Background: Previous studies have shown that intracoronary nitroprusside injection is safe and effective after slow reflow complicates percutaneous coronary intervention (PCI).
Objectives: We sought to determine the safety and efficacy of selective intracoronary administration of nitroprusside through the drug delivery catheter before balloon dilatation to prevent no or slow reflow during PCI for acute myocardial infarction (AMI).
Methods: We studied 120 consecutive patients with AMI treated by PCI. In 60 patients (nitroprusside group), nitroprusside (120 μg) was selectively administered through the drug delivery catheter into the distal coronary artery to reach the target lesion before balloon dilatation. Clinical and angiographic data, as well as in-hospital outcomes, of the nitroprusside group were retrospectively compared with 60 patients who had conventional PCI without nitroprusside (control group).
Results: There were no significant differences in the baseline clinical and angiographic characteristics between the 2 groups. Compared to the control group, the nitroprusside group had 1) less slow reflow during the procedure (12% versus 35%, P = 0.0025), 2) a shorter fluoroscopic time (14.4 ± 7.9 versus 18.7 ± 9.1 minutes, P = 0.0093), 3) a shorter procedure time (57.6 ± 20.6 versus 78.1 ± 26.4, P < minutes, P < 0.0001), 4) a better final TIMI flow grade (III:II:I:0 = 59:1:0:0 versus 53:6:1:0, P = 0.0284), 5) a better blush grade (III:II:I:0 = 49:10:1:0 versus 33:15:8:4, P = 0.0006), and 6) a better corrected TIMI coronary flame count (30.8 ± 13.7 versus 46.5 ± 44.7, P = 0.0102). There were no particular complications with nitroprusside use.
Conclusions: The selective intracoronary administration of nitroprusside prior to PCI is safe and well tolerated, prevents no or slow reflows, and improves reperfusion of the infarcted myocardium.

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Background: Angiotensin II induces various growth factors such as vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor, and recent studies suggest that the expression of these growth factors promotes collateral growth. We hypothesized that the blockage of angiotensin II production by ACE inhibitors might interfere with collateral development in patients with coronary occlusion.
Methods: The study group consisted of 187 patients (114 males, mean ages, 62 ± 11 years) who had chronic (> 1 month) coronary occlusion (TIMI flow grade ≤ 1) in one of 3 epicardial coronary arteries. Collaterals were graded using the Rentrop classification, and the patients were divided into 2 groups according to having good (grade 2 and 3) or poor (grade 0 and 1) collaterals (n = 127 and 60, respectively). Clinical and angiographic characteristics were compared in the 2 groups.
Results: ACE inhibitor use (52% versus 35%, P = 0.04) and the prevalence of diabetes mellitus (DM) (43% versus 27%, P = 0.02) was higher in patients with poor collaterals. Patients with poor collaterals had a higher frequency of circumflex artery (Cx) occlusion, worse wall motion, and lower ejection fraction. In multivariate analysis, ACE inhibitor use (OR: 2.4; 95% CI = 1.23-4.68, P = 0.01) and the occlusion of Cx (OR: 3.3, 95% CI; 1.33-8.12, P = 0.01) were found to be independent predictors for poor collateral development, whereas there was a trend for DM as a predictor for poor collaterals (OR: 1.9, 95% CI = 0.97-3.8, P = 0.06).
Conclusion: The findings suggest that ACE inhibitor therapy may contribute to poor collateral development in patients with coronary occlusion.

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This study enrolled 536 patients who underwent successful coronary stenting with bare-metal stents and 6-month angiographic follow-up examinations between 1998 and 2000. Baseline characteristics and angiographic and procedural parameters for these patients were obtained. Primary endpoints were all-cause mortality and nonfatal myocardial infarction. Patients were assigned to instent restenosis or non-instent restenosis groups based on 6-month angiographic follow-up results. Restenosis inside a bare-metal stent was defined as more than 50% stenosis at the intervention site. In total, 178 (33.2%) patients had restenosis inside bare-metal stents, while 358 (66.8%) patients were without. At mean follow-up of 56.8 ± 20.3 months, 36 (6.7%) patients had a primary endpoint event while 500 (93.3%) patients had no primary endpoint event. Survival rates for patients free from primary endpoints in the instent restenosis and non-instent restenosis groups were 96.0 versus 99.4% at 1 year and 89.8% versus 94.8% at 5 years, respectively (P = 0.0033). Survival rates for patients free of all-cause mortality in the instent restenosis and non-instent restenosis groups were 96.0% versus 99.4% at 1 year and 91.6% versus 96.3% at 5 years, respectively (P = 0.0079). Multivariate Cox regression analysis showed that restenosis inside bare-metal stents was an independent predictor of primary endpoint events (odds ratio: 2.053; 95% CI: 1.048-4.022; P = 0.036) and was a predictor of total mortality with borderline significance (odds ratio: 2.036; 95% CI: 0.936-4.431; P = 0.073). In conclusion, in this study, restenosis inside bare-metal stents at 6-month angiographic follow-up was an independent predictor of long-term outcome-all-cause mortality and nonfatal myocardial infarction. Thus, this study provides clinical evidence that patients with restenosis inside bare-metal stents at 6-month angiographic follow-up likely warrant aggressive follow-up.

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The impact of drug-eluting stents (DES) on the characteristics and operative results of patients referred for coronary artery bypass grafting (CABG) was studied. We reviewed data from isolated CABG patients 24 months before (group A, n = 134) and 24 months after (group B, n = 98) the introduction of DES for clinical use at Teikyo University Hospital in Tokyo. Group B patients were significantly older than those of group A (66 ± 9 versus 69 ± 9 years old). The number of diseased vessels was significantly larger in group B (2.5 ± 0.6 versus 2.7 ± 0.5) and left main trunk disease decreased in group B (27% versus 17%). Preoperative IABP support was more frequent in group B (9% versus 17%) and beating heart surgery was significantly more frequent in group B (26% versus 59%). The number of grafts was similar in the 2 groups (3.2 ± 1.4 versus 3.0 ± 1.1). The operative mortality rates were 0.7% and 4.1% in group A and B, respectively. Incomplete revascularization followed by postoperative percutaneous coronary intervention (PCI) was performed in 11% and 12%, respectively, and all the patients survived surgery. The operative mortality rates for arrested heart and beating heart surgery were 2% and 2%, respectively. In conclusion, after the introduction of DES, more clinically ill patients were referred to CABG. Combination therapy consisting of CABG and PCI (Hybrid) may be a treatment of choice in critical patients.

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Purpose: This study was designed to illustrate the effects of C-reactive protein (CRP) and interleukin polymorphisms on serum CRP levels.
Methods: A total of 390 patients with coronary heart disease (CHD) were recruited and high-sensitivity CRP levels were measured. Six polymorphic alleles on the genes of CRP, IL-1, and the IL-1 receptor antagonist were identified. A classification tree was applied to determine their effects and interactions on serum CRP levels.
Results: In the hypertensive CHD patients, the presence of CRP + 1059 GC heterozygotes was associated with a lower risk for elevated CRP levels (OR = 0.318, P = 0.001). The coexistence of CRP + 1059 GC and IL-1β-511 (CT or TT) might result in reduction in the CRP levels compared to IL-1β-511 CC (OR = 0.222, P = 0.088 and OR = 0.148, P = 0.060, respectively).
Conclusion: The results demonstrated the distribution of CRP-related polymorphisms and the interactions in Taiwanese patients with CHD.

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Objective: Myocardial fractional flow reserve (FFR) is utilized to determine the hemodynamic significance of coronary stenoses. We sought to determine the effect, if any, of metoprolol on FFR in patients with coronary stenoses of intermediate severity.
Methods and results: Eighteen patients (10 males, mean age, 59.4 ± 7.7 years) with isolated, intermediate (30% to 70% narrowing on coronary angiogram) lesions on the proximal LAD and a preserved ejection fraction, underwent FFR measurement using a 0.014 inch pressurewire and intracoronary adenosine injection before and after intravenous metoprolol at a dose that achieved at least a 10% decrease in the heart rate. Heart rate dropped significantly with metoprolol. At the premetoprolol measurement, aortic pressure (Pa) remained essentially the same (105.7 ± 11.5 versus 105.6 ± 11.6 mmHg, P > 0.05) and distal coronary pressure (Pd) dropped significantly by 9% from 96.3 ± 12.7 to 87.4 ± 13.4 mmHg (P < 0.001) after adenosine injection yielding an FFR₁ of 0.83 ± 0.07. At the postmetoprolol phase, Pa dropped nonsignificantly by 2% from 104.4 ± 12.8 to 102.4 ± 14.3 mmHg (P = 0.09) and Pd dropped significantly by 11% from 95.7 ± 14.4 to 85.3 ± 16.4 mmHg (P < 0.001) after adenosine injection, yielding an FFR₂ of 0.83 ± 0.08, which was almost exactly the same as FFR₁ (P > 0.05).
Conclusion: In this study, FFR was found not to be influenced by metoprolol treatment in patients with intermediate coronary stenoses and a preserved ejection fraction.

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Background: Brain natriuretic peptide (BNP) level has been shown to increase in patients with chronic atrial fibrillation (CAF) without overt heart failure (HF). Although atrial electrical remodeling associated with CAF has been described, little is known about the effects of the BNP level on the electrophysiological properties in CAF patients.
Methods and results: In 42 CAF patients without overt HF, the atrial monophasic action potential duration (MAPD) at pacing cycle lengths (CLs) of 300-800 msec and P-wave signal-averaged electrograms were recorded after cardioversion. The MAPDs for all CLs were significantly longer in patients with a BNP concentration greater than the 50th percentile (group 1, BNP = 215 ± 118.2 pg/mL) than in patients with a concentration less than the 50th percentile (group 2, BNP = 68.3 ± 20.9 pg/mL), resulting in a similar value in the MAPDs at CLs of 350 and 600 msec for group 1 and the control patients (n = 8). The slope value of the MAPDs between CLs of 350 and 600 msec was normal in group 1, but slightly lower in group 2 than in group 1 and control patients. The filtered P-wave duration did not differ between the two groups.
Conclusions: These electrophysiological characteristics related to the BNP level suggest that the atrial repolarization may be affected by a latent ventricular dysfunction.

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Although several studies have demonstrated that cardiac diastolic function is impaired but cardiac systolic function is preserved with aging, no large-scale analysis of cardiac function by echocardiography in subjects aged ≥ 90 years exists. The purpose of the present study was to elucidate the cardiac structure and function in the oldest old in order to assess the effect of aging on cardiac function. Echocardiographic examination was performed in 1793 subjects who were in their fifties, sixties, seventies, eighties, and nineties. Left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. LV ejection fraction (LVEF) was calculated and used as the parameter representing LV systolic function. LV diastolic function was assessed using the peak velocity of early rapid filling (E velocity) and the peak velocity of atrial contraction (A velocity), and the ratio of E to A (E/A) by the transmitral flow. The Tei index, which reflects both LV diastolic and systolic function, was also calculated. The E/A decreased progressively with aging, and demonstrated the closest correlation with age among all the indexes of cardiac function (r = -0.44, P < 0.001). In contrast, LVEF and the Tei index demonstrated a very weak correlation with age (r = -0.13, P < 0.001 and r = 0.16, P < 0.001, respectively). The mean value for LVEF remained normal with aging in all age strata (50s: 71 ± 8%, 60s: 71 ± 8%, 70s: 70 ± 9%, and 80s: 71 ± 10%), but decreased significantly in subjects in their 90s (66 ± 10%, P < 0.001). In addition, the mean value for the Tei index also remained normal with aging in subjects in their 50s (0.35 ± 0.10), 60s (0.38 ± 0.14), 70s (0.38 ± 0.12), and 80s (0.39 ± 0.15), but showed an abnormal value in subjects in their 90s (0.45 ± 0.12, P < 0.001). In conclusion, both diastolic dysfunction and systolic dysfunction with advancing age were observed in the oldest old aged ≥ 90 years. The age-related impairment of systolic function as well as diastolic function should be considered when echocardiography is used to evaluate the causes of heart failure in the oldest old.

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The aim of this study was to elucidate the cardiac function in bed-bound patients following cerebrovascular accidents. In accord with the criteria for activities of daily living (ADL) of the Japanese Ministry of Health, Labour and Welfare, 51 age-matched poststroke patients without heart disease were classified into 3 groups: rank A (house-bound) (n = 16, age, 85 ± 6 years), rank B (chair-bound) (n = 16, age, 84 ± 8 years), and rank C (bed-bound) (n = 19, age, 85 ± 9 years). Using echocardiography, the left ventricular (LV) diastolic function was assessed by the ratio of early filling (E) and atrial contraction (A) transmitral flow velocities (E/A) of LV inflow. LV systolic function was assessed by LV ejection fraction (LVEF), and the Tei index was also measured to assess both LV systolic and diastolic function. No difference was observed in the E/A and LVEF among the 3 groups. The Tei index was higher in rank C (0.56 ± 0.17) than in rank A (0.39 ± 0.06) and rank B (0.48 ± 0.17), and a statistically significant difference was observed between rank A and rank C (P < 0.05). Serum albumin and blood hemoglobin were significantly lower in rank C (3.1 ± 0.4 and 10.6 ± 1.8 g/dL) than in rank A (4.1 ± 0.3 and 12.4 ± 1.2 g/dL) (P < 0.001 and P < 0.05, respectively). These results indicate that latent cardiac dysfunction and poor nutritional status may exist in bed-bound patients (rank C) following cerebrovascular accidents. The Tei index may be a useful index of cardiac dysfunction in bed-bound patients because it is independent of the cardiac loading condition.

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Background: The American College of Physicians (ACP) and the American College of Emergency Physicians (ACEP) recently published practice guidelines and recommendations for evaluation of patients with syncope based on historical, physical, and ECG findings. The objective of the present study was to determine if risk stratification using these practice resources is valid in a series of Japanese patients.
Methods and Results: A total of 912 consecutive patients brought to our emergency department between 1988 and 1997 because of syncope were identified. Follow-up information about mortality was obtained for 707 patients by means of mailed questionnaires and from medical records, and the mortality data were analyzed by the actuarial life-table method. A total of 187 patients who fulfilled the admission criteria according to the ACP guidelines were found to have higher overall and cardiac mortality than the other 520 patients (P < 0.0001), and 153 patients who fulfilled the admission criteria according to the ACEP recommendations also had higher overall and cardiac mortality than the other 554 patients (P < 0.0001).
Conclusions: The recent American practice recommendations can be used for risk stratification of syncope patients in Japan. Historical, physical, and ECG findings available on presentation can be used to stratify the risk of mortality in patients brought to Japanese emergency departments because of syncope.

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Background: Pulmonary arterial hypertension (PAH) has been identified as a life threatening complication of connective tissue disease. However, the association between serum uric acid (UA) levels and long-term outcome in PAH with connective tissue disease has not been evaluated. We therefore assessed whether serum UA levels are related to the mortality of such patients.
Methods and results: We investigated 90 consecutive patients with connective tissue disease who were initially diagnosed with PAH by echocardiography, and assessed the long-term clinical outcome in populations with higher (≥ 4.7 mg/dL) and lower serum UA levels. Kaplan-Meier analysis showed that patients with higher median serum UA values had a significantly worse survival rate for any cause of death (54.5% versus 84.7%, log-rank, P < 0.01) and PAH-related death (72.7% versus 93.4%, log-rank, P < 0.01) than those with low values. Multivariate analysis showed that an elevated serum UA level was an independent predictor for survival (hazard ratio, 1.88, 95% CI [1.24- 2.84], P < 0.01).
Conclusion: Elevated serum UA levels are associated with a poor prognosis and can serve as a prognostic predictor for patients with PAH secondary to connective tissue disease.

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This study tests the hypothesis that peroxisome proliferator activated receptor-γ coactivator 1α (PGC-1α) and the integrity of gap junctions (GJs) were suppressed and the number of apoptotic bodies was increased in remote viable areas of left ventricle following acute myocardial infarction (AMI), which can be reversed by losartan therapy. Open chest surgery was consecutively performed on 32 adult male Sprague-Dawley rats. These rats were classified into 4 groups (n = 8/each group): group I, AMI (by ligation of left coronary artery (LCA) without treatment); group II, AMI with losartan 20 mg/kg/day; group III, sham control (without LAD ligation); and group IV, sham control with losartan 20 mg/kg/day. Echocardiography was performed on day 1 prior to AMI and on day 14 just before the rats were to be sacrificed for cellular and molecular studies. The results showed that mRNA expression of PGC-1α, integrated area (μm²) of clustered connexin43 (Cx43) spots, and Cx43 GJs were substantially down-regulated and the number of apoptotic bodies was markedly increased in nontreated AMI rats compared with healthy control and losartan-treated AMI rats on day 14 following AMI (all values of P < 0.001). Additionally, day14 left ventricular (LV) ejection fraction was significantly lower in nontreated AMI rats than in healthy control and losartan-treated AMI rats (all values of P < 0.0001).
Down-regulation of GJs and PGC-1α gene expression and cellular death were frequently observed in remote viable areas of LV following AMI. Losartan therapy reversed the adverse effects of AMI and preserved LV function.

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Although late stent thrombosis is not uncommon with the use of drug-eluting stents, it is unusual with the use of bare-metal stents (BMS) because stent endothelialization is considered to be completed 4 weeks after the intervention.¹⁾
A 64 year-old male had undergone percutaneous coronary intervention (PCI) for a proximal left anterior descending (LAD) artery lesion with a BMS and excellent angiographic results were obtained. Two hundred mg of ticlopidine was prescribed for one month and 100 mg of aspirin daily was continued. One year after stent implantation, coronary angiography (CAG) showed no restenosis. Ten years and 7 months after stent implantation, he suffered an acute myocardial infarction due to stent thrombosis. Intra-coronary aspiration thrombectomy was successful. To the best of our knowledge, the longest delayed case of BMS thrombosis is 5 years after stent implantation.²⁾ Our report demonstrated evidence of the latest reported case of stent thrombosis with the use of a BMS.

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