Integrated Clinical and Magnetic Resonance Imaging Assessments Late After Fontan Operation

Integrated Clinical and Magnetic Resonance Imaging Assessments Late After Fontan Operation.

Meyer SL, St Clair N, Powell AJ, Geva T, Rathod RH.J Am Coll Cardiol. 2021 May 25;77(20):2480-2489. doi: 10.1016/j.jacc.2021.03.312.PMID: 34016261


Take Home Points:

  • Increased ventricular dilation was the strongest independent predictor of death or transplant (listing).
  • Patients with both ventricular dilation and worse GCS were at highest risk.
  • These data highlight the value of integrating CMR and clinical parameters for risk stratification in this population.

Dr Soha Romeih

Commentary by Dr. Soha Romeih (Aswan, Egypt), section editor of ACHD Journal Watch: Meyer et al presented the largest study, to our knowledge, to determine the relative importance and interactions of clinical and CMR parameters for risk of death, heart transplantation, or listing for transplant in a large cohort of patients late after the Fontan operation.


Despite important improvements in mortality and morbidity over the years, adverse outcomes are increasingly common as Fontan patients enter adulthood. Several risk factors for death or heart transplant have been identified, including clinical parameters, such as history of protein-losing enteropathy and congestive heart failure. Reported ventricular parameters associated with this endpoint include right-dominant ventricular morphology, increased indexed end-diastolic volume (EDVi) of the functional single ventricle, increased ventricular mass, worse ventricular strain, and worse functional single ventricle global function index (SVGFI).


Cardiac magnetic resonance (CMR) remains the preferred modality for the assessment of ventricular size and function in these patients. Although some risk factors for death or heart transplant have been identified, information is lacking on their relative importance and how these variables relate to different subgroups.


The aim of this study was to identify the relative importance and interactions of clinical and CMR parameters for risk of death or transplant after the Fontan operation using CART analysis.



All Fontan patients who had a postoperative CMR study at Boston Children’s Hospital between 2019 and 2002 were retrospectively reviewed. Patients were included for analysis if they had a minimum of 1 year of follow-up since the CMR or if they reached the defined endpoint.


Patients were excluded from analysis if cine imaging was not performed or if technical limitations precluded reliable measurements of ventricular size and function parameters.


Fontan patients were retrospectively reviewed. Clinical and CMR parameters were analyzed using univariable Cox regression. The primary endpoint was time to death or (listing for) heart transplant. To identify the patients at highest risk for the endpoint, classification and regression tree survival analysis was performed, including all significant variables from Cox regression.


STUDY ENDPOINT. The primary clinical endpoint was time to all-cause mortality and listing for or receiving a heart transplant. For survival analyses, follow-up was measured from the date of CMR to either the first occurrence of the endpoint or the last known follow-up date with documentation of transplant-free survival. Any reference in this manuscript to transplant-free survival or death/transplant includes patients who met any of the 3 criteria of our composite endpoint (listing for heart transplant, receiving a heart transplant, or death)


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The cohort consisted of 416 patients (62% male) with a median age of 16 years (25th, 75th percentiles: 11, 23 years). Over a median follow-up of 5.4 years (25th, 75th percentiles: 2.4, 10.0 years) after CMR, 57 patients (14%) reached the endpoint (46 deaths, 7 heart transplants, 4 heart transplant listings). Lower total indexed end-diastolic volume (EDVi ) was the strongest predictor of transplant-free survival. Among patients with dilated ventricles (EDVi 156 ml/BSA1.3), worse global circumferential strain (GCS) was the next most important predictor (73% vs. 44%). In patients with smaller ventricles (EDVi)


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In this large cohort of patients late after the Fontan operation, lower CMR-derived EDVi emerged as the strongest independent predictor of transplant-free survival. Furthermore, in patients with moderate or worse ventricular dilation, worse GCS had additional discriminating power for predicting death, heart transplant, or listing for transplant. Asymptomatic patients with smaller ventricles had the highest transplant-free survival. These data introduce important interactions between ventricular dilation, measures of systolic function, and symptoms in this population and highlight the utility of CMR for risk stratification.


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The data highlight the importance of combining variables to identify clinically meaningful subgroups that are at highest or lowest risk for death and transplantation in patients late after the Fontan operation.