Conduction of the sino-atrial impulse from the high right atrium to the ventricles was studied by intracardiac electrography in 21 unoperated patients, age 3 months to 11 years, with endocardial cushion defects (ECD). The high right atrium-to-low right atrium conduction time was prolonged in 15 of 18 subjects (mean 57 +/- 20 msec). The low right atrium-to-His bundle conduction time (LRA-H) was normal in 16 of 17 subjects (mean 82 +/- 30 msec), prolonged in one. The His-to-ventricle conduction time (H-V) was normal in 16 of 17 subjects (mean 37 +/- 8 msec), equivocally short in one. Nine patients with ECD, age 3 to 21 years, were studied postoperatively. One had an acquired complete atrioventricular block in the His bundle. Two had prolonged LRA-H and two prolonged LRA-H and two prolonged H-V. The surface ECG failed to identify accurately either prolonged atrioventricular conduction or the site of prolongation.

Echocardiograms of 52 patients with the Wolff-Parkinson-White (WPW) syndrome were investigated. Abnormal patterns of motion were observed in the left ventricular posterior wall (LVPW) and the interventricular septum (IVS). The abnormal LVPW motion was presumably specific for the syndrome and included early onset of the anterior motion which preceded the first heart sound (S1) and a premature peak formation of the anterior displacement which occurred before the second heart sound. The latter was usually followed by a second lower peak. These findings seem to suggest that both contraction and relaxation of LVPW begin earlier than normal due to ventricular pre-excitation initiated at or near the LVPW. The IVS abnormality characteristic of the syndrome was a posterior protrusion, the onset of which preceded S1. Subsequent motion of IVS was either paradoxical or hypokinetic during ejection. These IVS abnormalities were quite similar to those observed in left bundle branch block. The abnormal LVPW motion was observed in all 20 Type A patients and 10 of the 32 Type B patients. The abnormal IVS motion was observed in 10 Type B patients. We feel that echocardiography could be used as an auxiliary noninvasive means of locating the pre-excitation site in patients with WPW.

A comparison of electrocardiographic manifestations of left atrial enlargement (LAE) and left atrial size by echocardiography was made in 307 patients in sinus rhythm. Electrocardiographic criteria used were L:P wave duration in lead II equal to or greater than 0.12 sec; Va: the ratio of the duration of negative terminal P in V1 to the P-R segment equal to or greater than 1.0; Vb: a negative P terminal force in V1 less than -0.03 mm sec. The echocardiographic diagnosis of left atrial enlargement was based on 1) transverse dimension greater than 4.0 cm; or 2) a ratio of transverse atrial to transverse aortic root dimension greater than 1.17. In the presence of left atrial enlargement, a combination of criteria occurred more often than a single criterion. The overall predictive index of the electrocardiogram for left atrial enlargement was 63% (excluding criterion Vb raised probability to 80%); and that for absence of left atrial enlargement was 78%. The index of coarse versus fine fibrillary waves was unreliable in predicting left atrial enlargement. Changes in P wave morphology may be used as a reasonably specific but less sensitive indicator of left atrial enlargement.

The relative benefits and risks of reserpine and guanethidine were compared in patients with thiazide-treated mild to moderate hypertension (diastolic pressure 95-115 mm Hg). Forty-nine ambulant patients )30 men, 19 women) were treated throughout the study with hydrochlorothiazide, 50 mg/day. In this double blind crossover study each drug was added in graded increments until a predetermined therapeutic response was obtained, blood pressure measurements and side effect scores were evaluated biweekly. Major conclusions of the study were: 1) guanethidine, as well as reserpine, will reduce mild to moderate blood pressures to normal; 2) in most cases, side effects which did occur while taking guanethidine or reserpine were well tolerated and neither drug was clearly superior. Side effects associated with larger doses of guanethidine employed in severe hypertension were absent or only slightly bothersome. Thus, guanethidine apppears to have a good benefit-to-risk ratio in the therapy of mild to moderate hypertension and offers a number of advantages over drugs commonly used in this syndrome. This study refutes the common belief that guanethidine must be reserved only for the treatment of more severe degrees of hypertension.

Among 166 specimens with classical complete transposition, pulmonary or subpulmonary stenosis was present in 22 cases. The bases for obstruction were pulmonary valvular stenosis (one case), membranous subpulmonary stenosis (nine cases), anomalous attachment of the mitral valve to the ventricular septum (five cases) and combinations of causes (seven cases). Conditions contributing to combinations of causes included the above, in addition to accessory mitral or pulmonary valvular tissue and herniation of a tricuspid valvular pouch through a related ventricular septal defect. In addition to the 166 cases mentioned, our collection contained six cases of atypical complete transposition characterized by a conus being present in the each ventricel. In three of these six, subpulmonary stenosis was present and caused by a narrow inlet to the left ventricular conus.

The mechanisms of supraventricular tachycardia were investigated in 35 children. Intracardiac electrograms including His bundle potentials were recorded. Atrial pacing and single premature atrial stimuli were performed in the right atrium. Tachycardia was observed and the mechanism elucidated in 33 patients. The atrial activation sequence during tachycardia, including high right atrium, low lateral right atrium, low septal right atrium, and left atrium, together with the ability to initiate or terminate the tachycardia with premature stimuli, were keys to defining the mechanisms. The observed mechanisms included atrioventricular (A-V) node reentry (8), sino atrial node re-entry (5), re-entry through manifest or concealed lateral anomalous pathway (8), re-entry through A-V node bypasses (3), and atrial (7) and junctional (2) ectopic focuses. The frequency of the various mechanisms of SVT is more varied in children than adults, with ectopic mechanisms being more common in children.

The effect of timolol versus propranolol on hypertension, hemodynamics, and plasms renin activity was evaluated in 20 men. After two weeks of placebo, 11 men received timolol 30 to 60 mg daily, and nine men received propranolol, 240 to 480 mg daily, for five weeks in a double-blind randomized study. The 20 men then received placebo again for two weeks. Right heart catheterization was performed in all 20 patients after two weeks of the first placebo and after five weeks of timolol or propranolol. Equipotent doses of timolol and propranolol were equally effective in significantly lowering supine and upright systolic and diastolic blood pressure and heart rate recorded on an outpatient basis. Equipotent doses of timolol and propranolol caused similar hemodynamic effects including similar significant depression of cardiac index. Equipotent doses of timolol and propranolol caused similar marked depression of plasma renin activity. The hypotensive action of timolol and of propranolol was unrelated to their effect on plasma renin activity.

One hundred and twenty patients undergoing aortocoronary bypass procedures were randomly placed into control and digitalized groups. All were initially in normal sinus rhythm and without evidence of congestive heart failure. Supraventricular arrhythmias occurred in 17 of 66 controls and in only three of 54 digitalized patients (P less than 0.01). There was no evidence of digitals toxicity. Based on this evidence we recommend prophylactic digitalization for patients having aortocoronary bypass operations.

The hypolipidemic effect of PAS-C-diet treatment was studied in 63 patients with Types IIa and IIb hyperlipoproteinemia for 6-36 months. Serum lipids and body weights of all patients were stabilized by a low cholesterol-saturated fat-refined carbohydrate diet before the initiation of an eight-week placebo-drug single-blind crossover study. During the placebo period the plasma lipids levels, mean +/- SD: cholesterol 355 +/- 63.5 mg%, triglyceride 141 +/- 68.7 mg%, and LDL-cholesterol 279 +/- 56.8 mg% were lowered to 274 +/- 53.1 mg+, 98 +/- 40.6 mg%, and 209 +/- 52.9 mg%, respectively (P less than 0.001 in each instance), with 7.5-11.0 grams of PAS-C/day given in one to three divided doses. In ten patients who have completed three years of treatment similar results were obtained. They showed no tendency to develop drug tolerance. Eight had watery diarrhea during the initial period which promptly subsided with interruption of drug therapy. Reintroduction of PAS-C in smaller dose (4.5 g/day) with gradual increment to effective dosage level was tolerated by all. No hematologic, hepatic, and ophthalmologic abnormalities were demonstrated by periodic monitoring. The hypoplipidemic effect of the drug was found to be diminished by alcohol and caloric excess.

The reliability of interpretation of coronary arteriography as a diagnostic tool was investigated in a sub-study of the VA Cooperative Study of Surgical Treatment for Coronary Arterial Occlusive Disease. Twenty-two physicians with varying levels of experience read 13 cine angiograms -- blind -- on two different occasions. Analysis of inter- and intraobserver variability showed that angiographic items about which observers were most inconsistent from one reading to the other had the largest interobserver disagreement as well. They were the distal portions of the left anterior descending and left circumflex arteries. Among the items on which there was most consistent agreement -- namely, the right main coronary artery and presence of ventricular aneurysm -- there was most often agreement between observers as well. When individual readers were evaluated, some observers were far more consistent in their own readings of all the angiographic items than others. This intraobserver agreement in turn correlated fairly well with how often they agreed with the other observers and with how much experience they reported having in reading coronary cineangiograms.

Twenty-six patients with complicated acute myocardial infarction were studied in order to compare the hemodynamic effects of sodium nitroprusside (NP) and nitroglycerin (GTN). All patients received NP and 18 of the 26 also received GTN to evaluate both drugs in the same individuals. Both agents produced significant declines in mean arterial pressure, total peripheral resistance (TPR), and heart rate systolic blood pressure product. However, in the 18 patients who received both drugs GTN produced a greater fall (P less than 0.05) in pulmonary capillary wedge pressure (PCW) (25 to 15 mm Hg) than did NP (24 to 17 mm Hg) and a greater increment (P less than 0.01) in (see article) (0.98 to 1.43) than NP (0.98 to 1.16). These data confirm the potent vasodilatory effects of NP and GTN and suggest that NP has a relatively balanced effect on the arterial and venous circulation, and GTN seems to produce more potent venodilatation than arterial dilatation. These observations provide a basis for a more rational choice of vasodilator agents based on initial hemodynamic measurements in complicated acute myocardial infarction.

The effect of sulfinpyrazone on the incidence of thrombosis of arterio-venous shunts was investigated in a double-blind crossover study in 45 patients on chronic hemodialysis over a period of 12 months. The incidence of thrombosis was reduced from 0.64 thrombi per patient month when on placebo to 0.21 thrombi per patient month when on sulfinpryazone (P less than 0.001). The therapeutic effect was more striking in men than in women and became evident within a week of starting the drug. The side effects were minimal, requiring withdrawal from the study of only one patient. This crossover study strengthens the findings in the previous report that sulfinpyrazone is of value in the prevention of thrombosis.

Vasodilators are known to be effective in improving the hemodynamics of congestive heart failure by increasing cardiac output and reducing left ventricular filling pressure (LVFP). Long acting agents are needed to augment the practicality and availability of chronic vasodilator therapy. In the present study the vascular effects of chewable isosorbide dinitrate (CHIS), sublingual nitroglycerin (NTG) and placebo (P) were compared in eight patients with high LVFP due to heart failure. Patients with LVFP (pulmonary wedge pressure) over 14 mm Hg were given CHIS, 10 mg, NTG, 0.6 mg, and P, two chewable tablets, in random fashion. Heart rate (HR), blood pressure (BP) and LVFP were monitored for three hours after each drug. HR was not significantly affected by any drug, although it rose slightly after NTG and fell after CHIS. Significant reduction of BP occurred only after NTG, with peak effect at five minutes, but lasting only 15 minutes. NTG reduced LVFP 5.1 mm Hg (19.5%, P, less than 0.05), at peak effect, but LVFP was no longer significantly lower by 20 minutes after NTG. After CHIS, LVFP fell significantly within five minutes, reached a peak reduction of 8.6 mm Hg (32;7%, P less than 0.01) at 15 minutes, and remained significantly lower through three hours. Thus CHIS provides a nitrate action of rapid onset and sustained effect that may be useful for chronic vasodilator therapy of heart failure.

Forty-one patients undergoing aortocoronary bypass surgery were divided into two groups: an "unclamped" group (17 patients) in whom the aorta was not cross-clamped during operation and a "clamped" group (24 patients) in whom the ascending aorta was cross-clamped during performance of distal anastomoses. Myocardial protection was provided during aortic clamping by cooling the anoxic heart with cold saline immersion. Immediate postoperative hemodynamic function was assayed in both groups, as was cardiopulmonary bypass time and cardiopulmonary bypass time/graft. Cardiopulmonary bypass time was 107 minutes in the unclamped group and 87 minutes in the clamped group (P less than 0.05). Cardiopulmonary bypass time/graft was 48 minutes in the unclamped group and 40 minutes in the clamped group (P less than 0.01). Results of hemodynamic studies with values for the unclamped group listed first were as follows: cardiac index (L/min/m2) 2.3 and 2.5 (NS), stroke index (ml/beat/m2) 23 and 25 (NS), left ventricular minute work index (kg-m/min/m2) 3.03 and 2.81 (NS), and stroke work index (g-m/min/m2) 31 and 30 (NS). These data indicate that aortic cross-clamping during performance of distal anastomoses expedites the performance of aortocoronary bypass surgery and does not adversely affect postoperative hemodynamics.

A total of 145 patients with greater than 50% obstruction of the left main coronary artery (LMC) were studied by coronary arteriography. Of the 140 who survived cardiac catheterization, 121 were considered operable by coronary arteriography, and 19 were inoperable. Of the 121 operable patients, 32 were treated medically, and 89 had aortocoronary bypass surgery. Surgical mortality was 11%. The follow-up was from 1 to 72 months with a mean follow-up of 15 months. A survival table was plotted over a 24-month period. At 90 days survival in surgical patients was 85%, medical patients 72%, and inoperable patients 64%. At one year 82% of surgical patients were alive compared with 61% of medically treated operable patients (P less than 0.05). Thereafter, the survival rate remained stable up to 23 months. Survival in inoperable patients was 38% at one year. Improved surgical survival was associated with the presence of preoperative collateral vessels and a left ventricular stroke index greater than 18 g-m/m2. The study demonstrates that survival is improved significantly by surgery in LMC patients. Since mortality occurs early after coronary arteriography, surgery should be offered early to operable patients.

In a prospective study to evaluate surgery for angina pectoris, 50 patients randomized to surgery and 50 treated medically have completed 8 to 34 months' follow-up (median, 24 months). Anginal symptoms improved in both groups (88%, 72%), but more operated patients are currently asymptomatic (70%, 8%) and using fewer medications (nitrates, 18%, 96%; propranolol, 8%, 72% of patients). Exercise tests with treadmill revealed increased exercise tolerance time in both groups, more so in the operated group (+ 89%, + 42%), and angina could not be provoked in 70% and 20% of patients, respectively. During the follow-up, fewer cardiac complications developed in the operated group (19 vs. 44; P = less than 0.02); there was no difference in mortality. Repeat catheterization in 83 of 84 survivors at 1 year did not reveal any significant differences in the progression of disease. Atrial pacing studies revealed improvement in anginal threshold in 70% of operated and 48% of nonoperated patients. The study suggests that although subjective and objective improvement occurs with surgical as well as nonsurgical treatment, the frequency and magnitude are higher with surgery. The quality of life appears to be better in the operated patients during the first 24 months. Further follow-up is necessary to determine the duration of such improvement and to assess the influence of surgery on the natural life history of this disease.

Cardiac output and pressure-flow measurements were made in left internal mammary artery-to-left anterior descending coronary artery grafts and left subclavian artery-to-left circumflex coronary artery vein grafts after proximal coronary artery ligation. Similar measurements were also made in left internal mammary artery-to-left anterior descending coronary artery grafts and aortocoronary saphenous vein grafts in patients with coronary artery disease. Hemodynamic parameters and graft blood flows were measured during control baseline conditions and after pharmacological interventions using isoproterenol, phenylephrine, and epinephrine in random order. Blood flow through vein grafts and internal mammary artery grafts was similar under basal conditions and increased similarly with each of these vasoactive agents. Other hemodynamic parameters changed variably with the various pharmacological agents used. There was no close correlation between mammary artery or vein graft blood flow and arterial mean pressure and cardiac output over the wide range observed with the different drugs was associated with either an increase in perfusion pressure or a decrease in coronary vascular resistance. If the percentage increase in coronary blood flow above the basal control value in response to pharmacological stress is considered as a reflection of coronary vascular reserve, these studies suggest that coronary vascular reserve in patients with coronary artery disease is less than that of the normal dog heart.

The rate at which arterial pressure rises after discontinuing active treatment was investigated in a group of 86 hypertensive patients who received treatment with hydrochlorothiazide, reserpine and hydralazine for two years or longer and whose diastolic pressures averaged below 96 mm Hg for the last year of treatment. Sixty patients were assigned double-blind to placebos and 26 were continued on active drugs. Forty-two of the placebo group of patients were removed over an 18 month follow-up because of return of elevated blood pressures, 39 being removed in the first six months. Six patients in the placebo group and none in the treated group were removed because of morbid events. Nine or 15% of the placebo patients remained normotensive. The rate of rise in arterial pressure in the placebo group appeared to be related directly to the height of the pressure prior to initiation of active treatment and inversely to the age of the patients. Serum uric acid fell significantly while serum potassium rose significantly after active treatment was discontinued. The glucose tolerance test changed slightly in a direction toward normal while serum creatinine showed no significant change.