Abstract
Echocardiography plays a central role in the assessment of left ventricular (LV) diastolic function, which is often a challenging task for the clinician. Normal diastolic function allows for the left ventricle to sufficiently fill and to generate the necessary stroke volume without exceeding certain pressure limits during filling. Diastolic dysfunction primarily results from increased resistance to ventricular filling, leading to an upward and leftward shift of LV pressure volume relation, often during exercise or tachycardia. The physiological hallmarks of LV diastolic dysfunction are impaired relaxation, loss of restoring forces, reduced diastolic compliance, and elevated filling pressure. When LV and left atrial pressures start to increase, patients may develop dyspnea and/or pulmonary congestion. The assessment of diastolic function has become particularly relevant, as approximately half of patients with heart failure have normal or near normal ejection fraction, a condition in which diastolic dysfunction is thought to be a key pathophysiologic mediator. Diastolic function is multifaceted, and there is no one echocardiographic measure that fully captures diastolic dysfunction. In this chapter, we review the measures routinely employed in the clinical evaluation of diastolic function and recommended by professional society guidelines, including mitral inflow Doppler, tissue Doppler early relaxation velocities, E / e ′ ratio, left atrial size, and pulmonary pressure. We also review approaches to integrating these measures into an assessment of diastolic dysfunction and/or grade of dysfunction. By using combination of different echocardiographic indexes, diastolic performance can be reasonably estimated in most patients.
Keywords
diastolic function, Doppler, filling pressures, left atrial size, tissue Doppler
Introduction
Echocardiography plays a central role in the assessment of left ventricular (LV) diastolic function, which is often a challenging task for the clinician. Normal diastolic function allows for the LV to sufficiently fill and to generate the necessary stroke volume without exceeding certain pressure limits during filling. Diastolic dysfunction primarily results from increased resistance to ventricular filling, leading to an upward and leftward shift of the LV pressure volume relation, often during exercise or tachycardia. The physiological hallmarks of LV diastolic dysfunction are impaired relaxation, loss of restoring forces, reduced diastolic compliance, and elevated filling pressure. When LV and left atrial (LA) pressures start to increase, patients may develop dyspnea and/or pulmonary congestion. The assessment of diastolic function has become particularly relevant, as approximately half of patients with heart failure have normal or near normal ejection fraction (HFpEF), a condition in which diastolic dysfunction is thought to be a key pathophysiologic mediator. Diastolic function is multifaceted, and there is no one echocardiographic measure that fully captures diastolic dysfunction. However, by using a combination of different echocardiographic indexes, diastolic performance can be reasonably estimated in most patients.
What is Diastolic Function and Dysfunction?
For normal cardiac performance, the LV should be able to eject an adequate stroke volume at arterial pressure (systolic function) and fill without requiring elevated LA pressure (diastolic function). Systolic and diastolic function must be adequate to meet the needs of the body both at rest and during stress. Diastole denotes the portion of the cardiac cycle between aortic valve closure and subsequent mitral valve closure, during which time the myocardium does not generate force or shorten and returns to its unstressed length ( Fig. 15.1 ). Diastolic function consists of both an early period of active relaxation, which is an adenosine triphosphate-dependent process that is also partially dependent on diastolic suction or restoring forces, and diastolic chamber compliance, which is operant throughout the diastolic period and determined by the elastic properties of the myocardium. Traditionally, these two aspects of diastolic function were evaluated by invasive hemodynamic assessment: the isovolumic relaxation rate of pressure decline (tau) as a measure of active relaxation, and the LV diastolic pressure-volume relationship as a measure of compliance ( Fig. 15.2 ). Impairment in active relaxation results in prolongation of the tau, while decrease in LV diastolic compliance is reflected in an upward and leftward shift of the LV pressure-volume relationship ( Fig. 15.3 ). Impairments in either or both of these components of LV diastolic performance can lead to slowed or incomplete LV diastolic filling, unless also accompanied by an increase in LA pressure. However, these methods are invasive, resource intensive, and not practical for routine or widespread clinical application.
Echocardiographic Measures of Diastolic Performance
Echocardiography allows for the noninvasive evaluation of LV diastolic performance and diastolic filling pressure with use of conventional two-dimensional (2D) imaging combined with spectral, tissue, and color Doppler. Several echocardiographic measures have been proposed as markers of diastolic performance. In the following sections, we will review the measures routinely employed in the clinical evaluation of diastolic function and recommended by professional society guidelines.
Transmitral Doppler: E Wave Peak Velocity, A Wave Peak Velocity, and E/A Ratio
Pulsed wave spectral Doppler allows for the assessment of the instantaneous LA-to-LV pressure gradient throughout the diastolic period and characterization of patterns of LV diastolic filling (see Fig. 15.1 ). Mitral inflow Doppler should be obtained from the apical four-chamber view with color flow imaging to optimally align the pulse wave sample volume (1–3 mm) between the tips of the mitral leaflets. The E wave is the peak early filling velocity, a measure of the peak LA to LV diastolic pressure gradient, and is therefore influenced by LA pressure at mitral valve opening, minimal LV diastolic pressure, compliance of the LA, and the rate of LV relaxation. The rate of decrease of velocity following the E wave is measured as the deceleration time ( Fig. 15.4 ). The A wave is the velocity at atrial contraction (AC), which usually occurs after relaxation is completed, and is influenced by LV chamber compliance and the volume and contractility of the left atrium. The normal mitral flow pattern (i.e., the height of the E wave and A wave, and the relationship between these) varies with loading conditions, age, and heart rate. In a normal middle-aged subject, the E velocity is slightly larger than the A velocity, and the deceleration time is 200 ± 40 ms. Mitral inflow E / A ratio and deceleration time (DT) have been used to define LV filling patterns as normal, impaired relaxation, pseudonormal, and restrictive filling, which correspond to progressively higher filling pressure ( Fig. 15.5 ). The age dependency of normal for these filling patterns cannot be overstated. The definitions provided below apply primarily to persons in middle age.
“Impaired relaxation,” also termed mild or grade 1 diastolic dysfunction, is characterized by a transmitral flow pattern with a low E wave, high A wave, low E / A ratio, and a prolonged deceleration time. These findings reflect a slower rate of decrease of LV early diastolic pressure, such that the duration of relaxation is prolonged into mid- or even late diastole, in the absence of elevation in LA pressure. As a result, early diastolic driving force across the mitral valve is reduced and the E wave is lower. There is a compensatory increase in transmitral flow at AC from the high residual atrial preload, resulting in a high A wave.
Worsening diastolic dysfunction is characterized by progressive decrease in the effective operative LV chamber compliance resulting in increased mean LV and LA diastolic pressures. A high LA pressure at the time of mitral valve opening and a large LA–LV gradient in early diastole results in a high E wave, shortened deceleration time, and higher E / A ratio, producing a pattern similar to a normal inflow pattern and termed “pseudonormalized.” Until the advent of tissue Doppler imaging (TDI; see later), distinguishing a normal from a “pseudonormal” pattern relied on pulmonary vein Doppler patterns (see below) and changes in the inflow pattern associated with the Valsalva maneuver, which decreases preload during the strain phase. A decrease of 50% in the E / A ratio with Valsalva is highly specific for a pseudonormal filling pattern ( Fig. 15.6 ).
Finally, the restrictive filling pattern, due to advanced abnormality of LV compliance and markedly elevated LA pressure, is characterized by a high E wave, a short deceleration time, and a small A wave. An E wave greater than twice the A wave amplitude or a deceleration time <150 ms identifies a restrictive pattern of filling.
Limitations to assessing LV filling patterns with peak E and A waves, and E / A ratio, include sinus tachycardia and first-degree atrioventricular (AV) block, which can result in partial or complete fusion of the E and A waves. Also, as previously mentioned, age must be acknowledged when assessing diastolic function, as filling patterns in even healthy elderly persons at low risk for heart failure may resemble mild diastolic dysfunction in younger patients. With increasing age, the mitral E velocity and E / A ratio decrease, while DT and A velocity increase.
Tissue Doppler Imaging e ′
Tissue Doppler-based mitral annular early relaxation velocity ( e ′) is a measure of the rate of early diastolic lengthening of LV. As the change in length of the LV has a direct relationship with the change in volume of the LV, e ′ is a correlate of the d V /d t and of tau. As such, e ′ reflects both LV restoring forces and active relaxation. Lower e ′ is related to worse diastolic function in a monotonic fashion, and e ′ is therefore helpful in discerning normal from pseudonormal mitral inflow patterns as noted above ( Fig. 15.7 ). As TDI measures the low-velocity, high-amplitude signal of myocardial tissue, high-velocity and low-amplitude signals of blood must be filtered. Annular velocities are typically measured at both the septal and lateral aspects of the mitral annulus in the apical four-chamber view ( Fig. 15.8 ). Similar to standard Doppler, the accuracy of tissue Doppler is dependent on a parallel angle of incidence of the ultrasound beam to myocardial motion. Therefore, the longitudinal motion of the LV must be optimally aligned with the ultrasound beam, and the tissue Doppler sample volume (typically 5–10 mm axial size) must be appropriately placed at the level of annulus. Septal e ′ is normally lower than lateral e ′. Per American Society of Echocardiography (ASE) 2016 guidelines, the abnormal values are considered: septal e ′ < 7 cm/s and lateral e ′ < 10 cm/s. These cutpoints are likely most relevant to a middle-aged population.
Despite early data to the contrary, e ′ is affected by both preload and afterload. However, in the context of LV systolic dysfunction, e ′ appears less load dependent than the transmitral velocities. Importantly, similar to the E / A ratio, prominent age-associated changes in the e ′ have been repeatedly observed in population-based studies. Older age is associated with lower septal and lateral e ′ values, even among persons free of cardiovascular disease or risk factors. At the writing of this chapter, it remains unclear whether these age-associated changes are prognostically benign or represent malignant cardiac senescence, although their presence even among persons at low clinical risk for incident cardiovascular disease perhaps suggests the former. Regardless, these age-related changes make interpretation of e ′ in the elderly particularly challenging, particularly as existing guideline recommendations for defining abnormal e ′ do not necessarily recognize these age-related differences.
E / e ′ Ratio
The early diastolic transmitral flow by Doppler ( E wave) reflects the early diastolic LA to LV pressure gradient and is therefore affected by both LA pressure and LV early diastolic relaxation. As e ′ is primarily a measure of early diastolic relaxation, dividing the E wave by e ′ ( E / e ′ ratio) provides an estimate of LA pressure. One advantage of E / e ′ ratio over the E / A ratio as an index of LV filling pressure is that it is monotonically related to LA pressure. Several studies have demonstrated robust correlation between E / e ′ ratio and invasively measured LV pressure in patients with heart failure. However, several studies in patients with less pronounced abnormalities of LV filling pressure have failed to demonstrate a robust association of E / e ′ with LA pressure or pulmonary artery wedge pressure (PAWP) or of changes in E / e ′ with changes in PAWP. Therefore, this measure is likely most useful in evaluating LV filling pressure when either clearly high or low.
As TDI e ′ is typically lower at the septal annulus than the lateral annulus, E / e ′ is normally lower when using the lateral e ′ compared to the septal e ′. Per ASE 2016 guidelines, abnormal values for E / e ′ include: average E / e ′ ratio >14, lateral E / e ′ ratio >13, and septal E / e ′ ratio >15. Importantly, conditions that alter either early diastolic transmitral flow (significant mitral regurgitation or stenosis, prior mitral repair or replacement) or e ′ (e.g., pericardial disease) make the E / e ′ ratio less reliable.
Left Atrial Size
Doppler-based measures reflect instantaneous pressure gradients and myocardial motion. In contrast, LA size is felt to be more stable over time, with LA enlargement reflective of chronic elevations in LA pressure and (in the absence of significant mitral valve disease) LV diastolic pressure. LA size can be measured by the LA anterior-posterior dimension in the parasternal long axis view or the LA maximal volume using the biplane Simpson’s method or the area-length method from the apical four-chamber and two-chamber views at end systole. As chamber size varies physiologically with body size, current guidelines favor the use of the LA volume indexed to body surface area as the primary measures of LA size in evaluating diastolic function. Per ASE 2016 guidelines, LA volume index >34 mL/m 2 is considered abnormal.
Color M-Mode Propagation Velocity
In the setting of diastolic dysfunction, the rate of propagation of blood into the LV is diminished, a phenomenon that can evaluated by color M-mode Doppler echocardiography performed in the apical four-chamber view ( Fig. 15.9 ). Color M-mode Doppler recordings show the early diastolic LA to LV flow stream, the slopes of which are functions of the transit rate of intracardiac LV filling. Color M-mode Doppler recordings exhibit a striking reduction in the slope of early filling with restrictive diastolic dysfunction and a milder reduction in the presence of impaired relaxation. Flow propagation velocity (Vp) is measured as the slope of the first aliasing velocity during early filling, measured from the mitral valve plane to 4 cm into the LV cavity. Alternatively, the slope of the transition from no color to color can be measured. Vp >50 cm/s is considered normal. In most patients with depressed LV ejection fraction (LVEF), Vp is reduced, and should other Doppler indices appear inconclusive, an E /Vp ratio >2.5 predicts PAWP >15 mm Hg with reasonable accuracy. The Color M mode Doppler is not routinely used in patients with normal LV volume and LVEF, where Vp may be normal despite elevated LV filling pressure.
