MicroRNAs associated with reverse left ventricular remodeling in humans identify pathways of heart failure progression
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE109051 | GEO | 2018/02/01
REPOSITORIES: GEO
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Project description:BACKGROUND:Plasma extracellular RNAs have recently garnered interest as biomarkers in heart failure (HF). Most studies in HF focus on single extracellular RNAs related to phenotypes and outcomes, and few describe their functional roles. We hypothesized that clusters of plasma microRNAs (miRNAs) associated with left ventricular (LV) remodeling in human HF would identify novel subsets of genes involved in HF in animal models. METHODS AND RESULTS:We prospectively measured circulating miRNAs in 64 patients with systolic HF (mean age, 64.8 years; 91% men; median LV ejection fraction, 26%) with serial echocardiography (10 months apart) during medical therapy. We defined LV reverse remodeling as a 15% reduction in LV end-systolic volume index. Using principal components analysis, we identified a component associated with LV reverse remodeling (odds ratio=3.99; P=0.01) that provided risk discrimination for LV reverse remodeling superior to a clinical model (C statistic, 0.58 for a clinical model versus 0.71 for RNA-based model). Using network bioinformatics, we uncovered genes not previously widely described in HF regulated simultaneously by >2 miRNAs. We observed increased myocardial expression of these miRNAs during HF development in animals, with downregulation of target gene expression, suggesting coordinate miRNA-mRNA regulation. Target mRNAs were involved in autophagy, metabolism, and inflammation. CONCLUSIONS:Plasma miRNAs associated with LV reverse remodeling in humans are dysregulated in animal HF and target clusters of genes involved in mechanisms implicated in HF. A translational approach integrating human HF, bioinformatics, and model systems may uncover novel pathways involved in HF. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov. Unique identifier: NCT00351390.
| S-EPMC5813824 | biostudies-other
Project description:MicroRNAs associated with reverse left ventricular remodeling in humans identify pathways of heart failure progression
| PRJNA429480 | ENA
Project description:This review provides a comprehensive overview of the past 25+ years of research into the development of left ventricular assist device (LVAD) to improve clinical outcomes in patients with severe end-stage heart failure and basic insights gained into the biology of heart failure gleaned from studies of hearts and myocardium of patients undergoing LVAD support. Clinical aspects of contemporary LVAD therapy, including evolving device technology, overall mortality, and complications, are reviewed. We explain the hemodynamic effects of LVAD support and how these lead to ventricular unloading. This includes a detailed review of the structural, cellular, and molecular aspects of LVAD-associated reverse remodeling. Synergisms between LVAD support and medical therapies for heart failure related to reverse remodeling, remission, and recovery are discussed within the context of both clinical outcomes and fundamental effects on myocardial biology. The incidence, clinical implications and factors most likely to be associated with improved ventricular function and remission of the heart failure are reviewed. Finally, we discuss recognized impediments to achieving myocardial recovery in the vast majority of LVAD-supported hearts and their implications for future research aimed at improving the overall rates of recovery.
| S-EPMC9132540 | biostudies-literature
Project description:Background:Due to ongoing left ventricular (LV) remodeling and consecutive geometric displacement of both papillary muscles, end-stage heart failure is frequently associated with relevant functional mitral regurgitation (FMR) Type IIIb. Treatment strategies of FMR and their prognostic impact are still controversial. Case summary:We present a case of an 80-year-old patient who suffered from recurrent symptoms of congestive heart failure due to dilated cardiomyopathy and concomitant severe FMR. To specifically address severe tethering of both mitral leaflets heart team decision was to perform minimally invasive mitral valve repair (MVR) including a subannular LV remodeling procedure, instead of an interventional edge-to-edge repair (MitraClip® procedure). In addition to mitral valve ring annuloplasty, standardized relocation of both papillary muscles was performed successfully, leading to a complete resolution of mitral leaflet tethering. There were no procedural complications and the patient was discharged with an excellent functional result without residual mitral regurgitation. Furthermore, after 12 and 24?months, he reported an increase of his functional exercise capacity and a remarkable reverse LV remodeling could be demonstrated. Discussion:Novel subannular repair techniques, especially the relocation of both papillary muscles, specifically address severe leaflet tethering in FMR and have an obvious potential to improve long-term competence of MVR. Therefore, they could be considered as a viable therapeutic option even in elderly patients presenting with end-stage cardiomyopathy and severe leaflet tenting.
| S-EPMC7319855 | biostudies-literature
Project description:Wild type, female, C57BL/6 mice were subjected to sham (n=6) surgery, or TAC + MI to cause progressive LV remodeling (n=12). At 2wks post-TAC, one group of mice underwent de-banding (HF-DB, n=6), whereas in a second group of mice the band remained intact (HF; n = 6). LV remodeling was evaluated by 2D echocardiography at 14 days post-TAC+MI , and 4 wks post-debanding. At 6 wks the hearts were excised and analyzed for changes in gene expression using transcriptional profiling. e-banding in the HF-DB mice resulted in normalization of LV volumes and LV mass, and normalization of cardiac myocyte hypertrophy at 6wks, without significant changes in myofibrillar collagen in the HF and HF-DB mice. Both LV ejection fraction (LVEF) and LV radial strain improved numerically following de-banding; however, both measurements remained significantly depressed in the HF-DB mice compared to sham, and were not significantly different from HF mice at 6wks. Reverse LV remodeling in the HF-DB mouse hearts was accompanied by a partial (80%) normalization of the genes that became dysregulated during LV remodeling, whereas 20% of genes remained persistently dysregulated following reverse LV remodeling.
2017-12-14 | GSE107568 | GEO
Project description:BACKGROUND:Women affected by Dilated Cardiomyopathy (DCM) experience better outcomes compared to men. Whether a more pronounced Left Ventricular Reverse Remodelling (LVRR) might explain this is still unknown. AIM:We investigated the relationship between LVRR and sex and its long-term outcomes. METHODS:A cohort of 605 DCM patients with available follow-up data was consecutively enrolled. LVRR was defined, at 24-month follow-up evaluation, as an increase in left ventricular ejection fraction (LVEF) ? 10% or a LVEF > 50% and a decrease ? 10% in indexed left ventricular end-diastolic diameter (LVEDDi) or an LVEDDi ? 33 mm/m2. Outcome measures were a composite of all-cause mortality/heart transplantation (HTx) or ventricular assist device (VAD) and a composite of Sudden Cardiac Death (SCD) or Major Ventricular Arrhythmias (MVA). RESULTS:181 patients (30%) experienced LVRR. The cumulative incidence of LVRR at 24-months evaluation was comparable between sexes (33% vs. 29%; p = 0.26). During a median follow-up of 149 months, women experiencing LVRR had the lowest rate of main outcome measure (global p = 0.03) with a 71% relative risk reduction compared to men with LVRR, without significant difference between women without LVRR and males. A trend towards the same results was found regarding SCD/MVA (global p = 0.06). Applying a multi-state model, male sex emerged as an independent adverse prognostic factor even after LVRR completion. CONCLUSIONS:Although the rate of LVRR was comparable between sexes, females experiencing LVRR showed the best outcomes in the long term follow up compared to males and females without LVRR. Further studies are advocated to explain this difference in outcomes between sexes.
| S-EPMC7464387 | biostudies-literature
Project description:BackgroundAlthough predictors of reverse left ventricular (LV) remodeling postmitral valve repair are critical for guiding perioperative decision-making, there remains a paucity of randomized, prospective data to support the criteria that potential predictor variables must meet.Methods and resultsThe CAMRA CardioLink-2 randomized trial allocated 104 patients to either leaflet resection or preservation strategies for mitral repair. The correlation of indexed left ventricular end-systolic volume (LVESVI), indexed left ventricular end-diastolic volume (LVEDVI), and left ventricular ejection fraction (LVEF) were tested with univariate analysis and subsequently with multivariate analysis to determine independent predictors of reverse remodeling at discharge and at 12 months postoperatively. At discharge, both LVESVI and LVEDVI were independently associated with their preoperative values (p < .001 for both) and LVEF by preoperative LVESVI (p < .001). Mitral ring size was favorably associated with the change in LVESVI (p < .05) and LVEF (p < .01) from predischarge to 12 months, while the mean mitral valve gradient after repair was adversely associated with the change in LVESVI (p < .05) and LVEDVI (p < .05). No significant associations were found between reverse remodeling and coaptation height nor mitral repair technique.ConclusionsBeyond confirming the lack of impact of mitral repair technique on reverse remodeling, this investigation suggests that recommending surgery before significant LV dilatation or dysfunction, as well as higher postoperative mitral valve hemodynamic performance, may enhance remodeling capacity following mitral repair.
| S-EPMC9451668 | biostudies-literature
Project description:Rheumatoid arthritis (RA) patients have a 1.5- to twofold higher risk of developing heart failure (HF) and a twofold increased risk of HF-associated mortality compared to those without RA. HF is preceded subclinically by left ventricular (LV) remodeling in the general population. There is a relative absence of prospective studies following RA patients from pre-clinical to clinical HF as well as prospective studies of LV remodeling in RA without clinical HF. In our study, 158 RA patients without clinical HF were enrolled and underwent transthoracic echocardiography (TTE) at baseline and on follow-up between 4 and 6 years. Extensive characterization of RA disease activity and cardiovascular risk factors were performed. LV remodeling was prevalent at 40% at baseline and increased to 60% over time. Higher levels of interleukin-6 (IL 6) were associated with concentric LV remodeling on follow-up. The use of tocilizumab was also significantly associated with baseline LV remodeling (relative wall thickness). These findings suggest a role for IL-6 as a biomarker for LV remodeling in RA patients without clinical HF. Future research should focus on prospective follow-up of LV remodeling and the effects of IL-6 inhibition on LV remodeling in RA patients.
| S-EPMC10362590 | biostudies-literature
Project description:Background: The prognosis of pediatric dilated cardiomyopathy (PDCM) is highly variable, ranging from death to cardiac function recovery. Left ventricular reverse remodeling (LVRR) represents a favorable prognosis in PDCM. Disturbance of lipid metabolism is associated with the change of cardiac function, but no studies have examined lipidomics data and LVRR. Methods: Discovery analyses were based on 540 targeted lipids in an observational, prospective China-AOCC (An Integrative-Omics Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China) study. The OPLS-DA and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined in Cox proportional hazards regression models. Furthermore, we developed a risk score comprising the significant lipids, with each attributed a score of 1 when the concentration was above the median. All significant findings were replicated in a validation set of the China-AOCC study. Results: There were 59 patients in the discovery set and 24 patients in the validation set. LVRR was observed in 27 patients (32.5%). After adjusting for age, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic dimension (LVEDD) z-score, lysophosphatidic acids (LysoPA) 16:0, LysoPA 18:2, LysoPA 18:1, and LysoPA 18:0 were significantly associated with LVRR in the discovery set, and hazard ratios (HRs) were 2.793 (95% CI, 1.545-5.048), 2.812 (95% CI, 1.542-5.128), 2.831 (95% CI, 1.555-5.154), and 2.782 (95% CI, 1.548-5.002), respectively. We developed a LysoPA score comprising the four LysoPA. When the LysoPA score reached 4, LVRR was more likely to be observed in both sets. The AUC increased with the addition of the LysoPA score to the LVEDD z-score (from 0.693 to 0.875 in the discovery set, from 0.708 to 0.854 in the validation set) for prediction of LVRR. Conclusions: Serum LysoPA can predict LVRR in PDCM patients. When the LysoPA score was combined with the LVEDD z-score, it may help in ascertaining the prognosis and monitoring effects of anti-heart failure pharmacotherapy.
| S-EPMC8415784 | biostudies-literature
Project description:Background and objectivesCompared to office blood pressure (OBP), central blood pressure (CBP) and ambulatory blood pressure (BP) are known to be better markers for predicting cardiovascular events. We evaluated the association between left ventricular reverse remodeling (LVRR) and ambulatory CBP in heart failure with reduced ejection fraction (HFrEF).MethodsThis study retrospectively analyzed 93 patients who performed ambulatory CBP and brachial BP (BBP) monitoring from 2018 to 2020 within 1 year after diagnosis of HFrEF at a single tertiary center. We analyzed the association between on-treatment ambulatory BPs and LVRR on follow-up echocardiography.ResultsThe mean age of participants was 59 years; 65.6% were men; mean LVEF was 29%. Ambulatory BP and follow-up echocardiography were done at 143 days (interquartile range [IQR], 64-267) and 454 days (IQR, 281-600) after diagnosis of HF, respectively. Baseline OBP was not different between 2 groups, but ambulatory systolic CBP was significantly higher in the LVRR group than the non-LVRR group (p=0.005). Systolic OBP (odds ratio [OR], 1.029; confidence interval [CI], 1.004-1.055; p=0.026), 24-hour ambulatory systolic CBP (OR, 1.048; CI, 1.015-1.082; p=0.004), and 24-hour ambulatory systolic BBP (OR, 1.049; CI,1.017-1.082; p=0.003) were associated with LVRR. Compared to ambulatory systolic CBP of 110-119 mmHg, 90-99 mmHg showed lower OR for LVRR.ConclusionsLow on-treatment ambulatory systolic CBP was closely related to a lower likelihood of LVRR in HFrEF than the normal range. Ambulatory CBP measured during treatment of patients with HFrEF appears to be useful in predicting outcomes.
| S-EPMC10406559 | biostudies-literature