Eugene A. Caracciolo

Comparison of Surgical and Medical Group Survival in Patients With Left Main Equivalent Coronary Artery Disease

BACKGROUND Observational and randomized studies designed to compare surgical and medical therapies in patients with left main coronary artery disease (LMCD) have shown that coronary artery bypass graft (CABG) surgery prolongs life in most patients with LMCD. The present report of 1484 patients with LMCD in the Coronary Artery Surgery Study (CASS) Registry extends the originally published 5-year surgical and medical group survival analysis to more than 16 years of follow-up and permits analysis of LMCD patient subgroups. METHODS AND RESULTS The CASS Registry contains 1484 patients with > or = 50% left main coronary artery stenosis initially treated with either surgical or nonsurgical therapy. The 15-year cumulative survival estimates were 37% for the 1153 patients in the surgical group compared with 27% for the 331 patients in the medical group. Median survival in the surgical group was 13.3 years (12.8 to 13.8 years, 95% confidence limits) compared with only 6.6 years (5.4 to 7.9 years) in the medical group (difference, 6.7 years; P < .0001). Median survival was also significantly longer in the surgical group stratified by age, sex, anginal class, left ventricular (LV) function, coronary anatomy, and the extent of LMCD. However, CABG surgery did not significantly prolong median survival in patient subgroups with (1) left main coronary stenosis of 50% to 59%; (2) normal LV systolic function; (3) normal or mildly abnormal LV systolic function and a right coronary artery stenosis > or = 70%; and (4) a nonstenotic (< or = 70%) right coronary artery. The 15-year cumulative survival for patients with normal LV systolic function in the surgical and medical groups was 42% and 51%, respectively. Median survival was 14.7 years in the surgical group and > 15 years in the medical group (P = NS). In patients with normal LV systolic function and a right coronary artery stenosis > or = 70%, the 15-year cumulative survival rates were also similar in the surgical and medical groups (40% and 48%, respectively). Median survival was 14.3 years in the surgical group and 14.2 years in the medical group (P = NS). The 15-year cumulative survival estimates for all subgroups were affected by convergence of the surgical and medical survival group curves owing to a disproportionate increase in the late surgical group mortality. Overall, 25% of patients in the medical group ultimately underwent CABG surgery. If all medical group patients had survived long enough, about 47% would be estimated to have had surgery by 15 years. CONCLUSIONS This report, which extends follow-up of more than 16 years in CASS Registry patients with LMCD, shows that CABG surgery prolongs life in most clinical and angiographic subgroups. However, median survival was not prolonged by CABG surgery in patients with normal LV systolic function, even if a significant right coronary artery stenosis (> or = 70%) also was present. These results extend our understanding of the natural history of LMCD and permit a more accurate estimate of long-term surgical and medical group survival.

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.

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.

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.

Role of Coronary Artery Lumen Enlargement in Improving Coronary Blood Flow After Balloon Angioplasty and Stenting: A Combined Intravascular Ultrasound Doppler Flow and Imaging Study

OBJECTIVES This study sought to examine the mechanism of increasing coronary flow reserve after balloon angioplasty and stenting. BACKGROUND Coronary vasodilatory reserve (CVR) does not improve after percutaneous transluminal coronary angioplasty in > or = 50% of patients, postulated to be due to impaired microvascular circulation or inadequate lumen expansion despite adequate angiographic results. METHODS To demonstrate the role of coronary lumen expansion, serial coronary flow velocity (0.014-in. Doppler guide wire) was measured in 42 patients before and after balloon angioplasty and again after stent placement. A subset (n = 17) also underwent intravascular ultrasound (IVUS) imaging of the target sites after angioplasty and stenting. CVR (velocity) was computed as the ratio of adenosine-induced maximal hyperemic to basal average peak velocity. RESULTS The percent diameter stenosis decreased from (mean +/- SD) 84 +/- 13% to 37 +/- 18% after angioplasty and to 8 +/- 8% after stenting (both p < 0.05). CVR was minimally changed from 1.70 +/- 0.79 at baseline to 1.89 +/- 0.56 (p = NS) after angioplasty but increased to 2.49 +/- 0.68 after stent placement (p < 0.01 vs. before and after angioplasty). IVUS lumen cross-sectional area was significantly larger after stenting than after angioplasty (8.39 +/- 2.09 vs. 5.10 +/- 2.03 mm2, p < 0.05). Anatomic variables were related to increasing coronary flow velocity reserve (CVR vs. IVUS lumen area: r = 0.47, p < 0.005; CVR vs. quantitative coronary angiographic percent area stenosis: r = 0.58, p < 0.0001). CONCLUSIONS In most cases, increases in CVR were associated with increases in coronary lumen cross-sectional area. These data suggest that impaired CVR after angioplasty is often related to the degree of residual narrowing, which at times may not be appreciated by angiography. A physiologically complemented approach to balloon angioplasty may improve procedural outcome.

Assessment of angiographically intermediate coronary artery stenosis using the Doppler flowire

Determination of the clinical and hemodynamic significance of coronary stenoses is often difficult and inexact. Angiography and coronary vasodilator reserve have been shown to be imperfect tools to determine the physiologic significance of coronary stenoses. Spectral flow velocity data, both proximal and distal to coronary stenoses, using an 0.018-in intracoronary Doppler-tipped angioplasty guidewire, were compared to translesional pressure gradients and angiography during cardiac catheterization. Patients were divided into 2 groups based on resting translesional gradients: Group 1 had gradients < 20 mm Hg and group 2 had gradients > or = 20 mm Hg. Proximal average peak velocity, diastolic velocity integral, and total velocity integral were statistically significantly lower in Group 1. The distal average peak velocity, and diastolic and total velocity integrals were all significantly (p < 0.01) decreased in patients with gradients > 20 mm Hg (group 2). The ratio of proximal-to-distal total flow velocity integral was also higher in group 2 patients (2.3 +/- 0.9) compared with group 1 (1.1 +/- 0.2; 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 relationship between quantitative angiography and pressure gradients (r = 0.6, p < 0.001). Angiography was a poor predictor of translesional gradients in angiographically intermediate stenoses (range 50-70%; r = 0.2, p = NS), while the flow velocity ratios continued to have a strong correlation (r = 0.8, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal Coronary Flow Velocity Reserve After Coronary Artery Stenting in Patients Role of Relative Coronary Reserve to Assess Potential Mechanisms

BACKGROUND Absolute coronary flow velocity reserve (CVR) after stenting may remain abnormal as a result of several different mechanisms. Relative CVR (rCVR=CVR(target)/CVR(reference)) theoretically normalizes for global microcirculatory disturbances and facilitates interpretation of abnormal CVR. METHODS AND RESULTS To characterize potential mechanisms of poststent physiology, CVR was measured using a Doppler-tipped angioplasty guidewire in 55 patients before and after angioplasty, after stenting, and in an angiographically normal reference vessel. For the group, the percent diameter stenosis decreased from 75+/-13% to 40+/-18% after angioplasty and to 10+/-9% (all P<0.05) after stent placement. After angioplasty, CVR increased from 1.63+/-0.71 to 1.89+/-0.55 (P<0.05) and after stent placement, to 2.48+/-0.75 (P<0.05 versus pre- and postangioplasty). After angioplasty, rCVR increased from 0.64+/-0.26 to 0.75+/-0.23 and after stent placement to 1.00+/-0.34. In 17 patients with CVR(stent) < or = 2.0, increased basal coronary flow, rather than attenuated hyperemia, was responsible in large part for the lower CVR(stent) compared with patients having CVR(stent) >2.0. In 8 patients with CVR(stent) <2.0, a normal rCVR supported global microvascular disease. The subgroup of 9 patients with CVR(stent) <2.0 and abnormal rCVR (16% of the studied patients) may require a pressure-derived fractional flow reserve to differentiate persistent obstruction from diffuse atherosclerotic disease or microvascular stunning. CONCLUSIONS Although a majority of patients after stenting normalize CVR for the individual circulation (ie, normal CVR or normal rCVR), in those with impaired CVR(stent), the analysis of coronary flow dynamics suggests several different physiological mechanisms. Additional assessment may be required to fully characterize the physiological result for such patients to exclude remediable luminal abnormalities.

Diabetics With Coronary Disease Have a Prevalence of Asymptomatic Ischemia During Exercise Treadmill Testing and Ambulatory Ischemia Monitoring Similar to That of Nondiabetic Patients: An ACIP Database Study

BACKGROUND There are conflicting data as to whether diabetics have a higher prevalence of asymptomatic ST-segment depression during exercise treadmill testing (ETT) and ambulatory ECG (AECG) monitoring. This study was conducted to determine whether diabetic patients with coronary disease enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) have more episodes of asymptomatic ischemia during ETT and 48-hour AECG monitoring than nondiabetic patients and to compare differences in angiographic variables and the magnitude of ischemia as measured by standard ETT and AECG criteria. METHODS AND RESULTS Angiographic variables and the prevalence and magnitude of ischemia during the qualifying ETT and 48-hour AECG were compared by the presence and absence of diabetes mellitus in 558 randomized ACIP patients. Seventy-seven patients had a history of diabetes and were taking oral hypoglycemics or insulin (diabetic group); 481 patients did not meet these criteria (nondiabetic group). Multivessel disease (87% versus 74%, P = .01) was more frequent in the diabetic group. The percentages of patients without angina during the ETT were similar in the diabetic and nondiabetic groups (36% and 39%, respectively). Time to onset of > or = 1-mm ST-segment depression and time to onset of angina were similar in both groups. The percentages of patients with only asymptomatic ST-segment depression during the 48-hour AECG were similar in the diabetic and nondiabetic groups (94% versus 88%, respectively). However, total ischemic time per 24 hours (15.0 +/- 21.4 versus 23.6 +/- 31.1 minutes, P = .02), ischemic time per episode (6.3 +/- 4.6 versus 9.0 +/- 8.7 minutes, P < .01), and the maximum depth of ST-segment depression tended to be less in the diabetic group. CONCLUSIONS Patients enrolled in ACIP were selected on the basis of an abnormal ETT and 48-hour AECG and ability to undergo coronary revascularization. When patients with diabetes mellitus were compared with those without diabetes, there was a similar prevalence of asymptomatic ischemia during ETT and 48-hour AECG monitoring. Despite more extensive and diffuse coronary disease, diabetic ACIP patients tended to have less measurable ischemia during the 48-hour AECG.

Quantitating coronary collateral flow velocity in patients during coronary angioplasty using a Doppler guidewire

Quantitation of coronary collateral flow in patients has been limited to angiographic techniques, which are subject to well-known methodologic limitations. The use of a Doppler-tipped angioplasty guidewire permits measurement of both antegrade and retrograde flow distal to totally or subtotally occluded vessels that may be supplied with acutely recruitable or angiographically mature collateral conduits. Using coronary flow velocity as an indicator of collateral flow, retrograde flow velocity was quantitated in 17 patients. Mean collateral flow velocity was approximately 30% of normal postangioplasty antegrade flow velocity. The phasic pattern of collateral flow was highly variable, but the retrograde diastolic and systolic flow velocity integrals were 20% and 40% (respectively) of post-procedure antegrade flow velocity. Preliminary studies with pharmacologic stimulation of the contralateral supply artery suggests that collateral flow is not increased by intracoronary nitroglycerin (200 micrograms) or adenosine (12 micrograms), but may be markedly augmented during mechanical stimulation of balloon occlusion. These data represent the first in a series of quantitative observations on control of the coronary collateral circulation in humans. Future investigations using the Doppler Flowire (Cardiometrics) will enhance understanding of factors modulating ischemia through collateral supply.

Comparison of quantitative angiographically derived and measured translesion pressure and flow velocity in coronary artery disease

Although quantitative coronary angiography (QCA) has been used to determine lesion severity, angiographically derived parameters of translesional physiology have not been compared with those directly measured in the same patients. Thus, the aim of this study was to correlate QCA-derived translesional pressure and flow data with directly measured data in patients. QCA (DCI-ACA program), translesional pressure gradient (2.2Fr fluid-filled tracking catheter), and intracoronary Doppler flow velocity (0.018-inch FloWire) measurements were simultaneously performed in 28 arteries (25 patients). Mean diameter stenosis was 51 +/- 2.3% (range 29 to 73). No patient had left ventricular hypertrophy or valvular heart disease. The arteries studied were left anterior descending in 14, circumflex in 8, and right coronary in 6 patients. Stenotic flow reserve and baseline and maximal gradients were calculated by the DCI program. Coronary flow reserve and baseline and maximal hyperemic gradients were also directly measured distal to the stenosis after administration of intracoronary adenosine (12 to 18 micrograms). QCA-derived pressure gradients did not correlate with the measured gradients at baseline (r2 = 0.005; p = 0.73) or at maximal hyperemia (r2 = 0.1; p = 0.13). No correlation was found between the QCA-predicted flow reserve and the coronary flow reserve measured distal to the stenosis (r2 = 0.02; p = 0.46). Furthermore, stenotic flow reserve and measured gradient were not significantly correlated (r2 = 0.1; p = 0.16). In this range of stenoses of intermediate severity, there was no correlation between the measured pressure gradient or coronary flow reserve and lesion diameter or cross-sectional area by QCA.(ABSTRACT TRUNCATED AT 400 WORDS)