CMR Associations of Diastolic Dysfunction in Fontan patients. A FORCE registry study.

Presenting Author(s)

• 

  Tarek Alsaied, MD

  Assistant Professor of Pediatrics
  Children's Hospital of Pittsburgh

Primary Author(s)

• 

  Tarek Alsaied, MD

  Assistant Professor of Pediatrics
  Children's Hospital of Pittsburgh

Co-Author(s)

• RL

  Runjia Li

  Assistant professor
  University of Pittsburgh
• HG

  Haley Grant, PhD

  Assistant professor
  Children's Hospital of Pittsburgh
• MS

  Mary Schiff, PhD, MPH

  Senior Statistician
  Children's Hospital of Pittsburgh of UPMC
• YL

  Yu Li, MD, MSc

  Resident Physician
  UPMC Children's Hospital of Pittsburgh
• AC

  Adam B. Christopher, MD

  Assistant professor
  UPMC Children's Hospital of Pittsburgh
• JK

  Jacqueline Kreutzer, MD

  Professor
  Children's Hospital of Pittsburgh
• BG

  Bryan Goldstein, MD

  Director of Cardiac Catheterization & Intervention
  Children's Hospital of Pittsburgh of UPMC
• 

  Jonathan Soslow, MD, MSCI

  Professor
  Vanderbilt University Medical Center
  Vanderbilt
• 

  Joshua D. Robinson, MD, FSCMR

  Section Head, Cardiac Imaging
  Lurie Children's Hospital of Chicago
  Lurie Children's Hospital
• 

  Yue-Hin Loke, MD

  Associate Professor
  Children's National Medical Center
• MF

  Mark A. Fogel, MD, FACC, FAHA, MSCMR, FNASCI, FAAP

  Professor
  University of Pennsylvania
• 

  Timothy Slesnick, MD

  Pediatric Cardiologist
  Children's Healthcare of Atlanta
• 

  Rajesh Krishnamurthy, MD

  Professor
  The Ohio State University
• 

  Vivek Muthurangu, MD

  Professor
  University College London, United Kingdom
• 

  Adam Dorfman, MD

  Professor
  University of Michigan
• 

  Christopher Z. Lam, MD

  Pediatric Cardiac Radiologist
  The Hospital for Sick Children, University of Toronto, Canada
• 

  Justin Weigand, MD

  Assistant Professor
  Baylor College of Medicine / Texas Children's Hospital
• 

  Laura Olivieri, MD

  Associate Professor of Pediatrics
  Children's Hospital of Pittsburgh of UPMC
• 

  Rahul H. Rathod, MD, MBA

  Associate Chair of Cardiology
  Boston Children's Hospital

Background: Fontan patients are at high risk of diastolic dysfunction (DD) and elevated end-diastolic pressure (EDP). Identifying the EDP threshold linked with adverse outcomes and recognizing clinical and imaging predictors of DD using CMR could inform early intervention and management strategies. This study aims to determine (1) the optimal EDP threshold correlated with adverse clinical outcomes in Fontan patients and (2) the clinical and imaging predictors of DD, utilizing data from the Fontan Outcomes Registry Using Cardiac MRI Examinations (FORCE).

Methods: The study included 861 patients from the FORCE registry who underwent cardiac catheterization and CMR within two years of each other. The primary composite outcome was defined as the time to the earliest occurrence of all-cause mortality, sustained atrial or ventricular arrhythmia, plastic bronchitis, protein-losing enteropathy, or listing for transplantation. We used Cox proportional hazards models to assess the association between EDP and outcomes. The EDP cutoff was determined using the lowest Brier score from the models. Multivariable regression analyses were conducted to identify risk factors associated with elevated EDP and DD.

Results: The mean age of participants was 16.4 ± 9.3 years, with a predominance of right ventricle morphology and lateral tunnel Fontan. The mean EDP was 9.0 ± 3.5 mmHg, with an optimal cutoff identified at >13 mmHg. Patients were followed for a median of 3.6 years after the cardiac catheterization. Univariate analysis demonstrated that EDP, end diastolic volume (EDV), atrioventricular valve regurgitation, non-left ventricular morphology, and EF were all associated with adverse outcomes. On stepwise multivariate analysis, only EDP (HR 1.11 per 1 mm Hg, 95% CI: 1.05-1.18, p< 0.001) and EDV (HR 1.08 per 10 ml/m2, 95% CI: 1.04-1.11, p=0.047) remained significant. DD, defined by EDP >13 mmHg, was associated with > threefold increase in the hazard of adverse outcomes (HR 3.18, 95% CI: 1.93-5.24, p< 0.001).
Ninety-seven patients (11.3%) met the definition of DD. Patients with DD were older (20.7 ± 9.7 vs. 15.8 ± 9.1 years, p< 0.001) and had higher BMI. Patients with DD had higher ventricular end diastolic volume, end systolic volume with lower ejection fraction. Patients with DD were also more likely to have at least moderate atrioventricular valve regurgitation or aortic regurgitation. The rate of late gadolinium enhancement in the systemic ventricle was higher in the group with DD compared to the group without diastolic dysfunction 15.5 vs 9.2% (p=0.05).
Multivariable analysis including clinical and imaging data showed that increased age at catheterization, increased body mass index, non-left ventricular morphology and higher ventricular end diastolic volume were associated with increased risk of DD.

Conclusion: DD defined as an EDP >13 mmHg is linked to threefold higher adverse outcomes. Risk factors for DD include older age, higher BMI, non-left ventricular morphology, and larger EDV. Ventricular dilation due to valvar disease and worse systolic function by CMR coupled with LGE may indicate higher EDP and should prompt evaluation for DD.  

Figure. Forest plot of Cox model showing increased hazard for the composite outcome with increased diastolic pressure (EDP) >13 mm Hg which is the cutoff for diastolic dysfunction in this study. End diastolic volume is also associated with the adverse outcome.