Epidemiologic studies suggest that nearly one-half of patients with heart failure have a normal ejection fraction; the proportion in those hospitalized has been reported to range from 24% to 55%. The survival of patients with heart failure and preserved ejection fraction was once thought to be better than those with a decreased ejection fraction, but recent evidence suggests similar mortality rates.

Heart failure with preserved ejection fraction (HFpEF) has become the preferred term in the literature. This clinical entity has also been referred to as diastolic heart failure and heart failure with preserved ejection fraction. In this chapter, we focus on HFpEF and provide a brief discussion of the restrictive cardiomyopathies, which are important differential diagnoses in patients presenting with heart failure and a normal ejection fraction.

Most pathophysiologic abnormalities in patients with HFpEF are related to diastolic function. There are two major determinants of diastolic function: LV relaxation and LV stiffness. LV relaxation relates to the cellular mechanisms involved with actin-myosin crossbridge detachment. This requires intracellular calcium uptake into the sarcoplasmic reticulum, an energy- or adenosine triphosphate (ATP)-dependent process. Thus, ischemia, which would decrease intracellular availability of ATP, would prolong the time required for ventricular relaxation. LV stiffness relates to the compliance of the myocardial tissue. One determinant of this is the extracellular matrix. For example, increase in fibrosis and collage deposition, as in patients with hypertensive heart disease, leads to an increase in LV stiffness. Restrictive cardiomyopathies share a similar pathophysiology, with increased LV stiffness; however, these differ in the pathology underlying the change in ventricular compliance: extracellular amyloid deposition (cardiac amyloidosis); endocardial fibrosis from eosinophilic injury (Loeffler’s endocarditis and endomyocardial fibrosis); intracellular lysosomal engorgement with sphingolipids (Fabry’s disease); and others.

A number of other pathophysiologic mechanisms have been implicated in patients with HFpEF. These include arterial stiffness, the relationship between arterial and ventricular stiffness, and chronotropic incompetence. The implications and relative importance of these mechanisms are still unclear.

When compared with patients with systolic dysfunction, those with HFpEF tend to be older and are more likely to be female. Associated comorbidities include hypertension, diabetes, obesity, and chronic kidney disease.

ECG is an insensitive test for HFpEF. In this scenario, the most important finding is the amplitude of QRS voltage. The presence of elevated voltages and other criteria for LVH would support this as a possible cause of HFpEF. Conversely, in a patient who has increased wall thickness (typically by echocardiography) but has low voltage or infarction patterns on ECG (in this case, “pseudoinfarction”), infiltrative or restrictive cardiomyopathy should be considered.

The chest x-ray has few specific findings for HFpEF. In a posterior—anterior film, a normal-sized heart (lateral heart width < 2/3 of a hemithorax) may be a clue to a normal-sized left ventricle. Otherwise, the findings are the same as in systolic dysfunction: fluffy alveolar opacities (alveolar pulmonary edema), increased interstitial markings (increased interstitial fluid), pulmonary vascular redistribution (increased pulmonary venous pressures), and pleural effusions.

BNP can be helpful in establishing the diagnosis of HFpEF (as stated above). When compared with patients with systolic heart failure, the elevation in BNP is generally lower. In patients with undifferentiated dyspnea, a normal BNP would argue against the presence of any heart failure syndrome.