Neurological Monitoring during pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA) for chronic thrombo-embolic pulmonary hypertension (CTEPH)

Chronic thromboembolic pulmonary hypertension (CTEPH) results when after
treatment of an acute pulmonary embolism, persistent thrombi occur. Pulmonary
endarterectomy (PEA) is the treatment of choice and can confer a near cure of
the condition [1]. PEA is a complicated surgical procedure however, requiring
two episodes of hypothermic cardiac arrest. A relatively high incidence of
postoperative delirium and neuropsychological complications following PEA and
thoracic surgery in general have been observed [2-5]. In one study, it was
suggested that any surgical neurological damage was offset by beneficial
effects of the postoperative hemodynamic improvement after PEA for CTEPH [6].
In recent years, a minimally invasive percutaneous procedure has become an
alternative for patients who are technically inoperable. This procedure
consists of a balloon mediated local destruction of obliterative lesions in the
lung vasculature (balloon pulmonary angioplasty, or BPA) and is performed by a
dedicated team of a cardiologist and radiologist and is performed in awake
patients [7]. As of yet there is still a paucity of data on the neurologic
impact of these two procedures on the brain [6]. Neuro-biomarkers could be of
novel added value in understanding these investigations.
Neurofilament light (NfL), Glial fibrillary acidic protein (GFAP) and
Tau protein (Tau) have been shown to be valid markers for axonal damage, glial
activation and synaptic pruning, respectively. These markers have been
investigated in relation to neuronal injury, delirium and after (neuro)surgical
intervention [8-11].
Analysing the post-operative cognitive decline (POCD) and supplementing
this with biomarkers could improve our understanding of the extent of
neurologic damage in CTEPH after PEA or BPA. Investigating such biomarkers
could offer new tools for monitoring neuronal damage during cardiopulmonary
bypass and hypothermic cardiac arrest.

To evaluate post-operative neurologic damage using clinical data on delirium
and neuropsychological testing for long term postoperative decline, in
combination with measures of NfL, GFAP and Tau in CTEPH patients treated with
PEA or BPA in the Netherlands

Prospective cohort study. CTEPH patients who are accepted for invasive
treatment with BPA or PEA will have extra blood drawn (during routine clinical
venapunction) at several time points during the pre- and postoperative period.
This will be analysed for NfL, GFAP and Tau and analysed in relation to short
term outcomes such as delirium (as measured by CAM-ICU score, DOS score and
chart review) and long term outcomes such as cognitive/affective function as
measured using neuropsychological testing. This will take place before PEA/BPA,
and again three and six months after the last day of treatment.

The study relies on venapunction performed as part of routine clinical care.
The extra blood drawn will amount to 10 ml of blood per venapunction totalling
70 ml over the course of 6 months.
The neuropsychological evaluation will take 60 minutes and be scheduled in
conjunction with their routine outpatient follow-up. The patient will not need
to travel to the hospital on additional dates other than those already
scheduled for their care. Of the post-operative appointments, the 3 and 6 month
appointment involve several hours at the hospital in between diagnostic tests
which are suited to perform the neuropsychological tests.