Prostacyclin Therapy Before Pulmonary Thromboendarterectomy in Patients With Chronic Thromboembolic Pulmonary Hypertension

doi:10.1378/chest.123.2.338

Chest

Volume 123, Issue 2, February 2003, Pages 338-343

https://doi.org/10.1378/chest.123.2.338 Get rights and content

Objectives:

The continuous IV administration of prostacyclin improves pulmonary hemodynamics and prognosis in patients with primary pulmonary hypertension. We investigated whether the administration of prostacyclin therapy to patients before they undergo pulmonary thromboendarterectomy ameliorates pulmonary hypertension in patients with the most severe form of chronic thromboembolic pulmonary hypertension (CTEPH).

Methods:

Of the 33 patients with CTEPH who were candidates for pulmonary thromboendarterectomy, 12 patients with severe pulmonary hypertension (pulmonary vascular resistance, > 1,200 dyne · s · cm⁻⁵) received IV prostacyclin prior to undergoing pulmonary thromboendarterectomy. Right heart catheterization and plasma brain natriuretic peptide (BNP) measurements were repeated at baseline, immediately before surgery, and 1 month after surgery.

Results:

During a mean (± SEM) follow-up period of 46 ± 12 days, the IV administration of prostacyclin resulted in a 28% decrease in pulmonary vascular resistance (1,510 ± 53 to 1,088 ± 58 dyne · s · cm⁻⁵; p < 0.001) before surgery. Prostacyclin therapy markedly decreased plasma BNP level (547 ± 112 to 188 ± 30 pg/mL; p < 0.01), suggesting improvement in right heart failure. Pulmonary thromboendarterectomy caused a further reduction of pulmonary vascular resistance (302 ± 47 dyne · s · cm⁻⁵) and plasma BNP levels (60 ± 11 pg/mL) compared to each preoperative value (p < 0.05). Operative mortality rates were relatively low (8.3%) in patients with the most severe form of CTEPH.

Conclusion:

The IV administration of prostacyclin caused beneficial hemodynamic effects in patients with severe CTEPH and may serve as pretreatment for patients undergoing pulmonary thromboendarterectomy.

Section snippets

Study Patients

This study included 33 consecutive patients with CTEPH (11 men and 22 women; mean age, 54 years; age range, 22 to 76 years) who had undergone pulmonary thromboendarterectomy from December 1998 to October 2001. The preoperative condition was New York Heart Association (NYHA) functional class III or IV. Twelve patients who had a pulmonary vascular resistance of > 1,200 dyne · s · cm⁻⁵ at diagnostic catheterization received IV prostacyclin before undergoing pulmonary thromboendarterectomy

Characteristics of Patients With and Without Prostacyclin Therapy

There was no significant difference in age or sex between the prostacyclin group and the conventional group (Table 1). NYHA functional class was significantly higher in the prostacyclin group than in the conventional group. Baseline heart rate, mean pulmonary arterial pressure, pulmonary vascular resistance, and mean right atrial pressure were significantly higher in the prostacyclin group than in the conventional group. Cardiac output, arterial oxygen saturation, and mixed venous oxygen

Discussion

In the present study, prostacyclin therapy was performed as pretreatment before pulmonary thromboendarterectomy for patients with the most severe form of CTEPH. We demonstrated the following: (1) that IV administration of prostacyclin markedly decreased pulmonary vascular resistance in patients with CTEPH; (2) that IV prostacyclin also decreased plasma BNP levels before surgery; and (3) that the surgical mortality rate of patients with severe CTEPH who had received prostacyclin were relatively

Conclusion

These preliminary results suggest that the IV administration of prostacyclin may have beneficial hemodynamic effects in patients with severe CTEPH and may serve as pretreatment before they undergo pulmonary thromboendarterectomy.

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Comparison of different treatment strategies in patients with chronic thromboembolic pulmonary hypertension: a single centre real-world experience
2023, International Journal of Cardiology
Pulmonary endarterectomy (PEA) has been the most effective therapy for chronic thromboembolic pulmonary hypertension (CTEPH). However, there is a substantial proportion of patients deemed not operable in whom other treatment strategies are available: medical therapy and balloon pulmonary angioplasty (BPA). We aimed to compare different CTEPH treatment strategies effect in a real-world setting.
All patients with CTEPH referred to our centre were included. We compare the short-term clinical, functional, exercise and haemodynamic effect of medical therapy (irrespective of subsequent treatment strategies), PEA and BPA (irrespective of previous/subsequent treatment strategies); we also describe the long-term outcome of the different patient groups.
We included 467 patients (39% were treated only with medical therapy, 43% underwent PEA, 13% underwent BPA and 5% were not treated with any therapy). Patients treated only with medical therapy were the oldest; compared to patients undergoing PEA, they had a lower exercise capacity, a higher risk profile and gained a lower haemodynamic, functional and survival benefit from the treatment. Patients undergoing BPA had a lower haemodynamic improvement but a comparable functional, exercise and risk improvement and a similar survival compared to patients undergoing PEA; their survival is anyway better than patients undergoing only medical treatment. Untreated historical control patients had the worst survival.
We confirm the superiority of PEA compared to any alternative treatment in CTEPH patients and we observe that BPA, in patients deemed not operable or with persistent/recurrent PH after PEA, leads to a better outcome than medical therapy alone.
Evaluation and management of patients with chronic thromboembolic pulmonary hypertension - consensus statement from the ISHLT
2021, Journal of Heart and Lung Transplantation
ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence.
Chronic thromboembolic pulmonary hypertension: initial experience of patients undergoing pulmonary thromboendarterectomy
2021, Revista Portuguesa de Cardiologia
A tromboendarterectomia pulmonar (TP) é um procedimento potencialmente curativo em doentes com hipertensão pulmonar (HP) tromboembólica crónica (TEC). O objetivo deste trabalho é reportar a experiência inicial de um centro português de tratamento de HP em doentes submetidos a TP num centro de referência cirúrgico internacional.
Estudo observacional prospetivo de doentes consecutivos com diagnóstico de HPTEC seguidos em centro nacional de tratamento de HP e submetidos a TP em centro de referência cirúrgico internacional entre outubro de 2015 e março de 2019. Parâmetros clínicos, funcionais, laboratoriais, imagiológicos e hemodinâmicos foram obtidos nos 12 meses precedentes à cirurgia e repetidos entre quatro a seis meses após a TP.
Foram submetidos a TP 27 doentes consecutivos (59% do sexo feminino) com mediana de 60 (49‐71) anos. Durante um seguimento mediano de 34 (21‐48) meses, verificou‐se melhoria da classe funcional em todos os doentes, tendo ocorrido apenas um óbito de causa cardíaca. Do ponto de vista hemodinâmico, observou‐se redução da pressão média na artéria pulmonar de 48 (42‐59) mmHg para 26 (22‐38) mmHg, aumento do débito cardíaco de 3,3 (2,9‐4,0) L/min para 4,9 (4,2‐5,5) L/min e redução das resistências vasculares pulmonares de 12,1 (7,2‐15,5) uW para 3,5 (2,6‐5,2) uW. Tendo em conta os parâmetros hemodinâmicos avaliados pós‐TP e a sua evolução durante o seguimento clínico, 44% (n = 12) dos doentes deixaram de ter critérios de HP, 44% (n = 12) mantiveram HP e 11% (n =3) evoluíram com recorrência de HP. Laboratorialmente, a salientar redução do NT‐proBNP de 868 (212‐1730) pg/mL para 171 (98‐382) pg/mL. Dos parâmetros de função sistólica ventricular direita, verificou‐se melhoria da excursão e velocidade de pico sistólicas longitudinais do plano do anel tricúspide de 14 (13‐14) mm e 9 (8‐10) cm/s para 17 (16‐18) mm e 13 (11‐15) cm/s, respetivamente. Dos 26 doentes com critérios de disfunção sistólica ventricular direita pré‐cirurgia, 85% (n = 22) apresentaram critérios de recuperação. A proporção de doentes sob terapêutica vasodilatadora específica diminuiu de 93% para 44% (p < 0,001) e a proporção daqueles requerendo OLD diminuiu de 52% para 26% (p = 0,003). A distância percorrida no teste dos seis minutos de marcha aumentou em cerca de 25% relativamente ao valor prévio à intervenção cirúrgica e apenas oito doentes mantiveram dessaturação significativa durante a prova.
A TP realizada em centro cirúrgico de elevado volume é um procedimento seguro e com impacto muito favorável em médio prazo nos parâmetros funcionais, hemodinâmicos e de função ventricular direita em doentes com HPTEC operável. É possível, para centros de tratamento de HP sem diferenciação em TP, a referenciação dos doentes com segurança e efetividade a um centro cirúrgico internacional em que para tal seja necessário aerotransporte.
Pulmonary endarterectomy (PEA) is a potentially curative procedure in patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study reports the initial experience of a Portuguese PH center with patients undergoing PEA at an international surgical reference center.
Prospective observational study of consecutive CTEPH patients followed at a national PH center, who underwent PEA at an international surgical reference center between October 2015 and March 2019. Clinical, functional, laboratory, imaging and hemodynamic parameters were obtained in the 12 months preceding the surgery and repeated between four and six months after PEA.
27 consecutive patients (59% female) with a median age of 60 (49‐71) years underwent PEA. During a median follow‐up of 34 (21‐48) months, there was an improvement in functional class in all patients, with only one cardiac death. From a hemodynamic perspective, there was a reduction in mean pulmonary artery pressure from 48 (42‐59) mmHg to 26 (22‐38) mmHg, an increase in cardiac output from 3.3 (2.9‐4.0) L/min to 4.9 (4.2‐5.5) L/min and a reduction in pulmonary vascular resistance from 12.1 (7.2‐15.5) uW to 3.5 (2.6‐5, 2) uW. During the follow‐up, 44% (n=12) of patients had no PH criteria, 44% (n=12) had residual PH and 11% (n = 3) had PH recurrence. There was a reduction of N‐terminal pro‐B‐type natriureticpeptide from 868 (212‐1730) pg/mL to 171 (98‐382) pg/mL. Rright ventricular systolic function parameters revealed an improvement in longitudinal systolic excursion and peak velocity of the plane of the tricuspid ring from 14 (13‐14) mm and 9 (8‐10) cm/s to 17 (16‐18) mm and 13 (11‐15) cm/s, respectively. Of the 26 patients with preoperative right ventricular dysfunction, 85% (n=22) recovered. The proportion of patients on specific vasodilator therapy decreased from 93% to 44% (p<0.001) and the proportion of those requiring oxygen therapy decreased from 52% to 26% (p=0.003). The six‐minute walk test distance increased by about 25% compared to the baseline and only eight patients had significant desaturation during the test.
Pulmonary endarterectomy performed at an experienced high‐volume center is a safe procedure with a very favorable medium‐term impact on functional, hemodynamic and right ventricular function parameters in CTEPH patients with operable disease. It is possible for PH centers without PEA differentiation to refer patients safely and effectively to an international surgical center in which air transport is necessary.
Interventional and pharmacological management of chronic thromboembolic pulmonary hypertension
2021, Respiratory Medicine
Citation Excerpt :
Clinical trial evidence supporting the efficacy of these therapies in CTEPH is, however, scarce. Several small retrospective and open-label trials of bosentan [59–61], treprostinil [62], epoprostenol [63–65] and sildenafil [66] (reviewed by Hoeper [67]) were limited by small patient cohorts, lack of randomization and blinding, or absence of a control arm [57,67]. Evidence from randomized controlled trials of medical therapies in patients with CTEPH is summarized in Table 2.
Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by obstruction of the pulmonary vasculature, leading to increased pulmonary vascular resistance and ultimately right ventricular failure, the leading cause of death in non-operated patients. This article reviews the current management of CTEPH. The standard of care in CTEPH is pulmonary endarterectomy (PEA). However, up to 40% of patients with CTEPH are ineligible for PEA, and up to 51% develop persistent/recurrent PH after PEA. Riociguat is currently the only medical therapy licensed for treatment of inoperable or persistent/recurrent CTEPH after PEA based on the results of the Phase III CHEST-1 study. Studies of balloon pulmonary angioplasty (BPA) have shown benefits in patients with inoperable or persistent/recurrent CTEPH after PEA; however, data are lacking from large, prospective, controlled studies. Studies of macitentan in patients with inoperable CTEPH and treprostinil in patients with inoperable or persistent/recurrent CTEPH showed positive results. Combination therapy is under evaluation in CTEPH, and long-term data are not available. In the future, CTEPH may be managed by PEA, medical therapy or BPA – alone or in combination, according to individual patient needs. Patients should be referred to experienced centers capable of assessing and delivering all options.
Macitentan for treatment of CTEPH: why MERIT merits attention
2017, The Lancet Respiratory Medicine
An Update on the Management of Chronic Thromboembolic Pulmonary Hypertension
2017, Current Problems in Cardiology
Citation Excerpt :
There is some evidence that medical therapy can be used in patients with severe life-threatening CTEPH as a therapeutic bridge to definitive PTE. In a case series of 12 patients with severe CTEPH as defined as PVR > 1200 dyn/s/cm−5, a continuous IV infusion of epoprostenol was administered for a mean of 46 days before surgery.108 A 28% decrease from baseline was seen in PVR preoperatively; however, no postoperative benefits were observed.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening form of pulmonary artery hypertension that is defined as a mean arterial pulmonary pressure greater than 25 mm Hg that persists for more than 6 months following anticoagulation therapy in the setting of pulmonary emboli. CTEPH is categorized by the World Health Organization as group IV pulmonary hypertension and is thought to be due to unresolved thromboemboli in the pulmonary artery circulation. Among the 5 classes of pulmonary hypertension, CTEPH is unique in that it is potentially curable with the use of pulmonary thromboendarterectomy surgery. Despite an increasing array of medical and surgical treatment options for patients with CTEPH over the past 2 decades, patients commonly present with advanced disease and carry a poor prognosis, thus, the need for early diagnosis and appropriate referral to an expert center. This review article first highlights the epidemiology, pathophysiology, and clinical presentation of CTEPH. The article then provides diagnostic and therapeutic algorithms for the management of the patient with suspected CTEPH.

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: This work was supported by Grant From Japan Cardiovascular Research Foundation and the Uehara Memorial Foundation.

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Chest

Clinical InvestigationsPULMONARY CIRCULATIONProstacyclin Therapy Before Pulmonary Thromboendarterectomy in Patients With Chronic Thromboembolic Pulmonary Hypertension*

Objectives:

Methods:

Results:

Conclusion:

Section snippets

Study Patients

Characteristics of Patients With and Without Prostacyclin Therapy

Discussion

Conclusion

Clin Chest Med

Thorac Cardiovasc Surg

Ann Thorac Surg

Lancet

Prog Cardiovasc Dis

Ann Thorac Surg

Am J Cardiol

J Am Coll Cardiol

Semin Thorac Cardiovasc Surg

Chronic major vessel thrombo-embolic pulmonary hypertension

Circulation

Clinical Investigations
PULMONARY CIRCULATION
Prostacyclin Therapy Before Pulmonary Thromboendarterectomy in Patients With Chronic Thromboembolic Pulmonary Hypertension^*