Fabio Vagnarelli

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.

Review of tenecteplase (TNKase) in the treatment of acute myocardial infarction.

TNKase is a genetically engineered variant of the alteplase molecule. Three different mutations result in an increase of the plasma half-life, of the resistance to plasminogen-activator inhibitor 1 and of the thrombolytic potency against platelet-rich thrombi. Among available agents in clinical practice, TNKase is the most fibrin-specific molecule and can be delivered as a single bolus intravenous injection. Several large-scale clinical trials have enrolled more than 27,000 patients with acute myocardial infarction, making the use of this drug truly evidence-based. TNKase is equivalent to front-loaded alteplase in terms of mortality and is the only bolus thrombolytic drug for which this equivalence has been formally demonstrated. TNKase appears more potent than alteplase when symptoms duration lasts more than 4 hours. Also, TNKase significantly reduces the rate of major bleeds and the need for blood transfusions. The efficacy of TNKase may be further improved by enoxaparin substitution for unfractionated heparin, provided that enoxaparin dose adjustment is made for patients more than 75 years old. Hitherto, the small available randomized studies and international clinical registries suggest that pre-hospital TNKase is as effective as primary angioplasty, thus laying the foundations for a new fibrinolytic, TNKase-based strategy as the backbone of reperfusion in acute myocardial infarction.

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.

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.

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.

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.

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.

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

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.

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.

Inferior Q waves in apparently healthy subjects: Should we take a deep breath? An electrocardiographic, echocardiographic and cardiac magnetic resonance study

AIM To evaluate the diagnostic accuracy of electrocardiographic inferior Q waves persistence during inspiration and echocardiographic segmental wall motion abnormalities for the detection of previously unsuspected silent myocardial infarction, by using cardiac magnetic resonance as the gold standard. METHODS We prospectively enrolled 50 apparently healthy subjects with inferior Q waves on routine electrocardiogram and high atherosclerotic risk profile. Patients underwent electrocardiogram during deep inspiration, standard transthoracic echocardiography, and cardiac magnetic resonance. RESULTS Inferior Q waves during deep inspiration persisted in 10 subjects (20%) and cardiac magnetic resonance was positive in 10 (20%). Between the 10 positive cardiac magnetic resonance subjects 8 showed persistence of inferior Q waves, giving a sensitivity of 80% (95%;CI 44.4-97.5%) and a specificity of 95% (95%;CI 83.1-99.4%). Segmental wall motion abnormalities were present overall in 10 subjects (20%), but only in 5 of the 10 positive cardiac magnetic resonance subjects, giving a sensitivity of 87.5% (95% CI 73.2-95.8) and specificity of 50% (95% CI 18.7-81.3). CONCLUSIONS Electrocardiographic inferior Q waves persistence during deep inspiration is a simple test with a high accuracy for diagnosis of silent myocardial infarction. Standard echocardiography resulted less accurate.