A substantial number of patients showing signs of abnormal diastolic function (including abnormal relaxation, filling or stiffness) also demonstrate left ventricular ejection fraction (LVEF) with values ranging from >40% to >55%. These patients are often said to have heart failure with preserved (or normal) ejection fraction. Considering its prevalence and outcomes, future projections and lack of effective therapies, this condition represents the single largest unmet need in cardiovascular medicine.
In order to definitely diagnose HFpEF, valvular heart disease, constrictive pericarditis and several non-cardiac diseases must first be ruled out. Diagnosis typically occurs through noninvasive echocardiographic assessment of the tissue Doppler-derived filling index E/E’ to estimate left ventricular filling pressures. When this is inconclusive, tests for elevated levels of B-type natriuretic peptides (BNP) must be relied upon.
Definitive objective evidence of ventricular diastolic dysfunction requires cardiac catheterization to demonstrate an increased LV end-diastolic filling pressure in the presence of a normal or reduced LV end-diastolic volume. Exercise testing during hemodynamic assessment may further unmask HFpEF[3,4,5].
Pressure-volume loops provide a direct method for demonstrating that patients with HFpEF have an abnormality of passive diastolic properties by measuring their ventricular end-diastolic pressure-volume relation (EDPVR). An upward shift in EDPVR during a change in pre-load or exercise compared with normal confirms diastolic dysfunction. This results from increased LV stiffness contributing to increased LVEDP during exercise in patients with HFpEF.
A significant proportion of stable outpatients with dyspnea may have HFpEF, and may be easily missed by non-invasive testing.
In a recent clinical trial, 30 patients with EF >50% and NYHA II-III dyspnea underwent cardiac catheterization with a PV loop catheter to confirm the diagnosis of suspected HFpEF. PV loops were recorded at rest, during hand-grip exercise, leg lifting and nitroprusside and dobutamine infusion. The patients were assessed non-invasively using echocardiography and their BNP values were tested.
The study also noted without the use of PV loops, only 25% of the diagnosed patients had heart failure with preserved ejection fraction according to the ESC definition of HFpEF and only 10% showed elevated BNP levels.
1. Butler J et al. Developing therapies for heart failure with preserved ejection fraction. JACC: Heart Failure 2014;2:97-112.
2. Borlaug B and Kass D. Invasive Hemodynamics Assessment in Heart Failure. Heart Fail Clin 2009;5:217-228.
3. Kawaguchi et al. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction. Circulation 2003;107:714-720.
4. Wachter et al. Blunted frequency-dependent upregulation of cardiac output is related to impaired relaxation in diastolic heart failure. Eur Heart J 2009;30:3027-36.
5. Westermann et al. Role of left ventricular stiffness in heart failure with normal ejection fraction. Circulation. 2008;117:2051-60.
6. Burkhoff et al. Heart failure with a normal ejection fraction. Circulation. 2003;107:656-658.
7. Penicka et al. Heart failure with preserved ejection fraction in outpatients with unexplained dyspnea. JACC 2010;55:1701-10.