Non-invasive imaging techniques and assessment of carotid vasa vasorum neovascularization: Promises and pitfalls.

Carotid adventitia vasa vasorum neovascularization (VVn) is associated with the initial stages of arteriosclerosis and with the formation of unstable plaque. However, techniques to accurately quantify that neovascularization in a standard, fast, non-invasive, and efficient way are still lacking. The development of such techniques holds the promise of enabling wide, inexpensive, and safe screening programs that could stratify patients and help in personalized preventive cardiovascular medicine. In this paper, we review the recent scientific literature pertaining to imaging techniques that could set the stage for the development of standard methods for quantitative assessment of atherosclerotic plaque and carotid VVn. We present and discuss the alternative imaging techniques being used in clinical practice and we review the computational developments that are contributing to speed up image analysis and interpretation. We conclude that one of the greatest upcoming challenges will be the use of machine learning techniques to develop automated methods that assist in the interpretation of images to stratify patients according to their risk.

[Hemodialysis prospective multicentric quality study]. / Estudio prospectivo multicentrico de calidad en hemodialisis.

In medicine a considerable amount of resources are used in research, but very little attention is paid to ensuring that the findings of research are implemented in routine clinical practice. This prospective study has the aim to evaluate the efficiency of some clinical management strategies (feedback, benchmarking and improving plans) on haemodialysis treatment results in 4 different dialysis centres. We collected consensus data related to haemodialysis results every 6-8 months and informed each centre about its own results (feedback) and how these related to the others(benchmarking). We designed improving plans for any bad result detected. By the end of two years of follow up, 294 patients had been included in the study. The results obtained at the end of the study had improved in comparison with those obtained at the beginning (statistically significant) for the following indicators: % of patients with Hb< 11 g/dl, % patients with Kt/v < 1.2, mean Kt/v, mean albumin, % patients with albumin< 3.5 g/dl y % patients with C reactive protein (CRP) > 5 mg/dl. No statistical changes were found in: mean erythropoietin (EPO) doses, blood pressure (BP), phosphorus plasmatic,calcium-phosphorus product, parathormone (PTHi) and vascular access distribution. We explained the absence of any improvement because of adequate start indicators in some areas (BP and vascular access), therapy with limited efficiency (calcitriol, calcium carbonate and others), lack of support resources (dietetic unit) or inadequate design/implementation of improving plans.In conclusion, our intervention illustrates that combined clinical management strategies(feedback, benchmarking and improving plans) are efficiency in improving some areas of haemodialysis treatment (anaemia, dialysis dose, nutrition and inflammation), although it does not improve calcium phosphate metabolism related indicators.

Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction: results from the global use of strategies to open occluded arteries in Acute Coronary Syndromes (GUSTO-IIb) trial.

BACKGROUND: Time to treatment with thrombolytic therapy is a critical determinant of mortality in acute myocardial infarction. Little is known about the relationship between the time to treatment with direct coronary angioplasty and clinical outcome. The objectives of this study were to determine both the time required to perform direct coronary angioplasty in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) trial and its relationship to clinical outcome. METHODS AND RESULTS: Patients randomized to direct coronary angioplasty (n=565) were divided into groups based on the time between study enrollment and first balloon inflation. Patients randomized to angioplasty who did not undergo the procedure were also analyzed. The median time from study enrollment to first balloon inflation was 76 minutes; 19% of patients assigned to angioplasty did not undergo an angioplasty procedure. The 30-day mortality rate of patients who underwent balloon inflation /=91 minutes after enrollment, 6.4%. The mortality rate of patients assigned to angioplasty who never underwent the procedure was 14.1% (P=0.001). Logistic regression analysis revealed that the time from enrollment to first balloon inflation was a significant predictor of mortality within 30 days; after adjustment for differences in baseline characteristics, the odds of death increased 1.6 times (P=0.008) for a movement from each time interval to the next. CONCLUSIONS: The time to treatment with direct PTCA, as with thrombolytic therapy, is a critical determinant of mortality.

Survival outcomes 1 year after reperfusion therapy with either alteplase or reteplase for acute myocardial infarction: results from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial.

BACKGROUND: New recombinant plasminogen activators have been developed to simulate the fibrinolytic action of the physiological serine protease tissue plasminogen activator (alteplase, t-PA), and have prolonged half-life features permitting bolus administration. One such activator, reteplase (r-PA), was compared with t-PA in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-III Trial. METHODS AND RESULTS: At 1-year follow-up, survival status was ascertained in 97.4% of the 15 059 patients enrolled in the GUSTO-III trial. At 1 year, the mortality rate for the t-PA-assigned group was 11.06%, and for r-PA it was 11.20% (P:=0. 77). The absolute mortality difference of 0.14% has 95% CIs of -1. 21% to 0.93%. There were no significant differences in outcome by intention-to-treat for the 2 different plasminogen activators in the prespecified groups (age, infarct location, time-to-treatment). The absolute difference in mortality rates between t-PA and r-PA progressively narrowed over the predetermined observation times after random assignment; it was 0.31% at 24 hours, 0.26% at 7 days, 0.23% at 30 days, and 0.14% at 1 year. Of note, mortality rate in the trial between 30 days and 1 year in 13 883 patients was 4.02% and did not differ between the treatment groups. However, this mortality rate was substantially greater than in GUSTO-I, in which mortality rate for t-PA versus streptokinase between 30 days and 1-year was 2.97% (heart rate 1.36, 95% CI 1.23, 1.50, P:<0.001). CONCLUSIONS: The r-PA and t-PA strategies yielded similar survival outcomes after 30 days in this trial. The increase in mortality rate during extended follow-up compared with previous trials may reflect higher-risk patients and highlights the need for improved secondary prevention strategies.

Carvedilol for prevention of restenosis after directional coronary atherectomy : final results of the European carvedilol atherectomy restenosis (EUROCARE) trial.

BACKGROUND: In addition to its known properties as a competitive, nonselective beta and alpha-1 receptor blocker, carvedilol directly inhibits vascular myocyte migration and proliferation and exerts antioxidant effects that are considerably greater than those of vitamin E or probucol. This provides the basis for an evaluation of carvedilol for the prevention of coronary restenosis. METHODS AND RESULTS: In a prospective, double-blind, randomized, placebo-controlled trial, 25 mg of carvedilol was given twice daily, starting 24 hours before scheduled directional coronary atherectomy and continuing for 5 months after a successful procedure. The primary end point was the minimal luminal diameter as determined during follow-up angiography 26+/-2 weeks after the procedure. Of 406 randomized patients, 377 underwent attempted atherectomy, and in 324 (88.9%), a

Unstable angina: outcome according to clinical presentation.

Unstable angina is a broad clinical diagnosis that includes patients at different levels of risk for an unfavorable outcome. Although, as in other categories of coronary artery disease, the state of left ventricular function and the extent of coronary artery disease will determine long-term prognosis, recognition of clinical markers of an early unfavorable course may be of value in defining management strategies. This review focuses on the relevance of baseline clinical characteristics and noninvasive data in assessing the prognostic significance of unstable angina in light of its presenting features. Recurrence of chest pain within 48 h after admission carries a reduction in likelihood of survival of about 20% in patients with progressive or prolonged angina. Similarly, ECG changes on admission have a negative prognostic implication, particularly in rest angina, as they predict recurrence of ischemia, myocardial infarction or need for revascularization in 80% of the patients. In variant angina, determinants of prognosis are level of disease activity, as judged by recurrence of pain, ECG changes and use of calcium channel antagonists. Patients with angina after a myocardial infarction who have more than one episode of either angina or silent ischemia in 24 h have a 10% reduction in probability of survival during the 1st year compared with that of asymptomatic patients. An abrupt course, or the rapidity with which symptoms develop, is the main determinant of prognosis in new onset angina. Thus, recurrent angina and ECG changes appear to be relevant prognostic markers in the patient subsets considered; if these are present, early coronary angiography must be performed and revascularization procedures should be considered without delay.

Coronary artery revascularization in patients with sustained ventricular arrhythmias in the chronic phase of a myocardial infarction: effects on the electrophysiologic substrate and outcome.

OBJECTIVES: The objective of this study was to analyze the influence of coronary artery revascularization in patients with ventricular arrhythmias. BACKGROUND: Coronary artery revascularization is an effective treatment for myocardial ischemia; however, its effect on ventricular arrhythmias not related to an acute ischemic event has not been carefully studied. METHODS: Sixty-four patients (58 men, mean age 65 +/- 8 years old) with prior myocardial infarction, spontaneous ventricular arrhythmias not related to an acute ischemic event (55 ventricular tachycardia, 9 ventricular fibrillation) and coronary lesions requiring revascularization were studied prospectively. Electrophysiological study was performed before and after revascularization, and events during follow-up were analyzed. RESULTS: At initial study 61 patients were inducible into sustained ventricular arrhythmias. After revascularization, in 62 survivors, 52 out of 59 patients previously inducible were still inducible (group A), and 10 patients were noninducible (group B). No differences were found in clinical, hemodynamic, therapeutic and electrophysiological characteristics between both groups. During 32 +/- 26 months follow-up, 28/52 patients in group A (54%) and 4/10 patients in group B (40%) had arrhythmic events (p = 0.46). An ejection fraction <30% predicted recurrent arrhythmic events (p = 0.02), but not the presence of demonstrable ischemia before revascularization (p = 0.42), amiodarone (p = 0.69) or beta-adrenergic blocking agent therapy (p = 0.53). Total mortality was 10% in both groups. CONCLUSIONS: In patients with ventricular arrhythmias in the chronic phase of myocardial infarction, probability of recurrence is high despite coronary artery revascularization, but mortality is low if combined with appropriate antiarrhythmic therapy. Recurrences are related to the presence of a low ejection fraction but not to demonstrable ischemia before revascularization, amiodarone or beta-blocker therapy nor are they the results of electrophysiological testing after revascularization.

Short-term effects of transdermal estrogen replacement therapy on coronary vascular reactivity in postmenopausal women with angina pectoris and normal results on coronary angiograms.

OBJECTIVES: This study sought to analyze the effect of short-term transdermal estradiol treatment on in vivo coronary endothelial function in postmenopausal women with angina and normal results on coronary arteriograms. BACKGROUND: The incidence of coronary heart disease increases in women after menopause. Estrogen replacement therapy has been associated with a global reduction in cardiovascular disease incidence and mortality. In addition, coronary endothelial dysfunction has been demonstrated in a group of postmenopausal women. It has been shown that intravenous or intracoronary estrogens improve endothelial function in postmenopausal women with coronary atherosclerosis. However, the efficacy of this treatment is unknown in patients with angina and normal coronary arteries. METHODS: Endothelium-dependent coronary reactivity was analyzed in 15 postmenopausal women with angina and normal coronary arteries at baseline and after 24 h of estradiol transdermal administration (100 microg). RESULTS: Estradiol concentration increased from 22 +/- 8 pg/ml (mean +/- SEM) at baseline to 76 +/- 13 pg/ml (p < 0.01) at 24 h. At baseline, acetylcholine induced vasoconstriction, with a mean diameter reduction of -23 +/- 6% (p = 0.002). After estrogen treatment, there was no vasoconstriction with acetylcholine, with a mean diameter change of 0 +/- 4%, significantly different from the pretreatment diameter reduction observed (p = 0.003). Similarly, estimated coronary blood flow significantly increased in response to acetylcholine after estrogen treatment, with a mean change of 50 +/- 30% compared with 5 +/- 24% before estradiol administration (p = 0.04). CONCLUSIONS: Early after transdermal estrogen administration, endothelium-dependent coronary vasomotion is improved in postmenopausal women with angina and normal coronary arteries.

Feasibility of early discharge after acute Q wave myocardial infarction in patients not receiving thrombolytic treatment.

OBJECTIVES: The purpose of this study was to analyze the feasibility of early discharge (4 days) after acute myocardial infarction in patients not receiving thrombolytic therapy by first identifying predictors of short-term prognosis and then testing the derived risk profile in an independent cohort of patients. BACKGROUND: Previous studies have shown that early discharge after acute myocardial infarction is possible. However, physicians are reluctant to shorten the standard 7- to 10-day hospital stay, presumably because of difficulty in selecting low risk patients. METHODS: From January 1985 to November 1986, 358 patients with acute myocardial infarction who did not receive thrombolytic therapy were screened. Those with a Q-wave infarction showing no complications on day 4 were considered candidates for early discharge and were transferred to the ward for a mean of 12 days. During this period, we looked for any event (cardiac or noncardiac) that would have prompted readmission if the patient had been previously discharged. Univariate and multiple regression analysis were performed to identify predictors of these events among 25 baseline variables. The derived risk profile was tested in an independent validation cohort. RESULTS: One hundred five (29.3%) of the 358 patients were free of symptoms on day 4, and 29 (27.6%) had at least one cardiac event, including four deaths and one reinfarction. Multivariate analysis selected diabetes, ejection fraction < 40% and age as independent predictors of events. Using the risk profile, 18 (13.2%) of the 136 validation cohort patients were categorized as low risk, and only 1 of them had a major event (progressive angina). Sensitivity for the risk profile was high (91%), but specificity was low (34%). CONCLUSIONS: The use of simple clinical variables may allow the safe reduction of hospital stay after infarction in selected patients. However because the proportion of candidates for early discharge is small (12.6%), it seems unlikely that the current policies on length of hospital stay will change in the near future.

Randomized comparison of coronary stent implantation and balloon angioplasty in the treatment of de novo coronary artery lesions (START): a four-year follow-up.

OBJECTIVE: The purpose of this study was to test the hypothesis that stent implantation in de novo coronary artery lesions would result in lower restenosis rates and better long-term clinical outcomes than balloon angioplasty. BACKGROUND: Placement of an intracoronary stent, as compared with balloon angioplasty, has proven to reduce the rate of restenosis. However, the long-term clinical benefit of stenting over angioplasty has not been assessed in large randomized trials. METHODS: We randomly assigned 452 patients with either stable (129 patients) or unstable (323 patients) angina pectoris to elective stent implantation (229 patients) or standard balloon angioplasty (223 patients). Coronary angiography was performed at baseline, immediately after the procedure and six months later. End points were the rate of restenosis at six months and a composite of death, myocardial infarction (MI) and target vessel revascularization over four years of follow-up. RESULTS: Procedural success rate was achieved in 84% and 95% (balloon angioplasty vs. stent, respectively). The increase in the minimal luminal diameter was greater in the stent group both after the intervention (2.02 +/- 0.6 mm vs. 1.43 +/- 0.6 mm in the angioplasty group; p < 0.0001), and at six-month follow-up (1.98 +/- 0.7 mm vs. 1.63 +/- 0.7 mm; p < 0.001). The corresponding restenosis rates were 22% and 37%, respectively (p < 0.002). After four years, no differences in mortality (2.7% vs. 2.4%) and nonfatal MI (2.2% vs. 2.8%) were found between the stent and the angioplasty groups, respectively. However, the requirement for further revascularization procedures of the target lesions was significantly reduced in the stent group (12% vs. 25% in the angioplasty group; relative risk 0.49, 95% confidence interval 0.32 to 0.75, p = 0.0006); most of the repeat procedures (84%) were carried out within six months of entry into the study. CONCLUSIONS: Patients who received an intracoronary stent showed a lower rate of restenosis than those treated with conventional balloon angioplasty. The benefit of stenting was maintained four years after implantation, as manifested by a significant reduction in the need for repeat revascularization.

Reactivation of ischemic events in acute coronary syndromes: results from GUSTO-IIb. Gobal Use of Strategies To Open occluded arteries in acute coronary syndromes.

OBJECTIVES: We sought to determine the incidence of and risk factors for thrombotic events early after discontinuing antithrombin therapy in patients with acute coronary syndromes. BACKGROUND: Discontinuation of treatment with heparin and other thrombin inhibitors in patients with unstable coronary syndromes has related to clinical and biochemical evidence of early reactivation of thrombosis. METHODS: We studied 8,943 of the 12,142 patients with acute coronary syndromes enrolled in the Global Use of Strategies To Open occluded arteries in acute coronary syndromes trial of hirudin versus heparin. We excluded patients who received no study drug, lacked timing data, died or had myocardial (re)infarction [(re)MI] during study-drug infusion, or began heparin treatment within 2 h after treatment with the study drug was stopped. We assessed the incidence and timing of (re)MI by type and timing of antithrombin treatment. RESULTS: In all, 215 patients (2.4%) suffered (re)MI, 49 within 12 h of antithrombin therapy discontinuation and 166 between hour 12 and hospital discharge. The duration of infusion did not differ between the hirudin and heparin groups. The rate of early re(MI) after drug therapy discontinuation was significantly higher in patients given heparin versus hirudin (0.8% vs. 0.3%, p = 0.002). Patients with (re)MI had higher mortality at 30 days (23.6% vs. 2.4%, p = 0.001) and 1 year (35.2% vs. 6.7%, p = 0.001) compared with patients without (re)MI. CONCLUSIONS: The incidence of (re)MI was clustered within 12 h of heparin therapy discontinuation, with the greatest risk within 4 h. There was no evidence of early reactivation of thrombotic events after hirudin. Patients who had (re)infarction had worse outcomes. Better understanding of the mechanism and possible prevention of recurrent thrombosis is needed.

Recurrent ischemia after thrombolysis: importance of associated clinical findings. GUSTO-I Investigators. Global Utilization of Streptokinase and t-PA [tissue-plasminogen activator] for Occluded Coronary Arteries.

OBJECTIVES: We sought to assess the incidence and clinical relevance of examination data to recurrent ischemia within an international randomized trial. BACKGROUND: Ischemic symptoms commonly recur after thrombolysis for acute myocardial infarction. METHODS: Patients (n = 40,848) were prospectively evaluated for recurrent angina and transient electrocardiographic (ECG) or hemodynamic changes. Five groups were developed: Group 1, patients with no signs or symptoms of recurrent ischemia; Group 2, patients with angina only; Group 3, patients with angina and ST segment changes; Group 4, patients with angina and hemodynamic abnormalities; and Group 5, patients with angina, ST segment changes and hemodynamic abnormalities. Baseline clinical and outcome variables were compared among the five groups. RESULTS: Group 1 comprised 32,717 patients, and Groups 2 to 5 comprised 20% of patients (4,488 in Group 2; 3,021 in Group 3; 337 in Group 4; and 285 in Group 5). Patients with recurrent ischemia were more often female, had more cardiovascular risk factors and less often received intravenous heparin. Significantly more extensive and more severe coronary disease, antianginal treatment, angioplasty and coronary bypass surgery were observed as a function of ischemic severity. The 30-day reinfarction rate was 1.6% in Group 1, 6.5% in Group 2, 21.7% in Group 3, 13.1% in Group 4 and 36.5% in Group 5 (p < 0.0001); in contrast, the 30-day mortality rate was significantly lower (p < 0.0001) in Groups 1, 2 and 3 (6.6%, 5.4% and 7.7%, respectively) than in Groups 4 and 5 (21.8% and 29.1%). CONCLUSIONS: Postinfarction angina greatly increases the risk of reinfarction, especially when accompanied by transient ECG changes. However, mortality is markedly increased only in the presence of concomitant hemodynamic abnormalities.

Coronary revascularization surgery after myocardial infarction: impact of bypass surgery on survival after thrombolysis. GUSTO Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: This study sought to investigate the impact of surgical revascularization on outcome after myocardial infarction. BACKGROUND: Small variations in rates of coronary artery bypass graft surgery (CABG) were noted among thrombolytic regimens in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, prompting the question of whether survival differences were partly related to differences in CABG rates. METHODS: Patients in the GUSTO trial were randomized to one of four thrombolytic strategies. Of 40,861 patients with complete data, 3,526 underwent surgical revascularization during their initial hospital admission. Thirty-day and 1-year mortality rates were estimated using Kaplan-Meier techniques, and the impact of CABG as a time-dependent covariate on death was evaluated using a Cox survival model, adjusting for baseline prognostic factors. RESULTS: The median time from study enrollment to CABG was 7 days across treatment groups. A 15% reduction in mortality for the tissue-type plasminogen activator (t-PA)-treated group was evident by the seventh day. Bypass surgery was a significant independent predictor of 30-day mortality (risk ratio 1.87) and a weaker predictor of 1-year mortality (risk ratio 1.21). Operative mortality was highest in patients with acute mitral regurgitation, ventricular septal defect or poor left ventricular function and in those undergoing CABG within the first 4 days of randomization. CONCLUSIONS: The survival benefit of accelerated t-PA was not related to surgical revascularization. Bypass surgery was associated with excess mortality in the first year, but the added short-term mortality associated with CABG may be balanced by anticipated long-term benefit in specific groups of patients.

Randomized, double-blind study comparing saruplase with streptokinase therapy in acute myocardial infarction: the COMPASS Equivalence Trial. Comparison Trial of Saruplase and Streptokinase (COMASS) Investigators.

OBJECTIVES: This study sought to demonstrate the equivalence of saruplase and streptokinase in terms of 30-day mortality. BACKGROUND: The use of thrombolytic agents in the treatment of acute myocardial infarction is well established and has been shown to substantially reduce post-myocardial infarction mortality. METHODS: Three thousand eighty-nine patients with symptoms compatible with those of acute myocardial infarction for < 6 h entered the study at a total of 104 centers and were randomized to receive streptokinase (1.5-MU infusion over 60 min) or saruplase (20-mg bolus and 60-mg infusion over 60 min). In the saruplase group, a bolus of heparin (5,000 IU) was administered before saruplase, and a corresponding blinded double-dummy placebo bolus was administered before streptokinase. All patients received intravenous heparin infusions for > or = 24 h starting 30 min after the end of the thrombolytic infusions; the infusions were titrated to maintain an activated partial thromboplastin time at 1.5 to 2.5 times that of normal. RESULTS: Death of any cause up to 30 days after randomization occurred in 88 (5.7%) of 1,542 patients randomized to receive saruplase and 104 (6.7%) of 1,547 patients randomized to receive streptokinase (odds ratio 0.84, p < 0.01 for equivalence). Hemorrhagic strokes occurred more often in patients receiving saruplase (0.9% vs. 0.3%), whereas thromboembolic strokes were more prevalent in the streptokinase-treated patients (0.5% vs. 1.0%). The rate of bleeding was similar in the two treatment groups (10.4% vs. 10.9%). Hypotension and cardiogenic shock occurred less frequently in the saruplase group. Reinfarction rates were similar. CONCLUSIONS: Saruplase is a clinically safe and effective thrombolytic medication. This profile ranks saruplase favorably among the currently available thrombolytic agents.

Outcome of Hispanic patients treated with thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I and III trials. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.

OBJECTIVES: We sought to describe the differences in the process of care and clinical outcomes between Hispanics and non-Hispanics receiving thrombolytic therapy for myocardial infarction (MI). BACKGROUND: Hispanics are the fastest growing and second largest minority in the U.S. but most cardiovascular disease data on Hispanics has been derived from retrospective studies and vital statistics. Despite their higher cardiovascular risk-factor profile, better outcomes after MI have been reported in Hispanics. METHODS: We studied the baseline characteristics, resource use and outcomes of 734 Hispanics and 27,054 non-Hispanics treated for MI in the GUSTO-I and -III trials. The primary end point of both trials was 30-day mortality. RESULTS: Hispanics were younger, shorter, lighter and more often diabetic and began thrombolysis 9 min later, compared with non-Hispanics. Measures of socioeconomic status (educational level, employment and health insurance) were lower among Hispanics. Fewer Hispanics than non-Hispanics underwent in-hospital angiography (70% vs. 74%, p = 0.013) or bypass surgery (11% vs. 13.5%, p = 0.04). Hispanics received more angiotensin-converting enzyme (ACE) inhibitors and less calcium-channel blockers, prophylactic lidocaine and inotropic agents. Mortality at 30 days and at one year did not differ significantly between Hispanics and non-Hispanics (6.4% vs. 6.7% and 9.0% vs. 9.7%, respectively). We noted no interactions between thrombolytic strategy and Hispanic status on major outcomes (30-day death, stroke and major bleeding). CONCLUSIONS: The care of Hispanics with MI differed slightly from that of non-Hispanics. Nevertheless, these differences in care did not affect long-term outcomes.

Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial.

OBJECTIVES: We examined the utility of early percutaneous coronary intervention (PCI) in a trial that encouraged its use after thrombolysis and glycoprotein IIb/IIIa inhibition for acute myocardial infarction (MI). BACKGROUND: Early PCI has shown no benefit when performed early after thrombolysis alone. METHODS: We studied 323 patients (61%) who underwent PCI with planned initial angiography, at a median 63 min after reperfusion therapy began. A blinded core laboratory reviewed cineangiograms. Ischemic events, bleeding, angiographic results, and clinical outcomes were compared between early PCI and no-PCI patients (n = 162), between patients with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 or 1 before PCI versus flow grade 2 or 3, and among three treatment regimens. RESULTS: Early PCI patients showed a procedural success (<50% residual stenosis and TIMI flow grade 3) rate of 88% and a 30-day composite incidence of death, reinfarction, or urgent revascularization of 5.6%. These patients had fewer ischemic events and bleeding complications (15%) than did patients not undergoing early PCI (30%, p = 0.001). Early PCI was used more often in patients with initial TIMI flow grade 0 or 1 versus flow grade 2 or 3 (83% vs. 60%, p < 0.0001). Patients receiving abciximab with reduced-dose reteplase (5 U double bolus) showed an 86% incidence of TIMI grade 3 flow at approximately 90 min and a trend toward improved outcomes. CONCLUSIONS: In this analysis, early PCI facilitated by a combination of abciximab and reduced-dose reteplase was safe and effective. This approach has several advantages for acute MI patients, which should be confirmed in a dedicated, randomized trial.

Evidence for both abnormal set point of PTH stimulation by calcium and adaptation to serum calcium in hemodialysis patients with hyperparathyroidism.

In vitro studies of parathyroid glands removed from dialysis patients with secondary hyperparathyroidism and hypercalcemia have demonstrated the presence of an increased set point of parathyroid hormone (PTH) stimulation by calcium (set point [PTHstim]), suggesting an intrinsic abnormality of the hyperplastic parathyroid cell. However, clinical studies on dialysis patients have not observed a correlation between the set point (PTHstim) and the magnitude of hyperparathyroidism. In the present study, 58 hemodialysis patients with moderate to severe hyperparathyroidism (mean PTH 780 +/- 377 pg/ml) were evaluated both before and after calcitriol treatment to establish the relationship among PTH, serum calcium, and the set point (PTHstim) and to determine whether changes in the serum calcium, as induced by calcitriol treatment, modified these relationships. Calcitriol treatment decreased serum PTH levels and increased the serum calcium and the setpoint (PTHstim); however, the increase in serum calcium was greater than the increase in the setpoint (PTHstim). Before treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium was r = 0.82, p < 0.001, and between the set point (PTHstim) and PTH was r = 0.39, p = 0.002. After treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium remained significant (r = 0.70, p < 0.001), but the correlation between the set point (PTHstim) and PTH was no longer significant (r = 0.09); moreover, a significant correlation was present between the change in the set point (PTHstim) and the change in serum calcium that resulted from calcitriol treatment (r = 0.73, p < 0.001). The correlation between the residual values (deviation from the regression line) of the set point (PTHstim), derived from the correlation between PTH and the set point (PTHstim), and serum calcium was r = 0.77, p < 0.001 before calcitriol and r = 0.72, p < 0.001 after calcitriol. In conclusion, the set point (PTHstim) increased after a sustained increase in the serum calcium, suggesting an adaptation of the set point to the existing serum calcium; the increase in serum calcium resulting from calcitriol treatment was greater than the increase in the set point (PTHstim); the set point (PTHstim) was greater in hemodialysis patients with higher serum PTH levels; and the correlation between PTH and the set point (PTHstim) may be obscured because the serum calcium directly modifies the set point (PTHstim).

Disabling angina pectoris with normal coronary arteries in patients undergoing long-term hemodialysis.

Reports of patients undergoing long-term hemodialysis presenting with angina pectoris have usually shown severe coronary atherosclerosis. We studied a series of nine patients undergoing regular maintenance dialysis referred for incapacitating angina. Of them, four had strictly normal coronary angiograms. The patients with normal angiograms were all females who were significantly younger (p less than 0.05) and had more severe hypertension and higher left ventricular wall stress than patients showing coronary artery lesions. Anemia and increased myocardial oxygen consumption due to high blood pressure may explain the syndrome of angina pectoris in the presence of long-term dialysis in patients with normal coronary arteries. The prevalence of this association cannot be ascertained unless prospective studies are conducted. However, our data suggest that it might not be an uncommon finding.

Collaborative Angiographic Patency Trial Of Recombinant Staphylokinase (CAPTORS II).

AIMS: A fibrinolytic agent more effective than streptokinase available for bolus injection with reasonable cost-effectiveness is a desirable goal. Pilot studies with bolus pegulated staphylokinase (PEG-Sak) have revealed excellent Thrombolysis In Myocardial Infarction (TIMI) 3 60-minute flow. METHODS AND RESULTS: We evaluated patients with acute ST-elevation myocardial infarction within 6 hours of chest pain onset to determine a dose of PEG-Sak that had at least equal efficacy to recombinant tissue plasminogen activator (rt-PA) while maintaining an acceptable safety profile. After the initial study of 38 patients, of whom 27 received PEG-Sak, enrollment was temporarily halted because 3 patients receiving PEG-Sak had intracranial hemorrhage: 1 at a dose of 0.15 mg/kg and 2 at a dose of 0.05 mg/kg. Overall, 378 patients were studied across a PEG-Sak dose range from 0.01 mg/kg to 0.015 mg/kg, and 122 patients received accelerated rt-PA. At the lowest dose of PEG-Sak studied, 0.01 mg/kg, there was suggestive evidence of attenuation of efficacy; the point estimate for TIMI 3 flow was 24% (95% CI 9%-38%). At doses of 0.01875 to 0.0375 mg/kg (n = 314), TIMI 3 flow rates were 33% (95% CI 27%-38%), whereas the TIMI 3 flow was 41% (95% CI 20%-61%) at the highest PEG-Sak dose studied, 0.05 mg/kg (n = 23), which was similar to that found with rt-PA, 41% (95% CI 32%-50%). CONCLUSION: The efficacy of PEG-Sak, coupled with its ease of administration, provide further impetus for further study in acute myocardial infarction.

Influence of partial sympathetic denervation on the results of myocardial revascularization in variant angina.

Poor results of the aortocoronary bypass graft operation in the treatment of variant angina have been ascribed to recurrent vasospastic activity due to autonomic imbalance. Cardiac sympathetic denervation (plexectomy) may represent a rational approach in the prevention of vasospasm. To test the value of plexectomy in the treatment of variant angina, 31 patients were studied, 17 of whom (Group 1) underwent conventional coronary artery grafting whereas the remaining 14 (Group 2) underwent cardiac sympathetic denervation also. The 2 groups were similar with respect to age (54 +/- 8 versus 50 +/- 7 years), sex distribution (male/female ratio 12/5 versus 9/5), prevalence of coexisting effort angina (10 versus 12 patients), previous myocardial infarction (7 versus 4 patients), and duration of variant angina (3.3 +/- 5.4 versus 2.4 +/- 2.7 months). The left ventricular ejection fraction was comparable in both groups (60 +/- 11 versus 60 +/- 4%) as were left ventricular end-diastolic pressure (15 +/- 4 versus 13 +/- 5 mm Hg) and extent of coronary artery disease (65 versus 71% prevalence of multivessel disease). The average duration of follow-up was 23 +/- 15 months in Group 1 and 22 +/- 18 months in Group 2 (p = not significant [NS]). There were no operative deaths. Four patients, 2 in each group, had a perioperative myocardial infarction. Seven patients in Group 1 and 1 patient in Group 2 had recurrent variant angina. There was sudden death and 2 infarcts in Group 1. Actuarial curves showed the cumulative probability of recurrent variant angina to be significantly lower (p less than 0.05 and p less than 0.001 at 6 and 10 months, respectively) in Group 2. This study suggests that cardiac sympathetic denervation may prevent recurrent vasospastic activity in variant angina.