Background ST-segment depression (STD) is predictive of adverse outcomes in non–ST-segment elevation acute coronary syndromes (NSTE-ACS), but there are conflicting data on the incremental prognostic ...value of T-wave inversions (TWIs) on the admission electrocardiogram. Methods Admission electrocardiograms of 7,343 patients with NSTE-ACS from the Global Registry of Acute Coronary Events (GRACE) and ACS I registry were independently analyzed at a core laboratory and stratified by TWI and STD status. We performed multivariable analyses to determine the independent prognostic significance of TWI and tested for interaction between TWI and STD for adverse outcomes. Results Patients with TWI and/or STD had a higher prevalence of cardiovascular risk factors, higher Killip class, and higher GRACE risk scores. Among the 2,708 patients with available angiographic data, rates of 3-vessel or left main disease were similar between patients with TWI and those without TWI/STD. After adjusting for other established prognosticators, TWI did not independently predict in-hospital (adjusted odds ratio 1.03, 95% CI 0.75-1.42, P = .85) or 6-month mortality (adjusted odds ratio 1.02, 95% CI 0.80-1.30, P = .88); STD remained a strong independent predictor. There was no interaction between TWI and STD for these outcomes. No contiguous lead groups or cumulative number of leads with TWI provided independent prognostic information. Conclusions TWI is associated with other high-risk clinical features but is not an independent predictor of adverse short- and long-term mortality in NSTE-ACS. T-wave inversion does not provide additional prognostication beyond the GRACE risk model, and its concomitant presence does not alter the prognostic value of STD.
The risk of stroke in patients hospitalized with an acute coronary syndrome (ACS) ranges from <1% to ≥2.5%. The aim of this study was to develop a simple predictive tool for bedside risk estimation ...of in-hospital ischemic stroke in patients with ACS to help guide clinicians in the acute management of these high-risk patients. Data were obtained from 63,118 patients enrolled from April 1999 to December 2007 in the Global Registry of Acute Coronary Events (GRACE), a multinational registry involving 126 hospitals in 14 countries. A regression model was developed to predict the occurrence of in-hospital ischemic stroke in patients hospitalized with an ACS. The main study outcome was the development of ischemic stroke during the index hospitalization for an ACS. Eight risk factors for stroke were identified: older age, atrial fibrillation on index electrocardiogram, positive initial cardiac biomarkers, presenting systolic blood pressure ≥160 mm Hg, ST-segment change on index electrocardiogram, no history of smoking, higher Killip class, and lower body weight (c-statistic 0.7). The addition of coronary artery bypass graft surgery and percutaneous coronary intervention into the model increased the prediction of stroke risk. In conclusion, the GRACE stroke risk score is a simple tool for predicting in-hospital ischemic stroke risk in patients admitted for the entire spectrum of ACS, which is widely applicable to patients in various hospital settings and will assist in the management of high-risk patients with ACS.
Objectives The authors sought to compare the radiation dose between radial and femoral access. Background Small trials have shown an increase in the radiation dose with radial compared with femoral ...access, but many were performed during the operators' learning curve of radial access. Methods Patients were randomized to radial or femoral access, as a part of the RIVAL (RadIal Vs. femorAL) trial (N = 7,021). Fluoroscopy time was prospectively collected in 5740 patients and radiation dose quantified as air kerma in 1,445 patients and dose-area product (DAP) in 2,255 patients. Results Median fluoroscopy time was higher with radial versus femoral access (9.3 vs. 8.0 min, p < 0.001). Median air kerma was nominally higher with radial versus femoral access (1,046 vs. 930 mGy, respectively, p = 0.051). Median DAP was not different between radial and femoral access (52.8 Gy-cm2 vs. 51.2 Gy·cm2 , p = 0.83). When results are stratified according to procedural volume, air kerma was increased only in the lowest tertile of radial volume centers (low 1,425 vs. 1,045 mGy, p = 0.002; middle 987 vs. 958 mGy, p = 0.597; high 652 vs. 621 mGy, p = 0.403, interaction p = 0.026). Multivariable regression showed procedural volume was the greatest independent predictor of lower air kerma dose (ratio of geometric means 0.55; 95% confidence interval 0.49 to 0.61 for highest-volume radial centers). Conclusions Radiation dose as measured by air kerma was nominally higher with radial versus femoral access, but differences were present only in lower-volume centers and operators. High-volume centers have the lowest radiation dose irrespective of which access site approach that they use. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention (PCI) Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy RIVAL; NCT01014273 )
We assessed the effect of previous peripheral arterial disease (PAD) and stroke on clinical outcomes in patients with acute coronary syndrome (ACS) and sought to ascertain the effectiveness of ...evidence-based therapies in these patients. We used data from the multinational Global Registry of Acute Coronary Events. Patients were enrolled at 102 hospitals in 13 countries between April 1999 and September 2005. Patients presenting with ACS were stratified according to the presence of previous PAD, stroke, PAD and stroke, or neither. In-hospital analysis included 48,418 patients and 6-month analysis included 32,735 patients. The primary end point was all-cause mortality and major adverse cardiac events during 6-month follow-up. Adverse in-hospital and 6-month events were lowest in patients with neither PAD nor stroke and highest in patients with PAD and stroke after adjustment for baseline demographics and co-morbidities. In-hospital mortality for the 4 groups (neither, PAD, stroke, PAD and stroke) was 4.5% versus 7.2% versus 8.9% versus 9.4% (p <0.001) and that for 6-month mortality was 3.9% versus 8.8% versus 9.3% versus 12%, and these differences persisted after accounting for differences in baseline characteristics. Use of evidence-based therapies was associated with significantly less morbidity and mortality in all ACS subgroups. In conclusion, outcomes after ACS are worse in patients with PAD or stroke, with the highest risk in patients with the 2 conditions and the use of evidence-based therapies are associated with improved outcomes in all ACS subgroups.
Background The Global Registry of Acute Coronary Events (GRACE) risk model provides a simple method for determining the probability of hospital death in acute coronary syndrome (ACS). The aim of this ...study was to explore the impact of modeling techniques on the risk model when generating predictions. Methods Patients with ACS (n = 48,023) with or without ST-segment elevation myocardial infarction (STEMI) were enrolled (123 hospitals, 14 countries) between April 1999 and June 2006. The original GRACE model did not include terms to account for possible differences in outcomes between patients with STEMI, non-STEMI, and unstable angina, nor did it account for changing risk across continuous measures. Results In this cohort, the influence on outcome of region of hospitalization and cardiac arrest at presentation changed over the 7-year study. Other interactions included previous percutaneous coronary intervention and age with type of ACS. However, these interactions were insufficient to affect the final risk score. The same variables as in the original score comprise the new score. Inclusion of nonlinearity and differential effects did little to change the model's discrimination but influenced predictions for patients at extremes of risk. Conclusions Irrespective of the inclusion of nonlinear and interaction terms, the updated GRACE risk model provides an excellent means to discriminate risk of death in patients with ACS and can be used as a simple nomogram to estimate risk in patients seen in clinical practice.
Background Limited data suggest that ST elevation (ST↑) in aVR is associated with higher mortality and more extensive coronary artery disease in the setting of non-ST↑ acute coronary syndromes (ACS). ...Methods In the prospective Global Registry of Acute Coronary Events (GRACE) electrocardiographic substudy, the admission electrocardiograms were analyzed by a blinded core laboratory. We performed multivariable analysis to determine (1) the independent prognostic significance of ST↑ in aVR and (2) its association with significant (≥50% stenosis) left main or 3-vessel disease (LM/3-vd). Results Among 5064 patients with non-ST↑ ACS, 4696 had no ST↑ in aVR, 292 (5.8%) had minor (0.5-1 mm) ST↑ in aVR, and 76 (1.5%) had major (>1 mm) ST↑ in aVR; their in-hospital mortality rates were 4.2%, 6.2%, and 7.9%, respectively ( P for trend =.03). At 6 months follow-up, the cumulative mortality rates were 7.6%, 12.7%, and 18.3%, respectively (log-rank P for trend <.001). However, minor and major ST↑ in aVR were not independent predictors of in-hospital or 6-month death after adjusting for other validated prognosticators in the GRACE risk model. Of the 2416 patients without prior coronary bypass surgery who underwent cardiac catheterization, the prevalence of LM/3-vd was 26.1%, 36.2%, and 55.9% for the groups with no, minor, and major ST↑ in aVR, respectively ( P for trend <.001). After adjusting for other clinical characteristics, major ST↑ in aVR remained an independent predictor of LM/3-vd (adjusted odds ratio, 2.68; 95% confidence interval, 1.29-5.58; P = .008). Conclusion ST↑ in aVR is less prevalent than reported in previous smaller studies. Although it is associated with higher unadjusted in-hospital and 6-month mortality, it does not provide incremental prognostic value beyond comprehensive risk stratification using the validated GRACE risk model. However, ST↑ greater than 1 mm in aVR may be useful in the early identification of LM/3-vd in ACS patients with ST depression.
Background Left ventricular hypertrophy (LVH) is frequently associated with ST depression (STD) on the electrocardiogram (ECG), a so-called strain pattern. Although STD is a well-established adverse ...prognosticator in non–ST-elevation acute coronary syndrome (NSTE-ACS), the relative prognostic importance of LVH and associated STD has not been elucidated. Methods A total of 7,761 patients with NSTE-ACS in the Global Registry of Acute Coronary Events (GRACE) and ACS-I registries had admission ECGs analyzed at a core laboratory. Left ventricular hypertrophy (determined by Sokolow-Lyon and/or Casale criteria) was observed in 296 (3.8%) patients. We examined the independent association between LVH (determined by the admission ECG) and outcomes in relation to STD. Results Patients with LVH were older, had more comorbidities and STD, and presented with a higher Killip class. They were less likely to undergo cardiac catheterization (43.1% vs 51.2%, P = .006) and percutaneous coronary intervention (18.3% vs 24.6%, P = .014). Patients with LVH had higher unadjusted mortality at 6 months (10.5% vs 7.1%, P = .038), but similar rates of in-hospital mortality (4.1% vs 3.4%, P = .54) and reinfarction (7.1% vs 7.6%, P = .75). Patients with LVH were more likely to have heart failure in-hospital (21.8% vs 11.8%, P < .001). Among LVH patients, degree of quantitative STD did not predict higher short- or long-term mortality, but was associated with in-hospital heart failure. Multivariable analysis adjusting for other clinical prognosticators of the GRACE risk models revealed that LVH was not a significant independent predictor of in-hospital mortality (adjusted odds ratio = 0.75, 95% CI 0.40-1.41, P = .37) or 6-month mortality (adjusted odds ratio = 0.83, 95% CI 0.52-1.35, P = .44). In contrast, STD remained a strong independent predictor of adverse outcomes. There was no significant interaction between STD and LVH. Conclusions Across the broad spectrum of NSTE-ACS, LVH is associated with adverse prognostic factors including STD. Electrocardiographic-determined LVH provides no significant additional prognostic utility beyond comprehensive risk assessment using the GRACE risk score. The adverse prognosis associated with LVH in NSTE-ACS may be attributable to other prognosticators such as STD.
In the prospective, multinational Global Registry of Acute Coronary Events (GRACE), patients diagnosed with non–ST-elevation acute coronary syndromes had their admission electrocardiogram ...independently evaluated by a central core laboratory, and its interpretation by the core laboratory and enrolling site were compared. One in 6 of these patients had clinically important features of left-bundle branch block or ST-segment deviation diagnosed by the core laboratory that were apparently not recognized at the local sites; this subgroup of patients was less likely to undergo risk stratification and revascularization. Importantly, failure to recognize these features as confirmed by the core laboratory in routine clinical practice was independently associated with higher mortality and recurrent myocardial infarction at 6 months (adjusted odds ratio 1.41, 95% confidence interval 1.01 to 1.96, p = 0.043). In conclusion, these findings underscore an urgent need to promote more accurate interpretation of electrocardiograms in contemporary clinical practice to bridge treatment gaps and improve patient outcome.
Among patients with non–ST-segment elevation acute coronary syndromes, recurrent ischemia and ventricular arrhythmias detected on continuous electrocardiographic monitoring remain common events that ...are associated with worse outcomes. The relative clinical significance of both events together is not well described. We determined the risk associated with ischemia (≥1 mm ST depression lasting ≥1 minutes) and ventricular tachycardia (VT) (≥4 beats) detected on 7-day continuous electrocardiographic monitoring in 6,355 patients with non–ST-segment elevation acute coronary syndromes from the Metabolic Efficiency with Ranolazine for Less Ischemia in Non–ST-elevation Acute Coronary Syndrome–Thrombolysis In Myocardial Infarction (MERLIN-TIMI) 36 trial. The patients were categorized into 4 groups according to the presence or absence of VT and ischemia. Cardiovascular death, sudden cardiac death (SCD), myocardial infarction, and recurrent ischemia were assessed during a median follow-up of 348 days. A total of 60.0% patients had no VT or ischemia, 20.0% had VT alone, 14.7% had ischemia alone, and 5.3% had both. The patients with either VT or ischemia were at increased risk of cardiovascular outcomes. The combination of ischemia and VT identified a particularly high-risk population for cardiovascular death (10.1% vs 3.0%, p <0.001), SCD (7.8% vs 0.9%, p <0.001), and myocardial infarction (15.4% vs 6.2%, p <0.001) compared to patients with neither. The addition of arrhythmia and ischemia significantly improved the clinical model for predicting cardiovascular death or SCD (p <0.001). In patients with both ischemia and VT, 66.6% of SCD occurred within 90 days of the non–ST-segment elevation acute coronary syndromes. In conclusion, in >6,300 patients with non–ST-segment elevation acute coronary syndromes, the presence of myocardial ischemia or VT alone, and particularly in combination, was independently associated with poor cardiovascular outcomes and thus provides incremental improvement in early risk stratification.
Objectives The purpose of this study was to assess the relationship between ischemia detected on continuous electrocardiographic (cECG) recording and cardiovascular outcomes after acute coronary ...syndrome (ACS). Background The small size of prior studies evaluating cECG prevented full evaluation of the risk associated with ischemia across subpopulations and compared with other methods of risk stratification. Ranolazine, a new antianginal agent, reduces ischemic symptoms in patients with chronic angina and after ACS but the anti-ischemic effect, as detected by cECG, is not known. Methods In all, 6,560 patients hospitalized with non–ST-segment elevation ACS were randomly assigned to ranolazine or placebo in the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndrome–Thrombolysis In Myocardial Infarction 36) trial. The cECG was performed for 7 days after randomization. Outcomes were followed for a median of 348 days. Clinical events that occurred during cECG recording were excluded from analysis. Results A total of 6,355 (97%) patients had cECG recordings evaluable for ischemia analysis. Patients with ≥1 episode of ischemia on cECG (n = 1,271, 20%) were at increased risk of cardiovascular death (7.7% vs. 2.7%, p < 0.001), MI (9.4% vs. 5.0%, p < 0.001), and recurrent ischemia (17.5% vs. 12.3%, p < 0.001). The relationship with cardiovascular death was independent of baseline characteristics or elevated biomarkers (adjusted hazard ratio: 2.46, p < 0.001). Ischemia on cECG was associated with significantly worse outcomes in several subgroups. Ranolazine did not reduce the rate of ischemia detected on cECG (19.9% vs. 21.0%, hazard ratio: 0.93, p = 0.21). Conclusions In more than 6,300 patients with ACS, ischemia detected on cECG occurred frequently and was strongly and independently associated with poor cardiovascular outcomes, including cardiovascular death. Continuous ECG monitoring to detect ischemia after ACS may help to identify patients at increased risk. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes MERLIN; NCT00099788 )