Recommendations for extraction of chronically implanted transvenous pacing and defibrillator leads: indications, facilities, training. North American Society of Pacing and Electrophysiology Lead Extraction Conference Faculty.

The procedure of lead removal has recently matured into a definable, teachable art with its own specific tools and techniques. It is now time to recognize and formalize the practice of lead removal according to the current methods of medicine and the health care industry. In addition, since at this time the only prospective scientific study of lead extraction is the PLEXES trial, we suggest that studies relating to the techniques of and indications for lead extraction be designed. Recommendations for a common set of definitions, for a framework of training and reviewing physicians in the art, for general methods of reimbursement, and for consistency among clinical trials have been made. Implementation of these recommendations will require additional effort and cooperation from practicing physicians, medical societies, hospital administrations, and industry.

Risks of spontaneous injury and extraction of an active fixation pacemaker lead: report of the Accufix Multicenter Clinical Study and Worldwide Registry.

BACKGROUND: The Telectronics Accufix pacing leads were recalled in November 1994 after 2 deaths and 2 nonfatal injuries were reported. This multicenter clinical study (MCS) of patients with Accufix leads was designed to determine the rate of spontaneous injury related to the J retention wire and results of lead extraction. METHODS AND RESULTS: The MCS included 2589 patients with Accufix atrial pacing leads that were implanted at or who were followed up at 12 medical centers. Patients underwent cinefluoroscopic imaging of their lead every 6 months. The risk of J retention wire fracture was approximately 5.6%/y at 5 years and 4.7%/y at 10 years after implantation. The annual risk of protrusion was 1.5%. A total of 40 spontaneous injuries were reported to a worldwide registry (WWR) that included data from 34 672 patients (34 892 Accufix leads), including pericardial tamponade (n=19), pericardial effusion (n=5), atrial perforation (n=3), J retention wire embolization (n=4), and death (n=6). The risk of injury was 0.02%/y (95% CI, 0.0025 to 0. 072) in the MCS and 0.048%/y (95% CI, 0.035 to 0.067) in the WWR. A total of 5299 leads (13%) have been extracted worldwide. After recall in the WWR, fatal extraction complications occurred in 0.4% of intravascular procedures (16 of 4023), with life-threatening complications in 0.5% (n=21). Extraction complications increased with implant duration, female sex, and J retention wire protrusion. CONCLUSIONS: Accufix pacing leads pose a low, ongoing risk of injury. Extraction is associated with substantially higher risks, and a conservative management approach is indicated for most patients.

Spontaneous versus extraction related injuries associated with Accufix J-wire atrial pacemaker lead: tracking changes in patient management.

UNLABELLED: To make recommendations for management of potentially fatal failure of the Accufix series of atrial J-wire permanent pacemaker leads, we closely monitored the number of injuries and fatalities resulting either from spontaneous fracture of the J-wire or from attempts to extract the lead. In a population of 30,357 patients, 2,298 patients are enrolled in a prospective follow-up Multicenter Study, the remainder are patients with known clinical status from voluntary reporting, and 2,992 patients died following implant. In the remaining 27,365 patients, 6 deaths have been attributed to J-wire related injury (J-inj) while 13 were complications (E-inj) associated with 4,076 lead extraction procedures (3,974 intravascular (intra)/102 primary thoracotomy (PT). The date of occurrences were from 1994 to November 1997. CONCLUSIONS: (1) Since lead extractions were not conducted in a controlled study, it is not known whether the deaths associated with lead extraction is in excess of what would have occurred if these leads had not been removed in this specific subset. (2) Awareness of the procedure related complication rate appears to have moderated the rate of lead extraction and may ultimately lead to management that reasonably balances the risks of patient injury.

Kaplan-Meier analysis of freedom from extraction or death in patients with an Accufix J retention wire atrial permanent pacemaker lead: a potential management tool.

UNLABELLED: Morbidity (36 cases) and mortality (6 cases) have been reported in patients with Accufix J retention wire atrial leads. This has resulted in ongoing patient fluoroscopic monitoring as well as lead extractions. The estimated implanted worldwide population is 40,860. Estimating the size of the remaining population at risk is an important tool for assessing patient management guidelines. RESULTS: The Kaplan-Meier method can be used to calculate the cumulative probability of remaining free of extraction and death for patients based on implant duration. The individual Kaplan-Meier curves for lead extraction and patient survival can also be computed. Based on the Multicenter Study (MCS) population of 2,298 patients, the probability that a patient is alive with the lead still implanted at 5 years implant duration is 52.5%. The event-free survival rate at 5 years implant duration is 81.3%. The corresponding probability of remaining free from injury due to the J-wire is 99.9% at 5 years implant duration. Assuming similar rates of death and extraction, these results can be extrapolated to the world wide population. CONCLUSIONS: The management of Accufix patients must consider patient longevity, the probability of J-wire morbidity/mortality, and the probability of extraction complication morbidity/mortality. The probability of remaining at risk as a function of time from implant can be calculated from the events known in the MCS patient population. These event-free survival estimates can be used to identify subsets of the population at greater or lesser risk based on various clinical parameters.

Cumulative hazard analysis of J-wire fracture in the Accufix series of atrial permanent pacemaker leads.

UNLABELLED: To permit a more complete analysis of J-wire fracture in the Accufix series of atrial permanent pacemaker leads, the time to occurrence of all known fractures and injuries has been redefined relative to the duration of risk exposure, that is, according to the interval of time between implant and occurrence of the event. This redefinition permits application of a cumulative hazards model to the data, which previously has not been explored. Predictors of J-wire fracture can be tested using this method. This also permits parametric curve-fitting for determination of linearity or constancy of risk of events over time. RESULTS: Among 2,063 Multicenter Study (MCS) leads analyzed, 381 fractures of the J-wire were identified. Stratified analysis based on cumulative hazard curves identified a more open shape of the J-wire as predictive of fracture, which supports the results previously reported based on logistic regression analysis. Fitting a Weibull curve to the cumulative hazard of J-wire fracture gives a shape parameter equal to 0.85. This value indicates that the instantaneous hazard of J-wire fracture decreased over time from implant. CONCLUSIONS: (1) The cumulative hazard function can be used to examine predictors of J-wire fracture and preliminary findings support the previously identified predictor of J shape; (2) Based on these analyses, the rate of J-wire fracture appears to decrease slightly as time from implant increases.

Actuarial outcome after catheter balloon commissurotomy in patients with mitral stenosis.

BACKGROUND: The goal of the present study was to determine the intermediate-term survival and the independent predictors of survival and event-free survival for patients who undergo catheter balloon commissurotomy (CBC). METHODS AND RESULTS: CBC for the treatment of mitral stenosis was performed in 132 patients from 1986 through 1994. The use of CBC increased the mitral valve area (MVA) from 1.0 +/- 0.3 to 1.9 +/- 0.6 cm2 (P < .001). There were six early deaths (4.5%) up to 1 month after CBC ("hospital" deaths). In the past 4.5 years, there have been no hospital deaths. Four late deaths occurred after elective mitral valve replacement (MVR). Actuarial 7-year survival was 95 +/- 1%; when mortality after MVR is included, 7-year survival was 83 +/- 6%. Actuarial 1-, 3-, 5-, and 7-year event-free survival (survival without MVR or repeat CBC) was 80 +/- 4%, 77 +/- 4%, 65 +/- 6%, and 65 +/- 6%. On multivariate analysis, the only two independent predictors (both after CBC) of 7-year event-free survival were MVA of > or = 1.5 versus < 1.5 cm2 (75 +/- 7% versus 32 +/- 12%) and mean pulmonary artery wedge pressure of < or = 18 versus > 18 mm Hg (84 +/- 6% versus 38 +/- 11%) (P < .001 for both). Patients with MVA of > or = 1.5 cm2 (n = 96) could be further subdivided into high- and low-risk subgroups for 7-year event-free survival by two post-CBC variables: mean pulmonary artery wedge pressure of < or = 18 versus > 18 mm Hg (90 +/- 6% versus 48 +/- 14%) (P = .0002) and cardiac index of > or = 2.5 versus < 2.5 L.min-1.m-2 (82 +/- 8% versus 61 +/- 13%) (P = .004). Patients with post-CBC MVA of < 1.5 cm2 (n = 24) had no additional predictors of event-free survival. Of patients who did not undergo MVR or repeat CBC, 8% were in New York Heart Association functional class III and 92% were in class I or early class II at the last follow-up. CONCLUSIONS: The rates for intermediate-term survival and event-free survival after CBC are very encouraging. Most patients without events were asymptomatic or minimally symptomatic. Thus, in selected patients with mitral stenosis who require an interventional procedure, CBC is the procedure of choice at centers with physicians who have experience and skill in performing this procedure.

Determination of coronary flow measurements by transesophageal echocardiography: dependence of flow velocity reserve on the location of stenosis.

Doppler velocimetry with the use of transesophageal echocardiography can record flow in the proximal left anterior descending artery (LAD). To assess whether this limited sampling ability influences the recording of velocity and the calculation of coronary flow reserve (CFR), 32 patients with LAD stenosis (4 ostial stenoses, 18 proximal stenoses, 10 mid-LAD stenoses) and 33 patients with arteriographically normal LADs were studied. Basal flow and dipyridamole-induced hyperemic flow rates were recorded. The mean basal flow velocity in ostial stenoses was greater than in other groups, and the mean basal flow velocity in proximal stenoses was less than that in mid-LAD stenoses and in the normal group. Maximal hyperemic velocity did not differ between the groups. CFR in all stenoses groups was less than that in the normal group. Ostial CFR was less than in all other groups, and proximal CFR was less than that in either the mid-LAD or the normal LAD groups. With this technique, coronary flow velocimetry and estimation of CFR is affected by the location of stenosis.

Failure rates of leads, pulse generators, and programmers have not diminished over the last 20 years: formal monitoring of performance is still needed. BILITCH Registry and STIMAREC.

Formal Monitoring of Performance is Still Needed. In order to detect trends in the number of device or component failures that have occurred among permanent pacemaker systems since the 1970s, we reviewed the data of the five largest pacemaker manufacturers from the Bilitch Registry of permanent pacemaker pulse generators, the Stimarec failure registry, the general accounting office summaries of the United States Veterans Administration (VA) Registry of Pacemaker Leads, and the Implantable Lead Registry, from the Cleveland Clinic Lead registry, and the recalls and safety alerts issued by the United States Food and Drug Administration (FDA) over the last 20 years. The definition of failure followed the criterion, or criteria, developed within each registry and differed significantly between the registries. The 20-year period between 1976 and 1995 was divided into 5-year quartiles (QT): QT 1 = 1976-1980; QT2 = 1981-1985; QT3 = 1986-1990; and QT4 = 1991-1995. For pulse generators, the number of models with failures in each quartile in the Bilitch Registry were: QT 1 = 9; QT 2 = 11; QT3 = 17; QT4 = 13. In Stimarec, the number of units reported as having reached a dangerous condition were: QT1 = 710; QT2 = 212; QT3 = 114; QT4 = 310. From the FDA reports, the number of units included in recalls or safety alerts were: QT3 = 6,085; QT4 = 135,766. For permanent pacemaker leads, the numbers of failed or dangerous leads recorded in Stimarec were: QT3 = 16; QT4 = 32. In the VA Registry, the number of models having a below average survival was 2/92 (2.7%). In the Implantable Lead Registry, the number of models having a below average survival was 3/21 (14%). In the Cleveland Clinic series, 6/13 (46%) of lead models were recognized to have some failure involving the conductor, insulation, or connector. In the FDA reports, the number of leads involved in either recall or safety alert were: QT3 = 20,354; QT4 = 332,105. For programmers, the number of units involved either in a recall or safety alert were: QT3 = 11,124; QT4 = 3,528. In all of these series, each of the five largest manufacturers had some models or units involved in each time period. This review of programs has revealed: 1. The incidence of failures, recalls, or safety alerts did not decline over time; and 2. Despite changes in technology, formal monitoring of pacemaker systems is still warranted.

Transesophageal assessment of coronary flow velocity reserve during "regular" and "high"-dose dipyridamole stress testing.

To assess the effect of regular and high-dose dipyridamole on coronary flow velocity in the left anterior descending artery (LAD), and to determine whether assessment of coronary flow velocity reserve (CFVR) is more sensitive for detection of ischemia than standard echocardiographic criteria, 47 patients were studied prospectively: 16 patients with stenosis of the LAD, 18 patients with angiographically normal LADs, and 13 patients with minimal disease. Patients underwent transesophageal echocardiographic study of wall motion and LAD flow velocity at baseline and at hyperemia, and for angina and electrocardiographic changes. The mean CFVR values after 0.56 mg/kg after 0.84 mg/kg of dipyridamole were similar: 2.52 +/- 0.87 versus 2.62 +/- 0.90. A CFVR <2.3 (normals mean -2 SDs) was more sensitive (88% at both doses) for the detection of underlying coronary obstruction than was wall motion monitoring (44% and 75%, respectively). The combination of CFVR <2.3 and wall monitoring was more sensitive than index alone (94% at both 0.56 and 0.84 mg/kg). The rate-pressure product was not significantly different at the two doses of dipyridamole. When flow response is the end point of stress testing, as with transesophageal monitoring, the 0.56 mg/kg dose of dipyrid mole is adequate, but when ischemia is the end point (as with wall motion monitoring by 2-dimensional echocardiography), the dose of 0.84 mg/kg is more sensitive.

Morphological characteristics of the regurgitant rheumatic mitral valve.

Reparative surgery for valvular insufficiency is attempted frequently. The success of surgery depends partly on the underlying etiology. To establish the morphological characteristics of rheumatic mitral valve disease (insufficiency) (n = 12), mitral insufficiency due to infective endocarditis (n = 12), mitral insufficiency postinfarction (n = 6), rheumatic (predominant) mitral insufficiency postinfarction (n = 6), rheumatic (predominant) mitral stenosis (n = 12) and normal patients (n = 12) were examined retrospectively. In the groups of patients with mitral insufficiency< the mobility of the posterior leaflet tip (change in angle from the annular plane) was significantly less than normal 48 +/- 9 degrees only in the rheumatic group (12 +/- 7 degrees, P < 0.01). The posterior mitral leaflet tip had greater than normal mobility in the other mitral insufficiency groups: infective endocarditis 53 +/- 15 degrees (P = 0.35 versus normals), postinfarction 63 +/- 11 degrees (P = 0.02 versus normals), myxomatous 63 +/- 19 degrees (P = 0.03 versus normals). The mobility of the posterior mitral leaflet tip was also significantly less than normal in the rheumatic mitral stenosis group: 16 +/- 7 degrees, P < 0.01 versus normals. In the two rheumatic groups, diastolic doming of the anterior mitral leaflet was seen solely in mitral stenosis. In the predominant regurgitant group, the tip of the anterior mitral leaflet was much more mobile than in the stenosis group. Doming of the anterior mitral leaflet was absent from the predominant regurgitant group (2.1 +/- 0.9 cm, P < 0.001). The stenotic mitral valves domed 0.75 +/- 0.15 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Transthoracic and transesophageal echocardiography pre and post percutaneous mitral catheter balloon valvulotomy.

Catheter balloon valvulotomy (CBV) is useful in the relief of rheumatic mitral stenosis. Morphologic scoring of the mitral valve by transthoracic echocardiography is predictive of success with CBV. Horizontal plane transesophageal echocardiography can obtain high quality images of the mitral valve and left atrium, but its value with routine use in the pre and post CBV setting is unknown. We prospectively examined 14 patients with mitral stenosis, pre and post CBV, noting scores, complications of mitral stenosis, and complications of CBV. Mitral valve scoring was similar by TTE and TEE pre and post CBV, but TEE did tend to underestimate scores pre CBV. There was a single thrombus, it was detected only by TEE. Post CBV, both TTE and TEE detected one of two torn chordae. Of three patients with ASD's by colour flow mapping, TTE and TEE each detected two. Increases in mitral insufficiency post CBV were seen equally frequently by TTE and TEE. The increases appeared to be of a higher grade (NS) by TEE. TTE and TEE yielded complementary findings, pre and post CBV. Other than for the detection of thrombi through, the net clinical contribution of routine use of TEE appears small, and large series would be needed to establish its contribution.

Clinical outcome following ICD removal. The Bilitch Registry Group.

The Bilitch ICD Registry includes 1,869 patients from 13 medical centers enrolled between March 1982 and April 1992. Of these, 95 patients had their units removed and not immediately replaced (77 males/18 females mean age 54.9 +/- 13.0 years, range 10-76). The mean duration of implanted ICD was 19.5 +/- 18.2 months, mean ejection fraction 30.1 +/- 11.7%. Coronary artery disease was present in 55 patients, absent in 30, and unknown in 10. The presenting clinical event was sudden death in 35 patients, symptomatic ventricular tachycardia in 34, other causes in 6, and unknown in 20. Reasons for ICD removal were: infection in 33 patients, cardiac transplant in 32, elective in 20, following battery depletion in 7, lead system failure in 2, and inappropriate shock in 1. Of all groups who had their ICD removed, the patients who had removal for cardiac transplantation had the highest incidence of appropriate ICD discharges while the device was implanted (43.8%). Of the 63 nontransplanted patients seven were lost to follow-up while alive. Of the 56 remaining, 17 died (1 cause unknown, 6 noncardiac, 3 sudden, 1 arrhythmic, 6 nonsudden nonarrhythmic cardiac death), 7 had an ICD reimplanted, and 32 are alive and well without an ICD. Follow-up for the 32 cardiac transplant patients: 2 were lost to follow-up while alive, 2 died of nonsudden nonarrhythmic death, and 28 are alive and well. The survival of patients who had their ICD removed and not reimplanted was not different from that of patients who never had their ICD removed up to 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind comparison of the clinical, hemodynamic, and electrocardiographic effects of sodium meglumine ioxaglate or iohexol during diagnostic cardiac catheterization.

The clinical effects and the maximal hemodynamic and electrocardiographic effects of two low-osmolality radiographic contrast media (ioxaglate and iohexol) were directly compared during diagnostic cardiac catheterization in a double-blind, randomized study in 80 patients. Because small changes were expected after injection of both of these agents, sensitive ECG and intracardiac-pressure-monitoring methods were used, and maximal changes, as well as mean changes in variables, were analyzed. Symptoms were absent, mild, or moderate in 67-77% of patients after left ventriculography and in 97-100% of patients after coronary arteriography. After left ventriculography, maximum and minimum left ventricular systolic pressure and end-diastolic pressure, the first derivative of left ventricular pressure (dp/dt), heart rate, were significantly altered over the two-minute observation period but were not different from the preinjection values at two minutes after both agents. Small but significant increases in mean aortic pressure, cardiac output, and pulmonary arterial wedge pressures were seen at two minutes after both agents.

Amlodipine combined with beta blockade for chronic angina: results of a multicenter, placebo-controlled, randomized double-blind study.

Amlodipine, a potent long-acting dihydropyridine calcium antagonist, was compared with placebo in a parallel, randomized, double-blind study in 134 patients with chronic stable angina pectoris maintained on beta-adrenergic blocking agents. After a single-blind, two-week placebo period, patients were randomized to receive either amlodipine (2.5, 5, and 10 mg) or placebo once daily for four weeks. The effects of amlodipine on maximal exercise time, work, time to angina onset, and subjective indices including angina frequency, nitroglycerin tablet consumption, and patient and investigator ratings were assessed. Each dose of amlodipine produced increases in exercise time and calculated total work accomplished compared to baseline. Improvements at 5 and 10 mg were significantly greater than placebo which produced no significant change (p less than 0.05). Qualitative improvements in the severity of angina were produced by amlodipine at 5 and 10 mg daily assessed by patient-rating questionnaires (p less than 0.05). Reductions in angina frequency attacks per week and weekly nitroglycerin tablet consumption occurred but were not statistically significant when compared with placebo. Adverse effects observed during amlodipine treatment prompted discontinuation of treatment in only 2 out of 100 patients. Three patients discontinued treatment for reported lack of efficacy. No laboratory abnormalities prompted treatment discontinuation and minor side effects of dizziness, nausea, headache, and fatigue were observed infrequently. The results of this controlled, large-scale multicenter trial suggest that amlodipine significantly increased exercise capacity and was well tolerated when added to the antianginal regimen of patients remaining symptomatic while receiving beta-blocking agents.

Response of angina and ischemia to long-term treatment in patients with chronic stable angina: a double-blind randomized individualized dosing trial of nifedipine, propranolol and their combination.

Seventy-four patients with chronic stable mild angina, mild coronary artery disease (83% had one- or two-vessel disease) and normal left ventricular function were studied to measure the response of treadmill exercise performance and painful and silent ischemia in the ambulatory setting to randomly assigned treatment with nifedipine or propranolol and their combination; titration to maximal tolerated dosages was performed in double-blind manner. At 3 months both nifedipine and propranolol reduced the weekly angina rate (p less than 0.05); during treadmill exercise testing, increases (p less than 0.05) were noted in time to angina and total exercise time and decreases in maximal ST depression at the end of exercise. There were no differences between the responses to nifedipine and propranolol and no significant additional changes were seen after another 3 months of therapy. The combination of nifedipine and propranolol reduced the number of patients with angina on exercise treadmill testing from 64% to 38% (p less than 0.05). During ambulatory electrocardiographic monitoring before treatment, there were 1.4 +/- 2.4 (mean +/- SD) episodes/24 h of painful ischemia and a very low silent ischemia frequency: mean 1.1 +/- 2.7 episodes/24 h, mean duration 16 +/- 25 min/24 h. Treatment with propranolol and nifedipine resulted in reduction of episodes and duration of painful and painless ischemia; approximately 77% of patients were free of all ischemic episodes. It is concluded that patients with chronic stable mild angina have a low incidence of silent ischemia. Nifedipine or propranolol alone, titrated to individualized maximally tolerated dosages, are equally effective in long-term control of painful and painless ischemia, anginal episodes and exercise-induced ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

A technique for improving accuracy of the pulmonary artery diastolic pressure as an estimate of left ventricular end-diastolic pressure.

Pulmonary artery diastolic pressure (PAD) is often used to estimate left ventricular end-diastolic pressure (LVEDP) when artifact, respiratory variation, or technical difficulties make the wedge pressure difficult to identify on the waveform. To determine which point on the PAD waveform best estimated LVEDP, we performed studies in 100 adults undergoing routine diagnostic cardiac catheterization. During normal spontaneous respiration, simultaneous recordings of the electrocardiogram, PAD, and LVEDP were obtained. Three end-expiratory measurements of PAD were recorded: at the lowest point on the waveform (PAD), at 0.04 seconds (PAD 0.04), and at 0.08 seconds (PAD 0.08) after the onset of the QRS complex. The PADs were correlated with LVEDP by linear regression. PAD 0.08 correlated best with LVEDP (r = 0.88, standard error of the estimate [SEE] = 3.6 mm Hg) whereas PAD 0.04 and PAD correlated slightly less strongly (r = 0.86, SEE = 4.0 mm Hg; r = 0.82, SEE = 4.4 mm Hg respectively). Therefore, when the wedge pressure is not easily determined, PAD 0.08 may be the best point on the waveform to use when attempting to estimate LVEDP in the clinical setting.

Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Differential effects on ambulatory ischemia, exercise performance, and anginal symptoms. The ASIS Study Group.

Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)