Go Hiasa

Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy.

OBJECTIVES This study was designed to evaluate the beneficial effect of beta-blockers on circulating cytokine levels in patients with dilated cardiomyopathy (DCM). BACKGROUND Elevated circulating levels of inflammatory cytokines have been reported in patients with DCM. However, alterations of the levels of inflammatory and anti-inflammatory cytokines in association with beta-blocker therapy are unknown. METHODS We studied 32 patients with idiopathic DCM who had been treated with digitalis, diuretics and angiotensin-converting enzyme inhibitors. In addition to this combination therapy, beta-blockers were started in all patients. Serum levels of interleukin (IL)-10, tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors (sTNF-R1 and R2) were measured at baseline and 12 weeks after the initiation of beta-blocker therapy. We also measured plasma levels of neurohumoral factors, as well as left ventricular (LV) size and function. Ten age-matched subjects with no cardiac disease served as the control group. RESULTS Baseline levels of IL-10, TNF-alpha and sTNF-R2 were significantly higher in patients with DCM than in control subjects (p < 0.05). There was a significant positive correlation between IL-10 and TNF-alpha levels (r = 0.545, p = 0.029). The TNF-alpha/IL-10 ratio correlated well with plasma epinephrine levels (r = 0.677, p = 0.025), and the level of sTNF-R2 was closely related to LV size. Serum levels of IL-10, TNF-alpha and sTNF-R2 were significantly decreased during beta-blocker therapy (p < 0.005). CONCLUSIONS Our findings indicate that beta-blockers have an important immunoregulatory role in modifying the dysregulated cytokine network in DCM. This effect of beta-blockers may be partly responsible for the efficacy of therapeutic drugs for heart failure.

Clinical significance of global two-dimensional strain as a surrogate parameter of myocardial fibrosis and cardiac events in patients with hypertrophic cardiomyopathy

AIMS Late gadolinium enhancement (LGE) on contrast-enhanced magnetic resonance imaging (MRI) in hypertrophic cardiomyopathy (HCM) has been reported to be associated with myocardial fibrosis and cardiac events. In patients with HCM, two-dimensional (2D) strain can identify subclinical global systolic dysfunction despite normal left ventricular (LV) chamber function. Therefore, this study tested the hypothesis that global 2D strain could detect subtle myocardial fibrosis and serve as a novel prognostic parameter in HCM patients. METHODS AND RESULTS Echocardiography and MRI were performed in 48 consecutive patients with HCM and normal chamber function. We measured global longitudinal strain (GLS) in apical two-chamber, four-chamber, and long-axis views using speckle-tracking analysis. The extent of LGE (%LGE = LGE volume/total LV volume) and LV mass index were calculated by MRI using Simpsons rule and custom software. All patients were followed up for major cardiac events. Global longitudinal strain in patients with LGE was significantly lower than that without LGE (-11.8 ± 2.8 vs. -15.0 ± 1.7%, P < 0.001). Multivariate analysis showed that GLS was an independent predictor of %LGE (standard coefficient = 0.627, P < 0.001). During a mean follow-up period of 42 ± 12 months, five patients had cardiac events. When the patients were stratified based on the median level of GLS (-12.9%), all events were observed in the worse GLS group (P = 0.018). CONCLUSION These results suggest that global 2D strain might provide useful information on myocardial fibrosis and cardiac events in HCM patients with normal chamber function.

Possible link between large artery stiffness and coronary flow velocity reserve

Background: Population studies have shown that increased large artery stiffness is an independent predictor of cardiovascular events. Experimental studies have shown that a stiff aorta is associated with decreased coronary blood flow. However, a link between large artery stiffness and coronary microvascular function in the clinical setting has not been demonstrated previously. Objective: To evaluate the relationship between large artery stiffness and coronary flow velocity reserve (CFVR). Patients and methods: 102 consecutive subjects (mean (SD) age 62 (10) years) without coronary and peripheral arterial disease were enrolled in the study. After 15 minutes’ rest, measurements were obtained of brachial-ankle pulse wave velocity (baPWV), augmentation index (AIx) from a carotid pulse tracing, and transthoracic echocardiographic measures, including coronary flow velocity in the left anterior descending coronary artery. In addition, coronary flow velocity during hyperaemia was measured during an intravenous infusion of adenosine triphosphate. CFVR was defined as the ratio of hyperaemic to basal coronary velocity. Results: Subjects with decreased CFVR (<2.5; n = 40) had significantly higher baPWV (1848 (369) cm/s vs 1548 (333) cm/s; p<0.001), greater AIx (25.3 (11.0)% vs 16.3 (20.0)%; p = 0.01) and greater pulse pressure (PP) (64 (13) mm Hg vs 54 (13) mm Hg; p<0.001) than those with normal CFVR (⩾2.5; n = 62). Multivariate analysis showed that AIx and PP were independent predictors of CFVR (r =  −0.32, p<0.001 and −0.25, p = 0.02, respectively). Conclusions: The data suggest that large artery stiffening is linked to a reduction of CFVR, which may partially explain the higher cardiac event rate in patients with increased large artery stiffness.

Determinants of left ventricular untwisting behaviour in patients with dilated cardiomyopathy: analysis by two-dimensional speckle tracking

Background/objective: Left ventricular (LV) untwisting velocity has emerged as a novel index of LV diastolic function since it is thought to be related to LV diastolic suction. However, the pathophysiology of LV untwisting behavior has not been fully investigated. The aim of this study was to investigate the determinants of LV peak untwisting velocity in patients with dilated cardiomyopathy (DCM). Methods: 101 patients with DCM (mean age 60 (SD 13) years) and 50 control subjects were evaluated. After a standard echocardiographic examination, peak torsion and peak untwisting velocity were measured using two-dimensional speckle-tracking imaging. Radial dyssynchrony was assessed by speckle-tracking radial strain analysis. Tissue Doppler derived systolic (Ts-SD) and diastolic (Te-SD) dyssynchrony indices were also assessed. Results: The patients with DCM had significantly smaller peak torsion (p<0.001) and peak untwisting velocity (p<0.001) and greater radial dyssynchrony (p<0.001) and Ts-SD (p<0.001) and Te-SD (p = 0.001) compared with the control subjects. The peak untwisting velocity was correlated with end-systolic volume index (r = 0.524, p<0.001), E/e′ (r = 0.365, p<0.001), radial dyssynchrony (r = 0.578, p<0.001), Ts-SD (p<0.001), Te-SD (p<0.001) and peak torsion (r = −0.635, p<0.001) in patients with DCM. Multivariate analysis revealed that peak torsion, radial dyssynchrony and E/e′ were independent predictors of peak untwisting velocity in patients with DCM (standard coefficient −0.483, p<0.001, 0.330, p<0.001 and 0.241, p = 0.001, respectively). Conclusion: These results suggest that strain-based LV radial dyssynchrony and E/e′ as well as LV torsion are related to diastolic untwisting behaviour in patients with DCM.

Right Ventricular Pacing from the Septum Avoids the Acute Exacerbation in Left Ventricular Dyssynchrony and Torsional Behavior Seen with Pacing from the Apex

OBJECTIVE The study objective was to compare the left ventricular (LV) dyssynchrony and torsional behavior between right ventricular apical (RVA) and right ventricular septal (RVS) pacing. METHODS Forty-six patients with symptomatic sick sinus syndrome and preserved LV function were assigned to 2 groups: RVA (n = 23) and RVS (n = 23). Echocardiographic study including two-dimensional speckle tracking imaging was performed in the AAI and DDD modes. RESULTS Mean QRS width during DDD mode was significantly longer with RVA pacing than with RVS pacing. Dyssynchrony, torsion, and untwisting rate during DDD mode were significantly worse with RVA than with RVS pacing. In patients with RVA pacing, there was an increase in longitudinal dyssynchrony from AAI to DDD mode that significantly correlated with the deterioration of untwisting rate. CONCLUSION In bradyarrhythmic patients with preserved LV function, RVS pacing resulted in a reduced LV dyssynchrony and better torsional behavior than RVA pacing.

The differences in left ventricular torsional behavior between patients with hypertrophic cardiomyopathy and hypertensive heart disease.

BACKGROUND The aim of this study was to investigate the differences in left ventricular (LV) twisting behavior between patients with hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD). METHODS Forty-four patients with HCM (mean age, 63±15 years), 35 patients with HHD (mean age, 63±13 years) and 20 age and sex-matched control subjects were evaluated. After a standard echocardiographic examination, LV twist and twisting velocity profiles from apical and basal short-axis images were analyzed using two-dimensional speckle tracking imaging. RESULTS LV diastolic and systolic dimensions, and ejection fraction were not significantly different among the groups. LV mass index and early diastolic mitral annular velocity were not significantly different between the HCM and HHD groups. The peak torsion in the HCM and HHD groups was significantly greater than that in the control group. The peak untwisting velocity in the HCM group was comparable with that in the control group. However, when the peak untwisting velocity was corrected by peak torsion, this ratio was significantly decreased in the HCM group compared with the values in the HHD and control groups. The time to peak untwisting velocity in the HCM group was significantly longer than the values in the HHD and control groups. CONCLUSIONS These results suggest that enhanced peak torsion in HCM may improve untwisting behavior, but this mechanism fails to fully compensate for impaired untwisting behavior compared with HHD.

Impact of type 2 diabetes on serial changes in tissue characteristics of coronary plaques: an integrated backscatter intravascular ultrasound analysis

AIMS Several studies have demonstrated that type 2 diabetes mellitus (T2DM) is associated with accelerated atherosclerosis, which results in an increased risk of coronary vascular events. However, serial changes in plaque characteristics have not been reported in vivo. We evaluated the progression of coronary atherosclerosis in patients with T2DM using an integrated backscatter intravascular ultrasound (IB-IVUS) examination. METHODS AND RESULTS Forty-two T2DM and 48 non-diabetic patients who underwent percutaneous coronary intervention were enrolled in the study. Non-culprit 20-mm length coronary lesions with mild-to-moderate stenosis were measured using a 40-MHz (motorized pullback of 0.5 mm/s) IVUS catheter. IVUS examinations were performed on one target lesion in each patient. Six months later, a follow-up IVUS examination was repeated in the same coronary segment imaged at the baseline examination. T2DM patients demonstrated a greater total plaque volume (TPV; 139 ± 53 vs. 114 ± 45 mm(3), P = 0.02) and total lipid volume (TLV; 67 ± 26 vs. 55 ± 30 mm(3), P = 0.039) at the baseline examination. The progression of TPV (8.6 ± 15.4 vs. -2.2 ± 16.0%, P < 0.01) and TLV (10.8 ± 28.8 vs. -2.5 ± 20.0%, P < 0.05) from the baseline was observed in T2DM patients, but not in non-diabetic patients. The increase in TLV was blunted in T2DM patients who achieved HbA1c levels of <6.5%. CONCLUSION Accelerated plaque progression with an increase in the lipid-rich component of non-culprit plaques was observed in T2DM, despite the use of standard medical treatment. Better glycaemic control ameliorated the worsening of plaque characteristics in T2DM.

Dysfunctional central hemodynamic regulation after daily meal intake in metabolic syndrome

OBJECTIVE Postprandial hyperlipidemia and insulin resistance play roles in the development of atherosclerosis in metabolic syndrome (MetS); however, the clinical significance of postprandial hemodynamic variables in this condition is still in question. The aim of this study was to investigate hemodynamic and metabolic indicators related to MetS after a mixed meal (Calorie mate, 500 kcal). METHODS Of 107 participants undergoing this investigation, 24 fulfilled ATPIII criteria for MetS. The remaining 83 subjects were controls. Both the augmentation index (AI) and late systolic blood pressure in the radial artery (rSBP2) as an index of central blood pressure were monitored using HEM-9000AI (Omron Healthcare, Kyoto, Japan) until 240 min after meal intake. RESULTS Both AI and rSBP2 showed significant decreases after meal intake in both groups. Changes in postprandial AI showed a similar trend in the groups. rSBP2 reduction 60 min after meal ingestion was also comparable, -7.5+/-2.3 mmHg in MetS; -7.8+/-0.9 mmHg in control; however, delta rSBP2-120, the degree of rSBP2 reduction 120 min after meal ingestion comparing the fasting level, showed a significant difference between 2 groups, -0.5+/-2.0 mmHg in MetS; -5.3+/-0.9 mmHg in control, P<0.02. Stepwise regression analysis revealed low-density-lipoprotein cholesterol (beta=0.333, P=0.001), high-density-lipoprotein cholesterol (beta=-0.209, P<0.05) and systolic blood pressure (beta=-0.377, P<0.001) as independent variables for determining delta rSBP2-120. CONCLUSION Subjects with MetS exhibit signs of blunted rSBP2 (=central blood pressure) regulation after food intake. Dysfunctional postprandial hemodynamic regulation is another feature of MetS that may contribute to the progression of cardiovascular disease.

Assessment of intermediate stenosis in the left anterior descending coronary artery with contrast-enhanced transthoracic Doppler echocardiography.

Background Visual or quantitative assessment of coronary angiography may not exactly predict the physiological significance of intermediate (40‐70%) coronary stenosis. Coronary flow reserve is a well‐established marker of the functional significance of coronary stenosis. Objectives The aim of this study was to compare the coronary flow velocity reserve (CFVR) using contrastenhanced transthoracic Doppler echocardiography (CETTDE) with thallium‐201 imaging in assessment of intermediate lesions in the left anterior descending coronary artery (LAD). Methods A consecutive series of 50 patients with intermediate stenosis in the LAD underwent pharmacological stress thallium‐201 imaging and CFVR measured by CETTDE. Results CFVR could be measured in 49 of 50 patients by the present method. A CFVR <2.0 predicted the presence of a stress thallium defect in 12 of 14 patients (agreement =90%, κ =0.76, P < 0.001). The sensitivity and specificity of CFVR for stress thallium‐201 results were 86 and 91%, respectively. In contrast, significant stenosis (> 50% by diameter) showed fair agreement for stress thallium defects (agreement = 59%, κ = 0.28, P < 0.05). Conclusions In the evaluation of intermediate lesions in the LAD, CFVR as assessed by CE‐TTDE could accurately predict the presence of ischemia on stress thallium imaging, whereas angiographic stenosis did not yield reliable results. Coron Artery Dis 14:247‐254

Carotid arterial circumferential strain by two-dimensional speckle tracking: a novel parameter of arterial elasticity

Recently, the development of two-dimensional speckle-tracking (2DST) technology has allowed the direct measurement of the elastic parameters of the carotid arterial wall. The aims of this study were to determine the feasibility of measuring peak circumferential strain (CS) of the carotid arterial wall using 2DST and to compare this value with conventional arterial stiffness parameters in subjects with and without hypertension. The study included 90 healthy subjects and 40 age-and sex-matched patients with hypertension. The short-axis view of the right common carotid artery was recorded. The CS in the posterior region of the carotid artery was calculated by 2DST using special software and corrected by the following equation: ɛcirc=ln (systolic blood pressure/diastolic blood pressure)/CS. We simultaneously measured the stiffness index β (β) at the same location and the brachial-ankle pulse wave velocity (baPWV). Sixty randomly selected healthy subjects were used to assess the inter/intra-observer variability of ɛcirc and β. In healthy subjects, ɛcirc was significantly correlated with β, age and baPWV. These correlations were slightly better than the corresponding correlations of β with age and baPWV. The hypertensive patients had a significantly larger ɛcirc than the healthy subjects (0.112±0.074 vs. 0.066±0.029/%, P<0.001). The inter/intra-observer variability for ɛcirc was significantly lower than that for β. Our data suggest that the measurement of carotid ɛcirc using 2DST is feasible and has better reproducibility than conventional carotid arterial stiffness.