Therapeutic alternatives in chronic thromboembolic pulmonary hypertension: from pulmonary endarterectomy to balloon pulmonary angioplasty to medical therapy. State of the art from a multidisciplinary team

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with a very complex pathophysiology differing from other causes of pulmonary hypertension (PH). It is an infrequent consequence of acute pulmonary embolism that is frequently misdiagnosed. Pathogenesis has been related to coagulation abnormalities, infection or inflammation, although these disturbances can be absent in many cases. The hallmarks of CTEPH are thrombotic occlusion of pulmonary vessels, variable degree of ventricular dysfunction and secondary microvascular arteriopathy. The definition of CTEPH also includes an increase in mean pulmonary arterial pressure of more than 25 mmHg with a normal pulmonary capillary wedge of less than 15 mmHg. It is classified as World Health Organization group 4 PH, and is the only type that can be surgically cured by pulmonary endarterectomy (PEA). This operation needs to be carried out by a team with strong expertise, from the diagnostic and decisional pathway to the operation itself. However, because the disease has a very heterogeneous phenotype in terms of anatomy, degree of PH and the lack of a standard patient profile, not all cases of CTEPH can be treated by PEA. As a result, PH-directed medical therapy traditionally used for the other types of PH has been proposed and is utilized in CTEPH patients. Since 2015, we have been witnessing the rebirth of balloon pulmonary angioplasty, a technique first performed in 2001 but has since fallen out fashion due to major complications. The refinement of such techniques has allowed its safe utilization as a salvage therapy in inoperable patients. In the present keynote lecture, we will describe these therapeutic approaches and results.

Keywords: Pulmonary hypertension; balloon angioplasty; hypothermia; pulmonary endarterectomy; vasodilator.

Figure 1

The natural history of the disease can be summarized as follows: once an acute pulmonary embolism has occurred, it can have a variable clinical expression, be asymptomatic or in the other extreme, lead to death of the patient. Although complete healing can certainly occur, in some cases, the fresh thrombus can also evolve towards the fibrotic organization, where further acute or thromboembolic events may even occur in situ. This situation would lead to evolution of the disease, in a variable time frame so-called the honeymoon period, which clinically corresponds to chronic thromboembolic pulmonary disease, giving rise in some cases to pulmonary hypertension, remodeling of the microcirculation and all the typical cardiopulmonary consequences of this disease. CTEPH, chronic thromboembolic pulmonary hypertension; CTED, chronic thromboembolic disease.

Figure 2

Leading experts in PEA suggest performing the surgery in hypothermic circulatory arrest, in order to ensure a complete, safe and effective endarterectomy. A crucial moment of the intervention is the recognition of the cleavage plane (B) after correct exposure and arteriotomy (A). The cleavage plane is not always recognizable at the proximal level when fibrosis is present in segmental or distal branches. Naturally, a cleavage plane that is too deep or too superficial would result in an extreme permeability of the vessel with the risk of parenchymal hemorrhage in the first case or a failure to resolve pulmonary hypertension in the second case. It is possible to extract up to the distal branches (D) using precise instruments, such as Jamiesson aspirators, following the cleavage plane (C) and maintaining a progressive and delicate traction of the fibrotic thrombus. PEA, pulmonary endarterectomy.

Figure 3

These two pictures represent the macroscopic differences between a fresh thrombus (A) and chronic fibrotic material (B) removed by pulmonary endarterectomy. In Figure 2A, there is a combination of both, with apposition of a fresh thrombus upstream to a fibrotic thrombus characteristic of CTEPH. A case like this might be very confounding, as the clinical condition of the patient was rapidly worsening, mimicking an acute high-risk pulmonary embolism. CTEPH, chronic thromboembolic pulmonary hypertension.

Video

Therapeutic alternatives in chronic thromboembolic pulmonary hypertension: from pulmonary endarterectomy to balloon pulmonary angioplasty to medical therapy. State of the art from a multidisciplinary team.