By Michael H. Crawford, MD
Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco
Dr. Crawford reports no financial relationships relevant to this field of study.
SYNOPSIS: Analysis of the ability of echo Doppler measures of diastolic function to predict heart failure and death in community subjects > 65 years of age was improved by applying age-adjusted normal values for e’, which are considerably lower than those recommended in the American Society of Echocardiography guidelines.
SOURCE: Shah AM, Claggett B, Kitzman D, et al. Contemporary assessment of left ventricular diastolic function in older adults: The Atherosclerosis Risk in Communities study. Circulation 2017;135:426-439.
Measures of diastolic function on echocardiography change with age, yet little is known about where values consistent with normal aging transition to pathological diastolic dysfunction. Thus, investigators from the Atherosclerosis Risk in Communities (ARIC) study, which enrolled 15,792 subjects between 1987 and 1989, analyzed those who returned for a fifth study visit between 2011-2013, which included an echocardiogram. This analysis included 5,801 of these subjects, mean age 75 years, who were free of heart failure. Also, a low-risk group of 401 subjects (7%) free of cardiovascular disease or risk factors for it was identified. In addition, the findings were validated by using the participants in the Copenhagen City Heart Study who were > 65 years of age. Six measures of diastolic function were assessed: tissue Doppler e’, septal, and lateral; mitral valve early diastolic velocity E to e’ ratio (E/e’) septal and lateral; left atrial (LA) width and volume index.
All diastolic measures were associated robustly with NT-proBNP and incident heart failure hospitalization or death (P < 0.001). Based on the low-risk group, the lower limits of e’, septal, and lateral were 4.6 and 5.2 cm/s, respectively. These values are considerably lower than the American Society of Echocardiography (ASE) guideline, which calls for lower limits of 7 and 10, respectively. The E/e’ upper limits for the low-risk group were 14.4 and 12.7, respectively, which are similar to guideline limits of 15 and 13. Similarly, the upper limit for low-risk LA diameter and volume of 3.7 cm and 30 mL/m² were similar to the guideline values of 4.0 cm and 34 mL/m².
In the total ARIC study sample free of prevalent heart failure, e’ (using the new reference limits) was abnormally low in 29%, E/e’ was high in 31%, and LA volume was higher in 23%. Using ARIC normal limits as compared to the guidelines, 42% of the ARIC population was reclassified to normal diastolic function.
These findings were replicated in the Copenhagen City Heart Study age > 65 years population, in which 46% exhibited normal diastolic function and demonstrated a low risk of heart failure hospitalization or death (1%/year over 1.7 years). Those with one or two abnormal measures of diastolic function were at moderate risk (2.4%/year) and those with all three measures abnormal, which occurred in 5% of this population, were at high risk (7.5%/year).
The authors concluded that tissue Doppler e’ velocity normally declines with healthy aging and is benign. Thus, age-based normal values improve the risk prediction of measures of diastolic function.
COMMENTARY
When the new ASE measurement of diastolic dysfunction guidelines came out, I was dismayed to see that an e’ of < 10 cm/s was considered abnormal and a point toward the diagnosis of diastolic dysfunction. I thought this was going to be like the E/A of mitral valve inflow velocity, where almost every older person was abnormal.
Shah et al must have felt my pain because they undertook this analysis of the echo data in the ARIC population. This represents the largest database of normative data in older adults. They found a group that was low risk by traditional factors who exhibited a lower limit of e’ of 5. When this criterion was applied to the larger ARIC database and the Copenhagen study, those with normal diastolic function (no abnormal echo measures) experienced a heart failure hospitalization and death rate of 1%. Analysis of two other large databases (ENGAGE AF-TIMI 48, TOPCAT) also confirmed these findings.
As I suspected, when the guideline e’ values were used, 95% of the ARIC population exhibited abnormal values, but when the new lower cut points were used, only 28% were abnormal. Clearly, 10 is too high of a lower limit of e’ for elderly subjects.
The investigators’ low-risk group’s E/e’ upper limit ranged from 12-15 depending on whether septal or lateral measurements were used and whether the subjects were male or female. The guideline range is 13-15. LA volume upper limit was 30 mL/m², vs. 34 by the guidelines. Race and sex minimally influenced these measures.
The authors recommended using the e’ lower limit of 5cm/s in subjects > 65 years of age. For the other measures, clinicians can use whichever number they are comfortable with, since there is very little difference between the ARIC values and the guidelines.
But how do clinicians treat patients 50-65 years of age? The jump from an e’ lower limit of 5-10 is large. It is likely that patients 50-65 years of age would exhibit a lower normal limit between these two points, but we don’t know that for sure.
Obviously, we need more robust age-based normal values for e’.
Analysis of the ability of echo Doppler measures of diastolic function to predict heart failure and death in community subjects > 65 years of age was improved by applying age-adjusted normal values for e’, which are considerably lower than those recommended in the American Society of Echocardiography guidelines.
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