Mirle A. Kellett

Diabetic and Nondiabetic Patients With Left Main and/or 3-Vessel Coronary Artery Disease: Comparison of Outcomes With Cardiac Surgery and Paclitaxel-Eluting Stents

OBJECTIVES This study was designed to compare contemporary surgical revascularization (coronary artery bypass graft surgery [CABG]) versus TAXUS Express (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stents (PES) in diabetic and nondiabetic patients with left main and/or 3-vessel disease. BACKGROUND Although the prevalence of diabetes mellitus is increasing, the optimal coronary revascularization strategy in diabetic patients with complex multivessel disease remains controversial. METHODS The SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) study randomly assigned 1,800 patients (452 with medically treated diabetes) to receive PES or CABG. RESULTS The overall 1-year major adverse cardiac and cerebrovascular event rate was higher among diabetic patients treated with PES compared with CABG, but the revascularization method did not impact the death/stroke/myocardial infarction rate for nondiabetic patients (6.8% CABG vs. 6.8% PES, p = 0.97) or for diabetic patients (10.3% CABG vs. 10.1% PES, p = 0.96). The presence of diabetes was associated with significantly increased mortality after either revascularization treatment. The incidence of stroke was higher among nondiabetic patients after CABG (2.2% vs. PES 0.5%, p = 0.006). Compared with CABG, mortality was higher after PES use for diabetic patients with highly complex lesions (4.1% vs. 13.5%, p = 0.04). Revascularization with PES resulted in higher repeat revascularization for nondiabetic patients (5.7% vs. 11.1%, p < 0.001) and diabetic patients (6.4% vs. 20.3%, p < 0.001). CONCLUSIONS Subgroup analyses suggest that the 1-year major adverse cardiac and cerebrovascular event rate is higher among diabetic patients with left main and/or 3-vessel disease treated with PES compared with CABG, driven by an increase in repeat revascularization. However, the composite safety end point (death/stroke/myocardial infarction) is comparable between the 2 treatment options for diabetic and nondiabetic patients. Although further study is needed, these exploratory results may extend the evidence for PES use in selected patients with less complex left main and/or 3-vessel lesions. (SYNergy Between PCI With TAXus and Cardiac Surgery [SYNTAX]; NCT00114972).

Do fish oils prevent restenosis after coronary angioplasty

BACKGROUND The omega-3 polyunsaturated fatty acids derived from fish oils have been shown to modulate many factors believed to affect the pathogenesis of atherosclerosis. Because certain features of restenosis following angioplasty mimic some of the early changes of atherogenesis, some researchers have suggested that fish oil might prevent restenosis following angioplasty. We report the effects of omega-3 fatty acids on the rate of restenosis following percutaneous intraluminal coronary angioplasty (PTCA). METHODS AND RESULTS From August 1989 through September 1992, 551 patients were randomized to start receiving a daily dietary supplement of ten 1.0-g capsules containing 80.6% ethyl esters of omega-3 fatty acids providing 4.1 g eicosapentaenoic acid (EPA) and 2.8 g docosahexaenoic acid (DHA) for 6 months or an equal amount of an ethyl ester of corn oil. Four hundred seventy subjects who were well matched for risk factors completed successful angioplasty of one or multiple lesions in native coronary vessels and constituted the study cohort, of whom 447 were evaluable at 6 months after PTCA. The criteria for restenosis were that the quantitative coronary angiography at 6 months show a > 30% increase in narrowing at the stenosis site or loss of at least half of the gain achieved at the time of PTCA and final restenosis with < 50% luminal diameter remaining. In 93% of the patients, the end point was determined by angiography and in all except 1% of these by quantitative coronary angiography. Compliance with the fish oil supplement was good as judged by incorporation of EPA and DHA in plasma and red blood cell phospholipids. The restenosis rate among analyzable patients was 46% for corn oil and 52% for fish oil (P = .37). The addition of 200 mg alpha-tocopherol for all subjects during the study had no effect on restenosis rates. CONCLUSIONS This was the largest of such trials to date, and a supplement of 8 g/d of omega-3 fatty acids failed to prevent the usual high rate of restenosis after PTCA. No adverse effects were attributable to this large daily supplement of omega-3 fatty acids.

A multicenter, randomized trial of coronary angioplasty versus directional atherectomy for patients with saphenous vein bypass graft lesions

BACKGROUND Directional coronary atherectomy and percutaneous transluminal coronary angioplasty have both been used in symptomatic patients with coronary saphenous vein bypass graft stenoses. The relative merits of plaque excision and removal versus balloon dilatation remain uncertain. We compared outcomes after directional coronary atherectomy or angioplasty in patients with de novo bypass graft stenoses. METHODS AND RESULTS Fifty-four North American and European sites randomized 305 patients with de novo vein graft lesions to atherectomy (n = 149) or angioplasty (n = 156). Quantitative coronary angiography at a core laboratory assessed initial and 6-month results. Initial angiographic success was greater with atherectomy (89.2% versus 79.0%), as was initial luminal gain (1.45 versus 1.12 mm, P < .001). Distal embolization was increased with atherectomy (P = .012), and a trend was shown toward more non-Q-wave myocardial infarction (P = .09). Although the 6-month net minimum luminal diameter gain was 0.68 mm for atherectomy and 0.50 mm for angioplasty, the restenosis rates were similar, 45.6% for atherectomy and 50.5% for angioplasty (P = .491). At 6 months, there was a trend toward decreased repeated target-vessel interventions for atherectomy (P = .092); in addition, 13.2% of patients treated with atherectomy versus 22.4% of the angioplasty patients (P = .041) required repeated percutaneous intervention of the initial target lesion. CONCLUSIONS Atherectomy of de novo vein graft lesions was associated with improved initial angiographic success and luminal diameter but also with increased distal embolization. There was no difference in 6-month restenosis rates, although primary atherectomy patients tended to require fewer target-vessel revascularization procedures.

Predicting vascular complications in percutaneous coronary interventions

OBJECTIVES Using a large, current, regional registry of percutaneous coronary interventions (PCI), we identified risk factors for postprocedure vascular complications and developed a scoring system to estimate individual patient risk. BACKGROUND A vascular complication (access-site injury requiring treatment or bleeding requiring transfusion) is a potentially avoidable outcome of PCI. METHODS Data were collected on 18,137 consecutive patients undergoing PCI in northern New England from January 1997 to December 1999. Multivariate regression was used to identify characteristics associated with vascular complications and to develop a scoring system to predict risk. RESULTS The rate of vascular complication was 2.98% (541 cases). Variables associated with increased risk in the multivariate analysis included age >or=70, odds ratio (OR) 2.7, female sex (OR 2.4), body surface area <1.6 m(2) (OR 1.9), history of congestive heart failure (OR 1.4), chronic obstructive pulmonary disease (OR 1.5), renal failure (OR 1.9), lower extremity vascular disease (OR 1.4), bleeding disorder (OR 1.68), emergent priority (OR 2.3), myocardial infarction (OR 1.7), shock (1.86), >or=1 type B2 (OR 1.32) or type C (OR 1.7) lesions, 3-vessel PCI (OR 1.5), use of thienopyridines (OR 1.4) or use of glycoprotein IIb/IIIa receptor inhibitors (OR 1.9). The model performed well in tests for significance, discrimination, and calibration. The scoring system captured 75% of actual vascular complications in its highest quintiles of predicted risk. CONCLUSION Predicting the risk of post-PCI vascular complications is feasible. This information may be useful for clinical decision-making and institutional efforts at quality improvement.

Comparing long-term survival of patients with multivessel coronary disease after CABG or PCI: Analysis of BARI-like patients in Northern New England

Background—Randomized trials comparing coronary artery bypass graft surgery (CABG) with percutaneous coronary interventions (PCIs) for patients with multivessel coronary disease (MVD) report similar long-term survival for CABG and PCI. These studies used a highly selected population of patients and providers, and their results may not be generalizable to actual care. Our goal in this study was to compare long-term survival of MVD patients treated with CABG vs PCI in contemporary practice. Methods and Results—From our northern New England registries of consecutive coronary revascularizations, we identified 10 198 CABG and 4295 PCI patients with MVD who may have been eligible for either procedure between 1994 and 2001. Vital status was obtained by linkage to the National Death Index. Proportional-hazards regression was used to calculate hazard ratios (HRs) for survival in CABG vs PCI patients after adjustment for comorbidities and disease characteristics. CABG patients were older; had more comorbidities, more 3-vessel disease, and lower ejection fractions; and were more completely revascularized. Adjusted long-term survival for patients with 3-vessel disease was better after CABG than PCI (HR, 0.60; P<0.01) but not for patients with 2-vessel disease (HR, 0.98; P=0.77). The survival advantage of CABG for 3-vessel disease patients was present in all patient populations, including women, diabetics, and the elderly and in the era of high stent utilization. Conclusions—In contemporary practice, survival for patients with 3-vessel coronary disease is better after CABG than PCI, an observation that patients and physicians should carefully consider when deciding on a revascularization strategy.

Incidence, Mechanisms, Predictors, and Clinical Impact of Acute and Late Stent Malapposition After Primary Intervention in Patients With Acute Myocardial Infarction An Intravascular Ultrasound Substudy of the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Trial

Background— The incidence and mechanisms of acute and late stent malapposition after primary stent implantation in ST-segment elevation myocardial infarction remain unclear. Methods and Results— The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial was a dual-arm, factorial, randomized trial comparing paclitaxel-eluting stents (PES) and otherwise equivalent bare metal stents (BMS) in ST-segment elevation myocardial infarction patients. The intravascular ultrasound substudy enrolled 241 patients with 263 native coronary lesions (201 PES, 62 BMS) with baseline and 13-month follow-up imaging. Postintervention acute stent malapposition (ASM) occurred in 34.3% PES- and 40.3% BMS-treated lesions. Of these, 39.1% PES- and 40.0% BMS-treated lesions resolved at follow-up, especially within the stent body (66.7%); complete resolution was accompanied by a reduction in external elastic membrane area. An ASM area >1.2 mm2 best separated persistent from resolved ASM. At follow-up, a higher frequency of late stent malapposition was detected in PES-treated lesions (46.8%) mainly because of more late acquired stent malapposition (30.8%) compared with BMS-treated lesions. Late acquired stent malapposition area correlated to the decrease of peri-stent plaque in the subset of lesions without positive remodeling and only to change in external elastic membrane in the group with positive remodeling. Independent predictors of late acquired stent malapposition were plaque/thrombus protrusion (odds ratio, 5.60; 95% confidence interval [CI], 2.32 to 13.54) and PES use (odds ratio, 6.32; 95% CI, 2.15 to 18.62). Conclusions— The incidence of ASM was similar in PES- and BMS-treated lesions, but late acquired stent malapposition was more common in PES-treated lesions. The reason for resolved ASM was negative remodeling, with larger ASM areas separating persistent from resolved ASM. Late acquired stent malapposition was due mainly to positive remodeling and plaque/thrombus resolution. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Increased risk of severe protamine reactions in NPH insulin-dependent diabetics undergoing cardiac catheterization.

Protamine is widely used for reversing systemic heparinization after cardiac catheterization. Although rare, major reactions to protamine that simulate anaphylaxis occasionally occur and have previously been associated only with an allergic reaction to fish. Because neutral protamine Hagedorn (NPH) insulin includes protamine, it might be anticipated that NPH insulin-dependent diabetic patients would develop sensitivity to protamine. Of 866 consecutive patients undergoing cardiac catheterization over a 20 month period, 651 received protamine for reversal of heparinization. Of these, 8.5% (56/651) were diabetics and 2.3% (15/651) were NPH insulin-dependent diabetics. During this period seven patients were observed immediately after administration of protamine to have major adverse reactions that required the administration of catecholamines. One death ensued. Of the seven major reactions, four occurred in NPH insulin-dependent diabetics and one occurred in a patient with an allergy to fish. The incidence of major protamine reactions was 27% (4/15) in the NPH insulin-dependent diabetics vs 0.5% (3/636) in those with no history of NPH insulin use (p less than .001). This represents a 50-fold increased risk of a major reaction to protamine if the patient was receiving NPH insulin. Accordingly, we recommend that diabetics on NPH insulin and patients with allergies to fish undergo cardiac catheterization without the use of protamine or, when necessary, that protamine be administered cautiously in anticipation of a major adverse reaction.

A randomized, double-blinded, placebo-controlled, dose-ranging study measuring the effect of an adenosine agonist on infarct size reduction in patients undergoing primary percutaneous transluminal coronary angioplasty: the ADMIRE (AmP579 delivery for myocardial infarction REduction) study

BACKGROUND Evidence suggests that myocardial ischemic preconditioning and reperfusion injury may be mediated by adenosine A1 and A2 receptors. AMP579 is a mixed adenosine agonist with both A1 and A2 effects. In animal models of acute myocardial infarction (MI), AMP579 reduced infarct size at serum levels of 15 to 24 ng/mL. METHODS The AMP579 Delivery for Myocardial Infarction REduction study evaluated AMP579 in a double-blind, multicenter, placebo-controlled trial of 311 patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) after acute ST-segment elevation MI. Patients were randomly assigned to placebo or to 3 different doses of AMP579 continuously infused over 6 hours. The primary end point was final MI size measured by technetium Tc-99m sestamibi scanning at 120 to 216 hours after PTCA. Secondary end points included myocardial salvage and salvage index at the same time interval (in a subset of patients who underwent baseline technetium Tc-99m sestamibi scan), left ventricular ejection fraction and heart failure at 4 to 6 weeks, duration of hospitalization, and cardiac events at 4 weeks and 6 months. RESULTS Final infarct size did not differ among the placebo group and the active treatment groups for either anterior MI or nonanterior MI. In patients with anterior MI, median myocardial salvage was increasingly higher in the groups receiving ascending dosages of AMP579 plus PTCA. Serum levels approaching levels shown to reduce infarct size in animal models were achieved only in the 60-mcg/kg treatment group. CONCLUSION AMP579 was safe at the doses tested, but it did not reduce infarct size. There was a trend toward greater myocardial salvage in treated patients with anterior MI.

Percutaneous coronary laser thermal angioplasty

Percutaneous coronary laser thermal angioplasty was successfully performed before conventional balloon angioplasty in a 55 year old white man with a 90% left anterior descending artery stenotic lesion and angina at rest (Canadian Heart Association class IV). The lesion was reduced to 50% residual stenosis using a 1.7 mm laser-heated metallic capped fiber and two pulses of 8 W of argon laser energy, each delivered for 5 seconds. With subsequent balloon angioplasty, the lesion was further decreased to 10% residual stenosis. The entire procedure was well tolerated without chest pain or burning, vessel perforation or spasm, thrombus formation or embolization of debris. The patient was free of pain at 1 month follow-up. This case demonstrates the feasibility of safely performing percutaneous coronary laser thermal angioplasty. Additional studies are indicated to determine the clinical role and potential benefits of coronary laser thermal angioplasty in relation to the established procedures of bypass surgery and conventional balloon angioplasty.

Gender-related changes in the practice and outcomes of percutaneous coronary interventions in Northern New England from 1994 to 1999.

OBJECTIVES We sought to determine whether the changing practice of interventional cardiology has been associated with improved outcomes for women, and how these outcomes compare with those for men. BACKGROUND Previous work from the early 1990s suggested women are at a higher risk than men for adverse outcomes after percutaneous coronary interventions (PCIs). From 1994 to 1999 data were collected on 33,666 consecutive hospital admissions for a PCI in Northern New England. Multivariate models were used to adjust for differences in case-mix across year of procedure when comparing outcomes. Direct standardization was used to calculate adjusted rates. RESULTS From 1994 to 1999, the case-mix worsened for both women and men, although women had more co-morbidities than did men throughout the period. Stent use increased over time (>75% in 1999). Concomitantly, the need for emergency coronary artery bypass graft surgery (CABG) decreased significantly (p(trend) < or = 0.001; in 1999: 0.06% for women, 0.05% for men). Although the emergency CABG rates were higher for women at the beginning of the study, by the end, they were comparable (adjusted odds ratio 1.34, 95% confidence interval 0.76 to 2.38, p = 0.315). The myocardial infarction (MI) rates decreased over time for both women (by 29.7%, p(trend) = 0.378) and men (by 37.6%, p(trend) = 0.009) and did not differ by gender. The mortality rates did not decrease significantly over time and were not significantly different between the genders (mean 1.21% for women, 1.06% for men; p = 0.096). CONCLUSIONS Concurrent with the changing practice of PCI, and despite treating sicker patients, there have been important improvements in post-PCI CABG and MI rates for women, as well as for men. Unlike in earlier years, there are no longer significant differences in outcomes by gender.