Diagnostic Criteria in Cardiac Sarcoidosis

Cardiac Sarcoidosis Clinical Trial

— ELDORADO  

Official title:

Evaluation of Diagnostic Criteria in Cardiac Sarcoidosis - an Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04737317
• Other study ID #: 20201231PV1
• Status: Recruiting
• Start date: May 1, 2023
• Est. completion date: January 1, 2027

Study information

• Verified date: May 2023
• Source: Heart Center Leipzig - University Hospital
• Contact: Borislav Dinov, MD
• Phone: +49 341 865 1431
• Email: borislav.dinov[@]helios-gesundheit.de
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of the study is to evaluate the accuracy of the current diagnostic criteria of cardiac sarcoidosis.

Description:

Sarcoidosis is an inflammatory condition rarely affecting the heart, exhibiting fluctuating disease activity and eventually leading to ventricular fibrosis. Clinical presentation ranges from no symptoms at all to life-threatening arrhythmias, heart failure and death in severe cases. The heart lesions show patchy distribution and can mimic virtually any other type of cardiomyopathy, which poses significant challenges for the accurate and eary diagnosis.

At present, there are four diagnostic tools and recomendations for diagnosis of cardiac sarcoidosis (CS) that utilize clinical, ECG, laboratory, imaging and biopsy criteria. Recently, it was demonstrated that there is a significant diagreement between these four diagnostic tools. On the other hand, earlier identification of patients with active inflammatory process is necessary, as they are those who will most likely benefit from immunosuppressive therapy.

The aim of this observational study is to evaluate the prognostic significance of the current clinical, ECG, laboratory, imaging and biopsy criteria for diagnosing cardiac sarcoidosis. Patients with suspected cardiac sarcoidosis based on clinical symptoms will recieve elaborate diagnostic work-up consisting of: evaluation of symptoms, family history, occupational hazards, ECG, chest X-ray, laboratory markers for sarcoidosis, positron emission tomography (PET), cardiac magnetic resonance (CMR) as well as endomyocardial biopsy.

In accordance to the recomendations of the current guidelines, the patients will be devided into 3 groups: 1) patients with proven CS; 2) patients with probable CS; and 3) unlikely CS that will serve as a reference group. The patients in first two groups will be treated with immunosuppressive therapy, mainly glucocorticoids (GC). The follow-up at 3, 6, 12 and 24 months will consist of evaluation of the symptoms using dedicated King's Sarcoidosis Questionaire (KSQ), fatigue assessment scale (FAS), Holter-ECG, pacemaker interrogation, laboratory findings, imaging with PET and CMR.

Clinical outcomes will be defined as: 1) improvement of symptoms (FAS score, heart failure class, AV block, ventricular arrhythmias, and KSQ score) and 2) improvement of imaging parameters ( left ventricular ejection fraction, PET activity, myocardial edema, scar in CMR). The outcomes between the groups will be compared using group 3 as reference. Furthermore, patients with improvement with GC (successful therapy) will be compared with those without improvement (unsuccessful therapy) and the predictive value of each diagnostic criterion will be evaluated. Finally, the odds ratios (OR) for each parameter will be used to calculate a diagnostic and predictive score which will be used prospectively to evaluate patients with suspected CS and to guide the therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 1, 2027
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients with suspected CS due to the following presentations:

1. age < 65 years and new higher degree AV block, causative coronary artery disease excluded

2. age < 65 years and new ventricular tachycardia, causative coronary artery disease excluded

3. age < 65 years and ventricular tachycardia, causative coronary artery disease excluded

4. extracardiac sarcoidosis and cardiac involvement suggested (palpitations, abnormal ECG, abnormal echocardiography)

To diagnose CS one of the following diagnostic tools will be used:

A) World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG)

B) Heart Rhythm Society expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis

C) Japanese Society of Nuclear Cardiology (JSNC)

Patients whit histological confirmation from myocardial tissue fullfil will be defined as proven CS. (Group 1)

Patients with clinical and imaging findings highly suggesting CS, but without histological confirmation from myocardial biopsy will be defined as probable CS (Group 2)

Patients who do not fullfil the criteria or exhibiting findings suggesting an alternative, more likely diagnosis, will be considered as unlikely CS (Group 3)

Exclusion Criteria:

• unable or unwilling to provide informed consent

• patients who are pregnant or lactating

• noncompliant patients refusing the recommended therapy

• age < 18 years

Related Conditions & MeSH terms

• Cardiac Sarcoidosis
• Sarcoidosis

Intervention

Diagnostic Test:
• ECG, Echo, laboratory tests, CMR, PET-CT, Biopsy
ECG - 12 leads ECG Echo: transthoracic echocardiography laboratory tests: full blood count, electrolytes, creatinine, high sensitive cardiac troponin T, angiontesin converting enzyme, soluble interleukin-2 receptor, cardiac magnetic resonance imaging: 1.5 Tesla scanner, Conventional cine imaging and late gadolinium enhancement imaging PET-CT: 18F-fluorodeoxyglucose (FDG)- positron emission tomograph Biopsy: cardiac biopsy = endomyocardial biopsy, left and right ventricle, at least 5 specimens in formaldehyd and 3 specimens for testing of infectious agents Biopsy: extracardiac biopsy, as accessible according to imaging

Locations

Country	Name	City	State
Germany	Heart Center of Leipzig	Leipzig

Sponsors (1)

Lead Sponsor	Collaborator
Heart Center Leipzig - University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical recovery with immunosuppressive therapy	Number of patients showing clinical recovery defined as improvement of at least one of the following: decrease of the heart failure class, decrease of fatigue assessed by FAS score, increase of KSQ score with at least 10 points, reduction of burden of ventricular arrhythmias assessed with Holter ECG or device interrogations, improvement of the AV block	1 year
Primary	Imaging recovery with immunosuppressive therapy	Number of patients with improvement of the cardiac imaging defined as one of the following: increase of the EF with at least 10%, decrease of the PET activity, decrease of the scar or edema in CMR	1 year
Secondary	Cardiac mortality	Number of patients who died of cardiac reasons	2 years
Secondary	All-cause mortality	Number of patients who died of cardiac or non-cardiac reasons	2 years
Secondary	Unplanned hospitalizations	Number of unplanned hospitalizations due to heart failure or ventricular arrhythmias	2 years
Secondary	Change in LV-EF from baseline	Measured in echocardiography or CMR as at least 10% change of the LV EF, LV EDD	2 years
Secondary	Change in RV function	Measured in echocardiography or CMR as 10% change of RV EF, RV diameter, TAPSE	2 years
Secondary	Patients' quality of life	A dedicated King's Sarcoidosis Questionnaire (KSQ) will be used to assess patients condition. Values from 1 to 100 define the patients' condition with higher scores indicating better condition. Improvement will be defined as increase of the KSQ score with at least 10 points.	2 years
Secondary	VT ablation success	Applies only for patients after VT ablation: Time to VT recurrence	2 years
Secondary	Adverse events of immunosuppressive therapy	Number of patients with significant adverse events related to the immunosuppressive therapy	2 years
Secondary	Changes of immunosuppressive therapy due to lack of success	Number of GC dose increase and/or switch to another medication and/or escalation of therapy adding other immunosuppressive drugs to the GC	2 years