Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: Understanding Mechanisms by Using Noninvasive Methods

Masaru Obokata, Yogesh N.V. Reddy, and Barry A. Borlaug

J Am Coll Cardiol Img. 2020 Jan, 13 (1_Part_2) 245–257


Research in the last decade has substantially advanced our understanding of the pathophysiology of heart failure with preserved ejection fraction (HFpEF). However, treatment options remain limited as clinical trials have largely failed to identify effective therapies. Part of this failure may be related to mechanistic heterogeneity. It is speculated that categorizing HFpEF patients based upon underlying pathophysiological phenotypes may represent the key next step in delivering the right therapies to the right patients. Echocardiography may provide valuable insight into both the pathophysiology and underlying phenotypes in HFpEF. Echocardiography also plays a key role in the evaluation of patients with unexplained dyspnea, where HFpEF is suspected but the diagnosis remains unknown. The combination of the E/e′ ratio and right ventricular systolic pressure has recently been shown to add independent value to the diagnostic evaluation of patients suspected of having HFpEF. Finally, echocardiography enables identification of the different causes that mimic HFpEF but are treated differently, such as valvular heart disease, pericardial constriction, and high-output heart failure or infiltrative myopathies such as cardiac amyloid. This review summarizes the current understanding of the pathophysiology and phenotyping of HFpEF with particular attention to the role of echocardiography in this context.


HFpEF is a heterogeneous syndrome, and categorizing patients based upon pathophysiology may provide phenotype-specific therapies.
Echocardiography provides valuable information for assessing pathophysiological mechanisms, phenotyping, and diagnosis in cases of HFpEF.
Further study is needed to establish the HFpEF phenotype and roles of noninvasive imaging in it.


Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome that is increasing in prevalence. Rather than having an isolated abnormality in left ventricular (LV) diastolic function, patients with HFpEF display multifaceted limitations in cardiac, vascular, and peripheral functions (1). Phenotyping based upon pathophysiology, comorbidities, or some combination may provide targeted therapies for the specific HFpEF subpopulations that are positioned to derive the greatest benefit (2).

Cardiovascular imaging plays a key role in the diagnosis and evaluation of HFpEF, particularly echocardiography, which allows for assessment of cardiac structure, function, and hemodynamics (3). This review summarizes the current understanding of the pathophysiology and phenotypes of HFpEF, with a focus on the essential role of imaging for the evaluation and care of patients with HFpEF.

Pathophysiology of HFpEF: Beyond Diastolic Dysfunction

LV diastolic dysfunction plays a fundamental, overarching role in the pathophysiology of HFpEF (1). LV diastolic dysfunction is defined by an impairment in relaxation, an increase in viscoelastic chamber stiffness, or some combination of the 2 (4,5) and leads to symptomatic HF by causing elevated filling pressures at rest or with exertion (6). Elevated filling pressures promote symptoms of dyspnea (7), impair exercise capacity (7,8), increase risk for HF hospitalization (9), and decrease survival in HFpEF (10). The importance and assessment of LV diastolic dysfunction in HFpEF are reviewed in detail in other articles in this issue.

Although diastolic dysfunction is central to HFpEF, it is also important to acknowledge that there are declines in LV relaxation and compliance with normal aging or with cardiometabolic comorbidities such as obesity, insulin resistance, and hypertension (11–13). Not all patients with diastolic dysfunction have or will develop clinical HFpEF (14,15). Research in the past decade has demonstrated that, in addition to LV diastolic dysfunction, multiple nondiastolic abnormalities in cardiovascular system contribute to the syndrome of HFpEF. These abnormalities include subtle LV systolic dysfunction, left atrial (LA) impairment, relative pericardial restraint, abnormal right ventricular-pulmonary artery coupling, pulmonary vascular disease, systemic vascular stiffening, coronary and peripheral microvascular dysfunction, and chronotropic incompetence…

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