By Michael H. Crawford, MD
A one-institution study of serial echocardiograms in patients with moderate to severe or severe aortic regurgitation demonstrated that changes in left atrial size and strain changed over time in a similar fashion regardless of sex and age, and were of incremental prognostic value compared to left ventricular size and function.
Akintoye E, El Dahdah J, Dabbagh MM, et al. Longitudinal assessment of left atrial remodeling in patients with chronic severe aortic regurgitation. JACC Cardiovasc Imaging. 2024:17(10):1133-1145.
Consideration of left ventricular size and function is recommended in the decision about when to intervene in patients with chronic aortic regurgitation, but these factors are widely recognized as being problematic for this application. Thus, these investigators from the Cleveland Clinic sought to investigate whether left atrial (LA) size and characteristics would perform better for this purpose.
After excluding those with other left heart valve disease greater than mild, prior aortic valve interventions, congenital heart disease, or inadequate echocardiogram images of the LA, 525 patients (mean age 56 years, 26% women) with moderate to severe (n = 65%) or severe AR (35%) who had 1.687 serial echocardiograms starting in 2010 through 2016 were studied.
The electronic medical record was used to obtain clinical information. The echocardiogram endpoints were indexed LA volume (iLAV) and LA reservoir strain (RS) using the four-chamber view at end-diastole as the zero reference.
Clinical endpoints included heart failure hospitalization (HFH), urgent surgical aortic valve replacement (SAVR) for symptoms or LV ejection fraction < 55%, and all-cause mortality. The patients were divided into two groups based on iLAV above or below the upper limit of normal (34 mL/m²).
The data were further analyzed based on age older or younger than 60 years, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and E/e’. Additional analyses based on clinical variables, iLV dimensions, atrial fibrillation, and the calculated survival benefit of SAVR at various iLAV cut points were performed. iLAV increased and LARS decreased with age, but there was no difference between the sexes. Both LA measures changed significantly with time. Also, they correlated with NT-proBNP and echo Doppler E/e’ but not LV volumes.
An adverse event occurred in 40% of the patients (urgent AVR, 52%; HFH, 34%; all-cause mortality, 14%). Both LA measures predicted adverse events with an iLAV discrimination threshold of 37 mL/m² and LARS of 35%. In addition, both were superior to LVV and EF in this regard. Survival post-SAVR was better if iLAV was higher than the discrimination threshold and LARS was lower, but not when iLAV was lower and LARS was higher.
The authors concluded that LA characteristics showed a similar rate of progression in sex and age categories and were of incremental prognostic value compared to LV parameters.
Commentary
Although the current guidelines for when to intervene on asymptomatic chronic AR patients are based on LV size and ejection fraction (EF), there is accumulating evidence that waiting until the LV reaches a certain size or EF falls below normal often results in less than ideal surgical outcomes because of persistent LV dysfunction.
Also, recent studies have shown that indexed LV volumes vary by age and sex in patients with chronic AR. Specifically, women and older men maintain smaller LV volumes over time compared to men and younger patients. Thus, women and older men may not reach the volume thresholds for intervention before significant LV damage has occurred. Also, the current guidelines use LV dimensions on echocardiography, which are known to be problematic in enlarged LVs.
Since LA parameters in the chronic AR population do not vary by age and sex, Akintoye et al hypothesized that they would be superior for predicting outcomes in chronic AR patients. The progressive increase in LV diastolic pressure caused by the volume load from AR is transmitted to the LA, which is a thin-walled structure. Thus, it is reasonable to assume that the LA would demonstrate alterations in size and function before the LV did. Consequently, patients with chronic AR may not demonstrate LV volume and function changes until late in the progression of the disease, when intervention is less likely to be of value.
Prospective studies of this concept would be ideal, but given the often decade-long progression of moderate AR to meeting current intervention criteria, we will not have these data for a while. A few more confirmatory retrospective studies could stimulate a change in the guidelines to add LA size and function criteria.
There are limitations to this study. Retrospective observational studies can have biases and unmeasured confounders. There was no protocol for when the echocardiograms were done, so the investigators used those done at six months or multiples of six months only.
About 10% of the subjects had a history of atrial fibrillation, which also could have affected LA size and function. However, when these patients were excluded, the results were the same. They only included moderate to severe or severe AR. Also, for this type of study, the number of patients was small. In addition, patients with normal LA parameters who met other criteria for intervention still could benefit from surgery.
Finally, measurements of LA parameters can carry measurement errors, so confirmatory studies with cardiac magnetic resonance imaging could be valuable.
Michael H. Crawford, MD, is a Professor of Medicine and Consulting Cardiologist, University of California Health, San Francisco.
