To evaluate coagulation status in patients with moderate-severe to severe MR, with concomitant atrial enlargement or atrial fibrillation, before and after M-TEER to explore the complex relationship between MR and coagulability.
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The difference in coagulation activation, as measured with prothrombin
fragments 1+2 and fibrinopeptide A+B, between baseline and 3 months after
M-TEER
Secondary outcome
Markers of the coagulation cascade, thrombin generation, clot breakdown, and
platelet activation will be measured before and 3 months after M-TEER:
• Coagulation cascade: Prothrombin fragments 1+2, Thrombin-AntiThrombin complex
(TAT), activated coagulation factors (Factor VIIa, Factor IXa, Factor Xa,
Factor Xia, and Factor XIIa in complex with their respective natural
inhibitors), thrombin-generation test (TGT)
• Platelet reactivity: P-selectin expression, beta-thromboglobulin
• Endothelial activation: VWF antigen, sICAM
• Fibrinolysis activity: fibrinogen, soluble fibrin, plasmin-alfa-2-antiplasmin
complex, D-dimer
• VWF multimeres
• Overall thrombus formation assessment (e.g. T-TAS AR chip)
• Full blood count + differentiation
• Clinical endpoints, i.e. bleeding, myocardial infarction, stroke/TIA,
systemic embolism, all-cause death
Background summary
Mitral Regurgitation (MR) is a condition characterized by abnormal backflow of
blood from the left ventricle to the left atrium. Patients are at an increased
risk of heart failure and mortality due to this condition. For this reason,
moderate to severe MR should be treated. Additionally, MR can lead to dilated
atria and atrial fibrillation (AF). Dilated atria and atrial fibrillation can
worsen the severity of MR through annular dilation (functional MR). Blood
stasis occurs in atrial fibrillation and severely dilated atria, increasing the
risk of clot formation in the left atrium and left atrial appendage. If such a
clot dislodges, it can cause a stroke. Some studies suggest that MR may have a
protective effect against the development of thrombi in the left atrial
appendage in patients with dilated atria and atrial fibrillation. The turbulent
blood flow associated with moderate to severe MR potentially reduces blood
stasis in the left atrium/left atrial appendage, reducing the risk of
thromboembolic events. However, conflicting results have been published,
showing an increased risk of clot formation in MR and AF.
This study aims to investigate the complex relationship between severe MR and
clotting to gain insight into the underlying mechanisms involved. By
determining several clotting parameters before and after Mitral Valve
Transcatheter Edge-to-Edge Repair (M-TEER), the effect of MR on clotting status
can be assessed. Comparing clotting parameters within the same patient can
provide insight into the altered clotting dynamics that may occur with MR.
The hypothesis of the study states: After an M-TEER procedure, the coagulation
tendency in patients with moderate-severe or severe MR, either with enlarged
atria or atrial fibrillation, increases compared to before the procedure.
Study objective
To evaluate coagulation status in patients with moderate-severe to severe MR,
with concomitant atrial enlargement or atrial fibrillation, before and after
M-TEER to explore the complex relationship between MR and coagulability.
Study design
The study is a monocenter, prospective pilot study in which the patient serves
as their own control. Blood samples will be taken at baseline and 3 months
after the procedure. Blood sampling for patients on anticoagulation will be
performed before medication intake (trough level). Clinical endpoints will be
collected over a period of 3 months.
Study burden and risks
All blood samples are drawn from venepuncture or drawn from a routinely placed
IV catheter at baseline (one day before the procedure) and 3 months after
M-TEER. Clinical information will be extracted from the patient*s medical file,
retrieved from the patient*s general practitioner if needed, or collected
during the follow-up moment at 3 months. No benefit or harm is to be expected
for the participants.
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Listed location countries
Age
Inclusion criteria
- >= 18 years old
- Echocardiographic-proven (TTE) moderate or severe MR with a planned M-TEER
procedure
Exclusion criteria
- Patients who are unable to provide informed consent
- Active malignancy excluding non-melanoma skin cancer
- Active liver disease (ALT, ASP, AP >3x ULN or active hepatitis A, B or C)
- Patients using, and unable to omit, nonsteroidal anti-inflammatory drugs,
corticosteroids, or hormone replacement therapy
- Known coagulopathy
- Severe anaemia requiring blood transfusion or thrombocytopenia <50 × 10^9/L
- Life expectancy <1 year
- Severe kidney failure (eGFR < 30 mL/min)
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 | NL84411.100.23 |