Case Presentation: An 81-year-old woman with a history of hypertrophic cardiomyopathy (HCM) and prior gastrointestinal (GI) bleeding of unknown origin in 2017 presented with lightheadedness and anemia after undergoing an ERCP the day before. She had multiple episodes of maroon-colored stool and melena while in the ED and was transfused one unit of packed red blood cells. Physical exam was notable for a grade IV/VI systolic murmur loudest at the left lower sternal border and radiated to the carotids and the back. CTA confirmed active mucosal bleeding in the ascending colon and cecum. She later underwent a bidirectional endoscopy, which was unremarkable and did not demonstrate any active bleeding. Her echocardiogram showed a thick interventricular septum measuring 1.6 cm, systolic anterior motion of the mitral valve, and a significant resting left ventricular outflow tract (LVOT) gradient of 75 mmHg. Her Factor VIII and von Willebrand factor (vWF) antigen levels were both elevated. vWF:ristocetin cofactor to vWF:antigen ratio was 0.63 (abnormal <0.7) and only 7% of high molecular weight multimers (HMWM) was present. This loss was consistent with an acquired von Willebrand syndrome (AvWS), raising concern for bleeding from an undetected GI angiodysplasia. Going forward, the patient would likely benefit from a septal myectomy.
Discussion: In Heyde syndrome, increased shear stress across a stenotic aortic valve causes AvWS, which is characterized by increased proteolysis of vWF HMWM. The loss of HMWM impairs primary hemostasis, predisposes the patient to mucosal bleeding and GI angiodysplasias, and resolves after replacement of the valve. Few reports of an AvWS in HCM patients describe a similar pathophysiology of proteolysis due to high shear stress from the LVOT obstruction. Le Tourneau et al. demonstrated that the degree of vWF impairment is strongly associated with the severity of obstruction, and a resting LVOT gradient of 15 mmHg is enough to cause abnormalities in vWF function. Furthermore, the association between angiodysplasias and vWF dysfunction is well-described in the literature. While angiodysplasias are considered a normal part of vascular aging, GI bleeding from these vascular malformations primarily occurs in patients selectively lacking VWF HMWM, suggesting that vWF multimers play an important role in regulation of angiogenesis in addition to hemostasis. This is further evidenced by cessation of spontaneous, mucosal, or excessive perioperative bleeding after a HCM patient with AvWS receives a septal myectomy and there is no longer a loss of HMWM. The relation between HMWM and GI bleeding therefore highlights the need for further investigation of AvWS in patients with conditions of high shear stress such as HCM. Workup should include vWF multimer analysis in addition to vWF antigen, ristocetin cofactor, and factor VIII levels, as it can often be the only abnormal finding. Management should be directed at decreasing the LVOT gradient with beta blockade, alcohol septal ablation, and most definitively with surgical septal myectomy.
Conclusions: HCM patients presenting with GI bleeding should be investigated for AvWS, as the hemostatic defect resolves with a septal myectomy.