Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study
Authors: Valerio Luca , Mavromanoli Anna C , Barco Stefano , Abele Christina , Becker Dorothea , Bruch Leonhard , Ewert Ralf , Faehling Martin , Fistera David , Gerhardt Felix , Ghofrani Hossein Ardeschir , Grgic Aleksandar , Grünig Ekkehard , Halank Michael , Held Matthias , Hobohm Lukas , Hoeper Marius M , Klok Frederikus A , Lankeit Mareike , Leuchte Hanno H , Martin Nadine , Mayer Eckhard , Meyer F Joachim , Neurohr Claus , Opitz Christian , Schmidt Kai Helge , Seyfarth Hans Jürgen , Wachter Rolf , Wilkens Heinrike , Wild Philipp S , Konstantinides Stavros V , Rosenkranz Stephan ,   FOCUS Investigators, Abele Christina , Barco Stefano , Becker Dorothea , Fischer Brunhilde , Hobohm Lukas , Käberich Anja , Keller Karsten , Klok Frederikus A. , Martin Nadine , Mavromanoli Anna C. , Konstantinides Stavros V. , Lankeit Mareike , Otto Silke , Quitzau Kurt , Rost Kathrin , Schmidt Kai-Helge , Schöneberger Doris , Valerio Luca , Wild Philipp S. , Bruch Leonhard , Geistert Stefanie , Schüler Katrin , Ewert Ralf , Pohl Claudia , Pieper Jeannette , Faehling Martin , Blaich Birgit , Landmesser Annika , Rosenkranz Stephan , Gerhardt Felix , Rudolph Jasmin , Gün Sibel , Ghofrani Hossein-Ardeschir , George Ute , Grünig Ekkehard , Egenlauf Benjamin , Salkić Amina , Heier Eva-Maria , Halank Michael , Tausche Kristin , Rink Tina , Jäkel Diana , Held Matthias , Schröder Barbara , Hoeper Marius M. , Freise Julia , Tayler Susanne , Leuchte Hanno H. , Horn Annika , Meyer F. Joachim , Emge-Rossa Dagmar , Thabaret Karine , Neurohr Claus , Barton Juergen , Opitz Christian , Bressem Ines , Seyfarth Hans-Jürgen , Berger Patricia , Hennig Angela , Wachter Rolf , Hellenkamp Kristian , Sentler Carmen , Schulte Martina , Wilkens Heinrike , Trudzinski Franziska , Holtz Ines 
Published: April 2022

Abstract

Aims
To systematically assess late outcomes of acute pulmonary embolism (PE) and to investigate the clinical implications of post-PE impairment (PPEI) fulfilling prospectively defined criteria.

Methods and results
A prospective multicentre observational cohort study was conducted in 17 large-volume centres across Germany. Adult consecutive patients with confirmed acute symptomatic PE were followed with a standardized assessment plan and pre-defined visits at 3, 12, and 24 months. The co-primary outcomes were (i) diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), and (ii) PPEI, a combination of persistent or worsening clinical, functional, biochemical, and imaging parameters during follow-up. A total of 1017 patients (45% women, median age 64 years) were included in the primary analysis. They were followed for a median duration of 732 days after PE diagnosis. The CTEPH was diagnosed in 16 (1.6%) patients, after a median of 129 days; the estimated 2-year cumulative incidence was 2.3% (1.2–4.4%). Overall, 880 patients were evaluable for PPEI; the 2-year cumulative incidence was 16.0% (95% confidence interval 12.8–20.8%). The PPEI helped to identify 15 of the 16 patients diagnosed with CTEPH during follow-up (hazard ratio for CTEPH vs. no CTEPH 393; 95% confidence interval 73–2119). Patients with PPEI had a higher risk of re-hospitalization and death as well as worse quality of life compared with those without PPEI.

Conclusion
In this prospective study, the cumulative 2-year incidence of CTEPH was 2.3%, but PPEI diagnosed by standardized criteria was frequent. Our findings support systematic follow-up of patients after acute PE and may help to optimize guideline recommendations and algorithms for post-PE care.