Levosimendan in outpatients with advanced heart failure: Single-center experience of 200 intermittent perfusions.

INTRODUCTION: Patients with advanced heart failure (HF) have high morbidity and mortality, with only a small proportion being eligible for advanced therapies. Intermittent outpatient levosimendan infusion has been shown to provide symptomatic relief and reduce the rate of HF events. Our aim was to assess the safety and efficacy of outpatient levosimendan administration in an advanced HF population. METHODS: This is a report of a single-center experience of consecutive advanced HF patients referred for intermittent intravenous outpatient administration of levosimendan, between January 2018 and March 2021. Baseline and follow-up evaluation included clinical assessment, laboratory tests, transthoracic echocardiography and cardiopulmonary exercise testing. Baseline and clinical follow-up data were compared using the Wilcoxon signed-rank test. RESULTS: A total of 24 patients (60.8 years, 83% male, mean left ventricular ejection fraction [LVEF] 24%), with a median of 1.5 HF hospitalizations in the previous six months, were referred for outpatient levosimendan pulses, the majority as a bridge to transplantation or due to clinical deterioration. At six-month follow-up there was a significant reduction in HF hospitalizations to 0.4±0.7 (p<0.001). NYHA class IV (52.2% to 12.5%, p=0.025) and NT-proBNP (8812.5 to 3807.4 pg/ml, p=0.038) were also significantly reduced. Exercise capacity was significantly improved, including peak oxygen uptake (p=0.043) and VE/VCO2 slope (p=0.040). LVEF improved from 24.0% to 29.7% (p=0.008). No serious adverse events were reported. CONCLUSION: Repeated levosimendan administration in advanced HF patients is a safe procedure and was associated with a reduction in HF hospitalizations, functional and LVEF improvement, and reduction in NT-proBNP levels during follow-up.

C-reactive protein reduction with sacubitril-valsartan treatment in heart failure patients.

OBJECTIVE: C-Reactive Protein (CRP) has emerged as an accessible measured product of inflammation. Whether systemic inflammation, a common feature of Heart Failure (HF), can be reduced by HF treatments in not well established. Sacubitril/Valsartan had prognosis benefit demonstrated in the PARADIGM-HF trial and was able to reduce proinflammatory cytokines in preclinical animal studies. However, no human studies evaluated if the benefits of this therapy are mediated by anti-inflammatory effects too. The aim of this study was to prospectively compare CRP values before and six months after Sacubitril-Valsartan therapy. METHODS: Prospective evaluation of chronic HF patients with left ventricular ejection fraction ≤ 40% despite optimized standard of care therapy, in which Sacubitril/Valsartan therapy was started and no additional HF treatment was expected to change. Clinical, laboratorial (including CRP values), electrocardiographic, transthoracic echocardiography and cardiopulmonary exercise test (CPET) data were gathered in the week before starting Sacubitril/Valsartan therapy and six months thereafter. RESULTS: There were 42 patients with a mean age of 59 ± 11 years, of which 35 completed the six months of follow-up, since 2 patients died and 5 discontinued treatment for adverse events. Patients with baseline CRP values above the median (> 2.5 mg/L) had a significantly higher percentage of New York Heart Association class ≥ III (65% vs. 33%, P=0.028) and a reduced exercise time in CPET (361 ± 297 vs. 575 ± 265 seconds, P=0.034). After 6 months of Sacubitril-Valsartan therapy, 24 (69%) patients had an improvement in CRP values with a significantly reduction as compared to baseline (median 2.5 mg/L (Interquartile range (IQR) 1.3-5.0) vs. 2.2 mg/L (IQR 0.9-4.0), P=0.014 in the Wilcoxon test). In the group of 17 (49%) patients with at least 25% improvement in CRP values with Sacubitril/Valsartan therapy, the benefit of several clinical, CPET and echocardiographic parameters were not significantly different from the benefit of patients with no improvement or an improvement inferior to 25% in CRP values. CONCLUSION: Sacubitril/Valsartan therapy was able to reduce CRP values in a chronic HF population. Whether this reduction was only a consequence of clinical improvement with Sacubitril/Valsartan or an anti-inflammatory effect is also present should be further evaluated.

Myocardial work improvement after sacubitril-valsartan therapy: a new echocardiographic parameter for a new treatment.

AIMS: Myocardial work is a new transthoracic echocardiogram (TTE) parameter that enhances the information provided through left ventricular (LV) global longitudinal strain (GLS). Nothing is known about the impact of sacubitril/valsartan (LCZ696) therapy on myocardial work parameters. The aim of this study was to evaluate the effects of LCZ696 on LV myocardial work in heart failure patients. METHODS: Prospective evaluation of chronic heart failure patients with LV ejection fraction of 40% or less despite optimized standard of care therapy, in which LCZ696 therapy was started and no other heart failure treatment was expected to change. TTE study was performed before and 6 months after LCZ696 therapy. A semiautomated analysis of LV GLS was made and myocardial work estimated using custom software of the GE Vivid E95 ultrasound system. RESULTS: Of the 42 patients, 35 (83.3%) completed the 6 months, follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment due to adverse events. Mean age was 58.6 ±â€Š11.1 years. TTE data showed a significant reduction in LV dimensions and atrial volumes, as well as an improvement in LV ejection fraction (29.3 vs. 35.2%, P = 0.001) and GLS (-7.0 vs. -8.9%, P = 0.001). Myocardial work had a significant increase in global constructive work (720.2 vs. 900.6 mmHg%, P = 0.016) and global work efficiency (78.6 vs. 86.6%, P = 0.027), with a nonsignificant decrease in global wasted work (150.2 vs. 136.8 mmHg%, P = 0.441) at 6 months. CONCLUSION: LCZ696 therapy was associated with signs of reverse remodelling by usual TTE parameters and LV myocardial work at 6 months, including an increase in global constructive work and work efficiency.

Prognostic value of VE/VCO2 slope in overweight heart failure patients.

BACKGROUND: A decreased hypercapnic ventilatory response of the overweight patients would lower the ventilation equivalent of carbon dioxide (VE/VCO2) slope but worsen prognosis. The aim of this study was to compare the prognostic ability of the VE/VCO2 slope and peak oxygen consumption (pVO2) between normal and overweight heart failure (HF) patients. METHODS: Prospective evaluation of ambulatory patients with reduced left ventricular ejection fraction who underwent baseline assessment with a cardiopulmonary exercise test. The primary endpoint was cardiac death or urgent heart transplantation in the 5-year period of follow-up. The predictive power of VE/VCO2 slope and pVO2 were compared (area under the curve (AUC) analysis and Hanley & McNeil test), in the subgroups of patients with body mass index (BMI) of 18.5-24.9 kg/m2 and ≥ 25 kg/m2. Statistical differences with a p value < 0.05 were considered significant. RESULTS: There were 270 enrolled patients, with a mean BMI of 27 ± 4 kg/m2. No differences between normal and overweight patients (38.0% vs 29.8%, P=0.170) were found during the 5-year period for the primary endpoint. The VE/VCO2 slope was non-inferior to pVO2 in both groups at 1, 3 and 5 years of follow-up. The comparison of VE/VCO2 slope between groups revealed a significant lower AUC at 3 (0.921 vs 0.787, P=0.022) and 5 years (0.898 vs 0.787, P=0.044) of follow-up for overweight patients. CONCLUSION: Despite VE/VCO2 slope provides a discriminative power at least as good as pVO2 for predicting adverse events in both normal and overweight HF patients, a significant lower predictive power was found in overweight patients.

Antiarrhythmic Effect of Sacubitril-Valsartan: Cause or Consequence of Clinical Improvement?

Sacubitril/Valsartan (LCZ696) reduced sudden cardiac death in the PARADIGM-HF trial. However, the mechanism by which LCZ696 reduces ventricular arrhythmias remains unclear. The aim of this study was to compare electrocardiographic (ECG) parameters and mechanical dispersion index, assessed by left ventricular (LV) global longitudinal strain (GLS), before and after LCZ696 therapy. We prospectively evaluated chronic Heart Failure (HF) patients with LV ejection fraction ≤40%, despite optimal medical and device therapy, in which LCZ696 therapy was started, while no additional HF treatment was expected to change. ECG and transthoracic echocardiographic data were gathered in the week before starting LCZ696 and at six months of therapy. A semiautomated analysis of LV GLS was performed and mechanical dispersion index was defined as the standard deviation from 16 time intervals corresponding to each LV segment. Of the 42 patients, 35 completed the six month follow-up, since two patients died and five discontinued treatment for adverse events. QTc interval (451.9 vs. 426.0 ms, p < 0.001), QRS duration (125.1 vs. 120.8 ms, p = 0.033) and mechanical dispersion index (88.4 vs. 78.1 ms, p = 0.036) were significantly reduced at six months. LCZ696 therapy is associated with a reduction in QTc interval, QRS duration and mechanical dispersion index as assessed by LV GLS.