Early detection of cardiac impairment and prediction of right ventricular hypertrophy in patients with connective tissue disease

Abstract

Progressive right ventricle (RV) failure and death in connective tissue disease (CTD) are related to RV hypertrophy (RVH) and dilation, irrespective of pulmonary arterial hypertension (PAH). Therefore, detecting cardiac impairment before RVH and determining RVH predictors is crucial for timely intervention. The present prospective cohort study aimed to identify cardiac markers that occur before RVH and to investigate predictors of RVH. CTD was diagnosed based on clinical features, laboratory findings and imaging data. The cardiac functions of patients with CTD were evaluated using echocardiography, cardiovascular magnetic resonance (CMR) and multi-modality cardiac imaging studies, including RV wall thickness, systolic functions, late gadolinium enhancement, T1 maps and biventricular strain analysis. A total of 52 patients with CTD with non-right ventricular hypertrophy (non-RVH), 34 patients with RVH and 50 healthy individuals were prospectively included. The impaired cardiac indices in patients with RVH included RV ejection fraction, ventricular dimensions, global myocardial deformation, late gadolinium enhancement and ventricular extracellular volume (ECV). The cardiac death rate did not differ significantly between the RVH and non-RVH groups (P=0.14). Conventional parameters, including serum cardiac markers and the left ventricular ejection fraction, showed no significant changes in the non-RVH group compared with the control group. Regarding fibrosis assessment using CMR, an elevated native T1 value (1,362±72 msec in the non-RVH group vs. 1,268±42 in the control group; P<0.001) and ECV (31±4% in the non-RVH group vs. 25±3% in the control group; P<0.001) were observed. By contrast, T1 myocardium/msec 15 min post-contrast of the left ventricle in the RVH group was significantly decreased compared with that in the non-RVH group, indicating an increase in the extracellular matrix at this stage. RVH was predicted by pulmonary arterial pressure (PAP) in patients in the non-RVH group (t-statistic, 2.84; P=0.01), whereas after RVH presentation, RV end-systolic volume (RVESV) became a progression predictor of RVH (t-statistic, 7.98; P<0.0001). No other cardiac imaging or laboratory findings predicted RVH. To the best of our knowledge, the present study was the first to highlight the non-invasive detection of cardiac tissue impairment using CMR and provide support for cardiac treatment initiation before RVH detection. The predictors of RVH vary with the heart disease stage. PAP in the non-RVH stage and incompetence of RVESV in the RVH stage predicted the progression of RVH. The present study was part of a clinical trial (NCT03271385), which was registered on July 1, 2017, and started on September 1, 2017.

Keywords: CMR; CTD; ECV; RVH; myocardial deformation.

Figure 1

Flow chart of the present study. The diagram shows participants in the screening. CAD, coronary artery disease; CTD, connective tissue disease; LV, left ventricle; RVH, right ventricular hypertrophy.

Figure 2

Example of regional and diffuse fibrosis distribution in patients in the non-RVH and RVH groups. Native myocardial T1 values and ECV are presented as values and a color map to show the increased fibrotic features in patients with non-RVH and RVH. Unlike the positive foci seen in patients with RVH (yellow arrow), there was no visual regional fibrosis present (blue arrows) in the patients with non-RVH. ECV, ventricular extracellular volume; LGE, late gadolinium enhancement; RVH, right ventricular hypertrophy.

Figure 3

Global strains in patients with non-RVH and RVH. (A) Global strain in the RV. (B) Global strain in the LV. Global longitudinal, circumferential and radial strains are shown from left to right. LV, left ventricle; RV, right ventricle; RVH, right ventricular hypertrophy.

Figure 4

Examples of global strain in patients with non-RVH and RVH. (A) Three examples from representative patients showing RV strain in longitudinal, circumferential and radial directions. The strain in each direction was decreased in patients with RVH (green line). Patients with non-RVH had no reduced strain in either direction. (B) In the left ventricle, global longitudinal strain in patients with non-RVH (red line) and RVH (green line) was reduced compared with that in control subjects (left panel). No strain reduction was observed among patients in terms of the circumferential and radial strains. LV, left ventricle; RV, right ventricle; RVH, right ventricular hypertrophy.