Introduction. Patients with rheumatic musculoskeletal diseases (RMDs) face a risk of cardiovascular disease (CVD) that is significantly higher than the general population. It has long been recognised that RMDs can affect the musculoskeletal system as the heart. However, RMDs-primary heart involvement (RMDs-pHI) has been poorly characterised, and it is difficult to ascertain its contribution to the increased CVD risk of RMDs patients. Other than the effect of traditional cardiovascular risk factors, several factors that are disease-specific may contribute to RMDs-pHI, such as a chronic inflammatory insult to the vessels, pro-inflammatory lipids, the effects of anti-rheumatic therapies, and autoimmune or post-repairing biological processes. Detection of RMDs-pHI has prognostic implications. Aim. This doctoral thesis aimed to investigate by ultrasound the plethora of cardiac abnormalities in patients with RMDs and to correlate those findings with the clinical characteristics of the diseases. Methods. This was a prospective observational study based at the Division of Rheumatology, University of Verona (Italy). We recruited outpatients with established diagnoses of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). All patients underwent a baseline assessment of cardiovascular and disease-related data. We also used standard transthoracic echocardiography (TTE) and additional investigational TTE techniques to determine cardiac abnormalities. Study outcomes were: 1) left ventricular (LV) volumes and mass, including an assessment of LV hypertrophy (LVH); 2) myocardial strain, using speckle-tracking echocardiography (STE); 3) arterial stiffness, as measured by the aortic stiffness index (AoSI); 4) myocardial fibrosis, identified by pulse-cancellation imaging (eSCAR). Results. We found that among RA patients, women were more likely to progress to LVH than men, irrespective of their CVD risk profile. Patients with RA also had an increased AoSI, but the use of tumor necrosis factor-alpha inhibitors compared to csDMARDs was protective against the progression of aortic stiffness, especially with accumulating CVD risk factors. SLE patients had myocardial fibrosis detected by eSCAR in the inferior and inferoseptal basal segments in 17%, which was associated with the long-term exposure to glucocorticoids. Patients with SSc had myocardial scars with a similar pattern to SLE patients in 25%, but also with ischemic patterns. However, digital ulcers were independently associated with non-ischemic fibrosis. In both SLE and SSc patients, myocardial fibrosis localized in areas of impaired myocardial deformation as shown by STE, suggesting that myocardial fibrosis was associated with subclinical myocardial dysfunction. Conclusion. We showed that myocardial abnormalities are frequent in RMDs patients and can be effectively detected with manageable TTE techniques. Moreover, specific cardiac lesions were associated with features of disease severity in SLE and SSc patients. The implementation of echocardiography studies in the Rheumatology core assessment could allow cardiovascular risk stratification of patients with RMDs. This could help reduce costs and optimise resources.

Investigational echocardiography for the detection of heart involvement in rheumatic musculoskeletal diseases

Giollo
2022-01-01

Abstract

Introduction. Patients with rheumatic musculoskeletal diseases (RMDs) face a risk of cardiovascular disease (CVD) that is significantly higher than the general population. It has long been recognised that RMDs can affect the musculoskeletal system as the heart. However, RMDs-primary heart involvement (RMDs-pHI) has been poorly characterised, and it is difficult to ascertain its contribution to the increased CVD risk of RMDs patients. Other than the effect of traditional cardiovascular risk factors, several factors that are disease-specific may contribute to RMDs-pHI, such as a chronic inflammatory insult to the vessels, pro-inflammatory lipids, the effects of anti-rheumatic therapies, and autoimmune or post-repairing biological processes. Detection of RMDs-pHI has prognostic implications. Aim. This doctoral thesis aimed to investigate by ultrasound the plethora of cardiac abnormalities in patients with RMDs and to correlate those findings with the clinical characteristics of the diseases. Methods. This was a prospective observational study based at the Division of Rheumatology, University of Verona (Italy). We recruited outpatients with established diagnoses of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). All patients underwent a baseline assessment of cardiovascular and disease-related data. We also used standard transthoracic echocardiography (TTE) and additional investigational TTE techniques to determine cardiac abnormalities. Study outcomes were: 1) left ventricular (LV) volumes and mass, including an assessment of LV hypertrophy (LVH); 2) myocardial strain, using speckle-tracking echocardiography (STE); 3) arterial stiffness, as measured by the aortic stiffness index (AoSI); 4) myocardial fibrosis, identified by pulse-cancellation imaging (eSCAR). Results. We found that among RA patients, women were more likely to progress to LVH than men, irrespective of their CVD risk profile. Patients with RA also had an increased AoSI, but the use of tumor necrosis factor-alpha inhibitors compared to csDMARDs was protective against the progression of aortic stiffness, especially with accumulating CVD risk factors. SLE patients had myocardial fibrosis detected by eSCAR in the inferior and inferoseptal basal segments in 17%, which was associated with the long-term exposure to glucocorticoids. Patients with SSc had myocardial scars with a similar pattern to SLE patients in 25%, but also with ischemic patterns. However, digital ulcers were independently associated with non-ischemic fibrosis. In both SLE and SSc patients, myocardial fibrosis localized in areas of impaired myocardial deformation as shown by STE, suggesting that myocardial fibrosis was associated with subclinical myocardial dysfunction. Conclusion. We showed that myocardial abnormalities are frequent in RMDs patients and can be effectively detected with manageable TTE techniques. Moreover, specific cardiac lesions were associated with features of disease severity in SLE and SSc patients. The implementation of echocardiography studies in the Rheumatology core assessment could allow cardiovascular risk stratification of patients with RMDs. This could help reduce costs and optimise resources.
2022
rheumatoid arthritis, scleroderma, systemic sclerosis, systemic lupus erhythematosus, cardiovascular, myocardial, fibrosis, echocardiography, ultrasound, heart, biological therapy
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1062742
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