Benefits of Neurohormonal Therapy in Patients With Continuous-Flow Left Ventricular Assist Devices.
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ABSTRACT:
SUBMITTER: Yousefzai R
PROVIDER: S-EPMC8330955 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Metabolic impairment is common in heart failure patients. Continuous-flow left ventricular assist devices (CF-LVADs) improve hemodynamics and outcomes in patients with advanced heart failure; however, the effect of CF-LVADs on metabolic status is unknown. This study aims to evaluate the changes in metabolic status following CF-LVAD implantation and measure the correlation of metabolic status with outcomes. Methods and Results Prospective data on CF-LVAD patients were obtained. Metabolic evaluation, including hemoglobin A1C, free and total testosterone, thyroid-stimulating hormone (TSH), and free T4, was obtained before and at multiple time points following implantation. Patients with nonelevated thyroid-stimulating hormone and normal hemoglobin A1C and testosterone levels were defined as having normal metabolic status. Baseline characteristics, hemodynamics, and outcomes were collected. One hundred six patients were studied, of which 56 had paired data at baseline and 1- to 3-month follow-up. Before implantation, 75% of patients had insulin resistance, 86% of men and 39% of women had low free testosterone, and 44% of patients had abnormal thyroid function. There was a significant improvement in hemoglobin A1C, free testosterone, and thyroid-stimulating hormone following implantation (P<0.001 for all). Patients with normal hemoglobin A1C (<5.7%) following implantation had higher 1-year survival free of heart failure readmissions (78% versus 23%; P<0.001). Patients with normal metabolic status following implantation also had higher 1-year survival free of heart failure readmissions (92% versus 54%; P=0.04). Conclusions Metabolic dysfunction is highly prevalent in advanced heart failure patients and improves after CF-LVAD implantation. Normal metabolic status is associated with a significantly higher rate of 1-year survival free of heart failure readmissions.
| S-EPMC6915293 | biostudies-literature
Project description:BackgroundThe prevalence of cerebral microbleeds (CMBs) in gradient echo T2*-weighted brain MRI has a positive correlation with hemorrhagic stroke incidence. However, the prevalence of CMBs in patients with left ventricular assist devices (LVADs) has not been evaluated. We evaluated the prevalence of CMBs and the relationship with hemorrhagic stroke incidence in patients with LVADs.Method and resultsWe analyzed results from brain MRI in prospective examinations of 35 consecutive patients who had undergone LVAD explantation for heart transplantation or recovery since 2011. The number and distribution of CMBs were counted, then the relationship between baseline characteristics and adverse events during LVAD support were analyzed. The mean age was 37.7±12.4 years and the mean LVAD duration was 2.43±1.08 years. Thirty-four (97%) patients had at least one CMB. Nine (26%) developed hemorrhagic stroke during LVAD support, and patients with hemorrhagic stroke had a significantly greater number of CMBs compared with patients without hemorrhagic stroke (5 [interquartile range (IQR), 4-7] versus 9 [IQR, 5-23]; odds ratio 1.14 [95% Confidence Interval (CI), 1.02-1.32], P=0.05). There was no significant relationship between age, LVAD support duration, or systolic blood pressure during LVAD. However, patients who had at least one episode of bacteremia (9 [IQR, 4-16] versus 5 [IQR, 3-7], P=0.06) and pump pocket infection (14 [IQR, 4-27] versus 5 [IQR, 3-7], P=0.08) showed a trend toward a greater number of CMBs than patients without bacteremia.ConclusionsThirty-four (97%) patients with continuous-flow LVAD had at least one CMB, and the number of CMBs were more prevalent in patients with hemorrhagic stroke and in patients with LVAD-related infection.
| S-EPMC5634264 | biostudies-literature
Project description:ObjectivesThis study sought to determine if obese patients had worse post-left ventricular assist device (LVAD) implantation outcomes and if the implantation of an LVAD allowed for weight loss.BackgroundObesity is a risk factor for cardiovascular disease including heart failure. Obese heart failure patients have better outcomes than those with normal weight; however, obese patients have worse outcomes after heart transplantation.MethodsPatients were identified in the United Network for Organ Sharing (UNOS) database that underwent LVAD implantation as bridge to transplantation from May 2004 and April 2014, with follow-up through June 2014. Patients were grouped according to body mass index (BMI) based on the World Health Organization classification.ResultsAmong 3,856 patients, the risk of death or delisting was not significantly different between BMI groups (p = 0.347). There was no increased risk of death (p = 0.234) or delisting (p = 0.918). The risk of complication requiring UNOS status upgrade was increased for those with class II obesity or greater (hazard ratio: 1.48; p = 0.004), driven by increased infection and thromboembolism. Obese patients had worse post-transplantation outcomes. Weight loss substantial enough to decrease BMI group was achieved by a small proportion of patients listed with class I obesity or greater (9.6% to 15.5%).ConclusionsPatients with obesity had similar freedom from death or delisting while on LVAD support. However, class II obese or greater patients had an increased risk of complications requiring UNOS status upgrade compared with those with normal BMI during LVAD support and decreased post-transplantation survival. Weight loss on device therapy was possible, but uncommon. Careful consideration is needed when a bridge to weight loss strategy is proposed.
| S-EPMC5654312 | biostudies-literature
Project description:Importance:Left ventricular assist devices (LVADs) improve outcomes in patients with advanced heart failure, but little is known about the role of neurohormonal blockade (NHB) in treating these patients. Objective:To analyze the association between NHB blockade and outcomes in patients with LVADs. Design, Setting, and Participants:This retrospective cohort analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) included patients from more than 170 centers across the United States and Canada with continuous flow LVADs from 2008 to 2016 who were alive with the device in place at 6 months after implant. The data were analyzed between February and November 2019. Exposures:Patients were stratified based on exposure to NHB and represented all permutations of the following drug classes: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, ?-blockers, and mineralocorticoid antagonists. Main Outcomes and Measures:The outcomes of interest were survival at 4 years and quality of life at 2 years based on Kansas City Cardiomyopathy Questionnaire scores and a 6-minute walk test. Results:A total of 12?144 patients in INTERMACS met inclusion criteria, of whom 2526 (20.8% ) were women, 8088 (66.6%) were white, 3024 (24.9%) were African American, and 753 (6.2%) were Hispanic; the mean (SD) age was 56.8 (12.9) years. Of these, 10?419 (85.8%) were receiving NHB. Those receiving any NHB medication at 6 months had a better survival rate at 4 years compared with patients not receiving NHB (56.0%; 95% CI, 54.5%-57.5% vs 43.9%; 95% CI, 40.5%-47.7%). After sensitivity analyses with an adjusted model, this trend persisted with patients receiving triple therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, ?-blocker, and mineralocorticoid antagonist having the lowest hazard of death compared with patients in the other groups (hazard ratio, 0.34; 95% CI, 0.28-0.41). Compared with patients not receiving NHB, use of NHB was associated with a higher Kansas City Cardiomyopathy Questionnaire score (66.6; bootstrapped 95% CI, 65.8-67.3 vs 63.0; bootstrapped 95% CI, 60.1-65.8; P?=?.02) and a 6-minute walk test (1103 ft; bootstrapped 95% CI, 1084-1123 ft vs 987 ft; bootstrapped 95% CI, 913-1060 ft; P?<?.001). Conclusions and Relevance:Among patients with LVADs who tolerated NHB therapy, continued treatment was associated with improved survival and quality of life. The optimal heart failure regimen for patients after LVAD implant may be the initiation and continuation of guideline-directed medical therapy.
| S-EPMC6865330 | biostudies-literature
Project description:Continuous-flow left ventricular assist devices (LVAD) are increasingly used for patients with end-stage heart failure (HF). We analyzed the effects of ventricular decompression by continuous-flow versus pulsatile-flow LVADs on myocardial structure and function in this population.Sixty-one patients who underwent LVAD implantation as bridge-to-transplant were analyzed (pulsatile-flow LVAD: group P, n=31; continuous-flow LVAD: group C, n=30). Serial echocardiograms, serum levels of brain natriuretic peptide (BNP), and extracellular matrix biomarkers (ECM) were compared between the groups. Myocardial BNP and ECM gene expression were evaluated in a subset of 18 patients. Postoperative LV ejection fraction was greater (33.2±12.6% versus 17.6±8.8%, P<0.0001) and the mitral E/E' was lower (9.9±2.6 versus 13.2±3.8, P=0.0002) in group P versus group C. Postoperative serum levels of BNP, metalloproteinases (MMP)-9, and tissue inhibitor of MMP (TIMP)-4 were significantly lower in group P compared with group C (BNP: 552.6±340.6 versus 965.4±805.7 pg/mL, P<0.01; MMP9: 309.0±220.2 versus 475.2±336.9 ng/dL, P<0.05; TIMP4: 1490.9±622.4 versus 2014.3±452.4 ng/dL, P<0.001). Myocardial gene expression of ECM markers and BNP decreased in both groups; however, expression of TIMP-4 decreased only in group P (P=0.024).Mechanical unloading of the failing myocardium using pulsatile devices is more effective as indicated by echocardiographic parameters of systolic and diastolic LV function as well as dynamics of BNP and ECM markers. Therefore, specific effects of pulsatile mechanical unloading on the failing myocardium may have important implications for device selection especially for the purpose of bridge-to-recovery in patients with advanced HF.
| S-EPMC3178740 | biostudies-literature
Project description:BACKGROUND:Non-surgical bleeding (NSB) due to angiodysplasia is common in left ventricular assist device (LVAD) patients. Thrombin-induced angiopoietin-2 (Ang-2) expression in LVAD patients leads to altered angiogenesis and is associated with lower angiopoietin-1 (Ang-1) and increased NSB. However, the mechanism for decreased Ang-1, made by pericytes, is unknown and the origin of thrombin in LVAD patients is unclear. We hypothesized that high tumor necrosis factor-? (TNF-?) levels in LVAD patients induce pericyte apoptosis, tissue factor (TF) expression and vascular instability. METHODS:We incubated cultured pericytes with serum from patients with heart failure (HF), LVAD or orthotopic heart transplantation (OHT), with or without TNF-? blockade. We performed several measurements: Ang-1 expression was assessed by reverse transcript-polymerase chain reaction (RT-PCR) and pericyte death fluorescently; TF expression was assessed by RT-PCR in cultured endothelial cells incubated with patient plasma with or without TNF-? blockade; and TF expression was assessed in endothelial biopsy samples from these patients by immunofluorescence. We incubated cultured endothelial cells on Matrigel with patient serum with or without TNF-? blockade and determined tube formation by microscopy. RESULTS:Serum from LVAD patients had higher levels of TNF-?, suppressed Ang-1 expression in pericytes, and induced pericyte death, and there was accelerated endothelial tube formation compared with serum from patients without LVADs. TF was higher in both plasma and endothelial cells from LVAD patients, and plasma from LVAD patients induced more endothelial TF expression. All of these effects were reversed or reduced with TNF-? blockade. High levels of TNF-? were associated with increased risk of NSB. CONCLUSIONS:Elevated TNF-? in LVAD patients is a central regulator of altered angiogenesis, pericyte apoptosis and expression of TF and Ang-1.
| S-EPMC5722712 | biostudies-literature
Project description:BackgroundBridge to transplantation (BTT) with left ventricular assist devices (LVADs) is a mainstay of therapy for heart failure in patients awaiting heart transplantation (HT). Criteria for HT listing do not differ between patients medically managed and those mechanically bridged to HT. The objectives of the present study were to evaluate the impact of BTT with LVAD on posttransplantation survival, to describe differences in causes of 1-year mortality in medically and mechanically bridged patients, and to evaluate differences in risk factors for 1-year mortality between those with and those without LVAD at the time of HT.MethodsUsing the United Network of Organ Sharing database, we identified 5486 adult, single-organ HT recipients transplanted between 2008 and 2015. Patients were propensity matched for likelihood of LVAD at the time of HT. Kaplan-Meier survival estimates were used to assess the impact of BTT on 1- and 5-year mortality. Logistic regression analysis was used to evaluate the odds ratio of 1-year mortality for patients BTT with LVAD compared with those with medical management across clinically significant variables at various thresholds.ResultsEarly mortality was higher in mechanically bridged patients: 9.5% versus 7.2% mortality at 1 year (P<0.001). BTT patients incurred an increased risk of 1-year mortality with an estimated glomerular filtration rate of 40 to 60 mL·min-1·1.73 m-2 (odds ratio, 1.69; P=0.003) and <40 mL·min-1·1.73 m-2 (odds ratio, 2.16; P=0.005). A similar trend was seen in patients with a body mass index of 25 to 30 kg/m2 (odds ratio, 1.88; P=0.024) and >30 kg/m2 (odds ratio, 2.11; P<0.001). When patients were stratified by BTT status and the presence of risk factors, including age >60 years, estimated glomerular filtration rate <40 mL·min-1·1.73 m-2, and body mass index >30 kg/m2, there were significant differences in 1-year mortality between medium- and high-risk medically and mechanically bridged patients, with 1-year mortality in high-risk BTT patients at 17.6% compared with 10.4% in high-risk medically managed patients.ConclusionsBridge to HT with LVAD, although necessary because of organ scarcity and capable of improving wait list survival, confers a significantly higher risk of early posttransplantation mortality. Patients bridged with mechanical support may require more careful consideration for transplant eligibility after LVAD placement.
| S-EPMC8223200 | biostudies-literature
Project description:The gold standard for noninvasive blood pressure (BP) measurement, the Doppler technique, does not provide systolic blood pressure (SBP) and diastolic blood pressure (DBP) and may limit therapy outcomes. To improve patient care, we tested specifically designed experimental BP (ExpBP) monitor and the Doppler technique by comparing noninvasive measures to the intraarterial (I-A) BP in 31 patients with end-stage heart failure (4 females) 2.6?±?3.4 days post-LVAD implantation (20 HeartMate II and 11 HeartWare). Bland-Altman plots revealed that the ExpBP monitor overestimated mean arterial pressure (MAP) by 1.2 (4.8) mm Hg (mean difference [standard deviation]), whereas the Doppler by 6.7 (5.8) mm Hg. The ExpBP SBP was overestimated by 0.8 (6.1) mm Hg and DBP by 1.9 (5.3) mm Hg compared with the respective I-A pressures. Both techniques achieved similar measurement reliability. In the measurement "success rate" expressed as a frequency (percent) of readable BP values per measurement attempts, Doppler accomplished 100% vs. 97%, 97%, and 94% of successful detections of MAP, SBP, and DBP provided by the ExpBP monitor. The ExpBP monitor demonstrated higher accuracy in the MAP assessment than the Doppler in addition to providing SBP and DBP in majority of subjects. Improved BP control may help to mitigate related neurologic adverse event rates.
| S-EPMC6136985 | biostudies-literature
Project description:Background The effect of implantable cardioverter defibrillators ( ICD ) in patients with continuous flow left ventricular assist devices ( LVAD s) on outcomes has not been evaluated in a randomized clinical trial. Methods and Results This is a retrospective single-center study that included patients who underwent continuous flow LVAD implantation at the Cleveland Clinic between October 2004 and March 2017. Patients were evaluated according to the presence or absence of ICD at the time of LVAD insertion. Among 486 patients in the study cohort, 387 (79.6%) had an ICD before LVAD insertion. Patients with ICD before LVAD were older and had lower use of pre- LVAD inotropes, extracorporeal membrane oxygenation, and mechanical ventilation. There were 81 patients (21.4% of patients with ICD ) who required 93 procedures after LVAD : 74 generator exchanges, 12 lead revisions, and 7 complete system removals because of infection. Of the 99 patients without ICD , 52 (53%) underwent ICD implantation: 29 for primary prevention and 23 for secondary prevention. Patients were followed for a median of 401 (interquartile range 150-966) days. The presence of a pre- LVAD ICD was not associated with mortality in a multivariable model (hazard ratio 1.19, 95% CI 0.73-1.93, P=0.492), nor was the presence of an ICD at any point when analyzed as a time-varying covariate (hazard ratio 1.05, 95% CI 0.50-2.20, P=0.907). Conclusions There is no apparent mortality benefit associated with an ICD in a contemporary cohort of patients with continuous flow LVAD s to balance considerable morbidity involving ICD -related procedures and complications.
| S-EPMC6662142 | biostudies-literature
Project description:ObjectiveTo study the status of oxidative stress and DNA damage repair in circulating blood leukocytes of heart failure patients supported by continuous flow left ventricular assist devices (LVADs).Materials and methodsTen HF patients implanted with LVAD as bridge to transplant or destination therapy were enrolled in the study and 10 age and sex matched volunteers were recruited as the study control. Reactive oxygen species (ROS) in blood leukocytes and superoxide dismutase (SOD) in erythrocytes were measured by flow cytometry/immunofluorescence microscopy and spectrophotometry, respectively. ELISA was used to measure oxidized low density lipoproteins (oxLDL) in plasma. Markers of DNA damage (?-H2AX) and repairs (Mre11, DNA ligase IV, Ku70, and Ku80) were quantified in blood lymphocytes by immunocytochemistry.ResultsLevels of ROS and oxLDL were significantly higher in HF patients with LVAD than baseline as well as the control group; moreover, SOD levels were decreased with increasing post-operative periods. All the changes indicated enhanced oxidative stress among LVAD recipients. Significantly higher ?-H2AX foci in lymphocytes confirmed DNA double strand breaks in LVAD recipients. ?-H2AX foci numbers in lymphocytes were positively correlated with the ROS and oxLDL and negatively with SOD levels (p<0.0001). Expressions of DNA ligase IV, Ku70 and Ku80 proteins were highest after one week and Mre11 protein after 3 months of LVAD transplantation; indicated abnormal DNA repair.ConclusionsThe study, for the first time shows that, continuous flow LVAD implanted HF patients not only exhibit elevated oxidative stress and DNA damage in blood leukocytes but also have abnormalities in DNA repair pathways.
| S-EPMC3675502 | biostudies-literature