Long-term prognostic role of cerebrovascular disease and peripheral arterial disease across the spectrum of acute coronary syndromes.

BACKGROUND: In acute coronary syndromes (ACS), the influence of cerebro-vascular disease (CVD) and/or peripheral artery disease (PAD) on short-midterm outcome has been well established. Data on long-term outcome however, are limited. Our study aimed to explore the effect of CVD and PAD on long-term outcome in a cohort of unselected ACS patients, including ST-elevation (STE-ACS) and non-ST-elevation (NSTE-ACS). METHODS AND RESULTS: The population consisted of 2046 consecutive patients with a confirmed final diagnosis of ACS; 896 (44%) had STE-ACS and 1150 (66%) NSTE-ACS. CVD alone was present in 98 patients (5%), 282 (14%) had PAD alone, and 30 (1.5%) had both. All cause mortality at 5 years was lowest in patients without CVD/PAD (33%), intermediate in patients with either CVD or PAD (62% and 63%, respectively) reaching 80% in those with both CVD and PAD. These findings were confirmed in the STE-ACS and NSTE-ACS subgroups. CVD and PAD remained independent predictors of mortality after multivariable analysis, the combined presence of both carrying the highest risk within each ACS type (HR 4.15, 95% CI 1.83-9.44 for STE-ACS; HR 2.14, 1.29-3.54 for NSTE-ACS). Patients with CVD and/or PAD were less likely to be treated invasively and received less evidence-based treatment at discharge. CONCLUSIONS: Across the spectrum of ACS, extracardiac vascular disease harbors a negative long-term prognosis that worsens progressively with the number of affected arterial beds.

Troponin T elevation in acute aortic syndromes: Frequency and impact on diagnostic delay and misdiagnosis.

AIMS: Despite troponin assay being a part of the diagnostic work up in many conditions with acute chest pain, little is known about its frequency and clinical implications in acute aortic syndromes (AASs). In our study we assessed frequency, impact on diagnostic delay, inappropriate treatments, and prognosis of troponin elevation in AAS. METHODS AND RESULTS: Data were collected from a prospective metropolitan AAS registry (398 patients diagnosed between 2000 and 2013). Cardiac troponin test, using either standard or high sensitivity assay, was performed according to standard protocol used in chest pain units. Troponin T values were available in 248 patients (60%) of the registry population; the overall frequency of troponin positivity was 28% (ranging from 16% to 54%, using standard or high sensitivity assay respectively, p = 0.001). Troponin positivity was frequently associated with acute coronary syndromes (ACS)-like electrocardiogram findings, and with a twofold increased risk of long in-hospital diagnostic time (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.05-3.52, p = 0.03). The combination of positive troponin and ACS-like electrocardiogram abnormalities resulted in a significantly increased risk of in-hospital delay/coronary angiography/antithrombotic therapy due to a misdiagnosis of ACS (OR 2.48, 95% CI 1.12-5.54, p = 0.02). However, troponin positivity was not associated with in-hospital mortality (OR 1.63, 95% CI 0.86-3.10, p = 0.131). CONCLUSIONS: Troponin positivity was a frequent finding in AAS patients, particularly when a high sensitivity assay was employed. Abnormal troponin values were strongly associated with ACS-like electrocardiogram findings and with in-hospital diagnostic delay but apparently they did not influence in-hospital mortality.

Acute heart failure in patients with acute aortic syndrome: pathophysiology and clinical-prognostic implications.

AIMS: Although acute heart failure (AHF) is a potential complication of acute aortic syndromes (AAS), its clinical details and management implications have been scarcely evaluated. This study aimed to assess prevalence, pathophysiological mechanisms, impact on treatment, and in-hospital mortality of AHF in AAS. METHODS AND RESULTS: Data were collected from a prospective AAS registry (398 patients diagnosed between 2000 and 2013). Patients with AHF were identified by the presence of dyspnoea as the presentation symptom or radiological signs of pulmonary congestion or cardiogenic shock, including patients with cardiac tamponade (CT). AHF frequency was 28% (Stanford type A 32% vs. type B 20%, P = 0.01). Four mechanisms leading to AHF were identified, alone or in combination: CT (26%), aortic regurgitation (25%), myocardial ischaemia (17%), and hypertensive crisis (10%). In type A patients, aortic regurgitation and CT were the most frequent mechanisms, whereas myocardial ischaemia and hypertensive crisis were the most frequent in type B patients. Although no difference was noted for diagnostic times, AHF at presentation led to a longer surgical delay in type A AAS. In-hospital mortality was higher in patients with AHF compared with those without (34% vs. 17%, P < 0.001). After multivariable analysis, AHF was associated with increased risk of in-hospital death (adjusted odds ratio 1.97, 95% confidence interval 1.14-3.36, P = 0.014). CONCLUSION: AHF occurs in more than a quarter of patients with AAS of both type A and type B, is due to a variety of pathophysiological mechanisms, and is associated with increased surgical delay and in-hospital mortality.

Long-term outcomes and causes of death after acute coronary syndrome in patients in the Bologna, Italy, area.

We sought to evaluate the rates, time course, and causes of death in the long-term follow-up of unselected patients with acute coronary syndromes (ACS). We enrolled 2046 consecutive patients hospitalized from January 2004 to December 2005 with an audited final diagnosis of ACS. The primary study end point was 5-year all-cause mortality. In our series, 896 patients had ST-segment elevation (STE) and 1,150 non-ST-segment elevation (NSTE). Mean age of the study population was 71.6 years. Primary percutaneous coronary intervention was performed in 86% of STE-ACS, and 70% of NSTE-ACS was managed invasively. The 5-year all-cause mortality was 36.4% for STE-ACS and 42.0% for NSTE-ACS, with patients with STE-ACS showing a trend boarding statistical significance toward a lower risk of mortality (hazard ratio [HR] = 0.88, 95% confidence interval [CI] 0.76 to 1.02, p = 0.08). Landmark analysis demonstrated that patients with STE-ACS had a higher risk of 30-day mortality (STE-ACS vs NSTE-ACS HR = 1.53, 95% CI 1.16 to 2.06, p = 0.003) whereas the risk of NSTE-ACS increased markedly after 1 year (STE-ACS vs NSTE-ACS HR = 0.67, 95% CI 0.53 to 0.84, p = 0.001). The contribution of noncardiovascular (CV) causes to overall mortality increased from 3% at 30 days to 34% at 5 years, with cancer and infections being the most common causes of non-CV death both in STE-ACS and NSTE-ACS. In conclusion, long-term mortality after ACS is still too high both for STE-ACS and NSTE-ACS. Although patients with STE-ACS have a higher mortality during the first year, the mortality of patients with NSTE-ACS increases later, when non-CV co-morbidities gain greater importance.

Impact of high-sensitivity Troponin T on hospital admission, resources utilization, and outcomes.

AIMS: The use of high-sensitivity cardiac Troponin T (hs-cTnT) assay might lead to overdiagnosis and overtreatment of Acute Coronary Syndromes (ACS). This study assessed the epidemiological, clinical and prognostic impact of introducing hs-cTnT in the everyday clinical practice of an Emergency Department. METHODS AND RESULTS: We compared all consecutive patients presenting with suspected ACS at the Emergency Department, for whom troponin levels were measured. In particular, we considered 597 patients presenting during March 2010, when standard cardiac Troponin T (cTnT) assay was used, and 629 patients presenting during March 2011, when hs-cTnT test was used. Patients with suspected ACS and troponin levels above the 99th percentile (Upper Reference Limit, URL) significantly increased when using an hs-cTnT assay (17.2% vs. 37.4%, p< 0.001). Accordingly, also the mean GRACE risk score increased (124.2 ± 37.2 vs. 136.7 ± 32.2; p< 0.001). However, the final diagnosis of Acute Myocardial Infarction (AMI) did not change significantly (8.7% vs. 6.8%, p=0.263) by using a rising and/or falling pattern of hs-cTnT (change ≥ 50% or ≥ 20% depending on baseline values). In addition, no significant differences were found between the two study groups with respect to in-hospital (2.7% vs. 1.9%, p=0.366) and 1-year mortality (9.8% vs. 7.6%, p=0.216). CONCLUSIONS: We did not observe overdiagnosis and overtreatment issues in presenters with suspected ACS managed by appropriate changes in hs-cTnT levels, despite the increase in the number of patients presenting with abnormal troponin levels. This occurred without a rise in short-term and mid-term mortality.

Diagnostic performance of standard electrocardiogram for prediction of infarct related artery and site of coronary occlusion in unselected STEMI patients undergoing primary percutaneous coronary intervention.

AIMS: To evaluate the relationship between ECG patterns and infarct related artery (IRA) in an all-comer population with ST-segment elevation myocardial infarction (STEMI) and validate current criteria for identifying IRA (right coronary artery (RCA) versus left circumflex artery (LCA)) in inferior STEMI and for diagnosing left main (LM) or left anterior descendent artery occlusion (LAD) in anterior STEMI. METHODS AND RESULTS: We retrospectively analysed ECGs at presentation and coronary angiogram in 885 consecutive patients undergoing primary percutaneous coronary intervention. Six ECG patterns were identified: anterior-STEMI (n=433; 49.0%), inferior-STEMI (i=365; 43.0%), lateral-STEMI (n=43; 5.0%), left bundle branch block (n=26; 3.0%), posterior-STEMI (n=7; 1.0%) and de Winter sign (n=7; 1.0%). The last two ECG patterns were univocally associated with LCA and proximal LAD occlusion respectively. In patients with inferior STEMI, predefined ECG algorithms showed high sensitivity(>90%) for RCA occlusion and high specificity(>90%) for LCA. The diagnostic performance was mainly determined by RCA dominance. In anterior STEMI the vectorial analysis of ST deviation in both frontal and horizontal planes could identify patients with LM/proximal LAD occlusion (adjusted-odds ratio for in-hospital mortality =2.45, 95% confidence interval: 1.31-4.56, p = 0.005) with low sensitivity (maximum 60%; using ST-depression in lead II, III, aVF + ΣSTE aVR + V1-ST depression V6≥0) and high specificity (maximum 95%; using ST-depression in inferior leads + ST-depression in V6). CONCLUSION: In STEMI undergoing primary percutaneous coronary intervention, six ECG patterns can be identified with a non-univocal relationship to the IRA. In inferior STEMI, vectorial analysis of ST deviation identifies IRA with a high appropriateness only when RCA is the dominant artery. In anterior STEMI, criteria derived from both frontal and horizontal planes identify LM/proximal LAD occlusion with high specificity but low sensitivity.

Baseline white blood cell count is an independent predictor of long-term cardiovascular mortality in patients with non-ST-segment elevation acute coronary syndrome, but it does not improve the risk classification of the GRACE score.

OBJECTIVES: To investigate the prognostic significance of baseline white blood cell count (WBCc) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and its additive predictive value beyond the Global Registry of Acute Coronary Events (GRACE) score. METHODS: We included 1,315 consecutive NSTE-ACS patients. Patients were divided in quartiles according to the WBCc (cells per 1 mm(3)) i.e. Q1 <6,850, Q2 = 6,850-8,539, Q3 = 8,540-10,857 and Q4 ≥10,858. The study end point was 3-year cardiovascular death (CVD). RESULTS: The median age of the study population was 76 years. Overall, 335 patients (25.5%) died with 211 of these (16%) suffering from CVD. Patients in Q4 showed a higher cumulative probability of CVD compared to patients in Q1-Q3. On multivariable analysis, patients in Q4 were at higher risk of CVD [hazard ratio (HR) = 1.47, 95% confidence interval (CI) 1.09-1.98, p = 0.011]. WBCc as a continuous variable was also independently associated with the study end point (HR = 1.043; 95% CI 1.02-1.07; p = 0.001). However, the incorporation of WBCc into the GRACE score did not improve either prediction of risk (C-index = 0.796 for GRACE score with or without WBCc) or classification of risk [relative integrated discrimination improvement = 0.0154, 95% CI) -0.029 to 0.0618; continuous net reclassification improvement = -0.0676, 95% CI -0.2149-0.0738). CONCLUSIONS: WBCc was an independent predictor of 3-year CVD in patients with NSTE-ACS. However, it did not add prognostic information beyond the GRACE score.

Predictors of complicated athero-thrombotic lesions in non-ST segment acute coronary syndrome.

AIMS: Non-ST segment elevation acute coronary syndrome (NSTE-ACS) is a heterogeneous syndrome in terms of patho-physiological mechanisms and prognosis. We sought to investigate the clinical features associated with complicated athero-thrombotic (CAT) coronary lesions and their prognostic relevance in NSTE-ACS. METHODS: We enrolled 701 consecutive NSTE-ACS patients without previous coronary bypass undergoing coronary angiography. The study population was divided into two groups according to the presence/absence of angiographic signs of endoluminal thrombi and/or plaque rupture, defined as CAT lesions. Multivariable analyses were used to identify predictors of CAT lesions. Their relation to composite endpoint of death, re-myocardial infarction, and re-unstable angina was investigated with the use of multivariable logistic regression. RESULTS: Patients with CAT lesions (n = 279, 40%) had a higher incidence of the combined endpoint (11.5 vs. 4.3%; P < 0.001). On multivariable analysis male sex [odds ratio (OR) 1.64, 95% confidence interval (CI) 1.17-2.30, P = 0.004], previous percutaneous coronary intervention (PCI) (OR 0.48, 95% CI 0.32-0.72, P < 0.001), severe angina (OR 1.72, 95% CI 1.18-2.52, P = 0.005) and anterior (i.e. V1-V4) ST segment depression (STD) were independently associated with CAT lesions (OR 1.71, 95% CI 1.14-2.57, P = 0.01). After adjustment for the Global Registry of Acute Coronary Events (GRACE) score only the presence of anterior STD emerged as an independent predictor of the clinical endpoint (OR 2.68, 95% CI 1.38-5.20, P = 0.003). The incorporation of anterior STD into the GRACE risk score showed an important trend toward improving prediction of endpoint as assessed by c-statistic (0.72 vs. 0.67; P = 0.08). CONCLUSION: In patients with NSTE-ACS male sex, severe angina and anterior STD were associated with an increased risk of CAT lesions. Patients with anterior STD were also at increased risk of in-hospital clinical events.

Prognostic significance of mean platelet volume on admission in an unselected cohort of patients with non ST-segment elevation acute coronary syndrome.

Mean platelet volume (MPV) has been proposed as a marker of platelet reactivity and cardiovascular risk. Its prognostic significance has not been thoroughly investigated in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). We included 1,041 consecutive patients with NSTE-ACS. Patients were divided in quartiles according to the MPV value on admission (fl) i.e. Q1<7.5; Q2=7.5-8.0; Q3=8.1-8.8; Q4≥8.9. The primary study endpoint was the composite of cardiovascular death and re-myocardial infarction (MI) at one year. Secondary study endpoints were individual cardiovascular death and re-MI. Patients in Q4 were older, had a higher prevalence of previous MI, peripheral artery disease and advanced Killip class compared to patients in Q1-Q3. Elevated MPV levels (Q4) was independently associated with gender, smoking status, platelet count and creatinine level. Overall, 210 patients (20.2%) reached the primary endpoint, 124 (12.1%) died from cardiovascular causes and 125 (12.0%) suffered from re-MI. On multivariable analysis patients in Q4 were at higher risk of primary endpoint (HR=1.41; 95%CI 1.06-1.89; p=0.02) whilst the association with cardiovascular death and re-MI was attenuated. MPV as continuous variable was independently associated with both primary endpoint (HR=1.19; 95%CI 1.06-1.33; p=0.003) and cardiovascular death (HR=1.23; 95%CI 1.06-1.42, p=0.006). The incorporation of MPV into a comprehensive model of risk significantly increased the likelihood ratio chi-square for prediction of both the composite endpoint (p=0.004) and cardiovascular death (p=0.009). Therefore, MPV may be useful to improve risk stratification in NSTE-ACS patients and should be included in future prospective studies evaluating the role of platelet function in promoting cardiovascular events.

Short- and long-term prognostic significance of ST-segment elevation in lead aVR in patients with non-ST-segment elevation acute coronary syndrome.

We sought to evaluate the prognostic significance of ST-segment elevation (STE) in lead aVR in unselected patients with non-STE acute coronary syndrome (NSTE-ACS). We enrolled 1,042 consecutive patients with NSTE-ACS. Patients were divided into 5 groups according to the following electrocardiographic (ECG) patterns on admission: (1) normal electrocardiogram or no significant ST-T changes, (2) inverted T waves, (3) isolated ST deviation (ST depression [STD] without STE in lead aVR or transient STE), (4) STD plus STE in lead aVR, and (5) ECG confounders (pacing, right or left bundle branch block). The main angiographic end point was left main coronary artery (LM) disease as the culprit artery. Clinical end points were in-hospital and 1-year cardiovascular death defined as the composite of cardiac death, fatal stroke, and fatal bleeding. Prevalence of STD plus STE in lead aVR was 13.4%. Rates of culprit LM disease and in-hospital cardiovascular death were 8.1% and 3.8%, respectively. On multivariable analysis, patients with STD plus STE in lead aVR (group 4) showed an increased risk of culprit LM disease (odds ratio 4.72, 95% confidence interval [CI] 2.31 to 9.64, p <0.001) and in-hospital cardiovascular mortality (odds ratio 5.58, 95% CI 2.35 to 13.24, p <0.001) compared to patients without any ST deviation (pooled groups 1, 2, and 5), whereas patients with isolated ST deviation (group 3) did not. At 1-year follow-up 127 patients (12.2%) died from cardiovascular causes. On multivariable analysis, STD plus STE in lead aVR was a stronger independent predictor of cardiovascular death (hazard ratio 2.29, 95% CI 1.44 to 3.64, p <0.001) than isolated ST deviation (hazard ratio 1.52, 95% CI 0.98 to 2.36, p = 0.06). In conclusion, STD plus STE in lead aVR is associated with high-risk coronary lesions and predicts in-hospital and 1-year cardiovascular deaths in patients with NSTE-ACS. Therefore, this promptly available ECG pattern could be useful to improve risk stratification and management of patients with NSTE-ACS.