We evaluated the relationship of rate-dependent changes in atrial refractoriness to atrial vulnerability in 39 patients. Vulnerability was considered present when sustained atrial tachyarrhythmias, lasting longer than 1 minute, could be provoked with one to three extra stimuli. Adaptation of atrial refractory period duration to rate was defined as: normal: steep rate reduction with a linear correlation slope value of 0.08 or more; non-adaptation: absence of rate reduction, the slope value being 0 to 0.01; poor adaptation: slight reduction with rate, the slope having values of 0.02 to 0.07. Increased vulnerability was demonstrable in 16 of 17 patients with non-adaptation of the effective refractory period (ERP), and in 10 of 10 with a similar defect of the functional refractory period (FRP); in the intermediate category (poor adaptation) the results for ERP and FRP were 7/11 and 5/6. By way of contrast when both measurements showed normal adaptation, vulnerability was elicited in 2/9 patients. The significance between these groups showed P less than 0.005. Of 17 patients with atrial arrhythmia by Holter, 14 showed poor or non-adaptation of the ERP. It is suggested that poor or absent rate adaptation of the atrial refractory period, and a propensity to atrial fibrillation or flutter, constitute a clinical entity not previously described.
We studied 42 subjects, each of whom demonstrated significant (greater than or equal to 50%) narrowing of a non-grafted coronary artery and a baseline cholesterol level greater than 250 mg%. All patients underwent repeat scheduled coronary arteriography after 2 years on the study. Twenty-five colestipol responders (cholesterol levels reduced at least 15% within 1 month of therapy) were compared to 17 non-responders who were given 23 months of placebo after a 1 month exposure to colestipol. Baseline risk factors and demographic characteristics were similar for the two groups. In comparison to baseline arteriography, only 3 of the 25 drug-treated patients showed progression, while 8 of 17 placebo treated patients demonstrated progression (P = 0.011). Drug-treated patients demonstrated a 20% decrease in cholesterol levels, while placebo patients did not experience a significant reduction in cholesterol levels. Our study suggests that significant reduction in serum cholesterol levels is associated with a reduced likelihood of progression of coronary atherosclerotic lesions assessed by scheduled repetitive coronary arteriography in hyperlipidemic subjects demonstrating significant coronary artery narrowing on their initial arteriograms.
We examined the role of the renin-angiotensin system in the regulation of systemic and coronary vascular tone by studying the effect of converting enzyme inhibition by teprotide on systemic and coronary hemodynamic parameters in 14 normal patients undergoing routine cardiac catheterization. Serial hemodynamic measurements were made before and up to 30 minutes after 1 mg/kg of intravenous teprotide. A significant rise in cardiac index and stroke volume index occurred with a fall in systemic vascular resistance. The increase in cardiac index was related to the level of resting plasma renin activity. Blood pressure, pulmonary artery and left ventricular end-diastolic pressures remained unchanged. Coronary sinus thermodilution blood flow also showed no significant change; however, some patients demonstrated dramatic increase in flow. The change in blood flow was highly correlated with the resting plasma renin activity (r = 0.939 P less than 0.001). The change in coronary vascular resistance and myocardial oxygen consumption were likewise related to the resting plasma renin level. Converting enzyme inhibition produces significant systemic hemodynamic changes in normal patients which implies that the renin-angiotensin system is important in normal cardiovascular homeostasis. The direct relationship between plasma renin activity and coronary blood flow suggests that the renin-angiotensin system may play an important role in coronary vasomotor regulation.
We measured blood pressure and heart rate at rest and during exercise on a bicycle ergometer in 19 patients with borderline hypertension, in 58 with sustained essential hypertension and in a group of 30 healthy subjects of the same age. On each subject, we determined the systolic blood pressure/heart rate curve during exercise and calculated the slope and intercept. In patients with borderline hypertension, blood pressure was elevated in basal conditions but was within the normal range at the end of exercise. This caused an increased intercept (P less than 0.001) and a reduced slope (P less than 0.05) of the curve. In patients with sustained hypertension, blood pressure was elevated throughout the exercise test. This caused an increased slope (P less than 0.001) of the blood pressure/heart rate curve. The slope of the curve correlated negatively with basal heart rate in borderline hypertensive patients (P less than 0.01) and correlated positively with basal total peripheral resistance in sustained hypertensive patients (P less than 0.01). Exercise testing can help one diagnose borderline and sustained hypertension and predict the evolution of borderline hypertension toward fixed hypertension.
We studied with M-mode echocardiography the morphology and function of the left ventricle in a group of 36 juvenile hypertensives with borderline hypertension, whose cuff arm pressure exceeded 150/90 mmHg in at least three separate sessions. The results were compared with those of 23 age-matched normotensives with no evidence of any cardiovascular disease. Left ventricular hypertrophy (i.e. septum and/or posterior wall thicknesses in diastole greater than or equal to 12 mm) was present in 13 subjects of the hypertensive group (36%). Significant increase of interventricular septal thickness together with higher septum/posterior wall ratio and a higher incidence of asymmetric septal hypertrophy were the most characteristic findings in juvenile hypertensives. Of the functional parameters the only observed difference between the two groups was an elevated peak velocity of left ventricular contraction in hypertensives which tended to correlate inversely with the values of septum/posterior wall ratio. Additional comparison of electrocardiographic and echocardiographic detection of left ventricular hypertrophy in young hypertensives revealed a lower sensitivity but a satisfactory specificity of electrocardiography (31 and 87% respectively). The results indicate that besides an elevated systemic arterial pressure, other factors such as increased sympathetic or humoral activity may play a role in the incipient stage of essential hypertension and that isolated septal hypertrophy seems to be an early sign of cardiac involvement.
A 29-year-old female with transposition of the great arteries, single ventricle, a small open ductus arteriosus and a mild aortic incompetence experienced two successful pregnancies without major complications. The benign course of pregnancy is attributed to the relatively low pulmonary vascular resistance and to the fact that the patient has not yet developed an Eisenmenger syndrome.
I studied the prevalence and symptoms of idiopathic mitral valve prolapse by auscultation in 972 consecutive patients in an adult general medical population. Forty-five patients (4.6%) had idiopathic mitral valve prolapse defined by a nonejection click with or without a late systolic murmur. The prevalence was not significantly different in men and women. The mean age (49.9 yr) and age distribution of patients with prolapse were similar to those of patients without prolapse (47.7 yr). The prevalence of dizziness (4.1% vs. 1.5%), fatigue (4.4% vs. 2.6%), and palpitations (4.4% vs. 1.3%), was not significantly greater in patients with or without prolapse. Atypical chest pain (13% vs. 4.3%) and chronic anxiety (8.8% vs. 2.9%) were more frequent (less than 0.05) in the patients with prolapse than in those without prolapse. Of the patients with prolapse, 29 were healthy without clinically identifiable diseases while 16 had medical diseases. In the group without prolapse, 184 patients were healthy and 707 had other diseases. When patients with isolated prolapse without other associated diseases were compared to healthy patients without prolapse, the prevalence of atypical chest pain (17.4% vs. 17.2%) and chronic anxiety (7.1% vs. 10.3%) were not significantly different. When patients with prolapse and other diseases were compared to patients without prolapse and other diseases, the prevalence of atypical chest pain (6.2% vs. 1.1%) and chronic anxiety (6.2% vs. 1.7%) was again not significantly different. Thirty-two patients without prolapse were suspected but not confirmed of having disease and were not included in this analysis. The results would have been unaltered by their inclusion in the diseased group without prolapse.
We evaluated a new slow-channel calcium-blocking agent, diltiazem hydrochloride, in 10 patients with documented fixed coronary artery disease who had reproducible angina and greater than or equal to 0.1 mV ST segment depression on ECG treadmill exercise testing after 1 week of single-blind placebo administration. Subsequently, over the next 6 weeks, either diltiazem (30 mg/tablet) or placebo were administered for 1 week each in a randomized double-blind triple crossover design, as one tablet four times a day, two tablets three times a day or two tablets four times a day, for a total diltiazem dose of 120, 180 and 240 mg/day, respectively. Treadmill (electrocardiogram) exercise testing was performed at the end of each week. Only diltiazem at 240 mg/day increased significantly the time to angina pectoris (P less than 0.05), time to ST segment depression (P = 0.01), time to maximal exercise (P less than 0.02), and heart rate at maximal exercise (P less than 0.05) without effecting significantly the maximal rate-pressure product compared to the corresponding placebo values. In addition, using only the diltiazem data, a significant high dose response was observed for time to angina (P less than 0.05), ST segment depression (P less than 0.005), and maximal exercise (P less than 0.025). No adverse reactions were reported during the study. Therefore, we conclude that 240 mg/day of diltiazem improves significantly exercise performance in patients with angina pectoris due to fixed coronary artery disease and adverse effects, rarely, if ever, occur at this dosage.
Clinical and experimental data indicate that some coronary stenoses can rapidly change shape thereby influencing the hemodynamic severity of the stenosis. In 7 closed chest dogs, we examined the effects of distal coronary arteriolar vasomotor tone and myocardial oxygen demands on a coronary stenosis created by partial intraluminal occlusion, using a small balloon catheter. Myocardial blood flow (ml/g per min) was measured with 15-microns radioactive microspheres. Stenotic resistance was calculated as the mean pressure gradient across the stenosis divided by the mean blood flow through the stenosis. The mean pressure gradient was calculated as the ascending aortic pressure minus the left anterior descending coronary artery pressure distal to the stenosis. Coronary arteriolar vasodilation induced by pacing (170 beats/min) increased stenotic resistance (1.64 +/- 0.27 to 26.48 +/- 13.77 mmHg/ml per min, P less than 0.05) and decreased myocardial blood flow (endocardial 0.42 +/- 0.04 to 0.17 +/- 0.04, P less than 0.05, midcardial 0.35 +/- 0.03 to 0.13 +/- 0.04, P less than 0.05; epicardial 0.22 +/- 0.05 to 0.15 +/- 0.05). Five dogs fibrillated within 10 min of continuous tachycardia and partial arterial occlusion. The change in arteriolar vasomotor tone and decreased aortic pressure induced by pacing altered the severity of the stenosis and resulted in a reduction of blood flow to the myocardium.
We evaluated the effects of isosorbide dinitrate on some of the major determinants of myocardial oxygen demand during upright exercise in ten normal subjects. In addition to heart rate and systolic blood pressure, we assessed left ventricular size and performance by echocardiography. Compared to the control study, heart rate was significantly faster after the nitrate administration at rest (67 +/- 14 versus 83 +/- 21 beats/minute), but there was no difference in heart rate at any stage during exercise. Systolic blood pressure also was significantly lower at rest after nitrate (104 +/- 8 versus 92 +/- 2 mm Hg) but was similar to control after 6 minutes of exercise. Echocardiographic end-diastolic dimension was decreased at rest post-nitrate (45.3 +/- 4.7 versus 40.2 +/- 4.2 mm) and remained significantly reduced during exercise by an analysis of variance. We conclude that a major beneficial effect of nitrates on myocardial oxygen demand during upright exercise is a decrease in left ventricular size which reduces wall tension.
We assessed left ventricular ejection fraction 47 times in 21 patients with sinus rhythm by a portable non-imaging nuclear probe. After 99mTc blood pool labelling, left ventricular ejection fraction was determined by probe in two different ways: on a beat-to-beat basis, and by the so-called ventricular function mode, based on the gated equilibrium principle, and subsequently compared with left ventricular ejection fraction measured by gated equilibrium radionuclide angiocardiography using a gamma camera. Left ventricular ejection fraction by probe correlated well with left ventricular ejection fraction by gamma camera: beat-to-beat versus gamma camera: r = 0.90, y = 0.75x + 0.12; ventricular function versus gamma camera: r = 0.88, y = 0.87x + 0.08. Also, left ventricular ejection fraction values determined by the two probe methods correlated closely: r = 0.97, y = 0.83x + 0.07. Compared with the gamma camera, the probe overestimated slightly the small values of left ventricular ejection fraction and underestimated high values. Correct determination of left ventricular ejection fraction by a non-imaging probe depends on correct positioning over the left ventricle and selection of a proper background activity level. The main application of this instrument is probably non-invasive bedside determination and monitoring of changes of left ventricular function occurring spontaneously or caused by cardiac arrhythmias or treatment with cardiac drugs.
We studied regional left ventricular contraction patterns and ejection fraction from real-time two-dimensional echocardiograms in 8 normal subjects, 11 patients with coronary artery disease and 2 with congestive cardiomyopathy. The ventricle was divided into 12 regions and for each region, we calculated ejection fraction using a method which integrated the incremental volumes of a series of hemicylinders constructed within that region. The data obtained were displayed graphically to provide a detailed picture of regional ventricular function. Normal subjects had a uniform regional ventricular pattern (regional ejection fraction 54-74%). In patients with coronary disease, we found varying degrees of regional ventricular contraction abnormalities. In congestive cardiomyopathy global hypokinesis was present, and regional ejection fraction was reduced in all areas (11-39%). The study showed that two-dimensional echocardiography is a useful non-invasive bedside technique which may provide detailed quantitative information relating to regional left ventricular contraction abnormalities.