Left Atrial Stiffness Index for Refining Diastolic Stress Test Selection in Suspected Heart Failure with Preserved Ejection Fraction

INTRODUCTION: Diagnosing heart failure with preserved ejection fraction remains challenging in patients with exertional dyspnea and inconclusive resting echocardiography. The left atrial stiffness index (LASI), calculated as E/e' divided by left atrial reservoir strain, reflects the relationship between estimated left ventricular filling pressure and left atrial compliance. OBJECTIVES: We aimed to evaluate the performance of the LASI for predicting a positive diastolic stress test (DST) response, its incremental value beyond the Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology (HFA-PEFF) algorithm, and its potential role as a resting pretest triage tool within the intermediate HFA-PEFF group. METHODS: We retrospectively analyzed 376 patients in a derivation cohort and 141 patients in an external validation cohort who underwent noninvasive DST at 2 tertiary referral centers. Patients with baseline septal E/e' ≥15 were excluded. A positive DST was defined as exercise septal E/e' ≥15, a guideline-based surrogate of exercise-induced elevation in left ventricular filling pressure. Machine learning models ranked predictors of a positive DST, followed by logistic regression and receiver operating characteristic analysis; the LASI was then examined within the intermediate HFA-PEFF group. RESULTS: Positive DST occurred in 49 patients (13.0%) in the derivation cohort and 25 patients (17.7%) in the external validation cohort. The LASI ranked among the stronger variables associated with positive DST and remained independently associated with positive DST after multivariable adjustment (adjusted odds ratio per 1 SD, 1.81 in the derivation cohort and 1.96 in the validation cohort). At the study-defined cutoff of 0.333, LASI showed high sensitivity and negative predictive value for positive DST in both cohorts (derivation, 80% and 96%; validation, 84% and 94%), although specificity was modest. Within the intermediate HFA-PEFF group, the LASI cutoff separated patients into higher and lower yield strata, with only 5% of patients below the cutoff having a positive DST. CONCLUSIONS: The LASI is a resting echocardiographic marker associated with positive DST and may help refine pretest selection for DST among patients with suspected heart failure with preserved ejection fraction, particularly those with intermediate HFA-PEFF scores. Rather than serving as a stand-alone diagnostic gatekeeper, LASI may serve as a rule-out triage aid to refine selection for DST.