Author + information
- Published online February 4, 2019.
- Eva van den Bosch, MD,
- Sjoerd S.M. Bossers, MD, PhD,
- Daniëlle Robbers-Visser, MD, PhD,
- Eric Boersma, PhD,
- Jolien W. Roos-Hesselink, MD, PhD,
- Hans M.P.J. Breur, MD, PhD,
- Nico A. Blom, MD, PhD,
- Lucia J.M. Kroft, MD, PhD,
- Miranda M. Snoeren, MD, PhD,
- Livia Kapusta, MD, PhD and
- Willem A. Helbing, MD, PhD∗ ()
- ↵∗Erasmus University Medical Center, Sophia Children's Hospital, Department of Pediatrics, Division of Pediatric Cardiology, SP-2426, P.O. Box 2060, 3000 CM Rotterdam, the Netherlands
Cardiovascular magnetic resonance (CMR) using exercise or pharmacological stress might detect early dysfunction (3). Our aim was to evaluate the value of dobutamine-stress CMR to predict adverse outcome in patients with a Fontan circulation.
In earlier multicenter prospective studies, we obtained results of low-dose (7.5 μg/kg/min) dobutamine-stress CMR, serum N-terminal pro–B-type natriuretic peptide (NT-proBNP) and cardiopulmonary exercise testing (4). In the current study, the composite endpoint included events during follow-up after baseline CMR: cardiac death or reintervention, protein-losing enteropathy, and hospitalization or cardioversion/ablation for arrhythmias.
Time-to-event analyses (Kaplan-Meier method) and Cox proportional hazard regression analyses were performed to determine the predictive value for the endpoint. A p value <0.05 was required for the parameter to remain in the multivariable model.
Ventricular volumes were analyzed according to common practice and were indexed for body surface area (4). Changes in CMR parameters during stress were calculated as follows: parameter change = parameterstress − parameterrest.
Ninety-two patients were included, median age at stress CMR 11.5 (interquartile range [IQR]: 9.8 to 15.3) years, median time after Fontan completion 8.0 (IQR: 6.9 to 11.3) years. Thirty-one patients had a dominant right ventricle, 56 had a dominant left ventricle, and in 5 the dominant ventricle was undefined. The intra-atrial tunnel Fontan technique was used in 45, an extracardiac conduit in 42, and an atriopulmonary connection in 5 patients.
During dobutamine-stress, end-diastolic volume index (85 ± 21 vs. 73 ± 21 ml/m2; p < 0.001) and end-systolic volume index (39 ± 16 vs. 26 ± 13 ml/m2; p < 0.001) decreased and ejection fraction increased (55 ± 10 vs. 65 ± 10%; p < 0.001).
Twenty-three patients developed an event, a median 3.1 (IQR: 1.5 to 5.7) years after baseline CMR. These events were death (n = 1), cardiac reoperations (n = 7), out-of-hospital cardiac arrest (n = 1), hospitalization/ablation for arrhythmias (n = 7), pacemaker implantation (n = 5), extracardiac conduit–conduit stenting (n = 1), and coiling collaterals (n = 1). Protein-losing enteropathy was not noted.
Age at baseline CMR was similar for the event and nonevent groups. There was no significant difference in the presence of moderate to severe atrioventricular valve regurgitation, present in 30% of the event group versus 29% of the nonevent group, p = 0.895. There was no significant difference in peak Vo2 (event group: 34.4 [IQR: 24.8 to 39.4] ml/min/kg; p = 0.66; n = 72), predicted Vo2 peak (event group: 77.5% [IQR: 57.7 to 88.3]; p = 0.14; n = 72), or NT-proBNP (event group: 13.7 [IQR: 8.2 to 47.8] pmol/l; p = 0.18; n = 83) at baseline for the event versus the nonevent group.
Patients who developed an event had a lower increase in ejection fraction during stress (functional reserve [FR]) and a higher ventricular wall mass, compared with the nonevent group (FR: 6 ± 7 vs. 11 ± 6%; p = 0.002, mass 73 ± 23 vs. 57 ± 16 g/m2; p < 0.001). We found no relation between right ventricle/left ventricle dominance or moderate and severe atrioventricular valve regurgitation and stress response.
In Figure 1, the event-free survival for the different quartiles of FR is shown. The event-free survival was better for the patients in the highest quartile of FR (≥14%) (log rank: 0.024). In the lowest, intermediate, and highest quartiles, respectively 10, 11, and 2 patients developed an event.
In univariable analysis age at CMR and Fontan, right ventricle morphology, (log transformed) NT-proBNP, peak Vo2, end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, and moderate and severe atrioventricular valve regurgitation were not found to be predictive for the composite study endpoint. In multivariable analyses with the significant predictors from the univariable analysis, FR (hazard ratio [HR]: 0.86%; 95% confidence interval [CI]: 0.79 to 0.93; p < 0.001) and ventricular mass (HR: 1.04 g/m2; 95% CI: 1.02 to 1.07; p = 0.001) were predictive for the study endpoint. There was no significant correlation (r = –0.069; p = 0.510) between ventricular mass and FR.
In this study we have demonstrated, using a composite endpoint derived of common outcomes in Fontan patients, that patients with a Fontan circulation with a good ventricular response to dobutamine stress have a lower risk of developing cardiac events during follow-up. The relation between stress CMR parameters and hard outcome measures has only been reported in congenital heart disease in adults (3). Because none of the other previously identified predictors (end-diastolic volume index >125 ml/m2, peak Vo2, NT-proBNP) (1,2,5) related to outcome in our young patients, who could be considered at relatively low risk, we think stress CMR parameters, particularly FR, may be useful early markers for outcome in Fontan patients.
Please note: Drs. van den Bosch and Bossers were supported by research grants from the Dutch Heart Foundation (grant 2013T091 to Dr. Helbing and grant 2008T037 to Dr. Helbing). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
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