Myocardial hibernation identified by hyperbaric oxygen treatment and echocardiography in postinfarction patients: comparison with exercise thallium scintigraphy.

To evaluate the potential for hyperbaric oxygen (HBO) to produce transient improvement in function in areas of myocardium ischemic at rest (hibernating myocardium), 24 patients were studied within 1 week of acute myocardial infarction. Results were compared with single-photon emission computed tomography (SPECT) thallium-201 exercise scintigraphy. Echocardiography demonstrated improved contraction following HBO in 20 of 62 damaged left ventricular segments in 12 of 24 patients. Thirteen of the 28 segments and 9 of the 14 patients showing reversible ischemia on SPECT imaging showed improvement with HBO. There were eight segments with apparently normal resting contraction that showed a reversible thallium defect. Of 42 segments with fixed contraction abnormalities following HBO, eight had reversible thallium defects, four had normal thallium kinetics, and 30 had fixed thallium defects. Thus hyperbaric oxygen can demonstrate improvement in function in some segments of left ventricle after infarction. There is some overlap with viability as determined by thallium studies, but the two techniques may be complementary in describing myocardial ischemia.


Long-term follow-up after percutaneous transluminal coronary angioplasty in patients with single-vessel disease.

Seven hundred ninety-eight patients with symptomatic single-vessel disease who underwent percutaneous transluminal coronary angioplasty (PTCA) between 1977 and 1985 were reevaluated by questionnaire 78 +/- 23 months after dilatation. Indication for PTCA was stenosis of > or = 70%, anginal symptoms, and objective signs of myocardial ischemia. The immediate success rate was 81.2%, and severe complications occurred in 7.1%, which included two fatal complications (0.3%). Repeat angiograms were performed in 582 of 648 patients who underwent successful dilatation and showed restenosis in 143 cases (24.6%). Within 1 year after the first dilatation, 586 patients had been successfully revascularized by PTCA (i.e., there was no evidence of restenosis or redilatation was successful), and 113 patients had undergone bypass surgery. The remaining 99 patients were treated medically if PTCA was unsuccessful or if restenosis (> or = 70%) that was not amenable to redilatation was present. The 8-year overall survival probability was 91.7%, and cardiac survival was 95.5%. The 8-year event-free survival probability was 52.7% for all patients: 62.5% in patients who had successful PTCA and 14.5% in patients who had unsuccessful PTCA (p = 0.0000). The cardiac survival probabilities of patients with lasting PTCA success at 1 year and of surgically treated patients were significantly better than those of patients who did not have successful revascularization (at 8 years 97.2% and 98.1% vs 88.9%; p < 0.04). Late events (> or = 1 year) occurred more often in patients who did not have successful revascularization compared with patients who had successful PTCA (at 8 years 57.9% were event-free vs 74.4%; p < 0.0001); even fewer late events were observed in surgically treated patients (at 8 years 88.2% were event-free; p < 0.004). Cox's proportional hazards regression analysis revealed left ventricular ejection fraction and revascularization status at 1 year as determinants of overall, cardiac, infarct-free, and event-free survival probabilities. At the time of reevaluation significantly more patients in the successful PTCA subgroup were still free of symptoms or had experienced improvement than patients in the bypass or medical subgroups (86.8% vs 68.9% and 59.5%, respectively; p < 0.0001), and more patients in the successful PTCA subgroup were still working (75.4% vs 53.3% and 56.9%, respectively; p < 0.001). We concluded that patients with single-vessel disease who have undergone successful dilatation have an excellent long-term prognosis with regard to survival, cardiac symptoms, and vocational status.(ABSTRACT TRUNCATED AT 400 WORDS)


Long-term efficacy of triple-vessel angioplasty in patients with severe three-vessel coronary artery disease.

Between May 1982 and December 1988, a total of 103 patients underwent angioplasty of all three major coronary arteries at a single institution. Angiographic success was achieved in 334 of 352 vessels (95%) and in 441 of 460 lesions (96%). No patients required urgent bypass surgery, and none died during the procedure; six had non-Q wave infarctions. The mean length of follow-up time was 49 +/- 15 months (range 28 to 107 months). There have been 11 deaths, and one patient has undergone cardiac transplantation. Thirty-six patients had a clinical recurrence; 30 had repeat angioplasty and five had bypass surgery. Another nine patients eventually had bypass surgery after the clinical recurrence. At 48 months actuarial event-free rates are myocardial infarction, 98%; bypass surgery, 88%; and death, 89%. Of 86 current survivors, 58 are in functional class O to I, 21 are in class II, and seven are in class III.


Aggressive clinical pattern of angina at restenosis following coronary angioplasty in unstable angina.

The frequency, clinical pattern, and timing of recurrent angina following successful single-lesion percutaneous transluminal coronary angioplasty (PTCA) was assessed in a consecutive group of 104 patients with stable angina and in 85 with unstable angina. In addition, the relationship between lesion morphology and angiographic features and the pattern of recurrent angina was determined. Restenosis, defined as recurrence of symptoms with > 50% stenosis at the site of PTCA, occurred in 25 (24%) of the stable group and in 23 (27%) of the unstable group (p = NS). The pattern of angina at repeat presentation was aggressive in nature in 8% of the stable group and in 48% of the unstable group (p = 0.002). The time interval between the recurrence of symptoms and repeat coronary angiogram or PTCA was longer in the nonaggressive group than in the aggressive group, 16 +/- 12.1 and 5 +/- 6.8 weeks, respectively (p < 0.003). The key factors predicting the recurrent angina pattern identified by multiple logistic regression analysis were the angina status pre-PTCA (p = 0.001) and the presence of double-vessel disease (p = 0.01). An aggressive pattern of angina at the time of restenosis is frequent in patients with unstable angina at the time of PTCA, and close post-PTCA surveillance is necessary in these patients.


Edge detection versus densitometry in the quantitative assessment of stenosis phantoms: an in vivo comparison in porcine coronary arteries.

The aim of this study was the in vivo validation and comparison of the geometric and densitometric technique of a computer-assisted automatic quantitative angiographic system (CAAS system). In six Landrace Yorkshire pigs (45 to 55 kg), precision-drilled phantoms with a circular lumen of 0.5, 0.7, 1.0, 1.4, and 1.9 mm were percutaneously introduced into the left anterior descending or left circumflex coronary artery. Twenty-eight coronary angiograms obtained with the phantom in a wedged intracoronary position could be quantitatively analyzed. Minimal lumen diameter, minimal cross-sectional area, percent diameter stenosis, and cross-sectional area stenosis were automatically measured with both the geometric and densitometric technique and were compared with the known phantom dimensions. When minimal lumen diameter was measured using the geometric approach, a nonsignificant underestimation of the phantom size was observed, with a mean difference of -0.06 +/- 0.14 mm. The larger mean difference observed with videodensitometry (-0.11 +/- 0.20 mm) was the result of the failure of the technique to differentiate the low lumen videodensities of two phantoms of smaller size (0.5 and 0.7 mm) from a dense background. Percent cross-sectional area stenosis measured with the two techniques showed a good correlation with the corresponding phantom measurements (mean difference between percent cross-sectional area stenosis calculated from the quantitative angiographic measurements and the corresponding phantom dimensions was equal to 2 +/- 6% for both techniques, correlation coefficient = 0.93 with both techniques, SEE = 5% with the geometric technique and 6% with the densitometric approach).(ABSTRACT TRUNCATED AT 250 WORDS)


Relationship between septal perfusion, viability, and motion before and after coronary artery bypass surgery.

The etiology of abnormal interventricular septal motion occurring after open-heart surgery using cardiopulmonary bypass has not been clarified. Intraoperative ischemic septal injury has been proposed as one explanation for this finding. To examine this possibility, resting septal perfusion and viability were studied using rest and redistribution thallium-201 scintigraphy in 16 patients before and after coronary artery bypass surgery. The results were compared with septal motion on preoperative and postoperative resting gated blood pool scans. Preoperatively, septal thallium uptake was normal in 10 of 16 patients, and septal motion was normal in 14 of 16. Postoperatively, septal thallium uptake was normal in 11 of 16 patients, while septal motion was abnormal in all. Thus abnormal postoperative septal motion is usually associated with normal septal perfusion and viability on thallium scans and therefore is not the result of septal ischemic injury in a majority of patients.


Detection of restenosis with dobutamine stress test after coronary angioplasty.

Dobutamine ECG tests were serially performed before, at 15 days, and at 2 and 6 months after successful coronary angioplasty in 58 patients. The dose of dobutamine was progressively increased from 5 micrograms/kg/min to a maximum of 40 micrograms/kg/min every 5 minutes, with ECG and blood pressure control. Coronary angiography was performed at the end of the study. At 15 days after coronary angioplasty, the dobutamine test was of little value for the diagnosis or prediction of restenosis. At the end of the study, both the presence of angina and the results of the dobutamine test were related to coronary angiography, and their accuracy was calculated for the detection of mild (> or = 50%) and severe (> or = 70%) restenosis or new coronary lesions. The accuracy of angina was 68% for the detection of mild lesions and 70% for that of severe lesions, whereas the accuracy of the dobutamine test was 78% for mild lesions and 80% for severe lesions. It is concluded that the dobutamine stress test is a simple and useful method for the detection of restenosis when it is performed at 2 and 6 months after coronary angioplasty. However, it cannot distinguish between restenosis or new coronary lesions.


Metabolic effects of adenosine on regional myocardial ischemia by phosphorus 31 nuclear magnetic resonance spectroscopy.

The metabolic effects of adenosine on regionally ischemic myocardium were investigated in an open-chest rabbit model by means of phosphorus 31 nuclear magnetic resonance (NMR) spectroscopy. Sixteen anesthetized New Zealand white rabbits were subjected to thoracotomy; a reversible snare occluder was placed around a large branch of the left circumflex coronary artery, and an NMR surface coil was positioned adjacent to the myocardium perfused by this vessel. The animals were placed in a 2.0 T CSI spectrometer (GE Medical Systems, Fremont, Calif.), and baseline spectra were acquired. Eight animals were treated with intravenous adenosine (25 mg/kg), and eight rabbits served as control subjects. All animals were subjected to a 10-minute period of ischemia followed by a period of reperfusion. NMR spectra were acquired during both intervals. During the occlusion period, expected increases in inorganic phosphate levels and decreases in phosphocreatine levels were observed in both groups; however, inorganic phosphate increased less in adenosine-treated animals (adenosine: 33 +/- 2.8% total spectral area during occlusion vs control: 41 +/- 3.1%) and phosphocreatine diminished less with adenosine (adenosine: 26 +/- 3% vs control: 13 +/- 1.2%; p < 0.002). No significant differences were seen in beta-adenosine triphosphate levels. In both groups the metabolite levels during reperfusion recovered to near baseline values, although phosphocreatine remained slightly higher in the treated group during early reperfusion. An apparent cardioprotective effect of adenosine on relative phosphocreatine and inorganic phosphate levels can be observed in intact rabbits by means of phosphorus 31 NMR spectroscopy.


Diagnostic and prognostic value of ambulatory electrocardiographic monitoring.

To evaluate the diagnostic and prognostic value of continuous ambulatory ECG (AECG) monitoring, we studied 124 patients with chest pain syndromes by stress myocardial perfusion scintigraphy (MPS) and AECG. MPS was classified as normal or with fixed or reversible defects involving one or more than one vascular territory. Positive AECGs were divided into those with mild (< or = 1.5 mm), moderate (1.5 to 2.5 mm), and severe (> or = 2.5 mm) ST segment displacement. Among 61 patients with a negative AECG, 93% had limited ischemia or normal scintigraphic studies. All 24 patients with moderately or severely positive AECGs had reversible defects on MPS. Among those with severely positive AECGs, nine (75%) had multivessel scintigraphic ischemia. Severe ST segment depression on AECG was highly related to multivessel perfusion defects and to a large amount of myocardium in jeopardy. A negative AECG generally indicated limited or absent ischemia and thus a more benign prognosis. Induced symptoms and the daily ischemic burden were not related to the severity of induced AECG or MPS abnormalities. AECG may provide independent information as to the severity and related risk of ischemia.


Power law analysis of the signal-averaged electrocardiogram for identification of patients with ventricular tachycardia: effect of bundle branch block.

Signal-averaged ECGs that use time-domain analysis are useful for the identification of patients at risk for ventricular tachycardia (VT). Bundle branch block (BBB) and other conduction defects reduce the value of this approach, but frequency-domain analysis has shown promise in such patients. The purpose of the present study was to examine a new frequency-domain approach to signal-averaged ECGs in patients with and without BBB: power law scaling (PLS). PLS was performed by plotting the power spectrum of the entire signal-averaged ECG on a plot of log power versus log frequency and determining the slope (beta) by least-squares regression. This method was studied in 346 patients. Results of discriminant analysis revealed better sensitivity, specificity, positive predictive value, negative predictive value, and percentage correctly predicted when this method was compared with time-domain indexes. A large proportion of the variance in PLS (19%) was found to be due to findings in patients with VT; whereas the best time-domain index, duration of the filtered QRS signal, explained only 6% of the variance in the group with VT. Mean levels of PLS (+/- standard deviation) were decreased for the group with VT (-3.55 +/- 0.95) as compared with the group without VT (-4.34 +/- 0.59; p < 0.001), suggesting a decrease in the time correlation of the signal. Thus this method of frequency-domain analysis of the signal-averaged ECG was useful in identifying patients with sustained VT despite the presence of significant conduction defects.(ABSTRACT TRUNCATED AT 250 WORDS)


Predictors of surgical mortality and long-term results of endocardial resection for drug-refractory ventricular tachycardia.

The results of surgical therapy performed in 51 consecutive patients with ventricular tachycardia were reviewed to determine short- and long-term predictors of success of such therapy in preventing recurrences of life-threatening ventricular arrhythmias. Of 41 patients (80%) who survived surgery, 40 had postoperative programmed stimulation and, of these patients, 78% (n = 31) had no inducible ventricular tachycardia on no antiarrhythmic therapy. This group had a very low incidence of arrhythmia recurrence, with only one nonfatal episode of ventricular tachycardia after a mean follow-up of 41 +/- 30 months. In contrast, two of the nine patients (22%) who had inducible arrhythmias postoperatively had cardiac arrest (p = 0.12). Multivariate analysis identified two significant predictors of perioperative mortality in our patients: increased duration of cardiopulmonary bypass time and increased baseline pulmonary capillary wedge pressure. It is concluded that (1) patients who do not have inducible ventricular tachycardia after arrhythmia surgery have a very low incidence of recurrent arrhythmia and (2) prolonged time of cardiopulmonary bypass and increased pulmonary capillary wedge pressure are predictive of perioperative mortality.


A prospective study of the efficacy and safety of adjuvant metoprolol and xamoterol in combination with amiodarone for resistant ventricular tachycardia associated with impaired left ventricular function.

Combination antiarrhythmic drug therapy may be more effective than treatment with a single agent for control of refractory cases of sustained ventricular tachycardia (VT). In a prospective randomized crossover study of 20 patients with impaired left ventricular function (ejection fraction of 28% +/- 8%) and recurrent VT in spite of treatment with amiodarone, we compared the efficacy and safety of adjuvant therapy with metoprolol, 50 mg two times daily and xamoterol, 200 mg two times daily. Metoprolol caused hemodynamic deterioration in five patients, and only one also experienced intolerance to xamoterol. Sustained VT was inducible in all 20 patients who were receiving amiodarone alone but was suppressed or rendered nonsustained in 8 of 20 patients during treatment with amiodarone plus xamoterol and in 6 of 17 patients during treatment with amiodarone plus metoprolol. Addition of xamoterol restored sinus rhythm in four patients who presented with incessant VT, and metoprolol was effective for three of them. Neither beta-blocker significantly altered tachycardia cycle length or any electrophysiologic parameter other than the slowing of the sinus rate. Both beta-blockers suppressed exercise-induced VT in 3 of 4 patients, and addition of xamoterol significantly increased treadmill exercise duration (7.1 +/- 1.8 min) compared with administration of amiodarone alone (3.8 +/- 1.5 min; p < 0.01). Fourteen patients were discharged with prescriptions for amiodarone-beta-blocker combinations. During a mean follow-up period of 13 months (range, 2 to 24 months), there were three cases of recurrent VT (in all patients VT remained inducible) and no sudden deaths.(ABSTRACT TRUNCATED AT 250 WORDS)


Subcutaneous lidocaine affects inducibility in programmed electrophysiology testing in children: a follow-up study.

Invasive cardiac electrophysiology testing during cardiac catheterization requires local anesthesia at the point of entry for the catheters. Frequently, lidocaine is employed for this purpose. A prospective study completed in 1990 indicated that subcutaneous administration of lidocaine adversely influenced the inducibility of arrhythmias in pediatric patients. Upon completion of that study, lidocaine concentration was reduced from 1% to 0.5%, and extra caution was taken to avoid deep penetration during administration. A follow-up, prospective study was performed to evaluate inducibility under these changed conditions. Because the depressant effect of lidocaine on inducibility was age- and weight-related, the second study group was required to have statistically indistinguishable age and weight distributions from the first group to eliminate these variables as factors in inducibility. A total of 177 subjects were collected in the second group before a periodic random computer match with the first group produced 99 individuals with the required age and weight distributions. Analysis of the electrophysiology tests in the second study revealed that: (1) incidence of inducibility was higher in the second group (58 of 99 versus 43 of 99, p < 0.05); (2) average lidocaine dose per kilogram was lower (1.8 mg/kg versus 3.28 mg/kg, p < 0.0001); (3) average lidocaine serum concentration was also lower (0.58 micrograms/ml versus 1.47 micrograms/ml, p < 0.0003); (4) in contrast to the first study, neither lidocaine dose nor serum concentration had any effect on inducibility. We conclude that the new procedures for lidocaine administration effectively removed lidocaine as a factor in inducibility.


Significance of coronary angiography, left heart catheterization, and endomyocardial biopsy for the diagnosis of idiopathic dilated cardiomyopathy.

Many physicians assume that a reliable diagnosis of idiopathic dilated cardiomyopathy can be made by noninvasive methods, mainly echocardiography. On the other hand, use of endomyocardial biopsy in those patients who have undergone left heart catheterization and who demonstrate left ventricular dysfunction of unknown origin is increasing. Therefore the purpose of this study was to investigate the yield of that diagnostic strategy in patients with the tentative diagnosis of idiopathic dilated cardiomyopathy. Between 1980 and 1988, 3.2% of our 15,442 patients were diagnosed as having idiopathic dilated cardiomyopathy on the basis of left heart catheterizations and coronary angiograms. Idiopathic dilated cardiomyopathy was diagnosed in 444 patients on the basis of clinical data and results of noninvasive tests before catheterization, but in only 295 of these cases was the diagnosis confirmed by means of coronary angiography and left heart catheterization (predictive value of noninvasive tests is 66%). The remaining 34% of patients demonstrated extensive coronary artery disease (13%), significant valvular heart disease (11%), and other or no heart disease (10%). The diagnostic sensitivity of noninvasive tools (patient history, ECG, stress test, echocardiography) was only 59%. Left heart catheterization can easily be combined with endomyocardial biopsy. With the use of histologic techniques, specific heart muscle diseases were detectable in 3.5% of 209 patients, but in only 1% could therapeutic consequences be determined. Thus coronary angiography and left heart catheterization are mandatory for the correct diagnosis of idiopathic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)


Point mutations in mitochondrial DNA in patients with hypertrophic cardiomyopathy.

Recent advances suggest that mutations in nuclear DNA are involved in the etiology of autosomal dominant hypertrophic cardiomyopathy. Mitochondria have their own DNA, and mutations in mitochondrial DNA have been shown to contribute to the genesis of various diseases. In this study, we developed rapid sequencing methods with the use of a fluorescence-based sequencing system and analyzed total mitochondrial DNA of seven patients with nonautosomal dominant hypertrophic cardiomyopathy. Multiple point mutations were observed in all patients with hypertrophic cardiomyopathy, although some of them were common among the subjects examined and the others are unique to each subject. Point mutations in transfer RNA genes were observed in five of the seven patients, and point mutations that replaced conserved amino acids were also observed. These mutations may result in the impairment of mitochondrial function. According to these results, mutations in mitochondrial DNA may contribute to the genesis of some cases of nonautosomal dominant hypertrophic cardiomyopathy, and our methods may be useful for the detection of point mutations in mitochondrial DNA.


Contrasting patterns of arterial and venous dilatation after intravenous captopril in patients with chronic cardiac failure and their relationship to plasma angiotensin II concentrations.

A 25 mg intravenous bolus injection of captopril caused an abrupt and rapid decrease in systemic vascular resistance (time to maximum effect 15 minutes), but a more gradual decrease in right atrial pressure (time to maximum effect 75 minutes) in 12 patients with chronic cardiac failure. Plasma angiotensin II concentrations fell significantly, reaching their lowest concentrations at 75 minutes after the injection of captopril, at which time systemic vascular resistance had begun to return toward control values. There was no correlation between the acute arteriodilator response and pretreatment plasma renin activity or plasma angiotensin II concentrations, or the decrease in plasma angiotensin II concentrations. There was a significant correlation between the decrease in plasma angiotensin II concentrations and the decrease in right atrial pressure (r = 0.67, p < 0.05). These findings suggest that in contrast to the venous response to intravenous captopril, the arterial response is not entirely dependent on a decrease in the circulating plasma angiotensin II concentration.


Additive myocardial depressant effects of cocaine and ethanol.

Although significant morbidity and mortality have been associated with the combined use of cocaine and ethanol, the cardiovascular effects of this combination are unknown. In this study, the effect of ethanol on cocaine-induced cardiovascular alterations was examined in two groups (n = 8 each) of dogs, which were randomized to receive either ethanol (1.68 gm/kg intravenously) or saline solution and cocaine (2 mg/kg intravenously). Ethanol had no effect on heart rate, mean arterial pressure, or rate-pressure product; but it increased ventricular end-diastolic pressure (p < 0.05), reduced coronary diameter (p < 0.02), and decreased ejection fraction by 16% +/- 4% (p < 0.005) from baseline. Cocaine produced increases in mean arterial pressure, rate-pressure product, and left ventricular end-diastolic pressure that were similar in both groups. After administration of cocaine, left ventricular ejection fraction decreased 16% +/- 2% (p < 0.001) from the baseline value in controls and 32% +/- 5% (p < 0.0002 vs baseline; p < 0.01 vs controls) in the ethanol group. Coronary diameter decreased (p < 0.05) in both groups after administration of cocaine; however, there was no difference between groups in the response of coronary circulation to cocaine. Cocaine and ethanol depress myocardial function, and their effects are additive. Failure of ethanol to enhance cocaine-induced coronary vasoconstriction suggests that the additive myocardial depressant effect of this combination is not related to ischemia but rather to a direct toxic effect of these drugs. Individuals who combine ethanol and cocaine may be at increased risk of hemodynamic compromise.


Relationship between plasma atrial and brain natriuretic peptide concentration and hemodynamic parameters during percutaneous transvenous mitral valvulotomy in patients with mitral stenosis.

Brain natriuretic peptide (BNP), a family of peptides with structural and biologic homologies to previously identified atrial natriuretic peptide (ANP), has been found in human cardiac tissue and plasma. To examine the secretion mechanism of these peptides, we have studied the relationship between their plasma concentrations and hemodynamic parameters before and at 0.5 and 24 hours after percutaneous transvenous mitral commissurotomy (PTMC) in 14 patients with mitral stenosis. We have also investigated the validity of measuring plasma natriuretic peptides as a means for estimating changes in hemodynamic parameters after PTMC. The procedure decreased left atrial pressure (p < 0.01) with an elevation in left ventricular end-diastolic pressure (p < 0.05). Plasma ANP levels decreased significantly after PTMC (before, 64.1 +/- 33.7 fmol/ml; at 0.5 hour, 58.9 +/- 27.7 fmol/ml; at 24 hours, 45.7 +/- 18.3 fmol/ml; p < 0.01), whereas plasma BNP levels remained unchanged after the procedure (before, 5.3 +/- 1.5 fmol/ml; at 0.5 hour, 5.6 +/- 1.9 fmol/ml; at 24 hours, 5.0 +/- 1.9 fmol/ml; p = NS). There was a significant relationship between basal plasma ANP and left atrial pressure (r = 0.88; p < 0.001), and changes in plasma ANP were correlated with those in left atrial pressure (r = 0.69; p < 0.01). Basal plasma BNP was significantly correlated with basal left ventricular end-diastolic pressure (r = 0.65; p < 0.05) but not with the other measured hemodynamic parameters or with plasma volume.(ABSTRACT TRUNCATED AT 250 WORDS)


Quantification of mitral regurgitation with the proximal flow convergence method: a clinical study.

Accurate quantitation of valvular incompetence remains an important goal in clinical cardiology. It has been shown previously that when color flow Doppler mapping is used, simple measurements of apparent jet size do not correlate closely with regurgitant flow rate and regurgitant fraction. Recently the proximal flow convergence method has been proposed to quantify valvular regurgitation by analysis of the converging flow field proximal to a regurgitant lesion. Flow rate Q can be calculated as Q = 2 pi r2v(a), where v(a) is the aliasing velocity at a distance r from the orifice. In 54 patients (43 with sinus rhythm and 11 with atrial fibrillation) who had at least mild mitral regurgitation according to semiquantitative assessment, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated with the proximal flow convergence method and compared with values that were obtained by the Doppler two-dimensional echocardiographic method. Regurgitant stroke volumes (Vr) as calculated by the proximal flow convergence method correlated very closely with values that were obtained by the Doppler two-dimensional method, with r = 0.93 (y = 0.95x + 0.55) and delta Vr = -0.3 +/- 4.0 cm3. Regurgitant flow rates (Q) as calculated by both methods showed a similar correlation: r = 0.93 (y = 0.95x + 54) and delta Q = -34 +/- 284 cm3/min. The correlation for regurgitant fraction (RF) as calculated by both techniques showed r = 0.89 (y = 0.98x + 0.006) and delta RF = -0.005 +/- 0.06. All correlations were slightly better for the group of patients with sinus rhythm than for the study group of patients with atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)


Aortic valve prolapse with aortic regurgitation assessed by Doppler color-flow echocardiography.

The incidence of and the Doppler color-flow echocardiographic characteristics of aortic valve prolapse with nonrheumatic aortic regurgitation were examined. Aortic valve prolapse was observed in 21 of 243 patients (15 men and 6 women) with aortic regurgitation as detected by Doppler color-flow echocardiography (rheumatic, 112; nonrheumatic, 131) in 1247 consecutive patients. Patients with aortic valve prolapse included three patients with essential hypertension and one with annuloaortic ectasia. The remaining 17 patients (7% of those with aortic regurgitation) had no other associated cardiovascular disease (idiopathic aortic valve prolapse). Prolapse of the mitral or the tricuspid valve or both was associated with aortic valve prolapse in seven patients. Aortic regurgitation jet was markedly deviated from the axis of left ventricular outflow tract toward the anterior mitral leaflet or the interventricular septum in 17 of 21 (81%) patients with aortic valve prolapse, whereas 28 of 110 (25%) patients with nonrheumatic aortic regurgitation without prolapse and 17 of 112 (15%) patients with rheumatic aortic regurgitation without prolapse showed the deviation of regurgitant jet (p < 0.001). In conclusion, idiopathic aortic valve prolapse is one of the significant causes of aortic regurgitation, and a marked deviation of regurgitant jet is a characteristic Doppler color-flow echocardiographic finding of aortic regurgitation that results from aortic valve prolapse.


Isovolumic relaxation time varies predictably with its time constant and aortic and left atrial pressures: implications for the noninvasive evaluation of ventricular relaxation.

The isovolumic relaxation time (IVRT) is an important noninvasive index of left ventricular diastolic function. Despite its widespread use, however, the IVRT has not been related analytically to invasive parameters of ventricular function. Establishing such a relationship would make the IVRT more useful by itself and perhaps allow it to be combined more precisely with other noninvasive parameters of ventricular filling. The purpose of this study was to validate such a quantitative relationship. Assuming isovolumic relaxation to be a monoexponential decay of ventricular pressure (pv) to a zero-pressure asymptote, it was postulated that the time interval from aortic valve closure (when pv = p(o)) until mitral valve opening (when pv = left atrial pressure, pA) would be given analytically by IVRT = tau[log(p(o))-log(pA)], where tau is the time constant of isovolumic relaxation and log is to the base e. To test this hypothesis we analyzed data from six canine experiments in which ventricular preload and afterload were controlled nonpharmacologically. In addition, tau was adjusted with the use of beta-adrenergic blockade and calcium infusion, as well as with hypothermia. In each experiment data were collected before and after the surgical formation of mitral stenosis, performed to permit the study of a wide range of left atrial pressures. High-fidelity left atrial, left ventricular, and aortic root pressures were digitized, the IVRT was measured from the aortic dicrotic notch until the left atrioventricular pressure crossover point, and tau was calculated by nonlinear least-squares regression.(ABSTRACT TRUNCATED AT 250 WORDS)


Doppler assessment of right ventricular filling dynamics in systemic hypertension: comparison with left ventricular filling.

To assess right ventricular filling dynamics in systemic hypertension, pulsed Doppler echocardiographic studies were obtained at the tricuspid and mitral anuli in 43 untreated hypertensive patients, aged 23 to 66 years, and in 42 age-matched normotensive control subjects. In hypertensive patients, the ratio of late to early peak filling velocity and atrial filling fraction were higher, while normalized peak filling rate, one third and one half filling fractions were lower, compared with control values. Right ventricular filling dynamics correlated poorly with age in hypertensive patients, and were unrelated to left ventricular mass or left ventricular wall thickness. Weak correlations were only found between right ventricular wall thickness and right ventricular peak late inflow velocity, first half and first third filling fractions. However, right ventricular filling dynamics were closely related to left ventricular filling dynamics in both hypertensive patients (r = 0.49 to 0.82) and normal individuals (r = 0.55 to 0.86). Thus right ventricular filling dynamics are altered in hypertension, independently of left ventricular mass or blood pressure, are weakly related to right ventricular thickness, but remain closely correlated to left ventricular filling dynamics.


The clinical relevance of myocardial viability in patient management.

This study examined the importance of viability as a clinical issue in 532 patients with angiographically proven CAD who underwent exercise SPECT thallium imaging. Conventional 4-hour delayed images were used to differentiate scar tissue from ischemia (20 segments per patient). There were 90 patients (17%) with normal images, 274 patients (52%) with reversible defects only, and 168 patients (31%) with scar tissue either with or without associated ischemia. The patients with scar tissue were subdivided according to the number of segments with fixed defects and the number of additional reversible defects. There were 114 patients with scar tissue alone or more scar tissue than ischemia. Contrast ventriculography in these 114 patients revealed normal wall motion or ejection fraction in 50 patients. On the basis of results of thallium imaging alone, the issue of viability was probably significant in 114 patients (21%); however, when the ventriculographic data were also included, the issue was significant in only 64 patients (12%) (p < 0.001). Thus myocardial viability is an important issue in 21% of patients with CAD when conventional thallium imaging is used, but this percentage decreases to 12% when wall motion and ejection fraction data are also included. These data may be important in considerations for the need of metabolic imaging and emerging scintigraphic techniques.


Cardiac manifestations of the antiphospholipid syndrome.

The antiphospholipid syndrome has been associated with multiple cardiac abnormalities. The earliest reports were of valvular disease, including verrucous endocarditis, as well as valvular thickening and insufficiency. Subsequently, antiphospholipid antibodies were implicated in coronary artery disease manifested by premature myocardial infarction and coronary artery bypass graft occlusion. In addition, there have been rare reports of intracardiac thrombi and diffuse cardiomyopathy in association with antiphospholipid antibodies. In this review, we discuss the nature and prevalence of the cardiac manifestations of the antiphospholipid antibody syndrome as well as some of the proposed pathophysiologic mechanisms. We also provide examples from our own experience. The expanding spectrum of cardiac disease associated with antiphospholipid antibodies suggests an important role for these antibodies in certain types of cardiac pathology.


Ambulatory (Holter) electrocardiography signal-averaging: a current perspective.

Signal-averaging is an emerging new application of the ambulatory ECG. Whereas real-time signal-averaging of the high-resolution ECG has led to the measurement of abnormal QRS complex parameters and to the detection of ventricular late potentials in patients with a history of ventricular tachycardia or fibrillation at increased risk of an arrhythmic event, similar measurements can also be derived from ambulatory ECG tape recordings. This review describes the technical differences between real-time and ambulatory high-resolution ECG signal-averaging, and the early clinical studies that correlated measured QRS complex parameters and defined the agreement of late potential detection with the two technologies. Although there appears to be a promising cost-effective benefit from ambulatory ECG signal-averaging, limitations imposed by the technical differences must be recognized, and additional investigation is needed to define the appropriate clinical use and criteria for best diagnostic and prognostic value.


Role of perfluorochemical emulsions in the treatment of myocardial reperfusion injury.

Perfluorochemicals are substances with small particle size, low viscosity, and high oxygen-carrying capacity. The role of one perfluorochemical preparation. Fluosol, an emulsion of two perfluorocarbons, a detergent Pluronic F-68 (poloxamer 188), and phospholipids on myocardial reperfusion injury was investigated in a closed-chest canine model of regional ischemia. Intracoronary and intravenous infusions of Fluosol in the perireperfusion period significantly reduced infarct size and improved ventricular function in animals that were examined for up to 2 weeks after reperfusion. Fluosol preserved endothelial structure and endothelium-dependent relaxation of large and small vessels. Fluosol reduced neutrophil plugging of capillaries and attenuated neutrophil infiltration into the reperfused bed. Ex vivo studies of neutrophil function demonstrated apparent suppression of chemotaxis and lysozyme degranulation in cells from animals that were treated with Fluosol. However, treatment of cells in vitro manifested enhanced superoxide anion production within 5 minutes of incubation even with low concentrations of Fluosol. This effect was found to be almost entirely attributable to the detergent, Pluronic F-68. The stimulation of neutrophils by Fluosol was found to result directly from phagocytosis and indirectly from activation of the complement cascade. These findings suggest that perfluorochemicals may provide a novel form of therapy to enhance myocardial salvage after successful reperfusion. The mechanism appears to be due to stimulation and subsequent "deactivation" of neutrophils peripherally, which thereby reduces their cytotoxic potential in the reperfused myocardium. The role of the oxygen-carrying ability of the perfluorocarbons in the reduction of reperfusion injury remains to be determined. In a pilot study in human beings, Fluosol that was used as adjunctive therapy with angioplasty has also been shown to improve regional ventricular function. Clinical trials with perfluorochemical emulsions appear warranted to determine the role of reperfusion injury in limiting myocardial salvage in patients who are undergoing pharmacologic or mechanical reperfusion.


Visualization of myocardial cellular architecture using acoustic microscopy.

The resolution of an ultrasound transducer depends on its frequency. The resolution improves when higher frequency transducers are used. A 1000 MHz transducer has a resolution of approximately 1 micron. Acoustic microscopy utilizes very high-frequency ultrasound (600 to 1000 MHz) to visualize structures on a microscopic level. Unstained, deparaffinized, 5 microns sections of myocardial biopsy specimens from 10 patients were placed on a slide and imaged using an Olympus UH3 scanning acoustic microscope. To compare with light microscopy, the section used for acoustic microscopy was subsequently stained with hematoxylin and eosin and a serial section from the paraffin block was stained with PTAH stain. Myocytes, myofibrils, and interstitial tissue were accurately imaged. Pathologic phenomena such as cell fallout, interstitial fibrosis, and lymphocytic infiltration were identified by acoustic microscopy. Intramural vessels, nuclei of endothelial cells, and the media were clearly identified by this technique. There was close correlation between findings by acoustic microscopy and light microscopy. Acoustic microscopy permitted the visualization of cardiac cellular detail with a resolution similar to that of light microscopy. Unlike light microscopy, acoustic microscopy requires no staining of the specimen.


Health care reform: to be or not to be? Part 2: Where are we heading?

The call for a new national health care system reflects the inability of the current system to provide access for all, control costs, and maintain quality. In Part 1 of this two-part series (September American Pharmacy, p. 28), the authors discussed the forces driving our current system.


DUE software highlights therapeutic issues.

Drug use evaluation (DUE) or drug use review (DUR) for the ambulatory care setting is creating many opportunities to improve the pharmaceutical care provided by pharmacists. This study documents one year of peer-review interventions based on a retrospective drug utilization review software system (Qualisure, Q-A, Inc.) that screens patient profiles for a high likelihood of drug therapy problems. Letters are written to physicians and pharmacists providing care to these patients. The software identifies frequent opportunities for selecting therapeutic class alternatives to prescribed agents. Antibiotics, antihistamines, nonsteroidal anti-inflammatory drugs, and antidepressants were the classes for which therapeutic class alternatives were most often recommended.


Unclaimed prescriptions: an overlooked opportunity.

Unclaimed prescriptions are an overlooked component of medication noncompliance. Of 21 pharmacies surveyed for prescriptions unclaimed for 30 days or more, pharmacies averaged 21.4 prescriptions each (450 total), with the mean age of 45.6 days. More than 50% of unclaimed prescriptions were new phoned-in prescriptions. Anti-infective agents were the largest class of unclaimed medications, followed by analgesics and respiratory agents. Pharmacists can use unclaimed prescriptions as a basis for increasing their patient-oriented services.


Counseling in special populations: the elderly patient.

This seventh installment in the series on value-added services provides pharmacists with a systematic approach to identifying and meeting the special counseling-related needs of the ambulatory elderly patient. The article describes the physical, mental, and social changes that characteristically accompany the aging process and that create special problems for pharmacists and their elderly patients during the delivery of pharmaceutical care. It also describes a systematic approach that pharmacists can use to evaluate whether their elderly patients need special counseling. Finally, it illustrates how the principles that are discussed can be applied in the practice setting.


Interpreting digoxin concentrations.

In all cases, clinical assessment of the patient is the most critical factor in determining dose and interpreting concentrations. When done accurately, laboratory assessment of drug concentrations represents only one source of information. Serum concentrations must be taken into account along with all other relevant clinical data before one can arrive at appropriate management decisions. They must not be considered in isolation and out of context. If the laboratory report is at variance with your clinical judgment, "it will often be the better part of wisdom to question (or reject) the report."


Choosing condoms.

Condoms for men are currently the most effective of the nonprescription contraceptive methods. They are readily available, simple to use, and relatively inexpensive, and they are not associated with major adverse effects. If used both properly and consistently, condoms can significantly reduce the risk of transmission of HIV and other STDs. The protection offered by the latex condom may be increased by the concurrent use of a vaginal foam or cream containing nonoxynol 9. The practicing pharmacist should know about the variety of condoms available, be able to explain their correct use to maximize effectiveness, and compare condom use with other types of contraceptives. The practitioner should be available to answer patrons' questions and provide counseling on contraceptives and "safe sex" practices.


Update on the treatment of Alzheimer's disease.

The research and clinical experience of the past decade have provided a wealth of new knowledge about the causes of AD and the treatment of individuals afflicted with this progressive, irreversible illness. Public awareness of the costs of the disease has increased both at a national level and at a family and individual level. Despite these advances, the care and treatment of the AD patient are complex in that the risks of therapy often outweigh benefits. The pharmacists can play a key role by ensuring rational therapy, providing professional support to AD care givers, and serving as a source of information in both the ambulatory and institutional patient settings.


Lung cancer mortality among industrial workers exposed to formaldehyde: a Poisson regression analysis of the National Cancer Institute Study.

The Formaldehyde Institute (FI) sponsored additional Poisson regression analysis of lung cancer mortality data from the joint National Cancer Institute (NCI)/FI cohort study of workers exposed to formaldehyde to investigate the previously reported effects of plant and latency period and to assess the impact of short-term workers (under 1 yr employment) on the results. There were 242 lung cancer deaths in this cohort of 20,067 white male workers. With OCMAP software, lung cancer death rates for the white males in this cohort were computed by plant, age, calendar time, and job type for several time-dependent formaldehyde exposures, including formaldehyde exposure in the presence of 12 selected co-exposures: ammonia (AM), antioxidants (AN), asbestos (AS), carbon black (CB), dyes/inks/pigments (DY), hexamethylenetetramine (HX), melamine (ME), particulates (PT), phenol (PH), plasticizers (PL), urea/urea compounds (UR), wood dust (WD), and a composite co-exposure (X5) involving AN, HX, ME, PH, and UR.A 1.6-fold increase in lung cancer risk was found, beginning approximately 16-20 yr after first employment in the study plants with no evidence of a differential effect of latency between hourly and salaried workers or among the various categories of formaldehyde exposure as measured by cumulative average intensity or length of exposure. The statistically significant heterogeneity in lung cancer risk among the 10 plants could not be explained by interplant differences in cumulative or average intensity of exposure to formaldehyde, either without regard to co-exposures or in the presence of any of the 12 co-exposures considered individually. Plant was not a statistically significant predictor of lung cancer risk when cumulative exposure to the composite X5 was included in the model, suggesting that some component of X5, or a correlate, could at least partly account for the overall heterogeneity. No significant associations were found for cumulative, average, or length of exposure to formaldehyde without regard to co-exposure, but positive associations were found for cumulative exposure to formaldehyde in the presence of several co-exposures (AN, HX, ME, PH, and UR). For workers who were never exposed to any of 10 co-exposures associated with an increased lung cancer risk, there was a decreasing pattern of estimated lung cancer risk ratios relative to cumulative formaldehyde exposure. Similar patterns were seen when the analysis was restricted to the long-term workers. Analysis of the internal cohort rates corroborates previous analyses of NCI/FI cohort data in that significant positive associations were found between the risk of lung cancer and cumulative exposure to formaldehyde in the presence of several of the same co-exposures. No such associations were found in the absence of these co-exposures.


Assessment of multiple markers of environmental tobacco smoke (ETS) in controlled, steady-state atmospheres in a dynamic test chamber.

Controlled test atmospheres of sidestream and mixed mainstream/sidestream tobacco smoke were produced in a dynamic test chamber of 16.9 m3 volume. University of Kentucky 1R4F research cigarettes were automatically smoked by a Borgwaldt smoking machine. Different target levels of smoke were attained by varying the number of cigarettes being smoked (one or two cigarettes continuously) and dilution airflow through the chamber (1.6 to 7.4 m3/min). For each level, a "smoke index" was calculated as the number of cigarettes being smoked divided by the dilution flow rate. Ultraviolet light-absorbing particulate matter (UVPM); aerosol counts and size distribution; and concentrations of CO, NO2, NH3, formaldehyde, acetaldehyde, acrolein, and nicotine were determined in the test atmospheres and background dilution air. Parameters exhibiting the highest correlations with smoke index (r2 > 0.98) included UVPM, aerosol counts, formaldehyde, and acetaldehyde. The other parameters were also highly correlated with r2 > 0.9 in each case. Differences in concentration for sidestream and mixed mainstream/sidestream atmospheres were statistically significant for acetaldehyde, formaldehyde, and CO; in each case the level was higher in mixed mainstream/sidestream smoke. These results demonstrate the utility of employing multiple markers for assessment of environmental tobacco smoke levels and for dichotomizing the contributions of sidestream and mainstream smoke to these levels. The generation factors developed in this work can be used for estimating required ventilation rates for attainment of target air quality conditions in smoking rooms.


Review of respirator performance testing in the workplace: issues and concerns.

Performance capability of respirators has traditionally been evaluated by testing components of the respirator (e.g., filter efficiency), facepiece fit, total inward leakage, or some other measure of performance evaluated under laboratory conditions. In recent years, increased emphasis has been placed on development of test methods suitable for evaluating respirator performance in the workplace. The goal of such testing is to evaluate the level of protection provided by respirators in the work environment. The AIHA Respiratory Protection Committee believes that workplace testing of respirators has the potential to be an excellent tool for increasing knowledge about the effectiveness of respiratory protection. However, a number of technical issues remain to be addressed before optimal test protocols and data analysis methods can be defined. The progress made to date in workplace testing will be reviewed, and broader discussion about key elements that must be considered when developing guidelines for testing respirators in the workplace will be initiated.


Determination of program protection factors for half-mask respirators used at a mineral sands separation plant.

A study was conducted at a mineral sands separation plant to evaluate the workplace performance of half-mask filter cartridge respirators. Inhalation exposure was estimated by measuring the dust and radioactivity concentration inside the respirator while it was worn or hanging around the worker's neck. The program protection factor was determined by simultaneously measuring inside-mask and ambient (outside-mask) concentrations. A total of 27 tests were conducted, covering three brands of half-mask respirators; facial hair on test subjects ranged from clean-shaven to bearded. Program protection factors varied from 1.8 to 13 for dust exposure and 2.5 to 21 for radioactivity exposure. The geometric mean program protection factor over all tests was 5.1 (geometric standard deviation [GSD] = 1.7) for dust exposure and 7.5 (GSD = 1.7) for radioactivity exposure. A minimum program protection factor of 3.5 could be applied to ambient airborne concentration data to obtain a conservative, but more realistic, estimate of inhalation exposure on a worker category basis.


Active noise control: a review of the field.

Active noise control (ANC) is the application of the principle of the superposition of waves to noise attenuation problems. Much progress has been made toward applying ANC to narrow-band, low-frequency noise in confined spaces. During this same period, the application of ANC to broad-band noise or noise in three-dimensional spaces has seen little progress because of the recent quantification of serious physical limitations, most importantly, noncausality, stability, spatial mismatch, and the infinite gain controller requirement. ANC employs superposition to induce destructive interference to affect the attenuation of noise. ANC was believed to utilize the mechanism of phase cancellation to achieve the desired attenuation. However, current literature points to other mechanisms that may be operating in ANC. Categories of ANC are one-dimensional field and duct noise, enclosed spaces and interior noise, noise in three-dimensional spaces, and personal hearing protection. Development of active noise control stems from potential advantages in cost, size, and effectiveness. There are two approaches to ANC. In the first, the original sound is processed and injected back into the sound field in antiphase. The second approach is to synthesize a cancelling waveform. ANC of turbulent flow in pipes and ducts is the largest area in the field. Much work into the actual mechanism involved and the causal versus noncausal aspects of system controllers has been done. Fan and propeller noise can be divided into two categories: noise generated directly as the blade passing tones and noise generated as a result of blade tip turbulence inducing vibration in structures. Three-dimensional spaces present a noise environment where physical limitations are magnified and the infinite gain controller requirement is confronted. Personal hearing protection has been shown to be best suited to the control of periodic, low-frequency noise.


Health and safety implications of European community 1992 (EC92). Management committee. American Industrial Hygiene Association.

Progress toward the implementation of a single, common market in Europe is well underway. European-wide standards and regulations are being formulated to remove the physical, fiscal, and technical barriers to the free movement of goods, services, capital, and people among member states. In 1992, the target year for implementation, members of the European Community are attempting to harmonize their health and safety standards so that each nation is on equal footing. The European Community has given high priority to health and safety to the extent that 1992 has been declared the "year of health and safety in the workforce." The EC-rulemaking bodies have developed requirements for significant hazards, including risk communication and risk assessment. Efforts are underway to develop directives addressing exposure limits, product safety, and environmental protection. The result of this ambitious strategy will present substantial opportunities and challenges for the member countries, American companies with EC-based subsidiaries, and any company that sells products in the European market. The end result could have a much farther reaching effect. To emphasize this, I will quote James Tye, president of the British Safety Council, who said, "The European Community will eventually be 700 to 800 million strong as other nations join it. I have no doubt it will be the dominant market in the world, assuredly as far as the field of health and safety is concerned. I also have no doubt that the standards we will be developing in the European Community will be followed by Japan and the United States.


Assessment of intermittent trichloroethylene exposure in vapor degreasing.

To validate various sampling strategies in assessment of trichloroethylene (TCE) exposure, urine and air samples were obtained from 29 metal workers involved in vapor degreasing. Urinary trichloroacetic acid and trichloroethanol were useful metabolites to estimate TCE exposure on a group basis, but the predictive value of a single urine sample was low when related to the air concentration. With intermittent TCE exposure, the best information is obtained by analyzing both metabolites.


Assessing viable myocardium with thallium-201.

Patients with chronic coronary artery disease and potentially reversible left ventricular dysfunction can often be successfully identified by one or more clinical indicators of myocardial viability, including regional wall motion, systolic wall thickening, regional myocardial perfusion as determined by perfusion tracers, and redistribution of thallium-201. In some patients, however, viable but "hibernating" myocardium will exist even when none of the above are evident. Myocardial viability in this situation can be detected with a high degree of accuracy by the demonstration of preserved metabolic activity by positron emission tomography (PET) scanning. Additionally, modifications of the standard exercise-redistribution thallium protocol may also produce accurate results. These modifications include late thallium-201 redistribution imaging, performed 8-72 hours following initial thallium injection, and thallium reinjection at rest after early (3-4 hours) or late (8-72 hours) redistribution imaging. These methods can identify viable myocardium in many thallium defects that appear to be irreversible on a standard 3-4 hour redistribution image. In addition, serial imaging after administration of thallium-201 at rest may also provide valuable insights into myocardial viability. These imaging modalities have important practical applications in the evaluation and management of patients with coronary artery disease and left ventricular dysfunction.


Myocardial thallium-201 scintigraphy for assessment of viability in patients with severe left ventricular dysfunction.

Many patients with ischemic heart disease and depressed left ventricular (LV) function have asynergic zones with sustained microcirculatory perfusion and myocardial metabolic activity that exhibit improved systolic function after coronary revascularization. The 2 predominant noninvasive techniques used to determine myocardial viability in patients with severely depressed LV function are thallium-201 (201Tl) scintigraphy and positron emission tomography (PET). Myocardial extraction of 201Tl is unaltered under experimental conditions of myocardial stunning or short-term hibernation (characterized by decreased flow and ischemic dysfunction). Akinetic or dyskinetic LV wall segments can exhibit normal or near normal 201Tl uptake as long as some residual flow is present. 201Tl scintigraphy can identify viable asynergic segments when performed on patients with severe coronary artery disease who are in the resting state. Many of these patients have initial resting defects that demonstrate delayed redistribution, or mild persistent defects that show improved perfusion and function after revascularization. There is a direct correlation between the extent of 201Tl uptake in zones of severe regional myocardial asynergy and the magnitude of improvement in resting LV ejection fraction after coronary bypass surgery. Rest 201Tl scintigraphy may help in the selection of patients with coronary artery disease and severely depressed LV function who would benefit the most from revascularization.


Prognostic value of thallium-201 myocardial perfusion imaging in three primary patient populations.

Knowledge of a patient's coronary anatomy alone is often insufficient to predict who will benefit from revascularization. Risk of cardiac events is related more to the presence of viable myocardium supplied by coronary arteries that are hemodynamically significant. Myocardial perfusion imaging with thallium-201 has been shown to reveal the presence and extent of jeopardized viable myocardium. In addition, thallium-201 imaging can demonstrate exercise-induced left ventricular dysfunction, manifested by increased thallium-201 myocardial imaging has important prognostic value in a wide spectrum of patients with coronary artery disease. The use of thallium-201 to predict cardiac events in patients with known or suspected coronary artery disease, in patients following myocardial infarction, and in patients undergoing noncardiac surgery is reviewed.


Thallium-201 single-photon emission computed tomography (SPECT) in the assessment of coronary artery disease.

Of all currently available techniques, thallium-201 single-photon emission computed tomography (SPECT) is the most time-tested noninvasive method for the detection of coronary artery disease (CAD). Recent pooled data show an overall sensitivity of 90% and a specificity of 70% for thallium-201 SPECT. Of patients with single-vessel coronary disease, 83% are identified by SPECT. Nearly all patients with double- and triple-vessel coronary disease (93% and 95%, respectively) are also identified. Thallium-201 SPECT imaging is also very effective in diagnosing CAD imaging is also very effective in diagnosing CAD using pharmacologic stress testing. In certain patient populations (e.g., in sedentary patients or those using anti-ischemic medications), pharmacologic stress testing with dipyridamole or adenosine may be a logical alternative to exercise testing. Moreover, many patients have physical disabilities that preclude appropriate exercise testing. Intravenous adenosine is a very potent direct coronary vasodilator, with the advantage of an ultrashort half-life, which eliminates the need to administer an antagonist in the majority of patients. In addition, the dosage of adenosine can be adjusted during the infusion, if necessary. The importance of thallium-201 SPECT during exercise or pharmacologic vasodilation transcends diagnosis, since it also plays an important role in the prognostic evaluation of patients with stable angina or postmyocardial infarction. Risk evaluation can be done with submaximal exercise electrocardiographic testing, but there is evidence that the addition of perfusion scintigraphy enhances the ability to predict future risk.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of thallium-201 and technetium-99m methoxyisobutyl isonitrile.

Thallium-201 (201Tl) is a well-established radionuclide used in myocardial perfusion imaging for assessing the presence and prognostic significance of coronary artery disease. Recently, technetium-99m hexakis-2-methoxyisobutyl isonitrile (99mTc-sestamibi) has become available for the same diagnostic and prognostic procedures. This discussion compares the imaging characteristics and clinical applications of 201Tl with those of 99mTc-sestamibi. There is a strong diagnostic concordance between the 2 agents in symptomatic patients. Various comparative clinical trials have shown in numerous patients that both agents have a similar diagnostic yield in both planar and single-photon emission computed tomography (SPECT) imaging. Because of better image quality of the 99mTc agent, there is a trend toward better specificity and normalcy rate, in comparison to 201Tl. However, when using reinjection imaging protocols, 201Tl retains a unique place as an imaging agent to identify viable myocardium.


Usefulness of ultrafast magnetic resonance imaging in healed myocardial infarction.

The value of ultrafast magnetic resonance imaging (MRI) in the assessment of dynamic contrast enhancement and myocardial perfusion abnormalities was evaluated in 20 patients with healed myocardial infarction, who also underwent 2-dimensional echocardiography. At baseline and after bolus injection of the paramagnetic contrast agent gadolinium-diethylenetriaminepentaacetic acid (DTPA) (0.04 mmol/kg body weight), single-level short-axis MRI was performed every third RR interval with an acquisition time of 500 ms. Myocardial signal intensities were measured in transmural myocardial regions of interest. After gadolinium-DTPA injection, infarcted and normal myocardium demonstrated a signal intensity enhancement of 50 and 134%, respectively (p < 0.001). A signal intensity of normal relative to infarcted myocardium increased from 1.25 +/- 0.22 (SD) before to 1.91 +/- 0.41 after gadolinium-DTPA (p < 0.001). The rate of signal increase in the infarcted and normal myocardium was 5.17 +/- 2.22 and 18.99 +/- 9.96 s-1 (p < 0.001), respectively. Ultrafast MRI using gadolinium-DTPA bolus administration clearly identifies myocardial perfusion abnormalities in patients with healed myocardial infarction. The infarct site on MRI corresponded with the location of wall motion asynergy determined by echocardiography. It is concluded that gadolinium-DTPA-enhanced ultrafast MRI provides noninvasive assessment of myocardial perfusion in patients with proven coronary artery disease.


Placebo effect of nitrate monotherapy for myocardial ischemia.

Nitrate monotherapy was assessed by treadmill exercise stress testing in 18 patients with significant but relatively asymptomatic myocardial ischemia who were receiving no other antianginal therapy. In addition, prolonged ambulatory electrocardiographic monitoring was performed in 7 patients with demonstrable ischemia during baseline monitoring. After baseline assessment, 5 treatment periods were used in a random order (each of 1 week duration), incorporating 2 dose levels of transdermal nitrate (10 and 20 mg/24 hours) and isosorbide dinitrate (ISDN) (30 and 60 mg/day in divided doses) with a 10-hour nitrate-free interval every 24 hours, as well as a placebo period using a double-blind technique. All treatment periods (including placebo) showed a significant (p < 0.01) 45 to 69% prolongation in the time to 1 mm ST depression during exercise. Paired baseline times of 231 +/- 28 and 233 +/- 30 seconds increased to 367 +/- 37 seconds with 30 mg/day of ISDN, 393 +/- 37 seconds with 60 mg/day of ISDN, 381 +/- 31 seconds with 10 mg/day of transdermal nitrate, and 372 +/- 33 seconds with 20 mg/day of transdermal nitrate. The value for placebo was 342 +/- 29 seconds, which was not significantly different from active treatment (p > 0.1). Some patients appeared to individually respond to > or = 1 nitrate preparation significantly more than to placebo, but this appeared to be unpredictable and largely independent of dosage level and route of administration. There was a qualitatively similar but statistically insignificant reduction in total ischemic time during ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)


Prediction of late cardiac events by dipyridamole thallium imaging in patients undergoing elective vascular surgery.

Dipyridamole thallium scintigraphy has previously been shown to have prognostic value in the preoperative assessment of patients scheduled to undergo vascular surgery, but its effect on the long-term outcome is less well-defined. In the largest series to date, dipyridamole thallium scanning was performed in 360 patients before elective vascular surgery and survivors were followed for a mean of 31 months. In the 327 patients who underwent vascular surgery, operative death and nonfatal myocardial infarction occurred in 4.9 and 6.7%, respectively. A cardiac event (nonfatal myocardial infarction or cardiac death) occurred in 14.4% of patients with a transient thallium defect, as opposed to 1% with a normal scan (p < 0.001). Logistic regression analysis revealed that the best predictor of a perioperative event was the presence of a reversible thallium defect, elevating the risk by 4.3-fold. Late cardiac events occurred in 53 (15.2%) surgical survivors or nonsurgically treated patients. Patients with a fixed perfusion abnormality had a 24% late event rate, compared with 4.9% in those with a normal dipyridamole thallium study (p < 0.01). Cox analysis demonstrated that a fixed thallium defect was the strongest factor for predicting a late event and increased the relative risk by almost fivefold. A history of congestive heart failure was the only significant variable that contributed additional value to that of a fixed defect alone. Life-table analysis confirmed the strong relation of a fixed defect to cardiac event free survival (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)


Prognosis of patients with sustained ventricular tachycardia and of survivors of cardiac arrest not inducible by programmed stimulation.

The aim of this study was to analyze the long-term clinical outcome of 60 prospectively studied patients with documented sustained ventricular tachyarrhythmia that was not inducible during baseline programmed ventricular stimulation: 39 with cardiac arrest due to noninfarction ventricular fibrillation (VF) and 21 with mild hemodynamically compromising sustained ventricular tachycardia (VT). Left ventricular ejection fraction was 55 +/- 14% in the VF group and 50 +/- 13% in the VT group (difference not significant). Patients were discharged without conventional antiarrhythmic drugs and received only empirical beta-blocker therapy. During a mean follow-up period of 21 +/- 16 months (mean +/- SD), 10 of 60 patients (17%) died suddenly. The actuarial incidence of sudden death at 1 and 4 years was similar in both groups (VF group, 10 and 20%; VT group, 16 and 16%) (p = 0.48). The actuarial incidence of sudden cardiac death was significantly higher in patients with left ventricular ejection fraction < or = 40% than in those with > 40% (1-year incidence in VF group, 40 vs 0%; VT group, 50 vs 0%) (p = 0.005 and p = 0.01, respectively). Multivariate regression analysis identified left ventricular ejection fraction < or = 40% and previous myocardial infarction as the only independent predictor of sudden cardiac death. The occurrence of frequent ventricular pairs during Holter monitoring was the only independent predictor of sustained VT recurrences. It is concluded that patients with sustained ventricular tachyarrhythmia in whom arrhythmia was non-inducible during baseline ventricular stimulation and not treated with antiarrhythmic therapy have a favorable outcome if left ventricular ejection fraction is high.(ABSTRACT TRUNCATED AT 250 WORDS)


Reproducibility of stress redistribution thallium-201 SPECT quantitative indexes of hypoperfused myocardium secondary to coronary artery disease.

To determine the reproducibility of quantitative indexes of hypoperfused myocardium by exercise thallium-201 single-photon emission computed tomography, duplicate studies were performed in 16 stable patients within 1 month. Twenty-three other patients, with intervals up to 13 months between studies, were retrospectively identified from medical records. Symptoms, weight, heart rate achieved and peak systolic blood pressure during the 2 studies were similar. Maximal counts circumferential profiles' polar maps were generated and divided into 3 vascular territories. The hypoperfused myocardium was defined as the percent stress profile points below the normal level. The observed values were compared between the 2 studies for each patient. Defect size ranged from 0 to 73%. The concordance correlation coefficient (a measure of the closeness of the data points to the line of identity) and mean absolute deviation were 0.94 and 4.5%, respectively, when all patients were considered together, 0.93 and 3.2%, respectively in the reproducibility group, and 0.94 and 5.1%, respectively, in the retrospective group. Inter- and intraobserver reproducibility were also very high. For individual vessels, the concordance correlation coefficients were all > or = 0.89 and the mean absolute deviations between 3.7 and 9%. Thus, in stable patients with repeat thallium studies within a year, the percent hypoperfused myocardium is highly reproducible.


Composition of atherosclerotic plaques in the epicardial coronary arteries in juvenile (type I) diabetes mellitus.

The composition of atherosclerotic plaques in 331 five-mm segments of the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries of 8 patients with juvenile (mean age at onset, 9 years; mean age at death, 29 years) diabetes mellitus was determined by computerized planimetric analysis. Analysis of all coronary segments disclosed that the plaques consisted primarily of dense (53%) and cellular (38%) fibrous tissue. Pultaceous debris (7%), foam cells (1.2%) and calcific deposits (0.7%) occupied a small percentage of the plaques. Thus, 91% of the coronary plaques in these young diabetic patients consisted of fibrous tissue and nearly all of the remaining 9% consisted of lipid deposits. Analysis of composition according to degrees of cross-sectional luminal narrowing revealed marked increases in dense fibrous tissue (from 31 to 74%), pultaceous debris (from 3 to 12%), and calcific deposits (from 0% to 3%) as the cross-sectional area narrowing increased from < or = 25% to > 75%. Compared with older patients with fatal coronary artery disease, the patients with juvenile diabetes had more dense fibrous tissue and pultaceous debris and less calcific deposits.


Effects of infusion of L-arginine into the left anterior descending coronary artery on acetylcholine-induced vasoconstriction of human atheromatous coronary arteries.

Hypercholesterolemia and atherosclerosis are conditions associated with impaired endothelium-dependent relaxation. In hypercholesterolemic animals, intravenous administration of L-arginine, the precursor of nitric oxide, normalizes endothelium-dependent vasodilator activity. In the present study, we questioned whether intracoronary administration of L-arginine in patients with coronary artery disease could improve coronary vascular reactivity to acetylcholine. Thirteen hypercholesterolemic patients with diffuse coronary atherosclerosis but nonstenotic lesions of the left anterior descending (LAD) coronary artery were investigated. Quantitative coronary angiography and subselective intracoronary Doppler flow velocity measurements were performed to determine LAD diameters and coronary blood flow. Intracoronary infusion of acetylcholine was performed during 3 consecutive 3-minute periods at incremental rates adjusted to achieve estimated final concentrations of 5 x 10(-7), 10(-6) and 5 x 10(-6) M. After evaluation of the response to acetylcholine, L-arginine was infused into the LAD at the rate of 25 mg/min (10(-3) M) and the same stepwise 3-minute infusions of acetylcholine were repeated during infusion of L-arginine. Infusion of acetylcholine induced a dose-dependent reduction of distal epicardial LAD diameter reaching -48.5 +/- 17% at 5 x 10(-6) M (p < 0.01 vs control values). L-arginine alone had no effect on the distal LAD diameter but attenuated acetylcholine-induced vasoconstriction to -21 +/- 9% at 5 x 10(-6) M acetylcholine (p < 0.01). Coronary blood flow showed a biphasic response to acetylcholine, increasing by 41 +/- 12% at 5 x 10(-7) M (p < 0.01) and decreasing by 21 +/- 13% at 5 x 10(-6) M (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Prognosis with abnormal thallium images in the absence of significant coronary artery disease.

In the presence of coronary artery disease (CAD), thallium imaging has been reported to add prognostic information that is independent of coronary anatomy. To investigate the prognostic importance of thallium imaging in the absence of significant CAD, 87 patients (65 men, 22 women) with abnormal thallium images without significant CAD were followed for a median duration of 22 months (range 11 to 50). Tomographic thallium images obtained immediately and 4 hours after exercise were interpreted by 2 experienced observers who graded thallium uptake in 24 segments in 3 views (short axis, horizontal long axis, vertical long axis) on a 5-point scale (normal; mildly, moderately, or severely reduced; absent). All patients had an abnormal thallium study, defined as a reversible defect of at least mild severity or a fixed defect of at least moderate severity seen in > or = 2 views, or a combination of these, and a coronary angiogram with stenosis not > or = 70% in diameter narrowing. Eighty-two patients had at least 1 reversible segment, and 26 patients had defects in > or = 2 coronary artery distributions. During follow-up there were no deaths or myocardial infarctions. Coronary angioplasty and bypass surgery were performed in 2 patients. Three-year survival without myocardial infarction or revascularization was 97%. Patients with abnormal thallium images in the absence of significant CAD have an excellent short-term prognosis.


Efficacy and tolerability of simvastatin and pravastatin in patients with primary hypercholesterolemia (multicountry comparative study). The European Study Group.

A total of 291 patients with primary hypercholesterolemia [total plasma cholesterol > or = 6.20 mmol/liter (> or = 240 mg/dl)] were enrolled in an open, randomized, parallel, comparative study of simvstatin and pravastatin. All patients started or continued a standard lipid-lowering diet for > or = 6 weeks before entry into the 4-week placebo baseline period. There were 145 patients who received simvastatin and 146 patients who received pravastatin, both at the commonly recommended starting dose of 10 mg once daily, for a treatment period of 6 weeks. Concentrations of total cholesterol in plasma were reduced by 23% with simvastatin, and by 16% with pravastatin. Concentrations of low-density lipoprotein cholesterol in plasma were reduced by 32 and 22%, and high-density lipoprotein cholesterol concentrations were increased by 7 and 5% with simvastatin and pravastatin, respectively. Plasma triglyceride concentrations were reduced by 13% with simvastatin and by 6% with pravastatin. Adverse experiences were similar between treatment groups and both drugs were well tolerated. In each treatment group, 3 patients were withdrawn from the study for clinical adverse experiences; 1 patient in the pravastatin group required a reduction in dose to 5 mg/day because of insomnia. At the commonly recommended starting dose for each, simvastatin had a significantly greater lipid-lowering effect than pravastatin. Both drugs were well tolerated.


Frequency and implications of resetting and entrainment with right atrial stimulation in atrial flutter.

Thirty-three patients (24 with typical and 9 with atypical flutter-wave morphology) were studied to evaluate the incidence and implications of resetting and entrainment of atrial flutter with right atrial stimulation. Resetting with single extrastimulus was present in 23 cases (group A) and absent in 10 (group B). Most cases of reset flutter were typical (20 of 23). Fixed fusion indicative of entrainment was observed in all 29 cases with pacing trains. Groups A and B did not differ significantly in flutter cycle length (230 +/- 20 vs 223 +/- 19 ms), atrial functional refractory period (165 +/- 18 vs 167 +/- 22 ms) or longest paced cycle length producing entrainment (213 +/- 19 vs 210 +/- 19 ms). In contrast, the return cycle after the longest paced cycle length producing entrainment was significantly shorter in group A (228 +/- 27 vs 284 +/- 56 ms; p = 0.001). The return cycle in group A was virtually identical to the flutter cycle length, whereas in group B it was greater (p = 0.002 compared with group A). Resetting was more frequent in typical than atypical flutter (20 of 24 vs 3 of 9; p = 0.01). Both typical and atypical flutter can be transiently entrained by right atrial pacing. Lack of resetting and longer return cycle, suggesting a longer conduction time between the reentrant circuit and the stimulation site, were mostly observed in atypical flutter. The data suggest a different location for both types of flutter, and may have implications for ablation techniques. A more cautious approach, with more extensive mapping, appears appropriate for ablation attempts of atypical flutter.


Crossover comparison of atenolol, enalapril, hydrochlorothiazide and isradipine for isolated systolic systemic hypertension.

The benefit of antihypertensive therapy in reducing cardiovascular morbidity and mortality associated with isolated systolic hypertension has now been established by the Systolic Hypertension in the Elderly Program. However, there is little information about the relative effectiveness of different drug regimens in this condition. This study compared the efficacy and tolerability of 50 mg of atenolol, 10 mg of enalapril, 25 mg of hydrochlorothiazide and 2.5 mg of isradipine in the treatment of isolated systolic hypertension. After a 3-week placebo run-in phase, 24 subjects were randomized into a 4-period double-blind crossover study by use of an orthogonal latin square design. Treatment periods were of 6 weeks' duration with titration to a higher dose after 4 weeks in those not reaching goal blood pressure (BP). Each active treatment was followed by a 3-week placebo washout. Casual clinic and 24-hour ambulatory BP (Accutracker II) were measured at the end of each treatment phase. Routine biochemistry was also performed after the placebo run-in, at the end of each active treatment phase, and after the placebo run-out. Of the 24 subjects entered (mean age 72.3 years, 38% men) 20 completed the whole study. Mean +/- standard deviation of supine clinic and daytime ambulatory BP on entry were 181/79 +/- 21/9 mm Hg and 165/82 +/- 23/15 mm Hg, respectively. All drugs reduced mean casual and ambulatory BP significantly relative to placebo but only hydrochlorothiazide and enalapril produced a consistent hypotensive effect throughout the entire 24-hour period. Isradipine and enalapril exhibited a relatively greater effect on reducing systolic BP than either hydrochlorothiazide or atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)


Systemic hypertension associated with tricyclic antidepressant treatment in patients with panic disorder.

In a sample of 114 patients, 6 patients developed hypertension while taking tricyclic antidepressants. All these patients were diagnosed as having panic disorder, with or without major depression. Half of the 6 patients had a previous diagnosis of hypertension, which had been well controlled by antihypertensive drugs for years. A comparison group of patients with major depression, who had never had panic attacks, had no cases of hypertension induced by these antidepressants. These findings raise the possibility that patients who have panic disorder may experience cardiovascular disregulation that increases their risk for antidepressant-induced hypertension.


Persistent hemodynamic improvement with short-term nitrate therapy in patients with chronic congestive heart failure already treated with captopril.

To evaluate the therapeutic potential of organic nitrates in patients with chronic congestive heart (CHF) failure already treated with angiotensin-converting enzyme (ACE) inhibitors, the temporal hemodynamic effects of oral isosorbide dinitrate, 40 to 120 mg administered every 6 hours to 11 nitrate responders who had been treated with captopril 89 +/- 32 mg/day, were studied. The administration of isosorbide dinitrate resulted in a significant decline in mean right atrial pressure, from 13 +/- 6 mm Hg at baseline (mean value of measurements performed every 2 hours for 24 hours with captopril therapy) to 9 +/- 4 mm Hg at 1 hour with persistent effect for most of the study period. Mean pulmonary artery pressure decreased from 38 +/- 7 mm Hg at baseline to 29 +/- 9 mm Hg at 1 hour, with effect persisting for 24 hours. Mean pulmonary artery wedge pressure also decreased from 24 +/- 6 to 15 +/- 7 mm Hg at 1 hour and remained significantly reduced for 20 hours. Systemic blood pressure demonstrated a transient decrease lasting 2 hours after initiation of therapy which was asymptomatic in all patients. The results of this study demonstrate a preserved vasodilatory effect of organic nitrates in patients already treated with ACE inhibitors. Nitrates mediated improvement in right and left ventricular filling pressures, and reduction of pulmonary hypertension demonstrates a rationale for the use of these therapeutic methods in combination and suggest the need for long-term evaluation of the effect of nitrate therapy in patients with chronic CHF already treated with ACE inhibitors.


Impaired forearm vasodilation to hyperosmolal stimuli in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy.

Patients with congestive heart failure (CHF) have impaired peripheral vasodilation during exercise. Hyperosmolality is one local stimulus that produces vasodilation during exercise in normal subjects. This study addressed the hypothesis that vasodilation to hyperosmolal stimuli is impaired in patients with CHF. Forearm blood flow responses to intrabrachial artery infusions of isoosmolar (280 mosm/kg) and hyperosmolal (480 and 660 mosm/kg) solutions of saline and glucose were compared in 9 patients with CHF and 13 normal subjects. Forearm blood flow was measured by strain gauge plethysmography. In the normal subjects, hyperosmolal infusions of 480 and 660 mosm/kg increased forearm blood flow by 3.12 +/- 0.40 and 6.80 +/- 0.67 ml/min/100 ml forearm volume, respectively (both p < 0.001 compared with isoosmolal infusions). In contrast, in the patients with CHF, these infusions increased forearm blood flow by 2.19 +/- 0.44 and 4.06 +/- 0.92 ml/min/100 ml forearm volume (p < 0.05 normal vs CHF). The impaired forearm blood flow responses in heart failure occurred despite significantly greater (p < 0.05, normal vs CHF) increases in venous osmolality (17.3 +/- 6.5 vs 9.6 +/- 1.3 mosm/kg for the 660 mosm/kg infusion). There were no differences between groups in forearm venous hematocrit, calcium, and sodium or potassium changes during hyperosmolal infusions. It is concluded that peripheral vasodilation to hyperosmolal stimuli is impaired in patients with CHF.


Long-term efficacy of physiologic dual-chamber pacing in the treatment of end-stage idiopathic dilated cardiomyopathy.

The long-term efficacy of physiologic dual-chamber (DDD) pacing in the treatment of end-stage idiopathic dilated cardiomyopathy was evaluated in a longitudinal study of up to 5 years in 17 patients. The considerable clinical improvement achieved after implantation of a pacemaker programmed for DDD pacing at an atrioventricular delay of 100 ms was maintained throughout the follow-up period or until death and was associated with a consistent decrease in New York Heart Association class and an increase in left ventricular ejection fraction. Cardiothoracic ratio, heart rate and echocardiographic dimensions progressively decreased, and systolic and diastolic blood pressures increased. Median survival time was 22 months. During follow-up, 4 patients received donor hearts, 9 had a sudden death at home without defined cause or after a thromboembolic event, and 1 died from adenocarcinoma. Three patients survived the follow-up. No patient needed rehospitalization owing to a worsening of heart failure after pacemaker implantation. An interruption of pacing in DDD mode for 2 to 4 hours was followed within the first months by a marked decrease in left ventricular ejection fraction and an increase in cardiothoracic ratio and echocardiographic dimensions, but this response consistently decreased during follow-up. The data indicate that DDD pacing can be recommended as a useful tool in the long-term treatment of end-stage idiopathic dilated cardiomyopathy, with progressive improvement in cardiac function and a reduction of the dilatation of the left ventricle.


Differences in direction-dependent shortening of the left ventricular wall in hypertrophic cardiomyopathy and in systemic hypertension.

To determine whether patients with hypertrophic cardiomyopathy (HC) have an altered mode of contraction of the left ventricular (LV) wall related to underlying myocardial abnormalities, geometric changes in the LV wall were analyzed at 2 points of the cardiac cycle (end-diastole and end-systole) using 2-dimensional echocardiography. The relations between meridional and circumferential shortening of the LV midwall, mean wall thickening, and the changes in the short-axis cross-sectional area of the LV wall at the level of chordae tendineae were determined in 18 patients with nonobstructive HC, and were compared with those in 31 normal subjects and 19 patients with essential systemic hypertension. In normal subjects, no significant difference was observed between meridional (16.3 +/- 2.4%) and circumferential (17.1 +/- 4.0%) shortening, whereas cross-sectional LV wall area increased significantly at end-systole (p < 0.001). In patients with hypertension, all measured indexes were not different from those in normal subjects. In contrast, patients with HC had significantly reduced meridional shortening (p < 0.001) and mean wall thickening (p < 0.01). Consequently, a striking difference was observed between meridional (8.9 +/- 2.4%) and circumferential (16.9 +/- 3.2%) shortening (p < 0.001). Furthermore, no increase in cross-sectional LV wall area was observed at end-systole. Thus, echocardiographic detection of direction-dependent contraction can be a useful index for distinguishing HC from systemic hypertension.


Myocardial disarray at junction of ventricular septum and left and right ventricular free walls in hypertrophic cardiomyopathy.

The abnormality of the myocardium in hearts with hypertrophic cardiomyopathy (HC) was assessed regarding whether the muscle bundle in the mid-wall layer maintains its normal circular and continuous orientation surrounding the left ventricular (LV) cavity. Forty-seven autopsied hearts with HC were examined. The LV wall midway between the base and apex was divided into 6 segments in the transverse plane. Histologically, the circular orientation was destroyed largely or completely due to marked fascicle disarray in 77% of the anterior and posterior junctional segments. In 33% of the middle portion of the ventricular septum and in 34% of the anterior and posterior portions of the LV free wall, the midwall layer showed disarray of muscle fibers or small fascicles. In contrast, the lateral LV free wall was devoid of disarranged fibers in its midwall layer. Myocardial fibrosis usually was predominant in the portion where disarray was marked. There were deep tissue clefts often in the area of junction. In 11 hearts (7 from patients aged > 65 years), the circular unit was intact in almost every segment, as it was in 9 of 10 control hearts. The destruction of the circular unit in the area of septal-free wall junctions in most patients with HC is a previously undescribed morphologic feature of HC. This discontinuity may result from retention of an abnormal fetal myocardial architecture in which the septal latitudinal muscle was continuous with the right ventricular free wall.


Intra- and interobserver reproducibility of Doppler-assessed indexes of left ventricular diastolic function in a population-based study (the Framingham Heart Study).

The reproducibility of a variety of Doppler indexes of diastolic function in an epidemiologic setting and in atrial fibrillation have not been reported. This study examined the reproducibility of left ventricular inflow in subjects in sinus rhythm (n = 80) and atrial fibrillation (n = 12), randomly selected from the original cohort of the Framingham Heart Study. The following Doppler indexes were assessed for all subjects: peak and integral of early (E) diastolic inflow velocity, acceleration slope and time, deceleration slope and time, and pressure half-time. For subjects in sinus rhythm, the following parameters also were measured: the peak and integral of late (A) diastolic inflow velocity, ratios of peak velocities and integrals E/A, and atrial filling fraction. Intraobserver and interobserver variability were evaluated by statistical methods including Student's t test of the systematic differences (bias), percent bias, correlation coefficients, measurement precision, and percent precision. In subjects in sinus rhythm, although the interobserver bias was statistically significant for most of the parameters, it was < 10% for all but 1 parameter (acceleration time). For the peak and integral measures, the intra- and interobserver correlations were > or = 0.89, with intra- and interobserver percent precision measures within 2.2 to 13.0% of the corresponding mean values. The acceleration, deceleration and pressure half-time measures had somewhat lower correlations (interobserver correlations ranging from 0.59 to 0.96), with percent precision measures further from the corresponding means (interobserver percent precision ranging from 10.1 to 19.5%).(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of omega-3 fatty acids on the vascular response to angiotensin in normotensive men.

There is a widespread interest in fish oil as a dietary supplement and possible nonpharmacologic adjunct in the treatment of hypertension. The effect of dietary fish oil on blood pressure is controversial and the effect on systemic hemodynamics and regional vascular reactivity in humans is unknown. To address these questions, a double-blind, placebo-controlled, crossover study on the effect of dietary fish oil substitution was performed during a carefully controlled diet in 8 normotensive men. Systemic hemodynamics and the forearm vascular response to intrabrachial artery infusions of norepinephrine, phentolamine and angiotensin II were obtained. Compared with a safflower oil placebo, dietary fish oil had no effect on cardiac output (6.42 +/- 0.38 vs 6.87 +/- 0.28 liters/min, p = not significant) or 24-hour blood pressure (122/68 +/- 3/3 vs 122/68 +/- 3/2 mm Hg, p = not significant). The vascular response to norepinephrine and phentolamine was unchanged. Fish oil, however, significantly (p < 0.05) reduced forearm vascular resistance responses to angiotensin II. These changes were associated with a reduction in plasma triglycerides (64 +/- 9 vs 39 +/- 4 mg/dl, p = 0.02) and an increase in plasma eicosapentaenoic acid levels (0.51 +/- 0.25 vs 1.72 +/- 0.35 microM, p < 0.05). Substitution of a moderate dose of fish oil for fat in a "Western diet" selectively attenuates the vascular response to angiotensin independently of changes in alpha-adrenergic vasoconstriction or systemic hemodynamics.


Comparison of Doppler and two-dimensional echocardiography for assessment of pericardial effusion.

Respiratory changes in left ventricular inflow velocities by Doppler echocardiography have been used to assess cardiac tamponade; however, Doppler echocardiography has not been compared to right atrial or right ventricular collapse. Pulsed Doppler echocardiography of left ventricular inflow velocities was performed with respiratory monitoring in 28 patients with small to large pericardial effusions. Ten of the 17 patients (59%) with large effusions had equalization of right-sided diastolic pressures before pericardial drainage. The measurements performed included percent change in left ventricular inflow peak early velocity, isovolumic relaxation time, change in inferior vena cava diameter from apnea to inspiration, and the presence of right atrial and right ventricular collapse. Percent change in early left ventricular inflow velocities significantly correlated with pericardial effusion size (p = 0.001) and right ventricular collapse (p = 0.007), and showed a trend with right atrial collapse (p = 0.10). Pericardial effusions with a left ventricular inflow velocity change > 22% were found to have right-sided equalization at a 95% confidence interval. Our data indicate that the respiratory changes in Doppler echocardiographic parameters are useful in the assessment of pericardial effusion and tamponade. This study concurs with the hypothesis that there is a continuum of hemodynamic compromise in pericardial effusion that is easily detected by Doppler echocardiography.