The Impact of Venous Outflow Obstruction on Venous Return to the Heart: Preload, Cardiac Function and Exercise Tolerance Before and after Endovascular Reconstruction

Up to 50% of patients develop post-thrombotic venous outflow obstruction (PTVO) after iliocaval deep venous thrombosis. Chronic venous hypertension can lead to severe limb pain, swelling and venous claudication, limiting exercise tolerance and daily activities. Patients presenting with exertional dyspnea and exercise intolerance may be investigated in the first instance for chronic thromboembolic pulmonary hypertension; however, these symptoms could also be due to insufficient venous return to heart, leading to an impairment in stroke volume and limitation in cardiac output. This study aimed to quantify cardiac function during exercise in patients with PTVO and evaluate changes after endovascular recanalization. Patients with PTVO without chronic thromboembolic pulmonary hypertension, and age and gender matched healthy controls underwent cardiopulmonary exercise testing (CPET) and exercise cardiac magnetic resonance imaging (ExCMR) using an MR-compatible supine cycle-ergometer. A real-time image acquisition and post-processing framework was used to obtain an electrocardiogram and respiratory gated two-dimensional flow and cine images at rest and during exercise, allowing measurement of flow in the aorta and vena cava and quantification of cardiac volumes. These measurements were used to calculate stroke volume and cardiac output. Patient-specific workloads for supine cycle exercise inside the scanner were determined from CPET performance (watts at anaerobic threshold +10%). Patients undergoing stenting repeated the tests 6 to 8 weeks after intervention. Twenty-seven patients (19 males and 8 females; aged 44.2 ± 13.7 years) and 10 controls (7 males and 3 females; aged 44 ± 13.5 years) completed CPET and exCMR. Participants were matched for body mass index (30 ± 5.4 vs 27.6 ± 4.3; P = .33) and physical activity levels (General Practice Physical Activity Questionnaire Score 3.14 ± 0.86 for patients, 3.4 ± 0.5 for controls; P = .4). Peak maximum oxygen uptake (VO2) was impaired in patients (median, 17.9 mL/min/kg; 66% of predicted) and lower than controls (30.65 mL/mL/kg; 100% of predicted; P < .0001) despite maximal tests being achieved. Anaerobic threshold, workload and VO2/heart rate ratio were also lower than controls (P < .0002; P < .05; P < .0007). Ten patients repeated testing after iliocaval stenting. Peak VO2 improved by 28% (P < .002), anaerobic threshold by 24% (P < .002), workload by 10% (P < .001), and VO2/heart rate ratio by 14% (P < .001). The increase in stroke volume and cardiac index during ExCMR was significantly lower in prestent patients vs controls (0.8% vs 16.5% P < .01; and 5.5 L/min/m2 vs 8.6 L/min/m2; P < .05, respectively) despite similar heart rates (approximately 135 bpm). On postoperative testing, patients were able to increase stroke volume significantly from rest to exercise (15% increase; P < .01), leading to improvement in cardiac index (5.5 L/min/m2 prestent to 7.1 L/min/m2 post-stent; P < .05). PTVO can limit peak VO2, stroke volume and cardiac output during exercise. Significant functional improvements are observed after stenting.