Evaluation of left ventricular diastolic function: state of the art after 35 years with Doppler assessment
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Left ventricular (LV) diastolic function can be evaluated by echocardiographic indices of LV relaxation/restoring forces, diastolic compliance, and filling pressure. By using a combination of indices, diastolic function can be graded and LV filling pressure estimated with high feasibility and good accuracy. Evaluation of diastolic function is of particular importance in patients with unexplained exertional dyspnea or other symptoms or signs of heart failure which cannot be attributed to impaired LV systolic function and to assess filling pressure in patients with heart failure and reduced LV ejection fraction. Furthermore, grading of diastolic dysfunction can be used for risk assessment in asymptomatic subjects and in patients with heart disease.
KeywordsLeft ventricular diastolic function Heart failure with preserved ejection fraction Pulmonary venous velocities Mitral velocities Left atrial pressure Left ventricular filling pressure
Left ventricular systolic function is evaluated clinically by measuring left ventricular (LV) ejection fraction (EF) and more recently by strain imaging as a supplementary method. Evaluation of LV diastolic function is more challenging, and a number of different noninvasive approaches have been proposed. Recently, important consensus was reached regarding use of echocardiography to assess diastolic function , and two large multicenter studies using invasive pressure measurement as reference method confirmed the validity of the new recommendations as a means to diagnose heart failure with preserved ejection fraction (HFpEF) [2, 3]. However, appropriate use and interpretation of echocardiographic indices of diastolic function require understanding of the physiology of LV filling. The present article reviews key elements of this physiology and how echocardiography can be used to diagnose diastolic dysfunction and identify elevated LV filling pressure in patients with suspected HFpEF.
Introduction to diastolic function
The transmitral pressure gradient represents the driving force for transmitral flow and, therefore, as illustrated in Fig. 2, mitral velocity increases as long as the pressure gradient is positive, and peak velocity occurs when the pressure gradient is zero. Then the gradient reverses, and the negative gradient represents the force which decelerates mitral flow. The etiology of the L-velocity is not entirely clear, but it is associated with elevated LV diastolic pressure and impaired myocardial relaxation . As seen in Fig. 2, after the sharp E deceleration, mitral flow continues during diastasis with no measurable pressure gradient. Velocity with no pressure gradient may represent inertia of E and possibly in part momentum-driven flow due to blood entering the LA from the pulmonary veins during diastasis.
The pulmonary venous D-velocity coincides with the transmitral E-velocity, and its magnitude is determined by essentially the same factors that modify mitral E. In normal individuals, the pulmonary venous S is usually higher than D. With advanced LV diastolic function which is characterized by elevated mitral E-velocity, there is typically elevated D velocity, and for reasons explained in the previous paragraph, there is reduced S-velocity. Therefore, the S/D ratio is usually <1 in patients with heart failure and elevated LV filling pressure. Young healthy subjects with excellent LV relaxation may also have S/D < 1, but in contrast to patients with advanced diastolic dysfunction, there is not a marked A r. With increasing LV diastolic pressure, which leads to reduction in operative LV compliance, atrial contraction pushes an increasing volume of blood back into the more compliant pulmonary veins, and this is evident as increase in peak value and duration of A r [7, 8].
Preload and filling pressure
The terms LV preload and LV filling pressure are often used interchangeably when discussing cardiac function, and in most clinical conditions there are concordant changes in the two parameters. Preload refers to how much the myocardium is stretched prior to contraction and is linked to the Frank–Starling law and sarcomere length. The term LV filling pressure refers to the pressure that fills the left ventricle and is used differently depending upon which pressure is available. Both LA mean pressure and LV end-diastolic pressure are used to represent LV filling pressure, but the latter should be preferred when the focus of the study is LV mechanical function. Direct measurement of LA pressure is rarely feasible, but it can be estimated as pulmonary capillary wedge pressure (PCWP) during right heart catheterization and as LV pre-a wave pressure during LV catheterization  (Fig. 2).
There are a few important clinical conditions in which LV end-diastolic pressure and left atrial mean pressure do not represent preload. First, in patients on mechanical ventilation and positive end-expiratory pressure (PEEP), there is reduction of LV end-diastolic volume, but elevation of LV end-diastolic pressure due to increase in extracardiac pressure (pericardial pressure). In these patients, LV preload can be measured as transmural end-diastolic pressure, which is the effective filling pressure. Since pericardial pressure can be approximated as mean right atrial pressure , LV transmural filling pressure during PEEP can be calculated as PCWP minus mean right atrial pressure . Another example of divergence between LV end-diastolic pressure and preload is in heart failure patients receiving intravenous vasodilator therapy. Then there may be marked acute reduction in LV diastolic pressures with little or no change in end-diastolic volume, and the reduction in LV end-diastolic pressure has been ascribed to reduction in pericardial pressure .
Relaxation, restoring forces, and diastolic compliance
Typical for normal diastolic function is rapid relaxation and vigorous restoring forces which result in low or even negative minimum LV diastolic pressure, causing high mitral pressure gradient and dominance of early diastolic LV filling. Myocardial relaxation reflects rate of calcium reuptake from the cytosol. Restoring forces reflect LV systolic function and are generated when the ventricle contracts below its unstressed volume, analogous to manual compression of a tennis ball which recoils back to its original round shape when compression is released. When there is normal rapid LV relaxation, restoring forces generate negative minimum diastolic pressures and imply that the LV wall performs work to pull blood into the ventricle, representing filling by suction. There is also an alternative definition of suction, which is LV filling during falling pressure, which does not include negative LV pressure or release of restoring forces. This definition also is useful, as shown in studies of LA filling, as illustrated in Fig. 3.
Left ventricular diastolic compliance is a lumped parameter and is determined not only by LV myocardial compliance, but also by elastic properties of extraventricular structures (pericardium and lungs) and by right ventricular diastolic pressure. The term LV chamber compliance is often used rather than just LV compliance, with the latter referring to myocardial compliance. Because the LV pressure–volume relationship is curvilinear, chamber compliance is a function of the operative LV diastolic pressure. As an example, elevation of LV diastolic pressure by volume loading, which moves the LV pressure–volume coordinate to a steeper part of the pressure–volume curve, causes reduction in chamber compliance in a ventricle which is entirely normal. Therefore, reduced chamber compliance does not necessarily mean there has been a change in myocardial elastic properties. Figure 5 shows diastolic pressure–volume curves from a group of normal individuals compared with patients with heart failure and preserved EF and reduced EF, respectively.
Reduction in LV chamber compliance is also reflected in attenuation and abbreviation of the transmitral A velocity and is typically combined with accentuation and prolongation of the pulmonary vein A r [7, 8]. When the atrium contracts against a ventricle with reduced compliance, little blood moves forward across the mitral valve, antegrade mitral flow is interrupted prematurely, and instead blood regurgitates into the more compliant pulmonary veins. When the duration of A r exceeds the duration of mitral A by >30 ms, it is consistent with elevated LV end-diastolic pressure. The limitations of A duration difference as an index of diastolic compliance include atrial mechanical failure and suboptimal quality of the pulmonary venous flow signal. Furthermore, even in patients with severe diastolic dysfunction, a large A r may be absent when there is prolonged atrioventricular conduction or tachycardia, so that atrial contraction takes place before diastolic pulmonary venous flow (D) is completed. In these cases, the difference in A duration does not reflect LV filling pressure.
Thus, a short mitral E deceleration time together with a small and abbreviated mitral A and a large A r of long duration are consistent with reduced LV compliance.
Left atrial volume and strain
Whereas Doppler-derived diastolic indices reflect LV filling pressures at the time of measurement, LA volume reflects the cumulative (chronic) effect of LV filling pressures over time in patients who are in sinus rhythm and do not have mitral disease, anemia, or other high-output states. LA volume >34 mL/m2 is considered enlarged . There is also an overlap of LA volume between healthy individuals and subjects with diastolic dysfunction, and LA volume can be increased in elite athletes.
More recently, global LA strain by two-dimensional (2D) speckle tracking echocardiography was introduced as a promising supplementary marker of LV filling pressure. Elevated LA pressure is associated with low values for LA reservoir strain. The incremental value of measuring LA strain remains to be defined, but preliminary data from smaller studies are promising.
Left ventricular geometry and strain
In patients with heart failure symptoms and normal LVEF, the finding of LV hypertrophy favors HFpEF as diagnosis. After introduction of strain imaging by speckle tracking echocardiography, it became apparent that patients with normal LVEF may have mildly reduced LV systolic function by global longitudinal strain. Therefore, LV strain imaging represents a supplementary test which is useful when echocardiographic indices of diastolic function are inconclusive and it is not clear whether the patient suffers from heart disease. Reduced global longitudinal strain provides support in favor of heart disease as underlying mechanism of symptoms.
Diastolic dysfunction is present in arterial hypertension, diabetes mellitus, obesity, and in a large number of cardiovascular disorders often at a preclinical stage, and is part of normal aging. Diastolic dysfunction may be graded as illustrated in Fig. 7. Since transition from normal function to diastolic dysfunction is gradual, it is not obvious what should be used be used as criteria for diastolic dysfunction. In the recent American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) recommendations, diastolic dysfunction was considered present when more than 50 % of the parameters e′, E/e′, LA volume index, and peak tricuspid regurgitation velocity were positive . This relatively strict definition was chosen to make the criteria more specific than in previous guidelines, but implies reduced sensitivity. Importantly, this recommendation is based on expert opinion and has not been validated against invasive reference methods for diastolic dysfunction.
When the purpose of the study is to determine whether a patient has elevated LV filling pressure, the ASE/EACVI guideline recommends using the algorithm presented schematically in Fig. 9. The rationale behind the conclusion that LA pressure is normal when mitral E is <50 cm/s combined with E/A < 1 is that a low E implies a small transmitral pressure gradient. The combination with E/A < 1 confirms that E is low also when compared with A. When E is tall and much higher than A, it implies a high transmitral gradient, which in turn implies high LA pressure. One exception is young healthy individuals, who may have negative early diastolic pressure and therefore high gradient and tall E with normal LA pressure. For intermediate mitral filling patterns, the recommendation is to use E/e′, LA volume, and peak TR velocity in combination (Fig. 9). The reason why elevated E/e′ is useful is because combination of high transmitral gradient (high E) on top of elevated minimum LV diastolic pressure (suggested by low e′) means high LA pressure. Large LA reflects long-term effect of elevated LA pressure. High TR regurgitation velocity implies high pulmonary artery systolic pressure. It was recently confirmed in two large multicenter studies that this algorithm can identify patients with elevated filling pressure with high feasibility and good accuracy [2, 3].
A common misinterpretation of the ASE/EACVI guideline  is that evaluation of filling pressure should start with a diagnostic algorithm to determine whether the patient has diastolic dysfunction or not. This is not needed when there is clinical suspicion of heart disease; Then one can go directly to the algorithm in Fig. 9. In a similar way as in HFpEF, the algorithm in Fig. 9 can be used to assess filling pressure in patients with reduced EF [1, 2].
When evaluating patients with potential HFpEF, one should always search to exclude diseases such as valve disease, coronary artery disease, pericardial disease, and right-sided heart disease before it is concluded that a patient suffers from HFpEF. Furthermore, since LV diastolic pressure may be entirely normal at rest in HFpEF, a noninvasive and sometimes invasive diastolic stress test is recommended when there is inconsistency between symptoms of heart failure and echocardiographic findings at rest [23, 24]. Importantly, one should consider pericardial disease as underlying disorder .
Pulmonary artery pressure
When pulmonary hypertension is observed in combination with signs of LV disease, it is consistent with elevated LV filling pressure. Pulmonary artery systolic pressure can be estimated in most patients by continuous wave Doppler of tricuspid regurgitation velocity and an estimate of right atrial pressure.
When the tricuspid velocity cannot be imaged or the peak of the velocity is not well defined, pulmonary artery acceleration time may be used as an index of elevated pulmonary artery pressure and is measured with high feasibility as the time interval between the onset and peak pulmonary arterial systolic flow velocity . Values <100 ms are consistent with elevated mean pulmonary artery pressure.
In patients with unexplained exertional dyspnea or other symptoms or signs of heart failure which cannot be attributed to reduced LV systolic function or to diseases such as coronary artery disease, valve disease, pulmonary vascular disease, lung disease or other diseases.
To determine if LV filling pressure is elevated in patients with heart failure and reduced LV ejection fraction when considering adjustment of diuretics or other heart failure medication.
Grading of diastolic function can be used for risk assessment in asymptomatic subjects and in patients with heart disease.
Compliance with ethical standards
Conflict of interest
There are no conflicts of interest.
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