Mechanisms in Heart Failure With Normal EF (HFpEF)

February 6, 2012 updated by: Barry Borlaug, Mayo Clinic

Invasive Characterization of the Mechanisms Underlying Exertional Intolerance and Increased Filling Pressures in Patients With Heart Failure and a Preserved EF

The guiding hypotheses are that (1) mechanisms in addition to diastolic dysfunction, while normal at rest, are compromised with stress, leading to symptoms of HF, and (2) that an increased proportion of the increase in LV diastolic pressures seen in HFpEF is mediated via exaggerated pericardial/right heart-LV coupling (restraint).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Nearly half of all patients with heart failure have a preserved ejection fraction (HFpEF)1-3. This group is increasing in prevalence, has similar morbidity and mortality to systolic HF, and, despite increasing awareness of the healthcare burden, is without proven treatments1. This is related largely to a limited understanding of the basic mechanisms causing the disease3. Recent studies have added to contemporary understanding, but the pathophysiology remains controversial and incompletely understood4-8. A limitation of most prior studies is that the noninvasive measurements employed are merely surrogates for gold standard, invasive hemodynamic assessment9. There is general consensus that HFpEF patients have increased left ventricular filling pressures (LVDP) and relatively normal systolic function at rest5,8,10, but two critical questions remain: what causes the increase in LVDP, and, are there important deficits in the cardiovascular response to exercise stress in HFpEF patients3,4? The current study will resolve these questions by performing comprehensive hemodynamic analysis in HFpEF patients referred to the cardiac cath lab, compared to age and gender matched controls without HF. LV systolic, diastolic, and vascular function will be examined at rest and during graded supine exercise at fixed and varied preload to definitively characterize both baseline differences and discrepancies in cardiovascular reserve function that only become apparent during stress, when HFpEF patients typically become symptomatic11. This study will yield valuable information describing the roles for systolic, diastolic and pericardial abnormalities in the pathogenesis of HFpEF, providing critical preliminary data upon which better targeted therapeutic trials of this common disorder can be based.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

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
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

HFpEF subjects (NYHA class ≥II) defined by modified Framingham criteria4 (2 major or 1 major + 2 minor): Major criteria: paroxysmal nocturnal dyspnea or orthopnea, jugular distension or venous pressure>16 mmHg, rales or pulmonary edema, cardiomegaly, hepatojugular reflex, weight loss>4.5 kg in response to diuretics, BNP>400; Minor criteria: ankle edema, nocturnal cough, exertional dyspnea, pleural effusion, HR>120, hepatomegaly, vital capacity<2/3 normal, BNP>200, LA volume index>40cc/m2.

Description

Inclusion Criteria:

  • Age>18, EF≥50% at echocardiography within 6 months, referred for cath. HFpEF subjects

Exclusion Criteria:

  • Patients with: any medical conditions that would limit study participation, pregnancy, myocardial infarction within 30 days of enrollment, hemodynamically significant valvular disease, HF due to thyroid disease, myocarditis, restrictive or hypertrophic cardiomyopathy, cor pulmonale (PVR>5 Wood units with RV dysfunction), LV thrombus, atrial fibrillation or other persistent irregular rhythm, dyspnea felt predominantly due to pulmonary disease, significant coronary artery stenoses (>70%, or 50-70% with FFR<0.8) or other abnormalities detected during the clinical catheterization procedure which require revascularization or other directed therapy.

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

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
HFpEF
Patients with a history of HFpEF
Procedure: RHC with VO2 consumption
All pressure-volume data is acquired at 250 Hz and stored on the Leycom system for offline analysis. Volume data will be calibrated using the most recent EF from echocardiogram and stroke volume from the Fick method. Measured O2 consumption will be utilized along with sampling of SVC and arterial blood oximetry to determine cardiac output at rest and during exercise
control
Patients with a without a history of CHF
Procedure: RHC with VO2 consumption
All pressure-volume data is acquired at 250 Hz and stored on the Leycom system for offline analysis. Volume data will be calibrated using the most recent EF from echocardiogram and stroke volume from the Fick method. Measured O2 consumption will be utilized along with sampling of SVC and arterial blood oximetry to determine cardiac output at rest and during exercise

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Specific Aim 1. Elucidate the relative roles of impaired ventricular systolic, diastolic, and vascular reserve functions during supine exercise in HFpEF
Time Frame: during catheterization
during catheterization

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Specific Aim 2. Determine whether resting and exercise-induced increases in LV diastolic pressures are related to exaggerated right-left heart coupling and to increased afterload.
Time Frame: during cardiac catheterization
during cardiac catheterization

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Barry A. Borlaug, M.D., Mayo Clinic

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.

Helpful Links

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 21, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 21, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 7, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 7, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 07-005202
  • HFpEF

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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