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............................................................................................................................................................................. 10 Long-term sequelae of pulmonary embolism

The patency of the pulmonary arterial bed is restored in the majority of PE survivors within the first few months following the acute episode; therefore, no routine follow-up CTPA imaging is needed in such patients treated for PE.427 However, in other patients, thrombi become persistent and organized, which in rare cases may result in CTEPH, a potentially life-threatening obstructing vasculopathy. The rarity of this condition is in contrast to the relatively large number of patients who report persisting dyspnoea or poor physical performance over several months after acute PE. Thus, the aims of an efficient follow-up strategy after PE should be to: (i) provide appropriate care (exercise rehabilitation, treatment of comorbidity, behavioural education, and modification of risk factors) to patients with persisting symptoms, and (ii) ensure early detection of CTEPH to refer the patient for further diagnostic workup and specific treatment.

10.1 Persisting symptoms and functional

limitation after pulmonary embolism Cohort studies conducted over the past decade (summarized in Klok et al.428) have revealed that persisting or deteriorating dyspnoea, and poor physical performance, are frequently present 6 months to 3 years after an acute PE episode. The proportion of patients claiming that their health status is worse at 6 month follow-up than it was at the time of PE diagnosis varies widely, ranging between 20 and 75%.429431 The following baseline parameters and findings could be identified as predictors of exertional dyspnoea at long-term followup after PE: advanced age, cardiac or pulmonary comorbidity, higher body mass index, and history of smoking;429 higher systolic PAP and RV dysfunction at diagnosis;430,432,433 and residual pulmonary vascular obstruction at discharge.434 More recently, a prospective cohort study enrolled 100 patients at five Canadian hospitals between 2010 and 2013, and followed them over 1 year.435 As many as 47% of the patients had reduced maximal aerobic capacity, defined as peak oxygen consumption <80% of the predicted value on cardiopulmonary exercise testing (CPET). This functional outcome was associated with significantly worse generic health-related quality of life and dyspnoea scores, as well as with a significantly reduced 6 min walk distance.435 Independent predictors of reduced functional exercise capacity and quality of life over time included female sex, higher body mass index, history of lung disease, higher pulmonary artery systolic pressures on the 10 day echocardiogram, and higher main pulmonary artery diameter on the baseline CTPA.436 Of note, pulmonary function tests and echocardiographic results at follow-up were largely within normal limits, both in patients with and without reduced maximal aerobic capacity.435 Lack of an association between exercise impairment, and persistent RV dilation or dysfunction, was also reported by a study of 20 survivors of massive or submassive PE.437 Taken together, older and more recent cohort studies have suggested that muscle deconditioning, particularly in the presence of excess body weight and cardiopulmonary comorbidity, is largely responsible for the frequently reported dyspnoea and signs of exercise limitation after acute PE. This also means that, at least in the majority of cases, poor physical performance after PE does not appear to be attributable to ‘large’ residual thrombi, or persisting/ progressive PH and RV dysfunction. Ongoing prospective studies in large numbers of patients may help to better identify predictors of functional and/or haemodynamic impairment after acute PE, and their possible implications for shaping follow-up programmes.438

As mentioned in section 6, it remains unclear whether early reperfusion treatment, notably thrombolysis, has an impact on clinical symptoms, functional limitation, or persistent (or new-onset) PH at long-term follow-up after PE. Consequently, prevention of long-term PE sequelae is, at present, no justification for thrombolytic treatment in the acute phase of PE.

10.2 Chronic thromboembolic

pulmonary hypertension 10.2.1 Epidemiology, pathophysiology, and natural history CTEPH is a disease caused by the persistent obstruction of pulmonary arteries by organized thrombi, leading to flow redistribution and secondary remodelling of the pulmonary microvascular bed. CTEPH has been reported with a cumulative incidence of between 0.1 and 9.1% in the first 2 years after a symptomatic PE event; the large margin of error is due to referral bias, the paucity of early symptoms, and the difficulty of differentiating acute PE from symptoms of preexisting CTEPH.439,440 A prospective, multicentre, observational screening survey for the detection of CTEPH included patients with acute PE from 11 centres in Switzerland, from March 2009 to November 2016. Screening for possible CTEPH was performed at 6, 12, and 24 months using a stepwise algorithm that included a phonebased dyspnoea survey, TTE, right heart catheterization, and radiological confirmation of CTEPH. Of 508 patients assessed for CTEPH screening over 2 years, CTEPH incidence following PE was 3.7 per 1000 patient-years, with a 2 year cumulative incidence of 0.79%.441 In Germany, the incidence of CTEPH in 2016 was estimated at 5.7 per million adult population.442 The hallmark of CTEPH is fibrotic transformation of a pulmonary arterial thrombus, causing fixed mechanical obstruction of pulmonary arteries and leading to overflow of the open pulmonary arterial bed. Together with collateral supply from systemic arteries downstream of pulmonary arterial occlusions, this contributes to microvascular remodelling causing a progressive increase in PVR.443 Owing to this complex pathophysiology, there is no clear correlation between the degree of mechanical obstruction found at imaging and haemodynamics, which can deteriorate in the absence of recurrent PE.444 Two historical trials assessed survival in patients with CTEPH before the availability of surgical treatment. In both studies, mean PAP >30 mmHg was related to poor survival, similar to that reported for idiopathic pulmonary arterial hypertension.445,446 The most frequently cited risk factors and predisposing conditions for CTEPH are shown in Table 13. In an international registry, a history of acute PE was reported by 75% of patients.447 Associated conditions and comorbidities included thrombophilic disorders, particularly antiphospholipid antibody syndrome and high coagulation factor VIII levels, cancer, a history of splenectomy, inflammatory bowel disease, ventriculo-atrial shunts, and infection of chronic i.v. lines and devices such as implantable pacemakers. Downloaded from academic.oup.com/eurheartj/article/41/4/543/5556136 by guest on 07 October 2026