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2. Association of Male Sex With Worse Right Ventricular Function and Survival in Pulmonary Hypertension in the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics Cohort

Author

Shelburne, Nicholas J., Nian, Hui, Beck, Gerald J., Casanova, Nancy G., Desai, Ankit A., DuBrock, Hilary M., Erzurum, Serpil, Frantz, Robert P., Hassoun, Paul M., Hill, Nicholas S., Horn, Evelyn M., Jacob, Miriam S., Jellis, Christine L., Joseloff, Elizabeth, Kwon, Deborah H., Larive, A. Brett, Leopold, Jane A., Park, Margaret M., Rischard, Franz P., Rosenzweig, Erika B., Vanderpool, Rebecca R., Yu, Chang, and Hemnes, Anna R.

Published
2024
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4. Classification and Predictors of Right Ventricular Functional Recovery in Pulmonary Arterial Hypertension

Author

Rischard, Franz P., Bernardo, Roberto J., Vanderpool, Rebecca R., Kwon, Deborah H., Acharya, Tushar, Park, Margaret M., Katrynuik, Austin, Insel, Michael, Kubba, Saad, Badagliacca, Roberto, Larive, A. Brett, Naeije, Robert, Garcia, Joe G.N., Beck, Gerald J., Erzurum, Serpil C., Frantz, Robert P., Hassoun, Paul M., Hemnes, Anna R., Hill, Nicholas S., Horn, Evelyn M., Leopold, Jane A., Rosenzweig, Erika B., Tang, W.H. Wilson, and Wilcox, Jennifer D.

Published
2023
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5. Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease

Author

Hemnes, Anna R., Leopold, Jane A., Radeva, Milena K., Beck, Gerald J., Abidov, Aiden, Aldred, Micheala A., Barnard, John, Rosenzweig, Erika B., Borlaug, Barry A., Chung, Wendy K., Comhair, Suzy A.A., Desai, Ankit A., Dubrock, Hilary M., Erzurum, Serpil C., Finet, J. Emanuel, Frantz, Robert P., Garcia, Joe G.N., Geraci, Mark W., Gray, Michael P., Grunig, Gabriele, Hassoun, Paul M., Highland, Kristin B., Hill, Nicholas S., Hu, Bo, Kwon, Deborah H., Jacob, Miriam S., Jellis, Christine L., Larive, A. Brett, Lempel, Jason K., Maron, Bradley A., Mathai, Stephen C., McCarthy, Kevin, Mehra, Reena, Nawabit, Rawan, Newman, John H., Olman, Mitchell A., Park, Margaret M., Ramos, Jose A., Renapurkar, Rahul D., Rischard, Franz P., Sherer, Susan G., Tang, W.H. Wilson, Thomas, James D., Vanderpool, Rebecca R., Waxman, Aaron B., Wilcox, Jennifer D., Yuan, Jason X.-J., and Horn, Evelyn M.

Published
2022
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7. Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes

Author

Courcoulas, Anita P., primary, Patti, Mary Elizabeth, additional, Hu, Bo, additional, Arterburn, David E., additional, Simonson, Donald C., additional, Gourash, William F., additional, Jakicic, John M., additional, Vernon, Ashley H., additional, Beck, Gerald J., additional, Schauer, Philip R., additional, Kashyap, Sangeeta R., additional, Aminian, Ali, additional, Cummings, David E., additional, and Kirwan, John P., additional

Published
2024
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8. Sleep-Related Hypoxia, Right Ventricular Dysfunction, and Survival in Patients With Group 1 Pulmonary Arterial Hypertension

Author

Lowery, Megan M., primary, Hill, Nicholas S., additional, Wang, Lu, additional, Rosenzweig, Erika B., additional, Bhat, Aparna, additional, Erzurum, Serpil, additional, Finet, J. Emanuel, additional, Jellis, Christine L., additional, Kaur, Sunjeet, additional, Kwon, Deborah H., additional, Nawabit, Rawan, additional, Radeva, Milena, additional, Beck, Gerald J., additional, Frantz, Robert P., additional, Hassoun, Paul M., additional, Hemnes, Anna R., additional, Horn, Evelyn M., additional, Leopold, Jane A., additional, Rischard, Franz P., additional, Mehra, Reena, additional, Hill, N., additional, Xiao, L., additional, Fu, Y.-P., additional, Postow, L., additional, Schmetter, B., additional, Stanton, K., additional, Tian, X., additional, Gray, M., additional, Wong, B., additional, Leopold, J., additional, Waxman, A., additional, DiCarli, M., additional, Lawler, L., additional, Maron, B., additional, Segrera, S., additional, Systrom, D., additional, Yu, P., additional, Rosenzweig, E.B., additional, Arcasoy, S., additional, Brady, D., additional, Chung, W., additional, Payne, D., additional, Grunig, G., additional, Haythe, J., additional, Krishnan, U., additional, Horn, E., additional, Akat, K., additional, Borczuk, A., additional, Devereux, R., additional, Gordon, J., additional, Kaner, R., additional, Karas, M., additional, Min, J., additional, Narula, N., additional, Ricketts, M., additional, Sobol, I., additional, Spiera, R., additional, Singh, H., additional, Tuschl, T., additional, Weinsaft, J., additional, Hassoun, P., additional, Mathai, S., additional, Barnes, K., additional, Damico, R., additional, Enobun, B., additional, Gao, L., additional, Halushka, M., additional, Kass, D., additional, Kolb, T., additional, Lin, T., additional, Tedford, R., additional, Zimmerman, S., additional, Frantz, R., additional, Behfar, A., additional, Block, L., additional, Borlaug, B., additional, Durst, L., additional, Foley, T., additional, Hammer, T., additional, Johnson, B., additional, Johnson, G., additional, Kane, G., additional, Krowka, M., additional, McNallan, A., additional, Olson, T., additional, Redfield, M., additional, Rohwer, K., additional, Terzic, A., additional, Williamson, E., additional, Rischard, F., additional, Yuan, J., additional, Abidov, A., additional, Garcia, J., additional, Cordery, A., additional, Desai, A., additional, Erickson, H., additional, Hansen, L., additional, Khalpey, Z., additional, Knox, K., additional, Lussier, Y., additional, Simon, M., additional, Vanderpool, R., additional, Hemnes, A., additional, Newman, J., additional, Austin, E., additional, Brittain, E., additional, Cunningham, J., additional, LaRochelle, C., additional, Pugh, M., additional, Robbins, I., additional, Wheeler, L., additional, Beck, G., additional, Erzurum, S., additional, Aldred, M., additional, Asosingh, K., additional, Barnard, J., additional, Collart, C., additional, Comhair, S., additional, DiFilippo, F., additional, Drinko, J., additional, Dweik, R., additional, Flinn, A., additional, Geraci, M., additional, Hu, B., additional, Jaber, W., additional, Jacob, M., additional, Jellis, C., additional, Kalhan, S., additional, Kassimatis, K., additional, Kirsop, J., additional, Koo, M., additional, Kwon, D., additional, Larive, B., additional, Lempel, J., additional, Li, M., additional, MacKrell, J., additional, Matuska, B., additional, McCarthy, K., additional, Mehra, R., additional, Neumann, D., additional, Nawabit, R., additional, Olman, M., additional, Park, M., additional, Radeva, M., additional, Sharp, J., additional, Sherer, S., additional, Tang, W., additional, Thomas, J., additional, Wiggins, K., additional, Willard, B., additional, Rounds, S., additional, Benza, R., additional, Bull, T., additional, Cadigan, J., additional, Fang, J., additional, Gomberg-Maitland, M., additional, and Page, G., additional

Published
2023
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9. Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension

Author

Simpson, Catherine E., primary, Ambade, Anjira S., additional, Harlan, Robert, additional, Roux, Aurelie, additional, Aja, Susan, additional, Graham, David, additional, Shah, Ami A., additional, Hummers, Laura K., additional, Hemnes, Anna R., additional, Leopold, Jane A., additional, Horn, Evelyn M., additional, Berman-Rosenzweig, Erika S., additional, Grunig, Gabrielle, additional, Aldred, Micheala A., additional, Barnard, John, additional, Comhair, Suzy A.A., additional, Tang, W. H. Wilson, additional, Griffiths, Megan, additional, Rischard, Franz, additional, Frantz, Robert P., additional, Erzurum, Serpil C., additional, Beck, Gerald J., additional, Hill, Nicholas S., additional, Mathai, Stephen C., additional, Hassoun, Paul M., additional, and Damico, Rachel L., additional

Published
2023
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10. Classification and Predictors of Right Ventricular Functional Recovery in Pulmonary Arterial Hypertension

Author

Rischard, Franz P., primary, Bernardo, Roberto J., additional, Vanderpool, Rebecca R., additional, Kwon, Deborah H., additional, Acharya, Tushar, additional, Park, Margaret M, additional, Katrynuik, Austin, additional, Insel, Michael, additional, Kubba, Saad, additional, Badagliacca, Roberto, additional, Larive, A Brett, additional, Naeije, Robert, additional, Garcia, Joe G.N., additional, Beck, Gerald J, additional, Erzurum, Serpil C, additional, Frantz, Robert P, additional, Hassoun, Paul M, additional, Hemnes, Anna R, additional, Hill, Nicholas S, additional, Horn, Evelyn M, additional, Leopold, Jane A, additional, Rosenzweig, Erika B., additional, Tang, W.H. Wilson, additional, and Wilcox, Jennifer D., additional

Published
2023
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11. Dynamic Remodeling of Human Arteriovenous Fistula Wall Obtained From Magnetic Resonance Imaging During the First 6 Months After Creation

Author

Li, Yingnan, primary, He, Yong, additional, Falzon, Isabelle, additional, Fairbourn, Brayden, additional, Tingey, Spencer, additional, Imrey, Peter B., additional, Radeva, Milena K., additional, Beck, Gerald J., additional, Gassman, Jennifer J., additional, Roy-Chaudhury, Prabir, additional, Berceli, Scott A., additional, Cheung, Alfred K., additional, Shiu, Yan-Ting, additional, Feldman, H., additional, Dember, L., additional, Farber, A., additional, Kaufman, J., additional, Stern, L., additional, LeSage, P., additional, Kivork, C., additional, Soares, D., additional, Malikova, M., additional, Allon, M., additional, Young, C., additional, Taylor, M., additional, Woodard, L., additional, Mangadi, K., additional, Roy-Chaudhury, P., additional, Munda, R., additional, Lee, T., additional, Alloway, R., additional, El-Khatib, M., additional, Canaan, T., additional, Pflum, A., additional, Thieken, L., additional, Campos-Naciff, B., additional, Huber, T., additional, Berceli, S., additional, Jansen, M., additional, McCaslin, G., additional, Trahan, Y., additional, Vazquez, M., additional, Vongpatanasin, W., additional, Davidson, I., additional, Hwang, C., additional, Lightfoot, T., additional, Livingston, C., additional, Valencia, A., additional, Dolmatch, B., additional, Fenves, A., additional, Hawkins, N., additional, Cheung, A., additional, Kraiss, L., additional, Kinikini, D., additional, Treiman, G., additional, Ihnat, D., additional, Sarfati, M., additional, Lavasani, I., additional, Maloney, M., additional, Schlotfeldt, L., additional, Himmelfarb, J., additional, Buchanan, C., additional, Clark, C., additional, Crawford, C., additional, Hamlett, J., additional, Kundzins, J., additional, Manahan, L., additional, Wise, J., additional, Beck, G., additional, Gassman, J., additional, Greene, T., additional, Imrey, P., additional, Li, L., additional, Alster, J., additional, Li, M., additional, MacKrell, J., additional, Radeva, M., additional, Weiss, B., additional, Wiggins, K., additional, Alpers, C., additional, Hudkins, K., additional, Wietecha, T., additional, Robbin, M., additional, Umphrey, H., additional, Alexander, L., additional, Abts, C., additional, Belt, L., additional, Vita, J., additional, Hamburg, N., additional, Duess, M., additional, Levit, A., additional, Higgins, H., additional, Ke, S., additional, Mandaci, O., additional, Snell, C., additional, Gravley, J., additional, Behnken, S., additional, Mortensen, R., additional, Chertow, G., additional, Besarab, A., additional, Brayman, K., additional, Diener-West, M., additional, Harrison, D., additional, Inker, L., additional, Louis, T., additional, McClellan, W., additional, Rubin, J., additional, Kusek, J., additional, and Star, R., additional

Published
2022
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12. Dynamic Remodeling of Human Arteriovenous Fistula Wall Obtained From Magnetic Resonance Imaging During the First 6 Months After Creation

Author

Feldman, H., Dember, L., Farber, A., Kaufman, J., Stern, L., LeSage, P., Kivork, C., Soares, D., Malikova, M., Allon, M., Young, C., Taylor, M., Woodard, L., Mangadi, K., Roy-Chaudhury, P., Munda, R., Lee, T., Alloway, R., El-Khatib, M., Canaan, T., Pflum, A., Thieken, L., Campos-Naciff, B., Huber, T., Berceli, S., Jansen, M., McCaslin, G., Trahan, Y., Vazquez, M., Vongpatanasin, W., Davidson, I., Hwang, C., Lightfoot, T., Livingston, C., Valencia, A., Dolmatch, B., Fenves, A., Hawkins, N., Cheung, A., Kraiss, L., Kinikini, D., Treiman, G., Ihnat, D., Sarfati, M., Lavasani, I., Maloney, M., Schlotfeldt, L., Himmelfarb, J., Buchanan, C., Clark, C., Crawford, C., Hamlett, J., Kundzins, J., Manahan, L., Wise, J., Beck, G., Gassman, J., Greene, T., Imrey, P., Li, L., Alster, J., Li, M., MacKrell, J., Radeva, M., Weiss, B., Wiggins, K., Alpers, C., Hudkins, K., Wietecha, T., Robbin, M., Umphrey, H., Alexander, L., Abts, C., Belt, L., Vita, J., Hamburg, N., Duess, M., Levit, A., Higgins, H., Ke, S., Mandaci, O., Snell, C., Gravley, J., Behnken, S., Mortensen, R., Chertow, G., Besarab, A., Brayman, K., Diener-West, M., Harrison, D., Inker, L., Louis, T., McClellan, W., Rubin, J., Kusek, J., Star, R., Li, Yingnan, He, Yong, Falzon, Isabelle, Fairbourn, Brayden, Tingey, Spencer, Imrey, Peter B., Radeva, Milena K., Beck, Gerald J., Gassman, Jennifer J., Roy-Chaudhury, Prabir, Berceli, Scott A., Cheung, Alfred K., and Shiu, Yan-Ting

Published
2022
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13. Supplemental Material, sj-pdf-1-ojs-10.1177_23259671211065447 - Design Features and Rationale of the BEAR-MOON (Bridge-Enhanced ACL Restoration Multicenter Orthopaedic Outcomes Network) Randomized Clinical Trial

Author

Spindler, Kurt P., Imrey, Peter B., Yalcin, Sercan, Beck, Gerald J., Calbrese, Gary, Cox, Charles L., Fadale, Paul D., Farrow, Lutul, Fitch, Robert, Flanigan, David, Fleming, Braden C., Hulstyn, Michael J., Jones, Morgan H., Kaeding, Christopher, Katz, Jeffrey N., Kriz, Peter, Magnussen, Robert, McErlean, Ellen, Melgaard, Carrie, Owens, Brett D., Saluan, Paul, Strnad, Greg, Winalski, Carl S., and Wright, Rick

Subjects
FOS: Clinical medicine, 110604 Sports Medicine, FOS: Health sciences, 110314 Orthopaedics
Abstract

Supplemental Material, sj-pdf-1-ojs-10.1177_23259671211065447 for Design Features and Rationale of the BEAR-MOON (Bridge-Enhanced ACL Restoration Multicenter Orthopaedic Outcomes Network) Randomized Clinical Trial by BEAR-MOON Design Group, Kurt P. Spindler, Peter B. Imrey, Sercan Yalcin, Gerald J. Beck, Gary Calbrese, Charles L. Cox, Paul D. Fadale, Lutul Farrow, Robert Fitch, David Flanigan, Braden C. Fleming, Michael J. Hulstyn, Morgan H. Jones, Christopher Kaeding, Jeffrey N. Katz, Peter Kriz, Robert Magnussen, Ellen McErlean, Carrie Melgaard, Brett D. Owens, Paul Saluan, Greg Strnad, Carl S. Winalski and Rick Wright in Orthopaedic Journal of Sports Medicine

Published
2022
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14. Ultrasound-guided Percutaneous Cryoneurolysis to Treat Chronic Postamputation Phantom Limb Pain: A Multicenter Randomized Controlled Trial.

Author

Ilfeld, Brian M., Smith, Cameron R., Turan, Alparslan, Mariano, Edward R., Miller, Matthew E., Fisher, Rick L., Trescot, Andrea M., Cohen, Steven P., Eisenach, James C., Sessler, Daniel I., Prologo, J. David, Mascha, Edward J., Liu, Liu, Gabriel, Rodney A., Hayek, Salim M., Wadhwa, Anupama N., Beck, Gerald J., Abdullah, Baharin, Esa, Wael Ali Sakr, and Altinpulluk, Ece Yamak

Published
2023
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15. Arteriovenous Fistula Maturation, Functional Patency, and Intervention Rates

Author

Huber, Thomas S., primary, Berceli, Scott A., additional, Scali, Salvatore T., additional, Neal, Dan, additional, Anderson, Erik M., additional, Allon, Michael, additional, Cheung, Alfred K., additional, Dember, Laura M., additional, Himmelfarb, Jonathan, additional, Roy-Chaudhury, Prabir, additional, Vazquez, Miguel A., additional, Alpers, Charles E., additional, Robbin, Michelle L., additional, Imrey, Peter B., additional, Beck, Gerald J., additional, Farber, Alik M., additional, Kaufman, James S., additional, Kraiss, Larry W., additional, Vongpatanasin, Wanpen, additional, Kusek, John W., additional, and Feldman, Harold I., additional

Published
2021
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16. Design Features and Rationale of the BEAR-MOON (Bridge-Enhanced ACL Restoration Multicenter Orthopaedic Outcomes Network) Randomized Clinical Trial.

Author

Spindler, Kurt P., Imrey, Peter B., Yalcin, Sercan, Beck, Gerald J., Calbrese, Gary, Cox, Charles L., Fadale, Paul D., Farrow, Lutul, Fitch, Robert, Flanigan, David, Fleming, Braden C., Hulstyn, Michael J., Jones, Morgan H., Kaeding, Christopher, Katz, Jeffrey N., Kriz, Peter, Magnussen, Robert, McErlean, Ellen, Melgaard, Carrie, and Owens, Brett D.

Published
2022
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17. Non‐invasive prediction of pulmonary vascular disease‐related exercise intolerance and survival in non‐group 1 pulmonary hypertension.

Author

Reddy, Yogesh N.V., Dubrock, Hilary, Hassoun, Paul M., Hemnes, Anna, Horn, Evelyn, Leopold, Jane A., Rischard, Franz, Rosenzweig, Erika B., Hill, Nicholas S., Erzurum, Serpil C., Beck, Gerald J., Mathai, Stephen C., Mukherjee, Monica, Tang, W.H. Wilson, Borlaug, Barry A., and Frantz, Robert P.

Subjects
*PULMONARY hypertension, *DISEASE risk factors, *AEROBIC capacity, *CARDIAC output, *CARDIAC catheterization, PULMONARY artery diseases
Abstract

Aims Methods and results Conclusions The clinical utility of pulmonary hypertension (PH) risk scores in non‐group 1 PH with pulmonary vascular disease (PVD) remains unresolved.We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH‐related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c‐statistic to predict death was compared separately in (i) pre‐capillary PH groups 3/4/5, and (ii) combined post‐ and pre‐capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular–pulmonary artery (RV‐PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c‐statistic for predicting death (0.699, 95% confidence interval [CI] 0.660–0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656–0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c‐statistic difference −0.072, 95% CI −0.123 to −0.020, p = 0.006, and −0.043, 95% CI −0.067 to −0.018, p = 0.0007, respectively). RV function and RV‐PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non‐invasively identified non‐group 1 PH with more advanced PVD with worse exercise capacity, RV‐PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all).Non‐invasive REVEAL risk predicts mortality in non‐group 1 PH without incremental prognostic value from detailed RV function or RV‐PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non‐invasively identifies greater pulmonary vascular dysfunction and right heart‐related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non‐group 1 PH. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension.

Author

Simpson CE, Ambade AS, Harlan R, Roux A, Aja S, Graham D, Shah AA, Hummers LK, Hemnes AR, Leopold JA, Horn EM, Berman-Rosenzweig ES, Grunig G, Aldred MA, Barnard J, Comhair SAA, Tang WHW, Griffiths M, Rischard F, Frantz RP, Erzurum SC, Beck GJ, Hill NS, Mathai SC, Hassoun PM, and Damico RL

Subjects
Humans, Kynurenine, Tryptophan, Familial Primary Pulmonary Hypertension, Biomarkers, Hypertension, Pulmonary metabolism, Pulmonary Arterial Hypertension complications, Scleroderma, Systemic complications
Abstract

Understanding metabolic evolution underlying pulmonary arterial hypertension (PAH) development may clarify pathobiology and reveal disease-specific biomarkers. Patients with systemic sclerosis (SSc) are regularly surveilled for PAH, presenting an opportunity to examine metabolic change as disease develops in an at-risk cohort. We performed mass spectrometry-based metabolomics on longitudinal serum samples collected before and near SSc-PAH diagnosis, compared with time-matched SSc subjects without PAH, in a SSc surveillance cohort. We validated metabolic differences in a second cohort and determined metabolite-phenotype relationships. In parallel, we performed serial metabolomic and hemodynamic assessments as the disease developed in a preclinical model. For differentially expressed metabolites, we investigated corresponding gene expression in human and rodent PAH lungs. Kynurenine and its ratio to tryptophan (kyn/trp) increased over the surveillance period in patients with SSc who developed PAH. Higher kyn/trp measured two years before diagnostic right heart catheterization increased the odds of SSc-PAH diagnosis (OR 1.57, 95% CI 1.05-2.36, P = 0.028). The slope of kyn/trp rise during SSc surveillance predicted PAH development and mortality. In both clinical and experimental PAH, higher kynurenine pathway metabolites correlated with adverse pulmonary vascular and RV measurements. In human and rodent PAH lungs, expression of TDO2 , which encodes tryptophan 2,3 dioxygenase (TDO), a protein that catalyzes tryptophan conversion to kynurenine, was significantly upregulated and tightly correlated with pulmonary hypertensive features. Upregulated kynurenine pathway metabolism occurs early in PAH, localizes to the lung, and may be modulated by TDO2 . Kynurenine pathway metabolites may be candidate PAH biomarkers and TDO warrants exploration as a potential novel therapeutic target. NEW & NOTEWORTHY Our study shows an early increase in kynurenine pathway metabolism in at-risk subjects with systemic sclerosis who develop pulmonary arterial hypertension (PAH). We show that kynurenine pathway upregulation precedes clinical diagnosis and that this metabolic shift is associated with increased disease severity and shorter survival times. We also show that gene expression of TDO2, an enzyme that generates kynurenine from tryptophan, rises with PAH development.

Published
2023
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19. Classification and Predictors of Right Ventricular Functional Recovery in Pulmonary Arterial Hypertension.

Author

Rischard FP, Bernardo RJ, Vanderpool RR, Kwon DH, Acharya T, Park MM, Katrynuik A, Insel M, Kubba S, Badagliacca R, Larive AB, Naeije R, Garcia JGN, Beck GJ, Erzurum SC, Frantz RP, Hassoun PM, Hemnes AR, Hill NS, Horn EM, Leopold JA, Rosenzweig EB, Tang WHW, and Wilcox JD

Abstract

Background: Normative changes in right ventricular (RV) structure and function have not been characterized in the context of treatment-associated functional recovery (RVFnRec). The aim of this study is to assess the clinical relevance of a proposed RVFnRec definition., Methods: We evaluated 63 incident patients with PAH by right heart catheterization and cardiac MRI (CMR) at diagnosis and CMR and invasive cardiopulmonary exercise (CPET) following treatment (∼11 months). Sex, age, race/ethnicity matched healthy control subjects (n=62) with one-time CMR and non-invasive CPET were recruited from the PVDOMICS project. We examined therapeutic CMR changes relative to the evidence-based peak oxygen consumption (VO2 peak )>15mL/kg/min to define RVFnRec by receiver operating curve analysis. Afterload was measured in the as mean pulmonary artery pressure, resistance, compliance, and elastance., Results: A drop in RV end-diastolic volume of -15 mL best defined RVFnRec (AUC 0.87, P=0.0001) and neared upper 95% CI RVEDV of controls. 22/63 (35%) of subjects met this cutoff which was reinforced by freedom from clinical worsening, RVFnRec 1/21 (5%) versus no RVFnRec 17/42, 40%, (log rank P=0.006). A therapy-associated increase of 0.8 mL/mmHg in compliance had the best predictive value of RVFnRec (AUC 0.76, CI 0.64-0.88, P=0.001). RVFnRec subjects had greater increases in stroke volume, and cardiac output at exercise., Conclusions: RVFnRec defined by RVEDV therapeutic decrease of -15mL predicts exercise capacity, freedom from clinical worsening, and nears normalization. A therapeutic improvement of compliance is superior to other measures of afterload in predicting RVFnRec. RVFnRec is also associated with increased RV output reserve at exercise., Clinical Perspective: What is new?: Right ventricular functional recovery (RVFnRec) represents a novel endpoint of therapeutic success in PAH. We define RVFnRec as treatment associated normative RV changes related to function (peak oxygen consumption). Normative RV imaging changes are compared to a well phenotyped age, sex, and race/ethnicity matched healthy control cohort from the PVDOMICS project. Previous studies have focused on RV ejection fraction improvements. However, we show that changes in RVEDV are perhaps more important in that improvements in LV function also occur. Lastly, RVFnRec is best predicted by improvements in pulmonary artery compliance versus pulmonary vascular resistance, a more often cited metric of RV afterload. What are the clinical implications?: RVFnRec represents a potential non-invasive assessment of clinical improvement and therapeutic response. Clinicians with access to cardiac MRI can obtain a limited scan (i.e., ventricular volumes) before and after treatment. Future study should examine echocardiographic correlates of RVFnRec.

Published
2023
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