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 (HFpEF) 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 (LARS), 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 HFA-PEFF algorithm, and its potential role as a resting pre-test 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 two 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 LV 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. 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. CONCLUSION LASI is a resting echocardiographic marker associated with positive DST and may help refine pre-test selection for DST among patients with suspected HFpEF, 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.