Which factors are associated with the application of reperfusion therapy in ST-elevation acute coronary syndromes?. Lessons from the Euro Heart Survey on Acute Coronary Syndromes I.

BACKGROUND/AIMS: A large proportion of patients with a ST-elevation acute coronary syndrome do not receive reperfusion therapy. In order to contribute to a better understanding of the clinical decision making process, we analyzed which factors are associated with the application of reperfusion therapy. METHODS: From the Euro Heart Survey of Acute Coronary Syndromes I, 4,260 patients with ST-elevation acute coronary syndrome were selected for the current analysis, of which 1,539 (36%) patients received fibrinolysis and 904 (21%) primary percutaneous coronary intervention (PCI). The analysis contained 32 variables on demographics, medical history, admission parameters and reperfusion therapy. RESULTS: A short pre-hospital delay, arrival in a hospital with PCI facilities, severe ST-elevation, and participation in a clinical trial were the strongest predictors for receiving reperfusion therapy. Primary PCI was more likely to be performed than fibrinolysis in patients with a long pre-hospital delay, arriving in a hospital with PCI facilities, not participating in a clinical trial, and with at least one previous PCI. CONCLUSION: Hospital facilities and culture, pre-hospital delay and infarction size play a major role in management decisions regarding reperfusion therapy in ST-elevation acute coronary syndrome. This analysis indicates which factors require special attention when implementing and reviewing the reperfusion guidelines.

Diabetes mellitus: clinical presentation and outcome in men and women with acute coronary syndromes. Data from the Euro Heart Survey ACS.

AIMS: To study clinical presentation, in-hospital course and short-term prognosis in men and women with diabetes mellitus and acute coronary syndromes (ACS). METHODS: Men (n = 6488, 21.2% with diabetes) and 2809 women (28.7% with diabetes) < or = 80 years old, with a discharge diagnosis of ACS were prospectively enrolled in the Euro Heart Survey of ACS. RESULTS: Women with diabetes were more likely to present with ST elevation than non-diabetic women, a difference that became more marked after adjustment for differences in smoking, hypertension, obesity, medication and prior disease [adjusted odds ratio (OR) 1.46 (1.20, 1.78)], whereas there was little difference between diabetic and non-diabetic men [adjusted OR 0.99 (0.86, 1.14)]. In addition, women with diabetes were more likely to develop Q-wave myocardial infarction (MI) than non-diabetic women [adjusted OR 1.61 (1.30, 1.99)], while there was no difference between men with and without diabetes [adjusted OR 0.99 (0.85, 1.15)]. There were significant interactions between sex, diabetes and presenting with ST-elevation ACS (P < 0.001), and Q-wave MI (P < 0.001), respectively. Of the women with diabetes, 7.4% died in hospital, compared with 3.6% of non-diabetic women [adjusted OR 2.13 (1.39, 3.26)], whereas corresponding mortality rates in men with and without diabetes were 4.1% and 3.3%, respectively [OR 1.13 (0.76, 1.67)] (P for diabetes-sex interaction 0.021). CONCLUSION: In women with ACS, diabetes is associated with higher risk of presenting with ST-elevation ACS, developing Q-wave MI, and of in-hospital mortality, whereas in men with ACS diabetes is not significantly associated with increased risk of either. These findings suggest a differential effect of diabetes on the pathophysiology of ACS based on the patient's sex.

Cardiovascular risk factors and clinical presentation in acute coronary syndromes.

OBJECTIVE: To investigate the hypothesis that risk factors may be differently related to severity of acute coronary syndromes (ACS), with ST elevation used as a marker of severe ACS. DESIGN: Cross sectional study of patients with ACS. SETTING: 103 hospitals in 25 countries in Europe and the Mediterranean basin. PATIENTS: 10,253 patients with a discharge diagnosis of ACS in the Euro heart survey of ACS. MAIN OUTCOME MEASURES: Presenting with ST elevation ACS. RESULTS: Patients with ACS who were smokers had an increased risk to present with ST elevation (age adjusted odds ratio (OR) 1.84, 95% confidence interval (CI) 1.67 to 2.02). Hypertension (OR 0.65, 95% CI 0.60 to 0.70) and high body mass index (BMI) (p for trend 0.0005) were associated with less ST elevation ACS. Diabetes mellitus was also associated with less ST elevation, but only among men. Prior disease (infarction, chronic angina, revascularisation) and treatment with aspirin, beta blockers, or statins before admission were also associated with less ST elevation. After adjustment for age, sex, prior disease, and prior medication, smoking was still significantly associated with increased risk of ST elevation (OR 1.53, 95% CI 1.38 to 1.69), whereas hypertension was associated with reduced risk (OR 0.75, 95% CI 0.69 to 0.82). Obesity (BMI > 30 kg/m2 versus < 25 kg/m2) was independently associated with less risk of presenting with ST elevation among women, but not among men. CONCLUSION: Among patients with ACS, presenting with ST elevation is strongly associated with smoking, whereas hypertension and high BMI (in women) are associated with less ST elevation, independently of prior disease and medication.

The safety and efficacy of repeated courses of tissue-type plasminogen activator in patients with stuck mitral valves who did not fully respond to the initial thrombolytic course.

In carefully selected patients with stuck mitral valves, thrombolytic therapy is becoming an established therapeutic modality. However, the management of patient with a suboptimal response to an initial thrombolytic course is unclear. The objective was to evaluate the efficacy and safety of re-administration of tissue-type plasminogen activator (rt-PA) in patients with stuck mitral valves in whom the first thrombolytic course has failed to restore normal prosthetic valve function. The study group included patients who received rt-PA and did achieve a full restoration of valve function after the initial course. Data were gathered on the safety and success rates of additional thrombolytic courses in the same hospitalization period, and their predictors. Twelve patients with stuck mitral valves experienced a total of 13 episodes in which a full resolution of leaflet abnormality was not achieved after the initial thrombolytic course. A repeated thrombolytic course was attempted in 10 patients (11 episodes). Six patients (60%) showed full success rate with repeated thrombolysis, one (10%) showed partial success, and three patients (30%) had no improvement following the second course. These last three were those with initial failure. Age, gender, valve model, worst functional class, time since valve implantation and International Normalized Ratio (INR) levels were similar in both groups. No major adverse events were noted. In this small group of patients with stuck mitral valves, re-administration of rt-PA after a partial response to an initial thrombolytic course was effective and safe. However, total failure of the first thrombolytic course predicted inefficiency of further courses.

A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin; the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS).

AIMS: To better delineate the characteristics, treatments, and outcomes of patients with acute coronary syndromes (ACS) in representative countries across Europe and the Mediterranean basin, and to examine adherence to current guidelines. METHODS AND RESULTS: We performed a prospective survey (103 hospitals, 25 countries) of 10484 patients with a discharge diagnosis of acute coronary syndromes. The initial diagnosis was ST elevation ACS in 42.3%, non-ST elevation ACS in 51.2%, and undetermined electrocardiogram ACS in 6.5%. The discharge diagnosis was Q wave myocardial infarction in 32.8%, non-Q wave myocardial infarction in 25.3%, and unstable angina in 41.9%. The use of aspirin, beta-blockers, angiotensin converting enzyme inhibitors, and heparins for patients with ST elevation ACS were 93.0%, 77.8%, 62.1%, and 86.8%, respectively, with corresponding rates of 88.5%, 76.6%, 55.8%, and 83.9% for non-ST elevation ACS patients. Coronary angiography, percutaneous coronary interventions, and coronary bypass surgery were performed in 56.3%, 40.4%, and 3.4% of ST elevation ACS patients, respectively, with corresponding rates of 52.0%, 25.4%, and 5.4% for non-ST elevation ACS patients. Among patients with ST elevation ACS, 55.8% received reperfusion treatment; 35.1% fibrinolytic therapy and 20.7% primary percutaneous coronary interventions. The in-hospital mortality of patients with ST elevation ACS was 7.0%, for non-ST elevation ACS 2.4%, and for undetermined electrocardiogram ACS 11.8%. At 30 days, mortality was 8.4%, 3.5%, and 13.3%, respectively. CONCLUSIONS: This survey demonstrates the discordance between existing guidelines for ACS and current practice across a broad region in Europe and the Mediterranean basin and more extensively reflects the outcomes of ACS in real practice in this region.

Management and outcome of cardiogenic shock complicating acute myocardial infarction in hospitals with and without on-site catheterisation facilities.

OBJECTIVE: To determine whether the availability of on-site catheterisation and revascularisation facilities influenced hospital management and outcome of patients with acute myocardial infarction complicated by cardiogenic shock. METHODS: Patients with acute myocardial infarction were enrolled prospectively in four nationwide surveys during 1992, 1994, 1996, and 1998. The characteristics, management, and outcome of patients with cardiogenic shock were compared between hospitals with on-site catheterisation facilities (group 1; 18 hospitals) and without such facilities (group 2; 8 hospitals). RESULTS: Of 5351 patients with acute myocardial infarction, 254 (4.7%) developed cardiogenic shock. Group 1 patients (n = 186 of 3854; 4.6%) were younger (mean (SD) age, 69.6 (12) v 73.7 (10) years, p = 0.006) and had a lower proportion of women (36% v 52%, p = 0.03) than group 2 (n = 68 of 1243; 5.2%). There was no difference in other characteristics including the use of thrombolysis. Group 1 patients more often underwent coronary angiography (26% v 4%, p < 0.001), angioplasty (21% v 4%, p = 0.002), and intra-aortic balloon counterpulsation (28% v 4%, p < 0.001). Seven day mortality was lower among group 1 than among group 2 patients (61% v 77%, p = 0.02), even after age and sex adjustment (odds ratio (OR) 0.54; 95% confidence interval (CI) 0.28 to 1.02). This outcome benefit persisted at 30 days (74% v 88%, p = 0.01; OR 0.45, 95% CI 0.18 to 0.98), and at 6 months (80% v 90%, p = 0.06; OR 0.57, 95% CI 0.22 to 1.33). CONCLUSIONS: The greater use of invasive and interventional procedures in hospitals with catheterisation facilities is associated with improved survival of patients with acute myocardial infarction complicated by cardiogenic shock. Immediate availability of invasive care facilities will improve the outcome of cardiogenic shock in the community setting.

Aspirin and percutaneous coronary angioplasty are associated with a decline in mortality from cardiogenic shock. Results from a national Israeli survey, 1992--1998.

BACKGROUND AND METHODS: Despite the significant progress in the care and outcome of patients with acute myocardial infarction (AMI), the impact of evolving therapies on the incidence and outcome of patients with cardiogenic shock complicating AMI has been questioned. We analyzed trends in the incidence, care and outcome of cardiogenic shock from four national surveys conducted during 1992--1998. RESULTS: Of the 5,351 AMI patients admitted to all coronary care units in Israel, 254 (4.7%) developed cardiogenic shock. The incidence of cardiogenic shock decreased over time (5.8, 5.1, 4.3 and 4.4% for the years 1992, 1994, 1996 and 1998, respectively, p = 0.08). Concomitantly, there was an increase in utilization of coronary angiography, urgent angioplasty and intra-aortic balloon counterpulsation. In addition, there was an increase in hospital use of aspirin, nitrates, ACE inhibitors and beta-blockers. Patients with shock were more likely to die within 7 days compared with AMI patients not having shock (65 vs. 4%; p < 0.001). During the study period, the mortality of patients with shock decreased: at 7 days (72% in 1992 to 60% in 1998; p = 0.09), at 30 days (87 to 70%, respectively; p = 0.01) and at 6 months (89 to 77%, respectively; p = 0.02). Both aspirin and angioplasty were independently associated with improved outcome after adjustment for baseline characteristics and study period. CONCLUSIONS: Although the mortality rate of cardiogenic shock complicating AMI remains high, the increased utilization of aspirin and angioplasty is associated with improved outcome.

Evaluation of long-term survival after successful percutaneous coronary intervention among patients with chronic renal failure.

We studied the long-term outcomes after percutaneous coronary intervention in dialysis patients and in patients with chronic renal failure (CRF) (serum creatinine > or = 3.0 mg/dl). All-cause mortality at 1 year was 2.9% for the control group, 16.2% for the group with CRF, and 14.1% for dialysis patients. Cardiac mortality at 1 year was 1.9% for ther control group, 15.2% for the group with CRF, and 10.0% for dialysis patients.

Glycemic control and outcome of diabetic patients after successful percutaneous coronary revascularization.

OBJECTIVE: Our purpose was to examine whether the outcome of diabetic patients after successful percutaneous coronary revascularization (PCR) is influenced by the degree of control of hyperglycemia at the time of revascularization. BACKGROUND: Diabetic patients have a worse outcome after PCR. METHODS: We examined whether the degree of glycemic control (HbA(1c) levels) affected the occurrence of all-cause death and death/myocardial infarction among diabetic patients after successful PCR from October 1979 through December 1998. HbA(1c) was analyzed both as a continuous and a categorical variable (good [HbA(1c) <8.0%, n = 700], moderate [8.0% < or = HbA(1c) < or =10%, n = 442], or poor [HbA(1c) >10%, n = 231] control). RESULTS: HbA(1c) levels were determined at a median (25th, 75th interquartiles) of 3 (1, 10) days after the index procedure for patients with good control, 2 (1, 7) days for moderate control, and 2 (1, 6) days for poor control. Median follow-up after successful PCR was 3.2 (1.2, 6.1) years, 3.9 (1.7,6.3) years, and 4.7 (2.1, 7.1) years, respectively. HbA(1c) as a continuous variable did not have an impact on either death (hazard ratio [95% confidence interval] 1.04 [0.98-1.10]) or death/myocardial infarction (1.02 [0.98-1.07]). As a categorical variable, patients with moderate and poor control had a similar hazard of death (0.99 [0.78-1.26] and 1. 14 [0.86-1.52], respectively) and death/myocardial infarction (1.01 [0.82-1.24] and 1.12 [0.87-1.45], respectively) relative to those with good control. CONCLUSIONS: The degree of glycemic control among diabetic patients at the time of their index intervention did not have an impact on long-term outcomes after successful PCR.

Increased coronary effects of stimulation of endothelin-B receptor in experimental hypercholesterolemia.

BACKGROUND: Vasoconstriction in response to endothelin-1 has been shown to be primarily related to its effects on the endothelin-A receptor. Experimental hypercholesterolemia is associated with an increase in coronary vasoconstrictor response to endothelin-1 in vivo, although the relative contributions of subtypes of endothelin receptor in this model remain unknown. OBJECTIVE: To test the hypothesis that there is an increase in coronary vasoconstriction in response to stimulation of endothelin-B receptor in hypercholesterolemia, which might be related to attenuation of activity of endothelin-derived relaxing factor. METHODS: We infused 5 ng/kg/min sarafotoxin, a specific endothelin-B receptor agonist, or 50 micrograms/kg/min NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthase, into the left anterior descending coronary arteries of pigs before and after feeding them a cholesterol-rich diet for 10 weeks. RESULTS: There was a significant increase in serum level of cholesterol. After 10 weeks, infusion of sarafotoxin resulted in an accentuated decrease in coronary blood flow (CBF) compared with baseline (decreases by 60 +/- 7 versus 34 +/- 6%, P < 0.05). There was no significant difference between the effects on diameter of coronary arteries for the two time periods. The effect of L-NMMA on CBF was attenuated after 10 weeks (by 5 +/- 10.1 versus 45.6 +/- 4.7%, P < 0.05). Endothelin-receptor status of epicardial coronary arteries remained unchanged. Sarafotoxin and L-NMMA were co-infused at the above-mentioned doses into normolipidemic animals; the decrease in CBF in response to this co-infusion was comparable to the decrease observed with sarafotoxin alone in hypercholesterolemic animals (decreases of 67 +/- 5 versus 60 +/- 7, NS). CONCLUSIONS: The present results demonstrate that selective stimulation of the endothelin-B receptor increases coronary vasoconstriction in experimental hypercholesterolemia, primarily at the level of the microvasculature. These findings may be related to the attenuation of activity of endothelin-derived relaxing factor in this model, and support the hypothesis that endothelin-B receptor plays a role in the regulation of coronary vascular tone in pathophysiologic states.

Cardiogenic shock complicating acute coronary syndromes.

Cardiogenic shock remains the major cause of death among patients with all types of acute coronary syndromes. Thus, there is a growing interest in the identification of patients who are at risk for developing cardiogenic shock, in the exploration of different therapeutic approaches to preventing its development, and in the improvement of outcome when it occurs. This article reviews the aetiology and pathophysiology of cardiogenic shock, its epidemiology, its treatment (including pharmaceutical agents, counterpulsation, and revascularisation), and its outcome. Algorithms are presented that predict its occurrence in both ST-segment-elevation myocardial infarction and unstable angina or non-ST-elevation myocardial infarction, and that predict its mortality in patients with ST-segment-elevation acute myocardial infarction. Such new areas as metabolic therapy and glycoprotein IIb/IIIa inhibitors are discussed, as are the economic implications of shock.

Lack of progress in cardiogenic shock: lessons from the GUSTO trials.

AIMS: We used the GUSTO-I and GUSTO-III databases to evaluate our performance in treating cardiogenic shock patients over much of the 1990s. METHODS AND RESULTS: GUSTO-I (1990-1993) and GUSTO-III (1995-1997) prospectively identified all patients with cardiogenic shock complicating acute myocardial infarction. Demographics, clinical presentation and outcomes for cardiogenic shock patients in the two trials were compared. Only patients enrolled with cardiogenic shock in countries common to both trials were included in these analysis. The 695 patients with cardiogenic shock in GUSTO-III were compared with the 2814 patients with cardiogenic shock in GUSTO-I. GUSTO-III patients were older (P=0.0001) and more likely to be diabetic (P=0.009) and hypertensive (P=0.025). They had a higher Killip class (P=0.002) and significantly greater index anterior infarction than cardiogenic shock patients enrolled in GUSTO-I. Time to treatment, presentation heart rate, and diastolic blood pressure were similar; however, systolic blood pressure at presentation was higher among GUSTO-III patients (P=0.002). Rates of coronary angiography, pulmonary artery catheterization, and mechanical ventilation declined in GUSTO-III compared with GUSTO-I (P=0.001); rates of angioplasty and bypass surgery were similar. Cardiogenic shock mortality in GUSTO-III was significantly higher than in GUSTO-I (62 vs 54%, P=0.001), as were rates of reinfarction (14 vs 11%, P=0.013) and recurrent ischaemia (35 vs 27%, P=0.00001). Mortality at non-U.S. sites (68 and 64%) was higher than at U.S. sites (53 and 50%) in both GUSTO-I and GUSTO-III studies, respectively. Angioplasty, bypass surgery, and balloon pump rates were lower for non-U.S. patients. CONCLUSIONS: Cardiogenic shock continues to be associated with high mortality in thrombolytic-treated patients. Lower mortality observed in the U.S.A. supports consideration for percutaneous and surgical revascularization.

Medical therapy in the era of percutaneous coronary revascularization: a critical review.

Percutaneous coronary revascularization (PCR) frequently results in relief of angina in patients with ischemic heart disease. The aim of this review is to put in perspective the role of PCR in the treatment of patients with coronary artery disease.

Platelet glycoprotein IIb/IIIa blockade and outcome of cardiogenic shock complicating acute coronary syndromes without persistent ST-segment elevation.

OBJECTIVES: The study examined whether antiplatelet treatment with eptifibatide affected the frequency and outcome of shock among patients in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial who had acute coronary syndromes but not persistent ST-segment elevation. BACKGROUND: Preliminary reports suggest a salutary effect of antiplatelet agents when shock complicates acute myocardial infarction. METHODS: We analyzed the impact of antiplatelet treatment with eptifibatide on the frequency and outcome of cardiogenic shock developing after enrollment. PURSUIT was a double-blind, randomized trial that examined the efficacy of eptifibatide (180 microg/kg bolus + continuous infusion of 2.0 microg/kg/min for < or =96 h) versus placebo among patients who had acute coronary syndromes but not persistent ST-segment elevation. RESULTS: Shock developed in 2.5% of the 9,449 patients at a median (25th, 75th interquartiles) of 94.0 (38, 206) h. Death by 30 days occurred in 65.8% of shock patients. Patients who had acute myocardial infarction upon enrollment had a greater incidence of shock (2.9% vs. 2.1%, p = 0.01), developed shock earlier (40.2% <48 h vs. 20.9%, p = 0.001), and had higher 30-day mortality from shock (77.2% vs. 52.7%, p = 0.001). Randomization to eptifibatide did not affect the occurrence of shock (p = 0.71, adjusted odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.72-1.25). However, shock patients treated with eptifibatide had significantly reduced adjusted odds of 30-day death (p = 0.03, adjusted OR = 0.51, 95% CI = 0.28-0.94). CONCLUSIONS: Patients with shock treated with eptifibatide had significantly reduced adjusted odds of death, suggesting a salutary effect of antiplatelet therapy on shock. This finding warrants verification in specifically designed studies.

Microparticle-containing oncotic solutions augment in-vitro clot disruption by ultrasound.

Echocardiographic contrast agents enhance blood clot disruption by ultrasound. It has been suggested that the microbubbles add nuclei for the enhancement of cavitation by ultrasound. However, microbubbles are rapidly destroyed by the ultrasound energy. We assessed whether non-gas filled colloidal solutions (hyperoncotic medium molecular hydroxyethyl starch and degraded gelatin polypeptides) will facilitate clot disruption by ultrasound. In two separate experiments human blood clots, 200-400 mg in weight, were weighed and then immersed for 15 seconds in 10 ml normal saline solution containing 0%, 0.1%, 1%, 2%, and 5% of hyperoncotic medium molecular hydroxyethyl starch or 0%, 0.035%, 0.175%, 0.35%, and 0.7% degraded gelatin polypeptides. Clots were randomized to 10 seconds 20 kHz ultrasound or immersion without ultrasound. After treatment, the clots were reweighed, and the percent difference in weight was calculated. Non-gas filled microparticle-containing solutions such as hyperoncotic medium molecular hydroxyethyl starch and degraded gelatin polypeptides significantly augmented blood clot disruption by ultrasound. The effect is dependent on the colloidal solution concentration with maximal effect achieved with 1% hyperoncotic medium molecular hydroxyethyl starch and 0.35% degraded gelatin polypeptides.