Katsuji Inoue

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.

Qualitative and Quantitative Assessment of Adenosine Triphosphate Stress Whole-Heart Dynamic Myocardial Perfusion Imaging Using 256-Slice Computed Tomography

Background The aim of this study was to investigate the correlation of the qualitative transmural extent of hypoperfusion areas (HPA) using stress dynamic whole-heart computed tomography perfusion (CTP) imaging by 256-slice CT with CTP-derived myocardial blood flow (MBF) for the estimation of the severity of coronary artery stenosis. Methods and Results Eleven patients underwent adenosine triphosphate (0.16 mg/kg/min, 5 min) stress dynamic CTP by 256-slice CT (coverage: 8 cm, 0.27 s/rotation), and 9 of the 11 patients underwent coronary angiography (CAG). Stress dynamic CTP (whole–heart datasets over 30 consecutive heart beats in systole without spatial and temporal gaps) was acquired with prospective ECG gating (effective radiation dose: 10.4 mSv). The extent of HPAs was visually graded using a 3-point score (normal, subendocardial, transmural). MBF (ml/100g/min) was measured by deconvolution. Differences in MBF (mean ± standard error) according to HPA and CAG results were evaluated. In 27 regions (3 major coronary territories in 9 patients), 11 coronary stenoses (> 50% reduction in diameter) were observed. In 353 myocardial segments, HPA was significantly related to MBF (P < 0.05; normal 295 ± 94; subendocardial 186 ± 67; and transmural 80 ± 53). Coronary territory analysis revealed a significant relationship between coronary stenosis severity and MBF (P < 0.05; non-significant stenosis [< 50%], 284 ± 97; moderate stenosis [50–70%], 184 ± 74; and severe stenosis [> 70%], 119 ± 69). Conclusion The qualitative transmural extent of HPA using stress whole-heart dynamic CTP imaging by 256-slice CT exhibits a good correlation with quantitative CTP-derived MBF and may aid in assessing the hemodynamic significance of coronary artery disease.

Takotsubo cardiomyopathy with a significant pressure gradient in the left ventricle

H. Matsuoka (*) · H. Kawakami · Y. Koyama · K. Inoue · K. Nishimura · H. Saeki · T. Ito Department of Cardiology, Ehime Prefectural Imabari Hospital, 4-5-5 Ishii-cho, Imabari, Ehime 794-0006, Japan Tel. 181-898-32-7111; Fax 181-898-22-1398 e-mail: matsuhi@dokidoki.ne.jp An 86-year-old woman was admitted to our hospital for sustained chest discomfort. She was suspected of having acute myocardial infarction from echocardiographical findings. The ECG revealed broad anterior and inferior STsegment elevation which did not change after intravenous administration of nitroglycerin. The level of serum creatine kinase was 230IU/l. Emergency coronary arteriography revealed normal coronary arteries. The left ventriculogram showed anterolateral and apical akinesis, but basal hyperkinesis. The endsystolic left ventriculogram was shaped like a flask (“Takotsubo” or “Ampulla”) and the akinetic area could not be explained by only single coronary artery disease, as shown in Fig. 1A. She was diagnosed as having so-called Takotsubo cardiomyopathy. A pullback study from apical to basal left ventricle showed a significant pressure gradient of 60mmHg (Fig. 1B). Hypotension under 90mmHg continued and she finally went into shock. Catecholamine was administrated but she failed to recover from shock. On the third day, sudden death occurred during defecation with ventricular fibrillation. The prognosis for “Takotsubo” cardiomyopathy is usually good. However, a poor prognosis has been reported in a few cases. In our patient, the administration of catecholamine for shock due to a significant pressure gradient in the left ventricle seems to have induced a greater pressure gradient, as in cases of obstructive hypertrophic cardiomyopathy, and resulted in ventricular fibrillation. Catecholamine should be carefully used for shock in “Takotsubo” cardiomyopathy patients with a pressure gradient in the left ventricle. Fig. 1. End-diastolic (a) and end-systolic (b) left ventriculogram (A) shows anterolateral and apical akinesis. The end-systolic left ventriculogram is shaped like a flask (“Takotsubo” or “Ampulla”). Pullback pressure analysis in the left ventricle (B) shows a significant pressure gradient. LV, left ventricle

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.

Clinical and angiographical characteristics of acetylcholine- induced spasm: relationship to dose of intracoronary injection of acetylcholine.

ObjectivesThe purpose of this study was to clarify clinical and angiographical characteristics of acetylcholine (ACh)-induced spasm in the right and left coronary artery. Methods and resultsWe performed 557 consecutive procedures of spasm provocation tests of ACh from January 1991 to December 2000 in patients without significant stenosis. ACh was injected in incremental doses of 20, 50 and 80 μg into the right coronary artery and in incremental doses of 20, 50 and 100 μg into the left coronary artery if spasm had not been provoked. Coronary spasm was defined as positive with more than 99% transient luminal narrowing. Proximal spasm was defined as that of segments 1, 2, 5, 6, 7 and 11 and distal spasm as that of segments 3, 4, 8, 9, 12, 13 and 14. Low-ACh-dose-induced spasms showed the clinical findings and angiographical characteristics of higher incidence of variant angina, proximal spasms, focal spasms, more ST elevation and ischemic heart disease. In contrast, angiographical characteristics of high-Ach-dose-induced spasms were distal spasms and diffuse spasms and there was less variant angina and less ST elevation. ConclusionsLower ACh doses induced spasms more proximally and focally in the coronary artery, while higher doses of ACh provoked spasms more distally and diffusely.

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.