A new therapeutic strategy for hypertrophic nonobstructive cardiomyopathy in humans. A randomized and prospective study with an Angiotensin II receptor blocker.

A randomized and prospective study was designed to prove the efficacy of angiotensin II receptor blockers (ARB) in the amelioration of myocardial impairment in hypertrophic nonobstructive cardiomyopathy (HNCM). Nineteen consecutive patients with HNCM were randomly assigned to two groups and then underwent cine magnetic resonance evaluation of left ventricular mass (LVM) twice just before and after one year of observation. In the ARB group, 50 mg of losartan potassium was administered once daily during the observation period. The ratio of LVM after the observation period over that before the period was blindly compared between the two groups to estimate morphologically the ameliorative effect of ARB. In the ARB group, LVM was 203 +/- 47 cm(3) before the treatment period and 190 +/- 55 cm(3) after the period and the ratio of the final LVM over the initial LVM was 0.93 +/- 0.10. In the non-ARB group the initial and final LVM values were 177 +/- 48 cm(3) and 179 +/- 45 cm(3), and the ratio of the final LVM over the initial LVM was 1.02 +/- 0.07. The ratio of the final LVM over the initial LVM in the ARB group was significantly smaller (P = 0.03) than that in the non-ARB group. The smaller ratio in the ARB group strongly indicates that ARB ameliorated the natural course of HNCM during the one year observation period. Thus, this is the first demonstration of the therapeutic efficacy of ARB in human HNCM.

Morbidity prevalence rate of kawasaki disease assessed by single cross-sectional history-taking.

The need for long-term follow-up in Kawasaki disease is poorly recognized although cardiac sudden death attacks asymptomatic young people with past illness after a long latent period. Therefore, in order to prevent cardiac disasters, high risk groups should be identified and the prevalence rate of the disease should be determined for crisis management. A total of 9,965 consecutive freshmen at the University of Tokyo were the subject of a questionnaire. Their parents/guardians who were briefed on the diagnostic criteria of the acute phase of Kawasaki disease actually completed the questionnaire. Students with a positive diagnosis underwent rest and exercise-stress electrocardiography and routine echocardiography. The overall prevalence rate was 0.57%. The rate in males (0.63%) was greater than that in females (0.32%) (P < 0.05). Electrocardiography and routine echocardiography identified no indices specific to a past illness of Kawasaki disease. The prevalence rate indicated that about 6 in 1000 students were high risk students who needed special care while at university. Since there are few symptoms and no signs indicating a past illness of Kawasaki disease, intensive history-taking from parents/guardians who are familiar with their acute symptoms during childhood is required in order to identify those at high risk of a coronary event.

Gender-specific clinical characteristics of deep Q waves in hypertrophic cardiomyopathy.

BACKGROUND: Despite male predominance in the prevalence of hypertrophic cardiomyopathy (HCM), repeated diagnosis at our institute indicates a possible higher prevalence of deep Q waves with HCM in women. OBJECTIVE: The current study examined gender similarities and differences in the prevalence of deep Q waves in HCM and in the morphologic and electrocardiographic features of HCM with deep Q waves. METHODS: Patients with HCM underwent cardiac magnetic resonance (CMR) imaging to identify the prevalence of deep Q waves in electrocardiographic limb leads, and to analyze the relationship between distribution patterns of deep Q waves and those of the localization of maximum amplitude of left ventricular (LV) hypertrophy. Contiguous LV short-axis images were obtained from the base toward the apex. RESULTS: Of the 200 consecutive patients (172 males, aged 20-78 years; 28 females, aged 16-79 years) with HCM who underwent CMR imaging, 10 male and 8 female patients had deep Q waves. Deep Q waves were more prevalent in females with HCM than in their male counterparts (28.6% vs 5.8%, respectively; P<0.001). Of the 18 patients with deep Q waves, maximum wall thickness was localized at either the basal anterior wall or the midventricular septum in 9 (90%) of the 10 male patients and 6 (75%) of the 8 female patients. In both sexes, the Q wave distribution pattern of I and aVL and of II and aVF indicated localization of maximum hypertrophy at the midventricular septum in 6 (75%) of the 8 patients with the former pattern, and at the basal anterior wall in 9 (90%) of the 10 patients with the latter pattern. CONCLUSIONS: Diagnostic deep Q waves were detected more frequently in female patients with HCM than in their male counterparts. In HCM with deep Q waves in limb leads, morphologic and electrocardiographic analysis showed similar features in both sexes.

A new method for measuring coronary artery diameters with CT spatial profile curves.

PURPOSE: Coronary artery vascular edge recognition on computed tomography (CT) angiograms is influenced by window parameters. A noninvasive method for vascular edge recognition independent of window setting with use of multi-detector row CT was contrived and its feasibility and accuracy were estimated by intravascular ultrasound (IVUS). METHODS: Multi-detector row CT was performed to obtain 29 CT spatial profile curves by setting a line cursor across short-axis coronary angiograms processed by multi-planar reconstruction. IVUS was also performed to determine the reference coronary diameter. IVUS diameter was fitted horizontally between two points on the upward and downward slopes of the profile curves and Hounsfield number was measured at the fitted level to test seven candidate indexes for definition of intravascular coronary diameter. The best index from the curves should show the best agreement with IVUS diameter. RESULTS: Of the seven candidates the agreement was the best (agreement: 16±11%) when the two ratios of Hounsfield number at the level of IVUS diameter over that at the peak on the profile curves were used with water and with fat as the background tissue. These edge definitions were achieved by cutting the horizontal distance by the curves at the level defined by the ratio of 0.41 for water background and 0.57 for fat background. CONCLUSIONS: Vascular edge recognition of the coronary artery with CT spatial profile curves was feasible and the contrived method could define the coronary diameter with reasonable agreement.

Focalized contractile impairment at hypertrophied myocardium proven in consideration of wall stress in patients with hypertrophic cardiomyopathy.

In hypertrophic cardiomyopathy (HCM) a hyperkinetic state is sometimes observed in spite of impaired systolic function in the hypertrophied myocardium. The aim of the present study was to determine the mechanism of this paradox. Seventeen patients with HCM and 10 normal subjects underwent cine magnetic resonance (MR) imaging to measure percent systolic wall thickening and percent fractional shortening. The ratio of systolic radial wall stress of the LV at the hypertrophied myocardium over that at the nonhypertrophied myocardium was evaluated to describe the focal advantageous condition for wall thickening. The ratio was 0.66 +/- 0.36 at the start of contraction and 0.78 +/- 0.31 at early-systole, indicating consistently smaller radial wall stress at the hypertrophied myocardium. Although the condition for contraction was favorable (a ratio less than 1.00), percent systolic wall thickening at the hypertrophied myocardium (23.0 +/- 11.8%) was smaller than that at the nonhypertrophied myocardium (70.5 +/- 32.3%). Smaller end-diastolic dimension (HCM group; 45.2 +/- 4.2 mm, reference group; 48.9 +/- 4.1 mm, P = 0.04) with a statistically identical value of systolic decrease in intraventricular dimension (HCM group; 19.7 +/- 3.9 mm, reference group; 18.9 +/- 3.2 mm, P = 0.60) yielded high percent fractional shortening in patients with HCM (43.5 +/- 7.6%). Although contractile impairment was proven at the hypertrophied region with low radial wall stress in the HCM group, the smaller end-diastolic dimension in this group resulted in high percent fractional shortening.

Vector analysis of the wall shear rate at the human aortoiliac bifurcation using cine MR velocity mapping.

OBJECTIVE: Small or oscillatory wall shear stress accelerates atherosclerosis. MR velocity mapping is feasible for vector analysis of wall shear rate (a spatial gradient of blood flow velocity at the vessel wall) in humans. A relationship between anatomic variations at the aortoiliac bifurcation and characteristics of wall shear rate was evaluated. SUBJECTS AND METHODS: To obtain two components of wall shear rate vectors, an axial component along the vessel axis and a nonaxial component perpendicular to the former at the inner and outer walls of the common iliac arteries just distal to the aortoiliac bifurcation, we performed cine MR velocity mapping with three orthogonal velocity-encoded directions in seven volunteers. RESULTS: The peak axial component at the outer wall (120.6 +/- 37.2 sec(-1)) was smaller than that at the inner wall (196.0 +/- 53.7 sec(-1)) (p < 0.01). Oscillation described by a time integral of the axial component in recessive blood flow direction over integrals in dominant and recessive directions at the outer wall was greater (0.24 +/- 0.11) than that at the inner wall (0.15 +/- 0.08) (p < 0.01). The intersecting angle between the extrapolation of the aortic axis and the direction of the axis of the common iliac artery correlated positively with the peak axial component (r = 0.577, p < 0.05) and inversely with oscillation (r = 0.603, p < 0.05). CONCLUSION: Three-dimensional vector analysis with MR velocity mapping revealed that the outer wall at the aortoiliac bifurcation showed low and oscillatory shear rate, and this inclination was increased when the takeoff angle of the iliac artery was small.

Rescue of hereditary form of dilated cardiomyopathy by rAAV-mediated somatic gene therapy: amelioration of morphological findings, sarcolemmal permeability, cardiac performances, and the prognosis of TO-2 hamsters.

The hereditary form comprises approximately 1/5 of patients with dilated cardiomyopathy (DCM) and is a major cause of advanced heart failure. Medical and socioeconomic settings require novel treatments other than cardiac transplantation. TO-2 strain hamsters with congenital DCM show similar clinical and genetic backgrounds to human cases that have defects in the delta-sarcoglycan (delta-SG) gene. To examine the long-term in vivo supplement of normal delta-SG gene driven by cytomegalovirus promoter, we analyzed the pathophysiologic effects of the transgene expression in TO-2 hearts by using recombinant adeno-associated virus vector. The transgene preserved sarcolemmal permeability detected in situ by mutual exclusivity between cardiomyocytes taking up intravenously administered Evans blue dye and expressing the delta-SG transgene throughout life. The persistent amelioration of sarcolemmal integrity improved wall thickness and the calcification score postmortem. Furthermore, in vivo myocardial contractility and hemodynamics, measured by echocardiography and cardiac catheterization, respectively, were normalized, especially in the diastolic performance. Most importantly, the survival period of the TO-2 hamsters was prolonged after the delta-SG gene transduction, and the animals remained active, exceeding the life expectancy of animals without transduction of the responsible gene. These results provide the first evidence that somatic gene therapy is promising for human DCM treatment, if the rAAV vector can be justified for clinical use.