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Background PTPN11 is ubiquitously expressed and has a variety of phenotypes even in a single heart. We examined LEOPARD syndrome (LS) in a patient with PTPN11 variants through pathological, electrophysiological, and anatomical studies. Case summary A 49-year-old man with no previous medical history was brought to our emergency department because of syncope. An electrocardiogram (ECG) revealed alternating bundle branch block, and echocardiography revealed hypertrophic cardiomyopathy-like morphology with systolic anterior motion of the posterior mitral valve. Atrioventricular block, left ventricular outflow tract (LVOT) obstruction, and ventricular tachycardia were considered the differential diagnoses; however, the treatment plan was difficult to determine. An electrophysiological study revealed the cause of the ECG abnormality to be accelerated idioventricular rhythm, and the programmed ventricular stimulation was negative. Genetic testing revealed LS with PTPN11 variant, which was speculated to be the cause of these various unique cardiac features. The cause of syncope was considered to be exacerbation of LVOT obstruction due to dehydration, and the patient was treated with oral beta-blockers. Implantable loop recorder observation for 1 year revealed no arrhythmia causing syncope, and an implantable cardioverter-defibrillator and pacemaker were deemed unnecessary for primary prevention of syncope. During 2.5 years of follow-up, the LVOT peak velocity fluctuated between 2.5 and 3.5 m/s, but the patient remained stable with no recurrent syncope. Conclusion We confirmed that LS is distinct from other cardiomyopathies using characterization, physiological, electrophysiological, and pathological examinations. Evidence supporting a specific treatment strategy for LS is limited, and understanding the pathogenesis may help establish effective treatment strategies. [ABSTRACT FROM AUTHOR]

Recently, there have been increasing opportunities to treat patients with peripheral arterial disease. Of those patients, both pathological conditions, such as acute limb ischemia (ALI) and chronic critical limb ischemia (CLI), are closely associated with high risks of major amputation, disability and death. We encountered a very rare case of CLI subsequent to ALI. An 83-year-old male showed the sudden onset of ALI, probably due to thromboembolism from an abdominal aortic aneurysm during an operation for gastric cancer. The patient was referred to another hospital for Fogarty thrombectomy. About 1 month after ALI onset, necrosis of the left first toe gradually progressed. On angiography of the left lower limb, we noted occlusions of both anterior and posterior tibial arteries. Then, we successfully conducted balloon angioplasty for the below-the-knee arteries. Thereby, favorable blood flow was achieved, which led to successful wound healing without amputations. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Neoatherosclerosis is emerging as a stent‐associated problem that has not yet been fully resolved. Because in‐stent restenosis with a neoatherosclerotic etiology is associated with a high risk of acute coronary syndrome and a poor survival prognosis, it is essential to precisely identify patients at risk using advanced imaging modalities. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that apoptosis and necrosis share common features in their signaling pathway and that apoptosis requires intracellular ATP for its mitochondrial/apoptotic protease-activating factor-1 suicide cascade. The present study was, therefore, designed to examine the role of intracellular energy levels in determining the form of cell death in cardiac myocytes. Neonatal rat cardiac myocytes were first incubated for 1 h in glucose-free medium containing oligomycin to achieve metabolic inhibition. The cells were then incubated for another 4 h in similar medium containing staurosporine and graded concentrations of glucose to manipulate intracellular ATP levels. Under ATP-depleting conditions, the cell death caused by staurosporine was primarily necrotic, as determined by creatine kinase release and nuclear staining with ethidium homodimer-1. However, under ATP-replenishing conditions, staurosporine increased the percentage of apoptotic cells, as determined by nuclear morphology and DNA fragmentation. Caspase-3 activation by staurosporine was also ATP dependent. However, loss of mitochondrial transmembrane potential ([Delta][[Psi].sub.m]), Bax translocation, and cytochrome c release were observed in both apoptotic and necrotic cells. Moreover, cyclosporin A, an inhibitor of mitochondrial permeability transition, attenuated staurosporine-induced apoptosis and necrosis through the inhibition of ([Delta][[Psi].sub.m]) reduction, cytochrome c release, and caspase-3 activation. Our data therefore suggest that staurosporine induces cell demise through a mitochondrial death signaling pathway and that the presence of intracellular ATP favors a shift from necrosis to apoptosis through caspase activation. cytochrome c; mitochondria; necrosis; staurosporine

Currently, there are more opportunities to treat patients complicated with critical limb ischemia (CLI), which is a very dismal medical condition associated with a high risk of major amputation, disability and death. Because CLI is usually caused by multi-level occlusive atherosclerotic disease, the condition of CLI induced by aorto-iliac occlusive disease (AIOD) alone is thought to be a rare pathological entity. We encountered a patient with severe CLI caused by solitary AIOD. Three vascular access routes were established and stiff guidewires retrogradely passed the occluded arteries on both sides. We deployed two self-expandable bare metal stents and complete revascularization led to wound healing. Recent improvements of catheter devices and procedural techniques related to endovascular treatment (EVT) have enabled us to safely recanalize complex vascular lesions of the lower extremities. Therefore, an EVT strategy is one of the favorable treatment options for CLI patients who are contraindicated for surgical treatments. [ABSTRACT FROM AUTHOR]

We encountered a case of blow-out type coronary perforation at the calcified stenosis of left anterior descending artery. First, we started immediate balloon tamponade through the initial guiding catheter (GC) with a GuideLiner catheter. Next, we introduced a second GC with a GuideLiner catheter and successfully deployed a covered stent. Two sets of the GC with GuideLiner catheter facilitated us to simultaneously perform temporary hemostasis with balloon tamponade and rapid delivery of a covered stent. To alternately manipulate the GuideLiner catheters, back and forth with seesaw-like motion enabled us to minimize the interruption of balloon tamponade. [ABSTRACT FROM AUTHOR]

Key Clinical Message Catheter-induced coronary dissection involving left main bifurcation is a rare complication during cardiac catheterization but can become lethal unless it is treated appropriately. Interventional cardiologists always have to pay attention to the risk of complications related to cardiac catheterization and prepare for determining the best bailout strategy for the situation. [ABSTRACT FROM AUTHOR]

Background: A lotus root appearance is a rare entity, and there is little opportunity to perform coronary intervention for this kind of lesion. Because of its peculiar anatomical characteristics, one of the problems regarding percutaneous coronary intervention (PCI) for these lesions is related to the involvement of branch vessels.Case Presentation: We encountered a case of PCI for a stenotic lesion with a lotus root appearance in the mid-portion of the right coronary artery (RCA). To avoid the risk of right ventricular (RV) branch occlusion due to stent deployment in the main RCA, we re-crossed the third guidewire into the main RCA via the nearest point to the RV branch ostium through the communicating vascular lumen. Thereafter, we deployed a drug-eluting stent in the main RCA crossing over the RV branch, and the ostium of the RV branch remained intact, as we expected.Conclusions: This case is the first report in the world describing the details of how to maintain the patency of the side branch bifurcating from a lesion with a lotus root appearance under optical coherence tomography guidance. [ABSTRACT FROM AUTHOR]

It is well known that silent myocardial ischemia (SMI) often complicates patients with cerebral infarction and that stroke patients often die of ischemic heart disease. Therefore, it is considered important to treat myocardial ischemia in stroke patients. This study investigated SMI complicating Japanese patients with fresh stroke, using Tc-tetrofosmin myocardial scintigraphy with pharmacologic stress testing to elucidate their clinical manifestations. This study included 41 patients (26 men, mean age 76.0 ± 10.7 years) with acute cerebral infarction and no history of coronary artery disease. All patients underwent Tc-tetrofosmin myocardial scintigraphy with intravenous administration of adenosine to diagnose SMI. Of the 41 patients, myocardial ischemia was confirmed in 17 patients (41.5%). Atherosclerotic etiology was the major cause of stroke in the ischemia(+) group and embolic origin was the major cause in the ischemia(−) group. Patients with myocardial ischemia had a higher incidence of diabetes mellitus (52.9 vs 20.8%; P = 0.0323) and more than two conventional cardiovascular risk factors (64.7 vs 25.0%; P = 0.0110) compared with the nonischemic patients. Infarction subtype of atherosclerotic origin was an independent positive predictor of asymptomatic myocardial ischemia in patients with stroke. These findings indicate that the prevalence of asymptomatic myocardial ischemia is relatively high, especially in patients with stroke of atherosclerotic origin. Therefore, it is beneficial for us to narrow the target population who are at the highest risk when screening for SMI in Japanese patients with acute cerebral infarction. [ABSTRACT FROM AUTHOR]

Summary: Background: Prolonged pre-hospital time for acute myocardial infarction (AMI) is associated with decreased indication for primary percutaneous coronary intervention (PCI). However, the efficacy of primary PCI in AMI patients with prolonged pre-hospital time has not been fully investigated in Japan. Methods and results: A total of 3010 consecutive AMI patients admitted to AMI-Kyoto Multi-Center Risk Study Group hospitals were retrospectively analyzed, and the clinical characteristics and in-hospital prognosis of these patients were reviewed. Patients with pre-hospital delay [elapsed time (ET)>12h] had a lower frequency of Killip≥3 (9.3%) and less frequently received primary PCI (77.7%) compared with patients with ET≤12h. In the ET>12h group, older patients or patients with MI history tended to be complicated by heart failure. Primary PCI was performed for patients with ET>12h, irrespective of the severity of heart failure [Killip 1 (78.7%) vs Killip≥2 (74.0%); p =0.3827]. On multivariate logistic regression analysis, age [odds ratio (OR) 1.053], MI history (OR 2.860), Killip≥2 (OR 10.235), and multi-vessels or left main coronary artery as culprit (OR 11.712) were significant independent positive predictors of in-hospital mortality for patients with ET>12h. Practice of primary PCI was not a significant negative predictor for patients with ET>12h (OR 0.812), but it was for patients with ET≤12h (OR 0.425). Conclusions: These findings indicate that patients with ET>12h have a less severe condition and less frequently receive primary PCI compared with patients with ET≤12h. Although primary PCI is often performed for these patients irrespective of the severity of heart failure, no preferable effect of primary PCI on the in-hospital mortality is demonstrated. In contrary, practice of primary PCI is a significant negative predictor of in-hospital mortality for patients with ET≤12h. [Copyright &y& Elsevier]

The mechanisms by which apoptotic myocytes are removed by macrophages have not been fully elucidated. This study examined whether apoptotic myocytes actively recruit macrophages by generating monocyte chemoattractant protein-i (MCP-1) in experiments in vitro and in vivo. Neonatal rat cardiac myocytes were incubated for 4 h in the presence or absence of staurosporine (STS, 0.2-1 μmol/l), an apoptosis inducer. Nuclear staining with DAPI showed that STS induced apoptosis in a dose-dependent fashion. STS (1 μmol/l) caused extensive DNA fragmentation and increased caspase-3 activity compared with a serum-deprived control. MCP-l mRNA and protein levels in myocytes increased twofold and fourfold, respectively, on STS treatment, and immunochemical staining revealed that apoptotic myocytes expressed MCP-l. To elucidate the role of MCP-1 expressed in apoptotic myocytes to recruit macrophages/monocytes, rat monocytes were incubated in the supernatant of STS-treated myocytes using a transwell system. The culture medium of STS-treated myocytes recruited monocytes in a MCP- I-dependent fashion. In addition, experiments were performed in vivo using ischemia-reperfused rat hearts. Rats were subjected to 30 mm of ligation of the left coronary artery followed by 24 h of reperfusion. After the reperfusion, in the ischemic border myocardium, 17.1 ± 1.1% of myocytes were terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) positive. Moreover, double staining using the TUNEL technique and immunohistochemistry with MCP- I antibody showed that 69.8 ± 3.9% of TUNEL-positive myocytes expressed MCP-l protein. Concomitantly, activated macrophages infiltrated the areas of apoptosis remarkably. These results suggest that apoptotic myocytes produce MCP-l, which have a critical role in the active recruitment of macrophages. [ABSTRACT FROM AUTHOR]

Examines the involvement of nitric oxide (NO) in the mechanisms by which endotoxemia causes cardiac depression. Infusion of rats with lipopolysaccharide (LPS) or saline; Isolation of hearts and mounting in a Langendorff apparatus; Determination of the left ventricular developed pressure before biochemical analysis of the myocardium; Finding that the myocardial adenosine triphosphate levels were not significantly altered after LPS injection.

Objectives: The present study examined the possibility that intracellular ATP levels dictate whether hypoxic cardiac myocytes die by apoptosis or necrosis. Background: Although apoptosis and necrosis may appear to be distinct forms of cell death, recent studies suggest that the two may represent different outcomes of a common pathway. In ischemic myocardium, apoptosis appears early, while energy stores are presumably still available, followed only later by necrosis. Methods: Neonatal rat cardiac myocytes were exposed to continuous hypoxia, during which the intracellular ATP concentration was modulated by varying the glucose content in the medium. The form of cell death was determined at the end of the hypoxic exposure. Results: Under total glucose deprivation, ATP dropped precipitously and cell death occurred exclusively by necrosis as determined by nuclear staining with ethidium homodimer-1 and smearing on DNA agarose gels. However, with increasing glucose concentrations (10, 20, 50, 100 mg/dl) cellular ATP increased correspondingly, and apoptosis progressively replaced necrosis until it became the sole form of cell death, as determined by nuclear morphology, DNA fragmentation on agarose gels, and caspase-3 activation. The data showed a significantly positive correlation between myocyte ATP content and the percentage of apoptotic cells. Hypoxia resulted in lactate production and cellular acidification which stimulates apoptosis. However, acidification-induced apoptosis was also increased in an ATP-dependent fashion. Loss of mitochondrial membrane potential and cytochrome c release from the mitochondria was observed in both the apoptotic and necrotic cells. Furthermore, translocation of Bax from cytosol into mitochondria preceded these events associated with mitochondrial permeability transition. Increased lactate production and a lack of effect by the mitochondrial inhibitor oligomycin indicated that ATP was generated exclusively through glycolysis. Conclusions: We demonstrate that ATP, generated through glycolysis, is a critical determinant of the form of cell death in hypoxic myocytes, independently of cellular acidification. Our data suggest that necrosis and apoptosis represent different outcomes of the same pathway. In the absence of ATP, necrosis prevails. However, the presence of ATP favors and promotes apoptosis. [Copyright &y& Elsevier]

Introduction: Because of the unusual anatomy of an anomalous origin of the right coronary artery from the left sinus of Valsalva, selective cannulation of the guiding catheter in percutaneous coronary intervention for these cases is always challenging.Case Presentation: A 58-year-old Japanese man was admitted to our hospital complaining of worsening exertional chest pain. He was suspected of having unstable angina pectoris and underwent cardiac catheterization. We found a subtotal occlusive lesion in the mid-portion of his right coronary artery that originated from the left sinus of Valsalva. On the previous percutaneous coronary intervention, we failed to cannulate the guiding catheter to the anomalous orifice of the right coronary artery. Therefore, we decided to use the GuideLiner catheter for stable back-up support from the beginning. A 6Fr GuideLiner catheter was introduced into the right coronary artery by anchoring it coaxially with a semi-compliant balloon catheter. And we successfully deployed two drug-eluting stents by crossing over the posterior-descending artery. Final angiography demonstrated favorable dilatation of the target lesion, and native blood flow in the right coronary artery was completely recovered.Conclusion: GuideLiner is a monorail-type "child" support catheter that facilitates coaxial guiding catheter engagement and an appropriate back-up force, achieving successful device delivery to target lesions in this kind of complex percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Introduction: Although several etiopathogenetic mechanisms have been proposed, the causes of left ventricular apical ballooning syndrome are still controversial.Case Presentation: A 51-year-old Japanese woman consulted the emergency room complaining of the sudden onset of anterior chest pain while shopping. We initially suspected her disease as left ventricular apical ballooning syndrome based on her clinical background and laboratory examinations. However, the initial coronary angiogram demonstrated diffuse lesions in her distal left anterior descending coronary artery, and she was finally diagnosed with apical myocardial infarction. The blood flow in her distal left anterior descending coronary artery had markedly improved in the chronic phase. If the reduced blood flow in her distal left anterior descending coronary artery was induced by coronary vasospasm and the vasospasm was relieved before the coronary angiogram was performed, this case must be diagnosed as left ventricular apical ballooning syndrome.Conclusion: We think this case may promote discussion regarding the pathophysiology of left ventricular apical ballooning syndrome. [ABSTRACT FROM AUTHOR]

Summary: A 45-year-old woman complaining of consciousness disturbance demonstrated multiple brain infarctions. Echocardiogram showed vegetation on the posterior mitral leaflet. Infectious endocarditis was initially suspected and we started empirical antibiotics. However, mitral vegetation grew rapidly and caused severe mitral regurgitation. Acute heart failure was so poorly controlled by conservative treatment that we concluded cardiac surgery was indicated. Mitral valve replacement was safely performed, and there was no sign of heart failure or recurrent thromboembolism during the postoperative course. Thereafter, multiple hepatic masses and a solid lesion in the pancreatic head were detected by computed tomography. The patient finally died of multiple organ failure that presumably resulted from malignancy in the terminal stage. The clinical course of this case can be explained by the pathology of nonbacterial thrombotic endocarditis (NBTE). The standard treatment for NBTE consists of systemic anticoagulation as well as controlling the underlying malignancy. However, we could not diagnose this case as NBTE before surgery. Although mitral valve replacement was finally effective to control acute heart failure in this case, NBTE should be exactly diagnosed as quickly as possible and the treatment policy should be deliberated. [ABSTRACT FROM AUTHOR]