C. Richard Conti

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study Improvement of Cardiac Ischemia at 1 Year After PTCA and CABG

BACKGROUND Cardiac ischemia on the ambulatory ECG (AECG) and/or on the exercise treadmill test (ETT) is associated with an increased risk of adverse outcome. Myocardial revascularization more often suppresses cardiac ischemia than does medical management alone. However, few studies have compared the effects of percutaneous transluminal coronary angioplasty (PTCA) with those of coronary artery bypass grafting (CABG) on cardiac ischemia and clinical outcome. METHODS AND RESULTS A total of 558 patients were randomly assigned to one of three treatment strategies in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study: angina-guided medical strategy (n = 184), ischemia-guided medical strategy (n = 182), or revascularization (n = 192). In patients assigned to revascularization, the choice of the procedure, PTCA or CABG, was made by the clinical unit staff and patient based on a coronary angiogram usually performed within 2 months of enrollment. CABG was selected in 78 patients and PTCA in 92 patients. At 12 weeks, ischemia on the AECG was suppressed in 70% of CABG patients versus 46% of PTCA patients (P = .002). Ischemia on the ETT was no longer present in 46% versus 23% of the patients, respectively (P = .005). Angina, within 4 weeks of the follow-up visit, was absent in 90% versus 68%, respectively (P = .001). These clinical variables remained improved in both groups at 1 year. Clinical events (myocardial infarction or repeat revascularization) occurred in 1 CABG patient versus 7 PTCA patients at 12 weeks, and in 1 versus 16 patients, respectively, at 12 months (P < .001). CONCLUSIONS Ischemia on the AECG and ETT and angina were relieved in many patients after both procedures; however, CABG was superior to PTCA, and it was associated with a lower incidence of clinical events at 1 year. These results suggest that more complete revascularization relates to better clinical outcome. However, a large trial is needed to confirm these results.

Ischemic heart disease

In this edition of the Journal, we release the first in a series of reviews of influential articles that have been previously published in ACC journals, including the American Journal of Cardiology (from 1958 to 1982), and JACC (from 1983 to the present). The publication of these articles is only

Effects of carbon dioxide, Nd-YAG, and argon laser radiation on coronary atheromatous plaques☆

Laser radiation has been successfully applied in several areas of medical practice. However, its use in cardiology and specifically its effects on obstructive atherosclerosis have largely been unexplored. To evaluate effects of laser radiation on atherosclerotic plaques 25 fresh necropsy atherosclerotic coronary artery segments were exposed to laser radiation with either a carbon dioxide, Nd-YAG, or argon laser. Split or intact segments were prepared under dry conditions or while immersed in saline solution or blood and exposed to laser radiation as power and duration of exposure varied. All 3 lasers were capable of creating controlled injury to atherosclerotic plaques. In general, the magnitude of injury varied according to the total energy delivered (that is, power times duration of exposure. Calcified and noncalcified plaques were penetrated with similar levels of injury. Histologic examination demonstrated that laser radiation produced a wedge incision in the atherosclerotic plaque which was surrounded by zones of thermal and acoustic injury.

Effects of age on ventricular-vascular coupling

The effects of age on the interrelation between the physical properties of the arterial tree (aortic input impedance) and left ventricular performance (cardiac output) were studied in 45 subjects, aged 19 to 62 years, without apparent cardiovascular disease. Ascending aortic pulsatile pressure and blood flow velocity were measured with a multisensor catheter and cardiac output by green dye or the Fick method. Heart rate and end-diastolic aortic pressure remained unchanged with age, whereas aortic systolic, mean and pulse pressures and aortic radius increased. In subjects younger than 30 years, early systolic pressure usually exceeded late systolic pressure (type C beat); in subjects older than 50 years, late systolic pressure usually exceeded early systolic pressure (type A beat). In 55% of subjects aged 30 to 50 years, early and late systolic pressures were essentially equal (type B beat). The impedance spectra from all subjects showed fluctuations about the characteristic impedance (index of elastance) that were greater in the older subjects. Peripheral resistance increased 37% (r = 0.47, p less than 0.001) over the age range of 20 to 60 years, whereas characteristic impedance increased 137% (r = 0.66, p less than 0.001). The fundamental impedance modulus increased, and the impedance modulus minimum shifted to a higher frequency. These changes in the impedance spectral pattern indicate that the ascending aorta becomes stiffer and the cross section of the peripheral vascular bed decreases with age, causing increased pulse wave velocity and wave reflection.(ABSTRACT TRUNCATED AT 250 WORDS)

Asymptomatic Cardiac Ischemia Pilot (ACIP) study : outcome at 1 year for patients with asymptomatic cardiac ischemia randomized to medical therapy or revascularization

OBJECTIVES This report discusses the outcome at 1 year in patients in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study. BACKGROUND Comparative efficacy of medical therapy versus revascularization in treatment of asymptomatic ischemia is unknown. The ACIP study assessed the ability of three treatment strategies to suppress ambulatory electrocardiographic (ECG) ischemia to determine whether a large-scale trial studying the impact of these strategies on clinical outcomes was feasible. METHODS Five hundred fifty-eight patients with coronary anatomy amenable to revascularization, at least one episode of asymptomatic ischemia on the 48-h ambulatory ECG and ischemia on treadmill exercise testing were randomized to one of three treatment strategies: 1) medication to suppress angina (angina-guided strategy, n = 183); 2) medication to suppress both angina and ambulatory ECG ischemia (ischemia-guided strategy, n = 183); or 3) revascularization strategy (angioplasty or bypass surgery, n = 192). Medication was titrated atenolol-nifedipine or diltiazem-isosorbide dinitrate. RESULTS The revascularization group received less medication and had less ischemia on serial ambulatory ECG recordings and exercise testing than those assigned to the medical strategies. The ischemia-guided group received more medication but had suppression of ischemia similar to the angina-guided group. At 1 year, the mortality rate was 4.4% in the angina-guided group (8 of 183), 1.6% in the ischemia-guided group (3 of 183) and 0% in the revascularization group (overall, p = 0.004; angina-guided vs. revascularization, p = 0.003; other pairwise comparisons, p = NS). Frequency of myocardial infarction, unstable angina, stroke and congestive heart failure was not significantly different among the three strategies. The revascularization group had significantly fewer hospital admissions and nonprotocol revascularizations at 1 year. The incidence of death, myocardial infarction, nonprotocol revascularization or hospital admissions at 1 year was 32% with the angina-guided medical strategy, 31% with the ischemia-guided medical strategy and 18% with the revascularization strategy (p = 0.003). CONCLUSIONS After 1 year, revascularization was superior to both angina-guided and ischemia-guided medical strategies in suppressing asymptomatic ischemia and was associated with better outcome. These findings require confirmation by a larger scale trial.

Laser angioplasty with angioscopic guidance in humans

An experimental study was conducted in 11 patients to evaluate the immediate effects of laser recanalization during peripheral arterial bypass surgery. Angioscopy allowed precise localization and identification of the occlusion. A 1 or 2 mm optical fiber probe was used. Laser energy was regulated using the least amount of energy necessary for recanalization. New vascular channels were made in 10 of the 11 patients. After recanalization the arterial segment was excised for histologic evaluation. Smaller channel diameters were made with the 1 mm probe (1.5 +/- 0.6 mm) than with the 2 mm probe (3 +/- 0.3 mm) (p less than 0.05). Flow through channels (mean pressure 80 mm Hg) made with the 2 mm probe was greater than that through channels made with the 1 mm probe (150 +/- 102 versus 19.7 +/- 10 cc/min) (p less than 0.05). The amount of debris formed was small with both probes. Vascular perforations were less frequent with the 2 mm probe (two of nine arteries) compared with the 1 mm probe (four of four arteries). Successful recanalization with flow rates expected to maintain vascular patency was achieved only with the 2 mm probe. Histologic studies at nonperforated sites demonstrated that the elastica of the artery appeared to be preserved whereas the overlying plaque and underlying media were thermally disrupted. This suggests that the elastic tissue acts as an optical window allowing the argon beam to go through it without causing morphologic damage. Except for fresh thrombus, atheromas including calcific plaque and old organized thrombus were readily vaporized. These results are encouraging for the use of the laser for vascular recanalization in humans.

Effects of treatment strategies to suppress ischemia in patients with coronary artery disease: 12-Week results of the Asymptomatic Cardiac Ischemia Pilot (ACIP) study

OBJECTIVES The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was initiated to determine the feasibility of a large trial in evaluating the effects of treatment of ischemia on outcome (mortality and myocardial infarction). The study was designed to examine the effects of medical treatment to control angina compared with treatment strategies guided by ambulatory electrocardiographic (ECG) ischemia or coronary anatomy. BACKGROUND Treatments to suppress ischemia (asymptomatic and symptomatic) have not been evaluated in a large prospective, randomized trial. Before undertaking such a trial, issues about recruitment and treatment strategies must be addressed. METHODS The 618 enrolled patients had coronary artery disease suitable for revascularization, ischemia on stress test and asymptomatic ischemia on ambulatory ECG. Patients were assigned randomly to one of three treatment strategies: 1) angina-guided medical strategy with titration of anti-ischemic medication to relieve angina (angina-guided strategy); 2) angina-guided plus ambulatory ECG ischemia-guided medical strategy with titration of anti-ischemic medication to eliminate both angina and ambulatory ECG ischemia (ischemia-guided strategy); and 3) revascularization by angioplasty or bypass surgery (revascularization strategy). RESULTS Ambulatory ECG ischemia was no longer present at the week 12 visit in 39% of patients assigned to the angina-guided strategy, 41% of patients assigned to the ischemia-guided strategy and 55% of patients assigned to the revascularization strategy. All strategies reduced the median number of episodes and total duration of ST segment depression during follow-up ambulatory ECG monitoring. Revascularization was the most effective strategy. Treadmill test results were concordant with those of ambulatory ECG monitoring. For most patients in the two medical strategies, angina was controlled with low to moderate doses of anti-ischemic medication, and the majority of patients (65%) in the revascularization strategy did not require medication for angina. CONCLUSIONS This pilot study demonstrated that cardiac ischemia can be suppressed in 40% to 55% of patients with either low or moderate doses of medication or revascularization and that a large trial is feasible.

Hemodynamic significance of the length of a coronary arterial narrowing.

The hemodynamic significance of the length of a coronary arterial narrowing is unclear. Accordingly, the influence of the length of a given coronary narrowing on coronary hemodynamic responses was studied in 14 dogs. Recordings were made as short fixed diameter reductions were progressivley lengthened to 5, 10 and 15 mm by the addition of plastic occluders. Resting coronary blood flow decreased and pressure gradients developed across short (snare) narrowings greater than 80 percent (critical stenosis). Short 40 to 60 percent narrowings had no significant resting hemodynamic influence, but increasing their length to 10 and 15 mm consistently resulted in significant pressure gradients and flow reductions. Reactive hyperemic coronary blood flow expressed as repayment of flow debt (after 10 seconds of coronary occlusion) decreased progressively as these narrowings were lengthed. The effect of 15 mm long narrowings on resting and reactive hyperemic flows was similar to that of short 90 percent narrowings. These data indicate that there is uncertainty about the significance of coronary diameter reductions previously considered hemodynamically unimportant. In our studies, significant changes in resting and reactive hyperemic coronary flows and resting pressure gradients occurred as the length of a given degree of narrowing was increased.

The Asymptomatic Cardiac Ischemia Pilot (ACIP) study: Design of a randomized clinical trial, baseline data and implications for a long-term outcome trial

OBJECTIVES The primary objectives of the Asymptomatic Cardiac Ischemia Pilot were 1) to compare the 12-week efficacy of three treatment strategies to suppress cardiac ischemia, and 2) to assess the feasibility of a prognosis trial in patients with asymptomatic cardiac ischemia. BACKGROUND Cardiac ischemia has been associated with increased morbidity and mortality. However, most cardiac ischemia is asymptomatic, and although therapeutic strategies ranging from no medication to revascularization are being used to treat ischemia, no prospective study evaluating different treatment strategies has been reported. METHODS Patients with angiographically documented coronary artery disease and ischemia on exercise and ambulatory electrocardiogram (ECG) in 11 clinical units were randomized to receive angina-guided medical therapy, angina-guided plus ambulatory ECG ischemia-guided medical therapy or revascularization (coronary angioplasty or bypass surgery). Patients were also randomized to receive either diltiazem plus isosorbide dinitrate or atenolol plus nifedipine when possible. After anti-ischemic medication adjustment to control angina, blinded medication was adjusted in the medical therapy groups to eliminate ischemia in the ischemia-guided group. The primary outcome was the absence of ischemia at 12 weeks. Follow-up was scheduled for 1 year. RESULTS A total of 1,959 patients were screened by ambulatory ECG monitoring; 982 (49%) had asymptomatic ischemia, and 618 (65%) were enrolled in the study. Most patients were men, were > 60 years old and had two or more ischemic episodes, early positive exercise tests and multivessel disease. CONCLUSIONS Design and baseline data for a pilot study of ischemia treatment strategies are described.

Randomized double-blind comparison of nifedipine and isosorbide dinitrate in patients with coronary arterial spasm.

The effects of nifedinpine and isosorbide dinitrate on the frequency of angina and consumption of nitroglycerin were studied in 19 patients with coronary arterial spasm. After a lead-in phase, the patients were randomized to treatment with either nifedipine or isosorbide dinitrate. After dose titration (40 to 120 mg/day) and evaluation, they were given the alternate therapy. During the initial segment of the double-blind phase, one patient died suddenly (nifedipine phase), one dropped out of the study (nifedipine phase) and another was unable to tolerate therapy (isosorbide dinitrate phase). In the other 16 patients, the mean frequency of angina was less during therapy with both nifedipine (0.69 episode/day, p less than 0.05) and isosorbide dinitrate (0.77 episode/day, p less than 0.05) phases than during the lead-in phase (1.71 episodes/day). The mean frequency of angina was similar in the nifedipine and isosorbide dinitrate phases. A 50 percent or greater decrease in frequency of angina compared with lead-in phase values occurred in 13 of 18 patients during treatment with nifedipine and in 10 of 16 during treatment with isosorbide dinitrate. Of the 16 patients who completed both double-blind phases, 7 showed greater improvement (that is, a 50 percent or greater decrease in frequency of angina) with nifedipine than with isosorbide dinitrate); 6 others showed greater improvement with isosorbide dinitrate, and the other 3 had a less than 50 percent difference in frequency of angina with the two drugs. These findings in a limited number of patients suggest that both nifedipine and isosorbide dinitrate are effective in certain patients with coronary spasm but that neither drug is clearly superior.