Estimation of coronary artery stenosis by low-dose adenosine stress real-time myocardial contrast echocardiography: a quantitative study.

BACKGROUND: Coronary microcirculation reserve is an important field in the research of coronary artery disease, but it is difficult to identify clinically. Currently it is widely accepted that myocardial contrast echocardiography (MCE) is a safe, inexpensive method and has comparatively high image resolution. The present study used quantitative low-dose adenosine stress real-time (RT)-MCE to estimate myocardial perfusion and the coronary stenosis. METHODS: Forty-nine left ventricular (LV) segments from 14 unselected patients were divided into three groups according to the coronary angiography or CT angiography results: group 1 (n = 20, 41%) without significant stenosis (< 70%), group 2 (n = 12, 24%) with successful percutaneous coronary intervention (PCI), and group 3 (n = 17, 35%) with significant stenosis (> 70%). RT-MCE was performed in these patients with low-dose adenosine stress and continuous infusion of Sonovue. The replenishing curves were drawn according to the contrast density measured at the end-diastolic frame of every cardiac circle by ACQ software. RESULTS: Forty-nine LV segments with satisfactory image quality were picked for quantitative contrast echo analysis. The replenishing curves were analyzed at baseline and after stress. Perfusion of group 3 did not decrease significantly at baseline, and showed no improvement during adenosine stress and was significantly different from groups 1 and 2 (P < 0.05). The A·ß and ß increased more significantly in group 1 than in groups 2 and 3 (P < 0.05). In a receiver operating characteristic (ROC) curve analysis, A·ß under adenosine stress < 1.74 dB/s had a sensitivity and specificity of 71% for diagnosis of coronary artery stenosis, reduced adenosine-induced rise (percentage of A·ß < 81%) had a sensitivity and specificity of 83% and 79% for the diagnosis of low-reserve, and ß < 54% had a sensitivity of 86% and specificity of 79%. CONCLUSIONS: Rest perfusion of severely stenosed arteries may be normal, but adenosine stress can detect the impaired perfusion reserve. Low-dose adenosine stress RT-MCE provides good accuracy for the evaluation of coronary perfusion reserve and hence coronary stenosis.

Left ventricular mechanical dyssynchrony impairs exercise capacity in patients with coronary artery disease with preserved left ventricular systolic function and a QRS duration ≤ 120 ms.

BACKGROUND: Left ventricular (LV) mechanical dyssynchrony can lead to impairment of LV function and is associated with adverse clinical outcomes in coronary artery disease (CAD) patients. The impact of LV dyssynchrony on exercise capacity (EC) in patients with CAD was investigated. METHODS AND RESULTS: An echocardiographic examination with tissue Doppler imaging and exercise treadmill testing in 151 CAD patients with normal LV ejection fraction was performed. LV intra- and inter-ventricular dyssynchrony were defined by the standard deviation of time interval between LV 6 basal segments (Ts-SD), and the time interval from the right ventricular (RV) free wall to LV lateral wall (Ts-RV) respectively, and EC was measured as metabolic equivalents (METs) on the treadmill. Patients with impaired EC (defined by a METs ≤ 8, which is the mean MET of the study population) were older (71 ± 7 vs. 62 ± 2 years, P<0.01), however, there were no differences in gender and clinical status such as prevalence of prior myocardial infarction (MI), regional wall motion abnormality (RWMA), and coronary revascularization between patients with (n=90) or without (n=61) impaired EC. Univariate analysis showed that age, body mass index, LV systolic and diastolic volume, mitral inflow A velocity, and Ts-SD were all significantly associated with METs (all P<0.05). However, multivariate regression analysis revealed that old age (odd ratio [OR]: 1.136, 95% confidence interval [CI]: 1.080-1.196, P<0.001), and Ts-SD (OR: 1.026, 95%CI: 1.003-1.049, P=0.027) only were independent predictors for impaired EC. CONCLUSIONS: In patients with CAD, LV systolic dyssynchrony predicts impaired EC independently of history of previous MI or RWMA.

Subclinical left ventricular dysfunction revealed by circumferential 2D strain imaging in patients with coronary artery disease and fragmented QRS complex.

BACKGROUND: Fragmented QRS (fQRS) complexes on a routine 12-lead electrocardiogram were associated with adverse cardiac events, including sudden death in patients with coronary artery disease (CAD). OBJECTIVE: To investigate the relationship between the fQRS complex and global and regional left ventricular (LV) functions in patients with CAD. METHODS: The study consisted of 176 patients (68 ± 9 years; 145 [82%] men) with CAD with narrow QRS duration and preserved LV ejection fraction (>45%). All patients underwent detailed 2-dimensional speckle-tracking echocardiography to determine global and segmental (basal, middle, and apical) LV strains and strain rates and were prospectively followed-up in the outpatient clinic. RESULTS: Fifty-five patients (31%) had fQRS complexes. Global, middle, and apical LV longitudinal, radial, and circumferential strains and strain rates were significantly lower in the fQRS group than in the non-fQRS group (all P <.05). Multivariate logistic regression analysis revealed that the fQRS complex was associated with decreased global circumferential strain (odds ratio 1.19; 95% confidence interval 1.06-1.33; P = .003) and multivessel disease (odds ratio 3.69; 95% confidence interval 1.35-10.08; P = .011). Kaplan-Meier analysis revealed that event-free survival for cardiac events was significantly lower in the fQRS group than in the non-fQRS group (P = .036). CONCLUSIONS: Our results demonstrated that the fQRS complex in patients with CAD with preserved LV ejection fraction was associated with subclinical global and regional LV dysfunctions as detected by 2-dimensional speckle-tracking imaging, and the results also predicted adverse cardiac events.

Impact of glycemic control on circulating endothelial progenitor cells and arterial stiffness in patients with type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (DM) have increased risk of endothelial dysfunction and arterial stiffness. Levels of circulating endothelial progenitor cells (EPCs) are also reduced in hyperglycemic states. However, the relationships between glycemic control, levels of EPCs and arterial stiffness are unknown. METHODS: We measured circulating EPCs and brachial-ankle pulse wave velocity (baPWV) in 234 patients with type 2 DM and compared them with 121 age- and sex-matched controls. RESULTS: Patients with DM had significantly lower circulating Log CD34/KDR+ and Log CD133/KDR+ EPC counts, and higher Log baPWV compared with controls (all P < 0.05). Among those 120/234 (51%) of DM patients with satisfactory glycemic control (defined by Hemoglobin A1c, HbA1c < 6.5%), they had significantly higher circulating Log CD34/KDR+ and Log CD133/KDR+ EPC counts, and lower Log baPWV compared with patients with poor glycemic control (all P < 0.05). The circulating levels of Log CD34/KDR+ EPC (r = -0.46, P < 0.001) and Log CD133/KDR+ EPC counts (r = -0.45, P < 0.001) were negatively correlated with Log baPWV. Whilst the level of HbA1c positively correlated with Log baPWV (r = 0.20, P < 0.05) and negatively correlated with circulating levels of Log CD34/KDR+ EPC (r = -0.40, P < 0.001) and Log CD133/KDR+ EPC (r = -0.41, P < 0.001). Multivariate analysis revealed that HbA1c, Log CD34/KDR+ and Log CD133/KDR+ EPC counts were independent predictors of Log baPWV (P < 0.05). CONCLUSIONS: In patients with type 2 DM, the level of circulating EPCs and arterial stiffness were closely related to their glycemic control. Furthermore, DM patients with satisfactory glycemic control had higher levels of circulating EPCs and were associated with lower arterial stiffness.

Relationship between ventricular dyssynchrony and T-wave alternans in patients with coronary artery disease.

INTRODUCTION: Coronary artery disease (CAD) is associated with increased dispersion of repolarization and sudden cardiac death. We sought to investigate whether ventricular dyssynchrony is associated with proarrhythmic repolarization dispersion as measured by T-wave alternans (TWA) in patients with CAD. METHODS AND RESULTS: We evaluated 154 patients (67 ± 9 years, 123 men) with documented CAD, who underwent exercise treadmill testing and echocardiographic examination. TWA was analyzed continuously during treadmill testing in all standard precordial leads by time-domain method. Tissue Doppler imaging was performed to measure inter- and intraventricular dyssynchrony. Increased TWA ≥ 60µV was observed in 42 (27%) patients. There was higher prevalence of females (31 vs 16%, P = 0.04) and greater body mass index (25.7 ± 2.6 vs 24.6 ± 3.0 kg/m², P = 0.04) in the TWA ≥ 60µV group of patients than theTWA< 60µV group. The index of interventricular dyssynchrony, Ts-RL, was significantly increased (75.6 ± 37.8 vs 59.9 ± 35.9 ms, P = 0.03) but not intraventricular dyssynchrony (all P > 0.05) in patients with TWA ≥ 60 µV compared with those with TWA < 60 µV. In addition, a weak but significant positive correlation was observed between TWA and Ts-RL (r = 0.25, P = 0.003). Multivariate analysis revealed that only Ts-RL (odds ratio 1.02, 95% confidence interval 1.00­1.03, P = 0.013) was independent predictor for increased TWA. CONCLUSIONS: Our results demonstrated that interventricular dyssynchrony in patients with CAD is associated with increased TWA. This suggests that interventricular dyssynchrony may contribute to proarrhythmic repolarization dispersion.

Effects of right low atrial septal vs. right atrial appendage pacing on atrial mechanical function and dyssynchrony in patients with sinus node dysfunction and paroxysmal atrial fibrillation.

AIMS: To study the effects of right low atrial septum (AS) and right atrial appendage (RAA) pacing on atrial mechanical function and dyssynchrony in patients with sinus node disease (SND) and paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: Detailed echocardiographic examination was performed on 30 patients with SND and paroxysmal AF and a dual-chamber, dual sensing, dual response pacemaker with atrial lead implantation at AS(n= 15) or RAA(n= 15). Peak atrial velocities were recorded by pulsed tissue Doppler spectrum. The timing of atrial contractions (Ta) was measured at the middle of the left atrial (LA) and right atrial (RA) free wall. Intra-[standard deviation (SD) of time of Ta (Ta-SD)] and inter-atrial delay(Ta-RL) was measured as the SD of time interval among LA six segments and time difference between the LA and RA wall, respectively. The baseline clinical statuses were similar between groups. Indexes of LA function, and intra- or inter-atrial dyssynchrony were also similar during intrinsic sinus rhythm in both groups (all P> 0.05). During atrial pacing, LA ejection fraction (52 ± 16 vs. 39 ± 14%, P= 0.029) and LA active emptying fraction (34 ± 7 vs. 23 ± 15%, P= 0.012) were higher in patients with AS than RAA pacing. Atrial velocity was also higher at the RA free wall (14.3 ± 3.1 vs. 10.3 ± 4.4 cm/s, P= 0.009), LA septal (7.5 ± 2.1 vs. 5.2 ± 1.7 cm/s, P= 0.004) and lateral wall (8.6 ± 2.4 vs. 6.3 ± 3.0 cm/s, P= 0.024) during AS compared with RAA pacing. There was no difference in Ts-SD during atrial pacing, nevertheless Ta-RL was significantly prolonged in patients with RAA compared with those with AS pacing (42 ± 36 vs. 27 ± 25 ms, P= 0.011). CONCLUSION: In patients with SND and paroxysmal AF, right low AS pacing significantly improved global and regional atrial mechanical function and synchronized inter-atrial electromechanical contraction compared with RAA pacing.

Smoking is associated with depletion of circulating endothelial progenitor cells and elevated pulmonary artery systolic pressure in patients with coronary artery disease.

Smoking is associated with depletion of endothelial progenitor cells (EPCs) and may subsequently contribute to the development of vascular dysfunction. The aim of this study was to investigate the relation between circulating EPCs and pulmonary artery systolic pressure (PASP) as determined by flow cytometry and echocardiography in 174 patients (mean age 69 ± 9 years, 95 smokers) with established coronary artery disease. Smokers had significantly lower circulating log CD34/KDR(+) (0.86 ± 0.03 vs 0.96 ± 0.03 × 10⁻³/ml, p = 0.032) and log CD133/KDR(+) (0.68 ± 0.03 vs 0.82 ± 0.03 × 10⁻³/ml, p = 0.002) EPCs and a higher prevalence of elevated PASP >30 mm Hg (52% vs 30%, p = 0.001) than nonsmokers. Smokers with elevated PASP also had significantly lower circulating log CD34/KDR(+) (0.74 ± 0.04 vs 0.88 ± 0.06 × 10⁻³/ml, p <0.001) and log CD133/KDR(+) (0.61 ± 0.04 vs 0.78 ± 0.05 × 10⁻³/ml, p <0.001) EPCs, higher pulmonary vascular resistance, and larger right ventricular dimensions with impaired function (all p values <0.05). Log CD34/KDR(+) and log CD133/KDR(+) EPC counts were significantly and negatively correlated with PASP (r = -0.30, p <0.001, and r = -0.34, p <0.001, respectively) and pulmonary vascular resistance (r = -0.29, p = 0.002, and r = -0.18, p = 0.013, respectively). In conclusion, this study demonstrated that in patients with coronary artery disease, smoking was associated with a reduced number of EPCs and elevated PASP. This suggests that in smokers, depletion of circulating EPCs might be linked to the occurrence of pulmonary vascular dysfunction.

Elevated pulmonary artery systolic pressure in patients with coronary artery disease and left ventricular dyssynchrony.

AIMS: We sought to determine whether inter- or intra-ventricular systolic dyssynchrony contributes to the occurrence of elevated pulmonary artery systolic pressure (PASP) in patients with coronary artery disease (CAD). METHODS AND RESULTS: One hundred and fifty-three consecutive CAD patients with preserved left ventricular ejection fraction (LVEF >40%) were enrolled. Detailed echocardiography was performed to measure PASP, inter-ventricular dyssynchrony (Ts-RL: time difference between lateral and right free wall), and intra-ventricular dyssynchrony (Ts-SD, standard deviation of time to peak systolic velocity of 12 LV segments; Ts-12, maximal difference in Ts between any 2 of 12 LV segments; Ts-6-basal, maximal difference in Ts between any 2 of 6 basal LV segments). Elevated PASP (>35 mmHg) was confirmed in 46 patients who had significantly prolonged intra-ventricular dyssynchrony (Ts-SD: 49.9 ± 19.6 vs.37.9 ± 19.8 ms; Ts-12: 147.9 ± 56.4 vs.110.9 ± 53.9 ms; Ts-6-basal: 114.2 ± 51.9 vs. 85.7 ± 48.5 ms, all P < 0.01) and inter-ventricular dyssynchrony (Ts-RL: 78.7 ± 46.4 vs. 62.7 ± 34.3 ms, P = 0.019) compared with those without elevated PASP. Indexes of intra- and inter-ventricular dyssynchrony and LV filling pressure (E/e') were significantly correlated with PASP. Multivariate analysis showed that left atrial dimension [odds ratio (OR) 4.23, 95% confidence interval (CI) 1.64-10.90], E/e' septal (OR 1.15, 95% CI 1.04-1.27), pulmonary vascular resistance (OR 5.38, 95% CI 1.55-18.74), and Ts-RL (OR 1.02, 95% CI 1.01-1.03) were independent predictors for the occurrence of elevated PASP (all P < 0.05). CONCLUSION: Elevated PASP is common in CAD patients with preserved LVEF and is associated with LV diastolic dysfunction and LV mechanical dyssynchrony.

Interatrial mechanical dyssynchrony worsened atrial mechanical function in sinus node disease with or without paroxysmal atrial fibrillation.

INTRODUCTION: Atrial electromechanical dysfunction might contribute to the development of atrial fibrillation (AF) in patients with sinus node disease (SND). The aim of this study was to investigate the prevalence and impact of atrial mechanical dyssynchrony on atrial function in SND patients with or without paroxysmal AF. METHODS: We performed echocardiographic examination with tissue Doppler imaging in 30 SND patients with (n = 11) or without (n = 19) paroxysmal AF who received dual-chamber pacemakers. Tissue Doppler indexes included atrial contraction velocities (Va) and timing events (Ta) were measured at midleft atrial (LA) and right atrial (RA) wall. Intraatrial synchronicity was defined by the standard deviation and maximum time delay of Ta among 6 segments of LA (septal/lateral/inferior/anterior/posterior/anterospetal). Interatrial synchronicity was defined by time delay between Ta from RA and LA free wall. RESULTS: There were no differences in age, P-wave duration, left ventricular ejection fraction, LA volume, and ejection fraction between with or without AF. Patients with paroxysmal AF had lower mitral inflow A velocity (70 +/- 19 vs 91 +/- 17 cm/s, P = 0.005), LA active empting fraction (24 +/- 14 vs 36 +/- 13%, P = 0.027), mean Va of LA (2.6 +/- 0.9 vs 3.4 +/- 0.9 cm/s, P = 0.028), and greater interatrial synchronicity (33 +/- 25 vs 12 +/- 19 ms, P = 0.022) than those without AF. Furthermore, a lower mitral inflow A velocity (Odd ratio [OR]= 1.12, 95% Confidence interval [CI] 1.01-1.24, P = 0.025) and prolonged interatrial dyssynchrony (OR = 1.08, 95% CI 1.01-1.16, P = 0.020) were independent predictors for the presence of AF in SND patients. CONCLUSION: SND patients with paroxysmal AF had reduced regional and global active LA mechanical contraction and increased interatrial dyssychrony as compared with those without AF. These findings suggest that abnormal atrial electromechanical properties are associated with AF in SND patients.