Image-Based Computational Model Predicts Dobutamine-Induced Hemodynamic Changes in Patients With Aortic Coarctation.

BACKGROUND: Pharmacological stress testing can help to uncover pathological hemodynamic conditions and is, therefore, used in the clinical routine to assess patients with structural heart diseases such as aortic coarctation with borderline indication for treatment. The aim of this study was to develop and test a reduced-order model predicting dobutamine stress induced pressure gradients across the coarctation. METHODS: The reduced-order model was developed based on n=21 imaging data sets of patients with aortic coarctation and a meta-analysis of subjects undergoing dobutamine stress testing. Within an independent test cohort of n=21 patients with aortic coarctation, the results of the model were compared with dobutamine stress testing during catheterization. RESULTS: In n=19 patients responding to dobutamine stress testing, pressure gradients across the coarctation during dobutamine stress increased from 15.7±5.1 to 33.6±10.3 mm Hg (paired t test, P<0.001). The model-predicted pressure gradients agreed with catheter measurements with a mean difference of -2.2 mm Hg and a limit of agreement of ±11.16 mm Hg according to Bland-Altman analysis. Significant equivalence between catheter-measured and simulated pressure gradients during stress was found within the study cohort (two 1-sided tests of equivalence with a noninferiority margin of 5.0 mm Hg, 33.6±10.33 versus 31.5±11.15 mm Hg, P=0.021). CONCLUSIONS: The developed reduced-order model can instantly predict dobutamine-induced hemodynamic changes with accuracy equivalent to heart catheterization in patients with aortic coarctation. The method is easy to use, available as a web-based calculator, and provides a promising alternative to conventional stress testing in the clinical routine. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02591940.

Hemodynamic Changes During Physiological and Pharmacological Stress Testing in Healthy Subjects, Aortic Stenosis and Aortic Coarctation Patients-A Systematic Review and Meta-Analysis.

Introduction: Exercise testing has become a diagnostic standard in the evaluation and management of heart disease. While different methods of exercise and pharmacological stress testing exist, only little is known about their comparability. We aimed to assess hemodynamic changes during dynamic exercise, isometric exercise, and dobutamine stress testing at different stress intensities in healthy subjects and patients with aortic stenosis (AS) and aortic coarctation (CoA). Methods: A systematic literature search (PROSPERO 2017:CRD42017078608) in MEDLINE of interventional trials was conducted to identify eligible studies providing evidence of changes in hemodynamic parameters under different stress conditions acquired by MRI or echocardiography. A random effects model was used to estimate pooled mean changes in hemodynamics. Results: One hundred and twenty-eight study arms with a total of 3,139 stress-examinations were included. In healthy subjects/(where available) in AS, pooled mean changes (95% CIs) during light dynamic stress were 31.78 (27.82-35.74) bpm in heart rate (HR) and 6.59 (2.58-10.61) ml in stroke volume (SV). Changes during light pharmacological stress were 13.71 (7.87-19.56)/14.0 (9.82-18.18) bpm in HR, and 5.47 (0.3-10.63)/8.0 (3.82-12.18) ml in SV. Changes during light isometric stress were 18.44 (10.74-26.14)/5.0 (-1.17-11.17) bpm in HR and -4.17 (-14.37-6.03)/-4.0 (-16.43-8.43) ml in SV. Changes during moderate dynamic stress were 49.57 (40.03-59.1)/46.45 (42.63-50.27) bpm in HR and 11.64 (5.87-17.42) ml in SV. During moderate pharmacological stress, changes in HR were 42.83 (36.94-48.72)/18.66 (2.38-34.93) bpm and in SV 6.29 (-2.0-14.58)/13.11 (7.99-18.23) ml. During high intensity dynamic stress changes in HR were 89.31 (81.46-97.17)/55.32 (47.31-63.33) bpm and in SV 21.31 (13.42-29.21)/-0.96 (-5.27-3.35) ml. During high pharmacological stress, changes in HR were 53.58 (36.53-70.64)/42.52 (32.77-52.28) bpm, and in SV 0.98 (-9.32-11.27)/14.06 (-1.62-29.74) ml. HR increase and age were inversely correlated at high stress intensities. In CoA, evidence was limited to single studies. Conclusion: This systematic review and meta-analysis presents pooled hemodynamic changes under light, moderate and high intensity exercise and pharmacological stress, while considering the potential influence of age. Despite limited availability of comparative studies, the reference values presented in this review allow estimation of the expected individual range of a circulatory response in healthy individuals and patients with AS and may contribute to future study planning and patient-specific models even when stress testing is contraindicated.