CF-LVAD Patients Research Articles

Retinal microvascular remodeling associates with adverse events in continuous-flow left ventricular assist device-supported patients

BackgroundContinuous-flow left ventricular assist device (cfLVAD) use is effective in supporting patients with end-stage heart failure (ESHF). Reduced flow pulsatility within the systemic circulation in cfLVAD-supported patients may lead to alterations within the microcirculation. Temporal changes in microvasculature in relation to adverse events in cfLVAD supported patients has not been studied. We aimed to profile changes within retinal microvasculature and its association with adverse events. MethodsRetinal photography was performed using Topcon TRC-NW8 non-mydriatic fundus camera in cfLVAD supported patients and ESHF control patients. Retinal measurements including arteriolar and venular caliber, fractal dimension, branching angle, and vessel tortuosity were evaluated using a validated semi-automated program. Demographic and adverse event data were documented. Results172 images were recorded from 48 patients (n=29 cfLVAD, n=19 ESHF, mean age 54.2 ± 11.9 years). There were significant trends in retinal arteriolar caliber (B = -0.53 µm, 95% CI: -0.96 – -0.10, p = 0.016) and retinal fractal dimension parameters (B = 0.014, 95% CI: 0.001 – 0.002, p = 0.016) in linear mixed model regressions. Amongst cfLVAD patients, there was a significant association between the incidence of gastrointestinal bleeding and stepwise increases in retinal arteriolar-venular caliber ratio (HR: 3.03, 95% CI: 2.06 – 4.45, p = 0.005), a measure of arteriolar narrowing. ConclusionsWe have observed for the first time that alterations in retinal microvasculature in cfLVAD-supported patients may be associated with gastrointestinal bleeding. While understanding these temporal changes may predict future adverse events in cfLVAD-supported patients, further multi-center studies are required to confirm the associations observed.

(381) Left Ventricular Contractile Reserve is Associated with Optimal Exercise Hemodynamics in Cf-lvad Patients: A Pressure-Volume Loop Analysis

(381) Left Ventricular Contractile Reserve is Associated with Optimal Exercise Hemodynamics in Cf-lvad Patients: A Pressure-Volume Loop Analysis

Management of hypertension in patients supported with continuous flow left ventricular assist devices.

Hypertension remains one of the most common clinical problems leading to devastating postleft ventricular assist device (LVAD) implant complications. This study reviews the pathophysiology of hypertension in the setting of continuous flow LVAD support and provides an update on currently available antihypertensive therapies for LVAD patients. The true prevalence of hypertension in the LVAD population remains unknown. Effective blood pressure (BP) control and standardization of BP measurement are key to prevent suboptimal left ventricular unloading, pump malfunction and worsening aortic regurgitation. Angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta blockers and mineralocorticoid receptor antagonists (MRA) are the preferred antihypertensive agents because of their additional potential benefits, including optimization of haemodynamics, prevention of stroke, gastrointestinal bleed and in some patients myocardial recovery. Angiotensin receptor-neprilysin inhibition (ARNI) may be a well tolerated and effective therapy for BP control especially among CF-LVAD patients with resistant hypertension. Similarly, sodium glucose co-transporter 2 inhibitors (SGLT2i) should be considered in the absence of contraindications. Hypertension is very common post-LVAD implant. Heart failure guideline directed medical therapies, including ACEI, ARB, beta blockers and MRA, are the preferred antihypertensive agents to improve post-LVAD outcomes.

Effect of Left Ventricular Unloading by Pump Speed Adjustment on Myocardial Flow in Continuous-flow Left Ventricular Assist Device Patients.

Resting myocardial blood flow (MBF) and myocardial flow reserve (MFR) are reduced in heart failure (HF) patients supported by pulsatile left ventricular assist devices (LVADs). The effect of continuous-flow (CF) physiology on these parameters is underexplored in CF-LVAD patients. We investigated the impact of CF-LVADs on resting MBF and MFR under two left ventricular (LV) loading conditions. Nine HeartMate II patients (42 ± 12 years, 100% male) on support for 370 ± 281 days were enrolled. Results were compared with 9 HF patients (58 ± 13 years, 67% male, LV ejection fraction 27 ± 9%) and 10 healthy volunteers (56 ± 10 years, 20% male). CF-LVAD patients underwent transthoracic echocardiography with ramp study. MBF and MFR were measured utilizing positron emission/computed tomography imaging under two LV loading conditions: "high-speed" (HS), promoting aortic valve (AV) closure and LV unloading; "low-speed" (LS), promoting AV opening and LV loading. Global resting MBF was similar in HS, LS, HF, and healthy: 0.8 ± 0.3, 0.7 ± 0.3, 0.7 ± 0.1, 0.9 ± 0.2 ml/min/g, respectively; p = NS. HS global MFR was reduced compared with LS and HF: 1.6 ± 0.6 versus 1.9 ± 0.5, p = 0.004; 1.6 ± 0.6 versus 2.4 ± 0.5, p = 0.01, respectively. HS regional MFR was reduced compared with LS in the left anterior descending (1.7 ± 0.7 vs. 2.0 ± 0.6, p = 0.027) and left circumflex (1.8 ± 0.7 vs. 2.2 ± 0.9, p = 0.008), but not in right coronary artery (1.7 ± 0.7 vs. 1.7 ± 0.6, p = 0.76). Resting MBF is preserved among CF-LVAD patients and is similar to HF and healthy. Promoting LV ventricular unloading with higher speed was associated with lower global and regional left coronary MFR, while right coronary MFR did not change.

Low major bleeding, pump thrombosis and death rates in continuous flow left ventricular assist devices patients with good anticoagulation control

Abstract Background Continuous-flow left ventricular assist device (CF-LVAD) patients require anticoagulation with vitamin K antagonists (VKAs). Good versus suboptimal anticoagulation control expressed as high versus low time in target range (TTR) of international normalized ratio results in less clinical events in atrial fibrillation patients. However, data in CF-LVAD patients are lacking. Purpose To study the association between TTR and clinical events in patients with CF-LVAD as destination therapy. Methods Single-centre cohort study in patients receiving CF-LVAD between 2010–2021. Patients were followed from start of VKAs until outcome or end of follow-up. Outcomes were combined major adverse events, thromboembolisms, major bleedings, neurologic events and all-cause mortality. The TTR (low vs. high; <50% vs. >50%) was calculated during the overall study period and over 1-month periods by the Rosendaal-method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression with time-dependent covariables, adjusted for confounding. Results 74 patients were included; median age 63 years [interquartile range 58–68], 77% males and 60%ischemic heart failure. During 191 years follow-up, 39 combined major adverse events, 14 thromboembolisms, 21 major bleeding, 22 neurologic events and 38 deaths occurred. For 1-month periods, high TTR was associated with less combined major adverse events (HR 0.3 95% CI 0.2–0.7), major bleeding (HR 0.4 95% CI 0.2–1.1), thromboembolism (HR 0.3 95% CI 0.1–1.3) and death (HR 0.2 95% CI 0.1–0.5) (Table 1). Results considering the overall study period were similar. Conclusion Good anticoagulation compared with suboptimal control during 1-month and the overall study period in CF-LVAD patients with destination therapy is associated with lower rates of combined major adverse events, major bleedings, pump thrombosis and death. Funding Acknowledgement Type of funding sources: None.

Association between postoperative hemodynamic metrics of pulmonary hypertension and right ventricular dysfunction and clinical outcomes after left ventricular assist device implantation.

While preoperative hemodynamic risk factors associated with early right heart failure (RHF) following left ventricular assist device (LVAD) surgery are well-established, the relationship between postoperative hemodynamic status and subsequent outcomes remains poorly defined. We analyzed adult CF-LVAD patients from the STS-INTERMACS registry surviving at least 3 months without evidence of early RHF and with hemodynamic data available at 3 months after LVAD implant. The association between metrics of RV afterload and function and the subsequent risk of death, right heart failure (RHF), gastrointestinal bleeding (GIB), or stroke were assessed using multivariable Cox proportional hazards modeling. Among 1,050 patients with available 3-month hemodynamics, pulmonary hypertension was common, with 585 (55.7%) having mPAP ≥ 20 mm Hg and 164 (15.6%) having PVR ≥ 3 WU. Pulmonary artery pulsatility index (PAPi, HR 0.62 per log-increase for values < 3, 95% CI 0.43-0.89) and PVR (HR 1.19 per 1 WU-increase for values > 1.5 WU, 95% CI 1.03-1.38) were independently associated with the composite of death or RHF. Postoperative RAP (HR 1.18 per 5 mm Hg increase, 95% CI 1.04-1.33), RAP:PCWP (HR 1.46 per log-increase, 95% CI 1.12-1.91), and PAPi (HR 0.76 per log-increase, 95% CI 0.61-0.95) were each associated with GIB risk. Postoperative hemodynamics was not associated with stroke risk. Hemodynamic metrics of postoperative RV dysfunction and elevated RV afterload are independently associated with RHF, mortality and GIB. Whether strategies targeting postoperative optimization of RV function and afterload can reduce the burden of these adverse events requires prospective study.

Validity and success rate of noninvasive mean arterial blood pressure measurements in cf-LVAD patients: A technical review.

The life expectancy of patients with a continuous flow left ventricular assist device (cf-LVAD) is increasing. Adequate determination and regulation of mean arterial pressure (MAP) is important to prevent adverse events. Given the low pulsatility characteristics in these patients, standard blood pressure equipment is inadequate to monitor MAP and not recommended. We provide an overview of currently available noninvasive techniques, using an extensive search strategy in three online databases (Pubmed, Scopus and Google Scholar) to find validation studies using invasive intra-arterial blood pressure measurement as a reference. Mean differences with the reference values smaller than 5 ± 8 mm Hg were considered acceptable. After deduplication, screening, and exclusion of incorrect sources, eleven studies remained with 3139 successful MAP measurements in 386 patients. Four noninvasive techniques, using Doppler, pulse oximetry, finger cuff volume clamp, or slow upper arm cuff deflation, were identified and evaluated for validity and success rate in cf-LVAD patients. Here, a comprehensive technical background of the blood pressure measurement methods is provided in combination with a clinical use comparison. Of the reported noninvasive techniques, slow cuff devices performed most optimally (mean difference 1.3 ± 5.2 mm Hg). Our results are encouraging and indicate that noninvasive blood pressure monitoring options with acceptable validity and success rate are available. Further technical development and validation is warranted for the growing population of patients on long-term cf-LVAD support.

Acquired platelet defects are responsible for nonsurgical bleeding in left ventricular assist device recipients.

Left ventricular assist devices (LVADs) have been used as a standard treatment option for patients with advanced heart failure. However, these devices are prone to adverse events. Nonsurgical bleeding (NSB) is the most common complication in patients with continuous flow (CF) LVADs. The development of acquired von Willebrand syndrome (AVWS) in CF-LVAD recipients is thought to be a key factor. However, AVWS is seen across a majority of LVAD patients, not just those with NSB. The purpose of this study was to examine the link between acquired platelet defects and NSB in CF-LVAD patients. Blood samples were collected from 62 CF-LVAD patients at pre- and 4 post-implantation timepoints. Reduced adhesion receptor expression (GPIbα and GPVI) and activation of platelets (GPIIb/IIIa activation) were used as markers for acquired platelet defects. Twenty-three patients experienced at least one NSB episode. Significantly higher levels of platelet activation and receptor reduction were seen in the postimplantation blood samples from bleeders compared with non-bleeders. All patients experienced the loss of high molecular weight monomers (HMWM) of von Willebrand Factor (vWF), but no difference was seen between the two groups. Multivariable logistic regression showed that biomarkers for reduced platelet receptor expression (GPIbα and GPVI) and activation (GPIIb/IIIa) have more predictive power for NSB, with the area under curve (AUC) values of 0.72, 0.68, and 0.62, respectively, than the loss of HMWM of vWF (AUC: 0.57). The data from this study indicated that the severity of acquired platelet defects has a direct link to NSB in CF-LVAD recipients.

Cardiac remodeling in patients with centrifugal left ventricular assist devices assessed by serial echocardiography.

The aim of the study was to characterize the remodeling process in a large cohort of patients supported with a centrifugal left ventricular assist device (cfLVAD) by standardized serial echocardiography. From 3/2018 all cfLVAD patients underwent transthoracic echocardiography at 6 and 12 months after implantation using a standardized protocol. A total of 512echocardiograms were reviewed (216preoperative, 156at 6 months, 140at 12 months). While on cfLVAD support, left ventricular (LV) diameter decreased (p<.001). LV ejection fraction (LVEF) and LV fractional area change improved (p<.001). Potential for cfLVAD explantation (as defined by an LVEF ≥45% and opening of the aortic valve [AV]) was seen in nine patients at 6 and 21patients at 12months. The tricuspid annular excursion decreased significantly, while the right ventricular fractional area change did not change. Tricuspid regurgitation (TR) and mitral regurgitation (MR) improved significantly during LVAD support. Opening of the AV was seen in >64% of the patients at 6 months and in 66% at 12 months. Moderate aortic regurgitation (AR) was rare with 3.8% at 6 months but increased with the duration of cfLVAD support (8.5% at 12 months). We found no significant difference in echocardiographic parameters between patients supported with a HeartWareHVAD™ or a HeartMate3™ device. LVAD therapy can lead to reverse LV remodeling and improvement of MR and TR. However, right ventricular function does not improve and prevalence of AR progressively increases during mechanical support.

Successful Cold Atmospheric Plasma Therapy of Driveline Infections in Patients with Left Ventricular Assist Devices

<h3>Purpose</h3> Driveline infections are still the Achilles heel of continuous flow left ventricular assist devices (cfLVAD) for morbidity and mortality in cfLVAD patients. Over the last years, cold atmospheric plasma (CAP) has been safely and effectively used to treat wound infections in different clinical indications. Thus, in this study we evaluated CAP therapy of superficial driveline infections (SDI). <h3>Methods</h3> 24 patients (20male, 4 female), who received a cfLVAD between 2012 and 2018, developed a SDI. In total 30 CAP plasma jet treatments were applied, 16 patients were treated in hospital, 8 patients in the ambulance and 6 patients were treated in both. All wounds were treated with CAP starting from the day of diagnosis of SDI. <h3>Results</h3> The average number of CAP applications per case was 9.06 times (1-101), median duration of hospital stay due to SDI was 41.35 days (5-254). 21 patients were additional treated with antibiotics (70%). In 9 patients (30%) an ascending driveline infection (ADI) occurred, which required surgical revision. The 3 month event free survival was 21 patients (70 %). There were no adverse side effects of CAP therapy observed and there were no abnormalities of cfLVAD during CAP treatment. <h3>Conclusion</h3> We demonstrate that CAP therapy could be effectively and safely applied in cfLVAD patients with SDI. Using CAP 70% of our cases with SDI were prevented from ADI. Future studies have to show if ambulant CAP therapy of superficial cfLVAD wound infections has the potential to prevent progression of infection or to avoid SDI infection at all.

Prognostic Value of Pressure-Volume Measures in Hemocompatibility-Related Clinical Adverse Events

<h3>Purpose</h3> Continuous-flow left ventricular assist device (cf-LVADs) can lead to hemocompatibility-related clinical adverse events (HRAEs) which are largely determined by mechanisms that underpin the pump-patient interaction. We assessed the association of pressure-volume (PV) measures [stroke work (SW) & pump arterial elastance (E_A)] with incidence of HRAEs. <h3>Methods</h3> Using a validated algorithm, brachial-pressure waveforms from oscillometric blood pressure cuff (SphygmoCor Xcel), echocardiography measures and Medtronic HVAD controller data were collected for estimation PV measures within the first 3 months. Patients (all Bridge-To-Transplantation) were divided into low, intermediate and high tertiles for each of SW (n=13, 14, 9) and E_A (n=12, 12, 12). HRAEs, including nonsurgical bleeding (NB), neurological (NE) and thromboembolic events (TE), was followed through a 12-month period post-implant. Hemocompatibility score (HCS) was calculated based on HRAEs in the 1^st year. Comparison between groups were conducted with one-way ANOVAs and Kruskal-Wallis analyses. Kaplan Meier survival analyses determined time-to-event. <h3>Results</h3> 36 HVAD patients (mean age 57±10, 83% males, 69% non-ischemic cardiomyopathy) were included. Baseline demographics and clinical parameters were comparable between SW and E_A tertile groups. Low E_A group had significantly higher rates of HRAEs in the 1^st year compared to intermediate and high groups (p=0.004). HRAE rates were marginally higher in the low SW group (p=0.080). There were no differences in HCS. Survival analysis showed significant differences in distribution of 1-year cumulative HRAE-free probabilities according to E_A tertiles (33.3%, 83.3% and 91.7% for low, intermediate and high E_A respectively, log-rank=0.003). <h3>Conclusion</h3> PV measures offer value in prognostication of LVAD patients. This study highlights the potential importance of assessing afterload and native ventricular contractility in circumventing HRAEs in cf-LVAD patients.

Comparing Velocity and Mean Arterial Pressure to Assess Pulsatility in Patients with Continuous Flow Left Ventricular Assist Devices

<h3>Purpose</h3> An increasing number of end-stage heart failure patients are supported by continuous-flow Left Ventricular Assist Devices (cfLVADs). In these patients, accurate assessment of arterial pulsatility remains a challenge because of diminished pulse pressure. Limited pulsatility in modern cfLVADs itself can be associated with adverse events such as stroke. Our study investigates the value of simultaneous arterial pressure and arterial blood velocity assessment in cfLVAD patients. <h3>Methods</h3> Both velocity (cm/s) and pressure (mmHg) data were collected during routine follow up. Pressure was measured using a brachial cuff oscillometry system (Sphygmocor XCel) providing a systolic and diastolic readings, while velocity was measured using a digital doppler (Huntleigh) from the brachial artery. Velocity measurements obtained included peak, minimum, average velocity and pulsatility index. Pressure measurements obtained were systolic and diastolic which allowed us to derive a mean arterial pressure (MAP) from the brachial artery. <h3>Results</h3> From a total of 24 patients (88% males), there were 44 velocity and pressure measurements. Mean device support duration was 240 days (SD 116). Mean derived brachial MAP was 85 mmHg (SD 9), whereas mean peak brachial artery velocity was 14 cm/s (SD 9). Mean pulsatility index was 2 (SD 2). Correlation analysis using Spearman's rho demonstrated a significant inverse relationship between Brachial derived MAP and Peak velocity (Rho=-0.41, p=0.007). <h3>Conclusion</h3> Arterial doppler measurements may provide incremental value over purely pressure-based measurements. The inverse relationship between derived MAP and peak velocity in this study may be partially explained by the degree of arterial compliance. In turn, this provides significant information on the relationship between higher MAP and lower blood velocity to subsequently explain increased thrombus formation and stroke rate due to longer transit time of blood.

Risk of Infection, Endoplasmic Reticular Stress and Systemic Activation of NLRP3 Inflammasome in Patients Supported by Continuous Flow Left Ventricular Assist Devices

<h3>Purpose</h3> We investigated changes in stress-associated endoplasmic reticulum (ER) protein 1 (SERP1), ER-stress response proteins and inflammasome activation in heart failure (HF) patients before and after CF-LVAD implantation, and relationship to subsequent infection within 3 months. <h3>Methods</h3> We analyzed blood samples from 24 CF-LVAD patients (pre- and 1week post-VAD) and 10 non-HF controls. Culture positive Infections was confirmed (median 42 days post-VAD) from bloodstream, GI, respiratory tracts, or driveline. SARP1, ER-stress proteins (ATF-6, GRP78) and NLRP3 inflammasome (NLRP3, ASC, Caspase1) in peripheral blood mononuclear cells (PBMC) were assessed. <h3>Results</h3> HF patients had significantly (p<0.05) elevated baseline (pre-VAD) PBMC protein levels of ATF6 (0.41±0.05 vs. 0.54±0.11), GRP78 (0.20±0.07 vs. 0.33±0.18), NLRP3 (0.28±0.17 vs. 0.78±0.28), and ASC (0.27±0.13 vs. 0.44±0.15) compared to controls. Among CF-LVAD recipients, SERP1 declined in those without subsequent infection (Group1) but significantly increased in those with infection (Group2) (<i>Fig.A,B</i>). Baseline ATF6 and GRP78 differed between Group1 and 2 (<i>Fig.C,D</i>). In Group2, the post-VAD ATF6, GRP78, NLRP3 and ASC were significantly elevated compared to pre-VAD; while in group1, only the post-VAD GRP78 was significantly elevated (<i>Fig.C-G</i>). Post-VAD caspase1 increased but not-significant (0.36±0.07 vs. 0.43±1.2) in group2 compared to pre-VAD (<i>Fig.H</i>). Baseline SERP1 and NLRP3 among patients who developed infection were positively correlated with ATF6 and GRP78 (<i>Fig.I-L</i>). <h3>Conclusion</h3> Post-VAD upregulation of SERP1 may be associated with ER-stress response, which in turn may activate NLRP3 inflammasome and predispose to early infection. Post-VAD decrease in SERP1 in group1 may protect against ER stress and NLRP3 activation. Further investigation of the role of SERP1 in ER-stress and inflammasome activation in CF-LVAD recipients is needed.

Surgical left atrial appendage occlusion in patients with left ventricular assist device.

Thromboembolic (TE) events are among the most common and devastating adverse events in patients with continuous-flow left ventricular assist device (cf-LVAD). Given the high burden of AF among cf-LVAD patients, we sought to evaluate the effect of concomitant surgical LAAO in patients receiving cf-LVAD. A systematic search using electronic databases was performed using the keywords: "left atrial appendage occlusion" and "left ventricular assist device." Statistical analysis was performed using metapackage for R version 4.0 and Rstudio version 1.2. Mantel-Haenszel risk ratio (RR) random-effects model was used to summarize data between two groups. The primary outcomes included: (a) stroke; (b) LVAD pump thrombosis; (c) all-cause mortality RESULTS: Three studies with a total of 305 patients (LAAO=68 and No-LAAO=237) were included in the analysis. HeartMate II (39%) and Heartware (27.5%) were the two most common cf-LVADs utilized, while only 5% received HeartMate III. At a mean follow up of 1.47 years, LAAO group had a lower risk of stroke (8.8%vs. 15.2%, RR 0.64; 95% CI 0.28-1.49), LVAD pump thrombosis (1.5%vs. 3.8%, RR 0.28; 95% CI 0.05-1.55) and all-cause mortality (5.9%vs. 20.2%, RR 0.69; 95% CI 0.19-2.52) when compared with no-LAAO group, but the difference did not reach statistical significance. Concomitant surgical LAAO at the time of cf-LVAD implantation demonstrated a trend toward positive outcomes and was not associated with adverse outcomes during the follow-up period, though the results were not statistically significant.

Competing Risks to Transplant in Bridging With Continuous-flow Left Ventricular Assist Devices

BackgroundContinuous-flow left ventricular assist device (CF-LVAD) support is a mainstay in the hemodynamic management of patients with end-stage heart failure refractory to optimal medical therapy. In this report we evaluated waitlist complications and competing outcomes for CF-LVAD patients compared with primary transplant candidates listed for orthotopic heart transplantation at a single center. MethodsAll patients listed for orthotopic heart transplantation between 2006 and 2020 at our institution were retrospectively reviewed (CF-LVAD, 300; primary transplant, 244). Kaplan-Meier methodology with log-rank testing was used to evaluate survival outcomes. Terminal outcomes of death, delisting, and transplant were assessed as competing risks and compared between groups using Gray’s test. Multivariable Fine-Gray regression was used to identify predictors of transplantation. ResultsOne-year rates of transplant, delisting, and death were 48%, 8%, and 2%, respectively, for CF-LVAD patients and 45%, 15%, and 9%, respectively, for primary transplant (all P < .001). Waitlist mortality at 5 years was 4% among CF-LVAD patients and 13% for primary transplants. All-cause mortality after listing was lower for CF-LVAD patients (P = .017). There was no difference in posttransplant survival between groups (P = .250). On multivariable Fine-Gray regression stroke (P = .017), respiratory failure (P = .032), right ventricular failure (P = .019), and driveline infection (P = .050) were associated with decreased probability of transplantation. Posttransplant survival was not significantly worse for CF-LVAD patients who experienced device-related complications (P = .901). ConclusionsAlthough device-related complications were significantly associated with decreased rates of transplant, CF-LVAD patients had excellent waitlist outcomes overall. In light of the 2018 allocation score change the risk of complications should be taken into account when deciding whether to offer CF-LVAD as a bridge to transplant.

Hallazgos clínicos asociados con una descarga hemodinámica del ventrículo izquierdo incompleta en pacientes con asistencia ventricular izquierda

Introduction and objectivesThe effect of a centrifugal continuous-flow left ventricular assist device (cfLVAD) on hemodynamic left ventricular unloading (HLVU) and the clinical conditions that interfere with hemodynamic optimization are not well defined. MethodsWe retrospectively evaluated the likelihood of incomplete HLVU, defined as high pulmonary capillary wedge pressure (hPCWP)> 15mmHg in 104 ambulatory cfLVAD patients when the current standard recommendations for cfLVAD rotor speed setting were applied. We also evaluated the ability of clinical, hemodynamic and echocardiographic variables to predict hPCWP in ambulatory cfLVAD patients. ResultsTwenty-eight percent of the patients showed hPCWP. The variables associated with a higher risk of hPCWP were age, central venous pressure, absence of treatment with renin-angiotensin-aldosterone system inhibitors, and brain natriuretic peptide levels. Patients with optimal HLVU had a 15.2±14.7% decrease in postoperative indexed left ventricular end-diastolic diameter compared with 8.9±11.8% in the group with hPCWP (P=.041). Independent predictors of hPCWP included brain natriuretic peptide and age. Brain natriuretic peptide <300 pg/mL predicted freedom from hPCWP with a negative predictive value of 86% (P <.0001). ConclusionsAn optimal HLVU can be achieved in up to 72% of the ambulatory cfLVAD patients when the current standard recommendations for rotor speed setting are applied. Age, central venous pressure and therapy with renin-angiotensin-aldosteron system inhibitors had a substantial effect on achieving this goal. Brain natriuretic peptide levels and the magnitude of reverse left ventricular remodeling seem to be useful noninvasive tools to evaluate HLVU in patients with functioning cfLVAD.

B-AB23-05 OUTCOMES AND COMPLICATIONS OF CARDIAC RESYNCHRONIZATION THERAPY IN PATIENTS WITH CONTINUOUS-FLOW LEFT VENTRICULAR ASSIST DEVICES

The effect of CRT on clinical outcomes and complications in patients with CF-LVAD is currently not well understood. To evaluate the outcomes and complications of CRT in patients with Continuous-Flow LVAD. We conducted a single-center retrospective analysis of a cohort of 478 subjects who underwent CF-LVAD implantation at the University of Rochester, Rochester, NY between May 2008 and January 2020. The study cohort was divided into three groups: no ICD, ICD only, and ICD+CRT (at LVAD implantation). The endpoints were all-cause mortality, and device complications. There were 166 of 478 (35%) LVAD patients implanted with a CRT, 191 implanted with ICD only (40%), and 121 (25%) had no ICD before LVAD implantation. During the mean follow-up of 2.7 years, there was no significant difference in the cumulative probability of all-cause mortality in patients with CRT, ICD-only, or no device (Figure, log-rank p=0.439). In the multivariate model there was no significant difference in death in patients with CRT vs. no device (HR= 1.18, 95% CI: 0.80-1.75, p=0.40), or in patients with an ICD vs. no device (HR=1.17, 95%CI: 0.79-1.74, p=0.44). In the CRT group, 31 (22%) of the 141 patients had device-related complications, 4 patients (12.5%) had device infection, 4 (12.5%) had lead infection, 15 (47%) had lead dislodgment or high threshold, and 9 (28%) had other complications. In CF-LVAD patients, CRT was not associated with improved survival. Device-related complications were frequently observed in patients with CRT. Further studies are warranted to investigate the risk-benefit ratio of an implanted CRT in patients with CF-LVADs.

Clinical findings associated with incomplete hemodynamic left ventricular unloading in patients with a left ventricular assist device

Introduction and objectivesThe effect of a centrifugal continuous-flow left ventricular assist device (cfLVAD) on hemodynamic left ventricular unloading (HLVU) and the clinical conditions that interfere with hemodynamic optimization are not well defined. MethodsWe retrospectively evaluated the likelihood of incomplete HLVU, defined as high pulmonary capillary wedge pressure (hPCWP)> 15mmHg in 104 ambulatory cfLVAD patients when the current standard recommendations for cfLVAD rotor speed setting were applied. We also evaluated the ability of clinical, hemodynamic and echocardiographic variables to predict hPCWP in ambulatory cfLVAD patients. ResultsTwenty-eight percent of the patients showed hPCWP. The variables associated with a higher risk of hPCWP were age, central venous pressure, absence of treatment with renin-angiotensin-aldosterone system inhibitors, and brain natriuretic peptide levels. Patients with optimal HLVU had a 15.2±14.7% decrease in postoperative indexed left ventricular end-diastolic diameter compared with 8.9±11.8% in the group with hPCWP (P=.041). Independent predictors of hPCWP included brain natriuretic peptide and age. Brain natriuretic peptide <300 pg/mL predicted freedom from hPCWP with a negative predictive value of 86% (P <.0001). ConclusionsAn optimal HLVU can be achieved in up to 72% of the ambulatory cfLVAD patients when the current standard recommendations for rotor speed setting are applied. Age, central venous pressure and therapy with renin-angiotensin-aldosteron system inhibitors had a substantial effect on achieving this goal. Brain natriuretic peptide levels and the magnitude of reverse left ventricular remodeling seem to be useful noninvasive tools to evaluate HLVU in patients with functioning cfLVAD.

Cerebral vasoreactivity in HeartMate 3 patients

While rates of stroke have declined with the HeartMate3 (HM3) continuous- flow (CF) left ventricular assist device (LVAD), the impact of non-pulsatile flow and artificial pulse physiology on cerebrovascular function is not known. We hypothesized that improved hemodynamics and artificial pulse physiology of HM3 patients would augment cerebrovascular metabolic reactivity (CVR) compared with HeartMate II (HMII) CF-LVAD and heart failure (HF) patients. Mean, peak systolic and diastolic flow velocities (MFV, PSV, MinFV, respectively) and cerebral pulsatility index were determined in the middle cerebral artery (MCA) before and after a 30 sec breath-hold challenge in 90 participants: 24 healthy controls; 30 HF, 15 HMII, and 21 HM3 patients. In HM3 patients, breath-holding increased MFV (Δ8 ± 10 cm/sec, p < .0001 vs baseline) to levels similar to HF patients (Δ9 ± 8 cm/sec, p > .05), higher than HMII patients (Δ2 ± 8 cm/sec, p < .01) but lower than healthy controls (Δ13 ± 7 cm/sec, p < .05). CF-LVAD altered the proportion of systolic and diastolic flow responses as reflected by a differential cerebral pulsatility index (p=.03). Baseline MFV was not related to CVR (r2=0.0008, p=.81). However, CF-LVAD pump speed was strongly inversely associated with CVR in HM II (r2=0.51, p=.003) but not HM3 patients (r2=0.01, p=.65). Compared with HMII, HM3 patients have a significantly improved CVR. However, CVR remains lower in HM3 and HF patients than in healthy controls, therefore suggesting that changes in cerebral hemodynamics are not reversed by CF-LVAD therapy. Further research on the mechanisms and the long-term impact of altered cerebral hemodynamics in this unique patient population are warranted.

Hyperhomocysteinemia and Oxidative Stress May Predict the Risk of Stroke in Patients Supported by Continuous Flow Left Ventricular Assist Devices

<h3>Purpose</h3> Stroke is one of the leading complications during CF-LVAD support. The purpose of this observational study was to investigate the temporal relationship of circulating homocysteine (Hcy) and oxidative stress as potential markers to identify CF-LVAD patients at risk for developing postoperative strokes. <h3>Methods</h3> We analyzed available blood samples from 24 selected subjects including non-heart failure control group(n=6) and heart-failure patients undergoing CF-LVAD implant(n=18). The CF-LVAD patients were selected in stroke group(n=6) those who developed stroke within a month after implant and were compared to selected matched patients who did not develop stroke(n=12). Baseline Hcy, malondialdehyde(MDA) and antioxidant were compared between groups. Weekly blood samples at 1,2,3 and 4 weeks were analyzed in selected stroke and no-stroke groups. <h3>Results</h3> At baseline, CF-LVAD patients had higher plasma Hcy and MDA and lower antioxidant than the control group(Fig1A-C). There was a significant 1.8-fold increase in baseline Hcy in stroke group compared to no-stroke group though there were no differences in the levels of MDA and antioxidant between them(Fig1A-C). In stroke group, post-implant levels of Hcy and MDA increased temporally and remained elevated while these trends were not seen in the no-stroke group(Fig1D-F). There was also a significant depletion in antioxidant in stroke group at week 4 compared to no-stroke group(Fig1F). <h3>Conclusion</h3> A near 2-fold rise in baseline Hcy was seen in stroke group patients compared to no-stroke patients, suggesting its utility as a potential biomarker to predict stroke risk after CF-LVAD implant. Elevated Hcy, oxidative stress and depleted antioxidant may be important indicators of systemic response of the body to CF-LVAD in patients who have stroke. These findings also suggest that vascular endothelial dysfunction may plan an important role in the development of stroke in CF-LVAD recipients.