Dataset Information

Myocardial T1 Measurement Predicts Beneficial LV Remodeling After Long-Term Heart Failure Therapy.

ABSTRACT:

Background

The myocardial longitudinal relaxation time (T1) on cardiac magnetic resonance imaging (CMR) can quantify myocardial fibrosis in the presence or absence of visually detectable late gadolinium (Gd) enhancement (LGE). Mineralocorticoid receptor antagonist (MRA) treatment produces beneficial remodeling in nonischemic dilated cardiomyopathy (NIDCM). We assessed the hypothesis that interstitial myocardial fibrosis measured with the use of CMR predicts left ventricular (LV) beneficial remodeling in NIDCM after heart failure (HF) treatment including MRAs.

Methods and results

Twelve patients with NIDCM, on stable beta-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor-blocking therapy, were studied before and after 6-29 months of treatment with MRAs, by means of CMR assessment of LV structure, function, and T1 from standard Look-Locker sequences (T1_LL). All patients had depressed cardiac function, dilated left ventricles, and no visual LGE. After adding MRA to HF treatment, the LV ejection fraction increased and the LV end-systolic volume index (LV end-systolic volume/m²) decreased in all patients (P < .0001). This this was inversely proportional to the baseline myocardial T1_LL (r = -0.65; P = .02).

Conclusion

Myocardial T1_LL, in the absence of visually detectable LGE, was quantitatively related to the degree of beneficial LV remodeling achieved in response to adding MRA to a HF regimen.

SUBMITTER: Bradham WS

PROVIDER: S-EPMC5350022 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

Myocardial T1 Measurement Predicts Beneficial LV Remodeling After Long-Term Heart Failure Therapy.

Bradham William S WS Bell Susan P SP Adkisson Douglas W DW Smith Holly M HM Harrell Frank E FE Lawson Mark A MA Ooi Henry H Sawyer Douglas B DB Kronenberg Marvin W MW

Journal of cardiac failure 20161208 3

<h4>Background</h4>The myocardial longitudinal relaxation time (T1) on cardiac magnetic resonance imaging (CMR) can quantify myocardial fibrosis in the presence or absence of visually detectable late gadolinium (Gd) enhancement (LGE). Mineralocorticoid receptor antagonist (MRA) treatment produces beneficial remodeling in nonischemic dilated cardiomyopathy (NIDCM). We assessed the hypothesis that interstitial myocardial fibrosis measured with the use of CMR predicts left ventricular (LV) benefici ...[more]

PMID: 27940336

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Project description:ImportanceMortality is high among patients heart failure (HF) who are receiving treatment, and therefore identifying new pathways rooted in preclinical cardiac remodeling phenotypes may afford novel biomarkers and therapeutic avenues. Circulating extracellular RNAs (ex-RNAs) are an emerging class of biomarkers with target-organ epigenetic effects relevant to myocardial biology, although large human investigations remain limited.ObjectiveTo measure the association of highly expressed circulating ex-RNAs with left ventricular remodeling and incident HF in a community-based cohort.Design, setting, and participantsThis is a prospective observational cohort study of individuals who were included in the eighth examination of the Framingham Offspring Cohort (2005-2008). Collected data include measurements of the left ventricle via electrocardiography, determination of circulating ex-RNAs in plasma, and incidence of heart failure. Data analysis was completed from December 2016 to June 2018.ExposuresA total of 398 circulating ex-RNA molecules in plasma were measured by reverse transcription polymerase chain reaction; disease ontology analysis was also performed.Main outcomes and measuresEchocardiographic indices of left ventricular (LV) remodeling and incident heart failure.ResultsA total of 2763 participants of the Framingham Heart Study with measured ex-RNAs (mean [SD] age, 66.3 [9.0] years; 1499 [54.3%] female) were included in this study. Of this sample, 2429 to 2432 individuals had echocardiographic measures recorded (depending on the measurement). A total of 2681 individuals had HF status determined, of whom 116 (4.3%) experienced HF (median [interquartile range] follow-up, 7.7 [6.6-8.6] years). We identified 12 ex-RNAs associated with LV mass and at least 1 other echocardiographic phenotype (LV end-diastolic volume or left atrial dimension). Of these 12 ex-RNAs, 3 micro RNAs (miR-17, miR-20a, and miR-106b) were associated with a 15% reduction in long-term incident HF per 2-fold increase in circulating level during the follow-up period, after adjustments for age, sex, established HF risk factors, and prevalent or interim myocardial infarction. These 3 RNAs shared sequence homology and targeted a shared group of messenger RNAs that specified pathways relevant to HF (eg, transforming growth factor-β signaling, growth/cell cycle, and apoptosis), and shared a disease association with hypertension in disease ontology analysis.Conclusions and relevanceThis study identifies a group of circulating, noncoding RNAs associated with echocardiographic phenotypes, long-term incident HF, and pathways relevant to myocardial remodeling in a large community-based sample. Further investigations into the functional biology of these ex-RNAs are warranted for surveillance for HF prevention.

Project description:BackgroundDuring the progression of chronic heart failure (CHF), decreased cardiac functioning is often associated with congestion in the inferior vena vein, which in turn induces splenomegaly and subsequent hypersplenism. Hypersplenism has been shown to exacerbate endothelial dysfunction and adverse cardiac remodeling in HF mice. However, it is unknown whether this effect also occurs in CHF patients with hypersplenism. Here, we compared different patterns of myocardial remodeling between patients with and without hypersplenism.Methods33 CHF patients with hypersplenism were selected and carefully examined. Clinical data and baseline hemogram measurements were included in the evaluation. Another 35 CHF patients were randomly chosen as controls. All patients received formal HF treatment to ameliorate their symptoms and to preserve heart structure and functioning. Peripheral blood-derived endothelial progenitor cells (EPCs) were cultured, and the experimenters were blinded to the patients' clinical characteristics. The biological properties of the cells were then compared. The groups were also compared in terms of the free plasma hemoglobin and heme levels, endothelial adhesion molecule expression, left ventricular ejection fraction (LvEF) and cardiovascular events (re-PCI, re-myocardial infarction, stent thrombosis, stroke and death due to cardiovascular or vascular causes).ResultsThe free plasma hemoglobin and heme levels were significantly higher in the CHF patients with hypersplenism compared with the controls (P<0.001). Additionally, the CHF patients with hypersplenism had increased levels of VCAM-1, ICAM-1, P-selectin and E-selectin (P<0.001). Echocardiography revealed a significant reduction in the LVEF in these patients compared with the controls at the 24(th) month (P=0.013). During a mean follow-up period of 24±1 months, cardiovascular events were observed in 16 patients in the CHF with hypersplenism group and 9 patients in the control group. Univariate Kaplan-Meier analysis further revealed a significant difference between the groups (P=0.021). The mRNA levels of endothelial NO synthase enzyme (eNOS) in EPCs from the CHF patients with hypersplenism were significantly lower than those in the control subjects (P<0.001). We also observed decreased proliferation potential of EPCs from the CHF patients with hypersplenism (P<0.001). Further, a significant increase in TUNEL(+) EPCs was observed in the CHF patients with hypersplenism after 6 h of stimulated ischemia compared with the control subjects (P<0.001).ConclusionsCHF patients with hypersplenism are susceptible to myocardial remodeling. Increased oxidative stress and endothelial dysfunction caused by excess free plasma hemoglobin and heme may partially explain this causality.

Project description:ObjectivesThis study sought to test the hypothesis that end-systolic volume (ESV), as a marker of severity of left ventricular (LV) remodeling, influences the relationship between myocardial viability and survival in patients with coronary artery disease and LV systolic dysfunction.BackgroundRetrospective studies of ischemic LV dysfunction suggest that the severity of LV remodeling determines whether myocardial viability predicts improved survival with surgical compared with medical therapy, with coronary artery bypass grafting (CABG) only benefitting patients with viable myocardium who have smaller ESV. However, this has not been tested prospectively.MethodsInteractions of end-systolic volume index (ESVI), myocardial viability, and treatment with respect to survival were assessed in patients in the prospective randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial of CABG versus medical therapy who underwent viability assessment (n = 601; age 61 ± 9 years; ejection fraction ≤35%), with a median follow-up of 5.1 years. Median ESVI was 84 ml/m(2). Viability was assessed by single-photon emission computed tomography or dobutamine echocardiography using pre-specified criteria.ResultsMortality was highest among patients with larger ESVI and nonviability (p < 0.001), but no interaction was observed between ESVI, viability status, and treatment assignment (p = 0.491). Specifically, the effect of CABG versus medical therapy in patients with viable myocardium and ESVI ≤84 ml/m(2) (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.56 to 1.29) was no different than in patients with viability and ESVI >84 ml/m(2) (HR: 0.87; 95% CI: 0.57 to 1.31). Other ESVI thresholds yielded similar results, including ESVI ≤60 ml/m(2) (HR: 0.87; 95% CI: 0.44 to 1.74). ESVI and viability assessed as continuous rather than dichotomous variables yielded similar results (p = 0.562).ConclusionsAmong patients with ischemic cardiomyopathy, those with greater LV ESVI and no substantial viability had worse prognosis. However, the effect of CABG relative to medical therapy was not differentially influenced by the combination of these 2 factors. Lower ESVI did not identify patients in whom myocardial viability predicted better outcome with CABG relative to medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Project description:BackgroundGiven high on-treatment mortality in heart failure (HF), identifying molecular pathways that underlie adverse cardiac remodeling may offer novel biomarkers and therapeutic avenues. Circulating extracellular RNAs (ex-RNAs) regulate important biological processes and are emerging as biomarkers of disease, but less is known about their role in the acute setting, particularly in the setting of HF.MethodsWe examined the ex-RNA profiles of 296 acute coronary syndrome (ACS) survivors enrolled in the Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education Cohort. We measured 374 ex-RNAs selected a priori, based on previous findings from a large population study. We employed a two-step, mechanism-driven approach to identify ex-RNAs associated with echocardiographic phenotypes (left ventricular [LV] ejection fraction, LV mass, LV end-diastolic volume, left atrial [LA] dimension, and LA volume index) then tested relations of these ex-RNAs with prevalent HF (N=31, 10.5%). We performed further bioinformatics analysis of microRNA (miRNAs) predicted targets' genes ontology categories and molecular pathways.ResultsWe identified 44 ex-RNAs associated with at least one echocardiographic phenotype associated with HF. Of these 44 exRNAs, miR-29-3p, miR-584-5p, and miR-1247-5p were also associated with prevalent HF. The three microRNAs were implicated in the regulation p53 and transforming growth factor-β signaling pathways and predicted to be involved in cardiac fibrosis and cell death; miRNA predicted targets were enriched in gene ontology categories including several involving the extracellular matrix and cellular differentiation.ConclusionsAmong ACS survivors, we observed that miR-29-3p, miR-584-5p, and miR-1247-5p were associated with both echocardiographic markers of cardiac remodeling and prevalent HF.Relevance for patientsmiR-29c-3p, miR-584-5p, and miR-1247-5p were associated with echocardiographic phenotypes and prevalent HF and are potential biomarkers for adverse cardiac remodeling in HF.

Dataset Information

Myocardial T1 Measurement Predicts Beneficial LV Remodeling After Long-Term Heart Failure Therapy.

Background

Methods and results

Conclusion

Publications

Myocardial T1 Measurement Predicts Beneficial LV Remodeling After Long-Term Heart Failure Therapy.

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