Anticardiolipin antibody and stroke: possible relation of valvular heart disease and embolic events.

To establish the etiology of strokes related to the anticardiolipin antibody (Acla) syndrome and to determine the relationship of valvular heart disease and stroke in the presence of the Acla, clinical and objective characteristics of 21 patients with Acla, focal cerebral ischemic events were retrospectively analyzed. Twelve (86%) of 14 patients with stroke and 3 (42%) of 7 patients with non-stroke cerebral ischemic events had echocardiographic evidence of left-sided valvular abnormalities. Features characteristic of cardioembolic stroke were present in 12 (86%) of the 14 patients with stroke. The strength of the association between valvular disease and stroke, combined with the clinical and radiologic features noted, suggest that strokes related to the Acla syndrome typically are embolic, from a cardiac source.

Recovery-phase patterns of ST segment depression in the heart rate domain. Identification of coronary artery disease by the rate-recovery loop.

Although the time course of ST segment depression after exercise has been related to the presence and severity of coronary artery disease, recovery-phase patterns of ST segment depression with reference to changing heart rate have not been quantified. We have found distinct recovery loop patterns of ST segment depression that distinguish subjects without coronary disease from patients with coronary artery disease when ST segment depression is examined in the heart rate domain. Continuous plots of ST segment depression and heart rate were constructed throughout treadmill exercise and recovery in 100 clinically normal subjects, in 124 patients with coronary artery disease proven by catheterization, and in 17 patients with no significant coronary disease at catheterization. Among clinically normal subjects, 95% (95 of 100) had normal (clockwise) rate-recovery loops, and 5% (five of 100) had abnormal (counterclockwise) rate-recovery loops. In these normal subjects, the resulting 95% specificity of a normal rate-recovery loop was similar to the 93% (93 of 100) specificity of standard end-exercise ST segment depression criteria. Among patients with coronary disease proven by angiography, 93% (115 of 124) had abnormal (counterclockwise) rate-recovery loops, and 7% (nine of 124) had normal rate-recovery loops. In contrast was the significantly lower 74% (92 of 124) sensitivity of standard ST segment criteria (p less than 0.001 vs. the rate-recovery loop). Specificity of a normal rate-recovery loop (71%, 12 of 17) and standard ST segment depression criteria (71%, 12 of 17) were similar in the patients with normal coronary arteries at angiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate adjustment of ST segment depression for improved detection of coronary artery disease.

Normal values for heart rate-adjusted indexes of ST segment depression during treadmill exercise electrocardiography (the ST segment/heart rate slope and the delta ST segment/heart rate index) were derived from evaluation of 150 subjects with a low likelihood of coronary artery disease, including 100 normal subjects and 50 subjects with nonanginal chest pain. Partitions chosen by the method of percentile estimation to include 95% of normal subjects remained highly specific in subjects with nonanginal pain syndromes. Sensitivities of the derived partitions for detection of myocardial ischemia were tested in an additional 150 patients with a high likelihood of coronary disease, including 100 patients with angiographically demonstrated coronary obstruction and 50 patients with stable angina. In contrast to the 68% (102 of 150 subjects) sensitivity of standard exercise electrocardiographic criteria for the detection of disease in this population, the sensitivity of an ST segment/heart rate slope partition of 2.4 muV/beats/min was 95% (142 of 150 subjects, p less than 0.001), and the sensitivity of a delta ST segment/heart rate index partition of 1.6 muV/beats/min was 91% (137 of 150 subjects, p less than 0.001). Analysis of receiver-operating curves confirmed the superior performance of the heart rate-adjusted indexes throughout a wide range of test specificities. These findings suggest that heart rate adjustment of ST segment depression can markedly improve the clinical usefulness of the treadmill exercise electrocardiogram.

Identification of anatomically extensive coronary artery disease by the exercise ECG ST segment/heart rate slope.

To assess the ability of the ST segment/heart rate (ST/HR) slope to identify three-vessel coronary disease and the relationship between the ST/HR slope and the anatomic extent of disease as determined by the Gensini and Duke jeopardy scores, the exercise ECGs of 128 patients with stable angina were compared with findings at coronary cineangiography. A ST/HR slope greater than or equal to 6 microV/beat/min identified three-vessel coronary disease with a sensitivity of 93% compared with sensitivities of only 50% for early positive standard test responses (p less than 0.001) and 66% for markedly positive standard test responses (p less than 0.01). The negative predictive value of this ST/HR slope partition for three-vessel disease was 94%. Patients with ST/HR slopes greater than or equal to 6 who did not have three-vessel disease had anatomically more extensive obstruction than did patients with lower test values (mean Gensini score 43 +/- 5 vs 22 +/- 3, p less than 0.002 and mean jeopardy score 4.8 +/- 0.4 vs 3.0 +/- 0.3, p less than 0.01). Test performance of the calculated ST/HR slope exceeded that of a simplified index derived by dividing the total change in ST segment depression by the total change in heart rate. These findings demonstrate that a ST/HR slope greater than or equal to 6 is highly sensitive for the identification of three-vessel coronary disease and also identifies patients with anatomically severe obstruction. A ST/HR slope less than 6 makes three-vessel coronary disease or otherwise anatomically extensive coronary obstruction unlikely.

Prevalence and clinical correlates of non-Wenckebach, narrow-complex second-degree atrioventricular block detected by ambulatory ECG.

Among 113 patients with transient, narrow-complex second-degree atrioventricular (AV) block detected by ambulatory ECG, there were 20 with non-Wenckebach behavior. Based on the presence or absence of PR interval shortening after single blocked complexes, patients with narrow-complex non-Wenckebach patterns could be separated into a pseudo-Mobitz II group of 16 patients (greater than or equal to 20 msec of PR shortening after the blocked complex) and a classic Mobitz II group of four patients (constant PR interval). These groups had additional distinct ECG and clinical features. Patients with the pseudo-Mobitz II pattern had a 44% prevalence of associated Wenckebach block during the same ambulatory recording, whereas Wenckebach behavior did not occur in patients with classic Mobitz II block. Pseudo-Mobitz II block occurred at significantly longer cycle lengths (876 vs 585 msec) and with significantly longer PR intervals (225 vs 165 msec) preceding the blocked complex than did classic Mobitz II block. Syncope was the presenting symptom in 38% of patients with pseudo-Mobitz II block and in all patients with classic Mobitz II block. Patients with pseudo-Mobitz II block had a 56% prevalence of associated coronary disease and a 44% prevalence of congestive heart failure; the mortality rate was 38% in this group over 4 years of follow-up, but in all instances death was due to associated disease rather than to conduction itself. In contrast, patients with classic Mobitz II block had hypertensive or valvular disease but no evidence of coronary disease or congestive failure; all are alive with pacemakers after 3 years of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of the electrocardiographic response to exercise to geometric and functional findings in aortic regurgitation.

The exercise ECGs of 30 patients with pure aortic regurgitation (AR) were compared with functional and geometric variables measured by echocardiography and radionuclide cineangiography. The 10 patients with positive ECG responses to exercise (greater than or equal to 0.1 mV additional downsloping or horizontal ST segment depression) were similar to the 20 patients with negative tests with respect to mean age, exercise duration, peak work load achieved, symptoms, and resting ECG findings. Patients with positive exercise tests had significantly reduced left ventricular (LV) ejection fractions at rest (44 +/- 4% vs 52 +/- 2%) and during peak exercise (38 +/- 3% vs 48 +/- 2%), lower fractional shortening at rest (27 +/- 1% vs 34 +/- 2%), higher end-systolic wall stress (150 +/- 18 vs 99 +/- 8 dynes/cm2 X 10(3], lower left ventricular relative wall thickness (0.26 +/- 0.01 vs 0.30 +/- 0.01), and greater end-systolic diameter (5.7 +/- 0.3 vs 4.5 +/- 0.2 cm) than patients with negative tests (p less than 0.05 for all comparisons). Among the 18 asymptomatic patients, positive tests were associated with lower resting fractional shortening, lower exercise ejection fraction, higher wall stress, and greater end-systolic diameter. These data demonstrate that a positive exercise ECG in aortic regurgitation identifies patients, even when asymptomatic, who have developed markedly abnormal left ventricular functional and geometric responses to volume load, while a negative exercise ECG identifies a subset of asymptomatic patients who are unlikely to have severe ventricular dysfunction.

A modified treadmill exercise protocol for computer-assisted analysis of the ST segment/heart rate slope: methods and reproducibility.

A new treadmill exercise protocol, modified from the standard Bruce method, was designed to improve ST segment/heart rate slope accuracy and applicability by reducing heart rate increments between exercise stages. In 150 patients exercised according to the new protocol and in 150 patients exercised according to the Bruce protocol, similar exercise tolerance and similar overall heart rate, systolic blood pressure and double product responses to exercise were observed. The mean increment in heart rate between exercise stages of the new protocol was ten beats/minute, which was significantly lower than the 27 beats/minute/stage found with the Bruce protocol. The accuracy of computer-measured ST segment depression was validated by comparison with physician measurement in a separate subgroup of patients with angina pectoris, and serial testing demonstrated stronger interest reproducibility for the ST segment/heart rate slope than for either measured ST segment depression, peak heart rate achieved or duration of exercise.

Evaluation of coronary artery disease by an improved method of exercise electrocardiography: the ST segment/heart rate slope.

Analysis of the rate-related change in exercise-induced ST segment depression, the ST/HR slope, has been shown to significantly improve the accuracy of the exercise ECG for the identification of patients with coronary artery disease and for the recognition of patients with stable angina pectoris who have anatomically or functionally severe coronary artery obstruction. This method, in effect, normalizes the extent of ST segment depression for heart rate, which serves as an index of exercise-induced augmentation of myocardial oxygen demand. While preserving the specificity of the exercise ECG at greater than 90%, an ST/HR slope value of 1.1 microV/bpm as an upper limit of normal improved exercise test sensitivity from 57% to 91% in patients with stable angina who were examined using standard Bruce protocols and three monitoring leads. In addition, an ST/HR slope value of 6.0 microV/bpm was found to partition patients with and without three-vessel coronary artery disease with a sensitivity of 78%, specificity of 97%, positive predictive value of 93%, and overall test accuracy of 90%. No other criteria based on standard ECG interpretation performed as well as the ST/HR slope for the recognition of three-vessel disease in these patients. Further, patients with high ST/HR slopes who did not have three-vessel coronary disease could be shown to have functionally severe two-vessel disease by radionuclide cineangiography. These data suggest that the ST/HR slope can improve the evaluation and management of patients with possible coronary disease. Additional improvement in ST/HR slope accuracy and applicability is likely to result from modification of exercise protocols to reduce heart rate increments between stages, an increase in monitoring leads to include CM5, and computer analysis of the ST segment depression.

Effects of recent and remote infarction on the predictive accuracy of the ST segment/heart rate slope.

The exercise electrocardiographic ST segment/heart rate slope accurately identifies three vessel coronary disease in patients with stable angina, but the method is less accurate in predischarge testing after recent myocardial infarction. To assess the effect of both recent (less than 3 weeks) infarction and remote (greater than 8 weeks) Q wave infarction on the ST segment/heart rate slope, the predictive value of a slope greater than 6.0 microV/beat per min for the identification of three vessel coronary artery disease was evaluated in 113 patients. The 58 patients with stable angina, including 17 with remote Q wave myocardial infarction, were similar to the 55 patients with recent myocardial infarction with respect to age and peak exercise heart rate. In patients with stable angina and no prior Q wave myocardial infarction, an ST segment/heart rate slope greater than 6.0 had a sensitivity of 92% (11 of 12), a specificity of 97% (28 of 29) and a positive predictive value of 92% (11 of 12) for three vessel coronary artery disease. In patients with stable angina and remote Q wave infarction, sensitivity was 83% (5 of 6), specificity was 91% (10 of 11) and positive predictive value was 83% (5 of 6). After recent infarction, test specificity for three vessel disease was preserved at 95% (39 of 41), but test sensitivity was poor (3 of 8). This was confirmed by evaluation of six additional recent patients with infarction and three vessel disease. Among the combined group with recent infarction, test sensitivity for three vessel disease was only 29% (4 of 14), significantly lower than in patients with stable angina (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of the exercise ST/HR slope with anatomic and radionuclide cineangiographic findings in stable angina pectoris.

A rate-related change in ST-segment depression with exercise (ST/HR slope) of 6.0 microV/beat/min or more has been proposed as an accurate predictor of 3-vessel coronary artery disease (CAD). To further assess the accuracy and functional correlates of this method, exercise electrocardiograms were compared with radionuclide rest and exercise left ventricular (LV) ejection fraction (EF) and angiography in 35 patients with stable angina. The ST/HR slope was significantly increased in patients with 3-vessel CAD. An ST/HR slope of 6.0 or more identified 3-vessel CAD with a sensitivity of 89% and specificity of 88%. The predictive value for 3-vessel CAD was 73% owing to the presence of 3 false-positive slopes. The patients from whom these slopes were derived had functionally severe 2-vessel CAD, with an average decrease in exercise LVEF of 13%. Two of these 3 had additional left main CAD and the third has unsuspected additional aortic regurgitation. For the entire group, the exercise ST/HR slope was linearly related to the exercise change in LVEF (r = -0.55, p less than 0.001). Mean exercise change in LVEF for stable angina patients with ST/HR slopes of 4.5 or more was significantly different from that for patients with lower ST/HR slopes (-12 +/- 1% vs + 2 +/- 2%, p less than 0.0001). Thus, the ST/HR slope is both sensitive and specific for the identification of 3-vessel CAD, and high ST/HR slopes in patients with less extensive anatomic disease may predict functionally severe ischemia.

Predictive value and limitations of the ST/HR slope.

To assess the value and predictive limitations of the exercise ST/HR slope, exercise test results were compared in 50 patients with stable angina and in 17 normal subjects with those in two groups known to have a high prevalence of inaccurate electrocardiographic responses to exercise. The last two groups included 51 patients tested within three weeks of acute myocardial infarction and 17 with important aortic regurgitation but no coronary disease. Of the normal subjects, 16 (94%) had ST/HR values less than or equal to 1 X 1 microV/beat/min. Of those with stable angina pectoris, 42 of 46 (91%) patients with coronary artery disease had ST/HR slopes ranging from 1 X 2 to 20 X 0 microV/beat/min, with false negative findings (slopes less than or equal to 1 X 1 microV/beat/min) in only four (9%). In contrast, of those with recent myocardial infarction, 15 of 42 (36%) with coronary disease had false negative slopes, including 12 of 20 (60%) with anterior wall injury. Of those with aortic regurgitation, conversely, 14 of 16 (88%) patients with calculable ST/HR slopes had values greater than 1 X 1 microV/beat/min despite the absence of coronary disease. Despite the accuracy of the test in patients with stable angina, false negative results are common in those after recent myocardial infarction, and false positive results occur often in those with abnormal volume loading due to aortic regurgitation.

Improved accuracy of the exercise electrocardiogram: identification of three-vessel coronary disease in stable angina pectoris by analysis of peak rate-related changes in ST segments.

Exercise electrocardiography has relatively poor specificity and predictive accuracy for 3-vessel coronary artery disease (CAD) when conventional diagnostic criteria are used. However, electrocardiographic evaluation using linear regression analysis of the heart-rate (HR)-related change in ST-segment depression (ST/HR slope) is reported to accurately distinguish patients with from those without CAD, and to accurately separate patients with 1-, 2- and 3-vessel CAD. To assess the applicability of this method and to compare it with conventional interpretation, retrospective evaluation of 50 patients in whom exercise electrocardiography and coronary cineangiography had been performed for suspected CAD was conducted using a modified ST/HR slope analysis limited to leads V5, V6 and aVF. Eighteen patients had 3-vessel, 22 had 2-vessel, 6 had 1-vessel and 4 had no CAD. Standard electrocardiographic criteria (1 mm or more of horizontal or downsloping ST depression) identified 3-vessel CAD with a sensitivity of 78%, specificity of 56% and positive predictive value of only 50%. Peak ST/HR slope criteria (greater than or equal to 6.0 microV/beat/min) identified 3-vessel CAD with a sensitivity of 78%, specificity of 97% and positive predictive value of 93%. The overall test accuracy using measured peak ST/HR slope was 90%, compared with 64% for standard ST-depression criteria. In conclusion, analysis of the peak ST/HR slope can greatly improve the diagnostic accuracy of exercise electrocardiography, and further prospective study of this method is indicated.