Vascular and right ventricular remodelling in chronic thromboembolic pulmonary hypertension

Abstract

In chronic thromboembolic pulmonary hypertension (CTEPH) increased pulmonary vascular resistance is caused by fibrotic organisation of unresolved thromboemboli. CTEPH mainly differs from pulmonary arterial hypertension (PAH) by the proximal location of pulmonary artery obliteration, although distal arteriopathy can be observed as a consequence of nonoccluded area over-perfusion. Accordingly, there is proportionally more wave reflection in CTEPH, impacting on pressure and flow wave morphology. However, the time constant, i.e. resistance6compliance, is not different in CTEPH and PAH, indicating only trivial effects of proximal wave reflection on hydraulic right ventricular load. More discriminative is the analysis of the pressure decay after pulmonary arterial occlusion, which is more rapid in the absence of significant distal arteriopathy.Structure and function of the right ventricle show a similar pattern to right ventricular hypertrophy, namely dilatation and wall thickening, as well as loss of function in CTEPH and PAH. This is probably related to similar loading conditions. Hyperventilation with hypocapnia is characteristic of both PAH and CTEPH. Ventilatory equivalents for carbon dioxide, as a function of arterial carbon dioxide tension, conform to the alveolar ventilation equation in both conditions, indicating a predominant role of increased chemosensitivity. However, a slight increase in the arterial to end-tidal carbon dioxide tension gradient in CTEPH shows a contribution of increased dead space ventilation. KEYWORDS: Chronic thromboembolic pulmonary hypertension, gas exchange, pulmonary arterial hypertension, pulmonary circulation, remodelling, right ventricular function C hronic thromboembolic pulmonary hypertension (CTEPH) is characterised by the presence of unresolved thromboemboli undergoing fibrotic organisation. This results in obstruction of proximal pulmonary arteries, increased pulmonary vascular resistance (PVR), pulmonary hypertension (PH) and progressive right ventricle remodelling and failure. Pulmonary embolism, either as single or recurrent episodes, is thought to be the initiating event followed by progressive pulmonary vascular remodelling. CTEPH mainly differs from pulmonary arterial hypertension (PAH) by the proximal location of pulmonary artery obliteration, although distal arteriopathy can be observed as a consequence of non-occluded area over-perfusion [1]. Also characteristic for CTEPH is the extensive collateral blood supply to the ischemic lung, developed from the systemic circulation.Diagnosis is based on the presence of pre-capillary PH, defined by a mean pulmonary arterial pressure (PAP) o25 mmHg and a wedge pressure f15 mmHg, in combination with a lung scan showing segmental perfusion defects after a prolonged period of anticoagulation [2]. Further

Is the time constant of the pulmonary circulation truly constant?

“…Thus, while we agree with J.C. Grignola's pertinent remarks, we humbly feel allowed to maintain our statement that the RC time of the pulmonary circulation is approximately the same in CTEPH and PAH [6], indicating surprisingly little impact of proximal obstruction-related increased wave reflection or stiffness on right ventricular afterload. We read with great interest the recently published article by LEERMAKERS et al [1] that takes an outstanding view of the relationship of maternal weight with the risk of preschool wheezing.…”

“…It has been highlighted that diabetes in pregnancy is associated with high birth weight. Furthermore, both poor maternal sleep and OSA can lead to increased proinflammatory cytokine levels [6]. Thus, this factor could be related to increase of proinflammatory cytokine levels in mothers, which might affect the immune system of the fetus, and the risk of infectious and atopic diseases post-natally.…”

Right ventricular reverse remodelling after balloon pulmonary angioplasty

“…The disease duration before BPA was positively correlated with the baseline mPAP, but not with any other haemodynamic or RV functional parameters, implying the increase of organised thromboembolic material itself or the existence of prevalent small vessel arteriopathy was a consequence of unobstructed area over-perfusion in patients with long durations of disease. The fact that the disease duration did not correlate with any baseline RV function parameters measured with CMR may suggest the variability of time-course in RV adaptation among patients as previously reported [3,32]. However, the disease duration before BPA was not significantly correlated with changes in any parameters related to RV volumes, function or haemodynamics.…”

Chronic thromboembolic pulmonary hypertension: advances from bench to patient management

“…The series begins with an article on the pathophysiology of the pulmonary circulation and the right ventricular adaptation by DELCROIX et al [15]. The next article, by LANG et al [16], describes the basic mechanisms involved in the vascular remodelling process in CTEPH.…”

“…In the current issue of the ERJ, DELCROIX et al [15] review the current knowledge on vascular and right ventricular remodelling in CTEPH with specific interest in the role of pressure and flow-wave morphology, highlighting the differences between pulmonary arterial hypertension (PAH) and CTEPH. These authors suggest that despite similar loading conditions in CTEPH and PAH, there is proportionally more wave reflection in CTEPH than in PAH, impacting on pressure and flow-wave morphology.…”