The current research project aims to improve the care of CABG patients, by a redefinition of PMI. In this research proposal, we focus on the diagnostic and clinical relevance of postoperative biomarker increases and will determine the association…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. The diagnostic accuracy of the various assessed cardiac biomarkers for
objectively quantified new myocardial cell necrosis on CMR at one month
follow-up, in relation to the pre-operative baseline CMR imaging results. The
area under the ROC curve will be used as the main diagnostic accuracy
parameter.
2. The prognostic value of the various assessed cardiac biomarkers for the
incidence of 1-year clinically relevant outcomes (defined as mortality,
myocardial infarction, and/or unplanned revascularisation). The prognostic
value of cardiac biomarkers will be compared using hazard ratios with 95%
confidence intervals derived from multivariable Cox regression models.
Secondary outcome
- The diagnostic accuracy of the continuous visual and functional coronary CTA
measurements will be assessed using the area under the ROC curve (AUC) as
primary parameter. The test results of invasive coronary angiography will be
used as reference standard. Presence of severe coronary stenosis based on the
invasive coronary angiography will be defined as a visual stenosis of >70% and
a fractional flow reserve (FFR) of <0.80.
- Bland-Altman plots of the objectively quantified volumes of myocardial
necrosis according to delayed enhancement on CTA and delayed enhancement on CMR
will be realized to evaluate the agreement between the two cross-sectional
imaging modalities.
- Biomarker release peaks, curves and patterns (normalized to the
99%-percentile of the biomarker in a reference population of seemingly healthy
adults).
- ECG changes, objectively quantified by an advanced ECG analytical method
(cine-ECG). The occurrence of classical true ECG-changes will be considered
(left bundle branch block de novo, Q-waves, and ST-elevation with reciprocal
depression), as well as percentual change as compared to baseline, quantified
by the advanced analytical method (cine-ECG).
- (Silent) graft failure upon postoperative coronary CTA, defined as non-patent
grafts.
- The objectively quantified amount of loss of viable myocardium (expressed as
mean and standard deviation or median and interquartile range, depending on the
distribution) as assessed by cross-sectional cardiac imaging studies at various
points in time (pre-operative, 3-days/1-month, one year)
Background summary
Coronary artery bypass grafting (CABG) is the most commonly performed cardiac
surgical procedure (approximately 500 patients per year in MUMC+, 7000 patients
in the Netherlands, and 1 million patients worldwide undergo CABG yearly). This
procedure is usually performed through sternotomy, and by use of
cardiopulmonary bypass (the heart-lung machine) under cardioplegic arrest (the
cessation of the heart). The surgery comprises the realization of bypass
grafts, rerouting the blood flow to myocardial territories beyond stenosed
vessels. Therefore, this intervention is aimed at the improvement of survival
and quality of life in patients with (extensive) coronary artery disease by,
amongst others, a reduction in future spontaneous myocardial infarction (MI).
Despite that the prevention of future MI is the aim of CABG, the occurrence of
periprocedural MI (PMI, also known as type 5 myocardial infarction) can be a
complication of this procedure. The prevalence of PMI is 3-40%(!) in patients
undergoing CABG, but is highly definition-dependent. Indeed, several
conflicting definitions of PMI are being applied, incorporating contradicting
statements.
The importance of a uniform definition of PMI:
The non-uniform use of the definitions of PMI in clinical practice and the
application in trials has led to substantial controverse, as it predisposes
patients to under- or overdiagnosis of PMI, and potential manipulability of
trials* outcomes. Still, a timely diagnosis of PMI is imperative, as prompt
(<12 hours) revascularization improves prognosis. Therefore the accurate and
timely diagnosis of PMI is of utmost importance to improve the outcomes of
patients undergoing coronary bypass surgery.
Causes of periprocedural myocardial infarction and injury:
Periprocedural myocardial infarction has a pluriform aetiology, which can
roughly be divided in irreversible and reversible causes. Although adequate
diagnosis of irreversible PMI is important for long-term medical treatment, the
adequate and timely diagnosis of reversible PMI is relevant, as immediate
treatment improves long-term prognosis. Still, some amount of myocardial injury
is inherent to the nature of cardiac surgery and CABG. During CABG, the heart
is cannulated, cardiopulmonary bypass and cardioplegic arrest are initiated,
and the heart is incised for graft anastomosis. Such injury can be monitored
postoperatively by measuring biomarker release, for which the causative
mechanisms are multifactorial. However, disproportionate myocardial injury,
resulting in excessive loss of viable myocardium, may lead to impaired
long-term prognosis. At a certain level of injury, such loss can be considered
an infarction, which is known as PMI.
Study objective
The current research project aims to improve the care of CABG patients, by a
redefinition of PMI. In this research proposal, we focus on the diagnostic and
clinical relevance of postoperative biomarker increases and will determine the
association between the release of various biomarkers and actual loss of viable
myocardium in relation to prognosis, using state-of-the-art diagnostic
modalities. As such, we divided our primary objective in two parts:
1. Diagnostic
To compare the diagnostic accuracy of CK-MB and high-sensitivity cardiac
troponin I and T in the direct postoperative phase after CABG for new loss of
viable myocardium as determined by cross-sectional cardiac imaging. This
endpoint will be primarily analysed based on the 1-month CMR study in relation
to baseline CMR findings. The 3-day and 1-year imaging studies will be used to
validate the definitiveness of the 1-month findings.
2. Prognostic
To compare the prognostic value of CK-MB, high-sensitivity cardiac troponin I
and T for the one year probability of all-cause mortality and major adverse
cardiovascular events in patients undergoing CABG.
Study design
This study comprises a prospective longitudinal observational cohort study of
patients undergoing CABG, with incorporation of state-of-the-art imaging
modalities and 1-year follow-up. The primary objectives are divided in a
diagnostic part (focused on the detection of myocardial injury at 1 month and 1
year as quantified by CMR) and a prognostic part (relating the direct
postoperative biomarker measurements and 30-day imaging findings to clinically
relevant events at 1-year follow-up).
Study burden and risks
The ionizing radiation exposure is limited to a minimal amount by the use of
most contemporary scanners and protocols. The use of contrast agent carries a
low risk of an adverse reaction. Finally, blood draws are limited to clinically
indicated points in time, posing minimal burden to the patients. Based on this
protocol and in agreement with the NFU* Kwaliteitsborging Mensgebonden
Onderzoek, there is a small chance of little to moderate injury. Therefore the
proposed study constitutes a *negligible risk*. We therefore believe that the
clinical importance of this study outweighs its minor risk.
P. Debyelaan 25
Maastricht 6229HX
NL
P. Debyelaan 25
Maastricht 6229HX
NL
Listed location countries
Age
Inclusion criteria
- Adult patients (>18 years of age).
- Surgery preceded by a heart-team discussion, in which the patient is planned
for multivessel CABG, receiving more than one graft (i.e., more than only left
internal mammary artery [LIMA] to left anterior descending artery [LAD]).
- Isolated on-pump planned multivessel CABG (defined as using cardiopulmonary
bypass and cardioplegic arrest).
- Able and willing to provide written informed consent.
- Elective or urgent surgery (defined as either planned surgery, or a surgical
procedure without which the patients cannot leave the hospital before the
surgery is performed24).
Exclusion criteria
- Non-adult patients (<18 years of age)
- Emergency surgery (defined as within 24 hours of indication and not waiting
until the following working day24).
- Recent acute coronary syndromes (including ST-elevation myocardial infarction
[STEMI] and non-STEMI [NSTEMI], recent defined as <14 days prior to surgery).
- Patients with contraindications to undergo cardiac magnetic resonance imaging
(including claustrophobia and CMR-incompatible implants).
- Prior adverse reactions to gadolinium- or iodine-based contrast agents.
- Moderate-severely compromised renal function (estimated glomerular filtration
[eGFR] <45mL/min/kg)
- In clinical heart failure upon admission for surgery.
- Pregnant or breast-feeding patients
Design
Recruitment
Medical products/devices used
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 | NL85076.068.23 |