Nanozyme-based therapeutic strategies for traumatic brain injury.

More than one-third of acute pulmonary embolism (PE) survivors suffer from chronic dyspnoea, exercise intolerance and impaired quality of life [–]. The term “post-PE syndrome” has been used to describe dyspnoea and functional limitation after PE from a variety of causes, including entities without cardiopulmonary dysfunction (physical deconditioning, post-traumatic stress, anxiety, ) and pre-existing conditions unrelated to PE resolution (coexisting COPD, congestive heart failure, ). However, the role of chronic thromboembolism itself, defined as physiologically consequential intravascular scars complicating acute PE [], in post-PE dyspnoea is unclear. The presentation and incidence of chronic thromboembolic pulmonary hypertension (CTEPH) after PE are well recognised []. Chronic thromboembolism that resembles CTEPH but does not manifest resting pulmonary hypertension has been termed chronic thromboembolic disease (CTED) or chronic thromboembolic pulmonary disease [, ]. CTED includes both chronic thromboembolism with exercise-induced pulmonary hypertension (CTEExPH) and other phenotypes []. However, much less is understood about the chronic thromboembolism phenotypes that cause physiological pathology other than pulmonary hypertension. We previously characterised the physiological profile of two symptomatic phenotypes of chronic thromboembolism after PE that are not necessarily associated with pulmonary hypertension []. Chronic thromboembolism with ventilatory inefficiency (CTEVI) is defined by increased ventilatory dead space proportions from maldistribution and reduction of pulmonary blood flow []. Chronic thromboembolism with small stroke volume augmentation (CTESSA) occurs when compensation for pulmonary vascular obstruction has already optimised right ventricular pre-load at rest and stroke volume does not substantially increase during exercise []. We studied a consecutive series of patients evaluated after acute PE to test the hypothesis that chronic thromboembolism occurs more commonly in pathophysiological phenotypes without pulmonary hypertension than phenotypes with pulmonary hypertension. Physician reviewers independently assigned patients into distinct diagnostic categories based on a hierarchical protocol of objective clinical tests of symptoms, exercise physiology, lung perfusion, echocardiography, chest imaging and haemodynamics []. Reviews were performed at two time-points, separated by at least 6 months. We measured the inter-reviewer agreement regarding post-PE diagnoses and the consistency of the diagnoses at the second assessment.