Myocardial Regional Function by Dobutamine Stress Echocardiography in the Metabolic Syndrome and Type 2 Diabetes

Sponsor

University of Avignon (Other)

Overall Status

Completed

CT.gov ID

NCT02505451

Collaborator

(none)

125

Enrollment

Location

Arms

42.1

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Summary.

Theoretical Rationale:

The left ventricular myocardial performance results from a complex interplay between linear deformations (longitudinal, circumferential and radial) and twist/ untwist mechanics. These components of myocardial mechanics can be assessed, at rest and during stress conditions, by high resolution echocardiography using the "2D-strain" technology and constitute good indexes of tissue intrinsic contractility / relaxation properties. Type 2 diabetes (T2DM) and metabolic syndrome (MS) are associated with an increased risk for cardiac diseases. While several clinical studies have reported, particularly in T2DM, a diastolic dysfunction (concept of "diabetic cardiomyopathy"), the existence of impaired regional myocardial function, with altered intrinsic contractility properties, remains largely unanswered, especially in the SM. Stress echocardiography is very interesting to reveal myocardial dysfunction, discrete or absent at rest. To the best of our knowledge, no scientific study is, however, today available on the kinetics of linear strains and twist/untwist dynamics in response to stress in T2DM as well as SM. The epicardial adipose tissue is the source of production of important pro-inflammatory cytokines that have the potential, through an exacerbation of oxidative stress, to impair coronary endothelial function, increase fibrosis, but also directly affect cardiomyocyte calcium homeostasis. An increase in epicardial adipose tissue is consensually reported in T2DM and SM and is clearly associated with coronary atherosclerosis. A link between cardiac adiposity and overall cardiac function, particularly diastolic, is now suggested but to our knowledge no study has challenged its association with myocardial dysfunction in T2DM as SM patients.

Objectives and Methodology: - To investigate regional myocardial linear deformations and torsion, at rest and in response to a dobutamine stress, in asymptomatic T2DM and SM patients without clinical complications, - to study the links between expected regional myocardial abnormalities and inflammation, hyperglycemia and cardiac adiposity. A control group of healthy individuals matched for sex and age will also be included.

All the subjects will benefit from a clinical, anthropometric and biological evaluation. In addition, conventional echocardiography (remodelling and global diastolic and systolic functions) complemented by a functional analysis by tissue Doppler imaging will be performed. Furthermore, 2D cine loops will be recorded in the apical 4, 3 and 2- chamber views for the objective assessment of myocardial longitudinal deformations as well as in the parasternal short axis (base and apex) for the evaluation of the circumferential deformations and basal and apical rotations and left ventricular torsion, at rest and under low dose of dobutamine (110 and 120 bpm).

Condition or Disease	Intervention/Treatment	Phase
Diabetes-related Complications	Drug: dobutamine	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

125 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Comprehensive Analysis of Regional Myocardial Function in Response to Dobutamine Stress in Metabolic Syndrome and Type 2 Diabetic Patients. Effect of Cardiac Adiposity, Inflammation and Hyperglycaemia

Actual Study Start Date :

Jul 1, 2015

Actual Primary Completion Date :

Jan 1, 2018

Actual Study Completion Date :

Jan 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Type 2 diabetic patients Regional myocardial function will be assessed during dobutamine stress echocardiography in asymptomatic patients with type II diabetes (according to the American Diabetes Association, 2012) free of coronary diseases.	Drug: dobutamine In each participant, dobutamine will be administered via intravenous infusion in doses of 10, 20, 30 and 40 lg/kg/min during 3-min stages and 2D strain echocardiography will be performed at each stage.
Experimental: Metabolic syndrom Regional myocardial function will be assessed during dobutamine stress echocardiography in asymptomatic patients with the Metabolic syndrome (according to Alberti et al 2009) free of diabetes and coronary diseases.	Drug: dobutamine In each participant, dobutamine will be administered via intravenous infusion in doses of 10, 20, 30 and 40 lg/kg/min during 3-min stages and 2D strain echocardiography will be performed at each stage.
Experimental: controls Regional myocardial function will be assessed during dobutamine stress echocardiography in healthy subjects.	Drug: dobutamine In each participant, dobutamine will be administered via intravenous infusion in doses of 10, 20, 30 and 40 lg/kg/min during 3-min stages and 2D strain echocardiography will be performed at each stage.

Arm

Intervention/Treatment

Experimental: Type 2 diabetic patients

Regional myocardial function will be assessed during dobutamine stress echocardiography in asymptomatic patients with type II diabetes (according to the American Diabetes Association, 2012) free of coronary diseases.

Drug: dobutamine

In each participant, dobutamine will be administered via intravenous infusion in doses of 10, 20, 30 and 40 lg/kg/min during 3-min stages and 2D strain echocardiography will be performed at each stage.

Experimental: Metabolic syndrom

Regional myocardial function will be assessed during dobutamine stress echocardiography in asymptomatic patients with the Metabolic syndrome (according to Alberti et al 2009) free of diabetes and coronary diseases.

Drug: dobutamine

Experimental: controls

Regional myocardial function will be assessed during dobutamine stress echocardiography in healthy subjects.

Drug: dobutamine

Outcome Measures

Primary Outcome Measures

Regional longitudinal strain [day 1]
Regional myocardial function will be evaluated for each participant at rest and during low dose dobutamine within a single session.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Male and female 40-65 years old, asymptomatic and free of coronary disease

Exclusion Criteria:

for all the subjects :
body mass index > 35 kg / m2, defining severe obesity,
Under insulin therapy,
Poorly controlled hypertension (> 140/95)
Peripheral vascular disease (> stage II of Leriche)
Heart disease or known coronary artery disease,
Known and poorly compensated thyroid dysfunction,
Nocturnal apnea syndrome,
Inability to give written informed consent,
Chronic diseases,
moderate to severe left ventricular hypertrophy :> 109 g / m2 in women and> 132 g / m2 in men and parietal thickness > 13mm.

for the diabetic patients only :

poor glycemic control (HbA1c > 9%)
severe autonomic or peripheral neuropathy,
Severe diabetic retinopathy,
Advanced Diabetic nephropathy (defined by documented proteinuria and / or renal failure).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Henri Duffaut	Avignon	Paca	France	84000

Sponsors and Collaborators

University of Avignon

Investigators

Study Director: Philippe Obert, PhD, Laboratory of Cardiovascular Pharm-Ecology, Faculty of Health and Sciences, university of Avignon, 33 rue louis pasteur 84000 Avignon, France.