Grading Diastolic Left Ventricular Function

This editorial refers to ‘Diagnosis of heart failure with preserved ejection fraction: which parameters and diagnostic strategies are more valuable?’, by X.-X. Shuai et al., published in this issue on page 737–745. The diagnosis of heart failure (HF) is based on symptoms and signs of HF, as well as evidence for a functional or structural abnormality of the heart. For patients with a reduced left ventricular ejection fraction (LVEF), the latter part of the diagnosis does not yield any problems. Assessment of LVEF can be easily performed with multiple techniques, including echocardiography. The diagnosis and treatment of diastolic heart failure (DHF) [or heart failure with a preserved ejection fraction (HFPEF)] is a much bigger challenge.1–3 In 1998, the first criteria for diagnosis of DHF were presented.4 At that time, DHF was believed to account for approximately one-third of all patients with HF. Diastolic heart failure was defined as signs or symptoms of congestive HF, normal or mildly reduced LVEF (≥45%), and evidence of abnormal LV relaxation, filling, diastolic distensibility or diastolic stiffness. The latter part of the diagnosis was evaluated by dimensional, volumic, or haemodynamic echocardiographic measurements indexed for body surface area or invasive LV measurements. In 2007, the European Society of Cardiology (ESC) published a consensus paper on how to diagnose DHF.5 The basis of the diagnosis of DHF remained more or less the same (signs or symptoms of HF, normal or mildly reduced LVEF (>50%)); however, the latter part was somewhat adjusted. At that time, relatively novel tissue Doppler imaging was more routinely used and validated, and biomarkers such as N-terminal pro-B-type natriuretic peptide obtained a prominent place beside the calculation of E/e’ in the recommended evaluation of DHF. Recent (2009) recommendations for echocardiographic evaluation of LV diastolic function from the European Association of Echocardiography (EAE) and American Society of Echocardiography (ASE) largely confirm the European consensus document from 2007. However, these recommendations focus on grading diastolic LV dysfunction rather than on the diagnosis of DHF. This document gives a good summary of all available measurements and their strengths and weaknesses in the evaluation of diastolic function as presented in the guidelines and consensus document.6 Despite these documents, echocardiographic criteria to establish diastolic dysfunction are still the topic of widespread discussion. In contrast to systolic dysfunction that can be evaluated through one measurement (LVEF), the diagnosis of diastolic dysfunction requires multiple measurements that all only partially correlate with the diagnosis. Furthermore, none of these measurements show 100% sensitivity and/or specificity, this always leaves an ‘intermediate group’ in which diastolic dysfunction can neither be acknowledged nor denied. In this issue of the European Journal of Heart Failure, Shuai et al.7 present a strategy to establish diastolic dysfunction by echocardiography. In their study, the authors evaluate several of the diastolic measurements proposed by the ESC, EAE, and ASE in a group of 236 subjects consisting of 48 healthy controls (subjects lacking signs of renal/pulmonary abnormality and no abnormalities on echocardiogram, chest X-ray, or blood tests), 87 patients with a hypertension without HF (screened on history of hypertension and/or echocardiographic signs of LV hypertrophy and/or enlargement or LA enlargement, without signs of HF), and 101 patients with HFPEF (defined as having history of hypertension and typical signs/symptoms of HF and LVEF ≥50%). The authors evaluated several echocardiographic measurements of diastolic function and different cut-offs on sensitivity and specificity. In general, all measurements showed decent specificity but moderate to low sensitivity except for left atrial volume index (LAVI) ≥28 mL/m2, which showed higher sensitivity than specificity. The authors concluded that a combination of E/e’-lateral ratio ≥12, left atrial volume index ≥34 mL/m2, and Ar–A >30 ms had a sensitivity of 77% and a specificity of 81% to diagnose HFPEF. Sensitivity and specificity were similar to the strategy proposed by Paulus et al.5 (sensitivity 72%, specificity 87%), albeit by a ‘simpler’ approach. It is however remarkable that the strategy proposed by Nagueh et al.6 showed only moderate sensitivity (47%) in this population. The current study confirms the findings of several other studies. Similar to previous studies, the authors showed that some measurements could not be obtained in a substantial number of patients. In particular, pulmonary vein flow was only achievable in 79% of patients, compared with almost 100% of tissue Doppler and mitral valve inflow parameters. This should be taken into account when applying these measurements in clinical practice. An important limitation of this study, however, is the lack of validation of echocardiographic abnormalities by the ‘gold standard’ of invasive pressure volume measurements. Instead, the authors evaluated diastolic function in patients with and without HF, but the diagnosis of HF should be based on diastolic function measurements as well. Several studies have shown that calculating E/e’ gives a well-validated estimation of LV end-diastolic pressures, and with this estimation a reliable differentiation can be made in patients in whom an increased left ventricular end-diastolic pressure (LVEDP) (E/e’ >15) or a normal LVEDP (E/e’ <8) is present. However, in the intermediate group (E/e’ 8–15) there is still the need for a method to either confirm or reject the presence of diastolic dysfunction. In the strategy proposed by Paulus et al. this is the preferred measurement for the diagnosis of HFPEF over all other echocardiographic measurements. In contrast, Nagueh et al. used measurements of e’ lateral (<10 cm/s), e’ septal (<8 cm/s), and LAVI (≥34 mL/m2). If these requirements are met, diastolic dysfunction is present. Consequently, if these requirements are not met, diastolic dysfunction is absent. When evaluating echocardiographic strategies, one should consider that all echocardiographic measurements are always subjected to the nature of echocardiography which relies heavily on image and measurement quality, and secondly on the physiology of LV diastolic function which is known to change gradually with age. This puts emphasis on the importance of the first part of the evaluation of diastolic dysfunction (i.e. signs/symptoms of HF).8 Furthermore, the prevalence of obesity and pulmonary disease in HF patients is high; this presents an additional possible negative effect on any echocardiographic examination (i.e. decreased image quality and problematic acquisition of curves at end-expiration). In addition, most echocardiographic measurements are volume dependent and we could therefore speculate that diastolic (dys)function fluctuates, which makes grading difficult. Therefore, the interpretation of echocardiographic diastolic measurements should always be based on a good balance between predictive value, sensitivity, and feasibility rather than on a short estimate of diastolic (dys)function. In the evaluation of echocardiographic diastolic LV function, it is necessary to acquire multiple echocardiographic variables. Currently, either e’ or E/e’ are considered to be the first parameters to establish, and to provide a first indication of the presence of diastolic dysfunction and/or elevated LV filling pressures. Additional measurements, such as left atrial volume index, mitral valve inflow parameters, and pulmonary flow measurements, should then provide additive information on the severity of LV diastolic dysfunction. Another option could be to create a scoring system, similar to the scoring method we know as the ‘Dukes criteria’ for infective endocarditis, dividing the best predictive echocardiographic measurement for LV diastolic dysfunction into major and minor criteria. In conclusion, the diagnosis of HFPEF should include evidence of diastolic dysfunction. The presence of diastolic dysfunction should be based on both major criteria (such as e’, E/e’, and LAVI) and minor criteria. Future studies should focus on finding evaluation strategies with higher sensitivity and specificity in the diagnosis of diastolic dysfunction. A promising development is two-dimensional speckle tracking and the validation of diastolic strain rate, and rotational and twist measurements in the evaluation of diastolic LV function. However, these methods need to be thoroughly validated before they can be incorporated into the clinical setting.