The Treatment of Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Chronic congestive heart failure is a common condition that, if untreated, markedly impairs the quality of life and is associated with a high risk of recurrent hospitalization and death. METHODS: This review is based on articles retrieved by a selective search in PubMed, as well as on relevant guidelines. RESULTS: Evidence-based treatment options are available only for congestive heart failure with a low ejection fraction. Pharma - cotherapy is based on neurohumoral inhibition of the renin-angiotensin-aldosterone system and the adrenergic system. The prognosis of patients with this condition has been further improved recently through the introduction of combined angiotensin receptor antagonists and neprilysin inhibitors. Modern implantable devices are a further component of treatment. Implantable defibrillators and special pacemakers for cardiac resynchronization are well established; the utility of alternative devices (baroreflex modulation or cardiac contractility modulation) needs to be investigated in further studies. It was recently shown that the catheter-based treatment of secondary mitral regurgitation with a MitraClip improves the outcome of selected patients. CONCLUSION: The treatment of chronic systolic heart failure as recommended in the relevant guidelines, with drugs and implanted devices if indicated, can significantly improve the clinical outcome.

Rationale and design of the DIGIT-HF trial (DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure): a randomized, double-blind, placebo-controlled study.

AIMS: Despite recent advances in the treatment of chronic heart failure (HF), mortality and hospitalizations still remain high. Additional therapies to improve mortality and morbidity are urgently needed. The efficacy of cardiac glycosides - although regularly used for HF treatment - remains unclear. DIGIT-HF was designed to demonstrate that digitoxin on top of standard of care treatment improves mortality and morbidity in patients with HF and a reduced ejection fraction (HFrEF). METHODS: Patients with chronic HF, New York Heart Association (NYHA) functional class III-IV and left ventricular ejection fraction (LVEF) ≤ 40%, or patients in NYHA functional class II and LVEF ≤ 30% are randomized 1:1 in a double-blind fashion to treatment with digitoxin (target serum concentration 8-18 ng/mL) or matching placebo. Randomization is stratified by centre, sex, NYHA functional class (II, III, or IV), atrial fibrillation, and treatment with cardiac glycosides at baseline. A total of 2190 eligible patients will be included in this clinical trial (1095 per group). All patients receive standard of care treatment recommended by expert guidelines upon discretion of the treating physician. The primary outcome is a composite of all-cause mortality or hospital admission for worsening HF (whatever occurs first). Key secondary endpoints are all-cause mortality, hospital admission for worsening HF, and recurrent hospital admission for worsening HF. CONCLUSION: The DIGIT-HF trial will provide important evidence, whether the cardiac glycoside digitoxin reduces the risk for all-cause mortality and/or hospital admission for worsening HF in patients with advanced chronic HFrEF on top of standard of care treatment.

Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial.

AIMS: To determine the effect of the glucagon-like peptide-1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes. METHODS AND RESULTS: LIVE was an investigator-initiated, randomised, double-blinded, placebo-controlled multicentre trial. Patients (n = 241) with reduced left ventricular ejection fraction (LVEF ≤45%) were recruited (February 2012 to August 2015). Patients were clinically stable and on optimal heart failure treatment. Intervention was liraglutide 1.8 mg once daily or matching placebo for 24 weeks. The LVEF was similar at baseline in the liraglutide and the placebo group (33.7 ± 7.6% vs. 35.4 ± 9.4%). Change in LVEF did not differ between the liraglutide and the placebo group; mean difference (95% confidence interval) was -0.8% (-2.1, 0.5; P = 0.24). Heart rate increased with liraglutide [mean difference: 7 b.p.m. (5, 9), P < 0.0001]. Serious cardiac events were seen in 12 (10%) patients treated with liraglutide compared with 3 (3%) patients in the placebo group (P = 0.04). CONCLUSION: Liraglutide did not affect left ventricular systolic function compared with placebo in stable chronic heart failure patients with and without diabetes. Treatment with liraglutide was associated with an increase in heart rate and more serious cardiac adverse events, and this raises some concern with respect to the use of liraglutide in patients with chronic heart failure and reduced left ventricular function. More data on the safety of liraglutide in different subgroups of heart failure patients are needed.

Prehospital lung ultrasound for the diagnosis of cardiogenic pulmonary oedema: a pilot study.

BACKGROUND: An improved prehospital diagnostic accuracy of cardiogenic pulmonary oedema could potentially improve initial treatment, triage, and outcome. A pilot study was conducted to assess the feasibility, time-use, and diagnostic accuracy of prehospital lung ultrasound (PLUS) for the diagnosis of cardiogenic pulmonary oedema. METHODS: A prospective observational study was conducted in a prehospital setting. Patients were included if the physician based prehospital mobile emergency care unit was activated and one or more of the following two were present: respiratory rate >30/min., oxygen saturation <90 %. Exclusion criteria were: age <18 years, permanent mental disability or PLUS causing a delay in life-saving treatment or transportation. Following clinical assessment PLUS was performed and presence or absence of interstitial syndrome was registered. Audit by three physicians using predefined diagnostic criteria for cardiogenic pulmonary oedema was used as gold standard. RESULTS: A total of 40 patients were included in the study. Feasibility of PLUS was 100 % and median time used was 3 min. The gold standard diagnosed 18 (45.0 %) patients with cardiogenic pulmonary oedema. The diagnostic accuracy of PLUS for the diagnosis of cardiogenic pulmonary oedema was: sensitivity 94.4 % (95 % confidence interval (CI) 72.7-99.9 %), specificity 77.3 % (95 % CI 54.6-92.2 %), positive predictive value 77.3 % (95 % CI 54.6-92.2 %), negative predictive value 94.4 % (95 % CI 72.7-99.9 %). DISCUSSION: The sensitivity of PLUS is high, making it a potential tool for ruling-out cardiogenic pulmonary. The observed specificity was lower than what has been described in previous studies. CONCLUSIONS: Performed, as part of a physician based prehospital emergency service, PLUS seems fast and highly feasible in patients with respiratory failure. Due to its diagnostic accuracy, PLUS may have potential as a prehospital tool, especially to rule out cardiogenic pulmonary oedema.