Left Ventricular Pseudoaneurysm With a Bead-Like Appearance After Myocardial Infarction: The Utility of Cardiac Computed Tomography.

A left ventricular pseudoaneurysm is a rare but life-threatening complication after myocardial infarction. Because untreated pseudoaneurysms have a 30%-45% risk of rupture, surgery is the preferred therapeutic option. However, its diagnosis is sometimes challenging, as a pseudoaneurysm presents with non-specific symptoms that can mimic myocardial infarction or heart failure. We report a male patient with a history of aortic dissection surgery who presented with recurrent chest pain probably due to acute coronary syndrome. Transthoracic echocardiography revealed a cavity at the apex of the left ventricle, indicating a mechanical complication after myocardial infarction. As the coronary angiography was considered difficult because of the patient's anatomical problem, contrast-enhanced computed tomography (CT) was performed. CT angiography revealed multiple nodular cavities continued from within the left ventricle. It seemed that the pseudoaneurysm was formed in stages in the adherent pericardium after myocardial infarction, resulting in a bead-like appearance. Emergent pseudoaneurysmectomy and left ventricular wall repair were performed, and the patient was discharged without any complications. This case illustrates the utility of cardiac CT to establish the diagnosis of left ventricular pseudoaneurysm and coronary artery atherosclerosis.

Cardiac amyloidosis screening using a relative apical sparing pattern in patients with left ventricular hypertrophy.

BACKGROUND: Cardiac amyloidosis (CA) mimics left ventricular hypertrophy (LVH). It is treatable, but its prognosis is poor. A simple screening tool for CA would be valuable. CA is more precisely diagnosed with echocardiographic deformation parameters (e.g., relative apical sparing pattern [RASP]) than with conventional parameters. We aimed to 1) investigate incremental benefits of echocardiographic deformation parameters over established parameters for CA screening; 2) determine the resultant risk score for CA screening; and 3) externally validate the score in LVH patients. METHODS: We retrospectively studied 295 consecutive non-ischemic LVH patients who underwent detailed diagnostic tests. CA was diagnosed with biopsy or 99mTc-PYP scintigraphy. The base model comprised age (≥65 years [men], ≥70 years [women]), low voltage on the electrocardiogram, and posterior wall thickness ≥ 14 mm in reference to the literature. The incremental benefit of each binarized echocardiographic parameter over the base model was assessed using receiver operating characteristic curve analysis and comparisons of the area under the curve (AUC). RESULTS: Fifty-four (18%) patients had CA. RASP showed the most incremental benefit for CA screening over the base model. After conducting multiple logistic regression analysis for CA screening using four variables (RASP and base model components), a score was determined (range, 0-4 points). The score demonstrated adequate discrimination ability for CA (AUC = 0.86). This result was confirmed in another validation cohort (178 patients, AUC = 0.88). CONCLUSIONS: We developed a score incorporating RASP for CA screening. This score is potentially useful in the risk stratification and management of LVH patients.

Semiquantitative assessment of the relative apical sparing pattern of longitudinal strain for cardiac amyloidosis identification.

BACKGROUNDS: The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, the visual assessment of RASP is inconsistent, and the quantitative assessment of RASP is time-consuming. This study aimed to compare assessments of RASP for the identification of CA with conventional assessments and investigate their reproducibility and relevance on the assessments. METHODS: Forty patients with biopsy-proven CA were compared with 80 hypertrophied patients matched for mean LV wall thickness. We compared the discriminative abilities of three assessments of RASP to identify CA (visual, quantitative, and semiquantitative). Nine patterns of semiquantitative RASP were investigated; finally, it was defined as "reduction of LS" (≥ -10%) in ≥5 (of 6) basal segments, relative to "preserved LS" (< -15%) in at least one apical segment. RESULTS: The concordance between the two observers for visual RASP was modest (κ = 0.65). On the other hand, the consistency for semiquantitative RASP was perfect (κ = 1.00). The discriminative ability of semiquantitative RASP (area under the curve [AUC]  = 0.74) was significantly better than that of visual RASP (AUC = 0.65) and equivalent to that of binary quantitative RASP. CONCLUSION: Semiquantitative RASP assessment is reproducible and accurately discriminates CA. This simple assessment may help readily refine the risk stratification of patients with diffuse LV hypertrophy.

Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI: The STOPDAPT-2 Randomized Clinical Trial.

Importance: Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option. Objective: To test the hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events. Design, Setting, and Participants: Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019. Interventions: Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522). Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding. Results: Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, -1.34% [95% CI, -2.57% to -0.11%]; hazard ratio [HR], 0.64 [95% CI, 0.42-0.98]), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, -0.55% [95% CI, -1.62% to 0.52%]; HR, 0.79 [95% CI, 0.49-1.29]), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, -1.13% [95% CI, -1.84% to -0.42%]; HR, 0.26 [95% CI, 0.11-0.64]; P = .004 for superiority). Conclusions and Relevance: Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02619760.

[Simultaneous Transapical Transcatheter Aortic Valve Implantation and Coronary Artery Bypass Grafting;Report of a Case].

Coronary artery disease(CAD) is often found concurrently in patients presenting with severe aortic stenosis(AS). Surgical aortic valve replacement(SAVR) and coronary artery bypass grafting(CABG) were usually selected with such patients. Recently, transcatheter aortic valve implantation (TAVI) is considered as a less invasive and more feasible treatment option in high-risk AS patients. A 74-year-old woman admitted due to acute myocardial infarction and treated with percutaneous coronary intervention revealed severe AS. Because of her comorbidities, concomitant transapical TAVI and CABG were performed with an excellent clinical course.

A calcified amorphous tumor that developed on both sides of the atrioventricular valve annulus.

We report a rare case of a hemodialysis patient with a calcified amorphous tumor (CAT) on both sides of the atrioventricular valve annulus. A 70-year-old female who had received hemodialysis for 23 years because of chronic glomerulonephritis presented to our hospital with acute heart failure. Echocardiography indicated the presence of mobile cardiac masses on the mitral valve and tricuspid valve annulus. We suspected the presence of a cardiac tumor or vegetation. The patient received 3 g/day sulbactam-ampicillin and 60 mg/day gentamicin. Surgery was performed on the 14th day after hospital admission. The patient underwent mitral valve replacement, tricuspid annuloplasty, and tumor resection. Based on the pathological findings, the cardiac tumor was diagnosed as a CAT.

Deletion of the angiotensin II type 1a receptor prevents atherosclerotic plaque rupture in apolipoprotein E-/- mice.

OBJECTIVE: Angiotensin II is involved in the genesis of atherosclerosis. As the role of the angiotensin II type 1a (AT(1a)) receptor in plaque rupture is poorly understood, we assessed the hypothesis that the AT(1a)receptor contributes to atherosclerotic plaque rupture. METHODS AND RESULTS: Atherosclerotic plaque rupture was induced by carotid artery ligation for 4 weeks followed by polyethylene cuff placement around the carotid in apolipoprotein E (ApoE)(-/-) and ApoE(-/-) AT(1a)(-/-) mice. The incidence of plaque rupture at 4 days after cuff placement was 72% in ApoE(-/-) mice compared with 24% in ApoE(-/-) AT(1a)(-/-) mice (P<0.01). Lipid accumulation, macrophage infiltration, expression of inflammatory cytokines, nicotinamide adenine dinucleotide phosphate-oxidase activity, and matrix metalloproteinase-9 activity in atherosclerotic plaque were markedly attenuated in ApoE(-/-) AT(1a)(-/-) compared with ApoE(-/-) mice. Oxidized low-density lipoprotein inhibited macrophage migration in ApoE(-/-) macrophages. In contrast, oxidized low-density lipoprotein-induced macrophage trapping was abolished in ApoE(-/-) AT(1a)(-/-) macrophages, and this was associated with decreased CD36 expression and focal adhesion kinase activity. CONCLUSIONS: Conclusion- These results suggest that blocking the AT(1) receptor may reduce atherosclerotic plaque rupture and that AT(1a) receptor-mediated macrophage trapping, inflammation, oxidative stress, and matrix metalloproteinase activation may play crucial roles in plaque vulnerability.

Role of angiotensin-converting enzyme 2 in cardiac hypertrophy induced by nitric oxide synthase inhibition.

OBJECTIVE: Angiotensin-converting enzyme 2 (ACE2) generates angiotensin-(1-7) [Ang-(1-7)], a peptide highlighted as exerting a pivotal role in cardiovascular remodeling. Moreover, the ACE2/Ang-(1-7)/Mas axis directly activates endothelial nitric oxide (NO) synthase and NO generation in the heart. However, the role of ACE2 in cardiovascular remodeling induced by persistent inhibition of NO under chronic activation of the renin-angiotensin system (RAS) remains poorly understood. METHODS AND RESULTS: Chimeric hypertensive mice that exhibit activation of the human RAS were produced by mating human renin (hRN) and human angiotensinogen (hANG) transgenic mice. Persistent NO inhibition with NG-nitro-L-arginine methyl ester (L-NAME) was started at 8 weeks of age for 4 weeks. After administration of L-NAME, blood pressure (BP) markedly increased in the chimeric mice (hRN/hANG-Tg), whereas wild-type mice (C57BL/6J) showed little increase in BP. Cardiovascular remodeling with enhanced oxidative stress in hRN/hANG-Tg was markedly accelerated by NO inhibition compared with that in wild-type mice. Moreover, ACE2 mRNA expression and activity in cardiac tissue were markedly reduced in L-NAME-treated hRN/hANG-Tg. Co-administration of an angiotensin II type 1 (AT1) receptor blocker (ARB), olmesartan, inhibited L-NAME-induced cardiovascular remodeling and improved the reduction in cardiac ACE2. The preventive effect of olmesartan on cardiac hypertrophy was blunted by co-administration of a selective Ang-(1-7) antagonist, [D-Ala7]-Ang-(1-7). CONCLUSION: Our findings demonstrate that cardiovascular remodeling induced by persistent NO inhibition was enhanced in hRN/hANG-Tg. An ARB, olmesartan, blunted cardiac remodeling induced by NO inhibition with RAS activation partially through the ACE2/Ang-(1-7)/Mas axis in addition to directly through its classical ACE/Ang II/AT1 receptor axis-blocking action.

Functional assessment of coronary artery flow using adenosine stress dual-energy CT: a preliminary study.

We attempted to assess coronary artery flow using adenosine-stress and dual-energy mode with dual-source CT (DE-CT). Data of 18 patients with suspected coronary arteries disease who had undergone cardiac DE-CT were retrospectively analyzed. The patients were divided into two groups: 10 patients who performed adenosine stress CT, and 8 patients who performed rest CT as controls. We reconstructed an iodine map and composite images at 120 kV (120 kV images) using raw data with scan parameters of 100 and 140 kV. We measured mean attenuation in the coronary artery proximal to the distal portion on both the iodine map and 120 kV images. Coronary enhancement ratio (CER) was calculated by dividing mean attenuation in the coronary artery by attenuation in the aortic root, and was used as an estimate of coronary enhancement. Coronary stenosis was identified as a reduction in diameter of >50% on CT angiogram, and myocardial ischemia was diagnosed by adenosine-stress myocardial perfusion scintigraphy. The iodine map showed that CER was significantly lower for ischemic territories (0.76 ± 0.06) or stenosed coronary arteries (0.77 ± 0.06) than for non-ischemic territories (0.95 ± 0.21, P=0.02) or non-stenosed coronary arteries (1.07 ± 0.33, P<0.001). The 120 kV images showed no difference in CER between these two groups. Use of CER on the iodine map separated ischemic territories from non-ischemic territories with a sensitivity of 86% and a specificity of 75%. Our quantification is the first non-invasive analytical technique for assessment of coronary artery flow using cardiac CT. CER on the iodine map is a candidate method for demonstration of alteration in coronary artery flow under adenosine stress, which is related to the physiological significance of coronary artery disease.

Visualization of traumatic tricuspid insufficiency by three-dimensional echocardiography.

A 19-year-old male was admitted to the emergency room of our hospital after a motor vehicle accident. During his first physical examination, a holosystolic murmur was heard at the fourth left parasternal border. Transthoracic echocardiography showed severe tricuspid insufficiency, but the cause of tricuspid insufficiency was unclear. Therefore, three-dimensional echocardiography was performed and demonstrated flail anterior, posterior and septal leaflets of the tricuspid valve. The diagnosis was tricuspid insufficiency due to papillary muscle rupture secondary to chest blunt trauma. Surgical repair of the tricuspid valve was performed in this patient. After surgery, the signs and symptoms of right ventricular heart failure were relieved. In this case, three-dimensional echocardiography was very useful for the evaluation of spatial destruction of the tricuspid valve and papillary muscle.

Relationship between smaller calcifications and lipid-rich plaques on integrated backscatter-intravascular ultrasound.

We evaluated the relationship between coronary calcification and plaque characteristics using integrated backscatter-intravascular ultrasound (IB-IVUS), focusing on spotty calcification. Seventy-two patients with culprit plaques containing spotty calcification were evaluated. The average degree of all the spotty calcifications (averaged arc) negatively correlated with the % lipid volume (LV) on IB-IVUS. Multivariate analysis showed the averaged arc was an independent predictor of % LV. Our observations suggest that smaller plaque calcifications are associated with lipid-rich characteristics in patients with a spotty calcification pattern.

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.

Insufficiency of pro-heparin-binding epidermal growth factor-like growth factor shedding enhances hypoxic cell death in H9c2 cardiomyoblasts via the activation of caspase-3 and c-Jun N-terminal kinase.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a cardiogenic and cardiohypertrophic growth factor. ProHB-EGF, a product of the Hb-egf gene and the precursor of HB-EGF, is anchored to the plasma membrane. Its ectodomain region is shed by a disintegrin and metalloproteases (ADAMs) when activated by various stimulations. It has been reported that an uncleavable mutant of Hb-egf, uc-Hb-egf, produces uc-proHB-EGF, which is not cleaved by ADAMs and causes dilation of the heart in knock-in mice. This suggests that the shedding of proHB-EGF is essential for the development and survival of cardiomyocytes: however, the molecular mechanism involved has remained unclear. In this study, we investigated the relationship between uc-proHB-EGF expression and cardiomyocyte survival. Human uc-proHB-EGF was adenovirally introduced into the rat cardiomyoblast cell line H9c2, and the cells were cultured under normoxic and hypoxic conditions. Uc-proHB-EGF-expressing H9c2 cells underwent apoptosis under normoxic conditions, which distinctly increased under hypoxic conditions. Furthermore, we observed an increased Caspase-3 activity, reactive oxygen species accumulation, and an increased c-Jun N-terminal kinase (JNK) activity in the uc-proHB-EGF-expressing H9c2 cells. Treatment of the uc-proHB-EGF transfectants with inhibitors of Caspase-3, reactive oxygen species, and JNK, namely, Z-VAD-fmk, N-acetylcysteine, and SP600125, respectively, significantly reduced hypoxic cell death. These data indicate that insufficiency of proHB-EGF shedding under hypoxic stress leads to cardiomyocyte apoptosis via Caspase-3- and JNK-dependent pathways.

Attenuation of cuff-induced neointimal formation by overexpression of angiotensin II type 2 receptor-interacting protein 1.

Recently we have cloned angiotensin II type 2 receptor-interacting protein 1 (ATIP1) as a novel protein that interacts specifically with the C-terminal tail of the angiotensin II type 2 receptor; however, the pathophysiological roles of ATIP1 in vascular remodeling are still unknown. Here, we generated ATIP1-transgenic (ATIP1-Tg) mice expressing mouse ATIP1 and investigated the role of ATIP1 in vascular remodeling using these transgenic mice. ATIP1-Tg mice exhibited no significant difference in blood pressure compared with wild-type (WT) mice. Angiotensin II type 2 receptor mRNA expression in the femoral artery was increased in injured femoral arteries, reaching a peak at 7 days after operation in WT mice, and a similar result of angiotensin II type 2 receptor expression was observed in ATIP1-Tg mice. In ATIP1-Tg mice, neointimal formation of the femoral artery 14 days after cuff placement was significantly smaller than that in WT mice. 5-Bromo-2'-deoxyuridine incorporation was significantly reduced in the injured arteries of ATIP1-Tg mice compared with WT mice. In ATIP1-Tg mice, superoxide anion production and the expression of a proinflammatory cytokine, tumor necrosis factor-alpha, were markedly attenuated. Moreover, cell proliferative signaling, such as extracellular signal-regulated kinase phosphorylation, was significantly attenuated in ATIP1-Tg mice compared with WT mice. Taken together, these results suggest that ATIP1 plays an important role in cuff-induced vascular remodeling in mice.

Prevention of vascular injury by combination of an AT1 receptor blocker, olmesartan, with various calcium antagonists.

BACKGROUND: A combination of different types of antihypertensive drugs is widely used for the treatment of hypertension. We examined the inhibitory effects of a combination of an AT(1) receptor blocker (ARB), olmesartan, with various calcium channel blockers (CCBs) on inflammatory vascular remodeling. METHODS: Inflammatory vascular remodeling was induced by polyethylene-cuff placement around the femoral artery of C57BL/6J mice at 10 weeks of age. Olmesartan (0.5 mg/kg/day) was administered intraperitoneally using an osmotic minipump. CCBs (nifedipine 1.0 mg/kg/day, amlodipine 0.1 mg/kg/day, azelnidipine 0.1 mg/kg/day), and hydrochlorothiazide (HCTZ 0.5 mg/kg/day) were administered orally. RESULTS: In the injured artery, superoxide anion production and expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p47(phox) and Rac-1 were markedly increased, together with expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor (TNF)-alpha. Administration of a single drug alone at each concentration did not significantly inhibit these changes in the injured artery. However, a combination of olmesartan with various CCBs inhibited neointimal formation as well as oxidative stress and inflammatory markers in the injured artery. Moreover, among these CCBs, inhibition of these markers by olmesartan with azelnidipine was stronger than that caused by a combination with other CCBs. On the other hand, a combination of subeffective doses of olmesartan and HCTZ did not significantly affect vascular changes after cuff placement. CONCLUSIONS: These results suggest that the combination of ARB with CCB synergistically inhibits vascular remodeling and that the inhibitory actions of ARB on vascular remodeling may vary depending on the combined CCB.

Quantification of regional myocardial blood flow using first-pass multidetector-row computed tomography and adenosine triphosphate in coronary artery disease.

BACKGROUND: The feasibility of using cardiac multidetector-row computed tomography (MDCT) technology in the quantitative assessment of myocardial blood flow (MBF) using the adenosine triphosphate (ATP) load technique was investigated in the present study. METHODS AND RESULTS: The study group comprised 14 patients (11 men, 3 women, age range 52-79 years, mean age 69.2 years) who underwent cardiac cine MDCT using the ATP-load technique. MBF was estimated from the slope of the linear regression equation with Patlak plots analysis. The overall average MBF was 1.83+/-0.62 ml . g(-1) . min(-1). Mean MBF in territories with stenosis on coronary angiography was 1.19+/-0.36 ml . g(-1) . min(-1) and 2.06+/-0.54 ml . g(-1) . min(-1) (p<0.01) in territories without stenosis. The average MBF in territories with moderate to severe ischemia on myocardial perfusion scintigraphy was 1.32+/-0.14 ml .g(-1 ). min(-1 )and 1.95+/-0.64 ml . g(-1) . min(-1) (p<0.01) in territories without ischemia. CONCLUSION: MDCT can be used to quantify MBF using first-pass dynamic data.

Assessment of flow velocity in a bypass graft of the gastroepiploic artery by contrast-enhanced transabdominal Doppler echocardiography: a case report.

An 81-year-old man with effort angina pectoris underwent coronary artery bypass grafting operation using the bilateral internal thoracic arteries and the right gastroepiploic artery (GEA). Angiography after operation showed that the bilateral internal thoracic arteries were patent. Abdominal angiography showed severe ostial stenosis in the celiac trunk. The GEA was not opacified by the celiac trunk but by the superior mesenteric artery, by collaterals. GEA flow could be detected from the epigastric lesion by contrast-enhanced Doppler echocardiography, and moreover, the flow velocity reserve of the graft was 2.4. This case suggests that the GEA graft can provide sufficient blood flow to the coronary artery despite ostial stenosis of the celiac trunk.