The Fuvid Study: Functional Characterization of Children with Pulmonary Embolism in a Prospective Multicenter Cohort Study
Authors: Primeaux Sharon , Stutzman Sonja E , Malone Kendra , Schaefer Beverly , Bhat Rukhmi , Khan Osman , Torres Marcela , Kumar Riten , Rajpurkar Madhvi , Bernstein Jonathan , Hege Kerry , Pacheco Martha , Crary Shelley E , O'Brien Sarah H. , Tarango Cristina , Whitworth Hilary , Woods Gary , Betensky Marisol , Cohen Clay , Amos Lauren E. , Beg Kisha A , Garcia Jessica , Goldenberg Neil , Male Christoph , Klok Frederikus A , Zhang Song , Babb Tony , Nelson Michael , Hussain Tarique , Greer Joshua , Ren Jimin , Mattrey Robert , Srivaths Lakshmi V , Jesudas Rohith , Wilson Hope P. , Weyand Angela C , Branchford Brian R. , Jaffray Julie , Gurunathan Arun , Martinelli Marie , Corley Susan , Sida Deseray , Zia Ayesha 
Published: December 2024

Background and Significance: Exercise intolerance and dyspnea on exertion (DOE) are frequent after pulmonary embolism (PE) despite anticoagulation and may impact quality of life. There is little research that fully explains why this occurs, nor are there specific treatments or guidelines for PE complications in children or young adults. The FUVID Program (NCT04583878) will examine the impact of 3 mechanisms underlying exercise intolerance and DOE: cardiac (right ventricular maladaptation and its coupling with the pulmonary circulation) dysfunction, pulmonary limitations secondary to persistent vascular obstruction, and skeletal muscle metabolic abnormalities on exercise intolerance and DOE after PE.

Study Design and Methods: This prospective, multi-center, observational study is enrolling previously healthy patients ages 8-21 years with acute, first-episode PE with or without DVT. A positive control group with no PE but with physical activity restrictions mimicking a deconditioning effect as patients with PE (cohort 1) and control group with no prescribed physical activity restrictions and otherwise considered healthy (cohort 2) will be enrolled. Patients will be enrolled within 8 weeks of diagnosis of PE from 13 enrollment and 25 recruitment sites across the US. Due to the complexity of the cutting-edge metabolic and functional tools only available at UTSW (namely, MR spectroscopy at 7 Telsa to study in-vivo muscle metabolic function and perfusion and exercise cardiac MRI), research assessments will occur centrally at 3- and 12-months post-diagnosis. Exercise capacity will be defined as peak oxygen uptake (VO2), expressed as a percent predicted based on ideal body weight during cardiopulmonary exercise testing. The primary comparison will be between participants with and without exercise intolerance. Key secondary subgroup analyses will include: sex (male/female), PE category (low risk/non-low-risk), and thrombolysis (yes/no).

Results/Discussion: We have enrolled 67 PE participants (planned=80) from participating enrollment sites and 30 case-controls (planned=30). We propose that 1) the right ventricle will be unable to overcome afterload placed on it during exercise, preventing optimal coupling with pulmonary circulation, 2) arterial desaturation during maximal cycling exercise combined with dysfunctional breathing of deconditioning will provoke greater DOE and intolerance, and 3) depletion and recovery of muscle phosphocreatine in-vivo will predict exercise intolerance. Our results will provide critically informative data to phenotype pediatric post-PE syndrome accurately and allow investigation of cardiac, vascular, and musculoskeletal mechanisms associated with post-PE syndrome assessed during exercise.