Myocardial Injury After Radical Nephrectomy
Patients undergoing nephrectomy have a greater risk of cardiac events requiring admission compared to the general population. For example, registry data report 21% of patients over 65 undergoing nephrectomy have at least one cardiovascular event after surgery. Myocardial injury after non-cardiac surgery (MINS) is a condition which is associated with increased mortality and a higher rate of major adverse cardiac events (MACE), in both the immediate perioperative period and within 1-year post-surgery. Diagnosis is via the presence of elevated troponin levels in the first 3 days post-surgery, in the absence of ischaemic symptoms and ECG changes. The occurrence of MINS following nephrectomy for renal cell carcinoma has not yet been explored. Risk factors for MINS include increasing age and post-operative acute kidney injury. Results from the British Association of Urological Surgeons (BAUS) Nephrectomy audit demonstrate that most patients undergoing nephrectomy are over 60 and that increasing age is associated with lower eGFR pre-operatively. The accepted further reduction in post-operative GFR with nephrectomy makes these patients at high risk of MINS. The BAUS Nephrectomy audit also demonstrates that elderly patients undergoing nephrectomy are likely to be anaemic preoperatively. In at-risk patients, any intraoperative haemodynamic instability may progress to myocardial injury and cardiac related complications due to a change in myocardial oxygen demand. Most radical nephrectomies are now performed using robotic or laparoscopic approaches. Current evidence from retrospective studies and a small prospective study suggests that there is no difference in perioperative nor oncological outcomes between laparoscopic and robotic radical nephrectomy, including blood loss. However, no studies to date have looked at MINS and large-scale prospective studies comparing the haemodynamic effects of laparoscopic vs robotic nephrectomy are needed. Understanding the spectrum of MINS and its potential impact on patients undergoing nephrectomy is pivotal. This could lead to better patient selection and stratified care to improve outcomes. Advances in systemic therapy for metastatic disease mean nephrectomy may become more prevalent in persons on multiple therapies. As patients undergoing nephrectomy are at high risk of MINS, it is vital to have a greater understanding of this potential complication. This aligns with the James Lind Alliance Priority Setting Partnership in perioperative care which highlights the importance of research into post-operative complications. Furthermore, this group also underlines the importance of adequate preoperative discussions with patients, which would include the risk of postoperative complications such as MINS. Eligible patients who have consented to the study will have their troponin levels measured on the day of the surgery and at day 1 post-op to diagnose MINS. A baseline quality of life assessment will also be made by asking patients to complete an EQ-5D-5L questionnaire. Any blood transfusions during the admission period will also be recorded. At day 90 post-op, the occurrence of MACE events and days out of hospital (DAOH90) will be checked, and the patient will be contacted to complete the quality-of-life questionnaire again. Baseline assessments: The following demographic information will be prospectively collected by reviewing the patient's medical notes: - Age, sex, and ethnicity - Previous history of ischaemic heart disease, congestive cardiac failure, cerebrovascular disease (stroke or TIA), diabetes - Tumour characteristics (radiological T stage, laterality) Pre-op renal function and baseline troponin will be measured on the day of surgery. Primary outcome measure: The primary outcome measure is the proportion of patients undergoing laparoscopic or robotic radical nephrectomy with evidence of myocardial injury (MINS). This will be defined as a raised troponin level >99th percentile upper reference limit on any sample taken within 72 hours following the operation. Patients will have troponin levels measured on the morning of surgery and at day 1 post-op. If applicable, this can be retrieved as an 'add on' test on routine samples, without the requirement for an additional "blood draw" to avoid extra burden to patients. Sites will be expected to manage patients post-operatively as per Trust guidelines - this may or may not include troponin monitoring. The European Society for Cardiology advocates testing of troponins but does not make treatment recommendations. If troponin monitoring is not part of usual care, the troponin samples will not be available to the clinical team to avoid any inadvertent additional investigations which may add to patient burden. Instead, we would arrange the troponin results to be processed after surgery. However, the clinical team can request troponin tests for clinical information, for example in the assessment of chest pain. In this situation, the troponin sample would be processed immediately and be available for the clinical team to view. The clinical team will be expected to follow local guidelines regarding the clinical management. If the clinical team requests a troponin level for clinical assessment, we will also note this in the research record. Secondary outcome measures: Perioperative assessments: ● Any blood transfusions during the intraoperative and/or postoperative period will be recorded. This will allow assessment of potential cardiovascular instability compared between the groups (laparoscopic vs robot-assisted) and how this translates to rates of MINS and MACE post-op. 90 days (+/- 7 days) post-procedure: Patients will be contacted by the research team via telephone to assess the following: - The occurrence of any major adverse cardiovascular event (myocardial infarction, stroke, arrhythmia, cardiac arrest, and cardiac related death) during admission will be recorded. This will be obtained as part of patient follow up at 90 days post-op. - Days out of hospital at 90 days (DAOH90). This will be recorded following discussion with the patient and review of local hospital data - Impact on quality of life will be assessed using the EQ-5D-5L via a telephone interview by the research team.
Phase
N/ASpan
59 weeksSponsor
Sheffield Teaching Hospitals NHS Foundation TrustRecruiting
Myocardial Injury in Treatment of AAA
Background: Traditional open surgery for abdominal aortic aneurysm (AAA) is burdened with complication risk from several organ systems, and also mortality figures of 3.5 - 5.5%. Over 50% of early mortality can be attributed to cardiovascular complications. Myocardial infarction is the dominant organ-specific cause of both early and late mortality in patients operated on for AAA. Endovascular surgery (EndoVascular Aortic Repair, EVAR) was developed during the 90's as an alternative method that is considered less invasive and more well-tolerated from a cardiovascular perspective. Troponin T is a very sensitive and specific marker that predicts mortality in patients with acute symptoms of unstable angina and/or heart attack. Previous studies have also shown a high incidence of elevated troponin levels in patients who underwent major surgical procedures, especially vascular surgery, even in the absence of corresponding clinical or ECG-related symptoms of cardiac muscle injury. Several studies have also demonstrated that elevated troponin levels after surgery predict increased morbidity and mortality both short-term and long-term. Objective: To prospectively compare elective open and endovascular surgery of AAA with respect to myocardial injury detectable with troponin T. Furthermore, to compare open and endovascular AAA surgery for the total number of periods of oxygen deficiency in cardiac muscle during and at early stages after surgery using a special ECG method (48-hour 3-channel Holter ECG with ST analysis). Main aim of the study: To assess whether EVAR induce less myocardial injury compared with open repair for AAA. Significance: Myocardial infarction is the predominant cause of mortality in open surgical procedure for AAA. In several previous studies, troponin T rise has been associated with impaired both short-term and long-term prognosis in elderly patients undergoing major elective surgery. This study may provide information on whether the endovascular technique provides a reduction in myocardial injury, measured as elevated troponin T or myocardial ischemia with 3-channel Holter ECG. In this way, our study can provide improved decision support in the choice of the most appropriate treatment method in the individual case.
Phase
N/ASpan
987 weeksSponsor
Göteborg UniversityRecruiting
TROPOnin FRAGMentation in Myocardial Injury Study
Modern cardiac troponin T (cTnT) tests are highly sensitive in diagnosing AMI and myocardial damage. Atrial fibrillation and many non-cardiac conditions and even strenuous exercise are associated with elevated cTnT levels which are problematic to clinicians and may lead to redundant use of diagnostic coronary angiography or "overdiagnosis" of ACS in the emergency room workup. The cardiac troponin (cTn) complex is part of the thin filaments of myocardium. Small part (approximately 5% of total content) of troponins are cytosolic. These smaller cytosolic fragments may more easily traverse across cell membranes that have become leaky for some reason but not irreversibly damaged. Only cytoplasmic forms of troponin are contained in the subcellular blebs which lyse upon early cTn release into the circulation. Bleb formation may explain how troponin can appear in blood in the absence of cell necrosis. Still many aspects of their intramyocardial degradation, their tissue release, and their degradation within and elimination from the human circulation are still incompletely understood. In the early hours of AMI, troponin is found in its full-size complex, but the complexed cTnT degrades in a time-dependent pattern after the first hours. Small molecular weight troponin fragments originating from the cytoplasm may traverse across leaky cell membranes not completely damaged in various conditions without irreversible myocardial cell necrosis. Commercial cTnT test detects all these fragments and may thus lead to false diagnosis of AMI. At present, there is limited information based on small studies using complicated gel filtration chromatography and Western blotting showing cTnT fragmentation in later phases of AMI and in renal failure. These time-consuming analytical methods are, however, not suitable for clinical purposes in the emergency room. ANALYTICAL METHODS In this study we test a novel sensitive time-resolved immunofluorometric assay, which has been developed at the biotechnology unit of the Department Biochemistry, University of Turku, which enables us to measure cTnT from blood samples in its intact or only slightly fragmented form. Thus, we can exclude the highly fragmented short forms of cTnT from the analysis. This selectivity can be achieved with specific capture and tracer antibodies that bind to carefully chosen epitopes located closer to the opposite ends of the cTnT molecule. In the assay one of the antibodies is attached to a surface and acts as an antigen capturing antibody. The capture-antigen pair can be detected with tracer antibody, thus forming capture-antigen-tracer complex. In our case this tracer antibody has been labeled with europium chelates which provide sensitive detection by time-resolved fluorometry. The aim of Tropo-Fragment study is to use the described preliminary assay format in the clinical studies to evaluate: - TnT fragmentation and its time course in STEMI and NSTEMI - TnT fragmentation in renal failure, sepsis, strenuous exercise, stroke, atrial fibrillation, takotsubo, myocarditis and healthy subjects
Phase
N/ASpan
352 weeksSponsor
University of TurkuRecruiting
Corticosteroids and Myocardial Injury in CAP (COLOSSEUM TRIAL)
Background. Community-acquired pneumonia (CAP) is often complicated by elevation of cardiac troponin, a marker of myocardial injury, that can be isolated or associated to myocardial infarction (MI). A retrospective study showed that corticosteroid treatment lowers incidence of MI during the hospital-stay. No data exist so far on the effect of corticosteroids on myocardial injury in CAP patients. Study design. Double-blind randomized placebo-controlled trial. One hundred twenty-two eligible patients will be randomized to a week treatment with iv methylprednisolone (20 mg b.i.d) or placebo from hospital admission. Serum hs-cTnT will be measured at admission and every day until up 3 days from admission. ECG will be monitored every day until discharge. After dismission, all patients will be followed-up 2 years. Aims of the study. Primary objective of the study is to evaluate if methylprednisolone is able to reduce myocardial injury, as assessed by serum high-sensitivity cardiac T Troponin (hs-cTnT), in a cohort of patients hospitalized for CAP. Secondary aims are to evaluate the potential effect of methylprednisolone on cardiovascular events during hospitalization, at 30 day from hospital admission and during 2 years' follow-up. The trial will also examine whether the potential protective effects of methylprednisolone might be due to platelet activation down-regulation.
Phase
3Span
190 weeksSponsor
University of Roma La SapienzaRecruiting
Prediction of Myocardial Injury After Laparoscopic Pheochromocytoma/ParaGangLioma Resection
MI-PPGL is a single-center observational ambispective cohort study.On the basis of retrospective study, the research team plans to build a structured database to investigate the incidence of myocardial injury in laparoscopic PPGL-resection, and further analyze myocardial injury related risk factors. In particular, timing data such as vital signs(blood pressure,heart rate)will be included to construct an efficient and robust myocardial injury prediction model. At the same time, a prospective cohort study is carried out to verify the model, so as to test the prediction ability of myocardial injury and reduce the incidence of myocardial injury. The investigators expect to enroll 700 patients, including at least 550 patients retrospectively and 150 patients prospectively.In this study, the main endpoint events of the prediction model are binary outcome. Conservatively estimated according to the "10EPV" principle, that is, each predictive factor included in the model needs at least 10 positive outcome endpoint for estimation (10 events per variable). The investigators expected 5 to 8 predictors to be included in the model, and at least 80 positive events to be included. The incidence of perioperative myocardial injury is 12~20%, so the estimated sample size was at least 666 patients. Considering the absence of data or subject withdrawal from the study. so the investigators expected to include 700 patients, including at least 550 retrospectively and 150 prospectively. STATA (version 15.0; Stata Corp., TX, USA) and R 3.6.1 software (R Foundation for Statistical Computing, Vienna, Austria) will be used for statistical analysis. Binary logistic regression was used to screen risk factors and stratify risk levels. P<0.05 was considered statistically significant. For predictive modeling, clinical databases were 9:1 or 8: 2. Randomly split into training samples and verification samples. In the training samples, optimal subset method and LASSO regression will be used for feature selection.Receiver operating characteristic curve (ROC curve) was used to represent the model differentiation, and Nomogram was used to represent the predictive factors of multiple logistic regression. In the verification samples, Hosmer-Lemeshow goodness of fit test was used to test the calibration degree of the model, and P>0.05 was the acceptable level of estimated fitting of the model. Decision curve analysis (DCA curve) was used to verify the clinical applicability.
Phase
N/ASpan
121 weeksSponsor
Peking Union Medical College HospitalRecruiting
Left Ventricular Global Longitudinal Strain and Postoperative Myocardial Injury
The incidence and risk of postoperative myocardial injury in patients with coronary artery disease is high, and there is no definitive monitoring tool to predict postoperative myocardial injury. Speckle tracking imaging (STI), which quantifies strain and ventricular torsion in all segments of the heart, is more sensitive to subtle changes in myocardial contractility than conventional ultrasound. This project proposes to use 4D-STI as a means of monitoring myocardial exercise function during anaesthesia in patients with coronary artery disease, to explore the association with the occurrence of postoperative myocardial injury, and to perform a predictive study of postoperative myocardial injury. The study was designed according to a prospective follow-up cohort. The protocol was developed with reference to the STROBE guidelines for cohort studies. In this study, 2.5 ml of venous blood specimens were collected before surgery and at the end of surgery and sent to the laboratory. Intraoperative data collection was performed in the operating theatre and follow-up was obtained on the ward and during telephone follow-up.
Phase
N/ASpan
53 weeksSponsor
The Second Affiliated Hospital of Chongqing Medical UniversityRecruiting
NAD+ Augmentation in Cardiac Surgery Associated Myocardial Injury Trial
This trial is a single-center, randomized, double-blind placebo-controlled Trial of Nam versus placebo in patients undergoing on-pump cardiac surgery. After screening and enrollment, patients will be stratified according to CKD status (eGFR<45 ml/min/m2) and surgical site and randomized in a 1:1 manner to receive either Nam 3 grams or placebo on the day of surgery and post-surgical days one and two. The overall trial duration is planned for 42 months, consisting of 39 months of active recruitment and treatment period and three months of follow-up from the last patient enrolled.
Phase
2Span
198 weeksSponsor
Kaiser PermanenteRecruiting
Randomized Evaluation of Shenfu Injection to Reduce Myocardial Injury
Shenfu injection is a traditional Chinese medicine formulation containing ginseng (Panax; family: Araliaceae) and aconite (Radix aconiti lateralis preparata, Aconitum carmichaeli Debx; family: Ranunculaceae) with Ginsenosides and aconite alkaloids as the main active ingredients. Its quality is strictly controlled in compliance with the standard of the China Ministry of Public Health (official approval code: certification number Z20043117; No. 110804, Ya'an, China). Animal studies have shown that Shenfu injection has protective effects against reperfusion injury through multiple pharmacologic effects, including scavenging free radicals, inhibiting inflammatory mediators, suppressing cell apoptosis, and inhibiting calcium overload. However, few data are available regarding its efficacy in humans. We aimed to determine whether perioperative use of Shenfu injection, as compared to placebo, might reduce infarct size in patients with STEMI undergoing primary PCI.
Phase
4Span
109 weeksSponsor
Beijing Anzhen HospitalRecruiting
Ruling Out Coronary Artery Disease and Myocardial Injury by Biomarkers
This is an observational study of patients with suspected coronary artery disease referred to coronary computed tomography angiography (CCTA). The plan is to include 1000 patients prior to CCTA at two centers. Blood samples for biomarker measurement will be obtained prior to the procedures. The diagnostic results of the imaging tests will be compared to the levels of circulating troponins. Patient will be followed for a minimum of 12 months and the incidence of cardiovascular death, all-cause mortality, acute coronary syndromes, revascularization, heart failure, stroke and cardiac arrhythmias requiring rehospitalization. Symptoms of angina pectoris according to the Canadian Cardiovascular Society grading of angina pectoris and symptoms of chronic heart failure according to the New York Heart Association classification of chronic heart failure will be recorded.
Phase
N/ASpan
537 weeksSponsor
University Hospital, AkershusRecruiting
Semaglutide to Reduce Myocardial Injury in PATIents With COVID-19
6.1 Background The current COVID-19 pandemic is rapidly spreading with a global total of ~35 million cases, with close to 170,000 cases and over 9,500 deaths in Canada alone (as of 10/05/2020). Most affected patients have mild or even no symptoms, however, those requiring hospitalization have a more severe presentation including pneumonia, acute respiratory distress syndrome (ARDS), cardiovascular collapse and death. There is mounting evidence that myocardial injury, occurring in 8-28% of hospitalized patients, has a major impact on mortality. In a study from Wuhan in China, mortality was 59.6% in COVID-19 patients with an elevated troponin and only 8.9% in those with a normal troponin level. ARDS was also more common in troponin-positive patients. The pathophysiology of myocardial injury following COVID-19 infection is not well understood, but may include viral myocarditis, cardiomyocyte injury from systemic cytokine storm, reductions in myocardial blood flow from micro- and macro-vascular thromboses, and severe hypoxemia in the setting of pre-existing cardiovascular disease (CVD).1 Higher rates of adverse outcomes with COVID-19 have also been noted in patients with hypertension and diabetes. Based on these data, approaches to prevent or reduce the vascular consequences of COVID-19 may be beneficial and should be prioritized for rapid evaluation in controlled clinical trials. Currently there is a paucity of approved therapies for COVID-19 infection. Current interventions are either supportive in nature or experimental anti-viral, anti-inflammatory, or anti-coagulant in nature. Only dexamethasone has recently been shown to reduce mortality. To date, there is no proposed treatment directly addressing the mechanisms of increased cardiovascular risk in this deadly disease. The investigators have strong rationale and world-leading expertise in this area. This is a prospective, randomized, controlled, open-label, blinded-evaluation, exploratory (vanguard) study in hospitalized symptomatic COVID-19 patients age with any two of the following high-risk features: age >60 years, obesity (BMI> 30), diabetes (by history - with or without medical treatment), hypertension (on any treatment), cardiovascular disease (by history), chronic kidney disease (eGFR <60) or elevated biomarkers on admission to hospital (troponin, d-dimer). Eligible and consented patients will be randomized to one of the following two treatment regimens in a 1:1 ratio: (1) semaglutide 0.25 mg s.c. immediately after randomization at baseline, then 0.5 mg s.c. at day 7, day 14, and day 21. The end of treatment period and primary outcome assessments will occur on day 28. Final secondary clinical outcome assessment will be at 180 days. With the results of this study the investigators aim to identify an effective treatment that will reduce morbidity and mortality of patients with symptomatic COVID-19 infection, which would in turn reduce the burden on the healthcare system by decreasing the need for intensive care. Objectives: The main objective of this research is to determine if once weekly treatment with the GLP-1 agonist semaglutide for 4 doses will reduce cardiac as well as non-cardiac complications of COVID-19 infection. Study Plan: The study design is prospective randomized open-label blinded-evaluation (PROBE). Eligible patients with symptomatic COVID-19 infection and an enhanced risk profile as described above, who have been admitted to hospital due to symptoms of COVID-19 infection but do not as yet require critical care will be approached to participate in this study. Provided there are no exclusion criteria and the participants agree by means of documented written informed consent, The participants will be randomized to receive s.c. semaglutide 0.25 mg s.c. or control immediately after randomization and then 0.5 mg s.c. at Day 7, Day 14 and Day 21. Blood will be drawn at Day 7 and Day 14 for the cardiac troponin biomarker and safety parameters. ECG will be obtained at Day 7±2 and Day 14±2. Primary outcome will be assessed on Day 28. Primary outcome measure: A composite on Day 28 after randomization of (1) death from any cause, (2) mechanical ventilation (invasive or non-invasive [bilevel positive airway pressure or BIPAP]) Major secondary outcome measure: (1) an elevation to >99th percentile URL upper reference limit (URL) in those with a baseline cardiac troponin level ≤99th percentile URL; or 3x elevation from baseline in those with a baseline cardiac troponin >99th percentile URL; measured at Day 7±2 and Day 14±2 post randomization. Other major secondary outcome measure: 1. A composite on Day 28 after randomization of (1) death from any cause, (2) mechanical ventilation (invasive or non-invasive [bilevel positive airway pressure] (3) an elevation to >99th percentile URL in those with a normal baseline troponin level; or 3x elevation from baseline in those with a baseline troponin; measured at Day 7±2 and Day 14±2 post randomization. 2. ECG at Day 7±2 and Day 14±2: QRS and ST-T wave changes 3. 28-day organ support-free days 4. A composite of death or intensification of medical therapy in hospitalized symptomatic patients infected with the COVID-19 virus, that includes the need for ECLS, mechanical ventilation (invasive or non-invasive [BIPAP]) and/or vasopressor/inotropic therapy on Day 180 post randomization. Sample size estimation: The study plan is to enroll 50 patients in an initial feasibility phase and continue to a total of 400 patients in the complete vanguard study based on the assumption of a 20% primary event rate in the control group, and a 50% relative risk reduction in the event rate in the active treatment arm. The rationale for the large effect size to be tested is the need for a rapid answer for this life-threatening pandemic. A conditional power analysis will allow the investigators to adjust the study size as needed. When 70% of the randomized patients have reached the 28-day time-point, conditional power will be estimated on the primary outcome. If the conditional power is between 60% and 80%, the sample size will be adjusted to raise the power to 80%. Planned subgroup analyses: Planned subgroup analyses for the primary endpoint include: 1) Diabetes vs. no diabetes, 2) baseline troponin >99% percentile URL vs. not, 3) age < 60 y vs. age ≥ 60 y, 4) eGFR < 60 mL/min vs. eGFR ≥ 60 mL/min, , 6) male vs. female. These subgroup effects will be explored using a treatment-interaction test.
Phase
2Span
29 weeksSponsor
Vladimír DžavíkRecruiting