Significant alterations of biodistribution and immune responses in Balb/c mice administered with adenovirus targeted to CD40(+) cells.

CD40 ligation has been shown to promote antigen-presenting functions of dendritic cells, which express CD40 receptor. Here we reported significantly altered biodistribution and immune responses with the use of CD40-targeted adenovirus. Compared with unmodified adenovirus 5, the CD40-targeted adenovirus following intravenous administration (i.v.) resulted in increased transgene expressions in the lung and thymus, which normally do not take up significant amounts of adenovirus. Intradermal injection saw modified adenovirus being mainly processed in local draining lymph nodes and skin. Following intranasal administration (i.n.), neither unmodified nor targeted viruses were found to be in the liver or spleen, which predominantly took up the virus following i.v. administration. However, inadvertent infection of the brain was found with unmodified adenoviruses, with the second highest gene expression among 14 tissues examined. Importantly, such undesirable effects were largely ablated with the use of targeted vector. Moreover, the targeted adenovirus elicited more sustained antigen-specific cellular immune responses (up to 17-fold) at later time points (30 days post boosting), but also significantly hampered humoral responses irrespective of administration routes. Additional data suggest the skewed immune responses induced by the targeted adenoviruses were not due to the identity of the transgene but more likely a combination of overall transgene load and CD40 stimulation.

Immediate and long-term clinical and angiographic results from Wiktor stent treatment for true bifurcation narrowings.

From January 1996 to December 1998, 90 consecutive patients with true bifurcation lesions underwent percutaneous coronary angioplasty with Wiktor stent implantation in our centers. In 1 group (group I, n = 45), a simple approach (main vessel stenting and balloon angioplasty of the side branch) was pursued. In the other group (group II, n = 45), both the main vessel and the side branch were stented ("T" technique). There was no significant difference in clinical and angiographic characteristics between the 2 groups. Angiographic and procedural successes were 100% and 95.6%, respectively, in both groups. Angiographic results for the side branch were better in group II than in group I. In-hospital and long-term (12 month) major cardiac events were similar in the 2 groups. Target lesion revascularization was 15.5% in group I and 35.5% in group II (p = 0.12). In the main vessel, restenosis rate was 12.5% in group I and 25% in group II (p = 0.15). In the side branch, restenosis rate was 37.5% in group II and 12.5% in group I (p = <0.05; odds ratio 2.42; 95% confidence interval 1.05 to 6.26). Event-free probability at 12 months was 61% in group II and 80% in group I (p = 0.10). When dealing with true bifurcation lesions, a simple strategy is associated with a lower risk of restenosis in the side branch. In contrast, a complex approach does not appear to give any benefit in terms of early or long-term outcome or restenosis rate.

Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation.

BACKGROUND: Circumferential radiofrequency ablation around pulmonary vein (PV) ostia has recently been described as a new anatomic approach for atrial fibrillation (AF). METHODS AND RESULTS: We treated 251 consecutive patients with paroxysmal (n=179) or permanent (n=72) AF. Circular PV lesions were deployed transseptally during sinus rhythm (n=124) or AF (n=127) using 3D electroanatomic guidance. Procedures lasted 148+/-26 minutes. Among 980 lesions surrounding individual PVs (n=956) or 2 ipsilateral veins with close openings or common ostium (n=24), 75% were defined as complete by a bipolar electrogram amplitude <0.1 mV inside the lesion and a delay >30 ms across the line. The amount of low-voltage encircled area was 3594+/-449 mm(2), which accounted for 23+/-9% of the total left atrial (LA) map surface. Major complications (cardiac tamponade) occurred in 2 patients (0.8%). No PV stenoses were detected by transesophageal echocardiography. After 10.4+/-4.5 months, 152 patients with paroxysmal AF (85%) and 49 with permanent AF (68%) were AF-free. Patients with and without AF recurrence did not differ in age, AF duration, prevalence of heart disease, or ejection fraction, but the LA diameter was significantly higher (P<0.001) in permanent AF patients with recurrence. The proportion of PVs with complete lesions was similar between patients with and without recurrence, but the latter had larger low-voltage encircled areas after radiofrequency (expressed as percent of LA surface area; P<0.001). CONCLUSIONS: Circumferential PV ablation is a safe and effective treatment for AF. Its success is likely due to both PV trigger isolation and electroanatomic remodeling of the area encompassing the PV ostia.

[Prospects of the treatment of atrial fibrillation. Circumferential radiofrequency ablation of pulmonary vein ostia]. / Prospettive nel trattamento della fibrillazione atriale. L'ablazione circonferenziale in radiofrequenza degli osti delle vene polmonari.

The dominance of the left atrium (LA) in the pulmonary vein (PV) regions for triggering and maintaining atrial fibrillation (AF) is now widely recognized. Radiofrequency (RF) PV isolation with electroanatomical guidance has recently emerged as a promising approach for AF treatment. We report the clinical outcome of the procedure in 251 consecutive patients with paroxysmal (n = 179) or permanent (n = 72) AF. Circular RF lesions were deployed transseptally during sinus rhythm or AF at 5 mm from PV ostia. Procedural and mapping times were 112 +/- 32 min and 75 +/- 27 min, respectively, with 29 +/- 11 min of fluoroscopy. Complete lesions (peak-to-peak bipolar electrogram amplitude < 0.1 mV inside the line and no double potentials) were achieved in 85% of the veins treated. Sinus rhythm was restored during RF delivery in 52% and by DC shock in the remaining. Major complications (cardiac tamponade) occurred in 3%. Extent of ablated area was 4.9 +/- 0.5 cm2, accounting for 28 +/- 9% of the total LA map surface. After 11 +/- 5 months, procedure success rates (freedom from AF without antiarrhythmic drugs) were 85% for paroxysmal and 68% for permanent AF. No PV stenoses were detected. By univariate analysis, an increased risk of recurrence was predicted by LA dilation (diameter > 50 mm), AF duration, and a low ablated area (< 15% of total LA surface). After adjustment, only the latter variable continued to be significant (odds ratio 3.5, 95% confidence interval, 1.6-5.8). In conclusion, RF PV isolation is safe and effective in either paroxysmal or permanent AF. Patients with enlarged left atrium may require wider lesions to achieve AF suppression.

Randomized comparison of a strategy of predischarge coronary angiography versus exercise testing in low-risk patients in a chest pain unit: in-hospital and long-term outcomes.

OBJECTIVES: This randomized trial compared a strategy of predischarge coronary angiography (CA) with exercise treadmill testing (ETT) in low-risk patients in the chest pain unit (CPU) to reduce repeat emergency department (ED) visits and to identify additional coronary artery disease (CAD). BACKGROUND: Patients with chest pain and normal electrocardiograms (ECGs) have a low likelihood of CAD and a favorable prognosis, but they often seek repeat evaluations in EDs. Remaining uncertainty regarding their symptoms and diagnosis may cause much of this recidivism. METHODS: A total of 248 patients with no ischemic ECG changes triaged to a CPU were randomized to CA (n = 123) or ETT (n = 125). All patients had a probability of myocardial infarction < or =7% according to the Goldman algorithm, no biochemical evidence of infarction, the ability to exercise and no previous documented CAD. Patients were followed up for > or =1 year and surveyed regarding their chest pain self-perception and utility of the index evaluation. RESULTS: Coronary angiography showed disease (> or =50% stenosis) in 19% and ETT was positive in 7% of the patients (p = 0.01). During follow-up (374+/-61 days), patients with a negative CA had fewer returns to the ED (10% vs. 30%, p = 0.0008) and hospital admissions (3% vs. 16%, p = 0.003), compared with patients with a negative/nondiagnostic ETT. The latter group was more likely to consider their pain as cardiac-related (15% vs. 7%), to be unsure about its etiology (38% vs. 26%) and to judge their evaluation as not useful (39% vs. 15%) (p < 0.01 for all comparisons). CONCLUSIONS: In low-risk patients in the CPU, a strategy of CA detects more CAD than ETT, reduces long-term ED and hospital utilization and yields better patient satisfaction and understanding of their condition.

Circumferential radiofrequency ablation of pulmonary vein ostia: A new anatomic approach for curing atrial fibrillation.

BACKGROUND: The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers or reentrant circuits critical to the genesis of atrial fibrillation (AF). We developed an anatomic approach aimed at isolating each PV from the left atrium (LA) by circumferential radiofrequency (RF) lesions around their ostia. METHODS AND RESULTS: We selected 26 patients with resistant AF, either paroxysmal (n=14) or permanent (n=12). A nonfluoroscopic mapping system was used to generate 3D electroanatomic LA maps and deliver RF energy. Two maps were acquired during coronary sinus and right atrial pacing to validate the lateral and septal PV lesions, respectively. Patients were followed up closely for >/=6 months. Procedures lasted 290+/-58 minutes, including 80+/-22 minutes for acquisition of all maps, and 118+/-16 RF pulses were deployed. Among 14 patients in AF at the beginning of the procedure, 64% had sinus rhythm restoration during ablation. PV isolation was demonstrated in 76% of 104 PVs treated by low peak-to-peak electrogram amplitude (0. 08+/-0.02 mV) inside the circular line and by disparity in activation times (58+/-11 ms) across the lesion. After 9+/-3 months, 22 patients (85%) were AF-free, including 62% not taking and 23% taking antiarrhythmic drugs, with no difference (P:=NS) between paroxysmal and permanent AF. No thromboembolic events or PV stenoses were observed by transesophageal echocardiography. CONCLUSIONS: Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.

A prospective evaluation of angiography-guided coronary stent implantation with high versus very high balloon inflation pressure.

BACKGROUND: High inflation pressure (HP) after coronary stent deployment has become a standard approach because it has been associated with a decreased subacute stent thrombosis (SAT) rate. However, the impact of HP on long-term outcomes is still unclear. We compared the long-term results of a strategy of increasing HP (>/=12 atm) until the achievement of angiographic success (<20% residual stenosis) with a prespecified very high inflation pressure (VHP) strategy of 20 atm without intermediate inflations. METHODS AND RESULTS: We conducted a parallel-group, nonrandomized study to evaluate the short- and long-term results in 136 consecutive eligible patients who underwent successful single Palmaz-Schatz stent implantation in vessels >/=3 mm. Major adverse cardiac events (MACE), that is, death, myocardial infarction, and target lesion revascularization (TLR), were monitored for a minimum of 6 months. No significant differences were observed between the two strategies in terms of final minimal lumen diameter (HP, 3.0 +/- 0.5 vs VHP, 3. 1 +/- 0.5 mm) and acute gain (HP, 2.1 +/- 0.7 vs VHP, 2.2 +/- 0.6). The overall rate of subacute stent thrombosis was 0.7%. During a 405 +/- 148-day follow-up, 21 (28.8%) patients in the VHP group and 6 (9. 5%) in the HP group (P =.005) had MACE, with a TLR rate of 27.4% versus 7.9% (P =.009), respectively. By multivariate analysis, the use of VHP increased the odds of long-term MACE by a factor of 3.48 (P =.009). Among patients undergoing TLR, those treated with VHP had a greater lumen loss (HP, 1.83 +/- 0.57 vs VHP, 2.15 +/- 0.36 mm, P =.02) and a more frequent pattern of diffuse restenosis (71% vs 16%, P =.06). CONCLUSIONS: In our study, the two strategies had similar acute and short-term results, but VHP was associated with a poorer long-term outcome. These data provide a rationale for a less aggressive strategy for stent deployment by optimizing rather than attempting to maximize inflation pressure and stent expansion.

Cardiac pacing in heart failure patients with left bundle branch block: impact of pacing site for optimizing left ventricular resynchronization.

BACKGROUND: Acute left ventricular pacing has been associated with hemodynamic improvement in patients with congestive heart failure and wide QRS complex. We hypothesized that pacing two left ventricular sites simultaneously would produce faster activation and better systolic function than single-site pacing. METHODS: We selected 14 heart failure patients (NYHA functional class III or IV) in normal sinus rhythm with left bundle branch block and QRS > 150 ms. An 8F dual micromanometer catheter was placed in the aorta for measuring +dP/dt (mmHg/s), aortic pulse pressure (mmHg), and end-diastolic pressure (mmHg). Pacing leads were positioned via coronary veins at the posterior base and lateral wall. Patients were acutely paced VDD at the posterior base, lateral wall, and both sites (dual-site) with 5 atrioventricular delays (from 8 ms to PR -30 ms). Pacing sequences were executed in randomized order using a custom external computer (FlexStim, Guidant CRM). RESULTS: Dual-site pacing increased peak +dP/dt significantly more than posterior base and lateral wall pacing. Dual-site and posterior base pacing raised aortic pulse pressure significantly more than lateral wall pacing. Dual-site pacing shortened QRS duration by 22 %, whereas posterior base and lateral wall pacing increased it by 2 and 12%, respectively (p = 0.006). CONCLUSIONS: In heart failure patients with left bundle branch block, dual-site pacing improves systolic function more than single-site stimulation. Improved ventricular activation synchrony, expressed by paced QRS narrowing, may account for the additional benefit of dual- vs single-site pacing in enhancing contractility. This novel approach deserves consideration for future heart failure pacing studies.

Involvement of aldose reductase in vascular smooth muscle cell growth and lesion formation after arterial injury.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is an important feature of atherosclerosis, restenosis, and hypertension. Although multiple mediators of VSMC growth have been identified, few effective pharmacological tools have been developed to limit such growth. Recent evidence indicating an important role for oxidative stress in cell growth led us to investigate the potential role of aldose reductase (AR) in the proliferation of VSMCs. Because AR catalyzes the reduction of mitogenic aldehydes derived from lipid peroxidation, we hypothesized that it might be a potential regulator of redox changes that accompany VSMC growth. Herein we report several lines of evidence suggesting that AR facilitates/mediates VSMC growth. Stimulation of human aortic SMCs in culture with mitogenic concentrations of serum, thrombin, basic fibroblast growth factor, and the lipid peroxidation product 4-hydroxy-trans-2-nonenal (HNE) led to a 2- to 4-fold increase in the steady-state levels of AR mRNA, a 4- to 7-fold increase in AR protein, and a 2- to 3-fold increase in its catalytic activity. Inhibition of the enzyme by sorbinil or tolrestat diminished mitogen-induced DNA synthesis and cell proliferation. In parallel experiments, the extent of reduction of the glutathione conjugate of HNE to glutathionyl-1,4-dihydroxynonene in HNE-exposed VSMCs was decreased by serum starvation or sorbinil. Immunohistochemical staining of cross sections from balloon-injured rat carotid arteries showed increased expression of AR protein associated with the neointima. The media of injured or uninjured arteries demonstrated no significant staining. Compared with untreated animals, rats fed sorbinil (40 mg. kg(-1). d(-1)) displayed a 51% and a 58% reduction in the ratio of neointima to the media at 10 and 21 days, respectively, after balloon injury. Taken together, these findings suggest that AR is upregulated during growth and that this upregulation facilitates growth by enhancing the metabolism of secondary products of reactive oxygen species.

Cardiac troponin T in chest pain unit patients without ischemic electrocardiographic changes: angiographic correlates and long-term clinical outcomes.

OBJECTIVES: We prospectively evaluated the relation between cardiac troponin T (cTnT) level, the presence and severity of coronary artery disease (CAD) and long-term prognosis in patients with chest pain but no ischemic electrocardiographic (ECG) changes who had short-term observation. BACKGROUND: Cardiac TnT is a powerful predictor of future myocardial infarction (MI) and death in patients with ECG evidence of an acute coronary syndrome. However, for patients with chest pain with normal ECGs, it has not been determined whether cTnT elevation is predictive of CAD and a poor long-term prognosis. METHODS: In 414 consecutive patients with no ischemic ECG changes who were triaged to a chest pain unit, cTnT and creatine kinase, MB fraction (CK-MB) were evaluated > or = 10 h after symptom onset. Patients with adverse cardiac events, including death, MI, unstable angina and heart failure were followed for as long as one year. RESULTS: A positive (>0.1 ng/ml) cTnT test was detected in 37 patients (8.9%). Coronary artery disease was found in 90% of 30 cTnT-positive patients versus 23% of 144 cTnT-negative patients who underwent angiography (p < 0.001), with multivessel disease in 63% versus 13% (p < 0.001). The cTnT-positive patients had a significantly (p < 0.05) higher percent diameter stenosis and a greater frequency of calcified, complex and occlusive lesions. Follow-up was available in 405 patients (98%). By one year, 59 patients (14.6%) had adverse cardiac events. The cumulative adverse event rate was 32.4% in cTnT-positive patients versus 12.8% in cTnT-negative patients (p = 0.001). After adjustment for baseline clinical characteristics, positive cTnT was a stronger predictor of events (chi-square = 23.56, p = 0.0003) than positive CK-MB (>5 ng/ml) (chi-square = 21.08, p = 0.0008). In a model including both biochemical markers, CK-MB added no predictive information as compared with cTnT alone (chi-square = 23.57, p = 0.0006). CONCLUSIONS: In a group of patients with chest pain anticipated to have a low prevalence of CAD and a good prognosis, cTnT identifies a subgroup with a high prevalence of extensive and complex CAD and increased risk for long-term adverse outcomes.

Development of biopharmaceuticals in plant expression systems: cloning, expression and immunological reactivity of human cytomegalovirus glycoprotein B (UL55) in seeds of transgenic tobacco.

Plant seeds offer unique opportunities for the production and delivery of oral subunit vaccines. We have used the immunodominant glycoprotein B complex of human cytomegalovirus (HCMV), introduced into tobacco plants, as a model system for studying the merit of this promising approach. Given the advantages of expressing proteins in seeds, a novel expression vector was developed incorporating regulatory sequences of glutelin, the major rice seed storage protein, to direct synthesis of recombinant glycoprotein B. Analysis of genomic DNA of 28 selected tobacco transformants by PCR amplification showed that 71% harboured the gB cDNA, a finding further documented by Southern blotting. Specific immunoassays of protein extracts from seeds of positive plants showed that all were producing antigenic glycoprotein B at levels ranging from 70-146 ng/mg extracted protein. In addition, similarity with native glycoprotein B produced in HCMV-infected cells was also demonstrated by inhibition of immunofluorescence on HCMV-infected human fibroblasts. These data are the first to report the expression of an immunodominant antigen of HCMV in plant tissues, indicating the fidelity with which this very large heterologous viral glycoprotein can be synthesized in this model system.

Queuing for coronary angiography during severe supply-demand mismatch in a US public hospital: analysis of a waiting list registry.

CONTEXT: Adverse cardiac events have been reported in patients waiting for either coronary surgery or angioplasty. However, data on the risk of adverse events while awaiting coronary angiography are limited, and none are available from a US population. OBJECTIVE: To quantify cardiac outcomes in patients waiting for elective coronary angiography. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 381 adult outpatients (mean [SD] age, 55 [12] years; 64% male; 61% white) on a waiting list for coronary angiography at a US tertiary care public teaching hospital during 1993-1994. MAIN OUTCOME MEASURES: Rates of cardiac death, nonfatal myocardial infarction, and hospitalizations for unstable angina or heart failure as a function of amount of time spent on a waiting list. RESULTS: Sixty-six patients were dropped from the waiting list but were included in the study analysis. During a mean (SD) follow-up of 8.4 (6.5) months, cardiac death, myocardial infarction, and hospitalization occurred in 6 (1.6%), 4 (1.0%), and 26 (6.8%) patients, respectively. The probability of events was minimal in the first 2 weeks and increased steadily between 3 and 13 weeks. By Cox multivariate analysis, 2 variables independently identified an increased risk of adverse events: a strongly positive treadmill exercise electrocardiogram or positive stress imaging result at referral (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.22-4.16; P=.01) and the use of 2 to 3 anti-ischemic medications (OR, 1.98; 95% CI, 1.19-3.96; P=.04). Among 311 patients who ultimately underwent angiography, those with adverse events had a higher prevalence of coronary disease (96% vs 60%; P<.001), more frequently required revascularization (93% vs 53%; P<.001), and had longer hospital stays (mean [SD], 6.2 [4.3] vs 1.3 [0.7] days; P=.001). CONCLUSION: Our data suggest that in a cohort referred for coronary angiography, delaying the procedure places some patients at risk for death, myocardial infarction, unplanned hospitalization, a longer hospital stay, and, potentially, a poorer prognosis. Waits longer than 2 weeks should be avoided, and patients with strongly positive stress test results and those who require 2 to 3 anti-ischemic medications should be prioritized for early intervention.

Prevention of restenosis after percutaneous coronary interventions: the medical approach.

Restenosis following successful percutaneous coronary revascularization continues to represent a major problem limiting the clinical efficacy of this procedure. The underlying mechanisms of restenosis are comprised of a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neointimal hyperplasia. Indeed, there are important interactions among all of these mechanisms. For example, neointimal hyperplasia is stimulated by growth factors, which are released by local thrombi and the injured arterial segment itself, and act to enhance the expression of other growth-regulating proteins, in particular "second messengers", proto-oncogenes and other cell cycle controlling proteins. This results in an inflammatory and myofibroproliferative response, which may worsen vessel narrowing caused by recoil and result in the formation of a clinically significant restenotic lesion. A multitude of pharmacologic trials have been conducted in an attempt to prevent restenosis, but most have demonstrated little benefit. Studies in smaller numbers of patients have suggested a potential benefit for several classes of agents, including: 1) the antiproliferatives, angiopeptin, trapidil and tranilast; 2) selective elimination or alteration of proliferating cells; 3) enhancement of natural growth inhibitors; and 4) signal transduction blockade or inhibition of the gene expression for various growth-stimulating proteins. Finally, there have been advances in related areas, including development of antithrombotic catheters, novel polymers, and more efficient methods for transferring genes into the vessel wall. All of these offer the possibility of delivering agents (drugs, genes, or antisense oligonucleotides) locally at the site of intervention in a way that may optimize antiproliferative effects while minimizing systemic effects--ultimately leading to a more specific inhibition of the restenosis process.

Diagnostic accuracy, angiographic correlates and long-term risk stratification with the troponin T ultra sensitive Rapid Assay in chest pain patients at low risk for acute myocardial infarction.

AIMS: This prospective study of acute chest pain patients clinically at low risk for a myocardial infarction was designed to: determine the diagnostic accuracy of a cardiac troponin T (cTnT) ultra sensitive Rapid Assay (RAII) compared with the quantitative cTnT assay; evaluate the association of a positive RAII with the presence and severity of coronary artery disease (CAD); and determine the ability of the RAII result to predict adverse events during long-term follow-up. METHODS AND RESULTS: A total of 199 patients referred for chest pain, without ST segment elevation on presenting ECG, underwent RAII, quantitative cTnT, CK and CK-MB tests drawn simultaneously > or = 10 h after symptom onset. An abnormal value for cTnT was defined as >0.1 ng.mL(-1). The presence and extent of CAD was recorded in patients undergoing angiography. Adverse events, including cardiac death, non-fatal infarction, and readmission for unstable angina or heart failure, were assessed long-term. An abnormal RAII was found in 41 (20-6%) patients. The RAII sensitivity for detecting abnormal quantitative cTnT levels was 100%, specificity 96.3% (158/164) and overall concordance 97.5%. Although the presenting ECG was normal or non-specific in 95%, ST depression or T wave inversion occurred in 17% of RAII-positive versus 2%, RAII-negative patients (P=0.004). Of RAII-positive patients who underwent angiography (79%), 87% had CAD and 60% had multivessel disease. Kaplan Meier event-free survival curves showed early separation and continued to modestly diverge for patients with positive and negative RAII (69% versus 90% one-year event-free survival, P=0.002). CONCLUSION: In a chest pain population anticipated to have a low prevalence of acute coronary syndromes and a good prognosis, the RAII is a quick and reliable test. It provides an important initial opportunity to identify patients with a high prevalence of CAD and increased incidence of future cardiac events.

Use of stress testing to evaluate patients with recurrent chest pain after percutaneous coronary revascularization.

Controversy exists regarding the diagnostic accuracy, optimal technique, and timing of noninvasive stress testing after percutaneous transluminal coronary angioplasty (PTCA). Many patients return with chest pain after PTCA, and because the incidence of restenosis has been reported to be as high as 50%, a noninvasive test with a high predictive value is needed to reduce the need for unnecessary coronary angiography. Studies have shown that the sensitivity and specificity of stress testing varies depending on the amount of time elapsed since the procedure. Soon after a successful PTCA, perfusion defects on nuclear imaging following exercise or pharmacologic stress may be detected in asymptomatic patients without angiographic restenosis. In many patients, abnormal stress myocardial perfusion scans will normalize spontaneously, and thus stress testing with nuclear imaging within 4 to 6 weeks of PTCA lacks specificity for detecting restenosis. In contrast, stress echocardiography which detects wall motion abnormalities rather than perfusion mismatch has been reported to offer more specific information on myocardial ischemia and restenosis early after PTCA. In patients who develop chest pain more than 6 weeks after PTCA, the ability to accurately identify restenosis is shared by both echocardiographic and nuclear imaging methods. The purpose of this review is to clarify the strengths, pitfalls, and prognostic value of different stress modalities and cardiac imaging techniques in patients who develop chest pain within 6 months of undergoing PTCA.

Wiktor stent for treatment of chronic total coronary artery occlusions: short- and long-term clinical and angiographic results from a large multicenter experience.

OBJECTIVES: This study reports the first multicenter experience with the Wiktor coil stent for treatment of chronic total coronary artery occlusions (CTOs). BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) of CTO is associated with very high restenosis and reocclusion rates. Coronary stenting has been proposed as a means of improving outcome. However, the Wiktor device for CTOs has never been tested in a large patient sample. METHODS: From January 1993 to December 1996, 89 patients with 91 CTOs underwent Wiktor stent implantation after successful PTCA. The post-stenting regimen consisted of warfarin (Coumadin) plus aspirin in the initial 49 patients (55%) and aspirin plus ticlopidine in 40 patients (45%). RESULTS: Stenting was successful in 87 patients (98%). At 1 month, 6% of patients had subacute stent thrombosis, 3% had a major bleeding event, and 1% had access-site complications. Subacute stent thrombosis showed univariate association with warfarin therapy (p = 0.009). Angiographic follow-up was obtained in 76 (93%) of 82 eligible patients. The restenosis rate was 32%, including 4% reocclusions. By multiple logistic regression analysis, restenosis was independently associated with multiple stents (adjusted odds ratio [OR] 27.67, 95% confidence interval [CI] 4.25 to 79.95, p = 0.0008) and increasing values of occlusion length (adjusted OR 1.23, 95% CI 1.09 to 1.39, p = 0.001). Freedom from death, myocardial infarction or stented vessel revascularization was 87% and 72% at 1 and 3 years, respectively. CONCLUSIONS: Short- and long-term clinical and angiographic outcomes are favorable in patients undergoing Wiktor stent implantation in CTO. Further technical improvement is needed to reduce the restenosis rate in patients with long lesions and multiple stents.

Clinical and prognostic usefulness of supine bicycle exercise echocardiography in the functional evaluation of patients undergoing elective percutaneous transluminal coronary angioplasty.

BACKGROUND: Supine bicycle exercise echocardiography (SBEE) has never been used before and early after percutaneous transluminal coronary angioplasty (PTCA) for assessing the functional outcome of the procedure and predicting late restenosis. METHODS AND RESULTS: We selected 76 subjects with stable angina, normal wall motion at rest, and exercise-induced wall-motion abnormalities before PTCA. SBEE with peak exercise imaging and the use of a 16-segment, four-grade score model was performed 54 +/- 15 hours after PTCA. No exercise-related adverse events occurred. Patients were grouped according to SBEE results: group 1 (n = 35, 46%) with negative exercise ECG and echo; group 2 (n = 19, 25%) with a positive exercise ECG but normal echo; and group 3 (n = 22, 29%) with a positive exercise echo with either a positive (n = 7, 32%) or negative (n = 15, 68%) ECG. Exercise performance significantly improved in all groups. In group 3, peak wall-motion score index decreased from 1.27 +/- 0.11 before to 1.15 +/- 0.06 after PTCA (P < .05), and duration of wall-motion abnormalities went from 81 +/- 24 to 47 +/- 19 seconds (P < .05). The rate of clinical restenosis (ie, angina recurrence or positive 6-month SBEE in asymptomatic patients, both associated with angiographic restenosis > 50%) was 37%. By multiple logistic regression analysis, clinical restenosis was associated with a positive post-PTCA exercise echo (odds ratio [OR] 3.08, 95% confidence interval [CI] 1.66 to 5.72; P = .0004) and with increasing values of pre-PTCA wall-motion score index (OR 2.86, 95% CI 1.92 to 4.27; P = .005) and duration of wall-motion abnormalities (OR 2.12, 95% CI 1.07 to 4.20; P = .04). CONCLUSIONS: SBEE is a safe and reliable tool to demonstrate changes in exercise-induced wall-motion abnormalities after PTCA and provides prognostic information in the risk assessment of clinical restenosis.

[Immediate and long-term clinical and angiographic results of the Wiktor stent in the treatment of chronic coronary occlusions]. / Risultati clinici ed angiografici immediati ed a lungo termine dello stent Wiktor nel trattamento delle occlusioni coronariche croniche.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) of chronic total coronary artery occlusions is associated with very high restenosis and reocclusion rates. Coronary stenting has been proposed as a means of improving outcome. However, the Wiktor device for chronic coronary occlusion has never been tested in a large patient sample. This study reports the first multicenter experience with the Wiktor stent for treatment of chronic occlusions. METHODS: From January 1993 to December 1996, 89 consecutive patients with 91 chronic occlusions underwent Wiktor stent implantation after successful PTCA. Post-stenting regimen consisted of coumadin plus aspirin in the first 49 (55%) patients and aspirin plus ticlopidine in the following 40 (45%). RESULTS: Stenting was successful in 87 (98%) patients. At 1 month, 6% of patients had subacute stent thrombosis, 1% access-site complications and 3% major bleeding events. Stent thrombosis showed a univariate association with coumadin therapy (p = 0.009). Angiographic follow-up was obtained in 93% of 82 eligible patients. Restenosis rate was 32%, including 4% reocclusions. Through multiple logistic regression analysis, restenosis was independently associated with multiple stents (odds ratio-OR = 27.67, 95% confidence interval-CI = 4.25 to 79.95, p = 0.0008) and increasing values of occlusion length (OR = 1.23, 95% CI = 1.09 to 1.39, p = 0.001). Freedom from death, myocardial infarction or stented vessel revascularization was 87 and 72% at one and three years, respectively. CONCLUSIONS: Short- and long-term clinical and angiographic outcomes are favorable in patients undergoing Wiktor stent implantation for chronic coronary occlusion. Further technical refinements are needed to reduce restenosis rate in patients with long lesions and multiple stents.