Ventricular assist devices in transposition and failing systemic right ventricle: role of tricuspid valve replacement.

OBJECTIVES: Ventricular assist device (VAD) for systemic right ventricular (RV) failure patients post-atrial switch, for transposition of the great arteries (TGA), and those with congenitally corrected TGA has proven useful to reduce transpulmonary gradient and bridge-to-transplantation. The purpose of this study is to describe our experience of VAD in systemic RV failure and our move towards concomitant tricuspid valve replacement (TVR). METHODS: This is a single-centre retrospective study of consecutive adult patients receiving HeartWare VAD for systemic RV failure between 2010 and 2019. From 2017, concomitant TVR was performed routinely. Demographic, clinical variables and echocardiographic and haemodynamic measurements pre- and post-VAD implantation were recorded. Complications on support, heart transplantation and survival rates were described. RESULTS: Eighteen patients underwent VAD implantation. Moderate or severe systemic tricuspid regurgitation was present in 83.3% of patients, and subpulmonic left ventricular impairment in 88.9%. One-year survival was 72.2%. VAD implantation was technically feasible and successful in all but one. Post-VAD, transpulmonary gradient fell from 16 (15-22) to 10 (7-13) mmHg (P = 0.01). Patients with TVR (n = 6) also demonstrated a reduction in mean pulmonary and wedge pressures. Furthermore, subpulmonic left ventricular end-diastolic dimension (44.3 vs 39.6 mm; P = 0.03) and function improved in this group. After 1 year of support, 72.2% of patients were suitable for transplantation. CONCLUSIONS: VAD is an effective strategy as bridge-to-candidacy and bridge-to-transplantation in patients with end-stage systemic RV failure. Concomitant TVR at the time of implant is associated with better early haemodynamic and echocardiographic results post-VAD.

Does infection predispose to thrombosis during long-term ventricular assist device support?

BACKGROUND: Infections and thrombotic events remain life-threatening complications in patients with ventricular assist devices (VAD). METHODS: We describe the relationship between both events in our cohort of patients (n = 220) supported with the HeartWare VAD (HVAD). This is a retrospective analysis of patients undergoing HVAD implantation between July 2009 and March 2019 at the Freeman Hospital, Newcastle upon Tyne, United Kingdom. RESULTS: Infection was the most common adverse event in HVAD patients, with 125 patients (56.8%) experiencing ≥ one infection (n = 168, 0.33 event per person year (EPPY)), followed by pump thrombosis (PT) in 61 patients (27.7%, 0.16 EPPY). VAD-specific infections were the largest group of infections. Of the 125 patients who had an infection, 66 (53%) had a thrombotic event. Both thrombotic events and infections were related to the duration of support, though there was only limited evidence that infections predispose to thrombosis. Those with higher than median levels of C-reactive protein during the infection were more likely to have an ischaemic stroke (IS) (34.5% vs 16.7%, p = .03), though not PT or a combined thrombotic event (CTE: first PT or IS). However, in multivariate analysis, there was no significant effect of infection predisposing to CTE. CONCLUSIONS: Infection and thrombotic events are significant adverse events related to the duration of support in patients receiving HVADs. Infections do not clearly predispose to thrombotic events.

Markers of Right Ventricular Dysfunction Predict Maximal Exercise Capacity After Left Ventricular Assist Device Implantation.

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.

Using existing technology better: Improving outcomes with the HeartWare left ventricular assist device.

BACKGROUND: The HeartWare left ventricular assist device has been in use for over 12 years. We sought to determine how outcomes at our centre have improved over time. METHODS: Review of electronic hospital records at the Freeman Hospital, Newcastle upon Tyne, United Kingdom. RESULTS: A total of 255 first time adult implants were divided into 2 eras: Era 1: 2009-2015 (N = 154) and Era 2: 2016-2020 (N = 101). We prospectively aimed to avoid higher risk Intermacs Classifications in Era 2, which resulted in significant changes in Intermacs class to lower risk in Era 2 (P < 0.001). There was a significant improvement in survival in Era 2, with 1 year survival increasing from 70 to 80% (P < 0.05). This was particularly associated with lower 30 day mortality in Era 2 (1.7 ± 2.3 vs 15.5 ± 7%, P < 0.005). This was associated with better right ventricular function in Era 2, and there was a trend to more temporary right ventricular assist devices used in Era 2 (28 ± 13 vs 12 ± 14%, P = 0.06). Deaths from intracranial haemorrhage, sepsis and right heart failure were unchanged between eras, though there was a trend towards less deaths in Era 2 from combined thromboses deaths (stroke and device thrombosis; 3.3 ± 5.4 vs 11.1 ± 7.4%, P = 0.07). CONCLUSIONS: Better patient selection in association with more use of temporary right ventricular assist support has resulted in a significant improvement in survival. Intracranial haemorrhage, sepsis and right heart failure remain significant problems.

Validity of Hemodynamic Monitoring Using Inert Gas Rebreathing Method in Patients With Chronic Heart Failure and Those Implanted With a Left Ventricular Assist Device.

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.

Left Ventricular Filling Pressures Contribute to Exercise Limitation in Patients with Continuous Flow Left Ventricular Assist Devices.

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.

Neutrophil to Lymphocyte Ratio Is Related to Thrombotic Complications and Survival in Continuous Flow Left Ventricular Assist Devices.

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.

Initial conservative management strategy of HeartWare left ventricular assist device thrombosis with intravenous heparin or bivalirudin.

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 < 0.05). In addition, percentage time in therapeutic range was greater for bivalirudin compared with heparin (68.5% ± 16.9% vs 37.4% ± 31.0%, p < 0.01). During the first pump thrombosis episode, 26.3% of the patients needed surgery (left ventricular assist device exchange (n = 8), transplant (n = 6) or decommissioning (n = 1)). The overall survival at 1 year was 61.4%, and there was no significant difference in survival. 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.

Effect of Preoperative Tricuspid and/or Mitral Regurgitation on Development of Late Right-Sided Heart Failure After Insertion of the HeartWare Left Ventricular Assist Device.

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%; p <0.001). 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.

Myocardial Recovery Strategy with Decommissioning for the HeartWare Left Ventricular Assist Device.

To manage myocardial recovery in patients with the HeartWare left ventricular assist device (HVAD), we describe a minimally invasive approach (decommissioning) that involves disconnecting the driveline and occluding the outflow tract through a small left thoracotomy incision, leaving the device in situ, in conjunction with optimal medical therapies and comprehensive assessment of left ventricular recovery. Nine patients (all male, 37 ± 12 years, all nonischemic dilated cardiomyopathy) had an HVAD implanted for 766 ± 343 days. When left ventricular function improved to mild impairment by echocardiography, patients underwent assessment at reduced flow (2578 ± 148 to 1822 ± 67 rpm) with documentation of compensated right heart hemodynamics and ejection fraction 52 ± 8%. Eight of nine patients underwent decommissioning, and 1 patient had a hybrid procedure of percutaneous occlusion of outflow graft and surgical division of driveline. Two patients died postoperatively at 413 days (sepsis) and 810 days (heart failure). In conclusion, in selected patients with nonischemic dilated cardiomyopathy, a prolonged period of HVAD support in conjunction with heart failure medications can lead to recovery of left ventricular function. Surgical decommissioning is then an option to remove these patients from support. These patients are, however, not cured and remain at risk for future deterioration in ventricular function and infections.

Impact of aortic valve closure on adverse events and outcomes with the HeartWare ventricular assist device.

BACKGROUND: This study examined whether aortic valve opening (AVO) and other echocardiographic parameters influence outcomes in patients on left ventricular (LV) assist device (LVAD) support. Pump thrombosis (PT) and ischemic stroke (IS) are known complications of LVAD, but mechanisms that could influence them are not completely understood. METHODS: This was a retrospective analysis of 147 patients who received a HeartWare Ventricular Assist Device ( HeartWare International) as a bridge to transplant or to candidacy between July 2009 and August 2015, of whom 126 had at least 30 days of follow-up before the first event (30-days-out cohort). Outcomes included survival, PT, IS, and PT+IS (combined thrombotic event; CTE). RESULTS: Median time on support was 518 days. Of the 30-days-out cohort, 29% had a first PT and 19% a first IS. AVO was associated with longer survival on device (1,081 vs 723 days; p = 0.01) in the entire cohort. In the 30-days-out cohort, the aortic valve was more frequently closed in patients with lower ejection fractions on support (14% ± 6% vs 18% ± 9%; p = 0.009), more dilated pre-event echocardiogram (LV end-diastolic diameter, 66 ± 12 mm vs 62 ± 10 mm; p = 0.04), and pre-implant LV end-diastolic diameter (70 ± 10 mm vs 66 ± 9 mm; p = 0.06). CTE-free survival on the device was lower with a closed aortic valve (897 vs 1,314 days; p = 0.003) as was PT-free survival on the device (1,070 vs 1,457 days; p = 0.02). Cox regression analysis showed that AVO was an independent predictor of CTE (p = 0.03) CONCLUSIONS: Thrombotic events are relatively frequent in patients on long-term LVAD support. A closed aortic valve was associated with decreased overall survival, thrombosis-free survival, and poorer LV function on support. These are high-risk patients, so whether they require more intense anti-coagulation or prioritizing for transplantation requires further research.

Development of de novo aortic valve incompetence in patients with the continuous-flow HeartWare ventricular assist device.

BACKGROUND: In this study we investigated the development of aortic incompetence (AI) and change in aortic root and left ventricular dimensions after implantation of the continuous-flow HeartWare ventricular assist device (HVAD) in our adult patient cohort. METHODS: A retrospective analysis of serial echocardiograms was performed on patients implanted with an HVAD between July 2009 and July 2013. Data from echocardiograms performed before and at 1 and 2 years (±3 months) were analyzed. Patients with native aortic valves (AoVs) with no previous intervention and HVAD in situ for ≥6 months were included. RESULTS: A total of 73 HVADs in 71 patients with a mean duration of support of 624 ± 359 days were included in our study. One patient developed moderate AI at 1 year (1.9%). Mild or greater AI was more likely in those with a closed or intermittently opening AoV at 1 year (p = 0.005). Aortic annulus dimensions increased significantly at 1 and 2 years, regardless of extent of AI. At 2 years, in those with mild or worse AI, the sinuses of Valsalva were also larger (p = 0.002). Left ventricular end-diastolic dimension (LVEDD) was significantly reduced in those with no or trace AI at 1 and 2 years (p = 0.012 and p = 0.008, respectively), but remained unchanged in those with AI at both time-points. CONCLUSIONS: The development of more than mild AI is rare in HVAD patients at our center. When encountered, it is more common with a closed AoV. Dilation of the aortic annulus, and root dilation in those with mild or more AI, is seen with HVAD support over time.

Four-year outcomes with third-generation centrifugal left ventricular assist devices in an era of restricted transplantation.

OBJECTIVES: Third-generation ventricular assist devices (VADs) are associated with improved outcomes, though in recent clinical trials bridge-to-transplant (BTT) rates are ∼30% at 6 months, so that transplantation can be used as a 'bail out' for serious complications. In the UK, there was a significant reduction in heart transplantation rates over the last decade, so that transplantation from VADs is much less frequent. The objective of this study was to determine outcomes and their predictors in this situation of low BTT rates, and as patients were exposed to long-term support, the incidence and outcomes of VAD thrombosis. METHODS: We analysed outcomes for 102 consecutive patients between 2009 and 2013 (mean age 47 ± 13; VentrAssist n = 6 and HeartWare n = 96). The median duration of support was 462 ± 426 days. RESULTS: Survival rates on the device were 75 and 66% at 1 and 2 years, respectively. Older age and more acute INTERMACS groups were significantly related to reduced survival within the first 90 days (P = 0.030 and 0.010, respectively). Poor preoperative right ventricular (RV) function had a negative effect on survival after 1 year (P = 0.009), though not earlier. VAD thrombosis (n = 24 HeartWare and n = 1 VentrAssist) occurred at 0.18 events per patient-year for HeartWare and 0.07 for VentrAssist devices at a median time of onset at 404 ± 281 days. There was no significant effect of VAD thrombosis on survival. Only 14 of 102 patients were transplanted at a median of 334 ± 347 days, and only 3 were transplanted within the first 6 months. CONCLUSIONS: Third-generation left ventricular assist device implants with a low rate of transplantation have similar survival to destination therapy, and are susceptible to long-term complications of VAD thrombosis and right heart failure.

Hemodynamic, echocardiographic, and exercise-related effects of the HeartWare left ventricular assist device in advanced heart failure.

The aim of this study was to determine the effects of the HeartWare left ventricular assist device (HVAD) (HeartWare International, Inc, Framingham, MA) on hemodynamics, ventricular function, and exercise capacity. Between July 2009 and March 2011, 46 patients with advanced heart failure had implantation of the HVAD. Of these patients, 30 had subsequent assessments for transplantation and these patients formed the study cohort. Thirty patients had assessments at a mean of 201±86 days and 13 went on to have a second assessment at 351±86 days. There were marked improvements in hemodynamics and exercise capacity at both assessments, with significant decreases in right and left heart filling pressures; increases in cardiac index, New York Heart Association class, and peak exercise oxygen consumption; and reduction in pulmonary vascular resistance (all P<.05). Left ventricular end-diastolic and end-systolic dimensions were unchanged at the first assessment, although there was a significant reduction in end-diastolic diameter at the second assessment (P<.01). There were no significant changes in a visual grade of right ventricular function. After up to 1 year of support, the HVAD system results in significant benefits in overall heart failure status, with improved hemodynamics and exercise capacity. This occurs in the absence of marked changes in left ventricular size or right ventricular function.