Combined Pressure and Doppler Flow Velocity Assessment In Pulmonary Hypertension

Pulmonary hypertension (PH) is an increase of blood pressure in the pulmonary
artery, pulmonary vein, or pulmonary capillaries, which can lead to dyspnea,
dizziness, fainting, leg swelling and other symptoms. PH can be a severe
disease with a markedly decreased exercise tolerance and heart failure. The
underlying cause of PH can be subdivided into five different classes according
to the World Health Organization (WHO) classification; pulmonary arterial
hypertension, PH due to left sided heart disease, PH secondary to lung disease
and/or hypoxemia, chronic thromboembolic pulmonary hypertension (CTEPH) and PH
with unclear mechanism. For the diagnosis PH a right heart catheterization is
required. Measurements of pulmonary artery pressure (PAP) and cardiac output
(CO) of the right ventricle using thermodilution are performed with the use of
a Swan-Ganz catheter. If mean PAP exceeds 25 mmHg, the diagnosis of PH is
confirmed. Measurements of PAP and CO using the thermodilution method provide
no specific information pertaining to the distal pulmonary arterial
vasculature. Furthermore, pulmonary arterial flow cannot be assessed in
relation to the phase of the cardiac or respiratory cycle and the instantaneous
relation between perfusion pressure and flow can also not be assessed. Finally,
in the setting of right ventricular overload, tricuspid regurgitation
frequently occurs and may cause backflow of the infusate when assessing
cardiac output and may hamper the reliability of the measurement.

In the coronary circulation, assessment of blood flow and pressure in the
distal coronary artery are readily available using the ComboWire XT® (Volcano
Corporation, San Diego, USA) . The ComboWire is a 0.014 inch guidewire equipped
with both a distal pressure and Doppler flow velocity sensor, allowing the
simultaneous measurement of flow velocity and pressure. In the coronary
vasculature, a wealth of data has been documented on the flow, pressure and
microvascular resistance (MVR) relationship using this combined assessment of
intracoronary Doppler flow velocity and pressure in both physiological and
pathological conditions. These measurements are used to estimate prognosis,
indicate the need for interventional therapy and to evaluate the result of
therapeutic interventions.

In the pulmonary circulation, data on the proximal pulmonary pressure, flow and
resistance relationship is abundantly available. The distal vasculature
however, remains uncharted territory. Theoretically, MVR derived using Doppler
flow velocity, is independent of certain confounding factors such as tricuspid
regurgitation or local anatomic variations and thus could provide a more
accurate estimate of the localized pulmonary MVR. As such, it is envisioned
that it can serve both a diagnostic purpose as well as guide interventional or
pharmaceutical therapy.

In this explorative study, we aim to investigate whether MVR obtained with
Doppler flow velocity, is a better predictor of adverse outcome than PVR
obtained with Swan-Ganz measurements.

This design of this study is a prospective cohort study.
At baseline, additional measurements will be performed during the elective and
clinically indicated right heart catheterization. Clinical follow-up will be
obtained at 1 year with a visit to the outpatient clinic and at 6 months, 2
years and 5 years via a telephone call. If patients have to undergo a repeat
right heart catheterization for clinical indications, measurements will be
repeated.

A substudy will take place in patients with a specific type of pulmonary
hypertension, namely chronic thromboembolic pulmonary hypertension. For these
patients, in addition to the main study Optical Coherence Tomography (OCT)
measurement of the distal vessel will also take place. Furthermore, in patients
where balloon angioplasty is used to open the vesel, measurements will be
repeated after the vessel is openend.

For the patients recruited in the study, no specific benefits with regards to
the study procedures are anticipated. However, a theoretical benefit is that
they will be monitored more strictly than regular care requires because of the
study related follow-up visits. Whether this is actually advantageous remains
unknown.

With regards to risks, as with any invasive procedure, there are always
procedural risks involved both related to the clinically indicated right heart
catheterization, but also to the additional study intervention. Arterial
dissection, perforation or thrombosis related to the study intervention can all
theoretically occur. Given that in the coronary circulation, these
complications very rarely occur (own VUmc data between 2012 and 2014: 1 event
in 519 coronary arteries measured from 205 patients), and the two previously
conducted studies using similar wires in the pulmonary circulation, did not
find any safety concerns, we anticipate the risk to be minimal and well below
1%. The study intervention will require the administration of additional
radiation (estimated 400 dGy×cm2) and contrast burden (estimated 50-100 cc).


This study does serve clear beneficial scientific purpose, given that it could
potentially improve the prognostic power of the index right heart
catheterization, which could in turn be clinically relevant in case of
treatment selection. The enrolled CTEPH patients will also contribute to this
end. Furthermore the substudy will aid in the understanding of the
pathophysiology, disease progression and effectiveness of balloon angioplasty
in CTEPH.