Elevated plasma total homocysteine (tHcy) has been considered to be a new risk factor for coronary atherosclerotic disease. However, the association has not been proven indisputably, and the strength of the relationship and the interaction of plasma tHcy with other conventional risk factors remain uncertain in the clinical setting of acute myocardial infarction (AMI). The aim of this study was to investigate whether an elevated plasma level of tHcy is an independent predictor of the late stage of coronary atherosclerotic lesions in Chinese patients with AMI, who are undergoing primary percutaneous coronary intervention (PCI).
Plasma levels of tHcy were prospectively measured in 178 consecutive patients with ST-segment elevated AMI undergoing primary PCI. The plasma level of tHcy was also measured in 30 control subjects with normal coronary angiographic findings. The plasma level of tHcy was significantly higher in the patients with AMI than in control subjects (10.5 ± 3.3 μmol/L versus 8.3 ± 2.4 μmol/L, P = 0.0004). Multiple stepwise logistic regression analysis of the baseline characteristics demonstrated that smoking (P = 0.004) and creatinine level (P < 0.0001) were independent predictors of an elevated plasma level of tHcy. Moreover, an increased plasma level of tHcy (P = 0.003), female gender (P = 0.008), diabetes mellitus (P = 0.020), and the presence of previous myocardial infarction (P = 0.003) were independent predictors of the late stage of multivessel diffuse atherosclerosis (defined by ≥ 2 epicardial vessels with moderate or severe diffuse atherosclerosis). In conclusion, this investigation supports the hypothesis that a raised homocysteine concentration is a strong risk factor for the late stage of diffuse coronary atherosclerosis in Chinese patients with AMI undergoing primary PCI. This result therefore raises the prospect of the need for major therapeutic research in Chinese patients.

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Low-grade inflammation as detected by increased C-reactive protein (CRP) levels predicts the risk of cardiovascular events. However, there is still controversy over the mid-term predictive value of CRP in patients referred for elective percutaneous coronary revascularization (PCI) for stable angina pectoris. The aim of this study was to assess the relationship between baseline CRP level and mid-term outcome of patients undergoing PCI.
Two groups of patients with stable angina pectoris were prospectively studied. Group A consisted of 150 consecutive patients with a CRP level ≤ 3 mg/L, and group B consisted of 150 consecutive patients with a CRP level > 3 mg/L undergoing PCI at our institution.
Comparing both groups of patients, the analysis confirmed a significant difference between medians of the CRP levels (0.5 versus 8 mg/mL; P < 0.001). A higher level of CRP in group B was associated with a lower presence of male gender (P < 0.05) and history of myocardial infarction (P < 0.05). On the other hand, in group B there was higher occurrence of smoking (P < 0.001), hypertension (P < 0.05), hypertriglyceridemia (P < 0.001), and diabetes mellitus (P < 0.01). The incidence of myocardial infarction based on postinterventional release of TnI > 1.5 ng/mL reached 12% in group A and 14% in group B (P = 0.73). Analyses were repeated with adjustment for significant baseline variables, which did not change our findings. The incidence of adverse cardiovascular events during a six month follow-up was 13% in both groups (NS).
Increased CRP serum prior to PCI was not associated with the risk and extent of procedure-related myocardial injury measured by TnI release and does not portend heightened cardiovascular risk at six months after percutaneous revascularization. On the other hand, a CRP level > 3 mg/L was associated with a higher occurrence of cardiovascular risk factors (smoking, hypertension, hypertriglyceridemia, and diabetes mellitus).

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In several epidemiological studies, it was suggested that a high titer of cytomegalo-virus (CMV) antibody meant CMV reactivation, and that this condition was a determinant of coronary artery disease (CAD). The purpose of this study was to investigate both the prevalence of the CMV infections in our study population and whether high CMV sero-positivity is a determinant of CAD. Blood samples from 179 (58 female, 121 male) individuals being evaluated for CAD suspicion by coronary angiography were tested for CMV seropositivity and CRP levels. Fifty-six patients had normal coronary arteries and 123 patients had CAD. Six patients did not have anti-CMV antibodies and 87 of the 173 seropositive patients had high levels of anti-CMV antibodies (≥ 8 U/mL). High CMV seropositivity (≥ 8 U/mL) was a significant CAD determinant even after adjustment for traditional CAD risk factors (odds ratio {OR} = 2.1 P = 0.04, respectively). The results indicate that the prevalence of high CMV seropositivity is an independent predictor of CAD in our study population and that our study population with CAD had a high rate of CMV infection.

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The measurement of the thrombosis in myocardial infarction (TIMI) frame count is a simple method for evaluating coronary blood flow. Although it is well known that slow coronary flow is present in patients with coronary artery ectasia (CAE), the effects of coexisting stenosis and the severity of ectatic involvement on coronory flow have not been adequately studied. Thus, we examined (1) the effect of coexistence of obstructive coronary artery disease on TIMI frame count (TFC) and (2) the relation between the severity of ectatic involvement and TFC in patients with CAE. Ninety-seven study patients with CAE were examined in two steps to determine if they were appropriate in terms of the aim of this study. In the first step, ectasias were divided into three groups: an isolated CAE group, a CAE group with coexisting nonsignificant stenosis, and CAE with coexisting significant stenosis. In the second step, ectasias were subdivided into three groups: CAE with one segment, two segments, and three segments (or diffuse) involvement. The TIMI frame counts for the right coronary artery (RCA), the left circumflex coronary artery (LCx), and the left anterior descending artery (LAD) in the ectasia group were significantly higher than that of the control group (P < 0.001, P < 0.05, P < 0.05, respectively). The presence of coexisting nonsignificant stenosis or coexisting significant stenosis in patients with CAE did not influence TFC (P > 0.05, for all). In addition, the severity of ectasia involvement, regardless of the localization of ectatic segments and the type of the affected vessel, did not change the TFC (P > 0.05, for all). These results suggest that neither the coexisting stenosis nor the extent of involvement significantly affect TFC in patients with coronary ectasia.

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The aims of this study were to evaluate myocardial metabolic activity during tepid blood cardioplegic infusion in the arrested heart in comparision with cold blood cardioplegia and to assess the early clinical outcomes of these patients.
Thirty patients undergoing first elective coronary artery bypass grafting surgery were included and randomized to two groups (T for tepid and C for cold), 15 patients in each. Myocardial protection was similar in both groups except for the reinfusion of blood cardioplegia, which was 6°C in group C and 28°C in group T (same temperature as the body perfusion). The route of cardioplegic reinfusion was antegrade during the first reinfusion and retrograde during the second reinfusion. In order to assess myocardial metabolic activity, myocardial oxygen consumption (MVO₂), myocardial glucose uptake, and myocardial lactate and acid production were all calculated. Arterial and coronary venous blood samples were obtained from the aortic root cannula and coronary sinus.
During cardioplegic reinfusions in the ischemic period, the calculated values of myocardial oxygen extraction, oxygen consumption, and glucose uptake were higher in group T than in group C (P < 0.05). This difference was observed during both antegrade and retrograde delivery of cardioplegic solution. Myocardial lactate production was greater in group C than in group T during cardioplegic reinfusion, both antegradely and retrogradely (P < 0.05). In all patients, cardiopulmonary bypass was terminated in the first attempt. The clinical outcome was similar in both groups.
The results of this study indicate that globally ischemic myocardium is able to utilize more oxygen and glucose during cardioplegic reinfusions at a tepid temperature in comparison to cold. In addition, the data showed evidence of less myocardial injury and better left ventricular function throughout the critical period of recovery from global ischemia for the heart protected by tepid cardioplegia.

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We examined the plasma levels of soluble Fas (sFas) or Fas ligand (sFas-L), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in patients with idiopathic nonobstructive (HNCM) and dilated-phase (DHCM) hypertrophic cardiomyopathy.
Patients with idiopathic hypertrophic cardiomyopathy (HCM) may deteriorate to DHCM and the pathogenesis is unknown.
The levels of these plasma cytokines were measured by ELISA and echocardiography was performed in 38 HNCM and 11 DHCM patients, and 10 normal subjects. The follow-up period was three years.
In HNCM, TNF-α (43.3 ± 45.2 versus 16.9 ± 4.3 pg/mL) and IL-6 (65.1 ± 86.4 versus 4.0 ± 2.1 pg/mL) were slightly higher compared to normal subjects and sFas (3.7 ± 1.2 versus 2.1 ± 0.7 ng/mL) increased significantly. sFas (3.9 ± 1.8), TNF-α (79.3 ± 72.4), and IL-6 (234.1 ± 135.2) in DHCM were significantly increased and only IL-6 was significantly different from HNCM. sFas-L (0.18 ± 0.08 versus 0.25 ± 0.05 ng/mL) in HNCM was significantly decreased, and the decrease was marked in DHCM (0.05 ± 0.02). In HNCM, TNF-α was negatively correlated with fractional shortening (r = -0.432, P = 0.0062) or positively with IL-6 (r = 0.665, P < 0.0001), while sFas-L was negatively correlated with IL-6 (r = -0.580, P < 0.0001). DHCM with high sFas had significantly higher cumulative incidences of worsening heart failure.
The Fas/Fas-L system and proinflammatory cytokines may play an important role in the status of HCM and its progression to DHCM.

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The association between homocysteine and sustained hypertension (HT) has been studied. The aim of this study was to assess homocysteine levels in white coat hypertension (WCH) as an indicator of increased risk in the development of cardiovascular diseases. WCH was defined as clinical hypertension and a daytime ambulatory blood pressure of < 135/85 mmHg. Plasma levels of homocysteine were determined in patients with WCH, hypertension, and normotension (NT). The study group included 100 subjects, 33 with WCH (16 males, 17 females) aged 49.1 ± 1.9; 35 sustained hypertensives (17 males,18 females) aged 48.5 ± 1.7 and 32 normotensive control subjects (15 males, 17 females) aged 48.8 ± 2.2. The subjects were matched for age, gender, and body mass index. Patients with a smoking habit, dyslipidemia, or diabetes mellitus were not included in the study. Homocysteine levels were analyzed by ELISA. Plasma homocysteine levels were significantly higher in the WCH group compared to the controls (12.32 ± 1.07 versus 5.35 ± 1.38 μmol/L; P < 0.001) and the WCH group had significantly lower homocysteine values than the hypertensives (19.03 ± 0.76 μmol/L P < 0.001). Total cholesterol and tri-glycerides were not different among the groups. There were no statistically significant differences in urinary albumin excretion (UAE) or creatinine clearence between the three groups. Hypertensive retinopathy was observed in the WCH group, but was less severe and less frequent compared to HTs. LVMI was greater in the WCH group compared to the NTs, but significantly less than HTs.
The data demonstrate that WCH is associated with high levels of homocysteine. The increase in homocysteine level in WCH is not as high as in SHT. Since an elevated plasma homocysteine level is a strong risk factor for coronary artery disease and there was target organ damage in our WCH group, we conclude that WCH should not be considered to be an innocent trait.

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Atherosclerosis is a disease of the arterial wall, with increasing wall thickness representing an early event in the progression of the disease. It has been suggested that iron overload, as assessed by increased serum ferritin concentration, may be a risk factor for atherosclerosis.
The aim of this study was to investigate the relationship between the influence of intravenous (IV) iron therapy and ferritin levels and carotid intima media thickness (C-IMT) in dialysis patients. Sixty patients (51 ± 14) years were divided into two groups according to their IMT obtained by ultrasound; group I (high risk) and group II (low risk). The parameters assessed were serum creatinine, urea, calcium, phosphorus, hemoglobin, albumin, uric acid, iron, ferritin, and lipid levels. Thirty-eight patients (88%) in group I and 5 patients (12%) in group II received IV iron therapy while 5 patients (29%) in group I and 12 patients (71%) in group II (P < 0.001) did not receive IV iron therapy. Ferritin levels were higher in group I than in group II (581 ± 303 and 306 ± 224) (P < 0.001). C-IMT measurements correlated with serum ferritin and with the intravenous iron dose received during the 24 months preceding the study (r = 0.315, P = 0.015; r = 0.471, P = 0.001).
The findings indicate that IV iron therapy and elevated serum ferritin levels may cause an increase in the incidence of atherosclerosis.

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Changes in the expression levels of several genes have been described in aortic aneurysm specimens, however, the spectrum of diverse molecular alterations remains to be elucidated. We attempted to identify key molecules that modulate the pathogenesis of aortic aneurysm, using a complimentary DNA microarray carrying approximately 13,000 human genes.
Segments of thoracic aortic aneurysms (TAA) and adjacent normal thoracic aortic tissues without aneurysmal changes (NTA) were obtained from 20 patients undergoing graft surgery. RNA obtained from five pairs of TAA and NTA samples was compared to determine aneurysm-specific alterations using microarray. Further, the expression levels of several genes of interest were verified in the remaining specimens by real-time reverse transcription-polymerase chain reaction (RT-PCR).
In microarray assays, several types of the matrix metalloproteinases were upregulated as reported previously. Also, 220 genes suggested to be involved in protein degradation, inflammation, apoptosis, stress response, intracellular signaling, and other processes were significantly upregulated. Many of these genes have not been previously implicated in cardiovascular disease. The real time RT-PCR independently confirmed that the expression levels of MMP-2, MMP-9, ADAMTS-1, and caspase 4 were consistently increased in TAA.
The results indicate that many genes are involved in a complicated manner in the pathogenesis of TAA. Investigation of these genes will help clarify the pathogenesis of this disease, and may lead to the discovery of novel therapeutic targets.

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Antiarrhythmic drugs exert their effects by inhibiting the ion channels of cardiomyocytes. However, these effects could also modify the ionic environment around them, and thereby affect the expression of ion channels, leading to biochemical enhancement or attenuation of the antiarrhythmic effects. To test this hypothesis, the physiological and biochemical effects of cibenzoline were evaluated in a rapid atrial pacing model in rats.
In rats with rapid atrial pacing, pretreatment with cibenzoline significantly inhibited the increases in Kv1.5 mRNA at 2 hours and immunoreactive protein at 4 hours by 35 ± 15% and 30 ± 10%, respectively. These effects were observed only in the rapid atrial pacing group, not in the sham-operated group. With cibenzoline pretreatment, 4-hour rapid atrial pacing resulted in significant prolongation of the atrial refractory period compared to the untreated group even after removal of cibenzoline. In contrast, the sham and rapid atrial pacing model with and without cibenzoline pretreatment showed similar acute physiological responses to cibenzoline.
In conclusion, in addition to the acute physiological effects, pretreatment with cibenzoline exerted pleiotropic effects of inhibition of Kv1.5 channel upregulation by rapid pacing, implying differences in the cibenzoline effects when administered before and after onset of paroxysmal atrial fibrillation.

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A reduction of coronary flow reserve has been reported in patients with hypertensive heart disease (HHD), which suggests that myocardial ischemia may contribute to the progression to cardiac failure in HHD. Therefore, we evaluated whether fibroblast growth factor (FGF)-2 and/or heparin, which induce angiogenesis, may affect cardiac function in the setting of HHD.
We used Dahl salt sensitive (DS) rats as an HHD model. Direct intramyocardial injection of 100 μg of FGF-2 plus 1.28 μg of heparin (n = 6), 100 μg of FGF-2 (n = 6), 1.28 μg of heparin (n = 6) or saline (n = 6) were performed in 9-week-old rats. Echocardiography was performed to evaluate cardiac function at 9, 11, and 13 weeks of age. Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations were measured at 8 and 13 weeks of age. DS rats were killed 4 weeks after myocardial injection (at 13 weeks of age), and myocardial capillary density was assessed by von Willebrand factor staining. Injection of FGF-2 plus heparin significantly decreased left ventricular end-diastolic diameter (P < 0.0001) and left ventricular end-systolic diameter (P < 0.0001), significantly improved the reduction of left ventricular fractional shortening (P = 0.0005), significantly decreased plasma ANP (P < 0.0001) and BNP (P = 0.016) concentrations, and significantly increased myocardial capillary density (P = 0.0002) compared with injection of saline.
These findings indicate that intramyocardial injection of FGF-2 plus heparin suppresses the progression of cardiac failure in DS rats. FGF-2 plus heparin administration may be a new therapeutic strategy for the treatment of HHD.

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Transplant vasculopathy is a leading cause of graft failure and a major contributor to the lack of success with small caliber vascular allografts.
In this study we evaluate techniques of bone marrow cell seeding on small caliber vessels and assess the impact of this tactic on neointimal hyperplasia in de-endothelialized rat aortic allografts.
In a preliminary study, bone marrow cells from Lewis rats were seeded onto the chemically de-endothelialized luminal surface of the abdominal aorta of WKY rats - with or without fibrin glue. In the allograft transplantation model, de-endothelialized fresh aortic allografts of WKY rats were orthotopically transplanted into Lewis recipients either directly (n = 6) or after recipient bone marrow cell seeding (n = 6). Histological evaluation was performed at 28 days.
Bone marrow cells were able to adhere to the de-endothelialized aortic wall owing to the use of fibrin glue, but were unable to do so without fibrin glue. In the de-endothelialized allograft transplantation model, recipient bone marrow seeding led to a significant reduction of the ratio of intimal to medial area (0.40 ± 0.08 versus 0.79 ± 0.08, P = 0.0077). Some of the seeded cells remained in the intima for 4 weeks and some infiltrated the media, expressing CD31 or α-SMA.
The results suggest that recipient bone marrow cell seeding on de-endothelialized aortic allograft is feasible with the use of fibrin glue and that this technique reduces neointimal hyperplasia of the graft.

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A 72-year-old woman was admitted to our institution because of sudden chest pain. Emergency coronary angiography revealed thrombotic occlusion of the distal right coronary artery. A large cylindrical thrombus was retrieved from her distal right coronary artery using a thrombus aspiration catheter. IVUS showed minimal atherosclerosis and moderate ectatic change at the proximal right coronary artery. A reconstructed IVUS image also showed that a mural thrombus with abrupt ending was still retained at the ectatic segment. Based on this evidence, coronary ectasia was thought to be the primary cause for the thrombus formation and acute myocardial infarction in this case.

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A single coronary artery with an anomalous origin between the pulmonary artery and aorta is an unusual congenital anomaly. We present a 60 year old female patient with stable angina pectoris. Her coronary angiogram revealed that the right coronary artery originated from the left main stem and coursed between the great vessels. There was 90% stenosis in the left anterior descending coronary artery. We performed a fractional flow reserve study of both the anomalous origin artery and stenosed vessel. Fractional flow reserve study of the anomalous RCA did not reveal functional ischemia. We did not refer the patient to coronary artery bypass grafting but instead performed percutaneous coronary revascularization of the LAD. The patient is alive and has been free of symptoms during the 1 year follow-up.

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Dissection of the sinus of Valsalva is an extremely rare accident during percutaneous coronary intervention (PCI), but it can lead to serious complications such as dissection of the ascending aorta. We experienced a localized dissection of the right coronary cusp without coronary artery involvement that was induced by a guiding catheter during PCI in a patient with acute myocardial infarction. The localized dissection showed pooling of the contrast medium in the acute phase, but it subsided spontaneously after 12 days without any sequelae. Manipulation of the guiding catheter should be performed with great caution not only in the coronary artery but also in the sinus of Valsalva.

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Although no-reflow phenomenon may occur in patients that experience reperfusion after ischemia, there have been no reports describing the postmortem findings in these patients. We describe the findings of an autopsy in a 56-year-old man who experienced acute coronary syndrome with no-reflow phenomenon after coronary intervention. Macroscopic study demonstrated myocardial infarction with diffuse hemorrhage, and microscopic analysis revealed vascular damage and microembolization in the no-reflow area. In conclusion, coronary microembolization and damage to the small coronary artery may contribute to the pathogenesis of no-reflow phenomenon following coronary intervention in humans.

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Studies on the mechanisms of atrioventricular nodal reentrant tachycardia (AVNRT) have yet to clarify whether the slow and fast pathways connect directly with the atria or via an upper common pathway. Although a "final common pathway" connecting the slow and fast pathways to the proximal His bundle was thought to be part of the reentrant circuit, debate on the presence of an upper common pathway continues. We report a case of AVNRT continuing despite the occurrence of ventriculoatrial block, thus supporting the existence of an upper common pathway.

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A 37-year old woman was suspected of having renovascular hypertension because of recent onset severe hypertension (blood pressure 220/135 mmHg; compared to 132/65 mmHg two years earlier) and an abdominal bruit. A captopril renal scan indicated the presence of right renal artery stenosis. Additionally, a captopril plasma renin activity (PRA) provocation test showed a positive result for renovascular hypertension (baseline PRA = 291 μU/mL; 1 hour post-captopril PRA = 1444 μU/mL). Selective renal angiography demonstrated a severe critical stenotic lesion at the distal portion of the right renal artery. Blood pressure (BP) decreased to 136/80 mmHg one day after successful percutaneous transluminal renal angioplasty and stenting. Repeat renal angiography six months after the procedure revealed no evidence of in-stent restenosis. Blood pressure (BP = 137/76 mmHg) and plasma renin profile (baseline PRA = 23.8 μU/mL; 1 hour post-captopril PRA=22.3 μu/mL) also were normal six months following initial revascularization. Moreover, blood pressure (137/84 mmHg) and renin profile remained normal 2.5 years after the procedure (baseline PRA = 24.3 μU/mL; 1 hour post-captopril = 25.6 μU/mL). The results of this study have thus demonstrated a case of renin-dependent renovascular hypertension in which both the blood pressure and plasma renin activity profile normalized following successful percutaneous transluminal angioplasty and stenting.

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A 24 year-old woman had a congenital solitary kidney with renovascular hypertension due to fibromuscular dysplasia. She had been treated as having essential hypertension until she developed preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome at 28 weeks of gestation. Plasma renin activity and captopril test results did not indicate any abnormalities. However, renography revealed captopril-induced deterioration. Magnetic resonance angiography was also useful to detect renal artery stenosis. These findings were confirmed by renal angiography. After successful percutaneous transluminal renal angioplasty, her blood pressure and the pattern of captopril renography normalized.

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A 45-year old man was admitted to our hospital with chest pain occurring suddenly upon exercise and disappearing with rest within several minutes. A continuous murmur was heard at the upper sternum border. Conventional electrocardiography showed no evidence of myocardial ischemia. Coronary angiography and cardiac catheterization demonstrated a fistula originating from the left coronary artery to the pulmonary artery with an aneurysm 2 cm in size, and Qp/Qs 1.08. Treadmill exercise testing showed no ST-T change at the maximum heart rate of 160 beats/min. Stress/Rest ^99mTechnetium-MIBI single-photon emission computed tomography (SPECT) and ¹²³I-15-(p-iodo-phenyl)-3,R,S-methylpentadecanoic acid (BMIPP) scintigraphy were performed to evaluate myocardial ischemia and ischemia was identified at the perfusion area of the left anterior descending artery. From these results, the patient was diagnosed as having a coronary artery to pulmonary artery fistula with myocardial ischemia. Consequently, surgical treatment was chosen under cardiopulmonary bypass. The determination of a surgical indication using stress/rest ^99mTc-MIBI SPECT and BMIPP scintigraphy is useful in cases showing normal TMT, such as this case.

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