Search

Abstract: Heart failure (HF) is a global epidemic that continues to cause significant morbidity and mortality despite advances in medical therapy. Ventricular assist device technology has emerged as a therapeutic option to bridge patients with end-stage HF to heart transplantation or as an alternative to transplantation in selected patients. In some patients, mechanical unloading induced by ventricular assist devices leads to improvement of myocardial function and a possibility of device removal. The implementation of this advanced technology requires multiple pharmacological interventions, both in the perioperative and long-term periods, in order to minimize potential complications and improve patient outcomes. We herein review the latest available evidence supporting the use of specific pharmacological interventions and current practices in the care of these patients: anticoagulation, bleeding management, pump thrombosis, infections, arrhythmias, right ventricular failure, hypertension, desensitization protocols, among others. Areas of uncertainty and ground for future research are also highlighted. [Copyright &y& Elsevier]

Predicting cardiac structural and functional improvement in advanced heart failure (HF) patients before durable left ventricular assist device (LVAD) implantation remains challenging. Identifying clinical predictors could improve patient selection and impact clinical management. Advanced chronic HF patients (N=652) supported with continuous-flow LVADs were evaluated. After excluding patients with acute HF etiologies or without adequate post-LVAD follow up (<3 months), they were divided into an internal Derivation cohort (n=339, UTAH program) and an external Validation cohort (n=227, 4 US programs). Patients with post-LVAD LVEF ≥40% and LVIDd ≤6.0cm within the 1st year post-implant, were defined as Responders (R). Multivariate Cox regression was used to predict R, in the Derivation cohort, and the fit of the model was tested in the Validation cohort. In total, 10% of the LVAD patients were R. Univariate analysis showed that R were younger, had shorter HF symptoms duration, less need for diuretics and their LV were less dilated pre-LVAD. Further, R had higher acuity disease as evidenced by the higher vasoactive agents need, higher BNP and higher incidence of abnormal liver enzymes. The multivariate Cox regression (AUC=0.74; p<0.001) predicted R using 3 clinical parameters: LVIDd<6.9 cm, age<50 years, and HF duration<36 months (Table). The model's predictive accuracy was validated in the external Validation cohort (AUC=0.78; p<0.001). Younger patients with less LV dilation and shorter duration of HF are more likely to improve their cardiac function during LVAD support. Whether these characteristics also predict sustainability of improved cardiac function after LVAD weaning warrants further investigation. [ABSTRACT FROM AUTHOR]

Recent studies have shown enhanced survival and reduced morbidity with centrifugal (HeartMate 3-HM3) left ventricular assist device (LVAD) compared with axial-flow (HeartMate II-HMII) LVAD. However, differences in LVAD-induced left ventricular (LV) reverse remodeling between the two devices remain uninvestigated. The aim of our study was to compare the LV structural and functional changes between these two types of mechanical unloading. Echocardiographic parameters of LV structure and function were obtained pre-implant and at 1, 3, 6, and 12 month of LVAD support. Statistical comparison of quantitative data was performed using 2-tailed Wilcoxon signed-rank test for paired samples and categorical data were compared using Fisher's exact test. A total of 32 consecutive patients (median age 62.5 [IQR 52-68] years, 15.6% female) received axial-flow LVAD (HMII) and 31 consecutive patients (median age 58 [IQR 47-71] years, 16.1% female) received centrifugal LVADs (HM3). There were no significant differences in the baseline characteristics between the study groups. Following LVAD support there were no differences in the LV ejection fraction or LV mass index between the two types of mechanical unloading across all time points (figure 1A and 1B). In centrifugal LVAD patients, LV end diastolic volume index was lower at 1 and 3 months and LV end systolic volume index was lower at 1 month. No differences were identified after 3 months of mechanical unloading (figure 1C and 1D). Both centrifugal and axial-flow LVADs resulted in improved LV function and structure. Although LV volumes were found to be lower at 1 and 3 months in centrifugal pump patients, long-term (> 3month) mechanical unloading seem to exert similar effects on LV structural and functional parameters. [ABSTRACT FROM AUTHOR]

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is a serious complication with poor prognosis. Improved selection of patients with greater risk of developing the condition is crucial, considering the growing need for destination therapy patients. However, predicting RVF remains a vexing clinical problem. From 2008 to 2019, 478 consecutive chronic heart failure (HF) patients supported with continuous-flow LVADs were prospectively evaluated. RVF was defined by the need for intravenous inotropes for >14 days and/or right ventricular assist device implantation. Data was analyzed based on the presence or absence of RVF in the early post-operative period and their baseline clinical, hemodynamic, imaging and laboratory data were compared. Multivariable logistic regression was used to develop a clinical model for RVF prediction. Overall, 77 (16.1%) patients developed RVF. Univariate analysis showed that the RVF was associated with higher acuity disease before LVAD implantation reflected by low INTERMACS profile, high vasoactive medication requirement, presence of IABP support, hyponatremia, thrombocytopenia, low serum albumin, and renal dysfunction. Additionally, RVF was associated with increased heart rate, right atrial (RA) and right atrial to wedge pressure (RA/PCWP) ratio, along with decreased systolic pulmonary artery pressure (PAP), right ventricular stroke work index (RVSWi) and pulmonary artery pulsatility index (PAPi), at baseline. Interestingly, patients who developed RVF had decreased left ventricular end-diastolic diameter at baseline, when compared to the no RVF group. The multivariate model (AUC=0.77; p<0.0001) predicted RVF using 7 clinical parameters: 1) Remote history of systemic hypertension, 2) Preoperative need for IABP, 3) Systolic PAP <60 mmHg, 4) RA/PCWP ≥0.66, 5) PAPi <1.44, 6) Na <135 mEq/L, & 7) PLT <100 × 103/microL Our model seems capable of distinguishing patients prone to develop RVF post-LVAD implantation. The identified pre-LVAD predictors include markers of globally advanced HF syndrome and higher acuity as well as markers specific to severity of RVF. [ABSTRACT FROM AUTHOR]

Although significant cardiac reverse remodeling is a prerequisite for a left ventricular (LV) assist device (LVAD) patient to be considered for device weaning, multiple factors including patient goals, physician comfort, and center experience, weigh in on this complex decision. Existing predictive models defining recovery as device withdrawal, entail the above-mentioned confounders, and may under detect patients that could benefit from a targeted bridge to recovery strategy. We sought to derive and validate a predictive tool to identify patients prone to reverse remodel, independent of the complex decision to remove a durable, surgically deployed device. Heart failure patients (N=782) requiring LVAD were enrolled at one (n=537) and five US programs (n=245). Baseline characteristics were recorded. The primary outcome was responder incidence, defined as follow-up LV ejection fraction ≥40% and LV end-diastolic diameter ≤6 cm within one year on LVAD support. Bootstrap imputation and lasso variable selection techniques were used to derive a predictive model which was then validated using our multicenter dataset. A predictive calculator was developed, and patients were classified into groups with varying potential for reverse remodeling. Patients were predominantly white (84%), male (82%), aged 56±1 years. Overall, 14.8% patients were identified as responders. Nine preoperative variables associated with reverse remodeling were included in the multivariate model achieving an optimism corrected C-statistic of 0.77 (95% CI: 0.71-0.82) (Figure). The UCAR calculator is a machine learning-based multicenter and validated risk tool, implementing routine clinical data, that effectively stratifies patients into groups with varying potential for reverse remodeling. This tool can be useful in selecting patients to implement diagnostic and therapeutic protocols that can promote reverse remodeling and myocardial recovery. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is prevalent among advanced heart failure (HF) patients, however its effect on the potential of left ventricular assist device (LVAD)-mediated cardiac recovery has not been described. Consecutive advanced chronic HF patients (N=425) requiring durable continuous-flow LVAD were prospectively evaluated. After excluding patients with acute HF etiologies or post-LVAD follow up <3 months, 336 patients were included. Patients with history of DM and/or pre-LVAD HbA1c ≥6.5 comprised the DM group (n=142), while those with no history of DM and a pre-LVAD HbA1c <6.5 comprised the non-DM group (n=194). Diabetics with a pre-LVAD HbA1c <7 were considered well-controlled (n=72) and those with a pre-LVAD HbA1c ≥7 not well-controlled (n=70). Relative changes between pre- and post-LVAD LVEF and LVEDD, were calculated. Cardiac recovery was defined as post-LVAD LVEF ≥40% and LVEDD <6.0cm. Baseline characteristics of the 2 groups are shown in the Table. Cardiac functional and structural improvement, as evidenced by relative LVEF and LVEDD changes, was more prominent in non-DM compared to DM patients, and in well- compared to not well-controlled DM patients (Figure). Overall, DM patients were less likely to experience cardiac recovery (8.4% vs 17.5%; p=0.032), while on LVAD support. This remained significant in a multivariate logistic regression after controlling for potential confounders. The presence of DM, and notably not well-controlled DM, appears to negatively affect the potential for LVAD-induced myocardial recovery. Further research is needed to investigate the dynamic cardiac metabolism in HF with DM. [ABSTRACT FROM AUTHOR]

Although significant reverse cardiac remodeling is required for an LVAD-supported patient to be considered for device weaning, multiple factors including patient willingness, physician expertise, and center experience influence this complex decision. Existing predictive models defining cardiac recovery as device removal might underestimate reverse remodeling rates and lack accuracy in identifying patients prone to improve cardiac structure and function. We sought to develop a predictive tool to identify patients with such potential, independent of the decision to deactivate a durable, surgically deployed device. Chronic HF patients (N=703) requiring continuous-flow LVADs were evaluated. After excluding patients with acute HF and/or <3 months post-LVAD follow up, 3 US programs contributed 390 patients (derivation cohort), while 5 US programs formed the validation cohort (n=245). We defined responders as patients with an LVEF ≥40% and LVEDD ≤6.0 cm within a year on LVAD support. Multivariable logistic regression on the derivation set yielded a predictive model, which was externally tested; a predictive score was developed. Overall, 18.5% of the patients were responders. Compared to the validation, patients in the derivation cohort were more likely white (83 vs 69%; p<0.001), with ischemic HF (42 vs 33%; p=0.04), and longer HF duration (88 vs 66 months; p<0.001). Multivariable predictors of responders and the derived scoring system are shown in the Figure (c-statistic 0.74 [95% CI: 0.66-0.83] and 0.71 [95% CI: 0.59-0.77] in the derivation and validation set). We propose a novel score to predict significant cardiac improvement on LVAD support achieving good discriminative performance in distinct, heterogeneous, contemporary cohorts. This tool can be useful in selecting patients to implement diagnostic and therapeutic protocols to promote reverse remodeling and myocardial recovery. [ABSTRACT FROM AUTHOR]

Centrifugal-flow left ventricular assist devices (CF-LVADs) have improved morbidity and mortality for LVAD recipients. Hospital readmissions, however, remain common and affect quality of life and survival. We sought to identify factors associated with readmissions on LVAD support. Patients receiving a CF-LVAD between February 2011 and March 2021 were prospectively evaluated. Hospital readmissions were dichotomized into HF/LVAD-related or non-HF/LVAD-related. Multivariable logistic regression models augmented using the least absolute shrinkage and selection operator method for variable selection were used to estimate associations between ≥1 HF/LVAD-related readmissions and clinical variables. Our study cohort included 201 patients. Seventy percent (140/201) were readmitted for HF/LVAD-related reasons and accounted for 74% (489/657) of total readmissions. The main reasons for HF or LVAD-related readmission were major bleeding, major infection, heart failure exacerbation, and neurological dysfunction. Using pre-LVAD variables we built a multivariable model of HF/LVAD-related readmission. The variables associated with readmission were age, previous cardiac surgery, inotrope dependency, percutaneous LVAD/VA-ECMO support, duration of LVAD support, LVAD type, serum sodium and aspartate aminotransferase, and LV ejection fraction (Table). The area under the ROC curve (AUC) was 0.825. The inclusion of intra- and post-operative variables did not significantly increase accuracy (AUC=0.831) (Table). We created models accurately identifying patients with a high likelihood of readmissions after LVAD implant. Most variables associated with readmission can be identified pre-operatively. Our findings can guide the implementation of therapeutic strategies to mitigate readmission risk and further improve outcomes. [ABSTRACT FROM AUTHOR]

Our understanding of how hemodynamics affect liver function in chronic heart failure (HF) is limited. A long-standing notion is that elevated right atrial pressure (RAP) predisposes to elevated liver enzymes and bilirubin, while decreased cardiac index (CI) increases aminotransferases. We sought to examine how liver function tests (LFTs) relate to hemodynamics in patients with advanced HF (AdvHF). Prospectively enrolled AdvHF patients who were evaluated in our program for advanced therapies and received a left ventricular assist device were studied (n=530). Univariate and multivariable logistic regression analyses were used to assess associations between abnormal LFTs (value >ULN) and non-invasive (mean arterial pressure [MAP], heart rate) and invasive (RAP, mean pulmonary artery pressure, wedge pressure, CI and systemic vascular resistance) hemodynamics. Variables identified as significant (P<0.05) in univariate analyses were included in the multivariable models together with use of inotropes and temporary mechanical circulatory support (tMCS). Mean age was 57±13 years, ejection fraction 18±8%, MAP 80±12 mmHg, RAP 11±6 mmHg and CI 1.8±0.5 L/min/m2, with 370 patients (70%) having NYHA class IV symptoms. Ninety-two (17%) patients were supported with tMCS and 374 (71%) were on inotropes. Prevalence of LFT abnormalities was 20% for alanine transaminase (ALT), 30% for aspartate transaminase (AST), 23% for alkaline phosphatase (ALP), 31% for bilirubin and 27% for albumin. Lower MAP was an independent predictor of abnormal ALT (OR: 1.03; 95% CI: 1.00-1.06, P=0.02), ALP (1.03; 1.00-1.06, P=0.008) and bilirubin (1.03; 1.00-1.05, P=0.01), while higher RAP was independently associated with abnormal ALT (1.05; 1.01-1.10, P=0.05) and bilirubin (1.09; 1.05-1.14, P<0.001). No association between LFTs and CI was demonstrated. In AdvHF patients RAP and MAP seem to be the most significant hemodynamic drivers of hepatic derangements. Given that LFT abnormalities negatively affect the prognosis of AdvHF patients, a pre- and post-advanced therapies strategy which prioritizes maintaining normal RAP and adequate MAP warrants further investigation [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (DM) and poor glycemic control portend a higher risk for cardiovascular morbidity and mortality. We sought to assess their impact on left ventricular assist device (LVAD)-mediated cardiac recovery in chronic advanced heart failure (HF). Consecutive patients (N=477) receiving a durable continuous-flow LVAD were prospectively evaluated. After excluding patients with acute HF etiologies or inadequate follow-up after LVAD (<3 months), 396 patients were stratified based on pre-LVAD DM status into non-diabetics (n=121; no history of DM and HbA1c <5.7) and diabetics/prediabetics (n=275; history of DM or HbA1c ≥5.7). Diabetics/prediabetics were further divided into 3 groups: prediabetics, n=106; well-controlled DM (HbA1c <7%), n=90; or not well-controlled DM, n=79. The absolute left ventricular ejection fraction (LVEF) change (ΔLVEF = LVEF post-LVAD - LVEF pre-LVAD) within one year on LVAD support was compared between groups with linear regression. DM is frequently associated with ischemic cardiomyopathy (ICM), so patients were stratified a priori into ICM and non-ICM (NICM). Compared to non-diabetics, diabetics/prediabetics were older, more likely male, with a higher BMI, and more commonly had an ICM, remote history of hypertension, and a longer HF symptoms duration. The Figure depicts the ΔLVEF between the study groups stratified into ICM or NICM. After adjusting for age, sex, BMI, HF symptoms duration, and history of hypertension, patients with well-controlled DM responded more favorably compared to patients with poor glycemic control. Overall, NICM patients responded more favorably than ICM patients. DM appears to negatively affect functional cardiac improvement on LVAD support and effective glycemic control seems to be beneficial in enhancing the favorable myocardial functional response. Further research is warranted to investigate the underlying mechanisms driving the differential responses. [ABSTRACT FROM AUTHOR]

The complex anatomy and different contraction patterns of the different right ventricular (RV) wall segments has made it challenging to predict acute RV failure (ARVF) in patients receiving a left ventricular assist device (LVAD). We sought to improve the prediction of ARVF after LVAD by performing a comprehensive 18-segment strain (ε) analysis of the RV. Prospectively enrolled LVAD recipients had a right heart catheterization and echocardiogram prior to implant. From RV-focused views (Figure 1A), 18-segment ε was performed and indexed to pulmonary arterial elastance (Ea [PV]). ARVF was defined as need for RVAD, inotropes for >14 days or pulmonary vasodilator for >48 hours post-LVAD. Logistic regression was used to identify associations between specific parameters and ARVF. ARVF occurred in 15 of 30 patients enrolled. Lower pulmonary artery pulsatility index (PAPi), TAPSE and basal free wall (FW) (basal anterior, lateral and posterior FW) segmental ε/Ea (PV) were significantly associated with ARVF. Indexed basal FW segmental strain provided incremental predictive value over PAPi and TAPSE (Figure 1B). Prediction of ARVF in LVAD candidates can be improved by adding comprehensive RV segmental strain analysis to traditional echocardiographic and hemodynamics parameters. [ABSTRACT FROM AUTHOR]

There is limited information on regional variation in rates of cardiac recovery and left ventricular assist device (LVAD) explantation at a global level. We aimed to compare the rates of cardiac recovery and LVAD explantation across several world regions. LVAD recipients registered in the International Registry for Mechanically Assisted Circulatory Support (IMACS) were analyzed. Cardiac recovery was defined as follow-up LVEF >40% and a pre-LVAD LVEF <30%. Cardiac recovery and LVAD explantation/deactivation due to recovery were evaluated in bridge-to-recovery (BTR) and non-BTR designation patients in the Americas, Asia-Pacific and Europe. A total of 16,029 patients met our inclusion criteria and were included in the analysis. Of these, 9,381 patients had at least one follow-up echocardiogram and a minimum of 3 months of LVAD support. Cardiac recovery was achieved in 13.3% (n=1,249) of patients, with a rate of 55.3% (n=21) in BTR compared with 13.1% (n=1,228) in non-BTR patients. Rates of cardiac recovery varied significantly by region: 12.7% (n=1,079) in the Americas, 15.9% (n=94) in Asia-Pacific and 29.5% (n=76) in Europe (p<0.001) (Figure 1A). Rates of LVAD explantation/deactivation were similar between the Americas (5.7%) and Asia-Pacific (4.6%) and lower in Europe (2.0%) (p<0.001) (Figure 1B). Global rates of both cardiac recovery and LVAD explantation are higher in patients implanted with a priori BTR strategy. Rates of cardiac recovery appear to be higher in Europe for reasons that warrant further investigation. The global rates of LVAD explantation are much lower compared to the corresponding cardiac recovery rates. This observation invites future investigations to identify the challenges in regards to LVAD weaning when recovery is identified, which could result in higher rates of LVAD explantation. [ABSTRACT FROM AUTHOR]

The variability of left ventricular structural and functional improvement following continuous flow left ventricular assist device (LVAD) implantation is poorly understood. The study consecutively enrolled 358 patients with confirmed chronic heart failure who required a durable LVAD across four study sites. Echocardiograms were performed preceding LVAD implantation and serially up to a year after. Patients were categorized by the degree of structural (left ventricular internal diastolic diameter, LVIDd) and functional (left ventricular ejection fraction, LVEF) change after LVAD. In the cohort, 34 patients (10%) experienced improvement of the LVEF ≥40% and LVIDd ≤6.0cm and were termed responders. The rest of the patients were distinguished in 3 groups based on the absolute change (Δ) in LVEF during follow up: Partial Responders had Δ-LVEF ≥10% (n=57, 16%), Borderline Responders Δ-LVEF 5-10% (n=55, 15%), Non-Responders Δ-LVEF <5% (n=212, 59%, Figure). The LVEF absolute change following mechanical unloading was: -3.2±5.9%, 6.3±1.4%, 15.5±5.4%, 27.7±9.7% in Non-Responders, Borderline Responders, Partial Responders and Responders, respectively (p<0.001). Structural changes in terms of LV dimensions followed a different pattern with significant improvements even in patients that had minimal systolic functional improvement. Multivariate logistic regression identified the following clinical characteristics as predictive of favorable reverse myocardial remodeling: smaller pre-LVAD implantation LVIDd, use of an axial flow device, and shorter heart failure duration preceding LVAD implant. Reverse left ventricular remodeling associated with durable LVAD support is not an all or none phenomenon and manifests in a continuous spectrum. Defining four stages across this continuum can inform clinical management and facilitate advancing the field of myocardial plasticity by informing the design of future investigations. [ABSTRACT FROM AUTHOR]

LVAD therapy has been primarily studied in patients with elevated pulmonary capillary wedge pressure (PCW) and low cardiac index (CI), "cold and wet". In daily practice, LVADs are often also offered to patients with low PCW and low CI, "cold and dry". The efficacy of LVAD therapy in this population is not well studied. Patients implanted with LVAD with a baseline CI <2.0 Lpm were categorized as "wet" (PCW>18mmHg) or "dry" (PCW<18mmHg). These values were derived from serial pre-LVAD right heart catheterization studies in order to reflect a sustainable hemodynamic profile. Variables of interest and 3-year survival were compared between groups. Independent predictors of mortality were identified using multivariate Cox regression analysis. Serial invasive hemodynamics data was available for 92 pts (cold-dry group, n=34 and cold-wet group, n=58) (Table). Diuretic and vasodilator use pre-LVAD was comparable in both groups. Cold-dry patients had no change in CVP or PCW with a smaller increase in CI after LVAD. Adjusted 3-year mortality was higher for cold-dry patients (Figure). Age (HR=1.09, 95%CI 1.02-1.2; p=006) and cold-dry profile (HR=5.4, 95%CI 1.4-21; p=0.016) were identified as independent predictors of mortality. "Cold and dry" patients with advanced heart failure may not derive equal benefit from LVAD therapy as those who are "cold and wet". This observation warrants further investigation. [ABSTRACT FROM AUTHOR]

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. 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. 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 (Figure) 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) (Figure). We propose a novel scoring system to predict post-LVAD RVF, achieving high discriminative performance in distinct, heterogeneous LVAD cohorts. [ABSTRACT FROM AUTHOR]

Although left ventricular (LV) reverse remodeling has been described in patients with left ventricular assist devices (LVADs), little is known about left atrial (LA) structural and functional changes. Echocardiographic parameters were obtained at pre-LVAD implant and following 1, 3, and 6 months of LVAD support. Favorable LV structural and functional response following LVAD support (i.e. Responders) was defined using previously published criteria. Structural and functional indices specific to LA such as LA volume index (LAVI) and LA total emptying fraction (LATEF) were compared in eighteen Responders versus twenty Non-Responders. Statistical comparison of quantitative data was performed using 2-tailed Wilcoxon signed-rank test for paired samples and categorical data were compared using Fisher's exact test. The magnitude and time course of functional changes as reflected by the LVEF and LATEF in Responders and Non-Responders are depicted in Figure 1A and 1B. LA remodeling structural changes over time in Responders and Non-Responders are depicted in Figure 1C. Patients experiencing post-LVAD favorable LV functional response had significantly better LA remodeling structural and functional indices before LVAD implantation and further improved those early after the initiation of LV mechanical support. LA reverse remodeling studies with longer follow-up and correlation with post LVAD-weaning patient outcomes are warranted. [ABSTRACT FROM AUTHOR]

Purpose A subset of end-stage heart failure (HF) patients on left ventricular assist device (LVAD) can significantly improve their native heart structure and function. Long-term stability of this cardiac improvement (CI) after LVAD weaning has not been well investigated. Methods We included chronic advanced non-ischemic cardiomyopathy patients (acute HF excluded) who were weaned from LVAD support based on predefined myocardial structural, functional and hemodynamic criteria. We defined "sustainable CI" after LVAD weaning as LVEF≥ 40% & LVEDD< 57mm. Regression analysis evaluated trends. Results Our cohort included 6 males and 6 females, mean age 33±12. Patients achieved LVAD weaning criteria after 532 [196, 2304] days of support. LVEF improved from 18±6 pre-implant to 46±10 % at LVAD explant (p<0.0001), LVEDD decreased from 65±7 to 46±6 mm (p<0.0001) and BNP decreased from 1438±1585 to 90±77 pg/ml (p<0.02). During a follow up post LVAD removal of 844 [15, 1241] days, we identified 2 groups, patients with sustainable (n=7) and with declining (n=5) CI (Figure). At the latest follow-up, the stable and declining groups differed with respect to LVEF (52 vs 17 %; p<0.0001), LVEDD (52 vs 65 mm; p=0.003) and BNP (58 vs 677 pg/ml; p=0.04). Quality of life assessment matched well with improvements in LV remodeling (Figure). The degree of CI pre-LVAD removal did not differ between the 2 groups and hence was not identified as a predictor of post weaning stability of CI. After LVAD weaning, 4/5 patients in the declining group had chronic systemic infection, drug abuse and HF medications therapy non-adherence, which likely affected negatively the stability of CI. A patient from this group was deceased due to HF recurrence. Conclusion In this single center report the long-term stability of CI after LVAD weaning appears to be encouraging. Larger and longer follow up clinical and translational studies are warranted to provide further clinical and mechanistic insights regarding factors associated with sustainable CI. [ABSTRACT FROM AUTHOR]

Purpose Occasionally new onset cardiomyopathy patients (pts) present late, in such advanced disease stage that they cannot tolerate heart failure (HF) drug therapy. We investigated the cardiac recovery (CR) potential following a combination of left ventricular assist device (LVAD) and guideline-directed HF drug therapy in this medication-naive population. Methods Chronic advanced HF pts requiring durable continuous-flow LVAD were prospectively evaluated. Pts with acute HF (myocarditis etc) or post LVAD follow up <3 months were excluded. The "meds-treated" group (n=203) comprised pts treated adequately with at least one neurohormonal blocking agent during their HF history (b-blocker, ACEI/ARB, Aldosterone antagonist) and "meds-naive" group (n=8) comprised pts who were never before treated adequately with any HF medication. A great variety of baseline and follow up data were analyzed. LVAD pts were phenotyped as CR responders or non responders, based on published predefined criteria. Results Univariate analysis showed that "med-naive" pts were younger, more likely to be on intravenous vasoactive agents, temporary MCS and with lower INTERMACS profile before LVAD implantation. Interestingly, no differences were seen in HF symptoms duration or other comorbidities. Baseline and follow up hemodynamics were similar in both groups, besides higher right atrial pressure pre-LVAD in the "meds-naive" group (16 vs 11 mmHg; p=0.04). Baseline echocardiographic (including LV dilation) and biochemical parameters revealed no differences between the groups, besides lower LVEF and higher BNP in the "meds-naive" group (14 vs 19 %; p=0.03 and 2352 vs 1270; p=0.03, respectively). CR rates were significantly higher on "meds-naive" versus "meds-failed" group (50.0 vs 13.8 %; p=0.005). Despite higher cardiac recovery rates in the "meds-naive" group the time course and magnitude of the favorable functional and structural response was similar among the CR responders of each of the 2 groups. Conclusion Young pts with new onset dilated cardiomyopathy sometimes present late, with advanced disease stage, unable to tolerate HF medications and requiring durable LVAD support. This patient population appears to have a potential for CR up to 50% and this could be factored in decisions surrounding their long-term therapeutic options. [ABSTRACT FROM AUTHOR]

Purpose Predicting cardiac recovery (CR) in advanced heart failure (HF) patients before left ventricular assist device (LVAD) implantation remains challenging. This study sought to investigate whether CR after LVAD unloading can be predicted by cardiac functional and structural parameters together with clinical characteristics. Methods From 2008 to 2016, consecutive advanced chronic HF patients (N=347) supported with durable continuous-flow LVADs were prospectively evaluated. Patients with acute HF etiologies or without adequate post-LVAD follow up (<3 months) were excluded. A great variety of clinical characteristics were evaluated in the remaining 285 subjects. LVAD patients were phenotyped while on support, as CR Responders or Non Responders, based on published predefined echocardiographic criteria. Multivariable logistic regression was used to form the model and the Utah Cardiac Recovery (UCAR) score was created from the regression beta coefficients of the final model. Results CR occurred in 13.7% of patients. Univariate analysis showed that responders were more likely to be young, female, non-ischemic cardiomyopathy, with shorter HF symptoms duration and no prior heart surgery. They had lower blood urea nitrogen and were less likely to be on temporary mechanical support before LVAD. The multivariable UCAR model (AUC=0.755; p<0.001) predicted CR using 3 clinical parameters - Table. Conclusion Univariate and multivariable predictors of CR include both modifiable and non-modifiable patient characteristics that are known prior to LVAD implantation. The UCAR score can serve as a practical tool for targeted patient selection to implement protocols that facilitate CR in the advanced HF patient subpopulation that is most likely to respond. [ABSTRACT FROM AUTHOR]