Diabetes as an independent predictor of left ventricular longitudinal strain reduction at rest and during dobutamine stress test in patients with significant coronary artery disease

Diabetes as an independent predictor of left ventricular longitudinal strain reduction at rest... Abstract Aims Diabetes (DM) is a strong cardiovascular risk factor modifying also the left ventricular (LV) function that may be objectively assessed with echocardiographic strain analysis. Although the impact of isolated DM on myocardial deformation has been already studied, few data concern diabetics with coronary artery disease (CAD), especially in all stages of dobutamine stress echocardiography (DSE). We compared LV systolic function during DSE in CAD with and without DM using state-of-the art speckle-tracking quantification and assessed the impact of DM on LV systolic strain. Methods and results DSE was performed in 250 patients with angina who afterwards had coronarography with ≥50% stenosis in the left main artery and ≥70% in other arteries considered as significant. In this analysis, we included 127 patients with confirmed CAD: 42 with DM [DM(+); mean age 64 ± 9 years] and 85 patients without DM [DM(−); mean age 63 ± 9 years]. The severity of CAD and LV ejection fraction (EF) were similar in both groups. Global and regional LV peak systolic longitudinal strain (PSLS) revealed in all DSE phases lower values in DM(+) group: 14.5 ± 3.6% vs. 17.4 ± 4.0% at rest; P = 0.0001, 13.8 ± 3.9% vs. 16.7 ± 4.0% at peak stress; P = 0.0002, and 14.2 ± 3.1% vs. 15.5 ± 3.5% at recovery; P = 0.0432 for global parameters, although dobutamine challenge did not enhance further resting differences. LV EF, body surface area, and diabetes were independent predictors for strain in 16-variable model (R2 = 0, 51, P < 0.001). Conclusion PSLS although diminished in both groups with CAD was lower in diabetics at all DSE stages, and DM was an independent predictor of this impairment. However, the dobutamine challenge did not deepen the resting differences, suggesting that the direct impact of coronary stenoses effaces the influence of DM during DSE. The comparison with our previous data revealed synergistic, detrimental effect of coexisting CAD and DM on myocardial strain. dobutamine stress echocardiography , coronary artery disease , diabetes , speckle tracking , automated function imaging , systolic longitudinal strain Introduction Diabetes mellitus (DM) accelerates atherosclerosis, doubles the risk of cardiovascular complications, contributes to the development of diastolic heart failure, and worsens the results of surgical treatment.1–3 Because the changes of heart function in DM may be initially subtle and poorly detectable with conventional echocardiography, the introduction of novel quantitative tools based on speckle-tracking analysis to assess myocardial deformation may improve the understanding of cardiac mechanics. Global left ventricular (LV) strain was proposed as a marker for diabetic cardiomyopathy, potentially more sensitive and precise than parameters of diastolic function and easier for obtaining than coronary flow reserve in distal left anterior descending artery (LAD).4,5 Moreover, the evaluation of longitudinal strain during stress echocardiography seems to offer additional diagnostic value in DM without significant coronary artery disease (CAD), revealing delayed recovery of peak systolic longitudinal strain (PSLS) in diabetics.6 Nevertheless, the objectively measured, quantitative influence of DM onto contractile myocardial function in subjects with confirmed CAD, especially in the settings of dobutamine stress echocardiography (DSE), was not so far adequately examined. The aim of our study was to compare quantitative, inherent indices of the LV systolic function during all stages of DSE (baseline, peak and recovery) in patients with significant CAD and coexistent DM [DM (+) group] and with CAD but without DM [DM (−) group] using automated function imaging (AFI), speckle tracking-based method available on board of advanced echocardiographic systems. Additionally, we evaluated the impact of DM on LV PSLS in multivariate analysis including 16 clinical and echocardiographic variables. Methods Study group and protocol As we previously described in the literature,6,7 we examined 250 subjects with angina by DSE with early atropine administration achieving 238 diagnostic tests (105 women, mean age 62 ± 90 years). The study flow chart is shown in Figure 1. All patients were in sinus rhythm and had no significant valve disease (except for mild-to-moderate insufficiency) as well as left bundle branch block conduction pattern. Exclusion criteria included contraindications to dobutamine and atropine. Study group in this analysis involved 127 patients with confirmed CAD: 42 with DM, diagnosed according to the standard criteria as type 2 of DM [DM (+) group], mean age 64 ± 9 years, 12 women and 85 patients with CAD but without DM [DM (−) group], mean age 63 ± 9, 25 women. All the included patients in this study were different from the group described in Wierzbowska-Drabik et al.6,7 (where 111 patients without significant CAD were analysed). Figure 1 View largeDownload slide Flow chart of the study patients examined by dobutamine stress echocardiography. CAD, coronary artery disease; CT, computed tomography; Cx, circumflex artery; DM, diabetes mellitus; DSE, dobutamine stress echocardiography. Figure 1 View largeDownload slide Flow chart of the study patients examined by dobutamine stress echocardiography. CAD, coronary artery disease; CT, computed tomography; Cx, circumflex artery; DM, diabetes mellitus; DSE, dobutamine stress echocardiography. Coronary arteries were evaluated by invasive coronary angiography or computed tomography no later than 3 months after DSE. Significant stenosis was defined as narrowing ≥50% in the left main coronary artery or ≥70% in other major arteries. All subjects gave written informed consent, and the protocol was approved by Ethical Commission of Medical University of Lodz. Resting and stress echocardiography Transthoracic echocardiography was performed with VIVID 7 Dimension (GE Vingmed Ultrasound AS, Horten, Norway) using M4S probe in harmonic mode 2.0/4.3 MHz with maximal frame per second (FPS) count available at necessary sector width, achieving on average 82 ± 8 FPS. Echocardiographic measurements were performed following American Society of Echocardiography/European Association of Echocardiography guidelines. LV EF fraction was calculated according to the modified Simpson method from triplane mode recorded with 3D probe. LV contractility was assessed visually and classified for each segment as normokinesis (Score 1), hypokinesis (Score 2), akinesis or dyskinesis (Score 3 or 4) using a 18-segment model dividing each of 6 walls into 3 segments: basal, mid, and apical. Wall motion score index (WMSI) was estimated as the sum of scores for all segments divided by the number of segments. The worsening of contractility by at least one grade in two or more adjacent segments was consistent with a positive DSE. Dobutamine was administered in the intravenous infusion in doses of 10, 20, 30 and 40 µg/kg/min during 3-min stages, whereas atropine was added in 0.5 mg fractional doses after the second stage of infusion, up to the total dose of 2 mg. The infusion of dobutamine was stopped when heart rate limit, positive test, or safety criteria were fulfilled. The assessment of myocardial deformation Standard echocardiographic views (three apical and three LV short axis) were stored at baseline, peak, and recovery. Recovery images were recorded 10 min after dobutamine stopping. The calculation of deformation was done using EchoPac 6.1.0 workstation (GE Vingmed Ultrasound). Regional and global PSLS was calculated using AFI method. Briefly, three points (two on basal and one on apical endocardium) were indicated in each apical view, and computer-generated region of interest was optimized and approved by the operator. Peak longitudinal deformation achieved for any segment before the aortic valve closure (AVC) was recorded as PSLS. AVC was defined with the Doppler recording. The rounded segmental values of PSLS were displayed as a polar map with additional calculation of the averaged (from 6 segments) and global (from 18 segments) parameters. For each LV segment, the value of PSLS was measured at baseline, peak, and recovery. Aiming at the simplification of analysis we chose the mid segments of lateral, inferior wall and anterior septum as marker, sentinel segments for the regions supplied by the circumflex (Cx), right coronary artery (RCA) and LAD, respectively. Statistical analysis Statistical analysis was performed using MedCalc version 12.1.4. (Frank Schoonjans, Belgium). Continuous variables were expressed as means and standard deviations. Mean values were compared with the Student’s t test. The χ2 test was used to test the dichotomous variables distribution. Correlations were assessed using Pearson and Spearman coefficients for continuous and categorical variables, respectively, and multivariate analysis by multiple regression was performed. The values of P < 0.05 were considered statistically significant. Data for interobserver and intraobserver variability of AFI analysis before and during DSE were calculated as coefficients of variation in randomly selected subgroups and published in former articles.7,8 Briefly, interobserver variability (coefficient of variance) calculated for segmental longitudinal strain was 8.7% and 16%, respectively, for AFI method at baseline and peak stage of DSE. Results The compared groups did not differ according to age and gender, as well as the prevalence of hypertension, smoking, and hypercholesterolaemia, although DM (+) patients had significantly higher body mass and waist circumference. Similarily, blood pressure, heart rate, history of myocardial infarction [45% in DM (+) group and 49% in DM (−) group, P = ns], and medical treatment of CAD (beyond diabetes medications) were also similar (Table 1). Moreover, both groups presented similar mean LV EF and WMSI (see Table 2) as well as comparable severity and localization of CAD lesions (Table 3). Table 1 Comparison of demographics, risk factors, and treatment between DM (+) and DM (−) groups Parameters DM (+) DM (−) P-value n = 42 n = 85 Age (years), mean ± SD 64 ± 9 63 ± 8 ns Gender (numbers F/M) 12/30 25/60 ns Height (cm), mean ± SD 169 ± 8 168 ± 9 ns Body mass (kg), mean ± SD 87.7 ± 16.6 80.0 ± 14.8 0.0091 Body mass index (kg/m2), mean ± SD 30.7 ± 5.7 28 ± 3.9 0.0022 Waist circumference (cm), mean ± SD 103.4 ± 15.8 96.1 ± 14.2 0.0097 Body surface area (m2), mean ± SD 2.02 ± 0.2 1.92 ± 0.2 0.0081 Blood pressure systolic (mmHg), mean ± SD 132 ± 17 129 ± 19 ns Blood pressure diastolic (mmHg), mean ± SD 73 ± 9 71 ± 11 ns Heart rate at baseline (bpm), mean ± SD 65 ± 7 67 ± 10 ns Obesity BMI ≥30 kg/m2, n (%) 16 (38) 26 (31) ns Hypertension, n (%) 41 (98) 79 (93) ns Smoking, n (%) 32 (76) 52 (61) ns Hypercholesterolaemia, n (%) 42 (100) 76 (89) ns Hypertriglicerydaemia, n (%) 39 (93) 49 (58) 0.0001 Total cholesterol, mean ± SD 193 ± 46 187 ± 46 ns LDL cholesterol, mean ± SD 111 ± 37 108 ± 42 ns HDL cholesterol, mean ± SD 49 ± 18 52 ± 21 ns Triglycerides, mean ± SD 183 ± 124 138 ± 90 0.0214 Family history of CAD, n (%) 8 (19) 14 (16) ns History of myocardial infarction 19 (45) 42 (49) ns Typical angina 29 (69) 66 (78) ns Non-typical angina 13 (31) 19 (22) Acetylsalicylic acid, n (%) 42 (100) 83 (98) ns Clopidogrel, n (%) 26 (62) 39 (46) ns Beta-blockers, n (%) 38 (90) 76 (89) ns Angiotensin-converting enzyme inhibitor, n (%) 41 (98) 74 (87) ns Statin, n (%) 42 (100) 82 (96) ns Long-acting nitrates, n (%) 30 (71) 64 (75) ns Parameters DM (+) DM (−) P-value n = 42 n = 85 Age (years), mean ± SD 64 ± 9 63 ± 8 ns Gender (numbers F/M) 12/30 25/60 ns Height (cm), mean ± SD 169 ± 8 168 ± 9 ns Body mass (kg), mean ± SD 87.7 ± 16.6 80.0 ± 14.8 0.0091 Body mass index (kg/m2), mean ± SD 30.7 ± 5.7 28 ± 3.9 0.0022 Waist circumference (cm), mean ± SD 103.4 ± 15.8 96.1 ± 14.2 0.0097 Body surface area (m2), mean ± SD 2.02 ± 0.2 1.92 ± 0.2 0.0081 Blood pressure systolic (mmHg), mean ± SD 132 ± 17 129 ± 19 ns Blood pressure diastolic (mmHg), mean ± SD 73 ± 9 71 ± 11 ns Heart rate at baseline (bpm), mean ± SD 65 ± 7 67 ± 10 ns Obesity BMI ≥30 kg/m2, n (%) 16 (38) 26 (31) ns Hypertension, n (%) 41 (98) 79 (93) ns Smoking, n (%) 32 (76) 52 (61) ns Hypercholesterolaemia, n (%) 42 (100) 76 (89) ns Hypertriglicerydaemia, n (%) 39 (93) 49 (58) 0.0001 Total cholesterol, mean ± SD 193 ± 46 187 ± 46 ns LDL cholesterol, mean ± SD 111 ± 37 108 ± 42 ns HDL cholesterol, mean ± SD 49 ± 18 52 ± 21 ns Triglycerides, mean ± SD 183 ± 124 138 ± 90 0.0214 Family history of CAD, n (%) 8 (19) 14 (16) ns History of myocardial infarction 19 (45) 42 (49) ns Typical angina 29 (69) 66 (78) ns Non-typical angina 13 (31) 19 (22) Acetylsalicylic acid, n (%) 42 (100) 83 (98) ns Clopidogrel, n (%) 26 (62) 39 (46) ns Beta-blockers, n (%) 38 (90) 76 (89) ns Angiotensin-converting enzyme inhibitor, n (%) 41 (98) 74 (87) ns Statin, n (%) 42 (100) 82 (96) ns Long-acting nitrates, n (%) 30 (71) 64 (75) ns CAD, coronary artery disease; DM, diabetes; n, number of subjects. Table 1 Comparison of demographics, risk factors, and treatment between DM (+) and DM (−) groups Parameters DM (+) DM (−) P-value n = 42 n = 85 Age (years), mean ± SD 64 ± 9 63 ± 8 ns Gender (numbers F/M) 12/30 25/60 ns Height (cm), mean ± SD 169 ± 8 168 ± 9 ns Body mass (kg), mean ± SD 87.7 ± 16.6 80.0 ± 14.8 0.0091 Body mass index (kg/m2), mean ± SD 30.7 ± 5.7 28 ± 3.9 0.0022 Waist circumference (cm), mean ± SD 103.4 ± 15.8 96.1 ± 14.2 0.0097 Body surface area (m2), mean ± SD 2.02 ± 0.2 1.92 ± 0.2 0.0081 Blood pressure systolic (mmHg), mean ± SD 132 ± 17 129 ± 19 ns Blood pressure diastolic (mmHg), mean ± SD 73 ± 9 71 ± 11 ns Heart rate at baseline (bpm), mean ± SD 65 ± 7 67 ± 10 ns Obesity BMI ≥30 kg/m2, n (%) 16 (38) 26 (31) ns Hypertension, n (%) 41 (98) 79 (93) ns Smoking, n (%) 32 (76) 52 (61) ns Hypercholesterolaemia, n (%) 42 (100) 76 (89) ns Hypertriglicerydaemia, n (%) 39 (93) 49 (58) 0.0001 Total cholesterol, mean ± SD 193 ± 46 187 ± 46 ns LDL cholesterol, mean ± SD 111 ± 37 108 ± 42 ns HDL cholesterol, mean ± SD 49 ± 18 52 ± 21 ns Triglycerides, mean ± SD 183 ± 124 138 ± 90 0.0214 Family history of CAD, n (%) 8 (19) 14 (16) ns History of myocardial infarction 19 (45) 42 (49) ns Typical angina 29 (69) 66 (78) ns Non-typical angina 13 (31) 19 (22) Acetylsalicylic acid, n (%) 42 (100) 83 (98) ns Clopidogrel, n (%) 26 (62) 39 (46) ns Beta-blockers, n (%) 38 (90) 76 (89) ns Angiotensin-converting enzyme inhibitor, n (%) 41 (98) 74 (87) ns Statin, n (%) 42 (100) 82 (96) ns Long-acting nitrates, n (%) 30 (71) 64 (75) ns Parameters DM (+) DM (−) P-value n = 42 n = 85 Age (years), mean ± SD 64 ± 9 63 ± 8 ns Gender (numbers F/M) 12/30 25/60 ns Height (cm), mean ± SD 169 ± 8 168 ± 9 ns Body mass (kg), mean ± SD 87.7 ± 16.6 80.0 ± 14.8 0.0091 Body mass index (kg/m2), mean ± SD 30.7 ± 5.7 28 ± 3.9 0.0022 Waist circumference (cm), mean ± SD 103.4 ± 15.8 96.1 ± 14.2 0.0097 Body surface area (m2), mean ± SD 2.02 ± 0.2 1.92 ± 0.2 0.0081 Blood pressure systolic (mmHg), mean ± SD 132 ± 17 129 ± 19 ns Blood pressure diastolic (mmHg), mean ± SD 73 ± 9 71 ± 11 ns Heart rate at baseline (bpm), mean ± SD 65 ± 7 67 ± 10 ns Obesity BMI ≥30 kg/m2, n (%) 16 (38) 26 (31) ns Hypertension, n (%) 41 (98) 79 (93) ns Smoking, n (%) 32 (76) 52 (61) ns Hypercholesterolaemia, n (%) 42 (100) 76 (89) ns Hypertriglicerydaemia, n (%) 39 (93) 49 (58) 0.0001 Total cholesterol, mean ± SD 193 ± 46 187 ± 46 ns LDL cholesterol, mean ± SD 111 ± 37 108 ± 42 ns HDL cholesterol, mean ± SD 49 ± 18 52 ± 21 ns Triglycerides, mean ± SD 183 ± 124 138 ± 90 0.0214 Family history of CAD, n (%) 8 (19) 14 (16) ns History of myocardial infarction 19 (45) 42 (49) ns Typical angina 29 (69) 66 (78) ns Non-typical angina 13 (31) 19 (22) Acetylsalicylic acid, n (%) 42 (100) 83 (98) ns Clopidogrel, n (%) 26 (62) 39 (46) ns Beta-blockers, n (%) 38 (90) 76 (89) ns Angiotensin-converting enzyme inhibitor, n (%) 41 (98) 74 (87) ns Statin, n (%) 42 (100) 82 (96) ns Long-acting nitrates, n (%) 30 (71) 64 (75) ns CAD, coronary artery disease; DM, diabetes; n, number of subjects. Table 2 Comparison of baseline echocardiographic parameters between DM (+) and DM (−) groups Parameters DM (+) DM (−) P-value n = 42 n = 85 LVd (mm) 47.9 ± 4.8 47.3 ± 5.1 ns LVd index (mm/m2) 23.9 ± 3.1 24.8 ± 3.1 ns LVs (mm) 34.2 ± 5.0 33.5 ± 6.1 ns LVs index (mm/m2) 17.1 ± 3.1 17.5 ± 3.2 ns PWd (mm) 12.3 ± 1.3 11.3 ± 1.1 <0.0001 PWd index (mm/m2) 6.1 ± 0.8 5.9 ± 0.7 ns PWs (mm) 15.1 ± 1.7 14.1 ± 1.6 <0.0015 PWs index (mm/m2) 7.5 ± 1.0 7.4 ± 0.9 ns IVSd (mm) 12.9 ± 1.6 11.9 ± 1.5 0.0007 IVSd index (mm/m2) 6.4 ± 0.9 6.2 ± 0.8 ns IVSs (mm) 15.7 ± 1.7 14.8 ± 1.6 0.0041 IVSs index (mm/m2) 7.8 ± 1.0 7.7 ± 1.0 ns Ao (mm) 33.1 ± 3.2 32.9 ± 3.6 ns Ao index (mm/m2) 16.5 ± 1.9 17.3 ± 1.9 0.0274 LA (mm) 42.4 ± 2.9 40.9 ± 3.7 0.0231 LA index (mm/m2) 21.1 ± 2.2 21.4 ± 2.3 ns RV (mm) 26.4 ± 2.0 26.4 ± 2.1 ns RV index (mm/m2) 13.2 ± 1.4 13.8 ± 1.5 0.0321 E/A 0.7 ± −0.2 0.9 ± 0.5 0.014 LV mass (g) 277 ± 57 244 ± 67 0.0071 LV mass index (g/m2) 137 ± 27 126 ± 30 0.0468 EF baseline (%) 53 ± 7 54 ± 8 ns WMSI at baseline 1.15 ± 0.2 1.17 ± 0.24 ns S′ lat at baseline (cm/s) 7.7 ± 1.8 8.5 ± 2.5 ns E′ lat at baseline (cm/s) 9.1 ± 3.1 9.6 ± 2.8 ns Parameters DM (+) DM (−) P-value n = 42 n = 85 LVd (mm) 47.9 ± 4.8 47.3 ± 5.1 ns LVd index (mm/m2) 23.9 ± 3.1 24.8 ± 3.1 ns LVs (mm) 34.2 ± 5.0 33.5 ± 6.1 ns LVs index (mm/m2) 17.1 ± 3.1 17.5 ± 3.2 ns PWd (mm) 12.3 ± 1.3 11.3 ± 1.1 <0.0001 PWd index (mm/m2) 6.1 ± 0.8 5.9 ± 0.7 ns PWs (mm) 15.1 ± 1.7 14.1 ± 1.6 <0.0015 PWs index (mm/m2) 7.5 ± 1.0 7.4 ± 0.9 ns IVSd (mm) 12.9 ± 1.6 11.9 ± 1.5 0.0007 IVSd index (mm/m2) 6.4 ± 0.9 6.2 ± 0.8 ns IVSs (mm) 15.7 ± 1.7 14.8 ± 1.6 0.0041 IVSs index (mm/m2) 7.8 ± 1.0 7.7 ± 1.0 ns Ao (mm) 33.1 ± 3.2 32.9 ± 3.6 ns Ao index (mm/m2) 16.5 ± 1.9 17.3 ± 1.9 0.0274 LA (mm) 42.4 ± 2.9 40.9 ± 3.7 0.0231 LA index (mm/m2) 21.1 ± 2.2 21.4 ± 2.3 ns RV (mm) 26.4 ± 2.0 26.4 ± 2.1 ns RV index (mm/m2) 13.2 ± 1.4 13.8 ± 1.5 0.0321 E/A 0.7 ± −0.2 0.9 ± 0.5 0.014 LV mass (g) 277 ± 57 244 ± 67 0.0071 LV mass index (g/m2) 137 ± 27 126 ± 30 0.0468 EF baseline (%) 53 ± 7 54 ± 8 ns WMSI at baseline 1.15 ± 0.2 1.17 ± 0.24 ns S′ lat at baseline (cm/s) 7.7 ± 1.8 8.5 ± 2.5 ns E′ lat at baseline (cm/s) 9.1 ± 3.1 9.6 ± 2.8 ns Indexes were calculated by body surface area. Values were expressed as mean ± SD. Ao, aortic dimension; DM, diabetes mellitus; E′ lat, peak early diastolic velocity of lateral part of mitral annulus; E, peak velocity of mitral inflow early phase; E/A, ratio of early to atrial mitral inflow peak velocity; EF, left ventricular ejection fraction; IVSd, end-diastolic left ventricular septum thickness; IVSs, end-systolic left ventricular septum thickness; LA, left atrial dimension; LV mass, left ventricular mass; LV mass index, left ventricular mass index; LVd, left ventricular end-diastolic dimension; LVs, left ventricular end-systolic dimension; n, number of subjects; PWd, end-diastolic left ventricular posterior wall thickness; PWs, end-systolic left ventricular posterior wall thickness; RV, right ventricular end-diastolic dimension; S′ lat, peak systolic velocity of lateral part of mitral annulus; WMSI, wall motion score index. Table 2 Comparison of baseline echocardiographic parameters between DM (+) and DM (−) groups Parameters DM (+) DM (−) P-value n = 42 n = 85 LVd (mm) 47.9 ± 4.8 47.3 ± 5.1 ns LVd index (mm/m2) 23.9 ± 3.1 24.8 ± 3.1 ns LVs (mm) 34.2 ± 5.0 33.5 ± 6.1 ns LVs index (mm/m2) 17.1 ± 3.1 17.5 ± 3.2 ns PWd (mm) 12.3 ± 1.3 11.3 ± 1.1 <0.0001 PWd index (mm/m2) 6.1 ± 0.8 5.9 ± 0.7 ns PWs (mm) 15.1 ± 1.7 14.1 ± 1.6 <0.0015 PWs index (mm/m2) 7.5 ± 1.0 7.4 ± 0.9 ns IVSd (mm) 12.9 ± 1.6 11.9 ± 1.5 0.0007 IVSd index (mm/m2) 6.4 ± 0.9 6.2 ± 0.8 ns IVSs (mm) 15.7 ± 1.7 14.8 ± 1.6 0.0041 IVSs index (mm/m2) 7.8 ± 1.0 7.7 ± 1.0 ns Ao (mm) 33.1 ± 3.2 32.9 ± 3.6 ns Ao index (mm/m2) 16.5 ± 1.9 17.3 ± 1.9 0.0274 LA (mm) 42.4 ± 2.9 40.9 ± 3.7 0.0231 LA index (mm/m2) 21.1 ± 2.2 21.4 ± 2.3 ns RV (mm) 26.4 ± 2.0 26.4 ± 2.1 ns RV index (mm/m2) 13.2 ± 1.4 13.8 ± 1.5 0.0321 E/A 0.7 ± −0.2 0.9 ± 0.5 0.014 LV mass (g) 277 ± 57 244 ± 67 0.0071 LV mass index (g/m2) 137 ± 27 126 ± 30 0.0468 EF baseline (%) 53 ± 7 54 ± 8 ns WMSI at baseline 1.15 ± 0.2 1.17 ± 0.24 ns S′ lat at baseline (cm/s) 7.7 ± 1.8 8.5 ± 2.5 ns E′ lat at baseline (cm/s) 9.1 ± 3.1 9.6 ± 2.8 ns Parameters DM (+) DM (−) P-value n = 42 n = 85 LVd (mm) 47.9 ± 4.8 47.3 ± 5.1 ns LVd index (mm/m2) 23.9 ± 3.1 24.8 ± 3.1 ns LVs (mm) 34.2 ± 5.0 33.5 ± 6.1 ns LVs index (mm/m2) 17.1 ± 3.1 17.5 ± 3.2 ns PWd (mm) 12.3 ± 1.3 11.3 ± 1.1 <0.0001 PWd index (mm/m2) 6.1 ± 0.8 5.9 ± 0.7 ns PWs (mm) 15.1 ± 1.7 14.1 ± 1.6 <0.0015 PWs index (mm/m2) 7.5 ± 1.0 7.4 ± 0.9 ns IVSd (mm) 12.9 ± 1.6 11.9 ± 1.5 0.0007 IVSd index (mm/m2) 6.4 ± 0.9 6.2 ± 0.8 ns IVSs (mm) 15.7 ± 1.7 14.8 ± 1.6 0.0041 IVSs index (mm/m2) 7.8 ± 1.0 7.7 ± 1.0 ns Ao (mm) 33.1 ± 3.2 32.9 ± 3.6 ns Ao index (mm/m2) 16.5 ± 1.9 17.3 ± 1.9 0.0274 LA (mm) 42.4 ± 2.9 40.9 ± 3.7 0.0231 LA index (mm/m2) 21.1 ± 2.2 21.4 ± 2.3 ns RV (mm) 26.4 ± 2.0 26.4 ± 2.1 ns RV index (mm/m2) 13.2 ± 1.4 13.8 ± 1.5 0.0321 E/A 0.7 ± −0.2 0.9 ± 0.5 0.014 LV mass (g) 277 ± 57 244 ± 67 0.0071 LV mass index (g/m2) 137 ± 27 126 ± 30 0.0468 EF baseline (%) 53 ± 7 54 ± 8 ns WMSI at baseline 1.15 ± 0.2 1.17 ± 0.24 ns S′ lat at baseline (cm/s) 7.7 ± 1.8 8.5 ± 2.5 ns E′ lat at baseline (cm/s) 9.1 ± 3.1 9.6 ± 2.8 ns Indexes were calculated by body surface area. Values were expressed as mean ± SD. Ao, aortic dimension; DM, diabetes mellitus; E′ lat, peak early diastolic velocity of lateral part of mitral annulus; E, peak velocity of mitral inflow early phase; E/A, ratio of early to atrial mitral inflow peak velocity; EF, left ventricular ejection fraction; IVSd, end-diastolic left ventricular septum thickness; IVSs, end-systolic left ventricular septum thickness; LA, left atrial dimension; LV mass, left ventricular mass; LV mass index, left ventricular mass index; LVd, left ventricular end-diastolic dimension; LVs, left ventricular end-systolic dimension; n, number of subjects; PWd, end-diastolic left ventricular posterior wall thickness; PWs, end-systolic left ventricular posterior wall thickness; RV, right ventricular end-diastolic dimension; S′ lat, peak systolic velocity of lateral part of mitral annulus; WMSI, wall motion score index. Table 3 The comparison of CAD advancement and localization between groups with and without DM Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Three-vessel disease, n (%) 12 (29) 14 (16) ns Two-vessel disease, n (%) 10 (24) 28 (33) ns One-vessel disease, n (%) 20 (48) 43 (51) ns LMCA stenosis >50% 6 (14) 6 (7) ns LAD stenosis >70% 21 (50) 49 (58) ns Cx stenosis >70% 21 (50) 42 (49) ns RCA stenosis >70% 23 (55) 42 (49) ns SYNTAX score (n 33/79), mean ± SD 17.3 ± 28.3 12.5 ± 8.5 ns History of CABG 1 (2.4) 1 (1.2) ns Number of patent/stenosed grafts, n (%) 3 (75)/1(25) 1 (100)/0(0) ns Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Three-vessel disease, n (%) 12 (29) 14 (16) ns Two-vessel disease, n (%) 10 (24) 28 (33) ns One-vessel disease, n (%) 20 (48) 43 (51) ns LMCA stenosis >50% 6 (14) 6 (7) ns LAD stenosis >70% 21 (50) 49 (58) ns Cx stenosis >70% 21 (50) 42 (49) ns RCA stenosis >70% 23 (55) 42 (49) ns SYNTAX score (n 33/79), mean ± SD 17.3 ± 28.3 12.5 ± 8.5 ns History of CABG 1 (2.4) 1 (1.2) ns Number of patent/stenosed grafts, n (%) 3 (75)/1(25) 1 (100)/0(0) ns Table 3 The comparison of CAD advancement and localization between groups with and without DM Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Three-vessel disease, n (%) 12 (29) 14 (16) ns Two-vessel disease, n (%) 10 (24) 28 (33) ns One-vessel disease, n (%) 20 (48) 43 (51) ns LMCA stenosis >50% 6 (14) 6 (7) ns LAD stenosis >70% 21 (50) 49 (58) ns Cx stenosis >70% 21 (50) 42 (49) ns RCA stenosis >70% 23 (55) 42 (49) ns SYNTAX score (n 33/79), mean ± SD 17.3 ± 28.3 12.5 ± 8.5 ns History of CABG 1 (2.4) 1 (1.2) ns Number of patent/stenosed grafts, n (%) 3 (75)/1(25) 1 (100)/0(0) ns Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Three-vessel disease, n (%) 12 (29) 14 (16) ns Two-vessel disease, n (%) 10 (24) 28 (33) ns One-vessel disease, n (%) 20 (48) 43 (51) ns LMCA stenosis >50% 6 (14) 6 (7) ns LAD stenosis >70% 21 (50) 49 (58) ns Cx stenosis >70% 21 (50) 42 (49) ns RCA stenosis >70% 23 (55) 42 (49) ns SYNTAX score (n 33/79), mean ± SD 17.3 ± 28.3 12.5 ± 8.5 ns History of CABG 1 (2.4) 1 (1.2) ns Number of patent/stenosed grafts, n (%) 3 (75)/1(25) 1 (100)/0(0) ns Diabetics had higher body mass index (BMI; 30.7 ± 5.7 vs. 28 ± 3.9 in controls, P = 0.0022) and had more often triglyceridaemia (see Table 1). Patients with CAD and DM had comparable standard echocardiograms except for higher LV mass and LV mass index (LVMI; 137 ± 27 g/m2 vs. 126 ± 30 g/m2, P = 0.0468, for mass index) as well as thicker LV walls and larger left atrial diameter (significance was lost after indexing for BSA; see Table 2). We did not found any correlation between LVMI and PSLS in patients with diabetes (r = 0.065, P = 0.68; r = 0.187, P = 0.24; r = 0.04, P = 0.81, respectively) for baseline, peak, and recovery of DSE. In contrast, we observed the significant correlation between LVMI and PSLS in group without DM, which was confirmed in all stages of DSE (r = 0.37, P = 0.0004; r = 0.34, P = 0.013; r = 0.43, P = 0.0001, respectively) for baseline, peak, and recovery. Severity of CAD was similar in both groups (Table 3) with comparable prevalence of significant stenosis (>70%) in each of the major epicardial coronary artery or its significant branch (diagonal arteries of diameter >2 mm were ascribed to LAD, marginal to Cx and posterior descending and posterolateral to RCA). SYNTAX score did not differ between DM (+) and DM (−) patients. Only two patients in the studied group had previous coronary artery bypass grafting (CABG). One patient belonged into DM (+) group and presented patent left interior mammary artery (LIMA) and two venous grafts, from which one venous graft (supplying RCA) had 95% stenosis. The other patient belonged to DM (−) group and had only one arterial graft—patent LIMA to LAD. Because of very small number, the proportion of previous CABG and graft patency did not differ significantly between the compared subgroups (see Table 3). During DSE, standard echocardiographic parameters did not differ between DM (+) and DM (−) groups. The percentage of positive DSE test (assessed visually) exceeded 80% in both groups with chest pain prevalence and electrocardiographic (ECG) changes recorded in about 60%. Peak stress values of EF, WMSI, heart rate, and blood pressure were also similar as well as the percentage of contractility impairment in myocardial regions supplied by respective coronary arteries (Table 4). Table 4 The comparison of the prevalence of chest pain, ECG changes, WMSI, and contractility impairments between group with and without DM during DSE Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Chest pain during DSE, n (%) 24 (57) 51 (60) ns ECG ischemic changes at peak DSE, n (%) 26 (62) 49 (58) ns WMSI at peak, mean ± SD 1.3 ± 0.21 1, 3 ± 0, 24 ns Delta WMSI (peak–baseline), mean ± SD 0.15 ± 0.14 0.13 ± 0, 13 ns Positive DSE test, n (%) 37 (88) 72 (85) ns Systolic blood pressure at peak stage (mmHg), mean ± SD 145 ± 28 142 ± 26 ns Diastolic blood pressure at peak stage (mmHg), mean ± SD 76 ± 11 75 ± 12 ns Atropine mean dose (mg), mean ± SD 1.08 ± 0.53 0.96 ± 0.5 ns Heart rate at peak stage (bpm), mean ± SD 138 ± 12 138 ± 16 ns Heart rate at recovery (bpm), mean ± SD 92 ± 13 89 ± 12 ns EF at peak DSE (%), mean ± SD 54 ± 7 55 ± 10 ns Induced contractility impairment in the region of LAD (number of subjects), n (%) 11 (26) 22 (26) ns Induced contractility impairment in the region of Cx (number of subjects), n (%) 21 (50) 38 (45) ns Induced contractility impairment in the region of RCA (number of subjects), n (%) 22 (52) 37 (44) ns Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Chest pain during DSE, n (%) 24 (57) 51 (60) ns ECG ischemic changes at peak DSE, n (%) 26 (62) 49 (58) ns WMSI at peak, mean ± SD 1.3 ± 0.21 1, 3 ± 0, 24 ns Delta WMSI (peak–baseline), mean ± SD 0.15 ± 0.14 0.13 ± 0, 13 ns Positive DSE test, n (%) 37 (88) 72 (85) ns Systolic blood pressure at peak stage (mmHg), mean ± SD 145 ± 28 142 ± 26 ns Diastolic blood pressure at peak stage (mmHg), mean ± SD 76 ± 11 75 ± 12 ns Atropine mean dose (mg), mean ± SD 1.08 ± 0.53 0.96 ± 0.5 ns Heart rate at peak stage (bpm), mean ± SD 138 ± 12 138 ± 16 ns Heart rate at recovery (bpm), mean ± SD 92 ± 13 89 ± 12 ns EF at peak DSE (%), mean ± SD 54 ± 7 55 ± 10 ns Induced contractility impairment in the region of LAD (number of subjects), n (%) 11 (26) 22 (26) ns Induced contractility impairment in the region of Cx (number of subjects), n (%) 21 (50) 38 (45) ns Induced contractility impairment in the region of RCA (number of subjects), n (%) 22 (52) 37 (44) ns Cx, circumflex artery; DSE, dobutamine stress echocardiography; ECG, electrocardiogram; LAD, left anterior descending artery; n, number of subjects; RCA, right coronary artery; WMSI, wall motion score index. Table 4 The comparison of the prevalence of chest pain, ECG changes, WMSI, and contractility impairments between group with and without DM during DSE Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Chest pain during DSE, n (%) 24 (57) 51 (60) ns ECG ischemic changes at peak DSE, n (%) 26 (62) 49 (58) ns WMSI at peak, mean ± SD 1.3 ± 0.21 1, 3 ± 0, 24 ns Delta WMSI (peak–baseline), mean ± SD 0.15 ± 0.14 0.13 ± 0, 13 ns Positive DSE test, n (%) 37 (88) 72 (85) ns Systolic blood pressure at peak stage (mmHg), mean ± SD 145 ± 28 142 ± 26 ns Diastolic blood pressure at peak stage (mmHg), mean ± SD 76 ± 11 75 ± 12 ns Atropine mean dose (mg), mean ± SD 1.08 ± 0.53 0.96 ± 0.5 ns Heart rate at peak stage (bpm), mean ± SD 138 ± 12 138 ± 16 ns Heart rate at recovery (bpm), mean ± SD 92 ± 13 89 ± 12 ns EF at peak DSE (%), mean ± SD 54 ± 7 55 ± 10 ns Induced contractility impairment in the region of LAD (number of subjects), n (%) 11 (26) 22 (26) ns Induced contractility impairment in the region of Cx (number of subjects), n (%) 21 (50) 38 (45) ns Induced contractility impairment in the region of RCA (number of subjects), n (%) 22 (52) 37 (44) ns Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Chest pain during DSE, n (%) 24 (57) 51 (60) ns ECG ischemic changes at peak DSE, n (%) 26 (62) 49 (58) ns WMSI at peak, mean ± SD 1.3 ± 0.21 1, 3 ± 0, 24 ns Delta WMSI (peak–baseline), mean ± SD 0.15 ± 0.14 0.13 ± 0, 13 ns Positive DSE test, n (%) 37 (88) 72 (85) ns Systolic blood pressure at peak stage (mmHg), mean ± SD 145 ± 28 142 ± 26 ns Diastolic blood pressure at peak stage (mmHg), mean ± SD 76 ± 11 75 ± 12 ns Atropine mean dose (mg), mean ± SD 1.08 ± 0.53 0.96 ± 0.5 ns Heart rate at peak stage (bpm), mean ± SD 138 ± 12 138 ± 16 ns Heart rate at recovery (bpm), mean ± SD 92 ± 13 89 ± 12 ns EF at peak DSE (%), mean ± SD 54 ± 7 55 ± 10 ns Induced contractility impairment in the region of LAD (number of subjects), n (%) 11 (26) 22 (26) ns Induced contractility impairment in the region of Cx (number of subjects), n (%) 21 (50) 38 (45) ns Induced contractility impairment in the region of RCA (number of subjects), n (%) 22 (52) 37 (44) ns Cx, circumflex artery; DSE, dobutamine stress echocardiography; ECG, electrocardiogram; LAD, left anterior descending artery; n, number of subjects; RCA, right coronary artery; WMSI, wall motion score index. Feasibility of longitudinal strain assessment with the standard 2D speckle-tracking echocardiography with and without the use of AFI was analysed for regional and global data and published in an earlier article,7 encompassing data from 238 patients including presently analysed 127 subjects with CAD. Global LV PSLS correlated very well for both methods (r = 0.90 at baseline and r = 0.86 at peak stage of DSE), but AFI analysis (used in this study) was less time-consuming (mean time for obtaining regional, averaged, and global data for LV in AFI was 168 ± 28 s vs. 367 ± 39 s by classical curves analysis with STE) and less operator dependent with interobserver variability of 8.7% and 16% for baseline at peak stage, respectively. Despite the inclusion of only patients with feasible visual assessment of all LV segments in our study, we still excluded some segments from speckle-tracking analysis because of suboptimal tracking quality. The respective percentage of excluded segments were significantly higher at peak stage (1.07%) than at rest (0.42%, P = 0.0007). In contrast to standard echocardiographic parameters, all assessed global, average, and segmental PSLS measurements had lower absolute values in patients with CAD and DM at all stages of DSE. In the majority of comparisons, observed differences were statistically significant (Table 5), e.g. for global strain (averaged from 18 LV segments) measured at baseline (14.5 ± 3.6% vs. 17.4 ± 4.0, P = 0.0001), peak (13.8 ± 3.9% vs. 16.7 ± 4.0%, P = 0.0002), and recovery (14.2 ± 3.1% vs. 15.5 ± 3.5%, P = 0.04) and for averaged values describing respective echocardiographic views (six segments from three-chamber, two-chamber and four-chamber views) measured at baseline as well as for segmental values (chosen from mid LV level as representative for Cx, RCA, and LAD supply) measured at baseline. At peak DSE stage and at recovery, some comparisons, encompassing less number of segments, did not reach statistical significance (Figure 2). Table 5 Comparison of longitudinal peak systolic strain measured by AFI method between groups with and without DM at baseline, peak, and during recovery phase of DSE (absolute values, without minus) Parameters DM (+) DM (−) P-value n = 42 n = 85 Global PSLS at baseline 14.5 ± 3.6 17.4 ± 4.0 0.0001 Global PSLS at peak 13.8 ± 3.9 16.7 ± 4.0 0.0002 Global PSLS at recovery 14.2 ± 3.1 15.5 ± 3.5 0.0432 Averaged 3ch PSLS at baseline 15.1 ± 4.3 17.6 ± 4.6 0.0039 Averaged 4 ch PSLS at baseline 14.4 ± 4.4 16.8 ± 4.1 0.003 Averaged 2 ch PSLS at baseline 14.5 ± 3.6 17.9 ± 4.3 <0.0001 Averaged 3ch PSLS at peak 14.2 ± 5.0 17.0 ± 4.7 0.0024 Averaged 4 ch PSLS at peak 14.6 ± 4.8 16.4 ± 5.4 ns Averaged 2 ch PSLS at peak 13.0 ± 4.6 16.4 ± 4.8 0.0002 Averaged 3ch PSLS at recovery 14.3 ± 4.0 15.6 ± 4.2 ns Averaged 4 ch PSLS at recovery 13.9 ± 3.8 15.5 ± 3.8 0.0274 Averaged 2 ch PSLS at recovery 13.9 ± 3.6 15.6 ± 3.6 0.0136 Mid lateral PSLS at baseline 9.8 ± 7.4 13.4 ± 7.0 0.0085 Mid inferior PSLS at baseline 16.5 ± 4.4 19.6 ± 5.7 0.0024 Mid anteroseptal PSLS at baseline 16.8 ± 5.7 19.7 ± 4.5 0.0022 Mid lateral PSLS at peak 9.1 ± 6.3 11.7 ± 9.7 ns Mid inferior PSLS at peak 15.4 ± 6.4 18.1 ± 5.5 0.0151 Mid anteroseptal PSLS at peak 16.1 ± 6.6 18.2 ± 6.7 ns Mid lateral PSLS at recovery 10.2 ± 6.5 13.1 ± 5.5 0.0096 Mid inferior PSLS at recovery 14.9 ± 5.0 17.1 ± 5.0 0.0213 Mid anteroseptal PSLS at recovery 15.3 ± 6.2 17.2 ± 5.1 ns Parameters DM (+) DM (−) P-value n = 42 n = 85 Global PSLS at baseline 14.5 ± 3.6 17.4 ± 4.0 0.0001 Global PSLS at peak 13.8 ± 3.9 16.7 ± 4.0 0.0002 Global PSLS at recovery 14.2 ± 3.1 15.5 ± 3.5 0.0432 Averaged 3ch PSLS at baseline 15.1 ± 4.3 17.6 ± 4.6 0.0039 Averaged 4 ch PSLS at baseline 14.4 ± 4.4 16.8 ± 4.1 0.003 Averaged 2 ch PSLS at baseline 14.5 ± 3.6 17.9 ± 4.3 <0.0001 Averaged 3ch PSLS at peak 14.2 ± 5.0 17.0 ± 4.7 0.0024 Averaged 4 ch PSLS at peak 14.6 ± 4.8 16.4 ± 5.4 ns Averaged 2 ch PSLS at peak 13.0 ± 4.6 16.4 ± 4.8 0.0002 Averaged 3ch PSLS at recovery 14.3 ± 4.0 15.6 ± 4.2 ns Averaged 4 ch PSLS at recovery 13.9 ± 3.8 15.5 ± 3.8 0.0274 Averaged 2 ch PSLS at recovery 13.9 ± 3.6 15.6 ± 3.6 0.0136 Mid lateral PSLS at baseline 9.8 ± 7.4 13.4 ± 7.0 0.0085 Mid inferior PSLS at baseline 16.5 ± 4.4 19.6 ± 5.7 0.0024 Mid anteroseptal PSLS at baseline 16.8 ± 5.7 19.7 ± 4.5 0.0022 Mid lateral PSLS at peak 9.1 ± 6.3 11.7 ± 9.7 ns Mid inferior PSLS at peak 15.4 ± 6.4 18.1 ± 5.5 0.0151 Mid anteroseptal PSLS at peak 16.1 ± 6.6 18.2 ± 6.7 ns Mid lateral PSLS at recovery 10.2 ± 6.5 13.1 ± 5.5 0.0096 Mid inferior PSLS at recovery 14.9 ± 5.0 17.1 ± 5.0 0.0213 Mid anteroseptal PSLS at recovery 15.3 ± 6.2 17.2 ± 5.1 ns Global—mean value from 18 segments, 2ch, 3ch, and 4ch—parameters measured as mean values from six segments in respective apical views, mid lateral, mid inferior, mid anteroseptal—parameters measured in respective segments of left ventricle considered ‘marker segments’ for Cx, RCA and LAD supply region. Values were expressed as mean ± SD. 2ch, apical two-chamber view; 3ch, apical three-chamber view; 4ch, apical four-chamber view; CAD, coronary artery disease; DM, diabetes mellitus; PSLS, peak systolic longitudinal strain; n, number of subjects. Table 5 Comparison of longitudinal peak systolic strain measured by AFI method between groups with and without DM at baseline, peak, and during recovery phase of DSE (absolute values, without minus) Parameters DM (+) DM (−) P-value n = 42 n = 85 Global PSLS at baseline 14.5 ± 3.6 17.4 ± 4.0 0.0001 Global PSLS at peak 13.8 ± 3.9 16.7 ± 4.0 0.0002 Global PSLS at recovery 14.2 ± 3.1 15.5 ± 3.5 0.0432 Averaged 3ch PSLS at baseline 15.1 ± 4.3 17.6 ± 4.6 0.0039 Averaged 4 ch PSLS at baseline 14.4 ± 4.4 16.8 ± 4.1 0.003 Averaged 2 ch PSLS at baseline 14.5 ± 3.6 17.9 ± 4.3 <0.0001 Averaged 3ch PSLS at peak 14.2 ± 5.0 17.0 ± 4.7 0.0024 Averaged 4 ch PSLS at peak 14.6 ± 4.8 16.4 ± 5.4 ns Averaged 2 ch PSLS at peak 13.0 ± 4.6 16.4 ± 4.8 0.0002 Averaged 3ch PSLS at recovery 14.3 ± 4.0 15.6 ± 4.2 ns Averaged 4 ch PSLS at recovery 13.9 ± 3.8 15.5 ± 3.8 0.0274 Averaged 2 ch PSLS at recovery 13.9 ± 3.6 15.6 ± 3.6 0.0136 Mid lateral PSLS at baseline 9.8 ± 7.4 13.4 ± 7.0 0.0085 Mid inferior PSLS at baseline 16.5 ± 4.4 19.6 ± 5.7 0.0024 Mid anteroseptal PSLS at baseline 16.8 ± 5.7 19.7 ± 4.5 0.0022 Mid lateral PSLS at peak 9.1 ± 6.3 11.7 ± 9.7 ns Mid inferior PSLS at peak 15.4 ± 6.4 18.1 ± 5.5 0.0151 Mid anteroseptal PSLS at peak 16.1 ± 6.6 18.2 ± 6.7 ns Mid lateral PSLS at recovery 10.2 ± 6.5 13.1 ± 5.5 0.0096 Mid inferior PSLS at recovery 14.9 ± 5.0 17.1 ± 5.0 0.0213 Mid anteroseptal PSLS at recovery 15.3 ± 6.2 17.2 ± 5.1 ns Parameters DM (+) DM (−) P-value n = 42 n = 85 Global PSLS at baseline 14.5 ± 3.6 17.4 ± 4.0 0.0001 Global PSLS at peak 13.8 ± 3.9 16.7 ± 4.0 0.0002 Global PSLS at recovery 14.2 ± 3.1 15.5 ± 3.5 0.0432 Averaged 3ch PSLS at baseline 15.1 ± 4.3 17.6 ± 4.6 0.0039 Averaged 4 ch PSLS at baseline 14.4 ± 4.4 16.8 ± 4.1 0.003 Averaged 2 ch PSLS at baseline 14.5 ± 3.6 17.9 ± 4.3 <0.0001 Averaged 3ch PSLS at peak 14.2 ± 5.0 17.0 ± 4.7 0.0024 Averaged 4 ch PSLS at peak 14.6 ± 4.8 16.4 ± 5.4 ns Averaged 2 ch PSLS at peak 13.0 ± 4.6 16.4 ± 4.8 0.0002 Averaged 3ch PSLS at recovery 14.3 ± 4.0 15.6 ± 4.2 ns Averaged 4 ch PSLS at recovery 13.9 ± 3.8 15.5 ± 3.8 0.0274 Averaged 2 ch PSLS at recovery 13.9 ± 3.6 15.6 ± 3.6 0.0136 Mid lateral PSLS at baseline 9.8 ± 7.4 13.4 ± 7.0 0.0085 Mid inferior PSLS at baseline 16.5 ± 4.4 19.6 ± 5.7 0.0024 Mid anteroseptal PSLS at baseline 16.8 ± 5.7 19.7 ± 4.5 0.0022 Mid lateral PSLS at peak 9.1 ± 6.3 11.7 ± 9.7 ns Mid inferior PSLS at peak 15.4 ± 6.4 18.1 ± 5.5 0.0151 Mid anteroseptal PSLS at peak 16.1 ± 6.6 18.2 ± 6.7 ns Mid lateral PSLS at recovery 10.2 ± 6.5 13.1 ± 5.5 0.0096 Mid inferior PSLS at recovery 14.9 ± 5.0 17.1 ± 5.0 0.0213 Mid anteroseptal PSLS at recovery 15.3 ± 6.2 17.2 ± 5.1 ns Global—mean value from 18 segments, 2ch, 3ch, and 4ch—parameters measured as mean values from six segments in respective apical views, mid lateral, mid inferior, mid anteroseptal—parameters measured in respective segments of left ventricle considered ‘marker segments’ for Cx, RCA and LAD supply region. Values were expressed as mean ± SD. 2ch, apical two-chamber view; 3ch, apical three-chamber view; 4ch, apical four-chamber view; CAD, coronary artery disease; DM, diabetes mellitus; PSLS, peak systolic longitudinal strain; n, number of subjects. Figure 2 View largeDownload slide Comparison of global and regional PSLS, recorded during baseline, peak, and recovery stage of DSE in patients with CAD and DM (red bars) and CAD without DM (green bars). Absolute strain values at baseline and majority at the peak and during recovery are lower in diabetics. The coexistence of diabetes significantly impairs left ventricular systolic function at rest, during, and after stress echocardiography in patients with coronary artery disease. Figure 2 View largeDownload slide Comparison of global and regional PSLS, recorded during baseline, peak, and recovery stage of DSE in patients with CAD and DM (red bars) and CAD without DM (green bars). Absolute strain values at baseline and majority at the peak and during recovery are lower in diabetics. The coexistence of diabetes significantly impairs left ventricular systolic function at rest, during, and after stress echocardiography in patients with coronary artery disease. As far as the comparison of observed changes of PSLS during DSE are concerned for global strain, it reached the mean value of 1.8 ± 2.3% in DM (−) group and 1.2 ± 2.6% in DM (+) patients for the drop of absolute PSLS value between baseline and recovery and they did not reveal statistically significant differences between groups. Figure 3 shows a typical example of positive DSE tests in CAD patients with and without DM, illustrating deeper impairment of PSLS in all stages of DSE in patient with coexisting DM. Figure 3 View largeDownload slide A representative example of two positive DSE tests (posteroinferior ischaemia in patient with CAD and DM vs. posterolateral ischaemia in patient without DM). Absolute values of PSLS in patient with CAD and DM are lower at all analysed stages (upper panel). Figure 3 View largeDownload slide A representative example of two positive DSE tests (posteroinferior ischaemia in patient with CAD and DM vs. posterolateral ischaemia in patient without DM). Absolute values of PSLS in patient with CAD and DM are lower at all analysed stages (upper panel). We found that in diabetics included in our DM (+) group, LV hypertrophy (LVMI) does not significantly affect the PSLS values at any of DSE stages. Moreover, in both subgroups of diabetics (stratified according to LVMI with average value found in the group accepted as cut-off), PSLS was impaired (see Table 6, upper part). In contrast, in patients without diabetes, PSLS was significantly decreased in subgroup with higher values of LVMI at baseline and recovery stages of DSE (subgroups divided according to the average value in non-diabetics, bottom lines of Table 6). Table 6 Separate comparison of PSLS recorded during all stages of DSE according to LVMI in patients with and without diabetes Parameters DM (+) and LVMI <137 g/m2 (n = 16) DM (+) and LVMI ≥137 g/m2 (n = 26) P-value PSLS baseline 14.1 ± 4.3 15.0 ± 3.2 ns PSLS peak 14.1 ± 4.6 13.6 ± 3.6 ns PSLS recovery 13.7 ± 3.3 14.6 ± 3.1 ns Parameters DM (−) and LVMI <126 g/m2 (n = 45) DM (−) and LVMI ≥126 g/m2 (n = 40) P-value PSLS baseline 18.3 ± 3.6 16.2 ± 4.1 0.0144 PSLS peak 17.4 ± 3.6 15.7 ± 4.3 ns PSLS recovery 16.4 ± 3.0 14.4 ± 3.6 0.0068 Parameters DM (+) and LVMI <137 g/m2 (n = 16) DM (+) and LVMI ≥137 g/m2 (n = 26) P-value PSLS baseline 14.1 ± 4.3 15.0 ± 3.2 ns PSLS peak 14.1 ± 4.6 13.6 ± 3.6 ns PSLS recovery 13.7 ± 3.3 14.6 ± 3.1 ns Parameters DM (−) and LVMI <126 g/m2 (n = 45) DM (−) and LVMI ≥126 g/m2 (n = 40) P-value PSLS baseline 18.3 ± 3.6 16.2 ± 4.1 0.0144 PSLS peak 17.4 ± 3.6 15.7 ± 4.3 ns PSLS recovery 16.4 ± 3.0 14.4 ± 3.6 0.0068 In contrast to non-diabetics group in patients with DM, the increase of LVMI did not seem to have further impact on PSLS. Values were expressed as mean ± SD. DM, diabetes mellitus; LVMI, left ventricular mass index; n, number of subjects; PSLS, peak systolic longitudinal strain. Table 6 Separate comparison of PSLS recorded during all stages of DSE according to LVMI in patients with and without diabetes Parameters DM (+) and LVMI <137 g/m2 (n = 16) DM (+) and LVMI ≥137 g/m2 (n = 26) P-value PSLS baseline 14.1 ± 4.3 15.0 ± 3.2 ns PSLS peak 14.1 ± 4.6 13.6 ± 3.6 ns PSLS recovery 13.7 ± 3.3 14.6 ± 3.1 ns Parameters DM (−) and LVMI <126 g/m2 (n = 45) DM (−) and LVMI ≥126 g/m2 (n = 40) P-value PSLS baseline 18.3 ± 3.6 16.2 ± 4.1 0.0144 PSLS peak 17.4 ± 3.6 15.7 ± 4.3 ns PSLS recovery 16.4 ± 3.0 14.4 ± 3.6 0.0068 Parameters DM (+) and LVMI <137 g/m2 (n = 16) DM (+) and LVMI ≥137 g/m2 (n = 26) P-value PSLS baseline 14.1 ± 4.3 15.0 ± 3.2 ns PSLS peak 14.1 ± 4.6 13.6 ± 3.6 ns PSLS recovery 13.7 ± 3.3 14.6 ± 3.1 ns Parameters DM (−) and LVMI <126 g/m2 (n = 45) DM (−) and LVMI ≥126 g/m2 (n = 40) P-value PSLS baseline 18.3 ± 3.6 16.2 ± 4.1 0.0144 PSLS peak 17.4 ± 3.6 15.7 ± 4.3 ns PSLS recovery 16.4 ± 3.0 14.4 ± 3.6 0.0068 In contrast to non-diabetics group in patients with DM, the increase of LVMI did not seem to have further impact on PSLS. Values were expressed as mean ± SD. DM, diabetes mellitus; LVMI, left ventricular mass index; n, number of subjects; PSLS, peak systolic longitudinal strain. We found that in patients with CAD and without or with only mild LV hypertrophy (for LVMI < 126 g/m2), the presence of DM was still related with decreased PSLS values measured at all stages of DSE. This finding was consistent with the relationships observed for the whole group not stratified according to the LVMI (compare data in Tables 5 and 7). Nevertheless, in the settings of moderate or severe LV hypertrophy (LVMI ≥ 126 g/m2 and <150 g/m2 or LVMI ≥ 150 g/m2), the decrease of strain values in diabetics when compared with respective non-diabetic group with LV hypertrophy lost its statistical significance and the additional impact of DM on PSLS was not then detectable (see Table 7). Table 7 Comparison of PSLS between diabetics and non-diabetics stratified according to LVMI Parameters DM (+) and LVMI <126 g/m2 (n = 14) DM (−) and LVMI <126 g/m2 (n = 45) P-value PSLS baseline 14.1 ± 4.0 18.3 ± 3.6 0.0005 PSLS peak 14.0 ± 4.5 17.4 ± 3.6 0.0066 PSLS recovery 13.9 ± 3.2 16.4 ± 3.0 0.0143 Parameters DM (+) and LVMI ≥126 and <150 g/m2 (n = 16) DM (−) and LVMI ≥126 and <150 g/m2 (n = 22) P-value PSLS baseline 15.2 ± 3.4 17.4 ± 4.0 ns PSLS peak 14.8 ± 4.0 17.1 ± 4.5 ns PSLS recovery 14.9 ± 3.9 15.6 ± 3.2 ns Parameter DM (+) and LVMI ≥150 g/m2 (n = 12) DM (−) and LVMI ≥150 g/m2 (n = 18) P-value PSLS baseline 14.4 ± 3.6 14.9 ± 3.9 ns PSLS peak 12.4 ± 2.9 14.1 ± 3.5 ns PSLS recovery 13.7 ± 2.1 13.2 ± 3.7 ns Parameters DM (+) and LVMI <126 g/m2 (n = 14) DM (−) and LVMI <126 g/m2 (n = 45) P-value PSLS baseline 14.1 ± 4.0 18.3 ± 3.6 0.0005 PSLS peak 14.0 ± 4.5 17.4 ± 3.6 0.0066 PSLS recovery 13.9 ± 3.2 16.4 ± 3.0 0.0143 Parameters DM (+) and LVMI ≥126 and <150 g/m2 (n = 16) DM (−) and LVMI ≥126 and <150 g/m2 (n = 22) P-value PSLS baseline 15.2 ± 3.4 17.4 ± 4.0 ns PSLS peak 14.8 ± 4.0 17.1 ± 4.5 ns PSLS recovery 14.9 ± 3.9 15.6 ± 3.2 ns Parameter DM (+) and LVMI ≥150 g/m2 (n = 12) DM (−) and LVMI ≥150 g/m2 (n = 18) P-value PSLS baseline 14.4 ± 3.6 14.9 ± 3.9 ns PSLS peak 12.4 ± 2.9 14.1 ± 3.5 ns PSLS recovery 13.7 ± 2.1 13.2 ± 3.7 ns The data show that in patients without or with only mild hypertrophy the presence of DM decreases the absolute value of longitudinal strain at all stages of DSE. Contrary this impact is abolished in patients with severe or moderate hypertrophy. Values were expressed as mean ± SD. DM, diabetes mellitus; LVMI, left ventricular mass index; n, number of subjects; PSLS, peak systolic longitudinal strain. Table 7 Comparison of PSLS between diabetics and non-diabetics stratified according to LVMI Parameters DM (+) and LVMI <126 g/m2 (n = 14) DM (−) and LVMI <126 g/m2 (n = 45) P-value PSLS baseline 14.1 ± 4.0 18.3 ± 3.6 0.0005 PSLS peak 14.0 ± 4.5 17.4 ± 3.6 0.0066 PSLS recovery 13.9 ± 3.2 16.4 ± 3.0 0.0143 Parameters DM (+) and LVMI ≥126 and <150 g/m2 (n = 16) DM (−) and LVMI ≥126 and <150 g/m2 (n = 22) P-value PSLS baseline 15.2 ± 3.4 17.4 ± 4.0 ns PSLS peak 14.8 ± 4.0 17.1 ± 4.5 ns PSLS recovery 14.9 ± 3.9 15.6 ± 3.2 ns Parameter DM (+) and LVMI ≥150 g/m2 (n = 12) DM (−) and LVMI ≥150 g/m2 (n = 18) P-value PSLS baseline 14.4 ± 3.6 14.9 ± 3.9 ns PSLS peak 12.4 ± 2.9 14.1 ± 3.5 ns PSLS recovery 13.7 ± 2.1 13.2 ± 3.7 ns Parameters DM (+) and LVMI <126 g/m2 (n = 14) DM (−) and LVMI <126 g/m2 (n = 45) P-value PSLS baseline 14.1 ± 4.0 18.3 ± 3.6 0.0005 PSLS peak 14.0 ± 4.5 17.4 ± 3.6 0.0066 PSLS recovery 13.9 ± 3.2 16.4 ± 3.0 0.0143 Parameters DM (+) and LVMI ≥126 and <150 g/m2 (n = 16) DM (−) and LVMI ≥126 and <150 g/m2 (n = 22) P-value PSLS baseline 15.2 ± 3.4 17.4 ± 4.0 ns PSLS peak 14.8 ± 4.0 17.1 ± 4.5 ns PSLS recovery 14.9 ± 3.9 15.6 ± 3.2 ns Parameter DM (+) and LVMI ≥150 g/m2 (n = 12) DM (−) and LVMI ≥150 g/m2 (n = 18) P-value PSLS baseline 14.4 ± 3.6 14.9 ± 3.9 ns PSLS peak 12.4 ± 2.9 14.1 ± 3.5 ns PSLS recovery 13.7 ± 2.1 13.2 ± 3.7 ns The data show that in patients without or with only mild hypertrophy the presence of DM decreases the absolute value of longitudinal strain at all stages of DSE. Contrary this impact is abolished in patients with severe or moderate hypertrophy. Values were expressed as mean ± SD. DM, diabetes mellitus; LVMI, left ventricular mass index; n, number of subjects; PSLS, peak systolic longitudinal strain. In the whole studied group, PSLS showed significant relationships with body mass, BMI, and waist circumference as well as diabetes for all stages of DSE in univariate analysis (see Table 8). In multivariate analysis including 16-variable LV EF, body surface area, and diabetes were independent predictors of PSLS in model with coefficient of determination (R2 = 0.51, P < 0.001). Table 8 Correlations between demographic and clinical factors and PSLS in subsequent stages of DSE in univariate analysis Parameters PSLS baseline PSLS peak PSLS recovery Body mass r = 0.35; P < 0.0001 r = 0.25; P = 0.0046 r = 0.24; P = 0.0102 Body mass index r = 0.33; P = 0.0001 r = 0.30; P = 0.0006 r = 0.27; P = 0.0029 Waist circumference r = 0.36; P < 0.0001 r = 0.35; P = 0.0001 r = 0.32; P = 0.0004 Body height r = 0.18; P = 0.044 ns ns Diabetes rho = 0.34; P = 0.0001 rho = 0.31; P = 0.0004 rho = 0.23; P = 0.013 Hypertension ns ns ns Hypertriglyceridaemia ns rho = 0.29; P = 0.0009 ns Smoking ns ns ns Parameters PSLS baseline PSLS peak PSLS recovery Body mass r = 0.35; P < 0.0001 r = 0.25; P = 0.0046 r = 0.24; P = 0.0102 Body mass index r = 0.33; P = 0.0001 r = 0.30; P = 0.0006 r = 0.27; P = 0.0029 Waist circumference r = 0.36; P < 0.0001 r = 0.35; P = 0.0001 r = 0.32; P = 0.0004 Body height r = 0.18; P = 0.044 ns ns Diabetes rho = 0.34; P = 0.0001 rho = 0.31; P = 0.0004 rho = 0.23; P = 0.013 Hypertension ns ns ns Hypertriglyceridaemia ns rho = 0.29; P = 0.0009 ns Smoking ns ns ns DSE, dobutamine stress echocardiography; PSLS, peak systolic longitudinal strain; r, Pearson correlation coefficient; rho, Spearman correlation coefficient. Table 8 Correlations between demographic and clinical factors and PSLS in subsequent stages of DSE in univariate analysis Parameters PSLS baseline PSLS peak PSLS recovery Body mass r = 0.35; P < 0.0001 r = 0.25; P = 0.0046 r = 0.24; P = 0.0102 Body mass index r = 0.33; P = 0.0001 r = 0.30; P = 0.0006 r = 0.27; P = 0.0029 Waist circumference r = 0.36; P < 0.0001 r = 0.35; P = 0.0001 r = 0.32; P = 0.0004 Body height r = 0.18; P = 0.044 ns ns Diabetes rho = 0.34; P = 0.0001 rho = 0.31; P = 0.0004 rho = 0.23; P = 0.013 Hypertension ns ns ns Hypertriglyceridaemia ns rho = 0.29; P = 0.0009 ns Smoking ns ns ns Parameters PSLS baseline PSLS peak PSLS recovery Body mass r = 0.35; P < 0.0001 r = 0.25; P = 0.0046 r = 0.24; P = 0.0102 Body mass index r = 0.33; P = 0.0001 r = 0.30; P = 0.0006 r = 0.27; P = 0.0029 Waist circumference r = 0.36; P < 0.0001 r = 0.35; P = 0.0001 r = 0.32; P = 0.0004 Body height r = 0.18; P = 0.044 ns ns Diabetes rho = 0.34; P = 0.0001 rho = 0.31; P = 0.0004 rho = 0.23; P = 0.013 Hypertension ns ns ns Hypertriglyceridaemia ns rho = 0.29; P = 0.0009 ns Smoking ns ns ns DSE, dobutamine stress echocardiography; PSLS, peak systolic longitudinal strain; r, Pearson correlation coefficient; rho, Spearman correlation coefficient. Finally, we compared the data from this analysis with the second part of our group which we previously described (Wierzbowska-Drabik et al.6) and which had no CAD and was divided according to DM presence. This comparison displayed a similar impairment of strain in patients with the presence of one factor DM (+) or CAD (+) and the deepest impairment of LV function when both factors were present. Interestingly, this relationship was observed at all DSE stages, (see Figure 4 displaying data from Wierzbowska-Drabik et al.6 and from this study). Figure 4 View largeDownload slide The comparison of mean absolute values of global PSLS at different stages of DSE according to the presence of CAD, DM, or both these factors. The data illustrate the equivalent impact of isolated DM and CAD without diabetes on LV myocardial strain and the synergistic influence of the coexistence of both these factors. The number of patients included in figure groups: 1. CAD (−) DM (−), n = 85; 2. CAD (−) DM (+), n = 25 (asterisk indicates data from the study by Wierzbowska-Drabik et al.6); 3. CAD (+) DM (−), n = 85; 4. CAD (+) DM (+), n = 42 (data from this study). In the majority of comparisons, the significantly lower strain values were observed in CAD patients when compared with their counterparts without CAD. Nevertheless, this significance was limited to trend only at peak stage of DSE in subgroup without DM and was totally effaced at recovery stage in subgroup with DM. The last finding may suggest the delayed recovery and even further impairment of contractile left ventricular function in patients with DM submitted to DSE. Figure 4 View largeDownload slide The comparison of mean absolute values of global PSLS at different stages of DSE according to the presence of CAD, DM, or both these factors. The data illustrate the equivalent impact of isolated DM and CAD without diabetes on LV myocardial strain and the synergistic influence of the coexistence of both these factors. The number of patients included in figure groups: 1. CAD (−) DM (−), n = 85; 2. CAD (−) DM (+), n = 25 (asterisk indicates data from the study by Wierzbowska-Drabik et al.6); 3. CAD (+) DM (−), n = 85; 4. CAD (+) DM (+), n = 42 (data from this study). In the majority of comparisons, the significantly lower strain values were observed in CAD patients when compared with their counterparts without CAD. Nevertheless, this significance was limited to trend only at peak stage of DSE in subgroup without DM and was totally effaced at recovery stage in subgroup with DM. The last finding may suggest the delayed recovery and even further impairment of contractile left ventricular function in patients with DM submitted to DSE. Moreover, the comparison of PSLS limited to the subgroup with negative visually assessed DSE results indicated on potential utility of longitudinal strain for differentiation between true-negative and false-negative DSE examinations (see Figure 5). The data show that patients with CAD with assessed visually negative DSE presents in the majority of comparisons lower absolute PSLS value than their true negative counterparts. As far as our data are concerned, the statistical significance was achieved only in non-diabetics during recovery phase, but it may depend from very limited number of false-negative subgroup. Figure 5 View largeDownload slide The comparison of mean absolute values of global PSLS at different stages of DSE according to the presence of CAD, DM, or both these factors limited to the patients with negative results of visually assessed DSE (negative tests according to wall mottion analysis). The data illustrate the potential of global longitudinal strain for the detection of systolic function impairment in patients with CAD which was not detected during conventional visually assessed DSE. Despite limited number of subjects in groups with false-negative DSE, the global PSLS was significantly diminished in CAD (+) group in patients without DM as measured during recovery stage. Moreover, all but one (unexpectedly concerning peak DSE stage) numeric values of GLS in CAD (+) were lower than the respective measurements for CAD (−) patients. The number of patients in all figure groups: 1. CAD (−) DM (−), n = 61; 2. CAD (−) DM (+), n = 22 (asterisk indicates data from study by Wierzbowska-Drabik et al.6); 3. CAD (+) DM (−), n = 13; and 4. CAD (+) DM (+), n = 4 (data from this study). Figure 5 View largeDownload slide The comparison of mean absolute values of global PSLS at different stages of DSE according to the presence of CAD, DM, or both these factors limited to the patients with negative results of visually assessed DSE (negative tests according to wall mottion analysis). The data illustrate the potential of global longitudinal strain for the detection of systolic function impairment in patients with CAD which was not detected during conventional visually assessed DSE. Despite limited number of subjects in groups with false-negative DSE, the global PSLS was significantly diminished in CAD (+) group in patients without DM as measured during recovery stage. Moreover, all but one (unexpectedly concerning peak DSE stage) numeric values of GLS in CAD (+) were lower than the respective measurements for CAD (−) patients. The number of patients in all figure groups: 1. CAD (−) DM (−), n = 61; 2. CAD (−) DM (+), n = 22 (asterisk indicates data from study by Wierzbowska-Drabik et al.6); 3. CAD (+) DM (−), n = 13; and 4. CAD (+) DM (+), n = 4 (data from this study). Discussion Our study documents decreased longitudinal function of LV in CAD patients with coexisting type 2 DM in comparison with CAD without diabetes at rest, during, and after dobutamine stress test, which, according to our knowledge, was not published so far. Importantly, this global and regional impairment could be detected only with deformation analysis, because EF, systolic velocity of mitral annulus motion or WMSI did not differ between the compared groups. Moreover, our groups were comparable according to diastolic function parameters: lateral mitral annular velocity and left atrial volume index, although LV mass index was higher in DM (+). Nevertheless, we did not find significant correlation between LVMI and PSLS in patients with diabetes, which allowed us to the assumption that observed lower results of PSLS in DM (+) group does not depend on higher mean LVMI in our diabetic subjects. On the other hand, in further subgroup analysis, lower values of PSLS in diabetics were still significant for all DSE stages in patients with the LVMI < 126 g/m2 so showing no or mild hypertrophy of LV walls, whereas in patients with moderate and severe hypertrophy, the additional impact of DM was not expressed (Table 7). However, these related to subgroups analysis pilot data are limited by small number of included subjects so they should be proved in further studies. Similar advancement (expressed as SYNTAX score) and localization of significant lesions in coronary arteries allow for assumption that the presence of diabetes and strictly related hypertriglyceridaemia are the main determinants of the observed PSLS impairment. Interestingly, in comparison with our previously published analysis in which we observed diminished PSLS in diabetics patients without CAD mainly during recovery stage of DSE, in this study, the detrimental impact of DM on cardiac function seems to be stronger and overt also at rest and peak stage of DSE.6 Moreover, counter-intuitive at first look observation that the dobutamine challenge did not deepen the differences observed at rest was accomplished. It may suggest that the direct impact of the significant coronary stenoses effaces the more subtle influence of DM on systolic myocardial function during DSE or that the assessment of PSLS is more difficult at higher heart rates (reaching in our study an average value of 138 bpm). The increase of technical challenge at peak stage of DSE was not only suspected but also documented as the deacresed feasibility (more segments excluded from the analysis) and nearly twice increased interobserver variability between baseline and peak stage of test (from 8.7% to 16%). Nevertheless, these technical limitations may not solely explain the observed relationships because the intrinsic features of strain values diminishing during very rapid heart rates (HRs) and shortened cardiac cycles may limit diagnostic utility of the recordings during high-level tachycardia. Currently, there are still few published data concerning strain analysis when the HR is close to 140 bpm in groups including >100 patients with confirmed CAD. The typical reaction of PSLS at lower level of induced HR is the increase of longitudinal deformation, whereas during further increase of tachycardia the deformation values decrease, as it was in our group. This biphasic pattern of strain changes increasing at low stress but constant or decreasing as the HR further increases was described in earlier and more recent studies with DSE or exercise test in healthy children.9–11 These observations, as well as recent studies documenting the lack of diagnostic benefit of strain assessment during peak stage of exercise test in such settings as aortic stenosis or better documented values of resting then exercise or dobutamine-related deformation in CAD diagnosis, may additionally prompt to focusing on recovery stage when the HR is close to baseline but some detrimental effects may be still present at least in the aspect of ischaemia detection.12–14 The diagnostic potential of PSLS assessment during DSE for myocardial ischaemia detection was in our study observed in the combined analysis of data from patients with and without CAD showing negative DSE test according to visual evaluation (Figure 5). Non-diabetics patients with false-negative visual test presented significantly lower PSLS during recovery phase of DSE than ‘true-negative’ subjects (15.1 ± 3.1% vs. 17.6 ± 3.1%, P = 0.0102). Strain analysis in patients with coexisting CAD and DM in comparison with patients without DM and similar severity of CAD, especially during all stages of stress test, is unique in the literature. Moreover, published data on resting assessment of myocardial deformation raise numerous controversies. Loncarevic et al.15 in group of 70 patients with type 2 DM without hypertension and CAD reported impaired global longitudinal strain and early diastolic strain rate in comparison with healthy group. The association of DM with arterial hypertension (HA) or CAD caused further decrease in the absolute values of longitudinal strain from 18.71 ± 1.86% in controls, through 17.36 ± 1.8% in isolated DM to 16.31 ± 2.79% in DM with HA, and 16.26 ± 2.84% in DM and CAD. Similarly in our data, patients without CAD and DM [CAD (−)/DM (−)] showed the highest absolute values of global PSLS (e.g. −18.7 ± 3.3% at rest), patients with one factor DM (+) or CAD (+) showed lowered and very similar values of strain, reflecting the equivalent impact of isolated DM or CAD without DM on myocardial function and at last patients with CAD and DM showed the deepest impairment of LV function. Interestingly this relationship was observed at all DSE stages (Figure 4, data from Wierzbowska-Drabik et al.6 and this study). In the study of Enomoto et al.,16 diabetics in comparison with healthy controls showed not only lowered longitudinal and circumferential strain but also area strain obtained with 3D speckle-tracking method (12.0 ± 3.0% vs. 16.2 ± 1.9%, 27.7 ± 7.1% vs. 32.2 ± 5.7%, 37.6 ± 7.6% vs. 44.0 ± 6.2%, respectively; P < 0.001), and these changes correlated with severity of microvascular dysfunction measured as the advancement of nephropathy, neuropathy, and retinopathy. In another study, Bonapace et al.17 observed in a 2-year follow-up that impaired longitudinal strain in patients with DM had predictive value for new onset of atrial fibrillation. In multivariate analysis in our study, the presence of type 2 DM, value of EF, and body surface area were independent predictors of PSLS. These results underlined the utility of strain analysis in the detection of functional LV changes related with DM and potentially its advancement and treatment. This seems especially important considering that some glucose-lowering medications were associated with an increased risk of developing heart failure.18 The following observations offer in our opinion significant novelty and belong to the potential clinical implications of our study: the presence of DM impairs global (and regional) LV myocardial function, which may be observed also in patients with coexisting CAD. The significant differences were observed at rest as well as during DSE and recovery when compared with CAD without DM. our data from this and previous studies provide some reference values of PSLS for patients who are often examined with stress echocardiography and may be categorized according to CAD and DM presence. Interestingly, the impact of isolated DM or CAD on PSLS seems to be similar, whereas the coexistence of CAD and DM exerts the strongest influence on myocardial contractility at all stages of DSE (Table 4). the observation that dobutamine challenge does not increase the resting difference of PSLS between patients with and without DM and CAD have hypothesis-generating character and should be confirmed in further, larger studies. Hypothetically, it may be related to the predominant effect of significant stenoses of coronary arteries that were present in both groups and effaced the impact of DM during stress test. Analogously, the presence of CAD reversed the protective effect of female sex on some diastolic function parameters and the presence of DM abolished the prognostic significance of anti-ischaemic therapy continued in the time of stress echocardiography in some of our previous studies.19,20 Our study is one of the first attempting at detailed characteristic of LV function in diabetics in the settings of coexisting CAD and stress challenge. Although focused on longitudinal strain, we tried to conduct comprehensive assessment during DSE, including also less examined recovery stage. Because of variability of PSLS values related to localization in the LV region, we looked also at segmental and regional functions and did separate analysis concerning middle LV segments. Our results confirm that PSLS can be considered as an emerging tool in the assessment of diabetic myocardial dysfunction. Limitations Small number of examined diabetics (42 subjects) and the lack of detailed biochemical characteristics represent the main limitations of our study which precludes also the potential subanalyses related to severity of DM. Despite similar age, gender, and basically assessed CAD advancement, the DM patients exhibited higher body mass, BMI, waist circumference, body surface area, and LVMI, which might influence the obtained PSLS results. According to clinically oriented guidelines,21 we chose to focus on longitudinal strain for practical aspects of easy, on-system automated imaging method, which can serve as a supplement to routine DSE analysis. Aiming at different stages of DSE, global and regional analyses, and integration of relevant data from previous part of study (four different groups of patients divided according to CAD and DM presence), we limited the analyses to the most popular parameter PSLS without including the postsystolic shortening. Similarly, the additional long-term analysis of prognostic significance of reduced global PSLS at rest and during DSE may potentially increase the clinical utility of our observations. Finally, our data were derived from a single vendor of echocardiographic equipment, and the studied patients were recruited from a single cardiology department. Conclusions Longitudinal LV deformation is more impaired in patients with CAD and DM in comparison with their counterparts with similar extent of coronary atherosclerosis but without DM. This finding was detectable not only at rest but also at peak and recovery stage of DSE and concerned not only on global parameters but also on individual LV segments. DM is an independent predictor of baseline PSLS, which suggests a specific impact on the development of LV dysfunction and, subsequently, heart failure. Moreover, the comparison with our previous data suggest that the severity of detrimental effect of isolated DM and CAD without DM on global LV PSLS is similar, but the coexistence of both these factors exerts the strongest influence at all stages of DSE. Funding The work was supported by a grant from the State Committee for Scientific Research (number N N402 5002 40). Conflict of interest: None declared. References 1 Ryden L , Grant PJ , Anker SD , Berne C , Cosentino F , Danchin N et al. ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD) . Eur Heart J 2013 ; 34 : 3035 – 87 . Google Scholar CrossRef Search ADS PubMed 2 Piepoli MF , Hoes AW , Agewall S , Albus C , Brotons C , Catapano AL et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European Society of Cardiology and other societies on Cardiovascular Disease Prevention in Clinical Practice. Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR) . Eur Heart J 2016 ; 37 : 2315 – 81 . Google Scholar CrossRef Search ADS PubMed 3 Zalewska-Adamiec M , Bachorzewska-Gajewska H , Malyszko J , Tomaszuk-Kazberuk A , Nowak K , Hirnle T et al. Impact of diabetes on mortality and complications after coronary artery by-pass graft operation in patients with left main coronary artery disease . Adv Med Sci 2014 ; 59 : 250 – 5 . Google Scholar CrossRef Search ADS PubMed 4 Ernande L , Bergerot C , Rietzschel ER , De Buyzere ML , Thibault H , PignonBlanc PG et al. Diastolic dysfunction in patients with type 2 diabetes mellitus: is it really the first marker of diabetic cardiomyopathy? J Am Soc Echocardiogr 2011 ; 24 : 1268 – 75 . Google Scholar CrossRef Search ADS PubMed 5 Nishino M. Echocardiographic surrogate marker for diabetic cardiomyopathy . Circ J 2015 ; 79 : 1687 – 8 . http://dx.doi.org/10.1253/circj.CJ-15-0540 Google Scholar CrossRef Search ADS PubMed 6 Wierzbowska-Drabik K , Hamala P , Kasprzak JD. Delayed longitudinal myocardial function recovery after dobutamine challenge as a novel presentation of myocardial dysfunction in type 2 diabetic patients without angiographic coronary artery disease . Eur Heart J Cardiovasc Imaging 2015 ; 16 : 676 – 83 . Google Scholar PubMed 7 Wierzbowska-Drabik K , Hamala P , Roszczyk N , Lipiec P , Plewka M , Kręcki R et al. Feasibility and correlation of standard 2D speckle tracking echocardiography and automated function imaging derived parameters of left ventricular function during dobutamine stress test . Int J Cardiovasc Imaging 2014 ; 30 : 729 – 37 . Google Scholar CrossRef Search ADS PubMed 8 Wierzbowska-Drabik K , Plewka M , Kasprzak JD. Variability of longitudinal strain in left ventricular segments supplied by non-stenosed coronary artery: insights from speckle tracking analysis of dobutamine stress echocardiograms in patients with high coronary risk profile . Arch Med Sci 2017 ; 1 : 82 – 92 . Google Scholar CrossRef Search ADS 9 Voigt JU , Exner B , Schmiedehausen K , Huchzermeyer C , Reulbach U , Nixdorff U et al. Strain-rate imaging during dobutamine stress echocardiography provides objective evidence of inducible ischemia . Circulation 2003 ; 107 : 2120 – 6 . 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Google Scholar CrossRef Search ADS PubMed 13 Norum BI , Ruddox V , Edvardsen T , Otterstad JE. Diagnostic accuracy of left ventricular longitudinal function by speckle tracking echocardiography to predict significant coronary stenosis. A systematic review . BMC Med Imaging 2015 ; 15 : 25 . Google Scholar CrossRef Search ADS PubMed 14 Aggeli C , Lagoudakou S , Felekos I , Panagopoulou V , Kastellanos S , Toutouzas K et al. Two-dimensional speckle tracking for the assessment of coronary artery disease during dobutamine stress echo: clinical tool or merely research method . Cardiovasc Ultrasound 2015 ; 13 : 43. Google Scholar CrossRef Search ADS PubMed 15 Loncarevic B , Trifunovic D , Soldatovic I , Vujisic-Tesic B. Silent diabetic cardiomyopathy in everyday practice, a clinical and echocardiographic study . BMC Cardiovasc Disord 2016 ; 16 : 242. DOI 10.1186/s12872-016-0395-z Google Scholar CrossRef Search ADS PubMed 16 Enomoto M , Ishizu T , Seo Y , Kameda Y , Suzuki H , Shimano H et al. Myocardial dysfunction identified by three-dimensional speckle tracking echocardiography in type 2 diabetes patients relates to complications of microangiopathy . J Cardiol 2016 ; 68 : 282 – 7 . Google Scholar CrossRef Search ADS PubMed 17 Bonapace S , Valbusa F , Bertolini L , Zenari L , Canali G , Lanzoni L et al. Early impairment in left ventricular longitudinal systolic function is associated with an increased risk of incident atrial fibrillation in patients with type 2 diabetes . J Diabetes Complications 2017 ; 31 : 413 – 8 . Google Scholar CrossRef Search ADS PubMed 18 Scirica BM , Braunwald E , Raz I , Cavender MA , Morrow DA , Jarolim P et al. ; SAVOR-TIMI 53 Steering Committee and Investigators . Heart failure, saxagliptin and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial . Circulation 2014 ; 130 : 1579 – 88 . Google Scholar CrossRef Search ADS PubMed 19 Wierzbowska-Drabik K , Krzemińska-Pakuła M , Kurpesa M , Trzos E , Rechciński T , Wejner-Mik P et al. Impact of gender on left ventricle function in postmenopausal women and age-matched men: analysis of echocardiographic parameters in healthy participants and patients with coronary artery disease . Menopause 2010 ; 17 : 560 – 5 . Google Scholar PubMed 20 Cortigiani L , Borelli L , Raciti M , Bovenzi F , Picano E , Molinaro S et al. Prediction of mortality by stress echocardiography in 2 835 diabetic and 11 305 nondiabetic patients . Circ Cardiovasc Imaging 2015 ; 8 : e002757 . Google Scholar CrossRef Search ADS PubMed 21 Lang RM , Badano LP , Mor-Avi V , Afilalo J , Armstrong A , Ernande L et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging . Eur Heart J Cardiovasc Imaging 2015 ; 16 : 233 – 71 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal – Cardiovascular Imaging Oxford University Press

Diabetes as an independent predictor of left ventricular longitudinal strain reduction at rest and during dobutamine stress test in patients with significant coronary artery disease

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Oxford University Press
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
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2047-2404
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10.1093/ehjci/jex315
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Abstract

Abstract Aims Diabetes (DM) is a strong cardiovascular risk factor modifying also the left ventricular (LV) function that may be objectively assessed with echocardiographic strain analysis. Although the impact of isolated DM on myocardial deformation has been already studied, few data concern diabetics with coronary artery disease (CAD), especially in all stages of dobutamine stress echocardiography (DSE). We compared LV systolic function during DSE in CAD with and without DM using state-of-the art speckle-tracking quantification and assessed the impact of DM on LV systolic strain. Methods and results DSE was performed in 250 patients with angina who afterwards had coronarography with ≥50% stenosis in the left main artery and ≥70% in other arteries considered as significant. In this analysis, we included 127 patients with confirmed CAD: 42 with DM [DM(+); mean age 64 ± 9 years] and 85 patients without DM [DM(−); mean age 63 ± 9 years]. The severity of CAD and LV ejection fraction (EF) were similar in both groups. Global and regional LV peak systolic longitudinal strain (PSLS) revealed in all DSE phases lower values in DM(+) group: 14.5 ± 3.6% vs. 17.4 ± 4.0% at rest; P = 0.0001, 13.8 ± 3.9% vs. 16.7 ± 4.0% at peak stress; P = 0.0002, and 14.2 ± 3.1% vs. 15.5 ± 3.5% at recovery; P = 0.0432 for global parameters, although dobutamine challenge did not enhance further resting differences. LV EF, body surface area, and diabetes were independent predictors for strain in 16-variable model (R2 = 0, 51, P < 0.001). Conclusion PSLS although diminished in both groups with CAD was lower in diabetics at all DSE stages, and DM was an independent predictor of this impairment. However, the dobutamine challenge did not deepen the resting differences, suggesting that the direct impact of coronary stenoses effaces the influence of DM during DSE. The comparison with our previous data revealed synergistic, detrimental effect of coexisting CAD and DM on myocardial strain. dobutamine stress echocardiography , coronary artery disease , diabetes , speckle tracking , automated function imaging , systolic longitudinal strain Introduction Diabetes mellitus (DM) accelerates atherosclerosis, doubles the risk of cardiovascular complications, contributes to the development of diastolic heart failure, and worsens the results of surgical treatment.1–3 Because the changes of heart function in DM may be initially subtle and poorly detectable with conventional echocardiography, the introduction of novel quantitative tools based on speckle-tracking analysis to assess myocardial deformation may improve the understanding of cardiac mechanics. Global left ventricular (LV) strain was proposed as a marker for diabetic cardiomyopathy, potentially more sensitive and precise than parameters of diastolic function and easier for obtaining than coronary flow reserve in distal left anterior descending artery (LAD).4,5 Moreover, the evaluation of longitudinal strain during stress echocardiography seems to offer additional diagnostic value in DM without significant coronary artery disease (CAD), revealing delayed recovery of peak systolic longitudinal strain (PSLS) in diabetics.6 Nevertheless, the objectively measured, quantitative influence of DM onto contractile myocardial function in subjects with confirmed CAD, especially in the settings of dobutamine stress echocardiography (DSE), was not so far adequately examined. The aim of our study was to compare quantitative, inherent indices of the LV systolic function during all stages of DSE (baseline, peak and recovery) in patients with significant CAD and coexistent DM [DM (+) group] and with CAD but without DM [DM (−) group] using automated function imaging (AFI), speckle tracking-based method available on board of advanced echocardiographic systems. Additionally, we evaluated the impact of DM on LV PSLS in multivariate analysis including 16 clinical and echocardiographic variables. Methods Study group and protocol As we previously described in the literature,6,7 we examined 250 subjects with angina by DSE with early atropine administration achieving 238 diagnostic tests (105 women, mean age 62 ± 90 years). The study flow chart is shown in Figure 1. All patients were in sinus rhythm and had no significant valve disease (except for mild-to-moderate insufficiency) as well as left bundle branch block conduction pattern. Exclusion criteria included contraindications to dobutamine and atropine. Study group in this analysis involved 127 patients with confirmed CAD: 42 with DM, diagnosed according to the standard criteria as type 2 of DM [DM (+) group], mean age 64 ± 9 years, 12 women and 85 patients with CAD but without DM [DM (−) group], mean age 63 ± 9, 25 women. All the included patients in this study were different from the group described in Wierzbowska-Drabik et al.6,7 (where 111 patients without significant CAD were analysed). Figure 1 View largeDownload slide Flow chart of the study patients examined by dobutamine stress echocardiography. CAD, coronary artery disease; CT, computed tomography; Cx, circumflex artery; DM, diabetes mellitus; DSE, dobutamine stress echocardiography. Figure 1 View largeDownload slide Flow chart of the study patients examined by dobutamine stress echocardiography. CAD, coronary artery disease; CT, computed tomography; Cx, circumflex artery; DM, diabetes mellitus; DSE, dobutamine stress echocardiography. Coronary arteries were evaluated by invasive coronary angiography or computed tomography no later than 3 months after DSE. Significant stenosis was defined as narrowing ≥50% in the left main coronary artery or ≥70% in other major arteries. All subjects gave written informed consent, and the protocol was approved by Ethical Commission of Medical University of Lodz. Resting and stress echocardiography Transthoracic echocardiography was performed with VIVID 7 Dimension (GE Vingmed Ultrasound AS, Horten, Norway) using M4S probe in harmonic mode 2.0/4.3 MHz with maximal frame per second (FPS) count available at necessary sector width, achieving on average 82 ± 8 FPS. Echocardiographic measurements were performed following American Society of Echocardiography/European Association of Echocardiography guidelines. LV EF fraction was calculated according to the modified Simpson method from triplane mode recorded with 3D probe. LV contractility was assessed visually and classified for each segment as normokinesis (Score 1), hypokinesis (Score 2), akinesis or dyskinesis (Score 3 or 4) using a 18-segment model dividing each of 6 walls into 3 segments: basal, mid, and apical. Wall motion score index (WMSI) was estimated as the sum of scores for all segments divided by the number of segments. The worsening of contractility by at least one grade in two or more adjacent segments was consistent with a positive DSE. Dobutamine was administered in the intravenous infusion in doses of 10, 20, 30 and 40 µg/kg/min during 3-min stages, whereas atropine was added in 0.5 mg fractional doses after the second stage of infusion, up to the total dose of 2 mg. The infusion of dobutamine was stopped when heart rate limit, positive test, or safety criteria were fulfilled. The assessment of myocardial deformation Standard echocardiographic views (three apical and three LV short axis) were stored at baseline, peak, and recovery. Recovery images were recorded 10 min after dobutamine stopping. The calculation of deformation was done using EchoPac 6.1.0 workstation (GE Vingmed Ultrasound). Regional and global PSLS was calculated using AFI method. Briefly, three points (two on basal and one on apical endocardium) were indicated in each apical view, and computer-generated region of interest was optimized and approved by the operator. Peak longitudinal deformation achieved for any segment before the aortic valve closure (AVC) was recorded as PSLS. AVC was defined with the Doppler recording. The rounded segmental values of PSLS were displayed as a polar map with additional calculation of the averaged (from 6 segments) and global (from 18 segments) parameters. For each LV segment, the value of PSLS was measured at baseline, peak, and recovery. Aiming at the simplification of analysis we chose the mid segments of lateral, inferior wall and anterior septum as marker, sentinel segments for the regions supplied by the circumflex (Cx), right coronary artery (RCA) and LAD, respectively. Statistical analysis Statistical analysis was performed using MedCalc version 12.1.4. (Frank Schoonjans, Belgium). Continuous variables were expressed as means and standard deviations. Mean values were compared with the Student’s t test. The χ2 test was used to test the dichotomous variables distribution. Correlations were assessed using Pearson and Spearman coefficients for continuous and categorical variables, respectively, and multivariate analysis by multiple regression was performed. The values of P < 0.05 were considered statistically significant. Data for interobserver and intraobserver variability of AFI analysis before and during DSE were calculated as coefficients of variation in randomly selected subgroups and published in former articles.7,8 Briefly, interobserver variability (coefficient of variance) calculated for segmental longitudinal strain was 8.7% and 16%, respectively, for AFI method at baseline and peak stage of DSE. Results The compared groups did not differ according to age and gender, as well as the prevalence of hypertension, smoking, and hypercholesterolaemia, although DM (+) patients had significantly higher body mass and waist circumference. Similarily, blood pressure, heart rate, history of myocardial infarction [45% in DM (+) group and 49% in DM (−) group, P = ns], and medical treatment of CAD (beyond diabetes medications) were also similar (Table 1). Moreover, both groups presented similar mean LV EF and WMSI (see Table 2) as well as comparable severity and localization of CAD lesions (Table 3). Table 1 Comparison of demographics, risk factors, and treatment between DM (+) and DM (−) groups Parameters DM (+) DM (−) P-value n = 42 n = 85 Age (years), mean ± SD 64 ± 9 63 ± 8 ns Gender (numbers F/M) 12/30 25/60 ns Height (cm), mean ± SD 169 ± 8 168 ± 9 ns Body mass (kg), mean ± SD 87.7 ± 16.6 80.0 ± 14.8 0.0091 Body mass index (kg/m2), mean ± SD 30.7 ± 5.7 28 ± 3.9 0.0022 Waist circumference (cm), mean ± SD 103.4 ± 15.8 96.1 ± 14.2 0.0097 Body surface area (m2), mean ± SD 2.02 ± 0.2 1.92 ± 0.2 0.0081 Blood pressure systolic (mmHg), mean ± SD 132 ± 17 129 ± 19 ns Blood pressure diastolic (mmHg), mean ± SD 73 ± 9 71 ± 11 ns Heart rate at baseline (bpm), mean ± SD 65 ± 7 67 ± 10 ns Obesity BMI ≥30 kg/m2, n (%) 16 (38) 26 (31) ns Hypertension, n (%) 41 (98) 79 (93) ns Smoking, n (%) 32 (76) 52 (61) ns Hypercholesterolaemia, n (%) 42 (100) 76 (89) ns Hypertriglicerydaemia, n (%) 39 (93) 49 (58) 0.0001 Total cholesterol, mean ± SD 193 ± 46 187 ± 46 ns LDL cholesterol, mean ± SD 111 ± 37 108 ± 42 ns HDL cholesterol, mean ± SD 49 ± 18 52 ± 21 ns Triglycerides, mean ± SD 183 ± 124 138 ± 90 0.0214 Family history of CAD, n (%) 8 (19) 14 (16) ns History of myocardial infarction 19 (45) 42 (49) ns Typical angina 29 (69) 66 (78) ns Non-typical angina 13 (31) 19 (22) Acetylsalicylic acid, n (%) 42 (100) 83 (98) ns Clopidogrel, n (%) 26 (62) 39 (46) ns Beta-blockers, n (%) 38 (90) 76 (89) ns Angiotensin-converting enzyme inhibitor, n (%) 41 (98) 74 (87) ns Statin, n (%) 42 (100) 82 (96) ns Long-acting nitrates, n (%) 30 (71) 64 (75) ns Parameters DM (+) DM (−) P-value n = 42 n = 85 Age (years), mean ± SD 64 ± 9 63 ± 8 ns Gender (numbers F/M) 12/30 25/60 ns Height (cm), mean ± SD 169 ± 8 168 ± 9 ns Body mass (kg), mean ± SD 87.7 ± 16.6 80.0 ± 14.8 0.0091 Body mass index (kg/m2), mean ± SD 30.7 ± 5.7 28 ± 3.9 0.0022 Waist circumference (cm), mean ± SD 103.4 ± 15.8 96.1 ± 14.2 0.0097 Body surface area (m2), mean ± SD 2.02 ± 0.2 1.92 ± 0.2 0.0081 Blood pressure systolic (mmHg), mean ± SD 132 ± 17 129 ± 19 ns Blood pressure diastolic (mmHg), mean ± SD 73 ± 9 71 ± 11 ns Heart rate at baseline (bpm), mean ± SD 65 ± 7 67 ± 10 ns Obesity BMI ≥30 kg/m2, n (%) 16 (38) 26 (31) ns Hypertension, n (%) 41 (98) 79 (93) ns Smoking, n (%) 32 (76) 52 (61) ns Hypercholesterolaemia, n (%) 42 (100) 76 (89) ns Hypertriglicerydaemia, n (%) 39 (93) 49 (58) 0.0001 Total cholesterol, mean ± SD 193 ± 46 187 ± 46 ns LDL cholesterol, mean ± SD 111 ± 37 108 ± 42 ns HDL cholesterol, mean ± SD 49 ± 18 52 ± 21 ns Triglycerides, mean ± SD 183 ± 124 138 ± 90 0.0214 Family history of CAD, n (%) 8 (19) 14 (16) ns History of myocardial infarction 19 (45) 42 (49) ns Typical angina 29 (69) 66 (78) ns Non-typical angina 13 (31) 19 (22) Acetylsalicylic acid, n (%) 42 (100) 83 (98) ns Clopidogrel, n (%) 26 (62) 39 (46) ns Beta-blockers, n (%) 38 (90) 76 (89) ns Angiotensin-converting enzyme inhibitor, n (%) 41 (98) 74 (87) ns Statin, n (%) 42 (100) 82 (96) ns Long-acting nitrates, n (%) 30 (71) 64 (75) ns CAD, coronary artery disease; DM, diabetes; n, number of subjects. Table 1 Comparison of demographics, risk factors, and treatment between DM (+) and DM (−) groups Parameters DM (+) DM (−) P-value n = 42 n = 85 Age (years), mean ± SD 64 ± 9 63 ± 8 ns Gender (numbers F/M) 12/30 25/60 ns Height (cm), mean ± SD 169 ± 8 168 ± 9 ns Body mass (kg), mean ± SD 87.7 ± 16.6 80.0 ± 14.8 0.0091 Body mass index (kg/m2), mean ± SD 30.7 ± 5.7 28 ± 3.9 0.0022 Waist circumference (cm), mean ± SD 103.4 ± 15.8 96.1 ± 14.2 0.0097 Body surface area (m2), mean ± SD 2.02 ± 0.2 1.92 ± 0.2 0.0081 Blood pressure systolic (mmHg), mean ± SD 132 ± 17 129 ± 19 ns Blood pressure diastolic (mmHg), mean ± SD 73 ± 9 71 ± 11 ns Heart rate at baseline (bpm), mean ± SD 65 ± 7 67 ± 10 ns Obesity BMI ≥30 kg/m2, n (%) 16 (38) 26 (31) ns Hypertension, n (%) 41 (98) 79 (93) ns Smoking, n (%) 32 (76) 52 (61) ns Hypercholesterolaemia, n (%) 42 (100) 76 (89) ns Hypertriglicerydaemia, n (%) 39 (93) 49 (58) 0.0001 Total cholesterol, mean ± SD 193 ± 46 187 ± 46 ns LDL cholesterol, mean ± SD 111 ± 37 108 ± 42 ns HDL cholesterol, mean ± SD 49 ± 18 52 ± 21 ns Triglycerides, mean ± SD 183 ± 124 138 ± 90 0.0214 Family history of CAD, n (%) 8 (19) 14 (16) ns History of myocardial infarction 19 (45) 42 (49) ns Typical angina 29 (69) 66 (78) ns Non-typical angina 13 (31) 19 (22) Acetylsalicylic acid, n (%) 42 (100) 83 (98) ns Clopidogrel, n (%) 26 (62) 39 (46) ns Beta-blockers, n (%) 38 (90) 76 (89) ns Angiotensin-converting enzyme inhibitor, n (%) 41 (98) 74 (87) ns Statin, n (%) 42 (100) 82 (96) ns Long-acting nitrates, n (%) 30 (71) 64 (75) ns Parameters DM (+) DM (−) P-value n = 42 n = 85 Age (years), mean ± SD 64 ± 9 63 ± 8 ns Gender (numbers F/M) 12/30 25/60 ns Height (cm), mean ± SD 169 ± 8 168 ± 9 ns Body mass (kg), mean ± SD 87.7 ± 16.6 80.0 ± 14.8 0.0091 Body mass index (kg/m2), mean ± SD 30.7 ± 5.7 28 ± 3.9 0.0022 Waist circumference (cm), mean ± SD 103.4 ± 15.8 96.1 ± 14.2 0.0097 Body surface area (m2), mean ± SD 2.02 ± 0.2 1.92 ± 0.2 0.0081 Blood pressure systolic (mmHg), mean ± SD 132 ± 17 129 ± 19 ns Blood pressure diastolic (mmHg), mean ± SD 73 ± 9 71 ± 11 ns Heart rate at baseline (bpm), mean ± SD 65 ± 7 67 ± 10 ns Obesity BMI ≥30 kg/m2, n (%) 16 (38) 26 (31) ns Hypertension, n (%) 41 (98) 79 (93) ns Smoking, n (%) 32 (76) 52 (61) ns Hypercholesterolaemia, n (%) 42 (100) 76 (89) ns Hypertriglicerydaemia, n (%) 39 (93) 49 (58) 0.0001 Total cholesterol, mean ± SD 193 ± 46 187 ± 46 ns LDL cholesterol, mean ± SD 111 ± 37 108 ± 42 ns HDL cholesterol, mean ± SD 49 ± 18 52 ± 21 ns Triglycerides, mean ± SD 183 ± 124 138 ± 90 0.0214 Family history of CAD, n (%) 8 (19) 14 (16) ns History of myocardial infarction 19 (45) 42 (49) ns Typical angina 29 (69) 66 (78) ns Non-typical angina 13 (31) 19 (22) Acetylsalicylic acid, n (%) 42 (100) 83 (98) ns Clopidogrel, n (%) 26 (62) 39 (46) ns Beta-blockers, n (%) 38 (90) 76 (89) ns Angiotensin-converting enzyme inhibitor, n (%) 41 (98) 74 (87) ns Statin, n (%) 42 (100) 82 (96) ns Long-acting nitrates, n (%) 30 (71) 64 (75) ns CAD, coronary artery disease; DM, diabetes; n, number of subjects. Table 2 Comparison of baseline echocardiographic parameters between DM (+) and DM (−) groups Parameters DM (+) DM (−) P-value n = 42 n = 85 LVd (mm) 47.9 ± 4.8 47.3 ± 5.1 ns LVd index (mm/m2) 23.9 ± 3.1 24.8 ± 3.1 ns LVs (mm) 34.2 ± 5.0 33.5 ± 6.1 ns LVs index (mm/m2) 17.1 ± 3.1 17.5 ± 3.2 ns PWd (mm) 12.3 ± 1.3 11.3 ± 1.1 <0.0001 PWd index (mm/m2) 6.1 ± 0.8 5.9 ± 0.7 ns PWs (mm) 15.1 ± 1.7 14.1 ± 1.6 <0.0015 PWs index (mm/m2) 7.5 ± 1.0 7.4 ± 0.9 ns IVSd (mm) 12.9 ± 1.6 11.9 ± 1.5 0.0007 IVSd index (mm/m2) 6.4 ± 0.9 6.2 ± 0.8 ns IVSs (mm) 15.7 ± 1.7 14.8 ± 1.6 0.0041 IVSs index (mm/m2) 7.8 ± 1.0 7.7 ± 1.0 ns Ao (mm) 33.1 ± 3.2 32.9 ± 3.6 ns Ao index (mm/m2) 16.5 ± 1.9 17.3 ± 1.9 0.0274 LA (mm) 42.4 ± 2.9 40.9 ± 3.7 0.0231 LA index (mm/m2) 21.1 ± 2.2 21.4 ± 2.3 ns RV (mm) 26.4 ± 2.0 26.4 ± 2.1 ns RV index (mm/m2) 13.2 ± 1.4 13.8 ± 1.5 0.0321 E/A 0.7 ± −0.2 0.9 ± 0.5 0.014 LV mass (g) 277 ± 57 244 ± 67 0.0071 LV mass index (g/m2) 137 ± 27 126 ± 30 0.0468 EF baseline (%) 53 ± 7 54 ± 8 ns WMSI at baseline 1.15 ± 0.2 1.17 ± 0.24 ns S′ lat at baseline (cm/s) 7.7 ± 1.8 8.5 ± 2.5 ns E′ lat at baseline (cm/s) 9.1 ± 3.1 9.6 ± 2.8 ns Parameters DM (+) DM (−) P-value n = 42 n = 85 LVd (mm) 47.9 ± 4.8 47.3 ± 5.1 ns LVd index (mm/m2) 23.9 ± 3.1 24.8 ± 3.1 ns LVs (mm) 34.2 ± 5.0 33.5 ± 6.1 ns LVs index (mm/m2) 17.1 ± 3.1 17.5 ± 3.2 ns PWd (mm) 12.3 ± 1.3 11.3 ± 1.1 <0.0001 PWd index (mm/m2) 6.1 ± 0.8 5.9 ± 0.7 ns PWs (mm) 15.1 ± 1.7 14.1 ± 1.6 <0.0015 PWs index (mm/m2) 7.5 ± 1.0 7.4 ± 0.9 ns IVSd (mm) 12.9 ± 1.6 11.9 ± 1.5 0.0007 IVSd index (mm/m2) 6.4 ± 0.9 6.2 ± 0.8 ns IVSs (mm) 15.7 ± 1.7 14.8 ± 1.6 0.0041 IVSs index (mm/m2) 7.8 ± 1.0 7.7 ± 1.0 ns Ao (mm) 33.1 ± 3.2 32.9 ± 3.6 ns Ao index (mm/m2) 16.5 ± 1.9 17.3 ± 1.9 0.0274 LA (mm) 42.4 ± 2.9 40.9 ± 3.7 0.0231 LA index (mm/m2) 21.1 ± 2.2 21.4 ± 2.3 ns RV (mm) 26.4 ± 2.0 26.4 ± 2.1 ns RV index (mm/m2) 13.2 ± 1.4 13.8 ± 1.5 0.0321 E/A 0.7 ± −0.2 0.9 ± 0.5 0.014 LV mass (g) 277 ± 57 244 ± 67 0.0071 LV mass index (g/m2) 137 ± 27 126 ± 30 0.0468 EF baseline (%) 53 ± 7 54 ± 8 ns WMSI at baseline 1.15 ± 0.2 1.17 ± 0.24 ns S′ lat at baseline (cm/s) 7.7 ± 1.8 8.5 ± 2.5 ns E′ lat at baseline (cm/s) 9.1 ± 3.1 9.6 ± 2.8 ns Indexes were calculated by body surface area. Values were expressed as mean ± SD. Ao, aortic dimension; DM, diabetes mellitus; E′ lat, peak early diastolic velocity of lateral part of mitral annulus; E, peak velocity of mitral inflow early phase; E/A, ratio of early to atrial mitral inflow peak velocity; EF, left ventricular ejection fraction; IVSd, end-diastolic left ventricular septum thickness; IVSs, end-systolic left ventricular septum thickness; LA, left atrial dimension; LV mass, left ventricular mass; LV mass index, left ventricular mass index; LVd, left ventricular end-diastolic dimension; LVs, left ventricular end-systolic dimension; n, number of subjects; PWd, end-diastolic left ventricular posterior wall thickness; PWs, end-systolic left ventricular posterior wall thickness; RV, right ventricular end-diastolic dimension; S′ lat, peak systolic velocity of lateral part of mitral annulus; WMSI, wall motion score index. Table 2 Comparison of baseline echocardiographic parameters between DM (+) and DM (−) groups Parameters DM (+) DM (−) P-value n = 42 n = 85 LVd (mm) 47.9 ± 4.8 47.3 ± 5.1 ns LVd index (mm/m2) 23.9 ± 3.1 24.8 ± 3.1 ns LVs (mm) 34.2 ± 5.0 33.5 ± 6.1 ns LVs index (mm/m2) 17.1 ± 3.1 17.5 ± 3.2 ns PWd (mm) 12.3 ± 1.3 11.3 ± 1.1 <0.0001 PWd index (mm/m2) 6.1 ± 0.8 5.9 ± 0.7 ns PWs (mm) 15.1 ± 1.7 14.1 ± 1.6 <0.0015 PWs index (mm/m2) 7.5 ± 1.0 7.4 ± 0.9 ns IVSd (mm) 12.9 ± 1.6 11.9 ± 1.5 0.0007 IVSd index (mm/m2) 6.4 ± 0.9 6.2 ± 0.8 ns IVSs (mm) 15.7 ± 1.7 14.8 ± 1.6 0.0041 IVSs index (mm/m2) 7.8 ± 1.0 7.7 ± 1.0 ns Ao (mm) 33.1 ± 3.2 32.9 ± 3.6 ns Ao index (mm/m2) 16.5 ± 1.9 17.3 ± 1.9 0.0274 LA (mm) 42.4 ± 2.9 40.9 ± 3.7 0.0231 LA index (mm/m2) 21.1 ± 2.2 21.4 ± 2.3 ns RV (mm) 26.4 ± 2.0 26.4 ± 2.1 ns RV index (mm/m2) 13.2 ± 1.4 13.8 ± 1.5 0.0321 E/A 0.7 ± −0.2 0.9 ± 0.5 0.014 LV mass (g) 277 ± 57 244 ± 67 0.0071 LV mass index (g/m2) 137 ± 27 126 ± 30 0.0468 EF baseline (%) 53 ± 7 54 ± 8 ns WMSI at baseline 1.15 ± 0.2 1.17 ± 0.24 ns S′ lat at baseline (cm/s) 7.7 ± 1.8 8.5 ± 2.5 ns E′ lat at baseline (cm/s) 9.1 ± 3.1 9.6 ± 2.8 ns Parameters DM (+) DM (−) P-value n = 42 n = 85 LVd (mm) 47.9 ± 4.8 47.3 ± 5.1 ns LVd index (mm/m2) 23.9 ± 3.1 24.8 ± 3.1 ns LVs (mm) 34.2 ± 5.0 33.5 ± 6.1 ns LVs index (mm/m2) 17.1 ± 3.1 17.5 ± 3.2 ns PWd (mm) 12.3 ± 1.3 11.3 ± 1.1 <0.0001 PWd index (mm/m2) 6.1 ± 0.8 5.9 ± 0.7 ns PWs (mm) 15.1 ± 1.7 14.1 ± 1.6 <0.0015 PWs index (mm/m2) 7.5 ± 1.0 7.4 ± 0.9 ns IVSd (mm) 12.9 ± 1.6 11.9 ± 1.5 0.0007 IVSd index (mm/m2) 6.4 ± 0.9 6.2 ± 0.8 ns IVSs (mm) 15.7 ± 1.7 14.8 ± 1.6 0.0041 IVSs index (mm/m2) 7.8 ± 1.0 7.7 ± 1.0 ns Ao (mm) 33.1 ± 3.2 32.9 ± 3.6 ns Ao index (mm/m2) 16.5 ± 1.9 17.3 ± 1.9 0.0274 LA (mm) 42.4 ± 2.9 40.9 ± 3.7 0.0231 LA index (mm/m2) 21.1 ± 2.2 21.4 ± 2.3 ns RV (mm) 26.4 ± 2.0 26.4 ± 2.1 ns RV index (mm/m2) 13.2 ± 1.4 13.8 ± 1.5 0.0321 E/A 0.7 ± −0.2 0.9 ± 0.5 0.014 LV mass (g) 277 ± 57 244 ± 67 0.0071 LV mass index (g/m2) 137 ± 27 126 ± 30 0.0468 EF baseline (%) 53 ± 7 54 ± 8 ns WMSI at baseline 1.15 ± 0.2 1.17 ± 0.24 ns S′ lat at baseline (cm/s) 7.7 ± 1.8 8.5 ± 2.5 ns E′ lat at baseline (cm/s) 9.1 ± 3.1 9.6 ± 2.8 ns Indexes were calculated by body surface area. Values were expressed as mean ± SD. Ao, aortic dimension; DM, diabetes mellitus; E′ lat, peak early diastolic velocity of lateral part of mitral annulus; E, peak velocity of mitral inflow early phase; E/A, ratio of early to atrial mitral inflow peak velocity; EF, left ventricular ejection fraction; IVSd, end-diastolic left ventricular septum thickness; IVSs, end-systolic left ventricular septum thickness; LA, left atrial dimension; LV mass, left ventricular mass; LV mass index, left ventricular mass index; LVd, left ventricular end-diastolic dimension; LVs, left ventricular end-systolic dimension; n, number of subjects; PWd, end-diastolic left ventricular posterior wall thickness; PWs, end-systolic left ventricular posterior wall thickness; RV, right ventricular end-diastolic dimension; S′ lat, peak systolic velocity of lateral part of mitral annulus; WMSI, wall motion score index. Table 3 The comparison of CAD advancement and localization between groups with and without DM Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Three-vessel disease, n (%) 12 (29) 14 (16) ns Two-vessel disease, n (%) 10 (24) 28 (33) ns One-vessel disease, n (%) 20 (48) 43 (51) ns LMCA stenosis >50% 6 (14) 6 (7) ns LAD stenosis >70% 21 (50) 49 (58) ns Cx stenosis >70% 21 (50) 42 (49) ns RCA stenosis >70% 23 (55) 42 (49) ns SYNTAX score (n 33/79), mean ± SD 17.3 ± 28.3 12.5 ± 8.5 ns History of CABG 1 (2.4) 1 (1.2) ns Number of patent/stenosed grafts, n (%) 3 (75)/1(25) 1 (100)/0(0) ns Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Three-vessel disease, n (%) 12 (29) 14 (16) ns Two-vessel disease, n (%) 10 (24) 28 (33) ns One-vessel disease, n (%) 20 (48) 43 (51) ns LMCA stenosis >50% 6 (14) 6 (7) ns LAD stenosis >70% 21 (50) 49 (58) ns Cx stenosis >70% 21 (50) 42 (49) ns RCA stenosis >70% 23 (55) 42 (49) ns SYNTAX score (n 33/79), mean ± SD 17.3 ± 28.3 12.5 ± 8.5 ns History of CABG 1 (2.4) 1 (1.2) ns Number of patent/stenosed grafts, n (%) 3 (75)/1(25) 1 (100)/0(0) ns Table 3 The comparison of CAD advancement and localization between groups with and without DM Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Three-vessel disease, n (%) 12 (29) 14 (16) ns Two-vessel disease, n (%) 10 (24) 28 (33) ns One-vessel disease, n (%) 20 (48) 43 (51) ns LMCA stenosis >50% 6 (14) 6 (7) ns LAD stenosis >70% 21 (50) 49 (58) ns Cx stenosis >70% 21 (50) 42 (49) ns RCA stenosis >70% 23 (55) 42 (49) ns SYNTAX score (n 33/79), mean ± SD 17.3 ± 28.3 12.5 ± 8.5 ns History of CABG 1 (2.4) 1 (1.2) ns Number of patent/stenosed grafts, n (%) 3 (75)/1(25) 1 (100)/0(0) ns Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Three-vessel disease, n (%) 12 (29) 14 (16) ns Two-vessel disease, n (%) 10 (24) 28 (33) ns One-vessel disease, n (%) 20 (48) 43 (51) ns LMCA stenosis >50% 6 (14) 6 (7) ns LAD stenosis >70% 21 (50) 49 (58) ns Cx stenosis >70% 21 (50) 42 (49) ns RCA stenosis >70% 23 (55) 42 (49) ns SYNTAX score (n 33/79), mean ± SD 17.3 ± 28.3 12.5 ± 8.5 ns History of CABG 1 (2.4) 1 (1.2) ns Number of patent/stenosed grafts, n (%) 3 (75)/1(25) 1 (100)/0(0) ns Diabetics had higher body mass index (BMI; 30.7 ± 5.7 vs. 28 ± 3.9 in controls, P = 0.0022) and had more often triglyceridaemia (see Table 1). Patients with CAD and DM had comparable standard echocardiograms except for higher LV mass and LV mass index (LVMI; 137 ± 27 g/m2 vs. 126 ± 30 g/m2, P = 0.0468, for mass index) as well as thicker LV walls and larger left atrial diameter (significance was lost after indexing for BSA; see Table 2). We did not found any correlation between LVMI and PSLS in patients with diabetes (r = 0.065, P = 0.68; r = 0.187, P = 0.24; r = 0.04, P = 0.81, respectively) for baseline, peak, and recovery of DSE. In contrast, we observed the significant correlation between LVMI and PSLS in group without DM, which was confirmed in all stages of DSE (r = 0.37, P = 0.0004; r = 0.34, P = 0.013; r = 0.43, P = 0.0001, respectively) for baseline, peak, and recovery. Severity of CAD was similar in both groups (Table 3) with comparable prevalence of significant stenosis (>70%) in each of the major epicardial coronary artery or its significant branch (diagonal arteries of diameter >2 mm were ascribed to LAD, marginal to Cx and posterior descending and posterolateral to RCA). SYNTAX score did not differ between DM (+) and DM (−) patients. Only two patients in the studied group had previous coronary artery bypass grafting (CABG). One patient belonged into DM (+) group and presented patent left interior mammary artery (LIMA) and two venous grafts, from which one venous graft (supplying RCA) had 95% stenosis. The other patient belonged to DM (−) group and had only one arterial graft—patent LIMA to LAD. Because of very small number, the proportion of previous CABG and graft patency did not differ significantly between the compared subgroups (see Table 3). During DSE, standard echocardiographic parameters did not differ between DM (+) and DM (−) groups. The percentage of positive DSE test (assessed visually) exceeded 80% in both groups with chest pain prevalence and electrocardiographic (ECG) changes recorded in about 60%. Peak stress values of EF, WMSI, heart rate, and blood pressure were also similar as well as the percentage of contractility impairment in myocardial regions supplied by respective coronary arteries (Table 4). Table 4 The comparison of the prevalence of chest pain, ECG changes, WMSI, and contractility impairments between group with and without DM during DSE Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Chest pain during DSE, n (%) 24 (57) 51 (60) ns ECG ischemic changes at peak DSE, n (%) 26 (62) 49 (58) ns WMSI at peak, mean ± SD 1.3 ± 0.21 1, 3 ± 0, 24 ns Delta WMSI (peak–baseline), mean ± SD 0.15 ± 0.14 0.13 ± 0, 13 ns Positive DSE test, n (%) 37 (88) 72 (85) ns Systolic blood pressure at peak stage (mmHg), mean ± SD 145 ± 28 142 ± 26 ns Diastolic blood pressure at peak stage (mmHg), mean ± SD 76 ± 11 75 ± 12 ns Atropine mean dose (mg), mean ± SD 1.08 ± 0.53 0.96 ± 0.5 ns Heart rate at peak stage (bpm), mean ± SD 138 ± 12 138 ± 16 ns Heart rate at recovery (bpm), mean ± SD 92 ± 13 89 ± 12 ns EF at peak DSE (%), mean ± SD 54 ± 7 55 ± 10 ns Induced contractility impairment in the region of LAD (number of subjects), n (%) 11 (26) 22 (26) ns Induced contractility impairment in the region of Cx (number of subjects), n (%) 21 (50) 38 (45) ns Induced contractility impairment in the region of RCA (number of subjects), n (%) 22 (52) 37 (44) ns Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Chest pain during DSE, n (%) 24 (57) 51 (60) ns ECG ischemic changes at peak DSE, n (%) 26 (62) 49 (58) ns WMSI at peak, mean ± SD 1.3 ± 0.21 1, 3 ± 0, 24 ns Delta WMSI (peak–baseline), mean ± SD 0.15 ± 0.14 0.13 ± 0, 13 ns Positive DSE test, n (%) 37 (88) 72 (85) ns Systolic blood pressure at peak stage (mmHg), mean ± SD 145 ± 28 142 ± 26 ns Diastolic blood pressure at peak stage (mmHg), mean ± SD 76 ± 11 75 ± 12 ns Atropine mean dose (mg), mean ± SD 1.08 ± 0.53 0.96 ± 0.5 ns Heart rate at peak stage (bpm), mean ± SD 138 ± 12 138 ± 16 ns Heart rate at recovery (bpm), mean ± SD 92 ± 13 89 ± 12 ns EF at peak DSE (%), mean ± SD 54 ± 7 55 ± 10 ns Induced contractility impairment in the region of LAD (number of subjects), n (%) 11 (26) 22 (26) ns Induced contractility impairment in the region of Cx (number of subjects), n (%) 21 (50) 38 (45) ns Induced contractility impairment in the region of RCA (number of subjects), n (%) 22 (52) 37 (44) ns Cx, circumflex artery; DSE, dobutamine stress echocardiography; ECG, electrocardiogram; LAD, left anterior descending artery; n, number of subjects; RCA, right coronary artery; WMSI, wall motion score index. Table 4 The comparison of the prevalence of chest pain, ECG changes, WMSI, and contractility impairments between group with and without DM during DSE Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Chest pain during DSE, n (%) 24 (57) 51 (60) ns ECG ischemic changes at peak DSE, n (%) 26 (62) 49 (58) ns WMSI at peak, mean ± SD 1.3 ± 0.21 1, 3 ± 0, 24 ns Delta WMSI (peak–baseline), mean ± SD 0.15 ± 0.14 0.13 ± 0, 13 ns Positive DSE test, n (%) 37 (88) 72 (85) ns Systolic blood pressure at peak stage (mmHg), mean ± SD 145 ± 28 142 ± 26 ns Diastolic blood pressure at peak stage (mmHg), mean ± SD 76 ± 11 75 ± 12 ns Atropine mean dose (mg), mean ± SD 1.08 ± 0.53 0.96 ± 0.5 ns Heart rate at peak stage (bpm), mean ± SD 138 ± 12 138 ± 16 ns Heart rate at recovery (bpm), mean ± SD 92 ± 13 89 ± 12 ns EF at peak DSE (%), mean ± SD 54 ± 7 55 ± 10 ns Induced contractility impairment in the region of LAD (number of subjects), n (%) 11 (26) 22 (26) ns Induced contractility impairment in the region of Cx (number of subjects), n (%) 21 (50) 38 (45) ns Induced contractility impairment in the region of RCA (number of subjects), n (%) 22 (52) 37 (44) ns Symptom/parameters DM (+) DM (−) P-value n = 42 n = 85 Chest pain during DSE, n (%) 24 (57) 51 (60) ns ECG ischemic changes at peak DSE, n (%) 26 (62) 49 (58) ns WMSI at peak, mean ± SD 1.3 ± 0.21 1, 3 ± 0, 24 ns Delta WMSI (peak–baseline), mean ± SD 0.15 ± 0.14 0.13 ± 0, 13 ns Positive DSE test, n (%) 37 (88) 72 (85) ns Systolic blood pressure at peak stage (mmHg), mean ± SD 145 ± 28 142 ± 26 ns Diastolic blood pressure at peak stage (mmHg), mean ± SD 76 ± 11 75 ± 12 ns Atropine mean dose (mg), mean ± SD 1.08 ± 0.53 0.96 ± 0.5 ns Heart rate at peak stage (bpm), mean ± SD 138 ± 12 138 ± 16 ns Heart rate at recovery (bpm), mean ± SD 92 ± 13 89 ± 12 ns EF at peak DSE (%), mean ± SD 54 ± 7 55 ± 10 ns Induced contractility impairment in the region of LAD (number of subjects), n (%) 11 (26) 22 (26) ns Induced contractility impairment in the region of Cx (number of subjects), n (%) 21 (50) 38 (45) ns Induced contractility impairment in the region of RCA (number of subjects), n (%) 22 (52) 37 (44) ns Cx, circumflex artery; DSE, dobutamine stress echocardiography; ECG, electrocardiogram; LAD, left anterior descending artery; n, number of subjects; RCA, right coronary artery; WMSI, wall motion score index. Feasibility of longitudinal strain assessment with the standard 2D speckle-tracking echocardiography with and without the use of AFI was analysed for regional and global data and published in an earlier article,7 encompassing data from 238 patients including presently analysed 127 subjects with CAD. Global LV PSLS correlated very well for both methods (r = 0.90 at baseline and r = 0.86 at peak stage of DSE), but AFI analysis (used in this study) was less time-consuming (mean time for obtaining regional, averaged, and global data for LV in AFI was 168 ± 28 s vs. 367 ± 39 s by classical curves analysis with STE) and less operator dependent with interobserver variability of 8.7% and 16% for baseline at peak stage, respectively. Despite the inclusion of only patients with feasible visual assessment of all LV segments in our study, we still excluded some segments from speckle-tracking analysis because of suboptimal tracking quality. The respective percentage of excluded segments were significantly higher at peak stage (1.07%) than at rest (0.42%, P = 0.0007). In contrast to standard echocardiographic parameters, all assessed global, average, and segmental PSLS measurements had lower absolute values in patients with CAD and DM at all stages of DSE. In the majority of comparisons, observed differences were statistically significant (Table 5), e.g. for global strain (averaged from 18 LV segments) measured at baseline (14.5 ± 3.6% vs. 17.4 ± 4.0, P = 0.0001), peak (13.8 ± 3.9% vs. 16.7 ± 4.0%, P = 0.0002), and recovery (14.2 ± 3.1% vs. 15.5 ± 3.5%, P = 0.04) and for averaged values describing respective echocardiographic views (six segments from three-chamber, two-chamber and four-chamber views) measured at baseline as well as for segmental values (chosen from mid LV level as representative for Cx, RCA, and LAD supply) measured at baseline. At peak DSE stage and at recovery, some comparisons, encompassing less number of segments, did not reach statistical significance (Figure 2). Table 5 Comparison of longitudinal peak systolic strain measured by AFI method between groups with and without DM at baseline, peak, and during recovery phase of DSE (absolute values, without minus) Parameters DM (+) DM (−) P-value n = 42 n = 85 Global PSLS at baseline 14.5 ± 3.6 17.4 ± 4.0 0.0001 Global PSLS at peak 13.8 ± 3.9 16.7 ± 4.0 0.0002 Global PSLS at recovery 14.2 ± 3.1 15.5 ± 3.5 0.0432 Averaged 3ch PSLS at baseline 15.1 ± 4.3 17.6 ± 4.6 0.0039 Averaged 4 ch PSLS at baseline 14.4 ± 4.4 16.8 ± 4.1 0.003 Averaged 2 ch PSLS at baseline 14.5 ± 3.6 17.9 ± 4.3 <0.0001 Averaged 3ch PSLS at peak 14.2 ± 5.0 17.0 ± 4.7 0.0024 Averaged 4 ch PSLS at peak 14.6 ± 4.8 16.4 ± 5.4 ns Averaged 2 ch PSLS at peak 13.0 ± 4.6 16.4 ± 4.8 0.0002 Averaged 3ch PSLS at recovery 14.3 ± 4.0 15.6 ± 4.2 ns Averaged 4 ch PSLS at recovery 13.9 ± 3.8 15.5 ± 3.8 0.0274 Averaged 2 ch PSLS at recovery 13.9 ± 3.6 15.6 ± 3.6 0.0136 Mid lateral PSLS at baseline 9.8 ± 7.4 13.4 ± 7.0 0.0085 Mid inferior PSLS at baseline 16.5 ± 4.4 19.6 ± 5.7 0.0024 Mid anteroseptal PSLS at baseline 16.8 ± 5.7 19.7 ± 4.5 0.0022 Mid lateral PSLS at peak 9.1 ± 6.3 11.7 ± 9.7 ns Mid inferior PSLS at peak 15.4 ± 6.4 18.1 ± 5.5 0.0151 Mid anteroseptal PSLS at peak 16.1 ± 6.6 18.2 ± 6.7 ns Mid lateral PSLS at recovery 10.2 ± 6.5 13.1 ± 5.5 0.0096 Mid inferior PSLS at recovery 14.9 ± 5.0 17.1 ± 5.0 0.0213 Mid anteroseptal PSLS at recovery 15.3 ± 6.2 17.2 ± 5.1 ns Parameters DM (+) DM (−) P-value n = 42 n = 85 Global PSLS at baseline 14.5 ± 3.6 17.4 ± 4.0 0.0001 Global PSLS at peak 13.8 ± 3.9 16.7 ± 4.0 0.0002 Global PSLS at recovery 14.2 ± 3.1 15.5 ± 3.5 0.0432 Averaged 3ch PSLS at baseline 15.1 ± 4.3 17.6 ± 4.6 0.0039 Averaged 4 ch PSLS at baseline 14.4 ± 4.4 16.8 ± 4.1 0.003 Averaged 2 ch PSLS at baseline 14.5 ± 3.6 17.9 ± 4.3 <0.0001 Averaged 3ch PSLS at peak 14.2 ± 5.0 17.0 ± 4.7 0.0024 Averaged 4 ch PSLS at peak 14.6 ± 4.8 16.4 ± 5.4 ns Averaged 2 ch PSLS at peak 13.0 ± 4.6 16.4 ± 4.8 0.0002 Averaged 3ch PSLS at recovery 14.3 ± 4.0 15.6 ± 4.2 ns Averaged 4 ch PSLS at recovery 13.9 ± 3.8 15.5 ± 3.8 0.0274 Averaged 2 ch PSLS at recovery 13.9 ± 3.6 15.6 ± 3.6 0.0136 Mid lateral PSLS at baseline 9.8 ± 7.4 13.4 ± 7.0 0.0085 Mid inferior PSLS at baseline 16.5 ± 4.4 19.6 ± 5.7 0.0024 Mid anteroseptal PSLS at baseline 16.8 ± 5.7 19.7 ± 4.5 0.0022 Mid lateral PSLS at peak 9.1 ± 6.3 11.7 ± 9.7 ns Mid inferior PSLS at peak 15.4 ± 6.4 18.1 ± 5.5 0.0151 Mid anteroseptal PSLS at peak 16.1 ± 6.6 18.2 ± 6.7 ns Mid lateral PSLS at recovery 10.2 ± 6.5 13.1 ± 5.5 0.0096 Mid inferior PSLS at recovery 14.9 ± 5.0 17.1 ± 5.0 0.0213 Mid anteroseptal PSLS at recovery 15.3 ± 6.2 17.2 ± 5.1 ns Global—mean value from 18 segments, 2ch, 3ch, and 4ch—parameters measured as mean values from six segments in respective apical views, mid lateral, mid inferior, mid anteroseptal—parameters measured in respective segments of left ventricle considered ‘marker segments’ for Cx, RCA and LAD supply region. Values were expressed as mean ± SD. 2ch, apical two-chamber view; 3ch, apical three-chamber view; 4ch, apical four-chamber view; CAD, coronary artery disease; DM, diabetes mellitus; PSLS, peak systolic longitudinal strain; n, number of subjects. Table 5 Comparison of longitudinal peak systolic strain measured by AFI method between groups with and without DM at baseline, peak, and during recovery phase of DSE (absolute values, without minus) Parameters DM (+) DM (−) P-value n = 42 n = 85 Global PSLS at baseline 14.5 ± 3.6 17.4 ± 4.0 0.0001 Global PSLS at peak 13.8 ± 3.9 16.7 ± 4.0 0.0002 Global PSLS at recovery 14.2 ± 3.1 15.5 ± 3.5 0.0432 Averaged 3ch PSLS at baseline 15.1 ± 4.3 17.6 ± 4.6 0.0039 Averaged 4 ch PSLS at baseline 14.4 ± 4.4 16.8 ± 4.1 0.003 Averaged 2 ch PSLS at baseline 14.5 ± 3.6 17.9 ± 4.3 <0.0001 Averaged 3ch PSLS at peak 14.2 ± 5.0 17.0 ± 4.7 0.0024 Averaged 4 ch PSLS at peak 14.6 ± 4.8 16.4 ± 5.4 ns Averaged 2 ch PSLS at peak 13.0 ± 4.6 16.4 ± 4.8 0.0002 Averaged 3ch PSLS at recovery 14.3 ± 4.0 15.6 ± 4.2 ns Averaged 4 ch PSLS at recovery 13.9 ± 3.8 15.5 ± 3.8 0.0274 Averaged 2 ch PSLS at recovery 13.9 ± 3.6 15.6 ± 3.6 0.0136 Mid lateral PSLS at baseline 9.8 ± 7.4 13.4 ± 7.0 0.0085 Mid inferior PSLS at baseline 16.5 ± 4.4 19.6 ± 5.7 0.0024 Mid anteroseptal PSLS at baseline 16.8 ± 5.7 19.7 ± 4.5 0.0022 Mid lateral PSLS at peak 9.1 ± 6.3 11.7 ± 9.7 ns Mid inferior PSLS at peak 15.4 ± 6.4 18.1 ± 5.5 0.0151 Mid anteroseptal PSLS at peak 16.1 ± 6.6 18.2 ± 6.7 ns Mid lateral PSLS at recovery 10.2 ± 6.5 13.1 ± 5.5 0.0096 Mid inferior PSLS at recovery 14.9 ± 5.0 17.1 ± 5.0 0.0213 Mid anteroseptal PSLS at recovery 15.3 ± 6.2 17.2 ± 5.1 ns Parameters DM (+) DM (−) P-value n = 42 n = 85 Global PSLS at baseline 14.5 ± 3.6 17.4 ± 4.0 0.0001 Global PSLS at peak 13.8 ± 3.9 16.7 ± 4.0 0.0002 Global PSLS at recovery 14.2 ± 3.1 15.5 ± 3.5 0.0432 Averaged 3ch PSLS at baseline 15.1 ± 4.3 17.6 ± 4.6 0.0039 Averaged 4 ch PSLS at baseline 14.4 ± 4.4 16.8 ± 4.1 0.003 Averaged 2 ch PSLS at baseline 14.5 ± 3.6 17.9 ± 4.3 <0.0001 Averaged 3ch PSLS at peak 14.2 ± 5.0 17.0 ± 4.7 0.0024 Averaged 4 ch PSLS at peak 14.6 ± 4.8 16.4 ± 5.4 ns Averaged 2 ch PSLS at peak 13.0 ± 4.6 16.4 ± 4.8 0.0002 Averaged 3ch PSLS at recovery 14.3 ± 4.0 15.6 ± 4.2 ns Averaged 4 ch PSLS at recovery 13.9 ± 3.8 15.5 ± 3.8 0.0274 Averaged 2 ch PSLS at recovery 13.9 ± 3.6 15.6 ± 3.6 0.0136 Mid lateral PSLS at baseline 9.8 ± 7.4 13.4 ± 7.0 0.0085 Mid inferior PSLS at baseline 16.5 ± 4.4 19.6 ± 5.7 0.0024 Mid anteroseptal PSLS at baseline 16.8 ± 5.7 19.7 ± 4.5 0.0022 Mid lateral PSLS at peak 9.1 ± 6.3 11.7 ± 9.7 ns Mid inferior PSLS at peak 15.4 ± 6.4 18.1 ± 5.5 0.0151 Mid anteroseptal PSLS at peak 16.1 ± 6.6 18.2 ± 6.7 ns Mid lateral PSLS at recovery 10.2 ± 6.5 13.1 ± 5.5 0.0096 Mid inferior PSLS at recovery 14.9 ± 5.0 17.1 ± 5.0 0.0213 Mid anteroseptal PSLS at recovery 15.3 ± 6.2 17.2 ± 5.1 ns Global—mean value from 18 segments, 2ch, 3ch, and 4ch—parameters measured as mean values from six segments in respective apical views, mid lateral, mid inferior, mid anteroseptal—parameters measured in respective segments of left ventricle considered ‘marker segments’ for Cx, RCA and LAD supply region. Values were expressed as mean ± SD. 2ch, apical two-chamber view; 3ch, apical three-chamber view; 4ch, apical four-chamber view; CAD, coronary artery disease; DM, diabetes mellitus; PSLS, peak systolic longitudinal strain; n, number of subjects. Figure 2 View largeDownload slide Comparison of global and regional PSLS, recorded during baseline, peak, and recovery stage of DSE in patients with CAD and DM (red bars) and CAD without DM (green bars). Absolute strain values at baseline and majority at the peak and during recovery are lower in diabetics. The coexistence of diabetes significantly impairs left ventricular systolic function at rest, during, and after stress echocardiography in patients with coronary artery disease. Figure 2 View largeDownload slide Comparison of global and regional PSLS, recorded during baseline, peak, and recovery stage of DSE in patients with CAD and DM (red bars) and CAD without DM (green bars). Absolute strain values at baseline and majority at the peak and during recovery are lower in diabetics. The coexistence of diabetes significantly impairs left ventricular systolic function at rest, during, and after stress echocardiography in patients with coronary artery disease. As far as the comparison of observed changes of PSLS during DSE are concerned for global strain, it reached the mean value of 1.8 ± 2.3% in DM (−) group and 1.2 ± 2.6% in DM (+) patients for the drop of absolute PSLS value between baseline and recovery and they did not reveal statistically significant differences between groups. Figure 3 shows a typical example of positive DSE tests in CAD patients with and without DM, illustrating deeper impairment of PSLS in all stages of DSE in patient with coexisting DM. Figure 3 View largeDownload slide A representative example of two positive DSE tests (posteroinferior ischaemia in patient with CAD and DM vs. posterolateral ischaemia in patient without DM). Absolute values of PSLS in patient with CAD and DM are lower at all analysed stages (upper panel). Figure 3 View largeDownload slide A representative example of two positive DSE tests (posteroinferior ischaemia in patient with CAD and DM vs. posterolateral ischaemia in patient without DM). Absolute values of PSLS in patient with CAD and DM are lower at all analysed stages (upper panel). We found that in diabetics included in our DM (+) group, LV hypertrophy (LVMI) does not significantly affect the PSLS values at any of DSE stages. Moreover, in both subgroups of diabetics (stratified according to LVMI with average value found in the group accepted as cut-off), PSLS was impaired (see Table 6, upper part). In contrast, in patients without diabetes, PSLS was significantly decreased in subgroup with higher values of LVMI at baseline and recovery stages of DSE (subgroups divided according to the average value in non-diabetics, bottom lines of Table 6). Table 6 Separate comparison of PSLS recorded during all stages of DSE according to LVMI in patients with and without diabetes Parameters DM (+) and LVMI <137 g/m2 (n = 16) DM (+) and LVMI ≥137 g/m2 (n = 26) P-value PSLS baseline 14.1 ± 4.3 15.0 ± 3.2 ns PSLS peak 14.1 ± 4.6 13.6 ± 3.6 ns PSLS recovery 13.7 ± 3.3 14.6 ± 3.1 ns Parameters DM (−) and LVMI <126 g/m2 (n = 45) DM (−) and LVMI ≥126 g/m2 (n = 40) P-value PSLS baseline 18.3 ± 3.6 16.2 ± 4.1 0.0144 PSLS peak 17.4 ± 3.6 15.7 ± 4.3 ns PSLS recovery 16.4 ± 3.0 14.4 ± 3.6 0.0068 Parameters DM (+) and LVMI <137 g/m2 (n = 16) DM (+) and LVMI ≥137 g/m2 (n = 26) P-value PSLS baseline 14.1 ± 4.3 15.0 ± 3.2 ns PSLS peak 14.1 ± 4.6 13.6 ± 3.6 ns PSLS recovery 13.7 ± 3.3 14.6 ± 3.1 ns Parameters DM (−) and LVMI <126 g/m2 (n = 45) DM (−) and LVMI ≥126 g/m2 (n = 40) P-value PSLS baseline 18.3 ± 3.6 16.2 ± 4.1 0.0144 PSLS peak 17.4 ± 3.6 15.7 ± 4.3 ns PSLS recovery 16.4 ± 3.0 14.4 ± 3.6 0.0068 In contrast to non-diabetics group in patients with DM, the increase of LVMI did not seem to have further impact on PSLS. Values were expressed as mean ± SD. DM, diabetes mellitus; LVMI, left ventricular mass index; n, number of subjects; PSLS, peak systolic longitudinal strain. Table 6 Separate comparison of PSLS recorded during all stages of DSE according to LVMI in patients with and without diabetes Parameters DM (+) and LVMI <137 g/m2 (n = 16) DM (+) and LVMI ≥137 g/m2 (n = 26) P-value PSLS baseline 14.1 ± 4.3 15.0 ± 3.2 ns PSLS peak 14.1 ± 4.6 13.6 ± 3.6 ns PSLS recovery 13.7 ± 3.3 14.6 ± 3.1 ns Parameters DM (−) and LVMI <126 g/m2 (n = 45) DM (−) and LVMI ≥126 g/m2 (n = 40) P-value PSLS baseline 18.3 ± 3.6 16.2 ± 4.1 0.0144 PSLS peak 17.4 ± 3.6 15.7 ± 4.3 ns PSLS recovery 16.4 ± 3.0 14.4 ± 3.6 0.0068 Parameters DM (+) and LVMI <137 g/m2 (n = 16) DM (+) and LVMI ≥137 g/m2 (n = 26) P-value PSLS baseline 14.1 ± 4.3 15.0 ± 3.2 ns PSLS peak 14.1 ± 4.6 13.6 ± 3.6 ns PSLS recovery 13.7 ± 3.3 14.6 ± 3.1 ns Parameters DM (−) and LVMI <126 g/m2 (n = 45) DM (−) and LVMI ≥126 g/m2 (n = 40) P-value PSLS baseline 18.3 ± 3.6 16.2 ± 4.1 0.0144 PSLS peak 17.4 ± 3.6 15.7 ± 4.3 ns PSLS recovery 16.4 ± 3.0 14.4 ± 3.6 0.0068 In contrast to non-diabetics group in patients with DM, the increase of LVMI did not seem to have further impact on PSLS. Values were expressed as mean ± SD. DM, diabetes mellitus; LVMI, left ventricular mass index; n, number of subjects; PSLS, peak systolic longitudinal strain. We found that in patients with CAD and without or with only mild LV hypertrophy (for LVMI < 126 g/m2), the presence of DM was still related with decreased PSLS values measured at all stages of DSE. This finding was consistent with the relationships observed for the whole group not stratified according to the LVMI (compare data in Tables 5 and 7). Nevertheless, in the settings of moderate or severe LV hypertrophy (LVMI ≥ 126 g/m2 and <150 g/m2 or LVMI ≥ 150 g/m2), the decrease of strain values in diabetics when compared with respective non-diabetic group with LV hypertrophy lost its statistical significance and the additional impact of DM on PSLS was not then detectable (see Table 7). Table 7 Comparison of PSLS between diabetics and non-diabetics stratified according to LVMI Parameters DM (+) and LVMI <126 g/m2 (n = 14) DM (−) and LVMI <126 g/m2 (n = 45) P-value PSLS baseline 14.1 ± 4.0 18.3 ± 3.6 0.0005 PSLS peak 14.0 ± 4.5 17.4 ± 3.6 0.0066 PSLS recovery 13.9 ± 3.2 16.4 ± 3.0 0.0143 Parameters DM (+) and LVMI ≥126 and <150 g/m2 (n = 16) DM (−) and LVMI ≥126 and <150 g/m2 (n = 22) P-value PSLS baseline 15.2 ± 3.4 17.4 ± 4.0 ns PSLS peak 14.8 ± 4.0 17.1 ± 4.5 ns PSLS recovery 14.9 ± 3.9 15.6 ± 3.2 ns Parameter DM (+) and LVMI ≥150 g/m2 (n = 12) DM (−) and LVMI ≥150 g/m2 (n = 18) P-value PSLS baseline 14.4 ± 3.6 14.9 ± 3.9 ns PSLS peak 12.4 ± 2.9 14.1 ± 3.5 ns PSLS recovery 13.7 ± 2.1 13.2 ± 3.7 ns Parameters DM (+) and LVMI <126 g/m2 (n = 14) DM (−) and LVMI <126 g/m2 (n = 45) P-value PSLS baseline 14.1 ± 4.0 18.3 ± 3.6 0.0005 PSLS peak 14.0 ± 4.5 17.4 ± 3.6 0.0066 PSLS recovery 13.9 ± 3.2 16.4 ± 3.0 0.0143 Parameters DM (+) and LVMI ≥126 and <150 g/m2 (n = 16) DM (−) and LVMI ≥126 and <150 g/m2 (n = 22) P-value PSLS baseline 15.2 ± 3.4 17.4 ± 4.0 ns PSLS peak 14.8 ± 4.0 17.1 ± 4.5 ns PSLS recovery 14.9 ± 3.9 15.6 ± 3.2 ns Parameter DM (+) and LVMI ≥150 g/m2 (n = 12) DM (−) and LVMI ≥150 g/m2 (n = 18) P-value PSLS baseline 14.4 ± 3.6 14.9 ± 3.9 ns PSLS peak 12.4 ± 2.9 14.1 ± 3.5 ns PSLS recovery 13.7 ± 2.1 13.2 ± 3.7 ns The data show that in patients without or with only mild hypertrophy the presence of DM decreases the absolute value of longitudinal strain at all stages of DSE. Contrary this impact is abolished in patients with severe or moderate hypertrophy. Values were expressed as mean ± SD. DM, diabetes mellitus; LVMI, left ventricular mass index; n, number of subjects; PSLS, peak systolic longitudinal strain. Table 7 Comparison of PSLS between diabetics and non-diabetics stratified according to LVMI Parameters DM (+) and LVMI <126 g/m2 (n = 14) DM (−) and LVMI <126 g/m2 (n = 45) P-value PSLS baseline 14.1 ± 4.0 18.3 ± 3.6 0.0005 PSLS peak 14.0 ± 4.5 17.4 ± 3.6 0.0066 PSLS recovery 13.9 ± 3.2 16.4 ± 3.0 0.0143 Parameters DM (+) and LVMI ≥126 and <150 g/m2 (n = 16) DM (−) and LVMI ≥126 and <150 g/m2 (n = 22) P-value PSLS baseline 15.2 ± 3.4 17.4 ± 4.0 ns PSLS peak 14.8 ± 4.0 17.1 ± 4.5 ns PSLS recovery 14.9 ± 3.9 15.6 ± 3.2 ns Parameter DM (+) and LVMI ≥150 g/m2 (n = 12) DM (−) and LVMI ≥150 g/m2 (n = 18) P-value PSLS baseline 14.4 ± 3.6 14.9 ± 3.9 ns PSLS peak 12.4 ± 2.9 14.1 ± 3.5 ns PSLS recovery 13.7 ± 2.1 13.2 ± 3.7 ns Parameters DM (+) and LVMI <126 g/m2 (n = 14) DM (−) and LVMI <126 g/m2 (n = 45) P-value PSLS baseline 14.1 ± 4.0 18.3 ± 3.6 0.0005 PSLS peak 14.0 ± 4.5 17.4 ± 3.6 0.0066 PSLS recovery 13.9 ± 3.2 16.4 ± 3.0 0.0143 Parameters DM (+) and LVMI ≥126 and <150 g/m2 (n = 16) DM (−) and LVMI ≥126 and <150 g/m2 (n = 22) P-value PSLS baseline 15.2 ± 3.4 17.4 ± 4.0 ns PSLS peak 14.8 ± 4.0 17.1 ± 4.5 ns PSLS recovery 14.9 ± 3.9 15.6 ± 3.2 ns Parameter DM (+) and LVMI ≥150 g/m2 (n = 12) DM (−) and LVMI ≥150 g/m2 (n = 18) P-value PSLS baseline 14.4 ± 3.6 14.9 ± 3.9 ns PSLS peak 12.4 ± 2.9 14.1 ± 3.5 ns PSLS recovery 13.7 ± 2.1 13.2 ± 3.7 ns The data show that in patients without or with only mild hypertrophy the presence of DM decreases the absolute value of longitudinal strain at all stages of DSE. Contrary this impact is abolished in patients with severe or moderate hypertrophy. Values were expressed as mean ± SD. DM, diabetes mellitus; LVMI, left ventricular mass index; n, number of subjects; PSLS, peak systolic longitudinal strain. In the whole studied group, PSLS showed significant relationships with body mass, BMI, and waist circumference as well as diabetes for all stages of DSE in univariate analysis (see Table 8). In multivariate analysis including 16-variable LV EF, body surface area, and diabetes were independent predictors of PSLS in model with coefficient of determination (R2 = 0.51, P < 0.001). Table 8 Correlations between demographic and clinical factors and PSLS in subsequent stages of DSE in univariate analysis Parameters PSLS baseline PSLS peak PSLS recovery Body mass r = 0.35; P < 0.0001 r = 0.25; P = 0.0046 r = 0.24; P = 0.0102 Body mass index r = 0.33; P = 0.0001 r = 0.30; P = 0.0006 r = 0.27; P = 0.0029 Waist circumference r = 0.36; P < 0.0001 r = 0.35; P = 0.0001 r = 0.32; P = 0.0004 Body height r = 0.18; P = 0.044 ns ns Diabetes rho = 0.34; P = 0.0001 rho = 0.31; P = 0.0004 rho = 0.23; P = 0.013 Hypertension ns ns ns Hypertriglyceridaemia ns rho = 0.29; P = 0.0009 ns Smoking ns ns ns Parameters PSLS baseline PSLS peak PSLS recovery Body mass r = 0.35; P < 0.0001 r = 0.25; P = 0.0046 r = 0.24; P = 0.0102 Body mass index r = 0.33; P = 0.0001 r = 0.30; P = 0.0006 r = 0.27; P = 0.0029 Waist circumference r = 0.36; P < 0.0001 r = 0.35; P = 0.0001 r = 0.32; P = 0.0004 Body height r = 0.18; P = 0.044 ns ns Diabetes rho = 0.34; P = 0.0001 rho = 0.31; P = 0.0004 rho = 0.23; P = 0.013 Hypertension ns ns ns Hypertriglyceridaemia ns rho = 0.29; P = 0.0009 ns Smoking ns ns ns DSE, dobutamine stress echocardiography; PSLS, peak systolic longitudinal strain; r, Pearson correlation coefficient; rho, Spearman correlation coefficient. Table 8 Correlations between demographic and clinical factors and PSLS in subsequent stages of DSE in univariate analysis Parameters PSLS baseline PSLS peak PSLS recovery Body mass r = 0.35; P < 0.0001 r = 0.25; P = 0.0046 r = 0.24; P = 0.0102 Body mass index r = 0.33; P = 0.0001 r = 0.30; P = 0.0006 r = 0.27; P = 0.0029 Waist circumference r = 0.36; P < 0.0001 r = 0.35; P = 0.0001 r = 0.32; P = 0.0004 Body height r = 0.18; P = 0.044 ns ns Diabetes rho = 0.34; P = 0.0001 rho = 0.31; P = 0.0004 rho = 0.23; P = 0.013 Hypertension ns ns ns Hypertriglyceridaemia ns rho = 0.29; P = 0.0009 ns Smoking ns ns ns Parameters PSLS baseline PSLS peak PSLS recovery Body mass r = 0.35; P < 0.0001 r = 0.25; P = 0.0046 r = 0.24; P = 0.0102 Body mass index r = 0.33; P = 0.0001 r = 0.30; P = 0.0006 r = 0.27; P = 0.0029 Waist circumference r = 0.36; P < 0.0001 r = 0.35; P = 0.0001 r = 0.32; P = 0.0004 Body height r = 0.18; P = 0.044 ns ns Diabetes rho = 0.34; P = 0.0001 rho = 0.31; P = 0.0004 rho = 0.23; P = 0.013 Hypertension ns ns ns Hypertriglyceridaemia ns rho = 0.29; P = 0.0009 ns Smoking ns ns ns DSE, dobutamine stress echocardiography; PSLS, peak systolic longitudinal strain; r, Pearson correlation coefficient; rho, Spearman correlation coefficient. Finally, we compared the data from this analysis with the second part of our group which we previously described (Wierzbowska-Drabik et al.6) and which had no CAD and was divided according to DM presence. This comparison displayed a similar impairment of strain in patients with the presence of one factor DM (+) or CAD (+) and the deepest impairment of LV function when both factors were present. Interestingly, this relationship was observed at all DSE stages, (see Figure 4 displaying data from Wierzbowska-Drabik et al.6 and from this study). Figure 4 View largeDownload slide The comparison of mean absolute values of global PSLS at different stages of DSE according to the presence of CAD, DM, or both these factors. The data illustrate the equivalent impact of isolated DM and CAD without diabetes on LV myocardial strain and the synergistic influence of the coexistence of both these factors. The number of patients included in figure groups: 1. CAD (−) DM (−), n = 85; 2. CAD (−) DM (+), n = 25 (asterisk indicates data from the study by Wierzbowska-Drabik et al.6); 3. CAD (+) DM (−), n = 85; 4. CAD (+) DM (+), n = 42 (data from this study). In the majority of comparisons, the significantly lower strain values were observed in CAD patients when compared with their counterparts without CAD. Nevertheless, this significance was limited to trend only at peak stage of DSE in subgroup without DM and was totally effaced at recovery stage in subgroup with DM. The last finding may suggest the delayed recovery and even further impairment of contractile left ventricular function in patients with DM submitted to DSE. Figure 4 View largeDownload slide The comparison of mean absolute values of global PSLS at different stages of DSE according to the presence of CAD, DM, or both these factors. The data illustrate the equivalent impact of isolated DM and CAD without diabetes on LV myocardial strain and the synergistic influence of the coexistence of both these factors. The number of patients included in figure groups: 1. CAD (−) DM (−), n = 85; 2. CAD (−) DM (+), n = 25 (asterisk indicates data from the study by Wierzbowska-Drabik et al.6); 3. CAD (+) DM (−), n = 85; 4. CAD (+) DM (+), n = 42 (data from this study). In the majority of comparisons, the significantly lower strain values were observed in CAD patients when compared with their counterparts without CAD. Nevertheless, this significance was limited to trend only at peak stage of DSE in subgroup without DM and was totally effaced at recovery stage in subgroup with DM. The last finding may suggest the delayed recovery and even further impairment of contractile left ventricular function in patients with DM submitted to DSE. Moreover, the comparison of PSLS limited to the subgroup with negative visually assessed DSE results indicated on potential utility of longitudinal strain for differentiation between true-negative and false-negative DSE examinations (see Figure 5). The data show that patients with CAD with assessed visually negative DSE presents in the majority of comparisons lower absolute PSLS value than their true negative counterparts. As far as our data are concerned, the statistical significance was achieved only in non-diabetics during recovery phase, but it may depend from very limited number of false-negative subgroup. Figure 5 View largeDownload slide The comparison of mean absolute values of global PSLS at different stages of DSE according to the presence of CAD, DM, or both these factors limited to the patients with negative results of visually assessed DSE (negative tests according to wall mottion analysis). The data illustrate the potential of global longitudinal strain for the detection of systolic function impairment in patients with CAD which was not detected during conventional visually assessed DSE. Despite limited number of subjects in groups with false-negative DSE, the global PSLS was significantly diminished in CAD (+) group in patients without DM as measured during recovery stage. Moreover, all but one (unexpectedly concerning peak DSE stage) numeric values of GLS in CAD (+) were lower than the respective measurements for CAD (−) patients. The number of patients in all figure groups: 1. CAD (−) DM (−), n = 61; 2. CAD (−) DM (+), n = 22 (asterisk indicates data from study by Wierzbowska-Drabik et al.6); 3. CAD (+) DM (−), n = 13; and 4. CAD (+) DM (+), n = 4 (data from this study). Figure 5 View largeDownload slide The comparison of mean absolute values of global PSLS at different stages of DSE according to the presence of CAD, DM, or both these factors limited to the patients with negative results of visually assessed DSE (negative tests according to wall mottion analysis). The data illustrate the potential of global longitudinal strain for the detection of systolic function impairment in patients with CAD which was not detected during conventional visually assessed DSE. Despite limited number of subjects in groups with false-negative DSE, the global PSLS was significantly diminished in CAD (+) group in patients without DM as measured during recovery stage. Moreover, all but one (unexpectedly concerning peak DSE stage) numeric values of GLS in CAD (+) were lower than the respective measurements for CAD (−) patients. The number of patients in all figure groups: 1. CAD (−) DM (−), n = 61; 2. CAD (−) DM (+), n = 22 (asterisk indicates data from study by Wierzbowska-Drabik et al.6); 3. CAD (+) DM (−), n = 13; and 4. CAD (+) DM (+), n = 4 (data from this study). Discussion Our study documents decreased longitudinal function of LV in CAD patients with coexisting type 2 DM in comparison with CAD without diabetes at rest, during, and after dobutamine stress test, which, according to our knowledge, was not published so far. Importantly, this global and regional impairment could be detected only with deformation analysis, because EF, systolic velocity of mitral annulus motion or WMSI did not differ between the compared groups. Moreover, our groups were comparable according to diastolic function parameters: lateral mitral annular velocity and left atrial volume index, although LV mass index was higher in DM (+). Nevertheless, we did not find significant correlation between LVMI and PSLS in patients with diabetes, which allowed us to the assumption that observed lower results of PSLS in DM (+) group does not depend on higher mean LVMI in our diabetic subjects. On the other hand, in further subgroup analysis, lower values of PSLS in diabetics were still significant for all DSE stages in patients with the LVMI < 126 g/m2 so showing no or mild hypertrophy of LV walls, whereas in patients with moderate and severe hypertrophy, the additional impact of DM was not expressed (Table 7). However, these related to subgroups analysis pilot data are limited by small number of included subjects so they should be proved in further studies. Similar advancement (expressed as SYNTAX score) and localization of significant lesions in coronary arteries allow for assumption that the presence of diabetes and strictly related hypertriglyceridaemia are the main determinants of the observed PSLS impairment. Interestingly, in comparison with our previously published analysis in which we observed diminished PSLS in diabetics patients without CAD mainly during recovery stage of DSE, in this study, the detrimental impact of DM on cardiac function seems to be stronger and overt also at rest and peak stage of DSE.6 Moreover, counter-intuitive at first look observation that the dobutamine challenge did not deepen the differences observed at rest was accomplished. It may suggest that the direct impact of the significant coronary stenoses effaces the more subtle influence of DM on systolic myocardial function during DSE or that the assessment of PSLS is more difficult at higher heart rates (reaching in our study an average value of 138 bpm). The increase of technical challenge at peak stage of DSE was not only suspected but also documented as the deacresed feasibility (more segments excluded from the analysis) and nearly twice increased interobserver variability between baseline and peak stage of test (from 8.7% to 16%). Nevertheless, these technical limitations may not solely explain the observed relationships because the intrinsic features of strain values diminishing during very rapid heart rates (HRs) and shortened cardiac cycles may limit diagnostic utility of the recordings during high-level tachycardia. Currently, there are still few published data concerning strain analysis when the HR is close to 140 bpm in groups including >100 patients with confirmed CAD. The typical reaction of PSLS at lower level of induced HR is the increase of longitudinal deformation, whereas during further increase of tachycardia the deformation values decrease, as it was in our group. This biphasic pattern of strain changes increasing at low stress but constant or decreasing as the HR further increases was described in earlier and more recent studies with DSE or exercise test in healthy children.9–11 These observations, as well as recent studies documenting the lack of diagnostic benefit of strain assessment during peak stage of exercise test in such settings as aortic stenosis or better documented values of resting then exercise or dobutamine-related deformation in CAD diagnosis, may additionally prompt to focusing on recovery stage when the HR is close to baseline but some detrimental effects may be still present at least in the aspect of ischaemia detection.12–14 The diagnostic potential of PSLS assessment during DSE for myocardial ischaemia detection was in our study observed in the combined analysis of data from patients with and without CAD showing negative DSE test according to visual evaluation (Figure 5). Non-diabetics patients with false-negative visual test presented significantly lower PSLS during recovery phase of DSE than ‘true-negative’ subjects (15.1 ± 3.1% vs. 17.6 ± 3.1%, P = 0.0102). Strain analysis in patients with coexisting CAD and DM in comparison with patients without DM and similar severity of CAD, especially during all stages of stress test, is unique in the literature. Moreover, published data on resting assessment of myocardial deformation raise numerous controversies. Loncarevic et al.15 in group of 70 patients with type 2 DM without hypertension and CAD reported impaired global longitudinal strain and early diastolic strain rate in comparison with healthy group. The association of DM with arterial hypertension (HA) or CAD caused further decrease in the absolute values of longitudinal strain from 18.71 ± 1.86% in controls, through 17.36 ± 1.8% in isolated DM to 16.31 ± 2.79% in DM with HA, and 16.26 ± 2.84% in DM and CAD. Similarly in our data, patients without CAD and DM [CAD (−)/DM (−)] showed the highest absolute values of global PSLS (e.g. −18.7 ± 3.3% at rest), patients with one factor DM (+) or CAD (+) showed lowered and very similar values of strain, reflecting the equivalent impact of isolated DM or CAD without DM on myocardial function and at last patients with CAD and DM showed the deepest impairment of LV function. Interestingly this relationship was observed at all DSE stages (Figure 4, data from Wierzbowska-Drabik et al.6 and this study). In the study of Enomoto et al.,16 diabetics in comparison with healthy controls showed not only lowered longitudinal and circumferential strain but also area strain obtained with 3D speckle-tracking method (12.0 ± 3.0% vs. 16.2 ± 1.9%, 27.7 ± 7.1% vs. 32.2 ± 5.7%, 37.6 ± 7.6% vs. 44.0 ± 6.2%, respectively; P < 0.001), and these changes correlated with severity of microvascular dysfunction measured as the advancement of nephropathy, neuropathy, and retinopathy. In another study, Bonapace et al.17 observed in a 2-year follow-up that impaired longitudinal strain in patients with DM had predictive value for new onset of atrial fibrillation. In multivariate analysis in our study, the presence of type 2 DM, value of EF, and body surface area were independent predictors of PSLS. These results underlined the utility of strain analysis in the detection of functional LV changes related with DM and potentially its advancement and treatment. This seems especially important considering that some glucose-lowering medications were associated with an increased risk of developing heart failure.18 The following observations offer in our opinion significant novelty and belong to the potential clinical implications of our study: the presence of DM impairs global (and regional) LV myocardial function, which may be observed also in patients with coexisting CAD. The significant differences were observed at rest as well as during DSE and recovery when compared with CAD without DM. our data from this and previous studies provide some reference values of PSLS for patients who are often examined with stress echocardiography and may be categorized according to CAD and DM presence. Interestingly, the impact of isolated DM or CAD on PSLS seems to be similar, whereas the coexistence of CAD and DM exerts the strongest influence on myocardial contractility at all stages of DSE (Table 4). the observation that dobutamine challenge does not increase the resting difference of PSLS between patients with and without DM and CAD have hypothesis-generating character and should be confirmed in further, larger studies. Hypothetically, it may be related to the predominant effect of significant stenoses of coronary arteries that were present in both groups and effaced the impact of DM during stress test. Analogously, the presence of CAD reversed the protective effect of female sex on some diastolic function parameters and the presence of DM abolished the prognostic significance of anti-ischaemic therapy continued in the time of stress echocardiography in some of our previous studies.19,20 Our study is one of the first attempting at detailed characteristic of LV function in diabetics in the settings of coexisting CAD and stress challenge. Although focused on longitudinal strain, we tried to conduct comprehensive assessment during DSE, including also less examined recovery stage. Because of variability of PSLS values related to localization in the LV region, we looked also at segmental and regional functions and did separate analysis concerning middle LV segments. Our results confirm that PSLS can be considered as an emerging tool in the assessment of diabetic myocardial dysfunction. Limitations Small number of examined diabetics (42 subjects) and the lack of detailed biochemical characteristics represent the main limitations of our study which precludes also the potential subanalyses related to severity of DM. Despite similar age, gender, and basically assessed CAD advancement, the DM patients exhibited higher body mass, BMI, waist circumference, body surface area, and LVMI, which might influence the obtained PSLS results. According to clinically oriented guidelines,21 we chose to focus on longitudinal strain for practical aspects of easy, on-system automated imaging method, which can serve as a supplement to routine DSE analysis. Aiming at different stages of DSE, global and regional analyses, and integration of relevant data from previous part of study (four different groups of patients divided according to CAD and DM presence), we limited the analyses to the most popular parameter PSLS without including the postsystolic shortening. Similarly, the additional long-term analysis of prognostic significance of reduced global PSLS at rest and during DSE may potentially increase the clinical utility of our observations. Finally, our data were derived from a single vendor of echocardiographic equipment, and the studied patients were recruited from a single cardiology department. Conclusions Longitudinal LV deformation is more impaired in patients with CAD and DM in comparison with their counterparts with similar extent of coronary atherosclerosis but without DM. This finding was detectable not only at rest but also at peak and recovery stage of DSE and concerned not only on global parameters but also on individual LV segments. DM is an independent predictor of baseline PSLS, which suggests a specific impact on the development of LV dysfunction and, subsequently, heart failure. Moreover, the comparison with our previous data suggest that the severity of detrimental effect of isolated DM and CAD without DM on global LV PSLS is similar, but the coexistence of both these factors exerts the strongest influence at all stages of DSE. Funding The work was supported by a grant from the State Committee for Scientific Research (number N N402 5002 40). Conflict of interest: None declared. References 1 Ryden L , Grant PJ , Anker SD , Berne C , Cosentino F , Danchin N et al. ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD) . Eur Heart J 2013 ; 34 : 3035 – 87 . 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European Heart Journal – Cardiovascular ImagingOxford University Press

Published: Dec 9, 2017

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