Bettia Celestin

All Publications

• A generalized equation for predicting peak oxygen consumption during treadmill exercise testing: mitigating the bias from total body mass scaling. Frontiers in cardiovascular medicine Santana, E. J., Cauwenberghs, N., Celestin, B. E., Kuznetsova, T., Gardner, C., Arena, R., Kaminsky, L. A., Harber, M. P., Ashley, E., Christle, J. W., Myers, J., Haddad, F. 2024; 11: 1393363

  Abstract

  Indexing peak oxygen uptake (VO2peak) to total body mass can underestimate cardiorespiratory fitness (CRF) in women, older adults, and individuals with obesity. The primary objective of this multicenter study was to derive and validate a body size-independent scaling metric for VO2peak. This metric was termed exercise body mass (EBM).In a cohort of apparently healthy individuals from the Fitness Registry and the Importance of Exercise National Database, we derived EBM using multivariable log-normal regression analysis. Subsequently, we developed a novel workload (WL) equation based on speed (Sp), fractional grade (fGr), and heart rate reserve (HRR). The generalized equation for VO2peak can be expressed as VO2peak = Cst × EBM × WL, where Cst is a constant representing the VO2peak equivalent of one metabolic equivalent of task. This generalized equation was externally validated using the Stanford exercise testing (SET) dataset.A total of 5,618 apparently healthy individuals with a respiratory exchange ratio >1.0 (57% men, mean age 44 ± 13 years) were included. The EBM was expressed as Mass (kg)0.63 × Height (m)0.53 × 1.16 (if a man) × exp (-0.39 × 10-4 × age2), which was also approximated using simple sex-specific additive equations. Unlike total body mass, EBM provided body size-independent scaling across both sexes and WL categories. The generalized VO2peak equation was expressed as 11 × EBM × [2 + Sp (in mph) × (1.06 + 5.22 × fGr) + 0.019 × HRR] and had an R 2 of 0.83, p < 0.001. This generalized equation mitigated bias in VO2peak estimations across age, sex, and body mass index subgroups and was validated in the SET registry, achieving an R 2 of 0.84 (p < 0.001).We derived a generalized equation for measuring VO2peak during treadmill exercise testing using a novel body size-independent scaling metric. This approach significantly reduced biases in CRF estimates across age, sex, and body composition.

  View details for DOI 10.3389/fcvm.2024.1393363

  View details for PubMedID 39720208

  View details for PubMedCentralID PMC11666446

• Novel Reference Equations for Pulmonary Artery Size and Pulsatility Using Echocardiography and their Diagnostic Value in Pulmonary Hypertension. Chest Bagherzadeh, S. P., Celestin, B. E., Santana, E. J., Salerno, M., Nadeau, K. C., Sweatt, A. J., Zamanian, R. T., Haddad, F. 2024

  Abstract

  BACKGROUND: According to the most recent pulmonary hypertension (PH) guidelines, a main pulmonary artery (MPA) diameter>25 mm on transthoracic echocardiography (TTE) supports the diagnosis of PH. However, the size of the pulmonary artery(PA) may vary according to body size, age, and cardiac phases.RESEARCH QUESTIONS: 1)What are the reference limits for PA size on TTE, considering differences in body size, sex, and age? 2)What is the diagnostic value of PA size for classifying pulmonary hypertension? 3)How does the selection of different reference groups (healthy volunteers versus patients referred for right heart catheterization (RHC)) influence the diagnostic odds ratio (DOR)?STUDY DESIGN AND METHODS: The study included a reference cohort of 248 healthy individuals as controls, 693 PH patients proven by RHC, and 156 non-PH patients proven by RHC. In the PH cohort, 300 had group-1 PH, 207 had group-2 PH, and 186 with group-3 PH. MPA and right PA(RPA) diameters and areas were measured in the upper sternal short-axis and the suprasternal notch views. Reference limits (5th-95th percentile) were based on absolute values and height-indexed measures. Quantile regression analysis was used to derive median and 95th quantile reference equations for the PA measures. DORs and probability diagnostic plots for PH were then determined using healthy controls and non-PH cohorts.RESULTS: The 95th percentile for indexed MPA diameter was 15mm/m in diastole and 19mm/m in systole in both sexes. Quantile regression analysis revealed a weak age effect (pseudo R2 of 0.08 to 0.10 for MPA diameters). Among measures, the MPA size in diastole had the highest DOR, 156.2(68.3-357.5), for detection of group-1 PH. Similarly, the DORs were also high for group-2 and 3 PH when compared to controls but significantly lower compared to non-PH cohort.INTERPRETATION: The study presents novel reference limits for MPA based on height indexing and quantile regression.

  View details for DOI 10.1016/j.chest.2024.06.3805

  View details for PubMedID 39025204

• Factors associated with lower quarter performance-based balance and strength tests: a cross-sectional analysis from the project baseline health study. Frontiers in sports and active living Taylor, K. A., Carroll, M. K., Short, S. A., Celestin, B. E., Gilbertson, A., Olivier, C. B., Haddad, F., Cauwenberghs, N. 2024; 6: 1393332

  Abstract

  Physical performance tests are predictive of mortality and may screen for certain health conditions (e.g., sarcopenia); however, their diagnostic and/or prognostic value has primarily been studied in age-limited or disease-specific cohorts. Our objective was to identify the most salient characteristics associated with three lower quarter balance and strength tests in a cohort of community-dwelling adults.We applied a stacked elastic net approach on detailed data on sociodemographic, health and health-related behaviors, and biomarker data from the first visit of the Project Baseline Health Study (N = 2,502) to determine which variables were most associated with three physical performance measures: single-legged balance test (SLBT), sitting-rising test (SRT), and 30-second chair-stand test (30CST). Analyses were stratified by age (<65 and ≥65).Female sex, Black or African American race, lower educational attainment, and health conditions such as non-alcoholic fatty liver disease and cardiovascular conditions (e.g., hypertension) were consistently associated with worse performance across all three tests. Several other health conditions were associated with either better or worse test performance, depending on age group and test. C-reactive protein was the only laboratory value associated with performance across age and test groups with some consistency.Our results highlighted previously identified and several novel salient factors associated with performance on the SLBT, SRT, and 30CST. These tests could represent affordable, noninvasive biomarkers of prevalent and/or future disease in adult individuals; future research should validate these findings.ClinicalTrials.gov, identifier NCT03154346, registered on May 15, 2017.

  View details for DOI 10.3389/fspor.2024.1393332

  View details for PubMedID 39081837

  View details for PubMedCentralID PMC11287662

• Tricuspid annular plane systolic excursion in pulmonary hypertension-Moving beyond the sector plane. Pulmonary circulation Ichimura, K., Celestin, B. E., Bagherzadeh, S. P., Zamanian, R. T., Salerno, M., Spiekerkoetter, E., Haddad, F. 2024; 14 (3): e12416

  Abstract

  Tricuspid annular plane systolic excursion (TAPSE) is usually measured with M-mode using sector line, however, this may not align with the anatomical shortening of the right ventricular (RV). In this study, we compared the different methods to measure TAPSE using three different reference lines (sector line, anatomical line, and apico-annular line). We included 148 patients diagnosed with pulmonary arterial hypertension (PAH) who underwent TTE and right heart catheterization within 2 weeks of each other. TAPSE was measured by M-mode (sector, anatomical), 2D (sector, anatomical), or as tricuspid apico-annular displacement (TAAD). Agreement between measures was assessed using coefficient of variation (COV), Spearman's correlation, and Bland-Altman analysis. Receiver-operating characteristics and Kaplan-Meier analysis were used to explore associations with the combined outcome of death or lung transplantation at 5 years. There was a good concordance between anatomical and sector M-mode with a COV of 15.5 ± 1.6% and a bias of -0.6 ± 3.2 mm. In contrast, anatomical M-mode TAPSE and TAAD differed significantly with the mean difference of 3.3 ± 3.8 mm (COV 30.5 ± 6.1%; p < 0.0001). Among the different 2D methods, anatomical 2D agreed well with anatomical M-mode TAPSE (COV of 11.8 ± 2.0%; r = 0.89; p < 0.0001). Among the five methods, TADD had the strongest association with the combined endpoint of death or transplantation at 5 years (C-statistic 0.64, 95% confidence interval [CI] 0.57-0.71). We concluded that different measures of TAPSE are not interchangeable.

  View details for DOI 10.1002/pul2.12416

  View details for PubMedID 39247630

  View details for PubMedCentralID PMC11377954

• Identifying consistent echocardiographic thresholds for risk stratification in pulmonary arterial hypertension. Pulmonary circulation Celestin, B. E., Bagherzadeh, S. P., Ichimura, K., Santana, E. J., Sanchez, P. A., Tobore, T., Hemnes, A. R., Noordegraaf, A. V., Salerno, M., Zamanian, R. T., Sweatt, A. J., Haddad, F. 2024; 14 (2): e12361

  Abstract

  Several indices of right heart remodeling and function have been associated with survival in pulmonary arterial hypertension (PAH). Outcome analysis and physiological relationships between variables may help develop a consistent grading system. Patients with Group 1 PAH followed at Stanford Hospital who underwent right heart catheterization and echocardiography within 2 weeks were considered for inclusion. Echocardiographic variables included tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) fractional area change (RVFAC), free wall strain (RVFWS), RV dimensions, and right atrial volumes. The main outcome consisted of death or lung transplantation at 5 years. Mathematical relationships between variables were determined using weighted linear regression and severity thresholds for were calibrated to a 20% 1-year mortality risk. PAH patients (n=223) had mean (SD) age of 48.1 (14.1) years, most were female (78%), with a mean pulmonary arterial pressure of 51.6 (13.8) mmHg and pulmonary vascular resistance index of 22.5(6.3) WU/m2. Measures of right heart size and function were strongly related to each other particularly RVFWS and RVFAC (R 2=0.82, p<0.001), whereas the relationship between TAPSE and RVFWS was weaker (R 2=0.28, p<0.001). Death or lung transplantation at 5 years occurred in 78 patients (35%). Guided by outcome analysis, we ascertained a uniform set of parameter thresholds for grading the severity of right heart adaptation in PAH. Using these quantitative thresholds, we, then, validated the recently reported REVEAL-echo score (AUC 0.68, p<0.001). This study proposes a consistent echocardiographic grading system for right heart adaptation in PAH guided by outcome analysis.

  View details for DOI 10.1002/pul2.12361

  View details for PubMedID 38800494

• The Echocardiographic Evaluation of the Right Heart: Current and Future Advances. Current cardiology reports O'Donnell, C., Sanchez, P. A., Celestin, B., McConnell, M. V., Haddad, F. 2023

  Abstract

  PURPOSE OF REVIEW: To discuss physiologic and methodologic advances in the echocardiographic assessment of right heart (RH) function, including the emergence of artificial intelligence (AI) and point-of-care ultrasound.RECENT FINDINGS: Recent studies have highlighted the prognostic value of right ventricular (RV) longitudinal strain, RV end-systolic dimensions, and right atrial (RA) size and function in pulmonary hypertension and heart failure. While RA pressure is a central marker of right heart diastolic function, the recent emphasis on venous excess imaging (VExUS) has provided granularity to the systemic consequences of RH failure. Several methodological advances are also changing the landscape of RH imaging including post-processing 3D software to delineate the non-longitudinal (radial, anteroposterior, and circumferential) components of RV function, as well as AI segmentation- and non-segmentation-based quantification. Together with recent guidelines and advances in AI technology, the field is shifting from specific RV functional metrics to integrated RH disease-specific phenotypes. A modern echocardiographic evaluation of RH function should focus on the entire cardiopulmonary venous unit-from the venous to the pulmonary arterial system. Together, a multi-parametric approach, guided by physiology and AI algorithms, will help define novel integrated RH profiles for improved disease detection and monitoring. Advances in right heart echocardiography will incorporate a physiologic, multi-parametric approach that is augmented by deep learning to develop integrated right heart phenotypes. Ao Aorta, LV left ventricle, RA right atria, RV right ventricle, PA pulmonary artery.

  View details for DOI 10.1007/s11886-023-02001-6

  View details for PubMedID 38041726

• Right Ventricular Dysfunction Patterns Among Patients with COVID-19 in the Intensive Care Unit - a Retrospective Cohort Analysis. Annals of the American Thoracic Society Sanchez, P. A., O'Donnell, C. T., Francisco, N., Santana, E. J., Moore, A. R., Pacheco-Navarro, A., Roque, J., Lebold, K. M., Parmer, C. M., Pienkos, S. M., Celestin, B. E., Levitt, J. E., Collins, W. J., Lanspa, M. J., Ashley, E. A., Wilson, J. G., Haddad, F., Rogers, A. J. 2023

  Abstract

  Right ventricular (RV) dysfunction is common among patients hospitalized with COVID-19; however, its epidemiology may depend on the echocardiographic parameters used to define it.To evaluate the prevalence of abnormalities in three common echocardiographic parameters of RV function among COVID-19 patients admitted to the intensive care unit, as well as the effect of RV dilatation on differential parameter abnormality and the association of RV dysfunction with 60-day mortality.Retrospective cohort study of COVID-19 ICU patients between March 4th,2020 to March 4th, 2021, who received a transthoracic echocardiogram within 48 hours before to at most 7 days after ICU admission. RV dysfunction and dilatation respectively defined by guideline thresholds for tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), RV free wall longitudinal strain (RVFWS), and RV basal dimension or RV end-diastolic area. Association of RV dysfunction with 60-day mortality assessed through logistic regression adjusting for age, prior history of congestive heart failure, invasive ventilation at time of TTE and APACHE II score.116 patients were included, of which 69% had RV dysfunction by > 1 parameter and 36.3% of these had RV dilatation. The three most common patterns of RV dysfunction included: Presence of 3 abnormalities, the combination of abnormal RVFWS and TAPSE, and isolated TAPSE abnormality. Patients with RV dilatation had worse RVFAC (24% vs 36%, p = 0.001), worse RVFWS (16.3% vs 19.1%, p = 0.005), higher RVSP (45mmHg vs 31mmHg, p = 0.001) but similar TAPSE (13mm vs 13mm, p = 0.30) compared to those with normal RV size. After multivariable adjustment, 60-day mortality was significantly associated with RV dysfunction (OR 2.91, 95% CI 1.01 - 9.44), as was the presence of at least 2 parameter abnormalities.ICU patients with COVID-19 had significant heterogeneity in RV function abnormalities present with different patterns associated with RV dilatation. RV dysfunction by any parameter was associated with increased mortality. Therefore, a multiparameter evaluation may be critical in recognizing RV dysfunction in COVID-19.

  View details for DOI 10.1513/AnnalsATS.202303-235OC

  View details for PubMedID 37478340