摘要:

BackgroundThe morning increase in asymptomatic ambulatory ischemia may be due to heightened coronary tone, increased physical activity, or both. If ambulatory ischemia is primarily due to physical activity, then alterations in the schedule of physical activity should be reflected in a corresponding alteration in the occurrence of ischemia. This study was designed to examine the relation between activity patterns and the frequency of ambulatory ischemic episodes and the effect of nadolol on these relations.Methods and ResultsA double-blind, randomized, placebocontrolled, crossover trial of nadolol versus placebo was performed in 20 patients with stable coronary artery disease. At the end of each 2-week treatment phase, patients were hospitalized for 48 hours. In the hospital, there was a regular activity day (awaken and assume normal activities at 8:00 AM) and a delayed activity day (awaken at 8:00 AM, arise at 10:00 AM, and begin normal activity at noon). Ambulatory ECG monitoring was performed throughout the hospitalization. On the regular activity day, there was a morning increase in heart rate and in the number of ischemic episodes during therapy with placebo that began at 8:00 AM. In contrast, on the delayed activity day, there was a 4-hour phase shift of the increases in heart rate and the increase in ischemic episodes (ie, at noon) corresponding to the onset of physical activities. Therapy with nadolol caused a 50% reduction in the total number of ischemic episodes (129 versus 65, placebo versus nadolol;P< .02). During nadolol therapy, there was no discernible circadian peak in the number of ischemic episodes on either activity day. During placebo treatment, 87% of ischemic episodes were preceded by an increase in heart rate ≤5 beats per minute. Although nadolol caused a significant reduction in the total number of episodes preceded by a heart rate increase compared with placebo (99 versus 38 episodes,P≤ .04), this therapy was associated with a significant increase in the number of episodes not associated with a heart rate increase (15 versus 21 episodes,P≤ .002).ConclusionsThe morning increase in ambulatory ischemic episodes is due to physical activity patterns. The majority of ischemic episodes are preceded by a heart rate increase, and it is these episodes that are primarily responsible for the morning increase in ischemia. Therapy with nadolol caused a reduction in the total number of ischemic episodes solely by reducing those episodes preceded by a heart rate increase. In contrast, nadolol caused a significant increase in the number of ischemic episodes not associated with a heart rate increase, perhaps in part because it potentiated coronary vasoconstriction.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThis study was designed to evaluate the prognostic value of symptom-limited maximal exercise treadmill testing with tomographic technetium-99m sestamibi (MIBI) myocardial imaging in patients referred for evaluation of stable angina. Exercise stress thallium-201 myocardial imaging provides prognostic information in coronary artery disease subsets including patients with stable chest pain. The prognostic value of exercise technetium-99m MIBI myocardial tomography has not been established.Methods and ResultsOf 548 consecutive patients with stable angina pectoris who underwent maximal exercise treadmill stress testing in combination with a same-day “rest-stress” tomographic technetium-99m MIBI myocardial imaging protocol, 521 patients were followed for 13±5 months to determine the univariate and multivariate variables associated with cardiac events and to define their cardiac event-free survival. Ten patients were lost to follow-up (98% complete), and 17 who had coronary revascularization within 6 months of testing were excluded. Major cardiac events occurred in 24 patients (9%) –nonfatal myocardial infarction in 11 and cardiac death in 13. Univariate Cox survival analysis demonstrated significant relative risk (RR) and 95% confidence intervals (CI) for exercise ST segment depression (RR=2.3; 95% CI, 1.0 to 5.3), an abnormal MIBI scan (RR=13.8; 95% CI, 1.9 to 102.3), and a reversible MIBI perfusion defect (RR=3.2; 95% CI, 1.4 to 7.5). Multivariate models demonstrated that both exercise MIBI perfusion abnormalities (RR= 11.9; 95% CI, 1.6 to 89.4) and reversible MIBI perfusion defects (RR=2.9; 95% CI, 1.2 to 7.0) had independent predictive value. During 1 year of follow-up, cardiac events occurred in only 0.5% of patients with normal MIBI scans compared with 7% of those with abnormal MIBI scans (P< .001). One-year, cardiac event-free survival was 92% in patients with reversible MIBI perfusion defects (P< .01 versus normal), 96% in patients with fixed defects (P< .01), and 93% in patients with combined reversible and fixed MIBI myocardial perfusion abnormalities (P< .02).ConclusionsAs with exercise thallium-201 myocardial imaging, exercise stress technetium-99m MIBI myocardial tomography provides significant independent information concerning the subsequent risk of serious cardiac events (death, myocardial infarction) in patients with stable angina pectoris. The identification of MIBI perfusion abnormalities, in particular, the presence of reversible MIBI defects, was associated with reduced 1-year, event-free survival. The recognized imaging and radiotracer biokinetic differences between thallium- 201 and MIBI do not appear to modulate the prognostic value associated with scintigraphic evidence of ischemic myocardial jeopardy in the stable angina population.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe beneficial effect of low-dose aspirin in the prevention of coronary vasospasm is well documented. In this study, we investigated the contractile effect of human washed platelets on the human isolated coronary artery. We concentrated on the effect of low-dose aspirin (40 mg/d) taken by the platelet donor and on the efficacy of thromboxane A2(TXA2) and 5-hydroxytryptamine (5-HT) receptor antagonists.Methods and ResultsHuman coronary artery segments were suspended in an organ bath set-up for isometric tension measurement. Platelets (109to 3 × 1010/L) elicited concentration- dependent contractile responses of the coronary artery segments, reaching 28.4±7.1% of contractions induced by 100 mmol/L K+. The contractile response tended to be decreased in vessel segments with histological signs of early atherosclerosis. Contraction was significantly attenuated after pretreatment of the vessel segments with ketanserin (5-HT2 receptor antagonist, 1 μmol/L) or SQ30741 (TXA2receptor antagonist, 0.01 μmol/L), reaching 8.8±2.3% and 3.2±2.2% of contraction to 100 mmol/L K+, respectively. Platelets obtained from the same platelet donors after they had taken aspirin (40 mg/d for 7 to 13 days) caused significantly lower contractile responses (7.6±2.7% of 100 mmol/L K+) associated with an almost selective inhibition of the synthesis of thromboxane measured in the organ bath solution (untreated platelets, 2.19±0.43 nmol/L; aspirin-treated platelets, 0.66±0.05 nmol/ L). The amount of 5 -HT secreted in the organ bath remained unaltered (65.17±9.94 and 64.03±8.98 nmol/L, respectively). This explains why ketanserin significantly attenuated the residual contractile responses caused by platelets obtained from aspirin-treated subjects, whereas SQ30741 caused minor, non-significant additional attenuation.ConclusionsThe results of the present study therefore suggest that additional antagonism of the contractile 5-HT receptors in the coronary artery may increase the efficacy of low-dose aspirin in vivo.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundCalcium antagonists such as verapamil are potent coronary and systemic vasodilators that are used in the treatment of coronary disease. They have also been shown to inhibit platelet aggregation in vitro, but whether they have beneficial antithrombotic effects in humans is unclear, and whether they can potentiate the antithrombotic effects of aspirin is unknown. Methods and Results Platelet thrombus formation andMethods and ResultsPlatelet thrombus formation and whole blood platelet aggregation were measured in 18 stable coronary patients on three separate occasions: at baseline when receiving no active medications, after 7 days of receiving oral verapamil SR (240 mg/d), and after 7 days of receiving a combination of oral verapamil SR and aspirin (325 mg/d). Thrombus formation on porcine aortic media that were placed into cylindrical flow chambers and exposed to flowing antecubital venous blood for 3 minutes was assessed morphometrically at a shear rate of 2546 s−1, which is typical of arterial flow at sites of stenoses. Thrombus formation under basal conditions was 7.0±1.6 μm2, and this was decreased to 3.1±0.5 μm2(P< .05) after 7 days of treatment with oral verapamil SR and to 2.6±0.5 μm2(P< .05) after 7 days of treatment with oral verapamil and aspirin. Whole blood platelet aggregation levels in response to 0.050 and 0.075 U of thrombin at baseline were 10.8±1.0 and 11.9±1.0 fQ; aggregation was inhibited after 7 days of treatment with verapamil to 6.5±1.1 and 7.8±0.9 fl (P< .05 versus baseline) and after 7 days of treatment with verapamil and aspirin to 6.1±1.1 and 7.2±1.0 Ω (P< .05), respectively.ConclusionsThe present study demonstrates that part of the benefit of verapamil in ischemic heart disease may occur by inhibition of platelet aggregation and thrombus formation. This beneficial antithrombotic effect may be important in preventing acute coronary ischemic events resulting from thrombus formation at sites of plaque rupture.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundPatients with mechanical heart valve prostheses may experience valve thrombosis and subsequent systemic embolism for which they are treated with oral anticoagulant therapy. It is essential to know reliable estimates of the risks and benefits of this therapy in order to answer a number of clinical questions rationally. We sought to obtain more precise estimates of the risks and benefits by combining the data from individual studies by using meta-analysis.Methods and ResultsWe searched for studies in which the incidences were reported of embolic or bleeding complications in patients with mechanical heart valve prostheses. They were collected from the Medline and Current Contents database and by cross-references between 1970 and 1992. Since most studies vary greatly in many respects, we used a number of inclusion criteria, thus selecting comparable studies of acceptable quality only. The influence of antithrombotic therapy, valve position, and valve type was analyzed by univariate and by multivariate analysis with Poisson regression techniques. Forty-six studies were found, including 13 088 patients studied for 53 647 patient-years. We found an incidence of major embolism in the absence of antithrombotic therapy of 4 per 100 patient-years. With antiplatelet therapy this risk was 2.2 per 100 patient-years, and with cumarin therapy it was reduced to 1 per 100 patient-years. This risk varied with the type and the site of the prosthesis. A prosthesis in mitral position increased the risk almost twice as compared with the aortic position. Tilting disc valves and bileaflet valves showed a lower incidence of major embolism than caged ball valves. An incidence of major bleeding was found in patients treated with cumarin derivatives of 1.4 per 100 patient-years. The incidence of bleeding became significantly higher with the addition of antiplatelet therapy, although this did not decrease the risk of thromboembolism any further.ConclusionsThese data provide a reference for future studies and give adequate risk estimates for clinical decision making.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundTo identify predictors of long-term outcome after balloon aortic valvuloplasty, we analyzed data on 674 adults (mean age, 78±9 years; 56% were women) undergoing this procedure at 24 clinical centers who had a mean initial increase in aortic valve area of 0.3 cm2.Methods and ResultsBaseline data included clinical, echocardiographic, and catheterization variables. Follow-up data included mortality, cause of death, rehospitalization, 6-month echocardiography, and functional status. Kaplan-Meier curves and log-rank tests were used to evaluate survival in subgroups. Multivariate Cox regression models were used to identify independent predictors of survival. Overall survival was 55% at 1 year, 35% at 2 years, and 23% at 3 years, with the majority of deaths (70%) classified as cardiac by an independent review committee. Rehospitalization was common (64%), although 61% of survivors at 2 years reported improved symptoms. Echocardiography at 6 months (n= 115) showed restenosis from the postprocedural valve area of 0.78±0.31 cm2 to 0.65±0.25 cm2(P< .0001). With stepwise multivariate analysis, sequentially adding clinical, echocardiographic, and catheterization variables, the overall model identified independent predictors of survival as baseline functional status, baseline cardiac output, renal function, cachexia, female gender, left ventricular systolic function, and mitral regurgitation. Baseline and postprocedural variables were examined to identify which subgroup of patients has the best outcome after aortic valvuloplasty. A “lower-risk” subgroup (28% of the study population), defined by normal left ventricular systolic function and mild clinical functional limitation, had a 3-year survival of 36% compared with 17% in the remainder of the study group.ConclusionsLong-term survival after balloon aortic valvuloplasty is poor with 1- and 3-year survival rates of 55% and 23%, respectively. Although survivors report fewer symptoms, early restenosis and recurrent hospitalization are common.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe study objective was to determine the association between reported alcohol consumption and total mortality, mortality from selected causes, and incident nonfatal chronic disease events in middle-aged (51 to 64 years old) and elderly (65 to 75 years old) men during an approximate 15-year follow-up period.Methods and ResultsWe conducted a prospective epidemiological study of Japanese-American men who were participating in the Honolulu Heart Program and were free from coronary heart disease, cerebrovascular disease, and cancer at baseline examination and at subsequent reexamination 6 years later. Self-reported alcohol consumption was determined twice: at the baseline examination in 1965 through 1968 and at reexamination approximately 6 years later (1971 through 1974). Four primary alcohol consumption groups who reported similar alcohol intake at the time of these two clinical examinations were considered: abstainers and light (1 to 14 mL of alcohol per day), moderate (15 to 39 mL of alcohol per day), and heavy (≥40 mL of alcohol per day) drinkers. Study end points were also determined in very light (1 to 4.9 mL of alcohol per day) drinkers and in men who reported a change in their alcohol intake between examinations. Longitudinal follow- up was carried out through the end of 1988 with determination of selected fatal and nonfatal events according to alcohol intake. After controlling for several potentially confounding factors, total mortality exhibited a J-shaped pattern in relation to alcohol consumption in middle-aged and elderly men. There was a trend for lower rates of occurrence of combined fatal and nonfatal coronary heart disease events with increasing alcohol consumption in both middle-aged and elderly men. Increasing alcohol consumption was related to an increased risk of fatal and nonfatal strokes in middle-aged men, whereas elderly light and moderate drinkers were at increased risk for fatal and nonfatal strokes. Heavy drinkers were at increased risk for fatal and nonfatal malignant neoplasms in the two age groups examined.ConclusionsThe results of this long-term prospective study provide a balanced perspective of the health effects of alcohol consumption in middle-aged and elderly men. High levels of alcohol consumption were shown to be related to an increasing risk of diseases of considerable public health importance. These findings suggest that caution be taken in formulating populationwide recommendations for increases in the population levels of alcohol consumed given the associated significant social and biological problems of high consumption levels.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThere is a high incidence of ventricular arrhythmia and sudden death in patients with heart failure. Unfortunately, currently available antiarrhythmic agents have only limited efficacy and may result in proarrhythmia and hemodynamic deterioration in these patients. Methods and Results We studied the acute effect of intravenousMethods and ResultsWe studied the acute effect of intravenous magnesium chloride on the frequency and severity of ventricular arrhythmia in 30 patients with symptomatic heart failure using a double-blind, placebo-controlled crossover design. The left ventricular ejection fraction was 23.0±8.0% (mean±SD). No patient had a history of symptomatic ventricular arrhythmia or was receiving antiarrhythmic agents, calcium channel antagonists, or P-blockers. Patients were randomized to receive placebo (5% dextrose [D5W] in water alone) or magnesium chloride in D5W given as a bolus of 0.3 mEq/kg over 10 minutes followed by a maintenance infusion of 0.08 mEq/kg per hour for 24 hours. The magnesium concentrations 30 minutes and 24 hours after the bolus were 3.6±0.1 and 4.2±0.1 mg/dL, respectively. There was no significant change in serum potassium concentration during magnesium administration. Blinded analysis revealed that administration of intravenous magnesium chloride, compared with placebo, significantly decreased total ventricular ectopy per hour (mean±SEM, 70±26 versus 149±64.P< .001), couplets per day (23±11 versus 94±59,P= .007), and episodes of ventricular tachycardia per day (0.8±0.2 versus 2.6±1.0,P= .051).ConclusionsIntravenous magnesium chloride administration reduces the frequency of ventricular arrhythmia in patients with symptomatic heart failure.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundIn patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), the frequent provocation of ventricular tachycardia during exercise, the sensitivity toward catecholamines, and the response toward antiarrhythmic drug regimen with antiadrenergic properties suggest an involvement of the sympathetic nervous system in arrhythmogenesis.Methods and ResultsTo analyze the presence, extent, and location of impaired myocardial sympathetic innervation in ARVC,123I–meta-iodobenzylguanidine (123I-MIBG) scintigraphy was performed in 48 patients with ARVC. For comparison, 9 patients with idiopathic ventricular tachycardia and a control group of 7 patients without heart disease were investigated. In patients with ARVC, the clinical sustained (n=25; 52%) or nonsustained (n=23; 48%) ventricular tachycardia originated in the right ventricular outflow tract in 38 patients (79%), whereas in the remaining 10 patients (21%), the site of origin was the apical (n=5) or inferior (n=5) right ventricle. In 33 patients (69%), nonsustained or sustained ventricular tachycardia was provocable by exercise (n=28 of 48; 58%) and/or by isoproterenol infusion (n= 16 of 37; 43%), whereas programmed ventricular stimulation induced sustained or nonsustained ventricular tachycardia in 16 patients each (33% each). With I MIBG scintigraphy, the right ventricle was not visible in any patient. No areas of intense 11I-MIBG uptake (“hot spots”) were observed. All patients of the control group and 7 of 9 patients (78%) with idiopathic ventricular tachycardia showed a uniform tracer uptake in the left ventricle. In contrast, only 8 of 48 ARVC patients (17%) showed a homogeneous distribution of123I-MIBG uptake, whereas 40 patients (83%) demonstrated regional reductions or defects of tracer uptake. In 3 of 48 patients (6%), the defect area was < 15%; in 21 patients (44%), it was 15% to 30%; and in 16 patients (33%), it was >30% of the polar map area of the left ventricle (mean, 23±15%; range, 0% to 57%). In 38 of 40 patients (95%) with an abnormal123I-MIBG scan, reduced tracer uptake was located in the basal posteroseptal left ventricle, involving the adjacent lateral wall in 10, the anterior wall in 2, and the apex in 12 patients. Only 2 patients demonstrated isolated defects of the anterior or lateral wall; one involved the apex. Perfusion abnormalities in the areas of123I-MIBG defects were excluded by stress/redistribution201Tl single-photon emission computed tomography scintigraphy and by normal coronary angiograms in all patients. Abnormalities in123I-MIBG scintigraphy in patients with ARVC correlated with the site of origin of ventricular tachycardia, demonstrating a regionally reduced tracer uptake in 36 of 38 patients (95%) with right ventricular outflow tract tachycardia compared with only 4 of 10 patients (40%) with other right ventricular origins of tachycardia. There was no correlation between the results of123I-MIBG scintigraphy and the extent of right ventricular contraction abnormalities, right ventricular ejection fraction, biopsy results, coronary anatomy, or left ventricular involvement in ARVC.ConclusionsIn patients with ARVC, regional abnormalities of sympathetic innervation are frequent and can be demonstrated by123I-MIBG scintigraphy. Sympathetic denervation appears to be the underlying mechanism of reduced123I-MIBG uptake and may be related to frequent provocation of ventricular arrhythmias by exercise or catecholamine exposure in ARVC. Therefore, in patients with ARVC, the noninvasive detection of localized sympathetic denervation by123I-MIBG imaging may have implications for the early diagnosis and for the choice of antiarrhythmic drugs in the treatment of arrhythmias.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe mechanisms that underlie cardiopulmonary resuscitation (CPR) in humans remain controversial and difficult to study. This report describes a new human model to evaluate CPR during the first 1 to 2 minutes after the onset of ventricular fibrillation (VF). With this model, standard CPR was compared with active compression-decompression (ACD) CPR, a method that uses a handheld suction device to actively compress and actively decompress the chest.Methods and ResultsDuring routine inductions of VF as part of a transvenous lead cardioverter/defibrillator implantation procedure, CPR was performed in 21 patients if the first defibrillation shock failed and until a successful rescue shock was delivered. Compressions during CPR were performed according to American Heart Association guidelines. For ACD CPR, decompression was performed with up to −30 lbs. Radial arterial and right atrial pressures were measured in all patients. Esophageal pressures, intratracheal pressures, or minute ventilation was measured in the last 13 patients. Application of both CPR techniques increased arterial and right atrial pressures. The mean coronary perfusion pressure was increased throughout the entire CPR cycle with ACD CPR (compression, 21.5±9.0 mm Hg; decompression, 21.9±8.7 mm Hg) compared with standard CPR (compression, 17.9±8.2 mm Hg; decompression, 18.5 ±6.9 mm Hg;P< .02 andP< .02, respectively). Ventilation per compression-decompression cycle was 97.3±65.6 mL with standard CPR and 168.4±68.6 mL with ACD CPR (n=7,P< .001). Negative inspiratory pressure was −0.8±4.8 mm Hg with standard CPR and −11.4±6.3 mm Hg with ACD CPR (n=6,P< .04).ConclusionsPatients undergoing multiple inductions of VF during cardioverter/defibrillator implantation with transvenous leads provide a well-controlled and reproducible model to study the mechanisms of CPR. Using this model, ACD CPR significantly increased arterial blood pressure, coronary perfusion pressure, minute ventilation, and negative inspiratory pressure compared with standard CPR.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID