Limitations of resting haemodynamics in chronic thromboembolic disease without pulmonary hypertension

Abstract

There is renewed interest in the haemodynamic definitions of pulmonary hypertension (PH), reigniting an old debate about diagnostic thresholds [1]. Recent prospective data support work dating back over 40 years demonstrating patients with "borderline" PH (mean pulmonary artery pressure (mPAP) <25 mmHg) can still have significant morbidity and mortality [2]. Therefore, lowering the mPAP threshold for the diagnosis of precapillary pulmonary arterial hypertension (PAH) has been discussed at World Symposium on Pulmonary Hypertension in Nice, France, in 2018. A potentially different approach has arisen in group 4 (chronic thromboembolic pulmonary hypertension (CTEPH)), where the concept of chronic thromboembolic disease without PH (CTED) has gained traction. This describes a population of patients with mPAP <25 mmHg, with no lower limit, who have persistent vascular obstructions, impaired response to exercise, and a high impact of disease on symptoms and quality of life (QoL). The 25-mmHg threshold is important partly because it excludes patients who might benefit from treatment, and then precludes their participation in clinical trials, forming a cycle that prevents regulatory approved treatment in the future. In the CTED to CTEPH spectrum, it is unclear if reducing the threshold is the best way to address this inequity, as minimal data exists detailing outcomes <25 mmHg. In the UK, we have undertaken pulmonary endarterectomy (PEA) on a selected, symptomatic cohort of operable CTED patients with good results [3], which were recapitulated by others [4,5]. A valid criticism of our previous work [3] is the retrospective, selective nature of the subjects and a lack of understanding about the natural history of the disease without treatment. Here, we present the first prospective cohort of patients with operable CTED (institutional review board project reference S02297), and hypothesised that clinically meaningful symptoms, limitation and physiology would relate to haemodynamics. Royal Papworth Hospital (Cambridge, UK) is the national PEA referral centre and to minimise tertiary speciality referral bias, we have included only regional nonspecialist referrals. Regional incident cases referred in 2015-2017 with suspected CTED/CTEPH were prospectively assessed. All patients were reviewed at the national CTEPH multidisciplinary team (MDT) meeting. Patients with operable CTED underwent standard CTEPH investigations [6] with additional exercise right heart catheterisation (RHC) and incremental cardiopulmonary exercise testing (CPET) [7]. The zero reference was set at the midthoracic level. During exercise RHC, patients were asked to pedal for 5 min at 40% of the workload achieved during incremental CPET (load range 9-104 W, maximal supine exercise test could not been performed due to technical limitation of ergometer). The mPAP, pulmonary wedge pressure (measured over three breath cycles, when feasible), mixed venous saturation, heart rate and systemic blood pressure were measured, followed by cardiac output (CO) measurement us...

2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension

“…However, it remains unclear to what extent PH and [31,54,55]. Patients with chronic thrombo-embolic pulmonary disease (CTEPD) without PH still represent a small proportion of the patients referred to CTEPH centres [56].…”

The revised definition of pulmonary hypertension: exploring the impact on patient management

“…In contrast, for patients with PH due to left heart disease or lung disease (Groups 2 and 3, respectively), such studies cannot be performed as there are currently no recommended treatment options available for these conditions 2 , 3 . For patients with Group 4 PH [chronic thromboembolic PH (CTEPH)], the lower mPAP threshold in the revised definition may lead to some patients who are classified based on the previous definition as having chronic thromboembolic disease without PH (CTED) being reclassified as having CTEPH 26 , 27 . As pulmonary endarterectomy—the gold-standard treatment recommended for operable CTEPH 2 , 3 —is also a beneficial treatment for operable CTED patients, 27 , 28 the revised definition is not expected to change the management of these patients.…”

Advances in balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension

“…28 A prospective study of 34 patients with CTED in the UK reported that up to 56% had mPAP ≤ 20 mmHg. 29 BPA has been performed in small numbers of patients with CTED. Preliminary data have shown improvements in functional parameters and hemodynamics after BPA in patients with symptomatic CTED, [30][31][32] although larger prospective studies are required to further investigate these findings.…”