A 6-month follow-up of intermittent levosimendan administration effect on systolic function, specific activity questionnaire, and arrhythmia in advanced heart failure

BackgroundLevosimendan (LS) improves cardiac contractility without increasing myocardial oxygen demand. We administrated LS on a monthly intermittent 24-hour protocol and evaluated the clinical effect after 6 months in a randomized, open, prospective study.Methods and ResultsFifty patients (age 45–65 years) with LV systolic dysfunction and New York Heart Association (NYHA) III or IV were randomized in 2 groups. LS group (n = 25) was compared with a control group (n = 25) matched for sex, age, and NYHA class. LS was given monthly on a 24-hour intravenous protocol for 6 months. Patients were evaluated by specific activity questionnaire (SAQ) and echocardiography (ECHO) before and 3 to 5 days after last drug administration, whereas 24-hour Holter recording was performed before and during last drug administration. Patients in LS and control group had same baseline SAQ, ECHO, and Holter parameters. At the end of the study, a larger proportion of patients in the levosimendan group reported improvement in symptoms (dyspnea and fatigue) (65% versus 20% in controls, P < .01). After 6 months, the LS group had a significant increase in LV ejection fraction versus controls (28 ± 7 versus 21 ± 4 %, P = .003), LV shortening fraction (15 ± 3 versus 11 ± 3 %, P = .006) and a decrease in mitral regurgitation (1.5 ± 0.8 versus 2.7 ± 0.6, P = .0001). There was no increase in supraventricular or ventricular beats or supraventricular tachycardia and VT episodes in LS group, compared with controls. Two patients from the LS group died in the 6-month follow-up period, compared with 8 patients in the control group (8% versus 32%, P < .05).ConclusionsA 6-month intermittent LS treatment in patients with decompensated advanced heart failure improved symptoms and LV systolic function.     

Efficacy and safety of high dose versus low dose furosemide with or without dopamine infusion: The Dopamine in Acute Decompensated Heart Failure II (DAD-HF II) Trial

Aims

The role of low-dose dopamine infusion in patients with acute decompensated heart failure (ADHF) remains controversial. We aim to evaluate the efficacy and safety of high- versus low-dose furosemide with or without low-dose dopamine infusion in this patient population.

Methods and results

161 ADHF patients (78 years; 46% female; ejection fraction 31%) were randomized to 8-hour continuous infusions of: a) high-dose furosemide (HDF, n = 50, 20 mg/h), b) low-dose furosemide and low-dose dopamine (LDFD, n = 56, 5 mg/h and 5 μg kg^− 1 min^− 1 respectively), or c) low-dose furosemide (LDF, n = 55, furosemide 5 mg/h). The main outcomes were 60-day and one-year all-cause mortality (ACM) and hospitalization for HF (HHF). Dyspnea relief (Borg index), worsening renal function (WRF, rise in serum creatinine (sCr) ≥ 0.3 mg/dL), and length of stay (LOS) were also assessed. The urinary output at 2, 4, 6, 8, and 24 h was not significantly different in the three groups. Neither the ACM at day 60 (4.0%, 7.1%, and 7.2%; P = 0.74) or at one year (38.1%, 33.9% and 32.7%, P = 0.84) nor the HHF at day 60 (22.0%, 21.4%, and 14.5%, P = 0.55) or one year (60.0%, 50.0%, and 47%, P = 0.40) differed between HDF, LDFD, and LDF groups, respectively. No differences in the Borg index or LOS were noted. WRF was higher in the HDF than in LDFD and LDF groups at day 1 (24% vs. 11% vs. 7%, P < 0.0001) but not at sCr peak (44% vs. 38% vs. 29%, P = 0.27). No significant differences in adverse events were noted.

Conclusions

In ADHF patients, there were no significant differences in the in-hospital and post-discharge outcomes between high- vs. low-dose furosemide infusion; the addition of low-dose dopamine infusion was not associated with any beneficial effects.     

A propensity-matched study of the association of cardiothoracic ratio with morbidity and mortality in chronic heart failure

A high cardiothoracic ratio (CTR) is a marker of an enlarged heart and is associated with poor outcomes in patients with heart failure (HF). To what extent this association is independent of other confounders is not well known. However, to study this, propensity score matching was used to design a study in which HF patients with normal (0.50) CTRs were well balanced on all measured baseline covariates. In the Digitalis Investigation Group trial (n=7,788), 4,690 patients had high (>0.50) CTRs. Propensity scores for high CTR were calculated for each patient and were then used to match 2,586 pairs of patients with normal and high CTRs. Matched Cox regression analyses were used to estimate associations of high CTR with mortality and hospitalization during 37 months of median follow-up. All-cause mortality occurred in 28.5% (rate 919 per 10,000 patient-years of follow-up) of patients with normal CTRs and 34.3% (rate 1,185 per 10,000 patient-years) of patients with high CTRs (hazard ratio 1.35, 95% confidence interval [CI] 1.21 to 1.51, p<0.0001). All-cause hospitalization occurred in 64.8% (rate 3,513 per 10,000 patient-years) of patients with normal CTRs and 66.2% (rate 3,932 per 10,000 patient-years) of patients with high CTRs (hazard ratio 1.10, 95% CI 1.01 to 1.20, p=0.032). Respective hazard ratios for other outcomes were 1.48 (95% CI 1.30 to 1.68, p<0.0001) for cardiovascular mortality, 1.57 (95% CI 1.28 to 1.92, p<0.0001) for HF mortality, 1.18 (95% CI 1.08 to 1.30, p=0.001) for cardiovascular hospitalization, and 1.27 (95% CI 1.13 to 1.44, p<0.0001) for HF hospitalization. In conclusion, a baseline CTR>0.50 was associated with increased mortality and morbidity in ambulatory patients with chronic HF.     

Glucose lowering does not necessarily reduce cardiovascular risk in type 2 diabetes

Diabetes mellitus (DM) is a health condition characterized by glucose dysregulation and affects millions of people worldwide. The presentation of heart failure in diabetic cardiomyopathy extends over a wide phenotypic spectrum, commencing from asymptomatic, subclinical structural abnormalities to severely symptomatic biventricular dysfunction with increased mortality risk. Similarly, the spectrum of systolic dysfunction in diabetic-induced heart failure is diverse. DM leads also to cardiac electrical remodeling reacting on various targets. Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce glucagon and blood glucose levels by raising levels of the endogenous hormones glucagon-like-peptide 1 and glucose-dependent insulinotropic peptide and constitute a safe and effective glucose lowering treatment option in patients with type 2 DM. Despite DPP-4 inhibitors’ efficacy regarding glycemic control, their effect on cardiovascular outcomes (myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization, and cardiovascular death) in diabetic patients has been neutral. The potential correlation between atrial flutter and DPP-4 inhibitors administration needs further investigation.     

The management of atrial fibrillation in heart failure: an expert panel consensus

Heart Failure Reviews - Heart failure (HF) and atrial fibrillation (AF) often coexist, being closely interrelated as the one increases the prevalence and incidence and worsens the prognosis of the...     

Diabetic cardiovascular autonomic neuropathy: clinical implications

Diabetic cardiovascular autonomic neuropathy (DCAN), the impairment of the autonomic balance of the cardiovascular system in the setting of diabetes mellitus (DM), is frequently observed in both Type 1 and 2 DM, has detrimental effects on the quality of life and portends increased mortality. Clinical manifestations include: resting heart rate disorders, exercise intolerance, intraoperative cardiovascular lability, orthostatic alterations in heart rate and blood pressure, QT-interval prolongation, abnormal diurnal and nocturnal blood pressure variation, silent myocardial ischemia and diabetic cardiomyopathy. Clinical tests for autonomic nervous system evaluation, heart rate variability analysis, autonomic innervation imaging techniques, microneurography and baroreflex analysis are the main diagnostic tools for DCAN detection. Aldose reductase inhibitors and antioxidants may be helpful in DCAN therapy, but a regular, more generalized and multifactorial approach should be adopted with inclusion of lifestyle modifications, strict glycemic control and treatment of concomitant traditional cardiovascular risk factors, in order to achieve the best therapeutic results. In the present review, the authors provide aspects of DCAN pathophysiology, clinical presentation, diagnosis and an algorithm regarding the evaluation and management of DCAN in DM patients.     

The Emerging Role of Galectin-3 and ST2 in Heart Failure: Practical Considerations and Pitfalls Using Novel Biomarkers

Heart failure (HF) is a leading cause of morbidity and mortality worldwide and, despite recent advances in therapy HF hospitalization rates remains unacceptably high. Prompt identification and optimal management of HF can affect long-term outcome. A valuable tool with diagnostic, prognostic, and treatment-guiding properties in this respect will be very useful, as exemplified by natriuretic peptides. However, natriuretic peptide levels show biological variation and are dependent on age, renal function, and body mass index. Recent advances in the field of molecular biology and HF pathophysiology have led to the discovery of other novel biomarkers that may have advantages. Among others, Galectin-3 (GAL3) and sST2 are 2 promising biomarkers that have been recently developed and can be used alone or in combination with natriuretic peptides in clinical practice. In the current paper, we review the existing data regarding GAL3 and sST2 in HF.     

Epidemiology and Importance of Renal Dysfunction in Heart Failure Patients

Renal dysfunction (RD) is a frequent comorbid condition and a major determinant of outcomes in patients with heart failure (HF). It is likely that the etiology of RD in patients with HF is much more complex than we first thought and represents a matrix of independent, albeit interacting, pathophysiological pathways with effects on both the kidney and the heart that share a common denominator: aging and inflammation. Renal dysfunction in HF has been attributed, among others, to biochemical, hormonal, and hemodynamic factors, coupled with pharmacological interventions. Regardless of the cause, the development of RD or worsening renal function is common in patients with HF, and is associated with increased morbidity and mortality. There is increasing evidence, however, that transient increases in creatinine in the setting of acute HF are not prognostically important, whereas persistent deterioration does portend a higher mortality in this patient population. In addition, congestion seems to play an important role in the course of renal deterioration, and the combination of congestion and worsening renal function is the most significant clinical prognosticator in HF patients. This review aims to provide an update on the epidemiology and prognostic significance of RD in HF patients, in both the acute and the chronic setting.