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Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

It has not been established whether the achievement of optimal medical therapy (OMT) before implantation of a drug-eluting stent has a clinical benefit for patients with stable coronary artery disease (CAD). This study included 3,004 patients with CAD treated with drug-eluting stent from 123 Japanese participating centers. The achievement of OMT was defined as control of blood pressure <130/80 mm Hg, hemoglobin A1c <7.0%, and low-density lipoprotein cholesterol <100 mg/dl. The primary end point was target vessel failure, a composite of death related to the target vessel, myocardial infarction, or clinically driven revascularization at 24 months after stent implantation. Immediately before the procedure, only 548 patients (18.2%) had achieved all 3 target criteria (the achieved OMT group), whereas the remaining 2,456 patients failed to achieve one or more criteria (the non-OMT group). At 24 months, the incidence of target vessel failure was 7.0% in the achieved OMT group versus 10.0% in the non-OMT group (hazard ratio 0.68, 95% CI 0.48 to 0.96, p = 0.03). The incidence of non-Q-wave myocardial infarction was also lower in the achieved OMT group than in the non-OMT group (0.5% vs 1.5%, p = 0.08). Multivariate logistic regression analysis identified that hemoglobin A1c <7.0% was the only protective predictor of 24-month target vessel failure (odds ratio 0.56, 95% CI 0.43 to 0.73, p <0.01). In conclusion, this study demonstrated that in patients with stable CAD scheduled for stent implantation, achievement of OMT before percutaneous coronary intervention significantly reduced subsequent cardiac events. Achievement of OMT is still insufficient in modern clinical practice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Three-year clinical follow-up of patients with diabetes mellitus (DM) in the Japan-Drug Eluting Stents Evaluation; a Randomized Trial (J-DESsERT) using 2 different drug eluting stents (DES). A recent study demonstrated that efficacy of sirolimus eluting stents (SES) attenuated over time in diabetic patients., Methods: In the largest trial of its kind, 1724 DM patients out of 3533 enrolled patients were randomized to either SES or paclitaxel eluting stents (PES)., Results: There were no significant differences in baseline clinical characteristics aside from hypertension. Incidence of major adverse cardiac cerebrovascular events (MACCE) mainly due to higher target vessel failure (TVF) initially indicated a benefit in SES (MACCE rate at 1 year: SES 9.4%, PES 12.2%, p=0.08); however this had attenuated by the time of the 3-year follow-up (MACCE rate from 1 to 3 years: SES 8.4%, PES 6.1%, p=0.10). A similar pattern was observed in insulin-treated patients: MACCE rate from 1 to 3 years was 10.5% in SES and 6.4% in PES (p=0.25). Angiographic follow-up also resulted in higher major adverse cardiac event (MACE) rates at 1 year (presence 11.5%, absence 8.3%, p=0.04); however by 3 years rates were similar regardless of the presence of angiographic follow-up (MACE rate at 3 years: presence 16.0%, absence 14.5%, p=0.35)., Conclusions: The superiority of SES over PES in MACCE at 1 year had attenuated by 3-year follow-up. Eventually, the 3-year safety and efficacy profiles were similar regardless of insulin treatment., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Recent research has suggested that patients with greater delayed contrast-enhanced size by multidetector computed tomography (MDCT) are more likely to experience adverse cardiac events and have poor prognoses over the long term. The myocardial hypoenhancement area in the delayed contrast-enhanced effect suggests microvascular obstruction. The outcomes of patients with a hypoenhancement area detected by MDCT have not been clear. We examined the clinical importance of myocardial hypoenhancement detected by delayed contrast-enhanced MDCT after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction., Methods and Results: In 80 patients with acute myocardial infarction, MDCT was performed immediately after primary PCI. We investigated the outcomes of the patients with hypoenhancement detected by MDCT. Myocardial hypoenhancement was observed in 14 patients (17.5%). All 14 of these patients with hypoenhancement had a transmural infarction, and their infarct volume was significantly higher than those of the patients without hypoenhancement (n=66). During the median follow-up period of 309 days, the appearance of myocardial hypoenhancement was associated with the presence of slow flow/no-reflow, time from onset to reperfusion ≥6 h, aging, smoking, chronic kidney disease, and hyper-low-density lipoprotein cholesterolemia. The incidence of major adverse cardiovascular events (MACE) was significantly higher in the patients with hypoenhancement compared to those without hypoenhancement, regardless of the myocardial infarct volume., Conclusions: These results indicate that the presence of myocardial hypoenhancement in delayed contrast-enhanced MDCT after PCI as well as the extent of infarct area is an important predictor of MACE., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The Japan drug-eluting stents evaluation: a randomized trial (J-DESsERT) was conducted to compare the effectiveness of 2 different drug-eluting stents (DES). It remains uncertain which is more efficacious in diabetic patients, sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES). In this trial, the largest of its kind, 3,533 patients including 1,724 diabetes mellitus (DM) patients were randomized to either SES or PES. Stratification was based on the presence or absence of DM. PES target vessel failure (TVF) non-inferiority at 8 months (primary endpoint) was not demonstrated when compared to SES (SES 4.5 % vs. PES 6.4 %, p = 0.23). In addition, PES TVF superiority at 8 months in the DM subset (secondary endpoint) was not shown (SES 5.6 % vs. PES 7.6 %, p = 0.10). Insulin treatment was associated with increased TVF rates, however, this was less pronounced in the PES group. At 8 months, the similar TVF rates for SES and PES up to that point diverged significantly, favoring SES out to 12 months. Patients undergoing routine angiographic follow-up demonstrated lower TVF prior to the 8-month point, and higher TVF after 8 months, as compared to those followed clinically. In conclusion, the current study failed to demonstrate the proposed superiority of PES for DM patients. In addition, the diversion of TVF at 8 months may reflect an "oculo-stenotic reflex" bias (the tendency to treat lesions found during routine, rather than clinically driven, angiographic follow-up), which could constitute an obstacle for evaluating the true clinical effect of new devices.

This study sought to assess clinical significance of angiographic peri-stent contrast staining (PSS) after sirolimus-eluting stent (SES) implantation in a large multicenter study with 5-year follow-up. The j-Cypher PSS substudy is a multicenter study including 5712 patients (7838 lesions) who underwent follow-up angiographic study within 12 months after SES implantation. Late acquired PSS was observed in 184 patients (3.2 %) or 194 lesions (2.5 %). Independent risk factors of PSS were chronic total occlusion and left anterior descending artery lesion, while negative risk factors were in-stent restenosis, diabetes mellitus, ≥70 years of age, and left circumflex coronary artery lesion. Cumulative incidence of definite very late stent thrombosis (VLST) at 4 years after the index follow-up angiography in lesions with PSS was significantly higher than that in lesions without PSS (5.3 versus 0.7 %, P < 0.0001). Late target-lesion revascularization (TLR) was also more frequently observed in the PSS group (13 versus 6.9 %, P = 0.01), while late TLR for restenosis excluding those TLR procedures for VLST tended to be higher in the PSS group (9.9 versus 6.3 %; P = 0.15). PSS found in 2.5 % of lesions within 12 months after SES implantation was associated with higher risk for subsequent VLST.

Background: New-onset atrial fibrillation in patients hospitalized for an acute myocardial infarction often leads to hemodynamic deterioration and has serious adverse prognostic implications; mortality is particularly high in patients with congestive heart failure and/or a reduced left ventricular ejection fraction. The mechanism of atrial fibrillation in the context of an acute myocardial infarction has not been well characterized and an effective treatment other than optimal medical therapy and mechanical hemodynamic support are expected., Case Presentation: A 71 year-old male with an acute myocardial infarction due to an occlusion of the left main coronary artery was treated with percutaneous coronary intervention. He had developed severe congestive heart failure with a left ventricular ejection fraction of 34%. The systemic circulation was maintained with an intraaortic balloon pump, continuous hemodiafiltration, and mechanical ventilation until atrial fibrillation occurred on day 3 which immediately led to cardiogenic shock. Because atrial fibrillation was refractory to intravenous amiodarone, beta-blockers, and a total of 15 electrical cardioversions, the patient underwent emergent radiofrequency catheter ablation on day 4. Soon after electrical cardioversion, ectopies from the right superior pulmonary vein triggered the initiation of atrial fibrillation. The right pulmonary veins were isolated during atrial fibrillation. Again, atrial fibrillation was electrically cardioverted, then, sinus rhythm was restored. Subsequently, the left pulmonary veins were isolated. The stabilization of the hemodynamics was successfully achieved with an increase in the blood pressure and urine volume. Hemodiafiltration and amiodarone were discontinued. The patient had been free from atrial fibrillation recurrence until he suddenly died due to ventricular fibrillation on day 9., Conclusions: To the best of our knowledge, this is the first report of pulmonary vein isolation for a rescue purpose applied in a patient with hemodymically unstable atrial fibrillation complicated with an acute myocardial infarction. This case demonstrates that ectopic activity in the pulmonary veins may be responsible for triggering atrial fibrillation in the critical setting of an acute myocardial infarction and thus pulmonary vein isolation could be an effective therapeutic option.

We report a case of fulminant myocarditis associated with N1H1 influenza virus infection. N1H1 was confirmed by a polymerase chain reaction assay and she was treated with oseltamivir phosphate. She was admitted to the hospital because of respiratory distress, however, echocardiography revealed severely depressed wall motion followed by refractory ventricular fibrillation. Extracorporeal circulation by emergent percutaneous cardiopulmonary support system was required to maintain hemodynamic stability. Cardiac function was spontaneously and gradually restored within a week. Findings from biopsy samples taken on day 1 and day 23 were consistent with acute myocarditis.

Objectives: This study was designed to examine the protective effects of atrial natriuretic peptide (ANP) on contrast-induced nephropathy (CIN) after coronary angiography., Background: Contrast-induced nephropathy is a common complication after angiography. Some studies have shown that ANP has renal protective effects, but the beneficial effects for CIN prevention remain to be clearly shown., Methods: In a prospective, controlled, randomized trial in 254 consecutive patients with serum creatinine concentrations of > or =1.3 mg/dl, patients received either ANP (0.042 microg/kg/min; ANP group, n = 126) or Ringer solution alone (control group, n = 128). Treatment of either type was initiated 4 to 6 h before angiography and continued for 48 h., Results: There were no significant differences in age, sex, diabetes mellitus, or baseline serum creatinine level between the 2 groups. The prevalence of CIN, defined as a 25% increase in creatinine or an increase in creatinine of > or =0.5 mg/dl from baseline within 48 h, was significantly lower in the ANP group than in the control group (3.2% vs. 11.7%, respectively; p = 0.015). Multivariate analysis revealed that the use of >155 ml of contrast medium (odds ratio: 6.89; p < 0.001) and ANP treatment (odds ratio: 0.24; p = 0.016) were significant predictors of developing CIN. The incidence of an increase in creatinine of > or =25% or of > or =0.5 mg/dl from baseline at 1 month was also significantly lower in the ANP group than in the control group (p = 0.006)., Conclusions: In addition to hydration, ANP administration is effective in the prevention of CIN in patients with chronic renal failure, and the effect was maintained for 1 month.

Accurate objective quantification of left ventricular (LV) dyssynchrony is a key to selecting candidates for cardiac resynchronization therapy (CRT), especially when screening among patients with a narrow QRS. CardioGRAF (cardio Gated single photon emission computed tomography Regional Assessment for left ventricular Function), a newly developed LV segmental time-volume analyzing program for myocardial perfusion single photon emission tomography, may be a promising tool. We describe the case of a 63-year-old male with non-ischemic cardiomyopathy with a QRS duration of 112 ms, in whom cardioGRAF successfully demonstrated baseline LV dyssynchrony and resynchronization achieved by CRT as evidenced by a significant decrease in dyssynchrony index (standard deviation of the duration from R to end-systole among 17 LV segments) x100/R-R interval).

Background: The Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) has shown that the prophylactic implantable cardiac defibrillator improves the survival rate of patients with prior myocardial infarction and advanced left ventricular (LV) dysfunction. However, a more accurate noninvasive predictor should be found to identify subgroups at high risk, one that would allow implantable cardiac defibrillator therapy to be directed specifically to the patients who would benefit most., Methods and Results: To elucidate whether technetium 99m tetrofosmin electrocardiogram-gated single photon emission computed tomography (SPECT) imaging at rest can determine the risk of arrhythmic death, 106 patients who met the MADIT-II criteria (LV ejection fraction 1 month earlier, and no sustained ventricular tachyarrhythmia) were recruited from a pool of 4628 consecutive patients who had undergone resting Tc-99m tetrofosmin SPECT imaging. By use of the endpoints of lethal arrhythmic events, which included documentation of sustained ventricular tachycardia, ventricular fibrillation, or diagnosis of sudden cardiac death, we performed follow-up for a mean of 30 months. Lethal arrhythmic events occurred in 14 patients. Patients with lethal arrhythmic events had a lower LV ejection fraction, greater LV end-systolic and end-diastolic volume indices, and a greater perfusion defect volume than the remaining patients. By receiver operating characteristic curve analysis, myocardial defect volume was the strongest predictor for the development of lethal arrhythmic events., Conclusion: Our results confirm that perfusion defect volume by Tc-99m tetrofosmin scintigraphy is the most pivotal predictor of the future occurrence of lethal arrhythmic events and of sudden cardiac death. Tc-99m tetrofosmin SPECT images may assist in identifying subsets of patients with a greater likelihood of arrhythmic death among patients with LV dysfunction.

Background: A 34-year-old postpartum woman presented at hospital with chest pain. She had experienced an uneventful delivery of a healthy infant and had no known coronary risk factors. Electrocardiography demonstrated an acute myocardial infarction, which resolved on intravenous glyceryl trinitrate infusion. Coronary angiography revealed diffuse narrowing of the left anterior descending artery and tapering of the left main trunk, but there were no obvious hallmarks of intimal dissection., Investigations: Electrocardiography, coronary angiography, multidetector CT and intravascular ultrasonography., Diagnosis: Postpartum coronary artery dissection., Management: The lesion was stabilized with orally administered amlodipine, aspirin, ticlopidine and pitavastatin, along with intravenous heparin and glyceryl trinitrate. The patient was later discharged on bisoprolol, aspirin, pitavastatin and temocapril.

Autonomic imbalance may work as a modifying factor for initiating lethal arrhythmia in patients with Brugada syndrome. A 26-year-old man with episodes of near syncope was given a diagnosis of an autonomic disorder, postural orthostatic tachycardia syndrome (POTS). The patient spontaneously showed typical Brugada-type ECG, and ventricular fibrillation was induced by programmed electrical stimulation, which allowed the further diagnosis of Brugada syndrome. Although it seems that Brugada syndrome is asymptomatic, its uncommon association of POTS may increase the risk for future arrhythmic events in this patient.

Objectives: The purpose of this study was to investigate the effects of angiotensin II receptor blockers on the prevention of cardiovascular events in patients with coronary artery disease (CAD)., Background: Angiotensin II may contribute to the pathogenesis of CAD. Long-term clinical trials have shown that blockade of the renin-angiotensin system can reduce cardiovascular events in patients with acute myocardial infarction complicated by heart failure., Methods: Patients with a history of coronary intervention and no significant coronary stenosis on follow-up angiography 6 months after intervention were randomly assigned into a candesartan group (n = 203; baseline treatment plus candesartan 4 mg/d) or a control group (n = 203; baseline treatment alone). The primary end point was a composite of revascularization, nonfatal myocardial infarction, or cardiovascular death. The secondary end point was hospitalization for cardiovascular causes., Results: There were no changes in blood pressure and in other coronary risk factors in either group during a mean follow-up of 24 months. Primary end point risk was significantly lower in the candesartan group (n = 12) than in control group patients (n = 25) (P =.03). Candesartan treatment reduced primary end point risk (5.9% vs 12.3% for control subjects; relative risk, 0.47; 95% CI, 0.24 to 0.93). The incidence of all events including secondary end points and noncardiovascular death was significantly lower in the candesartan group than in control group patients (23 vs 40 cases) (P =.02)., Conclusions: Relatively low-dose candesartan, which did not alter blood pressure levels, reduces cardiovascular risk in high-risk patients with CAD.

A patient with an implantable cardioverter defibrillator (ICD) received incessant inappropriate shocks due to a lead fracture 3 years after implantation. Routine lead measurements at 3-month intervals had shown no abnormal findings even at the most recent measurement performed 2 months prior to the event. In contrast, serial observation of chest X rays clearly disclosed progressive lead narrowing starting 11 months prior to the event. This case indicates the importance of the routine chest X rays in long-term follow-up of ICDs and sets a precedent for interpreting lead narrowing in such X rays.

We investigated the effects of angiotensin II type 2 (AT2) receptor blockade on the antihypertrophic effects of type 1 receptor (AT1) blockade in pressure-overload cardiac hypertrophy in adult rats. Cardiac hypertrophy was induced by banding the abdominal aorta above the renal arteries. The rats were treated with either an AT1 receptor antagonist TCV-116 (TCV, 10 mg/kg/day), an AT2 receptor antagonist PD123319 (PD, 20 mg/kg/day), or both for 4 weeks after the aortic banding. We measured systolic and diastolic blood pressure (BP), body weight (BW), left ventricular weight (LVW), and serum and cardiac angiotensin converting enzyme (ACE) activities. Aortic banding increased BP and LVW/BW, and TCV reversed both these increases. PD affected neither BP nor LVW/BW. TCV+PD reversed the increase in BP but not LVW/BW. Thus, PD was considered to counteract the antihypertrophic effect of TCV without affecting BP. All three treatments reduced cardiac ACE activity without affecting serum ACE activity. Our data demonstrated that AT2 receptor blockade negates the antihypertrophic effects of AT1 receptor blockade in an adult rat model of pressure-overload cardiac hypertrophy. AT2 receptors may mediate the signaling pathways involved in growth inhibition, which could counteract mediation of the cellular growth signaling pathways by AT1 receptors.

Background: Reduced or impaired synthesis of nitric oxide promotes the proliferation of vascular smooth muscle cells, and thus may induce the neointimal formation leading to coronary in-stent restenosis. Recent reports have suggested that the Glu298Asp polymorphism in exon 7 of the endothelial nitric oxide synthase gene is associated with coronary spasm and acute myocardial infarction. In this study, we have examined the implication of this polymorphism with regard to coronary restenosis after Palmaz-Schatz stent deployment., Methods: Eighty-nine lesions in 85 consecutive patients were treated with Palmaz-Schatz stents, and were prospectively followed up for 6 months. The lesions were classified into a restenosis group (% diameter stenosis=50%) and a non-restenosis group. Assessment was made using an automated quantitative angiographic system. We performed polymerase chain reaction-restriction fragment length polymorphism analysis to detect the missense Glu298Asp variant in exon 7 of the endothelial nitric oxide synthase gene., Results: Coronary risk factors and angiographic findings of stenotic lesions did not differ between the groups. Univariate analyses showed that the missense Glu298Asp variant was the only statistically significant predictor of restenosis (odds ratio, 4.27; P=0.025). In addition, multiple logistic regression analysis revealed the missense Glu298Asp variant as the only independent predictor for in-stent restenosis (odds ratio, 3.90; P=0.036)., Conclusions: The missense Glu298Asp variant may be an independent risk factor for in-stent restenosis.

Restenosis after coronary artery stent implantation is attributed chiefly to intimal hyperplasia, which is prevented experimentally by angiotensin-converting enzyme (ACE) inhibitors. Therefore, the present study investigated whether the effect of quinapril, a tissue-specific ACE inhibitor, on the prevention of coronary restenosis differs according to ACE polymorphism. One hundred consecutive patients with successful stent implantation were randomly assigned to quinapril and control groups. Both follow-up angiography and ACE polymorphism analysis were obtained from 92 patients (control, 46; quinapril treatment, 46). The prevalence of risk factors did not differ statistically according to quinapril treatment or ACE genotypes. There was no statistically significant difference in the occurrence of restenosis 6 months after stenting between the groups. Quantitative coronary angiography revealed that quinapril treatment resulted in significantly higher minimal lumen diameter and significantly lower percent diameter stenosis (22.9 +/- 22.6 vs 37.1 +/- 19.7% in the control group, p < 0.05) in patients with the D allele although there was no difference in those with the II genotype. In addition, intravascular ultrasound revealed that quinapril treatment significantly prevented the loss of minimal lumen cross-sectional area and the increase in percent area stenosis (34.5 +/- 14.0 vs 53.3 +/- 16.4% in the control group, p < 0.05) in patients with the D allele compared to those with the II genotype. These results suggest that the administration of ACE inhibitors for the attenuation of lumen loss after coronary stent implantation is best for subjects with the D allele of the ACE genotype.

Background: C-reactive protein (CRP) directly participates in the myocardial injury of acute myocardial infarction (MI). Although high plasma CRP levels in the acute phase strongly indicate a poor early clinical outcome of patients with MI, the impact of CRP levels on late left ventricular (LV) function and remodeling, which are closely associated with long-term prognosis, remains unknown., Hypothesis: Acute plasma CRP levels may predict late LV function and remodeling after MI., Methods: We prospectively studied 12 consecutive patients with a first acute anterior MI recanalized by angioplasty. We measured plasma CRP levels on Days 0, 1, 2, 3, 4, and 7, and calculated the area under the curve (AUC). We also measured plasma brain natriuretic peptide (BNP) levels on Day 3 as the referential indicator of LV dysfunction and late LV remodeling. Late LV indices were independently assessed on a left ventriculogram obtained at 5.3 months to estimate the extent of LV remodeling., Results: Plasma CRP reached its peak at Day 2.8 (8.68+/-4.57 mg/dl). On linear regression analysis, the AUC of CRP (35.21+/-19.33 mg/dl x day) correlated positively with BNP (316.5+/-418.6 pg/ml) (r = 0.646, p = 0.023). The AUC of CRP, peak CRP, and BNP correlated significantly with late LV indices. Among these, the AUC of CRP showed the best correlation with end-diastolic volume index (r = 0.765, p = 0.004), end-systolic volume index (r = 0.907, p < 0.001), and ejection fraction (r = -0.862, p < 0.001)., Conclusions: Patients with high plasma CRP levels may be at risk for late LV dysfunction and remodeling; theoretically, their long-term prognosis may be poor. Measuring plasma CRP levels may provide valuable information for long-term risk stratification after MI.

Background: Hyperhomocysteinemia has been identified as an independent risk factor for coronary artery disease. Recent studies have shown that a common mutation (nucleotide 677 C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene may contribute to mild hyperhomocysteinemia and, therefore, to the incidence of coronary artery disease. No information exists, however, regarding the association between the mutation of the MTHFR gene or plasma homocysteine levels and morphological analysis of coronary atherosclerosis using intravascular ultrasound., Methods and Results: To examine the potential influence of MTHFR genotype and homocysteine on coronaryarteries morphologically, we screened 62 patients with 65 lesions that were treated with 93 Palmaz-Schatz stents. The plasma homocysteine levels in the patients with the TT genotype were not significantly higher than those in the patients with non-TT (CC+CT) genotypes (13.1 +/- 5.5 versus 11.5 +/- 3.1 mmol/L, P=0.16). Angiographic analysis showed that the percent diameter stenosis in the patients with the TT genotype was significantly greater than that in those with non-TT genotypes (43.7 +/- 17.8% versus 29.0 +/- 22.0%, P=0.015). Intravascular ultrasound analysis showed that the TT genotype was significantly associated with greater intimal hyperplasia area (5.70 +/- 1.94 versus 3.72 +/- 1.38 mm2, P=0.001). In multiple stepwise regression analysis, the number of the T alleles was the only independent predictor of intimal hyperplasia after intervention (r2=0.21, P=0.004)., Conclusions: The homozygous mutant genotype of the MTHFR gene may increase the risk of in-stent restenosis more than does the normal homozygous or heterozygous genotype.

Objectives: Conventional thrombolytic therapy for acute myocardial infarction is effective for early reperfusion but has the disadvantage of a higher rate of bleeding complications. The purpose of this study is to elucidate efficacy and safety of a combined approach using a bolus injection of low dose of mutant tissue plasminogen activator (mt-PA) with heparin and aspirin to ensure definite antithrombin and antiplatelet efficacy, followed by back-up percutaneous transluminal coronary angioplasty(PTCA)., Methods: Patients with acute myocardial infarction aged < 80 years who were admitted to our institution within 3 hr of onset of symptoms were immediately treated with oral aspirin 330 mg and intravenous heparin 5,000 IU and were randomized to receive an intravenous bolus of mt-PA (monteplase) 15,000 IU/kg (thrombolytic group, n = 25) or no mt-PA (control group, n = 21), followed by angiography with PTCA if indicated., Results: There were no differences between the two groups in patient characteristics, time from onset to hospital arrival, time to initial angiography, or infarct-related arteries. Significantly more patients had Thrombolysis in Myocardial Infarction flow grade 3 and grade 2/3 at the initial angiography in the thrombolytic group than in the control group (32.0% vs 4.8%, 68.0% vs 14.3%; p = 0.020, p = 0.0003, respectively). PTCA was performed in 88% of the thrombolytic group (stenting employed in 64%) and 95.5% of the control group (stenting in 57%), and the success rate was 95.5% and 100%, respectively. No acute or subacute coronary occlusion was found in either group. Bleeding complications occurred in only one patient in the thrombolytic group, which was bleeding associated with vomiting, and no difference was found in other complications between the two groups. Radionuclide ventriculography using quantitative gated single photon emission computed tomography showed left ventricular end-diastolic volume and left ventricular end-systolic volume tended to be smaller, and the ejection fraction after 3 months of treatment tended to be higher in the thrombolytic group. Myocardial salvage volume was significantly higher in the thrombolytic group., Conclusions: Hybrid thrombolysis using a low dose of mt-PA with aspirin and heparin promoted significantly early reperfusion. Also, successful reperfusion is achievable at higher rates with back-up PTCA without an increase in complications.

We studied whether angiotensin-converting enzyme inhibition with quinapril treatment can prevent in-stent restenosis after successful implantation of Palmaz-Schatz stents. Intravascular ultrasound study, but not quantitative coronary angiography analysis, revealed that quinapril treatment significantly prevented the loss of both minimal lumen cross-sectional area and lumen volume in stents, in addition to reducing the increase in intimal hyperplasia volume.

Objectives: We sought to elucidate the long-term prognostic importance of angiographic no-reflow phenomenon after percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI)., Background: Angiographic no-reflow phenomenon, a reduced coronary antegrade flow (Thrombolysis in Myocardial Infarction [TIMI] flow grade < or =2) without mechanical obstruction after recanalization, predicts poor left ventricular (LV) functional recovery and survival in the early phase of AMI. We hypothesized that angiographic no-reflow phenomenon also predicts long-term clinical outcome., Methods: We studied 120 consecutive patients with their first AMI treated by PTCA without flow-restricting lesions. The patients were classified as either no-reflow (n = 30) or reflow (TIMI-3) (n = 90) based on post-PTCA cineangiograms to follow up (5.8 +/- 1.2 years) for cardiac death and nonfatal events., Results: Patients with no-reflow had congestive heart failure (p < 0.0001), malignant arrhythmia (p = 0.038), and cardiac death (p = 0.002) more often than did those with reflow. Kaplan-Meier curves showed lower cardiac survival and cardiac event-free survival (p < 0.0001) in patients with no-reflow than in those with reflow. Multivariate analyses disclosed that no-reflow phenomenon was an independent predictor of long-term cardiac death (relative risk [RR] 5.25, 95% confidence interval [CI] 1.85 to 14.9, p = 0.002) and cardiac events (RR 3.71, 95% CI 1.79 to 7.69, p = 0.0004). At follow-up, survivors with no-reflow had higher end-diastolic and end-systolic LV volume indices and plasma brain natriuretic peptide levels, and lower LV ejection fractions (p = 0.0002, p < 0.0001, p = 0.002, p < 0.0001, respectively) than did those with reflow, indicating that no-reflow may be involved in LV remodeling., Conclusions: Angiographic no-reflow phenomenon strongly predicts long-term cardiac complications after AMI; these complications are possibly associated with LV remodeling.

This study evaluated the role of adrenomedullin in patients with vasospastic angina pectoris. Adrenomedullin may be involved in regulating a basal tone of the coronary artery in these patients.

We examined effects of a prostaglandin E1 analogue alprostadil on intimal thickening and arterial remodeling in balloon-injured rat carotid arteries. Right common carotid arteries were balloon-injured, and their left counterparts were sham-operated (uninjured). Rats were given alprostadil (0.3 microgram/kg/min, continuous subcutaneous (s.c.) infusion) or vehicle for 1 week after the injury and sacrificed at 4 weeks or 8 weeks. Segments of common carotid arteries corresponding to balloon-injured and uninjured sites were excised and subjected to elastica van Gieson staining. Cross-sectional areas were measured by computed planimetry. Alprostadil prevented intimal thickening at both 4 and 8 weeks. In addition, alprostadil prevented the increase in intimal area/area surrounded by external elastic lamina at both 4 and 8 weeks. Alprostadil had no effects on body weight, heart rate, or systolic blood pressure. Our study demonstrated that alprostadil administered only for the initial 1 week had long-term (up to 8 weeks) preventive effects on intimal thickening. Alprostadil may be useful to prevent restenosis after balloon angioplasty.

To study the ovarian function of the common tree shrew (Tupaia glis), monoclonal antibodies (MAb) against its ovarian antigen were produced. Several positive hybridomas were cloned and MAb-T2C9 (IgG) was examined for reactivity. Strong immunoreactivity of MAb-T2C9 was localized within the cytoplasm of luteal cells and in the theca interna cells of Graafian follicles. MAb-T2C9 reacted also with testicular interstitial cells and adrenocortical cells, except those of the zona glomerulosa. Similar reactions were seen in the goat and sheep. Western blotting analysis of the ovine corpus luteum after reaction with MAb-T2C9 revealed a single positive band of approximately 60 kDa. These findings suggest that MAb-T2C9 recognized protein molecules related to steroid synthesis.

Nitroglycerin (NTG), a nitric oxide (NO) donor, is considered to relax vascular smooth muscle by stimulating soluble guanylate cyclase, which in turn increases cyclic GMP (cGMP) level. Recently it became evident that NO-induced vasodilatation is also mediated by stimulating Ca-activated K (K(Ca)) channels directly and/or indirectly through cGMP. We, therefore, tried to investigate the possible involvement or the alteration of K(Ca) channels in the mechanism of vasodilation induced by NTG in physiological and pathological conditions. Using rings prepared from thoracic aortas of spontaneously hypertensive rats (SHR) and those of age-matched Wistar-Kyoto rats (WKY), we studied changes in isometric tension of the rings in response to NTG to evaluate effects of a soluble guanylate cyclase inhibitor methylene blue (MB), and a specific blocker of K(Ca) channel charybdotoxin (CTX). Rings from WKY and SHR precontracted with norepinephrine showed similar aortic relaxation to NTG. MB markedly suppressed the NTG-induced relaxation in both strains, leaving about 30% of MB-resistant relaxation. CTX nearly completely eliminated this MB-resistant relaxation in WHY but did not affect this relaxation in SHR. These results suggest that NTG-induced vasorelaxation is mediated through i) cGMP-dependent and ii) cGM P-independent K(Ca) channel involving mechanisms, the latter may be diminished or virtually eliminated in hypertensive state.

Adriamycin (ADR) is a potent, broad-spectrum chemotherapeutic agent whose clinical use is limited by its cardiotoxicity. Since the pathogenesis of ADR-induced cardiomyopathy may involve free radicals and lipid peroxidation, the antioxidant, melatonin (MEL) may protect against toxic effects of ADR. We therefore tested this hypothesis using a rat model of ADR-induced cardiomyopathy. Sprague-Dawley rats were given ADR (cumulative dose, 15 mg/kg), MEL (cumulative dose, 84 mg/kg), ADR+MEL, ADR plus probucol (PRB, cumulative dose, 90 mg/kg), or vehicle alone, according to known regimens. The rats were maintained for 3 weeks following treatment, after which their cardiac performance was measured. Following sacrifice, their myocardial ultrastructure was examined, and their myocardial lipid peroxidation was assessed. Mortality was observed only in rats treated with ADR alone. When compared to control rats, surviving rats in the ADR group showed significant decreases in ratio of heart to body weight, arterial pressure, and left ventricular fractional shortening as well as a significant accumulation of ascites. The amount of myocardial thiobarbituric acid reactive substances was significantly higher in ADR-treated than in control rats. Both antioxidants, MEL and PRB, significantly prevented these ADR-induced changes. Electron microscopic examination revealed myocardial lesions indicative of ADR-induced cardiomyopathy in the ADR-treated rats. In contrast, treatment of these rats with MEL or PRB preserved myocardial ultrastructure. By preventing lipid peroxidation, MEL may be highly effective in protecting against ADR-induced cardiomyopathy.

Objective: To investigate the roles of the renin-angiotensin system and blood pressure in cardiac hypertrophy caused by a pressure overload., Methods: Cardiac hypertrophy was induced by constricting the abdominal aorta above the renal arteries. After they had been banded, the rats were treated with the lower (1 mg/kg per day) or the higher (10 mg/kg per day) dose of quinapril [an angiotensin converting enzyme (ACE) inhibitor], or the lower (1 mg/kg per day) or the higher (10 mg/kg per day) dose of TCV-116 [an angiotensin II (AngII) AT1 receptor antagonist], for 4 weeks. Then, we measured the mean blood pressure (MBP), body weight, left ventricular weight (LVW), and serum and cardiac ACE activities., Results: The higher dose of quinapril and that of TCV-116 prevented left ventricular hypertrophy and MBP elevation. Both the higher and the lower doses of quinapril reduced the serum and cardiac ACE activities significantly, whereas the higher dose of TCV-116 reduced the cardiac ACE activity and increased the serum ACE activity. The lower dose of quinapril, however, exerted no significant effect on MBP and the LVW:body weight ratio, although it reduced the cardiac and serum ACE activities significantly. There was a significant positive correlation between the MBP and the LVW:body weight ratio regardless of the cardiac ACE activity in data from all groups (r = 0.676, P < 0.0001)., Conclusions: Our data indicate the importance of the blood pressure as a determinant of cardiac hypertrophy because inhibition of cardiac ACE activity alone without lowering of the blood pressure is insufficient to prevent cardiac hypertrophy. Our results suggest the presence of other pathways for AngII production not mediated by ACE, or growth factors other than AngII in pressure-overload cardiac hypertrophy.

Background: Abnormal lipid metabolism associated with diabetes mellitus has been proposed to be involved in the pathogenesis of diabetic cardiomyopathy. Oxysterols, oxidation derivatives of cholesterol, are known to be highly cytotoxic., Objective: To monitor changes in myocardial oxysterols and to assess the effect of probucol, a lipid lowering agent, on myocardial lipids and oxysterols in diabetic rats., Methods and Results: Streptozotocin-induced diabetic rats were divided into two groups; one group was put on a standard diet, and the other a diet containing 1% (weight/weight) probucol for eight weeks. Two oxysterols, 7 beta-hydroxycholesterol and 7-ketocholesterol, were identified in myocardium by capillary gas chromatography. Both 7 beta-hydroxycholesterol and 7-ketocholesterol were significantly increased in diabetic rats (49.9 +/- 9.4 ng/mg dry weight versus 5.8 +/- 1.2 in controls, P < 0.05; and 5.3 +/- 1.2 ng/mg dry weight versus 1.7 +/- 0.1 in controls, P < 0.01, respectively). Probucol reduced not only plasma lipids but also myocardial lipids except for cholesterol and sphingomyelin fractions. However, probucol did not improve insulin deficiency, glucose metabolism or myocardial oxysterol contents., Conclusions: This study demonstrated an increase in oxysterols in the myocardium of diabetic rats, suggesting that oxysterols may play a role in the development of diabetic cardiomyopathy. Probucol did not decrease the myocardial oxysterol content at the dose used in this study, suggesting that the increase in oxysterols may not be attributed to high circulating concentrations of lipids, but rather to disturbed myocardial metabolism due to insulin deficiency.

1,2-Diacylglycerol (DAG) is an intracellular signal mediator that may initiate protein synthesis and cardiac hypertrophy via activation of protein kinase C. The amounts of 1,2-DAG and its fatty acid components in the myocardium was assessed and compared with the concentrations of RNA and DNA in cardiac hypertrophy induced by administering triiodothyronine (T3) with and without cycloheximide, an inhibitor of protein synthesis. After the first injection of T3 no cardiac hypertrophy was observed, and there were no differences in myocardial 1,2-DAG content or in RNA and DNA concentrations. Cardiac hypertrophy was present on days 3 and 7 after a daily injection of T3. Myocardial RNA concentration was increased by 26% on day 3 and by 34% on day 7, whereas the myocardial 1,2-DAG content was decreased by 8% on day 3 and by 24% on day 7. Pretreatment with cycloheximide of T3-treated rats prevented the development of cardiac hypertrophy, but elevated the RNA concentration and lowered the 1,2-DAG content compared with the findings in T3-treated rats. Analysis of the fatty acid components of 1,2-DAG revealed that the amounts of 16:0, 18:1 and 18:2 were decreased, accompanied by an elevation of RNA concentration and a decrease in 1,2-DAG content. It seems that RNA synthesis preceded the alteration in 1,2-DAG. These findings suggest that 1,2-DAG is not involved in the initiation of cardiac hypertrophy induced by T3, but is affected by the enhanced concentration of RNA resulting from the introduction of thyroid hormones into the myocardium.