Mathematical Modeling to Determine Basic Muscle Properties in the Failing Heart

August 26, 2023 updated by: University of Nebraska
According to the most recent information released by the American Heart Association, heart failure affects 5.8 million Americans and over 23 million people worldwide. In particular, diastolic heart failure (DHF) has emerged in approximately half of those suffering from heart disease and has become a major public health problem for many reasons, including the complexity of the disease, lack of effective drugs/therapies, requirement of invasive tests to diagnose and monitor DHF, and the absence of a suitable scientific model to study the disease. Scientists and physicians alike still do not fully understand what happens to the muscles in the heart (myocardium) patients who present with diastolic dysfunction or DHF. Therefore, the medical field is in need of an accurate model that can evaluate how diastolic dysfunction leads to heart failure and what happens at a cellular level as this disease emerges and progresses.

Study Overview

Status

Terminated

Conditions

Detailed Description

Our group has developed a mathematical model of the heart that gathers data from a procedure called an echocardiograph (echo) to analyze how muscles in the heart are functioning. This model incorporates how the heart muscle functions on a cellular level along with the overall functionality of the heart.

We hypothesize that this model will measure the specific properties of the heart muscle that affect their ability to contract and relax. This study will determine whether these properties will be different in patients with DHF compared to healthy controls. We also propose that these abnormalities in the heart muscle will correlate with the patient's degree of heart failure and their prognosis when doctors evaluate using standard clinical tests.

This study will be conducted at the University of Nebraska Medical Center (UNMC). 40 subjects will be enrolled, 20 healthy controls with no history of heart disease and 20 subjects who have been diagnosed with diastolic heart failure. Healthy controls will be required to undergo 1 echocardiograph procedure at UNMC. Subjects diagnosed with DHF will be required to undergo 6 echocardiograph procedure over the course of 2 years.

Study Type

Observational

Enrollment (Actual)

37

Contacts and Locations

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

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center

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

15 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Normal controls will be recruited from the Omaha community. Subjects with Diastolic Heart Dysfunction and/or Failure will be selected from The University of Nebraska Medical Center Heart Clinic or from The Nebraska Medical Center Hospital.

Description

Inclusion Criteria:

  • Subjects must be 19 years of age or older
  • Control subjects must have no prior history or current signs of heart disease.
  • Subjects with heart failure must meet one or more of the following criteria:
  • Documented Diastolic Heart Failure, Grade II or greater (via NYHA functional class)
  • Grade II or greater Diastolic Dysfunction by echocardiographic evaluation

Exclusion Criteria:

  • Subjects under the age of 19 or unable to give consent will be excluded from this study.
  • Greater than mild valvular disease
  • Prior valve repair/replacement

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

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Healthy Control
Healthy controls with no history of heart disease or heart failure. Subjects will undergo a medical history review and 1 echocardiograph procedure.
>Grade 2 Diastolic Dysfunction
Diastolic Heart Failure, > Grade II (NYHA functional class) and/or > Grade II Diastolic Dysfunction as evaluated by echocardiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The longitudinal assessment of myocardial properties in subjects with Diastolic Heart Failure.
Time Frame: 2 years
Our mathematical model of the heart integrates the cellular mechanisms of sarcomere dynamics with the overall functional properties of the ventricle. Utilizing specific measurements captured by echo, estimates of basic muscle properties in subjects suffering from DHF will be compared to observed properties. Echo measurements will be taken at baseline and 2 weeks, 4 months, 8 months, 1 year, and 2 years following therapy.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of observed muscle properties to clinical outcomes/status.
Time Frame: 2 years
Clinical outcome measurements, including hospitalizations, New York Heart Association (NYHA) class, and mortality, will be collected to determine effectiveness of current therapy for diastolic heart failure. By tracking patient outcomes and measured clinical endpoints, the degree of material parameter abnormality affecting clinical outcomes of subjects will be tested using multivariate regression with the material parameters derived from the model. The dependent variables and covariates such as age, sex, ejection fraction, presence of co-morbidities such as coronary artery disease, diabetes, and hypertension will also be included in the analysis.
2 years
Validation of the developing mathematical model using the data points collected from echocardiographic procedures
Time Frame: 1 baseline echocardiograph
An optimization driver program that controls the parameter estimation has been developed and will be validated. To estimate unknown material parameters, multiple forward model simulations are obtained to estimate the partial derivatives of the least squares objective function with respect to the material parameters. Best-fit parameters will be determined for each DHF patient and each control using cylindrical, spherical and ellipsoidal models. Each of these parameters represents a unique aspect of sarcomere and ventricular matrix constitutive behavior. Best-fit material parameters for each patient will be compared with those obtained from the control groups.
1 baseline echocardiograph

Collaborators and Investigators

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

Sponsor

University of Nebraska

Investigators

  • Principal Investigator: Moulton J Moulton, MD, University of Nebraska

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

September 1, 2013

Primary Completion (Actual)

February 3, 2022

Study Completion (Actual)

February 3, 2022

Study Registration Dates

First Submitted

January 25, 2013

First Submitted That Met QC Criteria

January 25, 2013

First Posted (Estimated)

January 29, 2013

Study Record Updates

Last Update Posted (Actual)

August 29, 2023

Last Update Submitted That Met QC Criteria

August 26, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0623-12-EP

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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