Mechanisms in Heart Failure With Normal EF "HFpEF"


Phase N/A Results N/A

Trial Description

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).

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.



  • RHC with VO2 consumption Procedure
    Intervention Desc: 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
    ARM 1: Kind: Experimental
    Label: HFpEF
    Description: Patients with a history of HFpEF
    ARM 2: Kind: Experimental
    Label: control
    Description: Patients with a without a history of CHF

Trial Design

  • Observation: Case Control
  • Perspective: Prospective
  • Sampling: Non-Probability Sample

Trial 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.


Type Measure Time Frame Safety Issue
Primary Specific Aim 1. Elucidate the relative roles of impaired ventricular systolic, diastolic, and vascular reserve functions during supine exercise in HFpEF during catheterization No
Secondary 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. during cardiac catheterization No