Dataset Information

Ventricular assist device implantation corrects myocardial lipotoxicity, reverses insulin resistance, and normalizes cardiac metabolism in patients with advanced heart failure.

ABSTRACT: Heart failure is associated with impaired myocardial metabolism with a shift from fatty acids to glucose use for ATP generation. We hypothesized that cardiac accumulation of toxic lipid intermediates inhibits insulin signaling in advanced heart failure and that mechanical unloading of the failing myocardium corrects impaired cardiac metabolism.We analyzed the myocardium and serum of 61 patients with heart failure (body mass index, 26.5±5.1 kg/m(2); age, 51±12 years) obtained during left ventricular assist device implantation and at explantation (mean duration, 185±156 days) and from 9 control subjects. Systemic insulin resistance in heart failure was accompanied by decreased myocardial triglyceride and overall fatty acid content but increased toxic lipid intermediates, diacylglycerol, and ceramide. Increased membrane localization of protein kinase C isoforms, inhibitors of insulin signaling, and decreased activity of insulin signaling molecules Akt and Foxo were detectable in heart failure compared with control subjects. Left ventricular assist device implantation improved whole-body insulin resistance (homeostatic model of analysis-insulin resistance, 4.5±0.6-3.2±0.5; P<0.05) and decreased myocardial levels of diacylglycerol and ceramide, whereas triglyceride and fatty acid content remained unchanged. Improved activation of the insulin/phosphatidylinositol-3 kinase/Akt signaling cascade after left ventricular assist device implantation was confirmed by increased phosphorylation of Akt and Foxo, which was accompanied by decreased membrane localization of protein kinase C isoforms after left ventricular assist device implantation.Mechanical unloading after left ventricular assist device implantation corrects systemic and local metabolic derangements in advanced heart failure, leading to reduced myocardial levels of toxic lipid intermediates and improved cardiac insulin signaling.

SUBMITTER: Chokshi A

PROVIDER: S-EPMC3464497 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ventricular assist device implantation corrects myocardial lipotoxicity, reverses insulin resistance, and normalizes cardiac metabolism in patients with advanced heart failure.

Chokshi Aalap A Drosatos Konstantinos K Cheema Faisal H FH Ji Ruiping R Khawaja Tuba T Yu Shuiqing S Kato Tomoko T Khan Raffay R Takayama Hiroo H Knöll Ralph R Milting Hendrik H Chung Christine S CS Jorde Ulrich U Naka Yoshifumi Y Mancini Donna M DM Goldberg Ira J IJ Schulze P Christian PC

Circulation 20120514 23

<h4>Background</h4>Heart failure is associated with impaired myocardial metabolism with a shift from fatty acids to glucose use for ATP generation. We hypothesized that cardiac accumulation of toxic lipid intermediates inhibits insulin signaling in advanced heart failure and that mechanical unloading of the failing myocardium corrects impaired cardiac metabolism.<h4>Methods and results</h4>We analyzed the myocardium and serum of 61 patients with heart failure (body mass index, 26.5±5.1 kg/m(2); ...[more]

PMID: 22586279

Similar Datasets

Project description:Patients with acute myocardial infarction (AMI) complicated by acute heart failure or cardiogenic shock have high mortality with conventional management.This study evaluated outcomes of patients with AMI who received durable ventricular assist devices (VAD).Patients in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry who underwent VAD placement in the setting of AMI were included and compared with patients who received VAD for non-AMI indications.VAD were implanted in 502 patients with AMI: 443 left ventricular assist devices; 33 biventricular assist devices; and 26 total artificial hearts. Median age was 58.3 years, and 77.1% were male. At implantation, 66% were INTERMACS profile 1. A higher proportion of AMI than non-AMI patients had pre-operative intra-aortic balloon pumps (57.6% vs. 25.3%; p < 0.01), intubation (58% vs. 8.3%; p < 0.01), extracorporeal membrane oxygenation (17.9% vs. 1.7%, p < 0.01), cardiac arrest (33.5% vs. 3.3%, p < 0.01), and higher-acuity INTERMACS profiles. At 1 month post-VAD, 91.8% of AMI patients were alive with ongoing device support, 7.2% had died on device, and 1% had been transplanted. At 1-year post-VAD, 52% of AMI patients were alive with ongoing device support, 25.7% had been transplanted, 1.6% had left VAD explanted for recovery, and 20.7% had died on device. The AMI group had higher unadjusted early phase hazard (hazard ratio [HR]: 1.24; p = 0.04) and reduced late-phase hazard of death (HR: 0.57; p = 0.04) than the non-AMI group did. After accounting for established risk factors, the AMI group no longer had higher early mortality hazard (HR: 0.89; p = 0.30), but it had lower late mortality hazard (HR: 0.55; p = 0.02).Patients with AMI who receive VAD have outcomes similar to other VAD populations, despite being more critically ill pre-implantation. VAD therapy is an effective strategy for patients with AMI and acute heart failure or shock in whom medical therapy is failing.

Project description:Rationale & objectiveNearly half the patients with heart failure have chronic kidney disease. Implantation of a left ventricular assist device (LVAD) improves kidney function in some but not all patients, and lack of improvement is associated with worse outcomes. Preimplantation factors that predict change in kidney function after LVAD placement are not well described.Study designSingle-center observational study.Setting & participantsConsecutive patients undergoing LVAD implantation.Predictors48 diverse preimplantation variables including demographic, clinical, laboratory, hemodynamic, and echocardiographic variables.OutcomesThe primary outcome was change in estimated glomerular filtration rate (eGFR) at 1 month after implantation. Secondary outcomes included eGFR changes at 3, 6, and 12 months.Analytic approachUnivariable and multivariable linear regression.ResultsAmong 131 patients, average age was 60 ± 13 years, 83% were men, 47% had pre-existing chronic kidney disease, and mean preimplantation eGFR was 57 ± 23 mL/min/1.73 m2. At 1-month following LVAD implantation, eGFR improved in 98 (75%) patients. Variables associated with 1-month increases in eGFR were younger age, absence of diabetes mellitus (DM), use of inotropes, lower implantation eGFR, and higher implantation serum urea nitrogen, alanine aminotransferase, bilirubin, and creatinine levels. In multivariable models, younger age (β = 7.14 mL/min/1.73 m2 per SD; 95% CI, 3.17-11.10), lower eGFR (β = 7.72 mL/min/1.73 m2 per SD; 95% CI, 3.10-12.34), and absence of DM (β = 10.36 mL/min/1.73 m2; 95% CI, 2.99-17.74) were each independently associated with 1-month improvement in eGFR. Only younger age and lower eGFR were associated with improvements in eGFR at later months.LimitationsSingle-center study. Loss to follow-up from heart transplantation and death over duration of study.ConclusionsOnly younger age, lower eGFR, and absence of DM were associated with improvement in eGFR at 1 month. Thus, prediction of eGFR change at 1 month and beyond is limited by using preimplantation variables.

Project description:AimsImplantation of left ventricular assist devices (LVADs) as a bridge to transplant or as destination therapy is increasing. The selection of suitable patients and outcome assessment belong to the key challenges. Mortality has traditionally been a focus of research in this field, but literature on quality of life is very limited. This study aimed to identify perioperative factors influencing patients' life as measured by days alive and out of hospital (DAOH) in the first year after LVAD implantation.Methods and resultsThis retrospective single-centre cohort study screened 227 patients who underwent LVAD implantation at the University Hospital Duesseldorf, Germany, between 2010 and 2020. First, the influence of 10 prespecified variables on DAOH was investigated by univariate analysis. Second, multivariate quantile regression was conducted including all factors with significant influence on DAOH in the univariate model. Additionally, the impact of all variables on 1 year mortality was investigated using Kaplan-Meier curves to oppose DAOH and mortality. In total, 221 patients were included into analysis. As pre-operative factors, chronic kidney disease (CKD), pre-operative mechanical circulatory support (pMCS), and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) stadium < 3 were associated with lower DAOH at 1 year [CKD: 280 (155-322) vs. 230 (0-219), P = 0.0286; pMCS: 294 (155-325) vs. 243 (0-293), P = 0.0004; INTERMACS 1: 218 (0-293) vs. INTERMACS 2: 264 (6-320) vs. INTERMACS 3: 299 (228-325) vs. INTERMACS 4: 313 (247-332), P ≤ 0.0001]. Intra-operative additional implantation of a right ventricular assist device (RVAD) was also associated with lower DAOH [RVAD: 290 (160-325) vs. 174 (0-277), P ≤ 0.0001]. As post-operative values that were associated with lower DAOH, dialysis and tracheotomy could be identified [dialysis: 300 (252-326) vs. 186 (0-300), P ≤ 0.0001; tracheotomy: 292 (139-325) vs. 168 (0-269), P ≤ 0.0001]. Multivariate analysis revealed that all of these factors besides pMCS were independently associated with DAOH. According to Kaplan-Meier analysis, only post-operative dialysis was significantly associated with increased mortality at 1 year (survival: no dialysis 89.4% vs. dialysis 70.1%, hazard ratio: 0.56, 95% confidence interval: 0.33-0.94; P = 0.031).ConclusionsThe results of this study indicate that there can be a clear discrepancy between hard endpoints such as mortality and more patient-centred outcomes reflecting life impact. DAOH may relevantly contribute to a more comprehensive selection process and outcome assessment in LVAD patients.

Dataset Information

Ventricular assist device implantation corrects myocardial lipotoxicity, reverses insulin resistance, and normalizes cardiac metabolism in patients with advanced heart failure.

Publications

Ventricular assist device implantation corrects myocardial lipotoxicity, reverses insulin resistance, and normalizes cardiac metabolism in patients with advanced heart failure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets