Elsevier

International Journal of Cardiology

Volume 317, 15 October 2020, Pages 181-187
International Journal of Cardiology

Long-term changes of exercise hemodynamics and physical capacity in chronic thromboembolic pulmonary hypertension after pulmonary thromboendarterectomy

https://doi.org/10.1016/j.ijcard.2020.05.083Get rights and content

Highlights

  • True PH severity is unmasked with exercise in CTEPH patients after successful PEA.

  • CO reserve remains compromised in CTEPH patients at 12 months post-PEA follow-up.

  • Improvement in physical capacity correlated with changes in CO, but not mPAP and PVR.

Abstract

Background

A substantial number of chronic thromboembolic pulmonary hypertension (CTEPH) patients experience dyspnea on exertion and limited exercise capacity despite surgically successful pulmonary endarterectomy (PEA). We sought to prospectively evaluate resting and peak exercise hemodynamics before, 3 and 12 months after PEA in consecutive CTEPH-patients and correlate it to physical functional capacity.

Methods and results

Twenty consecutive CTEPH-patients were examined. Twelve months after PEA, 75% of patients with severely increased pre-PEA mean pulmonary arterial pressure (mPAP) at rest had normal or mildly increased mPAP. However, mPAP reduction was less pronounced during exercise where only 45% had normal or mildly increased mPAP at 12 months. Hemodynamic changes during exercise were tested using the pressure-flow relationship (i.e. mPAP/cardiac output (CO) slope). The average mPAP/CO slope was 7.5 ± 4.2 mm Hg/L/min preoperatively and 3.9 ± 3.0 mm Hg/L/min at 12 months (p < .005). CO reserve (CO increase from rest to peak exercise) was increased (5.7 ± 2.9 L/min) 12 months after PEA compared with pre-PEA (2.5 ± 1.8 L/min), p < .0001. However, 12 months after PEA, the CO reserve was only 49% of that of healthy controls, p < .0001. Changes in cardiac output (∆CO), calculated as the difference between CO before PEA and 12 months later, were significantly correlated with six-minute-walk-test and peak oxygen uptake (VO2), both at rest and peak exercise.

Conclusion

Invasive exercise hemodynamic examination in CTEPH-patients demonstrates that after otherwise successful PEA surgery, >50% of patients have a significant increase in exercise mPAP, and the CO reserve remains compromised 12 months after PEA. Improvement in physical capacity is correlated with ∆CO.

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease associated with significant morbidity and mortality [1,2]. It is widely underdiagnosed, and both diagnosis and treatment are frequently suboptimal [[3], [4], [5], [6], [7]]. CTEPH is characterized by obstruction and/or thickening of pulmonary vasculature due to multiple, chronic thrombi-emboli causing pulmonary hypertension (PH). Untreated, CTEPH leads to severe dyspnea, chest pain, reduced functional capacity, progressive right ventricular (RV) dysfunction, and ultimately death [1,2,8,9].

CTEPH is potentially curable with surgical treatment in the form of pulmonary endarterectomy (PEA) [10]. Without treatment, CTEPH has a 5-year survival of 10% if the mean pulmonary arterial pressure (mPAP) is 50 mm Hg or higher, which is not unusual at the time of presentation [9]. In patients undergoing PEA, the average 5-year survival is reported to be 79–90% [[11], [12], [13]]. In addition, invasive hemodynamic studies have demonstrated that PEA is associated with a significant reduction in resting mPAP and pulmonary vascular resistance (PVR) [[14], [15], [16]] along with improvement in six-minute-walk test (6MWT) and cardiopulmonary exercise test [11]. Nevertheless, a substantial number of patients still experience dyspnea on exertion and limited exercise capacity despite surgically successful PEA for CTEPH. In recent years, studies assessing exercise hemodynamics in different cardiac disease entities have given us a better understanding of symptoms, exercise capacity, and cardiac performance in relation to the hemodynamic changes occurring from the resting to the peak exercise condition [[17], [18], [19], [20]]. Most of the previous invasive hemodynamic studies in CTEPH or post-PEA patients have been performed only while the patients were resting and not when they were doing exercise [12,15,16]. Only a few invasive exercise hemodynamic studies have been performed on selective CTEPH patients. Yet, these studies are either retrospective or case-control studies comparing CTEPH patients with other patients who had PEA [7,21].  Guido Claessen and collegues performed a prospective invasive study, but was limited by selective CTEPH patients and short term follow up [22]. There is therefore a lack of data on consecutive CTEPH patients studied prospectively with invasive exercise hemodynamics during a long follow-up period. The aim of the present study was therefore, firstly, to prospectively evaluate resting and peak exercise hemodynamics before PEA and 3 and 12 months after PEA in consecutive patients with CTEPH. Secondly, we examined the physical functional capacity and related it to invasive hemodynamics before and after PEA.

Section snippets

Definition, diagnosis and study population

In the present study, CTEPH is defined in accordance with the WHO classification as mPAP ≥ 25 mm Hg, pulmonary capillary wedge pressure (PCWP) ≤ 15 mm Hg, and mismatched perfusion defects on lung scan after at least 3 months of effective anticoagulation treatment [1]. The final diagnosis of CTEPH and assessment of the patient's suitability for PEA require computed tomography pulmonary angiography, right heart catheterization (RHC) and selective pulmonary angiography [1].

Patients with confirmed

Patient characteristics

The clinical characteristics of the 20 consecutive Danish patients with CTEPH who underwent PEA are shown in Table 1. There were no procedural PEA deaths within 30 days. All patients were on warfarin treatment throughout the study period. The number of patients using diuretics was unchanged throughout the study period; however, the total dosage of diuretics was reduced 12 months after PEA. None of the patients received any additional vasodilators after PEA during the study period.

Discussion

The present prospective study describes the long-term changes in resting and exercise hemodynamics and the relation of these changes to exercise capacity in CTEPH patients before and after PEA. As expected and similar to other studies [11,15,16], we demonstrated an extensive reduction in mPAP and PVR and an increase in CO during resting conditions after PEA along with an improvement in functional capacity. More specifically, our study revealed that 75% of the patients with moderately to

Limitation

We acknowledge the limitation that the present study reflects the experiences of a single center and a limited number of patients. The control group was 10 years younger than the patient group and without similar comorbidities. We did not include a new age- and gender-matched healthy group in this study due to ethical considerations associated with inserting invasive Swan-Ganz catheters again in healthy subjects.

Conclusion

Invasive exercise hemodynamic examination in CTEPH patients demonstrates that <50% of those who undergo otherwise successful PEA operation achieve normal or near-normal exercise mPAP, and the CO reserve remains compromised at 12 months post-PEA. Improvement in physical capacity correlated well with changes in CO, whereas resting mPAP and PVR did not. Invasive exercise hemodynamic evaluation contains additional information that may inform resting studies and may potentially be used to guide

Disclosure statement

The authors report no conflicts of interest.

Acknowledgement

This study was funded by the Danish Heart Foundation, Aarhus University, Arvid Nilssons Fond, Eva & Henry Frænkels Mindefond, and Snedkermester Sophus Jacobsen & Hustru Astrid Jacobsens Fond.

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