Orthostatic intolerance with Klippel-Trenaunay syndrome

Abstract

Orthostatic intolerance (OI) can result from inadequate cerebral perfusion and excessive sympathetic activation in patients with cardiovascular autonomic dysregulation [1]. Postural pooling of circulating fluid is one of its main pathophysiological mechanisms [1, 2]. Klippel-Trenaunay syndrome (KTS) is a genetic condition belonging to PIK3CA-related overgrowth spectrum (PROS) [3]. Vascular and lymphatic anomalies in KTS may cause dependent fluid stasis intensifying orthostatic stress. OI can concur with various hemodynamic changes including orthostatic hypotension (a drop in systolic blood pressure by ≥ 20 mmHg) and an exaggerated postural tachycardia (a sustained increase in heart rate by ≥ 30 bpm without orthostatic hypotension in 10 min of standing) [1, 4]. We present two cases of KTS with chronic OI and exaggerated postural tachycardia. A 44-year-old man with a history of clinically diagnosed KTS presented with chronic OI. KTS mainly affected the right leg. Despite repeated surgical debulking of vascular malformation from KTS during childhood, OI had become worse gradually over the past 2 decades. While walking or standing for a few minutes, he felt lightheaded with dyspnea and palpitations. Standing heart rate (HR) could go up to 190 bpm. In a few minutes of standing, the right leg increased in size with prominent venous engorgement. He had to put the leg on a stool in order to stand longer at home. Physical examination showed a large, red–purple, vascular stain overlapped with venous varicosities over the right buttock. There was an extensive skin area with vascular blebs and prominent torturous varicosities over the right leg, worse on the lateral aspect. The right leg was longer than the left by a few inches. Shortly after standing, the right leg became swollen and bigger with accentuated engorgement of varicosities, which lying down with leg elevation reversed (Fig. 1a, b). Neurological examination was unremarkable except for mild right foot weakness. A duplex ultrasound on the leg showed enlarged superficial veins with excessive connections to the deep veins. Angiogram of the abdomen did not show vascular malformation. Cardiovascular reflexes during a deep breathing and Valsalva maneuver were normal. A 10-min-long tilt-table test (TTT) showed intermittent delayed drop in blood pressure (BP) with recovery with compensatory increase in HR from a baseline of 97 bpm up to 175 bpm. It reproduced usual symptoms and the dynamic morphological changes of the leg. To investigate effects of blood pooling, a second TTT was done with a large-sized BP cuff wrapped around the right thigh after 20 min of rest in a supine position. The cuff pressure was maintained at 120 mmHg by clamping its tube. Standing HR increased again without a drop in BP. However, its change from 102 bpm to 141 was less dramatic. The patient reported milder and delayed symptoms compared to the first TTT. Vascular surgeons were already consulted. Midodrine was tried without significant improvement. Four months later, he had cyanoacrylate embolization in the right saphenous vein and reported immediate symptom improvements. A third TTT without a cuff around the thigh after the embolization revealed normal hemodynamic changes (Fig. 1c, d). In the second case, a 33-year-old man with an unspecified over-growth syndrome affecting his right arm and leg presented with a 10-year history of postural palpitations, chest pain, and sweating, which disappeared upon lying down. These symptoms were worse in summertime. Midodrine was tried but intolerable because of side effects. On physical examination, there were patches of port-wine stain on the skin of the right arm, partially covered by tattoos. * Dong In Sinn [email protected]