Mechanisms in Heart Failure With Normal EF (HFpEF)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Barry Borlaug, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00587808
First received: December 21, 2007
Last updated: February 6, 2012
Last verified: May 2011
  Purpose

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).


Condition Intervention
Heart Failure
Procedure: RHC with VO2 consumption

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Invasive Characterization of the Mechanisms Underlying Exertional Intolerance and Increased Filling Pressures in Patients With Heart Failure and a Preserved EF

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: November 2007
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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.
  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: NCT00587808

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Barry A. Borlaug, M.D. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Barry Borlaug, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00587808     History of Changes
Other Study ID Numbers: 07-005202, HFpEF
Study First Received: December 21, 2007
Last Updated: February 6, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Heart Failure
Heart Failure, Diastolic
Stroke Volume

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on October 29, 2014