The Force Frequency Relationship in Heart Failure and Diabetes Mellitus: a Metabolic Aetiology?

NCT07309523 | Recruiting

• 1 other identifier: 2024-NCT17
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

The present investigation is a non-randomised, observational study involving an unselected but highly phenotyped cohort of patients undergoing pacemaker or defibrillator implantation from whom a small sample of fat and muscle will be taken from the operation site, and, in a subgroup, from the thigh muscle. A sample of blood wil also be taken from the vein of the heart, a peripheral vein and the artery at the wrist during the procedure at different heart rates and pacing modes, to describe how heart rate and heart contraction power relate to cardiac and peripheral metabolism. The coded blood and tissue samples and anonymised clinical data will be stored in a Human Tissue Authority-approved freezer until analysis. Following the procedure, during routine visits, patients' left ventricular force frequency relationship will be assessed using cardiac ultrasound and a non-invasive cardiac monitor to further phenotype the severity and progression of their heart function over 6 months. For most patients, their involvement will end at that point although they will be monitored through electronic health records on an annual basis from that point forward for up to 5 years after the end of the study (for up to ten years after that point) to gain information on the prognostic value of the metabolic and haemodynamic testing. The present investigation will allow the investigators to advance the understanding of heart-muscle crosstalk with the goal of developing targeted interventions that could open new treatment avenues.

Conditions

Heart Failure; Diabetes (DM)

Keywords

Force frequency relationship, heart failure, diabetes mellitus, Treppe

Outcome Measures

Primary Outcomes (1)

• Relationship between FFR and cardiac metabolomics

  Is cardiac metabolism in patients with diabetes and diabetes with heart failure as assessed by mass spectrometry-based metabolomics and lipidomics abnormal at higher heart rates and is the degree of the impairment correlated with the heart rate at which peak contractility occurs?

  At baseline

Study Arms (4)

HFrEF without DM

People with heart failure due to reduced ejection fraction

HFrEF with DM

People with heart failure due to reduced ejection fraction who also have diabetes mellitus

No HF, no DM

People without heart failure who also do not have diabetes mellitus

No HF but with DM

People without heart failure but who do have diabetes mellitus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

People having an implantable cardiac device procedure

You may qualify if:

• Guideline-compliant, clinical indication for pacemaker implantation
• Age \>18 years
• Ability to provide written informed consent
• Persons who are legally competent and mentally able to follow the instructions of the study staff

You may not qualify if:

• Anemia Hb \<8 mg/dl
• Patients with acute infectious diseases (e.g. pneumonia)
• Patients with heart failure due to sepsis
• People with acute myocardial ischemia, which is manifested, for example, by angina pectoris or ECG changes under stress
• Patients with acute liver or kidney failure
• Pregnant and breastfeeding women
• People who are institutionalized on official or court orders
• People who are dependent or employed by the sponsor or investigator
• Taking study medication (of an investigational drug) 30 days before the start of the study
• Known contrast allergy or eGFR \<20ml/min/1.73m2
• Pregnancy not excluded by bedside pregnancy test in premenopausal women

Sponsors & Collaborators

• University of Leeds: lead

Study Sites (1)

Leeds Teaching Hospitals NHS Trust

Leeds, West Yorkshire, LS2 9JT, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Skeletal muscle, blood, fat

MeSH Terms

Conditions

Heart Failure; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Central Study Contacts

Klaus K Witte, MD

CONTACT

00441133926642; k.k.witte@leeds.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer in Cardiology

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: December 30, 2025
• Study Start: September 1, 2024
• Primary Completion (Estimated): August 30, 2034
• Study Completion (Estimated): August 30, 2034
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 1 year after the publication of the main results
• Access Criteria: By an email to the PI access to the file through a secure site.

Locations

GB (1)