ASE/EACVI Diastolic Guidelines: Strength and Limitations

Definition and Grading of Diastolic Dysfunction

One important change from the ASE/EACVI 2009 to 2016 guidelines for evaluation of diastolic function is that the definition of diastolic dysfunction was changed. In the 2009 ASE/EACVI guidelines, diastolic dysfunction was defined according to Fig. 19.6 and included a scheme for grading of diastolic dysfunction as mild (grade I), moderate (grade II), and severe (grade III). In the 2009 ASE/EACVI guidelines, the idea was that grade I diastolic dysfunction (mitral E/A <0.8) represented mainly patients with normal LV filling pressure, grade II (E/A 0.8–1.5) mild to moderate elevation of LV filling pressure, and grade III (E/A >1.5) patients with more marked elevation of LV filling pressure. In addition to mitral E/A, other Doppler indices that are related to filling pressure were used as criteria for grading (see Fig. 19.6 ).

In the 2016 guidelines, diastolic dysfunction is defined according to the scheme in Fig. 19.7 , which represents a simplification relative to the 2009 guidelines. There are four criteria in the 2016 definition of diastolic dysfunction, with cutoff values for three of these criteria being consistent with elevated LV filling pressure. Therefore, even for patients with mild diastolic dysfunction, elevated LV filling pressure is probably present in many if not most subjects. For patients with reduced EF, it is assumed that there is coexisting diastolic dysfunction. Therefore patients with reduced EF are not included in the scheme for diagnosis of diastolic dysfunction. This is also the case in patients where the presence of diastolic dysfuncion for other reasons is likely, for instance in patients with LV hypertrophy. One problem with the algorithm to define whether there is diastolic dysfunction in the 2016 ASE/EACVI guidelines is that with four parameters, many patients remain unclassified, as they have two positive and two negative parameters.

With regards to grading, the 2016 guidelines recommend as a first step to use the algorithm in Fig. 19.7 to determine if there is diastolic dysfunction. The second step is to determine the grade of dysfunction by using the algorithm in Fig. 19.4B . By definition, grade I refers to patients without elevated LV filling pressure and grades II and III to diastolic dysfunction with elevated LV filling pressure. Furthermore, grade III is differentiated from grade II by a restrictive mitral filling pattern.

After the publication of the 2016 ASE/EACVI guidelines, there was debate regarding the definition of diastolic dysfunction. Since the definition used in the 2016 guidelines is based mainly on markers of elevated LV filling pressure, this definition would favor more advanced , diastolic dysfunction than the 2009 guidelines. Fig. 19.8 illustrates how this difference in diagnostic criteria alters the prevalence of diastolic dysfunction. In a study of 1000 apparently heart healthy individuals with a mean age of 62 years, Almeida et al. confirmed that the prevalence of diastolic dysfunction was much lower when using the 2016 guidelines than the 2009 recommendations. Only 1% had diastolic dysfunction with the 2016 recommendations as compared to 38% when using the 2009 recommendations. This observation is consistent with the study of Huttin et al.

Therefore, when applying the 2016 ASE/EACVI recommendations, the prevalence of diastolic dysfunction is much lower than with the 2009 recommendations, reflecting that the specificity is much higher, apparently at the cost of sensitivity. These differences do not necessarily imply limitations of the different versions of the ASE/EACVI guidelines but have a major impact on prevalence data.

Redfield et al. used a grading system somewhat similar to the 2009 version of the ASE/EACVI guidelines, showing in a cross-sectional survey that mild diastolic dysfunction was associated with increased mortality. The prevalence of diastolic dysfunction was 28%, and of these 4.5% had clinical evidence of congestive heart failure. This included 21% with mild diastolic dysfunction, defined as filling pattern of impaired LV relaxation. The latter group would not be identified by the ASE/EACVI 2016 recommendations, which are less suited to identify early stage diastolic dysfunction.

The validity and rationale for the grading scheme in the 2009 ASE/EACVI guidelines were challenged by a study that showed a relatively weak relationship between grades of diastolic dysfunction and LV filling pressure. As shown by several studies, the criteria and cutoff values for diastolic dysfunction used in the 2016 version of the ASE/EACVI guidelines are relatively strong markers of elevated filling pressure. The validity of relating grading based on the 2016 recommendations to filling pressure is supported by the study of Andersen et al., which showed that LV filling pressure differed significantly when comparing the three grades of diastolic dysfunction. It increased from 10 mmHg in grade I (interquartile range [IQR]: 7–12 mmHg) to 18 mmHg in grade II (IQR: 14–24 mmHg) and 24 mmHg in grade III (IQR: 19–30 mm Hg) (grade I vs. grade II: p < 0.001; grade I vs. grade III: p < 0.001; and grade II vs. grade III: p < 0.006 by the Dunn method).

Since elevated LV filling pressure is a compensatory mechanism, a diagnosis of diastolic dysfunction according to the 2016 guidelines will tend to reflect more advanced diastolic dysfunction. The utility of the relatively high specificity of the 2016 ASE/EACVI definition was demonstrated in a recent study, which showed that patients undergoing transcatheter aortic valve replacement (TAVR) had markedly increased cardiovascular risk when there was diastolic dysfunction.

The issue of what is an optimal definition of diastolic dysfunction depends entirely on the purpose of the study. As shown in several studies, the demonstration of mild diastolic dysfunction provides important prognostic information, which may be lost when using the 2016 ASE/EACVI definition of diastolic dysfunction. On the other hand, it is likely that the 2016 definition will help to identify patients with the highest risk; this may be important in clinical practice, as suggested by the study of TAVR patients. The 2016 EACVI/ASE guidelines were written with the intent of increasing specificity, which explains the lower prevalence of diastolic dysfunction. A strength of the 2016 ASE/EACVI guidelines is that the parameters E/e′, LA volume, and systolic pulmonary artery pressure, which are used in the definition, are all relatively age independent.

The next step is to determine in outcome studies how evaluation of diastolic function can be utilized to improve patient management. Due to the change in definition of diastolic dysfunction, it would be of particular interest to investigate whether identification of early stage diastolic dysfunction has clinical consequences.

Diagnosing HFpEF and Estimation of LV Filling Pressure

LV filling pressure refers to the pressure that fills the ventricle and is used differently depending on which pressure is available and what the purpose of the study is. When the issue is pulmonary congestion, the most relevant pressure is mean LA pressure, which may be approximated as pulmonary capillary wedge pressure (PCWP) and as LV pre-atrial contraction (pre-A) pressure. When the issue is LV mechanical function, however, LV end-diastolic pressure (EDP) (ideally transmural end-diastolic pressure), which represents LV preload, is the preferred parameter of LV filling pressure. All these parameters are valid measures of LV filling pressure, although their relationships to Doppler parameters are slightly different. Fig. 19.9 illustrates how the different pressures are acquired.

Since early symptoms of heart failure are often nonspecific, an accurate noninvasive method to estimate LV filling pressure would be of great clinical value. The ASE/EACVI task force presented an algorithm for evaluating LV filling pressure (see Fig. 19.4 ). The algorithm suggested the use of four echocardiographic parameters to determine whether LV filling pressure was elevated:

• 1.

  The ratio between early mitral inflow velocity (E) and atrial-induced mitral inflow velocity (A) (E/A), and peak E velocity

• 2.

  The ratio between early mitral inflow velocity (E) and early mitral annular velocity (e′) (E/e′)

• 3.

  Peak TR velocity

• 4.

  LA volume indexed to body surface area (LAVI)

This algorithm was recently tested in two large multicenter studies, which used invasive filling pressure as the reference method. Lancellotti et al. in the Euro-Filling study investigated 159 patients at nine European centers with simultaneous evaluation of echo estimates of filling pressures and invasive measurements of LVEDP. Additionally, the ASE/EACVI recommendations from 2009 were compared to the 2016 recommendations. The study showed that the 2016 recommendations for noninvasive assessment of LV filling pressure were reliable and clinically useful and, importantly, superior to the 2009 recommendations for estimating invasive LVEDP. In the other study, Andersen et al. included 450 patients in a multicenter trial with PCWP in 293 patients and LV pre-A pressure in 157 patients as references. The study demonstrated that the ASE/EACVI recommendations for echocardiographic assessment of LV filling pressure are readily available and can be performed with high feasibility and good accuracy. These two studies confirm that the new ASE/EACVI recommendations are clinically valuable and accurate and therefore very helpful in making a correct diagnosis of our patients. The algorithm for estimation of LV filling pressure may be applied in patients with normal LV EF and unexplained exertional dyspnea, and in patients with heart failure with reduced ejection fraction (HFrEF) when considering adjustment of diuretics or other medication.

The rationale behind the conclusion that LA pressure is normal when mitral E is less than 50 cm/sec combined with an E/A less than 0.8 is that a low E implies a small transmitral pressure gradient. The combination with E/A less than 0.8 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 a 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 (see Fig. 19.4 ). The reason why elevated E/e′ is useful is because the combination of a high transmitral gradient (high E) on top of elevated minimum LV diastolic pressure (suggested by low e′) means high LA pressure.

An enlarged LA reflects the long-term effect of elevated LA pressure. High TR regurgitation velocity implies high pulmonary artery systolic pressure, which in the absence of either pulmonary disease or pulmonary vascular disease reflects elevated LV filling pressure.

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.

A limitation of this diagnostic algorithm is that patients with heart failure may have normal filling pressure at rest. However, when cardiac output increases with activity in these patients, it can only be done at the expense of elevated LV filling pressure. Therefore further development of a diastolic stress test is needed, in particular in patients with grade I diastolic dysfunction (see Chapter 18 ). In the 2016 ASE/EACVI guidelines, a diastolic stress test is recommended when resting echocardiography does not explain the symptoms of heart failure or dyspnea, especially with exertion. Fig. 19.10 shows how echocardiographic parameters change during activity as a reflection of elevated LV filling pressure.

A common misinterpretation of the ASE/EACVI guidelines is that echocardiographic evaluation of filling pressure should start with a diagnostic algorithm to determine whether the patient has diastolic dysfunction. This is not needed when there is clinical suspicion of heart disease. Then one can go directly to the algorithm used to decide whether LV filling pressure is elevated (see Fig. 19.4 ). This can be illustrated by our chapter-opening case study, where the patient presented with LV hypertrophy and dyspnea, both indicative of underlying cardiac disease. In a similar way this algorithm can be used to assess filling pressure in patients with reduced LV EF. Fig. 19.11 provides a flow chart of how to evaluate LV diastolic function, suggested by This flow chart demonstrates how a conclusion about diastolic function using the suggested algorithm can be reached in most patients, but also how further steps are sometimes needed to accurately diagnose patients. Of special notice, though many patients can be correctly classified as having normal or elevated LV filling pressure using a noninvasive approach, invasive measurement of PCWP, EDP, or pre-A pressure is still the gold standard to decide if heart failure is present.

Additional Parameters to Be Used in the Evaluation of Diastolic Function

The combination of echocardiographic parameters suggested to decide whether LV filling pressure is elevated had an accuracy of 87% when investigated in a large multicenter trial. This implies that a wrong conclusion about LV filling pressure was made in at least 1 in 10 patients. Therefore it is always important to interpret echocardiographic data on diastolic function in a clinical context. One should always consider symptoms and clinical findings such as auscultation of lungs, jugular veins, and peripheral edema. Furthermore, pulmonary congestion on chest x-ray and elevated proBNP provide strong support of elevated LV filling pressure.

Of note, the algorithm suggested in Fig. 19.4 should not be used when there is not clinical suspicion of heart failure.

Furthermore, novel echocardiographic parameters as LA reservoir strain and LV global longitudinal strain (GLS) have been shown to correlate well with LV filling pressure. A reduction in LA reservoir strain is consistent with, but does not represent standalone evidence of elevated LV filling pressure. A reduction in LV GLS does not in itself indicate diastolic dysfunction, but it represents important evidence of LV disease as a mechanism of symptoms. As shown in Fig. 19.11 , these parameters are of particular use when a conclusion about diastolic function cannot be made using the four parameters suggested for this purpose by the ASE/EACVI recommendations.