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A systematic review of micro-RNAs in aortic stenosis and cardiac fibrosis.

ABSTRACT: Aortic stenosis (AS) is the commonest valve lesion requiring surgery in the Western world. The presence of myocardial fibrosis is associated with mortality even after valve replacement. MicroRNAs could serve as biomarkers of fibrosis and risk stratify patients for earlier intervention. This study aimed to systematically review reports of micro-RNA (miR) associated with fibrosis in AS and identify potential biomarkers. We searched EMBASE, Medline, and Web of Science up to May 2020. Studies that reported on the role of miRs in AS and cardiac fibrosis were included. Study quality was assessed using the Newcastle-Ottawa scale. Of 4230 reports screened, 25 were included. All studies were of low to moderate quality. MiRs were analyzed in myocardial tissue (n = 10), aortic valve tissue (n = 5), plasma (n = 5), and serum (n = 5). A total of 365 miRs were reported, of which only a few were reported in more than one paper (3 in the myocardium, 5 in the aortic valve, and 1 in plasma). miR-21 was upregulated in plasma and myocardial tissue. MiR-19b was downregulated in the myocardium. Papers reporting myocardial miR-1 contradicted each other, and miR-133a was associated with increased left ventricular mass regression post-surgery. In the aortic valve, miRs-665, 602 and 939 were downregulated, and miRs-193b and 214 were upregulated. The data on miR in fibrosis in AS is scarce and of low to moderate quality. Further studies are needed to identify novel miRs as biomarkers, especially at an earlier asymptomatic phase of the disease.

SUBMITTER: Adewuyi JO

PROVIDER: S-EPMC9372411 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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A systematic review of micro-RNAs in aortic stenosis and cardiac fibrosis.

Adewuyi Jemima Osekafore JO Patel Roshan R Abbasciano Riccardo R McCann Gerry P GP Murphy Gavin G Woźniak Marcin J MJ Singh Anvesha A

Clinical and translational science 20220521 8

Aortic stenosis (AS) is the commonest valve lesion requiring surgery in the Western world. The presence of myocardial fibrosis is associated with mortality even after valve replacement. MicroRNAs could serve as biomarkers of fibrosis and risk stratify patients for earlier intervention. This study aimed to systematically review reports of micro-RNA (miR) associated with fibrosis in AS and identify potential biomarkers. We searched EMBASE, Medline, and Web of Science up to May 2020. Studies that r ...[more]

PMID: 35579611

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Project description:ObjectivesCardiac magnetic resonance (CMR) was used to investigate the extracellular compartment and myocardial fibrosis in patients with aortic stenosis, as well as their association with other measures of left ventricular decompensation and mortality.BackgroundProgressive myocardial fibrosis drives the transition from hypertrophy to heart failure in aortic stenosis. Diffuse fibrosis is associated with extracellular volume expansion that is detectable by T1 mapping, whereas late gadolinium enhancement (LGE) detects replacement fibrosis.MethodsIn a prospective observational cohort study, 203 subjects (166 with aortic stenosis [69 years; 69% male]; 37 healthy volunteers [68 years; 65% male]) underwent comprehensive phenotypic characterization with clinical imaging and biomarker evaluation. On CMR, we quantified the total extracellular volume of the myocardium indexed to body surface area (iECV). The iECV upper limit of normal from the control group (22.5 ml/m2) was used to define extracellular compartment expansion. Areas of replacement mid-wall LGE were also identified. All-cause mortality was determined during 2.9 ± 0.8 years of follow up.ResultsiECV demonstrated a good correlation with diffuse histological fibrosis on myocardial biopsies (r = 0.87; p < 0.001; n = 11) and was increased in patients with aortic stenosis (23.6 ± 7.2 ml/m2 vs. 16.1 ± 3.2 ml/m2 in control subjects; p < 0.001). iECV was used together with LGE to categorize patients with normal myocardium (iECV <22.5 ml/m2; 51% of patients), extracellular expansion (iECV ≥22.5 ml/m2; 22%), and replacement fibrosis (presence of mid-wall LGE, 27%). There was evidence of increasing hypertrophy, myocardial injury, diastolic dysfunction, and longitudinal systolic dysfunction consistent with progressive left ventricular decompensation (all p < 0.05) across these groups. Moreover, this categorization was of prognostic value with stepwise increases in unadjusted all-cause mortality (8 deaths/1,000 patient-years vs. 36 deaths/1,000 patient-years vs. 71 deaths/1,000 patient-years, respectively; p = 0.009).ConclusionsCMR detects ventricular decompensation in aortic stenosis through the identification of myocardial extracellular expansion and replacement fibrosis. This holds major promise in tracking myocardial health in valve disease and for optimizing the timing of valve replacement. (The Role of Myocardial Fibrosis in Patients With Aortic Stenosis; NCT01755936).

Project description:AimsAortic stenosis (AS) and cardiac amyloidosis (CA) are typical diseases of the elderly. Up to 16% of older adults with severe AS referred to transcatheter aortic valve replacement (TAVR) have a concomitant diagnosis of CA. CA-AS population suffers from reduced functional capacity and worse prognosis than AS patients. As the prognostic impact of TAVR in patients with CA-AS has been historically questioned and in light of recently published evidence, we aim to provide a comprehensive synthesis of the efficacy and safety of TAVR in CA-AS patients.Methods and resultsWe performed a systematic review and meta-analysis of studies: (i) evaluating mortality with TAVR as compared with medical therapy in CA-AS patients and (ii) reporting complications and clinical outcomes of TAVR in CA-AS patients as compared with patients with AS alone. A total of seven observational studies were identified: four reported mortality with TAVR, and four reported complications and clinical outcomes after TAVR of patients with CA-AS compared with AS alone patients. In patients with CA-AS, the risk of mortality was lower with TAVR (n = 44) as compared with medical therapy (n = 36) [odds ratio (OR) 0.23, 95% confidence interval (CI) 0.07-0.73, I2 = 0%, P = 0.001, number needed to treat = 3]. The safety profile of TAVR seems to be similar in patients with CA-AS (n = 75) as compared with those with AS alone (n = 536), with comparable risks of stroke, vascular complications, life-threatening bleeding, acute kidney injury, and 30 day mortality, although CA-AS was associated with a trend towards an increased risk of permanent pacemaker implantation (OR 1.76, 95% CI 0.91-4.09, I2 = 0%, P = 0.085). CA is associated with a numerically higher rate of long-term mortality and rehospitalizations following TAVR in patients with CA-AS as compared with those with AS alone.ConclusionsTAVR is an effective and safe procedure in CA-AS patients, with a substantial survival benefit as compared with medical therapy, and a safety profile comparable with patients with AS alone except for a trend towards higher risk of permanent pacemaker implantation.

Project description:BackgroundAortic stenosis is accompanied by progressive left ventricular hypertrophy and fibrosis. We investigated the natural history of these processes in asymptomatic patients and their potential reversal post-aortic valve replacement (AVR).MethodsAsymptomatic and symptomatic patients with aortic stenosis underwent repeat echocardiography and magnetic resonance imaging. Changes in peak aortic-jet velocity, left ventricular mass index, diffuse fibrosis (indexed extracellular volume), and replacement fibrosis (late gadolinium enhancement [LGE]) were quantified.ResultsIn 61 asymptomatic patients (43% mild, 34% moderate, and 23% severe aortic stenosis), significant increases in peak aortic-jet velocity, left ventricular mass index, indexed extracellular volume, and LGE mass were observed after 2.1±0.7 years, with the most rapid progression observed in patients with most severe stenosis. Patients with baseline midwall LGE (n=16 [26%]; LGE mass, 2.5 g [0.8-4.8 g]) demonstrated particularly rapid increases in scar burden (78% [50%-158%] increase in LGE mass per year). In 38 symptomatic patients (age, 66±8 years; 76% men) who underwent AVR, there was a 19% (11%-25%) reduction in left ventricular mass index (P<0.0001) and an 11% (4%-16%) reduction in indexed extracellular volume (P=0.003) 0.9±0.3 years after surgery. By contrast midwall LGE (n=10 [26%]; mass, 3.3 g [2.6-8.0 g]) did not change post-AVR (n=10; 3.5 g [2.1-8.0 g]; P=0.23), with no evidence of regression even out to 2 years.ConclusionsIn patients with aortic stenosis, cellular hypertrophy and diffuse fibrosis progress in a rapid and balanced manner but are reversible after AVR. Once established, midwall LGE also accumulates rapidly but is irreversible post valve replacement. Given its adverse long-term prognosis, prompt AVR when midwall LGE is first identified may improve clinical outcomes.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifiers: NCT01755936 and NCT01679431.

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A systematic review of micro-RNAs in aortic stenosis and cardiac fibrosis.

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A systematic review of micro-RNAs in aortic stenosis and cardiac fibrosis.

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