Longitudinal changes in ventricular size and function are associated with death and transplantation late after the Fontan operation

Abstract

Background Cross-sectional studies have reported that ventricular dilation and dysfunction are associated with adverse clinical outcome in Fontan patients; however, longitudinal changes and their relationship with outcome are not known. Methods This was a single-center retrospective analysis of Fontan patients with at least 2 cardiovascular magnetic resonance (CMR) scans without intervening interventions. Serial measures of end-diastolic volume index (EDVI), end-systolic volume index (ESVI), ejection fraction (EF), indexed mass (massi), mass-to-volume ratio, and end-systolic wall stress (ESWS) were used to estimate within-patient change over time. Changes were compared for those with and without a composite outcome (death, heart transplant, or transplant listing) as well as between patients with left (LV) and right ventricular (RV) dominance. Results Data from 156 patients were analyzed with a mean age at 1st CMR of 17.8 ± 9.6 years. 490 CMRs were included with median of 3 CMRs/patient (range 2–9). On regression analysis with mixed effects models, volumes and ESWS increased, while mass, mass-to-volume ratio, and EF decreased over time. With a median follow-up of 10.2 years, 14% met the composite outcome. Those with the composite outcome had a greater increase in EDVI compared to those without (4.7 vs. 0.8 ml/BSA1.3/year). Compared with LV dominance, RV dominance was associated with a greater increase in ESVI (1.4 vs. 0.5 ml/BSA1.3/year), a greater decrease in EF (− 0.61%/year vs. − 0.24%/year), and a higher rate of the composite outcome (21% vs. 8%). Conclusions Ventricles in the Fontan circulation exhibit a steady decline in performance with an increase in EDVI, ESVI, and ESWS, and decrease in EF, mass index, and mass-to-volume ratio. Those with death or need for heart transplantation have a faster increase in EDVI. Patients with rapid increase in EDVI (> 5 ml/BSA1.3/year) may be at a higher risk of adverse outcomes and may benefit from closer surveillance. RV dominance is associated with worse clinical outcomes and remodeling compared to LV dominance.

Cardiovascular magnetic resonance reference values of right ventricular volumetric variables in patients with hypoplastic left heart syndrome

“…As the population of HLHS patients is growing and aging, there is increasing concern about the performance of the systemic RV. Previous imaging studies, including research from this group, have shown that ventricular function in HLHS patients declines over the years [5] , [14] although changes in functional parameters in pediatric and adolescent patients are relatively small [5] , [6] . Others have shown that CMR-derived variables seem to be predictive of long-term outcomes in Fontan patients [14] , [15] , [16] , [17] .…”

“…Previous imaging studies, including research from this group, have shown that ventricular function in HLHS patients declines over the years [5] , [14] although changes in functional parameters in pediatric and adolescent patients are relatively small [5] , [6] . Others have shown that CMR-derived variables seem to be predictive of long-term outcomes in Fontan patients [14] , [15] , [16] , [17] . It was shown that increased indexed end-diastolic volumes (EDVi) and rapid increase in EDVi predict adverse outcomes [14] , [16] , [17] .…”

Ventricular Dyssynchrony Late after the Fontan Operation is Associated with Decreased Survival and the Presence of Arrhythmias

“…This study reaffirmed that impaired ventricular ejection fraction, ventricular dilation, and RV or mixed ventricular morphology are established risk factors for poor clinical outcomes in patients with a Fontan circulation. 3,43,44 Multivariable analysis revealed that the association of adverse outcomes with markers of dyssynchrony is not independent of established conventional markers such as ventricular systolic dysfunction and dilation. Our findings of lower event-free survival in RV or mixed ventricular subtypes agree with prior large multicenter observational studies on Fontan patients, which have demonstrated lower long-term survival.…”

Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study

“…The preteen period may be too early to detect systolic dysfunction by CMR. Ghelani et al 18 recently described longitudinal changes in ventricular function and showed that on consecutive CMR, ejection fraction decreased over time among patients undergoing the Fontan procedure who were followed into early adulthood. Moreover, despite many risk factors considered and comprehensive prospective collection of data, even extensive modeling provided little insight into risk factors for lower RVEF.…”

“…Right ventricular function was measured with CMR as well as with 2-dimensional transthoracic echocardiography. Participants who underwent CMR were 10.9 years of age (interquartile range, 10.4-11.5) at the time of CMR, and, compared with those who did not have CMR, they had a significantly shorter hospital length of stay after the Norwood procedure (22 [interquartile range, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] versus 28 days [interquartile range, 20-39]; P=0.02) and were more likely to be male (66% versus 47%; P=0.01; Table S2). Among the 177 participants who underwent CMR, RVEF was measurable in 168 (95%); the mean±SD for the overall cohort was 51.5±8.6% (RVPAS 51±9.…”