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Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson-Fabry disease.

ABSTRACT: Enzyme replacement therapy (ERT) is a mainstay of treatment for Anderson-Fabry disease (AFD), a pathology with negative effects on the heart and kidneys. However, no reliable biomarkers are available to monitor its efficacy. Therefore, we tested a panel of four microRNAs linked with cardiac and renal damage in order to identify a novel biomarker associated with AFD and modulated by ERT. To this end, 60 patients with a definite diagnosis of AFD and on chronic ERT, and 29 age- and sex-matched healthy individuals, were enrolled by two Italian university hospitals. Only miR-184 met both conditions: its level discriminated untreated AFD patients from healthy individuals (c-statistic = 0.7522), and it was upregulated upon ERT (P < 0.001). On multivariable analysis, miR-184 was independently and inversely associated with a higher risk of cardiac damage (odds ratio = 0.86; 95% confidence interval [CI] = 0.76-0.98; P = 0.026). Adding miR-184 to a comprehensive clinical model improved the prediction of cardiac damage in terms of global model fit, calibration, discrimination, and classification accuracy (continuous net reclassification improvement = 0.917, P < 0.001; integrated discrimination improvement [IDI] = 0.105, P = 0.017; relative IDI = 0.221, 95% CI = 0.002-0.356). Thus, miR-184 is a circulating biomarker of AFD that changes after ERT. Assessment of its level in plasma could be clinically valuable in improving the prediction of cardiac damage in AFD patients.

SUBMITTER: Salamon I

PROVIDER: S-EPMC8665928 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson-Fabry disease.

Salamon Irene I Biagini Elena E Kunderfranco Paolo P Kunderfranco Paolo P Roncarati Roberta R Ferracin Manuela M Taglieri Nevio N Nardi Elena E Laprovitera Noemi N Tomasi Luciana L Santostefano Marisa M Ditaranto Raffaello R Vitale Giovanni G Cavarretta Elena E Pisani Antonio A Riccio Eleonora E Aiello Valeria V Capelli Irene I La Manna Gaetano G Galiè Nazzareno N Spinelli Letizia L Condorelli Gianluigi G

Cell death & disease 20211211 12

Enzyme replacement therapy (ERT) is a mainstay of treatment for Anderson-Fabry disease (AFD), a pathology with negative effects on the heart and kidneys. However, no reliable biomarkers are available to monitor its efficacy. Therefore, we tested a panel of four microRNAs linked with cardiac and renal damage in order to identify a novel biomarker associated with AFD and modulated by ERT. To this end, 60 patients with a definite diagnosis of AFD and on chronic ERT, and 29 age- and sex-matched heal ...[more]

PMID: 34897278

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Project description:ObjectivesCardiac involvement in Anderson-Fabry disease (AFD) results in myocardial lipid depositions. An early diagnosis can maximize therapeutic benefit. Thus, this study aims to investigate the potential of cardiac MRI (CMR) based parameters of left atrial (LA) function and strain to detect early stages of AFD.MethodsPatients (n = 58, age 40 (29-51) years, 31 female) with genetically proven AFD had undergone CMR including left ventricular (LV) volumetry, mass index (LVMi), T1, and late gadolinium enhancement, complemented by LA and LV strain measurements and atrial emptying fractions. Patients were stratified into three disease phases and compared to age and sex-matched healthy controls (HC, n = 58, age 41 [26-56] years, 31 female).ResultsA total of 19 early-, 20 intermediate-, and 19 advanced-phase patients were included. LV and LA reservoir strain was significantly impaired in all AFD phases, including early disease (both p < 0.001). In contrast, LA volumetry, T1, and LVMi showed no significant differences between the early phase and HC (p > 0.05). In the intermediate phase, LVMi and T1 demonstrated significant differences. In advanced phase, all parameters except active emptying fractions differed significantly from HC. ROC curve analyses of early disease phases revealed superior diagnostic confidence for the LA reservoir strain (AUC 0.88, sensitivity 89%, specificity 75%) over the LV strain (AUC 0.82).ConclusionsLA reservoir strain showed impairment in early AFD and significantly correlated with disease severity. The novel approach performed better in identifying early disease than the established approach using LVMi and T1. Further studies are needed to evaluate whether these results justify earlier initiation of therapy and help minimize cardiac complications.Key points• Parameters of left atrial function and deformation showed impairments in the early stages of Anderson-Fabry disease and correlated significantly with the severity of Anderson-Fabry disease. • Left atrial reservoir strain performed superior to ventricular strain in detecting early myocardial involvement in Anderson-Fabry disease and improved diagnostic accuracies of approaches already using ventricular strain. • Further studies are needed to evaluate whether earlier initiation of enzyme replacement therapy based on these results can help minimize cardiac complications from Anderson-Fabry disease.

Project description:BackgroundTo date, only limited data are available on right atrium (RA) morphofunctional remodeling in Fabry disease (FD).PurposeWe aimed to investigate RA structural and functional remodeling in patients with FD vs. healthy controls using 2D speckle tracking echocardiography (STE) and to explore whether any differences exist in FD patients with and without left ventricular hypertrophy (LVH).MethodsWe prospectively enrolled patients with FD and controls matched for age, sex, and cardiovascular risk factors. Patients with FD were divided in two groups according to the presence/absence of LVH (LVH+: left ventricular wall thickness >12 mm). All patients underwent standard echocardiography and STE analysis investigating the mechanics of all cardiac chambers, including RA reservoir, contractile and conduit strain.ResultsA total of 64 patients with FD (50% males; mean age 50 ± 17 years; 51.5% LVH+) and 64 control patients were included in the study. Focusing on right chambers, RA and right ventricular (RV) dimensions were similar between FD and controls. No differences were found for tricuspid annular plane systolic excursion (p = 0.073) and RV fractional area change (p = 0.461), while RV systolic Tissue Doppler velocity was reduced in patients with FD (p = 0.041). STE analysis revealed impaired strain values for all cardiac chambers in FD vs controls, specifically: left ventricular global longitudinal strain (LV-GLS, p < 0.001), left atrial (LA) reservoir strain (p = 0.001), conduit strain (p = 0.012), and contractile strain (p < 0.001), RV-GLS and RV free wall strain (p < 0.001). Similarly, all RA strain phases were significantly reduced in patients with FD compared with control patients (RA reservoir 27.4 ± 11.1 vs. 41.9 ± 8.3%, p < 0.001; RA contractile 9.9 ± 5.1 vs. 18.0 ± 4.9%, p < 0.001; RA conduit 19.1 ± 8.1 vs. 24.1 ± 8.1%, p = 0.001). When comparing FD patients without LVH to controls, it was found that RA reservoir and contractile strains were significantly reduced in the former (p < 0.001). In multivariable linear regression analyses, LA reservoir strain (p = 0.010) and LV-GLS (p = 0.044) emerged as independent correlates of RA mechanics after adjustments were made for RA dimensions, RV systolic function parameters and hypertrophy, and LV maximal wall thickness.ConclusionsIn FD impaired RA strain is a common finding. RA reservoir and contractile strains are reduced in FD patients even before LVH ensues, as compared to controls. LA reservoir strain and LV-GLS show an independent correlation with RA reservoir strain.

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Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson-Fabry disease.

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Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson-Fabry disease.

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