The prognostic impact of diastolic dysfunction in patients with chronic heart failure and post-acute myocardial infarction: Can age-stratified E/A ratio alone predict survival?

Abstract

Objective

To determine the prognostic implications of diastolic filling grades and identify whether age-stratified E/A ratio alone can identify patients at high risk of death post-AMI and HF. We hypothesized that in response to ageing and pathology, a normal E/A (> 1) could be considered abnormal in patients post-AMI older than 65 years, and that in patients with symptomatic HF, a normal E/A always represents advanced diastolic dysfunction.

Methods and results

This is a sub-analysis of the Meta-analysis Research Group in Echocardiography (MeRGE) which combined individual patient data from 30 prospective studies and demonstrated that restrictive filling was an important and independent predictor of all-cause mortality. This sub-analysis is restricted to those studies in which continuous E/A data were available (20 studies) and includes a total of 3082 AMI and 2321 HF patients. Patients were classified at the time of echocardiography into four filling patterns: normal, abnormal relaxation, pseudonormal, and restrictive filling. Post-AMI patients were divided into four groups on the basis of age and E/A, while patients with HF were classified into three groups, based on only E/A. Mortality across groups was compared using Kaplan–Meier survival analysis and Cox proportional hazards. In multivariable analyses in the AMI patients, age-stratified E/A was an independent predictor of outcome (HR 1.43 (95% CI: 1.31–1.56)), and in the HF cohort, E/A was confirmed as an independent predictor of mortality (HR 1.12 (95% CI 1.09–1.16)) alongside age and ejection fraction.

Conclusions

Age-stratified E/A is an independent predictor of mortality after AMI and in HF patients, regardless of left ventricular ejection fraction, age and gender. E/A ratio could be a first step echocardiographic risk stratification, which could precede and indicate the need for more advanced diagnostic and prognostic considerations in high-risk AMI and HF patients.

Introduction

The clinical utility of Doppler echocardiography to assess diastolic filling is well established, driven partly by numerous studies linking diastolic Doppler parameters with prognosis [1], [2]. In particular, the presence of restrictive filling pattern (RFP) is associated with a 2–3 fold increase in the risk of death in patients post-acute myocardial infarction (AMI) [3] independently of left ventricular ejection fraction (LVEF), age and aetiology; and in patients with chronic heart failure (HF) [2], [4], regardless of LVEF, chamber size and severity of HF symptoms. The restrictive diastolic filling pattern (RFP) also predicts rehospitalisation in patients with HF [5], which is another one of the strongest prognostic predictors for increased mortality [6]. However, in daily clinical practice, the majority of patients (80% post-AMI [3] and 60% of HF [4]) present with non-restrictive diastolic filling patterns and further clarification of risk beyond a simple binary approach is desirable.

Doppler echocardiographic assessment of diastolic filling uses a variety of techniques, which are widely accepted as reliable non-invasive evaluations of diastolic function and LV filling pressures [7]. Four distinct phases of diastolic filling, all associated with increasing left atrial pressure, can be identified: normal filling, abnormal relaxation, pseudonormal filling, and restrictive filling. When patients are classified according to filling pattern, patients with pseudonormal filling have been shown to have increased risk of death compared with patients with abnormal relaxation [8], [9], [10]. Moreover, in patients with HF, the risk of death associated with pseudonormal filling is similar to that observed in patients with RFP [11] and the stage of diastolic dysfunction is a stronger predictor of mortality than EF [7]. Recently, progression of LV filling abnormalities in outpatients with preserved LV systolic function has been proven as a strong, independent predictor of all-cause mortality [12].

Although measures of LV diastolic function are powerful predictors of all-cause mortality, clinical implementation of comprehensive diastolic assessment has been troublesome. Difficulties with interpretation (especially of pseudonormal filling) have created uncertainty regarding clinical application of these parameters. Furthermore, due to the recent growth in hand-carried ultrasound devices echocardiography is increasingly being performed by non-experts according to abbreviated protocols. If the prognostic role of E/A ratio used in isolation was proven, this would potentially simplify and streamline the risk assessment for many patients.