ISSN:0009-7322    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

BackgroundSilent myocardial ischemia is an adverse prognostic marker in patients with coronary disease; however, controlled data on the effect of treatment are sparse and contradictory, and the relations among the occurrence of ST segment depression, drug efficacy, and heart rate are unclear.Methods and ResultsSixty patients with stable coronary artery disease, a positive treadmill exercise test and asymptomatic ST segment depression on ambulatory electrocardiographic recording were assessed in a multicenter, double-blind, placebo-controlled, cross-over trial. Treadmill exercise tests and 72-hour electrocardiographic recordings were obtained at the end of two 2-week treatment periods with sustained-release diltiazem 180 mg b.i.d. or equivalent placebo. Episodes of asymptomatic ST depression decreased by 50% or more in 70% of the patients from a median number of 4.5 (range, 0-19) to 1.5 (range, 0-13) (p=0.0001); their cumulative duration also decreased from 78.5 (range, 0-60) to 24.5 (range, 0-411) minutes (p=0.001). No circadian variation was found in the efficacy of diltiazem. The occurrence of ischemic type ST segment depression was modulated by changes in heart rate rather than by absolute heart rate. Diltiazem also improved exercise test end points but to a lesser extent. Time to ST segment depression increased to 341 ± 148 from 296 ± 154 seconds (p=0.005). Although less frequent with diltiazem administration (45 versus 54 patients,p< 0.03), exercise-induced ST depression Was more often asymptomatic (98% versus 72% of patients,p< 0.0001).ConclusionsDiltiazem reduces the frequency and severity of ischemic type ST depression in patients with stable coronary artery disease. (Circulation1991;84:15–22)

ISSN:0009-7322    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

BackgroundThe ability to predict outcome after mitral valve replacement remains limited in patients with symptomatic chronic mitral regurgitation. The aims of this study were to determine the preoperative predictors of postoperative cardiac-related mortality and to assess the additive prognostic value of tests performed in such patients.Methods and ResultsAccordingly, 176 patients (mean age, 57 ± 14 years) who underwent mitral valve replacement were followed up for 3.8 ± 0.5 years. Four categories of variables were analyzed to predict postoperative cardiac-related mortality: clinical, laboratory, two-dimensional echocardiographic (2DE), and cardiac catheterization. There were 39 cardiac-related deaths (29 due to congestive heart failure and 10 sudden). When the four categories were analyzed separately, two clinical, one laboratory, two 2DE, and one catheterization variable best predicted postoperative death. When these six variables were examined simultaneously, only three (one clinical and two 2DE) remained significant predictors of cardiac-related mortality: presence of pulmonary rales, left atrial size, and the ratio of left ventricular wall thickness to left ventricular cavity dimension in end systole. A model based on these three variables may predict cardiac-related death with considerable accuracy. Laboratory data did not add to clinical information for predicting death. 2DE variables provided significant additional information in this regard (p< 0.001). Further addition of catheterization variables was not useful. Prognostic value did not change significantly when 50 patients with prior mitral valve surgery or 49 patients undergoing concomitant aortic valve replacement or coronary artery bypass surgery were excluded from analysis.ConclusionsWe conclude that 1) measures of both left ventricular systolic function and leftatrial size are equally important in predicting postoperative cardiac-related mortality in patients with symptomatic chronic mitral regurgitation undergoing mitral valve replacement; 2) left atrial size may be important because it reflects the “history” (severity and duration) of mitral regurgitation; 3) 2DE assessment. of left atrial size and left ventricular function provides prognostic information that is significantly greater than that obtained from clinical and laboratory parameters alone; the addition of catheterization variables does not increase the prognostic value of the clinical and 2DE data. (Circulation1991;84:23–34)

ISSN:0009-7322    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

BackgroundOrganic nitrates such as nitroglycerin and isosorbide dinitrate are useful in the treatment of congestive heart failure (CHF), but tolerance develops rapidly during continuous administration. Because combination therapy of nitrate and hydralazine has been shown to provide both short- and long-term benefit but nitrate alone produces hemodynamic tolerance, we questioned whether hydralazine can preserve the favorable preload effects of nitroglycerin.Methods and ResultsUsing an in vivo model of nitroglycerin tolerance in the CHF rat, we examined the effects of hydralazine bolus dosing during continuous nitroglycerin infusion. Continuous infusion of nitroglycerin alone (10 jpg/mmn) produced initial reductions in left ventricular end-diastolic pressure of 40-50%, which returned to baseline by 8 hours (tolerance development). Coadministration of hydralazine (2X0.1 mg) maintained the effects of nitroglycerin infusion on left ventricular end-diastolic pressure (45% reduction at 10 hours). This hydralazine dose alone reduced left ventricular peak systolic pressure by approximately 12 ± 3% but had no effect on left ventricular end-diastolic pressure. Hydralazine dosing did not affect steady-state plasma concentrations of nitroglycerin or metabolites, and hydralazine was unable to prevent nitroglycerin tolerance induced in vitro.ConclusionsThe beneficial interaction of hydralazine on the preload effects of nitroglycerin may explain the long-term clinical efficacy of hydralazine/nitrate combination in CHF. Our results also suggest that the mechanism of in vivo nitrate tolerance in CHF may be systemic rather than vascular in origin. (Circulation1991;84:35–39)

ISSN:0009-7322    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

BackgroundAtrial fibrillation is common in advanced heart failure, but its prognostic significance is controversial.Methods and ResultsWe evaluated the relation of atrial rhythm to overall survival and sudden death in 390 consecutive advanced heart failure patients. Etiology of heart failure was coronary artery disease in 177 patients (45%) and nonischemic cardiomyopathy or valvular heart disease in 213 patients (55%). Mean left ventricular ejection fraction was 0.19 ± 0.07. Seventy-five patients (19%o) had paroxysmal (26 patients) or chronic (49 patients) atrial fibrillation. Compared with patients with sinus rhythm, patients with atrial fibrillation did not differ in etiology of heart failure, mean pulmonary capillary wedge pressure on therapy, or embolic events but were more likely to be receiving warfarin and antiarrhythmic drugs and had a slightly higher left ventricular ejection fraction. After a mean follow-up of 236 ± 303 days, 98 patients died: 56 (57%) died suddenly, and 36 (37%) died of progressive heart failure. Actuarial 1-year overall survival was 68%, and sudden death-free survival was 79%. Actuarial survival was significantly worse for atrial fibrillation than for sinus rhythm patients (52% versus 71%, p =0.0013). Similarly, sudden death-free survival was significantly worse for atrial fibrillation than for sinus rhythm patients (69% versus 82%,p= 0.0013). By Cox proportional hazards model, pulmonary capillary wedge pressure on therapy, left ventricular ejection fraction, coronary artery disease, and atrial fibrillation were independent risk factors for total mortality and sudden death. For patients who had pulmonary capillary wedge pressure of less than 16 mm Hg on therapy, atrial fibrillation was associated with poorer 1-year survival (44% versus 83%,p= 0.00001); however, in the high pulmonary capillary wedge pressure group, atrial fibrillation did not confer an increased risk (58% versus 57%).ConclusionsAtrial fibrillation is a marker for increased risk of death, especially in heart failure patients who have lower filling pressures on vasodilator and diuretic therapy. Whether aggressive attempts to maintain sinus rhythm will reduce this risk is unknown. (Circulation1991;84:40–48)

ISSN:0009-7322    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

BackgroundRecent reports critical of the performance of heart rate-adjusted indexes of ST depression during exercise electrocardiography have used J-point rather than ST segment measurements. However, no standard exists for the optimal time after the J-point at which to measure ST segment deviation.Methods and ResultsTo assess the effect of ST segment measurement position on performance of standard exercise electrocardiographic criteria, the AST segment/heart rate (AST/HR) index, and the ST segment/heart rate (ST/HR) slope for the detection of coronary artery disease, the exercise electrocardiograms of 50 clinically normal subjects and 80 patients with known or likely coronary disease were analyzed using ST depression measured at both the J-point and at 60 msec after the J-point (J+60). A positive exercise electrocardiogram by standard criteria, defined as 0.1 mV or more of additional horizontal or downsloping ST depression at end exercise, had a specificity of 96% when ST depression was measured at either the J-point or J+60. There was no difference in sensitivity of standard electrocardiographic criteria at J+60 and J point (both 59%, p=NS). However, at matched specificity of 96%, the AST/HR index and ST/HR slope calculated using ST depression at J+60 were significantly more sensitive (90% and 93%) than when calculated using J-point depression (64% and 61%, eachp< 0.001). Comparison of areas under respective receiver operating characteristic curves confirmed the superior performance of J+60 as opposed to J-point measurements for both the AST/HR index (0.98 versus 0.89,p=0.006) and the ST/HR slope (0.96 versus 0.87,p=O0.007) and also demonstrated modestly improved overall test performance for standard electrocardiographic criteria using J+60 measurements (0.88 versus 0.82,p= 0.001).ConclusionsUse of J-point measurements significantly degrades performance of heart rate-adjusted indexes of ST depression but has less effect on standard criteria. (Circulation1991;84:57–66)

ISSN:0009-7322    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

BackgroundConventional cardiac imaging methods do not depict true segmental myocardial shortening, since they cannot determine segment length between fixed points in the myocardium.Methods and ResultsWe used electrocardiographically gated magnetic resonance imaging with spatial modulation of magnetization to noninvasively “tag” the myocardium with dark stripes at uniform 7-mm intervals center to center at end diastole. We then determined end-systolic stripe separation and thereby calculated circumferential shortening. When end systole was not reached in the first image series, a second temporally overlapped series starting in late systole was used to determine late-systolic shortening. Septal, anterior, lateral, and inferior segments were assessed at endocardium, midwall, and epicardium on five midventricular short-axis sections each in 10 normal volunteers. A transmural gradient in circumferential shortening was observed, with the percentage of endocardial segment shortening consistently greater than epicardial segment shortening (epicardial, 22 ± 5%; midwall, 30 ± 6%; and endocardial, 44 ± 6%;p< 0.0001 by analysis of variance). Circumferential shortening varied from apex to base with slices closer to the base of the left ventricle showing less shortening at the midwall (28 ± 9%o) and endocardium (39 ± 6%) than more apical slices at the midwall (34 ± 13%) and endocardium (49 ± 9%o) (p< 0.05 andp< 0.01, respectively, by analysis of variance).ConclusionsTransmural and longitudinal heterogeneity of circumferential shortening is present in the normal human left ventricle. Magnetic resonance imaging with spatial modulation of magnetization is a powerful new tool for assessment of circumferential shortening and provides information unobtainable with conventional imaging methods. (Circulation1991;84:67–74)

ISSN:0009-7322    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

BackgroundClonidine, a partial presynaptic and postsynaptic a-adrenoceptor agonist, has been shown to lower blood pressure in normal subjects but not in tetraplegics; however, the mechanisms of this action have not been elucidated.Methods and ResultsThe hemodynamic and hormonal basis of the hypotensive action of clonidine was investigated in tetraplegics with complete cervical spinal cord transection and preganglionic sympathetic denervation, in patients with unilateral brachial plexus injury and postganglionic sympathetic denervation, and in normal subjects. In normal subjects, the fall in blood pressure after clonidine infusion was accompanied by a reduction in cardiac output that was predominantly due to a fall in stroke volume and in heart rate. The lack of fall in blood pressure, cardiac output, and stroke volume in tetraplegics indicates that these effects are exerted at a supraspinal level and require intact descending sympathetic pathways. After clonidine infusion, digital skin vasodilatation occurred in normal subjects, in the innervated but not the denervated limb of patients with unilateral brachial plexus injury, and in tetraplegics, indicating that this response is due to the central sympatholytic effect of clonidine. Plasma norepinephrine was much lower in tetraplegics compared with normal subjects, and after clonidine infusion, it fell substantially in normal subjects alone. Plasma renin activity did not change. Bladder stimulation in tetraplegics resulted in a rise in blood pressure and vasoconstriction in digital skin vessels. The inability of clonidine to significantly reduce or abolish the pressor and digital vasoconstrictor responses after bladder stimulation in tetraplegics indicates that clonidine does not exert a major effect on spinal preganglionic neurons or peripheral presynaptic a2-adrenoceptors.ConclusionsTherefore, clonidine is a suitable drug for use in analyzing the central supraspinal levels of control in varying circulatory disorders, such as hypertension and postural hypotension. (Circulation1991;84:75–83)

ISSN:0009-7322    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

BackgroundStreptokinase (SK) is a bacteria-derived protein and one of the plasminogen activators that is currently available for therapeutic use. Exposure to SK induces synthesis of specific antibodies that may initiate platelet aggregation and paradoxical clot propagation during treatment.Methods and ResultsUsing platelet-rich plasma (PRP), we found that SK (5,000 units/ml) but not urokinase (2,500 units/ml) or recombinant tissue-type plasminogen activator (2,500 units/ml) caused platelet aggregation in PRP from 14 of 100 normal volunteers. In 13 consecutive patients teated with SK for acute myocardial infarction, SK-mediated platelet aggregation was induced in five patients within 1 week after treatment. SK-mediated platelet aggregation was associated with significantly increased titers of both anti-SK antibodies and SK-neutralizing activity in plasma; it was partially inhibited by aspirin (1 mM) and by aprotinin (500 kallikrein inhibitor units/ml) and completely inhibited by tranexamic acid (1 mM) and by prostaglandin E1 (9, M). Addition of SK (1,000 or 5,000 units/ml) induce a statistically significant dose-dependent thromboxane B2 release in mixtures of PRP with plasma from subjects with SK-induced aggregation but not in samples of PRP mixed with plasma from nonresponders; addition of recombinant tissue-type plasminogen (1 50 jug/ml) did induce thromboxane B2 release. Mixing experiments with PRP and immunoglobulin G from reactive and nonreactive donors revealed that SK-induced aggregation rquires the presence of anti-SK antibodies. When 1251-SK (50 nM) was used, platelets preincubated with plasminogen (0.5 μM) bound 9,500 ± 600 (mean ± SEM,n= 6) molecules SK/platelet, which increased to 25,000 ± 3,100 molecules/platelet after thrombin stimulation. Tranexamic acid (1 mM) blocked specific binding of SK to resting platelets.ConcluionsThese data demonstrate that SK-induced platelet aggregation is initiated by the binding of anti-SK antibodies to the SK-plasminogen complex located on the platelet surface. SK-induced platelet activation may limit the therapeutic effectiveness of the drug, and in view of the high prevalence of aggregation in a normal population, prospective evaluation of the effects of platelet aggregation during treatment with SK is warranted. (Circulation1991;84:84–91)

ISSN:0009-7322    

出版商:OVID    

年代:1991

数据来源: OVID