Pericarditis caused by herpes zoster.

A 53-year-old immunocompetent male visited our hospital complaining of chest pain which persisted for 6 h. After detailed examination, the patient was diagnosed with viral pericarditis and treated with aspirin. On day 3 after admission, rash with blisters appeared on the right side of chest. Paired serum evaluation on the day of admission and 3 weeks later revealed that varicella zoster virus(VZV)titer had significantly increased, and the patient was diagnosed with pericarditis caused by herpes zoster. Although VZV is known to cause various complications, there are few reports of pericarditis associated with VZV. We should consider the possibility of concomitant pericarditis with herpes zoster. .

Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome.

BACKGROUND: Marfan syndrome can cause life-threatening aortic complications. We investigated the relationship between FBN1 genotype and severe aortopathy (aortic root replacement, type A dissections, and related death). METHODS: We evaluated 248 patients with pathogenic or likely pathogenic FBN1 variants. The variants were classified as haploinsufficient type (HI, n=93) or dominant-negative type (DN, n=155) based on their location and predicted amino acid alterations, and we examined the effects of the FBN1 genotype on severe aortic events (aortic root replacement, type A dissections, and related death). RESULTS: The cumulative event-free probability was significantly lower in the HI group than in the DN group (adjusted hazard ratio, 2.1; 95% confidence interval, 1.4 -3.2; P<0.001). CONCLUSIONS: DN-CD+HI patients should be monitored more carefully than DN-nonCD patients for rapid development of aortic root aneurysms.

Spontaneous closure of ventricular septal perforation following percutaneous coronary intervention for acute myocardial infarction.

We report on an 84-year-old woman with anteroseptal acute myocardial infarction. Emergency coronary angiography revealed the occlusion of proximal left anterior descending artery without collateral circulation, and percutaneous coronary intervention was performed. Two drug eluting stents were implanted, and the procedure was concluded with thrombolysis in myocardial infarction grade 3 without complications. Postoperatively, no murmur was audible on auscultation and no shunt flow was observed on transthoracic echocardiography (TTE), and normal blood pressure was maintained. On day 2, however, the patient's vital signs deteriorated to a state of shock and systolic murmur appeared at the apical region. TTE showed a left-to-right shunt in the apical septal region, and ventricular septal perforation was diagnosed. Although emergency surgery was considered, the patient's vital signs improved the following day. The disappearance of the cardiac murmur and the shunt was confirmed. The clinical course was uneventful thereafter, and the patient was discharged.

Antimitochondrial antibodies-positive myositis accompanied by cardiac involvement.

We report a 55-year-old man who experienced proximal muscle weakness accompanied by the atrial flutter (AFL) with 1:1 conduction. Detailed examination revealed elevated antimitochondrial antibodies (AMA) and creatine kinase (CK). AFL was converted to sinus rhythm by cardioversion. He was diagnosed as AMA-positive myositis-associated AFL and was treated by prednisolone. Although his muscle weakness and CK level improved, AFL with 1:1 conduction reappeared. Therefore, radiofrequency catheter ablation (RFCA) was needed to treat the AFL, resulting in maintenance of sinus rhythm. This case report describes cardiac involvement in a patient with AMA-positive myositis.

Delayed cardiac tamponade 8 months after pulmonary vein isolation.

We herein report the case of a 55 year-old male who underwent pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation. From 8 months after PVI, exertional dyspnea rapidly appeared. When he was referred to our hospital, massive pericardial effusion was observed by transthoracic echography. The pericardiocentesis revealed bloody pericardial effusion, and improved symptoms. Although aortic dissection, autoimmune disease, infection, metastatic pericardial tumor, primary pericardial tumor, and malignant neoplasm were considered as differential diagnosis, the cause of pericardial effusion failed to be found. From these findings, the cause of hemorrhagic pericardial effusion was considered delayed cardiac tamponade induced by PVI performed 8 months earlier. .

An Adult Case of Unicommissural Unicuspid Aortic Valve Diagnosed Based on the Intraoperative Findings.

We herein report an adult case of unicommissural unicuspid aortic valve (UAV). A 59-year-old man, who was noted to have a cardiac murmur at 31 years of age, was admitted to our hospital due to acute heart failure. Severe calcification in the aortic valve with severe low-flow/low-gradient aortic stenosis and moderate aortic regurgitation was observed and thought to be the cause of heart failure, however, the etiology of aortic valve dysfunction was not clear. Aortic valve replacement was subsequently performed, and unicommissural UAV was diagnosed according to the intraoperative findings. UAV is very rare congenital aortic valve disease which is rarely diagnosed preoperatively.

Periodontitis May Deteriorate Sinus of Valsalva Dilatation in Marfan Syndrome Patients.

Marfan syndrome (MFS) is a systemic connective tissue disorder that is caused by mutations of fibrillin-1. While MFS patients are at a high risk of periodontitis and aortic diseases, little causal information has been provided to date. To clarify the relationship, their oral condition and sinus of Valsalva (SoV) were evaluated.The subjects were patients with MFS (n = 33) who attended the University of Tokyo Hospital. We divided them into two groups; MFS patients with highly dilated (the diameters were equal to or more than 39 mm) SoV (high group, n = 18) and MFS patients with mildly dilated (less than 39 mm) SoV (mild group, n = 15). Blood examinations, echocardiograms, and full-mouth clinical measurements, including number of teeth, probing pocket depth (PPD), bleeding on probing (BOP), and community periodontal index (CPI) were performed.We found that the high group patients had greater rates of BOP compared to that of the mild group. Furthermore, the high group tended to have higher serum levels of C-reactive protein, matrix metalloproteinase-9, and transforming growth factor-ß compared to the mild group.Periodontitis may deteriorate SoV dilatation in MFS patients.

Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice.

Chronic hypertension causes vascular remodeling that is associated with an increase in periostin- (postn) positive cells, including fibroblasts and smooth muscle cells. Krüppel-like factor (KLF) 5, a transcription factor, is also observed in vascular remodeling; however, it is unknown what role KLF5 plays in postn-positive cells during vascular remodeling induced by deoxycorticosterone-acetate (DOCA) salt. We used postn-positive cell-specific Klf5-deficient mice (Klf5PostnKO: Klf5flox/flox; PostnCre/-) and wild-type mice (WT: Klf5flox/flox; Postn-/-). We implanted a DOCA pellet and provided drinking water containing 0.9% NaCl for 8 weeks. The DOCA-salt treatment induced hypertension in both genotypes, as observed by increases in systolic blood pressure. In WT animals, DOCA-salt treatment increased the aortic medial area compared with the non-treated controls. Similarly, Tgfb1 was overexpressed in the aortas of the DOCA-salt treated WT mice compared with the controls. Immunofluorescence staining revealed that fibroblast-specific protein 1 (FSP1)+-α smooth muscle actin (αSMA)+ myofibroblasts exist in the medial area of the WT aortas after DOCA-salt intervention. Importantly, these changes were not observed in the Klf5PostnKO animals. In conclusion, the results of this study suggest that the presence of KLF5 in postn-positive cells contributes to the pathogenesis of aortic thickening induced by DOCA-salt hypertension.

Serum neutrophil gelatinase-associated lipocalin concentration reflects severity of coronary artery disease in patients without heart failure and chronic kidney disease.

Serum neutrophil gelatinase-associated lipocalin (NGAL) is recognized as a useful biomarker for acute kidney injury. Recently, elevated NGAL levels were reported in patients with heart failure and cardiac events, but the association between serum NGAL and severity of coronary artery disease (CAD) has not been investigated adequately. This study aimed to evaluate the association between serum NGAL concentration and CAD severity in patients without heart failure and chronic kidney disease. Two-hundred thirteen patients [mean age: 66.2 ± 9.2 (SD)] without heart failure and chronic kidney disease (estimated glomerular filtration rate >60 mL/min/1.73 m(2)) who underwent coronary angiography were retrospectively analyzed using the SYNTAX score. The mean concentration of serum NGAL was 134.3 ± 111.3 ng/mL. A statistically significant correlation was observed between serum NGAL levels and the SYNTAX score (R = 0.18, P = 0.0091). Multivariable analysis also showed elevated serum NGAL as an independent risk factor for a high SYNTAX score (P < 0.01). Moreover, we evaluated the association of serum NGAL and brain natriuretic peptide (BNP) with the SYNTAX score. Patients with high levels of serum NGAL (>100 ng/mL) and high levels of BNP (>25 pg/mL) had a higher SYNTAX score (low-low vs. high-high: 13.8 ± 13.4 vs. 20.8 ± 18.9, P < 0.05). Serum NGAL levels were positively and significantly associated with CAD severity, and the evaluation of both serum NGAL and BNP was useful for predicting CAD in patients without renal dysfunction and heart failure. Serum NGAL might be a biomarker for CAD severity.

Plasma neutrophil gelatinase-associated lipocalin predicts major adverse cardiovascular events after cardiac care unit discharge.

BACKGROUND: Emerging acute kidney injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), have a high potential for predicting worsening renal function. Acute exacerbation of renal dysfunction has a great impact on the outcomes of cardiovascular patients in critical conditions. This study aimed to evaluate whether plasma NGAL can predict the mortality and major adverse cardiovascular events (MACEs) after discharge from the cardiac care unit (CCU). METHODS: Patients who were admitted to the CCU of the Tokyo University Hospital were prospectively enrolled (101 patients). Blood and urinary markers, including the blood NGAL, brain natriuretic peptide, creatinine, cystatin C, urinary albumin, N-acetyl-ß-d-glucosaminidase, and L-type fatty acid-binding protein, were measured at CCU discharge. The primary outcome was MACEs until at least 6 months after CCU discharge. RESULTS: Thirty-five patients experienced MACEs (35%). Multivariate logistic analysis revealed that the plasma NGAL, length of CCU stay, and existence of diabetes and heart failure were independent predicting factors for MACEs. Patients with the highest NGAL at discharge (>75th percentile) showed a significantly higher risk of MACEs than those with the lowest NGAL (<25th percentile) (log-rank test; hazard ratio, 5.15; 95% confidence interval 1.84-18.20; p<0.01). CONCLUSION: Plasma NGAL at CCU discharge is a significant prognostic indicator of outcomes at 6 months in critically ill cardiac patients treated in a CCU.

Diverse contribution of bone marrow-derived late-outgrowth endothelial progenitor cells to vascular repair under pulmonary arterial hypertension and arterial neointimal formation.

AIMS: It is still controversial whether bone marrow (BM)-derived endothelial progenitor cells (EPCs) can contribute to vascular repair and prevent the progression of vascular diseases. We aimed to characterize BM-derived EPC subpopulations and to evaluate their therapeutic efficacies to repair injured vascular endothelium of systemic and pulmonary arteries. METHODS AND RESULTS: BM mononuclear cells of Fisher-344 rats were cultured under endothelial cell-conditions. Early EPCs appeared on days 3-6. Late-outgrowth and very late-outgrowth EPCs (LOCs and VLOCs) were defined as cells forming cobblestone colonies on days 9-14 and 17-21, respectively. Among EPC subpopulations, LOCs showed the highest angiogenic capability with enhanced proliferation potential and secretion of proangiogenic proteins. To investigate the therapeutic effects of these EPCs, Fisher-344 rats underwent wire-mediated endovascular injury in femoral artery (FA) and were concurrently injected intraperitoneally with 60mg/kg monocrotaline (MCT). Injured rats were then treated with six injections of one of three EPCs (1×10(6) per time). After 4weeks, transplanted LOCs, but not early EPCs or VLOCs, significantly attenuated neointimal lesion formation in injured FAs. Some of CD31(+) LOCs directly replaced the injured FA endothelium (replacement ratio: 11.7±7.0%). In contrast, any EPC treatment could neither replace MCT-injured endothelium of pulmonary arterioles nor prevent the progression of pulmonary arterial hypertension (PAH). LOCs modified protectively the expression profile of angiogenic and inflammatory genes in injured FAs, but not in MCT-injured lungs. CONCLUSION: BM-derived LOCs can contribute to vascular repair of injured systemic artery; however, even they cannot rescue injured pulmonary vasculature under MCT-induced PAH.

Congenital contractural arachnodactyly complicated with aortic dilatation and dissection: Case report and review of literature.

Congenital contractural arachnodactyly (CCA) is a connective tissue disease caused by mutations of the FBN2, which encodes fibrillin-2. CCA patients have a marfanoid habitus; however, aortic dilatation and/or dissection as observed in Marfan syndrome have been rarely documented. Here, we report on a Japanese familial case of CCA resulting from a FBN2 splicing mutation (IVS32+5g→a), which leads to exon 32 being skipped, and the patients developed aortic dilatation and type A dissection. Although CCA patients have been believed to have favorable prognoses, repetitive aortic imaging studies must be performed in some patients to detect possible aortic disease early, and genetic testing of FBN2 might be useful to identify such high-risk patients.

Impact of the distance from the stent edge to the residual plaque on edge restenosis following everolimus-eluting stent implantation.

OBJECTIVES: This study aimed to assess the relation between stent edge restenosis (SER) and the distance from the stent edge to the residual plaque using quantitative intravascular ultrasound. BACKGROUND: Although percutaneous coronary intervention with drug-eluting stents has improved SER rates, determining an appropriate stent edge landing zone can be challenging in cases of diffuse plaque lesions. It is known that edge vascular response can occur within 2 mm from the edge of a bare metal stent, but the distance to the adjacent plaque has not been evaluated for drug-eluting stents. METHODS: A total of 97 proximal residual plaque lesions (plaque burden [PB] >40%) treated with everolimus-eluting stents were retrospectively evaluated to determine the distance from the stent edge to the residual plaque. RESULTS: The SER group had significantly higher PB (59.1 ± 6.1% vs. 51.9 ± 9.1% for non-SER; P = 0.04). Higher PB was associated with SER, with the cutoff value of 54.74% determined using receiver operating characteristic (ROC) curve analysis. At this cutoff value of PB, the distance from the stent edge to the lesion was significantly associated with SER (odds ratio = 2.05, P = 0.035). The corresponding area under the ROC curve was 0.725, and the cutoff distance value for predicting SER was 1.0 mm. CONCLUSION: An interval less than 1 mm from the proximal stent edge to the nearest point with the determined PB cutoff value of 54.74% was significantly associated with SER in patients with residual plaque lesions.

Midterm follow-up after retrievable inferior vena cava filter placement in venous thromboembolism patients with or without malignancy.

BACKGROUND: A clear indication and strategy for placement of retrievable inferior vena cava filters (IVCFs) have not been established. This study was designed to evaluate the efficacy and disadvantages of the retrievable IVCF use particularly in venous thromboembolism (VTE) patients with malignancy. HYPOTHESIS: Retrievable IVCFs might be safe and useful in VTE patients with malignancy. METHODS: The study population consisted of 56 consecutive patients undergoing IVCF placement at our institution from January 1, 2008 to December 31, 2011. Prognostic data were retrospectively reviewed in April 2013. RESULTS: Mean follow-up period was 584.6 (range, 1-1857) days. Twenty-six of the 56 patients had a malignancy. In 16 of the 30 patients without malignancy, the filter was retrieved, whereas the other 14 patients eventually received permanent implantation. There was no significant difference in the survival rate between the retrieval group and the nonretrieval group in the nonmalignancy patients (1-year survival rates, 94% vs 85%). In patients with malignancy, the nonretrieval group showed a significantly lower survival rate (P < 0.01). The 1-year and 2-year survival rates were 100% vs 46% and 100% vs 18%, respectively. There was no medical record of pulmonary thromboembolism occurrence or recurrence. All deaths in the patients with malignancy were malignancy related. In 4 of 5 malignancy patients who could undergo tumor resection surgery, adequate thrombus regression enabled us to retrieve the IVCF after surgery. CONCLUSIONS: Permanent use of a retrievable IVCF is relatively safe in short- or midterm follow-up regardless of malignancy status. Retrievable filter use might be reasonable in malignancy patients.

Effect of periodontitis on cardiovascular manifestations in Marfan syndrome. Critical common role of TGF-ß.

Marfan syndrome (MFS) is a systemic connective tissue disorder that is caused by mutations in the extracellular matrix protein fibrillin-1. While MFS patients are considered to be at high risk of dental disorders and cardiovascular complications, little causal relationship has been provided to date. It is well known that an elevated level of active TGF-ß in the plasma is a major manifestation of MFS. TGF-ß is known to play a critical role in the development of cardiovascular diseases and its levels were also elevated in the serum and saliva of periodontitis patients. These findings may suggest an association between periodontitis and the cardiovascular complications of MFS. In this article, we review the influence of periodontitis in MFS patients with cardiovascular complications in order to identify critical therapeutic targets of TGF-ß.

Involvement of P2Y12 receptor in vascular smooth muscle inflammatory changes via MCP-1 upregulation and monocyte adhesion.

Antiplatelet drugs, frequently used for cardiovascular events with thrombotic involvement, are also regarded as possible promising agents for cardiovascular primary prevention. The roles of P2Y12, an ADP receptor and the target of thienopyridine antiplatelet drugs, are not satisfactorily known in the vascular wall. We investigated the hypothesis that vascular smooth muscle cell (VSMC) P2Y12 is involved in vascular wall inflammatory changes by upregulating monocyte chemoattractant protein-1 (MCP-1) and promoting monocyte adhesion. ADP at 10(-5) M induced a 3.6 ± 0.3-fold upregulation of MCP-1 mRNA in cultured rat VSMCs, which was significantly inhibited by R-138727, the active metabolite of P2Y12 inhibitor prasugrel and siRNAs against P2Y12. ADP also induced MCP-1 protein upregulation, which was diminished by R-138727 and P2Y12 siRNAs. JNK (c-Jun NH2-terminal kinase) inhibition attenuated ADP-induced MCP-1 mRNA and protein upregulation. R-138727 and P2Y12 siRNAs inhibited ADP-induced JNK activation. The reactive oxygen species (ROS) inhibitors N-acetylcysteine (NAC), diphenyleneiodonium (DPI), and Tempol also diminished MCP-1 upregulation and JNK activation induced by ADP. ADP induced MCP-1 promoter activation, which was inhibited by R-138727 and P2Y12 siRNAs. Nuclear factor-κB (NF-κB) consensus sites in the MCP-1 promoter region were involved in this activation. ADP-induced NF-κB pathway activation, examined by a plasmid containing multiple NF-κB sites, was diminished by P2Y12 inhibition. For cellular function analysis, stimulation of VSMC with ADP increased subsequent THP-1 monocyte adhesion. P2Y12 siRNAs and CCR2 antagonism diminished this ADP-induced monocyte adhesion. These data suggested that ADP, via the VSMC P2Y12 receptor, induces vascular inflammatory changes by upregulating MCP-1 and promoting monocyte adhesion.

A case of radiation-induced subclavian artery stenosis treated with percutaneous transluminal angioplasty.

We report on a female patient who underwent a standard radical mastectomy and radiation therapy for right breast cancer at the age of 50 years without recurrence. At the age of 76 years, she started to experience fatigue in the right upper limb. The symptom gradually worsened and she was admitted to our hospital for further investigation. With computed tomography scan and angiography, we observed a high degree of subclavian artery (SCA) stenosis and asymptomatic right common carotid artery (CCA) stenosis. After undergoing carotid artery stenting to the right CCA stenosis at another hospital, we performed percutaneous transluminal angioplasty to SCA. Although we chose to treat the highly calcified lesion only with a balloon and slightly decreased the degree of stenosis, her symptoms clearly improved. Since arterial severely stenotic lesions were limited in the area of radiation exposure while other part of the arteries looked smooth and relatively free of sclerosis, it was highly suspected that arterial injury was induced by radiation. There are few reports of radiation-induced injury of upper limbs. However, this case suggests that we need to consider the possibility of radiation-induced arterial injury in patients with a history of radiation therapy. .

Response of urinary liver-type fatty acid-binding protein to contrast media administration has a potential to predict one-year renal outcome in patients with ischemic heart disease.

Urinary liver-type fatty acid-binding proteins (uL-FABP) have recently been recognized as a useful biomarker for predicting contrast-induced nephropathy. Although accumulating studies have evaluated short-term outcomes, its prognostic value for long-term renal prognosis in patients undergoing coronary angiography (CAG) has not been fully examined. This study aimed to evaluate the predictive value of uL-FABP for long-term renal outcome in patients with ischemic heart disease (IHD). Consecutive 24 patients with impaired renal function (serum creatinine >1.2 mg/dL) who underwent CAG were enrolled. uL-FABP was measured before CAG, 24 and 48 h after CAG. The changes in estimated glomerular filtration rate (eGFR) throughout CAG and at 1 year later were compared with the uL-FABP levels. The patients with a greater decrease in eGFR 1 year later had higher uL-FABP levels at all points, but only the value at 48 h after CAG reached statistical significance (lower vs. higher decreased eGFR group, 4.61 ± 3.87 vs. 17.71 ± 12.96; P < 0.01). Measurement of uL-FABP at 48 h after CAG (48h-uL-FABP) showed better correlation with the change in eGFR (pre-CAG uL-FABP vs. 48h-uL-FABP: R = 0.27, P = 0.20 vs. R = 0.65, P < 0.01). Moreover, the high-pre and high-48h-uL-FABP group showed a significantly larger decrease in eGFR compared with the high-pre and low-48h-uL-FABP group (change in eGFR; 8.12 ± 4.06 vs. 1.25 ± 2.23 mL/min/1.73 m2, P < 0.01), although the baseline eGFR levels were similar between these two groups. In this pilot study, measurement of uL-FABP levels at 48 h after CAG may be useful in detecting renal damage, and in predicting 1-year renal outcome in IHD patients undergoing CAG.

High incidence and severity of periodontitis in patients with Marfan syndrome in Japan.

Marfan syndrome (MFS) is a systemic connective tissue disorder caused by mutations in the extracellular matrix protein fibrillin-1. While it is known that patients with MFS are at high risk of dental disorders and cardiovascular diseases, little information has been provided to date. To clarify the prevalence of periodontitis in patients with MFS, their oral condition and cardiovascular complications were evaluated. The subjects were patients with MFS (n = 40) who attended the University of Tokyo hospital; age- and gender-matched healthy individuals (n = 14) constituted a control group. Cardiovascular complications and full-mouth clinical measurements, including number of teeth, probing of pocket depth (PD), bleeding on probing (BOP), and community periodontal index (CPI) were recorded. MFS patients had more frequent cardiovascular complications (95 %) compared with the controls (0 %). MFS patients had periodontitis (CPI 3 and 4) more frequently (87.5 %) than the age- and gender-matched control subjects (35.7 %). Furthermore, MFS patients had significantly more severe periodontitis (CPI 2.90 ± 0.12 vs 1.64 ± 0.32) and fewer remaining teeth (26.7 ± 0.4 vs 28.4 ± 0.4) compared with the controls. However, PD and BOP were comparable between MFS patients and the control group. A high incidence of periodontitis and cardiovascular complications was observed in Japanese MFS patients.