Mathematical Modeling to Determine Basic Muscle Properties in the Failing Heart

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University of Nebraska
Sponsor:
Information provided by (Responsible Party):
Michael J Moulton, MD, FACS, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01778894
First received: January 25, 2013
Last updated: October 12, 2013
Last verified: October 2013
  Purpose

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.

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.


Condition
Diastolic Dysfunction, Diastolic Heart Failure, Diastolic

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Mathematical Modeling to Determine Basic Muscle Properties in the Failing Heart

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • The longitudinal assessment of myocardial properties in subjects with Diastolic Heart Failure. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Correlation of observed muscle properties to clinical outcomes/status. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.

  • Validation of the developing mathematical model using the data points collected from echocardiographic procedures [ Time Frame: 1 baseline echocardiograph ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 40
Study Start Date: September 2013
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
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 and/or Heart Failure
Diastolic Heart Failure, > Grade II (NYHA functional class) and/or > Grade II Diastolic Dysfunction as evaluated by echocardiography

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
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.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01778894

Contacts
Contact: Natalie M Kamtz, BS 402-559-3293 natalie.kamtz@unmc.edu

Locations
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Natalie M Kamtz, BS    402-559-3293    natalie.kamtz@unmc.edu   
Principal Investigator: Michael J Moulton, MD         
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Michael J Moulton, MD University of Nebraska
  More Information

Publications:
Responsible Party: Michael J Moulton, MD, FACS, Professor and Chief, Cardiothoracic Surgery, University of Nebraska
ClinicalTrials.gov Identifier: NCT01778894     History of Changes
Other Study ID Numbers: 623-12
Study First Received: January 25, 2013
Last Updated: October 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Nebraska:
Diastolic Dysfunction, Diastolic Heart Failure, Diastolic
Echocardiography

Additional relevant MeSH terms:
Heart Failure
Heart Failure, Diastolic
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 22, 2014