Biomaterial Collection - and Analysis in Cardiac Sarcoidosis

Pathomechanisms in Patients With Cardiac Sarcoidosis and Other Inflammatory and Familial Cardiomyopathies of Similar Phenotypic Appearance

Cardiac sarcoidosis (CS) is a complex disease that is characterized by the formation of inflammatory granulomas in the myocardium. The exact underlying pathophysiology of the disease is not yet fully understood, but it is believed to be related to dysregulation of the immune system. Despite significant progress in recent years, the disease remains difficult to diagnose, and there is a high risk of severe complications such as life-threatening cardiac arrhythmias, severe heart failure, and sudden cardiac death in affected patients.

Moreover, the clinical presentation of CS can be similar to other inflammatory heart diseases or familial cardiomyopathies. Thus, it is challenging to differentiate between these diseases, which can lead to a delayed diagnosis and poor prognosis. It is unclear whether certain genetic variants play a role in the clinical course and prognosis of CS, which highlights the need for more research in this area.

The diagnosis of CS requires cardiac or extracardiac biopsy with granuloma detection, which is an invasive and complex procedure. Consequently, the disease is thought to be underdiagnosed, and many affected patients may not receive timely treatment, resulting in excess mortality. Early diagnosis and immunosuppressive treatment, as well as defibrillator implantation if necessary, are crucial in delaying disease progression, preventing complications, and improving prognosis.

To better understand the key molecular pathological mechanisms underlying the development and maintenance of CS, a prospective, multicenter, exploratory study has been initiated. The project involves the collection, storage, and analysis of biological samples from blood, myocardium, and lymph nodes of patients with cardiac sarcoidosis or cardiomyopathies that present clinically and image morphologically similar. The samples will be used for scientific investigations on disease mechanisms of cardiomyopathies as well as for identification of new biomarkers in cardiomyopathy diagnostics and for follow-up of therapeutic measures.

The study will employ a range of classical biochemical methods such as ELISA, RIA, as well as more modern methods of molecular biology (single cell sequencing, single nucleus sequencing) and systems biology (genomics, metabolomics, or proteomics) to identify key molecular pathological mechanisms in the development and maintenance of CS.

In addition, genetic analysis will be performed to investigate cardiomyopathy- and ion channel-associated genetic variants, which is critical for improving diagnostics and early, individualized therapy. The study will be conducted on a multicenter basis, with the Heart Center Leipzig serving as the initiator and lead center and the University Hospital Leipzig as the second study center. Biochemical and molecular biological analyses will be performed on behalf of the study management at the Heart Center Leipzig, the University Hospital Leipzig, and the Erich and Hanna Klessmann Institute for Cardiovascular Research and Development of the Heart and Diabetes Center NRW and Max Delbrück Center for Molecular Medicine in Berlin.

In conclusion, CS is a complex and challenging disease that requires further research to better understand its underlying mechanisms and improve diagnostic and therapeutic strategies. The prospective, multicenter, exploratory study will provide valuable insights into the disease's key molecular pathological mechanisms and identify new biomarkers for better diagnostics and individualized therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiac Sarcoidosis

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Hans Ebbinghaus, MD; Phone Number: 0049341865252550; Email: Hans.Ebbinghaus@helios-gesundheit.de
• Study Contact Backup: Name: Borislav Dinov, MD; Email: Borislav.Dinov@helios-gesundheit.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

tertiary care clinic patients with suspected inflammatory cardiomyopathy and/or conduction disorders and/or ventricular arrhythmias, suspected cardiac sarcoidosis.

Description

Inclusion Criteria:

(a) patients with a history of symptomatic cardiac sarcoidosis/inflammatory cardiomyopathy or b) patients with newly diagnosed heart failure with cardiac arrhythmias (ventricular tachycardia, conduction disturbances, etc.) that may indicate sarcoidosis or inflammatory cardiomyopathy or c) patients with image morphological suspicion of cardiac sarcoidosis or inflammatory cardiomyopathy (MRI, PET-CT) or (d) patients who require or have received a ventricular assist device (VAD) or cardiac transplantation due to suspected cardiac sarcoidosis or inflammatory cardiomyopathy and (e) written informed consent has been obtained from patients for study participation and consent for analysis of patient samples. Studies on pseudoanonymized samples will only be performed with appropriately signed informed consent.

Exclusion Criteria:

1. Patients with psychiatric illness that impairs business or insight capacity.
2. Patients with chronic heart failure due to coronary artery disease or valvular vitiation.
3. severe underlying disease other than sarcoidosis that is likely to result in death within one year.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Endomyocardial biopsy-positive Cardiac sarcoidosis
Endomyocardial biopsy-negative non ischemic cardiomyopathy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD14++CD16+ - monocytes/macrophages in myocardial samples and peripheral blood correlates with disease activity	Sarcoidosis leads to a cellular TH1-mediated immune response with formation of non-necrotizing granulomas in affected organs, including the heart. Monocyte/macrophage subpopulations play an important role in the initiation of the TH1 immune response. Detection of specific immune cells such as CD14++CD16+ - monocytes/macrophages in myocardial samples and peripheral blood correlates with disease activity.	Baseline
Specific genetic variants, single nucleotide polymorphisms, and epigenetic markers are associated with an individually increased risk of disease.	Modern genetic testing methods can detect an individually increased risk of disease.	Baseline

Collaborators and Investigators

• Sponsor: Heart Center Leipzig - University Hospital
• Collaborators: University of Leipzig Medical Center, Department of Cardiology; Heart and Diabetes Center North Rhine-Westphalia, Erich and Hanna Klessmann Institute for Cardiovascular Research and Development; Max Delbrück Center for Molecular Medicine (MDC), Berlin

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): April 1, 2028
• Study Completion (Anticipated): April 1, 2029

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): March 31, 2023

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 30, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphoproliferative Disorders; Lymphatic Diseases; Sarcoidosis
• Other Study ID Numbers: CD1022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No