Initial decrease in the lipoprotein(a) level is a novel prognostic biomarker in patients with acute coronary syndrome.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular diseases; however, its role in acute coronary syndrome (ACS) remains unclear. AIM: To investigate the hypothesis that the Lp(a) levels are altered by various conditions during the acute phase of ACS, resulting in subsequent cardiovascular events. METHODS: From September 2009 to May 2016, 377 patients with ACS who underwent emergent coronary angiography, and 249 who completed ≥ 1000 d of follow-up were enrolled. Lp(a) levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention (PCI) to 48 h after PCI. The primary endpoint was the occurrence of major adverse cardiac events (MACE; cardiac death, other vascular death, ACS, and non-cardiac vascular events). RESULTS: The mean circulating Lp(a) level decreased significantly from pre-PCI (0 h) to 12 h after (19.0 mg/dL to 17.8 mg/dL, P < 0.001), and then increased significantly up to 48 h after (19.3 mg/dL, P < 0.001). The changes from 0 to 12 h [Lp(a)Δ0-12] significantly correlated with the basal levels of creatinine [Spearman's rank correlation coefficient (SRCC): -0.181, P < 0.01] and Lp(a) (SRCC: -0.306, P < 0.05). Among the tertiles classified according to Lp(a)Δ0-12, MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups (66.2% vs 53.6%, P = 0.034). A multivariate analysis revealed that Lp(a)Δ0-12 [hazard ratio (HR): 0.96, 95% confidence interval (95%CI): 0.92-0.99] and basal creatinine (HR: 1.13, 95%CI: 1.05-1.22) were independent determinants of subsequent MACE. CONCLUSION: Circulating Lp(a) levels in patients with ACS decreased significantly after emergent PCI, and a greater decrease was independently associated with a worse prognosis.

Response to pre-dilatation with POBA can predict target lesion revascularization after DCB angioplasty for de novo small coronary artery lesions.

OBJECTIVE: To assess the determinants of target lesion revascularization (TLR) after drug-coated balloon (DCB) angioplasty for de novo small coronary artery lesions. METHODS: This retrospective study enrolled consecutive lesions from patients that were in a stable condition and had undergone successful DCB treatment for de novo small coronary artery lesions. The study endpoint was TLR and major adverse cardiac events at 12 months. RESULTS: A total of 68 patients with 83 lesions were enrolled in the study. Of these, 11 (13.3%) lesions required TLR. Mean ± SD pre-dilatation balloon diameters were similar in the non-TLR (2.33 ± 0.72 mm) and TLR (2.18 ± 0.36 mm) groups. A comparison of the two groups showed that post/pre-lumen area ratio during pre-dilatation (%) by plain old balloon angioplasty (POBA) was significantly and negatively associated with TLR and the optimal cut-off point was 170%. Cox proportional hazard and multivariate regression analyses showed that post/pre-lumen area ratio was the only independent predictor of TLR (hazard ratio 0.9318; 95% confidence interval 0.9001, 0.9645). CONCLUSION: Greater pre-dilatation using POBA, assessed as the post/pre-lumen area ratio, may be independently associated with a lower 12-month TLR rate in patients undergoing DCB angioplasty for de novo small coronary lesions.

Increased plasma glutamate in non-smokers with vasospastic angina pectoris is associated with plasma cystine and antioxidant capacity.

Objectives. Endothelial dysfunction caused by oxidative stress plays an important role in the development of vasospastic angina pectoris (VSAP). Glutamate causes endothelial dysfunction by generating oxidative stress, and it inhibits cystine import into endothelial cells via the cystine/glutamate antiporter (XC-), which leads to depletion of antioxidant glutathione. However, whether glutamate and cystine are implicated in the pathogenesis of VSAP remains unclear. We investigated plasma glutamate and cystine levels, oxidative stress markers and antioxidant capacity in non-smoker patients with VSAP to determine whether glutamate and cystine are associated with the development of VSAP. We assessed 49 non-smokers assigned to groups with (n = 27) and without (n = 22) VSAP, and also measured plasma glutamate, cystine, nitrotyrosine, reactive oxygen metabolites and biological antioxidant potential. Results. Plasma glutamate and cystine values were significantly higher in the group with, than without VSAP (59.8 ± 25.7 vs. 43.5 ± 18.7 µmol/L, p = .016 and 35.3 ± 14.2 vs. 25.2 ± 9.1 µmol/L, p = .0056, respectively). Plasma glutamate and cystine values were significantly and positively associated (r = 0.32, p = .027). Levels of the oxidative stress markers nitrotyrosine and reactive oxygen metabolites, and biological antioxidant potential of as a measure of antioxidant capacity, did not significantly differ between the two groups. However, glutamate and biological antioxidant potential values were significantly and negatively associated (r = -0.3, p = .036). Conclusion. Plasma glutamate levels were increased in patients with VSAP who did not smoke, and they were positively associated with plasma cystine and negatively associated with the biological antioxidant potential levels.

The circulating furin-cleaved/mature PCSK9 ratio has a potential prognostic significance in statin-naïve patients with acute ST elevation myocardial infarction.

Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates as mature and furin-cleaved forms, but their biological functions are uncertain. We investigated whether their levels associate with prognosis in patients with acute ST elevation myocardial infarction (STEMI). Methods: We enrolled 160 statin-naïve patients with acute STEMI and followed for 3 years. PCSK9 subtype levels were determined by an enzyme-linked immunosorbent assay before and at five timepoints up to 48 h after emergent coronary intervention. The occurrence of coronary and cardiac events was compared between subjects stratified by the PCSK9 level. Results: One hundred and twenty-six patients completed 3 years of follow-up. In the acute phase, both PCSK9 subtype levels decreased, and thereafter increased from 6 to 48 h (mature: from 198 ± 67 to 334 ± 116 ng/mL, furin-cleaved: from 20 ± 7 to 39 ± 16 ng/mL, both p < 0.01). Major cardiac events occurred in 46 patients. The furin-cleaved/mature PCSK9 ratio at 48 h after coronary intervention predicted the likelihood of experiencing of events; patients in the third tertile had lower event-free survival than those in the first and second tetiles in Kaplan-Meier analysis (p = 0.004). Multivariate Cox regression analysis revealed that this ratio had a greater impact (HR: 1.92; 95% CI: 1.06-3.45, p = 0.03) on events than other known atherosclerosis risk factors. Conclusions: The furin-cleaved/mature PCSK9 ratio was associated with 3-year cardiovascular events in statin-naïve patients with acute STEMI, suggesting a potential link between furin cleavage process of PCSK9 and its effect on prognosis. (249 words).

Possible effect of direct oral anti-coagulant for preventing long stenting lesion from in-stent restenosis in femoropopliteal segment: Case report with angioscopy findings.

A 64-year-old female underwent a successful first percutaneous intervention using MISAGO stents for a de novo femoropopliteal lesion. Subsequently, three more effective procedures were done using balloon catheters for in-stent restenosis. In May 2016, a fourth procedure using Zilver PTX stent for in-stent restenosis was carried out. For this final procedure, we added direct oral anti-coagulant as she had additional problem of popliteal vein thrombosis and her femoropopliteal segment remained clear. A Zilver PTX stent, a drug-eluting stent for a peripheral artery, was expected to bring superior outcomes compared to conventional bare nitinol stents (i.e. MISAGO stent). But subsequent studies reported that Zilver PTX stent was not more effective than conventional bare nitinol stents. In our above mentioned case, her angioscopy findings suggest that her successful outcome appears to be related to the added direct oral anti-coagulant.

Healing of femoral artery dissection after drug-coated balloon angioplasty: A case report with intravascular ultrasonography and angioscopy images.

Early 80s male with intermitted claudication underwent endovascular therapy for atherosclerotic stenosis at left external iliac artery and middle of superficial femoral artery. Patient also had chronic atrial fibrillation, diabetes mellitus, and hypertension. After stent deployment for external iliac artery lesion, a short superficial femoral artery lesion was performed with angioplasty using drug-coated balloon. The drug-coated balloon angioplasty resulted in 50% residual stenosis with linear dissection; however, provisional stenting was not performed as decent ante-grade blood flow allowed 10 extra minutes. Medication involved ongoing use of aspirin 100 mg and rivaroxaban 15 mg. Angiography post 3 months from index procedure showed external iliac artery and superficial femoral artery patency and healing of intimal dissection at superficial femoral artery lesion was estimated by intravascular ultrasonography. In angioscopy findings, red thrombus was seen in dissection cavity.

Overview of the 81st Annual Scientific Meeting of the Japanese Circulation Society　- Cardiovascular Medicine for the Next Generation.

The 81stAnnual Scientific Meeting of the Japanese Circulation Society was held in Kanazawa, Japan, on March 17-19, 2017 under a miraculously clear sky. The frontlines of healthcare and medicine are dramatically changing. Thus, "Cardiovascular Medicine for Next Generation" was chosen as the main theme of this meeting. The program was constructed around major identified issues, including renewal of our understanding of basic cardiovascular medicine, translational research, and preventive molecular medicine, all of which are anticipated to transcend the medical field over the next generation. Despite the provincial location, 15,672 participants, including more than 400 from overseas countries, attended the 3-day meeting, and there were in-depth discussions in the various sessions. In particular, to our great pleasure, Her Imperial Highness Princess Takamado kindly attended the opening ceremony and extended congratulations to us. The meeting successfully completed and we sincerely appreciate the great cooperation and support from all affiliates.

Circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL) as a novel predictor of clinical outcome after endovascular therapy in patients with peripheral artery disease (PAD).

BACKGROUND AND AIMS: Despite advances in the treatment of peripheral artery disease (PAD), cardiovascular events and death rates remain high. This study aimed at identifying markers of outcome in patients with PAD undergoing endovascular therapy (EVT). METHODS: Consecutive patients undergoing EVT were recruited. Markers of oxidative stress (malondialdehyde-modified low-density lipoprotein [MDA-LDL]), inflammation (IL-6; high-sensitivity C-reactive protein [hsCRP]) and fibrinolysis (D-dimer) were measured pre-EVT and at post-EVT time-points to 36 h. Clinical follow-up assessed major cardiovascular and/or limb events. RESULTS: In the 35 patients enrolled, mean MDA-LDL levels decreased from a baseline level of 106.2 U/L to 72.6 U/L immediately post-EVT (p<0.0001); levels remained significantly reduced at all time-points. IL-6, hsCRP and D-dimer increased and were significantly higher at the 36 h time-point. A significant, negative association was seen between decreased MDA-LDL and pre-EVT hsCRP levels (r = -0.42, p=0.012). Clinical follow-up data were obtained for a mean period of 16 months. MDA-LDL ratios (obtained by comparison of post- and pre-EVT values) allowed assessment of high (≥0.495) and low (<0.495) ratio groups. A significantly higher rate of major adverse events, including limb-related events or death, was seen in the low ratio group (p<0.001). Cox proportional hazard analysis including traditional risk factors indicated that this ratio is a significant predictor of clinical endpoints (HR = 0.4210, p=0.0154). An association with clinical outcome was not observed with the other candidate biomarkers. CONCLUSIONS: Assessment of pre- and post-EVT MDA-LDL levels is a promising marker of clinical outcome in patients with PAD.

Diurnal glycemic fluctuation is associated with severity of coronary artery disease in prediabetic patients: Possible role of nitrotyrosine and glyceraldehyde-derived advanced glycation end products.

BACKGROUND: Glucose fluctuation (GF) is a risk factor for coronary artery disease (CAD). However, it remains unknown whether specific indices of GF are risk factors for CAD. Therefore, we evaluated the relationship between GF, as determined by a continuous glucose monitoring system (CGMS) or the glucose level at 2h after a 75-g oral glucose tolerance test (75g OGTT 120), and the severity of CAD in prediabetic patients. We also evaluated whether nitrotyrosine (NT) and glyceraldehyde-derived advanced glycation end-products (Glycer-AGE) were induced by GF. METHODS: Twenty-eight prediabetic patients underwent coronary angiography (CAG), and the Gensini score and the SYNTAX score were evaluated as the severity of CAD, while the mean amplitude of glycemic excursions (MAGE) by CGMS and 75g OGTT 120 were evaluated. Serum NT and Glycer-AGE were measured. RESULTS: The MAGE was closely associated with the Gensini score (r=0.742, p<0.001) and the SYNTAX score (r=0.776, p<0.001), respectively. The 75g OGTT 120 was not associated with the Gensini score (r=0.36, p=0.06), but it was significantly associated with the SYNTAX score (r=0.413, p=0.036). Multiple linear regression analysis showed that the MAGE was the only independent determinant for the severity of CAD. The levels of NT and Glycer-AGE were significantly higher in the high MAGE group than in the low MAGE group. CONCLUSIONS: Diurnal GF is associated with the severity of CAD, even in prediabetic patients. GF, NT, and Glycer-AGE may play a pathological role in the progression of CAD.

Clinical impact and risk stratification of balloon angioplasty for femoropopliteal disease in nitinol stenting era: Retrospective multicenter study using propensity score matching analysis.

OBJECTIVE: Nitinol stenting could bring the better outcome in endovascular therapy for femoropopliteal disease. However, it might be expected that recent marked advances in both device technology and operator technique had led to improved efficacy of balloon angioplasty even in this segment. The aims of this study were to evaluate the clinical impact of balloon angioplasty for femoropopliteal disease and make risk stratification clear by propensity score matching analysis. METHODS: Based on the multicenter retrospective data, 2758 patients (balloon angioplasty: 729 patients and nitinol stenting: 2029 patients), those who underwent endovascular therapy for femoropopliteal disease, were analyzed. RESULTS: The propensity score matching procedure extracted a total of 572 cases per group, and the primary patency rate of balloon angioplasty and nitinol stenting groups after matching was significantly the same (77.2% vs 82.7% at 1 year; 62.2% vs 64.3% at 3 years; 47.8% vs 54.3% at 5 years). In multivariate Cox hazard regression analysis, significant predictors for primary patency were diabetes mellitus, regular dialysis, cilostazol use, chronic total occlusion, and intra-vascular ultra-sonography use. The strategy of balloon angioplasty was not evaluated as a significant predictor for the primary patency. After risk stratification using five items (diabetes mellitus, regular dialysis, no use of intra-vascular ultra-sonography, chronic total occlusion, and no use of cilostazol: the DDICC score), the estimated primary patency rates of each group (low, DDICC score 0-2; moderate, DDICC score 3; high risk, DDICC score 4-5) were 88.6%, 78.3%, and 63.5% at 1 year; 75.2%, 60.7%, and 39.8% at 3 years; and 66.0%, 47.1%, and 26.3% at 5 years (p < 0.0001). The primary patency rate of balloon angioplasty and nitinol stenting groups was significantly the same in each risk stratification. CONCLUSION: This study suggests that balloon angioplasty does not have inferiority to nitinol stenting but does have favorable efficacy in femoropopliteal segment by careful risk stratification with the recent advance of technique.

Chronic total occlusions of the right coronary and left anterior descending coronary arteries in a young adult patient with antiphospholipid syndrome.

A 36-year-old male appeared to have an old myocardial infarction on electrocardiogram, and coronary angiography (CAG) was performed. The CAG showed total occlusions of the right coronary artery and left anterior descending artery. He was successfully treated with drug-eluting stent implantation for both occluded coronary arteries. Such serious coronary lesions are uncommon for his young age. The patient was diagnosed as having antiphospholipid syndrome (APS) based on elevation of anticardiolipin antibody and anti-ß2 glycoprotein I antibody. Two years after stent implantation, the patient was well without ischemia or thrombosis. APS should be considered a potential cause of serious coronary disease in young adults. .

A case of coronary rupture and pseudoaneurysm formation after fracture of implanted paclitaxel-eluting stents.

A 48-year-old man who had undergone implantation of two paclitaxel-eluting stents (PESs) at the right coronary artery was admitted to our hospital with progressive dyspnea. In the coronary care unit, he developed cardiogenic shock due to cardiac tamponade treated by pericardiocentesis. A coronary angiogram showed a large pseudoaneurysm at the site of the previously implanted stents, suggesting coronary rupture due to implanted stent fracture. The pseudoaneurysm was completely sealed by polytetrafluoroethylene-covered stent implantation. Although this case is very rare, coronary rupture by stent fracture should be considered when cardiac tamponade occurs after drug-eluting stent implantation, especially PES.

Clinical characteristics of patients with Rutherford category IV, compared with V and VI.

OBJECTIVE: Patients categorized Rutherford category IV might have different characteristics compared with Rutherford category V and VI. Our study aims were to estimate the clinical differences between Rutherford category IV and Rutherford category V and VI, for those underwent endovascular therapy for isolated infrapopliteal disease, and also to find risk factors for endovascular therapy in Rutherford category IV. METHODS: Based on the Japanese multi-center registry data, 1091 patients with 1332 limbs (Rutherford category IV: 226 patients with 315 limbs, Rutherford category V and VI: 865 patients with 1017 limbs) were analyzed retrospectively. RESULTS: Patients' backgrounds and lesions' characteristics had significant differences. Both freedom rate from major adverse limb event with perioperative death and amputation-free survival rate at 1 year were better in Rutherford category IV than Rutherford category V and VI (93.6% vs 78.3%, 87.7% vs 66.7%) and those maintained to 3 years (p < 0.0001). Significant predictors for major adverse limb event/perioperative death were small body mass index (<18.5 kg/m(3)) and initial endovascular therapy success, and those for amputation-free survival were small body mass index (<18.5 kg/m(3)), non-ambulatory status, high systematic inflammatory reaction (C-reactive protein > 3.0 mg/dL), chronic obstructive pulmonary disease, and coronary artery disease in Rutherford category IV. CONCLUSION: From the present results, Rutherford category IV should be recognized to have quite different backgrounds and better outcome from Rutherford category V and VI.

Increased levels of the oxidative stress marker, nitrotyrosine in patients with provocation test-induced coronary vasospasm.

BACKGROUND: Endothelial dysfunction of the coronary arteries caused by oxidative stress plays an important role in the pathogenesis of coronary vasospasm. However, it is not clear whether circulating biomarkers for oxidative stress are altered after coronary vasospasm. We investigated temporal changes in the levels of oxidative stress biomarkers after coronary vasospasm induced by intracoronary acetylcholine provocation testing, resulting in transient myocardial ischemia. METHODS AND RESULTS: Thirty consecutive patients with suspected vasospastic angina pectoris (VSAP) were enrolled in the study. Patients were categorized into the VSAP-positive group (n=14) and the VSAP-negative group (n=16) on the basis of test results. Serum samples were examined for the levels of the oxidative stress markers 4-hydroxynonenal (HNE) and nitrotyrosine (NT) before, and 15min, 3h, and 12h after the provocation test. The serum HNE levels did not change in either group after the test. The serum NT levels in the VSAP-positive group significantly increased at 3h and 12h after the test (11.3±3.3µg/ml at 3h, p=0.015, and 12.1±5.7µg/ml at 12h, p=0.03), as compared with baseline (8.1±3.2µg/ml). In the VSAP-negative group, the serum NT levels significantly decreased from baseline at each of the 3 time points. CONCLUSIONS: Serum NT significantly increased after coronary vasospasm induced by acetylcholine provocation, suggesting that serum NT could be a biomarker of transient myocardial ischemia and could contribute to the development of VSAP.

Nutri-pharmacogenomics of warfarin anticoagulation therapy: VKORC1 genotype-dependent influence of dietary vitamin K intake.

Warfarin is the most widely prescribed oral anticoagulant, but large interindividual variations exist in the dose required to achieve comparable therapeutic effects. Several clinical and genetic variables have been identified that influence warfarin dosing. However, interactions between genotype and nutrition remain uncertain in terms of dietary vitamin K intake. To investigate genotype-nutrient interactions in warfarin anticoagulation therapy, 202 consecutive outpatients (M/F = 142/60, mean age, 69 years) undergoing treatment with warfarin were enrolled. Prevalent single nucleotide polymorphisms in VKORC1 and CYP2C9 were genotyped, and dietary vitamin K intake during the week preceding the blood sampling was quantitatively estimated by a dietitian-assisted questionnaire. Patients were classified according to low, medium, or high vitamin K intake. The mean daily warfarin dose in subjects with a VKORC1-1639 A/A genotype was significantly smaller than that with a -1639A/G genotype (2.74 vs. 3.91 mg/day, respectively, p < 0.0001). Dose requirements did not differ between subjects with a CYP2C9 *1/*3 genotype versus a CYP2C9 *1/*1 genotype. In subjects with a variant VKORC1-1639 G allele, the mean daily warfarin dose was significantly attenuated by low vitamin K intake compared with medium and high intake after adjustment for covariates (3.4 vs. 5.0 vs. 4.0 mg/day, respectively, p = 0.028). No such genotype effects were observed in homozygous patients for the VKORC1-1639 A allele. The results of the present study suggest that the capacity of dietary vitamin K intake to influence warfarin dose requirements during anticoagulation therapy is VKORC1 genotype-dependent, at least in part.

Serum deoxyribonuclease I activity can be a useful diagnostic marker for the early diagnosis of unstable angina pectoris or non-ST-segment elevation myocardial infarction.

BACKGROUND AND PURPOSE: Recently, serum deoxyribonuclease I (DNase I) activity has been highlighted as a potential diagnostic marker for transient myocardial ischemia. To evaluate whether serum DNase I activity can be a useful biomarker for diagnosing unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI), we investigated serial changes in DNase I levels after chest pain in UAP and NSTEMI (UAP/NSTEMI) patients. METHODS AND RESULTS: Thirty-three and ten patients classified into the UAP/NSTEMI and the chest pain syndrome (CPS) group, respectively, were enrolled. The serum DNase I activity levels within 3h after chest pain and the absolute median value of percentage differences in serum DNase I activity levels from admission to 3h after hospitalization in the UAP/NSTEMI patients was significantly higher than those in the CPS patients. We evaluated the patients to show positive results for DNase I activity if the serum levels or percentage differences exceeded the corresponding cut-off values. The sensitivity and specificity of DNase I within 6h after chest pain in the UAP/NSTEMI patients without elevated levels of cardiac troponin T and the MB isoenzyme of creatine kinase were 89% and 88%, respectively. CONCLUSIONS: Serum DNase I activity can be a useful marker for the early diagnosis of UAP/NSTEMI after the onset of chest pain, irrespective of the evidence of myocardial injury.

A quantitative coronary angiography-matched comparison between a prospective randomised multicentre cutting balloon angioplasty and bare metal stent trial (REDUCE III) and the Rapamycin-Eluting Stent Evaluation At Rotterdam Cardiology Hospital (RESEARCH) study.

AIMS: There remains significant concern about the long-term safety of drug-eluting stents (DES). However, bare metal stents (BMS) have been used safely for over two decades. There is therefore a pressing need to explore alternative strategies for reducing restenosis with BMS. This study was designed to examine whether IVUS-guided cutting balloon angioplasty (CBA) with BMS could convey similar restenosis rates to DES. METHODS AND RESULTS: In the randomised REstenosis reDUction by Cutting balloon angioplasty Evaluation (REDUCE III) study, 521 patients were divided into four groups based on device and IVUS use before BMS (IVUS-CBA-BMS: 137 patients; Angio-CBA-BMS: 123; IVUS-BA-BMS: 142; and Angio-BA-BMS: 119). At follow-up, the IVUS-CBA-BMS group had a significantly lower restenosis rate (6.6%) than the other groups (p=0.016). We performed a quantitative coronary angiography (QCA) based matched comparison between an IVUS-guided CBA-BMS strategy (REDUCE III) and a DES strategy (Rapamycin-Eluting-Stent Evaluation At Rotterdam Cardiology Hospital, the RESEARCH study). We matched the presence of diabetes, vessel size, and lesion severity by QCA. Restenosis (>50% diameter stenosis at follow-up) and target vessel revascularisation (TVR) were examined. QCA-matched comparison resulted in 120-paired lesions. While acute gain was significantly greater in IVUS-CBA-BMS than DES (1.65±0.41 mm vs. 1.28±0.57 mm, p=0.001), late loss was significantly less with DES than with IVUS-CBA-BMS (0.03±0.42 mm vs. 0.80±0.47 mm, p=0.001). However, no difference was found in restenosis rates (IVUS-CBA-BMS: 6.6% vs. DES: 5.0%, p=0.582) and TVR (6.6% and 6.6%, respectively). CONCLUSIONS: An IVUS-guided CBA-BMS strategy yielded restenosis rates similar to those achieved by DES and provided an effective alternative to the use of DES.

Levels of serum deoxyribonuclease I activity on admission in patients with acute myocardial infarction can be useful in predicting left ventricular enlargement due to remodeling.

OBJECTIVES: Serum deoxyribonuclease I (DNase I) activity has recently been highlighted as a potential diagnostic marker for the early detection of an acute myocardial infarction (AMI). We evaluated whether the serum DNase I activity was associated with the parameters of the left ventricular (LV) remodeling after an AMI. METHODS: We measured the serum DNase I activity in 45 patients with an AMI who were admitted to our hospital within approximately 4 h of the onset of their chest pain. We also evaluated the LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) of each patient by echocardiography at the time of admission and at 6 months after the onset of the AMI. RESULTS: The serum DNase I activity peaked at 3.5+/-2.0 h after the onset of the symptoms in the patients with an AMI, thereafter exhibiting a time-dependent decline within 12 h, and a return to the basal level within 24 h in almost all cases. Neither the LVEF, LVEDV, nor LVESV in each patient on admission exhibited a significant correlation to the peak levels of the serum DNase I activity. Although there was no correlation between the peak DNase I activity and LVEF at 6 months after the onset, a significant positive correlation of the peak DNase I activity with LVEDV and LVESV (r=0.48, p<0.001 and r=0.34, p=0.02, respectively) was found. Furthermore, the LVEDV at 6 months after the onset in the high DNase I activity group (> 17.9 U/L) were significantly higher than those in the low DNase I activity group (< or = 17.9 U/L) (118.0+/-28.2 ml vs 89.3+/-25.4 ml, p=0.026). CONCLUSIONS: The serum DNase I activity level may predict LV enlargement associated with remodeling after an AMI.

[Marked PT-INR prolongation associated with appetite loss due to urinary tract infection in a late elderly case with chronic atrial fibrillation].

An 80-year old woman presented with macroscopic hematuria on June 4(th), 2008. She had been suffering from general malaise and appetite loss since about 10 days previously. She had received anticoagulant therapy with warfarin due to chronic atrial fibrillation and PT-INR was well controlled between 1.6-2.2. When she presented, PT-INR was 12.88, and urinary tract infection (UTI) and hypoalbuminemia (2.2 g/dl) were observed. Therefore, warfarin therapy was discontinued, and antibiotics and vitamin K were administered. Normalization of PT-INR resulted in the disappearance of hematuria and UTI improved as a result of antibiotics administration. As the appetite loss improved, for serum albumin level increased. The previous dose of warfarin achieved PT-INR around 1.8. Her drug compliance had been good, and she took no drug nor food which could interact with warfarin. We also found no liver dysfunction, acute renal failure, malignancy, nor hyper- or hypo-thyroidism. Hypoalbuminemia caused by appetite loss due to UTI seems very likely to increase concentration of circulating free warfarin resulting in extreme prolongation of PT-INR. Our findings in the present case may suggest that we should pay more attention on changes of drug pharmacokinetics in elderly patients because of their poor adaptation to their circumstances such as infection or dehydration.

Serum deoxyribonuclease I activity can be used as a novel marker of transient myocardial ischaemia: results in vasospastic angina pectoris induced by provocation test.

AIMS: Serum deoxyribonuclease I (DNase I) activity has recently been highlighted as a potential diagnostic marker for detection of acute myocardial infarction. To evaluate whether serum DNase I activity is useful for detection of myocardial ischaemia, we investigated alteration of its levels after onset of vasospastic angina pectoris (VSAP), resulting in transient myocardial ischaemia, induced by the intracoronary ergonovine provocation test. METHODS AND RESULTS: Twenty-nine consecutive patients with suspected VSAP were subjected to the test. Patients were categorized as VSAP-positive (n = 13) or -negative (n = 16) based on development of angina. Serum samples were examined for DNase I activity before, immediately after, and 3, 6, and 24 h after the provocation tests. The serum DNase I activity increased significantly from the baseline 3 h after the provocation test in 11 patients of the VSAP-positive group whose levels of troponin T were within the normal range. Median of the percentage differences from the baseline in serum DNase I activity 3 h after the test was 32.1% (25th and 75th percentile: 28.6 and 42.0%, respectively; P = 0.000012). In the VSAP-negative group, levels of DNase I activity remained unchanged at any point of time after the provocation test. CONCLUSION: Transient myocardial ischaemia resulting from VSAP induces a significant elevation of serum DNase I activity. Therefore, serum DNase I activity may be applicable as a useful marker for detecting transient myocardial ischaemia.