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Diffuse left ventricular interstitial fibrosis is associated with sub-clinical myocardial dysfunction in Alstrom Syndrome: an observational study.

ABSTRACT: BACKGROUND:Alström syndrome is a rare inherited ciliopathy with progressive multisystem involvement. Dilated cardiomyopathy is common in infancy and recurs or presents de novo in adults with high rates of premature cardiovascular death. Although Alström syndrome is characterised by fibrosis in solid organs such as the liver, the pathogenesis of related cardiomyopathy are not clear. To date it is not known whether diffuse interstitial myocardial fibrosis is present before the onset of heart failure symptoms or changes in conventional parameters of left ventricular function. METHODS:In this observational study, 26 patients with Alström syndrome (mean age 27?±?9 years, 65 % male, 24 h ABPM 130?±?14 / 77?±?9 mmHg) without symptomatic cardiovascular disease were recruited from a single centre and compared to matched healthy controls. All subjects underwent cardiac MRI (1.5 T) to assess ventricular function, diffuse interstitial myocardial fibrosis by measurement of extracellular volume on T1-mapping (MOLLI) and coarse replacement fibrosis using standard late gadolinium enhancement imaging. RESULTS:Global extracellular volume was increased in Alström syndrome with wider variation compared to controls (0.30?±?0.05 vs. 0.25?±?0.01, p?

SUBMITTER: Edwards NC

PROVIDER: S-EPMC4483224 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Diffuse left ventricular interstitial fibrosis is associated with sub-clinical myocardial dysfunction in Alström Syndrome: an observational study.

Edwards Nicola C NC Moody William E WE Yuan Mengshi M Warfield Adrian T AT Cramb Robert R Paisey Richard B RB Geberhiwot Tarekegn T Steeds Richard P RP

Orphanet journal of rare diseases 20150624

<h4>Background</h4>Alström syndrome is a rare inherited ciliopathy with progressive multisystem involvement. Dilated cardiomyopathy is common in infancy and recurs or presents de novo in adults with high rates of premature cardiovascular death. Although Alström syndrome is characterised by fibrosis in solid organs such as the liver, the pathogenesis of related cardiomyopathy are not clear. To date it is not known whether diffuse interstitial myocardial fibrosis is present before the onset of hea ...[more]

PMID: 26104972

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Project description:BackgroundAlström syndrome (ALMS) is a rare ciliopathy characterised by early onset insulin resistance, obesity, and dyslipidaemia and is a model for diseases that have huge social, health and economic impact. Cardiomyopathy develops in the majority, with high rates of morbidity and mortality, the definitive features of which are coarse replacement fibrosis and diffuse myocardial fibrosis (DIF). The pathogenesis of heart failure is thought to involve fibroblast accumulation and expansion of the extracellular matrix with excess protein deposition, leading to distorted organ architecture and impaired contractile function. Consecutive adults with genetically proven ALMS attending the National Centre for Rare Disease in Birmingham, England were studied. All patients underwent serial CMR, echocardiography and venous blood sampling, with computed tomography coronary angiography (CTCA) performed to assess severity of CAD. The aims of this study were: 1) to evaluate changes over time in DIF by cardiovascular magnetic resonance tissue characterization in ALMS; 2) to examine whether changes in DIF are associated with alteration in systolic or diastolic function; and 3) to evaluate the frequency and severity of coronary artery disease as a confounder for progression of ischaemic versus non-ischaemic fibrosis.ResultsIn total, 30/32 adults (63% male; 67% White British) participated. The median age at first scan was 21.3 years (interquartile range: 19.0-32.6) and participants were followed for a maximum of 67 months. Only 4 patients had significant coronary artery stenosis on post-mortem, invasive coronary angiography or CTCA. Mid short axis myocardial T1 times, myocardial extracellular volume, and left ventricular mass increased significantly over time, by an average of 21.8 ms (95% CI 17.4-26.1; p < 0.001), 1.1 percentage points (0.6-1.6, p < 0.001), and 2.8 g/m2 (1.9-3.7; p < 0.001) per year, respectively. These changes were not associated with significant deterioration in myocardial structure or function.ConclusionsThis is the first comprehensive prospective study demonstrating progression of DIF in ALMS over time, although no structural or functional consequences were noted within a median three and a half years' follow up. Further study is warranted to define whether DIF is a by-stander or the driver to impaired contractile function, heart failure and death.

Project description:BACKGROUND:Myocardial fibrosis leads to impaired cardiac function and events. Extracellular volume fraction (ECV) assessed with an iodinated contrast agent and measured by cardiac CT may be a useful noninvasive marker of fibrosis. OBJECTIVE:The purpose of this study was to develop and evaluate a 3-dimensional (3D) ECV calculation toolkit (ECVTK) for ECV determination by cardiac CT. METHODS:Twenty-four subjects (10 systolic heart failure, age, 60 ± 17 years; 5 diastolic failure, age 56 ± 20 years; 9 matched healthy subjects, age 59 ± 7 years) were evaluated. Cardiac CT examinations were done on a 320-multidetector CT scanner before and after 130 mL of iopamidol (Isovue-370; Bracco Diagnostics, Plainsboro, NJ, USA) was administered. A calcium score type sequence was performed before and 7 minutes after contrast with single gantry rotation during 1 breath hold and single cardiac phase acquisition. ECV was calculated as (?HUmyocardium/?HUblood) × (1 - Hct) where Hct is the hematocrit, and ?HU is the change in Hounsfield unit attenuation = HUafter iodine - HUbefore iodine. Cardiac magnetic resonance imaging was performed to assess myocardial structure and function. RESULTS:Mean 3D ECV values were significantly higher in the subjects with systolic heart failure than in healthy subjects and subjects with diastolic heart failure (mean, 41% ± 6%, 33% ± 2%, and 35% ± 5%, respectively; P = 0.02). Interobserver and intraobserver agreements were excellent for myocardial, blood pool, and ECV (intraclass correlation coefficient, >0.90 for all). Higher 3D ECV by cardiac CT was associated with reduced systolic circumferential strain, greater end-diastolic and -systolic volumes, and lower ejection fraction (r = 0.70, r = 0.60, r = 0.73, and r = -0.68, respectively; all P < 0.001). CONCLUSION:3D ECV by cardiac CT can be performed with ECVTK. We demonstrated increased ECV in subjects with systolic heart failure compared with healthy subjects. Cardiac CT results also showed good correlation with important functional heart biomarkers, suggesting the potential for myocardial tissue characterization with the use of 3D ECV by cardiac CT. This trial is registered at www.ClinicalTrials.gov as NCT01160471.

Project description:PurposeTo quantitatively evaluate the dynamic changes of extracellular volume (ECV) and native T1 in hypertensive swine over time using histologic findings as standard of reference.Materials and methodsEighteen hypertensive (hypertension group) and six healthy (control group) swine aged 6-12 months were studied. Both groups underwent cardiac MRI, including pre- and postcontrast T1 mapping and late gadolinium enhancement (LGE) imaging at three time points: baseline, 1 month, and 3 months after hypertensive model induction. The left ventricular function, strain, and strain rate were also calculated using the cine images. Animals were killed after the last MRI examination. Histopathologic examination of the heart was performed later. Analysis of the relationship between strain, ECV, and native T1 was carried out by Pearson correlation and linear regression models.ResultsThe mean systolic and diastolic pressure increased from 111 mg Hg and 68 mm Hg to 160 mm Hg and 97 mm Hg, respectively, over 3 months during developing hypertension (P = .03, .02, respectively). There was no LGE detected at any of three imaging times. The ECV and native T1 value of myocardium in the hypertension group increased over 3 months (ECV, increased from 21.5% ± 4.4 to 27.3% ± 5.4; native T1, increased from a mean of 1056 msec ± 32 [standard deviation] to 1218 msec ± 66; all P < .001). The collagen volume fraction (CVF) was calculated and correlated with ECV (r = 0.63, P = .01) and native T1 (r = 0.80, P < .001). In addition, ECV was associated with longitudinal diastolic strain rate (r =-.34, P = .04). Native T1 was associated with radial strain (r = -0.62, P < .001) as well as circumferential strain (r = 0.57, P < .001).ConclusionNative T1 and ECV correlated significantly with the CVF, indicating that early myocardial interstitial fibrosis exists in hypertensive heart disease. As hypertension progresses, the values of ECV fraction and T1 native increase. Supplemental material is available for this article. © RSNA, 2020.

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Diffuse left ventricular interstitial fibrosis is associated with sub-clinical myocardial dysfunction in Alstrom Syndrome: an observational study.

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Diffuse left ventricular interstitial fibrosis is associated with sub-clinical myocardial dysfunction in Alström Syndrome: an observational study.

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