Dynamic Changes in SDF-1α Levels in Acute and Stabilized Heart Disease
Dynamic Changes in SDF-1α Levels in Acute and Stabilized Heart Disease
The aims of the present study are to measure dynamic changes over time in the plasma level of
 SDF-1α in patients with confirmed diagnoses of AMI, AF and CHF and in so doing:

 1. Monitor the plasma level of SDF-1α at the diagnosis, during and after the long term
 treatment of AMI, AF and CHF. The SDF-1α level of patients is expected to decrease
 during treatment of the aforementioned conditions.

 2. Correlate the plasma level of SDF-1α in relation to clinical, biochemical
 characteristics of Acute Myocardial Infarction(AMI), Atrial Fibrillation(AF) and
 Congestive Heart Failure (CHF). In so doing, the investigators expect that SDF-1α will
 correlate with the severity of heart disease.

 3. Study the dynamic of SDF-1α pertaining to its property as prognostic indicator for the
 long term follow up risk of readmission and mortality of patients diagnosed with AMI, AF
 or CHF.
The study considers changes in SDF-1α levels in response to treatment of cardiac disease
 (myocardial infarction, heart failure or atrial fibrillation). SDF-1α levels will be measured
 at the acute stages of the disease, after stabilization and at longer term as detailed below.
 Levels of SDF-1α will be correlated to the outcome of disease.

 BLOOD SAMPLING AND MEASUREMENT OF SDF-1Α A blood sample of about 5 ml will be sampled by
 peripheral venepuncture and anticoagulated with heparin. Blood samples will be spun for 15
 minutes at 1000g within 30 minutes of collection. The resulting plasma will be stored at
 -80°C until analysis. Levels of SDF-1α in the plasma will be determined using a commercially
 available ELISA kit according to the manufacturer's instructions.

 Analyses will be performed at the Clinical Research Centre, Copenhagen University Hospital
 Hvidovre.

 PATIENTS Patients are included from the in-patient department of the Department of
 Cardiology, Hvidovre University Hospital. Patients are eligible for inclusion if diagnosed
 with myocardial infarction, atrial fibrillation or heart failure, provided they do not suffer
 from malignant disease, diabetes mellitus types I or II and have a life expectancy of at
 least one year.

 Exclusion criteria are based upon the fact that serum SDF-1α levels are elevated in malignant
 diseases as SDF-1α contributes to neoangiogenesis of the tumour mass, and SDF-1α levels have
 recently been demonstrated to be elevated in diabetes.

 The investigators will include 20 patients with each of the cardiac conditions mentioned as
 well as a control group of 20 subjects without cardiac disease (including hypertension),
 diabetes, hypercholesterolemia, and malignant disease.

 PATIENTS WITH MYOCARDIAL INFARCTION Patients presenting with non-ST elevation myocardial
 infarction (NSTEMI) are included. The diagnostic criteria are symptoms of cardiac ischaemia
 (angina or angina-equivalent symptoms) and elevated troponin T (above 14 ng/mL) and/ or ECG
 changes of ischemia (horizontal or downsloping ST depression ≥ 0.5 mm at the J-point in ≥ 2
 contiguous leads).

 Patients are excluded if they are diagnosed with a "type 2 myocardial infarction", i.e.
 myocardial ischaemia due to mismatch between myocardial oxygen demand and supply due to
 conditions such as severe anaemia, arrhythmia or hypotension. Patients are also excluded if
 they are not referred for coronary angiography, if they have atrial fibrillation or if they
 have cardiac failure with LVEF ≤ 40%.

 The SDF-1α levels of patients will be measured on the first day of hospitalization, after
 coronary angiography, before discharge (approximately day 3-5), and three months after
 inclusion.

 PATIENTS WITH ATRIAL FIBRILLATION Patients presenting with ECG-documented atrial fibrillation
 are included if unstable, i.e. if heart rate exceeds 100 and in-patient treatment is
 indicated. Patients are excluded if they suffer from unstable ischaemic heart disease
 (unstable angina or myocardial infarction), heart failure with LVEF ≤ 40% or if the
 arrhythmia is secondary to another condition such as an infection.

 SDF-1α levels will be measured on the first day of the hospitalization, at the time of
 discharge (after medical or electrical cardioversion or after stabilization of the heart
 rate) and three months after inclusion.

 PATIENTS WITH CONGESTIVE HEART FAILURE Patients are included if presenting with decompensated
 heart failure. They must have symptoms of heart failure (dyspnoea and/ or oedema) severe
 enough to warrant in-patient treatment. The diagnosis must be confirmed by echocardiography
 showing LVEF ≤ 40%. Patients are excluded if suffering from unstable ischaemic heart disease
 (unstable angina or myocardial infarction) or atrial fibrillation.

 The SDF-1α levels of will be measured on the first day of the hospitalization, after medical
 stabilization at the time of discharge, and three months after inclusion.

 PATIENT INCLUSION AND DATA COLLECTION Patient inclusion will take place during three
 consecutive months. Patients are included within the first day of hospital admittance. Each
 day, members of the project group will screen all patients admitted within the last day and
 personally contact those eligible for inclusion. Patients will be informed verbally and given
 the written participant information. Patients will be given time for consideration and if
 they accept participation, they will be asked to sign the consent form. Due to the project
 design, according to which the first blood samples are to be taken within the first day of
 hospitalization, patients are asked to consent to project participation on the day of initial
 contact with the research group member. Conversations will be held in a private setting in
 the department, and patients are invited to bring relations, if they so prefer.

 As regards the control group, these will be included from patients initially referred for
 outpatient evaluation at the Department of Cardiology, but in whom no cardiac disease is
 found. Members of the project group will screen the patients in the Outpatients Department
 and personally contact those eligible for inclusion in the control group. The control group
 will be selected so as to be age-matched with the patients. Information about the project
 will be provided as for the patients.

 Based upon information in the patients' medical files, it will be registered whether patients
 suffer from hypertension, peripheral vascular disease, stroke, transient cerebral ischaemia,
 chronic obstructive pulmonary disease or renal insufficiency.

 Medication at time of admittance to hospital and medication given during the hospitalization
 will be registered. Clinical status (dyspnoea, palpitations, oedema, blood pressure and heart
 rate) at the time of inclusion and at the time discharge from hospital will be noted. This
 information will be sought from patient files and the Kiso system used for recording vital
 parameters in patients.

 The recorded information (pre-existing conditions, medication and clinical status at the two
 time-points) will be available for the project group. This information will be used for
 background demographics, in the evaluation of how levels of SDF-1α correlate to clinical
 status, and to allow for correction of factors, such as medication, on the levels of SDF-1α.

 FOLLOW-UP All patients are expected to be seen in the Outpatients' Department 2-3 months
 after discharge from hospital. This appointment is part of the standard treatment and control
 plan for patients with AF, CHF and NSTEMI, respectively and not arranged as a part of the
 project. Certain information will be registered from the patient files at the time of
 follow-up: Clinical status (NYHA class, oedema, pulmonary congestion, and angina), heart
 rhythm, medication, and any intercurrent hospital admissions.

 One year after inclusion, patient files will be reviewed and the following information
 registered: Whether the patient is alive and any cardiovascular rehospitalisation. In the
 case of hospitalization, the date of admission, duration and diagnosis will be registered.
 Statistical considerations and data analysis Baseline data of SDF-1α levels and patient
 demographics (including comorbidities and use of medication) will be evaluated using
 descriptive statistics. Normally distributed data will be presented as mean and standard
 deviation, whereas skewed data will be presented as median and range. If necessary, skewed
 data will be transformed.

 The influence of patient characteristics (such as age, sex and comorbidities) on SDF-1α
 levels will be evaluated using multiple regression analysis with SDF-1α level as dependent
 variable and patient characteristics as explanatory variables. SDF-1α levels will be compared
 between the patient groups using analysis of variance (ANOVA).

 Within each group of patients, the changes in SDF-1α levels over time (three time points)
 will be analysed using ANOVA.

 The investigators have previously measured SDF-1α levels in patients with various types of AF
 (permanent versus paroxysmal). Based upon these results (SDF-1α levels and standard
 deviations in the different groups), the investigators have estimated that the proposed
 sample size of 20 patients in each disease group will confer the study sufficient statistical
 power.

 The statistical analyses will be performed in collaboration with statistician Steen Ladelund
 (Clinical Research Centre, Hvidovre University Hospital).

 THE RESEARCH GROUP

 The study will be conducted in close collaboration between the Department of Cardiology and
 the Clinical Research Centre at Hvidovre University Hospital. The research group will consist
 of the following persons:

 Dr L. Vimal Hurry, MD, is project responsible. He is a junior doctor at the Department of
 Cardiology and doing research work beside his clinical employment.

 Dr Ulrik Dixen, MD, PhD, is a consultant at the Department of Cardiology. Dr Ulrik Dixen has
 conducted AF research for several years and is experienced in planning and conducting
 clinical studies, as well as in supervising junior researchers.

 Dr Nadia Landex, MD, PhD, is training in cardiology, currently at Roskilde University
 Hospital. She did her PhD in histochemistry and has used her experience in basic research to
 initiate research in biomarkers in AF at Hvidovre University Hospital, including research
 topic, project planning and the initial laboratory work.

 Medical student Maha Alsawaf has written her bachelor thesis in the cardiology research group
 and has basic research experience. Maha Alsawaf will assist with inclusion of the patients.

 Medical student Ema Rastoder is experienced in clinical research and skilled in patient
 communication. Ema Rastoder will assist with inclusion of patients.

 Project members from the Clincial Research Centre are:

 Head of Department Ove Andersen, MD, PhD, who has extensive experience in biomarker research
 at all stages from project development to implementation of research results.

 Anne Langkilde, MSc, PhD, is likewise experienced in biomarker research, particularly in the
 prognostic importance of biomarkers in disease. Anne Langkilde has been a close collaborator
 in the initial projects regarding measurement of biomarkers in AF.

 Together, the research team has experience of biomarker research as well as access to
 research laboratory with highly skilled laboratory technicians.
Inclusion Criteria:

 Patients are included from the in-patient department of the Department of Cardiology,
 Hvidovre University Hospital. Patients are eligible for inclusion if diagnosed with one of
 the following diseases:

 -  myocardial infarction

 -  atrial fibrillation

 -  heart failure

 Exclusion Criteria: Patients must not suffer from one of the follwing conditions:

 -  malignant disease

 -  diabetes mellitus types I or II

 -  have a life expectancy of at least one year.