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

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

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).

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).