Richard G. Bach

Prevalence, Predictors, and Outcomes of Premature Discontinuation of Thienopyridine Therapy After Drug-Eluting Stent Placement Results From the PREMIER Registry

Background— Although drug-eluting stents (DES) significantly reduce restenosis, they require 3 to 6 months of thienopyridine therapy to prevent stent thrombosis. The rate and consequences of prematurely discontinuing thienopyridine therapy after DES placement for acute myocardial infarction (MI) are unknown. Methods and Results— We used prospectively collected data from a 19-center study of MI patients to examine the prevalence and predictors of thienopyridine discontinuation 30 days after DES treatment. We then compared the mortality and cardiac hospitalization rates for the next 11 months between those who stopped and those who continued thienopyridine therapy. Among 500 DES-treated MI patients who were discharged on thienopyridine therapy, 68 (13.6%) stopped therapy within 30 days. Those who stopped were older, less likely to have completed high school or be married, more likely to avoid health care because of cost, and more likely to have had preexisting cardiovascular disease or anemia at presentation. They were also less likely to have received discharge instructions about their medications or a cardiac rehabilitation referral. Patients who stopped thienopyridine therapy by 30 days were more likely to die during the next 11 months (7.5% versus 0.7%, P<0.0001; adjusted hazard ratio=9.0; 95% confidence interval=1.3 to 60.6) and to be rehospitalized (23% versus 14%, P=0.08; adjusted hazard ratio=1.5; 95% confidence interval=0.78 to 3.0). Conclusions— Almost 1 in 7 MI patients who received a DES were no longer taking thienopyridines by 30 days. Prematurely stopping thienopyridine therapy was strongly associated with subsequent mortality. Strategies to improve the use of thienopyridines are needed to optimize the outcomes of MI patients treated with DES.

Baseline Risk of Major Bleeding in Non–ST-Segment–Elevation Myocardial Infarction The CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Bleeding Score

Treatment of non–ST-segment elevation myocardial infarction (NSTEMI) has traditionally focused on preventing or minimizing ischemic complications with potent antithrombotic medications and catheter-based interventions.1–3 Yet these reductions in recurrent ischemic events have come at the cost of increased major bleeding,4–7 which is itself associated with worse clinical outcomes.7–13 Bleeding complications have received attention recently, in part because newer antithrombotic agents for NSTEMI have unique ischemia and bleeding profiles. Some agents demonstrate low rates of major bleeding with similar efficacy,5,14 while others demonstrate higher rates of major bleeding with superior efficacy.15 Given the importance of safety and efficacy,12 the recent American College of Cardiology (ACC)/American Heart Association (AHA) practice guidelines placed renewed emphasis on risk stratification to guide treatment for NSTEMI.3 While tools for ischemic risk stratification are well described (i.e., TIMI, PURSUIT, and GRACE risk scores),16–18 bleeding risk stratification is more limited. The few bleeding risk stratification models in existence include treatments known to influence bleeding or are derived from subgroups or trial populations not representative of those at greatest risk.10,13,19 Consequently, better estimation of baseline risk of bleeding in NSTEMI patients is needed to facilitate optimal treatment selection. Using data from the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) Quality Improvement Initiative, we developed and validated a scoring system to estimate baseline risk of in-hospital major bleeding in patients with NSTEMI. The CRUSADE bleeding score provides a tool that equips clinicians with the means to consider safety outcomes when making treatment decisions for patients with NSTEMI.Background— Treatments for non–ST-segment–elevation myocardial infarction (NSTEMI) reduce ischemic events but increase bleeding. Baseline prediction of bleeding risk can complement ischemic risk prediction for optimization of NSTEMI care; however, existing models are not well suited for this purpose. Methods and Results— We developed (n=71 277) and validated (n=17 857) a model that identifies 8 independent baseline predictors of in-hospital major bleeding among community-treated NSTEMI patients enrolled in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) Quality Improvement Initiative. Model performance was tested by c statistics in the derivation and validation cohorts and according to postadmission treatment (ie, invasive and antithrombotic therapy). The CRUSADE bleeding score (range 1 to 100 points) was created by assignment of weighted integers that corresponded to the coefficient of each variable. The rate of major bleeding increased by bleeding risk score quintiles: 3.1% for those at very low risk (score ≤20); 5.5% for those at low risk (score 21–30); 8.6% for those at moderate risk (score 31–40); 11.9% for those at high risk (score 41–50); and 19.5% for those at very high risk (score >50; Ptrend <0.001). The c statistics for the major bleeding model (derivation=0.72 and validation=0.71) and risk score (derivation=0.71 and validation=0.70) were similar. The c statistics for the model among treatment subgroups were as follows: ≥2 antithrombotics=0.72; <2 antithrombotics=0.73; invasive approach=0.73; conservative approach=0.68. Conclusions— The CRUSADE bleeding score quantifies risk for in-hospital major bleeding across all postadmission treatments, which enhances baseline risk assessment for NSTEMI care.

Correlation of pharmacological 99mTc-sestamibi myocardial perfusion imaging with poststenotic coronary flow reserve in patients with angiographically intermediate coronary artery stenoses.

BACKGROUND The physiological assessment of angiographically intermediate-severity stenoses remains problematic. Functional measurements of poststenotic intracoronary Doppler coronary flow reserve can be performed in humans but have not been correlated with hyperemic myocardial perfusion imaging or angiographic data in this patient population. METHODS AND RESULTS Thirty-three patients undergoing diagnostic quantitative coronary angiography (QCA) for assessment of intermediate-severity coronary artery disease (mean QCA percent diameter stenosis, 56 +/- 14%) were studied. Proximal and distal poststenotic Doppler coronary flow velocities were measured (left anterior descending coronary artery, 16; right coronary artery, 10; left circumflex artery, 7 patients) before and during peak maximal hyperemia with intracoronary adenosine (8 to 12 micrograms). Intravenous pharmacological stress (adenosine, 20 patients; dipyridamole, 13 patients) 99mTc-sestamibi tomographic perfusion imaging was performed within 1 week of coronary flow-velocity studies. kappa statistics were calculated to measure the strength of correlation among coronary flow velocities, perfusion imaging data, and QCA results. QCA stenosis severity (abnormal, > or = 50% diameter stenosis) and poststenotic Doppler coronary flow reserve (ratio of abnormal distal hyperemic to basal flow, < or = 2.0) were correctly correlated in 20 of 27 patients (74%; kappa = .48). QCA stenosis severity and 99mTc-sestamibi imaging (abnormal if one or more reversible myocardial segments were present in the poststenotic zone) were correlated in 28 of 33 patients (85%; kappa = .63). 99mTc-sestamibi imaging results agreed with the basal (nonhyperemic) proximal-to-distal velocity ratio (normal, < 1.7) in 15 of 31 patients (48%; kappa = .17). The strongest correlation occurred between hyperemic distal flow-velocity ratio measurements and 99mTc-sestamibi perfusion imaging results in 24 of 27 patients (89%; kappa = .78). All 14 patients with abnormal distal hyperemic flow-velocity values had corresponding reversible 99mTc-sestamibi tomographic defects. More reversibly hypoperfused segments were present in patients with abnormal poststenotic hyperemic flow-velocity ratios (abnormal, 2.4 +/- 0.7 segments; normal, 0.6 +/- 1.0 segments; P < .05). The number of poststenotic myocardial 99mTc-sestamibi perfusion defects was correlated with the QCA percent cross-sectional area reduction (P < .02) and with minimal luminal diameter (P < .05) of intermediate-severity coronary artery stenoses. CONCLUSIONS Two technologically diverse functional measures of stenosis severity--Doppler-derived poststenotic hyperemic intracoronary flow reserve and vasodilator stress 99mTc-sestamibi myocardial perfusion imaging--are highly (89%) correlated. The physiological assessment of coronary stenoses of angiographically intermediate severity may be improved by the use of these techniques.

Coronary Revascularization in Diabetic Patients A Comparison of the Randomized and Observational Components of the Bypass Angioplasty Revascularization Investigation (BARI)

BACKGROUND Patients with treated diabetes in the randomized-trial segment of the Bypass Angioplasty Revascularization Investigation (BARI) who were randomized to initial revascularization with PTCA had significantly worse 5-year survival than patients assigned to CABG. This treatment difference was not seen among diabetic patients eligible for BARI who opted to select their mode of revascularization. We hypothesized that differences in patient characteristics, assessed and unmeasured, together with the treatment selection in the registry, at least partially account for this discrepancy. METHODS AND RESULTS Among diabetics taking insulin or oral hypoglycemic drugs at entry, angiographic and clinical presentations were comparable between randomized and registry patients. However, more registry patients were white, and registry diabetics tended to be more educated and more physically active and to report better quality of life. Procedural characteristics and in-hospital complications were comparable. The 5-year all-cause mortality rate was 34.5% in randomized diabetic patients assigned to PTCA versus 19.4% in CABG patients (P=0.0024; relative risk [RR]=1.87); corresponding cardiac mortality rates were 23.4% and 8.2%, respectively (P=0.0002; RR=3.10). The CABG benefit was more apparent among patients requiring insulin. In the registry, all-cause mortality was 14.4% for PTCA versus 14.9% for CABG (P=0.86, RR=1.10), with corresponding cardiac mortality rates of 7.5% and 6. 0%, respectively (P=0.73; RR=1.07). These RRs in the registry increased to 1.29 and 1.41, respectively, after adjustment for all known differences between treatment groups. CONCLUSIONS BARI registry results are not inconsistent with the finding in the randomized trial that initial CABG is associated with better long-term survival than PTCA in treated diabetic patients with multivessel coronary disease suitable for either surgical or catheter-based revascularization.

Augmentation of coronary blood flow by intra-aortic balloon pumping in patients after coronary angioplasty.

BackgroundControversy exists regarding the ability of intra-aortic balloon pumping to increase coronary blood flow in patients with obstructive coronary artery disease. To assess the effects of intra-aortic balloon pumping on coronary hemodynamics, we measured coronary blood flow velocity with a 0.018-in. Doppler-tipped angioplasty guide wire in 15 patients who received an intra-aortic balloon pump for typical clinical indications. Methods and ResultsIntra-aortic balloon pumping augmented diastolic pressure 83±35%. In nine patients before angioplasty, peak diastolic coronary flow velocity beyond the stenosis (mean diameter narrowing, 95±7%) was 5.3±9.6 cm/sec and was unaffected by intra-aortic balloon pumping. After angioplasty, the improved coronary luminal diameter narrowing (n=12; mean narrowing, 18±12%) was associated with increased distal diastolic flow velocity integral and peak diastolic and mean velocities (13.3±8.4 units: 36.4±18.3 and 24.0±+11.4 cm/sec, respectively; all p<0.01 versus before angioplasty), which were further augmented (36±37%, 54±49%o, and 26+17%, respectively; allp<0.01) with intra-aortic balloon pumping. Intra-aortic balloon pumping did not significantly increase the distal systolic velocity integral (10+59%o) or peak systolic velocity (3±33%). Similar degrees of balloon pump augmentation of distal coronary flow velocity values were observed in five angiographically normal reference arteries in four patients. ConclusionThese data demonstrate lack of significant flow improvement beyond most critical stenoses with intra-aortic balloon pumping and the unequivocal restoration and intra-aortic balloon pump-mediated augmentation of both proximal and distal coronary blood flow velocities after amelioration of severe coronary obstructions in patients after successful coronary angioplasty.

Clinical outcome of deferring angioplasty in patients with normal translesional pressure-flow velocity measurements.

OBJECTIVES The objective of this study was to determine the feasibility, safety and outcome of deferring angioplasty in patients with angiographically intermediate lesions that are found not to limit flow, as determined by direct translesional hemodynamic assessment. BACKGROUND The clinical importance of some coronary stenoses of intermediate angiographic severity frequently requires noninvasive stress testing. Direct translesional pressure and flow measurements may assist in clinical decision making in patients with such stenoses. METHODS Translesional spectral flow velocity (Doppler guide wire) and pressure data were obtained in 88 patients for 100 lesions (26 single-vessel and 74 multivessel coronary artery lesions) with quantitative angiographic coronary narrowings (mean +/- SD diameter narrowing 54 +/- 7% [range 40% to 74%]). Target lesion angioplasty was prospectively deferred on the basis of predetermined normal values, defined as a proximal/distal velocity ratio < 1.7 or a pressure gradient < 25 mm Hg, or both. Patients were followed up for 9 +/- 5 months (range 6 to 30). RESULTS In the deferred angioplasty group, translesional velocity ratios were similar to those of a normal reference group (mean 1.1 +/- 0.32 vs. 1.3 +/- 0.55) and significantly lower than those of a reference cohort of patients who had undergone angioplasty (2.27 +/- 1.2, p < 0.05). The mean translesional pressure gradient in the deferred angioplasty group was also lower than that in the angioplasty group (10 +/- 9 vs. 45 +/- 22 mm Hg, p < 0.001). At follow-up in the deferred angioplasty group, four, six, zero and two patients, respectively, had had subsequent angioplasty, coronary artery bypass graft surgery or myocardial infarction or had died. In one patient, death was related to angioplasty of a nontarget artery lesion, and one patient with multivessel disease had a cardiac arrest due to ventricular fibrillation 12 months after lesion assessment. Among the 10 patients requiring later angioplasty or coronary artery bypass grafting, only six procedures were performed on target arteries. No patient had a complication of translesional flow or pressure measurements. CONCLUSIONS These data demonstrate the safety, feasibility and clinical outcome of deferring angioplasty of coronary artery narrowings associated with normal translesional coronary hemodynamic variables. Given the practice of performing angioplasty without ischemic testing or when testing is inconclusive, translesional hemodynamic data obtained at diagnostic catheterization can identify patients in whom it is safe to postpone angioplasty.

Assessing the hemodynamic significance of coronary artery stenosis: Analysis of translesional pressure-flow velocity relations in patients☆

OBJECTIVES The purpose of this study was to examine the relation among the angiographic severity of coronary artery lesions, coronary flow velocity and translesional pressure gradients. BACKGROUND Determination of the clinical and hemodynamic significance of coronary artery stenoses is often difficult and inexact. Angiography has been shown to be an imperfect tool for determining the physiologic significance of eccentric or irregular coronary lumen narrowing. METHODS Using a 0.018-in. (0.046 cm) intracoronary Doppler-tipped angioplasty guide wire, spectral flow velocity data both proximal and distal to coronary stenoses were compared with translesional pressure gradient measurements and angiographic data obtained during cardiac catheterization in 101 patients. There were 17 patients with normal angiographic findings and 84 with coronary artery disease, with lesions ranging from 28% to 99% diameter narrowing. Patients with coronary disease were assigned to two groups on the basis of translesional gradients at rest. Group A (n = 56) had gradients < 20 mm Hg, and Group B (n = 28) had gradients > or = 20 mm Hg. RESULTS Proximal average peak velocity, diastolic velocity integral and total velocity integral were slightly but statistically lower in Group A; however, the distal average peak velocity and diastolic and total velocity integrals were all markedly (all p < 0.01) decreased in patients with gradients > or = 20 mm Hg (Group B). In addition, the ratio of proximal to distal total flow velocity integral was higher in Group B (2.4 +/- 1.0) than in group A (1.1 +/- 0.3, p < 0.001). There was a strong correlation between translesional pressure gradients and the ratios of the proximal to distal total flow velocity integrals (r = 0.8, p < 0.001), with a weaker relation between quantitative angiography and pressure gradients (r = 0.6, p < 0.001). In angiographically intermediate stenoses (range 50% to 70%), angiography was a poor predictor of translesional gradients (r = 0.2, p = NS), whereas the flow velocity ratios continued to have a strong correlation (r = 0.8, p < 0.001). Only two patients with a proximal/distal total flow velocity ratio < 1.7 had a translesional gradient > 30 mm Hg. Both patients had a very proximal lesion in a nonbranching right coronary artery. CONCLUSIONS These data demonstrate that in branching human coronary arteries, a close relation exists between translesional hemodynamics and distal coronary flow velocity. Translesional coronary flow velocity is a new and easily applicable method for determining the hemodynamic significance of coronary artery stenoses that is superior to angiography and can be applied at the time of diagnostic catheterization. These data will provide a rational approach to making decisions on the use of coronary interventional techniques when angiographic findings are questionable.

Variations in normal coronary vasodilatory reserve stratified by artery, gender, heart transplantation and coronary artery disease

OBJECTIVES The purpose of the study was to assess the spectrum of coronary vasodilatory reserve values in patients with angiographically normal arteries who had atypical chest pain syndromes or remote coronary artery disease or were heart transplant recipients. BACKGROUND The measurement of post-stenotic coronary vasodilatory reserve, now possible in a large number of patients in the cardiac catheterization laboratory, is increasingly used for decision making. Controversy exists regarding the range of normal values obtained in angiographically normal coronary arteries in patients with different clinical presentations. METHODS Quantitative coronary arteriography was performed in 214 patients classified into three groups: 85 patients with chest pain syndromes and angiographically normal arteries (group 1); 21 patients with one normal vessel and at least one vessel with > 50% diameter lumen narrowing (group 2); and 108 heart transplant recipients (group 3). Coronary vasodilatory reserve (the ratio of maximal to basal average coronary flow velocity) was measured in 416 arteries using a 0.018-in. (0.04 cm) Doppler-tipped angioplasty guide wire. Intracoronary adenosine (8 to 18 micrograms) was used to produce maximal hyperemia. RESULTS Coronary vasodilatory reserve was higher in angiographically normal arteries in patients with chest pain syndromes (group 1:2.80 +/- 0.6 [group mean +/- SD]) than in normal vessels in patients with remote coronary artery disease (group 2: 2.5 +/- 0.95, p = 0.04); both values were significantly higher than those in the post-stenotic segment of the diseased artery (1.8 +/- 0.6, p < 0.007). Coronary vasodilatory reserve in transplant recipients (group 3) was higher than that in the other groups (3.1 +/- 0.9, p < 0.05 vs. groups 1 and 2) as a group and for individual arteries. When stratified by vessel, coronary vasodilatory reserve was similar among the left anterior descending, left circumflex and right coronary arteries. There were no differences between coronary vasodilatory reserve values on the basis of gender for patients with coronary artery disease and transplant recipients. In group 1 (chest pain), there was a trend toward higher coronary vasodilatory reserve in men than in women (2.9 +/- 0.6 vs 2.7 +/- 0.6, p = 0.07). CONCLUSIONS These findings identify a normal reference range for studies assessing the coronary circulation and post-stenotic coronary vasodilatory reserve in patients with and without coronary artery disease encountered in the cardiac catheterization laboratory.

Predictors of Mortality and Mortality From Cardiac Causes in the Bypass Angioplasty Revascularization Investigation (BARI) Randomized Trial and Registry

BACKGROUND The impact of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) on long-term mortality rates in the presence of various demographic, clinical, and angiographic factors is uncertain in the population of patients suitable for both procedures. METHODS AND RESULTS In the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial and registry, 3610 patients who were eligible to receive PTCA and CABG were revascularized between 1989 and 1992. Multivariate Cox models were used to identify factors associated with 5-year mortality and cardiac mortality, with particular attention to factors that interact with treatment. Diabetic patients receiving insulin had higher mortality and cardiac mortality rates with PTCA compared with CABG (relative risk [RR] 1.78 and 2.63, respectively, P<0.001), and patients with ST elevation had higher cardiac mortality rates with CABG than with PTCA (RR 4.08, P<0.001). Factors most strongly associated with high overall mortality rates were insulin-treated diabetes, congestive heart failure, kidney failure, and older age. Black race was also associated with higher mortality rates (RR 1.49, P=0.019). CONCLUSIONS A set of variables was identified that could be used to help select a revascularization procedure and to evaluate risk of long-term mortality in the population of patients considering revascularization.

Determination of Angiographic (TIMI Grade) Blood Flow by Intracoronary Doppler Flow Velocity During Acute Myocardial Infarction

BACKGROUND This study compared angiographically graded coronary blood flow with intracoronary Doppler flow velocity in patients during percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction. Different TIMI angiographic flow grades (flow grades based on results of the Thrombolysis in Myocardial Infarction trial) have been associated with different clinical results after reperfusion for acute myocardial infarction. However, intracoronary blood flow velocity has not been compared with the angiographic method of determining flow grade in patients. METHODS AND RESULTS Coronary flow velocity (measured by use of a Doppler guidewire) during primary or rescue PTCA in 41 acute myocardial infarction patients was compared with TIMI grade and cineframes-to-opacification count. Before PTCA, 34 patients had TIMI grade 0 or 1, 5 had TIMI grade 2, and 2 had TIMI grade 3 flow in the infarct artery. Flow velocity was similar among patients with TIMI grades 0, 1, or 2 but was lower than in those with TIMI grade 3 flow (9.4 +/- 5.4 versus 16.0 +/- 5.4 cm/s for TIMI grades < or = 2 versus TIMI grade 3, respectively; P < .05). After PTCA, 1 patient had TIMI grade 1, 5 had TIMI 2, and 35 had TIMI 3 flow. Poststenotic flow velocity increased from 6.6 +/- 6.1 to 20.0 +/- 11.1 cm/s (P < .01). TIMI grade 3 flow increased to 21.8 +/- 10.9 cm/s (P < .05 versus before PTCA). Although post-PTCA flow velocity correlated with angiographic cineframes-to-opacification count (r = .45; P < .02) for TIMI grade 3, there was a large overlap with TIMI grades < or = 2 that had low flow velocity (< 20 cm/s). Nine of 11 clinical events (unstable angina and coronary artery bypass graft surgery) occurred in patients with low coronary flow velocity. CONCLUSIONS Determination of flow velocity after reperfusion may enhance patient characterization and provide the physiological rationale for clinical variations after reperfusion therapy.