Efficacy of cardioselective beta adrenergic blockade with intravenously administered tolamolol in the treatment of cardiac arrhythmias.

The efficacy of tolamolol, a cardioselective beta adrenergic blocking agent, was evaluated in the treatment of cardiac arrhythmias in 27 patients. Nineteen patients had supraventricular arrhythmias and eight had ventricular arrhythmias. Evaluation was by doulbe-blind randomized trial in 23 patients. Tolamolol was effective in reducing ventricular rate in 17 (85 percent) of 19 patients with supraventricular arrhythmias and resulted in conversion to sinus rhythm in 2 of the 17. The mean ventricular rate in 17 patients decreased from 135 to 102/min 10 minutes after initiation of administration of tolamolol and gradually decreased further to 93/min after 60 minutes. Reduction in ventricular rate was sustained for 2 hours of monitoring undergone by all patients and for 4 and 6 hours monitoring in two subgroups. Among the eight patients with ventricular ectopic beats, tolamolol reduced their frequency in four patients and had no effect in four. Six patients had chronic obstructive pulmonary disease and experienced no adverse clinical effects on respiratory function in association with administration to tolamolol. Untoward effects occurred in 10 patients, including hypotension in 3, 1 of whom required vasopressor therapy. Other side effects were sedation, nausea, dyspnea and warmth in the chest, all of which were mild and transient, requiring no treatment. Cardioselective beta adrenergic blockade with tolamolol was highly effective in controlling ventricular rate in supraventricular arrhythmias and reduced the frequency of ventricular ectopic beats in half of the small group of patients with this arrhythmia. It is particularly applicable in patients with obstructive pulmonary disease in whom cardiac beta adrenergic blockade is indicated. Hypotension is an important potential side effect.     

Effects of digitalis on sinus nodal function in patients with sick sinus syndrome

The effect on sinus rhythmicity and automaticity of complete digitalization in a 24 hour period was observed in 14 patients with sick sinus syndrome. Sinus nodal function was evaluated in these patients by assessing sinus nodal recovery time and by treadmill exercise testing and 24 hour Holter monitoring, before and after digoxin administration. Corrected sinus nodal recovery times ranged from 240 to 2,065 msec (average 714) before digoxin and were shortened to 250 to 1,260 msec (average 565) after the glycoside. Further, digoxin induced accelerated infra sinus escape pacemaker activity in five patients: junctional and ventricular in one and atrial in four. Spontaneous sinus rate evaluated with Holter monitoring revealed an average of 56 beats/min (range 43 to 69) before digitalis that was unchanged (average 58 beats/min; range 48 to 74) after digoxin therapy. Similarly, the sinus nodal response to exercise was unaffected after digitalization (average 118 beats/min both before and during digitalis therapy). It is concluded that digoxin does not exert adverse effects on sinus nodal function in patients with sick sinus syndrome. The glycoside can be used safely in these patients when indicated for cardiac pump dysfunction or for control of tachyarrhythmia.     

Cardiocirculatory effects of afterload reduction with oral trimazosin in severe chronic congestive heart failure.

Because improved long-term oral vasodilator therapy for chronic congestive heart failure is needed, the cardiocirculatory effects of the new antihypertensive quinazoline derivative, trimazosin, were evaluated with use of concomitant cardiac catheterization and forearm plethysmography in nine patients with severe chronic congestive heart failure due to coronary disease. After ingestion of 100 to 300 mg (average 172 mg) of trimazosin, the greatly elevated left ventricular filling pressure decreased from 30 to 23 mm Hg and the lowered cardiac index rose from 2.02 to 2.59 liters/min per m2. Considerable improvement in cardiac function occurred within 1 hour after ingestion of trimazosin; peak efficacy was achieved after 2 hours and persisted in the 3rd hour. Heart rate was unchanged and systemic blood pressure was mildly reduced. Because pump performance was enhanced while indexes of myocardial oxygen consumption declined, ventricular efficiency increased. Vascular relaxation was produced in both the systemic resistance and capacitance beds, with venodilation slightly more prominent. This clinical investigation of the acute hemodynamic effects of trimazosin objectively demonstrates that the drug provides considerable hemodynamic benefit in cardiac dysfunction and is therefore a potentially salutary agent for treatment of patients with chronic severe congestive heart failure.     

Comparison of hemodynamic actions of pirbuterol and dobutamine on cardiac function in severe congestive heart failure

There is considerable interest in the development of beneficial oral inotropic agents for sustained ambulatory management of patients with severe chronic congestive heart failure. Therefore, the hemodynamic actions of the oral beta adrenergic receptor agonist pirbuterol and of intravenous dobutamine were compared in nine patients with severe heart failure. Both agents produced similar effects on ventricular pump function: The cardiac index was markedly increased from 1.8 to 2.6 liters/min per m² (p < 0.005) by dobutamine and from 1.8 to 2.9 liters/min per m² (p < 0.001) by pirbuterol; stroke index was increased from 24 to 32 ml/beat per m² (p < 0.02) by dobutamine and from 23 to 35 ml/beat per m² (p < 0.001) by pirbuterol; the stroke work index was increased from 19 to 27 g-m/m² (p < 0.005) by dobutamine and from 20 to 28 g-m/m² (p < 0.005) by pirbuterol. However, although dobutamine did not change mean blood pressure or left ventricular filling pressure (p < 0.05), pirbuterol modestly decreased mean blood pressure from 83 to 75 mm Hg (p < 0.02) and moderately decreased left ventricular filling pressure from 23 to 18 mm Hg (p < 0.005). Dobutamine reduced total systemic vascular resistance 22 percent from 2,049 to 1,582 dynes s cm^?5 (p < 0.001), whereas pirbuterol reduced this index 42 percent (p < 0.05 versus dobutamine) from 2,068 to 1,150 dynes s cm^?5. Neither agent altered heart rate or the heart rate-systolic blood pressure product (p < 0.05).Thus, oral pirbuterol has dobutamine-like beneficial hemodynamic effects on left ventricular pump function but causes a greater decrease in total systemic vascular resistance consistent with the combined inotropic and peripheral vasodilator actions of this oral beta adrenergic receptor agonist. These salutary hemodynamic responses suggest that oral pirbuterol may be useful for the prolonged treatment of severe chronic congestive heart failure.     

Apparent reduction of aortic and left heart chamber size in atrial septal defect

Although it is widely held that the size of the aorta and left atrium is diminished in patients with atrial septal defect, few data are available to support this contention. Therefore, aortic and left heart chamber dimensions in 24 patients with documentation of an atrial septal defect at cardiac catheterization were compared with those of 22 normal persons. The data were obtained using echocardiography, cineangiography and qualitative estimation of aortic size from chest X-ray films. Aortic size was similar in the patients with an atrial septal defect and normal subjects (1.7 cm/m² for both groups on angiography). Although the aortic diameter was estimated to be small in 12 of the 24 patients with an atrial defect on chest X-ray films, no difference existed in aortic measurements on echocardiography or angiography in patients judged to have normal as opposed to those judged to have reduced aortic size. Although the left atrial echographic dimension tended to be slightly greater in the patient group than in normal subjects (2.2 versus 1.9 cm/m²), this difference was not statistically significant. The echographic ratio of left atrial to aortic size was greater in the patient group (1.3 versus 1.1) (P < 0.02). Stroke index was similar in the two groups (37.5 versus 42.8 ml/m² with the dye-dilution technique and 35.1 versus 36.3 ml/m² on angiography). Although echocardiographic left ventricular diastolic dimension was slightly smaller in the patient group than in normal subjects (2.5 versus 3.0 cm/m²) (P < 0.02), diastolic volume index on angiography was similar in the two groups (50.1 versus 52.9 ml/m²). Thus, these data do not support the conventional belief that, because of a reduced stroke volume, the size of the aorta and left atrium is diminished in patients with an atrial septal defect.     

Disturbances of cardiac rhythm and conduction induced by exercise. Diagnostic, prognostic and therapeutic implications

Alterations of cardiac rhythm and conduction occur frequently during exercise stress testing and may provide significant information regarding cardiovascular status. Exertion may induce arrhythmias as a result of sympathetically enhanced phase 4 depolarization of ectopic foci or the induction of myocardial ischemia secondary to increased myocardial oxygen demand. Exercise may abolish arrhythmias present in the resting state, an effect attributed to overdrive suppression and inhibition related to sinus tachycardia. Although a wide spectrum of electro-physiologic changes may be elicited by stress testing, ventricular dysrhythmias are of primary importance. Premature ventricular contractions that are frequent, multifocal, repetitive or associated with light work loads have been particularly indicative of coronary artery disease. Exertional ventricular irritability has been observed more frequently in patients with coronary atherosclerosis involving two or more coronary vessels and accompanied by abnormalities of left ventricular wall motion. Exercise testing may have advantages over portable monitoring in the detection of ventricular arrhythmias. The mere presence of ventricular ectopic beats at rest does not preclude carefully performed graduated stress testing nor does their disappearance during effort exclude the presence of coronary artery disease.     

Echocardiography in aortic root dissection and dilatation.

Six patients with aortic root dissection proved by angiography, surgery or autopsy, and six patients with aortic root dilatation were studied by echocardiography. Echocardiography was diagnostic in five or six patients with dissection and suggestive in the sixth, disclosing anterior and posterior dissection in three, anterior dissection in one and posterior dissection in one. The recording of a double echo in the aorta was the diagnostic feature. Angiography was diagnostic in four of the six patients, yielded a false negative result in one and was not performed in one. Six patients with dilatation had an enlarged aortic root by echocardiography. Left ventricular size, stroke volume, ejection fraction, aortic regurgitant flow and velocity of circumferential fiber shortening were calculated in 11 patients. Echocardiography was extremely helpful in the diagnosis, management and follow-up in patients with aortic dissection or dilatation.     

Improved longevity due to reduction of sudden death by aortocoronary bypass in coronary atherosclerosis: Prospective evaluation of medical versus surgical therapy in matched patients with multivessel disease

To evaluate the efficacy of coronary bypass surgery in reduction of sudden death, the prognosis of 286 similar patients with multivessel coronary stenosis was studied prospectively and the results of medical therapy (Group I, 114 patients) were compared with those of surgical therapy (Group II, 172 patients) after cardiac catheterization and coronary arteriography. During 39 months' evaluation of both groups, mortality from congestive heart failure and noncardiac causes did not differ (Group I, 14 percent; Group II, 8 percent) (P greater than 0.05). Sudden was evaluated in the remaining 217 patients (Group I, 96; Group II, 121 patients) who were matched for age (Group I, 52 years; Group II, 51 years); duration of overt coronary disease (Group I, 3.8 years; Group II, 4.0 years); angina pectoris (Group I, 83 percent; Group II, 95 percent); prior myocardial infarction (Group I, 77 percent; Group II, 74 percent); and congestive heart failure (Group I, 30 percent; Group II, 23 percent) (all P greater than 0.05). In addition, the prevalence of coronary risk factors was the same (P greater than 0.05) in both groups (hypertension, cigarette smoking, diabetes mellitus, lipid abnormalities and family history of coronary disease). Importantly, arteriography and catheterization established a similar extent and location of major coronary arterial stenoses and of ventricular dysfunction; two vessel disease (Group I, 32 percent; Group II, 33 percent) and three vessel disease (Group I, 68 percent; Group II, 67 percent); left ventricular end-diastolic pressure (Group I, 13; Group II, 14 mm Hg);cardiac index (Group I, 2.85; Group II, 2.91 liters/min per m2); and coronary collateral vessels (Group I, 58 percent; Group II, 61 percent) (all P greater than 0.05). Fifty-six percent of patients in Group II had multiple bypass grafts and a late patency rate (average 21 months) of 87 percent of one or more grafts. During subsequent prospective evaluation of over 3 years, bypass surgery provided greater symptomatic benefit of improved functional capacity (Group I, 12 percent; Group II, 69 percent) (P less than 0.05) and complete anginal relief (Group I, 30 percent; Group II, 60 percent) (P less than 0.05). Moreover, bypass surgery was associated with marked reduction in sudden death (Group I, 24 percent; Group II, 6 percent) (P less than 0.05). Thus, in patients with multivessel coronary disease carefully matched for clinical factors, hemodynamics, atherogenic precursors and coronary pathoanatomy, effective aortocoronary bypass surgery appeared to prolong survival by decreasing the incidence of sudden death, possibly by a decrease of unexpected fatal arrhythmias.     

New approach to interpretation of technetium-99m pyrophosphate scintigraphy in detection of acute myocardial infarction: clinical assessment of diagnostic accuracy.

A modified classification for interpreting technetium-99m pyrophosphate scintigrams defines the 2+ diffuse pattern of tracer uptake as equlvocal rather than positive for acute myocardial infarction. Results of scintigraphy using this classification were compared with results of standard diagnostic tests for myocardial infarction in 235 patients admitted to a coronary care unit with acute chest pain. Of 81 patients with acute transmural infarction by standard clinical, electrocardiographic and serum enzyme criteria, 76 had a positive, 5 an equivocal and none a negative scintigram. Of 18 with acute nontransmural infarction by standard criteria, 7 had a positive, 9 an equivocal and 2 a negative scintigram. This it was uncommon for a patient with acute myocardial infarction, transmural or nontransmural, to have a definitely negative technetium-99m pyrophosphate study. Ten patients had equivocal evidence of infarction by standard criteria. Of the remaining 126 patients with no evidence of acute myocardial infarction by standard criteria, 87 had a negative, 35 an equivocal and 4 a definitely positive scintigram. Thus the definitely positive scintigraphic pattern was relatively highly specific for acute myocardial infarction. If the 2+ pattern had been considered positive, the specificity of the technique would have been greatly decreased. Computer processing strengthened observer certainty of the visual impression but changed the scintigraphic evaluation in only eight cases. Thus, use of an equivocal pattern renders technetium-99m pyrophosphate imaging both an extremely sensitive and specific method for detecting acute myocardial infarction.     

Atrial induction of ventricular tachycardia: reentry versus triggered automaticity.

Atrial stimulation induced a sustained ventricular tachycardia in two patients with mitral valve prolapse and in one patient who had mild hypertension without cardiac abnormalities. Exercise-induced sinus tachycardia also started the ventricular tachycardia in one patient. Evidence is presented to suggest that the mechanism of ventricular tachycardia in one patient was reentrant excitation and in another patient triggered automaticity. It is likely that the origin of the ventricular tachycardia was confined to a relatively protected small area near the posteroinferior portion of the left ventricle and was not due to macroreentry.     

Efficacy of Disopyramide Phosphate in the Treatment of Refractory Ventricular Tachycardia

The effects of intravenously administered disopyramide phosphate were evaluated in seven patients with refractory ventricular tachycardia. All patients had organic heart disease, including acute infarction (three patients), chronic coronary artery disease (two patients) and cardiomyopathy (two patients). The severity of the heart disease was reflected in the advanced patient age (average 64 years) and the occurrence before disopyramide therapy of cardiac arrest in five patients and congestive heart failure in all seven patients. In five patients, disopyramide was given as a bolus injection, 2 mg/kg body weight, followed by an infusion of 20 to 40 mg/hour. The final two patients received 4 mg/kg divided as a bolus injection and an infusion over 1 hour followed by a 0.4 mg/kg infusion during the next hour. Intravenous administration of disopyramide resulted in more effective electrical stability in all patients and completely eliminated ventricular tachycardia in six. Recurrence of ventricular tachycardia was prevented in six patients with subsequent long-term oral administration of disopyramide. Possible dose-related cardiac pump depression occurred in two patients, but disopyramide was otherwise well tolerated. Therefore, these data document the therapeutic efficacy of disopyramide in the treatment of refractory life-threatening ventricular tachyarrhythmias.     

Reduction of S-T segment elevation with infusion of nitroprusside in patients with acute myocardial infarction

The effect of infusion of sodium nitroprusside on S-T segment elevation was evaluated in 12 patlents with acute anterior myocardial infarction. Precordial 35 lead S-T segment maps were obtained in each patient immediately before and 10 minutes after infusion of 53 μ/min (range 20 to 100 μg/min) of nitroprusside. The following measurements were made from each S-T map: ∑ST (total S-T elevation in all leads), NST (number of leads with S-T elevation greater than 1 mm) and $\text{ST}$ (average S-T elevation in leads with more than 1 mm elevation). After administration of nitroprusside, evidence of myocardial ischemic injury as assessed by S-T mapping decreased in association with reduction of the myocardial oxygen consumption index of pressure-time per minute. Group mean values diminished significantly for ∑ST (41.7 to 28.6 mm, P <0.001), NST (20.3 to 14.6, P <0.001) and $\text{ST}$ (1.6 to 1.2 mm, P <0.005). Pressure-time per minute decreased from 2,690 to 2,372 mm Hg-sec/min (P <0.001). Because there was no significant relation (P >0.05) between reductions in S-T elevation and lower indexes of myocardial oxygen consumption, it is suggested that nitroprusside may possess a separate action of augmenting regional blood flow to ischemic myocardium. Evaluation with the precordial S-T mapping technique suggested that intravenous administration of nitroprusside was associated with evidence of reduced ventricular ischemic injury in patients with acute myocardial infarction. This effect appears to be related to reduction of myocardial oxygen demand by the peripheral cardiac unloading mechanisms of nitroprusside as well as to a possible direct action of the drug in improving regional blood flow to ischemic heart muscle.