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.

AIMS: Myocardial diastolic dysfunction (MDD) and impaired coronary flow reserve (CFR) are early signs of myocardial involvement in patients with diabetes. The important question of whether this may be reversed by glucose normalization has not been tested in a controlled clinical trial. We hypothesized that strict glycaemic control, particularly if insulin based, will improve MDD and CFR. METHODS AND RESULTS: Thirty-nine type 2 diabetes patients (mean age 61.0 +/- 7 years) with signs of diastolic dysfunction were randomly assigned to strict metabolic control by insulin (I-group; n = 21) or oral glucose lowering agents (O-group; n = 18). MDD and CFR were studied with Doppler-echocardiography including Tissue Doppler Imaging and myocardial contrast enhanced echocardiography. Fasting glucose (I-group = -2.2 +/- 2.1; O-group -1.5 +/- 0.8 mmol/L) and HbA(1c) were normalized (-0.6 +/- 0.4 and -0.7 +/- 0.4%, respectively) in both groups, but this did not significantly improve MDD in either of the groups (P = 0.65). There was no difference in CFR before and after improved glycaemic control. CONCLUSION: The hypothesis that strict glycaemic control would reverse early signs of MDD and improve CFR in patients with type 2 diabetes could not be confirmed, despite achieved normalization. Whether it is possible to influence a more pronounced diastolic dysfunction, particularly in less well-controlled diabetic patients, remains to be established.

Left atrial velocity vector imaging for the detection and quantification of left ventricular diastolic function in type 2 diabetes.

UNLABELLED: Left ventricular (LV) diastolic dysfunction (DD) is diagnosed by Doppler echocardiography (DE) and Tissue Doppler imaging (TDI). Velocity vector imaging (VVI) evaluates myocardial deformation (strain). We studied left atrial (LA) deformation and volumes by VVI in relation to established Doppler-derived indices of LV diastolic function in diabetic patients. MATERIAL: Using DE and TDI , 87 patients (males 49%; age 60+/-7 years) with type 2 diabetes mellitus were classified as having no (n=60), mild (n=13) or moderate (n=14) DD. RESULTS: LA volume was larger in moderate (72.3+/-22.4 ml) than in mild DD (58.8+/-16.1 ml; p=0.01) and no DD (57.9+/-16.0 ml; p=0.01). LA roof strain distinguished no DD from mild and moderate DD (p=0.0073). Systolic LA strain correlated to total emptying fraction (r=0.70, p<0.0001), and inversely to LA volume (r=-0.35, p=0.0009). A cross-validated analysis of no versus mild or moderate DD expressed by LA strain revealed a positive predictive value of 48% and negative of 84%. CONCLUSION: LA strain by VVI is impaired in patients with type 2 diabetes mellitus and mild or moderate LV DD. LA strain seems of value in distinguishing normal from abnormal diastolic function. VVI offers new information on regional LA function and LA volumes but has too limited discriminative power to detect early LV DD.

BNP and NT-proBNP predict echocardiographic severity of diastolic dysfunction.

AIMS: To evaluate the best combination of clinical parameters and brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), to predict diastolic dysfunction (DD) in heart failure with preserved left ventricular ejection fraction (HF-PLEF) as determined by Doppler-echocardiography. METHODS AND RESULTS: HF patients with EF >40% in the CHARM Echocardiographic Substudy were included and classified to have normal diastolic function, or mild, moderate or severe diastolic dysfunction. Plasma BNP and NT-proBNP levels were measured and relevant clinical characteristics recorded. 181 participants were included in this analysis, 72 (40%) had moderate to severe DD. A model including age, sex, BNP, body mass index, history of atrial fibrillation, coronary artery disease, diabetes mellitus, hypertension and left atrial volume was highly predictive of moderate to severe DD; AUC 0.81 (0.73-0.88; p<0.0001). Similarly, substitution of BNP with NT-proBNP resulted in an AUC 0.79 (0.72-0.87; p<0.0001). In these models; BNP>100 pg/ml (OR 6.24 CI 2.42-16.09, p=0.0002), history of diabetes (OR 3.52 CI 1.43-8.70, p=0.006) and NT-proBNP >600 pg/ml (OR 5.93 CI 2.21-15.92, p=0.0004), history of diabetes mellitus (OR 2.75 CI 1.12-6.76, p=0.03) respectively remained independent predictors of DD in HF-PLEF. CONCLUSIONS: Natriuretic peptides were the strongest independent predictors of DD, as determined by Doppler-echocardiography, in HF-PLEF.

Longitudinal development of left ventricular diastolic function in patients with type 2 diabetes.

OBJECTIVE: Left ventricular diastolic dysfunction (LVDD) is considered to be common in patients with type 2 diabetes mellitus (T2DM), but information on its progression over time is lacking. We studied the longitudinal development of left ventricular diastolic function (LVDF) and myocardial blood flow reserve in patients with T2DM who were free from clinically detectable cardiovascular disease. RESEARCH DESIGN AND METHODS: The LVDF was assessed in 73 patients with T2DM (mean age 67 ± 7 years; males 51%) on two occasions separated by 6.4 ± 0.8 years. RESULTS: At baseline, LVDD was observed in 23 of the patients (32%). During follow-up, the LVDF normalized in 10 of these patients (43%) and remained unchanged in 13 of them (57%). Of the 50 patients (68%) with normal LVDF at baseline, LVDD developed in 9 (18%). Paired evaluation of myocardial blood volume index was available from 22 patients with LVDD and remained unchanged over time. CONCLUSIONS: The condition of the majority of the investigated patients with LVDD improved or remained stable over a period of 6 years.

Strict glycaemic control improves skin microcirculation in patients with type 2 diabetes: a report from the Diabetes mellitus And Diastolic Dysfunction (DADD) study.

BACKGROUND: Microcirculatory and endothelial dysfunction are signs of cardiovascular engagement in patients with type 2 diabetes. This study tested whether glucose normalisation may reverse this. METHODS: Thirty-nine T2DM patients (age 61±7 years, 58% females) with signs of mild diastolic dysfunction were randomised to strict glucose control based on insulin (I-group; n=21) or oral agents (O-group; n=18) for four months. Skin microcirculation was studied with laser Doppler fluxmetry and endothelial function with brachial artery flow-mediated dilatation. RESULTS: Glucose control improved (reduction of HbA(1c) I-group = -0.5%; O-group -0.7%; p=0.69). Microcirculation improved in the entire group (n=39) determined by foot laser Doppler fluxmetry (32.2±13.6 vs. 35.3±13.1 perfusion units; p<0.001) and laser Doppler fluxmetry following heating (68.8±34.0 vs. 69.3±25.1 PU; p=0.007). Improvement was more consistent with oral agents than insulin. Endothelial function expressed as flow-mediated dilatation decreased in the I-group (6.0±2.2 to 4.7±3.0%; p=0.037) but remained unchanged in the O-group (4.8±2.3 to 5.0±3.7%; n.s.). CONCLUSIONS: Glycaemic normalisation improved skin microcirculation but not endothelial function in patients with type 2 diabetes with mild cardiovascular engagement.

Prognosis in myocardial infarction patients with heart failure and normal or mildly impaired systolic function.

PURPOSE: To assess factors of importance for long term prognosis in patients with acute myocardial infarction (AMI) and heart failure and normal or mildly reduced left ventricular systolic function. SUBJECTS AND METHODS: Seventy-one consecutive AMI-survivors with clinical or radiological signs of heart failure and an echocardiographically determined wall motion score >1.2 (EF >35-40%) were followed during 11 years for mortality, heart failure readmissions and new ischemic events. RESULTS: Seventeen patients died (24%) while the combined endpoint of death or a new ischemic event (MI or hospitalisation for angina pectoris) occurred in 40 (56%) and fatal or non-fatal heart failure in 20 (28%) patients, respectively. A pre-discharge echocardiographic assessment of diastolic function was obtained in 67 patients out of whom 56 (84%) had diastolic dysfunction, most frequently relaxation abnormalities (43%). Wall motion score did not differ between survivors and non-survivors (1.48+/-0.20 vs. 1.44+/-0.18; p=0.46). Adjusting for age, sex and wall motion score N-terminal pro-ANP, prolongation of the isovolumic relaxation time and exercise induced ST-depressions at discharge (global chi2=26.2; p<0.0001) remained as independent mortality predictors while re-admission for heart failure was predicted by wall motion score, N-terminal pro-ANP and previous heart failure (global chi2=23.7; p<0.001). Death or new ischemic events were associated with low Doppler A-wave flow velocity and male sex (global chi2=14.0; p<0.01). CONCLUSIONS: Evaluation of diastolic function and a natriuretic peptide adds prognostically important information in AMI-patients with clinical heart failure and normal or mildly reduced left ventricular systolic function. Isovolumic relaxation time is an independent predictor of long term mortality and N-terminal pro-ANP of mortality and heart failure.