S.Ben Freedman

Prognostic significance of a predischarge exercise test in risk stratification after unstable angina pectoris

The prognostic significance of exercise testing was compared with clinical and electrocardiographic (ECG) variables in a prospective study of 107 patients with unstable angina discharged from the hospital on medical therapy. During a follow-up period of 12.8 +/- 1.4 months, 10 patients (9%) had a nonfatal myocardial infarction (n = 8) or died (n = 2) and 22 (20%) were readmitted with recurrent unstable angina. The relation between 20 clinical, ECG and exercise test variables and the risk of adverse outcome (death, nonfatal myocardial infarction or recurrent unstable angina) was analyzed using both univariate and multivariate (logistic regression) analysis. Univariate predictors of adverse outcome included diabetes mellitus, evolutionary T wave changes, T wave changes on the preexercise ECG and low maximal rate-pressure product during exercise. Independent predictors of adverse outcome in multivariate analysis included diabetes mellitus, evolutionary T wave changes after admission, rest pain during hospitalization, ST depression during exercise and low maximal rate-pressure product. A predictive model constructed using the regression equation and all independent predictors stratified patients into high and low risk groups (41% and 5% risk of adverse outcome, respectively). The result of a predischarge exercise test adds independent prognostic information to clinical and ECG data in medically treated patients with unstable angina and could be used in combination with clinical and ECG data to identify patients at risk of adverse events.

Relation Between Ischemia Time, Infarct Size, and Left Ventricular Function in Humans

BACKGROUNDnExperimental studies indicate that duration of ischemia is a major determinant of myocardial infarct size, but only limited information is available about the relation between ischemia time and infarct size in individual patients. This prospective study sought to document the role of ischemia time as a determinant of infarct size in humans.nnnMETHODS AND RESULTSnWe studied 61 patients (50 men, 11 women) 57 +/- 11 years old admitted with a first infarct (31 anterior, 30 inferior) who underwent continuous 12-lead ECG monitoring to document ischemia time. Infarct size (32-point QRS score on day 7) and changes in regional myocardial wall motion (echocardiography) during the following month were related to ischemia time. Among patients with < 3 hours of ischemia (n = 16), mean infarct size on day 7 was 21 +/- 13% of potential infarct size; in patients with 3 to 6 hours of ischemia (n = 23), infarct size was 38 +/- 18% of potential (P < .05 versus 0 to 3 hours of ischemia); and in patients with 6 to 9 hours of ischemia (n = 10), infarct size was 66 +/- 14% of potential (P < .05 versus 3 to 6 hours). In contrast, the 12 patients with an ischemia time > 9 hours had a final infarct size of 77 +/- 10% of potential (P < .01 versus 3 to 6 hours). Multivariate regression identified size of risk region, duration of ischemia, and degree of initial ST-segment elevation as independent predictors of infarct size, of which the most important variable was ischemia time. The regression models accurately predicted both individual absolute infarct size (R2 = .83) and individual infarct/risk ratio (R2 = .74). Patients with < 6 hours of ischemia exhibited significant recovery of myocardial wall motion by day 7 (wall motion score, 2.1 +/- 1.4 versus 5.7 +/- 3.2 on day 1, P < .01). Patients with 6 to 9 hours of ischemia had some recovery by 1 month (score, 6.3 +/- 4.4 versus 10.9 +/- 3.8 on day 1, P < .01), but patients with > 9 hours of ischemia had little recovery of wall motion by 1 month (score, 10.3 +/- 4.5 versus 12.8 +/- 3.1 on day 1, P < .05).nnnCONCLUSIONSnMeasurement of ischemia time allows improved prediction of infarct size in humans. Significant myocardial salvage and functional recovery may be achieved by reperfusion up to 9 hours after coronary occlusion. Continuous ST-segment monitoring should be used to measure ischemia time and guide interventions to reperfuse the infarct artery.

Electrocardiographic measurement of infarct size after thrombolytic therapy.

OBJECTIVESnWe examined the utility of the 32-point QRS score from the 12-lead electrocardiogram (ECG) for measurement of the ischemic risk region and infarct size in patients receiving thrombolytic therapy.nnnBACKGROUNDnThe QRS score offers a means of evaluating the therapeutic benefit of thrombolytic therapy by comparing final infarct size with the initial extent of ischemic myocardium.nnnMETHODSnThe study included 38 patients (34 men, 4 women; mean [+/-SD] age 54 +/- 10 years) with a first infarction (18 anterior, 20 inferior). The maximal potential QRS score (QRS0) was assigned to all leads with >/= 100-microV ST elevation on the initial ECG. The QRS scores were calculated at 7 and 30 days after infarction. Left ventricular ejection fraction was measured by radionuclide ventriculography at 1 month. Twenty-eight patients had thallium (Tl)-201 and technetium (Tc)-99m pyrophosphate tomographic measurement of the ischemic region and infarct size.nnnRESULTSnThe QRS0 was 10.3 +/- 3.1 (mean +/- SD) for anterior and 10.4 +/- 3.5 for inferior infarcts. The QRS scores were similar at 7 and 30 days for both anterior (5.6 +/- 3.4 vs. 5.5 +/- 3.4) and inferior infarcts (3.7 +/- 2.6 vs. 2.9 +/- 2.2). The day 7 QRS score and ejection fraction at 1 month were inversely correlated (r = -0.74, p < 0.01). The Tl-201 perfusion defect was 34 +/- 11% of the left ventricle for anterior and 32 +/- 7% for inferior infarcts. Subsequent Tc-99m pyrophosphate infarct size was 15 +/- 9% of the left ventricle for anterior and 17 +/- 9% for inferior infarcts. The QRS0 was correlated with the extent of the Tl-201 perfusion defect (r = 0.79, p < 0.001), and the day 7 QRS score was correlated with Tc-99m pyrophosphate infarct size (r = 0.79, p < 0.005).nnnCONCLUSIONSnThe 32-point QRS score can provide useful immediate measurements of the ischemic risk region and subsequent infarct size.

Clinical significance of silent ischemia in unstable angina pectoris

In a prospective study the significance of silent ischemia was evaluated in 66 patients with a clinical diagnosis of unstable angina (no requirement for reversible ST-T changes during pain on 12-lead electrocardiograms before entry), and the results of continuous 2-channel electrocardiographic (ECG) recordings, begun within 24 hours of admission, were compared with other clinical and ECG predictors of adverse outcome. Ischemic changes were detected in 7 patients (11%) during a mean of 41 hours of recording. There were 37 episodes of transient ST-segment change (16 ST elevation, 21 ST depression) of which 11 (30%) were symptomatic and 26 (70%) were silent. All 7 patients had at least 1 silent episode and 5 also had symptomatic episodes during the recording but only 2 patients had exclusively silent episodes. During a mean follow-up of 13.3 months, 3 patients died, 5 had a nonfatal myocardial infarction and 32 required revascularization. Although transient myocardial ischemia during the continuous ECG recording, whether silent or symptomatic, was a specific predictor of subsequent nonfatal myocardial infarction or death (specificity 92%), its sensitivity for these events was low (25%). In contrast, recurrent rest pain (greater than or equal to 1 episode) occurred in all patients with these serious adverse events (sensitivity 100%, specificity 49%). Transient ischemia occurs infrequently during continuous ECG recordings in patients with unstable angina not selected by reversible ST-T changes on a 12-lead electrocardiogram at entry. Recurrent rest pain after hospital admission is a more sensitive predictor of serious events in this group.

Mechanism and significance of precordial ST-segment depression during inferior wall acute myocardial infarction associated with severe narrowing of the dominant right coronary artery

The mechanism and significance of precordial ST depression during inferior wall acute myocardial infarction (AMI) is debated. This study assessed the location and extent of arterial perfusion distribution responsible for this electrocardiographic finding. Intracoronary thallium-201 was injected in 11 patients with 1-vessel right coronary disease to delineate perfusion distribution that was quantitated by a new angiographic distribution score. The angiographic score correlated with posterior (r = 0.84), posterolateral (r = 0.88) and total (r = 0.73) extent of intracoronary thallium distribution. The angiographic distribution score was related to electrocardiographic changes in 16 patients showing an inferior ST-segment elevation during angioplasty (7 with and 9 without precordial ST depression), of which 6 received intracoronary thallium injection. None had thallium distribution in the anterior or septal segment, but there was a trend toward a greater angiographic distribution score and posterior segment thallium score in patients with precordial ST depression. In another 77 patients with inferior wall AMI due to right coronary occlusion (24 with concomitant left anterior descending narrowing), precordial ST depression was present in 16 with and 31 without left anterior descending narrowing (p = NS). The angiographic distribution score was higher in those with than without precordial ST depression (0.59 +/- 0.10 vs 0.44 +/- 0.11, p < 0.001) in both patients with and without left anterior descending disease. The magnitude of both inferior ST elevation and precordial ST depression correlated with the angiographic distribution score, but only precordial ST depression was independently related in multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Intermittent transdermal nitrates do not improve ischemia in patients taking beta-blockers or calcium antagonists: potential role of rebound ischemia during the nitrate-free period.

OBJECTIVESnThis study was conducted to determine whether rebound ischemia occurs during nitrate-free periods with intermittent cutaneous nitroglycerin therapy in patients with angina pectoris who are receiving background antianginal therapy.nnnBACKGROUNDnRebound angina has been suggested to be a complication of the nitrate-free period with long-term cutaneous nitroglycerin therapy given intermittently to prevent tolerance.nnnMETHODSnFifty-two patients with stable effort angina taking either a beta-adrenergic blocking agent (n = 25) or diltiazem (n = 22) or their combination (n = 5) completed a randomized, double-blind, placebo-controlled crossover study of cutaneous nitroglycerin patches (50 mg). Active or placebo patches were worn for 1 week, applied at 8 AM and removed at 10 PM to provide a 10-h daily nitrate-free (or placebo-free) period. During the last 48 h of each study phase, a Holter monitor was used to detect ischemia.nnnRESULTSnOnly 31 patients experienced ischemia during either phase of the study (23 during the patch-off period). A total of 463 ischemic episodes were recorded: 246 during placebo and 217 during nitroglycerin (p = 0.8, for per patient comparison). The majority (88%) of ischemic episodes were silent. Mean (+/- SEM) duration of ischemia during the total 48-h period was similar during active and placebo phases (35.5 +/- 15.0 min/24 h for active therapy vs. 29.7 +/- 9.8 for placebo, p = 0.8). This was due to an increase in duration of ischemia with active therapy during the patch-off period (46.9 +/- 17.9 min/24 h for active therapy vs. 22.5 +/- 9.2 for placebo, p = 0.07) and a decrease during the patch-on period (27.5 +/- 14.0 min/24 h for active therapy vs. 34.5 +/- 11.0 min/24 h for placebo, p = 0.16). The pattern of diurnal distribution of ischemic episodes differed between active and placebo phases. During placebo there was a nadir in the incidence of ischemia in the overnight patch-off period, with a significantly lower incidence between midnight and 6 AM (25 episodes) compared with the mean number of episodes during the three other 6-h periods (73 episodes, p < 0.001). During the nitroglycerin patch-off period, there was a loss of this overnight nadir, with the same incidence of ischemia between midnight and 6 AM (53 episodes) as the mean number of episodes for the three other 6-h periods (54 episodes).nnnCONCLUSIONSnThe majority of patients taking background antianginal therapy experienced no ischemia during the patch-off period. In the 44% of patients with ischemia during this period, there was a nonsignificant increase in the duration of ischemia with active therapy. Although this result was statistically inconclusive, the change in the distribution of diurnal ischemia offers suggestive evidence that rebound ischemia may be a problem with regard to intermittent cutaneous nitroglycerin.

Validation of a real-time electrocardiographic monitor for detection of myocardial ischemia secondary to coronary artery disease

A new real-time electrocardiographic (ECG) monitor (QMED Monitor OneTM) was evaluated to assess its accuracy in detecting ischemic ST-segment changes in 43 patients (34 men, 9 women, mean age 56 +/- 11 years) during exercise stress testing. The output of QMED was compared with ST-segment measurements from a Marquette CASE-II computer (ECGM) using a bipolar lead CM5, defining a positive ECG as at least 1 mm of planar or downsloping ST depression. Results were concordant in 33 patients, 15 with both positive and 18 both negative responses, yielding an accuracy (expressed as sensitivity, specificity, positive and negative predictive accuracy) of 83%, 72%, 68% and 86%, respectively. Seven false-positive QMED episodes occurred: 4 due to excess baseline wander or noise in the control ECG, which may have been prevented by reapplication of electrodes, and all 7 episodes were correctly discounted by inspection of the sample ischemic ECG output, yielding an accuracy of 81%, 100%, 100% and 85%. Mean duration and maximal magnitude of ST depression in patients with a positive ECG response was 7.9 +/- 7 minutes and 1.7 +/- 0.6 mm for QMED and 8.9 +/- 7 minutes and 2.2 +/- 0.7 mm for ECGM. The 3 false-negative QMED events were relatively brief and mild ischemic episodes and slight differences in electrode placement between the 2 systems may account for this discrepancy in 2 of the patients. Real-time ST monitoring with QMED is sufficiently reliable for clinical use. Optimal specificity depends on the ability to inspect sample ECG traces to verify a stable baseline and confirm episodes of ischemic ST-segment shift.

Late follow-up (41 to 102 months) of medically treated patients with coronary artery spasm and minor atherosclerotic coronary obstructions.

From a series of 37 patients with coronary artery spasm and less than 70% diameter narrowing treated initially with verapamil and nitrates, 33 were followed up 41 to 102 months (mean 62). One patient died from carcinoma of the lung and 3 could not be traced. Before diagnosis, 3 had nontransmural myocardial infarction and 10 had either ventricular tachycardia and fibrillation or atrioventricular block. During follow-up there were no cardiac deaths or myocardial infarctions. Asymptomatic periods of more than 3 months occurred in 23 patients during follow-up: 18 with asymptomatic periods of more than 1 year were pain free at the time of study and 5 with asymptomatic periods of 3 to 6 months had infrequent pain. Ten patients had no asymptomatic periods. Symptomatic status at last review was related to initial response to therapy: 13 of 18 patients (72%) currently asymptomatic became asymptomatic with initial therapy compared with 5 of 15 patients (33%) currently experiencing pain (p = 0.06). Twenty-six patients were currently receiving therapy: 22 verapamil, 80 to 640 mg/day (mean 280), 2 nifedipine, 1 diltiazem and amiodarone and 1 isosorbide (15 were receiving additional isosorbide). Twelve patients were not receiving therapy or were receiving very low dosage therapy, including 8 with asymptomatic periods of more than 1 year. Patients with coronary spasm and less than 70% diameter narrowing treated medically have low mortality and morbidity rates over 5-year follow-up. Many have long asymptomatic periods and some may be able to stop therapy indefinitely.

ST monitoring for myocardial ischemia during and after coronary angioplasty.

We performed 12-lead electrocardiographic monitoring in 97 patients during coronary angioplasty (PTCA) of a single vessel to correlate ischemic ST changes with clinical, angiographic and coronary hemodynamic variables and to determine the optimum lead or combination of leads for their detection. Ischemia (chest pain or ST change, group A) occurred in 79 patients (80%), but in only 15 of 23 patients (65%) with collaterals (p less than 0.05). Ischemia occurred more often in left anterior descending and left circumflex PTCA than right coronary PTCA, but pain was the only manifestation more often in left circumflex and right coronary PTCA. Ischemic ST change was silent in 16% and this proportion did not differ in clinical or angiographic groups except for diabetes with 3 of 5 (60%) having silent ischemia (p less than 0.05). Patients in group A (ischemia) compared to group B (no ischemia) had less severe lesions (85 +/- 9 vs 91 +/- 7%, p less than 0.01), higher transstenotic gradients (62 +/- 19 vs 53 +/- 9 mm Hg, p less than 0.05) and lower distal occluded pressures (24 +/- 11 vs 33 +/- 10 mm Hg, p less than 0.01), suggesting less collateral flow. Compared with a 12-lead electrocardiogram, the best single lead for detecting ST change during PTCA in each artery had a sensitivity of 80% and this increased to 93% using the best 2 leads. The best 3 leads (V3/III/V5 for left anterior descending and III/V2/V5 for right coronary and left circumflex) increased sensitivity to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of adverse outcome in patients admitted to the coronary care unit with suspected unstable angina pectoris

One hundred ninety-six consecutive patients admitted to the coronary care unit with suspected unstable angina were classified clinically as having either definite (113 patients) or suspected unstable angina (83 patients) within 24 hours of admission. Patients were followed prospectively to determine their outcome in the hospital and in the first 4 months after discharge. Three patients had a non-fatal myocardial infarction in the hospital and 2 died (1 fatal myocardial infarction, 1 death immediately after coronary bypass surgery). During follow-up (mean 4.2 +/- 2.3 months), 6 additional patients had a nonfatal myocardial infarction, 4 died and 22 were readmitted with definite unstable angina. The incidence of nonfatal infarction or death was significantly lower in patients with suspected unstable angina during both the primary hospital admission (0 of 83 vs 5 of 113, p less than 0.05) and after discharge from the hospital (1 of 83 vs 9 of 113, p less than 0.05), and fewer patients with suspected unstable angina were readmitted with a recurrence of definite unstable angina (1 of 83 vs 21 of 113, p less than 0.001). Thus, a simple clinical classification into definite or suspected unstable angina performed within 24 hours of admission to the coronary care unit identified a substantial group with a low short-term risk of adverse events.