Right Coronary Artery with an Intramural and Interarterial Course as a Unique Cause of Myocardial Ischemia: The Unroofing Method Might Still Be the Best Solution.

A 39-year-old man was admitted because of cardiac arrest. Emergent coronary angiography revealed a preserved coronary blood flow; however, multiple-row detector computed tomography (MDCT) revealed that the proximal right coronary artery (RCA) was running inside the aortic wall, creating proximal stenosis without atherosclerotic changes. Surgical intervention with unroofing was performed; however, postoperative stenosis of the proximal RCA required additional coronary artery bypass grafting (CABG). Intraoperative findings during CABG did not reveal hematoma or coronary dissection. However, MDCT one year after CABG depicted improvement of the RCA and graft stenoses, suggesting that the post-unroof stenosis may have been caused by an inflammatory reaction after surgical intervention.

Plaque modification using a cutting balloon is more effective for stenting of heavily calcified lesion than other scoring balloons.

Cutting balloons (CBs) and other scoring balloons are known to be useful for plaque modification in heavily calcified lesions. There have been some reports of the efficacy of these balloons compared to conventional balloons. However, there have been no reports exploring which balloon is most effective among these three types of balloons. We, therefore, compared these three balloons with respect to effectiveness in plaque modification of calcified lesions. We retrospectively investigated 201 cases using these three balloons from April 2015 to December 2017. Of these cases, 156 with severe calcified lesions that had undergone intravascular ultrasound (IVUS) or optical frequency domain imaging (OFDI) were enrolled. The ratio of severe calcified lesion was higher in the CB group than in the groups of other balloons (p = 0.001), and IVUS and OFDI showed that a CB was more effective in plaque modification than the other balloons. The acute gain (minimum stent diameter minus minimum lumen diameter) and acute cross-sectional area (CSA) gain (minimum stent area minus minimum lumen area) were both larger in the CB group than in the others, and the stent symmetry index (minimum stent diameter/maximum stent diameter) showed that the CB group more closely approximated a perfect circle than the other groups (p = 0.0001, 0.006 and 0.002 for the acute gain, acute CSA gain and the stent symmetry index). Similar results were obtained in cases without rotational atherectomy. These data suggest that CB is more effective for plaque modification in cases of severe calcified lesions than other scoring balloons.

Ratio of eicosapentaenoic acid to arachidonic acid is a critical risk factor for acute coronary syndrome in middle-aged older patients as well as younger adult patients.

BACKGROUND: Coronary risk factors for the onset of acute coronary syndrome (ACS), including polyunsaturated fatty acids (PUFAs), in younger adult patients may be different from those in older patients. METHODS AND RESULTS: We enrolled 578 patients who underwent coronary angiography at Fukuoka Saiseikai Hospital, and divided them into a younger adult group (YG) (<50 years, n=47) and a middle-aged older group (OG) (≥50 years, n=531). In a multivariate analysis, lower levels of high-density lipoprotein cholesterol and the ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) (EPA/AA), and less aspirin, oral hypoglycemic agent, and calcium channel blocker (CCB) use were independent risk factors for ACS in all patients. In YG, lower levels of EPA/AA and less angiotensin II receptor blocker/angiotensin-converting enzyme inhibitor use were the independent risk factors. In OG, smoking, lower levels of EPA/AA, less aspirin and CCB use were the risk factors. While lower levels of EPA/AA was the only risk factor for ACS that was common to all patients, YG and OG, docosahexaenoic acid/AA was not associated with ACS in YG and OG. CONCLUSIONS: Lower level of EPA/AA is a common critical risk factor for ACS in middle-aged older patients as well as younger adult patients. Some of the risk factors for the onset of ACS in younger patients were different from those in older patients.

A case of biopsy-proven cardiac sarcoidosis without any other extracardiac manifestations.

A 49-year-old woman was referred to our hospital for uncontrollable heart failure. She had never been diagnosed as having sarcoidosis. Chest X-ray showed cardiomegaly without bilateral hilar lymphadenopathy. Echocardiography showed diffuse hypokinesis of the left ventricle mimicking idiopathic dilated cardiomyopathy. No specific manifestations implying sarcoidosis were observed. On cardiac catheterization, coronary angiograms were normal, whereas concurrent routine endomyocardial biopsy showed foci of non-caseating granuloma, indicating sarcoidosis. Pathological finding was the only clue to diagnose cardiac sarcoidosis among our standard examinations for heart failure. No other additional investigations found any extracardiac features of sarcoidosis. All serological and immunological examinations were within normal range. This is a challenging case of biopsy-proven cardiac sarcoidosis without any other extracardiac involvement.

Nifekalant hydrochloride terminated electrical storms after coronary surgery.

An "electrical storm" is a life-threatening condition defined as a recurrent attack of ventricular tachycardia or fibrillation. The current report is a case study of a patient who had electrical storms developing unexpectedly after undergoing coronary artery bypass grafting. The electrical storms were terminated dramatically by the administration of nifekalant hydrochloride. We suggest that nifekalant hydrochloride has great therapeutic potential for the suppression of intractable ventricular tachyarrhythmias refractory to amiodarone.

[Combined therapy with weight loss and amiodarone improved cardiac function in a patient with idiopathic dilated cardiomyopathy complicated with severe obesity: a case report].

Obesity is associated with an increased risk of development of chronic heart failure, but recent epidemiological studies indicate that a higher body mass index (BMI) is associated with a better survival rate. This is described as the 'obesity paradox' or 'reverse epidemiology'. A 42-year-old male was admitted because of recurrent episodes of decompensated heart failure, and the diagnosis was idiopathic dilated cardiomyopathy complicated with severe obesity (BMI 46.0), nonsustained ventricular tachycardia, and central type sleep apnea syndrome. Combined therapy with weight loss (BMI 46.0 to 30.8) and amiodarone (200 mg/day) was instituted in addition to the previous regimen including angiotensin converting enzyme inhibitor, beta blocker, diuretics and pimobendan, improved cardiac function, exercise tolerance, and cardiac sympathetic nerve activity evaluated by cardiac 123I-metaiodobenzylguanidine scintigraphy. Furthermore, we succeeded in uptitration of carvedilol(5 to 10mg/day). This case highlights the possible beneficial effect of weight loss in patients with chronic heart failure complicated with obesity, and the resultant improvement of cardiac sympathetic nerve activity suggests that weight loss may partially mimic beta blocker effects in patients with systolic heart failure.

Statins blunt thrombin-induced down-regulation of endothelial nitric oxide synthase expression in human endothelial cells.

Thrombin plays a pivotal role in the pathophysiology of acute coronary syndromes by mediating thrombus formation and endothelium-dependent vasomotor dysfunction. In human endothelial cells, prolonged incubation with thrombin down-regulates endothelial nitric oxide synthase (eNOS) expression via activation of Rho. Statins are effective in patients with acute coronary syndromes. These beneficial effects are attributed to their pleiotropic effects and also to an improved lipid profile. We hypothesized that statins may prevent the down-regulation of eNOS induced by thrombin in human endothelial cells. Human umbilical vein endothelial cells were used. Expression and activity of eNOS protein were evaluated by Western blotting and L-citrulline assay, respectively. Rho A membrane translocation was evaluated by Wesern blotting after fractionation. Stimulation of human umbilical vein endothelial cells with thrombin (4 U/mL, 24 h) significantly decreased eNOS expression. The addition of simvastatin significantly prevented thrombin-induced down-regulation of eNOS expression in a concentration-dependent manner (100 nmol/L to 10 micromol/L). Cerivastatin (10 micromol/L) also reversed the down-regulation of eNOS by thrombin. Both simvastatin and cerivastatin-blocked thrombin-induced decrease in NOS activity. Stimulation with thrombin (4 U/mL, 10 min) significantly increased the membrane translocation of Rho A. Simvastatin (10 micromol/L) and cerivastatin (10 micromol/L) significantly decreased thrombin-induced membrane translocation of Rho A. Therefore, statins blunt thrombin-induced down-regulation of eNOS expression in human endothelial cells. This finding provides a novel mechanism of the pleiotropic effects of statins, which may be beneficial for patients with acute coronary syndromes.

Statins prevent pulsatile stretch-induced proliferation of human saphenous vein smooth muscle cells via inhibition of Rho/Rho-kinase pathway.

OBJECTIVE: Pulsatile forces regulate vascular remodeling and trigger vascular diseases such as saphenous vein graft disease. The saphenous vein is exposed to high pressure and pulsatility only after implantation. Statins have been proved to reduce the incidence of vein graft failure. Thus, we investigated the molecular mechanisms of pulsatile stretch-induced saphenous vein smooth muscle cell (SMC) proliferation and potential beneficial effects of statins. METHODS AND RESULTS: Human saphenous vein SMCs were subjected to cyclic stretch (60 cycles/min) in Flex I plates. Cerivastatin and simvastatin significantly prevented stretch-induced increase in SMC proliferation. Stretch induced the membrane accumulation of Rho A and Rho kinase inhibitors (Y-27632 and hydroxyfasudil) and dominant negative Rho A mutant significantly prevented stretch-induced SMC proliferation. In addition, stretch increased the levels of both p44/42 mitogen-activated protein (MAP) kinase and Akt phosphorylation. MAP kinase kinase (MEK)1/2 inhibitor U0126, phosphatidylinositol (PI) 3-kinase inhibitors (wortmannin and LY294002), and dominant negative Akt mutant significantly prevented stretch-induced SMC proliferation. Cerivastatin significantly prevented stretch-induced membrane accumulation of Rho A. On the other hand, stretch-induced phosphorylation of p44/42 MAP kinase and Akt was not prevented by cerivastatin. Mevalonate restored the preventive effect of cerivasatain on stretch-induced Rho A membrane accumulation. Stretch induced hyperphosphorylation of retinoblastoma protein (pRb), which was prevented by cerivastatin and the Rho kinase inhibitors. CONCLUSION: Statins prevent stretch-induced saphenous vein SMC proliferation via inhibition of the Rho/Rho-kinase pathway. This may explain the beneficial effects of this class of drug, especially for patients after coronary artery bypass grafting.

Postprandial increase in plasma concentrations of remnant-like particles: an independent risk factor for restenosis after percutaneous coronary intervention.

Postprandial increase in remnant lipoprotein concentrations has been suggested as an important atherogenic factor. However, the influence of these remnants on the development of restenosis after percutaneous coronary intervention (PCI) remains to be examined. The present study was designed to address this point. In 60 consecutive patients with successful PCI, the influences of possible risk factors on the development of restenosis, including remnant-like particles (RLP) cholesterol (RLP-C) and triglyceride (RLP-TG), were examined. While mean concentrations of RLP-C and RLP-TG were normal in fasting state, postprandial change in RLP-C concentrations was a significant and independent risk factor for restenosis after PCI. The calculated cut-off index (COI) for the change was +64%. When the patients were divided into 2 groups according to this COI, minimal lumen diameter (MLD) and reference coronary diameter were comparable before and immediately after PCI between the high- (COI < 64%) and the low- (COI < 64%) responders. However, follow-up coronary angiography 3 to 6 months after PCI demonstrated that MLD, late loss, and loss index were all worse in the high responders compared with the low responders. These results indicate that post-prandial increase in RLP-C concentrations is an independent risk factor for restenosis after successful PCI, even in patients with normal fasting RLP-C levels.

Statin prevents tissue factor expression in human endothelial cells: role of Rho/Rho-kinase and Akt pathways.

BACKGROUND: Tissue factor plays a pivotal role in thrombus formation in acute coronary syndromes. However, the regulatory mechanisms underlying tissue factor expression are poorly understood. Statins are effective in patients with acute coronary syndromes. Hence, the aim of this study was to clarify in human endothelial cells the signaling pathways of thrombin-induced tissue factor expression and potential inhibitory effects of statins. METHODS AND RESULTS: In human aortic endothelial cells, simvastatin prevented tissue factor induction by thrombin (4 U/mL) in a concentration-dependent manner. The increase in tissue factor activity on the cell surface was also blocked by simvastatin. Simvastatin also prevented the upregulation of tissue factor expression and activity in human aortic smooth muscle cells. Mevalonate (100 micromol/L) reversed the inhibitory effect of simvastatin on tissue factor expression. Thrombin induced rapid activation of Rho A and p38 MAP kinase. The Rho-kinase inhibitor Y-27632 and the p38 MAP kinase inhibitor SB203580 prevented tissue factor induction. Akt was dephosphorylated by thrombin; the phosphoinositol 3-kinase inhibitor wortmannin enhanced its dephosphorylation as well as thrombin-induced tissue factor expression. Simvastatin prevented thrombin-induced Rho A activation but not p38 MAP kinase activation. Akt dephosphorylation by thrombin was blocked by both simvastatin and Y-27632. CONCLUSIONS: Endothelial tissue factor induction by thrombin is regulated by Rho/Rho-kinase, Akt, and p38 MAP kinase. Simvastatin prevents its induction through inhibition of Rho/Rho-kinase and activation of Akt. These findings provide new insights into the action of statins in acute coronary syndromes.

Felodipine inhibits nuclear translocation of p42/44 mitogen-activated protein kinase and human smooth muscle cell growth.

OBJECTIVE: Smooth muscle cell (SMC) proliferation contributes to vascular structural changes in cardiovascular disease. Ca(2+) antagonists exert antiproliferative effects and may also be clinically beneficial in the patients. However, the underlying mechanisms of action remain elusive. Activation of mitogen-activated protein kinases (MAPK), in particular p42/44mapk plays a central role in cell proliferation. We hypothesise that Ca(2+) antagonists inhibit cell proliferation by interfering with the p42/44mapk pathway in human SMC. METHODS: SMC were cultured from human aorta. Cell proliferation was analysed by [3H]thymidine incorporation. Activation of p42/44mapk and the nuclear target protein Elk-1 was analysed by phosphorylation and p42/44mapk nuclear translocation by confocal microscope. RESULTS: PDGF-BB (10 ng/ml) stimulated [3H]thymidine incorporation, phosphorylated p42/44mapk, caused nuclear translocation of the enzymes and phosphorylated the nuclear target protein Elk-1. Felodipine (10(-7) to 10(-5) mol/l) inhibited [3H]thymidine incorporation to PDGF-BB, had no effect on p42/44mapk phosphorylation. However, p42/44mapk nuclear translocation and Elk-1 activation stimulated by PDGF-BB were prevented by the Ca(2+) antagonist. CONCLUSION: Activation of p42/44mapk, subsequent nuclear translocation and activation of Elk-1 are essentially associated with human SMC proliferation. The Ca(2+) antagonist felodipine prevents p42/44mapk nuclear translocation (but not its activation) associated with inhibition of human SMC growth.