Prevalence and significance of reversible radionuclide ischemic perfusion defects in symptomatic aortic valve disease patients with or without concomitant coronary disease

To determine the prevalence and significance of exercise-induced localized perfusion defects in symptomatic patients with aortic valve disease, thallium-201 rest and exercise studies were performed in a consecutive series of 29 such patients prior to left heart catheterization with coronary arteriography. Eight patients had repeat studies after aortic valve replacement. Twelve of 17 patients with predominant aortic regurgitation (AR) had distinct LV apical defects during exercise despite normal coronary arteries, while 10 of 12 patients with aortic valve disease and associated coronary artery disease (CAD) had localized perfusion defects in LV areas other than the apex. In patients with AR, reversible apical perfusion defects can occur without CAD; these apical detects are probably a reflection of severe LV volume overload in AR. LV perfusion defects in areas other than the apex are specific for CAD in aortic valve disease, and concomitant CAD may not provoke regional LV perfusion deficits in aortic stenosis patients with severe LV hypertrophy.     

Hemodynamic effects of intravenous prenalterol in severe heart failure

Nine patients with chronic severe low output heart failure (radionuclide left ventricular ejection fraction 17 ± 5 percent [mean ± standard deviation], left ventricular filling pressure 26 ± 6 mm Hg, cardiac index 1.9 ± 0.4 liters/min per m², left ventricular stroke work index 18 ± 6 g-m/m²) from various causes were treated with intravenous prenalterol (a new catecholamine-like inotropic agent) in doses of 1, 4 and 8 mg. Significant hemodynamic improvement occurred as measured by increased left ventricular ejection fraction (to 26 ± 4 percent), decreased left ventricular filling pressure (to 21 ± 8 mm Hg) and increased cardiac index (to 2.4 ± 0.6 liters/min per m²) and left ventricular stroke work index (to 25 ± 8 g-m/m²). Significant increases in heart rate (from 87 ± 18 to 91 ± 18 beats/min) and mean systemic arterial pressure (from 87 ± 8 to 92 ± 7 mm Hg) also occurred. Peak hemodynamic response occurred at various doses. Significant adverse effects associated with prenalterol consisted of increased ventricular ectopic beats in two patients and asymptomatic ventricular tachycardia in two patients. Thus, intravenous prenalterol produces hemodynamic improvement in patients with a chronic severe low output state but may be associated with increased ventricular ectopic activity.     

Transient electrocardiographic changes in patients with unstable angina: Relation to coronary arterial anatomy

The relation between the spontaneous electrocardiographic changes and coronary arterial anatomy in unstable angina pectoris was examined in 97 patients with coronary artery disease and transient electrocardiographic changes during chest pain. Sinus rhythm was maintained during pain in all patients. Heart rate increased significantly in 61 percent (mean ± standard error of the mean 72 ± 2 to 93 ± 2 beats/min, probability [p] < 0.001) and was unchanged or decreased in 39 percent of patients (73 ± 2 to 72 ± 2 beats/min; p = not significant) during pain. S-T segment changes developed in 97 percent of patients, of whom 42 percent had S-T segment elevation and 55 percent S-T depression. The magnitude of the S-T segment shift was greater in patients with triple vessel disease (2.2 ± 0.4 mm) than in those with double (1.5 ± 0.1 mm) or single (1.4 ± 0.1 mm) vessel disease (p < 0.05). In 43 patients with single vessel disease S-T segment elevation developed in 78 percent of those with right coronary artery disease and in only 9 percent of those with left circumflex disease (p < 0.02). Maximal S-T segment changes were more frequent in the inferior leads in patients with right coronary artery disease (56 percent) and in the anterior leads in patients with left anterior descending (65 percent) and circumflex (64 percent) disease (p < 0.05).Thus, patients with coronary artery disease and unstable angina maintain regular sinus rhythm during chest pain, and the heart rate usually increases but may be unchanged or decreased in a significant proportion. S-T segment elevation is common in these patients and the magnitude of the S-T segment shift is related to the extent of the underlying coronary disease. This study suggests that the type and distribution of the repolarization changes are a reflection of the location and severity of the atherosclerotic process.     

Double-blind, placebo-controlled trial of propranolol given once, twice and four times daily in stable angina pectoris: a multicenter study using serial exercise testing

To determine if propranolol given twice daily (b.i.d.) or once daily (q.d.) was as effective as 4 times daily (q.i.d.) for treatment of stable angina pectoris, 78 patients with exercise-induced ST depression of 1.5 mm were randomized to q.i.d., b.i.d., q.d. and placebo groups. All patients received 5 tablets per day, and propranolol groups received 80, 160 and 320 mg/day on successive weeks. At weekly visits, patients underwent treadmill exercise testing before the 8:00 AM dose and at 2 and 9 hours afterward. Exercise duration (seconds) was significantly improved at the final visit compared with baseline by b.i.d. (120 +/- 36 [mean +/-] standard error of the mean p less than 0.001 n = 18) and q.i.d. (100 +/- 37, p less than 0.01; n = 17) regimens, but not by the q.d. (30 +/- 33; n = 18) and placebo regimens (27 +/- 37; n = 17). There was a significant decrease from baseline in the magnitude of ST depression at the final visit, measured at maximal common exercise duration in b.i.d. (-0.96 +/- 0.20 mm, p less than 0.001), q.i.d. (-0.84 +/- 0.20 mm, p less than 0.01) and q.d. (-0.58 +/- 0.18 mm, p less than 0.05) groups, but not in the placebo group (0.03 +/- 0.2 mm). Hourly heart rate by Holter was reduced in all 3 propranolol groups; however, the mean serum propranolol level was significantly lower just before the first dose with q.d. group (56 +/- 20 ng/ml) compared with b.i.d. and q.i.d. groups (146 +/- 22 and 119 +/- 28 ng/ml) with 320 mg/day (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Editorials: Updating sphygmomanometry

Left ventricular function in two cases of restrictive pericardial disease is described. In one, calcification of the pericardium was absent and the restrictive process, as judged by the response to atrial systole, was incomplete. In the other, calcification was extensive and the restrictive process was severe. Both patients had normal myocardial function in the presence of greatly depressed pump function. This apparent discrepancy may be explained on the basis of restriction of end-diastolic fiber stretch and reduction in the potential to augment stroke volume by way of the Frank-Starling mechanism.     

Large dose sublingual nitroglycerin in acute myocardial infarction: Relief of chest pain and reduction of Q wave evolution

Thirty patients with acute myocardial infarction admitted 2.1 ± 1.1 (mean ± standard deviation) hours after the onset of pain and with S-T segment elevation in multiple leads in the standard electrocardiogram were given either intravenous morphine (15 patients) or sublingual nitroglycerin (15 patients), and the effect on pain and QRS changes was observed. Nitroglycerin was administered repetitively in large doses while systolic blood pressure was maintained above 100 mm Hg. Chest pain failed to respond within 30 minutes In two patients who received nitroglycerin. In the remaining 13 patients nitroglycerin produced partial relief of pain in 17 ± 5 minutes and complete relief in 127 ± 65 minutes, requiring a cumulative dosage of 23.7 ± 38.7 mg in 16 ± 7 divided doses. An average of 14.9 ± 7.1 mg of morphine in 3.3 ±1.5 divided doses produced complete relief of pain in a similar period (134 ± 77 minutes [difference not significant]). In patients receiving morphine, Q waves developed at 24 and 48 hours, respectively, in 62 (72 percent) and 66 (77 percent) of a total of 86 sites with initial S-T segment elevation in the standard 12 lead electrocardiogram. In nitroglycerin responders, Q waves developed at 24 and 48 hours, respectively, in only 21 (28 percent, p < 0.001) and 22 (29 percent, p < 0.001) of the 76 sites with initial S-T segment elevation. Other electrocardiographic estimates of the extent of myocardial necrosis, including the percent reduction in R wave amplitude and the relative changes in R and Q wave amplitude, also were significantly less in those receiving nitroglycerin. There was no in-hospital mortality. Thus, large and frequent doses of nitroglycerin when used in the hyperacute phase of acute myocardial infarction can effectively abolish chest pain and limit later electrocardiographic signs of myocardial necrosis.     

Constrictive pericarditis after myocardial revascularization: report of three cases.

Although postoperative constrictive pericarditis is rare, the diagnosis should be considered when unexplained right-sided heart failure develops after cardiac surgery. Within a 6 week interval, evidence of constrictive pericarditis developed in three patients who had recently undergone myocardial revascularization. One patient presented with biventricular failure, pericardial effusion and suspected tamponade. Severe constrictive pericarditis was demonstrated at subsequent operation. An apparent postpericardiotomy syndrome preceded evidence of right heart failure in the other two patients. Etiologic considerations include the possibility that pericardial irrigation with povidone-iodine (Betadine) solution may have contributed to subsequent fibrosis.     

Effects of glucose-insulin-potassium on myocardial substrate availability and utilization in stable coronary artery disease: Studies on myocardial carbohydrate, lipid and oxygen arterial-coronary sinus differences in patients with coronary artery disease

To assess the metabolic effects of myocardial substrate alteration In patients with coronary artery disease, glucose-insulin-potassium solution was administered intravenously for 30 minutes to 14 men with stable angiographically documented coronary artery disease. The glucose-insulin-potassium solution (300 g of glucose, 50 units of regular insulin and 80 mEq of potassium chloride per liter of water) was infused at a constant rate in each patient, but individual infusion rates ranged from 0.013 to 0.032 ml/kg per min (4 to 10 mg glucose/kg per min) in the 14 patients. Simultaneous arterial and coronary sinus samples were obtained at 15 minute intervals during a stable 30 minute control period and again at 15 minute intervals during the infusion; samples were assayed for glucose, lactate, free fatty acid and oxygen content.

In all 14 patients, during the glucose-insulin-potassium infusion, arterial glucose and lactate increased and arterial free fatty acid levels fell; the magnitude of the changes in arterial lactate and free fatty acids as related to the rate of infusion. Arterial-coronary sinus differences (A-C_s) for glucose, lactate and free fatty acid levels correlated with the arterial concentrations of these substrates (r = 0.66, 0.87 and 0.79, respectively). Regression analyses demonstrated myocardial thresholds for the uptake of these substrates as follows: glucose 79 mg/100 ml; lactate 300 μmole/liter; and free fatty acids 100 to 200 μEq/liter. Finally and most importantly, the reduction in A-C_s oxygen values after glucose-insulin-potassium infusion correlated with the reduction in A-C_s free fatty acid levels (r = 0.64, P < 0.0001). This observation suggests that, in patients with coronary artery disease, glucose-insulin-potassium infusion may significantly diminish myocardial oxygen requirements by reduction of myocardial free fatty acid utilization and simultaneous enhancement of myocardial carbohydrate utilization.

Myocardial substrate availability may be an important determinant of myocardial oxygen demand in patients with coronary artery disease. Infusion of glucose-insulin-potassium solution has the potential to alter myocardial substrate availability, thus improving the balance between myocardial oxygen demand and supply.     

Impact of radionuclide techniques on evaluation of patients with ischemic heart disease

Radiotracer studies of the heart have become clinically important in the last decade, especially for evaluation of patients with known or suspected ischemic heart disease. Radionuclide ventriculography provides quantitative measures of biventricular function and regional wall motion. Recent technical advances include the development of computer programs for analyzing diastolic function, parametric imaging methods such as "phase" analysis and methods for calculating absolute ventricular volumes. Thallium-201 scans provide maps of regional myocardial perfusion. Recent advances include development of computer programs to quantitate regional thallium-201 uptake and to calculate thallium-201 turnover rates and the development of tomographic imaging systems. Technetium-99m pyrophosphate localizes in irreversibly damaged myocardium and provides a method for diagnosing, localizing and sizing acute myocardial infarcts. Recent applications include tomographic imaging to improve image contrast and development of criteria to identify high risk patients after infarction. Two important trends affecting the application of all the radionuclide studies in clinical cardiologic practice are the increasing use of decision analysis for incorporating results of multiple tests into single diagnostic probability statements, and the use of diagnostic algorithms that include the radionuclide studies to optimize the cost effectiveness of evaluation of patients with ischemic heart disease.     

Effects of a new nonionic and a conventional ionic contrast agent on coronary sinus ionized calcium and left ventricular hemodynamics in dogs

Transient myocardial depression associated with intracoronary injections of contrast medium has been attributed to hypertonicity and to calcium binding. To further assess the importance of calcium binding, a new technique for continuous monitoring of coronary sinus ionized calcium with an intravascular calcium-selective electrode was used. With this calcium-selective electrode the effects of intracoronary injection in dogs of a conventional ionic contrast agent, sodium meglumine diatrizoate (Renografin-76), and a new nonionic agent, iohexol, were assessed and compared. Left ventricular pressure was measured with a micromanometer catheter. After bolus injection of 0.2 ml/kg body weight of Renografin-76 (n = 10), coronary sinus pCa increased by 0.27 from 2.98 +/- 0.02 to 3.25 +/- 0.03, indicating a decrease in ionized calcium from 2.0 to 1.1 mEq/liter. With iohexol (n = 9), pCa increased by only 0.05 +/- 0.01 (p less than 0.001), indicating a decrease in ionized calcium from 2.0 to 1.8 mEq/liter. Peak changes occurred approximately 6 seconds after injection. Renografin-76 caused a marked decrease in left ventricular systolic pressure (140 +/- 7 to 106 +/- 8 mm Hg) and in heart rate (122 +/- 7 to 101 +/- 5 beats/min) with an increase in end-diastolic pressure (5 +/- 1 to 12 +/- 1 mm Hg), whereas iohexol did not significantly alter these variables. Using Renografin-76 with calcium added to achieve an ionized calcium level of 2 (n = 4), 4 (n = 4) or 6 (n = 4) mEq/liter, the changes in coronary sinus pCa were abolished and the hemodynamic changes attenuated. These findings indicate that Renografin-76 results in greater myocardial depression than the new nonionic agent iohexol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative coronary arteriography. Coronary anatomy of patients with unstable angina pectoris reexamined 1 year after optimal medical therapy

The effect of optimal medical therapy on coronary arterial anatomy was evaluated in 25 patients with unstable angina pectoris. Coronary arterial diameter and the extent of stenosis were exactly quantified in two successive coronary angiograms performed in each patient at approximately a 1 year interval (range 4 to 31 months, average 12.4 months). The measuring device was a vernier caliper with an accuracy of 0.05 mm. After 1 year of medical treatment 69 stenoses of the three major coronary branches showed no significant change: The average degree of area obstruction of 27 stenoses of the right coronary artery was 79 and 84 percent in the initial and second studies, respectively; that of 26 stenoses of the left anterior descending artery 78 and 77 percent, respectively, and that of 16 stenoses of the left circumflex artery 73 and 83 percent, respectively. In 11 patients, 14 stenoses showed a distinct progression of more than 20 percent area obstruction. All six stenoses showing more than 90 percent obstruction in the first angiogram progressed to complete obstruction within 1 year. In five other patients area obstruction in five stenoses regressed by more than 20 percent. The anatomy of vessel segments distal to obstructions remained unchanged within 1 year. It is concluded from these quantitative measurements that the distribution and severity of coronary lesions are similar in patients with stable and unstable angina pectoris. Coronary anatomy showed no significant change after 1 year of medical treatment. The rate of progression was substantially lower than previously reported in patients with stable angina pectoris.     

Silent myocardial ischemia: hemodynamic changes during dynamic exercise in patients with proven coronary artery disease despite absence of angina pectoris

The hemodynamic changes during exercise occurring in 36 patients with proven coronary artery disease (10 without and 26 with previous myocardial infarction) who tolerated the stress test without angina were analyzed and compared with changes observed in a control group of 36 carefully matched patients whose exercise was limited by angina. All patients were exercised to the same extent, reaching a similar rate-pressure product at the end of the stress test (19,508 +/- 4,828 [SD] versus 19,247 +/- 4,117 beats/min X mm Hg [NS] in the study and control groups without prior infarction, and 19,665 +/- 3,950 versus 17,701 +/- 4,600 beats/min X mm Hg [NS] in the respective groups with infarction). In all groups left ventricular end-diastolic pressure increased from rest to exercise (from 18 +/- 4 to 36 +/- 11 and from 13 +/- 5 to 29 +/- 9 mm Hg, respectively, in the study and control groups without prior infarction and from 17 +/- 7 to 32 +/- 13 and from 19 +/- 7 to 36 +/- 9 mm Hg in the respective groups with prior infarction). Left ventricular ejection fraction decreased (from 59 +/- 7 to 50 +/- 15 and from 60 +/- 4 to 52 +/- 9% in the study and control groups without prior infarction and from 54 +/- 9 to 47 +/- 10 and 55 +/- 9 to 50 +/- 4% in the respective groups with prior infarction). Whereas the changes from rest to exercise were highly significant within each group, no significant differences were noted between the corresponding groups. Regional de novo hypokinesia appeared in all patients without prior infarction and in 25 and 22 patients, respectively, of the groups with prior infarction. Thus, under similar physical stress conditions, comparable hemodynamic changes indicative of ischemia are observed in patients with significant coronary artery lesions with or without previous myocardial infarction irrespective of the occurrence of angina. Therefore, angina pectoris cannot be considered a prerequisite for hemodynamically significant ischemia during exertion.     

Clotted hemopericardium with the hemodynamic characteristics of constrictive pericarditis

Cardiac catheterization in a patient 4 weeks after coronary arterial bypass surgery demonstrated the typical hemodynamic findings of constrictive pericarditis, which completely resolved after removal of 500 ml of clotted pericardial blood. The pericardium was not responsible for the findings because it was left in place. This case demonstrates that clotted hemopericardium may mimic constrictive pericarditis.