Heyde Syndrome Complicated by Pulmonary Embolism Before Transcatheter Aortic Valve Replacement: A Clinical Dilemma Between Bleeding and Thrombosis

Introduction

Severe aortic stenosis (AS) is a common and potentially life-threatening valvular heart disease among older adults. If left untreated, the 2-year mortality rate can approach 50% [1]. The association of severe AS with gastrointestinal bleeding is classically referred to as Heyde syndrome [2]. Severe AS generates chronic high shear stress across the stenotic valve, contributing to progressive cardiac dysfunction and a range of systemic complications [3–5]. Traditionally, the clinical course of Heyde syndrome is dominated by recurrent or refractory gastrointestinal bleeding, whereas concomitant thromboembolic events have rarely been described. We report a patient with Heyde syndrome complicated by acute pulmonary embolism (PE) who was treated at the Department of Cardiology, Tianjin Union Medical Center. The coexistence of severe bleeding and acute thromboembolism posed substantial diagnostic and therapeutic challenges. This report highlights the dilemma of balancing anticoagulation against the risk of recurrent hemorrhage and proposes a practical management approach for similar complex clinical scenarios.

Case Report

A 70-year-old woman presented with massive hematochezia and progressive dyspnea and was subsequently diagnosed with Heyde syndrome complicated by acute PE and bilateral lower-extremity deep vein thrombosis (DVT). We describe the diagnostic evaluation, staged therapeutic management, and 5-month clinical follow-up. Her past medical history included hypertension for 20 years, type 2 diabetes mellitus for 10 years, and longstanding bilateral lower-limb muscle atrophy for approximately 30 years. She had no history of chronic liver disease, chronic gastrointestinal disorders, malignancy, or spontaneous bleeding events. Family history was unremarkable for hematologic disorders, inherited bleeding tendencies, or other hereditary diseases. Subsequent investigations excluded primary gastrointestinal malignancy as a cause of bleeding.

Four days before admission, the patient developed recurrent episodes of painless, spontaneous bright-red hematochezia, with an estimated blood loss of 200 to 300 mL per episode. One day before transfer, computed tomography (CT) performed at a local hospital demonstrated increased pulmonary vascular markings, bilateral interstitial pulmonary changes, cardiomegaly, irregular gastric morphology, and linear hyperdense lesions within the rectum. Given the persistence of unexplained gastrointestinal bleeding, she was referred to the emergency surgery department of our institution for further evaluation and management. Laboratory investigations on admission revealed profound anemia consistent with acute blood loss, including a red blood cell count of 1.38×1012/L, hemoglobin of 44 g/L, and hematocrit of 13.7%. The platelet count remained within the normal range (122×109/L), suggesting that thrombocytopenia was unlikely to have contributed to the bleeding episode.

Emergency upper and lower gastrointestinal endoscopy revealed several potential bleeding-related lesions, including diffusely pale gastric mucosa, a diverticulum in the descending duodenum, multiple colonic diverticula containing blood-stained luminal contents, and tortuous dilated vascular clusters in the ascending colon (Figure 1). Initial management consisted of bowel rest, proton pump inhibitor therapy, intravenous fluid resuscitation, and packed red blood cell transfusion. Despite these interventions, the patient developed sudden-onset dyspnea and orthopnea approximately 12 hours after admission. Laboratory testing demonstrated markedly elevated brain natriuretic peptide levels, supporting a diagnosis of acute decompensated heart failure. Given the coexistence of ongoing gastrointestinal hemorrhage and acute cardiac decompensation, the patient was promptly transferred to the coronary care unit (CCU) for intensive hemodynamic monitoring and specialized management.

On admission to the CCU, the patient’s vital signs were as follows: temperature, 36.5 °C; heart rate, 93 beats/min; respiratory rate, 17 breaths/min; and blood pressure, 104/63 mm Hg. The patient was alert and oriented, with marked pallor of the conjunctivae, lips, and nail beds. Pulmonary examination revealed coarse breath sounds with bilateral basal crackles, findings consistent with pulmonary congestion. Cardiac examination demonstrated a regular rhythm and a grade 4/6 harsh systolic ejection murmur best heard at the aortic area with radiation to the carotid arteries, a classic finding of severe AS. The abdomen was soft and non-tender, and no peripheral edema was observed. Bilateral calf muscle atrophy was noted on examination.

Routine laboratory investigations revealed no significant abnormalities in liver function, renal function, lipid profile, electrolyte levels, or tumor markers. Persistent fecal occult blood positivity was observed, while N-terminal pro–B-type natriuretic peptide was markedly elevated at 5663.61 pg/mL. Electrocardiography demonstrated diffuse ST-segment depression accompanied by ST-segment elevation in lead aVR, findings that raised suspicion for extensive myocardial ischemia, including possible left main coronary artery disease, multivessel disease, or subendocardial ischemia related to severe AS. Arterial blood gas analysis revealed mild metabolic acidosis without significant impairment of oxygenation. The initial D-dimer level was mildly elevated at 0.99 mg/L. Transthoracic echocardiography demonstrated severe AS, characterized by an aortic valve area of 0.8 cm2, peak transvalvular velocity of 4.2 m/s, and mean pressure gradient of 71 mm Hg. Left ventricular systolic function was preserved, with a left ventricular ejection fraction of 55%. These findings established severe AS as the principal cardiac abnormality underlying the patient’s clinical presentation.

Given the coexistence of severe AS and recurrent gastrointestinal bleeding, further evaluation of von Willebrand factor (vWF) function was undertaken to investigate the possibility of acquired von Willebrand syndrome. Laboratory testing demonstrated reduced vWF antigen (vWF: Ag) levels of 38.5% (reference range, 50%–160%) and markedly decreased vWF ristocetin cofactor activity (vWF: RCo) of 25.3% (reference range, 48.8%–163.4%), resulting in a vWF: RCo/vWF: Ag ratio of < 0.7. In conjunction with endoscopic evidence of vascular malformations and recurrent gastrointestinal bleeding, these findings supported a diagnosis of acquired von Willebrand syndrome and established the diagnosis of Heyde syndrome. Differential diagnoses, including peptic ulcer disease, inflammatory bowel disease, gastrointestinal malignancy, immune thrombocytopenia, and inherited coagulation disorders, such as hemophilia, were excluded based on endoscopic findings, clinical history, and laboratory investigations. Genetic testing was not performed because of financial limitations. Repeat contrast-enhanced CT revealed no evidence of intrathoracic or intra-abdominal mass lesions or occult malignancy.

A staged and individualized treatment strategy was adopted according to the relative urgency of the patient’s competing clinical conditions. Initial management focused on stabilization of active gastrointestinal bleeding through gastric mucosal protection, hemostatic therapy, and blood product replacement, including transfusion of 9 units of packed red blood cells and 400 mL of plasma. These interventions achieved effective bleeding control and increased the hemoglobin concentration to 103 g/L. The patient’s EuroSCORE II was calculated at 8.05%, indicating an elevated operative risk for conventional surgical aortic valve replacement (SAVR). Consequently, transcatheter aortic valve replacement (TAVR) was selected as the preferred definitive intervention to reduce procedural risk while addressing the underlying pathophysiological driver of Heyde syndrome.

On hospital day 10, preprocedural aortic and coronary computed tomography angiography (CTA) unexpectedly revealed acute right-sided segmental and subsegmental pulmonary emboli. Retrospective review of clinical data demonstrated persistent mild hypoxemia, with oxygen saturation ranging from 90% to 95% on room air. Repeat laboratory testing showed a marked increase in D-dimer levels to 14.04 mg/L, while ultrasound of the lower limb vessels confirmed bilateral calf DVT.

Risk stratification demonstrated a PE Severity Index (PESI) score of 86 and a Bova score of 3, consistent with an intermediate-risk PE profile. At that time, gastrointestinal bleeding had ceased and hemoglobin levels had stabilized above 90 g/L, allowing consideration of therapeutic anticoagulation despite the recent hemorrhagic event. Although the HAS-BLED score was 3, indicating a moderate bleeding risk, the anticipated benefits of anticoagulation were considered to outweigh the potential risk of recurrent hemorrhage. In accordance with contemporary guideline recommendations [6], a staged anticoagulation strategy was initiated with subcutaneous low-molecular-weight heparin (4000 IU every 12 hours), followed by transition to oral rivaroxaban (15 mg once daily) after 3 days. The patient remained clinically stable without recurrent bleeding and was discharged after a total hospital stay of 16 days.

One month after discharge, follow-up CT pulmonary angiography demonstrated complete resolution of the pulmonary emboli (Figure 2). The patient was subsequently readmitted for preprocedural reassessment, during which pulmonary function testing revealed no significant abnormalities. Elective TAVR was successfully performed under general anesthesia using a TaurusElite AV21 bioprosthetic valve (Figure 3). Postprocedural transthoracic echocardiography demonstrated marked improvement in aortic valve hemodynamics, with a peak transvalvular velocity of 1.8 m/s and a mean pressure gradient of 13.8 mm Hg (Figure 4). Follow-up laboratory testing demonstrated normalization of von Willebrand factor parameters (vWF: Ag 370.5%, vWF: RCo 269.5%), consistent with correction of acquired von Willebrand syndrome following relief of valvular obstruction. The patient recovered uneventfully and was discharged in stable condition. A detailed timeline of diagnostic evaluation, therapeutic interventions, and follow-up is provided in Table 1.

At the 4-month follow-up, the patient demonstrated sustained clinical improvement, with no recurrence of dyspnea or gastrointestinal bleeding. Follow-up transthoracic echocardiography confirmed normal prosthetic valve function with preserved left ventricular systolic performance. The patient successfully resumed routine daily activities without functional limitation. No recurrent thromboembolic events, heart failure exacerbations, or valve-related complications were observed during follow-up, indicating a favorable mid-term clinical outcome.

Discussion

CLINICAL DECISION-MAKING: BALANCING PE AND BLEEDING RISK:

The incidental detection of PE during preprocedural CTA for TAVR created a significant therapeutic dilemma. Risk stratification demonstrated an intermediate-risk PE (PESI grade III, Bova stage II) according to the PESI and Bova scoring systems [26,27], whereas the HAS-BLED score of 3 indicated a moderate risk of recurrent bleeding. Following multidisciplinary discussion, anticoagulation was prioritized over immediate TAVR for several reasons. First, untreated PE carried a substantial risk of clinical deterioration and recurrent thromboembolic events. Second, gastrointestinal bleeding had been effectively controlled, and no further transfusion support was required. Third, heart failure symptoms had stabilized under medical therapy. Accordingly, anticoagulation was initiated with low-molecular-weight heparin 10 days after confirmed hemostasis, followed by transition to rivaroxaban once clinical stability had been achieved. Follow-up CT pulmonary angiography performed 1 month later demonstrated complete resolution of PE without recurrent gastrointestinal bleeding. Rivaroxaban was selected because of its rapid onset of action, predictable pharmacokinetic profile, and absence of a requirement for routine coagulation monitoring [28–30]. The delayed initiation of anticoagulation following confirmation of hemostasis was consistent with contemporary recommendations for balancing thrombotic and bleeding risks after major gastrointestinal hemorrhage [31].

In patients with recent or active gastrointestinal bleeding, prioritizing TAVR before anticoagulation may reduce bleeding-related complications but may also delay treatment of concomitant thromboembolic disease. In the present case, the decision to postpone TAVR and initiate anticoagulation first was based on the presence of intermediate-risk PE, stable hemostasis, and adequately controlled heart failure. Follow-up imaging confirmed complete thrombus resolution without recurrent bleeding, supporting the safety and effectiveness of this staged approach. The sequencing of anticoagulation and valve intervention should therefore be individualized according to thrombotic burden, bleeding risk, and overall clinical status. Should recurrent gastrointestinal bleeding occur during anticoagulant therapy, temporary interruption of anticoagulation, accompanied by gastrointestinal protective measures and endoscopic hemostasis when appropriate, may be considered, followed by multidisciplinary reassessment of treatment priorities [32].

Aortic valve replacement, either surgical (SAVR) or transcatheter (TAVR), is the definitive treatment for Heyde syndrome as it eliminates the pathological shear stress responsible for acquired von Willebrand syndrome and recurrent gastrointestinal bleeding [33,34]. Given the elevated operative risk reflected by a EuroScore II of 8.05%, TAVR was selected as the preferred treatment strategy in this patient. Following successful anticoagulation and complete resolution of PE, TAVR was performed without complications. Subsequent normalization of vWF parameters, marked improvement in aortic valve hemodynamics, and the absence of recurrent gastrointestinal bleeding during follow-up collectively support successful reversal of the underlying disease process. This case underscores that correction of AS remains the cornerstone of treatment in Heyde syndrome and may facilitate the safe management of coexisting thromboembolic complications through a staged, individualized therapeutic approach [35].

Conclusions

Clinicians should consider underlying high-shear cardiovascular conditions, such as severe AS or hypertrophic obstructive cardiomyopathy, in patients presenting with unexplained gastrointestinal bleeding and should remain vigilant for potential thromboembolic complications. This rare case of Heyde syndrome complicated by acute PE and DVT highlights the therapeutic challenge of balancing hemorrhagic and thrombotic risks. Because severe AS is the primary driver of acquired von Willebrand syndrome, correction of valvular obstruction through TAVR may effectively reverse the underlying hemostatic abnormalities. In the present case, a staged strategy involving bleeding stabilization, carefully timed anticoagulation, multidisciplinary assessment, and subsequent TAVR was feasible and was associated with favorable clinical outcomes. This case expands the recognized clinical spectrum of Heyde syndrome and offers valuable clinical insights into the treatment of patients with coexisting bleeding and thromboembolic complications.