Prognostic Significance of Left Ventricular Diastolic Dysfunction in the Community: A Project Baseline Health Study

Background: Left ventricular diastolic dysfunction (LVDD) is an important predictor of cardiovascular outcomes. LVDD assessment guidelines are valuable in clinical practice, yet a significant proportion of individuals remain indeterminate. Objectives: We aimed to develop an easy-to-use LVDD score and compare its prognostic value to American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) guidelines. Methods: Participants in the Project Baseline Health Study (PBHS) were included (n=1,952). Minor and major criteria for the PBHS diastolic score (0-6 points) were defined by percentile deviation from a healthy reference cohort (n=565), including early mitral annular tissue Doppler velocity (e'), the ratio of early diastolic inflow velocity to e' (E/e'), and left atrial volume index. Multivariable Cox regression estimated associations between LVDD assessments and major adverse cardiovascular events (MACE). Results: At enrollment, mean age was 50±16; 56% were female. LVDD according to ASE/EACVI guidelines was present in 8.4% of participants, of whom 54.3% had an indeterminate grade. PBHS diastolic scores of ≥3 and ≥4 were observed in 14.1% and 5.8%, respectively. ASE/EACVI grades 2-3 corresponded with PBHS scores >3, whereas indeterminate categories corresponded with scores of 1-5. After multivariable adjustment, both LVDD grading systems equally predicted MACE (ASE/EACVI grades 2-3: aHR 5.7 [95%CI: 3.01-10.7]; PBHS scores 4 and 5-6: aHRs 2.3 [95%CI: 1.25-4.33] and 5.3 [95%CI: 2.44-11.56], respectively). Conclusion: The PBHS diastolic score predicted MACE similarly to the ASE/EACVI. Its simplicity and prognostic value can make it useful in clinical settings, particularly for quantifying abnormalities and risk-stratifying patients with indeterminate LVDD. ### Competing Interest Statement All authors acknowledge institutional research grants from Verily Life Sciences. MKC and SAS report employment and equity ownership in Verily Life Sciences. FH received an institutional research grant from Actelion Ltd. within the last 2 years and an institutional research grant from Precordior Ltd. KM reports grants from Verily, Afferent, the American Heart Association (AHA), Cardiva Medical Inc, Gilead, Luitpold, Medtronic, Merck, Eidos, Ferring, Apple Inc, Sanifit, and St. Jude; grants and personal fees from Amgen, AstraZeneca, Bayer, CSL Behring, Johnson & Johnson, Novartis, and Sanofi; and personal fees from Anthos, Applied Therapeutics, Elsevier, Inova, Intermountain Health, Medscape, Mount Sinai, Mundi Pharma, Myokardia, Novo Nordisk, Otsuka, Portola, SmartMedics, and Theravance outside the submitted work. AH reports grants from Verily; grants and personal fees from AstraZeneca, Amgen, Bayer, Merck, and Novartis; and personal fees from Boston Scientific outside the submitted work. NC reports grants from the Research Foundation Flanders. The other authors have no conflicts of interest to disclose. ### Funding Statement The Project Baseline Health Study and this analysis were funded by Verily Life Sciences, San Francisco, California. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Stanford University and Duke University Institutional Review Boards, and participants provided written informed consent before participation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The deidentified PBHS data corresponding to this study are available upon request for the purpose of examining its reproducibility. Requests are subject to approval by PBHS governance.