Diagnosis of acute aortic syndromes : imaging and beyond.

Acute aortic syndromes are fatal medical conditions including classic acute aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer. Given the nonspecific symptoms and signs, a high clinical index of suspicion followed by an imaging study, namely transesophageal echocardiography, computed tomography, and magnetic resonance imaging (sensitivity 98-100% and specificity 95-100%), is a conditio sine qua non for prompt diagnosis of acute aortic syndromes. This article provides an overview of established and emerging approaches for the assessment of acute aortic syndromes, with focus on imaging and biomarkers. In this regard, D-dimer levels (cut-off: 500 ng/ml) may be useful to rule out aortic dissection, if used within the first 24 h after symptom onset.

Influence of clinical presentation on the outcome of acute B aortic dissection: evidences from IRAD.

AIM: In-hospital outcome of acute type B dissection (ABAD) is strongly related to preoperative aortic conditions. In order to clarify the influence of the clinical presentation on the outcome, we analyzed the patients of the International Registry of Acute Aortic Dissection (IRAD). All patients affected by complicated ABAD, enrolled in the IRAD from 1996-2004, were included. Complications were defined as the presence of shock, periaortic hematoma, spinal cord ischemia, preoperative mesenteric ischemia/infarction, acute renal failure, limb ischemia, recurrent pain, refractory pain or refractory hypertension (group I). All other patients were categorized as uncomplicated (group II). A comprehensive analysis was performed of all clinical variables in relation to in-hospital outcome. RESULTS: The overall in-hospital mortality among 550 patients was 12.4%. Mortality in group I (250 patients) was 20.0 %, compared to 6.1% in group II (300 patients) (P<0.001). Univariate predictors of ABAD complications were Marfan syndrome, abrupt onset of pain, migrating pain, any focal neurological deficits, need for higher number of diagnostic examinations and use of magnetic resonance and/or aortogram, abdominal vessels involvement at aortogram, larger descending aortic diameter, especially >6 cm, pleural effusion, and widened mediastinum on chest X-ray. Univariate predictors of a non complicated status were normal chest X-ray and medical management. In group I, in-hospital mortality following surgical and endovascular intervention were 28.6% and 10.1% (P=0.006), respectively. Independent predictors of overall in-hospital mortality included age >70 years, female gender, ECG showing ischemia, preoperative acute renal failure, preoperative limb ischemia, periaortic hematoma, and surgical management. The only independent variable protective for mortality was magnetic resonance as diagnostic test. CONCLUSION: ABAD is a heterogeneous disease that produces dissimilar clinical subsets, each of which can have specific clinical signs, management and in-hospital results. In IRAD ABAD uncomplicated patients, medical therapy was associated with best hospital outcome, while endovascular interventions were associated with better results than surgery when invasive treatments were required. Although selection bias may be possible, and irrespective of treatments, knowledge of significant risk factors for mortality may contribute to a better management and a more defined risk-assessment in patients affected by ABAD.

Acute aortic syndromes.

Acute aortic syndromes (AAS) comprise a group of potentially lethal conditions that require prompt recognition, diagnosis as well as acute medical stabilization and surgical intervention. The purpose of this article is to review the relevant variants of AAS presentation, as well as diagnostic and management issues, including adequate long-term medical therapy and follow-up imaging. In this context, the American College of Cardiology and the American Heart Association recently published guidelines on the management of thoracic aortic disease, drawing greater attention to these processes.

The Global Registry of Acute Coronary Events, 1999 to 2009--GRACE.

The aim of GRACE was to provide a large multinational registry of the full spectrum of patients with acute coronary syndromes (ACS) in order to define patient characteristics and outcomes and derive predictive risk scores. The study was designed and administered by an independent steering committee; data analyses were performed under the guidance of the steering committee at the Center for Outcomes Research of the University of Massachusetts. Regular feedback regarding local, regional and international guideline and performance measures was provided to individual hospitals and clusters of hospitals. Regional and international benchmark data were available to all sites. Main GRACE involved 123 hospitals in 14 countries in North and South America, Europe, Australia and New Zealand. GRACE2 (Expanded GRACE) comprised 154 hospitals in Europe, North and South America, Asia, Australasia and China. Continuous recruitment and follow-up took place between 1999 and 2009. The first 10 -20 patients per site (depending on hospital size) were enrolled each month, resulting in the recruitment of 102 341 patients, who were categorized as having ST-segment elevation myocardial infarction, non-ST-elevation myocardial infarction or unstable angina. Standardized case report forms (datafax or electronic) were completed by trained study coordinators, and included fields relating to demographic factors, comorbid conditions, treatments and in-hospital and post-discharge (6-month) events. Blood sampling, genetic analyses and longer-term follow-up were undertaken in GRACE substudies. Prospective individual patient follow-up was carried out. All sites were audited locally; 10% of individual patient records were audited in a 2-year cycle. Less than 1% of 20 key baseline fields, and less than 1% of discharge diagnosis and discharge status data, were missing. Six-month follow-up was 85% complete. Publications and risk scores are available at http://www.outcome.org/grace. Proposals for specific analyses were considered, in competition, by an independent publications committee.

Six-month survival benefits associated with clinical guideline recommendations in acute coronary syndromes.

AIMS: The authors sought to define which guideline-advocated therapies are associated with the greatest benefit with respect to 6-month survival in patients hospitalised with an acute coronary syndrome (ACS). METHODS AND RESULTS: The authors conducted a nested case-control study of ACS patients within the Global Registry of Acute Coronary Events cohort between April 1999 and December 2007. The cases were ACS patients who survived to discharge but died within 6 months. The controls were patients who survived to 6 months, matched for ACS diagnosis, age and the Global Registry of Acute Coronary Events risk score. Rates of use of evidence-based medications and coronary interventions (angiography, percutaneous coronary intervention and coronary artery bypass graft surgery) were compared. Logistic regression including matched variables was used, and the attributable mortality from incomplete application of each therapy was calculated. A total of 1716 cases and 3432 controls were identified. Coronary artery bypass graft surgery and percutaneous coronary intervention were associated with the greatest 6-month survival benefit (OR for death 0.60 (95% CI 0.39 to 0.90) and 0.57 (0.48 to 0.72), respectively). Statins and clopidogrel provided the greatest independent pharmacologic benefit (ORs for death 0.85 (0.73 to 0.99) and 0.84 (0.72 to 0.99)) with lesser effects seen with other pharmacotherapies. CONCLUSIONS: A diminishing benefit associated with each additional ACS therapy is evident. These data may provide a rational basis for selecting between therapeutic options when compliance or cost is an issue.

Six-month survival benefits associated with clinical guideline recommendations in acute coronary syndromes

AIMS: The authors sought to define which guideline-advocated therapies are associated with the greatest benefit with respect to 6-month survival in patients hospitalised with an acute coronary syndrome (ACS).METHODS AND RESULTS: The authors conducted a nested case-control study of ACS patients within the Global Registry of Acute Coronary Events cohort between April 1999 and December 2007. The cases were ACS patients who survived to discharge but died within 6 months. The controls were patients who survived to 6 months, matched for ACS diagnosis, age and the Global Registry of Acute Coronary Events risk score. Rates of use of evidence-based medications and coronary interventions (angiography, percutaneous coronary intervention and coronary artery bypass graft surgery) were compared. Logistic regression including matched variables was used, and the attributable mortality from incomplete application of each therapy was calculated. A total of 1716 cases and 3432 controls were identified. Coronary artery bypass graft surgery and percutaneous coronary intervention were associated with the greatest 6-month survival benefit (OR for death 0.60 (95% CI 0.39 to 0.90) and 0.57 (0.48 to 0.72), respectively). Statins and clopidogrel provided the greatest independent pharmacologic benefit (ORs for death 0.85 (0.73 to 0.99) and 0.84 (0.72 to 0.99)) with lesser effects seen with other pharmacotherapies.CONCLUSIONS: A diminishing benefit associated with each additional ACS therapy is evident. These data may provide a rational basis for selecting between therapeutic options when compliance or cost is an issue.

Predicting freedom from clinical events in non-ST-elevation acute coronary syndromes: the Global Registry of Acute Coronary Events.

OBJECTIVE: To identify patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) with a low likelihood of any adverse in-hospital event. DESIGN, SETTING AND PATIENTS: Data were analysed from 24 097 patients with NSTEMI or unstable angina included in the Global Registry of Acute Coronary Events (January 2001 to September 2007). MAIN OUTCOME MEASURES: In-hospital events were myocardial infarction, arrhythmia, congestive heart failure or shock, major bleeding, stroke or death. Two-thirds of the patients were randomly chosen for model development and the remainder for model validation. Multiple logistic regression identified predictors of freedom from an in-hospital event, and a Freedom-from-Event score was developed. RESULTS: Of the 16 127 patients in the model development group, 19.1% experienced an in-hospital adverse event. Fifteen factors independently predicted freedom from an adverse event: younger age; lower Killip class; unstable angina presentation; no hypotension; no ST deviation; no cardiac arrest at presentation; normal creatinine; decreased pulse rate; no hospital transfer; no history of diabetes, heart failure, peripheral arterial disease, or atrial fibrillation; prehospital use of statins, and no chronic warfarin. In the validation group, 18.6% experienced an adverse event. The model discriminated well between patients experiencing an in-hospital event and those who did not in both derivation and validation groups (c-statistic = 0.77 in both). Patients in the three lowest risk deciles had a very low in-hospital mortality (<0.5%) and an uncomplicated clinical course (>93% event-free in hospital). The model also predicted freedom from postdischarge events (death, myocardial infarction, stroke; c-statistic = 0.77). CONCLUSIONS: The GRACE Freedom-from-Event score can predict the in-hospital course of NSTE-ACS, and identifies up to 30% of the admitted population at low risk of death or any adverse in-hospital event.

Delay to angiography and outcomes following presentation with high-risk, non-ST-elevation acute coronary syndromes: results from the Global Registry of Acute Coronary Events.

OBJECTIVE: To test if delay-to-angiography (>72 hours from admission) in patients presenting with high-risk non-ST-elevation acute coronary syndromes (NSTE-ACS) is associated with adverse outcomes. DESIGN: GRACE (Global Registry of Acute Coronary Events) is a multinational registry of patients admitted with NSTE-ACS. SETTING: 14 countries with varying healthcare systems. PATIENTS: 23 396 high-risk NSTE-ACS patients with complete initial data collection entered into GRACE between 1999 and 2006 were analysed. INTERVENTIONS: Data were analysed according to delay-to-angiography and subsequent in-hospital or post-discharge adverse outcomes. MAIN OUTCOME MEASURES: Outcomes recorded included death, myocardial infarction, recurrent ischaemia, stroke, new heart failure and composite major adverse cardiovascular event (MACE) comprising death, cerebrovascular accident and myocardial infarction. Revascularisation procedures were recorded. RESULTS: 10 089 (43.1%) had no in-hospital angiography. Median delay-to-angiography was 46 hours; 3680 (34%) patients waited >72 hours. 9.3% waited >7 days before angiography. Patients waiting longest were more often older, diabetic, women and had a history of heart failure, previous myocardial infarction or hypertension. Recurrent in-hospital ischaemia (33% vs 22%), reinfarction (8.4% vs 5.0%) and heart failure (14% vs 9.1%) were more common with delayed angiography. Delayed angiography was associated with better outcomes than no angiography (MACE 18.9% vs 22.2%, p = 0.015). MACE rates within six months of admission were higher with longer delay-to-angiography and highest of all with no angiography. CONCLUSIONS: High-risk NSTE-ACS is suboptimally managed with 43% not undergoing angiography. One-third of those undergoing angiography are delayed >72 hours. Longer delays were more likely with higher risk, sicker patients. These delays were associated with adverse outcomes at six months. Very long delay was associated with lower MACE, but not mortality, compared to conservative management.

Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events.

OBJECTIVE: To assess whether sex differences exist in the angiographic severity, management and outcomes of acute coronary syndromes (ACS). METHODS: The study comprised 7638 women and 19 117 men with ACS who underwent coronary angiography and were included in GRACE (Global Registry of Acute Coronary Events) from 1999-2006. Normal vessels/mild disease was defined as <50% stenosis in all epicardial vessels; advanced disease was defined as >or=one vessel with >or=50% stenosis. RESULTS: Women were older than men and had higher rates of cardiovascular risk factors. Men and women presented equally with chest pain; however, jaw pain and nausea were more frequent among women. Women were more likely to have normal/mild disease (12% vs 6%, p<0.001) and less likely to have left-main and three-vessel disease (27% vs 32%, p<0.001) or undergo percutaneous coronary intervention (65% vs 68%, p<0.001). Women and men with normal and mild disease were treated less aggressively than those with advanced disease. Women with advanced disease had a higher risk of death (4% vs 3%, p<0.01). After adjustment for age and extent of disease, women were more likely to have adverse outcomes (death, myocardial infarction, stroke and rehospitalisation) at six months compared to men (odds ratio 1.24, 95% confidence interval 1.14 to 1.34); however, sex differences in mortality were no longer statistically significant. CONCLUSIONS: Women with ACS were more likely to have cardiovascular disease risk factors and atypical symptoms such as nausea compared with men, but were more likely to have normal/mild angiographic coronary artery disease. Further study regarding sex differences related to disease severity is warranted.

A school-based health education program can improve cholesterol values for middle school students.

BACKGROUND: This prospective study aimed to measure the impact of a school-based multidisciplinary education program on risk factors for atherosclerosis in sixth-grade students. METHODS: A prospective study was performed in which patients served as their own controls. Healthy sixth-grade students from three middle schools in a city of approximately 100,000 were exposed to an educational program promoting healthful habits through behavioral and environmental change. Risk factors including body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), cholesterol panel, and random blood glucose were measured before program initiation, then 5 months afterward. RESULTS: Of 711 sixth-graders at three middle schools, 287 (47% boys; mean age, 11.5 +/- 0.37 years) consented to participate in the study. The mean total cholesterol value decreased from 169 +/- 26 to 154 +/- 26 mg/dl (p < 0.0001). The low-density lipoprotein (LDL) cholesterol value decreased from 86 +/- 25 to 84 +/- 23 mg/dl (p = 0.01), and the high-density lipoprotein (HDL) cholesterol value decreased from 56 +/- 13 to 50 +/- 13 mg/dl (p < 0.0001). The random glucose value decreased from 96 +/- 13 to 93 +/- 15 mm/dl (p = 0.01). The mean SBP did not change, showing 109 +/- 12.5 mmHg before the program and 108 +/- 11.5 mmHg afterward. The DBP decreased from 63.6 +/- 8.6 to 62.3 +/- 7.8 mmHg (p = 0.01). CONCLUSIONS: The Project Healthy Schools program is feasible and appears to be effective. The results showed significant improvement in risk factors for early atherosclerosis among sixth-grade students including total cholesterol, LDL cholesterol, random glucose levels, and diastolic blood pressure. Further study with a larger group and a longer follow-up period would be valuable.

Outcomes with the use of glycoprotein IIb/IIIa inhibitors in non-ST-segment elevation acute coronary syndromes.

OBJECTIVE: To compare the characteristics, management, and outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) who would have been eligible for inclusion in clinical trials of glycoprotein (GP) IIb/IIIa inhibitors with those of ineligible patients. DESIGN: Multinational, prospective, observational study (GRACE, Global Registry of Acute Coronary Events). SETTING: Patients hospitalised for a suspected acute coronary syndrome and enrolled in GRACE between April 1999 and December 2004. PATIENTS: 29 039 patients with NSTE ACS. MAIN OUTCOME MEASURES: Characteristics and outcomes were compared for trial-eligible (75.0%) and trial-ineligible (25.0%) patients. RESULTS: GP IIb/IIIa inhibitors were administered to 20.0% of eligible and 15.3% of ineligible patients. Compared with eligible patients, ineligible patients who received GP IIb/IIIa inhibitors had significantly higher rates of hospital death (6.8% vs 3.7%) and major bleeding (4.9% vs 2.2%). After adjustment for their higher baseline risk, ineligible patients still experienced higher hospital death rates (adjusted odds ratio (OR) 1.60; 95% confidence interval (CI) 1.01 to 2.39), but not higher bleeding rates, than the eligible group. Use of GP IIb/IIIa inhibitors was associated with a trend towards lower 6-month mortality in eligible (OR 0.86, 95% CI 0.72 to 1.02) and ineligible (OR 0.82, 95% CI 0.65 to 1.05) patients compared with those in whom this therapy was not used. CONCLUSIONS: GP IIb/IIIa inhibitors were markedly underused in the real-world population, irrespective of whether patients were trial-eligible or not. Despite the higher risk of ineligible patients, the benefits of GP IIb/IIIa inhibitors appear to be no less than in eligible patients.

Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention. The Global Registry of Acute Coronary Events.

OBJECTIVE: Treatment delays may result in different clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy vs primary percutaneous coronary intervention (PCI). The aim of this analysis was to examine how treatment delays relate to 6-month mortality in reperfusion-treated patients enrolled in the Global Registry of Acute Coronary Events (GRACE). DESIGN: Prospective, observational cohort study. SETTING: 106 hospitals in 14 countries. PATIENTS: 3959 patients who presented with STEMI within 6 h of symptom onset and received reperfusion with either a fibrin-specific fibrinolytic drug or primary PCI. MAIN OUTCOME MEASURES: 6-month mortality. METHODS: Multivariable logistic regression was used to assess the relationship between outcomes and treatment delay separately in each cohort, with time modelled with a quadratic term after adjusting for covariates from the GRACE risk score. RESULTS: A total of 1786 (45.1%) patients received fibrinolytic therapy, and 2173 (54.9%) underwent primary PCI. After multivariable adjustment, longer treatment delays were associated with a higher 6-month mortality in both fibrinolytic therapy and primary PCI patients (p<0.001 for both cohorts). For patients who received fibrinolytic therapy, 6-month mortality increased by 0.30% per 10-min delay in door-to-needle time between 30 and 60 min compared with 0.18% per 10-min delay in door-to-balloon time between 90 and 150 min for patients undergoing primary PCI. CONCLUSIONS: Treatment delays in reperfusion therapy are associated with higher 6-month mortality, but this relationship may be even more critical in patients receiving fibrinolytic therapy.

Lack of clopidogrel-CYP3A4 statin interaction in patients with acute coronary syndrome.

OBJECTIVE: To assess a clinically significant interaction between cytochrome P450 3A4 (CYP3A4) metabolised statin and clopidogrel. DESIGN: Prospective single centre cohort study. SETTING: Academic teaching hospital in the USA. PATIENTS: 1651 patients presenting with acute coronary syndromes between January 1999 and February 2003 were studied. Data on baseline demographics, co-morbidities, and in-hospital management were collected. MAIN OUTCOME MEASURE: Association of CYP3A4 metabolised statin and clopidogrel use with in-hospital and six month mortality. The impact of the combined use of a CYP3A4 statin and clopidogrel on six month mortality and major adverse cardiac events was analysed by a risk adjusted logistic regression model. RESULTS: The odds ratios for six month mortality were: for CYP3A4 statin, 0.43 (95% confidence interval (CI) 0.27 to 0.71, p = 0.0009); for CYP3A4 statin plus clopidogrel, 0.36 (95% CI 0.23 to 0.60, p < 0.001); for non-CYP3A4 statin, 0.22 (95% CI 0.08 to 0.59, p = 0.002); and for non-CYP3A4 statin plus clopidogrel, 0.22 (95% CI 0.06 to 0.75, p = 0.016). CONCLUSIONS: Use of a combination of a CYP3A4 statin plus clopidogrel was associated with lower six month mortality and morbidity in patients with acute coronary syndromes. There was no significant difference in clinical benefit between a CYP3A4 statin and a non-CYP3A4 statin when used in conjunction with clopidogrel. This suggests that the proposed interaction is probably an ex vivo phenomenon and may not be clinically relevant.

Chronobiology of rupture and dissection of aortic aneurysms.

A growing body of evidence suggests that the occurrence of cardiovascular events is not evenly distributed over time, but shows peculiar temporal patterns that vary with time of day, day of the week, and month (season) of the year. These patterns coincide with the temporal variation in the pathophysiologic mechanisms that trigger cardiovascular events and the physiologic changes in body rhythms. These two factors in combination contribute to the periodicity in susceptibility to acute cardiovascular events. The classic assumption of epidemiologic studies that there is a constancy in risk for disease during the various time domains has now been challenged by the emerging new concept of chronorisk. In the last two decades temporal patterns (circadian, weekly, seasonal) have been identified for several acute cardiovascular diseases, such as acute myocardial infarction, sudden death, pulmonary embolism, and stroke, with peak incidence for most in the morning and during winter. One of the most life-threatening cardiovascular emergencies, aortic aneurysm rupture or dissection, also demonstrates periodicity, characterized by a similar temporal distribution, which suggests a common pathophysiologic mechanism or triggers similar to other cardiovascular acute emergencies. We review the data on chronobiology of acute aortic rupture or dissection, and discuss various pathophysiologic mechanisms that account for this variability. It is likely that identification of consistent recurring patterns in the underlying risk mechanisms could provide potential new insights for more precise diagnosis and efficacious therapeutic intervention.