Clinical trial NCT02956577: Cardiac Function and Microcirculation: Type 2 DIABetes and ECHOcardiographic Changes Over Time
Official title: Systolic and Diastolic Left Ventricular Function in Patients With Type 2 DIABetes Mellitus: Changes Over Time and Comparison With Cardiac Microcirculation. An ECHOcardiographic Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Left Ventricular Dysfunction
Keywords: Global Longitudinal Strain (GLS)
Coronary Flow Velocity Reserve (CFVR)
Cardiac dysfunction
Microcirculation
Coronary Computed Tomography Angiography (CCTA)
Type 1 Diabetes
Type 2 Diabetes
Lead sponsor: Svendborg Hospital
Sponsor class: OTHER
First posted: 2016-11-06
Enrollment: 300
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with diabetes type 1+2 and non-diabetic subjects from the DANCAVAS trial (NCT00662480)

Brief summary: The purpose of this study was to investigate the influence of micro- and macrovascular changes on the cardiac function in relation to left ventricular function and coronary arteries during one year in patients with type 2 diabetes.

Detailed description: The most frequent heart disease in patients with Type 2 Diabetes Mellitus (T2DM) is the premature development of coronary atherosclerosis, which often leads to overt ischemic heart disease (IHD). T2DM can lead to both cardiac dysfunction due to IHD or to diabetic cardiomyopathy. Diabetic cardiomyopathy is defined as an impairment of left ventricular (LV) function without overt obstructive coronary vessel disease. Diabetic cardiomyopathy has been associated with microvascular dysfunction, which leads to the inability of the heart to circulate blood effectively. The microvascular atherosclerotic changes are well known in patients with diabetes, such as impaired vision, kidney function and sensibility. The macrovascular atherosclerotic changes such as plaques in the coronary arteries are strongly associated with reduced left ventricular function.

However, the relationship between micro- and macrovascular atherosclerotic changes and the impact on cardiac function is less certain.

Estimation of cardiac function includes: Left Atrial (LA) Strain, LA Strain Rate (SR), LA Emptying Function (LAEF), LV Ejection Fraction (EF), Fractional Shortening (FS), Global Longitudinal Strain (GLS), Circumferential Strain (CS) and Radial Strain (RS), Strain Rate (SR), Peak Systolic Strain, Post Systolic Strain, Early mitral filling velocity (E), late mitral filling velocity (A), E/A ratio, Deceleration Time (DCT) of early mitral filling velocity, medial and lateral mitral velocities using tissue doppler (e' , a' and s'), E/e' ratio, Isovolumetric Relaxation Time (IVRT), Isovolumetric Closing Time (IVCT), Ejection Time (ET), Myocardial Performance Index (MPI) and Myocardial Work Index (MWI).

In this study, participants will be consisting of non-diabetic subjects and patients with diabetes type 1 + 2. All of the participants have no history of myocardial infarction, heart failure and current symptoms of cardiac disease.

The study population will undergo following examinations:

1. 12-lead electrocardiogram (ECG)
2. Urine- and blood samples.
3. Measurements of anthropometric data and vital parameters
4. Recording of medical history
5. 2D transthoracic echocardiography
6. Coronary flow velocity reserve (CFVR) with adenosine infusion.
7. Coronary computed tomography angiography (CCTA).
8. Free fractional reserve computed tomography (FFR-CT)

The examinations will be repeated at follow-up (however non-diabetic subjects will only have 1 CCTA performed at baseline).

The non-invasive FFR-CT will only be performed once in a subgroup of diabetic patients and non-diabetic subjects from November 2016 until May 2017.

Eligibility criteria: Inclusion criteria:

* Ability to give informed consent
* Estimated glomerular filtration rate (eGFR) \> 45 ml/min
* NYHA I + II

Exclusion criteria:

* 2° or 3° AV-block at baseline
* Long QT-syndrome at baseline
* Sinus node dysfunction with long sinus arrest at baseline
* Angina pectoris at baseline
* Ejection fraction (EF) \< 40% at baseline
* Atrial fibrillation at baseline
* Usage of dipyridamol at baseline
* Aortic stenosis and left ventricle hypertrophia at baseline
* Aortic insufficiency and left ventricle dilatation at baseline
* Medication for asthma within the last 4 years prior to baseline
* Medication for chronic obstructive pulmonary disease (COPD) at baseline
* Allergy to contrast agent at baseline
* Significant stenosis in left main (LM) / left anterior descending (LAD) artery at baseline
* Not feasible to measure or perform coronary flow velocity reserve (CFVR)
* Poor quality of echocardiographic images
* History of pacemaker
* History of myocardial infarction (MI)
* History of heart failure (HF)
* History of coronary artery bypass grafting (CABG)
* History of aortic valve replacement
* History of atrial fibrillation

Primary outcomes:
measure: Changes in Global Longitudinal Strain (GLS) stratified by Coronary Artery Calcium Score (CAC) in patients with diabetes during one year of follow-up
timeFrame: baseline, 12 months
Secondary outcomes:
measure: Changes in GLS stratified by Coronary Flow Velocity Reserve (CFVR) in patients with diabetes during one year of follow-up
timeFrame: baseline, 12 months
measure: Correlation between biomarkers and GLS stratified by CFVR
timeFrame: 12 months
measure: Correlation between biomarkers and GLS stratified by CAC
timeFrame: 12 months
measure: Changes in LV function stratified by CAC
timeFrame: baseline, 12 months
measure: Changes in LV function stratified by CFVR
timeFrame: baseline, 12 months
measure: Changes in LV function stratified by micro- and macrovascular diabetic status
timeFrame: baseline, 12 months
measure: Correlation between CFVR and Free Fractional Reserve -Computed Tomography (FFR-CT)
timeFrame: baseline
measure: Correlation between GLS and FFR-CT
timeFrame: baseline
measure: Changes in GLS in patients with long-term diabetes and no macrovascular disease
timeFrame: baseline
Other outcomes:
measure: Relationship between strain values and framerate
timeFrame: baseline, 12 months
measure: Relationship between strain values and omitted myocardial segments
timeFrame: baseline, 12 months
measure: Correlation between dysglycaemia and Left Ventricle Mass (LVM)
timeFrame: Baseline
measure: Left Ventricle (LV) and Left Atrial (LA) function stratified by New York Heart Association (NYHA) functional class
timeFrame: baseline
measure: Changes in cardiac systolic and diastolic function stratified by CAC during five years of follow-up in patients with diabetes
timeFrame: baseline, 60months
measure: Changes in cardiac systolic and diastolic function stratified by CFVR during five years of follow-up in patients with diabetes
timeFrame: baseline, 60months
measure: Changes in cardiac systolic and diastolic function stratified by plaque morphology during five years of follow-up in patients with diabetes
timeFrame: baseline, 60months
measure: LA function stratified by CFVR
timeFrame: baseline
measure: LA function stratified by micro- and macrovascular status
timeFrame: baseline
Locations:
city: Svendborg
country: Denmark
facility: Cardiovascular Research Unit, OUH Svendborg Hospital
Study officials:
affiliation: Odense University Hospital (OUH) Svendborg Hospital
name: Kenneth Egstrup, DMSci
role: STUDY_DIRECTOR
References: