Research Ideas and Outcomes : Small Grant Proposal
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Corresponding author: Robert Jeenchen Chen (rjcc@ntu.edu.tw)
Received: 14 Apr 2016 | Published: 21 Apr 2016
© 2016 Robert Jeenchen Chen.
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation: Chen R (2016) Clinical roles of soluble ST2 for the outcomes of cardiac valve operations. Research Ideas and Outcomes 2: e8849. doi: 10.3897/rio.2.e8849
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Soluble ST2 is a novel cardiac biomarker that reflects cardiac injury and the response to treatment. Previous studies showed that ST2 has less confounding and more specific than NT-proBNP. ACCF/AHA has proposed 2013 Guidelines for the Management of Heart Failure that includes ST2 in the recommendations. In the research proposal, we will assess the clinical role of serum ST2 level in cardiac non-coronary valve surgical patients.
We will recruit 70 patients who undergo cardiac non-coronary valve operations. Serum levels of ST2 and NT-proBNP and troponin-T will be measured at preoperative baseline, postoperative 24 hours, and postoperative 5 to 10 days in the routine blood sampling. The endpoints include hospital mortality, all-cause mortality, unexpected ICU return, MACE, time to extubation, and total length of stay. We will also collect various preoperative, operative, and postoperative variables, such as EuroScore-II. Their relationships will be analyzed.
We expect to demonstrate the superior role of ST2 to NT-proBNP and other variables in risk stratification and outcome prediction and assessment in our cohort.
ST2, NT-proBNP, heart failure, troponin-T, biomarker
Cardiovascular Surgery, Cardiology, and Clinical Research, Taipei Tzuchi Hospital, New Taipei City, Taiwan;
Surgery, Tzuchi University College of Medicine, Hualian, Taiwan.
Health One Network Co., Ltd. New Taipei City Taiwan, (telephone: 886-2-22993688--x13; cellphone: 886-930142606); Critical Diagnostics.
Soluble ST2 (sST2) is a novel biomarker (
Conventional biomarkers for assessing heart failure are BNP / NT-proBNP. But they have various confounders like age, BMI, and renal disease (
Soluble ST2 can reflect the process of cardiac remodeling and myocardial post-injury fibrosis in heart failure (
As above, there are also various prior research studies that demonstrated the association of sST2 with acute and chronic heart failure (
Currently we can implement ST2 in the following scenarios:
We will collect ST2, and other cardiac biomarkers at different time points of cardiac valve surgical patients and investigate their relationships with different outcome measures and also may compare the performance of these biomarkers on predicting various outcomes (
Prospective observational longitudinal clinical study
(1) Serum biomarker levels of ST2, NTproBNP, and troponin-T from blood sample drawing at the same time of clinical routine blood drawing: preop, postop 24-hour, postop 5-10 days; three time points.
(2) ST2 will be done by special kits sponsored by the vendor. NTproBNP and troponin-T will be measure in hospital central lab.
(3) Preop, op, postop, and outcome variables will be collected as the following details.
Since the study does not alter routine clinical practice, little resistance from patients and family is anticipated. Thorough explanation of the informed consent will be helpful for recruiting participating patients.
Inadequate sample size or insufficient power to detect difference may be encountered. Since we have many dependent variables or outcome variables, we may select the some to present.
The research protocol will be evaluated by the institutional review board.
All participating patients will have thorough understanding of the study regarding the aims and potential risks as explained by the research staff members. They also sign the informed consensus personally or by a qualified proxy.
We have a conflict of interest to declare: the laboratory kits are partially sponsored by the local distributor, Health One Network Co., Ltd. New Taipei City Taiwan, (telephone: 886-2-22993688--x13; cellphone: 886-930142606).
We will prospectively recruiting the valvular heart patients who are admitted for elective corrective operations in Far Eastern Memorial Hospital.
The recruited patients must meet all of the inclusion criteria: adult with age over 20 years, pure valvular operations, elective setting, single or multiple valves, conventional or minimally-invasive approach, either without or with previous cardiac or major aorta operations.
The exclusion criteria are: pregnant, combined concurrent major cardiac procedures such as coronary or aorta operations, non-elective settings such as urgent or emergency, refusal of participation by the patient or family due to any reason.
If the inclusion or exclusion of a case is in doubt, the decision is made by the consensus or majority of principal investigators (PI and co-PI).
Each patient will have three serum samples collected before operation, 24 hours after operation, and around one week (from five to ten days) after operation. The blood drawing will be made concurrently with other laboratory tests as needed clinically. There is no extra blood drawing purely just for the study. For cardiac biomarkers, we will measure sST2, NT-proBNP, and troponin-T.
Our routine cardiac surgery database will also collect preop, op, and postop variables for all the patients, such as EuroScore-II. The outcome-related variables will include: time to extubation (TOE), intensive care unit (ICU) time, total length of stay (LOS), and hospital mortality.
The variables for each patients are listed but not limited as below:
Biomarkers (preop, postop 24 hour, postop 5-10 days): sST2, NT-proBNP, troponin-T (
Biomarker sampling schedule
Biomarkers | Preop | Postop 24 hour | Postop 5~10 days |
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sST2 | |||
NT-proBNP | |||
Troponin-T |
Preop: Birthday, date of operation, op diagnosis, last preop LVEF, last preop RVSP (SPAP), creatinine, dialysis or not, diabetes, hypertension, COPD;
Op: operation procedure, op time, ischemia time, pump time
Postop: time to extubation, ICU time, total LOS, unexpected ICU return, hospital mortality (also date), major adverse cardiac event (MACE) (also date), first postop LVEF, and first postop RVSP (SPAP).
To measure sST2 serum levels, we will use the kits and protocols as advised by the vendor (
We plan to recruit 70 patients and measure three serum samples per case. There will be 210 laboratory tests. Due to budget limitation, we set the sample size to be 7, since we can only afford 210 laboratory tests. We set the alpha-level to be 0.05.
The outcome variables (dependent variables) will be the following and we will select more appropriate variables to present according to the interim analysis results. The primary endpoints include: hospital mortality, all-cause mortality, unexpected ICU return, and MACE. The secondary endpoints include: time to extubation, ICU time, and total LOS.
We will transform several variables to facilitate analysis. Renal function will be graded by GFR (glomerular filtration rate) as estimated by creatine-related formulae. Comorbidity such as diabetes or hypertension will be determined by clinical judgment. For biomarker analysis (sST2, NT-proBNP, troponin-T), in addition to absolute values, we will use relate values for better demonstrate the change from baseline and the trends. Relative serum level (RSL) is a dimensionless value defined as the ratio of serum level to the baseline (level divided by baseline).
For comparing scale or ordinal (quasi-scale) variables, we will use Mann-Whitney U test for two groups and Kruskall-Wallis test for three or more groups. For comparing nominal variables, we will use Fisher’s exact test. For comparing time-event variables, we will use log-rank test. For modeling predictions, we will choose appropriate statistical regression methods based upon dependent variables. For scale dependent variable, we will use linear or log-linear regression models depending the likelihood of normality violation. For binary dependent variables, we will use logistic regression model. For time-event variables, we will use Cox regression model. For evaluating biomarker performance on accuracy of classification, we will receiver operating characteristic (ROC) analysis. The truth variables will be one of the outcome variables and the classifier variables will be ordinal-ranged biomarker absolute level or RSL. The tentative optimal cutoff values for each biomarker may be proposed depending on the outcome variables or clinical scenarios.
The backbone for the results presentation will be: cohort background statistics, time trends of biomarkers, biomarker and predictors for the outcomes, and comparisons of biomarkers.
The statistical software we used will be Stata/MP 13.1 for Mac (64-bit Intel).
(1) ST2 and other cardiac biomarker lab assay;
(2) Statistical analysis of the study;
(3) Interpretation and implement of the study results.
(
Research working timetable
Time (month) |
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5-6 |
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9-10 |
11-12 |
Data collection |
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Statistical analysis |
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Result interpretation |
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Report writing |
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We would like to show our gratitude to the ST2 vendor, Critical Diagnostics, who provides scientific advice and offers the agreed quantity of free lab kits via our local distributor.
Pending; maybe yearly university hospital research grant.
University and hospital cardiovascular research project.
Cardiovascular research call.
Taipei Tzuchi Hospital, Tzuchi University College of Medicine, Buddhist Tzuchi Medical Foundation.
Consenting, safety, and data policy all comply to ICH (International Conference on Harmonisation) Good Clinical Practice (GCP). University and hospital institutional review board (IRB) will evaluate the approval.
The research is partially sponsored by the local distributor who donates some of the laboratory kits, Health One Network Co., Ltd. New Taipei City Taiwan, (telephone: 886-2-22993688--x13; cellphone: 886-930142606).