To evaluate the presence and extent of myocardial inflammation, fibrosis and myocardial perfusion in SSc patients with either PH-LHD or PAHPAH and/or PH-LHD, in comparison to patients with idiopathic pulmonary arterial hypertension (IPAH) by means…
ID
Source
Brief title
Condition
- Heart failures
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In this study we will explore parametric mapping to characterize the
myocardium. Native T1 mapping is able to detect local and diffuse necrosis and
fibrosis, whereas T2 mapping detects the extent of edema, which is used to
assess activity of (subclinical) myocardial inflammation. Stress and rest
perfusion CMR using adenosine will be used to assess focal perfusion defects
and exclude relevant epicardial coronary stenosis, and additional T1-mapping
will assess global myocardial (microvascular) perfusion. The presence and
extent of myocardial inflammation, fibrosis and myocardial perfusion will be
compared with the control group of IPAH patients. Additionally, the relation
between disease severity and clinical status will be explored, and compared
with the traditional late gadolinium enhanced images for the detection of focal
disease.
The established ShMOLLI (Shortened Modified Look-Locker Inversion Recovery)
sequence will be used for T1 mapping. Although T1-relaxation using ShMolli is a
reproducible and consistent sequence to distinguish normal from diseased
myocardium, the normal value needs to be determined for each MRI-scanner, since
the normal value is scanner (i.e. vendor, field strength, location) dependent.
In order to validate the T1-relaxation times in healthy individuals in this
CMR, 20 patients without myocardial disease scheduled for a non-myocardial CMR
scan (e.g. for the follow-up of aortic dilatation) will be asked to
participate. Patients will be asked to give written informed consent to acquire
this additional sequence and to use the results for scientific purposes.
Secondary outcome
To compare SSc-patients with PH and IPAH-patients in regards to features on
electrocardiogram (such as right axis deviation, right ventricular strain
pattern, right atrial dilatation), and echocardiography parameters (estimated
pulmonary arterial pressures by tricuspid valve- and pulmonary valve
regurgitation velocity, right atrial area, right ventricle (RV) fractional area
change, TAPSE, global longitudinal RV strain, the RV- and left ventricle (LV)-
end diastolic and systolic volume, the LV ejection fraction and diastolic
function). Besides high-sensitive troponin-T, NT-proBNP and CRP, differences in
blood result analyses will include characterization of T-cells subset and
pro-inflammatory and pro-fibrotic mediators in peripheral blood mononuclear
cells.
Background summary
Systemic sclerosis (SSc) is a systemic immune-mediated disease that is
characterized by vasculopathy and fibrosis of the skin and internal organs.
Pulmonary hypertension due to left heart disease (PH-LHD) and pulmonary
arterial hypertension (PAH) are frequent and severe complications of SSc.
Despite recent advances in the treatment armamentarium, SSc-PAH survival is
still poor with a median survival of 4 years. There is growing evidence this
may be due to intrinsic right ventricular dysfunction caused by primary cardiac
involvement of SSc, which results in earlier right ventricle failure, but the
mechanism of action is still unknown. Since systemic sclerosis in the skin (and
other internal organs) is characterized by fibrosis, inflammation and
vasculopathy, it is speculated that the same process takes place in the
myocardium. Parametric mapping in cardiovascular magnetic resonance imaging
(CMR) is evolving as a new technique, which provides a non-invasive tool for
quantifying tissue alterations in myocardial disease, such as diffuse, more
subtle edema, necrosis and fibrosis. The myocardial microvasculature can be
determined by adenosine stress perfusion CMR imaging and stress T1 mapping.
Thesehis techniques haves the potential to detect cardiac involvement in this
patient group and could therefore be of additional value in monitoring therapy
or early recognition of PH in SSc patients, as well as gaining insight in the
underlying pathophysiology.
Study objective
To evaluate the presence and extent of myocardial inflammation, fibrosis and
myocardial perfusion in SSc patients with either PH-LHD or PAHPAH and/or
PH-LHD, in comparison to patients with idiopathic pulmonary arterial
hypertension (IPAH) by means of CMR parametric mapping and adenosine stress
perfusion CMR imaging.
Study design
Feasibility study, with prospective enrollment of consecutive patients.
Study burden and risks
There are minimal risks for subjects included in this feasibility study. CMR
bears only minimal risks and is largely part of their regular clinical
treatment. During a stress perfusion CMR, adenosine is administrated. Patients
might suffer from side effects of adenosine administration, such as headache,
nausea, chest pain, and flushing. Serious side effects, such as high degree
AV-block, are relatively rare, and almost all reverse quickly when adenosine
infusion is terminated. Discomfort may be caused since the subject has to stay
in a fixed position in the CMR. Peripheral blood samples will be taken once,
which may also cause some discomfort. Possible side effect from blood drawing
include faintness, inflammation of the vein, pain, bruising, or bleeding at the
site of puncture. There is also a slight possibility of infection.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- Age >=18
- Diagnosis of SSc according to the 2013 ACR-EULAR classification criteria
- Diagnosed with pulmonary hypertension WHO group 1 (PAH) and (in combination with)/or WHO group 2 (PH due to LHD) according to ESC[6]/ERS guidelines.
- Written informed consent
Exclusion criteria
- Severe lung diseases (severe interstitial lung disease with a forced vital capacity <40%, COPD GOLD stadium III-IV), history of pulmonary embolisms.
- History of myocardial infarction, ischemic heart failure, moderate to severe valve stenosis or regurgitations (with or without heart failure).
- Patients with WHO group 3 PH (due to lung disease), defined as a pulmonary capillary wedge <15mmHg in combination with a forced vital capacity <60% (of 65%?) and/or moderate to severe interstitial lung disease on a high resolution computed tomography.
- Known contra-indications for CMR (e.g.: severe claustrophobia, metal implants, severe renal failure, severe astma, high degree AV-block)
- Known GFR < 30 ml/min
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL66117.091.18 |