David T. Kelly

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.

Localization of coronary artery disease with exercise electrocardiography: correlation with thallium-201 myocardial perfusion scanning☆

In 61 patients with single vessel coronary artery disease (70 percent or greater obstruction of luminal diameter in only one vessel) and no previous myocardial infarction, the sites of ischemic changes on 12 lead exercise electrocardiography and on thallium-201 myocardial perfusion scanning were related to the obstructed coronary artery. The site of exercise-induced S-T segment depression did not identify which coronary artery was obstructed. In the 37 patients with left anterior descending coronary artery disease S-T depression was most often seen in the inferior leads and leads V4 to V6, and in the 18 patients with right coronary artery disease and in the 6 patients with left circumflex artery disease S-T depression was most often seen in leads V5 and V6. Although S-T segment elevation was uncommon in most leads, it occurred in lead V1 or a VL, or both, in 51 percent of the patients with left anterior descending coronary artery disease. A reversible anterior defect on exercise thallium scanning correlated with left anterior descending coronary artery disease (probability [p] less than 0.0001) and a reversible inferior thallium defect correlated with right coronary or left circumflex artery disease (p less than 0.0001). In patients with single vessel disease, the site of S-T segment depression does not identify the obstructed coronary artery; S-T segment elevation in lead V1 or aVL, or both, identifies left anterior descending coronary artery disease; and the site of reversible perfusion defect on thallium scanning identifies the site of myocardial ischemia and the obstructed coronary artery.

Prediction of multivessel coronary artery disease and prognosis early after acute myocardial infarction by exercise electrocardiography and thallium-201 myocardial perfusion scanning.

Exercise electrocardiography and thallium scanning were performed a mean of 24 days after uncomplicated acute myocardial infarction in 103 patients, aged 36 to 60 years, who also underwent coronary angiography. The purpose of the study was to determine the ability of the noninvasive tests to predict multivessel coronary artery disease (CAD) and prognosis. Patients were followed up to document medical complications (incidence 12%: 3 deaths, 1 resuscitated cardiac arrest, 4 recurrent infarctions, 4 admissions with unstable angina) and combined events (medical events or bypass surgery, incidence 23%). The sensitivity, specificity and predictive accuracy for predicting multivessel CAD were 64%, 77% and 64% for a positive exercise electrocardiographic (ECG) response, 64%, 88% and 80% for a remote thallium defect, and 42%, 96% and 88% for a combination of the 2 tests. With 2 tests yielding negative findings the probability of multivessel CAD was 13%. No variable (positive exercise ECG response, remote thallium defect and presence of multivessel CAD) predicted medical events, although there were nonsignificant trends to more events in patients with any of those findings. The relative risk of combined events was 2.5 (p less than 0.05) for a positive exercise ECG response; 1.8 (NS) for a remote thallium defect; 2.6 (p less than 0.05) for multivessel CAD; and 3.1 (p less than 0.025) for both positive ECG response and remote defect. A combination of exercise electrocardiography and thallium scanning early after acute myocardial infarction helps to identify subsets of patients with high and low probabilities of multivessel CAD and combined medical or surgical events.

The QRS scoring system for estimating myocardial infarct size: clinical, angiographic and prognostic correlations.

The relation between a QRS score derived from the routine electrocardiogram and left ventricular function was investigated in 181 patients after myocardial infarction. Patients with left ventricular hypertrophy and conduction defects were excluded. The QRS score correlated closely with the severity of wall motion abnormalities and left ventricular ejection fraction. The more severe the dyssynergy, the higher the QRS score (hypokinesia = 3.0; akinesia = 5.4; dyskinesia = 9.1). The left ventricular ejection fraction (percent) = 66 - (3.3 x QRS score) (correlation coefficient [r] = -0.81, probability [p] less than 0.001). With use of this regression equation, the QRS score predicted angiographic left ventricular ejection fraction to within 12% of the angiographic ejection fraction in 29 of 30 additional patients studied prospectively. The QRS score was also related to clinical functional class. The worse the clinical manifestation of left ventricular dysfunction, the higher the QRS score (Killip class I = 3.5; class II = 6.5; class III = 7.1). A QRS score greater than or equal to 7 had a specificity of 97% and a sensitivity of 59% for predicting an ejection fraction of less than 45%. Patients with a QRS score of 7 or greater had severe wall motion abnormalities, higher peak serum creatine kinase levels, higher prevalence of multivessel coronary disease, poor clinical functional class and an unfavorable outcome. The QRS score provides an inexpensive, clinically useful estimate of left ventricular function after myocardial infarction and can identify patients at high risk.

Verapamil in Stable Effort Angina: Effects on Left Ventricular Function Evaluated With Exercise Radionuclide Ventriculography

A double blind placebo-controlled study was performed in 12 patients with stable angina pectoris to evaluate the effects of oral verapamil (320 mg/day) on left ventricular function, as measured at rest and during exercise with gated equilibrium radionuclide ventriculography. On verapamil, patients had a lower heart rate-blood pressure product at each work load than with placebo. Anginal threshold increased by 28 +/- 19 watts (p less than 0.005), and maximal exercise capacity increased by 20 +/- 14 watts (p less than 0.001) with verapamil, but the rate-pressure product at the onset of angina and at maximal exercise was unchanged. Left ventricular ejection fraction at rest during verapamil therapy was the same as with placebo therapy. On exercise during placebo therapy, the ejection fraction decreased from 40 +/- 9 to 35 +/- 11 percent (p less than 0.025) because end-systolic volume increased disproportionately compared with end-diastolic volume. On exercise during verapamil therapy, the ejection fraction did not decrease (44 +/- 8 versus 45 +/- 12 percent) and was significantly higher at identical work loads than on placebo because of a smaller increase in end-systolic volume. Oral verapamil is effective treatment for effort angina and may prevent the decrease in left ventricular ejection fraction due to exercise-induced ischemia.

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.

Hemodynamic and metabolic basis of impaired exercise tolerance in patients with severe left ventricular dysfunction

Hemodynamic and metabolic changes were measured at rest and during exercise in 23 patients with chronic heart failure and in 6 control subjects. Exercise was limited by leg fatigue in both groups and capacity was 40% lower in the patients with failure. At rest, comparing patients with control subjects, heart rate and right atrial and pulmonary wedge pressure were higher; cardiac output, stroke volume and work indexes and ejection fraction were lower; mean arterial and right atrial pressure and systemic resistance were similar. During all phases of exercise in patients with heart failure, pulmonary wedge pressure and systemic vascular resistance were higher and pulmonary vascular resistance remained markedly elevated compared with values in control subjects. Cardiac output was lower in the patients with failure, but appeared to have the same physiologic distribution in both groups during exercise. Although arterial-femoral venous oxygen content difference was higher in patients with heart failure, this increase did not compensate for the reduced blood flow. Even though the maximal oxygen consumption was significantly reduced, femoral venous lactate and pH values were higher than values in control subjects, but femoral venous pH was similar in both groups at their respective levels of maximal exercise. Ejection fraction was lower in those with heart failure at rest and did not increase with exercise. Ventilation in relation to oxygen consumption was higher in patients with failure than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term follow-up of verapamil and nitrate treatment for coronary artery spasm

Thirty-seven patients with coronary artery spasm and minor coronary atherosclerosis (34) or normal coronary arteries (3) were followed up long-term. All had angina at rest, 32 had nocturnal angina, and 13 had a positive exercise test with S-T elevation. Three had a previous subendocardial infarction; 10 had had serious arrhythmias, which caused syncope in 7. At last review, 21 months (range 1 to 61) after starting therapy, 27 patients continued on verapamil, 314 (120 to 600) mg/day; 4 who did not respond to verapamil were taking nifedipine, 58 (30 to 80) mg/day; and 16 were also taking isosorbide dinitrate, 41 (20 to 80) mg/day. Of the 31 patients on therapy, 21 were asymptomatic, 9 were improved (1 to 4 attacks/month), and 1 had an average of 8 anginal attacks/month; the remaining 6 had stopped therapy and 5 were asymptomatic a mean of 10 (3 to 18) months after stopping. The exercise test became negative in all 12 patients tested on therapy, although 3 required nitrates in addition to verapamil or nifedipine. In 26 supervised treatment withdrawals in the hospital, a mean of 15 (1 to 55) months on therapy, 10 developed angina in less than 48 hours. Angina recurred in all 6 unsupervised, patient-initiated withdrawals. Failure to stop smoking was positively associated with recurrence of angina on treatment withdrawal (p less than 0.02). Long-term treatment of coronary artery spasm with verapamil or nifedipine together with isosorbide dinitrate was well tolerated and effectively relieved angina. No documented serious arrhythmias, syncopal episodes, myocardial infarction, or death occurred during follow-up.

Prognosis after an initial non-Q-wave myocardial infarction related to coronary arterial anatomy☆

Eighty-six consecutive hospital survivors (aged less than or equal to 60 years) of a first non-Q-wave acute myocardial infarction (MI) were followed up prospectively. Coronary arteriography was performed a median of 2 weeks after MI. The size of the MI was small (as judged by a mean peak creatine kinase level of 906 IU/liter); 90% were in Killip class I, and the mean left ventricular ejection fraction was 60 +/- 11% (+/- standard deviation). Forty-nine patients had 1 vessel significantly narrowed by disease (greater than or equal to 70% luminal diameter reduction), 19 had 2-vessel, 2 had 3-vessel, 3 had left main (greater than or equal to 50% luminal diameter reduction), and 13 minimal or no coronary artery disease (CAD). Complete occlusion of the MI-related vessel was present in 33 patients. All 33 and an additional 5 patients had collateral vessels to the MI area. During a mean follow-up of 25 months, 1 cardiac death and 4 recurrent infarcts (3 with non-Q-wave MI) occurred. Angina occurred in 53 patients (62%) and responded medically in all but 7 who underwent coronary artery surgery. Angina after MI occurred frequently in patients with severe proximal left anterior descending CAD (greater than or equal to 90%), and in those with CAD (greater than or equal to 50%) in a vessel supplying collaterals to the infarct area. Because angina can be managed medically in most patients and the outcome is good, routine coronary angiography is not indicated in asymptomatic survivors less than or equal to 60 years of a first non-Q-wave MI.

Influence of heart rate and atrial transport on left ventricular volume and function: relation to hemodynamic changes produced by supraventricular arrhythmia.

The response of the left ventricle to pacing-induced changes in heart rate and the atrioventricular (A-V) relation was examined with equilibrium gated radionuclide ventriculography in 20 patients who had normal ventricular function after surgery for recurrent supraventricular tachycardia. In 10 patients count-derived left ventricular ejection fraction, end-diastolic volume and stroke volume were measured during sinus rhythm and during atrial pacing at 120, 140 and 160 beats/min. In the other 10 patients similar determinations were made during sequential A-V and simultaneous ventricular and atrial (V/A) pacing, both at rates of 100 and 160 beats/min. Left ventricular ejection fraction did not change significantly with atrial pacing (from 0.65 +/- 0.02 [mean +/- standard error of the mean] at a baseline sinus rate of 91 +/- 3 beats/min to 0.62 +/- 0.03 at 160 beats/min) despite a progressive decrease in end-diastolic volume. The percent reduction in end-diastolic volume (% delta EDV) and stroke volume (+ delta SV) from the baseline values was linear and related to change in heart rate (delta HR) as % delta EDV = -0.60 delta HR + 5.19 (r = 0.71; p less than 0.01) and % delta SV = -0.62 delta HR + 5.03 (r = 0.76; p less than 0.001). Left ventricular ejection fraction with baseline sequential A-V pacing at 100 beats/min was 0.67 +/- 0.03 and not significantly altered by either sequential A-V or simultaneous V/A pacing at 160 beats/min. At 100 beats/min, loss of atrial transport with simultaneous V/A pacing resulted in a small reduction in end-diastolic volume from a baseline value of -9.0 +/- 1.9 percent (p less than 0.01) and a nonsignificant reduction in stroke volume of -3.7 +/- 1.6 percent. During simultaneous V/A pacing at 160 beats/min, the reduction in end-diastolic and stroke volumes from the baseline value was -26.6 +/- 3.8 percent and -28.8 +/- 4.3 percent, respectively (both p less than 0.01), but was significantly smaller (-16.1 +/- 3.6 percent and -19.2 +/- 4.1 percent, respectively [p less than 0.05]) when atrial transport was maintained during sequential A-V pacing at the same heart rate. During simultaneous V/A pacing at 160 beats/min, two thirds of the reduction in end-diastolic and stroke volumes from the baseline value was due to the increment in heart rate as assessed from sequential A-V pacing and the other third was due to loss of atrial transport. The data indicate that the hemodynamic consequences of supraventricular tachyarrhythmias in patients with normal ventricular function are due primarily to decreases in ventricular volume as heart rate is increased and atrial contribution is lost rather than to any changes in left ventricular ejection fraction.