Continuous-flow Left Ventricular Assist Device Support Research Articles

Machine Learning Multicenter Risk Model to Predict Right Ventricular Failure After Mechanical Circulatory Support

The existing models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support might be limited, partly due to lack of external validation, marginal predictive power, and absence of intraoperative characteristics. To derive and validate a risk model to predict RVF after LVAD implantation. This was a hybrid prospective-retrospective multicenter cohort study conducted from April 2008 to July 2019 of patients with advanced heart failure (HF) requiring continuous-flow LVAD. The derivation cohort included patients enrolled at 5 institutions. The external validation cohort included patients enrolled at a sixth institution within the same period. Study data were analyzed October 2022 to August 2023. Study participants underwent chronic continuous-flow LVAD support. The primary outcome was RVF incidence, defined as the need for RV assist device or intravenous inotropes for greater than 14 days. Bootstrap imputation and adaptive least absolute shrinkage and selection operator variable selection techniques were used to derive a predictive model. An RVF risk calculator (STOP-RVF) was then developed and subsequently externally validated, which can provide personalized quantification of the risk for LVAD candidates. Its predictive accuracy was compared with previously published RVF scores. The derivation cohort included 798 patients (mean [SE] age, 56.1 [13.2] years; 668 male [83.7%]). The external validation cohort included 327 patients. RVF developed in 193 of 798 patients (24.2%) in the derivation cohort and 107 of 327 patients (32.7%) in the validation cohort. Preimplant variables associated with postoperative RVF included nonischemic cardiomyopathy, intra-aortic balloon pump, microaxial percutaneous left ventricular assist device/venoarterial extracorporeal membrane oxygenation, LVAD configuration, Interagency Registry for Mechanically Assisted Circulatory Support profiles 1 to 2, right atrial/pulmonary capillary wedge pressure ratio, use of angiotensin-converting enzyme inhibitors, platelet count, and serum sodium, albumin, and creatinine levels. Inclusion of intraoperative characteristics did not improve model performance. The calculator achieved a C statistic of 0.75 (95% CI, 0.71-0.79) in the derivation cohort and 0.73 (95% CI, 0.67-0.80) in the validation cohort. Cumulative survival was higher in patients composing the low-risk group (estimated <20% RVF risk) compared with those in the higher-risk groups. The STOP-RVF risk calculator exhibited a significantly better performance than commonly used risk scores proposed by Kormos et al (C statistic, 0.58; 95% CI, 0.53-0.63) and Drakos et al (C statistic, 0.62; 95% CI, 0.57-0.67). Implementing routine clinical data, this multicenter cohort study derived and validated the STOP-RVF calculator as a personalized risk assessment tool for the prediction of RVF and RVF-associated all-cause mortality.

Computational evaluation of heart failure and continuous flow left ventricular assist device support in anaemia.

Anaemia is common in end-stage heart failure patients supported with continuous flow left ventricular assist device (CF-LVAD) and is associated with adverse outcomes such as heart failure readmission. This study evaluates the haemodynamic effects of anaemia on cardiac function and cerebral blood flow in heart failure patients supported with CF-LVAD using computational simulations. A dynamic model simulating cardiac function, systemic, pulmonary and cerebral circulations, cerebral flow autoregulatory mechanisms and gas contents in blood was used to evaluate the effects of anaemia and iron deficiency in heart failure and during CF-LVAD support. CF-LVAD therapy was simulated by a model describing HeartMate 3. Anaemia and iron deficiency were simulated by reducing the haemoglobin level from 15 to 9 g/dL and modifying scaling coefficients in the models simulating heart chamber volumes. Reduced haemoglobin levels decreased the arterial O2 content, which increased cerebral blood flow rate by more than 50% in heart failure and during CF-LVAD assistance. Reduced haemoglobin levels simulating anaemia had minimal effect on the arterial and atrial blood pressures and ventricular volumes. In contrast, iron deficiency increased end-diastolic left and right ventricular diameters in heart failure from 6.6 cm to 7 cm and 2.9 cm to 3.1 cm and during CF-LVAD support from 6.1 to 6.4 cm and 3.1 to 3.3 cm. The developed numerical model simulates the effects of anaemia in failing heart and during CF-LVAD therapy. It is in good agreement with clinical data and can be utilised to assess CF-LVAD therapy.

Preoperative higher right ventricular stroke work index increases the risk of de novo aortic insufficiency after continuous-flow left ventricular assist device implantation

During continuous-flow left ventricular assist device (CF-LVAD) support, hemodynamic shear stress causes a burden on aortic valve (AV) leaflets, leading to de novo aortic insufficiency (AI). This study investigated the influence of preoperative hemodynamic parameters on de novo AI in CF-LVAD recipients. We reviewed 125 patients who underwent CF-LVAD implantation without concomitant AV surgery between 2005 and 2018. De novo AI was defined as moderate or severe AI in those with none or trivial preoperative AI. During mean 30 ± 16 months of CF-LVAD support, de novo AI-free rate was 86% and 67% at 1 and 2 years, respectively. Multivariable analysis showed that higher right ventricular stroke work index (RVSWI) (hazard ratio, 1.12 /g/m2/beat; 95% confidence interval, 1.00–1.20; p = 0.047) and trivial grade AI (hazard ratio, 2.8; 95% confidence interval, 1.2–6.4; p = 0.020) were independent preoperative risk factors for de novo AI. The longitudinal analysis using generalized mixed effects model showed that higher RVSWI was associated with continuous AV closure after LVAD implantation (Odd ratio, 1.20/g/m2/beat; 95% confidence interval, 1.00–1.43 /g/m2/beat; p = 0.047). Right heart catheterization revealed that preoperative RVSWI was positively correlated with postoperative pump flow index in patients with continuously closed AV (r = 0.44, p = 0.04, n = 22). Preoperative higher RVSWI was a significant risk factor for de novo AI following CF-LVAD implantation. In patients with preserved right ventricular function, postoperative higher pump flow may affect AI development via hemodynamic stress on the AV.

Transcatheter valvular therapies in patients with left ventricular assist devices.

Aortic, mitral and tricuspid valve regurgitation are commonly encountered in patients with continuous-flow left ventricular assist devices (CF-LVADs). These valvular heart conditions either develop prior to CF-LVAD implantation or are induced by the pump itself. They can all have significant detrimental effects on patients' survival and quality of life. With the improved durability of CF-LVADs and the overall rise in their volume of implants, an increasing number of patients will likely require a valvular heart intervention at some point during CF-LVAD therapy. However, these patients are often considered poor reoperative candidates. In this context, percutaneous approaches have emerged as an attractive "off-label" option for this patient population. Recent data show promising results, with high device success rates and rapid symptomatic improvements. However, the occurrence of distinct complications such as device migration, valve thrombosis or hemolysis remain of concern. In this review, we will present the pathophysiology of valvular heart disease in the setting of CF-LVAD support to help us understand the underlying rationale of these potential complications. We will then outline the current recommendations for the management of valvular heart disease in patients with CF-LVAD and discuss their limitations. Lastly, we will summarize the evidence related to transcatheter heart valve interventions in this patient population.

Continuous-flow left ventricular assist devices associated survival awaiting heart and heart-kidney transplant.

Improvement in continuous-flow left ventricular assist device (CF-LVAD) technology has translated to better outcomes for patients on CF-LVAD support as a bridge-to-transplant. However, data are lacking regarding the subset of CF-LVAD patients with renal failure awaiting simultaneous heart-kidney transplant (HKTx). We sought to better understand the characteristics and outcomes of patients in this group. The United Network for Organ Sharing (UNOS) database was used to identify adult patients listed for heart transplant (HTx) or HKTx from January 1, 2009 to March 31, 2017. Patients were followed from time on waitlist to either removal from waitlist or transplantation. Demographic and clinical data for HTx and HKTx patients were assessed. Kaplan-Meier analysis assessed waitlist and post-transplant survival. For waitlisted patients, both death and removal from the waitlist due to deteriorating medical condition were considered events. Overall, 26 638 patients registered for transplant were analyzed. 25 111 (94%) were listed for HTx, and 1527 (6%) for HKTx. 7683 (29%) patients listed for HTx had CF-LVAD support. For those listed for HKTx, 441 (28%) underwent dialysis alone, 256 (17%) had CF-LVAD support alone, and 85 (6%) were treated with both CF-LVAD and dialysis. 15 567 (58%) underwent HTx, and 621 (2%) underwent HKTx. In these groups, post-transplant survival was similar (p=0.06). Patients listed for HKTx treated with both dialysis and CF-LVAD had significantly worse waitlist survival compared to HKTx recipients (p < 0.001). Post-transplant survival is comparable between HTx and HKTx, and early survival is similar between HTx patients and those listed for HTx with CF-LVAD support. However, outcomes on the waitlist for HKTx in CF-LVAD patients on dialysis is significantly worse compared to HKTx recipients. This highlights the need to better account for this patient population when allocating organs.

Pulsatile Pressure Delivery of Continuous-Flow Left Ventricular Assist Devices Is Markedly Reduced Relative to Heart Failure Patients.

Although continuous-flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in vivo data regarding systemic pulsatility on support. Patients supported on CF-LVAD therapy (n = 71) who underwent combined left/right catheterization ramp study were included. Aortic pulsatility was defined by the pulsatile power index (PPI), which was also calculated in a cohort of high-output heart failure (HOHF, n = 66) and standard HF cohort (n = 44). PPI was drastically lower in CF-LVAD-supported patients with median PPI of 0.006 (interquartile range [IQR], 0.002-0.012) compared with PPI in the HF population at 0.09 (IQR, 0.06-0.17) or HOHF population at 0.25 (IQR, 0.13-0.37; p < 0.0001 among groups). With speed augmentation during ramp, PPI values fell quickly in patients with higher PPI at baseline. PPI correlated poorly with left ventricular ejection fraction (LVEF) in all groups. In CF-LVAD patients, there was a stronger correlation with LV dP/dt (r = 0.41; p = 0.001) than LVEF (r = 0.21; p = 0.08; pint < 0.001). CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with speed. Further work is needed to determine the applicability to the next generation of device therapy.

Concomitant or late aortic valve intervention and its efficacy for aortic insufficiency associated with continuous-flow left ventricular assist device implantation.

Moderate to severe aortic insufficiency (AI) in patients who underwent continuous-flow left ventricular assist device (CF-LVAD) implantation is a significant complication. According to the INTERMACS registry analysis, at least mild AI occurs in 55% of patients at 6 months after CF-LVAD implantation and moderate to severe AI is significantly associated with higher rates of re-hospitalization and mortality. The clinical implications of these data may underscore consideration of prophylactic aortic valve replacement, or repair, at the time of CF-LVAD implantation, particularly with expected longer duration of support and in patients with preexisting AI that is more than mild. More crucially, even if a native aortic valve is seemingly competent at the time of VAD implantation, we frequently find de novo AI as time goes by, potentially due to commissural fusion in the setting of inconsistent aortic valve opening or persistent valve closure caused by CF-LVAD support, that alters morphological and functional properties of innately competent aortic valves. Therefore, close monitoring of AI is mandatory, as the prognostic nature of its longitudinal progression is still unclear. Clearly, significant AI during VAD support warrants surgical intervention at the appropriate timing, especially in patients of destination therapy. Nonetheless, such an uncertainty in the progression of AI translates to a lack of consensus regarding the management of this untoward complication. In practice, proposed surgical options are aortic valve replacement, repair, closure, and more recently transcatheter aortic valve implantation or closure. Transcatheter approach is of course less invasive, however, its efficacy in terms of long-term outcome is limited. In this review, we summarize the recent evidence related to the pathophysiology and surgical treatment of AI associated with CF-LVAD implantation.

Pulsatile Pressure Delivery of Continuous Flow LVAD is Speed Dependent and Markedly Reduced Relative to Heart Failure Patients

<h3>Purpose</h3> Although continuous flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in-vivo data regarding systemic pulsatility on support. <h3>Methods</h3> A retrospective cohort study was performed in patients supported on CF-LVAD therapy (n=67) who underwent a combined left and right heart catheterization ramp protocol. Aortic pulsatility was defined by the pulsatile power index (PPI), a quantity derived from the amplitudes of the harmonics of the pressure waveform. PPI was calculated in a cohort of high-output heart failure (HOHF, n=66) and standard HF cohort (n=44) and invasive hemodynamics and pulsatility were compared. <h3>Results</h3> Systemic, pulmonary artery, and pulmonary capillary wedge pressures were lower in the LVAD cohort (<i>P</i>≤.04 for each) compared with HOHF or HF. PPI was drastically lower in CF-LVAD supported patients with median PPI .006 (IQR .002-.012) vs PPI .09 (IQR .06-.17) in HF and PPI .25 (IQR .13-.37) in HOHF (<i>P</i><.0001 among groups). PPI more significantly differed between groups than aortic pulse width. With speed augmentation during ramp, PPI values fell more quickly in centrifugal flow pumps than axial flow (slopes -3.3 × 10⁻⁵ and -1.1 × 10⁻⁵ vs -6.9 × 10⁻⁶ for HW, HM3, and HMII respectively). PPI correlated poorly with LV ejection fraction (LVEF) in CF-LVAD patients and HOHF (<i>P</i>>.05) and modestly (r=.38, <i>P</i>=.01) in HF but in CF-LVAD patients, there was a stronger correlation with LV dP/dt (r=.41, <i>P</i>=.002) than LVEF (r=.21, <i>P</i>=.09, <i>P_int</i> <.001). <h3>Conclusion</h3> CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with increasing speed. Further work is needed to determine the applicability to the next generation of device therapy.

Metabolic and Hemodynamic Determinants of Exercise with the HeartMate 3 LVAD

<h3>Purpose</h3> Several studies have reported that peak oxygen consumption (pVO2) is diminished after continuous flow (CF) LVAD support and recent data shows that pVO2 post LVAD predicts outcomes. It has been suggested that augmentation of native cardiac output (NCO) and not LVAD flow supports exercise. Using simultaneous metabolic and hemodynamic measures, we further studied the determinants of maximal exercise with the Heartmate 3 (HM3) LVAD. <h3>Methods</h3> Subjects underwent maximal upright bicycle exercise testing utilizing a 10-15 W ramp protocol with hemodynamic measurements from a right heart and radial arterial catheter, and CPET testing with a metabolic cart (Metalyzer 3B, Cortex, Germany). Mid-point hemodynamics were acquired to plot pressure/flow relationships. NCO was calculated by subtracting LVAD flow from Fick cardiac output (FCO). Arterial lactate and regional tissue oxygenation (rSO2) with the NIRS SenSmart™ were also measured. <h3>Results</h3> Six HM3 subjects (43-76 yrs) were studied at least 12 weeks post implant, all were on at least 2 neurohormonal agents. All patients performed maximal exercise (RER 1.10-1.34). Most did not demonstrate chronotropic incompetence; achieving median 80.8 (63.5- 90.9) % of predicted heart rate. We saw robust oxygen extraction, with median peak A-VO2 difference 14.2 (10.5-15.8) mL/100mL with no change in rSO2 and median peak lactate 6.5 (3.5-9.9) mmol/L. However, 5/6 subjects achieved pVO2 ≤14 ml/kg/min. During exercise, there was minimal augmentation of LVAD flow (0.4-1.6 L/min) while NCO increased by 2.0-7.1 L/min. Mean pulmonary artery (mPA)/FCO relationships were available for 5 subjects (Fig.1), demonstrating abnormal rate of rise of mPA in all patients (slope 3.7-7.0, normal < 3). <h3>Conclusion</h3> Neither chronotropic response nor peripheral extraction appeared to limit exercise. Steep rise in mPA suggests either impaired pulmonary vasoreactivity and or cardiac reserve may be the key determinants of exercise capacity during HM3 support. Further study will clarify these factors.

Progression of aortic insufficiency with durable mechanical support.

As survival rates with continuous flow left ventricular assist device (LVAD) support have improved, the use of these devices as permanent therapy has considerably expanded [1]. Destination therapy refers to this long-term use of LVADs as an alternative to transplantation in patients with end-stage heart failure who are ineligible for transplantation. The current, third generation of LVADs, such as the HeartMate 3 (HM3, Abbott Inc, Chicago, IL, USA), is more durable than their predecessors and has lower complication rates [2]. Patients can be maintained on them for much longer with lower morbidity, making destination therapy now a realistic option. Development of de novo aortic insufficiency (AI) has been observed in up to a third of patients supported by a continuous flow LVAD [3–5]. Worse clinical outcomes have been reported among patients suffering from significant AI while on support [6]. Development of symptomatic AI negatively impacts haemodynamics, increases rehospitalizations for heart failure and decreases survival on continuous flow LVAD support [6]. Thorough assessment of aortic valve functionality is mandated in the decision process for durable LVAD implantation. Those LVAD candidates that suffer from greater than mild AI should be treated with concomitant aortic valve surgery. Contemporary approach in these patients is aortic valve replacement with a biological prosthesis. Mechanical prostheses are contraindicated, due to persistent AI associated with mechanical valve design as well as increased risk of thrombus formation. Park’s central stitch, a simple central coaptation stitch, has been used to reduce AI in patients on continuous flow LVAD support who develop significant insufficiency and some surgeons have proposed prophylactic use of this stitch at the time of device implantation to prevent this complication [7]. Transcatheter aortic valve implantation (TAVI) might be considered as an off-label strategy.

The Interaction of Amiodarone and Continuous-flow Left Ventricular Assist Device Use in Risk of Severe Primary Graft Dysfunction Following Heart Transplantation.

Primary graft dysfunction (PGD) increases morbidity and mortality after heart transplant. Here we investigated (1) the association of continuous-flow left ventricular assist device (CF-LVAD), amiodarone, and severe PGD and (2) the safety of amiodarone discontinuation in CF-LVAD patients. Retrospective, single-center study of heart transplant recipients was conducted to investigate the association of risk factors and severe PGD. Patients were grouped into 4 groups based on the presence (denoted +) or absence (denoted -) of amiodarone and CF-LVAD. Prospective amiodarone discontinuation was undertaken to investigate its safety in a cohort of CF-LVAD patients. Study endpoints were severe PGD and recurrence of arrhythmia. Severe PGD was strongly associated with CF-LVAD and amiodarone use, and its prevalence is highest if both risk factors were present (CF-LVAD-/amiodarone - 1.5%, CF-LVAD -/amiodarone+ 4.5%, CF-LVAD+/amiodarone - 7.1%, CF-LVAD+/amiodarone+ 21.8%; P < 0.01). The product of every 1-y additional CF-LVAD support by every 100 mg amiodarone was associated with severe PGD (adjusted odds ratio, 1.43; 95% confidence interval, 1.15-1.78; P < 0.01). Amiodarone was prospectively discontinued in 28 CF-LVAD patients. Of them, 6 patients had recurrence of arrhythmia requiring treatment or heart failure admission. There were no deaths. Nine patients in whom amiodarone had been discontinued had heart transplants with no severe PGD. Amiodarone and CF-LVAD were independently associated with severe PGD. The combination of both risk factors was associated with a higher prevalence of severe PGD. Amiodarone discontinuation was associated with recurrence of arrhythmia in 6 CF-LVAD patients. There was no mortality associated with amiodarone discontinuation.

Association between early ventricular arrhythmias and mortality in destination vs. bridge patients on continuous flow LVAD support

The association between ventricular arrhythmias (VAs) and mortality in patients supported by continuous flow left ventricular assist devices (LVAD) remains controversial. To evaluate the association between pre-implantation, early (≤ 30 day) post-implantation VAs and mortality in bridge to transplant (BTT) and destination therapy (DT) LVAD patients, separately. The risk factors for post LVAD VAs were also investigated. In this observational cohort study, we included 341 patients who received a first time, continuous flow LVAD between January 1st 2010 and July 30th 2018. We used Kaplan–Meier curves and multivariable cox regression analyses to study the association between VAs and mortality in the BTT and DT populations. The mean age of the cohort was 58 ± 14 years, with 82% males, 53% had ischemic cardiomyopathy, and 45% were DT. The mean follow-up was 2.2 ± 2.1 years. In both BTT and DT cohorts, pre LVAD VAs were not associated with mortality after LVAD implantation (log-rank p = 0.95 and p = 0.089, respectively). In the BTT population, early post-LVAD VAs were not statistically associated with increased mortality (log rank p = 0.072). In the DT patients, early post LVAD VAs were associated with a 67% increase in the hazards rate of mortality on LVAD support (HR 1.67 [1.05–2.65], p = 0.029). The final model was adjusted for type of cardiomyopathy, INTERMACS profile, glomerular filtration rate, post LVAD atrial fibrillation, age and cerebrovascular events. Early post-LVAD VA is common after LVAD implantation and is an independent predictor of mortality in the DT LVAD population.

Long-Term Neurocognitive Outcome in Patients With Continuous Flow Left Ventricular Assist Device

ObjectivesThe authors sought to examine the long-term cognitive outcome of patients with continuous flow left ventricular assist device (CF-LVAD). BackgroundData on long-term neurocognitive outcome in LVAD are limited. We examined the neurocognitive outcome of patients who received a CF-LVAD as destination therapy. MethodsPatients with HeartWare (HVAD) and HeartMate II who were enrolled in the ENDURANCE and ENDURANCE Supplemental trials were eligible. Cognition was evaluated with neuropsychological testing preoperatively and at 6, 12, and 24 months after implantation. General linear models identified demographic, disease, and treatment factors that predicted decline on each neurocognitive measure. ResultsOf 668 patients who completed baseline testing and at least 1 follow-up evaluation, 552 were impaired at baseline on at least 1 cognitive measure. At each follow-up, approximately 23% of tested patients declined and 20% improved relative to baseline on at least 1 cognitive measure. Of those who were intact at baseline, only 10%-12% declined in delayed memory and 11%-16% declined in executive function at all 3 follow-ups. For patients impaired at baseline, delayed memory decline was associated with the HVAD device and male sex, whereas executive function decline was associated with the HVAD device and stroke during CF-LVAD support. For patients intact at baseline, male sex and history of hypertension were associated with decline in immediate memory and executive function, respectively. ConclusionsNeurocognitive function remained stable or improved for most patients (∼80%) with CF-LVAD at 6, 12, and 24 months after implantation. Male sex, hypertension, HVAD, and stroke were associated with cognitive decline.

CardioMEMS Pulmonary Artery Pressure Guided Management of Advanced HF Patients Supported with a HeartMate LVAD: INTELLECT 2-HF Study

PurposeHemodynamic-guided management with a pulmonary artery pressure (PAP) sensor (CardioMEMS) is effective in reducing HF hospitalization (HFH) in chronic HF patients. We sought to determine the utility of managing patients on continuous-flow LVAD support using the CardioMEMSTM HF system.MethodsIn this multi-center observational study, we enrolled patients with a HeartMate 2 (HM2) (n=52) or HM3 (n=49) LVAD who either already had a CardioMEMS sensor (n=53) or were clinically implanted after enrollment for residual HF (n=48). Patients underwent assessments at baseline, 1, 3 and 6 months for endpoints: 6-minute walk distance (6MWD), change in PAP, quality of life score (EQ-5D-5L scores), and HFH rates. Patients were stratified post-hoc as clinical responders (cR) if there was a reduction in PA diastolic pressure (PAD) of at least 1 mmHg at 6 months, and the remainder were deemed non-responders (cNR).ResultsOf 101 patients enrolled, 88 patients completed 6-month follow-up. PAP measurement was feasible with excellent weekly patient compliance (91.1% ± 19.8%). There were no clinically relevant differences between cR (n=37) and cNR (n=46) patients at baseline (data not shown). PAD at 6 months was 3.5 ± 4.6 mmHg lower than baseline within the cR group (20.8 to 17.3 mmHg, p=0.0002) (Figure-panel A). While there were no observed differences in QoL or HFH between cR and cNR, significant increases in 6MWD occurred among cR (286 vs 332 meters, p=0.03, Figure-panel B). Those individuals who maintained a PAD < 20mmHg had significantly reduced HFH (Figure-panel C).ConclusionThe use of CardioMEMS system in HeartMate LVAD patients is feasible. Significant reduction in PAD at 6 months was associated with improvements in 6MWD and achieving a PAD < 20 mmHg was associated with lower HFH events. These findings provide justification and guidance for prospective investigations utilizing the CardioMEMS system to improve the management and outcomes of LVAD patients. Hemodynamic-guided management with a pulmonary artery pressure (PAP) sensor (CardioMEMS) is effective in reducing HF hospitalization (HFH) in chronic HF patients. We sought to determine the utility of managing patients on continuous-flow LVAD support using the CardioMEMSTM HF system. In this multi-center observational study, we enrolled patients with a HeartMate 2 (HM2) (n=52) or HM3 (n=49) LVAD who either already had a CardioMEMS sensor (n=53) or were clinically implanted after enrollment for residual HF (n=48). Patients underwent assessments at baseline, 1, 3 and 6 months for endpoints: 6-minute walk distance (6MWD), change in PAP, quality of life score (EQ-5D-5L scores), and HFH rates. Patients were stratified post-hoc as clinical responders (cR) if there was a reduction in PA diastolic pressure (PAD) of at least 1 mmHg at 6 months, and the remainder were deemed non-responders (cNR). Of 101 patients enrolled, 88 patients completed 6-month follow-up. PAP measurement was feasible with excellent weekly patient compliance (91.1% ± 19.8%). There were no clinically relevant differences between cR (n=37) and cNR (n=46) patients at baseline (data not shown). PAD at 6 months was 3.5 ± 4.6 mmHg lower than baseline within the cR group (20.8 to 17.3 mmHg, p=0.0002) (Figure-panel A). While there were no observed differences in QoL or HFH between cR and cNR, significant increases in 6MWD occurred among cR (286 vs 332 meters, p=0.03, Figure-panel B). Those individuals who maintained a PAD < 20mmHg had significantly reduced HFH (Figure-panel C). The use of CardioMEMS system in HeartMate LVAD patients is feasible. Significant reduction in PAD at 6 months was associated with improvements in 6MWD and achieving a PAD < 20 mmHg was associated with lower HFH events. These findings provide justification and guidance for prospective investigations utilizing the CardioMEMS system to improve the management and outcomes of LVAD patients.

Arrhythmia Burden from Implantable Device Interrogation during Long-Term Follow-Up in LVAD Patients

<h3>Purpose</h3> The burden of atrial arrhythmias (AA) and ventricular tachycardia/fibrillation (VT/VF) during long-term continuous-flow (CF) LVAD support is not well described. <h3>Methods</h3> Our Arrhythmia Database included all implantable cardioverter-defibrillator interrogations completed from September 2015 to August 2019 for 101 consecutive CF-LVAD patients at a single center. Endpoints included first occurrence of any arrhythmia, AA, and VT/VF. <h3>Results</h3> Patients (mean age at LVAD implant 59±12 years, 83% male, 51% with ischemic cardiomyopathy, 60% with history of AA before LVAD implant, and 75% with history of VT/VF before LVAD implant) were supported by an LVAD for a median of 2.1 years before entering the Arrhythmia Database. Subsequent follow-up in the Database extended over >2 years. At 2.5 years from Arrhythmia Database entry (median of 4.5 years from LVAD implant), the cumulative rate of any arrhythmia was 74%, the rate of AA was 66%, and the rate of VT/VF was 47% (Figure). <h3>Conclusion</h3> Both atrial and ventricular arrhythmias remain common during long-term LVAD support (median >4 years). Our findings support the role of generator replacement of implantable devices for continued detection and treatment of arrhythmic events in LVAD patients.

Comparison of Cardiac Reverse Remodeling between Older and Newer Generation Continuous-Flow LVAD

<h3>Purpose</h3> The purpose of our study is to compare the left ventricular (LV) functional and structural changes following mechanical circulatory support (MCS) between continuous-flow left ventricular assist devices (CF-LVADs) that provide mechanical unloading characterized by specific bioengineering differences. <h3>Methods</h3> The study enrolled 311 chronic HF patients undergoing MCS with HVAD (HW, hybrid levitation centrifugal pump, n=95), HeartMate 3 (HM3, full magnetic levitation centrifugal pump, n=140), and HeartMate II (HM2, axial flow pump, n=76) at four sites across the US. Echocardiographic parameters of LV structure and function were obtained pre-implant and at 1, 3, 6, and 12 months of CF-LVAD support. <h3>Results</h3> There were no significant differences in baseline characteristics between groups. At 3 months post-LVAD support the LV ejection fraction (LVEF) was higher (p=0.03, Figure 1A) and left ventricular end diastolic diameter (LVEDD) was lower (p=0.04, Figure 1B) in HMII patients, but there were no significant difference in LVEF and LVEDD between devices at 6 or 12 months. The proportion of patients achieving "cardiac reverse remodeling responder" status (defined as improvement of LVEF to ≥40% and LVEDD <6.0cm) was 9.32%, and comparable between the CF-LVADs. <h3>Conclusion</h3> The newest generation full magnetically levitated CF-LVAD results in similar cardiac reverse remodeling as older generation CF-LVADs. These findings suggest that the fully magnetically levitated device technology could provide an adequate platform to further study and promote reverse cardiac remodeling clinically.

Continuous-flow LVAD exchange to a different pump model: Systematic review and meta-analysis of the outcomes.

Despite improved outcomes of modern continuous-flow left ventricular assist devices (CF-LVADs), device exchange is still needed for various indications. While the majority of CF-LVADs are exchanged to the same model, exchange to a different pump model is occasionally warranted. In this meta-analysis, we sought to consolidate the existing evidence to better elucidate the indications and outcomes in these cases. A comprehensive systematic search of adult patient cohorts who underwent CF-LVAD exchange to a different CF-LVAD model was performed. Study-level data from 10 studies comprising 98 patients were extracted and pooled for analysis. Mean patient age was 58 (95% CI: 48-65) and 81% were male. Indication for initial CF-LVAD was ischemic cardiomyopathy in 45% (34-57). Initial device was HeartMate II LVAD (HMII) in 93 (94.9%) and HeartWare HVAD (HW) in 5 (5.1%) patients. After mean CF-LVAD support time of 18.8 (15.2-22.4) months, exchange indications included thrombosis in 71% (43-89), infection in 21% (8-47) and device malfunction in 12% (7-21). HMII to HW exchange occurred in 53 (54.1%) patients, HMII to HeartMate III (HM3) in 32 (32.7%), and HM II to either HW or HM3 in 13 (13.2%) patients. Postoperatively, right ventricular assist device was required in 16% (8-32). Overall, 20% (8-40) of patients experienced a stroke, while HW patients had a significantly higher stroke incidence than HM3 patients (HW: 21% (8-47) vs. HM3: 5% (1-24), P < .01). Overall 30-day mortality was 10% (6-17), while HW had a significantly worse 30-day mortality than HM3 (HW: 13% (7-24) vs. HM3: 5% (1-24), P = .03). Following device exchange from a different CF-LVAD model, HM3 is associated with lower stroke and higher survival when compared to HW.

Right ventricular function and cardiopulmonary performance among patients with heart failure supported by durable mechanical circulatory support devices

Patients with continuous-flow left ventricular assist devices (CF-LVADs) experience limitations in functional capacity and frequently, right ventricular (RV) dysfunction. We sought to characterize RV function in the context of global cardiopulmonary performance during exercise in this population. A total of 26 patients with CF-LVAD (aged 58 ± 11 years, 23 males) completed a hemodynamic assessment with either conductance catheters (Group 1, n = 13) inserted into the right ventricle to generate RV pressure‒volume loops or traditional Swan‒Ganz catheters (Group 2, n = 13) during invasive cardiopulmonary exercise testing. Hemodynamics were collected at rest, 2 sub-maximal levels of exercise, and peak effort. Breath-by-breath gas exchange parameters were collected by indirect calorimetry. Group 1 participants also completed an invasive ramp test during supine rest to determine the impact of varying levels of CF-LVAD support on RV function. In Group 1, pump speed modulations minimally influenced RV function. During upright exercise, there were modest increases in RV contractility during sub-maximal exercise, but there were no appreciable increases at peak effort. Ventricular‒arterial coupling was preserved throughout the exercise. In Group 2, there were large increases in pulmonary arterial, left-sided filling, and right-sided filling pressures during sub-maximal and peak exercises. Among all participants, the cardiac output‒oxygen uptake relationship was preserved at 5.8:1. Ventilatory efficiency was severely abnormal at 42.3 ± 11.6. Patients with CF-LVAD suffer from limited RV contractile reserve; marked elevations in pulmonary, left-sided filling, and right-sided filling pressures during exercise; and severe ventilatory inefficiency. These findings explain mechanisms for persistent reductions in functional capacity in this patient population.

Computational analyses of aortic blood flow under varying speed CF-LVAD support

Continuous Flow Left Ventricular Assist Devices (CF-LVADs) generally operate at a constant speed whilst supporting a failing heart. However, constant speed CF-LVAD support may cause complications and increase the morbidity rates in the patients. Therefore, different varying speed operating modes for CF-LVADs have been proposed to generate more physiological blood flow, which may reduce complication rates under constant speed CF-LVAD support. The proposed varying speed CF-LVAD algorithms simulate time-dependant dynamics and three dimensional blood flow patterns in aorta under varying speed CF-LVAD support remain unclear. The aim of this study is to evaluate three dimensional blood flow patterns in a patient-specific aorta model under co-pulsating and counter-pulsating CF-LVAD support modes driven by speed and flow rate control algorithms using numerical simulations. Aortic blood flow was evaluated for 10,000 rpm constant speed CF-LVAD support generating 4.71 L/min mean flow rate over a cardiac cycle. Co-pulsating and counter-pulsating CF-LVAD speed control operated the pump at the same average speed over a cardiac cycle and co-pulsating and counter-pulsating CF-LVAD flow rate control generated the same average flow rate over cardiac cycle as in the constant speed pump support. Simulation results show that the utilised counter-pulsating pump flow rate control may decrease the haemolysis to a third compared to the most commonly employed constant speed pump operating mode. Moreover, CF-LVAD support utilising counter-pulsating pump flow rate control generated the most favourable hemodynamic characteristics, i.e. low Dean number, least wall shear stress and least haemolysis values among the investigated cases.

Endothelial Dysfunction-related Neurological Bleeds with Continuous Flow-Left Ventricular Assist Devices Measured by Digital Thermal Monitor.

Endothelial dysfunction has been demonstrated in patients with Continuous Flow-Left Ventricular Assist Devices (CF-LVADs) but association with adverse events has not been shown. We used a noninvasive, operator-independent device called VENDYS® to assess vasodilatory function based on digital thermal measurements postrelease of a brachial artery occlusion in ambulatory patients with CF-LVAD (n = 56). Aortic valve opening and pulse perception were also documented before the test. Median duration of CF-LVAD support was 438 days. The VENDYS® test generates a vascular reactivity index (VRI). Outcomes for the CF-LVAD patients were compared between VRI < 1 and VRI ≥ 1. The bleeding events were driven primarily by a difference in neurologic bleeds. Multivariate analysis showed that VRI < 1 correlated with future bleeding events (HR: 5.56; P = 0.01). The C-statistic with the VRI dichotomized as above was 0.82. There was a trend toward a worse survival in patients with poor endothelial function. Endothelial vasodilatory dysfunction measured by a simple test utilizing digital thermal monitoring can predict adverse bleeding events in patients with CF-LVADs.