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Objective The present study assessed agreement between resting cardiac output estimated by inert gas rebreathing (IGR) and thermodilution methods in patients with heart failure and those implanted with a left ventricular assist device (LVAD). Methods and Results Hemodynamic measurements were obtained in 42 patients, 22 with chronic heart failure and 20 with implanted continuous flow LVAD (34 males, aged 50 ± 11 years). Measurements were performed at rest using thermodilution and IGR methods. Cardiac output derived by thermodilution and IGR were not significantly different in LVAD (4.4 ± 0.9 L/min vs 4.7 ± 0.8 L/min, P = .27) or patients with heart failure (4.4 ± 1.4 L/min vs 4.5 ± 1.3 L/min, P = .75). There was a strong relationship between thermodilution and IGR cardiac index (r = 0.81, P = .001) and stroke volume index (r = 0.75, P = .001). Bland–Altman analysis showed acceptable limits of agreement for cardiac index derived by thermodilution and IGR, namely, the mean difference (lower and upper limits of agreement) for patients with heart failure –0.002 L/min/m2 (–0.65 to 0.66 L/min/m2), and –0.14 L/min/m2 (–0.78 to 0.49 L/min/m2) for patients with LVAD. Conclusions IGR is a valid method for estimating cardiac output and should be used in clinical practice to complement the evaluation and management of chronic heart failure and patients with an LVAD.

We sought to determine hemodynamic mechanisms of exercise intolerance in a group of patients with the HeartWare ventricular assist device (VAD) compared to a group of heart failure patients. Twenty VAD and 22 heart failure patients underwent symptom-limited active straight leg raising exercise during right heart catheterization with thermodilution (TD), and upright cycling cardiopulmonary stress testing with cardiac output measurement by inert gas rebreathing (IGR) method. The TD and IGR exercise cardiac indexes were higher in VAD compared with heart failure group (both P < 0.05), although there was only a borderline increase in peak exercise oxygen consumption (VO2) (P = 0.06). Baseline and exercise right heart catheterization pressures were not significantly different between the two groups. The only significant independent predictors of peak VO2 in the heart failure group were exercise heart rate and cardiac index (both P < 0.05). In contrast, for the VAD group only, resting pulmonary arterial wedge and pulmonary arterial mean pressures were independently related to peak VO2 (both P < 0.05). Thus, in heart failure, exercise cardiac index is an important limitation to exercise capacity, and VADs increase exercise cardiac index. However, in VAD patients, this only produces limited benefits as increased pulmonary and pulmonary wedge pressures limit increases in exercise capacity.

Although left ventricular assist device (LVAD) improves functional capacity, on average LVAD patients are unable to achieve the aerobic capacity of normal healthy subjects or mild heart failure patients. The aim of this study was to examine if markers of right ventricular (RV) function influence maximal exercise capacity. This was a single-center prospective study that enrolled 20 consecutive HeartWare ventricular assist device patients who were admitted at the Freeman Hospital (Newcastle upon Tyne, United Kingdom) for a heart transplant assessment from August 2017 to October 2018. Mean peak oxygen consumption (Peak VO2) was 14.0 ± 5.0 ml/kg/min, and mean peak age and gender-adjusted percent predicted oxygen consumption (%VO2) was 40.0% ± 11.5%. Patients were subdivided into two groups based on the median peak VO2, so each group consisted of 10 patients (50%). Right-sided and pulmonary pressures were consistently higher in the group with poorer exercise tolerance. Patients with poor exercise tolerance (peak VO2 below the median) had higher right atrial pressures at rest (10.6 ± 6.4 vs. 4.3 mmHg ± 3.2; p = 0.02) and the increase with passive leg raising was significantly greater than those with preserved exercise tolerance (peak VO2 above the median). Patients with poor functional capacity also had greater RV dimensions (4.4 cm ± 0.5 vs. 3.7 cm ± 0.5; p = 0.02) and a higher incidence of significant tricuspid regurgitation (moderate or severe tricuspid regurgitation in five patients in the poor exercise capacity group vs. none in the preserved exercise capacity group; p = 0.03). In conclusion, echocardiographic and hemodynamic markers of RV dysfunction discriminate between preserved and nonpreserved exercise capacity in HeartWare ventricular assist device patients.

Objectives: The aim of the present study was to assess the validity and trending ability of the bioreactance method in estimating cardiac output at rest and in response to stress in advanced heart failure patients and heart transplant candidates. Design: This was a prospective single-center study. Setting: This study was conducted at the heart transplant center at the Freeman Hospital, Newcastle upon Tyne, UK. Participants: Eighteen patients with advanced chronic heart failure due to reduced left ventricular ejection fraction (19 ± 7%), and peak oxygen consumption 12.3 ± 3.9 mL/kg/min. Interventions: Participants underwent right heart catheterization using the Swan-Ganz catheter. Measurements and Main Results: Cardiac output was measured simultaneously using thermodilution and bioreactance at rest and during active straight leg raise test to volitional exertion. There was no significant difference in cardiac index values obtained by the thermodilution and bioreactance methods (2.26 ± 0.59 v 2.38 ± 0.50 L/min, p > 0.05) at rest and peak straight leg raise test (2.92 ± 0.77 v 3.01 ± 0.66 L/min, p > 0.05). In response to active leg raise test, thermodilution cardiac output increased by 22% and bioreactance by 21%. There was also a strong relationship between cardiac outputs from both methods at rest (r = 0.88, p < 0.01) and peak straight leg raise test (r = 0.92, p < 0.01). Cartesian plot analysis showed good trending ability of bioreactance compared with thermodilution (concordance rate = 93%) Conclusions: `Cardiac output measured by the bioreactance method is comparable to that from the thermodilution method. Bioreactance method may be used in clinical practice to assess hemodynamics and improve management of advanced heart failure patients undergoing heart transplant assessment.

Introduction and objectives: Pump thrombosis is a serious left ventricular assist device complication, though there are no guidelines regarding its treatment. The main aim of this study was to describe a strategy of intravenous anticoagulation as the initial treatment in these patients and then to compare intravenous heparin with bivalirudin. Methods: All consecutive patients who received a HeartWare left ventricular assist device from July 2009 to March 2019 were retrospectively analysed. Patients developing a pump thrombosis were selected, and treatment, outcomes and complications were recorded. Results: During this period of time (116 months), 220 patients underwent HeartWare left ventricular assist device implantation and 57 developed pump thrombosis, with an incidence rate of first pump thrombosis of 0.17 events per patient-year of support (incidence rate of all episodes of pump thrombosis: 0.30 events per patient-year of support). All the patients were initially treated medically, predominantly with either intravenous heparin (n = 26) or bivalirudin (n = 16). Patients treated with bivalirudin during the first pump thrombosis episode had less subsequent re-thrombosis episodes (18.7% vs 57.7%, p Conclusion: Left ventricular assist device thrombosis is a serious life-threatening complication; hence, we propose an initial conservative management of pump thrombosis with enhanced intravenous anticoagulation with either intravenous heparin or bivalirudin, with surgery reserved for refractory cases.

Introduction and purpose Pump thrombosis (PT) is a serious left ventricular assist device (LVAD) complication, though there are no guidelines regarding its treatment. We have adopted a strategy of intravenous anticoagulation as the initial treatment strategy in these patients. Methods All consecutive patients who received a HeartWare LVAD from July-2009 to January-2018 were retrospectively analyzed. Patients developing a PT were selected, and treatment, outcomes and complications were recorded. Results 197 patients underwent HVAD, and 49 developed PT. All the patients were initially treated medically, though during the first PT 26.5% of the patients needed surgery [VAD exchange (n=6), transplant (n=6), or decommissioning (n=1)]. The overall survival at 1 year was 63.3%. Patients were treated predominantly with either intravenous heparin or bivalirudin. There were no significant differences neither in complications nor in survival between the 2 treatments (Figure 1); however, patients treated with bivalirudin during the first PT episode had less subsequent re-thrombosis episodes (18.2% vs 57.7%, p Table 1. Comparison of baseline characteristics and outcomes between Heparin and Bivalirudin Heparin (n=26) Bivalirudin (n=11) p-value Male, gender n (%) 20 (76.9) 9 (81.8) 1.00 Age when implant (years) 48±11.8 49.8±11.4 0.67 AF n (%) 9 (34.6) 6 (54.5) 0.50 Diagnosis: Dilated cardiomyopathy n (%) 13 (50) 7 (63.6) Ischemic heart disease n (%) 12 (46.2) 3 (27.3) Congenital heart disease n (%) 1 (3.8) 1 (9) 0.50 Thrombolysis (+ alteplase) n (%) 19 (73.1) 4 (36.4) 0.08 Treatment duration (days) 11.5±7.2 15.3±6.5 0.15 % Time in range 36.3±7.1 59.7±4.2 0.009 Hospitalisation (days) 19.1±16.4 31.9±18.2 0.06 Complications: Ischemic Stroke n (%) 2 (7.7) 4 (36.4) 0.09 Intracraneal bleeding n (%) 2 (7.7) 0 (0) 0.88 Gastrointestinal bleeding n (%) 1 (3.8) 0 (0) 1.00 Serious bleeding n (%) 5 (19.2) 0 (0) 0.29 Any bleeding n (%) 7 (26.9) 2 (18.2) 0.88 LDH Baseline 271.7±79.3 221.6±41.3 0.10 Admision 727.8±448.2 517.5±171.3 0.21 Maximum 827.1±424.7 1217.6±1004 0.03 Discharge 334.9±135.9 308.6±111.8 0.70 Time to normalisation (days) 10.2±4.5 17.2±2.6 0.004 Outcomes: Transplant (total) n (%) 7 (26.9) 2 (18.2) 0.88 VAD Exchange (total) n (%) 8 (30.8) 4 (36.4) 1.00 Mortality at 2 years n (%) 15 (57.7) 5 (45.4) 0.831 Rethrombosis: Rethrombosis n (%) 15 (57.7) 2 (18.2) 0.03 Number of episodes of rethrombosis 0.15 +1 n=6 n=1 +2 n=4 n=1 +3 n=4 n=0 +4 n=1 n=0 Figure 1 Conclusion VAD thrombosis is a serious life threatening complication, though an initial strategy with enhanced intravenous anticoagulation is an acceptable strategy with either intravenous heparin or bivalirudin. Acknowledgement/Funding N. Bouzas-Cruz would like to thank the Spanish Society of Cardiology (Sociedad Española de Cardiología), for her research grant and fellowship.

Introduction Left Ventricular Assist Devices (LVAD) improve survival and functional capacity in patients with advanced heart failure (HF). However, there are potential complications. Purpose We sought to determine parameters of exercise intolerance in a group of patients with the HeartWare LVAD (HVAD) compared to a group of HF patients. Methods This was a single-centre parallel prospective group-study. Briefly, echocardiograms, right heart catheterisation (RHC) and cardiopulmonary exercise tests were performed in forty-two patients admitted for a heart transplant assessment between August2017 and October2018.Of them 20 belonged to the HVAD group and 22 to the HF group. Results In our study, HVAD patients had a better exercise capacity than HF patients, although no significant differences were noted (14.0±5.0 ml/kg/min vs 11.3±3.9 ml/kg/min, p=0.06). To determine exercise tolerance, both HVAD and HF groups were subdivided into 2 groups based on the median peak exercise oxygen consumption (peakVO2) for that group. The table shows the comparison between preserved and non-preserved exercise tolerance in HF and HVADpatients. First of all, in the HVADgroup, all resting RHC pressures were significantly lower in the preserved exercise capacity group. However, in HFpatients there were no statistically significant differences between both subgroups in right-sided pressures, but Thermodilution exercise-induced change in cardiac output (ΔCO) and cardiac index (ΔCI) was significantly higher in the patients with preserved exercise tolerance. Secondly, in the HVADgroup the right ventricle was significantly larger in the reduced exercise tolerance subgroup. Moreover, patients with lower peak VO2 had more significant tricuspid regurgitation. Nevertheless, in HFpatients none of the echocardiographic parameters were related to the exercise capacity. HF HVAD > Median Peak V02 < Median Peak V02 p > Median Peak V02 < Median Peak V02 p Thermodilution CO, l/min: • Rest 4.3±1.0 4.4±1.8 0.82 4.8±0.8 4.2±1.2 0.21 • Exercise 5.6±1.7 4.8±1.8 0.36 7.1±3.2 4.8±0.8 0.05 • ΔCO 1.26±1.0 0.26±0.7 0.02 2.2±2.5 0.4±0.7 0.05 Right Atrium pressure, mmHg 7.0±4.5 6.8±4.10 0.92 4.3±3.2 10.6±6.40 0.02 Mean Pulmonary Artery pressure, mmHg 26.4±12.6 26.5±10.9 0.97 16.8±5.4 30.5±12.5 0.01 Tricuspid Regurgitation, n (%): • None 1 (9) 1 (9) 1 (12) 0 (0) • Mild 7 (64) 8 (73) 7 (88) 4 (44) • Moderate 2 (18) 0 (0) 0 (0) 4 (44) • Severe 1 (9) 2 (18) 0.36 0 (0) 1 (12) 0.03 Right Ventricle Basal Diastolic Diameter, cm 4.0±1.0 4.1±1.0 0.83 3.7±0.5 4.4±0.5 0.02 Conclusion Right-sided parameters in the echocardiogram and RHC pressures discriminate between preserved and non-preserved exercise capacity in HVADpatients, but not in HFpatients. In these last patients only ΔCO and ΔCI were statistically correlated with peak exercise oxygen consumption Acknowledgement/Funding N. Bouzas-Cruz would like to thank the Spanish Society of Cardiology (Sociedad Española de Cardiología), for her research grant and fellowship

Right-sided heart failure (RHF) after left ventricular assist device implantation is a significant cause of morbidity and mortality. Although multiple predictors of early RHF have been described, information on late RHF is scarce. The aim of this study was to identify predictors of late RHF in left ventricular assist device patients. A retrospective analysis of all adult patients who underwent HeartWare-ventricular assist device implantation as a bridge to transplantation in a single-centre was performed. Late RHF was defined as RHF requiring rehospitalization after 30 days of implantation. A total of 16 (10.3%) patients from 156 implantations developed late RHF. Median time to late RHF onset was 182.5 (interquartile range 105 to 618) days. Patients developing late RHF were older at surgery. A significantly higher rate of moderate or severe tricuspid regurgitation before implantation was found in patients presenting with late RHF (81.2% vs 33.5%; p0.001). Several echocardiographic parameters at discharge postimplant, such as significant mitral regurgitation, demonstrated a strong association with late RHF. A multivariate Cox regression analysis revealed that significant preoperative tricuspid regurgitation was the strongest predictor of late RHF (hazard ratio 5.50, 95% confidence interval [1.34 to 22.58]; p = 0.02). Significant mitral regurgitation postimplantation and older age also significantly predicted late RHF. In conclusion, preoperative significant tricuspid regurgitation and mitral regurgitation after implantation predict the occurrence of late RHF.

Left ventricular assist devices (LVADs) have become an established treatment for advanced heart failure, although with long-term support these patients are potentially exposed to serious complications. Our purpose was to assess the role of the neutrophil to lymphocyte ratio (NLR) in LVAD complications and to evaluate if higher values of NLR after 4-6 months on LVAD support (NLR 4_6m) are associated with worse prognosis. All consecutive patients who received a HeartWare LVAD (N = 188, age 50 ± 13 years), as bridge to transplant from December 2009 to January 2018 were included. Neutrophil to lymphocyte ratio was recorded pre-LVAD, post-LVAD, after 4-6 months on support and in case of a first adverse event to occur after the 4-6 months NLR was recorded. Median NLR values were pre-LVAD 4.26 (interquartile range [IQR], 3.1-6.9), at 1 day postoperative 11.6 (IQR, 8.3-16.6), and NLR 4_6m 4.4 (IQR, 3.0-6.4) (p < 0.001). Neutrophil to lymphocyte ratio increased significantly when patients had an infection, stroke, or pump thrombosis, as compared with the NLR 4_6m (all p < 0.05). Patients with NLR 4_6m ≥ median had higher rates of stroke and mortality. Survival time was shorter among patients with NLR 4_6m ≥ 4.4 (log-rank test p = 0.006). Neutrophil to lymphocyte ratio 4_6m was found to be predictive of increased mortality (area under the curve of 0.62, p = 0.007). After multivariate analysis, NLR 4_6m remained independently associated with increased mortality (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.03-2.7; p = 0.037). Neutrophil to lymphocyte ratio 4_6m values significantly increase in association with adverse events on LVAD support and are independently associated with mortality. This association suggests presence of inflammation adversely affects LVAD outcomes.

Purpose To determine parameters of exercise intolerance in a group of patients with HeartWare Ventricular Assist Device(HVAD) compared to a group of heart failure(HF)patients Methods This was a single-centre parallel prospective group-study.Echocardiograms,right heart catheterisation(RHC) and cardiopulmonary exercise tests were performed in 42patients admitted for a heart transplant assessment between August2017 and October2018:20 belonged to the HVAD group and 22 to the HF group Results HVADpatients had a better exercise capacity than HFpatients, although no significant differences were noted(14.0±5.0ml/kg/min vs 11.3±3.9ml/kg/min, p=0.06).To determine exercise tolerance,both HVAD and HFgroups were subdivided into 2 groups based on the median peakVO2.The table shows the comparison between preserved and non-preserved exercise tolerance in HF and HVADpatients. In the HVAD group,all resting RHC pressures were significantly lower in the preserved exercise capacity group.However,in HFpatients there were no statistically significant differences between both subgroups in right-sided pressures,but Thermodilution exercise-induced change in cardiac output(ΔCO) and cardiac index(ΔCI) was significantly higher in the patients with preserved exercise tolerance.In the HVADgroup the right ventricle was significantly larger in the reduced exercise tolerance subgroup.Patients with lower peakVO2 had more significant tricuspid regurgitation.Nevertheless,in HFpatients none of the echocardiographic parameters were related to the exercise capacity Conclusion Right-sided parameters in the echocardiogram and RHC pressures discriminate between preserved and non-preserved exercise capacity in HVADpatients,but not in HFpatients.In these last patients only ΔCO and ΔCI were statistically correlated with peak exercise oxygen consumption.