Prevention of Right Heart Failure After Left Ventricular Assist Device Implantation by Phosphodiesterase 5 Inhibitor

Right ventricular (RV) function immediately after left ventricular assist device (LVAD) implantation is a crucial prognostic factor. RV failure is linked to increased mortality and worse outcome. A phosphodiesterase 5 inhibitor, sildenafil, was shown to decrease pulmonary vascular resistance and pulmonary artery pressure post‐LVAD. We report on a series of heart failure patients, and the effect of sildenafil on the incidence of RV failure after LVAD implantation. We retrospectively analyzed the data of end‐stage heart failure patients who underwent LVAD implantation with pulmonary hypertension and RV dysfunction prior to surgery. Patients were divided into two groups; group 1: patients who received sildenafil perioperatively, and group 2: patients who did not receive sildenafil. Hemodynamic and echographic data were collected before and after surgery. Fourteen patients were included, 8 patients in group 1 and 6 in group 2. Sildenafil was administered with a mean dose of 56.2 ± 9.4 mg in group 1 and was able to significantly reduce right heart failure incidence, and to demonstrate a significant reduction in pulmonary vascular resistance, pulmonary artery pressure, transpulmonary gradient, and a significant increase in cardiac output. In conclusion, sildenafil seems to have a promising role perioperatively in preventing acute RV failure postsurgery in patients with RV dysfunction and pulmonary hypertension, requiring LVAD therapy.     

Clinical Outcomes of Patients Treated With Pulmonary Vasodilators Early and in High Dose After Left Ventricular Assist Device Implantation

Right ventricular failure (RVF) is common after left ventricular assist device (LVAD) implantation and a major determinant of adverse outcomes. Optimal perioperative right ventricular (RV) management is not well defined. We evaluated the use of pulmonary vasodilator therapy during LVAD implantation. We performed a retrospective analysis of continuous‐flow LVAD implants and pulmonary vasodilator use at our institution between September 2004 and June 2013. Preoperative RVF risk was assessed using recognized variables. Sixty‐five patients (80% men, 50 ± 14 years) were included: 52% HeartWare ventricular assist device (HVAD), 11% HeartMate II (HMII), 17% VentrAssist, 20% Jarvik. Predicted RVF risk was comparable with contemporary LVAD populations: 8% ventilated, 14% mechanical support, 86% inotropes, 25% BUN >39 mg/dL, 23% bilirubin ≥2 mg/dL, 31% RV : LV (left ventricular) diameter ≥0.75, 27% RA : PCWP (right atrium : pulmonary capillary wedge pressure) >0.63, 36% RV stroke work index <6 gm‐m/m²/beat. The majority (91%) received pulmonary vasodilators early and in high dose: 72% nitric oxide, 77% sildenafil (max 200 ± 79 mg/day), 66% iloprost (max 126 ± 37 μg/day). Median hospital stay was 26 (21) days. No patient required RV mechanical support. Of six (9%) patients meeting RVF criteria based on prolonged need for inotropes, four were transplanted, one is alive with an LVAD at 3 years, and one died on day 35 of intracranial hemorrhage. Two‐year survival was 77% (92% for HMII/HVAD): transplanted 54%, alive with LVAD 21%, recovery/explanted 2%. A low incidence of RVF and excellent outcomes were observed for patients treated early during LVAD implantation with combination, high‐dose pulmonary vasodilators. The results warrant further investigation in a randomized controlled study.     

Driving After Left Ventricular Assist Device Implantation

Literature on driving capacities of ventricular assist device patients is rare and driving restrictions differ from center to center. Currently, no guidelines exist on whether and when left ventricular assist device (LVAD) patients are allowed to begin driving cars after device implantation. In this study, we assess the driving abilities of patients after LVAD implantation. Three hundred and ninety LVAD patients have been surveyed in a worldwide, multicenter study. The single survey followed a multi‐method design, including online, phone, and face‐to‐face interviews. Out of 390 patients, 72% are still driving and 28% did not continue driving after LVAD implantation. Reasons for discontinuation were capability (24%), insecurity (17%), and disapproval by family members (9%) or doctors (5%). Ninety percent of the patients describe their ability to drive as perfect or adequate. Sixty‐nine percent state that they are not restricted in their general driving capacity. Forty‐nine percent report not to be restricted in agility to drive by the device equipment. The majority of patients have not been involved in car accidents or major complications (94%). Eight accidents were reported (3%). Out of those, all were minor collisions. No patient reported the occurrence of a fatal accident or casualties. LVAD alarms did occur in six incidents (2%) with the majority being low battery alarms. The results of this study suggest that driving with a left ventricular assist device is safe for stable patients and driving can be resumed 3 months after LVAD implantation after careful patient assessment.     

Experimental Assessment of Right Ventricular Function in Normal Pigs with a Left Ventricular Assist Device

Abstract: Right ventricular (RV) failure during the use of a left ventricular assist device (LVAD) is the leading cause of death in circulatory support patients. Previous work, both experimentally and clinically, has shown the difficulties in predicting the behavior of the right ventricle at the start of LVAD. An experimental study has been designed to evaluate RV functional changes during LVAD and its relation to preload changes. The model used adult mongrel pigs (n = 10). Right ventricular functional parameters were measured with a thermodilution RV ejection fraction catheter. The left ventricle was supported by a Nippon Zeon blood pump. Two groups were studied, the first one was the LVAD–off group (n = 5) and the other was the LVAD–on group (n = 5) which was supported by LVAD at maximum flow. Change of cardiac output, mean pulmonary artery pressure (PAP), RV stroke work, and RV ejection fraction in both groups were not significantly different. However, the relationship between right ventricular end–diastolic pressure (RV–EDP) and right ventricular stroke volume (RVSV) was significantly changed at a high level of RV–EDP. When RV–EDP was over 6. 5 mm Hg in the LVAD–off group, RVSV decreased to 52. 3 ± 11. 5 ml while in the LVAD–on group, RVSV increased to 97. 2 ± 22. 0 ml. The change in PAP in the LVAD–on group was lower than in the LVAD–off group. We conclude that, at the volume overload state, LVAD can reduce the afterload of the right ventricle and maintain Frank–Starling's effect, thus having a beneficial effect on right ventricular performance.     

Development of a Direct Mechanical Left Ventricular Assist Device for Left Ventricular Failure

Abstract: We have developed a direct mechanical left ventricular assist device (DMLVAD) for severe left ventricular failure. The DMLVAD was attached to the left ventricle and compressed the heart by a pneumatic driving unit. In a mock circulation model with an extracted non-beating heart, a cardiac output (CO) of 1.93 L/min was obtained at a driving pressure of 200 mm Hg. In a canine left ventricular failure model induced by injection of sodium hydroxide into the myocardium, the systolic arterial pressure, systolic left ventricular pressure, maximum LV dP/dt, peak flow, and CO increased by 21, 24, 58, 144, and 37%, respectively. The mean left atrial pressure also decreased by 15% when the DMLVAD was driven. These effects were most prominent when the mean left atrial pressure was over 15 mm Hg, and the driving pressure was over 100 mm Hg. Compression at late systole was more effective in obtaining greater CO. We suggest that the DMLVAD could be an optional circulatory assist device for patients with left ventricular failure awaiting heart transplantation.     

Systematic Review of Phosphodiesterase‐5 Inhibitor Use in Right Ventricular Failure Following Left Ventricular Assist Device Implantation

Our aim was to identify relevant literature supporting the use of phosphodiesterase‐5 (PDE5) inhibitors in patients with persistent pulmonary hypertension with signs of postprocedural right ventricular (RV) dysfunction following left ventricular assist device (LVAD) implantation. We searched MEDLINE, SCOPUS, and Web of Science from inception through November 27, 2014 for citations evaluating patients with end‐stage heart failure necessitating LVAD, continuous and pulsatile, who received a PDE5 inhibitor to prevent RV failure. Outcomes of interest included changes in mean pulmonary artery pressure, pulmonary vascular resistance, central venous pressure, cardiac index, and mean arterial pressure. Results are presented qualitatively. Four citations (n = 83 patients) were included. These included a single case report, two retrospective case series, and a prospective open‐label study with a historical control. All four studies utilized the PDE5 inhibitor sildenafil with various doses for up to 3 months. Sildenafil routinely reduced mean pulmonary artery pressures as soon as 90 min after administration. Reductions in pulmonary vascular resistance were also seen shortly after the procedure and maintained through 12–15 weeks. While one study saw improvements in postoperative central venous pressures, another did not. Evidence supporting PDE5 inhibitor use to attenuate RV failure in patients requiring an LVAD is weak.     

Changes in Spirometry After Left Ventricular Assist Device Implantation

Left ventricular assist devices (LVADs) are increasingly being used as life‐saving therapy in patients with end‐stage heart failure. The changes in spirometry following LVAD implantation and subsequent unloading of the left ventricle and pulmonary circulation are unknown. In this study, we explored long‐term changes in spirometry after LVAD placement. In this retrospective study, we compared baseline preoperative pulmonary function test (PFT) results to post‐LVAD spirometric measurements. Our results indicated that pulmonary function tests were significantly reduced after LVAD placement (forced expiratory volume in one second [FEV₁]: 1.9 vs.1.7, P = 0.016; forced vital capacity [FVC]: 2.61 vs. 2.38, P = 0.03; diffusing capacity of the lungs for carbon monoxide [DLCO]: 14.75 vs. 11.01, P = 0.01). Subgroup analysis revealed greater impairment in lung function in patients receiving HeartMate II (Thoratec, Pleasanton, CA, USA) LVADs compared with those receiving HeartWare (HeartWare, Framingham, MA, USA) devices. These unexpected findings may result from restriction of left anterior hemi‐diaphragm; however, further prospective studies to validate our findings are warranted.     

Effects of Right Ventricular Failure on Renal Function During Pneumatic Left Ventricular Assist

Abstract: In an experimental dog model of acute biventricular failure, the effects of left ventricular (LV) assist on renal hemodynamics and function were evaluated. After the induction of severe cardiac failure by multiple ligation of the coronary arteries, LV assist with a 40 ml pneumatic pulsatile pump was initiated, and the aortic flow was maintained at control values. The right atrial pressure (RAP) rose to 21.3 mm Hg with the appearance of profound right ventricular (RV) failure. Renal arterial blood flow (RAF) decreased to about 60% of the control value after 2 h of LV assist. The urine volume decreased and renal function deteriorated progressively. RV assist decreased the RAP to 4.8 mm Hg, and the reduced RAF recovered. After 3 h of RV assist, the RAF returned to initial values and the urine volume increased, but renal function did not recover. Advanced biventricular failure with elevated RAP during LV assist reduced renal perfusion and impaired renal function and may be an indication for early RV assist     

Remote Monitoring of Left Ventricular Assist Device Parameters After HeartAssist‐5 Implantation

Although several left ventricular assist devices (LVADs) have been used widely, remote monitoring of LVAD parameters has been available only recently. We present our remote monitoring experience with an axial‐flow LVAD (HeartAssist‐5, MicroMed Cardiovascular, Inc., Houston, TX, USA). Five consecutive patients who were implanted a HeartAssist‐5 LVAD because of end‐stage heart failure due to ischemic (n = 4) or idiopathic (n = 1) cardiomyopathy, and discharged from hospital between December 2011 and January 2013 were analyzed. The data (pump speed, pump flow, power consumption) obtained from clinical visits and remote monitoring were studied. During a median follow‐up of 253 (range: 80–394) days, fine tuning of LVADs was performed at clinical visits. All patients are doing well and are in New York Heart Association Class‐I/II. A total of 39 alarms were received from three patients. One patient was hospitalized for suspected thrombosis and was subjected to physical examinations as well as laboratory and echocardiographic evaluations; however, no evidence of thrombus washout or pump thrombus was found. The patient was treated conservatively. Remaining alarms were due to insufficient water intake and were resolved by increased water consumption at night and summer times, and fine tuning of pump speed. No alarms were received from the remaining two patients. We believe that remote monitoring is a useful technology for early detection and treatment of serious problems occurring out of hospital thereby improving patient care. Future developments may ease troubleshooting, provide more data from the patient and the pump, and eventually increase physician and patient satisfaction. Despite all potential clinical benefits, remote monitoring should be taken as a supplement to rather than a substitute for routine clinical visits for patient follow‐up.     

Implantation of the Left Ventricular Assist Device

Development of mechanical devices for support of the failing heart is a major goal in cardiac surgery. The application of left ventricular assist device (LVAD) is a promising approach in the case of severe and otherwise untreatable cardiac failure. In our experience we have used two external centrifugal pumps for the extracorporeal biventricular cardiac support in a post-transplantation patient who experienced severe rejection six months after heart transplantation. Our own series includes a total of ten implantations of LVAD's with six patients who could be weaned from the device but only one long-term survivor. The clinical results are not encouraging which suggests that the heart of the patient who needs an LVAD has been damaged beyond any chance for later recovery. Obviously timing is the most crucial aspect of the decision to implant the device. It would appear that orthotopic implantation of the transplanted heart remains the method of definitive treatment.     

Pulse Oximeter Derived Blood Pressure Measurement in Patients With a Continuous Flow Left Ventricular Assist Device

Currently, blood pressure (BP) measurement is obtained noninvasively in patients with continuous flow left ventricular assist device (LVAD) by placing a Doppler probe over the brachial or radial artery with inflation and deflation of a manual BP cuff. We hypothesized that replacing the Doppler probe with a finger‐based pulse oximeter can yield BP measurements similar to the Doppler derived mean arterial pressure (MAP). We conducted a prospective study consisting of patients with contemporary continuous flow LVADs. In a small pilot phase I inpatient study, we compared direct arterial line measurements with an automated blood pressure (ABP) cuff, Doppler and pulse oximeter derived MAP. Our main phase II study included LVAD outpatients with a comparison between Doppler, ABP, and pulse oximeter derived MAP. A total of five phase I and 36 phase II patients were recruited during February–June 2014. In phase I, the average MAP measured by pulse oximeter was closer to arterial line MAP rather than Doppler (P = 0.06) or ABP (P < 0.01). In phase II, pulse oximeter MAP (96.6 mm Hg) was significantly closer to Doppler MAP (96.5 mm Hg) when compared to ABP (82.1 mm Hg) (P = 0.0001). Pulse oximeter derived blood pressure measurement may be as reliable as Doppler in patients with continuous flow LVADs.     

Temporary Right Ventricular Mechanical Support in High‐Risk Left Ventricular Assist Device Recipients Versus Permanent Biventricular or Total Artificial Heart Support

Early planned institution of temporary right ventricular assist device (RVAD) support with the CentriMag (Levitronix LLC, Waltham, MA, USA) in left ventricular assist device (LVAD) recipients was compared with permanent biventricular assist device (BVAD) or total artificial heart (TAH) support. Between 2007 and 2011, 77 patients (age range: 25–70 years) with preoperative evidence of biventricular dysfunction (University of Pennsylvania score >50; University of Michigan score >5) were included. Forty‐six patients (38 men; median age 54.5 years, range: 25–70 years) underwent LVAD placement combined with temporary RVAD support (group A); in 31 patients (25 men; median age 56.7 years, range: 28–68 years), a permanent BVAD or TAH implantation (group B) was performed. Within 30 days, 12 patients from group A (26.08%) and 14 patients from group B (45.1%) died on mechanical support (P = 0.02). Thirty patients (65.2%) in group A were weaned from temporary RVAD support and three (6.5%) underwent permanent RVAD (HeartWare, Inc., Framingham, MA, USA) placement. A total of 26 patients (56.5%) were discharged home in group A versus 17 (54.8%) in group B (P = 0.56). Three patients (8.5%) received heart transplantation in group A and six (19.3%) in group B (P = 0.04). In group A, 90‐day and 6‐month survival was 54.3% (n = 25) versus 51.6% (n = 16) in group B (P = 0.66). In group A, 1‐year survival was 45.6% (n = 21) versus 45.1% (n = 14) in group B (P = 0.81). The strategy of planned temporary RVAD support in LVAD recipients showed encouraging results if compared with those of a similar permanent BVAD/TAH population. Weaning from and removal of the temporary RVAD support may allow patients to be on LVAD support only despite preoperative biventricular dysfunction.     

A Physiological Controller for Turbodynamic Ventricular Assist Devices Based on Left Ventricular Systolic Pressure

The current article presents a novel physiological feedback controller for turbodynamic ventricular assist devices (tVADs). This controller is based on the recording of the left ventricular (LV) pressure measured at the inlet cannula of a tVAD thus requiring only one pressure sensor. The LV systolic pressure (SP) is proposed as an indicator to determine the varying perfusion requirements. The algorithm to extract the SP from the pump inlet pressure signal used for the controller to adjust the speed of the tVAD shows robust behavior. Its performance was evaluated on a hybrid mock circulation. The experiments with changing perfusion requirements were compared with a physiological circulation and a pathological one assisted with a tVAD operated at constant speed. A sensitivity analysis of the controller parameters was conducted to identify their limits and their influence on a circulation. The performance of the proposed SP controller was evaluated for various values of LV contractility, as well as for a simulated pressure sensor drift. The response of a pathological circulation assisted by a tVAD controlled by the introduced SP controller matched the physiological circulation well, while over‐ and underpumping events were eliminated. The controller presented a robust performance during experiments with simulated pressure sensor drift.     

Human Clinical Fitting Study of the DexAide Right Ventricular Assist Device

The DexAide right ventricular assist device (RVAD) has been developed as an implantable RVAD. The purpose of this study was to determine the final design and optimal anatomical placement of the DexAide RVAD when implanted simultaneously with either of two commercially available left ventricular assist devices (LVADs) in patients. A mock-up DexAide RVAD was used to assess configuration with each of two types of commercially available LVADs at the time of LVAD implantation in three human clinical cases. The pump body of the DexAide RVAD was placed either in the preperitoneal space or in the right thoracic cavity. The DexAide RVAD placed into the right thoracic cavity is suitable for use with the Novacor or HeartMate II LVADs. The results of this study will guide the finalization of the inflow cannula and optimal placement of the DexAide RVAD for human clinical trials.     

Minimally Invasive Left Ventricular Assist Device Explantation After Cardiac Recovery: Surgical Technical Considerations

The new generation of left ventricular assist devices (LVADs) has enabled minimally invasive surgical procedures for implantation. Herein we present two alternative approaches for minimally invasive LVAD explantation following cardiac recovery, avoiding a sternotomy and improving patient safety.