Approximately 2% to 3% of patients who experience acute pulmonary thromboembolism develop chronic thromboembolic pulmonary hypertension (CTEPH) within the following 2 years.1 The prevalence of CTEPH is estimated at 26 to 38 cases per million population. The prognosis of this condition depends on clinical, analytic, hemodynamic, and imaging parameters, with a 1-year mortality rate of >20% in high-risk patients.1 Pulmonary balloon angioplasty (PBA) is a key treatment in patients who are not candidates for surgery.2 This intervention provides a demonstrated hemodynamic and functional improvement, which, according to some studies, is maintained over medium- and long-term follow-up.3 However, certain clinical situations may predispose to recurrence of the disease despite initially successful PBA. This report describes 2 patients with CTEPH and severe pulmonary hypertension (PH) who underwent successful PBA but experienced disease recurrence with severe resting PH several years after completing treatment.

The first case involves a patient with congenital hydrocephalus secondary to stenosis of the aqueduct of Silvius, initially managed with a ventriculoperitoneal shunt, and later with 2 ventriculoatrial shunts (VAS). At the age of 19 years the patient was diagnosed with inoperable CTEPH and underwent 9 PBA procedures, which resulted in a pronounced clinical and hemodynamic improvement (table 1). Three years later, following suboptimal adherence to acenocoumarol anticoagulation therapy, the patient experienced clinical deterioration. Cardiopulmonary exercise testing revealed findings indicative of a poor prognosis: reduced peak VO2 (14.2mL/kg/min, 28% of predicted) and elevated VE/VCO2 ratio (62.7). Pulmonary angiography confirmed rethrombosis of the pulmonary arteries and severe PH (table 1). The case was discussed in a multidisciplinary session. The group decided to repeat PBA and switch from acenocoumarol to edoxaban to ensure proper anticoagulation. The neurosurgery team ruled out the possibility of removing the VAS, the potential embolic source; hence, aspirin was added to the patient's therapy. The improvements achieved after 4 additional PBA procedures are shown in table 1 and figure 1.

Figure 1.

Patient 1. A and B: ventriculoatrial shunt (arrows). C: baseline pulmonary angiography showing distal thrombotic involvement in the middle lobe. D: pulmonary rethrombosis in right lower lobe branches 6 years after PBA. Changes in the right ventricle: baseline echocardiogram (E), after the first PBA program (F), before the second PBA program (G), and after completing the second PBA program (H). PBA, pulmonary balloon angioplasty.

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The second patient had a posterior fossa brain tumor, which led to the development of hydrocephalus. Surgery and VAS implantation were carried out in infancy. At the age of 27 years, the patient experienced bilateral pulmonary thromboembolism and later developed inoperable CTEPH. Six PBA procedures were performed, resulting in a marked improvement (table 1), and he was discharged with acenocoumarol therapy. Six years later, the patient was reassessed due to clinical deterioration. Recurrence of severe HP was detected (table 1), as well as evidence of pulmonary rethrombosis despite adequate coagulation. Five new PBA sessions were carried out and the neurosurgery team removed the VAS.

Although it has been reported that the hemodynamic and functional results of PBA persist over time,3 the true rate of recurrent CTEPH after PBA is unknown. We present 2 patients with inoperable CTEPH who experienced recurrence years after successful PBA, possibly related to persistent emboli resulting from the VAS. In a recent report,4 13 of 200 patients (6%) who underwent PBA experienced recurrent CTEPH, and 9 of them were treated with new PBA procedures. No predisposing factors were identified. In our experience, the incidence of recurrent HP due to rethrombosis is lower, affecting only 2 of the 197 patients treated with PBA in our center.5

The presence of permanent catheters in the right heart chambers is a known risk factor for CTEPH. In addition, inconsistent anticoagulation may promote rethrombosis, although other factors are usually involved, as it does not occur in all patients with inadequate anticoagulation. While there are no clinical trials comparing direct-acting anticoagulants with non-vitamin K antagonists in CTEPH, the former seem to be linked to higher rates of venous rethrombosis.1 Studies have shown that the combination of low-dose aspirin and vitamin K antagonists (international normalized ratio, 2-3) reduces rethrombosis without increasing major bleeding events in patients with antiphospholipid syndrome.6 This strategy is also used in CTEPH patients with rethrombosis to mitigate the bleeding risk associated with more aggressive anticoagulation regimens. In any case, long-term studies are needed to determine the true recurrence rate of this complication after BPA and precisely identify any predisposing factors. Considering the possibility that VAS could be a risk factor, we recommend close monitoring of patients undergoing this treatment to enable early detection of recurrent CTEPH.