Takumi Sumimoto

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.

Clinical evidence for an association between left ventricular geometric adaptation and extracardiac target organ damage in essential hypertension

Objectives To elucidate an association between left ventricular geometric adaptation to sustained hypertension and preclinical extracardiac target organ damage in essential hypertension. We also studied the clinical significance of neurohumoral factors for cardiovascular structural changes. Design One hundred and forty patients with essential hypertension were divided into four subgroups, based on left ventricular mass index and relative wall thickness. With respect to extracardiac target organ damage, we measured the funduscopic grade of retinal changes and serum creatinine levels. Results Among the hypertensive patients, only 19 (14%) had a typical concentric hypertrophy (increase in left ventricular mass index and relative wall thickness). Hypertensive patients with concentric hypertrophy had the most advanced funduscopic abnormalities and the greatest renal involvement, and hypertensive patients without left ventricular hypertrophy had the least extracardiac target organ damage. Plasma renin activity and plasma aldosterone concentration were higher in hypertensive patients with than in those without concentric hypertrophy. In a multiple regression model there was a strongly significant correlation between the degree of left ventricular mass index and the severity of hypertensive retinopathy and renal involvement, independent of office blood pressure. Conclusions These results clearly demonstrate that echocardiographically determined left ventricular mass and geometry stratify extracardiac target organ damage in patients with essential hypertension more closely than office blood pressure. The present study also suggests that, in addition to blood pressure load, the renin-angiotensin-aldosterone system appears to play an important role in myocardial hypertrophy and peripheral vascular damage in hypertension.

Plasma Adrenomedullin Concentrations and Cardiac and Arterial Hypertrophy in Hypertension

It has been reported that plasma concentrations of adrenomedullin (AM), a novel vasodilator peptide, are higher in patients with essential hypertension than those in normotensive subjects. To clarify the clinical significance of increased levels of AM in patients with essential hypertension, in this study we examined the relationship between plasma concentrations of AM and the structure of the left ventricle or carotid artery. Plasma AM concentrations; renin activity; and norepinephrine, epinephrine, and creatinine concentrations in 50 patients with untreated essential hypertension without renal dysfunction and heart failure were measured. We also measured the mean wall thickness of the left ventricle and left ventricular mass index by M-mode echocardiography and intimal-medial thickness and arterial distensibility of the carotid artery by ultrasonography. Hypertensive patients were divided into two groups: hypertensives with and those without left ventricular hypertrophy. Plasma AM concentrations in hypertensive patients with left ventricular hypertrophy were significantly higher than in hypertensive patients without left ventricular hypertrophy (7.87+/-2.70 vs 5.74+/-1.65 fmol/mL, P<.01). In all hypertensive patients, plasma AM concentrations were not correlated with blood pressure, plasma renin activity, plasma norepinephrine, plasma epinephrine, or plasma creatinine concentration. Plasma AM concentrations were positively correlated with left ventricular mass index or mean wall thickness (r=.37, P=.009; r=.40, P=.004, respectively) and inversely correlated with carotid artery distensibility (r=-.33, P=.02), whereas plasma AM concentrations were not correlated with intimal-medial thickness. These results suggest that the observed elevation of plasma AM in patients with essential hypertension with normal renal function may be partly related to cardiac hypertrophy and decreased carotid artery distensibility.

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.

Morphologic and Histologic Characterization of Cardiac Myxomas by Magnetic Resonance Imaging

The purpose of this study was to assess the role of ECG-gated spin-echo (SE) magnetic resonance (MR) images, cine MR images, and gadolinium-diethylenetriaminepen taacetic acid (Gd-DTPA)-enhanced MR images for the morphologic and histologic diagnosis of atrial myxomas. Four patients with left atrial myxoma were imaged with a 1.5-T MR imager. The T1-weighted images and the cine MR images were obtained before injection of Gd- DTPA. After the injection of Gd-DTPA, the T1-weighted images were obtained again. Gd-DTPA-enhanced images of the myxomas were histologically compared with the extracted specimens. (continued on next page) The tumors were represented more clearly on the cine MR images as low-intensity areas than on the SE images as high-intensity areas. On post-Gd-DTPA images, the 2 tumors were homogeneously enhanced and the other 2 were inhomogeneously enhanced. The locus of enhancement on post-Gd-DTPA images fitted with histologic myxoma or inflammation, and the unenhanced region reflected the necrosis or cystic changes in the specimens, respectively. The morphologic diagnosis of cardiac myxomas by MRI first should be done with SE images, and when the images are unclear, the cine MR images must be supplemented to depict the tumor clearly. Moreover, Gd-DTPA-enhanced MRI could elucidate histo logic characteristics in myxomas.

Precise assessment of myocardial damage associated with secondary cardiomyopathies by use of Gd-DTPA-enhanced magnetic resonance imaging.

To evaluate the myocardial damage in patients with secondary cardiomy opathies, the authors examined gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) in 5 patients (2 with cardiac amyloidosis, 2 with acute myocarditis, 1 with cardiac thyrotoxicosis). MR images were performed at 1.5-T by using a spin echo pulse sequence before and after intravenous administration of Gd-DTPA (0.2 mmol/kg). All patients revealed distinct high-intensity areas on postcontrast images. Moreover, MRI with Gd-DTPA could determine the severity and precise regions of myocardial damage associated with secondary cardiomyopathies. It is suggested that gated cardiac MRI with Gd-DTPA enhancement is useful for detecting the myocardial damage in secondary cardiomyopathies.

Measurement of cardiac chamber volumes by cine magnetic resonance imaging.

Cardiac chamber volumes (both atria and ventricles) in 19 healthy volun teers were measured noninvasively by cine magnetic resonance imaging (MRI). First, cardiac localization was determined from the coronal image by 0.5-T superconducting magnetic imager. Then, transaxial ECG gated multislice spin echo images were obtained from the bottom to the top of the heart. In the last step, cine MRI was performed at each level of all these transaxial spin echo MR images involving the heart. Each cardiac chamber volume at the same phase was calculated by adding chamber areas in each anatomic section multiplied by slice thickness. Left ventricular (LV) end-diastolic volume (EDV) (132.0±26.9 mL) and LV end-systolic volume (ESV) (47.8 ±13.9 mL) were smaller than right ventricular (RV) EDV (141.1 ±24.8 mL) and RVESV (57.0± 12.6 mL), respec tively (p < 0.01). LV stroke volume (84.3±17.9 mL) was equivalent to RV stroke volume (84.2±17.6 mL) (r=0.91, p < 0.01). Left atrial (LA) and right atrial (RA) maximal volumes were 75.8 ±15.4 mL and 84.4±18.7 mL, respectively. LA minimal volume (37.5 ± 10.7 mL) was smaller than RA minimal volume (47.8 ± 12.2 mL). These values measured by cine MRI are satisfactory and cine MRI will be a useful method of determining cardiac chamber volumes, espe cially atrial volumes.

Effect of age on left ventricular geometric patterns in hypertensive patients.

Objectives To investigate the effect of age on left ventricular structure and geometry in hypertensive patients, we studied the relationship between age and echocardiographic variables in patients with uncomplicated essential hypertension. Patients and methods We divided 168 patients with hypertension into three groups according to age: young (<40 years), middle-aged (40–59 years) and an elderly group (±60 years). They were further categorized according to relative wall thickness and the left ventricular mass index. We then evaluated the prevalence of left ventricular geometric patterns in these patients according to age. Results The left ventricular end-diastolic dimension decreased with age, both in normotensive control subjects and in hypertensive patients. The magnitude of this decrease was similar for both. The relative wall thickness and left ventricular mass index were greater in the hypertensive patients than in the normotensive control subjects, and these increased with age both in the controls and the hypertensives. The differences between normotensives and hypertensives in these variables remained unchanged with age. The prevalence of a normal left ventricle (normal relative wall thickness and left ventricular mass index) in the hypertensive patients decreased with age. Conversely, the prevalence of concentric remodeling (increased relative wall thickness with normal left ventricular mass index) and concentric hypertrophy (increased relative wall thickness and left ventricular mass index) increased with age. Conclusions These results demonstrate that age significantly affects left ventricular structure both in normotensive control subjects and in hypertensive patients. Thus, the differences in left ventricular geometric patterns with age may have important implications in assessing left ventricular structure and geometric patterns in hypertensive patients.

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.