Copeptin levels and invasive hemodynamics in patients with advanced heart failure.

AIM: Arginine vasopressin is a potent vasoconstrictory hormone and arginine vasopressin release is upregulated in heart failure (HF). The aim of this study was to evaluate if copeptin (the C-terminal part of provasopressin) is related to invasive hemodynamics in HF. METHODS & RESULTS: Right heart catheterization was performed in patients with advanced HF referred for evaluation for heart transplantation. Sixty-five patients (mean age 54 ± 12 years, left ventricular ejection fraction 19 ± 8% and median copeptin levels of 16.7 pmol/l (interquartile range: 11-30 pmol/l) were included. In multivariate analysis, increased levels of log (copeptin) were associated with a reduced CI (r = 0.65 and p = 0.04). CONCLUSION: Increased copeptin levels in plasma are associated with hemodynamic parameters obtained at right heart catheterization in patients with HF, in particular-reduced cardiac index. Copeptin could be a useful biomarker for abnormal resting hemodynamics in HF.

Pump speed modulations and sub-maximal exercise tolerance in left ventricular assist device recipients: A double-blind, randomized trial.

BACKGROUND: The effect of pump speed increase on sub-maximal exercise tolerance, corresponding to activities of daily living (ADLs), is unknown. The aim of this study was to determine the effects of increasing pump speed during exercise at a sub-maximal level below anaerobic threshold (AT). METHODS: Patients each completed 3 exercise sessions on an ergometer cycle. On Day 1 workload at AT was defined. On Day 2 of the study, 2 sub-maximal tests at a workload below AT were undertaken: one at fixed baseline pump speed (Speedbase) and the other with baseline pump speed + 800 rpm (Speedinc). The sequence of the 2 sub-maximal tests was determined by randomization. Both patient and physician were blinded to the sequence. Exercise duration, oxygen consumption (VO2) and rate of perceived exertion (RPE), using the Borg scale (score 6 to 20), were recorded. RESULTS: Nineteen patients (all with a HeartMate II ventricular assist device) completed 57 exercise tests. Baseline pump speed was 9,326 ± 378 rpm. At AT, workload was 63 ± 26 W (25 to 115 W) and VO2 was 79 ± 14% of maximum. Exercise duration improved by 106 ± 217 seconds (~13%) in Speedinc compared with Speedbase (837 ± 358 vs 942 ± 359 seconds; p = 0.048). The RPE was 13.2 ± 2.5 in Speedbase vs 12.7 ± 2.4 in Speedinc (p = 0.2). CONCLUSION: Increasing pump speed by 800 rpm during sustained, low-intensity physical activity is safe and prolongs exercise duration in patients supported with a HeartMate II device. Automated pump speed increase during light exercise may contribute to improved quality of life by facilitating ADLs.

Neurohormonal activation and exercise tolerance in patients supported with a continuous-flow left ventricular assist device.

BACKGROUND: Neurohormones play a key role in regulating hemodynamics in heart failure (HF) both at rest and during exercise. In contrast, little is known about the importance of neurohormonal regulation for exercise capacity in continuous-flow left ventricular assist device (CF-LVAD) patients. The aim of this study was to assess the relation between neurohormonal activation patterns in CF-LVAD patients and exercise capacity. METHODS: Plasma concentrations of the C-terminal portion of pro-arginine vasopressin precursor (copeptin), pro-adrenomedullin (proADM), pro-B-type (proBNP) and pro-atrial (proANP) natriuretic peptides were measured in 25 CF-LVAD patients (HeartMate II) in the morning prior to maximal cardiopulmonary exercise testing determining peak oxygen uptake (peak VO2). Quality of life (QOL) was determined by questionnaires. RESULTS: Peak VO2 was severely reduced averaging 13.0±5.3ml/kg/min and exhibited strong negative correlations with copeptin, r=-0.61 (p=0.001) and proADM, r=-0.56 (p=0.005). Additionally comparing patients with peak VO2<14 vs≥14ml/kg/min demonstrated significant differences in copeptin and proADM concentrations, 2.8±0.8 vs 2.1±0.7pmol/l (p=0.03) and 1.0±0.5 vs 0.7±0.2nmol/l (p=0.01), respectively. In contrast natriuretic peptides were not associated with maximal exercise capacity. Lower QOL correlated with increasing proBNP. CONCLUSION: Resting plasma levels of proADM and copeptin are significantly correlated with peak VO2 in CF-LVAD patients. Future studies should address if interventions to lower the levels of these markers are associated with restoration of exercise tolerance.

Outcomes and hospital admissions during long-term support with a HeartMate II.

OBJECTIVES: Continuous-flow left ventricular assist devices like the HeartMate II (HMII) improves survival in severe heart failure but little is known about the incidence and causes of hospitalizations during long-term support which was evaluated in this study. DESIGN: Observational follow-up study comprising all patients who received a HMII at our institution either as bridge-to-transplantation (BTT) or destination therapy (DT). All patients were followed from HMII implantation to transplantation, device explantation, death, or May 2015. RESULTS: The HMII was implanted in 66(44 BTT, 22 DT) patients with a median (range) duration of support since implantation of 329(2-2707) days with 260(2-1080) days in the BTT group and 608(6-2707) days in the DT group. Thirty-day mortality was 12% and one-year survival 76%, comparable for DT and BTT. Among 56 (19 DT and 37 BTT) patients discharged alive with a HMII there were 161 hospital readmissions during a follow-up of 336(37-2682) days corresponding to a hospitalization rate of 1.3(0-19) per patient year and with a length of stay of 5(2-72) days per admission. Most frequent cause of readmission was infections (29%). A history of atrial fibrillation was the only independent factor associated with increased readmission rates. CONCLUSIONS: Our single-center study demonstrated encouraging survival following HMII implantation. Hospital readmissions were frequent, mostly of short duration, mainly due to infections and increased in patients with atrial fibrillation.

Exercise in heart failure patients supported with a left ventricular assist device.

After implantation of a continuous-flow left ventricular assist device (CF-LVAD), exercise capacity in heart failure patients remains reduced with peak oxygen uptake (peak VO2) values averaging from 11 to 20 ml/kg/min. Total cardiac output in CF-LVAD patients during exercise is predominantly determined by pump speed, the pressure difference across the pump, and in some cases ejection through the aortic valve. Fixed pump speed utilized in CF-LVADs may provide insufficient support, resulting in a moderate cardiac output increase during increased physical strain. Ongoing studies are evaluating whether pump speed changes in response to varied loading conditions may enable LVADs to provide sufficient support even during strenuous exercise. In the currently used devices, evidence suggests that focus on optimizing non-cardiac peripheral parameters is vital. Extra-cardiac potentially reversible factors are anemia with low oxygen-carrying capacity, obesity and general deconditioning with low muscle mass. In addition, exercise training in CF-LVAD patients can improve peak VO2. To design interventions to improve functional capacity in patients treated with modern durable LVADs, a detailed understanding of exercise physiology in a continuous-flow circulatory system is necessary. In this review we address the different components of exercise physiology in LVAD patients and point out potential solutions or areas of future research.

Effect of increasing pump speed during exercise on peak oxygen uptake in heart failure patients supported with a continuous-flow left ventricular assist device. A double-blind randomized study.

AIMS: Continuous-flow left ventricular assist device (CF-LVAD) implantation is associated with improved quality of life, but the effect on exercise capacity is less well documented. It is uncertain whether a fixed CF-LVAD pump speed, which allows for sufficient circulatory support at rest, remains adequate during exercise. The aim of this study was to evaluate the effects of fixed versus incremental pump speed on peak oxygen uptake (peak VO2) during a maximal exercise test. METHODS AND RESULTS: In CF-LVAD (HeartMate II) patients exercise testing measuring peak oxygen uptake (VO2) was performed on an ergometer bike twice in one day: once with fixed pump speed (testfix) and once with incremental pump speed (testinc). The order of testfix and testinc in each patient was determined by randomization. During testinc pump speed was increased from the baseline value by 400 rpm/2 min. Fourteen patients (aged 23­69 years) were included with a mean support duration of 465±483 days. Baseline CF-LVAD speed was 9357±238 rpm and during testinc speed was increased by a mean of 1486±775 rpm. Mean peak VO2 was significantly higher in testinc compared with testfix (15.4±5.9 mL/kg/min vs. 14.1±6.3 mL/kg/min; P=0.012), corresponding to a 9.2% increase. All exercise tests (n=28) were adequately performed with RER>1. CONCLUSION: Increasing pump speed during exercise augments peak VO2 in patients supported with CF-LVADs. An automatic speed-change function in future generations of CF-LVADs might improve functional capacity.