The main objective of the current study is to evaluate which patients in the twilight zone of PH will benefit from PAH specific therapy. We will assess the (early) response to PAH specific treatment and determine potential predictors of adverse…
ID
Source
Brief title
Condition
- Heart failures
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Improvement in exercise capacity, as measured by 6-minute walk testing (6MWT)
will be used as primary outcome measure.
Secondary outcome
Change in PCWP after treatment, as measured by RHC during follow up, will be
evaluated as secondary outcome measure. Other physiological parameters of
interest are: diastolic pressure gradient, reaction of PCWP to fluid challenge
at the time of the first RHC, reaction of PCWP on NO inhalation at first RHC,
exercise echocardiography measures, NT-proBNP, cardiac index, LV (diastolic)
function, additional CMR measures (including assessment of diastolic strain and
left atrial dimensions), use and dosage of diuretics and quality of life.
Background summary
Pulmonary hypertension (PH) due to left heart failure is a common form of PH.
Distinguishing PH due to heart failure with preserved ejection fraction (HFPEF)
is notoriously difficult but is of particular importance as therapeutic
management in this group is different.
Traditionally, patients with an increased mean pulmonary artery pressure (mPAP)
and high pulmonary capillary wedge pressure (PCWP >15 mmHg) will be diagnosed
with heart failure (including HFPEF) and clinicians focus mainly on treating
the underlying cardiac diseases. In the contrary in patients with a low PCWP,
pulmonary arterial hypertension (PAH) is diagnosed and these patients benefit
from PAH specific medication (provided other causes of PH are excluded).
However in some cases the cut-off value of 15 mmHg seems arbitrary. Especially
in the twilight zone of PH (when PCWP is between 10-15 mmHg) uncertainties
remain regarding the best diagnostic and treatment strategy.
We hypothesize that the twilight zone of PH is a heterogeneous group of
patients in which both patients with HFPEF like- and PAH phenotype can be
found. If this hypothesis proves to be correct, this raises the question
whether the use of PAH specific medication in all patients in the Twilight zone
of PH is beneficial. Nevertheless, differences in treatment response and the
correlation to clinical characteristics in this sub-group of PH has never been
investigated.
By characterizing patients in the twilight zone of PH and evaluating initial
response to PAH-specific medication we will gain insight in pathophysiological
differences in this group and we will be able to develop a more
disease-targeted therapy in the future.
Study objective
The main objective of the current study is to evaluate which patients in the
twilight zone of PH will benefit from PAH specific therapy. We will assess the
(early) response to PAH specific treatment and determine potential predictors
of adverse treatment outcome.
Study design
In this explorative, prospective, single centre intervention study, all adult
patients referred for new evaluation of PH and suspected of either PAH (with a
PCWP between 8-15 mmHg) or HFPEF (PCWP >15 mmHg) will be included. Treatment
response on initial PAH-specific medication, following a standardized treatment
protocol, will be our primary outcome parameter. Clinical and physiological
characteristics of responders and non-responders to treatment will be compared.
Clinical parameters of interest are: change in pulmonary capillary wedge
pressure and mPAP after treatment at 4 months of follow-up, diastolic pressure
gradient, several cardiac MRI (CMR) parameters (including strains, atrial
dimensions and 4Dflow velocities), (exercise) echocardiographic measures (e.g.
LV (diastolic) function and left atrial dimensions), NT-proBNP, cardiac index,
quality of life (QoL) and the use and dosage of diuretics.
Intervention
Right heart catheterisation, CMR, echocardiography, NT-proBNP and 6MWD at
baseline and at follow-up are already part of our routine diagnostic work-up.
For the purpose of this study, we will extend the routine diagnostic work-up by
adding a fluid challenge, exercise echocardiography and additional CMR
measures. In addition, patients will be requested to complete QoL
questionnaires.
Study burden and risks
The proposed tests are safe and operational at the VUmc. They add little
discomfort to the patients, as the study measurements only extend routine
clinical investigations. In this study, we will treat patients with a PCWP >15
mmHg with PAH-specific medication. Although this is in contrast with current
guidelines (which recommend only treating patients with a wedge below 15mmHg),
this treatment strategy is not uncommon in PH expert centres and is considered
safe. Importantly, it is not known whether HFPEF patients with PH and an
elevated PCWP higher wedge pressures and HFPEF-like PH may benefit from
PAH-specific medication. This is very well possible as they may still express
PAH-like pathophysiology. As such, withholding therapy from these patients may
not be justified.
Although participating patients will not directly profit from the additional
measurements obtained in this study, they might benefit from the results of
this study in the future.
We consider the burden and risks associated with participation to be low,
whereas the benefit for the PH-patient group in general is considered high.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
- Referred to the VUmc for analyses of PH;
- Suspected of PAH(PCWP 8-15mmHg) or
- PH secondary to HFPEF (wedge pressure >15mmHg) AND out of proportion PH (defined as pulmonary vascular resistance (PVR) > 3 Woods units (WU) or PVR between 2.5 -3.0 WU AND elevated transpulmonary gradient >12)
Exclusion criteria
- Hemodynamic instability
- Contra-indication for diagnostic right heart catheterisation, MRI, echocardiography (e.g. pregnancy)
- Other diagnosis than PAH/ diastolic heart failure
- No informed consent for the complete study protocol
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL46196.029.14 |