Disturbances in myocardial diastolic and vascular function with the emphasis on type 2 diabetes : diagnostic and therapeutic opportunities

Background and aims: Cardiovascular involvement is common in diabetes and diastolic myocardial and endothelial dysfunction are early signs. The prognosis is serious and tools for early detection and a search for improved management strategies are important. This thesis explores tools for the early detection of myocardial involvement and examines whether intensive glucose control could improve diastolic and endothelial dysfunction in patients with type 2 diabetes mellitus.

Study I: In comparison with mitral pulse wave Doppler, Tissue Doppler Imaging (TDI), a relatively pre-load independent technique, may improve the early identification of patients with diastolic dysfunction. Fifteen controls without heart failure, 30 patients with heart failure, were studied, 15 patients with diastolic left ventricular dysfunction and 15 with systolic left ventricular dysfunction. All the patients with diastolic heart failure were identified by mitral pulse wave Doppler or TDI, but only 11 were identified by atrio-ventricular plane displacement. The number of false positive patients were eight, ten and nine, respectively (p<0.01, p<0.05 and NS) for each of the three methods.

Study II: Eighty-seven patients with type 2 diabetes classified as having no (n=60), mild (n=13) or moderate (n=14) left ventricular diastolic dysfunction by Doppler echocardiography and TDI were investigated with Velocity Vector Imaging (VVI) which evaluates myocardial deformation (strain). Left atrial volume was larger in patients with moderate diastolic dysfunction compared with mild or no diastolic dysfunction (p=0.01). Left atrial roof strain distinguished no diastolic dysfunction from mild and moderate diastolic dysfunction (p=0.0073). Systolic left atrial strain correlated to total emptying fraction (r=0.70, p<0.0001) and inversely to left atrial volume (r=-0.35, p=0.0009).

Studies III-IV: Thirty-nine patients with type 2 diabetes and signs of diastolic dysfunction but no other cardiovascular disease manifestations were randomly assigned to glucose normalisation by insulin (I-group; n=21) or oral glucose-lowering agents (O-group; n=18). Myocardial diastolic dysfunction and coronary flow reserve were studied with Doppler echocardiography, including TDI and myocardial contrast-enhanced echocardiography. Fasting glucose and HbA1c were normalised in both groups, but this did not significantly influence myocardial diastolic dysfunction in either group (p=0.65). There was no difference in coronary flow reserve before and after improved glycaemic control. Twenty-two of the patients (I-group n=10; O-group n=12) were also investigated in terms of endothelial function and skin microcirculation by brachial artery flowmediated dilatation (FMD) and laser Doppler fluxmetry respectively. Glycaemic normalisation did not improve microcirculation. A reduction in FMD from 6.0 ± 2.2 to 4.7 ± 3.0% was observed in the I-group (p=0.037), but there was no change in the O-group (4.3±2.3 to 4.7±3.3%; p=0.76). The between-group difference was not significant (p=0.12).

Conclusions: TDI is useful for diagnosing diastolic myocardial dysfunction, with accuracy similar to that of conventional echocardiography including mitral pulse wave Doppler flow. Left atrial deformation, measured as regional and overall systolic strain, is impaired in patients with type 2 diabetes mellitus and mild to moderate left ventricular diastolic dysfunction and offers new information on regional LA function and LA volumes. Further, it may add to traditional Doppler echocardiography measurements for diagnosis of diastolic dysfunction. The hypothesis that improved glycaemic control would reverse early signs of myocardial diastolic and endothelial dysfunction in patients with type 2 diabetes was not proven. Whether it is possible to influence more pronounced dysfunction, particularly in patients with less well-controlled and long-standing diabetes, remains to be further explored in controlled clinical trials.

List of scientific papers

I. Jarnert C, Mejhert M, Ring M, Persson H, Edner M (2000). "Doppler tissue imaging in congestive heart failure patients due to diastolic or systolic dysfunction: a comparison with Doppler echocardiography and the atrio-ventricular plane displacement technique." Eur J Heart Fail 2(2): 151-60
https://pubmed.ncbi.nlm.nih.gov/10856728

II. Jarnert C, Melcher A, Caidahl K, Persson H, Rydén L, Eriksson MJ (2008). "Left atrial velocity vector imaging for the detection and quantification of left ventricular diastolic function in type 2 diabetes." Eur J Heart Fail 10(11): 1080-7. Epub 2008 Oct 5
https://pubmed.ncbi.nlm.nih.gov/18838296

III. Jarnert C, Landstedt-Hallin L, Malmberg K, Melcher A, Ohrvik J, Persson H, Rydén L (2009). "A randomized trial of the impact of strict glycaemic control on myocardial diastolic function and perfusion reserve: a report from the DADD (Diabetes mellitus And Diastolic Dysfunction) study." Eur J Heart Fail 11(1): 39-47
https://pubmed.ncbi.nlm.nih.gov/19147455

IV. Jarnert C, Kalani M, Rydén L, Böhm F (2009). "The impact of strict glycaemic control on endothelial function and skin microcirculation in patients with type 2 diabetes." (Manuscript)