Left ventricular assist device weaning: hemodynamic response and relationship to stroke volume and rate reduction protocols

Clinical evidence of myocardial recovery in a small cohort of patients supported with a left ventricular assist device (LVAD) has been reported. Development of an optimal LVAD weaning protocol is needed for these patients to sustain recovery after device explant. In this study, we tested the hypothesis that LVAD stroke volume reduction produces a steady-state mechanical reloading of left ventricular (LV) pressures and volumes compared with LVAD rate reduction that results in transient mechanical reloading of the heart due to beat-to-beat variation in LV pressures and volumes. The relationship of LVAD flow to LVAD stroke volume and systolic interval over a range of LVAD rates (60, 80, 100, 120, and 140 bpm) was validated in a mock circulatory flow loop. In six acute experiments, calves were implanted with a pneumatic paracorporeal LVAD (PVAD, Thoratec, Pleasanton, CA). The PVAD was operated asynchronously in the auto volume mode (full decompression) for 30 minutes to establish a baseline control condition. The calf hearts were then mechanically reloaded by LVAD rate reduction (80, 60, and 40 bpm) or LVAD stroke volume reduction (100, 120, and 140 bpm) protocols consisting of 30 minutes of support at each LVAD beat rate. The order of weaning protocols was randomized with a 30-minute recovery period (LVAD volume mode to fully decompress heart allowing it to rest) between protocols to enable return to baseline control state. Aortic pressure and flow, LV pressure and volume, pulmonary artery flow, and LVAD flow waveforms were recorded for each test condition. The LVAD stroke volume reduction protocol produced steady-state mechanical reloading compared with VAD rate reduction that resulted in transient LV mechanical reloading. This distinction is due to differences in their temporal relationships between LVAD and LV filling and emptying cycles. The acute hemodynamic benefit of LVAD stroke volume reduction was greater reduction in LV end-diastolic pressure and increase in LV segmental shortening than LVAD rate reduction. The long-term effects of steady-state and transient LV mechanical reloading on myocardial structure and function toward achieving sustained myocardial recovery warrant further investigation.     

Prolonged but successful weaning from left ventricular assist device after cardiac decompensation due to late-recognized coarctation of the aorta in a toddler

A 2-year-old boy was presented with late-recognized coarctation of the aorta and pulmonary hypertension due to left ventricular failure. The coarctation was corrected at the day of admission with a good postoperative result. However, weaning from the respirator failed despite multiple drug support due to left ventricular failure. Consequently, a left ventricular assist device (LVAD) was implanted 22 days later. The further course was complicated by systemic hypertension and ongoing pulmonary hypertension requiring extensive antihypertensive therapy. The first attempt to wean from LVAD failed and the left ventricle was left completely unloaded for additional 4 weeks. The second weaning attempt, using a very smooth weaning protocol, led to a recovered left ventricle and facilitated the removal of the assist device after a total of 120 days. The patient was discharged with normal cardiac function, but he still requires antihypertensive therapy. We believe that the slow reduction of the LVAD support was the key measure that leads to the successful weaning of the patient, thereby avoiding heart transplantation.     

Successful bridge to recovery with VAD implantation for anthracycline-induced cardiomyopathy

Anthracyclines are effective antineoplastic drugs, but they are known to be cardiotoxic. Recovery of cardiac function is rare. A few studies on implantation of a ventricular assist device (VAD) have been performed for anthracycline-induced cardiomyopathy. Recovery of left ventricular (LV) function with an LVAD is also rare. Recently, several adjunctive therapies were attempted to restore ventricular function. We report a successful bridge to recovery of ventricular function using VAD implantation for anthracycline-induced cardiomyopathy. The patient was a 57-year-old man who had been diagnosed with diffuse large B-cell lymphoma (DLBCL) at age 52. Combination chemotherapy including hydroxydaunorubicin was started. Complete remission was achieved after chemotherapy. Heart failure symptoms such as fatigue, dyspnea on exertion, and weight gain appeared 5 months later. A cardiac resynchronization device was implanted. His heart function deteriorated. He underwent implantation of a Toyobo LVAD and mitral annuloplasty. After implantation, he was prescribed carvedilol with spironolactone. He was weaned from the LVAD on postoperative day (POD) 239 and discharged on POD 37 after weaning. He remained in New York Heart Association classes within the first- to second-degree range, the LV dimention diastolic/systolic ratio was 56/46 mm, ejection fraction 38%, and mitral regurgitation mild at 3 years after weaning from the LVAD. Our patient could be weaned from LVAD probably due to the combination management strategy employing mitral valvuloplasty, use of cardiac resynchronization therapy, and taking carvedilol with spironolactone. Further studies will be needed to clarify the efficacy of these adjunctive therapies.     

Preoperative beta-blocker treatment is a key for deciding left ventricular assist device implantation strategy as a bridge to recovery

To date, there have been few reports demonstrating preoperative predictors for left ventricular reverse remodeling (LVRR) after LV assist device (LVAD) implantation, especially among patients with dilated cardiomyopathy (DCM). We retrospectively analyzed 60 patients with stage D heart failure due to DCM who had received LVAD treatment [pulsatile flow (PF) type, 26; continuous flow type, 34]. Data were evaluated at 6 months or just before explantation of the LVAD. We defined “LV reverse remodeling” (LVRR) by the achievement of an LV ejection fraction (LVEF) of ≥35 % after 6 months of LVAD support or explantation of LVAD within 6 months. LVRR occurred in 16 of our patients (26.7 %). Uni/multivariate logistic regression analyses for LVRR demonstrated that of the preoperative variables evaluated, PF LVAD usage and insufficient preoperative β-blocker treatment were independent predictors for LVRR. Patients who accomplished LVRR had a better clinical course, including lower levels of aortic valve insufficiency and lower levels of plasma B-type natriuretic peptide. Of the six patients (10.0 %) in whom LVADs were eventually explanted, all had an LVEF of ≥35 % before explantation or at 6 months. Based on these results, we conclude that DCM patients with insufficient preoperative β-blocker treatment have a chance to achieve LVRR under LVAD support as a bridge to recovery.     

Simulation of systolic and diastolic left ventricular dysfunction in a mock circulation: the effect of arterial compliance

Arterial compliance (AC) is expected to play a major role on cardiac efficacy by acute or long-term mechanisms. The aim of this study was to investigate the purely mechanical effect of AC on left ventricular (LV) performance, for different conditions of LV dysfunction (systolic versus diastolic). A hydraulic, Windkessel model of systemic circulation was used. LV function and aortic flow were simulated using a left ventricular assist device (LVAD). Two cases of LV dysfunction were simulated: Case A, systolic and Case B, diastolic dysfunction. In Case A, AC increased from 1.14 to 2.85 ml mm Hg(-1) leading to an increase in LVAD stroke volume up to 6%, while no significant effect was observed in Case B. LVAD systolic work was decreased by 4% in systolic and by 11% in diastolic LVAD dysfunction. The purely mechanical effect of AC changes on LVAD function was different between systolic and diastolic dysfunction. It might be expected that even an acute reduction in arterial stiffness could enhance LV performance by different means in systolic compared to diastolic dysfunction.     

Simulation of systolic and diastolic left ventricular dysfunction in a mock circulation: the effect of arterial compliance

Arterial compliance (AC) is expected to play a major role on cardiac efficacy by acute or long-term mechanisms. The aim of this study was to investigate the purely mechanical effect of AC on left ventricular (LV) performance, for different conditions of LV dysfunction (systolic versus diastolic). A hydraulic, Windkessel model of systemic circulation was used. LV function and aortic flow were simulated using a left ventricular assist device (LVAD). Two cases of LV dysfunction were simulated: Case A, systolic and Case B, diastolic dysfunction. In Case A, AC increased from 1.14 to 2.85 ml mm Hg &#109 1 leading to an increase in LVAD stroke volume up to 6%, while no significant effect was observed in Case B. LVAD systolic work was decreased by 4% in systolic and by 11% in diastolic LVAD dysfunction. The purely mechanical effect of AC changes on LVAD function was different between systolic and diastolic dysfunction. It might be expected that even an acute reduction in arterial stiffness could enhance LV performance by different means in systolic compared to diastolic dysfunction.     

Myocardial size and fibrosis changes during left ventricular assist device support

Previous studies have demonstrated that left ventricular assist device (LVAD) implantation significantly decreases myocyte size and reduces fibrosis of the left ventricle (LV). The objectives of the present study were to evaluate LV functional recovery after LVAD implantation and to assess its predictive factors, including histological findings of LV. Six patients with idiopathic cardiomyopathy underwent LVAD support with an EVAHEART implantable centrifugal pump (Sun Medical Technology Research, Nagano, Japan) for an average support duration of 2.91 years. Histologic samples were obtained from their LV apexes at the time of implantation. At 1 month and at 24 months after implantation, brain natriuretic peptide (BNP) and echocardiographic parameters were evaluated. Brain natriuretic peptide values, LV end-diastolic dimension, LV end-systolic dimension, functional shortening, and right ventricular systolic pressure (RVSP) were improved after LVAD implantation. Patients with developing fibrosis had longer durations of heart-failure history and higher pulmonary artery pressures. Patients with hypertrophic myocytes had smaller FS preoperatively. There was a correlation between the amount of fibrosis and the rate of BNP value change after LVAD implantation. In patients with less fibrosis and smaller myocytes preoperatively, improvement in LV function was observed during LVAD support.     

Triple-site pacing: a new supported therapy approach for bridge to recovery with a left ventricular assist system in a patient with idiopathic dilated cardiomyopathy

Left ventricular assist devices (LVAD) are widely used as bridges to cardiac transplantation or for destination therapy. LVAD support may also function as a bridge to ventricular recovery, but a sufficient rate of recovery has not been obtained, even with various adjuvant therapies. Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure, and there is a report of successful weaning off LVAD with CRT. However, some patients with CRT could not improve their cardiac function because of residual dyssynchrony. Herein, we describe a case of a successful bridge to recovery with triple-site pacing for residual dyssynchrony after biventricular pacing. A 34-year-old woman with heart failure due to dilated cardiomyopathy whose condition deteriorated underwent Toyobo LVAD implantation, resulting in improvement of the left ventricular ejection fraction (LVEF) from 12 to 36%. Because of left ventricular dyssynchrony, we performed CRT, but residual dyssynchrony impeded cardiac recovery. We inserted an additional ventricular lead at the right ventricular outlet to achieve triple-site pacing in order to obtain complete synchronization. The LVEF improved to 45%, and the patient was successfully weaned off the LVAD. In LVAD-supported cases of persistent left ventricular dyssynchrony with CRT, implantation of triple-site pacing could potentially accelerate recovery.     

左心室辅助装置控制模式影响双心室搏动同步性的数值研究

右心室(RV)衰竭已成为左心室辅助装置(LVAD)治疗的一种致命并发症。由LVAD引起的双心室搏动的不同步是引发RV功能障碍的重要因素。本文采用数值方法研究LVAD的控制模式对左、右心室搏动同步性的影响。数值结果表明:左心室(LV)与RV的收缩持续时间在无泵模式下没有显著差异(分别为48.52%和51.77%)。连续模式下,LV收缩期明显短于RV收缩期(LV vs.RV:24.38%vs.49.16%)和无泵模式的LV收缩期。搏动模式下,LV收缩期明显短于RV收缩期(LV vs.RV:28.38%vs.50.41%)但长于连续模式的LV收缩期。反搏动模式中的LV、RV收缩期差异较小(LV vs.RV:43.13%vs.49.23%),而LV收缩期短于无泵模式,并且长于连续模式。与连续和搏动模式相比,由反搏动模式提供的收缩期转速(RS)降低显著地校正了LV收缩持续时间,连续模式下缩短的收缩持续时间在反搏动模式下被校正为LV和RV之间的重新同步。因此,本文认为LV和RV收缩的再同步有助于预防RV功能障碍。总之,使用在收缩期间降低RS的反搏动模式有望用于由LVAD引起的双心室搏动不同步的临床校正。     

Computational analysis of the effect of mitral and aortic regurgitation on the function of ventricular assist devices using 3D cardiac electromechanical model

Valvular insufficiency affects cardiac responses and the pumping efficacy of left ventricular assist devices (LVADs) when patients undergo LVAD therapy. Knowledge of the effect of valvular regurgitation on the function of LVADs is important when treating heart failure patients. The goal of this study was to examine the effect of valvular regurgitation on the ventricular mechanics of a heart under LVAD treatment and the pumping efficacy of an LVAD using a computational model of the cardiovascular system. For this purpose, a 3D electromechanical model of failing ventricles in a human heart was coupled with a lumped-parameter model of valvular regurgitation and an LVAD-implanted vascular system. We used the computational model to predict cardiac responses with respect to the severity of valvular regurgitation in the presence of LVAD treatment. An LVAD could reduce left ventricle (LV) pressure (up to 34%) and end-diastolic ventricular volume (up to 80%) and maintain cardiac output at the estimated flow rate from the LVAD under the condition of mitral regurgitation (MR); however, the opposite would occur under the condition of aortic regurgitation (AR). Considering these physiological responses, we conclude that AR, and not MR, diminishes the pumping function of LVADs.     

Clinical evaluation of right ventricular function in patients with left ventricular assist device (LVAD).

Right ventricular function (RVF) during LVAD support can be a threat for patient survival. Despite extensive research, RVF and its interference with left heart function is unclear. This study examines RVF in a retrospective analysis of 14 patients. Hemodynamic data were collected, including heart rate (HR), central venous pressure (CVP), mean pulmonary artery pressure (mPAP), total cardiac output (CO), calculated stroke volume index (SVI) and right ventricular stroke work index (RVSWI). In all patients, CO increased gradually throughout the study period; CVP showed no significant decrease; mPAP and PCWP decreased significantly over the time period; SVI improved and RVSWI increased from the starting level prior to implantation of the LVAD. We conclude that the CO improved with a lowering of the right ventricular afterload combined with a decrease in total circulating volume. The improvement of RVF with LV assist makes this device an option as a bridge to transplant.     

Pitfalls in the development of a rotary blood pump controller

The controller presents a major obstacle in the development of the rotary blood pump as a left ventricular assist device (LVAD). Clinically, LVAD flow is a good indicator in the regulation of circulatory conditions and pump flow changes, depending on pump preload and afterload. Many investigators have tried estimating pump flow by referencing the motor current. There have been pitfalls in in vitro experimental settings, however. Using a test loop with a pneumatically driven LV chamber and a centrifugal pump as an LVAD, we monitored pump flow and pressure head to evaluate the pump performance curve (H-Q curve). Under pulsatile LV conditions, the H-Q curve was a loop that changed, depending on LV contractility. The pneumatically driven LV chamber cannot mimic the Starling phenomenon, so the developed LV pressure does not change according to the LV preload. Rotary pump flow estimation is the most effective control method. In pulsatile conditions, however, the H-Q curve is a loop that changes under various LV contractility conditions, complicating determination of linear equation for calculating flow. In addition, the LV chamber in the test loop cannot mimic native heart contractility as described by Starling's law. This finding can lead to a misanalysis of the H-Q curve under pulsatile conditions.     

Catch 22: a case of incessant ventricular tachycardia post-left ventricular assist device resulting in right ventricular failure,left ventricular cavity obliteration and failure of endocardial ventricular tachycardia ablation

Ventricular tachycardia (VT) in the setting of left ventricular assist device (LVAD) therapy has been well described. We present a case of incessant ventricular tachycardia resulting in severe right ventricular (RV) failure and subsequent left ventricular (LV) cavity obliteration, which in turn diminished the feasibility of initial attempt at VT ablation.     

Development of a novel drive mode to prevent aortic insufficiency during continuous-flow LVAD support by synchronizing rotational speed with heartbeat

Aortic insufficiency (AI) is a serious complication for patients on long-term support with left ventricular assist devices (LVAD). Postoperative aortic valve opening is an important predictor of AI. A system is presently available that can promote native aortic flow by reducing rotational speed (RS) for defined intervals. However, this system can cause a reduction in pump flow and lead to insufficient support. We therefore developed a novel “delayed copulse mode” to prevent AI by providing both minimal support for early systole and maximal support shortly after aortic valve opening by changing the RS in synchronization with heartbeat. To evaluate whether our drive mode could open the aortic valve while maintaining a high total flow (sum of pump flow and native aortic flow), we installed a centrifugal LVAD (EVAHEART^®; Sun Medical) in seven goats each with normal hearts and acute LV dysfunction created by micro-embolization of the coronary artery. We intermittently switched the drive mode from continuous (constant RS) with 100 % bypass to delayed copulse mode with 90 % bypass. Total flow did not significantly change between the two modes. The aortic valve opened when the delayed copulse mode was activated. The delayed copulse mode allowed the aortic valve to open while maintaining a high total flow. This novel drive mode may considerably benefit patients with severe heart failure on long-term LVAD support by preventing AI.     

Recovery directed left ventricular assist device: a new concept

To promote cardiac recovery, we developed a recovery directed left ventricular assist device (RDLVAD) that consists of a valved apical conduit, an afterload controlling chamber (ACC), and a pump. We evaluated its efficacy by comparison with an ordinary LVAD. In each of six pigs with ischemia-induced heart failure, flow and pressure measurements were made while maintaining the total blood flow and arterial pressure equal in the two groups. RDLVAD was able to direct all the blood ejected from the LV into the ACC (0-15 mm Hg) but not into the aorta (73 mm Hg). In the ordinary LVAD, however, some ejection occurred into the aorta despite vigorous suction of the LV. Thus, RDLVAD increased DPTI/SPTI 2.3 times (p < 0.005) and decreased left ventricular end-diastolic pressure by 40% and maximum dP/dt by 20% (p < 0.05). Even the apical valve, at approximately half the diameter of the aortic valve, was able to allow all the blood ejected from the LV to enter the ACC. In one control group pig that achieved almost no ejection into the aorta, left ventricular relaxation and dilatation was extremely limited. RDLVAD may promote cardiac recovery by ensuring less LV work, a greater blood supply/demand ratio in the coronary circulation, and full ventricular relaxation.     

Atrial, ventricular, or both cannulation sites to optimize left ventricular assistance?

The efficiency of left ventricular assist devices (LVADs) depends on the capacity of the inflow cannula to drain blood into the pump. Left atrial (LA) and left ventricular (LV) sites were compared in an animal model mimicking different hemodynamic conditions. Three calves (56.3+/-5.0 kg) were equipped with a Thoratec LVAD. A regular cardiopulmonary bypass (CPB) circuit was used as a right ventricular assist device (RVAD) (jugular vein/pulmonary artery), and preload conditions were adjusted by storage (or perfusion) of blood into (or from) the venous reservoir. LA and LV drainage, tested separately or simultaneously, was measured by its effect on the LVAD's performance. The LVAD was used alone on a beating heart or together with the RVAD (biVAD) on a beating and on a fibrillating heart. Increasing the central venous pressure (CVP) highlighted the differences between the LA and LV cannulation sites when the LVAD was tested either alone or together with the RVAD (biVAD) on a beating heart. Drainage through the LA or the LV was similar when CVP was set at 8 mm Hg, and increasing CVP to 14 mm Hg allowed for better drainage through the LV cannula. In contrast, after induction of fibrillation to mimic extreme heart failure, the drainage was better through the LA cannula. Using both LA and LV cannulae simultaneously did not improve the LVAD output in any of the conditions tested. LV cannulation provides better blood drainage when used on a normal beating heart and, therefore, allows for increased LVAD performance. However, in severe heart failure, blood drainage through the LV cannula decreases and the LA cannulation site is superior.     

Simple implantation of a temporary right ventricular device for right ventricular failure after left ventricular device implantation via a left lateral thoracotomy

Right ventricular (RV) support in the case of RV failure after left ventricular assist device (LVAD) implantation is a well-established surgical therapeutic option. However, there is a serious limitation of RV support after the insertion of a LVAD through lateral thoracotomy in patients who have undergone previous multiple cardiac operations. We describe a modified surgical approach for implantation of right ventricular assist devices (RVADs) via left lateral thoracotomy, with venous cannulation via a femoral vein and transpericardial outflow cannulation of the main pulmonary artery by Seldinger technique under echocardiographic monitoring. This technique was successfully used in a case with subsequent weaning from the RVAD after 10 days of support.     

Emergency implantation of a left ventricular assist device in adolescents with biventricular failure

Adolescents with congestive cardiomyopathy who present with intractable arrhythmia or progressive ventricular failure have a very poor prognosis and often die awaiting cardiac transplantation (CTx). We present our recent experience with a pneumatically powered left ventricular assist device (LVAD) implanted emergently to salvage adolescents with severe biventricular failure. Four patients, aged 15-17 years, body surface areas of 1.5-1.7 m2, with dilated cardiomyopathy (LV diastolic dimension, 7.1-8.3 cm); two presented with cardiovascular collapse, one with refractory ventricular tachycardia, and one with cardiac arrest. Hemodynamic and biochemical data before and 1 week after LVAD placement are expressed as mean and range values. None of the patients required right ventricular assist, and all patients achieved functional recovery while on LVAD support (8-71 days). Currently, all four patients are alive (11-22 months) after successful CTx. We conclude that emergency implantation of an LVAD in adolescents with biventricular heart failure can be life saving. As has been shown in the adult population, such a ventricular assist system restores normal circulatory hemodynamics, reverses multi-organ dysfunction, and provides a "safe" bridge to transplantation.     

Prediction of aortic valve regurgitation after continuous-flow left ventricular assist device implantation using artificial intelligence trained on acoustic spectra

Significant aortic regurgitation (AR) is a common complication after continuous-flow left ventricular assist device (LVAD) implantation. Using machine-learning algorithms, this study was designed to examine valuable predictors obtained from LVAD sound and to provide models for identifying AR. During a 2-year follow-up period of 13 patients with Jarvik2000 LVAD, sound signals were serially obtained from the chest wall above the LVAD using an electronic stethoscope for 1 min at 40,000 Hz, and echocardiography was simultaneously performed to confirm the presence of AR. Among the 245 echocardiographic and acoustic data collected, we found 26 episodes of significant AR, which we categorized as “present”; the other 219 episodes were characterized as “none”. Wavelet (time–frequency) analysis was applied to the LVAD sound and 19 feature vectors of instantaneous spectral components were extracted. Important variables for predicting AR were searched using an iterative forward selection method. Seventy-five percent of 245 episodes were randomly assigned as training data and the remaining as test data. Supervised machine learning for predicting concomitant AR involved an ensemble classifier and tenfold stratified cross-validation. Of the 19 features, the most useful variables for predicting concomitant AR were the amplitude of the first harmonic, LVAD rotational speed during intermittent low speed (ILS), and the variation in the amplitude during normal rotation and ILS. The predictive accuracy and area under the curve were 91% and 0.73, respectively. Machine learning, trained on the time–frequency acoustic spectra, provides a novel modality for detecting concomitant AR during follow-up after LVAD.

     

Bone-destroying candida infection following left ventricular assist device explant

Infections associated with left ventricular assist devices (LVADs) constitute an important clinical issue because they are difficult to completely eradicate without removal of the LVAD itself and can sometimes be fatal. We encountered a case of extracorporeal LVAD-related candida infection in a patient who was successfully weaned from LVAD support. Although the patient appeared to have recovered from the infection, the patient was readmitted to our institute due to a relapse of candida infection 9 months after LVAD removal. Although the patient did not demonstrate any systemic sign of infection on admission, computed tomography images clearly showed that the residual apical cuff of the LVAD inflow cannula, which was infected with Candida albicans during the initial admission, resulted in re-infection that involved the chest wall with destruction of the adjacent rib.