Prospective cardiovascular magnetic resonance imaging in adults with Alström syndrome: silent progression of diffuse interstitial fibrosis

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Prospective cardiovascular magnetic resonance imaging in adults with Alström syndrome : silent progression of diffuse interstitial fibrosis. / Baig, Shanat; Dowd, Rory; Edwards, Nicola C; Hodson, James; Fabritz, Larissa; Vijapurapu, Ravi; Liu, Boyang; Geberhiwot, Tarekegn; Steeds, Richard P.

In: Orphanet Journal of Rare Diseases, Vol. 15, 139, 05.06.2020.

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Baig, Shanat ; Dowd, Rory ; Edwards, Nicola C ; Hodson, James ; Fabritz, Larissa ; Vijapurapu, Ravi ; Liu, Boyang ; Geberhiwot, Tarekegn ; Steeds, Richard P. / Prospective cardiovascular magnetic resonance imaging in adults with Alström syndrome : silent progression of diffuse interstitial fibrosis. In: Orphanet Journal of Rare Diseases. 2020 ; Vol. 15.

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@article{f4c7c84f750348ebbca3c07c9432b60e,
title = "Prospective cardiovascular magnetic resonance imaging in adults with Alstr{\"o}m syndrome: silent progression of diffuse interstitial fibrosis",
abstract = "Background: Alstr{\"o}m 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. Results: In 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/m 2 (1.9-3.7; p < 0.001) per year, respectively. These changes were not associated with significant deterioration in myocardial structure or function. Conclusions: This 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. ",
keywords = "Alstr{\"o}m syndrome, Cardiovascular magnetic resonance, Diffuse interstitial fibrosis, Extracellular volume, Ischaemic heart disease, Progression",
author = "Shanat Baig and Rory Dowd and Edwards, {Nicola C} and James Hodson and Larissa Fabritz and Ravi Vijapurapu and Boyang Liu and Tarekegn Geberhiwot and Steeds, {Richard P}",
year = "2020",
month = jun,
day = "5",
doi = "10.1186/s13023-020-01426-4",
language = "English",
volume = "15",
journal = "Orphanet Journal of Rare Diseases",
issn = "1750-1172",
publisher = "Springer",

}

RIS

TY - JOUR

T1 - Prospective cardiovascular magnetic resonance imaging in adults with Alström syndrome

T2 - silent progression of diffuse interstitial fibrosis

AU - Baig, Shanat

AU - Dowd, Rory

AU - Edwards, Nicola C

AU - Hodson, James

AU - Fabritz, Larissa

AU - Vijapurapu, Ravi

AU - Liu, Boyang

AU - Geberhiwot, Tarekegn

AU - Steeds, Richard P

PY - 2020/6/5

Y1 - 2020/6/5

N2 - Background: Alström 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. Results: In 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/m 2 (1.9-3.7; p < 0.001) per year, respectively. These changes were not associated with significant deterioration in myocardial structure or function. Conclusions: This 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.

AB - Background: Alström 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. Results: In 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/m 2 (1.9-3.7; p < 0.001) per year, respectively. These changes were not associated with significant deterioration in myocardial structure or function. Conclusions: This 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.

KW - Alström syndrome

KW - Cardiovascular magnetic resonance

KW - Diffuse interstitial fibrosis

KW - Extracellular volume

KW - Ischaemic heart disease

KW - Progression

UR - http://www.scopus.com/inward/record.url?scp=85086051677&partnerID=8YFLogxK

U2 - 10.1186/s13023-020-01426-4

DO - 10.1186/s13023-020-01426-4

M3 - Article

VL - 15

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

SN - 1750-1172

M1 - 139

ER -