Predictors of clinical outcome following percutaneous intervention for in-stent restenosis.

Percutaneous intervention for the first episode of in-stent restenosis was performed in 177 patients 5.4 +/- 0.3 months after native coronary stent implantation. Medical records were reviewed and patients contacted 13.3 +/- 1.2 months after in-stent intervention to ascertain the subsequent clinical course. The effects of demographic, procedural, and angiographic variables on clinical outcomes were determined. At 2 years, Kaplan-Meier estimated survival was 93 +/- 3% and freedom from death, myocardial infarction, and a third target artery revascularization (TAR) was 67 +/- 4%. The actuarial frequency of a third TAR was 26 +/- 4% at 1 year. Stratification of outcomes according to timing of in-stent intervention revealed an approximate twofold higher frequency of adverse events among patients with early (

Antithrombin activity during the period of percutaneous coronary revascularization: relation to heparin use, thrombotic complications and restenosis.

OBJECTIVES: This study evaluated changes in antithrombin (AT) activity around the time of percutaneous transluminal coronary revascularization (PTCR) with unfractionated heparin anticoagulation and the effects these changes had on major thrombotic complications of PTCR. BACKGROUND: Heparin is used during PTCR to prevent thrombosis. However, heparin, a cofactor for AT, causes AT activity to fall. AT activity <70% is associated with thrombosis. There is a prothrombotic state after heparin discontinuation that has not been well explained. METHODS: Antithrombin activity was sampled at the start and end of PTCR and the next two mornings in 250 consecutive patients. We recorded occurrence of major thrombotic events, defined as 1) major thrombotic complications of PTCR; 2) major in-lab thrombus formation; or 3) subacute occlusion. Discriminant analysis was employed to evaluate the relationship of AT activity to these events. Change in AT activity and its relationship to heparin was evaluated. Evidence of restenosis at six months was obtained. RESULTS: There were 14 major thrombotic events. Antithrombin activity <70% was strongly (p = 0.006) associated with these events. The AT activity fell significantly through the morning after PTCR when 21% of patients had AT activity <70%; AT activity did not normalize until >20 h after heparin discontinuation. Pre-PTCR use of heparin led to lower AT activity in proportion to duration of heparin use. There was no relationship between AT activity and restenosis. CONCLUSIONS: Low AT activity may contribute to major thrombotic complications of PTCR. The way heparin is used before and after PTCR is important to development of low AT activity.

Internal mammary arteriography without selective cannulation using a new balloon occlusion catheter.

Internal mammary artery (IMA) angiography can be difficult and time-consuming. We evaluated a custom designed balloon-tipped catheter, a Berman catheter (Arrow International, Reading, PA) modified by creating an end-hole to allow passage of a wire through the central lumen, for imaging the IMA without selective cannulation. We compared ease of use, procedure time, and image quality of the new catheter with the standard selective catheter technique. Thirty-six patients with IMA grafts were randomly assigned to imaging with either the study catheter or a standard catheter. Image quality, graded from poor to excellent, time to catheter placement in the subclavian artery (TIME 1), time to initial IMA angiography (TIME 2), and the difference between these two (TIME 3) were recorded. TIME 3 defined the time required to find and seat the catheter at the IMA site. The image quality was good or excellent in all but one patient. This one patient, randomized to the standard catheter technique, had poor image quality with the selective catheter. However, exchange for the study catheter resulted in excellent image quality. There was no difference in TIME 1 (P = 0.57) or TIME 2 (P = 0.55) between the two techniques. There was a significant difference in TIME 3 (P = 0.05) favoring the study catheter. There were no complication using either technique and the total contrast volume used was not significantly different between the two techniques (P = 0.32). We conclude that a new catheter technique for imaging the IMA without selective cannulation is safe, fast, easy to use, and may offer particular advantage in patients whose internal mammary artery is difficult to access.

Economic assessment of platelet glycoprotein IIb/IIIa inhibition for prevention of ischemic complications of high-risk coronary angioplasty. EPIC Investigators.

BACKGROUND: In the EPIC trial, c7E3 Fab, an antiplatelet IIb/ IIIa receptor antibody, reduced 30-day ischemic end points after high-risk coronary angioplasty by 35% and 6-month ischemic events by 23% but increased in-hospital bleeding episodes. METHODS AND RESULTS: Of the 2099 patients randomized in EPIC, data were collected on 2038 (97%) for prospective hospital cost and major resources. Physician fees were estimated from the Medicare Fee Schedule. Regression analysis was used to examine the economic tradeoff between reduced ischemic events and increased major bleeding during the initial hospitalization. A potential cost savings of $622 per patient during the initial hospitalization from reduced acute ischemic events with c7E3 Fab was offset by an equivalent rise ($521) in costs as the result of an increase in bleeding episodes. Baseline medical costs for the bolus and infusion c7E3 Fab arm averaged $13,577 (exclusive of drug cost) compared with $13,434 for placebo (P = .42). During the 6-month follow-up, c7E3 Fab decreased repeat hospitalization rates by 23% (P = .004) and repeat revascularization by 22% (P = .04), producing a mean $1270 savings per patient (exclusive of drug cost) (P = .018). With a cost of $1407 for the bolus and infusion c7E3 Fab regimen, the cumulative net 6-month cost to switch from standard care to routine c7E3 Fab averaged $293 per patient. CONCLUSIONS: In high-risk coronary angioplasty, aggressive platelet inhibition with c7E3 Fab, by significantly reducing ischemic events and repeat revascularization, recoups most of the cost of therapy and has the potential to pay for itself.

Initial experience with an intracoronary flow support device providing localized drug infusion: the Scimed Dispatch catheter.

Two cases are presented illustrating the use of a new intracoronary infusion catheter providing flow support using a unique spiral coil design. Good clinical outcomes were obtained employing 4-hr inflations with localized infusion of urokinase at the site of dissection and extensive clot formation, respectively. This low-profile catheter-mounted device may provide an alternative to stent placement in cases of acute dissection complicated by thrombus formation.

Identification of high-risk patients with left main and three-vessel coronary artery disease by adenosine-single photon emission computed tomographic thallium imaging.

The purpose of this study was to examine the ability of SPECT imaging with thallium-201 during adenosine-induced coronary hyperemia to detect high-risk patients with left main or three-vessel CAD. There were 339 patients: 102 with either left main or three-vessel CAD (group 1) and 237 with no CAD, one-, or two-vessel disease (group 2). By means of univariate analysis, several variables were found to differ between groups 1 and 2: Q wave myocardial infarction (35% vs 25%, p < 0.05), ST segment depression (35% vs 19%, p < 0.001), age (67 +/- 9 vs 62 +/- 10 years, p < 0.001), resting systolic blood pressure (142 +/- 22 vs 135 +/- 20 mm Hg, p < 0.01), abnormal thallium images (95% vs 74%, p < 0.0001), multivessel thallium abnormality (76% vs 39%, p < 0.0001), extent of thallium abnormality (24 +/- 11% vs 19 +/- 13%, p < 0.0001), and increased lung thallium uptake (39% vs 15%, p < 0.01). According to stepwise discriminant analysis, only three variables were predictors of high risk: multivessel thallium abnormality (chi 2 = 27), increased lung thallium uptake (chi 2 = 10), and ST depression (chi 2 = 5). On the basis of these variables, patients were divided into three groups with different prevalence rates for left main and three-vessel CAD: 63% in 68 patients, 30% in 137 patients, and 13% in 137 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Early thallium imaging after percutaneous transluminal coronary angioplasty: tomographic evaluation during adenosine-induced coronary hyperemia.

This study examined the immediate results of 201Tl imaging during adenosine-induced coronary hyperemia in 25 patients with one-vessel coronary artery disease, 4 +/- 3 days after percutaneous transluminal coronary angioplasty (PTCA). There were special features in our study: use of quantitative angiography and single-photon emission computed tomography (SPECT); a homogeneous group of patients (one-vessel disease) and a uniform stress (adenosine infusion). As a group, quantitative coronary angiography showed a decrease in percent diameter stenosis from 72% +/- 12% to 23% +/- 14%, p < 0.001. The thallium images were normal in 17 patients and abnormal in eight patients. However, of the eight patients, four had residual stenosis either in a secondary branch or downstream; one patient had local dissection (the residual stenosis could not be assessed reliably), two patients had > 50% residual diameter stenosis, and one patient had previous Q-wave myocardial infarction with a corresponding fixed thallium defect. In each of the eight patients with an abnormal image, a logical explanation could be identified. Thus, our results suggest that maximum reactive coronary hyperemia returns to normal immediately after PTCA, and that abnormal thallium results are due to inadequate dilatation or associated lesions.

The perfusion pattern in coronary artery occlusion: comparison of exercise and adenosine.p6.

This study compared exercise to adenosine thallium-201 single photon emission computed tomography in detecting occlusion of left anterior descending or right coronary arteries in patients with no previous myocardial infarction. There were 41 patients who underwent adenosine thallium imaging (adenosine infusion at a rate of 140 micrograms/kg/min for 6 min), and 143 patients who underwent exercise thallium imaging. There were more patients with right coronary than left anterior descending coronary artery occlusion. Thus, in the adenosine group, there were 15 patients with left anterior descending artery occlusion, and 26 with right coronary artery occlusion, and in the exercise group, there were 46 patients with left anterior descending artery occlusion, and 97 patients with right coronary artery occlusion. In the adenosine group, the thallium images were abnormal in 41 patients (100%), while in the exercise group, the thallium images were abnormal in 125 patients (87%, P < 0.02) in the territories of the occluded arteries. ST segment depression was noted in 19 patients (46%) in the adenosine group, and 69 patients (48%) in the exercise group (P:NS). In patients with isolated single vessel occlusion, the size of the perfusion abnormality was 28 +/- 9% with adenosine, and 21 +/- 12% with exercise (P:NS). Thus, most patients with occlusion of the left anterior descending or right coronary artery have regional perfusion abnormality during stress; the different role of collaterals with each type of stress may explain the higher percentage of abnormal results with adenosine than exercise.

Effect of intravenous adenosine infusion on myocardial perfusion and function. Hemodynamic/angiographic and scintigraphic study.

BACKGROUND: Myocardial perfusion imaging during adenosine-induced hyperemia with dipyridamole or adenosine is an accepted method to diagnose coronary artery disease (CAD) and risk assessment. The mechanism of perfusion abnormality may be caused by disparate flow responses or coronary steal. This study examined the relation between 201Tl perfusion pattern and hemodynamic/angiographic changes during intravenous adenosine infusion. METHODS AND RESULTS: Patients with suspected CAD underwent sequential hemodynamic, coronary arteriographic, and left ventriculographic studies simultaneously with 201Tl imaging during adenosine infusion (140 micrograms.kg-1.min-1 for 6 minutes). There were 33 patients with CAD and 12 patients without CAD. The 201Tl images (using single-photon emission computed tomography) were abnormal in 31 patients with CAD (sensitivity, 94%) and normal in the patients without CAD (specificity, 100%). In patients with and without CAD, there were significant increases in heart rate and cardiac output (p less than 0.0001) and decreases in systemic vascular resistance and blood pressure (p less than 0.0001). There was a 77 +/- 38% increase in pulmonary capillary wedge pressure in normal subjects and a 125 +/- 83% increase in patients with CAD (p = 0.02). ST segment depression was observed in 11 patients with CAD (33%). In CAD patients, there was no change in percent diameter or area stenosis measured quantitatively during adenosine infusion. In 15 patients, contrast left ventriculography was repeated during adenosine infusion. In these patients, 201Tl perfusion defects were seen in 31 of 75 segments (41%) whereas only six of 75 segments (8%) developed regional wall motion abnormality (p less than 0.001); the remaining segments showed either no change or improved function. The left ventricular ejection fraction did not change significantly (73% versus 75%). CONCLUSIONS: There is a disparity between the effects of adenosine on left ventricular perfusion and function; most patients with CAD have perfusion defects whereas the global and regional systolic function remains unchanged or improves. Diastolic left ventricular dysfunction is a probable mechanism of the increase in pulmonary capillary wedge pressure.

Delayed resolution of obstructing thrombus following acute closure.

A case of acute thrombotic closure following percutaneous coronary angioplasty demonstrating delayed clearance of obstructing thrombus is reported. Although common in other clinical scenarios this has not been reported following coronary angioplasty.

Systolic and diastolic performance in normal human subjects as measured by ultrafast computed tomography.

Ultrafast computed tomography (ultrafast-CT) is a minimally invasive imaging modality with very short acquisition time and excellent anatomic definition. It shows promise of providing precise measurement of right and left ventricular volumes, left ventricular mass, and left ventricular diastolic function with a single test. We expand on the knowledge regarding normal humans by studying ten normal volunteers in the short axis. Cardiac volumes and mass (mean +/- 1 S.D.) were as follows: 1) left ventricle: end-diastolic volume index (ml/m2) = 61 +/- 15, end-systolic volume index (ml/m2) = 19 +/- 7, stroke volume index (ml/m2) = 43 +/- 9, cardiac index (liters/min/m2) = 2.7 +/- .5, ejection fraction (%) = 70 +/- 7, end-diastolic mass (g/m2) = 95 +/- 15; 2) right ventricle: end-diastolic volume index (ml/m2) = 76 +/- 19, end-systolic volume index (ml/m2) = 35 +/- 13, stroke volume index (ml/m2) = 40 +/- 8, cardiac index (liters/min/m2) = 2.6 +/- .5, ejection fraction (%) = 55 +/- 6. Stroke volume index differed by 1.6 +/- 2.0 ml/m2 between ventricles. Measurement of global and segmental left ventricular diastolic function revealed: 1) Peak filling rate (end-diastolic volumes/second): global = 2.29 +/- .40, base = 1.78 +/- .49, midventricle = 2.49 +/- .57, apex = 3.13 +/- .39 (P less than .001, base vs. apex; P less than .01, base vs. midventricle and midventricle vs. apex); 2) time to peak filling rate (msec): global = 193 +/- 24, base = 192 +/- 20, midventricle = 194 +/- 26, apex = 190 +/- 19 (P = NS between levels).(ABSTRACT TRUNCATED AT 250 WORDS)

Prosthetic valve visualization by cine-computed tomography: a case report.

The use of cine-computed tomography scanning is described in evaluating cardiac function in a patient with a bileaflet mitral valve prosthesis (St. Jude medical valve) and in a second patient with both mitral and aortic bileaflet prostheses. Both biventricular and prosthesis function were assessed successfully.

Ventricular activation in normal sinus rhythm: abnormalities with recurrent sustained tachycardia and a history of myocardial infarction.

Left ventricular activation was studied in 21 patients: 7 with normal electrocardiograms (group I), 7 with prior transmural myocardial infarction (group II) and 7 with prior transmural myocardial infarction (MI) and recurrent sustained ventricular tachycardia (VT) (group III). Fragmented electrograms were defined as those less than 3 mV in amplitude and longer than 60 ms in duration. Such electrograms were found in no group I patients, 6 of 7 group II patients and all 7 group III patients. An average of 2 of the 12 sites mapped in each patient displayed fragmented electrograms in group II; an average of 6 of the 12 sites displayed fragmented electrograms in group III (p less than 0.01). Twelve of the 84 total sites mapped in group II displayed fragmented electrograms, whereas 39 of the 84 sites mapped in group III patients did (p less than 0.01). The longest fragmented electrogram found in the 6 group II patients in whom such electrograms were found was shorter in duration than the longest electrogram found in each of the 7 group III patients with fragmented electrograms (76 ms vs 135 ms, p less than 0.005). The duration of endocardial activation was longer in group II patients (79 +/- 7 ms) than in group I patients (39 +/- 4 ms, p less than 0.001). Duration of activation was also longer in group III patients (151 +/- 12 ms) than in either of the other groups (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of high dose aspirin on coronary hemodynamics during pacing-induced myocardial ischemia.

The effects of aspirin on coronary hemodynamics and transcardiac concentrations of thromboxane B2 (the stable metabolite of thromboxane A2) were determined at rest and during pacing-induced myocardial ischemia in 11 patients with coronary disease. Control coronary sinus pacing increased both arterial thromboxane B2 (331 +/- 70 to 623 +/- 132 pg/ml, p less than 0.02) and coronary sinus thromboxane B2 (184 +/- 3 to 403 +/- 156 pg/ml, p less than 0.05), but positive transmyocardial gradients developed in only three patients. After 650 mg of oral aspirin, more than 90% inhibition of in vitro thromboxane B2 production was demonstrated and circulating thromboxane B2 was undetectable at rest and during pacing in all patients. Despite these changes in thromboxane B2 concentrations, coronary blood flow was unchanged by aspirin at rest (107 +/- 14 versus 112 +/- 13 ml/min, p = NS) and during pacing (189 +/- 29 versus 181 +/- 25 ml/min, p = NS). Myocardial lactate extraction was also unchanged at rest (24 +/- 7 versus 19 +/- 5%, p = NS) and during pacing (5 +/- 6 versus 9 +/- 5%, p = NS). No change occurred in the anginal threshold. Thus, aspirin does not have the vasoconstrictive properties that have been reported with another cyclo-oxygenase inhibitor, indomethacin. These findings also suggest that thromboxane A2 production does not play a major role in the pathogenesis of stress-induced ischemia. Nonetheless, intracoronary thromboxane A2 production in some patients may potentiate platelet activation and coronary thrombosis. Such patients may benefit from long-term aspirin therapy and can be treated with aspirin without risk of adverse coronary hemodynamic effects.

Endocardial mapping in humans in sinus rhythm with normal left ventricles: activation patterns and characteristics of electrograms.

Endocardial catheter mapping was performed in 15 patients in sinus rhythm who had no evidence of structural heart disease and normal left ventricles. Mapping was performed with the use of 10 mm interelectrode distance from various left ventricular endocardial sites. In 10 patients a quantitative analysis of electrographic amplitude, duration, and amplitude/duration ratio was performed. The normal left ventricular bipolar electrograms had an amplitude of greater than 3 mV, a duration of less than 70 msec, and an amplitude/duration ratio of greater than 0.045. Local activation times were also assessed in the 15 patients. This analysis revealed two endocardial breakthrough sites, one on the midinferior septum and a second on the anterior wall near the insertion of the anterior papillary muscle. We therefore have defined normal quantitative characteristics of left ventricular bipolar electrograms and the normal left ventricular activation sequence in the intact normal human left ventricle.

Role of triple extrastimuli during electrophysiologic study of patients with documented sustained ventricular tachyarrhythmias.

Electrophysiologic studies were performed in 172 consecutive patients for evaluation of documented sustained ventricular tachyarrhythmias. One hundred thirteen patients presented with sustained ventricular tachycardia that was hemodynamically stable, and 59 patients presented with cardiac arrest. Seventy-one patients without previously documented or suspected ventricular arrhythmias were also studied to determine the specificity of our electrophysiologic study protocol. The stimulation protocol included single, double, and triple right ventricular extrastimuli and rapid ventricular pacing at multiple cycle lengths performed at one or more right ventricular sites. Stimulation was performed at one or more left ventricular sites in patients with documented spontaneous arrhythmias when right ventricular programmed stimulation failed to induce sustained ventricular tachycardia. Ventricular tachyarrhythmias were induced in 110 (97%) of the patients who presented with sustained ventricular tachycardia, in 48 (81%) of the patients who presented with cardiac arrest, and in 28 (40%) of the patients without documented spontaneous arrhythmias. Right ventricular triple extrastimuli induced tachycardia in 22% of patients who presented with sustained ventricular tachycardia vs 46% of those who presented with cardiac arrest (p less than .001). Left ventricular stimulation was required for tachycardia induction in 3% of patients with stable tachycardia vs 19% of those with cardiac arrest (p less than .01). Triple extrastimuli induced 57% of tachycardias in the 28 patients without spontaneous arrhythmias, and virtually all of these tachycardias were polymorphic and nonsustained. The cycle lengths of tachycardias induced in each group by double and triple extrastimuli were similar, but the tachycardias induced in patients with cardiac arrest were significantly faster than those induced in the ventricular tachycardia group (mean cycle length 218 vs 291 msec, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Matching of myocardial oxygen consumption to mechanical load in human left ventricular hypertrophy and dysfunction.

The coupling of myocardial oxygen consumption (MVO2) with its determinants in left ventricular hypertrophy in human beings is poorly understood. Therefore, thermodilution-derived coronary blood flow, MVO2 and left ventricular wall stress, obtained from simultaneous left ventricular M-mode echogram and pressure, were compared in 32 patients with various degrees of left ventricular hypertrophy. Patients were studied at rest and after mechanical load alteration with nitroglycerin or phenylephrine. Decreases in MVO2 (-5.7 +/- 0.8 ml/min; p less than 0.001) and the time integral of meridional ejection stress or shortening load (-1,297 +/- 152 X 10(3) dynes X s/cm2; p less than 0.001) were observed after nitroglycerin administration while increases in MVO2 (+5.5 +/- 0.7 ml/min; p less than 0.001) and shortening load (+1,412 +/- 137 X 10(3) dynes X s/cm2; p less than 0.001) were noted after phenylephrine. An index relating the change in MVO2 to the corresponding change in shortening load (SL), % delta MVO2/% delta SL, was significantly different in patients without (Group 1) and with (Group 2) clinical left ventricular failure. Left ventricular mass was similar in both groups. The mean % delta MVO2/% delta SL with phenylephrine in Group 1 (79.6 +/- 9.6) was greater than the index for Group 2 (35.5 +/- 6.1; p less than 0.005). With nitroglycerin, Group 2 patients exhibited a greater reduction in % delta MVO2/% delta SL (110.5 +/- 17.8) than Group 1 (54.0 +/- 9.4; p less than 0.01). In conclusion, in patients with left ventricular hypertrophy and dysfunction there appears to be a state of diminished coronary flow response to load augmentation. However, load reduction in patients with clinical left ventricular failure results in a more balanced relation between oxygen uptake and ejection stress.

Sequential changes in regional coronary flow during pacing-induced angina pectoris: coronary flow limitation precedes angina.

To investigate the sequence of changes in regional myocardial perfusion which precedes stress-induced angina, we measured great cardiac vein flow (GCVF), draining the anterior left ventricle, during incremental atrial pacing in 10 patients with normal anterior perfusion (group I) and in 11 patients with greater than or equal to 50% diameter stenosis of the left main or proximal left anterior descending coronary artery (group II). Pacing produced angina in 11 of 11 and regional lactate production in 9 of 11 group II patients. Both groups had comparable resting GCVF (group I = 62 +/- 7 ml/min vs group II = 76 +/- 9 ml/min; p = NS) and both exhibited progressive increases in GCVF with pacing. However, the entire flow-demand relationship was displaced downward in group II, as evidenced by a reduction in the percent increase in GCVF both following the first 20-beat pacing increment (group I = 46 +/- 6% vs group II = 16 +/- 4%; p less than 0.001) and at angina (group I = 113 +/- 16% vs group II = 44 +/- 9%; p less than 0.001). The first 20-beat pacing increment increased the heart rate to only 77 +/- 2 bpm in group II whereas angina and ECG changes did not occur until a pacing rate of 117 +/- 6 bpm. These data indicate that regional flow abnormalities precede the onset of pacing-induced angina in patients with coronary disease (CAD) and that these flow abnormalities frequently are detectable at heart rates substantially below the anginal threshold.

Developmental changes in action potential duration, refractoriness, and conduction in the canine ventricular conducting system.

The purpose of these studies was to determine the age-related changes that occur in refractoriness and conduction in the canine Purkinje system and ventricle. We used standard microelectrode techniques to study the isolated left and right ventricular specialized conducting system of neonatal and 2-, 5-, and 10-year-old beagles. We mapped the preparations with microelectrodes and bipolar surface electrodes and recorded action potential duration, conduction velocity, and refractoriness. We found five age-related changes. (1) The region of maximum action potential duration in the adult Purkinje system occurred in the distal false tendon near its subendocardial insertion. In neonates, the entire proximal subendocardial Purkinje system and free running false tendon had a uniformly long action potential, which then shortened in the distal subendocardial fibers. (2) Conduction block of responses to induced premature stimuli occurred proximally, near the origin of the false tendon in all groups. (3) The effective refractory period of the ventricular specialized conduction system did not vary among different age groups and was the same for the left and right ventricles. (4) Conduction velocity of basic and premature impulses was significantly lower in neonates and higher in 2-year-olds than in older age groups; (5) values for amplitude and maximum upstroke velocity of phase 0 were reduced in the neonatal and 10-year-old beagles with respect to values for 2- and 5-year-old beagles.