Late outcomes after acute pulmonary embolism: rationale and design of FOCUS, a prospective observational multicenter cohort study

Abstract

Acute pulmonary embolism (PE) is a frequent cause of death and serious disability. The risk of PE-associated mortality and morbidity extends far beyond the acute phase of the disease. In earlier follow-up studies, as many as 30 % of the patients died during a follow-up period of up to 3 years, and up to 50 % of patients continued to complain of dyspnea and/or poor physical performance 6 months to 3 years after the index event. The most feared ‘late sequela’ of PE is chronic thromboembolic pulmonary hypertension (CTEPH), the true incidence of which remains obscure due to the large margin of error in the rates reported by mostly small, single-center studies. Moreover, the functional and hemodynamic changes corresponding to early, possibly reversible stages of CTEPH, have not been systematically investigated. The ongoing Follow-Up after acute pulmonary embolism (FOCUS) study will prospectively enroll and systematically follow, over a 2-year period and with a standardized comprehensive program of clinical, echocardiographic, functional and laboratory testing, a large multicenter prospective cohort of 1000 unselected patients (all-comers) with acute symptomatic PE. FOCUS will possess adequate power to provide answers to relevant remaining questions regarding the patients’ long-term morbidity and mortality, and the temporal pattern of post-PE abnormalities. It will hopefully provide evidence for future guideline recommendations regarding the selection of patients for long-term follow-up after PE, the modalities which this follow-up should include, and the findings that should be interpreted as indicating progressive functional and hemodynamic post-PE impairment, or the development of CTEPH.Electronic supplementary materialThe online version of this article (doi:10.1007/s11239-016-1415-7) contains supplementary material, which is available to authorized users.

An epidemiological analysis of the burden of chronic thromboembolic pulmonary hypertension in the USA, Europe and Japan

“…While it is not clear how many patients experiencing a PE develop CTEPH, the ongoing Follow-Up after Acute Pulmonary Embolism (FOCUS) study is investigating this question. FOCUS is a prospective, multicentre, observational cohort study that will monitor patients with acute PE for 2 years for signs and symptoms of CTEPH, and collect data on the incidence of CTEPH following PE [60]. The rate of PE in Japan appears to be substantially lower than that observed in the USA and Europe, although these data are from a single study.…”

Quality of life and functional limitations after pulmonary embolism and its prognostic relevance

“…However, diagnostic criteria and thresholds to define “post‐PE syndrome” are not available thus far. The ongoing “FOllow‐up after aCUte pulmonary emboliSm” (FOCUS) study aims to determine the incidence of CTEPH and persisting or progressive functional and/or hemodynamic PPEI over a 2‐year follow‐up period after an index episode of acute symptomatic PE . For this purpose, a definition of PPEI was introduced by the FOCUS steering committee and was used in slight modification in the present study.…”

“…Assuming that persisting or progressive functional and/or hemodynamic impairment after acute PE is an early indicator of the subsequent development of CTEPH, PPEI has been defined as a coprimary outcome in the FOCUS study . Indeed, a recent cohort study demonstrated that patients fulfilling all diagnostic criteria of CTEPH despite elevation of mean pulmonary artery pressure (a condition called “chronic thromboembolic disease”) showed similar objective functional impairment using cardiopulmonary exercise testing compared to patients with CTEPH .…”

“…Right ventricular dysfunction on TTE was defined according to Rudski et al and Konstantinides et al as the presence of one or more of the following parameters: RV basal diameter >4.2 cm, tricuspid annular plane systolic excursion <1.6 cm, elevated right atrial pressure based on the absence of an inspiratory collapse of the inferior vena cava, tricuspid regurgitant velocity ≥2.8 m/s. and presence of pericardial effusion.…”

“…The validation pro- (Table S2). 26 In the case of missing items, no score for the respective dimension was calculated. 27 Quality criteria of the PEmb-QoL questionnaire that were tested comprised outcome measures validity, reliability with internal consistency, and reproducibility and interpretability.…”