Primary objective is to analyse vasoreactivity of the vascular system of patients with and without heart failure, in and ex vivo. Secondary objectives are to identify signal transduction pathways associated with the altered vasoreactivity in this…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Change in SVR after phenylephrine administration (phase 1).
Secondary outcome
In vivo (phase 1):
- Systemic arterial pressure waveform morphology.
- Pulse transit time.
- Change in MAP, systemic arterial pressure waveform morphology and pulse
transit time after phenylephrine administration.
- Change in MAP, cardiac index and SVR after nitroglycerin administration.
- Vasoplegia: the continuous need of vasopressors (norepinephrine *0.2 µg/
kg/min for at least 12 consecutive hours, terlipressin or methylene blue) in
combination a state with a cardiac index *2,2 l/min/m2 for at least 12
consecutive hours, starting within the first 3 days postoperatively.
- Copeptin, norepinephrine, epinephrine, atrial natriuretic peptide (ANP),
brain natriuretic peptide (BNP), N-terminal prohormone of BNP (NTproBNP),
angiotensin II, cortisol, aldosterone, renin and vanillylmandelic acid (VMA)
levels.
Ex vivo (phase 1 and 2):
- Change in vessel diameter in response to vasoactive drugs.
- Activated signalling proteins which are associated with vasoresponsiveness.
- Receptors (quantity and function) which are associated with
vasoresponsiveness.
Background summary
Vasoplegia is a state defined by hypotension, a high cardiac index and the
continuous need of vasopressors. It occurs in 5-25% of the patients undergoing
cardiac surgery on cardiopulmonary bypass (CPB) and is associated with an
increased morbidity and mortality. Vasoplegia is a result of activation of
several vasodilator pathways, inactivation of vasoconstrictor pathways and the
resistance to vasopressors, but the precise aetiology remains unclear.
Important risk factors for the development of vasoplegia after cardiac surgery
are a left ventricular ejection fraction <30%, CPB and CPB duration. We
hypothesize that in patients with chronic heart failure, the responsiveness of
the vascular system is permanently altered due to chronic endogenous adrenergic
stimulation, resulting in down regulation and/or desensitization of vascular *1-
adrenoreceptors. The vascular system of patients with heart failure is easily
pushed out of balance by the systemic inflammatory reaction caused by the CPB
and surgical trauma, making these patients more prone for developing
vasoplegia. Also activation of inducible nitric oxide synthase, activation of
adenosine triphosphate dependent potassium channels and deficiency of arginine
vasopressin may play an important role.
Study objective
Primary objective is to analyse vasoreactivity of the vascular system of
patients with and without heart failure, in and ex vivo. Secondary objectives
are to identify signal transduction pathways associated with the altered
vasoreactivity in this patient group and to analyse vasoreactivity of the
vascular system of patients with and without vasoplegia, in and ex vivo.
Study design
Prospective, cross-sectional study.
Intervention
Not applicable
Study burden and risks
During phase 1, the protocol follows standard care, except for 5 phenylephrine
challenges, 1 biopsy from the incision area, 5 blood samples (20 ml each, 100
ml total), 1 urine sample and 2 vasodilation tests. During phase 2 only a
biopsy from the incision area is taken. Patients included in the study will not
have a direct benefit from the study, but understanding the difference in
vascular responsiveness between patients with and without heart failure in
detail, might yield therapeutic options or preventive strategies for
vasoplegia, leading to safer surgical interventions and improvement in outcome.
The measurements necessary to assess the defined study parameters are not
expected to negatively influence the result of treatment.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
Group 1:
- Diagnosed with heart failure in line with the European Society of Cardiology
guidelines;
- Left ventricular ejection fraction <=<35%;
- Undergoing cardiac surgery on CPB., Group 2:
- Not diagnosed with heart failure;
- Left ventricular ejection fraction >50%;
- Undergoing cardiac surgery on CPB.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in the phase 1 of this study:
- Age <18 years;
- Incapacitated adults;
- Emergency operation;
- Patients in need of moderate of high dosages of intravenous inotropic support
(>4 gamma dobutamine or dopamine), vasopression and/or mechanical support;
- Patients with aortic valve insufficiency > grade 1;
- Patients using a daily dosage of nitroglycerine or isosorbide dinitrate;
- Patients using alpha blockers.
For phase 2, patients that meet any of the following criteria will be excluded
from the study:
- Age <18 years;
- Incapacitated adults;
- Emergency operation;
- Patients in need of moderate or high dosages of intravenous inotropic support
(>4 gamma dobutamine or dopamine) and/or vasopression;
- Patients using a daily dosage of nitroglycerine or isosorbide dinitrate;
- Patients using alpha blockers.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL51125.058.14 |
| OMON | NL-OMON22119 |