Sotatercept for Decompensated Pulmonary Arterial Hypertension Requiring VA ECMO: First Canadian ICU Experience

ABSTRACT

Pulmonary arterial hypertension (PAH) is a rare and progressive disease resulting in increased workload of the right ventricle (RV). Despite advances in therapies, PAH remains highly morbid from a progressive vasculopathy and RV failure. For patients admitted to hospital with RV failure, transplant remains the only option for a select few. Sotatercept, a novel activin signaling inhibitor approved for the treatment of PAH, has demonstrated significant improvement in clinical outcomes across a wide spectrum of disease severity. However, descriptions of its use to treat acute RV failure in an intensive care unit (ICU) setting are limited. We report a case of cardiogenic shock and respiratory failure secondary to decompensated PAH requiring veno‐arterial extracorporeal membrane oxygenation (VA ECMO), with rapid improvement following sotatercept initiation.

1.

A 50‐year‐old female with high‐risk precapillary idiopathic PAH on baseline oral triple therapy was admitted to our ICU with cardiogenic shock and acute hypoxemic respiratory failure after self‐discontinuing her selexipag. Initial echocardiogram (TTE) demonstrated a severely dilated and dysfunctional RV with a small pericardial effusion. Despite intravenous epoprostenol, inotropes, and diuretics, she clinically worsened, and was initiated on VA ECMO on hospital day (HD) 2. Her ECMO course was complicated by sepsis and a small subdural hemorrhage. She was successfully decannulated from ECMO on HD17 (ECMO Day 15) but remained hypoxemic requiring 100% oxygen via high flow nasal oxygen and dependent on inotropes to maintain adequate tissue perfusion. Serial echocardiograms failed to show improvement in RV function despite continuation of parenteral prostanoids. In the ICU, she was assessed and accepted for lung transplantation. On HD 57, she received her first dose of sotatercept 0.3 mg/kg; over the ensuing days she experienced rapid improvements in hemodynamics and oxygen requirements in the absence of other new therapeutic interventions. Ultimately, she was transitioned back to her prior oral regimen with Tadalafil, Macitentan, and Selexipag and discharged on room air. After 4 doses of Sotatercept, repeat TTE showed improved RV function, and follow‐up right heart catheterization demonstrated improved hemodynamics in comparison to her prior outpatient catheterization, with reductions in mean pulmonary artery pressure and pulmonary vascular resistance, along with an improved cardiac output (Table 1).

Table 1.

Pertinent PAH markers of disease activity before and after sotatercept therapy.

Test	Before sotatercept	After sotatercept
N‐terminal pro‐B‐type natriuretic peptide (ng/L)	803	312
6 min walk (meters)	300	336
Right atrial pressure (mmHg)	10	8
Mean pulmonary artery pressure (mmHg)	47	28
Pulmonary capillary wedge pressure (mmHg)	9	7
Cardiac output (L/min)	3.6	3.9
Pulmonary vascular resistance (Woods Units)	10.5	6.1
Echocardiographic fractional area change (%)	30	43

To our knowledge, this is the first report of sotatercept use in a Canadian ICU setting to treat RV failure due to decompensated PAH, with subsequent rapid clinical and hemodynamic improvement. Although sotatercept has been extensively evaluated in outpatient populations, evidence in hospitalized or critically ill patients remains limited. Sotatercept is recommended as adjunct therapy for PAH patients who have not achieved low‐risk status despite combination therapy [1]. Clinical trials have shown significant benefits in pulmonary vascular resistance (PVR), exercise capacity, and clinical outcomes [2, 3, 4], even among patients with severely impaired hemodynamics, including 51 patients with cardiac indices < 2.0 [5]. In select series, some patients treated with Sotatercept were able to discontinue parenteral Treprostinil therapy [6]. The concept of Sotatercept “super‐responders” has been proposed to refer to those who derive a marked benefit from therapy [7]. The ZENITH trial highlighted that in PAH patients at high risk for death, those randomized to Sotatercept demonstrated a 76% reduction in the risk of a composite of all‐cause death, lung transplantation, and hospitalization for PAH ≥ 24 h [3]. Our case extends these findings by demonstrating sotatercept's potential as a rescue therapy in acute RV failure refractory to maximal conventional treatment.

Following initiation, our patient was liberated from inotropes and oxygen, transitioned off parenteral prostacyclin, and stabilized to defer lung transplantation. The rapidity of her clinical and hemodynamic response is striking, as sotatercept's proposed mechanism of action involves pulmonary vascular remodeling, a process expected to occur over weeks to months. This raises the possibility that sotatercept may also exert more immediate effects on the pulmonary vasculature or right ventricular loading conditions, which could explain the dramatic improvement in this setting.

Hypoxemia in pulmonary hypertension (PH) arises from multiple interacting mechanisms, including ventilation–perfusion (V/Q) mismatch, impaired alveolar–capillary diffusion, right‐to‐left shunting, and reduced mixed venous oxygen content (SvO2). Pulmonary vascular remodeling reduces the functional capillary bed and disrupts perfusion, producing V/Q mismatch. Thickened and remodeled vessel walls further increase the oxygen diffusion barrier, while RV dysfunction and reduced cardiac output (CO) lower SvO2 through increased peripheral oxygen extraction. We theorize that Sotatercept may have improved oxygenation in our patient via improved perfusion distribution, reduced RV afterload, increased CO, and higher SvO2. In the STELLAR trial, sotatercept improved SvO2 by 3.84% compared with placebo, and was associated with improvements in pulmonary artery (PA) compliance, PA–RV coupling, and RV function [2]. Olsson et al. also reported improvements in diffusion capacity for carbon monoxide (DLCO) and arterial oxygen tension (PaO₂) with sotatercept versus placebo [8]. By increasing functional pulmonary capillary surface area, sotatercept may enhance diffusion capacity and gas exchange.

Current treatment options for acute RV failure remain extremely limited, often restricted to mechanical circulatory support or lung transplantation. Our case illustrates that sotatercept may represent a novel therapeutic option in this critically ill population, a group not well captured in existing studies. Further research into the role of sotatercept in critically ill PAH patients with RV failure should be pursued.

Beyond its clinical impact, this case raises an urgent issue of access. Sotatercept is not currently covered by public drug programs in Canada, leaving patients dependent on private insurance or exceptional access mechanisms. For those with advanced PAH and right heart failure, this represents a critical barrier that can mean the difference between stabilization and progression to end‐stage disease, transplantation, or death. Given the high morbidity, mortality, and economic burden of PAH, including prolonged hospitalizations and the cost of advanced therapies, the absence of sotatercept from public coverage represents a sizeable gap in care.

Incorporation of sotatercept into Canadian public drug benefit programs would align practice with international treatment recommendations, reduce hospitalizations, defer transplantation, and improve survival and quality of life for patients with PAH. Policymakers should prioritize expedited review and timely funding decisions of sotatercept to ensure access to this transformative therapy for all Canadians with PAH.

All tests measured in the ambulatory setting; Before sotatercept measurements obtained prior to her hospitalization/decompensation. After sotatercept measurements obtained after 4 doses of Sotatercept therapy.

Author Contributions

Jonathan Taylor concept, data gathering, interpretation, drafting of the manuscript. Eddy Fan concept, interpretation, revision of the manuscript. John Thenganatt concept, interpretation, revision of the manuscript. John Granton concept, interpretation, revision of the manuscript.

Funding

The authors received no specific funding for this work.

Ethics Statement

Informed consent for patient information to be published was provided by the patient.

Conflicts of Interest

J.T.: No conflicts of interest to disclose. E.F: Reports personal fees from Aerogen, Boehringer Ingelheim, Getinge, Inspira, Mallinckrodt, Vantive, and Vasomune outside the submitted work. J.T.: Advisory Board and Speaker Bureau for Johnson and Johnson. J.G.: Reports financial support from Janssen Pharmaceuticals for a hospital foundation Pulmonary Hypertension fellowship and reports speaking honorarium from Merck.