Multiparametric cardiovascular magnetic resonance characterisation of myocardial inflammation in patients with rheumatic heart disease

Abstract

INTRODUCTION: Rheumatic heart disease (RHD) is the major sequel of acute rheumatic fever (ARF) and occurs in approximately 60% of the cases. Globally, RHD is the most common acquired cardiovascular disease, affecting more than 15 million people per year, causing approximately 233,000 deaths. RHD remains a significant cause of heart failure in low- and middle-income countries, including sub-Saharan Africa, contributing to considerable morbidity and mortality, often affecting young economically active members of society. OBJECTIVE: The aim of the study was to document the extent of myocardial fibrosis in subjects with RHD, in order to determine the degree of altered myocardial tissue characteristics using a multiparametric cardiovascular magnetic resonance (CMR) approach; assess left ventricular (LV) function and strain, and to assess focal and diffuse myocardial fibrosis in subjects with RHD. METHODOLOGY: Enrolled subjects with a confirmed diagnosis of RHD, and age- and sex-matched healthy controls underwent CMR using a 3T Siemens Skyra (Erlangen, Germany) scanner. CMR parameters included steady-state-free-precession (SSFP) cine, cine tagging, T1-weighted imaging, T2 short Tau inversion-recovery (STIR), native T1 mapping (Modified-Look-Locker inversion recovery), T2 mapping and late gadolinium enhancement (LGE) imaging and extracellular volume (ECV) estimation. RESULTS: Forty-four (44) subjects (mean age 42.8 ± 13.8 years; female 63.6%) with a confirmed diagnosis of RHD, and 30 age- and sex-matched healthy controls (mean age 38.87 ± 12.31 years; female 53.3%) were enrolled in the study. RHD subjects showed an increased indexed LV end-diastolic, end-systolic, and stroke volume and mass, compared to controls (p = 0.001). LV ejection fraction (LVEF) was reduced in the RHD cohort compared to controls (44.0 ± 13.26% versus 56.9 ± 5.19%, p < 0.001). There was significant left atrial dilatation in RHD subjects compared to controls (41.37 ± 11.84 mm versus 21.77 ± 3.13 mm, p < 0.001). Increased indexed RV end-diastolic, end-systolic and stroke volumes were found. RV ejection fraction was significantly lower in RHD subjects compared to controls (41.07 ± 16.19% versus 53.60 ± 7.46%, p < 0.001). Valvular lesions most commonly observed were mixed mitral valve disease (27%) and mixed mitral and aortic valve disease (43%). Native T1 values were elevated in RHD subjects compared to controls (1279.98 ± 54.14 ms versus 1212.85 ± 33.34 ms, p = 0.004). T2 mapping values to assess oedema were normal, in both RHD subjects and controls (39.26 ± 2.92 versus 38.72 ± 2.19, p = 0.32); relative T2 STIR imaging parameters were 1.31 ± 0.34 versus 1.48 ± 0.22, p = 0.02. Late gadolinium enhancement (LGE) was evident in all 44 (100%) RHD subjects, with linear (26%), patchy (36%) and diffuse (38%) patterns of enhancement. ECV values were elevated in RHD subjects compared to controls (0.36 ± 0.05 versus 0.28 ± 0.01 %, p < 0.001). Linear regression analysis showed moderate negative correlation between native T1 and peak diastolic circumferential strain rate (R = -0.412, p = 0.001) and strong correlation between ECV and peak diastolic circumferential strain rates (R = -0.43, p = 0.00). CONCLUSION: This study showed a high prevalence of fibrosis throughout the myocardium in all RHD subjects, irrespective of valvular pathology. Increased native T1 and ECV indicate increased myocardial fibrosis. Normal signal intensity ratio on T2-weighted oedema imaging (STIR) and T2 values indicated absence of active inflammation in advanced, chronic RHD. These data, showing a high fibrotic burden, may provide an explanation for increased mortality in RHD as excess myocardial fibrosis has been strongly linked with mortality in other disease contexts.