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.     

Thallium-201 versus technetium-99m pyrophosphate myocardial imaging in detection and evaluation of patients with acute myocardial infarction

Thallium-201 myocardial imaging is of value in the early detection and evaluation of patients with suspected acute infarction. The extent of a thallium defect in an initial myocardial image may have important prognostic value. Tomographic imaging techniques hold promise for increased diagnostic sensitivity and more accurate quantitation of both infarcted and residual viable myocardium. Thallium imaging may have a special value in characterizing patients with cardiogenic shock and in detecting patients at risk for subsequent infarction or death or both, before hospital discharge.

Approximately 95 percent of patients with transmural or nontransmural myocardial infarction can be detected with technetium-99m pyrophos-phate myocardial imaging if the imaging is performed 24 to 72 hours after the onset of symptoms. Pyrophosphate imaging has been useful in localizing the site and determining the extent of acute myocardial infarction. The “doughnut” pattern is associated with a relatively large incidence of subsequent congestive heart failure and death. However, the clinical utility of this information is limited because it is usually not available when it is most needed, on admission to the coronary care unit. Pyrophosphate imaging may have an important role in the evaluation of patients during the early follow-up period after hospital discharge from an episode of acute infarction. The finding of a persistently positive pyrophosphate image suggests a poor prognosis and is associated with a relatively large incidence of subsequent myocardial infarction and death.     

Rate-dependent effects of intravenous lidocaine, procainamide and amiodarone on intraventricular conduction

In this study, the duration of the QRS complex during ventricular pacing was used as an index of intraventricular conduction to quantitate the rate-dependent effects of intravenous lidocaine, procainamide and amiodarone. Right ventricular apical pacing (15 to 20 beats) was performed at cycle lengths of 600, 500, 400, 350, 300, 275 and 250 ms, before and 5 minutes after the intravenous administration of lidocaine in 11 patients (serum level 3.2 +/- 0.8 micrograms/ml [mean +/- SD] ), procainamide in 14 patients (serum level 8.2 +/- 1.9 micrograms/ml) and amiodarone in 12 patients (serum level 3.9 +/- 1.2 micrograms/ml). Electrocardiographic recordings were made at a paper speed of 150 mm/s. QRS duration was measured in a blinded fashion, with reproducibility within 5%. In the control state, QRS duration was the same at all paced cycle lengths. After lidocaine, procainamide and amiodarone administration, the shortest paced cycle length with complete ventricular capture was 250 +/- 0, 275 +/- 38 and 264 +/- 20 ms, respectively. At a paced cycle length of 600 ms, the increase in QRS duration compared with the control state was 1 +/- 2% with lidocaine (p greater than 0.05), 21 +/- 7% with procainamide (p less than 0.001) and 6 +/- 6% with amiodarone (p less than 0.05). At the shortest paced cycle length with complete capture, the increase in QRS duration compared with the control state was 20 +/- 6% with lidocaine (p less than 0.001), 42 +/- 11% with procainamide (p less than 0.001) and 26 +/- 4% with amiodarone (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of minoxidil on blood pressure and hemodynamics in severe hypertension

Eighteen patients with diastolic hypertension (100 to 120 mm Hg), in addition to propranolol, 160 mg daily, and hydrochlorothiazide, 100 mg daily, received progressively increased doses of either minoxidil or placebo in a double-blind crossover study. With minoxidil (average dose 19.7 mg) blood pressure decreased from 165/109 to 138/89 mm Hg without the appearance of orthostatic hypotension. Hypertrichosis and fluid retention did occur, with an average weight gain of 1.8 kg, concomitant with an increased plasma volume. Pulse rate and cardiac output increased; no significant changes were observed in plasma renin activity, renal plasma flow, glomerular filtration rate or excretion of catecholamines or aldosterone. Minoxidil appears to be a useful antihypertensive drug for treating patients who do not respond adequately to therapy with diuretic and beta adrenergic blocking agents.     

Noninvasive quantification of jeopardized myocardial mass in dogs using 2-dimensional echocardiography and thallium-201 tomography

The evaluation of jeopardized myocardial mass is important in defining the effect of interventions during myocardial infarction. To quantitate the in vivo mass at risk, 2-dimensional echocardiography (2-D echo) and thallium-201 single-photon emission computed tomography (SPECT) was performed in 10 closed-chest dogs after circumflex coronary artery occlusion. The 2-D images were manually digitized to compute left ventricular (LV) mass using a modified Simpson's rule algorithm. This measure of LV mass correlated well with the actual LV mass (r = 0.97). Perfused myocardial mass was estimated from thallium SPECT images 4 hours after occlusion using a region-growing algorithm. After the dogs were killed, the jeopardized mass was outlined using a dual perfusion staining technique using triphenyltetrazolium chloride and Evans blue dye. The actual perfused mass was well estimated by the thallium images (r = 0.96). The noninvasively determined mass at risk was calculated as: 2-D mass — thallium SPECT mass, and correlated well with the pathologically determined mass at risk (r = 0.91). Thus, the jeopardized mass may be determined noninvasively by using 2-D echo and thallium-201 tomography. This approach may provide further information regarding the effect of intervention therapy on jeopardized myocardium.     

Spontaneous changes in thallium-201 myocardial perfusion imaging after myocardial infarction

To examine regional myocardial perfusion after myocardial infarction, 26 patients underwent exercise electrocardiographic testing with thallium-201 myocardial perfusion imaging 3 weeks and 3 months after infarction. At 3 weeks, 9 of 26 patients (35%) had myocardial ischemia by exercise electrocardiographic testing, whereas 18 of 26 (69%) had ischemia by thallium-201 imaging. The thallium-201 scintigrams were scored by dividing each image, in 3 views, into 5 segments, using a 5-point scoring scheme. The exercise thallium-201 score was 44.3 ± 1.2 and increased to 47.3 ± 1.2 in the redistribution study (p < 0.001). Three months after infarction, although there was a significantly greater rate-pressure product which would predict a larger ischemic defect and a decrease in the stress thallium-201 score, the stress score was improved (48.3 ± 1.1, p < 0.001). The redistribution score was similar, that is, 48.9 ± 1.0. The improvement in thallium-201 myocardial perfusion was associated with a loss of stress-induced ischemia in 8 patients (30%). These results indicate that spontaneous improvements in thallium-201 myocardial perfusion imaging may occur after myocardial infarction.     

Automatic computer processing of digital 2-dimensional echocardiograms

Quantitative studies of left ventricular function using 2-dimensional echocardiography have been limited because of a lack of computerized methods to automatically analyze the echocardiographic images. Previous computer efforts have been directed at digitizing the video output of the 2-D echocardiogram, but this digitizing method has significant limitations. A direct digitization method that produces improvement in signal-to-noise ratio and, subsequently, improved automatic detection of endocardial and epicardial borders, was developed. With definition of these edges, left ventricular global and regional analysis is possible frame by frame so that dynamic changes in cardiac function may be assessed throughout the cardiac cycle. Further technologic advances in 2-D echocardiographic acquisition and image processing should allow computer processing of 2-D echocardiographic data in real time.     

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)     

Electrophysiologic testing in bundle branch block and unexplained syncope

Thirty-two patients with bundle branch block and unexplained syncope underwent electrophysiologic testing, including programmed ventricular stimulation with up to triple extrastimuli. The infranodal conduction time (HV) was 70 ms or greater in 12 patients. Pathologic infranodal block during atrial pacing occurred in 2 patients. Unimorphic ventricular tachycardia (VT) was induced in 9 patients (28%) and polymorphic VT in 5 (16%). A permanent pacemaker was implanted in patients with infranodal block during atrial pacing and, generally, in patients with an HV of 70 ms or more. Patients with inducible unimorphic or sustained polymorphic VT were treated with an antiarrhythmic drug. The mean follow-up period was 19 ± 14 months (± standard deviation). Three patients died suddenly: a noncompliant patient with inducible sustained VT; a patient with a normal electrophysiologic study treated empirically with quinidine for premature ventricular complexes; and a patient with an HV of 70 ms and no inducible VT treated with a permanent pacemaker. The actuarial incidence of sudden death was 10% at 45 months of follow-up. Only 2 patients had recurrent syncope; both had a normal electrophysiologic study.Approximately 50% of patients with bundle branch block and unexplained syncope who undergo electrophysiologic testing are found to have a clinically significant abnormality (HV of 70 ms or more, infranodal block during atrial pacing and inducible unimorphic VT), and some patients have more than 1 abnormality. Long-term management guided by the results of electrophysiologic testing generally is successful in preventing recurrent syncope. Patients who have a normal electrophysiologic study or who have inducible nonsustained polymorphic VT usually have a benign prognosis when left untreated.     

Radionuclide evaluation of postextrasystolic potentiation of left ventricular function induced by atrial and ventricular stimulation

Postextrasystolic potentiation of left ventricular function induced by ventricular and atrial stimulation was compared in 10 patients using radionuclide ventriculography. After insertion of pacing wires, a preliminary radionuclide ventriculogram was obtained and then ventricular and atrial trigeminy was induced in random order, each with identical R-R coupling intervals, each for 6 to 10 minutes. During the stimulation studies, radionuclide data were acquired in electrocardiographic gated list mode format. Left ventricular ejection fraction and relative end-diastolic and end-systolic volume changes were measured for each reformatted composite sinus, atrial and ventricular premature beat and potentiated beat. The volume changes were normalized to the count-based values obtained for the sinus beat of the appropriate study. Postextrasystolic potentiation induced by either ventricular or atrial stimulation was characterized by similar significant increases in left ventricular ejection fraction (mean ± standard deviation 7 ± 3 percent, p < 0.01 versus 7 ± 5 percent, p < 0.01; difference not significant [NS]) and decreases in relative end-systolic volume (?12 ± 12 percent, p < 0.01 versus ?12 ± 8 percent, p < 0.01; NS) but little change in relative end-diastolic volume (+5 ± 10 percent, NS versus +4 ± 7 percent, NS; NS). This was despite a longer compensatory pause (1,120 ± 220 versus 1,050 ± 190 ms, p < 0.01) after the ventricular premature beat. It is concluded that there is no difference in the postextrasystolic potentiation induced by atrial or ventricular premature stimulation.     

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.     

Use of balloon angioplasty to treat peripheral pulmonary stenosis

Balloon angioplasty was attempted in 13 children with peripheral pulmonary arterial (PA) stenosis. In 5 patients, angioplasty was successful in relieving the peripheral PA stenosis as judged by an increase in PA size of more than 75% over the predilatation size and a more than 50% reduction in the distal PA to main PA peak systolic pressure gradient. Each child has been followed for 6 to 30 months. All remain well, without signs of subsequent deterioration, and follow-up angiograms in 2 patients (at 10 and 12 months) showed persistence of anatomic and hemodynamic improvement. In 8 patients, angioplasty was unsuccessful: In 4 patients, stenosis at the site of a previous systemic-to-PA shunt could not be dilated and in 4 patients, angioplasty could not be performed because of technical difficulties. Thus, we could not dilate the stenosis in more than 60% of the patients; we also had a significant complication with the angioplasty procedure (perforation of a distal branch of the right pulmonary artery). Thus, although balloon angioplasty was not effective in all patients, it did provide significant improvement in some patients in whom traditional operative management is usually unsuccessful.     

Atrioventricular block: natural history after permanent ventricular pacing

The preimplantation status, postimplantation morbidity and causes of late mortality were summarized for 246 patients who underwent pacing for atrioventricular (A-V) block at the University of Michigan for the 14 years from 1961 to 1974. The survival rate at 1, 5 and 10 years was 88, 61 and 49 percent, respectively. Risk of death was greatest among patients with antecedent ischemic or hypertensive heart disease or congestive heart failure in the period before pacemaker implantation, patients older than 74 years at initial implantation and those receiving a pacemaker before 1965. Forty-two percent of the 109 deaths were related to apparent progression of underlying cardiac disease. Pacing system malfunction was a contributing documented cause of only 3 deaths. Even with permanent pacemaker implantation, patients with A-V block have a higher age-specific mortality rate than the general U.S. population. Survival improved steadily over the period of study. This change is attributed to apparent improvements in treatment of cardiovascular disease including more effective treatment of congestive heart failure and valve replacement for selected patients as well as elimination of immediate postoperative mortality.     

Two-dimensional echocardiographic determination of aortic and pulmonary artery sizes from infancy to adulthood in normal subjects

The aorta, right pulmonary artery and pulmonary trunk were measured from the 2-dimensional echocardiogram (2?D echo) of 110 normal subjects aged 1 day to 18 years. The vessel diameters were measured from the parasternal short-axis view, the suprasternal long-axis view and the suprasternal short-axis view. Measurements were made at end-systole and at end-diastole and in both an axial and lateral direction where possible. When analyzed with respect to body surface area (BSA), the echocardiographic measurements were linearly related to the square root of the BSA, and there was inequality of variance around the relation. To establish a range of normal values for each vessel dimension, a weighted regression analysis was used to produce estimates of the regression line and a set of tolerance intervals. The systolic vessel dimension was larger than the diastolic vessel dimension and the measurement of a vessel in an axial direction was larger than the measurement of the same vessel in a lateral direction. In general, when a vessel was measured in several views, the largest diameter was obtained using the view that imaged the vessel in cross section. These data on normal values for the echocardiographic measurement of the aorta and pulmonary arteries at different BSAs should be useful for identifying patients with abnormalities in arterial size and for the serial assessment of arterial size in children who have undergone surgical or medical therapy.     

Chronic verapamil therapy in pediatric and young adult patients with hypertrophic cardiomyopathy

Oral verapamil, 5.2 +/- 1.1 mg/kg/day (range 2.8 to 7), was administered to 13 pediatric patients with hypertrophic cardiomyopathy for 13 +/- 6 months (range 2 to 20). The patients had significant symptomatic improvement on verapamil therapy. Murmur intensity diminished in 6 patients during therapy and left ventricular (LV) electromotive forces on the electrocardiogram diminished in 4, increased in 5 and did not change in 4. Exercise endurance increased from 8.4 +/- 3.9 to 10.9 +/- 2.8 minutes (p less than 0.01). Seven patients had ST-segment depression (0.38 +/- 0.28 mV) before verapamil therapy, which improved after verapamil therapy in 5 (0.24 +/- 0.17 mV, p less than 0.02). Of 4 patients with exercise-induced ventricular ectopic activity, 3 had diminution or abolishment of ectopy following verapamil. By echocardiography, the patients had an increase in LV end-diastolic dimension from 3.4 +/- 0.7 to 3.9 +/- 0.8 cm (p less than 0.01), with no significant change in shortening fraction (46.1 +/- 8.0% vs 44.6 +/- 8.0%). When adjusted for body size and age there was a significant decrease in LV septal thickness (from 106 +/- 70 to 45 +/- 52% of predicted normal values, p less than 0.05) and LV posterior wall thickness (from 40 +/- 45 to 5 +/- 26% of predicted normal values p = 0.05) after verapamil. Isovolumic relaxation time decreased from 69 +/- 26 to 42 +/- 19 ms after verapamil (p less than 0.01). Systolic anterior motion of the anterior mitral leaflet disappeared in 5 of 8 patients and midsystolic closure of the aortic valve was no longer present in 4 of 8.(ABSTRACT TRUNCATED AT 250 WORDS)     

echocardiographic measures in 6 to 7 year old children after an 8 month exercise program

The influence of an exercise intervention program on cardiac dimensions was studied in 79 normal children (aged 6 to 7 years) in an experimental (n = 38) and control (n = 41) group. The experimental group participated in an aerobic exercise session that met four days/week for 8 months. Anthropometric measurements and M mode echocardiograms were obtained before and after the intervention program. Comparison of the data between groups revealed no significant (probability [p] > 0.05) differences in left ventricular end-diastolic dimension, shortening fraction or resting heart rate. Left ventricular posterior wall thickness exhibited a significant increase (p < 0.0256) from 3.9 to 4.7 mm in the experimental group compared with an increase from 4.3 to 4.6 mm in the control group after correcting for preintervention differences with an analysis of covariance. Likewise, left ventricular mass increased significantly (p < 0.0004) from 21.2 to 27.4 g in the experimental group compared with 23.4 to 25.8 g in the control group. These findings indicate that when compared with control subjects, young children involved in an aerobic exercise program showed progressive increases in left ventricular posterior wall thickness and left ventricular mass and no change in left ventricular end-diastolic dimension, shortening fraction or resting heart rate.     

Altered baroreceptor function in children with systolic hypertension after coarctation repair

To determine whether altered baroreceptor function may contribute to systemic hypertension after coarctation of the aorta (C of A) repair, baroreceptor function was evaluated in 6 children with repaired C of A mild arm systolic hypertension. Data were compared with those from 7 normotensive control children with hemodynamically mild heart disease. Age at C of A repair averaged 9.9 ± 3.1 years (mean ± standard deviation [SD]). Arm systolic pressure was 143.8 ± 2.9 mm Hg in the C of A repair group, compared with 118.3 ± 9.9 for control subjects (p < 0.001). At catheterization, steady-state sigmoidal baroreceptor function curves relating mean arterial pressure to R-R interval were derived by increasing and decreasing mean arterial pressure with small injections of phenylephrine and nitroprusside. Compared with control subjects, the baroreceptor function curves of children with repaired C of A (1) are reset about a higher baseline mean arterial pressure (108.8 ± 6.6 versus 90.3 ± 8.6 mm Hg, p < 0.01), (2) have a decreased slope (7.9 ± 3.7 versus 17.4 ± 3.6 ms/mm Hg, p < 0.001), and (3) have a diminished R-R interval range (246.7 ± 81.5 versus 535.7 ± 97.2 ms, p < 0.001). Thus, in children with hypertension after C of A repair, the baroreflex is reset to an elevated mean arterial pressure level and has a diminished sensitivity to changes in arterial pressure.     

Rationale of therapy in the patient with acute myocardial infarction and life-threatening arrhythmias: a focus on bretylium

Experimental evidence suggests a number of pathologic and electrophysiologic mechanisms that may help initiate ventricular arrhythmias accompanying myocardial ischemia and infarction. Early and late phase events are associated with reentry or an enhancement of focal mechanisms, or both. These can initiate ventricular tachycardia (VT) or ventricular fibrillation (VF), or both. The presence of distinct mechanisms that may initiate and maintain life-threatening dysrhythmias early in myocardial ischemia suggest different pharmacologic approaches for their prevention or suppression. Another consideration concerns patients subjected to coronary artery angioplasty or thrombolytic therapy and the development of arrhythmias associated with reperfusion of the once ischemic myocardium. The electrophysiologic mechanisms associated with reperfusion arrhythmias are unknown, and little is known about appropriate therapy for each episode of cardiac dysrhythmia. Ventricular extrasystoles or VT usually precedes VF. These premonitory arrhythmias are poor criteria for the institution of antiarrhythmic drug therapy, because VF develops within 1 to 10 minutes after the appearance of the rhythmic disturbances. Some authorities suggest that all patients with acute myocardial infarction should receive prophylactic antiarrhythmic therapy, because warning arrhythmias either do not occur at all or provide insufficient time to intervene pharmacologically. Many of the new class I antiarrhythmic agents effectively reduce the frequency of premature ventricular depolarizations, but lack specific antifibrillatory activity. However, the recent introduction of bretylium into clinical cardiology opens a new approach to preventing life-threatening ventricular dysrhythmias. Along with other members of class III, bretylium exerts different cardiac electrophysiologic effects than do the other 3 classes of drugs.(ABSTRACT TRUNCATED AT 250 WORDS)