A case of acute and late coronary events after blunt chest trauma: Attention to the late onset angina.

Mechanisms of acute myocardial infarction caused by traumatic coronary artery injury have been reported. However, late-onset coronary artery stenosis associated with trauma is less well known. We experienced a case in which acute myocardial infarction of the right coronary artery occurred at the time of blunt chest trauma (BCT) caused by a traffic accident and an increase in coronary artery stenosis in the left anterior descending artery (LAD) branch about 1 year later. A comparison of a volume-rendering image created from enhanced-contrast computed tomography at the time of trauma and coronary angiography revealed that the trauma site and the stenotic lesion in the LAD were in very close proximity, suggesting to us that traumatic coronary artery injury without flow limitation may have developed into high-grade stenosis in the LAD 1 year later. In this case we were able to demonstrate a causal relationship between BCT and delayed coronary artery stenosis. After BCT, it is necessary to be aware of the possibility of delayed coronary artery stenosis even if coronary injury is absent in the acute phase. .

Partial left superior pulmonary vein potential elimination by an inferior ganglionated plexus ablation.

Ganglionated plexus (GP) plays an important role in the initiation and maintenance of atrial fibrillation (AF). The GP ablation has been found to be effective for AF treatment. In this case, we reported an AF case in which the pulmonary vein (PV) potentials of the anterior region of the left superior PV were eliminated by an inferior right GP ablation.

Atrial electrical abnormality in patients with Brugada syndrome assessed by signal-averaged electrocardiography.

BACKGROUND: Ventricular fibrillation and atrial fibrillation are well-known arrhythmias in patients with Brugada syndrome. This study evaluated the characteristics of the atrial arrhythmogenic substrate using the signal-averaged electrogram (SAECG) in patients with Brugada syndrome. METHODS: SAECGs were performed during normal sinus rhythm in 23 normal volunteers (control group), 21 patients with paroxysmal atrial fibrillation (PAF; PAF group), and 21 with Brugada syndrome (Brugada group). RESULTS: The filtered P wave duration (fPd) in the control, Brugada, and PAF groups was 113.9±12.9ms, 125.3±15.0ms, and 137.1±16.3ms, respectively. The fPd in the PAF group was significantly longer compared to that in the control and Brugada groups (p<0.05). The fPd in the Brugada group was significantly longer than that in the control group (p<0.05) and significantly shorter than that in the PAF group (p<0.05). CONCLUSION: Patients with Brugada syndrome had abnormal P waves on the SAECG. The abnormal P waves on the SAECG in Brugada syndrome patients may have intermediate characteristics between control and PAF patients.

Relevance of transthoracic left atrial appendage wall velocity measurement in addition to left atrial volume for noninvasive and quantitative assessment of left atrial thrombogenesis in patients with atrial fibrillation and normal D-dimer levels.

PURPOSE: This study examined the role of left atrial (LA) appendage wall velocity (LAAWV) measurement in addition to LA size for the noninvasive assessment of thrombogenesis in patients with atrial fibrillation (AF) and normal plasma D-dimer levels. METHODS: In 58 non-valvular AF patients, LAAWV and the LA volume index (LAVI) were determined by transthoracic echocardiography. LA appendage flow velocity and severity of spontaneous echo contrast (SEC) were determined by transesophageal echocardiography. RESULTS: LAAWV was strongly correlated with LA appendage flow velocity (r = 0.82), and LAVI was weakly correlated with LA appendage flow velocity (r = -0.37). As SEC severity increased, LAAWV decreased (p < 0.001) and LAVI increased (p < 0.001). Among 52 patients with normal D-dimer levels, LAAWV < 10 cm/s had 71 % sensitivity and 94 % specificity for diagnosing severe SEC. Severe SEC was not found in 18/32 large LAVI patients (>34 mL/m(2)), but 17 of the 18 patients (94 %) had LAAWV < 10 cm/s. Severe SEC was found in 3/20 patients with normal LAVI, but all of them showed LAAWV < 10 cm/s. CONCLUSION: The noninvasive measurement of transthoracic LAAWV in addition to LA volume is clinically relevant for quantitatively assessing thrombogenesis in AF patients with normal D-dimer levels.

High plasma human atrial natriuretic peptide and reduced transthoracic left atrial appendage wall-motion velocity are noninvasive surrogate markers for assessing thrombogenesis in patients with paroxysmal atrial fibrillation.

BACKGROUND: The clinical relevance of examining human atrial natriuretic peptide (HANP) or left atrial appendage (LAA) wall-motion velocity during sinus rhythm in paroxysmal atrial fibrillation (AF) patients has not been clearly elucidated. METHODS: The subjects were 38 patients with paroxysmal AF who underwent transesophageal and transthoracic echocardiography during sinus rhythm. The presence of spontaneous echocontrast (SEC) was examined with transesophageal echocardiography and LAA wall-motion velocity (LAAWV) was measured with transthoracic tissue Doppler echocardiography. Plasma HANP was measured within 3 hours after echocardiography. RESULTS: Human atrial natriuretic peptide ranged from 12 to 106 pg/mL with an average of 43 ± 24 pg/mL and had a significant correlation with LAAWV (r = -0.57) or LAA flow velocity (r = -0.41). HANP was significantly higher in patients with SEC than in patients without SEC (64 ± 29 vs. 34 ± 15 pg/mL, P = 0.008) and LAAWV was significantly lower in patients with SEC than in patients without SEC (13 ± 5 vs. 20 ± 5 cm/sec, P = 0.002). HANP >44 pg/mL had a sensitivity of 73% and specificity of 89% for diagnosing SEC. SEC was more frequently observed (73%) in patients with HANP >44 pg/mL and/or LAAWV <10 cm/sec as compared with patients (11%) with normal HANP and LAA wall-motion velocity (P < 0.0001). CONCLUSION: Higher plasma HANP and lower LAA wall-motion velocity may be noninvasive surrogate markers for assessing left atrial thrombogenesis during sinus rhythm in paroxysmal AF patients.

Efficacy of pulmonary vein isolation on left atrial function in paroxysmal and persistent atrial fibrillation and the dependency on its baseline function.

BACKGROUND: The effects of pulmonary vein (PV) isolation in atrial fibrillation (AF) on left atrial (LA) function or PV flow have not been well documented. METHODS: We examined the LA function and PV flow before and 3-6 months after PV isolation in 67 AF patients (34 paroxysmal [PAF] and 33 persistent [CAF]) using transesophageal echocardiography. RESULTS: AF recurred in 6/34 patients with PAF and in 6/33 patients with CAF 6 months after PV isolation. A larger LA dimension, a lower systolic PV flow velocity, and a lower ratio of systolic to diastolic PV flow velocity were related to a higher incidence of AF recurrence. The increment of left atrial appendage (LAA) flow velocity (55% vs. 22%) and systolic PV flow velocity (57% vs. 20%) after PV isolation tended to be greater in CAF than in PAF. The changes in LAA flow velocity had reverse correlations with the baseline values before PV isolation (PAF: r = -0.73, CAF: r = -0.58). The changes in mitral flow velocity during atrial contraction in PAF had reverse correlations with the baseline values before PV isolation (r = -0.84). The changes in systolic and diastolic PV flow velocity of PAF had reverse correlations with the baseline values before PV isolation (r = -0.56, r = -0.66). CONCLUSION: The baseline LA function may affect AF recurrence as well as the improvement of LA function, and the benefit of successful PV isolation might be greater in CAF than in PAF.

An extremely large coronary aneurysm associated with a quadricuspid aortic valve in an adult patient.

A 68-year-old woman exhibited an increasingly protruding mass on the left heart border on chest X-ray. Transthoracic echocardiography revealed an echo-free mass in the anterior pericardial space. Transesophageal echocardiography revealed blood flow from the proximal left anterior descending coronary into a large coronary artery aneurysm measuring 61 mm × 51 mm in diameter and a quadricuspid aortic valve with a small cusp between the left and right coronary cusps. Coronary angiography demonstrated the presence of a coronary aneurysm connected to the proximal left coronary anterior descending artery. A giant coronary artery aneurysm and pulmonary artery fistulas extending from the left and right coronary arteries were confirmed by surgeons and successfully treated with surgery.

Recurrent takotsubo cardiomyopathy can appear as transient midventricular ballooning syndrome.

We report a rare female case of typical takotsubo cardiomyopathy at the first admission and recurrent takotsubo cardiomyopathy with a unique pattern of contraction at the second admission. The condition manifested as akinesis in the middle portion of the left ventricle and hyperkinesis of the apex and base. Our case indicates that recurrent takotsubo cardiomyopathy can appear as transient midventricular ballooning syndrome, but it remains to be determined whether both diseases have a tendency to coexist.

Role of the angiotensin II type 2 receptor in arterial remodeling after wire injury in mice.

The angiotensin II type 2 (AT2) receptor promotes apoptosis and inhibits cell proliferation. In the present study, we investigated the role of the AT2 receptor in vascular repair and remodeling following severe vascular injury using AT2 knockout (AT2KO) mice. Left femoral arteries of AT2KO mice and wild-type (WT) control mice were injured by a 0.38 mm steel wire inserted from the lumen. Twenty-eight days after the injury, a concentric vascular wall thickening, composed largely of neointima, was noted both in AT2KO and WT mice. The area occupied by the neointima and the cell count within it were not different in the two mouse strains. However, the area of the medial layer and the cell count within it were significantly larger in AT2KO mice than in WT mice. A BrdU incorporation assay showed that the proliferative activity was high in the neointima but it was not different between the strains. On the other hand, apoptosis assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was significantly inhibited in the neointima and the media of AT2KO mice compared to the levels in WT mice. However, the number of TUNEL-positive cell was much smaller in the neointima than in the medial layer in both strains. Taken together, these results indicate that AT2 receptors promote the apoptosis of vascular cells but have no net effect on the neointimal cell growth or luminal narrowing after wire injury. The AT2 receptor may be involved in the control of medial layer thickness, at least in part, through medial cell apoptosis.

Ablation of the bach1 gene leads to the suppression of atherosclerosis in bach1 and apolipoprotein E double knockout mice.

This study was designed to determine whether Bach1 gene ablation leads to suppression of atherosclerosis in apolipoprotein E (Apo E)/Bach1 double knockout (DKO) mice. Apo E/Bach1 DKO mice were generated by intercrossing Apo E knockout (KO) and Bach1 KO mice. The animals were fed a high-fat diet for 8 weeks, and the atherosclerotic plaques in the thoracic and abdominal aorta were visualized by oil red O staining. In DKO mice, the total plaque area was reduced by 32% compared with that in Apo E KO mice. In DKO mice, heme oxygenase-1 (HO-1) was upregulated in the endothelium and, to a lesser extent, in vascular smooth muscles. In atherosclerotic plaques in Apo E KO mice and DKO mice, HO-1 was abundantly expressed in the endothelium and macrophages. Urine excretion of 8-iso-prostaglandin (PG) F2alpha, a marker for lipid peroxidation, was reduced in DKO mice compared with that in Apo E KO mice. The effects of Bach1 ablation on the plaque area and 8-iso-PG F2alpha excretion were almost completely abolished by treating DKO mice with Sn protoporphyrin, an inhibitor of HO activity. Disruption of the Bach1 gene in Apo E KO mice caused inhibition of atherosclerosis through upregulation of HO-1. Inhibition of Bach1, conversely, may be a novel therapeutic strategy to treat atherosclerotic diseases.

Myocardial protection against pressure overload in mice lacking Bach1, a transcriptional repressor of heme oxygenase-1.

Bach1 is a stress-responsive transcriptional factor that is thought to control the expression levels of cytoprotective factors, including heme-oxygenase (HO)-1. In the present study, we investigated the roles of Bach1 in the development of left ventricular (LV) hypertrophy and remodeling induced by transverse aortic constriction (TAC) in vivo using Bach1 gene-deficient (Bach1(-/-)) mice. TAC for 3 weeks in wild-type control (Bach1(+/+)) mice produced LV hypertrophy and remodeling manifested by increased heart weight, histological findings showing increased myocyte cross-sectional area (CSA) and interstitial fibrosis (picro Sirius red staining), reexpressions of ANP, BNP, and betaMHC genes, and echocardiographic findings showing wall thickening, LV dilatation, and reduced LV contraction. Deletion of Bach1 caused significant reductions in heart weight (by 16%), CSA (by 36%), tissue collagen content (by 38%), and gene expression levels of ANP (by 75%), BNP (by 45%), and betaMHC (by 74%). Echocardiography revealed reduced LV dimension and ameliorated LV contractile function. Deletion of Bach1 in the LV caused marked upregulation of HO-1 protein accompanied by elevated HO activity in both basal or TAC-stimulated conditions. Treatment of Bach1(-/-) mice with tin-protoporphyrin, an inhibitor of HO, abolished the antihypertrophic and antiremodeling effects of Bach1 gene ablation. These results suggest that deletion of Bach1 caused upregulation of cytoprotective HO-1, thereby inhibiting TAC-induced LV hypertrophy and remodeling, at least in part, through activation of HO. Bach1 repressively controls myocardial HO-1 expression both in basal and stressed conditions, inhibition of Bach1 may be a novel therapeutic strategy to protect the myocardium from pressure overload.

[Assessment of oxidative stress in patients with atherosclerosis focusing on heme oxygenase].

Excessive oxidative stress plays an important role in the mechanism of atherosclerosis. An increased level of reactive oxygen speices (ROS) within the vascular endothelium eventually impedes the vasodilatative and cytoprotective actions of nitric oxide (NO). Such a condition is considered to be an early feature of atherosclerosis, and is physiologically detectable as a decrease in endothelium-dependent vasodilatation. Increased intracellular ROS levels are involved in the mechanisms of hypertension, diabetes, and hyperlipidemia, all of which are major risk factors of atherosclerosis; therefore, the assessment of "oxidative status" is obviously relevant to clinical medicine. However, most of the currently available clinical tests just measure oxidized waste. Considering that the ROS level is determined by the balance between production and elimination, assessment of the ability to eliminate ROS may be a major determinant of the oxidative state and may be useful to assess individual susceptibility to atherosclerotic diseases. Focusing on heme oxygenase (HO)-1, one of the major stress defense mechanisms, we found that the capacity to upregulate HO-1 mRNA is tightly associated with the severity of coronary artery disease. Furthermore, individual differences in stress-induced HO-1 levels were determined by HO-1 gene polymorphism. We propose that clinical use of the HO-1 expression profile as a measure of tolerability against oxidative stress may be relevant in the early diagnosis of atherosclerotic diseases.

Reduced expression of heme oxygenase-1 in patients with coronary atherosclerosis.

Heme oxigenase-1 (HO-1) is known to be an inducible cytoprotective enzyme that copes with oxidative stress. However, changes in HO-1 expression and their association with human diseases have not been studied. To test the hypothesis that the capacity to upregulate HO-1 in response to oxidative stress is an intrinsic marker for susceptibility to coronary atherosclerosis, we assessed stimulation-induced change in HO-1 expression in blood cells in 110 patients who underwent coronary angiography, comparing the results with the extent of coronary atherosclerosis and (GT)(n) repeat polymorphism in the HO-1 gene promoter region, which is believed to affect the gene expression level. The extent of coronary atherosclerosis was assessed by coronary score. Mononuclear cells were incubated with 10 micromol/l hemin or vehicle for 4 h to maximally stimulate HO-1 expression, then the HO-1 expression level was determined by real-time polymerase chain reaction (PCR). The difference between the HO-1 mRNA levels of hemin- and vehicle-treated cells (DeltaHO-1 mRNA) was taken as an index of the capacity to upregulate HO-1 mRNA. The coefficient of variance of DeltaHO-1 mRNA was 7.2%. Consistent with previous studies, DeltaHO-1 mRNA was significantly lower in patients carrying a long (GT)(n) repeat. DeltaHO-1 mRNA negatively and significantly correlated with the coronary score (r(2)=0.50, p<0.01). In conclusion, the capacity to upregulate HO-1 expression may be determined, at least in part, by genetics, and reduced ability to induce HO-1 may be involved in the mechanism of coronary atherosclerosis.