摘要:

BackgroundThe degree to which antithrombotic drugs suppress thrombin generation is unknown. Because hirudin, unlike antithrombin III, binds intravascular thrombin rapidly and selectively to yield a circulating inactive complex of 3- to 4-hour half-life, we used intravenous hirudin in humans to investigate the course of thrombin generation during and early after anticoagulation with this potent, direct antithrombin.Methods and ResultsIntravascular thrombin was measured with an ELISA for the thrombin-hirudin complex formed during and for 18 hours after stopping a 6-hour infusion of hirudin at 0.1, 0.2, and 0.3 mg.kg−1·h−1in three groups of six patients each. With free hirudin in 20- to 10,000-fold molar excess of thrombin and peak activated partial thromboplastin times of 2.3 to 3.0 times baseline, mean plasma thrombin- hirudin complex increased from 794 ± 85 pg/mL (mean ± SEM) 15 minutes after the start of the infusion to 1617 ± 151 pg/mL at 6 hours of infusion to 2667 ± 654 pg/mL at 24 hours. During the 24-hour observation period, plasma concentration of fragment 1.2 (the peptide released during conversion of prothrombin to thrombin) never fell below baseline but rather increased transiently during the hirudin infusion. Plasma concentrations of thrombin-antithrombin III complex (in ng/mL) decreased from 4.34 ± 0.40 at baseline to 1.64 ± 0.13 at 6 hours (P< .001) and gradually increased after stopping the infusion to 5.7 ± 0.87 at 24 hours (nonsignificant compared with baseline).ConclusionsMeasurement of thrombin-hirudin complex may be used as a marker of thrombin generation in humans. Persistent accumulation of thrombin- hirudin complex and generation of fragment 1.2 during and after completion of potent anticoagulation with hirudin suggest thrombin generation is not blocked by high-affinity thrombin inhibition. The persistent formation of thrombin during declining plasma levels of hirudin may contribute to the pathogenesis of rethrombosis early after antithrombin therapy or during inadequate anticoagulation.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe blood coagulation cascade was reported to be activated in patients with arteriosclerotic disease of the lower limbs (peripheral arterial disease, PAD). There is more thrombin and fibrin formation compared with healthy control subjects. In many studies, however, the presence of arteriosclerotic disease had not been thoroughly ruled out in the control group. Therefore, markers of the activation of the blood coagulation cascade were measured in patients with PAD and in a carefully defined control group, both groups being subjected to an exercise test.Methods and ResultsTwenty-two patients with angiographically documented PAD of grade II (Fontaine classification) and 13 control subjects in whom the presence of arteriosclerotic lesions was ruled out by noninvasive means in the carotid arteries, abdominal aorta, leg arteries, and coronary arteries took part in the study. Before and immediately after a treadmill stress test, the concentrations of prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA; this peptide was measured in spot urine also), and D-dimers were measured. Before exercise, the concentrations of F1 + 2 (1.0 ± 0.6 versus 0.7 ± 0.3 nmol/L), TAT (2.9 ± 2.1 versus 1.9 ± 0.8 μg/L), and D-dimers (318.2 ± 270.1 versus 150.0 ± 91.4 μg/L) were significantly higher in the patients with PAD compared with the healthy control subjects. FPA concentrations in plasma (1.9 ± 1.0 versus 1.4 ± 0.6 μg/L) and spot urine were not different, however. F1 + 2, FPA, and D-dimer concentrations correlated with the severity of the PAD as assessed by the ankle systolic blood pressure index (ABPI). The symptom-limited stress test did not lead to further activation of the blood coagulation cascade. However, concentrations of F1 + 2 (P< .001) and TAT (P< .01) after exercise correlated with the presence of ischemic changes in the stress-test ECG.ConclusionsThere is evidence of enhanced thrombin formation in patients with PAD compared with an age- and sex-matched control group without clinical and sonographic evidence of arteriosclerosis. The thrombin formed, however, appears to be almost completely neutralized by antithrombin III. No direct evidence of fibrin formation was obtained, since the FPA concentrations were not different. In the patients with PAD, the higher concentrations of D-dimers are indicative of in vivo fibrinolysis. Thus, some fibrin formation must be postulated to occur in patients with arteriosclerosis.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe uptake of F-18 deoxyglucose into dysfunction segments after myocardial infarction identifies metabolically active (FDG+) or inactive (FDG−) myocardium. Although patients with FDG+ segments have been found to be at risk for adverse events, the prognostic significance of viable myocardium in relation to other influences on postinfarction prognosis, including revascularization, remain ill defined. The purpose of this study was to investigate the relative prognostic significance of FDG+ tissue and to establish whether myocardial revascularization in patients with viable tissue attenuates the risk of adverse outcome.Methods and ResultsOne hundred thirty-seven patients with left ventricular dysfunction and resting perfusion defects after myocardial infarction underwent positron emission tomography with both dipyridamole stress Rb-82 perfusion imaging and FDG imaging. After the exclusion of 4 patients proceeding to transplantation, 2 with uninterpretable scans and 2 lost to follow-up, 129 patients were followed clinically for 17 ± 9 months. Four groups were defined: patients with FDG+ dysfunctional myocardium who were revascularized (n = 49) or treated medically (n = 21) and those with FDG− segments who were revascularized (n = 19) or treated medically (n = 40). The groups of patients with FDG+ or FDG− findings, with and without revascularization, did not differ with respect to known determinants of postinfarction prognosis: age, left ventricular ejection fraction, or the prevalence of multivessel disease. Nonfatal ischemic events occurred in 48% of medically treated FDG+ patients compared with 8% of revascularized patients with FDG+ tissue (P< .001) and 5% of patients with FDG- myocardium (P< .001). Thirteen patients died from cardiac causes; 11 (85%) had a left ventricular ejection fraction of < 30%, and these patients were evenly distributed between FDG+ and FDG− groups. Using Cox's proportional hazards model, only the presence of FDG+ myocardium (odds ratio, 12.9;P< .001) and the absence of revascularization (odds ratio, 5.8;P= .002) independently predicted ischemic events, while only age (P= .02) and ejection fraction (P< .001) but not the presence of viable myocardium were predictive of death.ConclusionsResidual viable myocardium after myocardial infarction may act as an unstable substrate for further events unless it is revascularized. Despite this association, age and left ventricular dysfunction remained the strongest predictors of cardiac death after myocardial infarction in these patients with a spectrum of left ventricular dysfunction.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundSublingual nitrates are much more effective in relieving angina pectoris in patients with coronary artery disease than in patients with syndrome X, but it is not known whether their effect on exercise tolerance is also different in these two groups of patients.Methods and ResultsTreadmill exercise testing was performed before and after administration of sublingual isosorbide dinitrate (ISDN, 5 mg) in 18 patients with syndrome X (effort angina and normal coronaries, group X) and in 33 patients with documented coronary artery disease (group C). As a selection criterion, all patients had ST- segment depression ≥ 1 mm on the control exercise test. Compared with the control test, the main differences in the two groups observed during the exercise test after administration of ISDN were (1) heart rate at 1-mm ST-segment depression was higher (126 ± 25 versus 104 ± 15 beats per minute [bpm],P< .01) in group C, whereas it was not different (125 ± 15 versus 126 ± 16 beats per minute) in group X; (2) the rate-pressure product at 1-mm ST-segment depression, the time to 1-mm ST-segment depression, and the exercise duration were significantly improved in group C (P< .01 for all) but were worsened in group X (18047 ± 4159 versus 20535 ± 4507 bpm · mm Hg,P= .014; 268 ± 312 versus 429 ± 214 seconds,P< .01; 494 ± 279 versus 622 ± 194 seconds, P = .013, respectively); (3) a normalization of the ECG (no ST-segment depression) was obtained in 10 patients (30%) of group C but in only 1 (5%) of group X (P< .01); (4) angina was prevented in 10 of 19 patients of group C but in no patient of group X (P< .01).ConclusionsIn patients presenting with anginal chest pain, the effects of sublingual nitrates on exercise testing appear to be clinically useful to distinguish patients with coronary artery stenoses from patients with syndrome X. Indeed, worsening of exercise tolerance is highly predictive of normal coronary arteries. Furthermore, the failure of nitrates to improve exercise tolerance in patients with syndrome X suggests that a deficiency in coronary prearteriolar nitric oxide production is unlikely to play a key role in the pathophysiology of the syndrome.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundExercise-induced hypotension in patients with coronary artery disease (CAD) has been considered to be due to an inability to achieve an adequate increase in cardiac output to match the demands of exercise. We investigated 10 consecutive patients (9 men and 1 woman; age, 38 to 71 years; mean, 52 years) with angiographically documented CAD and exercise-induced hypotension (EIH) (BPPeak< BPRest). Ten approximately age- and sex-matched patients with documented CAD and normal exercise blood pressure response (NBP) served as control subjects.Methods and ResultsNine patients with EIH and all 10 control subjects underwent forearm plethysmography and radionuclide ventriculography (RNV) during semierect cycle exercise. Forearm vascular resistance (FVR) fell by 35 ± 21% in exercise-induced hypotension patients versus an increase of 78 ± 65% in patients with an NBP response (P< .0001). Left ventricular ejection fraction increased by 5.1 ± 7.5% in the group with EIH versus a fall of 4.1 ± 6.2% in the control group (P= .004). Cardiac output at peak exercise (RNV) increased by 2.2 ± 0.89-fold in the group with EIH versus 1.49 ± 0.47-fold in the control group (P= .04). The tenth patient in the group with EIH underwent invasive hemodynamic evaluation during erect exercise. Systolic blood pressure fell (136/80Restto 50/40Peak) and cardiac output (Fick) tripled, whereas calculated systemic vascular resistance decreased by a factor of 10. Successful angioplasty to an isolated circumflex lesion resulted in resolution of symptoms and abnormal hemodynamic responses during exercise.ConclusionsAbnormal vasodilation associated with a normal or even increased rather than decreased cardiac output response appears to be an important mechanism underlying EIH in some patients with CAD. In the present study, this appears to have been the dominant mechanism in 8 and contributory in 2 of the consecutive patients studied.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundTrapidil is an antiplatelet drug with specific platelet- derived growth factor antagonism and antiproliferative effects in the rat and rabbit models after balloon angioplasty.Methods and ResultsThe Studio Trapidil versus Aspirin nella Restenosi Coronarica (STARC) is a multicentric, randomized, double-blind trial to assess the effects of trapidil in angiographic restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either trapidil 100 mg TID or aspirin at the same dosage at least 3 days before angioplasty and for 6 months thereafter. Coronary angiograms before PTCA, after PTCA, and at 6-month follow-up were quantitatively analyzed with manual calipers. Of the initial 384 patients recruited, 254 were evaluable for restenosis analysis (128 trapidil, 126 aspirin). Restenosis, defined as a loss of initial percent gain after PTCA of at least 50% (primary end point), occurred in 24.2% of the trapidil group and 39.7% of the aspirin group (P< .01). A similar result was obtained when restenosis per vessel was considered (trapidil, 23.3%; aspirin, 36.9%;P= .018). Clinical events at follow-up were similar in the two groups except that recurrent angina was significantly more frequent in the aspirin group, 43.7% versus 25.8% in the trapidil group (P< .01). Trapidil was well tolerated: only 6 patients had to discontinue the drug because of side effects, which was not different from the aspirin group.ConclusionsTrapidil reduces restenosis after PTCA at the dosage of 100 mg TID and favorably influences the clinical outcome thereafter.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundAbrupt vessel closure after percutaneous transluminal coronary angioplasty (PTCA) is associated with major adverse events. Different surgical and nonsurgical approaches have been advocated to treat or prevent this complication. This study summarizes our 4-year experience with Palmaz-Schatz stenting for the management of 339 patients with present or threatened occlusion after PTCA.Methods and ResultsStent implantation was attempted in a total of 339 and 4959 patients with PTCA during the study period and was successful in 327 (96.5%). During the follow-up, events like death, myocardial infarction, need for revascularization (bypass surgery and repeat in- stent angioplasty), and major vascular complications were recorded. Angiographic follow-up at 6 months was performed in 89.3% of the eligible patients. As part of an initial policy, stenting was intended as a bridge to nonemergency bypass surgery in 26 patients. In 301 patients for whom stenting was intended as permanent treatment, early clinical course (first 4 weeks) was characterized by a 1.3% cardiac mortality and a 4.0% nonfatal myocardial infarction rate; bypass surgery was necessary in 1%, and 6.3% required early repeat PTCA. Surgical repair for peripheral vascular complications was required in 5.6%, and major bleeding events were encountered in 9%. The incidence of subacute stent closure was 6.9%, with subsequent recanalization successful in 86%; subacute stent closure was predicted by presence of vessel occlusion before stenting and localization of the stent in a vessel other than the right coronary artery. Survival rate at 2 years was 95.4%, survival without myocardial infarction was 91.1%, and event-free survival was 70.7%. Survival at 2 years was lower for patients with stents in bypass vein grafts and with myocardial infarction after stenting. Six-month control angiography revealed a restenosis rate of 29.6%.ConclusionsPatients with present or threatened occlusion after PTCA may benefit from Palmaz-Schatz stenting. It is associated with a low mortality and myocardial infarction rate and with a long-term event- free rate comparable to that of uncomplicated PTCA.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe incidence of coronary perforation using new percutaneous revascularization techniques may be increased compared with PTCA. Still, perforation is uncommonly reported, and the optimal management and expected outcome remain unknown. The objectives of the study were to determine the incidence of coronary perforation using balloon angioplasty (percutaneous transluminal coronary angioplasty, PTCA) and new revascularization techniques and to develop optimal strategies for its management based on classification and outcome.Methods and ResultsEleven sites with frequent use of new revascularization devices and prospective coding of consecutive procedures for coronary perforation during 1990 to 1991 contributed to a perforation registry. Patients with perforation were matched by device with an equal-sized cohort without perforation. Data were collected centrally, and all procedural cineangiograms were reviewed at a core angiographic laboratory. A classification scheme based on angiographic appearance of the perforation (I, extraluminal crater without extravasation; II, pericardial or myocardial blushing; III, perforation ≥ 1-mm diameter with contrast streaming; and cavity spilling) was evaluated as a predictor of outcome and as a basis for management. Perforation was observed in 62 of 12900 procedures reported (0.5%; 95% confidence interval, 0.4% to 0.6%), more commonly with devices intended to remove or ablate tissue (atherectomy, laser) than with PTCA (1.3%, 0.9% to 1.6% versus 0.1%, 0.1% to 0.1%;P< .001). The perforation population was notable for its advanced age (67 ± 10 years) and high incidence of female sex (46%) (bothP< .001 compared with patients without perforation). Perforation could be treated expectantly or with PTCA but without cardiac surgery in 85%, 90%, and 44% of class I, II, and III perforations, respectively. Class I perforations (n = 13, 21%) were associated with death in none, myocardial infarction in none, and tamponade in 8%. The incidences of these adverse events were 0%, 14%, and 13% in class II perforations (n = 31, 50%) and 19%, 50%, and 63% in non-cavity spilling class III perforations, respectively (n = 16, 26%). Two of the 15 instances of cardiac tamponade (13%) were delayed, occurring within 24 hours after dismissal from the catheterization laboratory.ConclusionThe incidence of perforation, while low, is increased with new devices. Women and the elderly are at highest risk. The clinical risk after perforation can be classified angiographically, but even low-risk perforations occasionally have poor clinical outcome. Patients should be observed for delayed cardiac tamponade for at least 24 hours.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundWe previously reported that 6 to 12 weeks of dual-chamber (DDD) pacing results in clinical and hemodynamic improvement in obstructive hypertrophic cardiomyopathy (HCM). This study examines the long-term results of DDD pacing in obstructive HCM.Methods and ResultsDDD devices were implanted in 84 patients (mean age, 49 ± 16 years) with obstructive HCM and severe drug-refractory symptoms. At a mean follow-up of 2.3 ± 0.8 years (maximum, 3.5 years), the New York Heart Association (NYHA) functional class had improved significantly (1.6 ± 0.6 versus 3.2 ± 0.5,P< .00001). Symptoms were eliminated in 28 patients (33%), improved in 47 patients (56%), but remained unchanged in 7 patients (8%). Two patients died suddenly (97% cumulative 3-year survival rate). In 74 patients with significant left ventricular outflow tract (LVOT) obstruction at rest, the LVOT gradients were significantly reduced at follow-up (27 ± 31 versus 96 ± 41 mm Hg,P< .00001). Symptoms and provokable LVOT gradients were also reduced in all 10 patients without significant resting but with provokable LVOT obstruction. Persistence of the LVOT obstruction and symptoms was attributed to inability to pre-excite the interventricular septum (n = 8) and onset of atrial fibrillation (n = 7). Fifty patients had two cardiac catheterization evaluations, 3 ± 1 and 16 ± 4 months after implantation of a pacemaker. In this subgroup, the NYHA functional class improved from 3.2 ± 0.5 at baseline to 1.8 ± 0.7 at the initial evaluation (P< .00001), but with a further significant improvement at the second evaluation: 1.4 ± 0.6,P< .001. This symptomatic improvement was associated with progressive reduction of LVOT gradient at the two evaluations: baseline, 100 ± 47 mm Hg; first evaluation, 41 ± 36 mm Hg (P< .0001); and second evaluation, 29 ± 34 mm Hg (P< .01). Despite the presence of left bundle branch block, DDD pacing reduced LVOT obstruction significantly in 15 patients (LVOT gradient, baseline 89 ± 36 mm Hg versus 18 ± 26 mm Hg at follow-up,P< .0001). There was a weak but significant correlation between the reduction in LVOT gradients accomplished by AV pacing before implantation of DDD device and the eventual reduction in LVOT gradients recorded at the follow-up evaluation (r= .38,P= .0017). Echocardiography demonstrated significant thinning of the anterior septum and distal anterior LV wall in the absence of deterioration of LV systolic function.Conclusions(1) Although most of the improvement of symptoms and hemodynamic indexes occurs during the first few months of DDD pacing, further changes are often observed a year later; (2) DDD pacing is associated with an excellent prognosis in a subgroup of severely disabled patients, many of whom present with syncope or presyncope; (3) baseline pacing studies are not essential to identify patients who may benefit from pacing; (4) preexisting left bundle branch block is compatible with severe LVOT obstruction, and DDD pacing is also beneficial in this subgroup; (5) DDD pacing reduces both resting and provokable LVOT obstruction; (6) additional therapy, for example, radiofrequency ablation of the AV node, may be necessary in some patients either to preexcite the interventricular septum or to control atrial fibrillation; and (7) although LV hypertrophy has been considered a primary feature of HCM, pacing appears to reverse LV wall thickness in a significant subset of adult HCM patients.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundIn the early 1980s, studies performed in highly selected referral patients with hypertrophic cardiomyopathy reported a strong association between the presence of brief episodes of ventricular tachycardia (VT) on ambulatory ECG monitoring and sudden death. These observations led to antiarrhythmic treatment in many patients with hypertrophic cardiomyopathy and brief episodes of VT. In recent years, however, a growing awareness of the potential arrhythmogenic effects of antiarrhythmic medications has raised doubts regarding such a therapeutic approach, particularly in less selected and lower-risk patient populations.Methods and ResultsIn the present study, we examined the prognostic significance of nonsustained VT in a population of 151 patients with hypertrophic cardiomyopathy who were asymptomatic or had only mild symptoms at the time of their initial ambulatory ECG recording. Of the 151 study patients, 42 had episodes of VT and 109 did not. The runs of VT ranged from 3 to 19 beats, with 35 patients (83%) having < 10 beats. The number of runs of VT ranged from 1 to 12 in 24 hours, with 36 patients (86%) having ≤ 5 episodes of VT. Thus, in most patients, the episodes of VT were brief and infrequent. Follow-up averaged 4.8 years. Of the 151 study patients, 6 died suddenly, 3 in the group with VT and 3 in the group without VT. Two other patients, both in the group without VT, died of congestive heart failure. The total cardiac mortality rate was 1.4% per year in the patients with VT (95% CI, 0.4% to 3.5%) and 0.9% in those without VT (95% CI, 0.4% to 2.0%;P= .43). The relative risk of cardiac death for patients with VT was 1.4 compared with patients without VT (95% CI, 0.6 to 6.1). The sudden death rate was 1.4% per year in the patients with VT (95% CI, 0.4% to 3.5%) and 0.6% in those without VT (95% CI, 0.2% to 1.5%;P= .24). The relative risk of sudden death for patients with VT compared with those without VT was 2.4 (95% CI, 0.5 to 11.9). Of the 151 patients included in the study, 88 (58%) remained asymptomatic and were not treated with cardioactive medications during follow-up. Of these 88 patients, 20 were in the group with VT and 68 in the group without VT. None of these patients died.ConclusionsOur results show that cardiac mortality is low in patients with hypertrophic cardiomyopathy who are asymptomatic or only mildly symptomatic and have brief and infrequent episodes of VT on ambulatory ECG monitoring. Our findings also suggest that brief and infrequent episodes of VT should not be considered, per se, an indication for antiarrhythmic treatment in such patients.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID