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@article{Lota:2022:10.1161/CIRCULATIONAHA.121.058457,
author = {Lota, A and Hazebroek, M and Theotokis, P and Wassall, R and Salmi, S and Halliday, B and Tayal, U and Verdonschot, J and Meena, D and Owen, R and de, Marvao A and Iacob, A and Yazdani, M and Hammersley, D and Jones, R and Wage, R and Buchan, R and Vivian, F and Hafouda, Y and Noseda, M and Gregson, J and Mittal, T and Wong, J and Robertus, JL and Baksi, AJ and Vassiliou, V and Tzoulaki, I and Pantazis, A and Cleland, J and Barton, P and Cook, S and Pennell, D and Cooper, L and Garcia-Pavia, P and Heymans, S and Ware, J and Prasad, S},
doi = {10.1161/CIRCULATIONAHA.121.058457},
journal = {Circulation},
pages = {1123--1134},
title = {Genetic architecture of acute myocarditis and the overlap with inherited cardiomyopathy},
url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.121.058457},
volume = {146},
year = {2022}
}

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TY  - JOUR
AB  - Background: Acute myocarditis is an inflammatory condition that may herald the onset of dilated (DCM) or arrhythmogenic cardiomyopathy (ACM). We investigated the frequency and clinical consequences of DCM and ACM genetic variants in a population-based cohort of patients with acute myocarditis. Methods: Population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht. All participants underwent targeted DNA-sequencing for well-characterised cardiomyopathy-associated genes with comparison to healthy controls (n=1053) sequenced on the same platform. Case ascertainment in England was assessed against national hospital admission data. The primary outcome was all-cause mortality. Results: Variants that would be considered pathogenic if found in a patient with DCM or ACM were identified in 8% of myocarditis cases compared to <1% of healthy controls (p=0.0097). In the London cohort (n=230; median age 33years; 84% men), patients were representative of national myocarditis admissions (median age 32years; 71% men; 66% case ascertainment), and there was enrichment of rare truncating variants (tv) in ACM-associated genes (3.1% cases vs 0.4% controls; odds ratio 8.2; p=0.001). This was driven predominantly by desmoplakin (DSP)-tv in patients with normal LV ejection fraction and ventricular arrhythmia. In Maastricht (n=106; median age 54years; 61% men), there was enrichment of rare truncating variants in DCM-associated genes, particularly TTN-tv found in 7% (all with LVEF<50%) compared to 1% in controls (OR 3.6; p=0.0116). Across both cohorts over a median of 5.0 years (IQR 3.9-7.8), all-cause mortality was 5.4%. Two thirds of deaths were cardiovascular, due to worsening heart failure (92%) or sudden cardiac death (8%). The 5-year mortality risk was 3.3% in genotype negative patients versus 11.1% for genotype positive patients (Padjusted=0.08). Conclusions: We identified DCM- or ACM-associated genetic variants in 8% of patients wit
AU  - Lota,A
AU  - Hazebroek,M
AU  - Theotokis,P
AU  - Wassall,R
AU  - Salmi,S
AU  - Halliday,B
AU  - Tayal,U
AU  - Verdonschot,J
AU  - Meena,D
AU  - Owen,R
AU  - de,Marvao A
AU  - Iacob,A
AU  - Yazdani,M
AU  - Hammersley,D
AU  - Jones,R
AU  - Wage,R
AU  - Buchan,R
AU  - Vivian,F
AU  - Hafouda,Y
AU  - Noseda,M
AU  - Gregson,J
AU  - Mittal,T
AU  - Wong,J
AU  - Robertus,JL
AU  - Baksi,AJ
AU  - Vassiliou,V
AU  - Tzoulaki,I
AU  - Pantazis,A
AU  - Cleland,J
AU  - Barton,P
AU  - Cook,S
AU  - Pennell,D
AU  - Cooper,L
AU  - Garcia-Pavia,P
AU  - Heymans,S
AU  - Ware,J
AU  - Prasad,S
DO  - 10.1161/CIRCULATIONAHA.121.058457
EP  - 1134
PY  - 2022///
SN  - 0009-7322
SP  - 1123
TI  - Genetic architecture of acute myocarditis and the overlap with inherited cardiomyopathy
T2  - Circulation
UR  - http://dx.doi.org/10.1161/CIRCULATIONAHA.121.058457
UR  - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.058457
UR  - http://hdl.handle.net/10044/1/98467
VL  - 146
ER  -

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