Stuart F. Seides

Sensitivity, specificity and predictive accuracy of radionuclide cineangiography during exercise in patients with coronary artery disease. Comparison with exercise electrocardiography.

Noninvasive radionuclide cineangiography permits the assessment of global and regional left ventricular function during intense exercise. To assess the sensitivity of the technique in detecting coronary artery disease, we studied 63 consecutive patients with ≥ 50% stenosis of at least one coronary artery. Fiftynine (94%) had regional dysfunction with exercise; 56 (89%) developed lower-than-normal ejection fractions during exercise. When both regional dysfunction and subnormal ejection fractions are considered together, the sensitivity was 95%. Each patient also underwent exercise electrocardiography to either angina or 85% of predicted maximal heart rate. Of the 42 patients who developed angina during exercise electrocardiography, 26 (62%) developed ≥1 mm ST-segment depression; four additional patients (10%) had Q waves diagnostic of previous myocardial infarction. In contrast, 39 (93%, p < 0.001) developed regional dysfunction during radionuclide study, and one additional patient developed a subnormal ejection fraction without regional dysfunction. To assess specificity, we studied 21 consecutive patients with chest pain who had normal coronary arteries. None developed regional dysfunction; ejection fraction increased in all to levels within the range previously defined as normal. The predictive accuracy in this symptomatic population was 100%. We conclude that radionuclide cineangiography is highly sensitive (more so than exercise electrocardiography), predictive and specific in detecting patients with coronary artery disease.

Prevalence of arrhythmias during 24-hour electrocardiographic monitoring and exercise testing in patients with obstructive and nonobstructive hypertrophic cardiomyopathy.

Many patients with hypertrophic cardiomyopathy die suddenly and unexpectedly, a significant number perhaps due to arrhythmia. Of 100 patients initially evaluated for signs or symptoms suggestive of heart disease or a family history of hypertrophic cardiomyopathy, 51 were selected solely because they met the echocardiographic criteria for the disease, and 49 patients were selected primarily because they had: 1) normal sinus rhythm despite left atrial enlargement, 2) a history of syncope, 3) a family history of premature death, or 4) a history of paroxysmal atrial fibrillation. All 100 patients were studied by 24-hour ambulatory electrocardiographic monitoring and 74 of them also underwent treadmill exercise testing. More than 50% of patients in repetitive ventricular premature depolarizations, including 19% who had ventricular tachycardia. Monitoring was superior to exercise testing for exposing these arrhythmias. Two patients experienced cardiac arrest within 2 months of monitoring; in each, monitoring had revealed ventricular tachycardia. Two patients with paroxysms of supraventricular tachycardia during monitoring developed fixed atrial fibrillation within 1 year. These preliminary observations suggest that monitoring may help identify patients at increased risk for significant arrhythmic events.

Verapamil therapy: a new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. I. Hemodynamic effects.

The hemodynamic effects of intravenous verapamil administration were examined in 27 patients with hypertrophic cardiomyopathy. Increasing doses of verapamil produced small increases in heart rate and cardiac output and a significant decrease in systolic blood pressure, but had no significance effect on mean pulmonary artery wedge pressure or left ventricular end-diastolic pressure. The highest dose of verapamil increased heart rate from 72 +/- 3 to 81 +/- 6 beats/min and reduced systolic blood pressure from 118 +/- 8 to 99 +/- 5 mm Hg (p less than 0.005). This dose decreased the basal left ventricular outflow tract gradient from 94 +/- 14 to 49 +/- 14 mm Hg and the average left ventricular outflow tract gradient during the Valsalva maneuver from 76 +/- 5 to 63 +/- 13 mm Hg, during amyl nitrite inhalation from 69 +/- 15 to 39 +/- 13 mm Hg, and during isoproterenol infusion from 108 +/- 29 to 70 +/- 21 mm Hg (p less than 0.01). These results indicate that verapamil can significantly decrease left ventricular outflow obstruction in patients with hypertrophic cardiomyopathy and thus may provide an important new therapeutic agent in the treatment of this disorder.

Electrocardiographic findings in patients with obstructive and nonobstructive hypertrophic cardiomyopathy.

SUMMARY One hundred and thirty-four patients with hypertrophic cardiomyopathy were evaluated by standard 12-lead electrocardiography. Normal electrocardiograms were extremely uncommon, occurring in less than 7% of each subgroup of patients (i.e., those with or without either symptoms or obstruction to left ventricular outflow), with the exception of those who were both asymptomatic and had no left ventricular outflow obstruction. Even in this subgroup, however, normal electrocardiograms occurred in only 27% of patients. Repolarization abnormalities and left ventricular hypertrophy were the most common abnormalities, occurring in 81% and 62%, respectively, of the total population. A broad spectrum of other electrocardiographic abnormalities was found, but none was unique to hypertrophic cardiomyopathy. Patients with vs those without electrocardiographic left ventricular hypertrophy or left atrial abnormality had significantly (P < 0.005) greater mean ventricular septal thickness (22 ± 0.6 vs 19 ± 0.6 mm) and left atrial dimension (48 ± I vs 40 ± I mm) measured by echocardiography, and significantly (P < 0.01) higher mean pulmonary capillary wedge pressure (16 ± I is 10 ± I mm Hg) and left ventricular end-diastolic pressure (20 ± I vs 15 ± I mm Hg). The high prevalence and diverse nature of electrocardiographic abnormalities suggest that any patient with an unusual and unexplained electrocardiogram should be suspected of having hypertrophic cardiomyopathy even if the physical examination is normal, as is often the case in patients without obstruction.

The electrophysiology of propranolol in man

Abstract The effects of intravenous propranolol (0.1 mg. per kilogram) on the electrophysiologic properties of the A-V conducting system were studied in 16 patients using His-bundle electrograms and the extrastimulus method. The drug was infused at a rate of 1 mg. per minute without significant side effects. Sinus cycle length was slowed in 15 out of 16 patients (average, 128 msec.). AVN conduction time was increased in 13 out of 16 patients (average, 10 msec.) during sinus rhythm and in all patients during atrial pacing. AVN Wenckebach block occurred at slower paced rates in 14 patients. Corrected QT interval was shortened in 9 out of 16 patients (average, 24 msec.). The functional and effective refractory periods (ERP) of the AVN were prolonged in 14 out of 14 patients (average, 29 msec.) and 9 out of 9 patients (average, 24 msec.), respectively. No significant changes were seen in His-Purkinje system (HPS) conduction time, ERP of the atrium, relative refractory period or ERP of the HPS, or ERP of the ventricle in all patients in whom these variables could be muasured. Mean end-study blood level was 13.6 ng. per milliliter. Effects on the AVN explain the efficacy of propranolol in (1) controlling the ventricular rate in atrial fibrillation and flutter and (2) the treatment and prophylaxis of re-entrant supraventricular tachycardias. Its lack of effects on the HPS make its use relatively safe in patients with infra-His conduction disturbances.

Long-Term Anatomic Fate of Coronary-Artery Bypass Grafts and Functional Status of Patients Five Years after Operation

To assess long-term results, coronary and graft angiography was performed 53 to 84 months after operation in 22 of 30 consecutive patients who had undergone coronary-artery bypass grafting before 1973, and who had at least one graft patent at an early (three to nine months) postoperative study. Of the 33 grafts, 31 were patent at late study. All patients had severe symptoms before operation. Of 16 who became asymptomatic early after operation, angina pectoris later redeveloped in 11. Progression of disease in ungrafted vessels accounted for symptomatic deterioration in nine of these 11 patients. We conclude that most grafts patent several months after operation remain so for at least 4 1/2 years, and that although most patients improve symptomatically after operation, symptomatic deterioration is common in the succeeding years and is most often due to progression of disease in ungrafted vessels.

Effect of Atrial Stimulation Site on the Electrophysiological Properties of the Atrioventricular Node in Man

The electrophysiological properties of the atrioventricular conduction system were compared in 16 patients using stimulation of the high right atrium (HRA) and a site within the coronary sinus (CS). The site of atrial stimulation significantly altered A-V nodal conduction time and refractoriness in eight patients (Group A) and did not change A-V nodal properties in the remaining patients. His-Purkinje conduction time and refractoriness were not affected by changing the atrial stimulation site. The atrial stimulation site may influence A-V nodal function by changing the site and/or mode of entry of the impulse into the A-V node.

The electrophysiological effects of intramuscular quinidine on the atrioventricular conducting system in man

Abstract The electrophysiological effects of intramuscular quinidine were evaluated using His bundle electrograms and the extrastimulus method. The mean mid-study plasma quinidine level was 4.6 mg. per liter. Our results show that quinidine tends to shorten A-V nodal conduction time while it routinely prolongs His-Purkinje and intraventricular conduction time. The refractory periods of the atrium and His-Purkinje system were prolonged by quinidine while the effective refractory period of the A-V node was consistently shortened. Those patients with evidence of infra-His conduction disturbances manifested no difference in their response to quinidine from the group as a whole. These studies suggest quinidine has antivagal properties which are of clinical significance. In addition, the effects of quinidine on His-Purkinje conduction and refractoriness may lead to the ventricular tachyarrhythmias implicated in “quinidine syncope” by a re-entrant mechanism.

Sinus node re-entrant tachycardia in man

Sinus node re-entry (SNR) usually appears as a single beat. Tachycardias (SNRT) consistent with sustained SNR were seen in six patients and were initiated by premature stimulation of the high right atrium (six patients) and coronary sinus (four patients), and after continuous pacing from the high right atrium (four patients) or right ventricle (one patient) at rates of 130 to 200 per minute. During SNRT: (1) atrial beats exhibited a high-to-low atrial activation sequence, (2) the P-waves were similar in morphology to P-waves during sinus rhythm, and (3) re-entry in the A-V node or at the site of stimulation could be excluded. The cycle length of SNRT ranged from 625 to 320 msec. and SNRT either terminated spontaneously (six patients) or after premature atrial capture and/or vagal maneuvers (two patients). The electrophysiologic characteristics of SNRT and differentiation of SNRT from A-V nodal re-entry are discussed.

Effect of septal myotomy and myectomy on left ventricular systolic function at rest and during exercise in patients with IHSS.

SUMMARY Patients with idiopathic hypertrophic subaortic stenosis (IHSS) have supernormal left ventricular systolic function at rest. Septal myotomy/myectomy reduces outflow obstruction and symptoms. However, it has been proposed that operation causes myocardial damage, with consequent reduction in left ventricular function and potentially deleterious long-term consequences, despite relief of symptoms. To evaluate the effect of myotomy and myectomy on left ventricular function, we employed noninvasive radionuclide cineangiography at rest and during maximal exercise in 21 consecutive patients with IHSS, before and 6 months after operation. In 30 normal subjects, the ejection fraction (EF) was 57 ± 2% at rest and 71 ± 2% during exercise. Before operation in patients with IHSS, the EF was supernormal at rest (76 ± 2%, p < 0.001), and normal during exercise (71 ± 3%, NS). All patients improved from NYHA functional class III-IV preoperatively to class I-II postoperatively; the maximal provocable gradient invariably diminished (average, 100 ± 8 mm Hg preop, 33 ± 9 mm Hg postop, p < 0.001). Postoperatively, the EF at rest was 67 ± 2%, still supernormal, but less than that noted preoperatively (p < 0.001). During exercise, the EF was 66 ± 4%, only mildly diminished (p < 0.01) from that preoperatively. We conclude that muscle resection during myotomy and myectomy usually does not cause any important impairment of global left ventricular function at rest or during exercise stress.