Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03523624 |
Other study ID # |
eXIST-DCTV |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
November 1, 2015 |
Est. completion date |
January 1, 2022 |
Study information
Verified date |
May 2022 |
Source |
University of Padova |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
In medical practice, a combination of clinical exam, electrocardiograms, circulating
biomarkers, and imaging is used to gain insights on the prognosis after myocardial
infarction. Novel molecular non-invasive tools are needed that help clinicians overcome the
adverse events of post-myocardial infarction remodelling and thereby achieve improved therapy
for its prevention.
Coagulation factor XIII (FXIII) decay has been linked to major adverse cardiac events (MACE)
in patients with acute coronary syndromes. Given the correlation between both intramyocardial
haemorrhage and microvascular damage with acute phase complications in ST-elevation
myocardial infarction, we hypothesise that excessive FXIII decay within the first week may
predict acute phase outcomes in these patients. If this holds true, FXIII determination could
be used as diagnostic and prognostic tool.
Description:
Background:
The reduction of mortality in acute myocardial infarction (AMI) is achieved by the efficacy
of the current therapeutic strategies focused on an early reopening of the culprit coronary
artery, by either medical or mechanical reperfusion. Primary percutaneous coronary
intervention (PCI) represents the most effective way to limit infarct size and reduce
transmural extension of necrosis. Although coronary artery recanalization represents the most
effective way to reduce infarct size, the process of reperfusion may itself produce a series
of consequences including intramyocardial haemorrhage (IMH) and microvascular injury (MVO)
contributing to the 'no reflow' phenomenon. MVO is an early event followed by intramyocardial
haemorrhage that plays a role later in reperfusion injury. Both luminal obstruction
(microvascular damage by neutrophil plugging, platelets and emboli) and external compression
(by oedema and haemorrhage) are allegedly linked with no-reflow, however, the real mechanism
underlying this complex time-sensitive phenomenon remains to be fully understood. MVO and IMH
in ST-elevation myocardial infarction are independent predictor of adverse left ventricle
remodelling, independently of the initial infarct size, and predict MACE.
The diagnosis of no-reflow is usually made when post-procedural thrombolysis in myocardial
infarction (TIMI) flow is <3, or in the case of a TIMI flow of 3 when myocardial blush grade
is 0 or 1, or when ST resolution within 4 h of the procedure is <70%. It can be assessed
using cardiac magnetic resonance (CMR) techniques, where they appear as dark zones on delayed
post-contrast sequences or contrast echocardiography.
FXIII is a protransglutaminase that becomes activated by thrombin and catalyses the formation
of crosslinked fibrin mesh in the final stage of the clotting cascade. Blood coagulation
FXIII is thought to play a role in wound healing and tissue repair. FXIII is present in
plasma, platelets, monocytes, and macrophages, all of which are involved in infarct healing.
In an experimental model, mice lacking FXIII suffer from impaired wound healing and fatal
rupture of the left ventricle after myocardial infarction. This phenomenon was observed in
100% of homozygous and, interestingly, in 100% of the heterozygous FXIII-knockout mice,
despite a FXIII plasma level of 70%. Replenishment of FXIII during the 5-day acute and
subacute period of infarct healing restored survival rates of FXIII-deficient mice to that of
wild-type mice. In addition, reduced FXIII activity imaged via single photon emission
computed tomography predicted adverse infarct healing after MI in mice. In contrast,
increased intracardiac FXIII activity via induction of high FXIII zymogen plasma levels
improved cardiac healing. Moreover, FXIII levels were significantly diminished in myocardial
biopsies of human ruptured MI. In a case series of 25 patients with acute MI, a mean decrease
of initially normal FXIII plasma values by 25% was reported during the first week after the
ischemic event. During the first week after MI, an acute phase reduction in FXIII plasma
levels has been described, with the nadir of reduction on day 3-6 after the acute event.
FXIII thus seems to mediate the formation of a well-cemented scar, reducing MVO and IMH and
improve healing and left ventricle remodelling.
Aim of the study:
We will perform a prospective observational study to identify how the differences in FXIII
levels in ST-elevation myocardial infarction patients relate with intramyocardial haemorrhage
and microvascular damage as detected by cardiac magnetic resonance.