Ignite Creation Date:
2024-05-06 @ 2:46 AM
Last Modification Date:
2024-10-26 @ 11:23 AM
Study NCT ID:
NCT02122497
Status:
UNKNOWN
Last Update Posted:
2014-04-24
First Post:
2014-04-22
Brief Title:
The Use of Cardiovascular Biomarkers in Abdominal Aortic Surgery
Sponsor:
Prim PD Dr Afshin Assadian
Organization:
Wilhelminenspital Vienna
Study Overview
Official Title:
The Use of Cardiovascular Biomarkers in Abdominal Aortic Surgery Possibility of Risk Assessment and Stratification
Status:
UNKNOWN
Status Verified Date:
2014-04
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BIAS
Brief Summary:
The aim of the present study is the evaluation of cardiovascular biomarkers in patients with abdominal aortic aneurysms AAA or abdominal aortic occlusive disease AOD undergoing open OR or endovascular aortic repair EVAR with regards to short- and long-term outcome
By blood collection and measurement of the serum biomarkers Copeptin N-terminal- pro Brain Natriuretic Peptide NT-proBNP cardiac Troponin I cTnI high sensitive Troponin T hs-cTnT and C-reactive Protein CRP we expect an improvement of patients stratification by assessment of cardiac stress tolerance Data gathered may help to simplify the decision whether an open or endovascular approach for abdominal aortic repair OR and EVAR should be performed
Study Hypothesis
The evaluation of the predictive value of cardiovascular biomarkers Copeptin NT-proBNP hsTnT cTnI CRP improve patient stratification and selection of surgical treatment
By blood collection and measurement of the serum biomarkers Copeptin N-terminal- pro Brain Natriuretic Peptide NT-proBNP cardiac Troponin I cTnI high sensitive Troponin T hs-cTnT and C-reactive Protein CRP we expect an improvement of patients stratification by assessment of cardiac stress tolerance Data gathered may help to simplify the decision whether an open or endovascular approach for abdominal aortic repair OR and EVAR should be performed
Study Hypothesis
The evaluation of the predictive value of cardiovascular biomarkers Copeptin NT-proBNP hsTnT cTnI CRP improve patient stratification and selection of surgical treatment
Detailed Description:
Background
The prevalence of coronary artery disease CAD in patients with aneurysmal or occlusive disease of the aorta is high more than 50 percent of patients suffering from peripheral arterial occlusive disease PAOD or abdominal aortic aneurysm AAA do also have coronary artery disease As a result cardiovascular disease is the leading cause of morbidity and mortality in patients undergoing aortic surgery
Identifying patients at increased risk of cardiac complications following major vascular surgery is also part of the decision-finding process when patients are assigned to open or endovascular surgery The 30-day mortality rate for elective open aneurysm repair OR is estimated to be 4 to 8 while endovascular aneurysm repair EVAR has a perioperative risk of 12 to 16 However the early survival advantage of patients undergoing EVAR disappears with time and all-cause mortality is similar for EVAR and open repair at late follow-up Patients treated by EVAR show a higher number of complications and reinterventions and a significant proportion of late deaths after EVAR are due to aneurysm rupture
Therefore patients who need abdominal aortic surgery are required to undergo a thorough medical examination on the one hand to assess cardiac capacity on the other hand to estimate life expectancy Current recommendations for the preoperative management of patients undergoing major non-cardiac vascular surgery include physical examination and routine performance of electrocardiogram and echocardiogram as part of a cardiovascular evaluation However guidelines do not include routine screening with cardiac enzymes or cardiac stress markers
Biomarkers
Brain natriuretic peptide BNP and the inactive precursor N-terminal prohormone of brain natriuretic peptide NT-proBNP are valuable screening tools for identifying patients who may suffer from heart failure NT-proBNP plays an important role in heart remodeling and volume homeostasis It is an important indicator of prognosis in heart failure and after acute myocardial infarction Elevated pre- and postoperative plasma NT-proBNP levels independently predict postoperative myocardial injury which is associated with adverse outcome in the short- and long-term regardless of the presence of symptoms of acute coronary syndrome
Copeptin is a novel marker that allows highly sensitive but unspecific assessment of stress Copeptin is the C-terminal fragment of provasopressin the precursor peptide of vasopressin antidiuretic hormone Vasopressin is released by the neurohypophysis in order to promote water absorption and vasoconstriction and thereby contributes to osmotic and cardiovascular homeostasis Due to the fact that Vasopressin is unstable in the peripheral circulation the stable Copeptin which is released in equimolar amounts is measured instead of Vasopressin Recent studies have shown that this peptide may also be applied for the assessment of the risk of morbidity and mortality increased copeptin levels are associated with poor short- and long- term prognosis after myocardial infarction and stroke
Troponins are widely used biomarkers for the diagnosis and management of acute myocardial infarction and acute coronary syndrome Troponin is an essential protein of muscle cells Thus damage to the heart muscle such as coronary vasospasm cardiomyopathy heart failure and myocarditis can be indicated by elevated serum levels of cardiac troponin The most common cause of raised troponins is myocardial ischemia as a result of acute coronary syndrome or myocardial infarction In patients undergoing major vascular surgery even early small postoperative rises in troponin have been shown to correlate with adverse short- and medium-term outcome
C-reactive protein CRP an acute-phase protein is a sensitive marker of inflammation and tissue damage Elevated CRP levels are able to predict future atherothrombotic events such as stroke coronary events and progression of peripheral arterial disease Furthermore inflammation is crucially involved in atherosclerosis and plaque development
Material and Methods
Study Design Prospective non-randomized open-labeled observational study
Patient Population
500 patients of the Department of Vascular and Endovascular Surgery of the Wilhelminenhospital Vienna Preoperative evaluation includes electrocardiography echocardiography and internal medical examination Comorbidities history of cardiac events previous operations routine laboratory tests and current medication are documented
Blood Sampling and Laboratory Measurements
Blood samples are obtained by venipuncture and collected in standard serum and EDTA tubes preoperatively 48 hours postoperatively ten days and six weeks after surgery centrifuged for 20 minutes at 2000 G and the plasma is stored in aliquots at minus 80 degrees Celsius until determination of the respective biomarkers
Surgical procedures
Surgery is standardized by performing endovascular aortic repair EVAR or open surgical procedures OR OR is performed in general anesthesia via a transabdominal or retroperitoneal approach that allows repair of the aneurysmal or stenosed aorta with tube- or bifurcated grafts In contrast groin access for EVAR is achieved in local anesthesia
Statistical Analysis
The study cohort consists of three study groups patients with AAA undergoing EVAR patients with AAA undergoing OR and patients suffering from AOD undergoing open surgical repair All patients will be observed until complete follow-up plasma samples at 0 2 days 10 days 6 weeks and an annual outpatient checkup thereafter or until a primary fatal outcome event The statistical distribution of the serum levels of the respective biomarkers is assessed by a histogram The skewed distribution prompts non-parametric tests Mann-Whitney-U for comparison of medians by gender and status of survival The effect of biomarkers on 5-year postoperative survival primary endpoint is estimated in uni- and multivariate proportional hazard models Cox Regression for establishment of a prognostic model In order to adjust for confounders the latter includes classic cardiovascular risk factors age hypertension nicotine abuse diabetes mellitus history of cardiac events high lipoproteins which are documented preoperatively and entered as covariates Survival estimates stratified by the three study groups will be shown in Kaplan Meier Curves log-rank test A two-sided p-value P of less than 005 is considered to indicate statistical significance Hosmer and Lemeshow tests are performed to test for adequacy for all regression models P 005 Tests for proportional hazard assumption is performed through linear regression of partial residuals Schoenfeld for each variable and 5-year survival time Cox proportional hazards model are presented as hazard ratio HR and 95 confidence interval CI All statistical analyses are performed with the use of SPSS 20 IBM Inc Somers NY 10589 USA
The prevalence of coronary artery disease CAD in patients with aneurysmal or occlusive disease of the aorta is high more than 50 percent of patients suffering from peripheral arterial occlusive disease PAOD or abdominal aortic aneurysm AAA do also have coronary artery disease As a result cardiovascular disease is the leading cause of morbidity and mortality in patients undergoing aortic surgery
Identifying patients at increased risk of cardiac complications following major vascular surgery is also part of the decision-finding process when patients are assigned to open or endovascular surgery The 30-day mortality rate for elective open aneurysm repair OR is estimated to be 4 to 8 while endovascular aneurysm repair EVAR has a perioperative risk of 12 to 16 However the early survival advantage of patients undergoing EVAR disappears with time and all-cause mortality is similar for EVAR and open repair at late follow-up Patients treated by EVAR show a higher number of complications and reinterventions and a significant proportion of late deaths after EVAR are due to aneurysm rupture
Therefore patients who need abdominal aortic surgery are required to undergo a thorough medical examination on the one hand to assess cardiac capacity on the other hand to estimate life expectancy Current recommendations for the preoperative management of patients undergoing major non-cardiac vascular surgery include physical examination and routine performance of electrocardiogram and echocardiogram as part of a cardiovascular evaluation However guidelines do not include routine screening with cardiac enzymes or cardiac stress markers
Biomarkers
Brain natriuretic peptide BNP and the inactive precursor N-terminal prohormone of brain natriuretic peptide NT-proBNP are valuable screening tools for identifying patients who may suffer from heart failure NT-proBNP plays an important role in heart remodeling and volume homeostasis It is an important indicator of prognosis in heart failure and after acute myocardial infarction Elevated pre- and postoperative plasma NT-proBNP levels independently predict postoperative myocardial injury which is associated with adverse outcome in the short- and long-term regardless of the presence of symptoms of acute coronary syndrome
Copeptin is a novel marker that allows highly sensitive but unspecific assessment of stress Copeptin is the C-terminal fragment of provasopressin the precursor peptide of vasopressin antidiuretic hormone Vasopressin is released by the neurohypophysis in order to promote water absorption and vasoconstriction and thereby contributes to osmotic and cardiovascular homeostasis Due to the fact that Vasopressin is unstable in the peripheral circulation the stable Copeptin which is released in equimolar amounts is measured instead of Vasopressin Recent studies have shown that this peptide may also be applied for the assessment of the risk of morbidity and mortality increased copeptin levels are associated with poor short- and long- term prognosis after myocardial infarction and stroke
Troponins are widely used biomarkers for the diagnosis and management of acute myocardial infarction and acute coronary syndrome Troponin is an essential protein of muscle cells Thus damage to the heart muscle such as coronary vasospasm cardiomyopathy heart failure and myocarditis can be indicated by elevated serum levels of cardiac troponin The most common cause of raised troponins is myocardial ischemia as a result of acute coronary syndrome or myocardial infarction In patients undergoing major vascular surgery even early small postoperative rises in troponin have been shown to correlate with adverse short- and medium-term outcome
C-reactive protein CRP an acute-phase protein is a sensitive marker of inflammation and tissue damage Elevated CRP levels are able to predict future atherothrombotic events such as stroke coronary events and progression of peripheral arterial disease Furthermore inflammation is crucially involved in atherosclerosis and plaque development
Material and Methods
Study Design Prospective non-randomized open-labeled observational study
Patient Population
500 patients of the Department of Vascular and Endovascular Surgery of the Wilhelminenhospital Vienna Preoperative evaluation includes electrocardiography echocardiography and internal medical examination Comorbidities history of cardiac events previous operations routine laboratory tests and current medication are documented
Blood Sampling and Laboratory Measurements
Blood samples are obtained by venipuncture and collected in standard serum and EDTA tubes preoperatively 48 hours postoperatively ten days and six weeks after surgery centrifuged for 20 minutes at 2000 G and the plasma is stored in aliquots at minus 80 degrees Celsius until determination of the respective biomarkers
Surgical procedures
Surgery is standardized by performing endovascular aortic repair EVAR or open surgical procedures OR OR is performed in general anesthesia via a transabdominal or retroperitoneal approach that allows repair of the aneurysmal or stenosed aorta with tube- or bifurcated grafts In contrast groin access for EVAR is achieved in local anesthesia
Statistical Analysis
The study cohort consists of three study groups patients with AAA undergoing EVAR patients with AAA undergoing OR and patients suffering from AOD undergoing open surgical repair All patients will be observed until complete follow-up plasma samples at 0 2 days 10 days 6 weeks and an annual outpatient checkup thereafter or until a primary fatal outcome event The statistical distribution of the serum levels of the respective biomarkers is assessed by a histogram The skewed distribution prompts non-parametric tests Mann-Whitney-U for comparison of medians by gender and status of survival The effect of biomarkers on 5-year postoperative survival primary endpoint is estimated in uni- and multivariate proportional hazard models Cox Regression for establishment of a prognostic model In order to adjust for confounders the latter includes classic cardiovascular risk factors age hypertension nicotine abuse diabetes mellitus history of cardiac events high lipoproteins which are documented preoperatively and entered as covariates Survival estimates stratified by the three study groups will be shown in Kaplan Meier Curves log-rank test A two-sided p-value P of less than 005 is considered to indicate statistical significance Hosmer and Lemeshow tests are performed to test for adequacy for all regression models P 005 Tests for proportional hazard assumption is performed through linear regression of partial residuals Schoenfeld for each variable and 5-year survival time Cox proportional hazards model are presented as hazard ratio HR and 95 confidence interval CI All statistical analyses are performed with the use of SPSS 20 IBM Inc Somers NY 10589 USA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None