Causes of Diastolic Dysfunction

Definitions

Diastolic dysfunction can be defined as an abnormality in the ability of the left ventricle to fill at normal pressure. Diastolic dysfunction, unlike heart failure with preserved ejection fraction (HFpEF) or diastolic heart failure, is not a clinical diagnosis but rather refers to a pathophysiologic abnormality that can be the basis of the clinical syndrome HFpEF.

Two principal mechanisms are responsible for diastolic dysfunction: impaired active ventricular relaxation and increased passive myocardial stiffness (or decreased compliance). Relaxation comprises a series of energy-consuming steps starting with the release of calcium from troponin C and ending with extension of the sarcomeres to their resting length. This process encompasses two distinct phases: isovolumetric relaxation (drop in left ventricular [LV] pressure at a constant volume) and auxotonic relaxation (contraction to accommodate an increasing volume load during LV filling). The relationship between LV diastolic pressure and volume characterizes ventricular stiffness (ΔP/ΔV) and ventricular compliance (ΔV/ΔP). Both intracellular and extracellular structures affect stiffness, including LV mass and LV mass-to-volume ratio, in addition to the intrinsic stiffness of the myocardium. ^, Echocardiographic assessment of diastolic dysfunction is performed using two-dimensional (2D) imaging, transmitral and pulmonary vein Doppler, tissue Doppler of the mitral annulus, and strain imaging. These are each addressed in their respective chapters.

Diastolic Heart Failure Versus Heart Failure with Preserved Ejection Fraction

Diastolic heart failure and HFpEF refer to a clinical syndrome of heart failure; the terms are overlapping but not synonymous. As we use the terms, HFpEF is a broader clinical syndrome wherein LV diastolic dysfunction may or may not be the primary pathophysiologic derangement. In this usage, HFpEF can be caused by valvular (e.g., acute, severe mitral regurgitation), pericardial disease (e.g., constrictive pericarditis), or myocardial (diastolic heart failure) disease. The term diastolic heart failure implies myocardial disease and is the most common cause of HFpEF. In this chapter, myocardial causes of diastolic dysfunction are discussed; pericardial and valvular etiologies are discussed elsewhere.

Comorbidities Associated with Heart Failure with Preserved Ejection Fraction

Diastolic dysfunction is highly prevalent. Using predefined echocardiographic criteria, some degree of diastolic dysfunction was found in nearly 30% of the total population, whereas systolic dysfunction was found in only 6.0%. Redfield and colleagues established that nearly 6% of patients had moderate to severe diastolic dysfunction. The incidence increases with age, and at any given age, it is more common among women by a factor of 2 to 1. It is associated with multiple comorbidities, such as hypertension, diabetes mellitus, obesity, coronary heart disease (CHD), and infiltrative cardiomyopathies ( Fig. 37.1 ). The prevalence of these comorbidities in diastolic dysfunction has been established through multiple large-scale, cross-sectional studies ( Table 37.1 ). Multiple population-based studies showing that 40% to 50% of all patients with congestive heart failure (CHF) can have a normal EF. As noted earlier, the term HFpEF is increasingly applied to this syndrome. The prevalences of preclinical (i.e., no diagnosis of CHF before participation in the study) diastolic dysfunction were 20.6% for mild diastolic dysfunction and 6.8% for moderate to severe diastolic dysfunction. In a high-risk population (age at least 65 years of age plus presence of hypertension or coronary artery disease [CHD]), the prevalence of preclinical diastolic dysfunction increased significantly to 47.6% in mild diastolic dysfunction and 16.5% in moderate to severe diastolic dysfunction. Table 37.2 lists the conditions resulting in diastolic dysfunction as well as their predominant mechanisms.