Oxygen Uptake During Activities of Daily Life in Patients Treated With a Left Ventricular Assist Device.

INTRODUCTION: Oxygen consumption during activities of daily life (ADL) is not described in recipients of left ventricular assist device (LVAD). We aimed to investigate the relation between oxygen consumption during predefined ADLs and measures of functional capacity (FC) in stable-phase LVAD recipients. METHODS: LVADs and controls were matched on gender, age, BMI, smoking status, and ethnicity. VO2 was measured using mobile equipment (K5, Cosmed, Rome, Italy) while putting on vest and LVAD equipment(1), folding towels(2), putting on socks and shoes(3), putting bottles in a cupboard(4), making a bed(5), walking on stairs without(6) and with extra weight(7), and sweeping the floor(8). Submaximal FC was tested by means of 6 minute walk test (6MWT) and peak oxygen uptake (pVO2) to test maximal FC. RESULTS: Fifteen LVAD patients and 16 controls were included; Patients were 61 ± 10years, all males with BMI 28 ± 5kg/m2 and implanted with Heartmate 3 (DT: 60%). PVO2 was 14.9 ± 2.2 ml/kg/min in patients and 39.6 ± 7.7 in controls (p < 0.001). Oxygen consumption expressed as percent of pVO2 for each task in patients vs controls was (%): ADL1: 41 ± 5 vs 21 ± 4, ADL2: 41 ± 6 vs 22 ± 5 %, ADL3: 50 ± 16 vs 24 ± 5%, ADL4: 45 ± 12 vs 22 ± 4, ADL5: 50 ± 8 vs 23 ± 4, ADL6: 66 ± 10 vs 30 ± 4, ADL7: 65 ± 10 vs 31 ± 5, ADL8: 75 ± 10 vs 39 ± 12, (p < 0.001 for all). During 6MWT LVAD patients used 96% ± 8 % of their pVO2. CONCLUSION: Recipients of durable LVADs perform daily life activities at oxygen uptake levels much closer to their peak cardiopulmonary reserve than matched healthy controls.

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.

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.

Relation between pressure and volume unloading during ramp testing in patients supported with a continuous-flow left ventricular assist device.

Pulmonary capillary wedge pressure (PCWP) is the key to describing left ventricular (LV) unloading; however, the relation between pressure and the echocardiography-derived surrogate of LV volume (LV end-diastolic diameter [LVEDD]) as a function of pump speed (revolutions per minute [RPM]) in continuous-flow LV assist device (CF-LVAD) patients is unknown. In this study, the pressure-volume relation as a function of RPM during ramp testing was investigated by simultaneously measuring PCWP by Swan-Ganz catheter and LVEDD by echocardiography. The ramp protocol started at usual pump setting (ramp-base) and then went from 8,000 RPM (ramp-low) increasing by 400 RPM/5 minutes until reaching 12,000 RPM or suction/arrhythmic event (ramp-high). The study was finalized by a 25 Watt exercise test at two ramp steps. Ten patients with ramp-base of 9,300 ± 241 RPM (at which 3 of 10 had aortic valve opening) were examined. At ramp-low, ramp-base, and ramp-high, PCWP was 20 ± 4, 14 ± 4, and 7 ± 3 mm Hg (p < 0.001 for all comparisons) and LVEDD 6.6 ± 1.0, 6.7 ± 0.9, and 5.5 ± 1.7 cm (p < 0.05 for all comparisons but ramp-low versus ramp-base). Correlation between PCWP and LVEDD slopes; R = 0.53 (p = 0.02). In conclusion, PCWP as a function of RPM is weakly correlated with changes in LVEDD. Thus, LVEDD is not an accurate measure of unloading in CF-LVAD patients.

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.

Apelin: a new plasma marker of cardiopulmonary disease.

OBJECTIVES: Dyspnea is a major symptom of both parenchymal lung disease and chronic heart failure. Underlying cardiac dysfunction can be assessed by measurement of cardiac-derived B-type natriuretic peptide or its precursor in plasma. However, no specific endocrine marker of the lung parenchyma has so far been identified. We therefore examined whether plasma concentrations of apelin, a novel inotropic hormone, is affected in patients with chronic parenchymal lung disease without cardiac dysfunction. METHODS AND RESULTS: Patients with severe chronic parenchymal lung disease and normal cardiac function (n=53), idiopathic pulmonary hypertension with increased right ventricular pressure (n=10), and patients with severe left ventricular systolic dysfunction (n=22) were enrolled. Plasma apelin-36 and proBNP concentrations were measured with radioimmunoassays. While proBNP plasma concentrations were unaffected in chronic parenchymal lung disease patients compared to normal subjects, the apelin-36 concentration was reduced 3.3-fold (median 35 pmol/l (0-162 pmol/l) vs. 117 pmol/l (55-232 pmol/l), P<0.001). Moreover, the apelin-36 concentration was decreased in chronic heart failure patients (2.1-fold, P<0.01) and in patients with idiopathic pulmonary hypertension (4.0-fold, P<0.001). In contrast, the proBNP concentration was highly increased in both chronic heart failure and idiopathic pulmonary hypertension patients. CONCLUSION: Plasma concentrations of apelin-36, a novel inotropic peptide, are decreased in patients with chronic parenchymal lung disease and preserved cardiac function. Combined measurement of apelin-36 and proBNP may be a new diagnostic approach in distinguishing pulmonary from cardiovascular causes of dyspnea.