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Aims: Chronic heart failure is associated with a bone‐catabolic state and increases the risk of osteoporosis and fractures. Prospective studies investigating the clinical relevance of bone disease in heart failure are lacking. We aimed to assess the prevalence and prognostic impact of osteoporosis and vertebral fractures (VFs) in chronic heart failure with reduced ejection fraction (HFrEF). Methods and results: Symptomatic outpatients with chronic heart failure and a previous diagnosis of overtly reduced left ventricular ejection fraction < 40% on stable, optimal HFrEF therapy and left ventricular ejection fraction < 50% at enrolment were included into a prospective single‐centre study. Osteoporosis was determined with dual‐energy X‐ray absorptiometry and defined as a T‐score ≤ 2.5 at any site. VFs were assessed using X‐ray of both thoracic and lumbar spine applying the semiquantitative Genant score. We enrolled 205 patients (22% women), with a median age of 66 (IQR 58–74) years. Median left ventricular ejection fraction was 37 (IQR 30–43) % and median N‐terminal pro B‐type natriuretic peptide was 964 (IQR 363–2173) pg/mL. Osteoporosis, as defined by bone mineral density, and at least one VF were prevalent in 31 (15%) and 29 patients (14%). Osteoporosis or VF were present in 55 patients (27%) and 5 patients (2%) had both osteoporosis and a VF. During a median follow‐up of 4.7 (IQR 4.0–5.3) years, 18 patients (9%) died due to cardiovascular (CV) cause, and 46 patients (22%) had a worsening heart failure (WHF) hospitalization. In multivariate Cox regression analyses, presence of VF independently predicted CV death (HR 2.82, 95% CI 1.04–7.65, P = 0.042), WHF hospitalizations (HR 2.39, 95% CI 1.18–4.82, P = 0.015), and a composite endpoint of CV death and WHF hospitalizations (HR 2.44, 95% CI 1.23–4.82, P = 0.011). Osteoporosis was not significantly associated with CV events. Conclusions: In a prospective study, bone disease affected every fourth patient with HFrEF, and patients with VF at baseline had a two‐fold risk of subsequent CV death or WHF hospitalization. Prevalent bone disease, particularly VF, should be considered as a clinically relevant comorbidity in HFrEF. [ABSTRACT FROM AUTHOR]

Aim: The LeoDOR trial explored the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute heart failure (HF). Methods and results: In this prospective multicentre, double‐blind, two‐armed trial, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or matching placebo for 12 weeks. All patients had left ventricular ejection fraction (LVEF) ≤30% during index hospitalization. Levosimendan was administered according to centre preference either as 6 h infusion at a rate of 0.2 μg/kg/min every 2 weeks, or as 24 h infusion at a rate of 0.1 μg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank score consisting of three hierarchical groups. Secondary clinical endpoints included the composite risk of tiers 1 and 2 at 14 and 26 weeks, respectively. Due to the COVID‐19 pandemic, the planned number of patients could not be recruited. The final modified intention‐to‐treat analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm), which reduced the statistical power to detect a 20% risk reduction in the primary endpoint to 60%. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint: the mean rank score was 72.55 for the levosimendan group versus 73.81 for the placebo group (p = 0.863). However, there was a signal towards a higher incidence of the individual clinical components of the primary endpoint in the levosimendan group versus the placebo group both after 14 weeks (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.12–7.68; p = 0.021) and 26 weeks (HR 1.64, 95% CI 0.87–3.11; p = 0.122). Conclusions: Among patients recently hospitalized with HF and reduced LVEF, intermittent levosimendan therapy did not improve post‐hospitalization clinical stability. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of basal‐bolus insulin therapy in managing glycaemia during fasting periods in hospitalized patients with type 2 diabetes. Materials and Methods: We performed a post hoc analysis of two prospective, uncontrolled interventional trials that applied electronic decision support system‐guided basal‐bolus (meal‐related and correction) insulin therapy. We searched for fasting periods (invasive or diagnostic procedures, medical condition) during inpatient stays. In a mixed model analysis, patientsʼ glucose levels and insulin doses on days with regular food intake were compared with days with fasting periods. Results: Out of 249 patients, 115 patients (33.9% female, age 68.3 ± 10.3 years, diabetes duration 15.1 ± 10.9 years, body mass index 30.1 ± 5.4 kg/m2, HbA1c 69 ± 20 mmol/mol) had 194 days with fasting periods. Mean daily blood glucose (BG) was lower (modelled difference [ModDiff]: −0.5 ± 0.2 mmol/L, P =.006), and the proportion of glucose values within the target range (3.9‐10.0 mmol/L) increased on days with fasting periods compared with days with regular food intake (ModDiff: +0.06 ± 0.02, P =.005). Glycaemic control on fasting days was driven by a reduction in daily bolus insulin doses (ModDiff: −11.0 ± 0.9 IU, P <.001), while basal insulin was similar (ModDiff: −1.1 ± 0.6 IU, P =.082) compared with non‐fasting days. Regarding hypoglycaemic events (BG < 3.9 mmol/L), there was no difference between fasting and non‐fasting days (χ2 0.9% vs. 1.7%, P =.174). Conclusions: When using well‐titrated basal‐bolus insulin therapy in hospitalized patients with type 2 diabetes, the basal insulin dose does not require adjustment during fasting periods to achieve safe glycaemic control, provided meal‐related bolus insulin is omitted and correction bolus insulin is tailored to glucose levels. [ABSTRACT FROM AUTHOR]

Amyloid light chain (AL) cardiomyopathy is the most malignant specific cardiomyopathy. According to international recommendations, it should be ruled out non‐invasively using the serum free light chain (FLC) ratio and immunofixation electrophoresis in both serum and urine. Here, we report on a 69‐year‐old female patient with new‐onset heart failure with mid‐range ejection fraction. Cardiac imaging was highly suggestive of cardiac amyloidosis. Amyloid scintigraphy showed faint myocardial tracer uptake according to Perugini Score 1, but immunofixation was negative and the FLC ratio was normal, despite a slight increase in lambda FLCs. Endomyocardial biopsy revealed advanced myocardial lambda immunoglobulin light chain deposition. Clinically relevant extracardiac amyloid organ infiltration could not be detected. Conclusively, non‐invasive testing can in rare cases fail to exclude isolated AL amyloid cardiomyopathy. We suggest that even slight increases in serum lambda or kappa FLCs should be considered abnormal in suspected cardiac amyloidosis if non‐invasive testing delivers discrepant results. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the influence of endomyocardial biopsy (EMB)-proven intramyocardial inflammation on mortality in patients with cardiac transthyretin amyloid (ATTR) or amyloid light-chain (AL) amyloidosis.Methods and Results: We included 54 consecutive patients (mean age 68.83 ± 9.59 years; 45 men) with EMB-proven cardiac amyloidosis. We followed up patients from first diagnostic biopsy to as long as 36 months (mean 11.5 ± 12 months) and compared their outcome with information on all-cause mortality with or without proof of inflammation on EMB. Intramyocardial inflammation was assessed by quantitative immunohistology. Patients suffering from amyloidosis revealed a significant poor prognosis with proof of intramyocardial inflammation in contrast to those without inflammation (log-rank P = 0.019). Re-grouping of patients indicated AL amyloidosis to have a significant impact on all-cause mortality (log-rank P = 0.012). The detailed subgroup analysis showed that patients suffering from AL amyloidosis with intramyocardial inflammation have a significantly worse prognosis compared with AL amyloidosis without inflammation and ATTR with or without inflammation, respectively (log-rank P = 0.014, contingency Fisher's exact test, P = 0.008).Conclusion: Our study reports for the first time a high incidence (48.1%) of intramyocardial inflammation in a series of patients with EMB-proven cardiac amyloidosis and could show that in patients with AL amyloidosis, intramyocardial inflammation correlated significantly with increased mortality. Our data have a direct clinical impact because one can hypothesize that additional immunomodulating/anti-inflammatory treatment regimens in patients with biopsy-proven inflammation of heart muscle tissue could be beneficial for patients suffering from cardiac AL amyloidosis. [ABSTRACT FROM AUTHOR]

Aims To evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure (HF) are adopted in clinical practice. Methods and results The ESC-HF Long-Term Registry is a prospective, observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries, members of the European Society of Cardiology (ESC). From May 2011 to April 2013, a total of 12 440 patients were enrolled, 40.5% with acute HF and 59.5% with chronic HF. Intravenous treatments for acute HF were heterogeneously administered, irrespective of guideline recommendations. In chronic HF, with reduced EF, renin–angiotensin system (RAS) blockers, beta-blockers, and mineralocorticoid antagonists (MRAs) were used in 92.2, 92.7, and 67.0% of patients, respectively. When reasons for non-adherence were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4% of the cases, respectively. About 30% of patients received the target dosage of these drugs, but a documented reason for not achieving the target dosage was reported in almost two-thirds of them. The more relevant reasons for non-implantation of a device, when clinically indicated, were related to doctor uncertainties on the indication, patient refusal, or logistical/cost issues. Conclusion This pan-European registry shows that, while in patients with acute HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines, when the reasons for non-adherence are taken into account. Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written. [ABSTRACT FROM AUTHOR]

Aims The primary objective of the new ESC-HF Pilot Survey was to describe the clinical epidemiology of outpatients and inpatients with heart failure (HF) and the diagnostic/therapeutic processes applied across 12 participating European countries. This pilot study was specifically aimed at validating the structure, performance, and quality of the data set, for continuing the survey into a permanent registry. Methods and results The ESC-HF Pilot study is a prospective, multicentre, observational survey conducted in 136 cardiology centres from 12 European countries selected to represent the different health systems and care attitudes across Europe. All outpatients with HF and patients admitted for acute HF were included during the enrolment period (1 day per week for 8 consecutive months). From October 2009 to May 2010, 5118 patients were included in this pilot survey, of which 1892 (37%) were admitted for acute HF and 3226 (63%) for chronic HF. Ischaemic aetiology was reported in about half of the patients. In patients admitted for acute HF, the most frequent clinical profile was decompensated HF (75% of cases), whereas pulmonary oedema and cardiogenic shock were reported, respectively, in 13.3 and 2.3% of the cases. The total in-hospital mortality rate was 3.8% and was cardiovascular in 90.1% of the cases. Lowest and highest mortality rates were observed in hypertensive HF and in cardiogenic shock, respectively. More than 80% of patients with chronic HF were treated with renin–angiotensin–aldosterone system blockers and β-adrenergic blockers. However, target doses of such drugs were reached in one-third to one-fourth of the patients only. Conclusion The ESC-HF Pilot Survey is an example of the possibility of utilizing an observational methodology to get insights into the current clinical practice in Europe, whose picture will be completed by the 1-year follow-up. Moreover, this study offered the opportunity to refine the organizational structure of a long-term, extended European network. [ABSTRACT FROM AUTHOR]

Abstract: Background: Beta-blockers are recommended therapy for patients with chronic heart failure (CHF). However, there remains concern regarding tolerability of these agents in the elderly, which has contributed to the limited uptake of these agents in clinical practice. Aims: We conducted a multi-national, prospective evaluation of tolerability to carvedilol in 1030 CHF patients aged >70 years selected by their treating physician to receive this agent in everyday practice. Methods and results: NYHA Class II–IV CHF patients were assessed at baseline for key demographic parameters that may predict tolerability, then followed for 6 months after starting carvedilol. Tolerability was defined as being on ≥6.25 mg bd of carvedilol at 6 months having received a total of ≥3 months therapy. Tolerability overall was 80% with age 70–75 years 84.3%, 76–80 years 76.8% and >80 years 76.8%. Mean carvedilol dose achieved was 31.2 mg. In multivariate analysis, advanced age, low diastolic BP, LVEF, obstructive airways disease and presence of diabetes were predictors of tolerability. Conclusions: Carvedilol appears to be well tolerated in this elderly CHF patient cohort. Therefore, elderly CHF patients should not be denied treatment with carvedilol because of concerns regarding tolerability. [Copyright &y& Elsevier]

Background: Treatment of chronic heart failure is based on the results of large clinical trials, which form the basis of treatment guidelines, such as those from the European Society of Cardiology (ESC). The aim of this study was to record treatment-modalities and the implementation of guidelines of chronic heart failure in clinical practice in Austria. Methods: Overall 96 general physicians, specialists for internal medicine in private practice or in hospital outpatient departments participated in the survey. Physicians were asked to prospectively document 30 consecutive patients with chronic heart failure. Results: 1880 patients were documented. The majority of patients were treated by general physicians (57%). Coronary artery disease was the most frequent aetiology for heart failure (47%). The most frequently used drugs were blockers of the renin–angiotensin-system (RAS-blocker including ACE-inhibitors and angiotensin-receptor-blockers, 78%), diuretics (76%) and beta-blockers (49%). Other drugs like digitalis and spironolactone were used infrequently. Average doses of ACE-inhibitors were approximately 90% of those recommended by the ESC, average doses of beta-blockers were approximately 50% of those recommended. Treatment among the three classes of physicians differed with respect to RAS-blockers and beta-blockers, which were used infrequently by general practitioners. Both groups of drugs were given more frequently to younger patients (<70 years) while digitalis was given more often to elderly patients. Conclusions: Results from this survey suggest that Austrian physicians treating patients with heart failure use the appropriate drugs in dosages that are suggested by recently published guidelines (ACE-inhibitors and beta-blockers). However, dosages of spironolactone clearly differed from current recommendations. [Copyright &y& Elsevier]

Background: Metoprolol is a beta(1)-selective beta-adrenergic antagonist while carvedilol is a non-selective beta-blocker with additional blockades of alpha(1)-adrenoceptors. Administration of metoprolol has been shown to cause up-regulation of beta-adrenoceptor density and to decrease nocturnal melatonin release, whereas carvedilol lacks these typical effects of beta-blocking drugs.Aims: To compare beta-blocking effects of metoprolol and carvedilol when applied orally in healthy subjects.Methods: We investigated the effects of single oral doses of clinically recommended amounts of metoprolol (50, 100 and 200 mg) and carvedilol (25, 50 and 100 mg) to those of a placebo in a randomised, double-blind, cross-over study in 12 healthy male volunteers. Two hours after oral administration of the drugs heart rate and blood pressure were measured at rest, after 10 min of exercise, and after 15 min of recovery.Results: Metoprolol tended to decrease heart rate during exercise (-21%, -25% and -24%) to a greater extent than carvedilol (-16%, -16% and -18%). At rest, increasing doses of metoprolol caused decreasing heart rates (62, 60 and 58 beats/min) whereas increasing doses of carvedilol caused increasing heart rates (62, 66 and 69 beats/min), 50 and 100 mg carvedilol failed to differ significantly from the placebo (71 beats/min).Conclusions: We conclude that clinically recommended doses of carvedilol cause a clinically relevant beta-blockade in humans predominantly during exercise where it appears to be slightly (although not significantly) less effective than metoprolol. On the other hand, the effects of carvedilol on heart rate at rest appear rather weak, particularly in subjects with a low sympathetic tone. This might be caused by a reflex increase on sympathetic drive secondary to peripheral vasodilation resulting from the alpha-blocking effects of the drug. These results might be helpful in explaining why carvedilol, in contrast to metoprolol, may fail to cause up-regulation of beta-adrenoceptor density and does not decrease nocturnal melatonin release. This, in turn, may be a reason for the weak side-effects of carvedilol resulting from the beta-blockade. In addition, our data might be of interest in the interpretation of the forthcoming results of the COMET trial, although it has to be emphasised that they were derived from healthy subjects and, therefore, cannot be directly extrapolated to patients with heart failure. [ABSTRACT FROM AUTHOR]