Evaluation of Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction (HFpEF)　― Is It Possible to Delineate the Phenotype of HFpEF? ―

Heart failure (HF) is classified according to left ventricular ejection fraction (LVEF), but HF with preserved EF (HFpEF) has a heterogeneous phenotype, which may result in failure to establish effective therapy.¹ We need to evaluate HFpEF from various aspects (Figure).

Figure.

Functional and structural abnormalities in heart failure with preserved EF (HFpEF) and echocardiographic parameters. Functional and structural abnormalities of the left ventricle (LV), left atrial (LA) dysfunction, and arterial stiffening interact to present the clinical picture of HFpEF. GLS, global longitudinal strain; LVMI, LV mass index; PV, pulmonary venous; RWT, relative wall thickness.

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The main mechanism of HFpEF is diastolic dysfunction, but diastolic function is not widely evaluated and has not been utilized as a determinant of the management of HFpEF in the real world of clinical practice, mainly because there are no definite diagnostic criteria of diastolic dysfunction.^2–6 Echocardiography is the method most used for noninvasive assessment of diastolic function, and there are many echocardiographic parameters of diastolic function, including the left ventricular (LV) inflow pattern (E wave velocity, A wave velocity, E/A ratio, deceleration time), early diastolic annular velocity (e’), E/e’, tricuspid regurgitation (TR) velocity, and pulmonary venous flow pattern. Each parameter has pitfalls and there is no single reliable index of diastolic function.⁷ The biggest problem in evaluating diastolic function is the existence of atrial fibrillation (AF) and patients with HFpEF include a significant number with AF. In patients with AF, disappearance of atrial contraction and irregular RR interval create difficulties in the evaluation of diastolic function. Previous studies of diastolic function and the prognosis of HFpEF usually exclude patients with AF,^3,5,6 which may not reflect the true picture of HFpEF. Furthermore, among the aforementioned echocardiographic parameters, E/e’, E/A, and TR velocity are not parameters of diastolic function per se, but parameters of filling pressure elevation induced by diastolic dysfunction; thus these parameters are largely influenced by the loading condition.

On the other hand, patients with HFpEF have a high prevalence of hypertension, diabetes mellitus, and renal dysfunction, and frequently show LV geometric abnormalities such as concentric remodeling, and concentric and eccentric hypertrophy. Pressure overload to the left atrium (LA) due to LV diastolic dysfunction may cause LA enlargement. It has been reported that geometric or structural abnormalities are stronger predictors of outcome in patients with HFpEF than diastolic function evaluated by Doppler echocardiography.³

The American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) guidelines in 2016⁷ recommended an algorithm for the diagnosis of LV diastolic dysfunction in patients with normal EF. With this algorithm, the existence of diastolic dysfunction is determined using 4 parameters: (1) average E/e’ >14, (2) septal e’ velocity <7 cm/s or lateral e’ velocity <10 cm/s, (3) TR velocity >2.8 m/s, and (4) LA volume index >34 mL/m². Because of the absence of a single reliable parameter of diastolic dysfunction, multiple parameters are integrated in the algorithm.

In this issue of the Journal, Oeun et al⁸ share their insights from the PURSUIT-HFpEF Registry, which is a prospective multicenter study of a large number of patients with HFpEF. The authors evaluated diastolic function using this algorithm and its relationship with outcome. Furthermore, they also evaluated LV geometry and the relationship between functional and structural abnormalities. The average age of the patients was 83 years, and 37.2% of the study population had AF. Among 1,024 enrolled patients, only 161 were excluded; thus, this study may reflect Japanese real-world clinical management of HFpEF with minimal selection bias. Diastolic dysfunction was seen in 48.0% of patients, while 22.7% of the study population had normal diastolic function according to the guideline algorithm. In patients with diastolic dysfunction, concentric geometry was frequently seen, but 25% had normal LV geometry. The presence of diastolic dysfunction, but not LV geometry, was an independent prognostic factor, including in patients with AF. These findings suggest the importance of evaluating diastolic function using echocardiography in patients with HFpEF. On the other hand, regarding the prognostic value of each echocardiographic parameter, average E/e’ >14 and TR velocity >2.8 m/s, but not septal e’ velocity <7 cm/s or lateral e’ velocity <10 cm/s, were strongly associated with outcome. The e’ is close to a parameter of diastolic function per se, but E/e’ and TR velocity are parameters of elevated LV filling pressure. At present, there are limitations in evaluating diastolic function per se with echocardiographic parameters.

Another mechanism of HFpEF is dysfunction of the LA, but data are limited on HFpEF from the standpoint of LA function. In an aging society, it is expected that the number of patients with LA dysfunction, “stiff LA syndrome”, will be increasing. Stiff LA is often associated with LV diastolic dysfunction, but isolated LA dysfunction may exist, which may present with a clinical picture of HFpEF. LA size and stiffness are not always in parallel, and LA stiffness has been reported to be associated with outcomes in HFpEF.⁹ Measurement of LA strain by speckle-tracking echocardiography is a promising method for evaluating LA function,¹⁰ but echocardiographic evaluation of LA function has not been widely conducted. About 20–30% of patients with HFpEF show normal LV diastolic function,^2,8 and in some of them, LA dysfunction may be the main mechanism of HFpEF.

Determining diastolic dysfunction with the guideline algorithm using 4 echocardiographic parameters remains imprecise, and about 20–30% of patients are classified into the indeterminate group. Integrating more echocardiographic and clinical parameters may achieve a better algorithm, but may increase the complexity. Therefore, a novel approach using deep-learning for more precise evaluation of diastolic function has recently attracted attention.^11,12 A deep-learning method can provide multiparametric integration of echocardiographic parameters to better delineate the phenotype of HFpEF and to achieve individualized management. A recent study¹¹ demonstrated the usefulness of deep-learning models for echocardiographic assessment of diastolic dysfunction. In the model, 9 routinely measured echocardiographic parameters were used: E wave velocity, A wave velocity, E/A ratio, septal e’, E/e’ ratio, LV mass index, TR velocity, LVEF, and LA volume index. The deep-learning model showed higher predictive value for elevated filling pressure and outcome than the algorithm in the 2016 ASE and EACVI guidelines. However, patients with AF were excluded from the study; thus, evaluation of diastolic dysfunction in patients with HFpEF, including those with AF, is still a challenging issue.

Disclosure

C.I. is a member of Circulation Journal’s Editorial Team.

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