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Background: The objective of this study was to investigate whether a distal protection (DP) device can preserve the index of microcirculatory resistance (IMR) after primary percutaneous coronary intervention (PCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI)., Methods and Results: The study group of 36 consecutive patients with anterior STEMI were randomized into 2 groups of primary PCI with or without DP: stenting without DP (non-DP group, n = 17) and with DP (DP group, n = 19). The DP in all cases was Filtrap (Nipro, Japan). Following final coronary angiography after successful PCI, IMR was measured using PressureWire™ Certus (St Jude Medical, USA) at maximal hyperemia. The averaged IMR of the 36 patients with STEMI after primary PCI was 31.6U. The IMR in the DP group was significantly lower than that in the non-DP group (26.6 ± 25.8U vs. 37.2 ± 23.2U, P = 0.03242)., Conclusions: DP as an adjunctive therapy of PCI for acute anterior STEMI may have beneficial effects on myocardial microcirculation because of preservation of IMR.

Background: Postsystolic shortening is a sensitive maker of myocardial ischemia. The aim of this study was to investigate whether diastolic dyssynchrony imaging is useful for the objective interpretation of dobutamine stress echocardiography., Methods: Postsystolic shortening was detected by using tissue Doppler imaging displacement timing analysis: the delays of the displacement peaks from end-systole were displayed from green to red, depending on the preset time window on diastolic dyssynchrony imaging. Dobutamine stress echocardiography was performed in 59 patients with suspected coronary artery disease who presented with normal left ventricular wall motion at rest (age range, 44-83 years; 20 women). The optimal time windows for diastolic dyssynchrony imaging at rest and at peak dobutamine were determined by receiver operating characteristic analysis by measuring the delays of the displacement peaks in the left ventricular myocardial segments. Diastolic dyssynchrony imaging was performed using time windows of 100 msec at rest and 80 msec at peak dobutamine. The diagnostic power of diastolic dyssynchrony imaging was assessed with quantitative coronary angiography as the gold standard (>50% diameter stenosis) both at rest and at peak dobutamine., Results: Coronary artery disease was present in 37 patients (63%). Diastolic dyssynchrony imaging at peak dobutamine predicted the presence of coronary artery disease with sensitivity of 89%, specificity of 77%, predictive accuracy of 85%, positive predictive value of 79%, and negative predictive value of 81%. Diastolic dyssynchrony imaging at rest yielded sensitivity of 62%, specificity of 73%, predictive accuracy of 66%, positive predictive value of 79%, and negative predictive value of 53%. Importantly, diastolic dyssynchrony imaging demonstrated excellent intraindividual (97%) and interindividual (90%) agreement., Conclusion: Diastolic dyssynchrony imaging is useful in the objective interpretation of dobutamine stress echocardiography., (Copyright © 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Long-term clinical outcomes after femoropopliteal (FP) stenting with nitinol stents have not yet been clear. We investigated the mid-term efficacy of FP stenting with nitinol stents., Methods: This study was a multicenter retrospective study. From April 2004 to December 2008, 511 consecutive patients (639 limbs; mean age 71 +/- 7 years; 71% male) who underwent successful FP stenting with nitinol stents for de novo lesions were retrospectively selected and analyzed in this multicenter study. All patients had a minimum follow-up of 6 months. Restenosis was defined as >2.4 of peak systolic velocity ratio by duplex or >50% stenosis by angiogram. Primary patency was defined as treated vessels without restenosis and repeat revascularization. Secondary patency was defined as target vessels that become totally occluded and are reopened by repeat revascularization., Results: Sixty-one percent of the patients had diabetes, 76% were claudicant, and 20% were on hemodialysis. Mean lesion length was 151 +/- 75 mm. Mean follow-up period was 22 +/- 11 months. Primary patency was 79.8%, 66.7%, and 63.1%, and secondary patency was 90.4%, 87.3%, and 86.2% at 1, 3, and 5 years, respectively. During the follow-up period, 53 patients (10%) died. Of them, cardiovascular death was 38% and stent fracture had occurred in 14%. On multivariate analysis by Cox proportional hazard ratio, cilostazol administration (hazard ratio [HR], 0.52;P < .0001), stent fracture (HR, 1.6; P = .03), hemodialysis (HR, 1.7; P = .01), and Trans Atlantic Inter-Society Consensus (TASC) II class C/D (HR, 2.4; P < .0001) were the independent predictors of primary patency after successful FP stenting., Conclusion: Clinical efficacy of nitinol stent implantation for FP disease was favorable for up to 5 years.

Background: Few studies have serially monitored the change of coronary plaque after statin therapy using multiple plaque imaging modalities., Methods and Results: A prospective open-label trial was performed to assess coronary plaque regression and stabilization following 52 weeks of pitavastatin treatment (2 mg/day). Coronary segments that included the most diseased plaque of 90 patients determined on angioscopy were analyzed using intravascular ultrasound (IVUS). The yellow grade of each plaque of 46 patients who had matched angioscopy and IVUS data was evaluated on angioscopy. Low-density lipoprotein-cholesterol (LDL-C) was reduced 34.5% (145.0+/-24.0 mg/dl to 93.6+/-22.6 mg/dl, P<0.001), and high-density lipoprotein cholesterol increased 17.8% (44.9+/-11.1 mg/dl to 51.9+/-11.7 mg/dl, P<0.001). Yellow grade decreased (2.9+/-0.8 to 2.6+/-0.7, P=0.040) during 52 weeks. The reduction of yellow grade was not correlated with the LDL-C level at 52 weeks or its change. The change of yellow grade was inversely correlated with maximum yellow grade at baseline. Percent atheroma volume on IVUS did not change during 52 weeks, but its change for 52 weeks was significantly correlated with LDL-C level at 52 weeks (Spearman's rank correlation coefficient 0.312, P=0.035)., Conclusions: Fixed dose pitavastatin stabilized vulnerable coronary plaques by the reduction of yellow grade without significant reduction of plaque volume. The stabilization and regression of atherosclerotic plaques by statin may differ, but both nonetheless contribute to the reduction of cardiovascular events (UMIN Clinical Trials Registry UMIN000001107).

Objective: We investigated the role of the angiosome concept in endovascular therapy (EVT) for limb salvage., Background: The angiosome concept is clinically useful in bypass surgery for critical limbs ischemia (CLI). However, comparison with direct and indirect flow to the site of ulceration based on angiosome concept regarding freedom from amputation has not been systematically studied for the patient with CLI undergoing EVT., Methods: We analyzed 203 limbs in 177 consecutive patients (male = 127, age = 70 +/- 11 years) with ischemic ulceration that was Rutherford 5 or 6 (5 in 145 limbs and 6 in 58 limbs; pretreatment ankle-brachial index = 0.74 +/- 0.27), who underwent EVT alone without bypass surgery. We classified these patients into direct and indirect groups depending on whether feeding artery flow to the site of ulceration was successfully acquired or not acquired based on the angiosome concept. Freedom from amputation was compared between the direct and the indirect groups by Kaplan-Meier analysis., Results: The overall limb salvage rate was 82% (167/203). Skin perfusion pressure was significantly higher in the direct group (67 +/- 25 mm Hg) than in the indirect group (41 +/- 20 mm Hg, P = 0.002). The limb salvage rate was also significantly (P = 0.03) higher in the direct group (86%) than in the indirect group (69%) for up to 4 years after the procedure. The number of vessels with run-off flow did not influence the limb salvage rate in either the direct group (P = 0.84) or the indirect group (P = 0.90)., Conclusion: Acquiring direct flow based on the angiosome concept is important for limb salvage by EVT in patients with CLI., (Copyright 2010 Wiley-Liss, Inc.)

Background: Although microvascular dysfunction following percutaneous coronary intervention (PCI) can be evaluated with the index of microcirculatory resistance (IMR), no method of treatment has been established. We hypothesized that intracoronary administration of nicorandil can improve IMR after successful primary PCI in patients with ST-segment elevation myocardial infarction (STEMI)., Methods and Results: In 40 patients with first STEMI after successful primary PCI, IMR was measured using PressureWire(TM) Certus (St. Jude Medical, MN, USA). In 20 of the patients (Group N), IMR was measured at baseline and after intracoronary nicorandil (2 mg/10 ml). In the other 20 patients (Control), IMR was measured at baseline, after intracoronary saline (10 ml) and after intracoronary nicorandil (2 mg/10 ml). In Group N, IMR significantly decreased after intracoronary nicorandil (median IMR, 27.7-18.7 U, P<0.0001). In the Control group, IMR did not change after saline administration (median IMR, 24.3-23.8 U, P=0.8193), but was significantly decreased after intracoronary nicorandil (median IMR, 23.8-14.9 U, P<0.0001). Next, all 40 patients were divided into subgroups by tertile of baseline IMR. In those with intermediate to high IMR (baseline IMR > or =21), intracoronary nicorandil significantly decreased IMR, although it did not change IMR in those with low IMR (baseline IMR <21)., Conclusions: High IMR levels in patients with STEMI after successful primary PCI can be improved by intracoronary administration of nicorandil.

Objectives: The aim of this study was to study the long-term clinical effects of routine angiographic follow-up and related reintervention after drug-eluting stenting., Background: Prior stent trials have shown that protocol-mandated angiographic follow-up increases repeat interventions compared with clinical follow-up alone. The long-term clinical impact of this practice is unknown., Methods: Long-term outcomes of patients assigned to routine angiographic follow-up in 3 large-scale TAXUS (Boston Scientific, Natick, Massachusetts) trials were compared with patients assigned to clinical follow-up alone, in a propensity score-adjusted patient-level meta-analysis. Outcomes were also compared in patients with treated versus untreated nonischemic intermediate lesions (quantitative angiographic stenosis between >or=40% and <70%) detected at angiographic follow-up., Results: Target lesion revascularization (TLR) rates at 5 years were significantly higher in the angiographic compared with clinical follow-up cohort (18.3% vs. 11.1%, p < 0.001). This was due to more frequent treatment of intermediate lesions, but there was no associated reduction in rates of cardiac death or myocardial infarction (8.9% vs. 8.8%, p = 0.93). Of patients with nonischemic intermediate lesions, 17% who were not revascularized at the time of angiographic follow-up had a subsequent TLR, whereas 7% of patients who had TLR at this follow-up angiogram required additional revascularization during long-term follow-up., Conclusions: A strategy of routine angiographic follow-up increases oculostenotic revascularization of nonischemic intermediate lesions without affecting subsequent rates of cardiac death or myocardial infarction, and TLR was not required in 83% of those lesions. A conservative approach, in which repeat angiography is limited to patients with recurrent ischemia or progressive symptoms, minimizes repeat revascularization of nonischemic intermediate lesions and optimizes long-term event-free survival after drug-eluting stent implantation., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although in clinical practice endovascular therapy (EVT) with a nitinol stent for femoro-popliteal artery (FPA) lesions has been widely applied for TASC II A/B lesions, primary patency beyond 2 years remains unknown, as do the factors associated with restenosis., Methods and Results: A prospectively maintained database that included 189 limbs treated with nitinol stents for de novo TASC II A/B FPA lesions was retrospectively analyzed. The outcomes were overall primary and secondary patency during the follow-up period and predictors associated with restenosis. Primary patency overall with nitinol stents was 84%, 82%, 80%, 80% and secondary patency was 96%, 93%, 90%, 90% at 12, 24, 36, 48 months, respectively. Primary patency was not statistically different between the 2 types of nitinol stents (Luminexx vs S.M.A.R.T. Control. stent, P=0.37) during follow-up period. From the multivariate analysis, administration of cilostazol was the strongest independent factor associated with restenosis (P=0.0012)., Conclusions: Nitinol stent implantation for TASC II A/B FPA lesions is suitable and durable in sustaining freedom from restenosis through 4 years of follow-up.

Objectives: The aim of this study was to explore the determinants of neointimal coverage after sirolimus-eluting stent (SES)., Background: Although SES has significantly reduced in-stent restenosis by inhibiting neointimal hyperplasia, insufficient neointimal coverage after stenting might result in adverse outcomes., Methods: We evaluated 28 SES lesions with both angioscopy and intravascular ultrasound (IVUS). Quantitative assessments of the lesions and stent expansion were performed by IVUS at the time of stent implantation, and degree of neointimal coverage was judged by angioscopy at follow-up (11 +/- 6 months) whether the stent struts were embedded by the neointima ("complete/incomplete" neointimal coverage)., Results: "Complete" coverage was identified in 10 (36%), and "incomplete" coverage was identified in 18 (64%). Time from the stenting to angioscopy as well as the lesion and procedural characteristics were similar between the complete and incomplete coverage groups. The IVUS parameters were also similar, except for the final minimum stent cross-sectional area (CSA) (7.0 +/- 1.8 mm(2) in complete vs. 5.3 +/- 1.9 mm(2) in incomplete, p = 0.02) and lumen CSA at the distal reference site (6.1 +/- 1.4 mm(2) in complete vs. 4.9 +/- 1.2 mm(2) in incomplete, p = 0.02). The ratio of the stent area to the vessel area was significantly larger in the complete coverage than in the incomplete coverage group (0.52 +/- 0.11 vs. 0.39 +/- 0.09, p = 0.002)., Conclusions: Adequate stent sizing relative to the vessel size might contribute to the angioscopically complete neointimal coverage after SES implantation.

Objectives: We investigated the time course of stent patency in the femoro-popliteal artery for as long as 4 years., Background: Stent fracture has been related to poor 2-year patency in the femoro-popliteal artery., Methods: We studied 239 consecutive patients who underwent provisional de novo stenting with nitinol stents for 333 limbs (Luminexx stent [C. R. Bard, Inc., Murray Hill, New Jersey] in 91 limbs; Smart stent [Cordis Corp., Miami Lakes, Florida] in 242 limbs) from April 2004 to December 2007. Stent fracture was determined by X-ray with multiple projections. Patency was assessed by duplex ultrasonography as peak systolic velocity ratio <2.4 or by angiography (% diameter stenosis <50%). Primary patency in those with and without stent fracture at follow-up was assessed along with factors influencing stent fracture., Results: Primary patency was 81%, 74%, 68%, and 65% at 1, 2, 3, and 4 years, respectively. Stent fracture occurred in 14% (78 of 544) per stent and 17% (55 of 333) per limbs. Stent fracture was significantly associated with multiple stent deployments (with fracture = 2.3 +/- 0.9 stents vs. without fracture = 1.5 +/- 0.7 stents, p < 0.001) and long lesions (with fracture = 208 +/- 84 mm vs. without fracture = 121 +/- 79 mm, p < 0.001). Primary patency was 68% with fracture versus 83% without fracture at 1 year, p = 0.03; 65% versus 75% at 2 years, p = 0.05; 61% versus 69% at 3 years, p = 0.06; and 61% versus 65% at 4 years, p = 0.07. Neither type 1 nor type 3 fracture affected patency, although type 2 showed the worst patency., Conclusions: Stent fracture worsened the patency during the first 2 years, but it did not apparently affect patency beyond 2 years. In particular, complete stent separation did not affect patency.

Objectives: We angioscopically compared paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) to explore differences in arterial healing., Background: Drug-eluting stents may demonstrate different arterial healing processes., Methods: Angioscopy was performed 9 +/- 2 months after 30 PES and 36 SES were implanted initially in the native coronary artery. Heterogeneity of the neointimal coverage (NIC) as well as the dominant grade was examined. Neointimal coverage was defined as follows: grade 0 = fully visible struts; grade 1 = struts bulged into the lumen, but covered; grade 2 = embedded, but translucent struts; grade 3 = invisible struts. Heterogeneity was judged when the NIC grade variation >or=1. Thrombi and yellow plaques (YP) were also explored., Results: In-stent late loss (0.44 +/- 0.44 mm vs. 0.13 +/- 0.33 mm; p < 0.0001) and dominant NIC grade (1.8 +/- 1.1 vs. 1.3 +/- 0.7; p = 0.02) were greater in PES than in SES. Of PES, 48% showed the heterogeneity of 1 grade; 26% showed that of 2 grades. Of SES, 53% showed homogeneous coverage; the remaining SES showed the heterogeneity of 1 grade; and 72% showed dominant grade 1. Thrombi were more common in PES than in SES (43% vs. 19%; p = 0.04). Both stents commonly revealed YP (83% vs. 78%; p = 0.76)., Conclusions: NIC was more heterogeneous in PES, associated with a higher incidence of thrombi. Homogeneous NIC may be an important factor for competent arterial healing.

Background: The aim of this study was to elucidate the time course of atorvastatin-induced changes in vulnerable plaque using angioscopy and intravascular ultrasound (IVUS)., Methods and Results: Fifty-seven hypercholesterolemic patients with coronary artery disease (CAD) were treated with atorvastatin (10-20 mg/day) for 80 weeks and then coronary plaques were evaluated with angioscopy and IVUS. Angioscopic images were classified into 6 grades (0-5) based on yellow color intensity. A 20-mm segment containing angioscopically-identified yellow plaque was also examined by IVUS to measure atheroma volume. The mean angioscopic grade of 58 yellow plaques significantly decreased from 1.5 (95% confidence interval [CI] 1.2 to 1.8) to 1.1 (95%CI 0.9 to 1.3, P=0.012) at week 28 and 1.2 (95%CI 0.9 to 1.4, P=0.024) at week 80. Mean volume of 30 lesions, including the 58 yellow plaques, significantly reduced -8.3% (95%CI -11.5 to -5.2) at week 28 (P<0.001 for baseline vs week 28) and -17.8% (95%CI -23.9 to -11.8) at week 80 (P<0.001 for baseline vs week 80)., Conclusions: In patients with CAD treated with atorvastatin, serial analysis with angioscopy demonstrated early loss of yellow color in plaques, and IVUS volumetric analysis showed subsequent plaque regression. Both changes possibly indicate reduction of plaque vulnerability in an additive manner.

Background: Post-systolic shortening (PSS) is a sensitive indicator of myocardial ischemia., Methods and Results: We have developed a tissue Doppler imaging technique that portrays PSS, and whether PSS correlates with coronary artery disease (CAD) was investigated in 186 patients presenting with chest pain and normal echocardiograms. Delays of the displacement peaks from end-systole were calculated in the apical views and displayed from green (0 ms) to red (>or=100 ms): detection of diastolic abnormality by dyssynchrony imaging (DADI). CAD was judged positive by DADI when the left ventricular segments were color-coded red. Patients subsequently underwent thallium-201 myocardial perfusion single-photon emission computed tomography (n=150), coronary angiography (CAG, n=74), or both (n=37). CAD(-) was defined as negative scintigraphy test and/or no significant coronary artery stenosis by CAG. In 43 patients (23%), CAD(+) was confirmed by CAG as >75% diameter stenosis. DADI predicted CAD with sensitivity of 60%, specificity of 75%, predictive accuracy of 72%, positive predictive value of 42%, and negative predictive value of 86%. Among 74 patients who underwent CAG, sensitivity was best for the left anterior descending artery., Conclusions: DADI detected the regional diastolic abnormality, which correlated with the presence of CAD in patients presenting with visibly normal wall motion.

Background: Despite the recent development of endovascular therapy (EVT), a high incidence of restenosis remains as an unsolved issue in patients presenting with femoropopliteal lesions. We investigated whether cilostazol reduces restenosis after successful EVT for de novo femoropopliteal lesions., Methods: This study was designed as a prospective, randomized, open-label, blinded end point study in a single institution. Between March 2004 and June 2005, we randomized 127 patients who were successfully treated with EVT for de novo femoropopliteal lesions to receive cilostazol (200 mg/d, n = 63) or ticlopidine (200 mg/d, n = 64) in addition to aspirin (100 mg/d). Antiplatelet medications were started at least 1 week before EVT and were continued until the end of follow-up. Patency was defined by duplex ultrasound imaging with peak systolic velocity ratio >2.4., Results: There were no significant differences in the patients and lesion characteristics. Sixteen patients dropped out of the study protocol, six of whom were withdrawn due to adverse drug effects (cilostazol, n = 5; ticlopidine, n = 1; P = .09). Ten patients died (cilostazol, n = 4; ticlopidine, n = 6; P = .53) during the follow-up period. Patency rates at 12, 24, and 36 months were 87%, 82%, and 73% in the cilostazol group and 65%, 60%, and 51% in ticlopidine group by intention-to-treat analysis (P = .013) and were 87%, 82%, and 73% in the cilostazol group and 64%, 57%, and 48% in the ticlopidine group (P = .0088) by as-treated analysis. Freedom from target lesion revascularization and all adverse events (restenosis, amputation, and death) was significantly higher in cilostazol group than in ticlopidine group (P = .036, P = .031). No acute, subacute, or chronic thrombotic occlusion was encountered, and bleeding complication rates were similar between the two groups., Conclusions: Cilostazol significantly reduces restenosis after EVT in femoropopliteal lesions.

Background: It is unclear whether early initiation of low-dose pravastatin therapy can reduce the occurrence of major adverse cardiac events after acute myocardial infarction (AMI)., Methods and Results: The study group comprised 353 patients with AMI who had plasma total cholesterol levels of 200-250 mg/dl and triglyceride levels <300 mg/dl. The patients were randomly assigned to either receive pravastatin (10 mg/daily, n=176) or not (n=177). The primary endpoint was a composite of death, nonfatal myocardial infarction (MI), unstable angina (UA), stroke, revascularization, and rehospitalization because of other cardiovascular disease. The follow-up period was 9 months. The primary endpoint occurred in 31 patients (17.9%) in the pravastatin group and 55 patients (31.4%) in the non-pravastatin group (relative risk, 0.56; 95% confidence interval, 0.36-0.87). There were no significant differences in the risk of death, nonfatal MI, UA, and stroke between the 2 groups, although the pravastatin group had a lower risk of need for revascularization., Conclusion: For patients with AMI, early and low-dose pravastatin therapy (10 mg/daily) reduces recurrent major adverse cardiac events, mostly the requirement for revascularization.

Recently, an association between minimally elevated cardiac troponin levels and cardiovascular risk in the general population has been reported. However, the prevalence and clinical importance of elevated cardiac troponin T (cTnT) levels remain unclear in patients with histories of myocardial infarction (MI). In this study, 1,807 consecutive patients with ST-segment elevation MIs were prospectively studied (77.1% men; mean age 64.4 years). Venous blood samples were obtained in the chronic stage of MI (28 +/- 7 days after onset), and serum cTnT levels were determined. During the average follow-up of 1,042 days, 84 patients died and 83 had nonfatal reinfarctions. Patients with cTnT levels in the highest quartile (> or = 0.040 ng/ml [n = 353]) had a higher incidence of all-cause death (8.2% vs 5.2%, p = 0.049) and nonfatal reinfarction (8.3% vs 5.1%, p = 0.048) than patients with cTnT levels from the lower 3 quartiles (<0.040 ng/ml [n = 1,064]). Multivariate Cox regression analysis revealed that a minimally elevated cTnT level (> or =0.040 ng/ml) was a significant predictor of all-cause mortality (hazard ratio 1.79, 95% confidence interval 1.10 to 2.90, p <0.02) and nonfatal reinfarction (hazard ratio 1.50, 95% confidence interval 1.13 to 2.20, p <0.03). Subgroup analysis showed that an elevated cTnT level was also a predictor of all-cause mortality and nonfatal reinfarction in patients without heart failure. In conclusion, minimally elevated cTnT levels in the chronic stage of MI predicted long-term adverse clinical outcomes.

Insertion of intracoronary thrombectomy (ICT) devices, as a precedent to percutaneous coronary intervention (PCI), theoretically could have a beneficial effect on the outcome in patients with acute myocardial infarction. To examine whether ICT was associated with a lower 30-day mortality rate in patients with acute myocardial infarction, we studied 3,913 patients who underwent PCI within 24 hours after onset. A total of 990 patients (25.3%) were treated with ICT before PCI. The 30-day mortality rate was lower in the patients receiving ICT than in those without (3.7% vs 6.2%, p = 0.004), but this beneficial effect disappeared after adjustment for baseline characteristics (hazard ratio [HR] 0.658, p = 0.166). We also divided the patients into tertiles according to the Thrombolysis In Myocardial Infarction (TIMI) risk score. After adjustment for baseline characteristics, ICT was associated with a lower 30-day mortality rate in patients from the highest TIMI risk score tertile (HR 0.407, p = 0.029), but not in patients from the lower 2 tertiles. ICT was also an independent predictor of a lower 30-day mortality risk in patients aged > or =70 years (HR 0.239, p = 0.007), patients with diabetes mellitus (HR 0.275, p = 0.039), and those with stent implantation (HR 0.437, p = 0.034). In conclusion, in selected patients with high TIMI risk scores, an age > or =70 years, diabetes mellitus, or stenting, ICT is associated with a lower 30-day mortality rate.

Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease that mostly affects the renal and internal carotid arteries, rarely complicating lower limbs. We report a case of FMD complicating critical limb ischemia due to the obstruction of below the knee arteries, diagnosed and treated with the support of skin perfusion pressure (SPP) measurement. Initial angiogram revealed the anterior tibial artery (ATA) was subtotally occluded showing a "strings of beads" pattern, which is typical of the arteries affected by FMD. SPP guided endovascular therapy was successful for ATA lesions. Intractable rest pain subsequently disappeared and the ulcer was completely healed without amputation.

Adenosine is known as an endogenous cardioprotectant. We previously reported that plasma adenosine levels increase in patients with chronic heart failure (CHF), and that a treatment that further elevates plasma adenosine levels may improve the pathophysiology of CHF. Therefore, we performed a prospective, open-randomized clinical trial to determine whether or not exposure to dipyridamole for 1 year improves CHF pathophysiology compared with conventional treatments. The study enrolled 28 patients (mean+/-SEM: 66+/-4 years of age) attending specialized CHF outpatient clinics with New York Heart Association (NYHA) class II or III, no major complications, and stable CHF status during the most recent 6 months under fixed medications. They were randomized into three groups with or without dipyridamole (Control: n=9; 75 mg/day: n=9; 300 mg/day: n=10) in addition to their original medications and were followed up for 1 year. The other drugs were not altered. Among the enrolled patients, 100%, 4%, 100%, and 79% received angiotensin-converting enzyme inhibitors, aldosterone analogue, loop diuretics, and beta-adrenoceptor blocker, respectively. Fifteen patients suffered from dilated cardiomyopathy, and 7/3/3 patients suffered from ischemic/valvular/hypertensive heart diseases, respectively. Mean blood pressure was comparable among the groups. While the baseline conditions were comparable, we found that echocardiographic ejection fraction (p<0.01 vs. baseline, p<0.01 vs. Control), left ventricular systolic diameter (p<0.05, p<0.05), Specific Activity Scale (SAS) score (p<0.05, p<0.01), maximal oxygen consumption (p<0.05, p<0.05) and plasma B-type natriuretic peptide level (p<0.01, p<0.01) were significantly improved in patients with dipyridamole after 1 year, generally in a dose-dependent manner. Therefore, we suggest that an additional administration of dipyridamole further improves CHF pathophysiology.

A 44-year-old male was admitted to our hospital for dyspnea, associated with severe pulmonary hypertension. The patient fell into a shock state on the next day. Hemodynamic measurements revealed high output heart failure with low peripheral vascular resistance. We suspected shoshin beriberi, a fulminant form of cardiac beriberi, by ruling out other common causes of pulmonary hypertension. The rapid recovery after intravenous thiamine administration and the patient's history of improper diet strongly supported the diagnosis. The present case of shoshin beriberi complicating severe pulmonary hypertension shows that history taking is important in elucidating the etiology and selecting the correct treatment.

Stent fracture has emerged as a new problem in the percutaneous transluminal angioplasty of the superficial femoral artery (SFA). The aim of our study was to delineate the factors influencing nitinol stent fracture in the SFA. Forty consecutive patients with peripheral artery disease who underwent rescue stenting with a nitinol stent (Luminexx, Bard) in the SFA were enrolled between May 2004 and January 2005. Follow-up angiography was performed 13.6+/-1.0 months later to detect stent fracture. Stent fracture occurred in 11 patients (28%). Lesion length>100 mm, the number of stents used, the lesion involving the distal SFA, chronic total occlusion, and walking>5,000 steps per day were more frequently observed in those with stent fracture than in those without fracture. Of these variables, walking>5,000 steps per day was the strongest independent determinant associated with stent fracture by discriminant analysis (p=0.0027). Vigorous exercise adversely affects stent fracture in patients implanted with a nitinol stent in the SFA.

Background: The nature of the vessel lumen following vascular brachytherapy (VBT) has not been extensively explored in the clinical setting., Methods and Results: By using angioscopy, 33 stents treated with percutaneous balloon angioplasty with or without VBT for in-stent restenosis after 8.9 +/- 2.1 months of the treatment were followed (VBT =14 lesions; control =19 lesions). Neointimal coverage, stent attachment, and the presence of red or white thrombi were factors that were assessed. The majority of the stents (74%) were fully covered with non-transparent neointima in the control group. In contrast, stent struts were clearly seen in 57% lesions with VBT. The absence of neointima with glittering stent struts were only seen in 29% of lesions in VBT (p = 0.03). Incomplete stent attachment was not detected in the controls, whereas 14% were in VBT (p = 0.17). Red thrombi were observed in 14% with VBT and in 16% in controls, which showed that there was a similar incidence regardless of the treatment. Neither exposure of stent struts (p = 0.5) nor incomplete stent attachment (p = 1.0) was related to thrombi., Conclusions: The exposure of stent struts and incomplete stent attachment were occasionally observed by angioscopy even 9 months after VBT for the treatment of in-stent restenosis.

Objectives: The goal of this study was to use angioscopy to investigate the amount of neointimal coverage after sirolimus-eluting stent (SES) implantation., Background: Sirolimus-eluting stents reduce intimal hyperplasia., Methods: We used angioscopy to evaluate 37 consecutive stented coronary artery lesions (15 SES and 22 bare-metal stents [BMS]) in 25 patients (18 men, 7 women) at 3 to 6 months after stent implantation. Angioscopic evaluation focused on: 1) neointimal coverage of stent struts, and 2) the existence of thrombi. The degree of neointimal coverage was classified as grade 0 when there was no neointimal coverage (similar to immediately after the implantation); grade 1 when stent struts bulged into the lumen, but were covered and still translucently visible; grade 2 when stent struts were visible but not clearly seen (not translucent); and grade 3 when stent struts were not visible because they were embedded in the neointima., Results: Thrombi were identified in eight stented segments, tended to be more common with SES (p = 0.14), but were not seen on angiography. Three of the 15 SES (20%) had grade 0 neointimal coverage, and only 2 SES (13.3%) had complete coverage (grades 2/3). In contrast, all 22 BMS showed complete intimal coverage (grades 2/3). Thrombi were more common in stents with incomplete neointimal coverage (p = 0.09)., Conclusions: The SES had incomplete neointimal coverage three to six months after implantation, and this was associated with subclinical thrombus formation.

Background: The hospital stay after acute myocardial infarction (AMI) is still extremely long in Japan and does not correspond with disease severity. The purpose of the present study was to identify a subgroup of AMI patients suitable for early discharge., Methods and Results: A total of 3,739 AMI patients treated with percutaneous coronary intervention (PCI) within 24 h after onset, who enrolled Osaka Acute Coronary Insufficiency Study between April 1998 and March 2004, were studied. Patients showing no complications within the first 7 days (n=1,786) were considered to be eligible for early discharge. In these patients, multivariate logistic regression analysis selected prior myocardial infarction, left anterior descending coronary artery disease and failed PCI as independent predictors of major complications from day 8 to discharge. Patients without any predictor had significant lower rates of major complications from day 8 to 6 months after discharge than those with 1 or more predictors. Furthermore, in the present study there were no deaths in patients without any predictors., Conclusion: Patients who either do not have serious complications during the first 7 days or any predictor are at very low risk of major complications from day 8 to 6 months after discharge. These carefully selected patients may be suitable for early (day 8) hospital discharge after AMI.

Background: Although percutaneous transluminal angioplasty (PTA) is being widely used for the treatment of stenosis of peripheral arteries, the high in-stent restenosis rate (50-60%) in the femoropopliteal artery still remains an unsolved issue. Cilostazol is a unique antiplatelet drug that has vasodilatory effects and inhibits smooth muscle cell proliferation., Methods and Results: A total of 141 consecutive patients scheduled for PTA in the femoropopliteal artery between September 1999 and April 2004 were retrospectively analyzed for the use of cilostazol. Target lesion revascularization (TLR) was defined as repeated PTA in patients who had a recurrence of symptoms with diameter stenosis >50% by angiography. Patient and lesion characteristics were similar between the cilostazol (+) and cilostazol (-) groups. Use of other medications was similar between the groups, except for ticlopidine, which was more frequently used in the cilostazol (-) than in the cilostazol (+) group (15% vs 61%, p<0.01). TLR was significantly reduced in the cilostazol (+) group (12% [8/68] vs 32% [23/73], p<0.01)., Conclusions: Although this study was retrospective and nonrandomized, the results suggest that cilostazol reduces TLR after PTA in the femoropopliteal artery.

Background: Although the elevation of circulating plasma matrix metalloproteinase (MMP)-9 levels in patients with acute myocardial infarction (AMI) has been documented, the origin of MMP-9 remains unclear., Methods and Results: Plasma MMP-9 levels in both the peripheral circulation and coronary arteries were measured in patients with AMI (n=23) and with stable angina pectoris (SAP, n=10) during percutaneous coronary intervention (PCI) with a distal protection device. Blood samples were collected from the femoral artery (FA) and the coronary artery before (Initial) and after (Second) dilation of the culprit lesion. Coronary sinus blood samples were obtained immediately after PCI (n=7). Coronary artery plaque fragments were aspirated in patients with AMI (n=20) and compared with those from patients with SAP who underwent directional atherectomy (n=10). MMP-9 levels in Initial and Second were significantly higher in patients with AMI than in patients with SAP (p<0.01). In AMI patients MMP-9 levels were significantly higher in Initial than in the FA (p<0.05), and were further increased in Second (p<0.0001), whereas those in the coronary sinus were similar to the FA. Immunohistochemistry revealed augmented MMP-9 expression in the coronary artery plaque fragments from AMI patients., Conclusions: MMP-9 is mainly released into the coronary circulation from the coronary artery plaque in patients with AMI.

Background: Cessation of smoking after a cardiovascular event has been shown in Western countries to have a beneficial effect on clinical events during long-term follow-up. However, knowledge of the effect of smoking status after acute myocardial infarction (AMI) on the long-term mortality based on a large-scale sample is still limited in Japan., Methods and Results: In the present study 2,579 AMI patients were enrolled in the Osaka Acute Coronary Insufficiency Study (OACIS) between April 1998 and March 2003. Smoking status was assessed at baseline and 3 months after hospital discharge by mailed questionnaire. Patients were divided into nonsmokers (n=823), former smokers (those who had stopped smoking before AMI onset, n=332), quitters (those who stopped smoking after AMI onset, n=1,056), and persistent smokers (those who smoked before and after AMI, n=368). Quitters had lower long-term mortality rates than persistent smokers (3.0% vs 5.2%; log rank, p=0.032). Multivariate Cox regression analysis revealed that smoking cessation was independently associated with a reduction in risk of long-term mortality (hazard ratio, 0.39; 95% confidence interval, 0.20-0.77)., Conclusions: Patients who continue to smoke after AMI are at greater risk for death than patients who quit smoking. Cessation of smoking benefits the long-term prognosis in patients with AMI.

Plaque characterization by intravascular ultrasound (IVUS) before percutaneous coronary intervention (PCI) was evaluated in 81 consecutive patients with acute myocardial infarction (AMI) to establish if IVUS can predict the occurrence of the 'no-reflow' phenomenon. Angiographic no-reflow was defined as TIMI flow grade 1 or 2 without any mechanical obstruction in the epicardial artery. Patients were divided into 2 groups according to the post-PCI angiograms: normal flow (group R, n=60) and no-reflow (group NR, n=21). Although the incidence of either soft or noncalcified plaque was not statistically different between the groups, positive vessel remodeling was more frequent in group NR than in group R (57.1% vs 31.6%, p<0.05). Lipid core was also more frequently found in group NR than in group R (61.9% vs 25.0%, p<0.01). Positively remodeled vessels with lipid-rich plaques as characterized by IVUS before PCI predicted the occurrence of angiographic no reflow with a sensitivity of 43% and a specificity of 60%.

Little is known about the alterations of the vascular surface after radiation therapy for in-stent restenosis in humans, even though animal experiments suggest that delayed healing of the neointima is a cause of late thrombosis. Coronary angioscopy, together with coronary angiography, was performed at 3 months follow-up of 7 patients with in-stent restenosis who underwent beta-radiation therapy. Minimal lesion diameter (MLD) of the lesion increased from 1.00+/-0.30 mm (immediately before) to 2.44+/-0.39 mm (immediately after) and the MLD was well maintained 3 months later (2.34+/-0.62 mm) without any cases of restenosis. In 5 patients, the intima was so thin that some stent struts could be seen through it on angioscopy and in 2 of those, the intima over the stent had disappeared and 1 patient showed ulceration of the vascular wall beneath the stent. After intracoronary radiation therapy, the intima can become so thin that some stent struts are exposed to the lumen, which may be related to the occurrence of late thrombosis. Accordingly, patients who are treated with intracoronary radiation therapy may need long-term antiplatelet therapy.

Background: No-reflow associated with direct angioplasty (PCI) of patients with acute coronary syndromes (ACS) is associated with unfavorable results., Methods and Results: We used a new thrombectomy device to treat 51 lesions in 48 consecutive ACS patients (40 male and 8 female; mean age 63 years) and conducted a microscopic analysis of aspirates and blood samples retrieved from the culprit coronary artery. The first aspirate was collected before PCI and the second was collected separately after percutaneous transluminal coronary angioplasty or stenting, including samples from the no-reflow lumen. Light microscopy showed that the materials obtained from the pre-PCI aspiration consisted of thrombus in 37.5%, thrombus and atheroma in 35.0%, and atheromatous plaque in 27.5%. The materials collected from the post-PCI aspiration were thrombus in 8.3%, thrombus and atheroma in 41.7%, and atheromatous plaque in 50.0%. We then compared the 9 lesions (19.1%) with no-reflow to those without no-reflow. There was no difference in the pre-PCI aspirates. However, after PCI, there was more atheromatous plaque retrieved from patients with no-reflow (P<0.001) as well as significantly more platelet and fibrin complex, macrophages, and cholesterol crystals in the blood aspirated from no-reflow cases. Aspiration of these elements improved the no-reflow in 7 of 9 lesions to TIMI-3 flow., Conclusions: No-reflow after angioplasty may be caused by gruel that formed from an atheroma attributable to mechanical plaque disruption during intervention.

Radiolucent findings of coronary angiogram are believed to usually represent intracoronary thrombus, but in the present case, were atheromatous plaque with a large lipid core. A 62-year-old man who suffered from an inferior acute myocardial infarction was admitted to hospital 6 h after onset. The first cine angiograms showed TIMI-1 flow in the distal-portion of the right coronary artery, so thrombectomy was initially carried out and TIMI-2 flow achieved. However, the radiolucent lesion did not disappear and so adjunctive mechanical dilatation of the lesion was prformed, which resulted in 'no-reflow' (TIMI-0). Finally, aspiration of the material from the stagnated lesion was attempted and immediately obtained TIMI-3 flow. The retrieved materials were macrophages (foam cells) and many cholesterol crystals, both of which are considered to be atheromatous gruel. Therefore, the sudden flow reduction following percutaneous transluminal coronary angioplasty was caused by mechanical disruption of an atheromatous plaque with a large lipid core.

Objective: To explore the association between multi-dimensional aspects of hostility and coronary heart disease among middle-aged urban Japanese., Subjects and Methods: We conducted a case-control study. Cases were consecutive patients with acute coronary syndrome admitted to a hospital in Japan. Fifty-three patients (45 men and 8 women) aged 35 to 65 were enrolled. For each case, two sex and age (+/-2 years) matched controls were recruited from among participants in a health check-up program at a health promotion center located in the same area as the hospital. Two questionnaires, both with four components, were used to measure hostility and coping with anger: the one was for anger, hostility, physical aggression and verbal aggression, and the other for aggression, social inhibition, guilt, and controlled affect., Results: The scores of all components from two questionnaires were higher for cases than controls, but the differences were not significant. Multivariate analysis showed that anger, fat intake, alcohol consumption and house size were significantly associated with the etiology of acute coronary syndrome., Conclusion: Anger, lifestyle, and socioeconomic status play important roles for the etiology of coronary heart disease in middle-aged urban Japanese.

The left ventricle's morphological adaptation to high blood pressure is classified into 4 patterns based on mass and wall thickness. The geometric changes caused by maladaptation to pressure overload possibly relate to progression of contractile dysfunction with abnormal energy metabolism. The present study assessed whether the geometric adaptation of the left ventricle (LV) to high blood pressure relates to changes in myocardial energy metabolism, especially free fatty acid (FFA) utilization. Thirty-five patients with essential hypertension underwent echocardiography and dual isotopes myocardial scintigraphy using iodine-123 labeled 15-p-iodophenyl-3-(R,S)-methylpentadecanoic acid (BMIPP, an analogue of a FFA) and thallium-201 (Tl-201). Systolic (endocardial fractional shortening; %FS) and diastolic indices (the ratio of early to atrial filling waves; E/A) of LV function were also assessed. Quantitative myocardial BMIPP uptake was evaluated by the BMIPP/TI-201 myocardial uptake ratio (B/T). The subjects were divided into 4 groups based on LV mass and wall thickness: (1) concentric hypertrophy (CH), (2) eccentric hypertrophy (EH), (3) concentric remodeling (CR), and (4) normal geometry (N). The %FS was lower in the EH group than in the other groups. The mitral E/A ratio in the CH group was lowest. B/T was significantly decreased in the EH group compared with the N group (p < 0.05). B/T correlated with the mitral E/A ratio significantly (p < 0.05, r = 0.42), whereas there was no relationship between %FS and B/T. These results indicate that the geometric changes occurring in hypertensive hearts strongly correlate with alternations in cardiac function and with abnormal myocardial FFA metabolism, and that the latter is associated with diastolic abnormality, but not with systolic function.

The present study seeks to estimate the difference between coronary zero flow pressure (Pzf) by analysis of the baseline pressure-flow relationship and the Pzf calculated during a long diastole in humans. Although Pzf is likely to provide meaningful information about the characteristics of coronary circulation, there are no available data on Pzf in humans because Pzf is overestimated when it is calculated during normal cardiac cycles. Actual Pzf was determined in 15 subjects by analyzing the coronary pressure-flow relationship during a long cardiac cycle induced by an intracoronary adenosine triphosphate (ATP) infusion, and it was compared with the Pzf calculated during a normal cardiac cycle in order to estimate the difference. Pzf calculated during a normal cardiac cycle was 47 +/- 15 mmHg, which decreased to 36 +/- 9mmHg after intracoronary administration of ATP (0.05 mg) whereas actual Pzf was 21 +/- 7 mmHg. Pzf calculated in a pressure-flow relationship during a normal cardiac cycle under vasodilation correlated well with that during a long diastole (r = 0.75, p < 0.01), although it was 15 +/- 6 mmHg greater than the actual Pzf. It was concluded that Pzf during a normal cardiac cycle could be used to anticipate Pzf.

The RADIUS coronary stent featuring a multisegmented slotted tube design and self-expanding nitinol delivery system has a high radial force and flexibility, uniform expansion, and contours to the shape of the vessel. Successful stent deployment was achieved in 104 stable angina patients (106 lesions; 44% LAD, 19% circumflex, and 37% RCA). Mean minimal lumen diameter (MLD) increased from 0.77 +/- 0.46 mm to 2.88 +/- 0.61 mm and mean percent diameter stenosis (% DS) decreased from 73 +/- 14% to 6 +/- 13% immediately after the procedure. At 6-month follow-up, two patients (2%) underwent urgent target revascularization, and cerebral bleeding occurred in one patient (1%). Angiographic follow-up was performed in 94 lesions (89%) and mean MLD and mean % DS were 2.08 +/- 0.92 mm and 30% +/- 24%, respectively. Stent restenosis (>50% diameter stenosis at follow-up) was observed in 16 (17%) of all lesions. The high success rate for stent deployment, low incidence of major adverse cardiac event, and lower restenosis rate after stent implantation indicate that the RADIUS stent is useful for coronary intervention.

Background: Recently, it has been reported that the luminal diameter shows phasic changes after stenting: the progression of luminal narrowing followed by its regression. To elucidate the mechanisms involved in the phasic changes in luminal diameter after stenting, we examined the changes in neointimal thickness and the appearance of neointima by a series of angiographic and angioscopic observations for 3 years after stent implantation., Methods and Results: In 12 patients who received a Wiktor coronary stent, serial angiographic and angioscopic examinations were performed immediately, 2 to 4 weeks, 3 months, 6 months, and 3 years after the stenting without repetition of angioplasty. Neointimal thickness was determined by angiography as the difference between stent and luminal diameters. The angioscopic appearance of neointima over the stent was classified as transparent or nontransparent according to the visibility of the majority of the stent. Neointimal thickness increased significantly at 3 months (0.75+/-0.32 mm) without further changes at 6 months (0.74+/-0.32 mm). Thereafter, however, it decreased significantly over 3 years (0.51+/-0.26 mm). The angioscopic appearance was classified as transparent in 8 patients (100) immediately after stenting, 6 patients (100%) at 2 to 4 weeks, 2 patients (17%) at 3 months, 2 patients (20%) at 6 months, and 7 patients (58%) at 3 years., Conclusions: The neointima became thick and nontransparent until 6 months and then became thin and transparent by 3 years. We conclude that neointimal remodeling exists after stenting and plays a major role in the alteration of coronary luminal diameter after stenting.

Adenosine triphosphate (ATP) is reported to be released mainly from presynaptic vesicles and cardiomyocytes. The released ATP, which can be degraded to adenosine, may cause coronary vasodilation. However, there is no clear evidence that ATP is degraded to adenosine and causes coronary vasodilation in humans. The present study was undertaken to test whether intracoronary administration of ATP increases myocardial adenosine levels and coronary blood flow. In 11 patients, 3 doses of ATP (0.1, 0.2, and 0.4 mg) were injected into the left anterior descending coronary artery. The velocity of coronary blood flow was measured by Doppler flow probe, and the adenosine concentration in the coronary sinus blood was measured. We also continuously infused ATP (0.2 mg/min) for 1 min in another 10 patients. Coronary blood flow increased dose dependently soon after injection of ATP. Coronary arteriovenous differences in adenosine concentration increased [from 21 +/- 15 to 178 +/- 15 pmol/ml (p < 0.05) 10 sec after the injection of ATP (0.4 mg)] and there were marked reductions in both aortic blood pressure and heart rate. The adenosine levels returned to baseline 20 sec after the injection of ATP, and aortic blood pressure and heart rate also recovered, although coronary blood flow remained increased. Furthermore, continuous infusion of ATP for 1 min increased coronary blood flow velocity and coronary arteriovenous differences in adenosine concentration from 25 +/- 14 to 71 +/- 13 pmol/ml (p < 0.05) in 10 patients. These results indicate that intracoronary administration of ATP immediately increases coronary blood flow and the adenosine concentration of coronary venous blood, which returns to the baseline level thereafter. The differences in the time courses of increases in coronary venous adenosine levels and coronary blood flow after ATP injections suggest that vasodilatory mechanisms other than adenosine, eg, nitric oxide and prostaglandins, may also be involved in the ATP-induced coronary vasodilation. ATP may be used as a cardioprotective agent as well as adenosine.

Improvement in regional wall motion after acute myocardial infarction has been described up to 2 to 3 weeks after the acute event despite restoration of blood flow by early successful reperfusion therapy. The prospective identification of potentially reversible ventricular dysfunction caused by stunned myocardium has significant clinical implications. Twenty-seven patients with acute myocardial infarction underwent myocardial contrast echocardiography (MCE) before, immediately after, and 4 weeks after successful reperfusion therapy. MCE was performed by imaging a parasternal short-axis view during intracoronary arterial injection of 2 ml sonicated ioxaglate (Hexabrix-320). The contrast defect area and contrast-filled area before reperfusion were defined as the risk area and noninfarct area, respectively. The normalized gray level was defined as the ratio of the gray level in the risk area/gray level in the noninfarct area. In 21 patients, wall motion was akinetic or dyskinetic immediately after reperfusion, and 10 of 21 patients in whom wall motion recovered during the chronic stage were defined as patients with stunned myocardium. In patients who showed asynergic wall motion immediately after reperfusion, MCE predicted the recovery of left ventricular wall motion (stunned myocardium) during the chronic stage with a sensitivity of 77%, specificity of 100%, and predictive accuracy of 86%, when a normalized gray level of more than 0.4 was presumed to predict stunned myocardium. We conclude that MCE provided the prospective identification of potentially reversible ventricular dysfunction caused by stunned myocardium, and wall motion in the area of nonenhanced myocardium on MCE immediately after reperfusion is not expected to show reversible dysfunction.

Unlabelled: Coronary pressure flow (P/F) relationship has been investigated mainly from the viewpoint of coronary resistance. However, recent experimental evidence suggests that the zero flow pressure intercept (Pzf) provides important characteristics of coronary circulation. Although Pzf is likely to provide meaningful information about characteristics of coronary circulation, no data are available about Pzf in humans. The authors attempted to determine Pzf in humans by analyzing P/F relationship during long cardiac pause. This relationship, provoked by intracoronary adenosine triphosphate (ATP) infusion, was analyzed in 9 patients (8 men, 1 woman) with coronary heart disease (ages: fifty-six +/- six years). After the diagnostic cardiac catheterization, ATP, 0.6 mg/3 mL, was administrated by bolus intracoronary injection during measurements of coronary blood flow velocity. Coronary blood flow velocity in the left anterior descending artery was measured with a 0.018-inch Doppler angioplasty guide wire (FloWire, Cariometrics, Inc., Mountain View, Calif.). The dynamic P/F relationship was obtained by correlation of the instantaneous aortic pressure and flow velocity with each other at constant intervals. The least square linear regression analysis was applied to the P/F data to yield the extrapolated Pzf axis. Immediately after intracoronary injection of ATP, long pause (5320 +/- 1498 msec) appeared and coronary blood flow velocity decreased to 11 +/- 8 cm/sec. Pzf calculated with P/F relationship was 14 +/- 7 mmHg., Conclusions: Thus, the results clearly demonstrate that Pzf is higher than right atrial and left ventricular end-diastolic pressure in humans, indicating the complexity of the determinants of the Pzf.

To determine whether hyperlipidemia affects the endothelium-dependent vasomotor response along the dilated vessel after percutaneous transluminal coronary angioplasty (PTCA), we evaluated 32 patients with one-vessel disease, 3-6 months after successful PTCA without restenosis. Fourteen patients had mild stenotic lesions not subjected to PTCA (non-PTCA sites) in addition to the PTCA sites. Vessel diameter changes at 32 PTCA and 36 non-PTCA sites were assessed by quantitative angiography, before and after intracoronary injection of acetylcholine (20 micrograms to the right and 50 micrograms to the left coronary artery) and of nitroglycerin (0.1-0.3 mg). The acetylcholine response ranged from 46% (dilation) to -100% (constriction). All coronary arteries were dilated in response to nitroglycerin, which suggested preservation of the function of vascular smooth muscle, and the presence of an abnormality in endothelial function in those patients with a constrictor response to acetylcholine. There was a negative correlation between the acetylcholine response and the serum total cholesterol level at PTCA sites (r = -0.37; P = 0.038) and at non-PTCA sites (r = -0.46; P = 0.005). These findings indicate that hyperlipidemia is associated with a loss of endothelium-dependent vasodilation, not only at non-PTCA but also at PTCA sites, at which restoration of endothelial function might have occurred. They also suggest that hyperlipidemia may be related to the functional state of the regenerated endothelium at sites where PTCA had been previously performed.

It has been difficult to assess myocardial salvage in patients with coronary reflow because of the lack of appropriate methods of determining the risk area and assessing effects of coronary reflow in patients, myocardial contrast echocardiography was performed in 28 patients with acute myocardial infarction before reperfusion, immediately after reperfusion, and in the chronic stage with the right and left coronary arterial injection of sonicated ioxaglate. Contrast-deficit and contrast-filled areas before reperfusion were defined as the risk area and noninfarct area, respectively. If the ratio of peak subtracted gray level in the risk area to that in the noninfarct area was < 0.4, the risk area was taken as a contrast defect. Contrast defect was observed even after reperfusion in 8 (29%) patients, and the defect was consistently observed in the chronic stage in all of them. Contrast defect disappeared after reperfusion in the other 20 patients but reappeared in 4 (20%) of them in the chronic stage despite the patent infarct-related vessel. Left ventricular function recovery of the risk area in the chronic stage as assessed with regional wall motion and wall thickness was better in the patients without contrast defect after reperfusion than in patients with persistent or reappeared contrast defect. In conclusion, (1) myocardial salvage is improbable in patients with contrast defect immediately after reperfusion, (2) contrast enhancement immediately after reperfusion does not necessarily imply myocardial salvage in the chronic stage, and (3) myocardial echocardiography in the chronic stage may provide clinically useful information about myocardial salvage in patients with myocardial infarction.

Objectives: This study was undertaken to examine the effects of coronary flow dynamics after thrombolysis on infarct size limitation., Background: It has been commonly accepted that early thrombolysis does not necessarily salvage infarcted myocardium. Plausible causes for myocardial necrosis include such factors as elapsed time to reperfusion, residual stenosis, collateral vessels, hemodynamic loads, preconditioning and reperfusion injury. Recently, the no reflow phenomenon has been elucidated to be associated with infarct extension in clinical studies employing contrast echocardiography or thallium scintigraphy., Methods: Nineteen patients with early reperfusion in acute anterior myocardial infarction and comparable clinical background were studied. The patients were classified into two groups on the basis of pattern of thermodilution measurements of great cardiac vein flow after reperfusion: group A, 9 patients with a progressive decrease in great cardiac vein flow during the 1st 24 h of the onset of infarction; and group B, 10 patients without this observation. Left ventricular ejection fraction and thallium perfusion defect were compared between the two groups at follow-up., Results: There were no significant differences in systemic hemodynamic variables between groups A and B, and neither group had recurrent ischemic events suggesting reocclusion or restenosis during the study. In group A, both great cardiac vein flow (mean +/- SD 44 +/- 17% reduction) and oxygen extraction (38 +/- 15% reduction) were progressively decreased after the onset of reperfusion. Compared with group B, this group showed a lower left ventricular ejection fraction (36 +/- 7% vs. 63 +/- 15%, p < 0.01) and a larger thallium-201 defect severity index (1,091 +/- 366 U vs. 247 +/- 261 U, p < 0.01) at follow-up. Although other patient characteristics were comparable between the two groups, antecedent angina occurred in 90% of group B patients in contrast to only 33% of group A patients., Conclusions: Salvage of myocardium from infarction by successful thrombolysis was not observed in the patients demonstrating progressive decreases in great cardiac vein flow (group A). In those patients, inadequate myocardial reperfusion on a microvascular basis might be associated with a much larger myocardial infarction. Antecedent angina may protect against a progressive decrease in coronary flow and may have beneficial effects on infarct size limitation.

In 100 patients who underwent coronary angioplasty with more than one balloon catheter for a lesion, these over-the-wire balloon catheters were changed by using a regular-length guidewire. In order to change to another balloon, the inflation device was connected to the central guide wire lumen of the catheter after pulling back the catheter until the proximal end of the regular length guide wire disappeared. By pulling back the balloon catheter from the guiding catheter by applying a pressure with the inflation device, the balloon was taken out of the guiding catheter leaving the wire in the coronary artery. One hundred forty-nine of 163 attempted procedures were completed successfully. Our technique helped in performing a fast, safe, and reliable changing procedure compared to the procedure with an extended guidewire.

Objectives: The aim of this study was to reveal the time course of the neointimal coverage of stents placed in the human coronary arteries., Background: In deciding the protocol of anticoagulant and antiplatelet therapy for patients who undergo stent implantation, the condition of the neointimal coverage of stents should be taken into consideration. However, the time course of the neointimal coverage of stents has not been elucidated in human coronary arteries., Methods: Serial angioscopic observations were performed immediately after stenting, at 8 to 45 days (short-term follow-up) and at 65 to 142 days (long-term follow-up) in patients who underwent implantation of the Wiktor coronary stent in the restenotic lesion or in the lesion of acute or threatened closure after balloon angioplasty., Results: Angioscopic observations were successfully performed in 14 cases immediately after stenting, in 11 cases at short-term follow-up and in 13 cases at long-term follow-up. Immediately after stenting and even at 8 to 18 days after stenting, the stent was not covered by the neointimal layer in any case. However, at 65 to 142 days after stenting, the stent was covered by the neointimal layer in all cases. Angioscopically, three types of neointimal layer were recognized: a white layer with a cottonlike surface in three cases, a white layer with a smooth surface in eight cases and a transparent layer with a smooth surface in two cases., Conclusions: Although some experimental results in animals have shown completion of neointimal coverage of stents in a few weeks, in this serial angioscopic follow-up study, the completion of neointimal coverage of stents in human coronary arteries required approximately 3 months.

The long-term effect of calcium channel blockers on chronic heart failure is disappointing, probably because of reflex sympathetic activation through arterial vasodilation. However, nilvadipine may be beneficial for treatment of chronic heart failure since this drug has minimal effects on sympathetic activation. In this study, the effects of 12-week administration of nilvadipine or placebo on symptoms of heart failure and cardiac function were investigated in 23 patients with mild-to-moderate chronic heart failure in a double-blind trial. The patients were randomly assigned to either a nilvadipine group (16 mg daily) or a placebo group. Intergroup comparisons did not show significant differences in any parameters. Serious adverse effects were not observed during the study. Thus, this study failed to show any beneficial effect of nilvadipine in the long-term treatment of patients with chronic heart failure. We conclude that the long-term administration of nilvadipine (16 mg daily) is neither effective nor harmful in the treatment of patients with chronic heart failure.