Biological Mechanisms Behind Resynchronization Therapy in Heart Failure

November 14, 2023 updated by: Marcus Stahlberg, Region Stockholm

Heart failure is a common disease, affecting 2-3% of the population in the western world. About 30% of patients with heart failure and reduced ejection fraction display signs of electrical dyssynchrony on ECG, usually left bundle branch block (LBBB), which is associated with a worse prognosis. Cardiac resynchronization therapy (CRT) reduce mortality for patients with dyssynchronic heart failure, defined as ejection fraction (EF) = or < 35% and LBBB. About 1/3 of the patients that fit CRT criteria will not respond to CRT. Which patients that will turn out to be non-responders cannot be anticipated beforehand.

We have started a clinical study to collect blood samples, heart tissue and clinical data from heart failure patients eligible for CRT and a control group of heart failure patients on medical therapy. Patients will be assessed before CRT implantation or early after initiation of medical treatment, at 3 months, 6 months and 12 months.

Blood samples and tissue will be analysed in the search for (i) biomarkers to separate CRT responders from non-responders and (ii) mechanisms behind the remodelling observed in CRT and with medical therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In dyssynchrony the conduction of electrical signals within the heart is prolonged causing a delay between the activation and contraction of septum and lateral left ventricular wall. In turn, this results in uncoordinated and ineffective heart work. Dyssynchrony is accompanied by cardiac remodeling with dilatation of the left chamber. Whether dilatation is an effect or a cause of dyssynchrony is unclear and likely different for different patients. Cardiac resynchronization therapy, CRT, is a pacemaker with an extra electrode that will stimulate the right and left ventricle simultaneously, resulting in resynchronization.

We have started a clinical study to collect blood samples, heart tissue and clinical data (echocardiography, ECG, medical records) from heart failure patients eligible for CRT and a control group of heart failure patients on medical therapy. Patients will be assessed before CRT implantation or early after initiation of medical treatment, at 3 months, 6 months and 12 months. A subset of the patients in the CRT group will also also be subjected to a heart biopsy before CRT implantation and at 3 months. At each time point all patients will be assessed with echocardiography, ECG and blood sampling. The blood samples will be analyzed regarding proteins and exosomal miRNA. The heart tissue will be frozen and analyzed regarding proteins, RNA and contractility.

Endothelial function is also known to play a crucial role in heart failure and will be evaluated at inclusion, 3 and 12 months using EndoPAT. Red blood cells (RBCs) are collected to determine whether they may affect endothelial cell function.

Study Type

Observational

Enrollment (Estimated)

220

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Heart failure patients followed at the Karolinska University Hospital in Stockholm, Sweden.

Description

Inclusion Criteria:

  1. Ejection fraction (EF) = or < 35% and A or B

    A) Left bundle branch block (LBBB) QRS = or > 150 ms or a high proportion ventricular pacing and planned for CRT at Karolinska University Hospital.

    B) Planned for medical treatment and followed at Karolinska University Hospital.

  2. Ability to understand the given information.
  3. Ability to give informed consent.

Exclusion Criteria:

  1. Pregnant or planning pregnancy
  2. Not able to give informed consent -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
CRT
Heart failure patients that receive a CRT
Diagnostic test: Proteomics, miRNA studies and studies of blood cells from blood samples
This is an observational study where we follow patients and save blood samples and biopsies for analysis as described above.
Other Names:
  • Force-calcium study from biopsy
Control
Heart failure patients treated with medicines, without a CRT indication.
Diagnostic test: Proteomics, miRNA studies and studies of blood cells from blood samples
This is an observational study where we follow patients and save blood samples and biopsies for analysis as described above.
Other Names:
  • Force-calcium study from biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarkers
Time Frame: 2023-2028
Proteins or exosomal miRNA from blood to separate CRT responders from non-responders
2023-2028

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelial function
Time Frame: 2023-2028
EndoPAT and RBC studies to separate CRT responders from non-responders
2023-2028

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mechanism behind the reverse remodelling in CRT responders and with medical treatment
Time Frame: 2023-2028
Proteomics, RNA studies, force-calcium studies
2023-2028

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Region Stockholm

Investigators

  • Principal Investigator: Marcus Ståhlberg, PhD, Karolinska Universitetssjukhuset

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2023

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

March 1, 2026

Study Registration Dates

First Submitted

November 14, 2023

First Submitted That Met QC Criteria

November 14, 2023

First Posted (Estimated)

November 21, 2023

Study Record Updates

Last Update Posted (Estimated)

November 21, 2023

Last Update Submitted That Met QC Criteria

November 14, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRT K 2022-8295

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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