Exercise MRI highlights heterogeneity in cardiovascular mechanics among patients with Fontan circulation: proposed protocol for routine evaluation

Abstract

Single ventricle physiology and palliation via the Fontan operation lead to a series of cardiovascular changes. In addition, organs such as the kidneys and liver have been shown to experience insults and subsequent injury. This has led to routine surveillance of patients. We present findings from a small cohort of patients that was deeply phenotyped to illustrate the need for comprehensive evaluation. A cohort of four Fontan patients with fairly high cardiovascular function was recruited 5-10 years post-Fontan. Patients underwent a rigorous clinical work-up after which a research MRI scan was performed during which (I) data were obtained during exercise to evaluate changes in stroke volume during supine exercise and (II) magnetic resonance angiograms with phase-contrast images were obtained for computational modeling of flows through the Fontan circulation at rest. Clinical measures were consistent with a fairly homogeneous high function cohort (peak oxygen consumption >20 mL/kg/min, robust response to exercise, peak ventilatory efficiency below levels associated with heart failure, MR-derived ejection fraction >50%). Liver evaluation did not reveal clear signs of cirrhosis or extensive fibrosis. However, we observed considerable variability (27-162%) in the increase in stroke index with exercise [100%±64% increase, 53.9±17.4 mL/beat m² (rest), 101.1±20.7 mL/beat m², (exercise)]. Computational flow modeling at rest in two patients also showed marked differences in flow distribution and shear stress. We report marked differences in both changes in stroke index during an exercise MRI protocol as well as computational flow patterns at rest suggesting different compensation strategies may be associated with high functioning Fontan patients. The observed heterogeneity illustrates the need for deep phenotyping to capture patient-specific adaptive mechanisms.

Keywords: Fontan; exercise; flow modeling; magnetic resonance imaging.

Figure 1

Stroke index (mL/beat m²) measured via MRI at rest and during exercise as well as absolute and percent changes as a function of Fontan-specific mICHF score. The mICHF score for each patient were as follows: Patient 1 Score = 1, Patient 2 Score = 2, Patient 3 Score =4, Patient 4 Score =3. mICHF, Modified Ishak Congestive Hepatic Fibrosis.

Figure 2

3D visualization of time averaged velocity, wall shear stress, and oscillatory shear index in Fontan conduit and pulmonary vasculature calculated from computation fluid dynamics utilizing MRI phase contrast flow measurement for patients 1 and 2 at rest. Patient 1 has a more even distribution of flow and wall shear stress whereas Patient 2 has high blood flow velocity and shear stress in the right pulmonary artery. Patient 1 is 12.4 years old with an extra-cardiac Fontan, systemic RV, low Fontan pressure (10 mmHg), and low transpulmonary gradient (3 mmHg), and has low Fibrosis measures (mICHF of 1, MRE of 3.7 kPa). Subject 2 is 19.2 years old with a lateral tunnel Fontan, low Fontan pressure (12 mmHg), low transpulmonary gradient (3 mmHg), Fibrosis scores of mICHF =2 and MRE of 3.5 kPa. mICHF, Modified Ishak Congestive Hepatic Fibrosis; MRE, magnetic resonance elastography; OSI, oscillatory shear index.