Disclosures J.B.S. reports research grants from the National Heart, Lung, and Blood Institute (1R01HL169517, 1R01HL173998) and National Institute on Aging (1R01AG063937), Anumana, Ultromics, Philips Healthcare, and Bracco Diagnostics; and consulting for Bracco Diagnostics, Edwards Lifesciences, Philips Healthcare, General Electric Healthcare, and EVERSANA; and is a member of the scientific advisory boards for Ultromics, HeartSciences, and EchoIQ and the data safety monitoring board for Pfizer. P.A.P. reports a research grant from Ultromics. A.P.A., W.H., H.P., P.L., G.W., and R.U. are employees of Ultromics. The remaining authors report no funding or relevant disclosures. Diastolic dysfunction, characterized by myocardial stiffening, increased left ventricular (LV) filling pressures, and atrial dilation and dysfunction, is an essential feature of heart failure (HF) with preserved ejection fraction (HFpEF). Presently, guidelines recommend an integrated approach, using a combination of echocardiographic measures and clinical information to grade the presence and severity of diastolic dysfunction.(1) While this approach has good interobserver variability and reproducibility(2) and may be incrementally prognostic(3) with respect to prior guideline iterations in several patient populations, up to 30% of patients are determined to have indeterminate diastolic function, suggesting a need for novel markers to improve diagnostic certainty.(4) In this setting, we hypothesized that the J wave, a seldom-measured late diastolic forward flow signal in the LV outflow tract (LVOT; Figure),(5) could serve as an additional marker of diastolic function. The J wave is theorized to result from a vortex of flow moving from the septum to aortic valve observed in a noncompliant left ventricle after atrial contraction and is closely associated with transmitral A-wave velocity.(5)(,)(6) Given these associations with atrial contraction and LV noncompliance, we hypothesized that J-wave velocities would be lower or absent in individuals with HFpEF and advanced diastolic dysfunction who frequently have diminutive contributions of atrial contractility to LV filling.(1) We previously conducted a retrospective case-control study as part of a clinical validation of artificial intelligence software,(7) including 496 individuals undergoing clinically indicated transthoracic echocardiograms (TTEs), 2018 to 2022, at Beth Israel Deaconess Medical Center, with a biplane LV ejection fraction ≥50% (Supplemental Table 1). Cases additionally had grade II to III diastolic dysfunction and evidence of HF hospitalization (primary discharge diagnosis of I50.X) within the year preceding the TTE. Controls with grade I, indeterminate, or no diastolic dysfunction and no evidence of HF hospitalization in the year preceding and following the TTE were exactly matched to cases on age, sex, and year of index TTE. In this prior study cohort, J-wave presence, peak velocity, velocity-time integral (VTI), and total time duration were measured using pulsed-wave Doppler LVOT spectra by a single experienced reviewer (T.A.) who was blinded to HFpEF status and clinical variables. Six patients with uninterpretable LVOT Doppler spectra were excluded (Supplemental Methods). Compared to controls (N = 256), cases (N = 234) were more frequently Black and had more comorbidities, higher NT-proBNP, greater LV mass, and more abnormal diastolic parameters (Supplemental Table 1). A total of 74 (15.1%) had indeterminate diastolic function, of which the J wave was present in 54 (73.0%). J-wave measurements showed good interrater and intrarater reliability on Bland-Altman analysis (Supplemental Table 2) and inversely correlated with diastolic grade (Supplemental Tables 3 and 4). Cases had a greater proportion with absent J waves (41.9% vs 16%; P < .001), but J-wave peak velocity (P = .055), VTI (P = .27), and duration (P = .59) were not significantly different. Absence of J wave was associated with increased odds of HFpEF (Table 1), which persisted despite adjustment for age, sex, race, transmitral peak A-wave velocity, average E/e’, left atrial volume index (LAVI), and estimated pulmonary artery systolic pressure (PASP; odds ratio [OR] = 3.03, 95% CI, 1.31-7.04; P = .01), but was no longer significant after adjustment for transmitral E-wave velocity (OR = 2.31; 95% CI, 0.95-5.62; P = .06). J-wave absence remained associated with HFpEF after adjustment for atrial fibrillation (AF) on prior electrocardiogram (ECG), age, sex, and race (OR = 3.21; 95% CI, 1.99-5.16; P < .001), and this association remained significant after adjustment for transmitral peak A-wave velocity (OR = 3.28; 95% CI, 1.88-5.70; P < .001; Table 1). Other J-wave parameters were not related to HFpEF after multivariable adjustment (Supplemental Table 5). The study design (i.e., conditioning on absence of HFpEF among controls including those with indeterminate diastolic function) did not allow for evaluation of J-wave parameters and HFpEF. In summary, in this case-control study, J-wave peak velocities were more likely to be absent in individuals with HFpEF, likely reflecting the decreased atrial contractility observed in advanced diastolic dysfunction with a weak negative correlation observed between both J-wave peak velocity and VTI and diastolic grade. Furthermore, J-wave absence remained associated with HFpEF status despite adjustment for prior AF on ECG and transmitral peak A-wave velocity, suggesting that it may capture information on atrial contractility beyond these 2 parameters, although it is unclear at present whether J-wave velocities are lower in those with recent AF. J-wave measurement was reliable and reproducible. Nevertheless, as J-wave absence did not improve HFpEF identification versus transmitral filling patterns alone, the J wave may have limited clinical utility, perhaps serving as a surrogate for atrial contractility when transmitral A-wave velocities are not discernible or measured. However, future investigation is warranted to evaluate whether the J-wave could be useful in reclassifying diastolic function stage in those with indeterminate diastolic function. Given her role as JASE Editor-in-Chief, Patricia A. Pellikka, MD, had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to guest editor Alan S. Pearlman, MD.