This study evaluates, in a real-world setting, to what extent the recommended therapies by international guidelines, are prescribed after a first hospitalization for heart failure (HF), and to analyse adherence and persistence, and the effect of treatment adherence on mortality and re-hospitalization. Methods From the Lombardy healthcare administrative database, we analysed patients discharged after their incident HF, from 2000 to 2012. Adherence was defined as the proportion of days covered (PDC) ≥80% adjusted for hospitalizations and persistence as the absence of discontinuation of therapy for >30 days. A logit model was used to determine the effect of patients' adherence on mortality and readmissions. Results Of 100422 HF patients (52% males, age 75 ± 12 years), 86846 (87%) had a prescription for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACE/ARBs), 64135 (64%) for beta-blockers (BB), and 36893 (37%) for mineralocorticoid receptor antagonists (MRAs), as mono-, bi- or tri-therapy. In patients on monotherapy, PDC was 78 ± 22% for ACE/ARBs, 69 ± 29% for BB and 54 ± 29% for MRAs; in those on bi-therapy, PDC was 63 ± 31% for ACEI/ARBs+BB, 41 ± 29% for ACEI/ARBs+MRAs, and 40 ± 26% for MRAs+BB; for patients on tri-therapy, PDC was 42 ± 28%. Medication persistence was present in 47% of patients treated with ACEI/ARBs, in 35% of patients treated with BB and in 14% of patients treated with MRAs. Re-hospitalizations and in mortality were significantly reduced in adherent patients (p Conclusions Polypharmacy is associated with an increased rate of non-adherence and non-persistence in incident HF. Non-adherence is associated with an increased risk of mortality and re-hospitalizations.

Background The prognostic role of diabetes mellitus (DM) in heart failure (HF) patients is undefined, since DM is outweighed by several DM-related variables when confounders are considered. We determined the prognostic role of DM, treatment, and glycemic control in a real-life HF population. Methods 3927 HF patients included in the Metabolic Exercise Cardiac Kidney Index (MECKI) score database were evaluated with a median follow-up of 3.66 years (IQR 1.70–6.67). Data analysis considered survival between DM (n = 897) vs. non-DM (n = 3030) patients, and, in diabetics, between insulin (n = 304), oral antidiabetics (n = 479), and dietary only (n = 88) treatments. The role of glycemic control was evaluated grouping DM patients according to glycated hemoglobin (HbA1c): 8% (n = 149). All analyses were performed also adjusting for ejection fraction, renal function, hemoglobin, sodium, exercise peak oxygen uptake, and ventilation/carbon dioxide relationship slope. Study primary endpoint was the composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Secondary endpoints were cardiovascular and all causes death. Results For all endpoints, upon adjustment for confounders, DM status and insulin treatment or dietary regimen were not significantly associated with adverse long-term prognosis compared to non-DM and oral antidiabetic treated patients, respectively. A worse prognosis was observed in HbA1c >8% patients (Log-Rank p Conclusion In HF patients, DM, insulin treatment and dietary regimen are not adverse outcome predictors. The only condition related to long-term prognosis, considering potential confounders, is poor glycemic control.

Background The presence of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has diagnostic and prognostic value in patients with acute myocarditis (AM). Aim of our study was to quantify the changes in LGE extension (LGE%) early after AM and evaluate its relations with biventricular function and morphology. Methods We investigated 76 consecutive patients with AM (acute onset of chest pain/heart failure/ventricular arrhythmias not explained by other causes, and raised troponin) that met CMR criteria based on myocardial oedema at T2-weighted images and LGE on post-contrast images at median time of 6 days from onset of symptoms. We quantified LGE% at baseline and after 148 days in 49 patients. Results Median left ventricular (LV)-ejection fraction (EF) was 64% (interquartile range [Q1–Q3]: 56–67%), and LGE% 9.4% (Q1–Q3: 7.5–13.2%). LGE% was correlated with LV end-systolic volume index (LV-ESVi; r = + 0.34; p = 0.003). LGE% was inversely correlated with LV-EF (r = − 0.31; p = 0.009) and time to CMR scan (r = − 0.25; p = 0.028). In the 49 patients with a second CMR scan, despite no significant variations in LV-EF, a significant decrease of LGE% was observed (p < 0.0001) with a relative reduction of 42% compared with baseline. Patients showing increased LV-ESVi at follow up had a lower decrease of LGE% (p = 0.038). Conclusions In the acute phase of AM the LGE extension is a dynamic process that reflects impairment of LV function and is time dependent. LGE% appears one of the CMR parameters with the largest relative variations in the first months after AM

Background Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established. Methods We performed 12‑lead ECGs and 12‑lead 24-h Holter ECG monitoring in all patients aged, Highlights • Combination therapy with hydroxychloroquine and azithromycin prolong QT-interval in patients with COVID-19 • The risk of QTc-prolongation is higher in COVID-19 patients with high levels of transaminase. • QTc values show temporal stability over the 24-h, with no differences among different times of the day. • A periodic, not daily, QTc surveillance in COVID-19 patients is recommendable.

Introduction: No data regarding the safety of continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with previous MitraClip have been reported. Thus, it remains unknown whether an initial treatment strategy with MitraClip therapy might complicate future heart failure management in patients who are also considered for CF-LVAD. Methods: We retrospectively identified 6 patients (median age of 62 years; 2 women) who had been treated with MitraClip, that were eventually implanted with a CF-LVAD (all Heartware HVAD) in 3 hospitals between 2013 and 2018. Results: Patients were treated in 4 cases with 2 clips, and in 2 cases with 1 clip. Median time from MitraClip implantation to CF-LVAD implant was 282 days (interquartile range 67 to 493), and median time on CF-LVAD support was 401 days (interquartile range 105 to 492 days). Two patients underwent a heart transplant, 3 patients died on support, and 1 is alive on support. In all cases, there was a reduction of functional mitral regurgitation without MitraClip-related complications. Conclusions: Based on this small case series, implantation of a CF-LVAD appears safe in patients with a previously positioned MitraClip system, at least, with 1 or 2 clips in place, with no need for additional mitral valve surgery. (c) 2019 Elsevier B.V. All rights reserved.

This study was undertaken to evaluate trends in heat failure hospitalizations (HFHs) and 1-year mortality of HFH in Lombardy, the largest Italian region, from 2000 to 2012.Hospital discharge forms with HF-related ICD-9 CM codes collected from 2000 to 2012 by the regional healthcare service (n=699797 in 370538 adult patients), were analyzed with respect to in-hospital and 1-year mortality; Group (G) 1 included most acute HF episodes with primary cardiac diagnosis (70%); G2 included cardiomyopathies without acute HF codes (17%); and G3 included non-cardiac conditions with HF as secondary diagnosis (13%). Patients experiencing their first HFH since 2005 were analyzed as incident cases (n=216782).Annual HFHs number (mean 53830) and in-hospital mortality (9.4%) did not change over the years, the latter being associated with increasing age (p0.0001) and diagnosis Group (G1 9.1%, G2 5.6%, G3 15.9%, p0.0001). Incidence of new cases decreased over the years (3.62 [CI 3.58-3.67] in 2005 to 3.13 [CI 3.09-3.17] in 2012, per 1000 adult inhabitants/year, p0.0001), with an increasing proportion of patients aged ≥85y (22.3% to 31.4%, p0.0001). Mortality lowered over time in75y incident cases, both in-hospital (5.15% to 4.36%, p0.0001) and at 1-year (14.8% to 12.9%, p=0.0006).The overall burden and mortality of HFH appear stable for more than a decade. However, from 2005 to 2012, there was a reduction of new, incident cases, with increasing age at first hospitalization. Meanwhile, both in-hospital and 1-year mortality decreased in patients aged75y, possibly due to improved prevention and treatment.

Background Aminothiols have a critical function as intracellular redox buffers and constitute furthermore an important extracellular redox system. Lipid peroxidation is increased in chronic heart failure (CHF), but the contribution of each thiol to oxidative stress in this syndrome has not been evaluated. Aim To assess the correlation between blood and plasma concentrations of aminothiols and lipid peroxidation as marker of oxidative stress in CHF patients. Methods Blood reduced glutathione (GSH), plasma total and reduced cysteine, cysteinylglycine, homocysteine, GSH, α-tocopherol, ascorbic acid, and free malondialdehyde (MDA) were assessed in samples obtained from 26 CHF heart transplant candidates and 26 age- and gender-matched controls with atherosclerotic risk factors and no history of cardiovascular disease. Results are expressed as median and interquartile range (I–III). Results MDA levels were significantly higher in CHF patients than in controls [1.03 (0.56–1.60) μM vs. 0.70 (0.40–0.83) μM, p =0.006]. Blood reduced GSH concentrations were significantly higher [662 (327–867) μM vs. 416 (248–571) μM, p =0.016], while α-tocopherol levels were significantly lower [15 (13–19) μM vs. 21 (17–32) μM, p =0.001] in CHF patients than in controls. By multivariate logistic regression analysis, the only independent predictors of lipid peroxidation, as expressed by MDA levels ≥1.00 μM, were increased blood GSH concentrations (OR 1.003 per unit, 95% CI 1.001 to 1.006, p =0.008), ischemic (OR 20, 95% CI 2.6 to 155, p =0.004) and non ischemic CHF etiology (OR 11, 95% CI 1.3 to 99, p =0.026). Conclusions Abnormalities in intracellular GSH cycling are associated to increased lipid peroxidation in CHF.

Background Heart failure (HF) and chronic obstructive pulmonary disease (COPD) share a common organ failure trajectory marked by prognostic uncertainty, which is a barrier to appropriate provision of palliative care. We describe in a prospective cohort from specialist hospital services the epidemiology and late clinical course of these chronic diseases to trace criteria for transition to palliative care in the community. Methods and results Seven centers enrolled 267 patients with advanced HF (n=174) or COPD (n=93) using common (multiple hospitalizations or severely impaired functional status or cachexia) and disease-specific (HF: systolic dysfunction, NYHA classes III–IV, end-organ hypoperfusion; COPD: very severe airflow obstruction, hypoxemia, hypercapnia, or long-term oxygen therapy) entry criteria. These patients represented 7.2% and 13% respectively of the overall HF and COPD population hospitalized during one year. They showed similar symptom burden, functional and quality of life impairment, recurrent hospitalizations, and 6-month mortality (39% and 37%, respectively). Organ failure progression was the cause of death in >75%. In-hospital overall stay during the previous year was the main mortality predictor in both. Disease-specific predictors included anemia, hyponatremia, no beta-blockers in HF; older age, hypercapnia in COPD. Conclusions Patients with advanced HF/COPD represent almost 10% of subjects hospitalized yearly with a primary diagnosis of HF or COPD, have similarly impaired functional status, disabling symptoms and reduced survival. Overall days spent in-hospital during the previous year, a "red flag" in the late clinical course of both diseases, might be used as a simple, reliable screening tool for appropriate transition to palliative care in the community.

Reverse remodeling and increased LVEF after CRT correlate with survival and heart failure hospitalizations, but their relationship with the risk of SCD is unclear. We aimed to evaluate whether exceeding a threshold value of 35% for left ventricular ejection fraction (LVEF) 1 year after cardiac resynchronization therapy (CRT) predicts survival and freedom from sudden cardiac death (SCD).330 patients who survived ≥ 6 months after CRT (males 80%, age 62 ± 11 years) were grouped according to 1-year LVEF ≤ 35% (Group 1, n=187, 57%) or35% (Group 2, n=143, 43%). According to changes vs. baseline (reduction of left end-systolic volume [LVESV] ≥ 10% or increase of LVEF%10 units), patients were also classified as echocardiographic (Echo) non-responders (Group A, n=152, 46%) or responders (Group B, n=178, 54%).At baseline, LVESV volume was larger and LVEF was lower in Group 1 vs. Group 2 (p0.001). After 1 year, echocardiographic improvement was greater in Group 2 vs. Group 1 (p0.001 for changes in both LVESV and LVEF). Over a median follow-up of 49 months, 47 patients (14%) died, 36 in Group 1 vs. 11 in Group 2 (19% vs. 8%, p=0.004). A significantly higher rate of freedom from all-cause mortality (p=0.002), cardiovascular mortality (p0.001) and SCD (p0.001) was observed in Group 2. Multivariate analysis demonstrated that only 1-year LVEF35% was associated with freedom from SCD/VF.LVEF35% after 1 year of CRT characterizes a favorable long-term outcome, with a very low risk for SCD.

Background NT-proBNP has been associated with prognosis in acute decompensated heart failure (ADHF). Whether NT-proBNP provides additional prognostic information beyond that obtained from standard clinical variables is uncertain. We sought to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) determination improves risk reclassification of patients with ADHF and to develop and validate a point-based NT-proBNP risk score. Methods This study included 824 patients with ADHF (453 in the derivation cohort, 371 in the validation cohort). We compared two multivariable models predicting 1-year all-cause mortality, including clinical variables and clinical variables plus NT-proBNP. We calculated the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Then, we developed and externally validated the NT-proBNP risk score. Results One-year mortalities for the derivation and validation cohorts were 28.3% and 23.4%, respectively. Multivariable predictors of mortality included chronic obstructive pulmonary disease, estimated glomerular filtration rate, sodium, hemoglobin, left ventricular ejection fraction, and moderate to severe tricuspid regurgitation. Adding NT-proBNP to the clinical variables only model significantly improved the NRI (0.129; p=0.0027) and the IDI (0.037; p=0.0005). In the derivation cohort, the NT-proBNP risk score had a C index of 0.839 (95% CI: 0.798–0.880) and the Hosmer–Lemeshow statistic was 1.23 (p=0.542), indicating good calibration. In the validation cohort, the risk score had a C index of 0.768 (95% CI: 0.711–0.817); the Hosmer–Lemeshow statistic was 2.76 (p=0.251), after recalibration. Conclusions The NT-proBNP risk score provides clinicians with a contemporary, accurate, easy-to-use, and validated predictive tool. Further validation in other datasets is advisable.

statistical significance in a cross-sectional study seems insufficient. I think that the significant relationships between indicators of heart rate variability and plasma lipid levels should be validated in different test situations and also by follow-up study. I wish to express my appreciation to the members of the Hygiene and Public Health, Nippon Medical School, for the preparation of this study. The author of this manuscript has certified that he complies with the Principles of Ethical Publishing in the International Journal of Cardiology. References

Friend or foe? Nuccia Morici , Alice Sacco , Fabrizio Oliva , Stefano Ferrari , Roberto Paino , Filippo Milazzo , Maria Frigerio , Roberto Pirola , Silvio Klugmann , Antonio Mafrici a,⁎ a Intensive Cardiac Care Unit, Cardiovascular Department at Niguarda Ca'Granda Hospital, Milan, Italy b Interventional Cardiology, Section 1, Cardiovascular Department at Niguarda Ca'Granda Hospital, Milan, Italy c Heart transplant program, Section 2, Cardiovascular Department at Niguarda Ca'Granda Hospital, Milan, Italy d Intensive Cardiothoracic Care Unit, Cardiovascular Department at Niguarda Ca'Granda Hospital, Milan, Italy