Influence of stenotic lesion morphology on immediate and long-term (6 months) angiographic outcome: comparative analysis of directional coronary atherectomy versus standard balloon angioplasty.

OBJECTIVES: This study sought to determine whether preprocedural lesion morphology differentially affects the outcome of directional coronary atherectomy versus standard balloon angioplasty. BACKGROUND: Despite previous studies (Canadian Coronary Atherectomy Trial [CCAT]/Coronary Angioplasty Verus Excisional Atherectomy Trial [CAVEAT]), directional coronary atherectomy continues to be recommended on the basis of lesion-specific features, although the validity of this approach has never been proved. METHODS: A retrospective, subgroup analysis of the CCAT data base (group average +/- SD) was performed. RESULTS: In the long term (6 months), both procedures were equally successful in the proximal left anterior descending coronary artery (directional atherectomy 0.62 +/- 0.70 mm vs. coronary angioplasty 0.70 +/- 0.72 mm, p = NS), with atherectomy tending to perform best in relatively "simple" lesions (American College of Cardiology/American Heart Association [ACC/AHA] type A: atherectomy 0.57 +/- 0.70 mm vs. angioplasty 0.50 +/- 0.77 mm; ACC/AHA type B1: atherectomy 0.65 +/- 0.68 mm vs. angioplasty 0.60 +/- 0.68 mm) and those with moderate dystrophic calcification (atherectomy 0.79 +/- 0.56 mm vs. angioplasty 0.45 +/- 0.73 mm). Although greatest minimal lumen diameter gains were seen in larger (> 3 mm) coronary arteries (atherectomy 0.76 +/- 0.62 mm vs angioplasty 0.80 +/- 0.72 mm, p = NS) and those with severe obstruction (preprocedural minimal lumen diameter < 1.0 mm: atherectomy 0.80 +/- 0.62 mm vs. angioplasty 0.84 +/- 0.63 mm, p = NS), neither technique was superior, and eccentric stenoses (symmetry index < 0.5) had similar outcomes (atherectomy 0.59 +/- 0.49 mm vs. angioplasty 0.62 +/- 0.65 mm, p = NS). CONCLUSIONS: These data refute many preconceptions regarding the choice of directional coronary atherectomy on the basis of anatomic criteria.

Randomized trials of directional coronary atherectomy: implications for clinical practice and future investigation.

OBJECTIVES: This study compared and contrasted the randomized trials of directional atherectomy and coronary angioplasty for de novo native coronary artery lesions. BACKGROUND: The results of two randomized trials, the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) and the Canadian Coronary Atherectomy Trial (CCAT), comparing initial and intermediate-term outcome of directional coronary atherectomy and conventional coronary angioplasty in de novo native vessels, have been reported. In CAVEAT any coronary artery segment that could be treated by either technique was included; in CCAT only nonostial proximal left anterior descending coronary artery stenoses were studied. METHODS: The primary end point was 6-month angiographic restenosis. Clinical outcome end points at 6 months included death, myocardial infarction, emergency bypass surgery and abrupt closure. RESULTS: Initial angiographic success rates were significantly improved with directional coronary atherectomy compared with conventional angioplasty (89% vs. 80% for CAVEAT; 98% vs. 91% for CCAT). Also, the initial improvement in minimal lumen diameter and final immediate postprocedural residual diameter stenosis were better with atherectomy. In CCAT, there was no difference in initial complications; in CAVEAT, non-Q wave myocardial infarction rates and abrupt closure were increased with atherectomy. Despite improved success rates and better lumen achieved with atherectomy, in CCAT there was no difference in angiographic restenosis (46% for directional atherectomy vs. 43% for angioplasty). In CAVEAT, in a prespecified subset analysis involving the proximal left anterior descending coronary artery, restenosis was both significantly and clinically less for directional atherectomy (51% vs. 63%). For non-left anterior descending coronary artery segments, there was no difference. CONCLUSIONS: These studies document the difference between achievement of an excellent initial angiographic result and the longer term issue of clinical restenosis. Widespread use of directional coronary atherectomy to treat lesions that would be well treated by angioplasty in an attempt to decrease restenosis rates substantially does not appear indicated by the data. In individual lesions, directional atherectomy should be selected with the view toward optimizing initial results. Further trials are needed to determine whether more aggressive or better targeted directional coronary atherectomy may improve not only the initial gain but the long-term outcome as well.

Therapy with nitroglycerin increases coronary vasoconstriction in response to acetylcholine.

OBJECTIVES: The purpose of this study was to investigate whether therapy with nitroglycerin (GTN) would lead to abnormal coronary artery responses to the endothelium-dependent vasodilator acetylcholine. BACKGROUND: Nitroglycerin therapy is associated with specific biochemical changes in the vasculature that may lead to increased vascular sensitivity to vasoconstrictors. METHODS: Patients were randomized to continuous transdermal GTN, 0.6 mg/h (n = 8), or no therapy (n = 7), for 5 days prior to a diagnostic catheterization. Patients had similar risk factors for endothelial dysfunction. Quantitative angiography was performed in the morning to measure the mean luminal diameter of the left anterior descending coronary artery (LAD) in response to intracoronary acetylcholine (peak concentration, 10(-4) mol/liter). The transdermal preparation was removed from the GTN group, and 3 h later experimental procedures were repeated. RESULTS: In the morning, the GTN group experienced greater coronary constriction in response to acetylcholine infusion than those not receiving GTN (-19.6+/-4.2 vs. -3.8+/-3.0%; p = 0.01). Three hours later, the GTN group continued to display greater constriction to acetylcholine (-24.1+/-5.9%) as compared to the non-GTN group (-1.8+/-4.8%). When the morning and afternoon responses to acetylcholine were compared, the increase in coronary constriction in the GTN group was greater than the change observed in the non-GTN group (p < 0.05). CONCLUSIONS: This study demonstrates that therapy with GTN causes abnormal coronary vasomotor responses to the endothelium-dependent vasodilator acetylcholine, changes that were persistent for up to 3 hours after GTN discontinuation. This nitrate-associated vasomotor dysfunction has implications with respect to the development of nitrate tolerance and the potential for adverse events during nitrate withdrawal.

Long-term endothelial dysfunction after coronary artery stenting.

OBJECTIVES: We assessed the endothelial-dependent vasomotor function in nonrestenotic coronary arteries more than six months following stent implantation, balloon angioplasty (BA), and directional atherectomy (DCA). BACKGROUND: Catheter-based coronary interventions are associated with extensive arterial injury. Endothelial function has been shown to remain chronically abnormal after vascular injury. The long-term effects of different percutaneous coronary interventions on endothelial function are not known. METHODS: Thirty-nine patients treated at least six months earlier with a coronary intervention for isolated proximal left anterior descending (LAD) stenosis, with no evidence of restenosis, were studied. Twelve patients had been stented, 15 had been treated with BA, and 12 had undergone DCA. Changes in diameter of the intervened LAD, and the unintervened circumflex coronary artery (Cx), in response to intracoronary acetylcholine infusions were assessed by quantitative angiography. RESULTS: The groups had similar angiographic characteristics and risk factors for endothelial dysfunction. The LAD constricted significantly more (p = 0.02) in previously stented patients (-21.8+/-4.3%), as compared to patients previously treated with BA (-9.5+/-2.8%) or with DCA (-9.1+/-3.6%). In contrast, acetylcholine infusion resulted in mild constriction in the Cx, which was similar in the three groups (p = 0.47). By multiple regression analysis, previous implant of a stent was the only significant predictor of LAD constriction (p = 0.008). CONCLUSIONS: More severe endothelial dysfunction was observed long term after stenting as compared to BA or DCA. These findings may have implications with respect to the progression of atherosclerosis in coronary arteries subjected to percutaneous interventions.

Prinzmetal's angina with coronary artery spasm. Angiographic, pharmacologic, metabolic and radionuclide perfusion studies.

We studied the effects of coronary artery spasm on perfusion of the microvasculature in a patient with Prinzmetal's angina. Intracoronary injections of 99mTc and 131I-labelled macroaggregated human serum albumin were performed (1) at rest, (2) during spontaneous angina, (3) after the administration of nitroglycerin and (4) during pacing-induced spasm and the resultant scans compared. The resting scan was normal. Pain and spasm were associated with a perfusion defect that was localized to the anterior and inferior walls of the left ventricle. The localization of the perfusion defect corresponded with angiographically demonstrated spasm involving left anterior descending and distal circumflex coronary arteries. A subsequent myocardial infarction was localized by 43K scanning to the same perfusion area. Metabolic and parasympathetic stimulation studies were performed but were inconclusive. The patient's recurrent pains were ultimately controlled with large oral doses of isosorbide dinitrate.

Effect of negative pleural pressure on left ventricular hemodynamics.

Negative pleural pressure alters left ventricular (LV) function. LV volume changes have been studied in human subjects, but little is known of the hemodynamic effects. The effect of changes of pleural pressure on LV hemodynamics during a Mueller maneuver (inspiration against an obstruction) was studied in 11 subjects and during quiet, unobstructed inspiration in 3. During the Mueller maneuver, there was an initial decrease in pulmonary wedge pressure and aortic systolic pressure, almost as great as the decrease in pleural pressure. Thereafter, these pressures increased despite a sustained reduction in pleural pressure. Toward the end of the Mueller maneuver, pulmonary wedge transmural pressure averaged 31 +/- 12 mm Hg and in 6 patients large v waves developed. The increase in aortic transmural pressure averaged 30 +/- 16 mm Hg. Aortic pulse pressure decreased on the first beat from control levels of 59 +/- 21 to 47 +/- 21 (p less than 0.001) and then returned to control levels. During normal breathing in 3 subjects, studied with intraesophageal balloons, there was a similar increase in both transmural aortic and transmural pulmonary wedge pressures with a decrease in pleural pressure 6 mm Hg during inspiration. Thus, increased negative pleural pressure was associated with a marked increase in pulmonary wedge transmural pressure; the increase was approximately proportionate to the decrease in pleural pressure. It is suggested that this increase was due to increased impedance to LV ejection and to right ventricular expansion interfering with LV diastolic filling.

Use of evidence-based medical therapy in patients undergoing percutaneous coronary revascularization in the United States, Europe, and Canada. Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I) and Canadian Coronary Atherectomy Trial (CCAT) investigators.

The objective of this study was to examine whether there are international variations in the use of evidence-based medical therapy in patients undergoing percutaneous coronary revascularization. We analyzed the medical therapy of patients in the United States (US) (n = 878), Europe (n = 134), and Canada (n = 274) who underwent percutaneous coronary revascularization in either the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I) (enrollment from August 1991 to April 1992) or the Canadian Coronary Atherectomy Trial (CCAT) (enrollment from July 1991 to August 1992). We found that at the time of hospital admission, Canadian patients had the highest rates of treatment with aspirin (95% vs 57% US and 78% Europe; p = 0.002), calcium antagonists (75% vs 48% US and 43% Europe; p 0.0001), beta blockers (60% vs 32% US and 46% Europe; p = 0.02), and combination anti-ischemic therapy (67% vs 43% US and 56% Europe; p = 0.0001). By discharge, however, Canadian patients had the lowest rates of treatment with nitrates (12% vs 40% US and 44% Europe; p = 0.0001) and combination anti-ischemic therapy (29% vs 53% US and 47% Europe; p < 0.01). At both admission and discharge, rates of treatment with angiotensin-converting enzyme inhibitors and lipid-lowering agents were < 15% in all 3 regions. We conclude that significant international variations exist in the use of evidence-based medical therapy in patients undergoing percutaneous coronary revascularization.

Acute outcome of directional coronary atherectomy vs standard balloon angioplasty in de novo left anterior descending stenoses.

To assess the immediate outcome of directional coronary atherectomy (DCA) versus standard balloon angioplasty (PTCA) in de novo left anterior descending coronary stenoses, 25 consecutive atherectomies (22 men, 3 women) performed at The Toronto Hospital, between July 1990 and March 1991 were compared with 25 (14 men, 11 women) temporally matched successful angioplasties. Coronary stenoses were analyzed by quantitative arteriography, using the Coronary Measurement System (Leiden, The Netherlands), with estimation of transstenotic hemodynamics by fluid dynamic equations. Before and after procedure qualitative blood flow (TIMI criteria) was also evaluated, as was intimal haziness and coronary dissection. In comparison to PTCA, coronary atherectomy produced less residual minimum stenotic diameter (DCA, 2.75 +/- 0.55 vs PTCA, 1.70 +/- 0.44 mm, p < 0.001), and relative percent diameter stenosis (DCA, 17.9 +/- 10.7 vs PTCA, 34.4 +/- 10.7 percent, p < 0.001), with less transstenotic obstructive gradient (DCA, 0.2 +/- 0.2 vs PTCA, 1.0 +/- 1.5 mm Hg, p < 0.05), and greater estimated stenotic flow reserve (DCA, 4.86 +/- 0.15 vs PTCA, 4.50 +/- 0.48 x baseline, p < 0.05). Coronary atherectomy "normalized" TIMI flow patterns in virtually all patients (DCA, 2.96 +/- 0.20 vs PTCA, 2.72 +/- 0.45, p < 0.05), while creating less intimal haziness (DCA, 10/25 [40 percent] vs PTCA, 23/25 [92 percent], p < 0.01), and coronary dissection (DCA, 6/25 [24 percent] vs PTCA, 16/25 [64 percent], p < 0.05). Therefore, when compared with standard balloon angioplasty, DCA produces less residual stenosis, better transstenotic hemodynamics, while decreasing the frequency of coronary artery damage, in de novo left anterior descending stenoses.

Experience with ergonovine provocative testing for coronary arterial spasm.

We reviewed our experience with the ergonovine provocative test for coronary arterial spasm in 40 patients with pain in the chest believed to be angina pectoris and in one patient with a myocardial infarction and normal coronary arteries. Twenty-nine patients had normal coronary arteries, while 12 had mild to moderate lesions. Ergonovine maleate was administered incrementally in total cumulative doses of 0.25 mg to 1.2 mg. The effect of ergonovine on coronary arterial caliber was determined by comparing the arterial diameter from the angiogram obtained after administration of ergonovine with that from the control. Measurements were made at the same preselected points in both films and also at points of greatest response. Excluding the three cases with complete occlusion, the mean reduction in coronary arterial diameter at preselected points was 12 +/- 15 percent. When the points of greatest response were examined, the maximum reduction in coronary arterial diameter was less than 25 percent in 13 patients, 25 to 50 percent in 20 patients, and more than 50 percent in eight patients. The patterns of response included complete occlusion of a vessel in the three patients with variant angina, diffuse narrowing in 16, diffuse and focal narrowing in six, and spasm at the catheter tip in three patients. All patients with maximum reductions of more than 50 percent in coronary arterial diameter and six of those with maximum reductions of 25 to 50 percent had pain in the chest, but only the three with complete occlusion had associated changes in the S-T segment. Thus, the response in patients with variant angina represents one end of a spectrum of responses to administration of ergonovine. In addition, a large number of patients may have ergonovine-induced pain in the chest without electrocardiographic changes and only an intermediate degree of coronary arterial spasm.

Analysis of atherosclerotic plaques obtained by coronary atherectomy: Foam cells correlated positively with subsequent restenosis.

Restenosis following coronary intervention is a complex process the mechanisms of which remains mostly unknown. Tissue obtained by atherectomy is an important means to study restenosis. Previous studies on atherectomy-retrieved tissue have not identified histologic features that correlate with restenosis. We performed an histopathologic evaluation on atherosclerotic plaque tissue obtained by atherectomy from 58 patients, all of whom had a 6-month angiographic follow-up. We identified macrophages and lymphocytes and localized tumor necrosis factor-α expression in the tissue by immunohistochemistry. Histopathology was correlated with late angiographic outcomes. Of 10 histologic features evaluated in the plaque tissue, only the presence of foam cells, identified in paraffin sections, correlated positively with restenosis (p = 0.04). Immunohistochemistry showed that macrophages (p = .07), tumor necrosis factor-α (p = .07), and lymphocytes (p = .14) were more prominent, but not significantly so, in lesions from patients with foam cells and restenosis than in lesions from patients without foam cells or restenosis. Thus the presence of foam cells in primary lesions obtained by atherectomy as identified in paraffin-embedded tissue appears to be a marker for restenosis.

Evolving indications for preoperative intraaortic balloon pump assistance.

Over a two-year period about 1,000 operations were performed with cardiopulmonary bypass. Intraaortic balloon pump assistance (IABP) was employed on 150 occasions, and a review of these has permitted clarification of the indications for its use. Sixty patients had IABP for carcinogenic shock either after infarction or cardiotomy, and 37 (62%) survived. Preoperative IABP in 90 high-risk patients resulted in survival for 79 (88%). The indications for prophylactic IABP included: (1) relief of severe pain, which occurred in 42 patients with acute coronary insufficiency, (2) improvement in the coronary perfusion pressure, which was accomplished in 20 patients with significant left main coronary artery occlusion or its equivalent, and (3) protection of left ventricular function, which war carried out in 28 patients with an LV ejection fraction of less than 0.40. The significance of the preoperative endocardial viability ratio (EVR) in relation to prophylactic IABP was also assessed: an EVR below 0.70 appears to be an indication for preoperative IABP.

Early experience with directional coronary atherectomy: documentation of the learning curve.

OBJECTIVE: To evaluate evolving selection criteria and angiographic outcome ('learning curve') for directional coronary atherectomy. SETTING: Tertiary referral, university-based hospital. PATIENTS: Initial 50 subjects undergoing directional coronary atherectomy of de novo left anterior descending stenoses at The Toronto Hospital from July 1990 to April 1991. INTERVENTIONS: Directional coronary atherectomy according to standard interventional techniques, with pre- and post procedure qualitative evaluation and quantitative coronary arteriography (Cardiac Measurement System; Leiden, The Netherlands) to define angiographic outcome. RESULTS: Comparing 'early' (group 1) versus 'late' (group 2) subjects, baseline demographics and clinical parameters were similar. Later subjects demonstrated increased coronary tortuosity (group 1, 1.40 versus group 2, 1.64, P < 0.01) and major side branch involvement within the stenosis (group 1, seven of 25 [28%] versus group 2, 18 of 25 [72%], P < 0.01). Regardless of experience, post procedure residual minimum stenotic diameters were equal (group 1, 2.75 +/- 0.55 versus group 2, 2.49 +/- 0.42 mm) in progressively longer lesions (group 1, 11.4 +/- 4.9 versus group 2, 13.3 +/- 5.5 mm, P < 0.1), with increased symmetry (group 1, 0.60 +/- 0.28 versus group 2, 0.73 +/- 0.19, P < 0.05). Analysis of consecutive pentiles (10 subjects per group) indicated gradual increases in post procedure residual lumen during early experience (the first 30 subjects), with an abrupt deterioration in outcome (fourth pentile), secondary to qualitative changes in coronary anatomy, before a return to satisfactory residual minimum stenotic diameters (fifth pentile). CONCLUSIONS: This study defines a distinct 'learning curve' during the initial 30 patients undergoing directional coronary atherectomy, with subtle changes in case selection, predominantly reflected by qualitative indices (eg, tortuosity, dystrophic calcification), resulting in a transient deterioration in final outcomes (patient 31 to 40). Subsequently, optimal results were re-established after defining appropriate case selection criteria, in conjunction with progressive expertise.

Directional coronary atherectomy at the Toronto and Mount Sinai Hospitals: report of the initial 120 procedures.

OBJECTIVE: To assess the procedural success and complication rates of the first 120 directional coronary atherectomy cases performed at two Toronto hospitals. DESIGN AND SETTING: Case series in tertiary referral centres. PATIENTS: One hundred and thirteen patients in whom 120 atherectomy procedures were attempted between July 1990 and April 1992. INTERVENTION: Directional coronary atherectomy. MAIN RESULTS: Angiographic success was obtained in 115 of 120 procedures (96%) involving 117 of 123 lesions (95%). Procedural success (angiographic success without death, myocardial infarction or coronary bypass surgery) was obtained in 110 of 120 procedures (92%). Adjunctive balloon angioplasty was required in 20 procedures (17%). There was one death at 36 h in an elderly patient who underwent an emergency procedure while in cardiogenic shock. Periprocedural non-Q wave myocardial infarction occurred in five patients. There were no Q wave myocardial infarctions. Three patients required coronary bypass surgery prior to discharge and vascular complications occurred in five patients. CONCLUSIONS: Directional coronary atherectomy can be performed with procedural success and complication rates comparable to conventional balloon angioplasty. Randomized trials are underway to determine if atherectomy results in a lower restenosis rate.

The role of glycoprotein IIb/IIIa platelet inhibition in percutaneous coronary intervention in the stent era.

In autumn 1996, shortly after the platelet glycoprotein (GP) IIb/IIIa inhibitor abciximab was approved for clinical use by the Health Protection Branch of Health Canada, seven interventional cardiologists met in a roundtable forum to review the use of abciximab in percutaneous transluminal coronary angioplasty (PTCA). While a compelling body of data was presented that argued strongly for adjunctive abciximab in conventional balloon angioplasty, the participants found in difficult to extrapolate the findings to contemporary interventional practice dominated by stent implantation. This uncertainty stemmed from the lack of clinical trials of abciximab during the stent era. Concerns were also raised that the unrestricted use of two expensive therapeutic modalities (stent implantation and GP IIb/IIIa inhibition) would place severe strains on catheterization laboratory budgets. The general consensus was that, pending the availability of further data, abciximab should probably be reserved for selected at-risk patients. This article summarized the roundtable discussions to provide cardiologists' perspectives on the use of abciximab in interventional practice. An overview of platelet physiology and the rationale for GP IIb/IIIa receptor inhibition; a summary of the results of recent randomized clinical trials that assessed the efficacy of abciximab in PTCA; an account of how stents became the most prevalent technique used in coronary intervention; a summary of the available data evaluating abciximab in conjunction with stent implantation; and a synopsis of the conference discussions are included.

Clinical outcomes of patients more than one year following randomization in the Canadian Coronary Atherectomy Trial (CCAT).

BACKGROUND: The Canadian Coronary Atherectomy Trial (CCAT) assessed, in a randomized comparison, the clinical and angiographic outcomes following atherectomy with those following balloon angioplasty for the treatment of de novo lesions in the proximal one-third of the left anterior descending artery (LAD). Although the procedural success rate was somewhat higher and the postprocedure lumen larger in patients treated with atherectomy, lumen dimensions, restenosis rates and clinical outcomes were similar in the two groups at six months. To determine whether late differences emerged between the groups, clinical follow-up was obtained at a median of 18 (range 10 to 31) months after randomization. METHODS AND RESULTS: Patients were contacted monthly by telephone for the first six months. Subsequent follow-up information was obtained in 272 (99%) of the 274 randomized patients via a clinic visit or telephone interview with the patient and/or a relative. Additional information was obtained from the referring physician as required. There were no differences in adverse events between the two groups during follow-up. In patients randomized to atherectomy compared with balloon angioplasty, death occurred in 1.5% versus 2.2% (cardiac death 0.7% versus 0.7%); myocardial infarction in 5.1% versus 5.9% (Q wave 1.5% versus 1.5%); coronary bypass surgery in 13.1% versus 12.6%; and repeat target lesion intervention in 22.6% versus 21.5%. Persistent or recurrent Canadian Cardiovascular Society class III/IV angina not treated by a further intervention was present in 1.5% versus 2.2%. The combined end-point of death or nonfatal myocardial infarction occurred in nine (6.6%) versus 11 (8.1%) patients and any adverse cardiac event in 50 (36.5%) versus 53 (39.3%). Multivariate logistic regression indicated that unstable angina, reference vessel size and preprocedure minimum lumen diameter were the only variables independently associated with adverse events. CONCLUSIONS: The initial choice of directional atherectomy or balloon angioplasty had no impact on clinical outcome over a period of 18 months in this patient population. With either technique, just over 60% of patients with proximal LAD disease experienced sustained symptomatic improvement without an adverse event following a single procedure, and 80% achieved this status following a repeat percutaneous intervention.