OT5 – Development and prevention of severe heart disease

Background: SSc heart disease is characterised morphologically by small intramyocardial coronary artery involvement and myocardial fibrosis involving both ventricles with a patchy distribution. It can cause the development of impaired diastolic ventricular filling (which appears to be the first detectable abnormality), CB and VA, and can ensue in CHF and SD. Short-term trials have suggested a favourable effect of CCBs and ACEi on myocardial ischemia which is thought to drive the development of myocardial fibrosis. Retrospective studies have also suggested a protective effect of CCBs on the development of a reduced left ventricular ejection fraction and of ACEi on the development of impaired diastolic ventricular filling. However, no data are presently available on the prevention and treatment of SHD.

Objective: To assess the efficacy and safety of CCBs and ACEi in asymptomatic SSc patients with cardiac involvement 

Cumulative incidence of CB, VA, pacemaker implantation, congestive heart failure and sudden death 

Secondary endpoints 

N/A 

Exploratory endpoints 

N/A 

Incidence of drug-related adverse events, incidence of withdrawal from treatment due to drug-related adverse events 

• All adult and juvenile systemic sclerosis patients, with diagnosis according to the ACR/EULAR adult SSc criteria and PRES/ACR/EULAR juvenile SSc criteria respectively.

• Systemic sclerosis patients will be subdivided into 2 subgroups: 1) without and 2) with risk factors for severe heart disease (i.e. : male sex and/or DLCO/SB < 80% and/or systolic PAP > 30 mmHg and/or synovitis and/or joint contractures and/or digital ulcers and/or proteinuria). 

• Any significant pulmonary parenchymal (FVC < 70% and/or DLCO/SB < 70%), pulmonary vascular (estimated systolic PAP > 40 mmHg), gastrointestinal (malabsorption syndrome or paralytic ileus diagnosed by physician ́s opinion) or renal (serum creatinine level >1.2 mg/dl, dialysis or previous scleroderma renal crisis) involvement.

• Patients symptomatic for cardiac disease as diagnosed by physician ́s opinion. 

Two different groups will be observed for analysis:
(1) Patients receiving CCB monotherapy, ACEi monotherapy, or CCB + ACEi combination therapy

(2) Patients receiving no CCB or ACEi therapy 

Patients will be assessed every 3 months by history, clinical examination and ECG, and every 6 months by Holter ECG and B-mode echocardiography until the end of the 1-year follow-up 

Randomisation 

No randomization (observational trial) 

Justification of recruitment centres/ countries 

The OT will be performed based on the EUSTAR database MEDSonline, which includes approximately 9,600 patients, and the jSScWG taking care of approximately 100 – 120 children and adolescents 

Pre-planned subgroup analyses (effect modification) 

Patients will be subdivided into those (i) without and (ii) with clinically inapparent CB or VA at inclusion as detected by Holter ECG to analyse the treatment effects separately 

Strenghts 

• Prospective design including patients at risk to develop SHD

• Large sample size

• Feasibility

• Recruiting centers are highly active in the field of SSc clinical research, which guarantees a high quality and accuracy of the collected data 

• Observational study

• Recruitment from tertiary medical centers, which may lead to inclusion of patients suffering from more active and severe disease