A novel real-time magnetic resonance imaging approach to study orthostatic intolerance mechanisms in patients with hypermobile Ehlers-Danlos syndrome

Abstract

Background: Patients diagnosed with the hypermobile Ehlers-Danlos syndrome often experience orthostatic intolerance, particularly the postural tachycardia syndrome (POTS). To discern hemodynamic mechanisms limiting orthostatic tolerance in these patients, we applied a novel approach combining real-time magnetic resonance imaging (MRI), physiological monitoring, and orthostatic testing through lower body negative pressure (LBNP). Materials and Methods: We recruited 9 women with hypermobile Ehlers-Danlos syndrome and POTS (33 ± 7 years; 22.5 ± 4.8 kg/ m²) and 5 matched healthy controls (35 ± 10 years; 23.8 ± 3 kg/ m²). One patient with pure autonomic failure (PAF) served as positive control. We performed real-time cardiac MRI without and during - 30 mmHg LBNP with 33 ms temporal resolution to measure stroke volume in the ascending aorta and venous flow in the inferior vena cava. We recorded brachial blood pressure, beat-to-beat finger arterial blood pressure, ECG, and respiration. Results: LBNP increased heart rate by 24.7 ± 10.9 bpm in patients and by 8.2 ± 6.7 bpm in control persons (p \0.01). Blood pressure did not change significantly in either group. Cardiac stroke volume decreased 24.3 ± 6.6 ml in patients and 19.7 ± 7.2 ml in control persons (p = 0.079). However, cardiac output responded similarly in both groups. With LBNP, inferior vena cava flow decreased 688 ± 25 ml/min (n = 4) in patients and 510 ± 42 ml/min in control persons. Middle cerebral artery blood flow remained unchanged during LBNP, only the right side showed a reduced peak velocity (p = 0.027). In the patient with PAF, blood pressure decreased from 118/74 to 58/35 mmHg with LBNP, heart rate remained unchanged, stroke volume decreased 45%, and middle cerebral artery blood flow decreased 0.06 ± 0.01 l/min during LBNP. Conclusion: Combination of cardiac real-time MRI and LBNP is a feasible approach to study hemodynamic mechanisms contributing to orthostatic intolerance in patients. The unobtrusive nature of the test, which does not require breath-holding or ECG triggering, and the ability to measure absolute vascular flow are distinct advantag