The prognostic significance of single-lead ST-segment resolution in ST-segment elevation myocardial infarction patients treated with primary PCI - A substudy of the randomized TOTAL trial.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with high morbidity and mortality worldwide. Simple electrocardiogram (ECG) tools, including ST-segment resolution (STR) have been developed to identify high-risk STEMI patients after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: We evaluated the prognostic impact of STR in the ECG lead with maximal baseline ST-segment elevation (STE) 30-60 minutes after primary PCI in 7,654 STEMI patients included in the TOTAL trial. Incomplete or no STR was defined as < 70% STR and complete STR as ≥ 70% STR. The primary outcome was the composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock, or new or worsening New York Heart Association (NYHA) class IV heart failure at 1-year follow-up. RESULTS: Of 7,654 patients, 42.9% had incomplete or no STR and 57.1% had complete STR. The primary outcome occurred in 341 patients (10.4%) in the incomplete or no STR group and in 234 patients (5.4%) in the complete STR group. In Cox regression analysis, adjusted hazard ratio for STR < 70% to predict the primary outcome was 1.56 (95% confidence interval 1.32-1.89; P < .001) (model adjusted for all baseline comorbidities, clinical status during hospitalization, angiographic findings, and procedural techniques). CONCLUSION: In a large international study of STEMI patients, STR < 70% 30-60 minutes post primary PCI in the ECG lead with the greatest STE at admission was associated with an increased rate of the composite of cardiovascular death, recurrent MI, cardiogenic shock, or new or worsening NYHA class IV heart failure at 1-year follow-up. Clinicians should pay attention to this simple ECG finding.

The prognostic significance of Q waves and T wave inversions in the ECG of patients with STEMI: A substudy of the TOTAL trial.

BACKGROUND: The prognostic significance of Q waves and T-wave inversions (TWI) combined and separately in STEMI patients undergoing primary PCI has not been well established in previous studies. METHODS: We included 7,831 patients from the TOTAL trial and divided the patients into categories based on Q waves and TWIs in the presenting ECG. The primary outcome was a composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock or new or worsening NYHA class IV heart failure within one year. The study evaluated the effect of Q waves and TWI on the risk of primary outcome and all-cause death, and whether patient benefit of aspiration thrombectomy differed between the ECG categories. RESULTS: Patients with Q+TWI+ (Q wave and TWI) pattern had higher risk of primary outcome compared to patients with Q-TWI- pattern [33 (10.5%) vs. 221 (4.2%); adjusted hazard ratio (aHR) 2.10; 95% CI, 1.45-3.04; p<0.001] within 40-days' period. When analyzed separately, patients with Q waves had a higher risk for the primary outcome compared to patients with no Q waves in the first 40 days [aHR 1.80; 95% CI, 1.48-2.19; p<0.001] but there was no additive risk after 40 days. Patients with TWI had a higher risk for primary outcome only after 40 days when compared to patients with no TWI [aHR 1.63; 95% CI, 1.04-2.55; p=0.033]. There was a trend towards a benefit of thrombectomy in patients with the Q+TWI+ pattern. CONCLUSIONS: Q waves and TWI combined (Q+TWI+ pattern) in the presenting ECG is associated with unfavourable outcome within 40-days. Q waves tend to affect short-term outcome, while TWI has more effect on long-term outcome.

The prognostic significance of the electrical QRS axis on long-term mortality in acute coronary syndrome patients - The TACOS study.

INTRODUCTION: There are several potential causes of QRS-axis deviation in the ECG, but there is limited data on the prognostic significance of QRS-axis deviation in ACS patients. SUBJECTS AND METHODS: We evaluated the long-term prognostic significance of acute phase frontal plane QRS-axis deviation and its shift during hospital stay in ACS patients. A total of 1026 patients who met the inclusion criteria were divided into three categories: normal (n = 823), left (n = 166) and right/extreme axis (n = 37). RESULTS: The median survival time was 9.0 years (95% CI 7.9-10.0) in the normal, 3.6 years (95% CI 2.4-4.7) in the left and 1.3 years (95% CI 0.2-2.4) in the right/extreme axis category. Both short and long-term all-cause mortality was lowest in the normal axis category and highest in the right/extreme axis category. Compared to normal axis, both admission phase QRS-axis deviation groups were independently associated with a higher risk of all-cause mortality. When including left ventricular hypertrophy in the ECG, only the right/extreme axis retained its statistical significance (aHR 1.76; 95% CI 1.16-2.66, p = 0.007). Axis shift to another axis category had no effect on mortality. CONCLUSION: In ACS patients, acute phase QRS-axis deviation was associated with higher risk of all-cause mortality. Among the axis deviation groups, right/extreme QRS-axis deviation was the strongest predictor of mortality in the multivariable analysis. Further studies are required to investigate to what extent this association is caused by pre-existing or by ACS-induced axis deviations. QRS-axis shift during hospital stay had no effect on all-cause mortality.

The Effect of Atrial Fibrillation on the Long-Term Mortality of Patients with Acute Coronary Syndrome: The TACOS Study.

INTRODUCTION: Atrial fibrillation (AF) is a frequent finding in acute coronary syndrome (ACS), but there is conflicting scientific evidence regarding its long-term impact on patient outcome. The aim of this study was to survey and compare the ≥10-year mortality of ACS patients with sinus rhythm (SR) and AF. METHODS: Patients were divided into 2 groups based on rhythm in their 12-lead ECGs: (1) SR (n = 788) at hospital admission and discharge (including sinus bradycardia, physiological sinus arrhythmia, and sinus tachycardia) and (2) AF/atrial flutter (n = 245) at both hospital admission and discharge, or SR and AF combination. Patients who failed to match the inclusion criteria were excluded from the final analysis. The main outcome surveyed was long-term all-cause mortality between AF and SR groups during the whole follow-up time. RESULTS: Consecutive ACS patients (n = 1,188, median age 73 years, male/female 58/42%) were included and followed up for ≥10 years. AF patients were older (median age 77 vs. 71 years, p < 0.001) and more often female than SR patients. AF patients more often presented with non-ST-elevation myocardial infarction (69.8 vs. 50.4%, p < 0.001), had a higher rate of diabetes (31.0 vs. 22.8%, p = 0.009), and were more often using warfarin (32.2 vs. 5.1%, p < 0.001) or diuretic medication (55.1 vs. 25.8%, p < 0.001) on admission than patients with SR. The use of warfarin at discharge was also more frequent in the AF group (55.5 vs. 14.8%, p < 0.001). The rates of all-cause and cardiovascular mortality were higher in the AF group (80.9 vs. 50.3%, p < 0.001, and 73.8 vs. 69.6%, p = 0.285, respectively). In multivariable analysis, AF was independently associated with higher mortality when compared to SR (adjusted HR 1.662; 95% CI: 1.387-1.992, p < 0.001). CONCLUSION: AF/atrial flutter at admission and/or discharge independently predicted poorer long-term outcome in ACS patients, with 66% higher mortality within the ≥10-year follow-up time when compared to patients with SR.

The prognostic significance of grade of ischemia in the ECG in patients with ST-elevation myocardial infarction: A substudy of the randomized trial of primary PCI with or without routine manual thrombectomy (TOTAL trial).

BACKGROUND: The importance of the grade of ischemia (GI) ECG classification in the risk assessment of patients with STEMI has been shown previously. Grade 3 ischemia (G3I) is defined as ST-elevation with distortion of the terminal portion of the QRS complex in two or more adjacent leads, while Grade 2 ischemia (G2I) is defined as ST-elevation without QRS distortion. Our aim was to evaluate the prognostic impact of the GI classification on the outcome in patients with STEMI. METHODS: 7,211 patients from the TOTAL trial were included in our study. The primary outcome was a composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within one year. RESULTS: The primary outcome occurred in 153 of 1,563 patients (9.8%) in the G3I group vs. 364 of 5,648 patients (6.4%) in the G2I group (adjusted HR 1.27; 95% CI, 1.04 - 1.55; p=0.022). The rate of cardiovascular death (4.8% vs. 2.5%; adjusted HR 1.48; 95% CI 1.09 - 2.00; p=0.013) was also higher in patients with G3I. CONCLUSIONS: G3I in the presenting ECG was associated with an increased rate of the composite of cardiovascular death, recurrent MI, cardiogenic shock, or NYHA class IV heart failure within one year compared to patients with G2I. Patients with G3I also had a higher cardiovascular death compared to patients with G2I.

The prognostic significance of a positive or isoelectric T wave in lead aVR in patients with acute coronary syndrome and ischemic ECG changes in the presenting ECG - Long-term follow-up data of the TACOS study.

BACKGROUND: A positive T wave in lead aVR (aVRT+) is an independent prognostic predictor of cardiovascular mortality in the general population as well as in cardiovascular disease. SUBJECTS AND METHODS: We evaluated the prognostic impact of aVRT+ in an ECG recorded as close to hospital discharge as possible in acute coronary syndrome patients (n = 527). We divided the patients into three categories based on the findings in the admission ECG: ST elevation, global ischemia and other ST/T changes. RESULTS: In the whole study population, and in all the three ECG subgroups, the 10-year all-cause mortality rate was higher in the aVRT+ group than in the aVRT- group. In Cox regression analysis, the age and gender adjusted hazard ratio (HR) for aVRT+ to predict all-cause mortality in the whole study population was 1.43 (95% confidence interval [CI] 1.12-1.83; p = 0.004). To predict cardiovascular mortality, the age and gender adjusted HR for aVRT+ was 1.54 (95% CI 1.14-2.07; p = 0.005) in the whole study population and 2.07 (95% CI 1.07-4.03; p = 0.032) in the category with other ST/T changes. CONCLUSION: In ACS patients with or without ST elevation, but with ischemic ST/T changes in their presenting ECG, a positive or isoelectric T wave in lead aVR in an ECG recorded in the subacute in-hospital stage is associated with all-cause and cardiovascular mortality during long-term follow-up. Clinicians should pay attention to this simple ECG finding at hospital discharge.

Long-term outcome of pre-specified ECG patterns in acute coronary syndrome.

BACKGROUND: Long-term outcome of real-life acute coronary syndrome (ACS) patients with selected ECG patterns is not well known. PURPOSE: To survey the 10-year outcome of pre-specified ECG patterns in ACS patients admitted to a university hospital. METHODS: A total of 1184 consecutive acute coronary syndrome patients in 2002-2003 were included and followed up for 10 years. The patients were classified into nine pre-specified ECG categories: 1) ST elevation; 2) pathological Q waves without ST elevation; 3) left bundle branch block (LBBB); 4) right bundle branch block (RBBB) 5) left ventricular hypertrophy (LVH) without ST elevation except in leads aVR and/or V1; 6) global ischemia ECG (ST depression ≥0.5 mm in 6 leads, maximally in leads V4-5 with inverted T waves and ST elevation ≥0.5 mm in lead aVR); 7) other ST depression and/or T wave inversion; 8) other findings and 9) normal ECG. RESULTS: Any abnormality in the ECG, especially Q waves, LBBB, LVH and global ischemia, had negative effect on outcome. In age- and gender adjusted Cox regression analysis, pathological Q waves (HR 2.28, 95%CI 1.20-4.32, p = .012), LBBB (HR 3.25, 95%CI 1.65-6.40, p = .001), LVH (HR 2.53, 95%CI 1.29-4.97, p = .007), global ischemia (HR 2.22, 95%CI 1.14-4.31, p = .019) and the combined group of other findings (HR 3.01, 95%CI 1.56-6.09, p = .001) were independently associated with worse outcome. CONCLUSIONS: During long-term follow-up of ACS patients, LBBB, ECG-LVH, global ischemia, and Q waves were associated with worse outcome than a normal ECG, RBBB, ST elevation or ST depression with or without associated T-wave inversion. LBBB was associated with the highest mortality rates.

Randomized trial of primary PCI with or without routine manual thrombectomy.

BACKGROUND: During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results. METHODS: We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days. RESULTS: The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). CONCLUSIONS: In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).

Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial.

BACKGROUND: Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice. METHODS: The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10,732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044. FINDINGS: Between Aug 5, 2010, and July 25, 2014, 10,732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10,064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio [HR] 1·00 [95% CI 0·87-1·15], p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 [95% CI 0·76-1·14], p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 [95% CI 1·10-2·51], p=0·015). INTERPRETATION: Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI. FUNDING: Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc.

Culprit lesion thrombus burden after manual thrombectomy or percutaneous coronary intervention-alone in ST-segment elevation myocardial infarction: the optical coherence tomography sub-study of the TOTAL (ThrOmbecTomy versus PCI ALone) trial.

AIMS: Manual thrombectomy has been proposed as a strategy to reduce thrombus burden during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the effectiveness of manual thrombectomy in reducing thrombus burden is uncertain. In this substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial, we compared the thrombus burden at the culprit lesion using optical coherence tomography (OCT) in patients treated with thrombectomy vs. PCI-alone. METHODS AND RESULTS: The TOTAL trial (N = 10 732) was an international, multicentre, randomized trial of thrombectomy (using the Export catheter, Medtronic Cardiovascular, Santa Rosa, CA, USA) in STEMI patients treated with primary PCI. The OCT substudy prospectively enrolled 214 patients from 13 sites in 5 countries. Optical coherence tomography was performed immediately after thrombectomy or PCI-alone and then repeated after stent deployment. Thrombus quantification was performed by an independent core laboratory blinded to treatment assignment. The primary outcome of pre-stent thrombus burden as a percentage of segment analysed was 2.36% (95% CI: 1.73-3.22) in the thrombectomy group and 2.88% (95% CI: 2.12-3.90) in the PCI-alone group (P = 0.373). Absolute pre-stent thrombus volume was not different (2.99 vs. 3.74 mm(3), P = 0.329). Other secondary outcomes of pre-stent quadrants of thrombus, post-stent atherothrombotic burden, and post-stent atherothrombotic volume were not different between groups. CONCLUSION: Manual thrombectomy did not reduce pre-stent thrombus burden at the culprit lesion compared with PCI-alone. Both strategies were associated with low thrombus burden at the lesion site after the initial intervention to restore flow.

Radial versus femoral access for elderly patients with acute coronary syndrome undergoing coronary angiography and intervention: insights from the RIVAL trial.

BACKGROUND: Radial access for percutaneous coronary intervention is associated with lower rates of access site complications and bleeding. However, elderly patients have more complex vascular anatomy and radial access may be more challenging in this population. There remains uncertainty regarding the role of radial access in elderly patients undergoing cardiac catheterization. METHODS AND RESULTS: The RIVAL trial randomized patients with acute coronary syndromes undergoing cardiac catheterization to radial versus femoral access. In this analysis, the rates of access site complications and access site cross-over were compared across different age groups. Among the 7,021 patients, 1035 (15%) were ≥75 years of age. Across all age categories, radial access was consistently associated with higher rates of access site cross over and lower rates of major access site complications, with no significant interaction between age and access site. Radial access was associated with lower rates of major vascular access site complications in patients ≥75 years of age (3.6% vs 6.6%; P = .03) and in patients <75 years of age (1.0% vs 3.2%; P < .001; P value for interaction = .2). The rates of access site crossover were higher with radial access among patients ≥75 (12.5% vs 2.6%; P < .001) and <75 (6.7% vs 1.9%; P < .001; P value for interaction = .9). There were no significant differences in the primary composite outcome (death, myocardial infarction, stroke or non coronary artery bypass graft major bleeding) or its individual components in either age group. In patients ≥75 years of age undergoing primary percutaneous coronary intervention, there was no significant difference in procedure time (120 vs 115 minutes; P = .3). CONCLUSIONS: Consistent with the overall RIVAL trial population, elderly patients undergoing cardiac catheterization have lower rates of major bleeding or access site complications and higher rates of access site crossover with radial access compared to femoral access.

Design and rationale of the TOTAL trial: a randomized trial of routine aspiration ThrOmbecTomy with percutaneous coronary intervention (PCI) versus PCI ALone in patients with ST-elevation myocardial infarction undergoing primary PCI.

BACKGROUND: A major limitation of primary percutaneous coronary intervention (PPCI) for the treatment of ST-elevation myocardial infarction (STEMI) is impaired microvascular perfusion due to embolization and obstruction of microcirculation with thrombus. Manual thrombectomy has the potential to reduce distal embolization and improve microvascular perfusion. Clinical trials have shown mixed results regarding thrombectomy. OBJECTIVE: The objective of this study is to evaluate the efficacy of routine upfront manual aspiration thrombectomy during PPCI compared with percutaneous coronary intervention alone in patients with STEMI. DESIGN: This is a multicenter, prospective, open, international, randomized trial with blinded assessment of outcomes. Patients with STEMI undergoing PPCI are randomized to upfront routine manual aspiration thrombectomy with the Export catheter (Medtronic CardioVascular, Santa Rosa, CA) or to percutaneous coronary intervention alone. The primary outcome is the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or new or worsening New York Heart Association class IV heart failure up to 180 days. The trial uses an event-driven design and will recruit 10,700 patients. SUMMARY: The TOTAL trial will determine the effect of routine manual aspiration thrombectomy during PPCI on clinically important outcomes.

Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial.

BACKGROUND: Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronary angiography with possible intervention. METHODS: The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group, multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voice response system to radial or femoral artery access. The primary outcome was a composite of death, myocardial infarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. FINDINGS: Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries. 3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in 128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72-1·17; p=0·50). Of the six prespecified subgroups, there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28-0·87; p=0·015) and in patients with ST-segment elevation myocardial infarction (0·60, 0·38-0·94; p=0·026). The rate of death, myocardial infarction, or stroke at 30 days was 112 (3·2%) of 3507 patients in the radial group compared with 114 (3·2%) of 3514 in the femoral group (HR 0·98, 95% CI 0·76-1·28; p=0·90). The rate of non-CABG-related major bleeding at 30 days was 24 (0·7%) of 3507 patients in the radial group compared with 33 (0·9%) of 3514 patients in the femoral group (HR 0·73, 95% CI 0·43-1·23; p=0·23). At 30 days, 42 of 3507 patients in the radial group had large haematoma compared with 106 of 3514 in the femoral group (HR 0·40, 95% CI 0·28-0·57; p<0·0001). Pseudoaneurysm needing closure occurred in seven of 3507 patients in the radial group compared with 23 of 3514 in the femoral group (HR 0·30, 95% CI 0·13-0·71; p=0·006). INTERPRETATION: Radial and femoral approaches are both safe and effective for PCI. However, the lower rate of local vascular complications may be a reason to use the radial approach. FUNDING: Sanofi-Aventis, Population Health Research Institute, and Canadian Network for Trials Internationally (CANNeCTIN), an initiative of the Canadian Institutes of Health Research.

Allelic variant of NOS1AP effects on cardiac alternans of repolarization during exercise testing.

INTRODUCTION: A repolarization abnormality manifested as T-wave alternans (TWA) in electrocardiogram (ECG) predicts cardiovascular mortality. A common variant in the NOS1AP gene is associated with mortality and QT interval duration, possibly in a gender-specific manner, but data is lacking on potential association with TWA. This study tested association between rs10494366 in NOS1AP and both TWA and 4-year mortality. MATERIAL AND METHODS: A total of 1963 Finnish Cardiovascular Study participants (36.6% female, 57.1 ± 13.0 years) were genotyped and their maximal TWA values were measured from continuous ECG recordings during clinical exercise test at rest, exercise and recovery. RESULTS: We observed a significant gender-specific effect of NOS1AP genotype on TWA. In all subjects, there was no statistically significant difference between the three genotypes (TT, TG, GG) in the responses of TWA over the entire exercise test (time-by-genotype interaction p = 0.057). In women, after adjustment for age, coronary heart disease and ß-blocker medication status, changes of TWA over different phases of exercise test were significantly associated with NOS1AP genotype (time-by-genotype interaction p = 0.001). In men, NOS1AP rs10494366 was not associated with TWA. During follow-up (mean 47 months), 113 patients died. NOS1AP rs10494366 was not a statistically significant predictor of mortality. CONCLUSION: The NOSIAP variant rs10494366 influences TWA and TWA response during clinical exercise test in females. Gender-specific effects have also been previously reported for the influence of the variant on QT interval. If replicated, these findings should prompt studies to further elucidate the mechanisms underlying the gender differences in NOS1AP effects on repolarization.

Prognostic Role of Residual Thrombus Burden Following Thrombectomy: Insights From the TOTAL Trial.

BACKGROUND: It is unclear whether more effective forms of thrombus removal than current aspiration catheters would lead to improved outcomes. We sought to evaluate the prognostic role of residual thrombus burden (rTB), after manual thrombectomy, in patients undergoing primary percutaneous coronary intervention with routine manual thrombectomy in the TOTAL trial (Thrombectomy Versus PCI Alone). METHODS: This is a single-arm analysis of patients from the TOTAL trial who underwent routine manual aspiration thrombectomy. The rTB was quantified by an angiographic core laboratory using the Thrombolysis in Myocardial Infarction criteria and validated using existing optical coherent tomography data. Large rTB was defined as grade ≥3. The primary outcome was death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or new or worsening heart failure within 180 days. RESULTS: Of 5033 patients randomized to routine thrombectomy, 2869 patients had quantifiable rTB (1014 [35%] had large rTB). Patients with large rTB were more likely to have hypertension, previous percutaneous coronary intervention, myocardial infarction, or Killip class III on presentation but less likely to have Killip class I. The primary outcome occurred more frequently in patients with large rTB, even after adjustment for known risk predictors (8.6% versus 4.6%; adjusted hazard ratio, 1.83 [95% CI, 1.34-2.48]). These patients also had a higher risk of cardiovascular death (adjusted hazard ratio, 1.83 [95% CI, 1.13-2.95]), cardiogenic shock (adjusted hazard ratio, 2.02 [95% CI, 1.08-3.76]), and heart failure (adjusted hazard ratio, 1.74 [95% CI, 1.02-2.96]) but not myocardial infarction or stroke. CONCLUSIONS: Large rTB is a common finding in primary percutaneous coronary intervention and is associated with increased risk of adverse cardiovascular outcomes, including cardiovascular death. Future technologies offering better thrombus removal than current devices may decrease or even eliminate the risk associated with rTB. This, potentially, can turn into a strategic option to be studied in clinical trials. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01149044.

Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial.

BACKGROUND: Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention (PCI). We assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis in patients undergoing PCI. METHODS: The CURRENT-OASIS 7 trial was undertaken in 597 centres in 39 countries. 25,086 individuals with acute coronary syndromes and intended early PCI were randomly assigned to double-dose (600 mg on day 1, 150 mg on days 2-7, then 75 mg daily) versus standard-dose (300 mg on day 1 then 75 mg daily) clopidogrel, and high-dose (300-325 mg daily) versus low-dose (75-100 mg daily) aspirin. Randomisation was done with a 24 h computerised central automated voice response system. The clopidogrel dose comparison was double-blind and the aspirin dose comparison was open label with blinded assessment of outcomes. This prespecified analysis is of the 17,263 individuals who underwent PCI. The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. Analyses were by intention to treat, adjusted for propensity to undergo PCI. This trial is registered with ClinicalTrials.gov, number NCT00335452. FINDINGS: 8560 patients were assigned to double-dose and 8703 to standard-dose clopidogrel (8558 and 8702 completed 30-day follow-up, respectively), and 8624 to high-dose and 8639 to low-dose aspirin (8622 and 8638 completed 30-day follow-up, respectively). Compared with the standard dose, double-dose clopidogrel reduced the rate of the primary outcome (330 events [3·9%] vs 392 events [4·5%]; adjusted hazard ratio 0·86, 95% CI 0·74-0·99, p=0·039) and definite stent thrombosis (58 [0·7%] vs 111 [1·3%]; 0·54 [0·39-0·74], p=0·0001). High-dose and low-dose aspirin did not differ for the primary outcome (356 [4·1%] vs 366 [4·2%]; 0·98, 0·84-1·13, p=0·76). Major bleeding was more common with double-dose than with standard-dose clopidogrel (139 [1·6%] vs 99 [1·1%]; 1·41, 1·09-1·83, p=0·009) and did not differ between high-dose and low-dose aspirin (128 [1·5%] vs 110 [1·3%]; 1·18, 0·92-1·53, p=0·20). INTERPRETATION: In patients undergoing PCI for acute coronary syndromes, a 7-day double-dose clopidogrel regimen was associated with a reduction in cardiovascular events and stent thrombosis compared with the standard dose. Efficacy and safety did not differ between high-dose and low-dose aspirin. A double-dose clopidogrel regimen can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI. FUNDING: Sanofi-Aventis and Bristol-Myers Squibb.

Design and rationale of the radial versus femoral access for coronary intervention (RIVAL) trial: a randomized comparison of radial versus femoral access for coronary angiography or intervention in patients with acute coronary syndromes.

BACKGROUND: Major bleeding in acute coronary syndromes (ACS) is associated with an increased risk of subsequent mortality and recurrent ischemic events. Observational data and small randomized trials suggest that radial instead of femoral access for coronary angiography/intervention results in fewer bleeding complications, with preserved and possibly improved efficacy. Radial access versus femoral access has yet to be formally evaluated in a randomized trial adequately powered for the comparison of clinically important outcomes. OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of radial versus femoral access for coronary angiography/intervention in patients with ACS managed with an invasive strategy. DESIGN: This was a multicenter international randomized trial with blinded assessment of outcomes. 7021 patients with ACS (with or without ST elevation) have been randomized to either radial or femoral access for coronary angiography/intervention. The primary outcome is the composite of death, myocardial infarction, stroke, or non-coronary artery bypass graft-related major bleeding up to day 30. The key secondary outcomes are (1) death, myocardial infarction, or stroke up to day 30 and (2) non-coronary artery bypass graft-related major bleeding up to day 30. Percutaneous coronary intervention (PCI) success rates will also be compared between the two access sites. CONCLUSIONS: The RIVAL trial will help define the optimal access site for coronary angiography/intervention in patients with ACS.

Poor long-term outcome in acute coronary syndrome in a real-life setting: Ten-year outcome of the TACOS study.

BACKGROUND: Long-term outcome of the three categories of acute coronary syndrome (ACS) in real-life patient cohorts is not well known. The objective of this study was to survey the 10-year outcome of an ACS patient cohort admitted to a university hospital and to explore factors affecting the outcome. METHODS: A total of 1188 consecutive patients (median age 73 years) with ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) or unstable angina pectoris (UA) in 2002-2003 were included and followed up for ≥ 10 years. RESULTS: Mortality for STEMI, NSTEMI and UA patients during the follow-up period was 52.5%, 69.9% and 41.0% (p < 0.001), respectively. In multivariable Cox regression analysis, only age and creatinine level at admission were independently associated with patient outcome in all the three ACS categories when analyzed separately. CONCLUSIONS: All the three ACS categories proved to have high mortality rates during long-term followup in a real-life patient cohort. NSTEMI patients had worse outcome than STEMI and UA patients during the whole follow-up period. Our study results indicate clear differences in the prognostic significance of various demographic and therapeutic parameters within the three ACS categories.

The Association of Atrial Fibrillation Before Percutaneous Coronary Intervention With 1-Year Outcome in ST-Elevation Myocardial Infarction Patients.

BACKGROUND: We aimed to determine the association of atrial fibrillation (AF) with 1-year outcome in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). METHODS: Patients (n = 8830) enrolled in the Trial of Routine Aspiration Thrombectomy with PCI vs PCI Alone in Patients With STEMI (TOTAL) were followed for 1 year. The primary outcome was a composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or new or worsening class IV heart failure. The presence or absence of AF was determined from a single pre-PCI electrocardiogram. RESULTS: Patients with AF (n = 437; 4.9%) were older, and more often had a history of stroke, hypertension, or myocardial infarction. The rate of the primary outcome was higher in the AF group than in the sinus rhythm (SR) group (17.4% vs 7.4%, P < 0.001), as was the rate of cardiovascular death (9.8% vs 3.3%, P < 0.001). In multivariable analysis, AF was independently predictive of the primary outcome (adjusted hazard ratio [aHR] 1.68; 95% confidence interval [CI], 1.30-2.16, P < 0.001), cardiovascular death (aHR 1.69; 95% CI, 1.19-2.40, P = 0.003), all-cause mortality (aHR 1.63; 95% CI, 1.18-2.24, P = 0.003), and severe heart failure (aHR 1.96; 95% CI, 1.25-3.07, P = 0.003). Among patients who were in SR, the primary outcome occurred in 307 of 4252 (7.2%) in the thrombectomy group and 310 of 4141 (7.5%) in the PCI alone group, and among those with AF, these rates were respectively 42 of 218 (19.3%) and 34 of 219 (15.5%) (P interaction = 0.26). CONCLUSIONS: In STEMI patients, AF on the pre-PCI electrocardiogram is associated with a higher risk of the primary composite cardiovascular outcome, all-cause and cardiovascular death, and severe heart failure during 1-year follow-up than it is in patients with SR.

CONTEXTE: Notre objectif était de déterminer le lien entre la fibrillation auriculaire (FA) et le résultat à un an de patients ayant subi un infarctus du myocarde avec élévation du segment ST (STEMI) puis une intervention coronarienne percutanée (ICP) primaire. MÉTHODOLOGIE: Les patients (n = 8 830) admis à l'étude TOTAL ( T rial o f Routine Aspiration T hrombectomy with PCI vs PCI Al one in Patients With STEMI) ont été suivis pendant une année. Le principal critère d'évaluation était composé des décès d'origine cardiovasculaire, de l'infarctus du myocarde récurrent, du choc cardiogénique ou de l'apparition/aggravation d'une insuffisance cardiaque de classe IV. La présence ou l'absence de FA était établie à partir d'un seul électrocardiogramme effectué avant l'ICP. RÉSULTATS: Les patients atteints de FA (n = 437; 4,9 %) étaient âgés, et la plupart avaient des antécédents d'AVC, d'hypertension ou d'infarctus du myocarde. La fréquence des manifestations liées au principal critère d'évaluation était plus élevée dans le groupe FA que dans le groupe en rythme sinusal (17,4 % vs 7,4 %, p < 0,001); il en était de même pour le taux de décès d'origine cardiovasculaire (9,8 % vs 3,3 %, p < 0,001). Dans une analyse multivariée, la FA était indépendamment prédictive des manifestations liées au principal critère d'évaluation (rapport des risques instantanés ajusté [RRIa] : 1,68; intervalle de confiance [IC] à 95 % : 1,30-2,16, p < 0,001), décès d'origine cardiovasculaire (RRIa : 1,69; IC à 95 % : 1,19-2,40, p = 0,003), mortalité toutes causes confondues (RRIa : 1,63; IC à 95 % : 1,18-2,24, p = 0,003) et insuffisance cardiaque grave (RRIa : 1,96; IC à 95 % : 1,25-3,07, p = 0,003). Parmi les patients en rythme sinusal, les manifestations du principal critère d'évaluation sont survenues chez 307 patients sur les 4 252 (7,2 %) du groupe ayant subi une thrombectomie, et chez 310 patients sur les 4 141 (7,5 %) du groupe ayant subi une ICP sans thrombectomie; parmi ceux atteints de FA, ces taux étaient respectivement de 42 sur 218 (19,3 %) et de 34 sur 219 (15,5 %) (p interaction = 0,26). CONCLUSIONS: Chez les patients ayant subi un STEMI, la détection d'une FA à l'électrocardiogramme réalisé avant l'ICP est associée à un risque accru de manifestation cardiovasculaire liée au principal critère d'évaluation composé, de décès toutes causes confondues et d'origine cardiovasculaire, et d'insuffisance cardiaque grave, pendant la première année de suivi comparativement aux patients en rythme sinusal.

The etiology and prognostic significance of cardiac troponin I elevation in unselected emergency department patients.

BACKGROUND: Cardiac troponin elevations are associated not only with acute coronary syndromes (ACS) but also with multiple other cardiac and non-cardiac conditions. STUDY OBJECTIVES: To investigate the etiology and clinical significance of cardiac troponin I elevations in an unselected Emergency Department (ED) patient cohort. METHODS: The study population consisted of 991 consecutive troponin-positive patients admitted to the ED of a university hospital with ACS as the presumptive diagnosis. Cardiac troponin I was measured on admission and a follow-up sample was obtained at 6-12 h. Clinical diagnosis was ascertained retrospectively using all the available information including electrocardiogram, clinical data, laboratory tests, and available coronary angiograms. RESULTS: At admission, 805 (81.2%) patients were already troponin positive; of these, the troponin elevation was related to myocardial infarction (MI) in 654 (81.2%) patients. Finally, 83.0% of the troponin elevations were due to MI, 7.9% were related to other cardiac causes, and 9.1% to non-cardiac diseases. The leading non-cardiac causes were pulmonary embolism, renal failure, pneumonia, and sepsis. Non-cardiac patients with elevated troponin I at admission showed significantly higher in-hospital mortality (26.7% vs. 13.4%, p = 0.002) compared to cardiac patients. CONCLUSION: Elevated troponin levels for reasons other than MI are common in the ED and are a marker of poor in-hospital prognosis.