post-LVAD Right Ventricular Failure Research Articles

677 PREDICTION OF RIGHT VENTRICULAR FAILURE AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION: ROLE OF VASODILATOR CHALLENGE

Abstract Pulmonary artery pulsatility index (PAPi) is an indicator of right ventricular (RV) function and an independent predictor of right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation. Administration of vasodilator challenge during right heart catheterization (RHC) could reduce RV workload allowing a better assessment of its functional reserve. Patients undergoing LVAD implantation at our Institution between May 2013 and August 2021 were enrolled. Only patients who had undergone RHC and vasodilator challenge with sodium nitroprusside were analyzed. We collected all available clinical, instrumental, and haemodynamic parameters, at baseline and after nitroprusside infusion and evaluated potential associations with post-LVAD RVF. Of the 54 patients analyzed, 19 (35%) developed RVF after LVAD implantation. Fractional area change (FAC) (OR: 0.647, CI: 0.481–0.871; P = 0.004), pulmonary artery systolic pressure (PASP)(OR: 0.856, CI: 0.761–0.964; P=0.010), and post-sodium nitroprusside (NTP) PAPi (OR: 0.218, CI: 0.073–0.653; P = 0.006) were independent predictors of post-LVAD RVF. The model combining FAC, PASP, and post-NTP PAPi demonstrated a predictive accuracy of 90.7%. Addition of post-NTP PAPi significantly increased the predictive accuracy of the European Registry for Patients with Mechanical Circulatory Support right-sided heart failure risk score [79.4 vs. 70.4%; area under the curve (AUC): 0.841 vs. 0.724, P = 0.022] and the CRITT score (79.6% vs. 74%; AUC: 0.861 vs. 0.767 P = 0.033). Post-NTP PAPi has observed to be an independent predictor of RVF following LVAD implantation. Dynamic assessment of PAPi using a vasodilator challenge may represent a method of testing RV functional reserve in candidates for LVAD implantation. Larger and prospective studies are needed to confirm this hypothesis.

Abstract 15585: Myocardial Reserve After Milrinone to Predict Right Ventricular Failure After LVAD Implantation

Introduction: Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is a common complication associated with increased morbidity and mortality. Identifying patients at risk for RVF remains challenging. We sought to assess pre-operative right ventricular myocardial reserve after milrinone loading as a risk predictor for post-LVAD RVF. Methods: Adult patients implanted with LVADs from 2013-2019 at a single center who had right heart catherization with milrinone drug study within 30-days preoperatively were included. In addition to standard hemodynamic variables, pulmonary artery pulsatility index (PAPI), right atrial to pulmonary capillary wedge pressure ratio (RA/PCWP), right ventricular stroke work index (RVSWI), pulmonary vascular resistance index (PVRi), and stroke volume index (SVI) were recorded before and after milrinone bolus (50 mcg/kg over ten minutes). Incidence of RVF defined by MCS-ARC criteria within one-year post LVAD were recorded. Student’s unpaired t-tests were used to compare mean of hemodynamic markers to RVF outcome. Results: A total 34 patients were included; 38% women, 50% African American, 68% had non-ischemic cardiomyopathy, 47% implanted with HeartMate 3 LVAD, 20.5% with HeartMate 2, and 32% with HeartWare HVAD. Final right atrial pressure (RAP) after milrinone was higher in those with post-LVAD RVF (15.5 + 7.8mmHg vs 9.2 + 3.9mmHg, p=0.005), as was final diastolic PA pressure (34.3 + 9.2mmHg vs 25.6 + 7.7mmHg, p=0.006). SVI post-milrinone was numerically higher in those without post-LVAD RVF (32.3 + 9.2 vs 26.0 + 7.9mL/m 2 , p=0.06). Percent change in PAPI (p=0.26), RA/PCWP (p=0.35), RVSWI (p=0.10), or PVRi (p=0.92) after milrinone were not associated with RVF. Conclusions: Persistently elevated RAP and diastolic PA pressure, despite milrinone infusion, are associated with RVF after LVAD implantation. Continued reduction in SVI post milrinone may also identify patients at risk for post-LVAD RVF.

Abstract 15169: Prediction of Right Ventricular Failure After Left Ventricular Assist Device Implantation: Role of Vasodilator Challenge

Introduction: pulmonary artery pulsatility index (PAPi) is an indicator of right ventricular (RV) function and an independent predictor of right ventricular failure (RVF) following LVAD implantation. Hypothesis: Administration of vasodilator challenge during right heart catheterization (RHC) could reduce RV workload allowing a better assessment of its functional reserve. Methods: patients undergoing LVAD implantation at our Institution between May 2013 and August 2021 were enrolled. Only patients with RHC and vasodilator challenge with sodium nitroprusside were analyzed. We collected all available clinical, instrumental and haemodynamic parameters, at baseline and after nitroprusside infusion, and we evaluated potential association with post-LVAD RVF. Results: of the 54 patients analyzed, 19 (35%) developed RVF after LVAD implantation. RV FAC (OR 0.647, CI 0.481-0.871; p=0,004), PASP (OR 0.856, CI 0.761-0.964; p=0.010) and post-NTP PAPi (OR 0.218, CI 0.073-0.653; p=0.006) were independent predictors of post-LVAD RVF. The model combining RV FAC, PASP and post-NTP PAPi presented a predictive accuracy of 90.7%. Addition of post-NTP PAPi led to increased EUROMACS-RHF risk score (79.4% vs 70.4%; AUC 0.841 vs 0.724, p=0.022) and CRITT score (79.6% vs 74%; AUC 0.861 vs 0.767, p=0.033) predictive accuracy. Conclusions: post-NTP PAPi has proven to be an independent predictor of RVF following LVAD implantation. Dynamic assessment of PAPi through vasodilator challenge could represent a test of RV functional reserve in candidates for LVAD implantation. Larger and prospective studies are needed in order to confirm this hypothesis.

Abstract 11629: Multicenter Development and Validation of a Machine Learning Risk Model to Predict Right Ventricular Failure Following Mechanical Circulatory Support: The STOP-RVF Score

Introduction: Existing models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support are limited due to lack of multicenter validation, absence of intraoperative characteristics, and marginal predictive power. We sought to derive and validate a risk model to predict post-LVAD RVF. Methods: Advanced heart failure (HF) patients (N=798) requiring continuous-flow LVAD were enrolled at the Utah Transplant Affiliated Hospitals (n=477), Inova Heart & Vascular Institute (n=183), and Henry Ford Medical Center (n=138). Baseline clinical and intraoperative characteristics were recorded. The primary outcome was RVF incidence, defined as the need for right VAD (RVAD) or intravenous inotropes for >14 days. Bootstrap imputation and lasso variable selection were used to derive a predictive model which was then validated. A risk calculator was developed classifying patients into risk groups, and survival was compared. Results: Patients were predominantly white (72%), males (84%), aged 56±13 years. Patients in the RVF and non-RVF groups were comparable in terms of sex, age, and LVAD indication, while RVF patients more commonly had a history of systemic hypertension, non-ischemic cardiomyopathy, lower INTERMACS profiles, and more commonly required inotropic or temporary circulatory support pre-LVAD. Overall, 193 (24.2%) patients developed RVF with 109 (56.5%) requiring inotropes and 84 (43.5%) an RVAD. Multivariable predictors for RVF are shown in the Figure and achieved a c-statistic of 0.74 (95% CI: 0.70-0.78). Inclusion of intraoperative characteristics did not improve model performance. Cumulative survival was higher in the minimal risk group compared to low, moderate, and high. Conclusions: The STOP-RVF calculator effectively stratifies the risk for RVF after LVAD support by implementing routinely collected clinical data. It could impact patient selection and peri-operative management of advanced HF patients.

Abstract 9957: Utility of Cardiac MRI Assessment of Right Ventricle Function Before LVAD Implantation

Introduction: Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is a feared complication. Right ventricle (RV) dysfunction by echocardiogram prior to LVAD implant is a significant risk factor for post-LVAD RVF. However, RV’s unique crescent shape makes it difficult for accurate assessment through echocardiogram. Cardiac MRI can image RV in its entirety and is the gold standard for evaluating RV size and function. Hypothesis: Our study aimed to assess RV comprehensively through cardiac MRI before LVAD implantation to predict severe RVF post-LVAD. Methods: This retrospective cohort study included 231 consecutive patients who underwent LVAD from January 2015 to July 2021. We utilized the commercially available QStrain Application (Medis Suite, the Netherlands) for feature-tracking myocardial strain using gated cine SSFP images. We also assessed for quantitative measurements of RV (systolic/ diastolic volume, stroke volume, and systolic function). Results: There were 12 patients with cardiac MRI before LVAD, of which 4 patients developed severe RVF after LVAD. There were 9 cardiac MRIs available for strain analysis (image quality and old studies before 2012). The RV end-systolic volume (ESV) was higher in severe RVF post-LVAD, but not RV ejection fraction. Endocardial and myocardial global longitudinal strain and global radial strain of RV were not different in severe RVF. Conclusions: In this small series investigating RV function before LVAD implant, we have shown that ESV was higher with severe RVF. Although feature tracking strain of RV was not different in patients with severe RVF, a larger cohort study is warranted to investigate this.

Prediction of right ventricular failure after left ventricular assist device implantation: role of vasodilator challenge.

Pulmonary artery pulsatility index (PAPi) is an indicator of right ventricular (RV) function and an independent predictor of right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation. Administration of vasodilator challenge during right heart catheterization (RHC) could reduce RV workload allowing a better assessment of its functional reserve. Patients undergoing LVAD implantation at our Institution between May 2013 and August 2021 were enrolled. Only patients who had undergone RHC and vasodilator challenge with sodium nitroprusside were analyzed. We collected all available clinical, instrumental, and haemodynamic parameters, at baseline and after nitroprusside infusion and evaluated potential associations with post-LVAD RVF. Of the 54 patients analyzed, 19 (35%) developed RVF after LVAD implantation. Fractional area change (FAC) (OR: 0.647, CI: 0.481-0.871; P = 0.004), pulmonary artery systolic pressure (PASP) (OR: 0.856, CI: 0.761-0.964; P = 0.010), and post-sodium nitroprusside (NTP) PAPi (OR: 0.218, CI: 0.073-0.653; P = 0.006) were independent predictors of post-LVAD RVF. The model combining FAC, PASP, and post-NTP PAPi demonstrated a predictive accuracy of 90.7%. Addition of post-NTP PAPi significantly increased the predictive accuracy of the European Registry for Patients with Mechanical Circulatory Support right-sided heart failure risk score [79.4 vs. 70.4%; area under the curve (AUC): 0.841 vs. 0.724, P = 0.022] and the CRITT score (79.6% vs. 74%; AUC: 0.861 vs. 0.767 P = 0.033). Post-NTP PAPi has observed to be an independent predictor of RVF following LVAD implantation. Dynamic assessment of PAPi using a vasodilator challenge may represent a method of testing RV functional reserve in candidates for LVAD implantation. Larger and prospective studies are needed to confirm this hypothesis.

Prediction of right ventricular failure after left ventricular assist device implantation in patients with heart failure: a meta-analysis comparing echocardiographic parameters

Between 10% and 40% of patients who receive a left ventricular assistance device (LVAD) suffer from right ventricular failure (RVF) shortly after the device is implanted. Patients with post-LVAD RVF tend to have poor outcomes. Only a few predictive factors concerning the right ventricle (RV) have been investigated. Our goal was to search for non-invasive variables that correlate with RV function, focusing on echocardiographic parameters of the RV. We selected 3 parameters: tricuspid annular plane systolic excursion, right ventricular fractional area change and right ventricular global longitudinal strain. We searched the literature and pooled relevant studies in a meta-analysis. Finally, we performed a statistical analysis to confirm whether each parameter was a reliable predictor of RVF after LVAD implantation. We retained 19 articles involving a total of 1561 patients. We found a pooled standardized mean deviation of -0.13 cm for the tricuspid annular plane systolic excursion, with the lower and upper tails of -0.21 and -0.04 cm, respectively. Concerning the right ventricular fractional area change, the averaged standardized mean deviation was equal to -2.61%, with the lower and upper extremities of -4.12% and -1.09%, respectively. Finally, regarding the global longitudinal strain, the standardized mean deviation was equal to -2.06% with an uncertainty value between -3.23% and -0.88%. The tricuspid annular plane systolic excursion could be a reliable parameter in RVF prediction. The right ventricular fractional area change and global longitudinal strain are likely to be stronger predictors of RVF after LVAD implantation. Prospective studies should be carried out to confirm this observation.

Pre-operative atrial fibrillation and early right ventricular failure after left ventricular assist device implantation: a systematic review and meta-analysis

Right ventricular failure (RVF) remains a major cause of morbidity and mortality after left ventricular assist device (LVAD). Atrial fibrillation (AF) is known for its deleterious effects on cardiac function and hemodynamics. The association of pre-operative AF with the risk of early post-LVAD RVF has not been well described. A comprehensive literature search was performed through April, 9 2021. Cohort studies comparing the risk of post-operative RVF and/or need for right ventricular assist device (RVAD) after LVAD in patients with or without AF were included. Pooled odds ratio (OR) with 95% confidence intervals (CI) and I2 statistic were calculated using the random-effects model. Six studies were included in the analysis. Post-operative RVF was reported in 5 studies (1,841 patients) and RVAD use was reported in 4 studies (1,355 patients). There is a non-significant trend toward a higher risk of post-operative RVF in the AF group (pooled OR=1.25, 95%CI=0.99-1.58). No significant association between AF and RVAD use is noted (pooled OR=1.17, 95%CI=0.82-1.66). Pre-operative AF is not significantly associated with higher risks of post-operative RVF and RVAD use after LVAD implantation, although the trend toward higher post-operative RVF is observed in patients with pre-operative AF. Additional research using a larger study population is warranted to better understand the association of pre-operative AF and the development of post-LVAD RVF.

Pressure-dimension index: A novel "morphologic-functional" index of right ventricle that predicts short-term survival after left ventricular assist device implantation.

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is a major cause of postoperative morbidity and mortality. Despite the availability of multiple imaging parameters, none of these parameters had adequate predictive accuracy for post-LVAD RVF. To study whether right ventricular pressure-dimension index (PDI), which is a novel echocardiographic index that combines both morphologic and functional aspects of the right ventricle, is predictive of post-LVAD RVF and survival. 49 cases that underwent elective LVAD implantation were retrospectively analyzed using data from an institutional registry. PDI was calculated by dividing systolic pulmonary artery pressure to the square of the right ventricular minor diameter. Cases were categorized according to tertiles. Patients within the highest PDI tertile (PDI>3.62mmHg/cm2 ) had significantly higher short-term mortality (42.8%) and combined short-term mortality and severe RVF (50%) compared to other tertiles (P<.05 for both, log-rank p for survival to 15th day 0.014), but mortality was similar across tertiles in the long-term follow-up. PDI was an independent predictor of short-term mortality (HR:1.05-26.49, P=.031) and short-term composite of mortality and severe RVF (HR:1.37-38.87, P=.027). Increased PDI is a marker of an overburdened right ventricle. Heart failure patients with a high PDI are at risk for short-term mortality following LVAD implantation.

Pre-implant right ventricular free wall strain predicts post-LVAD right heart failure.

The aim of this study is to evaluate the predictive utility of preoperative right ventricular (RV) global longitudinal strain (GLS) and free wall strain (FWS) on outcomes following left ventricular assist devices (LVADs) implantation. Preoperative transthoracic echocardiograms were retrospectively reviewed in adults undergoing continuous-flow LVAD implantation between 2004 and 2018 at a single center. Patients undergoing pump exchange were excluded. RV GLS and FWS were calculated using commercially available software with the apical four-chamber view. The primary outcome was RV failure as defined by the Interagency Registry for Mechanically Assisted Circulatory Supportwithin 1-year post-LVAD insertion. A total of 333 patients underwent continuous-flow LVAD implantation during the study period and 137 had adequate preoperative studies for RV strain evaluation. RV FWS was found to be a significant predictor of postoperative RV failure in univariate analysis (odds ratio [OR] = 1.12, p = .03), and this finding persisted after risk adjustment in multivariable analysis (OR = 1.14, p = .04). Using the optimal cutoff value of -5.64%, the c-index of FWS in predicting RV failure was 0.65. RV GLS was not associated with post-LVAD RV failure (OR = 1.07, p = .29). PCWP was the only additional significant predictor of RV failure using multivariable analysis (OR = 0.90, p = .02). Pre-implant RV FWS is predictive of RV failure in the first postoperative year after LVAD implantation.

Predicting Significant Right Ventricular Failure Post-LVAD Implantation Using CMR Compared to Echocardiography and Right Heart Catheterisation

Purpose Right ventricular failure (RVF) complicates 10-40% of LVAD implants. Significant RVF is associated with increased mortality and reduced chance of being bridged to transplant. It is therefore crucial to identify patients at high risk of RVF using pre-operative investigations. We investigated markers of RV function on pre-LVAD echocardiography (echo), right heart catheterization (RHC) and cardiovascular magnetic resonance imaging (CMR) in predicting significant post-LVAD RVF. Methods We performed a single centre retrospective analysis of 220 patients who underwent LVAD implantation between 2011-18. 33 patients had CMR within 15 months pre-LVAD implantation. CMR was used to derive RV volumes, TAPSE, RV ejection fraction, strain and scar burden. RV function parameters were derived from echo and RHC just prior the LVAD implantation. INTERMACS criteria was used to categorize RVF based on duration of pharmaceutical support (post-implant IV inotropes/vasodilators/inhaled nitrous oxide) - mild ( 14 days). The latter also included the need for RVAD or death due to RVF. Moderate and severe RVF were considered as significant RVF. Results The median age was 49 (IQR 39-56). 31 were males. 18 patients had no/mild RVF; 14 had significant RVF (8 moderate RVF, 6 severe RVF); 1 patient was not categorised due to incomplete data. 29 survived to discharge. Dilated cardiomyopathy was the commonest aetiology of heart failure (17/33) followed by ischaemic heart disease (11/33). Echo derived pulmonary hypertension (42 vs 36mmHg) and proportion of those with tricuspid regurgitation (83.3% vs 92.8%) were not different in the two groups. PVR on RHC was not different between the groups (2.82 vs 3.68 WU). CMR derived volumes, TAPSE (12.2 vs 12.1mm), Global longitudinal strain (-9.1% vs -7.2%) and radial strain (-12.4% vs -10.0%) and the presence of scar were not different between the two groups. CMR-RVEF however was lower in the group significant RVF (23.5 ± 8.2%) when compared to the group with no/mild RVF (31.0 ± 10.7%) (p=0.03). Conclusion When compared to indices from RHC and echo, pre-operative RVEF on CMR is the only marker that differentiated the group who developed significant post-LVAD RVF from the group that did not. A larger study with CMR closer to the time of LVAD implant is needed to validate this.

Predicting Right Ventricular Failure Following Left Ventricular Assist Device Support: A Derivation-Validation Multicenter Risk Score

<h3>Purpose</h3> Despite several models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support, poor performance when externally validated has limited their widespread use. We sought to derive a predictive model for RVF after LVAD implantation, and ascertain its performance in an independent cohort. <h3>Methods</h3> End-stage heart failure (HF) patients requiring continuous-flow LVAD were prospectively enrolled at one US program (n=477, derivation cohort), with two other US medical centers forming the validation cohort (n=321). The primary outcome was RVF incidence, defined as the need for right ventricular assist device or inotropes for >14 days. Multivariable logistic regression in the derivation set yielded a RVF predictive model, which was subsequently applied to the validation cohort, and a risk score was ultimately developed. <h3>Results</h3> Derivation cohort included patients less likely to be African-Americans (7% vs 37%; p<0.001), Hispanics (7% vs 30%; p<0.001), have a remote history of hypertension (49% vs 60%; p=0.002) or be bridged with short-term MCS (8% vs 16%; p=0.001), compared to the validation set. RVF incidence was 16% in the derivation and 36% in the validation cohort (p<0.001). Multivariable analysis identified 7 variables <b>(Figure)</b> as predictive of RVF, with the model achieving a C statistic of 0.734 (95% CI=0.674-0.794) in the derivation and 0.709 (95% CI=0.651-0.767) in the heterogeneous validation cohort. Patients were stratified into 3 RVF risk groups (all comparisons; p<0.001) <b>(Figure)</b>. <h3>Conclusion</h3> We propose a novel scoring system to predict post-LVAD RVF, achieving high discriminative performance in distinct, heterogeneous LVAD cohorts.

Right ventricular failure after left ventricular assist device implantation: a review of the literature.

Right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation remains a major complication which may significantly impair patient outcome. The genesis of RVF is, however, multifactorial, and the mechanisms underlying such a condition have not been fully elucidated, making its prevention challenging and the course not always predictable. Although preoperative risks factors can be associated with RV impairment, the physiologic changes after the LV support, can still hamper the function of the RV. Current medical treatment options are limited and sometimes, patients with a severe post-LVAD RVF may be unresponsive to pharmacological therapy and require more aggressive treatment, such as temporary RV support. We retrieved 11 publications which we assessed and divided in groups based on the RV support [extracorporeal membrane oxygenation (ECMO), right ventricular assist device (RVAD), TandemHeart with ProtekDuo cannula]. The current review comprehensively summarizes the main studies of the literature with particular attention to the RV physiology and its changes after the LVAD implantation, the predictors and prognostic score as well as the different modalities of temporary mechanical cardio-circulatory support, and its effects on patient prognosis for RVF in such a setting. In addition, it provides a decision making of the pre-, intra and post-operative management in high- and moderate- risk patients.

Abstract 15339: Prediction of Severe Right Ventricular Failure After Left Ventricle Assist Device Using Echocardiographic Right Ventricular Dp/dt

Introduction: Right ventricular failure (RVF) remains a major cause of morbidity and mortality after continuous flow Left Ventricle Assist Device (CF-LVAD) implantation. Previous risk assessments using pre-operative data to predict RVF have performed only modestly well. Methods: We retrospectively studied the potential of echocardiographic RV dP/dt - a non-invasive measure of right ventricular contractility derived from the Doppler signal of tricuspid regurgitation, to predict post-LVAD RVF in patients who were inotrope-independent and those who were on inotropic therapy prior to LVAD. Sixty-five consecutive CF-LVAD recipients at Vanderbilt University Medical Center from 2013-2019 who had a baseline echocardiogram without inotrope support within 3 months prior to LVAD implantation were included. Forty patients from the cohort were started on inotropes prior to LVAD implantation. Baseline off-inotrope and on-inotrope RV dP/dt data were analyzed. Severity of post-LVAD RVF was defined by INTERMACS criteria. Results: Of the 65 studied patients, 30 patients had none or mild RVF, 17 had moderate RVF, and 18 had severe RVF. Patients with severe RVF had markedly poorer survival outcome than no/mild and moderate RVF patients. Baseline RV dP/dt was significantly lower in patients who developed post-LVAD severe RVF. A baseline off-inotrope, or on-inotrope RV dP/dt ≥ 300 mmHg/s predicted a low risk of severe RVF with high sensitivity (89% and 80%, respectively) and negative predictive value (91% and 88% respectively); while the presence of both off-inotrope and on-inotrope RV dP/dt &lt; 300 mmHg/s was associated with a high likelihood of post-LVAD RVF (OR 10.5, 95% 1.8-59.4 compared to the rest of the cohort on inotrope therapy). Conclusion: Echocardiographic RV dP/dt may be a valuable adjunct tool for prediction of post-LVAD severe RVF in patients undergoing evaluation for LVAD implantation.

Abstract 15452: Low Dp/dt Max , When Indexed to Central Venous Pressure, is Associated With Severe Right Ventricular Failure Following Left Ventricular Assist Device Implantation

Introduction: Right ventricular failure (RVF) is a common complication following LVAD implantation and a significant driver of post-LVAD mortality. dP/dt max , the maximum rate of rise in ventricular pressure, is a validated hemodynamic parameter of ventricular contractility that, when indexed to CVP, accounts for loading conditions. This parameter has not, however, been studied in the context of post-LVAD RVF. We therefore evaluated the relationship between dP/dt max /CVP and post-LVAD RVF in a cohort of LVAD recipients at Stanford. Methods: We conducted a retrospective, single-center analysis of patients who underwent continuous-flow LVAD implant at Stanford between January 2010 and June 2019. Preoperative RV dP/dt max /CVP values were extracted from right heart catheterization (RHC) reports. For cases in which dP/dt max /CVP was not reported, preoperative RA and RV pressure tracings were utilized to manually calculate the index. We then performed unpaired t-tests to evaluate for the presence of associations between dP/dt max /CVP and early post-LVAD RVF, defined as the prolonged (&gt;7 days) requirement for inotropic or pulmonary vasodilator therapy or the need for RVAD support, and between dP/dt max /CVP and severe post-LVAD RVF, defined only by the requirement for RVAD support. Results: This cohort included 202 LVAD recipients who had available preoperative RHC data. Of these, 14.4% (n = 29) required an RVAD and 50.5% (n = 102) experienced early post-LVAD RVF. Mean values of dP/dt max /CVP amongst patients with and without early post-LVAD RV failure were 94.9 ± 128.5 s -1 and 105.6 ± 125.5 s -1 (p = 0.56), respectively, while mean values of dP/dt max /CVP amongst those who did and did not require an RVAD were 53.2± 42.0 s -1 and 108.2 ± 129.5 s -1 (p = 4.2 х 10 -5 ), respectively. Conclusion: In continuous-flow LVAD recipients, low preoperative RV dP/dt max /CVP is strongly associated with severe post-LVAD RVF requiring RVAD support but not early post-LVAD RVF more generally.

A Novel Risk Score Predicts Early Right Ventricular Failure after Lvad: A Derivation-validation Multicenter Study

Introduction Right ventricular failure (RVF) after LVAD implantation is associated with increased morbidity and mortality. Despite several RVF predictive models, poor performance in external validation cohorts has limited their widespread clinical adoption. Objective To develop a novel RVF predictive model, ascertain its performance in an independent validation cohort, and develop an RVF risk score. Methods Consecutive LVAD patients were prospectively enrolled at the Utah Transplantation Affiliated Hospitals (U.T.A.H) Cardiac Transplant Program (n=477, Derivation cohort). LVAD patients from Inova Heart & Vascular Institute and Henry Ford Medical Center formed the external dataset (n=321, Validation cohort). The primary outcome was early RVF, defined as the need for RVAD or intravenous inotropes for >14 days. The secondary outcome was 3-year all-cause mortality. Multivariable logistic regression analysis was used to develop a predictive model. An RVF risk score was developed using weighted points based on the β-regression coefficients of the multivariable predictors. Results The study included 798 patients, with a mean age of 56y, 84% male, and 30% INTERMACS Profile 1-2. Compared to the derivation cohort, the validation cohort had a higher proportion of African-Americans (37% vs 7%; p 35mg/dL, PA pulse pressure 0.5). The model had a c-statistic of 0.73 ([95% CI:0.67-0.79]; p Conclusion We propose a novel scoring system to predict post-LVAD RVF, achieving high discriminative performance after being tested in distinct and highly heterogeneous populations. This simple predictive tool could impact patient selection and perioperative management of LVAD patients.

Right Ventricular Failure Post-Implantation of Left Ventricular Assist Device: Prevalence, Pathophysiology, and Predictors.

Despite advances in left ventricular assist device (LVAD) technology, right ventricular failure (RVF) continues to be a complication after implantation. Most patients undergoing LVAD implantation have underlying right ventricular (RV) dysfunction (either as a result of prolonged LV failure or systemic disorders) that becomes decompensated post-implantation. Additional insults include intra-operative factors or a sudden increase in preload in the setting of increased cardiac output. The current literature estimates post-LVAD RVF from 3.9% to 53% using a diverse set of definitions. A few of the risk factors that have been identified include markers of cardiogenic shock (e.g., dependence on inotropes and Interagency Registry for Mechanically Assisted Circulatory Support profiles) as well as evidence of cardiorenal or cardiohepatic syndromes. Several studies have devised multivariable risk scores; however, their performance has been limited. A new functional assessment of RVF and a novel hepatic marker that describe cholestatic properties of congestive hepatopathy may provide additional predictive value. Furthermore, future studies can help better understand the relationship between pulmonary hypertension and post-LVAD RVF. To achieve our ultimate goal-to prevent and effectively manage RVF post-LVAD-we must start with a better understanding of the risk factors and pathophysiology. Future research on the different etiologies of RVF-ranging from acute post-surgical complication to late-onset RV cardiomyopathy-will help standardize definitions and tailor therapies appropriately.

CCR5 Expression is Lower in Women, and Mediates Sex-Based Differences in Post-LVAD Right Ventricular Failure

Purpose Women have increased risk of right ventricular failure (RVF) after LVAD implant, however the underlying pathophysiology is unknown. Chemokines are inflammatory signaling molecules, and fundamental to cardiac homeostasis and stress adaptation. Prior studies have demonstrated a cardio-protective role for chemokine receptor-5 (CCR5) in viral myocarditis and severe Chagas cardiomyopathy, and that sex hormones modulate CCR5 gene expression. We have previously shown that CCR 3-8 down-regulation is predictive of RVF and 1-year survival after implant. We hypothesized that CCR5 expression mediates sex-based differences in post-LVAD RVF. Methods CCR expression was examined in patient's peripheral blood 24 hours pre-LVAD. RNA was isolated using PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR array, Qiagen). Results were expressed as PCR cycles to threshold (CT). ΔCT was calculated as (CCR gene CT) - (HPRT1 control gene CT), and log2 transformed for analysis. Log-fold differences in expression were reported using 2−ΔΔCT method. RVF was defined as both planned and unplanned RVAD requirement. Multivariable logistic regression was used to determine the association of sex with RVF, adjusting for significantly different covariates (p Results We analyzed 111 LVAD patients (mean age: 53.57 ± 13 years, 18% female, 17.1% black). The criteria for RVF was met in 35 (31.5%) patients. Women had increased incidence of RVF (50% vs. 27.5%, p=0.047), and under-expressed CCR5 (1.41 fold decrease, p=0.012) compared to men. After controlling for age, heart failure etiology, albumin, BUN, creatinine and cardiac output, women had a higher risk of RVF (HR: 3.18, 95% CI: 1.04-9.8, p=0.043). Addition of CCR5 as a covariate to the model attenuated the association of female sex with RVF (HR: 2.86, 95% CI: 0.91-8.97, p=0.071). Conclusion Pre-implant CCR5 expression is lower in women than in men and may mediate sex disparities in post-LVAD RVF.

Right Ventricular Strain as a Predictor of Post-LVAD Early Right Ventricular Failure

Purpose Early right ventricular failure (RVF) occurs in up to 40% of patients following left ventricular assist device (LVAD) implantation and is associated with increased peri-operative mortality and prolonged hospitalization. We sought to determine the effectiveness of RV longitudinal strain (RVLS) in predicting post-LVAD RVF. Methods We retrospectively analyzed 55 patients who underwent LVAD implantation between 2013-2018 in an academic hospital. Global longitudinal and segmental (septum and free wall) RV strain in the 4-chamber, right ventricular outflow tract (RVOT), and subcostal views were measured on pre-LVAD echocardiograms using 2D strain software (TomTec, Chicago, USA). Early RVF was defined as the requirement of more than two weeks of ionotropic support post LVAD implantation or the need for right ventricular assist device (RVAD). Results 27 patients (49%) suffered from RVF. RV global longitudinal strain (RVLS) was significantly reduced in patients who developed RVF compared to those who did not (Table 1). At a cutoff of -10.0%, RVLS measured in the 4-chamber view had a sensitivity of 88% and specificity of 75% in predicting early RVF, with an AUC of 0.84 and an OR of 1.4. Segmental analysis of free wall and septal strain in the apical 4-chamber and subcostal views were also significantly reduced in patients with RVF. ROC calculations were performed on previously described metrics including pulmonary artery pulsatility index (PAPi), right ventricular stroke work index (RVSWI), and Michigan risk score demonstrating an AUC of 0.46 for PAPi, 0.41 for RVSWi, and 0.58 for Michigan risk score. Conclusion Pre-operative RVLS was a useful predictor of RVF in multiple views. In this cohort study, 2D RVLS outperformed previously used clinical, hemodynamic, and echocardiographic based metrics as a predictive marker for early RVF and may be a useful tool in risk stratification of pre-operative LVAD patients.

Serial Assessment of Pulmonary Artery Pulsatility Index Provides Incremental Risk Assessment for Early Right Ventricular Failure after Left Ventricular Assist Device Implantation

Purpose PAPi (pulmonary artery pulsatility index) is a predictor of early right ventricular failure (RVF) post left ventricular assist device (LVAD) implantation and has been studied using hemodynamics from single, isolated time points. Since multiple clinical factors and therapies are known to impact RV function in pre-LVAD patients, we hypothesized that serial PAPi measurements would provide incremental risk stratification for early post-LVAD RVF. Methods A total of 394 consecutive patients undergoing primary durable LVAD implantation at our center from 2004 to 2017 were retrospectively enrolled. Serial invasive hemodynamics obtained during inpatient swan guided therapy (77%) or consecutive outpatient right heart catheterizations were recorded. The lowest, highest (“Best”), change (“Delta”) and most proximal PAPi to LVAD implant were calculated. RVF was defined as need for RVAD or prolonged inotrope use > 14 days post-operatively. Multivariate logistic regression determining independent associates of early RVF was performed. Results RVF occurred in 82 of the 394 patients (21%). Those who developed early RVF had significantly lower mean Delta PAPi (2.0 vs 5.3, p Conclusion The best PAPi achieved during medical optimization prior to LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying RV reserve.