Loss of apoptosis regulator through modulating IAP expression (ARIA) protects blood vessels from atherosclerosis.

Atherosclerosis is the primary cause for cardiovascular disease. Here we identified a novel mechanism underlying atherosclerosis, which is provided by ARIA (apoptosis regulator through modulating IAP expression), the transmembrane protein that we recently identified. ARIA is expressed in macrophages present in human atherosclerotic plaque as well as in mouse peritoneal macrophages. When challenged with acetylated LDL, peritoneal macrophages isolated from ARIA-deficient mice showed substantially reduced foam cell formation, whereas the uptake did not differ from that in wild-type macrophages. Mechanistically, loss of ARIA enhanced PI3K/Akt signaling and consequently reduced the expression of acyl coenzyme A:cholesterol acyltransferase-1 (ACAT-1), an enzyme that esterifies cholesterol and promotes its storage, in macrophages. Inhibition of PI3K abolished the reduction in ACAT-1 expression and foam cell formation in ARIA-deficient macrophages. In contrast, overexpression of ARIA reduced Akt activity and enhanced foam cell formation in RAW264.7 macrophages, which was abrogated by treatment with ACAT inhibitor. Of note, genetic deletion of ARIA significantly reduced the atherosclerosis in ApoE-deficient mice. Oil red-O-positive lipid-rich lesion was reduced, which was accompanied by an increase of collagen fiber and decrease of necrotic core lesion in atherosclerotic plaque in ARIA/ApoE double-deficient mice. Analysis of bone marrow chimeric mice revealed that loss of ARIA in bone marrow cells was sufficient to reduce the atherosclerogenesis in ApoE-deficient mice. Together, we identified a unique role of ARIA in the pathogenesis of atherosclerosis at least partly by modulating macrophage foam cell formation. Our results indicate that ARIA could serve as a novel pharmacotherapeutic target for the treatment of atherosclerotic diseases.

Manipulation of cardiac phosphatidylinositol 3-kinase (PI3K)/Akt signaling by apoptosis regulator through modulating IAP expression (ARIA) regulates cardiomyocyte death during doxorubicin-induced cardiomyopathy.

PI3K/Akt signaling plays an important role in the regulation of cardiomyocyte death machinery, which can cause stress-induced cardiac dysfunction. Here, we report that apoptosis regulator through modulating IAP expression (ARIA), a recently identified transmembrane protein, regulates the cardiac PI3K/Akt signaling and thus modifies the progression of doxorubicin (DOX)-induced cardiomyopathy. ARIA is highly expressed in the mouse heart relative to other tissues, and it is also expressed in isolated rat cardiomyocytes. The stable expression of ARIA in H9c2 cardiac muscle cells increased the levels of membrane-associated PTEN and subsequently reduced the PI3K/Akt signaling and the downstream phosphorylation of Bad, a proapoptotic BH3-only protein. When challenged with DOX, ARIA-expressing H9c2 cells exhibited enhanced apoptosis, which was reversed by the siRNA-mediated silencing of Bad. ARIA-deficient mice exhibited normal heart morphology and function. However, DOX-induced cardiac dysfunction was significantly ameliorated in conjunction with reduced cardiomyocyte death and cardiac fibrosis in ARIA-deficient mice. Phosphorylation of Akt and Bad was substantially enhanced in the heart of ARIA-deficient mice even after treatment with DOX. Moreover, repressing the PI3K by cardiomyocyte-specific expression of dominant-negative PI3K (p110α) abolished the cardioprotective effects of ARIA deletion. Notably, targeted activation of ARIA in cardiomyocytes but not in endothelial cells reduced the cardiac PI3K/Akt signaling and exacerbated the DOX-induced cardiac dysfunction. These studies, therefore, revealed a previously undescribed mode of manipulating cardiac PI3K/Akt signaling by ARIA, thus identifying ARIA as an attractive new target for the prevention of stress-induced myocardial dysfunction.

Apoptosis regulator through modulating IAP expression (ARIA) controls the PI3K/Akt pathway in endothelial and endothelial progenitor cells.

Endothelial and endothelial progenitor cells (ECs and EPCs) play a fundamental role in angiogenesis that is essential for numerous physiological and pathological processes. The phosphatase and tensin homolog (PTEN)/ phosphoinositide 3-kinase (PI3K) pathway has been implicated in angiogenesis, but the mechanism in the regulation of this pathway in ECs and EPCs is poorly understood. Here we show that ARIA (apoptosis regulator through modulating IAP expression), a transmembrane protein that we recently identified, regulates the PTEN/PI3K pathway in ECs and EPCs and controls developmental and postnatal angiogenesis in vivo. We found that ARIA is abundantly expressed in EPCs and regulates their angiogenic functions by modulating PI3K/Akt/endothelial nitric oxide synthase (eNOS) signaling. Genetic deletion of ARIA caused nonfatal bleeding during embryogenesis, in association with increased small vessel density and altered expression of various vascular growth factors including angiopoietins and VEGF receptors. Postnatal neovascularization induced by critical limb ischemia was substantially enhanced in ARIA-null mice, in conjunction with more bone marrow (BM)-derived ECs detected in ischemic muscles. Administration of PI3K or NO synthase inhibitor completely abolished the enhanced neovascularization in ARIA(-/-) mice. Mechanistically, we identified that ARIA interacts with PTEN at the intracellular domain independently of the PTEN phosphorylation in its C-terminal tail. Overexpressed ARIA increased PTEN in the membrane fraction, whereas ARIA-silencing reduced the membrane-associated PTEN, resulting in modified PI3K/Akt signaling. Taken together, our findings establish a previously undescribed mode of regulation of the PTEN/PI3K/Akt pathway by ARIA, and reveal a unique mechanism in the control of angiogenesis. These functions of ARIA might offer a unique therapeutic potential.

Periaortic adipose tissue-specific activation of the renin-angiotensin system contributes to atherosclerosis development in uninephrectomized apoE-/- mice.

Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease. The perivascular adipose tissue is closely implicated in the development of atherosclerosis; however, the contribution to CKD-associated atherogenesis remains undefined. Eight-week-old apoE-deficient mice were uninephrectomized and fed a high-cholesterol diet starting at 12 wk of age. The atherosclerotic lesion area in the thoracic aorta was comparable in 16-wk-old uninephrectomized (UNX) mice and sham control mice; however, the lesion area was markedly exaggerated in 20-wk-old UNX mice compared with the control (54%, P < 0.05). While the accumulation of monocytes/macrophages and the mRNA expression levels of inflammatory cytokines/chemokines in the thoracic periaortic adipose tissue (PAT) did not differ between the two groups, angiotensinogen (AGT) mRNA expression and the angiotensin II (ANG II) concentration in the PAT were significantly higher in 16-wk-old UNX mice than in the control (1.9- and 1.5-fold increases vs. control, respectively; P < 0.05). ANG II concentrations in both the plasma and epididymal white adipose tissue (WAT) were comparable between the two groups, suggesting that PAT-specific activation of the renin-angiotensin system (RAS) is primarily involved in CKD-associated atherogenesis. The homeostasis model assessment-insulin resistance (HOMA-IR) index and plasma insulin level after glucose loading were significantly elevated in 16-wk-old UNX mice. In vitro stimulation of preadipocytes with insulin exaggerated the AGT mRNA expression along with increased mRNA expression of PPARγ. These findings suggest that PAT-specific RAS activation probably primarily contributes in accelerating atherosclerotic development in UNX mice and could thus represent a therapeutic target for preventing CKD-associated atherogenesis.

Macrophages play a unique role in the plaque calcification by enhancing the osteogenic signals exerted by vascular smooth muscle cells.

Vascular calcification is a major risk factor for the cardiovascular disease, yet its underlying molecular mechanisms remain to be elucidated. Recently, we identified that osteogenic signals via bone morphogenetic protein (BMP)-2 exerted by vascular smooth muscle cells (VSMCs) play a crucial role in the formation of atherosclerotic plaque calcification. Here we report a synergistic interaction between macrophages and VSMCs with respect to plaque calcification. Treatment with conditioned medium (CM) of macrophages dramatically enhanced BMP-2 expression in VSMCs, while it substantially reduced the expression of matrix Gla-protein (MGP) that inhibits the BMP-2 osteogenic signaling. As a result, macrophages significantly accelerated the osteoblastic differentiation of C2C12 cells induced by VSMC-CM. In contrast, macrophage-CM did not enhance the osteoblastic gene expressions in VSMCs, indicating that macrophages unlikely induced the osteoblastic trans-differentiation of VSMCs. We then examined the effect of recombinant TNF-α and IL-1ß on the VSMC-derived osteogenic signals. Similar to the macrophage-CM, both cytokines enhanced BMP-2 expression and reduced MGP expression in VSMCs. Nevertheless, only the neutralization of TNF-α but not IL-1ß attenuated the effect of macrophage-CM on the expression of these genes in VSMCs, due to the very low concentration of IL-1ß in the macrophage-CM. On the other hand, VSMCs significantly enhanced IL-1ß expression in macrophages, which might in turn accelerate the VSMC-mediated osteogenic signals. Together, we identified a unique role of macrophages in the formation of plaque calcification in coordination with VSMCs. This interaction between macrophages and VSMCs is a potential therapeutic target to treat and prevent the atherosclerotic plaque calcification.

Paracrine osteogenic signals via bone morphogenetic protein-2 accelerate the atherosclerotic intimal calcification in vivo.

OBJECTIVE: Vascular calcification is an important risk factor for cardiovascular diseases. Here, we investigated a role of dedifferentiated vascular smooth muscle cells (VSMCs) in the atherosclerotic intimal calcification. METHODS AND RESULTS: We prepared human cultured VSMCs in either redifferentiatiated or dedifferentiated state and analyzed the gene expressions of bone-calcification regulatory factors. Expression of bone morphogenetic protein-2 (BMP-2), a potent initiator for osteoblast differentiation, was significantly enhanced in dedifferentiated VSMCs. Furthermore, endogenous BMP-2 antagonists, such as noggin, chordin, and matrix gamma-carboxyglutamic acid protein, were all downregulated in the dedifferentiated VSMCs. Conditioned medium from dedifferentiated VSMCs, but not from redifferentiated VSMCs, stimulated the osteoblastic differentiation of the mesenchymal progenitor C2C12 cells, which was abolished by BMP-2 knockdown. In atherosclerotic intima from apolipoprotein (apo)E-deficient mice, αSM-actin-positive cells, presumably dedifferentiated VSMCs, expressed BMP-2. We generated BMP-2-transgenic mice using αSM-actin promoter and crossed them with apoE-deficient mice (BMP-2-transgenic/apoE-knockout). Significantly accelerated atherosclerotic intimal calcification was detected in BMP-2-transgenic/apoE-knockout mice, although serum lipid concentration and atherosclerotic plaque size were not different from those in apoE-knockout mice. Enhanced calcification appeared to be associated with the frequent emergence of osteoblast-like cells in atherosclerotic intima in BMP-2-transgenic/apoE-knockout mice. CONCLUSIONS: Our findings collectively demonstrate an important role of dedifferentiated VSMCs in the pathophysiology of atherosclerotic calcification through activating paracrine BMP-2 osteogenic signals.

Kinetics of Thallium-201 in Acute Phase of Myocardial Infarction: A Case Report.

BACKGROUND Thallium-201 has been widely used in clinical practice for the management of coronary heart disease, but little is known regarding its kinetics in the acute phase of myocardial infarction. CASE REPORT We report a 78-year-old man who developed acute inferior myocardial infarction during exercise thallium-201 scintigraphy. The patient underwent exercise testing with thallium-201 myocardial scintigraphy because of a single episode of chest pain. The workload was started with 25 watts and increased by 25 watts every 2 min on a bicycle ergometer with continuous monitoring of 12-lead electrocardiography. Thallium-201 was injected intravenously at 85% of the age-predicted maximal heart rate, and ST-segment elevations refractory to medication subsequently developed in the inferior leads, followed by chest pain. Scintigraphic image acquisition was deferred and he was transferred to the catheter laboratory in this hospital. Emergency coronary angiography showed occlusion in the right coronary artery, and stent implantation was successfully performed. The peak level of creatine kinase in the clinical course was 201 U/l. Scintigraphic images obtained 4 h after the onset of ST-segment elevation showed severely reduced activity in the left ventricular inferior wall, with partial redistribution 24 h later. Follow-up imaging performed 4 months later revealed increased accumulation of thallium-201 in the inferior wall. CONCLUSIONS Our case highlights the kinetics of thallium-201 during acute myocardial infarction.

Prorenin induces ERK activation in endothelial cells to enhance neovascularization independently of the renin-angiotensin system.

Prorenin is an enzymatically inactive precursor of renin, and its biological function in endothelial cells (ECs) is unknown despite its relevance with the incidence of diabetic microvascular complications. Recently, (pro)renin receptor was identified, and the receptor-associated prorenin system has been discovered, whereas its expression as well as function in ECs remain unclear. In the present study, we found that ECs express the (pro)renin receptor, and that prorenin provoked ERK activation through (pro)renin receptor independently of the renin-angiotensin system (RAS). Prorenin stimulated the proliferation, migration and tube-formation of ECs, while it inhibited endothelial apoptosis induced by serum and growth factor depletion. MEK inhibitor abrogated these proangiogenic effects of prorenin, while AT1 receptor antagonist or angiotensin-converting enzyme inhibitor failed to block them. In vivo neovascularization in the Matrigel-plugs implanted into mouse flanks was significantly enhanced by prorenin, in which significant ERK activation was detected in ECs. Furthermore, tumor xenografts stably transfected with prorenin demonstrated the significantly accelerated growth rate concomitantly with enhanced intratumoral neovascularization. Our data demonstrated that the RAS-independent (pro)renin receptor-mediated signal transduction plays a pivotal role in the regulation of ECs function as well as in the neovascularization, and thus prorenin is potentially involved in the pathophysiology of diabetic microvascular complications as well as cancers.

Vagal enhancement as evidence of residual ischemia after inferior myocardial infarction.

BACKGROUND: Acute inferior myocardial infarction (MI) often induces transient sinus bradycardia through vagal enhancement, known as Bezold-Jarisch reflex, which is explained by preferential distribution of vagal nerve in the inferior wall. We examined vagal activity in relation to the occurrence of residual ischemia in patients with old inferior MI and assessed its diagnostic usefulness. METHODS: Exercise myocardial scintigraphy was performed in 15 patients with old inferior MI, 19 angina pectoris (AP) patients with inferior ischemia but no MI, and 32 control subjects who had no evidence of cardiac disease. We analyzed the connection of residual ischemia in old MI with ST-segment response to exercise and with vagal activity as determined by coefficient of component variance of high frequency (CCV(HF)). RESULTS: Exercise-induced percentage change in CCV(HF) was higher in patients with old MI and residual ischemia (18.8 +/- 13.5%) and AP (5.5 +/- 9.7%) than old MI but no residual ischemia (-24.1 +/- 4.9%) or control (-22.8 +/- 4.5%, P = 0.006). Percentage change in CCV(HF) > -5% had a good diagnostic value for the detection of residual ischemia in patients with old inferior MI with sensitivity of 83%, specificity of 89%, accuracy of 87%, and positive likelihood ratio of 7.50, which was higher than that of ST-segment depression (67%, 50%, 56%, and 1.33). CONCLUSIONS: Vagal enhancement was associated with residual ischemia in old inferior MI as well as inferior AP. Measurement of CCV(HF) is useful in improving the diagnostic reliability of exercise electrocardiography in patients with old inferior MI.

R-wave amplitude response to myocardial ischemia in hypertrophic cardiomyopathy.

BACKGROUND AND PURPOSE: R-wave amplitude change during exercise has been reported to enhance diagnostic value for myocardial ischemia in coronary heart disease. METHODS: We summed up R-wave amplitude in all the 12 leads during exercise testing and correlated the results with regional myocardial ischemia or diffuse subendocardial ischemia as detected by scintigraphy in 49 patients with hypertrophic cardiomyopathy (HCM) and 16 controls. RESULTS: The sum of R-wave amplitude decreased during exercise in patients with HCM (mean, 12.4 mV to 11.7 mV, P < .01) as well as in controls (8.0 mV to 7.7 mV, P < .05). Percent changes in the sum of R-wave amplitude did not differ between 4 subgroups of patients with HCM: one having both regional and subendocardial ischemia, one only the former, one only the latter, and one neither of them (mean, 6.5%, 7.7%, 4.6%, and 5.1%; P = .79). CONCLUSIONS: R-wave amplitude response to exercise failed to demonstrate myocardial ischemia in our patients with HCM.

Ecscr regulates insulin sensitivity and predisposition to obesity by modulating endothelial cell functions.

Insulin resistance is closely associated with obesity and is one of the earliest symptoms of type-2 diabetes. Endothelial cells are involved in the pathogenesis of insulin resistance through their role in insulin delivery and adipose tissue angiogenesis. Here we show that Ecscr (endothelial cell surface expressed chemotaxis and apoptosis regulator; also known as ARIA), the transmembrane protein that regulates endothelial cell signalling, is highly expressed in white and brown adipose tissues, and regulates energy metabolism and glucose homeostasis by modulating endothelial cell functions. Ecscr-deficient mice fed a normal chow show improved glucose tolerance and enhanced insulin sensitivity. We demonstrate that Ecscr deletion enhances the insulin-mediated Akt/endothelial nitric oxide synthase activation in endothelial cells, which increases insulin delivery into the skeletal muscle. Ecscr deletion also protects mice on a high-fat diet from obesity and obesity-related metabolic disorders by enhancing adipose tissue angiogenesis. Conversely, targeted activation of Ecscr in endothelial cells impairs glucose tolerance and predisposes mice to diet-induced obesity. Our results suggest that the inactivation of Ecscr enhances insulin sensitivity and may represent a new therapeutic strategy for treating metabolic syndrome.

Loss of bcl-2 during the senescence exacerbates the impaired angiogenic functions in endothelial cells by deteriorating the mitochondrial redox state.

Ageing is an important risk factor for ischemic cardiovascular diseases, although its underlying molecular mechanisms remain to be elucidated. Here, we report a crucial role of Bcl-2 in the impaired angiogenic functions in senescent endothelial cells (ECs) by modulating the mitochondrial redox state. Cellular senescence impaired angiogenic functions in ECs without attenuating the mitogen-activated protein kinase or Akt signaling, and vascular endothelial growth factor receptor 2 or Tie-2 expressions. We identified that Bcl-2 expression was markedly reduced in 3 independent models for senescent ECs, and pharmacological inhibition, as well as small interfering RNA-mediated gene silencing of Bcl-2, significantly impaired the angiogenic functions in young ECs. Bcl-2 has an antioxidative role by locating the glutathione at mitochondria, and we found that mitochondrial oxidative stress was significantly augmented in senescent ECs, in association with reduced mitochondria-associated glutathione. Transfection of Bcl-2 in senescent ECs significantly reduced the mitochondrial oxidative stress, restored the mitochondrial membrane potential, and improved the angiogenic capacity. Furthermore, gene transfer of Bcl-2 using adenovirus significantly improved the in vivo angiogenesis in the Matrigel plugs implanted into aged mice, whereas the Bcl-2 inhibitor reduced the angiogenesis in the Matrigel plugs implanted into young mice. Together, Bcl-2 plays a crucial role in the regulation of the mitochondrial redox state in ECs, and, thus, loss of Bcl-2 during the senescence exacerbates the impaired angiogenesis by augmenting the mitochondrial oxidative stress.

Spontaneous pericardial hematoma with familial amyloid polyneuropathy.

There are more than a few risks of hemorrhage complication in patients with amyloidosis. Although most cases with amyloidosis exhibit minor bleeding manifestations, they can be occasionally associated with life-threatening problems. To our knowledge, there are only a few cases of spontaneous pericardial hematoma associated with amyloidosis. We here report a patient who suddenly died of cardiac tamponade with massive pericardial hematoma 7 years after the diagnosis of familial amyloid polyneuropathy (FAP). A 69-year-old female with FAP with cardiogenic shock was admitted to our emergency room. Although she previously underwent permanent pacemaker implantation for atrial fibrillation with slow ventricular response, electrocardiogram showed a critical pacing failure. Emergent telemetry check revealed a sudden extreme increase of pacing capture threshold in the right ventricle. Maximum pacing voltage could not improve the critical condition, and she died 7 h after arrival. Autopsy showed a massive pericardial hematoma in the right ventricular free wall, and microscopic examination revealed typical amyloid deposition in the arterial wall of the pericardium. In this case, it is assumed that a sudden rupture of fragile pericardial vessels with amyloid deposition led to the lethal pericardial hematoma.

Septal Q wave as a marker of septal ischemia in hypertrophic cardiomyopathy.

BACKGROUND: Small Q waves in the left lateral leads are termed septal q waves, and their response to exercise has been reported to be a marker of septal ischemia in coronary artery disease. Patients with hypertrophic cardiomyopathy (HCM) sometimes develop septal ischemia in the absence of coronary stenosis, but little data are available concerning the association of the septal q wave response with septal ischemia. METHODS AND RESULTS: Exercise electrocardiography and Tc-99m-tetrofosmin myocardial scintigraphy were recorded to detect myocardial ischemia in 29 HCM patients with asymmetric septal hypertrophy. The septal q wave amplitude was summed up in V(5) and V(6) during exercise testing, and the results were correlated with septal ischemia defined as a regional septal ischemia or a part of diffuse subendocardial ischemia. A decrease in the sum of the septal q wave amplitude during exercise testing yielded a sensitivity of 100% and specificity 33% for regional septal ischemia, and a sensitivity of 100% and specificity of 43% for diffuse subendocardial ischemia, although an absent septal q wave at rest provided a low sensitivity for the detection of regional septal ischemia (43%) and diffuse subendocardial ischemia (33%). CONCLUSIONS: The septal q wave response to exercise is a useful marker of septal ischemia in HCM with asymmetric septal hypertrophy.

Vagal enhancement due to subendocardial ischemia as a cause of abnormal blood pressure response in hypertrophic cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) often develop myocardial ischemia in association with abnormal blood pressure response to exercise. Vagal nerves mediate cardioinhibitory stimuli, with little knowledge regarding vagal response to myocardial ischemia in patients with HCM. METHODS: Exercise Tc-99m-tetrofosmin myocardial scintigraphy was performed in 59 HCM patients and 39 controls who had no evidence of cardiac disease. We examined how reversible regional perfusion abnormality and transient left ventricular cavity dilation, a parameter of subendocardial ischemia, are related to vagal modulation as assessed by coefficient of high frequency component variance (CCV(HF)) on heart rate variability. We then correlated the results with abnormal blood pressure response to exercise, defined as failed increase >or=25 mm Hg during exercise. RESULTS: Regional perfusion abnormality and left ventricular cavity dilation were observed in 26 and 21 HCM patients, respectively. The percentage change of CCV(HF) from before to after exercise was higher in HCM patients with left ventricular cavity dilation than without or controls (5.2+/-9.8%, -23.5+/-5.7%, -14.5+/-5.5%, P=0.004). By contrast, the change of CCV(HF) was similar in HCM patients with regional perfusion abnormality, those without, and controls. The change of CCV(HF) was correlated with exercise-induced increase in systolic blood pressure (rho=-0.64, P<0.001); HCM patients with abnormal blood pressure response were characterized by a higher percentage change in CCV(HF) (50.0+/-18.3%). CONCLUSIONS: Subendocardial ischemia provoked vagal enhancement in patients with HCM, which may be related to the development of abnormal blood pressure response to exercise.

Gated single-photon emission computed tomography detects subendocardial ischemia in hypertrophic cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) sometimes develop subendocardial ischemia (SEI) in the left ventricle (LV). In the present study it was examined whether volumetric variables obtained by gated single-photon emission computed tomography (SPECT) are useful in detecting exercise-induced SEI in patients with HCM. METHODS AND RESULTS: Exercise 99mTc-tetrofosmin myocardial scintigraphy was performed in 26 HCM patients having non-obstruction and mild hypertrophy with a ventricular septal thickness < or = 20 mm. SEI was quantified using software developed previously, and the results were correlated with volumetric variables obtained using Quantitative Gated SPECT software. Exercise-induced percentage change in LV end-systolic volume was higher in 9 HCM patients with SEI (25.8+/-3.1%) than in 17 patients without (10.0+/-2.5%, p=0.009), although the percentage change in LV end-diastolic volume was similar in the 2 groups. The receiver-operator characteristics curve of the percentage changes in LV end-systolic volume for the detection of SEI showed that the optimal cutoff was 17%. This cutoff point yielded a good diagnostic value for the presence of SEI with a sensitivity of 89%, specificity 82%, and likelihood ratio 5.04. CONCLUSIONS: Gated SPECT technique is useful in detecting SEI during exercise in a select population of HCM patients.

[Biventricular noncompaction detected by magnetic resonance imaging: a case report].

We report a case of biventricular noncompaction in whom magnetic resonance imaging revealed prominent trabeculations in the right ventricle as in the left ventricle. A 58-year-old man was referred to our hospital complaining of appetite loss and leg edema. Chest radiography showed cardiomegaly without pulmonary congestion. The diagnosis was right ventricular heart failure with congestive liver causing elevated liver enzyme. Transthoracic echocardiography showed prominent trabeculations and deep recesses in the inferolateral wall and apex of the left ventricle with the end-diastolic dimension of 64mm and ejection fraction of 29%. Magnetic resonance imaging demonstrated right ventricular noncompaction which remained unclear on echocardiography. Prominent trabeculations in the dilated right ventricle were confirmed by right ventriculography. The ejection fraction was 23%.