Table 2.
General and cohort-specific exclusion criteria for the IHD-EPITRAN study. CCS, Canadian cardiovascular society (for angina pectoris grading); GFReEPI, Glomerular filtration rate estimated with CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation; IHD, ischemic heart disease; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; NYHA, New York Heart Association (for heart failure grading); PCI, percutaneous coronary intervention; RR, Scipione Riva-Rocci (eponym for sphygmomanometric blood pressure gauge).
| General | Justification |
|---|---|
| Condition that limits life expectancy | May modify blood epitranscriptomes hampering reliable biomarker identification |
| Active inflammatory state (i.e., gout, systemic lupus erythematosus) | Cimplement, cytokines and leukocyte activation may infuence blood epitranscriptomes |
| Primary desease of blood or bone marrow | Expectable to alter epotranscriptomic regulation precluding reliable biomarker discovery |
| Major congenital heart disease of atrial fibrillation | To exclude the effects of remodelling in atrial appendges |
| Renal insufficiency (GTReEPI < 45 mL/min) | To exclude the effects of altered blood solute dynamics for reliable biomarker discovery |
| Uncontrolled hypertension (RR > 180/100 mmHg) or diabetes (HbA1c > 60 mmol/L), insulin us diabetes | Hight blood pressure and significant hyperglycemia damage endothelium and blood cells |
| Prior open-heart surgery (i.e., coronary artery bypass surgery) | To exclude very high-morbidity IHD and support the goal to identify biomarkers for early-to-moderate IHD |
| Other manifestations of atherosclerosis: a. Arteriosclerosis oblitierans/claudication b. Earlier stroke, cerebral hemorrhage or transient ischemic attach (TIA) c. Vascular or mixed type dementia d. Clinically releveant carotid artery stenosis e. Mesenteric ischemia |
To exclude effects of other manifestations of atherosclerosis in blood epitranscriptomes as extensively as possible; Except for surveying vascular claudication, prospective investigations to exclude these manifestations will not be performed; Ankle-brachial index is recorded for any asymptomatic peripheral artery disease in cohort II |
| Transthoracic echocardiography: a. Cardiomyopathy (Hypertrophic/Dilated) b. Left ventricular hypertrophy (LVH) c. Clear heart failure (i.e., LVEF < 25%) d. Indication of atrial remodeling e. Functionally significant valve defects |
To exclude remodeling effects due to intrinsic myocardial pathology, significant heart failure or valve defects; LVH is considered as an exception for the cohort III (part of pathophysiology) |
| Study cohort I, patients with myocardial infarction revascularized with urgent PCI | |
| Stent thrombosis, vasospastic coronary occlusion | This is IHD-focused study, myocardial infartions of other than atherothrombotic etiology are excluded |
| MI complications (e.g., chordal rupture, aorthic disserction, acute heart failure, cardiogenic shock) | To focus biomarker discovery to the IHD-induced infarction-specific epitranscriptomic alterations |
| Global ischemia on electrocardiogram | High rish of insufficient PCI and ischemia relievement |
| Study cohort II, patients with stable IHD undergoing coronary artery bypass surgery | |
| Duration of stable angina pectoris or exertional dyspneas < 1-month, crescendo angina | To exclude acute and subacute IHD related alterations in blood epitranscriptomes |
| Complex surgeries (e.g., valve/aneurysm repair) | To exclude other major cardiac remodeling effects |
| Study cohort III, patients with stable aortic valve stenosis undergoing valve replacement surgery | |
| Clinically mild-to-moderate stenosis with mild symptoms (NYHA/CCA 0-I) | Indicate less pronounced pathophysiology that might be reflected with blunted changes in the alterations of the blood epitranscriptomes regarding AVS |
| Documented IHD or complex operations | As a control cohort with non-IHD cardiac pathology, any indication of IHD will lead to exclusion |
| Transcatheter asortic valve implantations | To enable right atrial appendage sample collection |
| Study cohort IV, patients screened negative for IHD with coronary computed tomography | |
| Any prior cardiovascular disease or medication currently or in history | As critical non-IHD controls, the aim is to also recruit patients that represent overall “cardiovascular health” |