Inflammation and long-term mortality after non-ST elevation acute coronary syndrome treated with a very early invasive strategy in 1042 consecutive patients.

BACKGROUND: This study sought to evaluate the predictive value of C-reactive protein (CRP) on long-term mortality in non-ST-elevation acute coronary syndromes (NSTACS) that were treated with a very early aggressive revascularization strategy. METHODS AND RESULTS: We conducted a prospective cohort study in 1042 consecutive patients with NSTACS who were undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularization strategy within 24 hours. Levels of CRP were determined on admission. The patients were followed for a mean of 20 months. In-hospital mortality was significantly higher in patients with a CRP>10 mg/L (3.7% versus 1.2% with CRP<3 mg/L and versus 0.8% with CRP of 3 to 10 mg/L; relative risk for CRP>10 mg/L compared with CRP< or =10 mg/L was 4.2, 95% confidence interval [CI] was 1.6 to 11.0; P=0.004). The increase in mortality in patients with CRP>10 mg/L persisted during follow-up. Long-term mortality was 3.4% with CRP<3 mg/L, 4.4% with CRP between 3 and 10 mg/L, and 12.7% with CRP>10 mg/L (relative risk for CRP>10 mg/L compared with CRP< or =10 mg/L, 0.8; 95% CI, 2.3 to 6.2; P<0.001). In addition, Kaplan-Meier survival analysis demonstrated a significantly reduced survival at 4 years in patients with a CRP>10 mg/L (78% versus 88% for a CRP of 3 to 10 mg/L and versus 92% for CRP<3 mg/L; P<0.001 by log-rank). In a multivariate analysis, CRP was an independent predictor of long-term mortality. Patients with a CRP>10 mg/L had >4 times the risk of death (odds ratio, 4.1; 95% CI, 2.3 to 7.2). CONCLUSION: CRP is a strong independent predictor of short and long-term mortality after NSTACS that are treated with very early revascularization.

A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents.

OBJECTIVES: The aim of the present study was to compare clopidogrel and ticlopidine after coronary stenting with regard to cardiovascular death during long-term follow-up. BACKGROUND: Randomized trials comparing clopidogrel and ticlopidine with a restricted use of intravenous glycoprotein IIb/IIIa inhibition have reported a trend toward a higher incidence of thrombotic stent occlusion with clopidogrel at 30 days. METHODS: After successful coronary stent implantation, 700 patients with 899 lesions were randomly assigned to receive a four-week course of either 500 mg ticlopidine (n = 345) or 75 mg clopidogrel (n = 355) in addition to 100 mg aspirin. Cardiovascular death was the primary end point and was recorded during a median follow-up period of 28 months. RESULTS: Cardiovascular death occurred in eight patients with ticlopidine versus 26 patients with clopidogrel (hazard ratio with ticlopidine compared with clopidogrel, 0.30; 95% confidence interval [CI], 0.14 to 0.66; p = 0.003). After adjustment for co-variables, ticlopidine reduced the risk of cardiovascular death by 63% compared with clopidogrel. The combined end point of cardiovascular death or nonfatal myocardial infarction was present in 19 patients assigned ticlopidine, compared with 40 patients assigned clopidogrel (hazard ratio, 0.45; p = 0.005). The hazard ratio for all-cause mortality with ticlopidine as compared with clopidogrel was 0.30 (95% CI, 0.14 to 0.64; p = 0.002). CONCLUSIONS: After the placement of coronary artery stents in unselected patients, ticlopidine was associated with a significantly lower mortality than clopidogrel. This raises concern about the current practice of substituting clopidogrel for ticlopidine after stenting and highlights the need for further long-term studies.

Evaluation of the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention: the randomized, double-blind, placebo-controlled, multicenter Verapamil Slow-Release for Prevention of Cardiovascular Events After Angioplasty (VESPA) Trial.

OBJECTIVES: We investigated the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention (PCI). BACKGROUND: Thus far, there is no established systemic pharmacologic approach for the prevention of restenosis after PCIs. Five small studies reported encouraging results for calcium channel blockers. METHODS: Our randomized double-blind trial included 700 consecutive patients with successful PCI of a native coronary artery. Patients received the calcium channel blocker verapamil, 240 mg twice daily for six months, or placebo. Primary clinical end point was the composite rate of death, myocardial infarction, and target vessel revascularization (TVR) during one-year follow-up; the angiographic end point was late lumen loss at the six-month follow-up angiography. RESULTS: We obtained complete clinical follow-up in 95% of the patients, and scheduled angiography was performed in 94%. The proportion of patients treated with stents was 83%. The primary clinical end point was reached in 67 (19.3%) patients on verapamil and in 103 (29.3%) patients on placebo (relative risk [RR] 0.66 [95% confidence interval (CI) 0.48 to 0.89]; p = 0.002). This difference between the groups was driven by TVR (17.5% with verapamil vs. 26.2% with placebo; RR 0.67 [95% CI 0.49 to 0.93]; p = 0.006). Late lumen loss was 0.74 +/- 0.70 mm with verapamil and 0.81 +/- 0.75 mm with placebo (p = 0.11). Compared with placebo, verapamil reduced the rate of restenosis > or =75% (7.8% vs. 13.7%; RR 0.57 [95% CI 0.35 to 0.92]; p = 0.014). CONCLUSIONS: Verapamil compared with placebo improves long-term clinical outcome after PCI of native coronary arteries by reducing the need for TVR. This was caused by a reduction in the rate of high-grade restenosis.

Women do have an improved long-term outcome after non-ST-elevation acute coronary syndromes treated very early and predominantly with percutaneous coronary intervention: a prospective study in 1,450 consecutive patients.

OBJECTIVES: This study sought to assess gender-based differences in long-term outcome after very early aggressive revascularization for non-ST-elevation acute coronary syndromes (NSTACS). BACKGROUND: The Fragmin and fast Revascularization during InStability in Coronary artery disease (FRISC) II study suggested that women have less to gain from an early invasive strategy. METHODS: We conducted a prospective cohort study in 1,450 consecutive patients with NSTACS undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularization strategy within 24 h of admission. The combined primary end point was defined as death or nonfatal myocardial infarction (MI) and recorded for a mean of 20 months. RESULTS: Percutaneous coronary intervention was performed in more than 50% of patients in women and men and accompanied with stenting in 80%. The percutaneous coronary intervention:coronary artery bypass grafting ratio was 4:1 in men and 5:1 in women. The primary end point occurred in 29 (7.0%) women as compared with 108 (10.5%) men (hazard ratio for women, 0.65; 95% confidence interval [CI] 0.42 to 0.99; p = 0.045). Backward-stepwise multivariate Cox regression analysis identified female gender as an independent predictor of death or MI (hazard ratio for female gender, 0.51; 95% CI, 0.28 to 0.92; p = 0.024). Kaplan-Meier analysis showed that women had consistently lower event rates during the entire follow-up period (p = 0.037 by log-rank for death or MI). CONCLUSIONS: Women treated with very early aggressive revascularization with coronary stenting of the culprit lesion as the primary revascularization strategy have a better long-term outcome as compared with men.

Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty.

BACKGROUND: The administration of radiographic contrast agents remains an important cause of acute renal failure. The optimal infusion for hydration has not been evaluated. OBJECTIVE: To compare the incidence of contrast media-associated nephrotoxicity with isotonic or half-isotonic hydration. DESIGN: Prospective, randomized, controlled, open-label study. METHODS: Patients scheduled for elective or emergency coronary angioplasty were randomly assigned to receive isotonic (0.9% saline) or half-isotonic (0.45% sodium chloride plus 5% glucose) hydration beginning the morning of the procedure for elective interventions and immediately before emergency interventions. An increase in serum creatinine of at least 0.5 mg/dL (44 micromol/L) within 48 hours was defined as contrast media-associated nephrotoxicity. Secondary end points were cardiac and peripheral vascular complications. RESULTS: A total of 1620 patients were assigned to receive isotonic (n = 809) or half-isotonic (n = 811) hydration. Primary end point analysis was possible in 1383 patients. Baseline characteristics were well matched. Contrast media-associated nephropathy was significantly reduced with isotonic (0.7%, 95% confidence interval, 0.1%-1.4%) vs half-isotonic (2.0%, 95% confidence interval, 1.0%-3.1%) hydration (P =.04). Three predefined subgroups benefited in particular from isotonic hydration: women, persons with diabetes, and patients receiving 250 mL or more of contrast. The incidence of cardiac (isotonic, 5.3% vs half-isotonic, 6.4%; P =.59) and peripheral vascular (isotonic, 1.6% vs half-isotonic, 1.5%, P =.93) complications was similar between the 2 hydration groups. CONCLUSION: Isotonic hydration is superior to half-isotonic hydration in the prevention of contrast media-associated nephropathy.

A defective angina pectoris pain warning system: experimental findings of ischemic and electrical pain test.

Ischemic pain threshold and tolerance levels using the tourniquet pain technique and electrical cutaneous pain thresholds were measured in patients with asymptomatic ischemic heart disease. Thirty asymptomatic patients, who repeatedly exhibited no angina pectoris pain during the occurrence of exercise-induced coronary ischemia (greater than or equal to 0.1 mV ST segment depression in exercise ECG) were compared to 30 randomly selected symptomatic control patients. In a smaller patient group (6 symptomatic, 6 asymptomatic) the degree of forearm ischemia during the tourniquet test was determined non-invasively by monitoring transcutaneous pO2. Results indicated that asymptomatic patients needed significantly more time to reach pain threshold following occlusion of forearm blood flow and exhibited significantly lower tcpO2 values at threshold than symptomatic patients. Electrical pain thresholds were also elevated in the asymptomatic group. These findings indicate that the phenomenon of asymptomatic myocardial ischemia can be explained by an extracardiac pain modifying mechanism.

Cost-effectiveness of intracoronary ultrasound for percutaneous coronary interventions.

The Strategy for Intravascular Ultrasound (IVUS) guided PTCA and Stenting trial included a prospectively designed economic analysis to investigate whether routine IVUS guidance intervention is cost-effective. Consecutive patients (n = 269) with 356 lesions were randomly assigned to receive provisional stenting with angiographic guidance only (ANGIO) or with IVUS guidance. The 2-year major adverse cardiac event-free survival (effectiveness) was significantly higher in the IVUS-guided group (80% vs 69%, p <0.04). In-hospital costs for procedural personnel, capital equipment, and disposable equipment were higher in the IVUS group. This was offset by lower costs for inpatient care and urgent target vessel revascularization in the IVUS group. Therefore, the total in-hospital cost was only slightly higher with IVUS (5,245 +/- $2,256 [IVUS] vs 4,776 +/- $2,961 [ANGIO], $/patient, p = 0.15). During a 2-year follow-up, costs for cardiac hospitalizations were slightly lower in the IVUS group, whereas costs for medication and indirect costs were similar. This resulted in identical total costs over the 2-year period (15,947 +/- $8,545 [IVUS] vs 16,103 +/- $9,954 [ANGIO], $/patient, p = 0.89). The incremental cost-effectiveness ratio for IVUS guidance calculated to -$1,417/major adverse cardiac event-free survival gained. In 55.3% of bootstrapping replications, IVUS was less expensive and more effective. In conclusion, when used in a provisional stenting strategy, routine IVUS imaging is cost-saving half the time.

Operator experience and long term outcome after percutaneous coronary intervention.

OBJECTIVES: To investigate the impact of operator experience on long term outcome of patients undergoing percutaneous coronary intervention (PCI). METHODS: Two hundred and fifty consecutive patients with 334 lesions undergoing elective PCI by three highly experienced (greater than 600 PCI, mean 1100) and three less experienced (fewer than 400 PCI, mean 250) high volume operators at a single tertiary care centre were prospectively studied. Quantitative assessment of the six-month angiography was possible in 273 lesions (82%). Clinical follow-up at 24 months was complete in all patients. RESULTS: Baseline characteristics of the 159 lesions treated by the highly experienced operators were comparable with the 175 lesions treated by the less experienced operators. Six months following PCI, the minimal lumen diameter at the lesion site was similar for both more experienced and less experienced operators (1.68+/-0.95 mm versus 1.63+/-0.89 mm, P=0.66), as was net lumen gain (0.97+/-1.02 mm versus 0.98+/-0.93 mm, P=0.96) and the rate of restenosis (33% versus 32%, P=0.87). By multivariate analysis, lower operator experience was not a predictor of restenosis (odds ratio 0.97, 95% CI 0.75 to 1.25, P=0.81). In addition, 24-month clinical follow-up did not reveal any relevant difference in the combined end point of death, myocardial infarction or clinically driven revascularization between more experienced (29 events in 116 patients) and less experienced operators (35 events in 134 patients; 25% versus 26%, P=0.84). CONCLUSIONS: Less experienced high volume operators seem to achieve similar long term results as more experienced high volume operators.

Gold coating and restenosis after primary stenting of ostial renal artery stenosis.

Predictors of restenosis after stent angioplasty of ostial renal artery stenosis (RAS) and long-term technical success, particularly the influence of gold coating, are unknown. During a 4-year period (1996-2000), we treated 156 consecutive patients with 219 ostial RAS of > or = 70% diameter stenosis. Gold-coated stents were used in 29% of RAS (n = 64); the vessel diameter ranged from 3 to 9 mm. The restenosis rate was 11.4% at 12 months, 12.2% for gold-coated stents and 11.1% for noncoated stents. Restenosis rates were 16% for < or = 4 mm, 17% for 5 mm, 10% for 6 mm, and 0% for > or = 7 mm (P < or = 0.05). In a backward stepwise logistic regression analysis including gold coating, vessel diameter, gender, diabetes, smoking status, as well as lesion diameter stenosis before and after stenting, vessel diameter was found the only independent predictor of restenosis (odds ratio = 0.57; 95% CI = 0.35-0.93; P = 0.02, for an increase in vessel diameter of 1 mm). Gold coating was not a significant predictor (odds ratio = 1.09; 95% CI = 0.39-3.03; P = 0.87). Seven major (4.5%) complications occurred. There were no procedural fatalities. The restenosis rate after stent angioplasty of ostial RAS is influenced by the vessel diameter but not by gold coating.

Acute thrombotic subclavian artery occlusion treated with a new rotational thrombectomy device.

PURPOSE: To report the use of a new rotational thrombectomy device for percutaneous thrombectomy of an acutely occluded subclavian artery. CASE REPORT: A 71-year-old woman with a history of multivessel coronary disease complained of sudden onset of pain at rest and paleness of the left arm. Duplex ultrasound showed a localized thrombotic occlusion of the postvertebral subclavian artery and another at the bifurcation of the brachial artery. After angiographic confirmation, the subclavian artery was recanalized with an 8-F Rotarex device via a percutaneous transfemoral access; the bifurcation of the brachial artery was recanalized by local thrombolysis (50 mg rtPA) because the thrombectomy device was too short to reach the occlusion. Follow-up examinations up to 1 year have shown normalized perfusion of the left arm. CONCLUSIONS: This new thrombectomy device is a useful tool for the percutaneous treatment of acute occlusion in the brachiocephalic arteries.

Survival after stenting of severe atherosclerotic ostial renal artery stenoses.

PURPOSE: To examine long-term survival after angioplasty and stenting of atherosclerotic renal artery stenosis (RAS). METHODS: Over a 5-year period, 241 consecutive patients (153 men; mean age 67+/-9 years, range 44-84) were treated with angioplasty and stent implantation for 355 ostial renal stenoses >70%. The procedures were performed in standard fashion using a variety of stents. For survival analysis, the patients were divided into 3 groups based on baseline creatinine levels: group 1: 115 (48%) patients with normal renal function (creatinine <1.2 mg/dL); group 2: 93 (39%) patients with moderately impaired renal function (creatinine 1.2 to 2.5 mg/dL); and group 3: 33 (13%) patients with severely impaired renal function (creatinine >2.5 mg/dL). RESULTS: All patients were treated successfully without any procedure-related mortality. The 30-day mortality was 0.4% (1/241). Twenty-two patients died during a follow-up of 27+/-15 months (range 1-60) (overall survival 91%). The causes of death were cardiac (congestive heart failure or myocardial infarction, 73%), stroke (13.5%), and malignant disease (13.5%). The survival rate was significantly lower (29.6%) in patients with a baseline serum creatinine >2.5 mg/dL (p<0.0001) than in groups 2 (89.1%) or 1 (95.4%). Long-term survival without hemodialysis or restenosis was 66.6% at 48 months. Independent predictors for a reduced survival were left ventricle function (HR 2.59, 95% CI 1.45 to 4.63, p=0.001 for each 15% incremental decrease), age (HR 1.13, 95% CI 1.03 to 1.25, p=0.011), and baseline renal function (HR 1.58, 95% CI 1.10 to 2.29, p=0.014). CONCLUSIONS: Survival after successful stenting for severe ostial RAS depends on baseline serum creatinine and left ventricle function. Efforts must be made to avoid the development of advanced ischemic nephropathy and congestive heart failure.

Late aortic dislocation of a stent following stent angioplasty for ostial renal artery stenosis.

A patient with left RAS was treated by stent angioplasty followed by a multivessel percutaneous coronary intervention. Six months later, an aortic dislocation of the stent was diagnosed. The fully expanded stent was caught with a balloon catheter and fixed in the left external iliac artery. Stent migration after initially successful stent angioplasty for RAS is possible. Fully expanded, dislocated balloon-expandable stents can be secured by implanting them into the iliac artery.

Gadodiamide as an alternative contrast agent during angioplasty in patients with contraindications to iodinated media.

PURPOSE: To evaluate gadodiamide as an alternative contrast agent for peripheral and renal angioplasty in patients with contraindications to iodinated contrast media. METHODS: Seventeen patients (10 men; mean age 74 years, range 68-83) with contraindication to iodinated contrast media were given gadodiamide as the contrast agent during peripheral and renal intra-arterial digital subtraction angiography (DSA) and subsequent percutaneous interventions (balloon angioplasty, stent placement). RESULTS: The mean volume of gadodiamide used was 136 +/- 46 mL (range 60-200). No serious side effects were observed, especially no change in renal or thyroid function; no exanthema or other allergic reactions were noted. In patients without renal artery intervention, serum creatinine at discharge remained unchanged (2.57 +/- 1.43 mg/dL to 2.40 +/- 1.28 mg/dL, p=NS). In patients undergoing angioplasty/stenting of renal artery stenoses, serum creatinine decreased significantly from 3.53 +/- 1.75 mg/dL to 2.36 +/- 1.15 mg/dL (p<0.01). All but 1 intervention was successful. Using a simple scoring system, 2 judges blinded to the contrast agent graded the quality of the peripheral DSAs as "good," whereas renal DSA images were only "sufficient." CONCLUSIONS: For patients with contraindications to iodinated materials, gadodiamide may be a suitable alternative for renal or peripheral DSA followed by angioplasty.

Stent-supported angioplasty of severe atherosclerotic renal artery stenosis preserves renal function and improves blood pressure control: long-term results from a prospective registry of 456 lesions.

PURPOSE: To report a prospective study evaluating the long-term impact of stent-supported angioplasty on renal function and blood pressure control. METHODS: In a 6-year period, 456 hemodynamically significant de novo renal artery stenoses > or =70% were treated in 340 consecutive hypertensive patients (223 men; mean age 66+/-10 years, range 44-84) with or without impaired renal function. Baseline data on serum creatinine (sCr), intrarenal resistance index, ambulatory 24-hour blood pressure monitoring, and documentation of the number and dose of antihypertensive drugs were compared to values obtained during follow-up. The primary endpoint was a 10% decrease in sCr; the glomerular filtration rate and changes in blood pressure control were additional outcome measures. RESULTS: During a mean follow-up of 34+/-20 months, sCr decreased significantly from 1.45+/-0.87 to 1.39+/-0.73 mg/dL (p=0.048). In 34% of the patients, sCr decreased >10%, 39% were unchanged, and 27% had an increase >10%. Glomerular filtration rate increased from 59+/-26 to 62+/-26 mL/min/1.73 m(2) (p=0.6). Systolic, diastolic, and mean blood pressure measurements significantly improved immediately after the intervention (132/72/93 versus 144/79/102 mmHg at baseline, p<0.0001) and remained improved during follow-up (p<0.0001). Blood pressure control was improved in 46%, unchanged in 43%, and deteriorated in 11%. Baseline sCr, bilateral intervention, percent diameter stenosis, and 3-vessel coronary disease were independent predictors of improved renal function during follow-up; the number of antihypertensive drugs taken before the intervention predicted improved blood pressure control. CONCLUSIONS: Stent-supported angioplasty of renal artery stenoses preserves renal function and improves blood pressure control in a broader spectrum of patients than previously thought.

Previous cytomegalovirus infection and restenosis after aggressive angioplasty with provisional stenting.

UNLABELLED: The aim of this study was to determine the impact of previous with cytomegalovirus (CMV) on restenosis after aggressive angioplasty with provisional stenting. DESIGN: We prospectively studied 78 consecutive patients scheduled for 6-month follow-up coronary angiography as part of the SIPS study. Anti-CMV IgG and IgM antibodies were measured on admission. RESULTS: Anti-CMV IgG positive and anti-CMV IgG negative patients had similar minimal lumen diameter (MLD) in the target vessel before (0.68 +/- 0.49 mm vs 0.71 +/- 0.52 mm, P = 0.84) and directly after the intervention (2.50 +/- 0.60 mm vs 2.57 +/- 0.52 mm, P = 0.58). After 6 months, however, the MLD was significantly smaller in CMV-positive as compared to CMV-negative patients (1.57 +/- 0.82 mm vs 2.00 +/- 0.83 mm, P < 0.03). Net lumen gain at 6 months was significantly lower in CMV-positive patients (0.89 +/- 0.79 mm vs 1.30 +/- 0.87 mm, P < 0.04) and the rate of clinically relevant restenosis was significantly higher (31% vs 7%, P < 0.02). In a multivariate logistic regression model, CMV seropositivity was an independent predictor of restenosis (odds ratio 5.7 (95% CI 1.2-30.3, P = 0.04). CONCLUSIONS: Six months after aggressive coronary angioplasty with provisional stenting, patients with prior CMV infection had a smaller MLD and a higher restenosis rate. CMV seropositivity was a strong independent predictor of restenosis.

Technological advances in the design of catheters and devices used in renal artery interventions: impact on complications.

PURPOSE: To analyze the impact of technical improvements in stent devices and guiding catheters (e.g., reduced device diameter, increased flexibility) on the complication rates associated with percutaneous renal artery interventions. METHODS: During a 5-year period (1997-2001), 268 consecutive patients (178 men; mean age 67+/-9 years) had 370 atherosclerotic renal artery stenoses (RAS) > or =70% treated with angioplasty/stenting in 320 procedures. The guiding catheter technique was used routinely until 2000; in 2001, a guiding sheath was used in 29% of cases. From 1997 to 2000, sealing devices were frequently used for sheath removal; during the last year, the sheaths were removed using the Femostop device. RESULTS: In 320 interventions, 32 (10%) complications occurred, with a decreasing frequency during the last 2 years (1996/97: 13% [7/53]; 1998: 16% [9/57]; 1999: 15% [11/74]; 2000: 4% [3/70]; 2001: 3% [2/66]). There were 21 (6.6%) local complications, including 4 cases requiring permanent hemodialysis after the intervention and 11 (3.4%) access site complications. No procedure-related death occurred. During the study period, the average sheath diameter was reduced from 8.15+/-0.76 F to 6.15+/-0.63 F (p<0.05). Mean procedural time was reduced from 42+/-13 minutes to 23+/-11 minutes (p<0.05). The initial heparin dose was reduced from 10,000 to 5000 units. CONCLUSIONS: In parallel with the use of more flexible catheters and premounted stents of lower profile, the complication rate of renal angioplasty/stenting of atherosclerotic RAS has been reduced significantly during a 5-year period.