Dynamic Risk Stratification After Pulmonary Endarterectomy

Editor's Note: Expert analysis based on the article Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United Kingdom National Cohort. Circulation 2016; 133:1761-71.

Chronic thromboembolic pulmonary hypertension (CTEPH) results from incomplete resolution of acute pulmonary emboli, which become organized into fibrotic material described as "webs, slits and bands". These adhere firmly to the arterial walls, obstructing large pulmonary arteries and are the target for the pulmonary endarterectomy surgery (PEA). Additionally, in areas without these obstructions there is increased blood flow, which induces a peripheral vasculopathy similar to that seen in pulmonary arterial hypertension. This is the target for pulmonary vasodilator therapy. Together these two mechanisms lead to increased pulmonary artery pressure, pulmonary vascular resistance (PVR), right heart failure and premature death.1 Pulmonary endarterectomy surgery (PEA) is the treatment of choice in carefully selected patients but the predictors of long-term outcome after surgery are not well understood. The authors of this expert analysis aimed to address the following questions by analyzing the outcome of 880 patients in the United Kingdom (UK) PEA cohort.2

Patient cohort

All patients with CTEPH who underwent PEA at a national single centre (Papworth Hospital, Cambridge, UK) from the first surgery in January 1997 until December 31, 2012 were included in the cohort. The mean age was 57 ± 15 years (range 15-84 years) and 53% were male. The baseline mean pulmonary artery pressure (mPAP) was 47 ± 11 mm Hg, PVR 830 ± 382 dyne/sec/cm-5 and 6 minute walk distance was only 260 ± 182m. Pre-surgery, 91% patients were in World Health Organization (WHO) functional class III or IV, and 64% patients were being "bridged to surgery" with at least 1 off-license pulmonary vasodilator drug. The patients underwent routine detailed re-assessment with right heart catheterization and non-invasive testing at 3-6 months after surgery and annually thereafter in specialist pulmonary hypertension (PH) centers. If clinically stable and not requiring pulmonary vasodilator therapy patients were discharged after 3-5 years of follow-up. The NHS summary care record tracking system was used for survival status and the causes of death obtained from local databases and from the England or Scotland General Register Offices. The overall survival after surgery was 86%, 84% 79% and 72% at 1, 3, 5 and 10 years for the whole cohort. With centre experience there were improved outcomes with survival at 1 and 3 years being 91% and 90% respectively in the second half of our cohort. The mean follow-up of patients post-PEA was 4.3 ± 3.6 years (range 0-15.5 years).

What is clinically significant PH post-PEA?

There is no expert consensus on the definition of the residual PH post-PEA. In our series there were significant improvements in exercise capacity, haemodynamics and WHO functional class after surgery. Despite this, only 28% had an mPAP < 20 mm Hg and 21% had an mPAP 21-24 mm Hg at their 3-6 month review. We chose two endpoints that we thought would identify clinically significant PH post PEA:

1) Initiation of pulmonary vasodilator therapy as a marker of clinical deterioration

In the UK, only specialist PH centers can prescribe pulmonary vasodilator therapy. Importantly, this is guided by WHO functional class (III or IV) rather than mPAP alone. A total of 187 patients were treated with vasodilator therapy, with 142 being started after surgery. The best threshold values for the initiation of pulmonary vasodilator therapy over long-term follow-up were identified for mPAP, cardiac index, and PVR as being 30 mm Hg, 2.14 L/min/m2, and 318 dynes/sec/cm-5, respectively. However, there was a rapid increase in log hazard ratio (largest likelihood ratio statistics) for treatment initiation for mPAP between 25 and 30 mm Hg, and after 30 mm Hg the log hazard ratio started to plateau. Our data analysis suggested that 30 mm Hg was a plausible threshold, and, therefore, patients with an mPAP ≥30 mm Hg were at risk of a deteriorating functional status, which triggered pulmonary vasodilator therapy initiation. We propose that this value represents clinically significant PH post-PEA and that these patients need close long-term follow-up. No apparent patterns were observed for cardiac index and PVR.

2) Survival

Long-term survival post-PEA is excellent, despite over half the patients after surgery having residual PH (mPAP ≥ 25mm Hg). The majority of deaths after the peri-operative period were not due to PH (right ventricular failure). For those patients who survived surgery but died during the follow-up period, 29 of 82 (35%) deaths were classified as directly caused by CTEPH (i.e. right ventricular failure away from the operative period), 13 (16%) were related to CTEPH (e.g. anticoagulation related bleeding); and 40 (49%) were attributable to unrelated causes (e.g. malignancy). We found that an mPAP ≥36 mm Hg and a PVR ≥416 dynes/sec/cm-5 (as time-varying measures) were the optimal thresholds that correlated with a higher risk of death from any cause, whereas an mPAP ≥38 mm Hg and a PVR ≥425 dynes/sec/cm-5 identified those patients at higher risk of death from CTEPH.

How should patients be risk stratified and monitored post-PEA?

We only found a moderate correlation (r=0.53) between the haemodynamics measured on day 1 post-PEA on the intensive care unit and the 3-6 month reassessment. In comparison, there was a much stronger correlation (r=0.79) between the 3-6 and 12 month haemodynamics. Patients should undergo repeat right heart catheterization 3-6 months post-PEA to stratify those patients (mPAP ≥ 30 mm Hg) who require close long-term follow-up and consideration of pulmonary vasodilator therapy3 or balloon pulmonary angioplasty4 if they deteriorate.

References

  1. Lang IM, Dorfmüller P, Vonk Noordegraaf A. The Pathobiology of Chronic Thromboembolic Pulmonary Hypertension. Ann Am Thorac Soc 2016; Suppl 3:S215-21.
  2. Cannon JE, Su L, Kiely DG, et al. Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results from the United Kingdom National Cohort. Circulation 2016;133:1761-71.
  3. Ghofrani H-A, D'Armini AM, Grimminger F, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013;369:319-29.
  4. Shimura N, Kataoka M, Inami T, et al. Additional percutaneous transluminal pulmonary angioplasty for residual or recurrent pulmonary hypertension after pulmonary endarterectomy. Int J Cardiol 2015;183:138-42.

Clinical Topics: Cardio-Oncology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Pulmonary Hypertension and Venous Thromboembolism, Acute Heart Failure, Pulmonary Hypertension

Keywords: Angioplasty, Cardiac Catheterization, Endarterectomy, Heart Failure, Hemodynamics, Hypertension, Pulmonary, Neoplasms, Pulmonary Artery, Vascular Resistance, Vasodilator Agents


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