Aims

Through a 4-year follow-up of the abstracts submitted to the European Society of Cardiology Congress in 2006, we aimed at identifying factors predicting high-quality research, appraising the quality of the peer review and editorial processes, and thereby revealing potential ways to improve future research, peer review, and editorial work.

Methods and results

All abstracts submitted in 2006 were assessed for acceptance, presentation format, and average reviewer rating. Accepted and rejected studies were followed for 4 years. Multivariate regression analyses of a representative selection of 10% of all abstracts (n= 1002) were performed to identify factors predicting acceptance, subsequent publication, and citation. A total of 10 020 abstracts were submitted, 3104 (31%) were accepted for poster, and 701 (7%) for oral presentation. At Congress level, basic research, a patient number ≥ 100, and prospective study design were identified as independent predictors of acceptance. These factors differed from those predicting full-text publication, which included academic affiliation. The single parameter predicting frequent citation was study design with randomized controlled trials reaching the highest citation rates. The publication rate of accepted studies was 38%, whereas only 24% of rejected studies were published. Among published studies, those accepted at the Congress received higher citation rates than rejected ones.

Conclusions

Research of high quality was determined by study design and largely identified at Congress level through blinded peer review. The scientometric follow-up revealed a marked disparity between predictors of full-text publication and those predicting citation or acceptance at the Congress.

Objective

Few data exist to guide antiarrhythmic drug therapy for sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) after acute myocardial infarction (MI). The objective of this analysis was to describe survival of patients with sustained VT/VF post-MI according to antiarrhythmic drug treatment.

Design & Setting

We conducted a retrospective analysis of ST-segment elevation MI patients with sustained VT/VF in GUSTO IIB and III and compared all-cause death in patients receiving amiodarone, lidocaine, or no antiarrhythmic. We used Cox proportional hazards modeling and inverse weighted estimators to adjust for baseline characteristics, beta-blocker use, and propensity to receive antiarrhythmics. Due to non-proportional hazards for death in early follow-up (0–3 hours after sustained VT/VF) compared with later follow-up (>3 hours), we analyzed all-cause mortality using time-specific hazards.

Patients & Interventions

Among 19,190 acute MI patients, 1126 (5.9%) developed sustained VT/VF and met the inclusion criteria. Patients received lidocaine (n=664, 59.0%), amiodarone (n=50, 4.4%), both (n=110, 9.8%), or no antiarrhythmic (n=302, 26.8%).

Results

In the first 3 hours after VT/VF, amiodarone (adjusted HR 0.39, 95% CI 0.21–0.71) and lidocaine (adjusted HR 0.72, 95% CI 0.53–0.96) were associated with a lower hazard of death—likely evidence of survivor bias. Among patients who survived 3 hours, amiodarone was associated with increased mortality at 30 days (adjusted HR 1.71, 95% CI 1.02–2.86) and 6 months (adjusted HR 1.96, 95% CI 1.21–3.16) but lidocaine was not at 30 days (adjusted HR 1.19, 95% CI 0.77–1.82) and 6 months (adjusted HR 1.10, 95% CI 0.73–1.66).

Conclusion

Among patients with acute MI complicated by sustained VT/VF who survive 3 hours, amiodarone, but not lidocaine, is associated with an increased risk of death; reinforcing the need for randomized trials in this population.

Aims

Recent genetic studies identified the rs1333049 variant on chromosome 9p21 as a major susceptibility locus for coronary artery disease and myocardial infarction (MI). Here, we evaluated whether this variant also contributes to recurrent MI or cardiac death following an acute coronary syndrome (ACS).

Methods and results

A total of 3247 patients with ACS enrolled in the Global Registry of Acute Coronary Events (GRACE) in three distinct populations (UK, Belgium and Poland) were prospectively followed for 6 months and genotyped for rs1333049, in addition to 3004 and 2467 healthy controls from the UK and Belgium. After having confirmed that the at-risk C allele of rs1333049 was associated with index ACS in the UK and Belgian populations, we found that the rs1333049 at-risk C allele was significantly and independently associated with recurrent MI [age- and gender-adjusted hazard ratio (HR) 1.48, CI = 1.00–2.19, P = 0.048; and multivariable-adjusted HR 1.47, CI = 0.99–2.18; P = 0.053] and with recurrent MI or cardiac death (age- and gender-adjusted HR 1.58, CI = 1.00–2.48; P = 0.045; and multivariable adjusted HR 1.49, CI = 1.03–1.98; P = 0.028) within 6 months after an index ACS. Inclusion of rs1333049 into the GRACE risk score significantly improved classification for recurrent MI or cardiac death (P = 0.040), as calculated by the integrated discrimination improvement method.

Conclusion

In this large observational study, the 9p21 variant was independently associated with adverse cardiac outcome after ACS.

Context

There is conflicting information about whether sex-differences modulate short-term mortality following acute coronary syndromes (ACS).

Objective

To investigate the relationship between sex and 30-day mortality in ACS, and determine whether this relationship is modified by clinical syndrome or coronary anatomy using a large database across the spectrum of ACS and adjusting for potentially confounding clinical covariates.

Design Setting and Participants

Data from 11 ACS trials from 1993 to 2006 were pooled. Of 136,247 patients, 38,048 (28%) were women; 102,004 (26% women) STEMI, 14,466 (29% women) NSTEMI and 19,777 (40% women) unstable angina (UA).

Main Outcome Measure

Thirty-day mortality following ACS.

Results

Mortality at 30 days was 9.6% in women and 5.3% in men (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.83–2.00). After multivariable adjustment, mortality was not significantly different between women and men (adjusted OR 1.06, 95% CI 0.99–1.15). Importantly, a significant sex by type of ACS interaction was demonstrated (P<0.001). In STEMI, 30-day mortality was higher among women (adjusted OR 1.15, 95% CI 1.06–1.24), whereas NSTEMI (adjusted OR 0.77, 95% CI 0.63–0.95), and UA mortality was lower among women (adjusted OR 0.55, 95% CI 0.43–0.70). In a cohort of 35,128 patients with angiographic data, women more often had non-obstructive (15% vs. 8%,) and less often had 2-vessel (25% vs. 28%) and 3-vessel (23% vs. 26%) coronary disease regardless of ACS type. After additional adjustment for angiographic disease severity, 30-day mortality among women was not significantly different than men, regardless of ACS type. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity (p-value for interaction =0.70),

Conclusions

Sex-based differences exist in 30-day mortality among ACS patients and vary depending on clinical presentation. However, these differences are markedly attenuated following adjustment for clinical differences and angiographic data.

Aims

To assess the incidence and timing of atrial fibrillation (AF), describe antithrombotic therapy use, and evaluate the association of AF with 90 day mortality and other secondary clinical outcomes.

Methods and results

We studied 5745 ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention (PCI) in APEX-AMI. Approximately 11% had AF during hospitalization. Atrial fibrillation prevalence at baseline and at discharge was 4.8% [confidence interval (CI) 4.3–5.4%] and 2.5% (CI 2.1–2.9%), respectively. The proportion of 5466 patients without AF at baseline who developed new onset AF was 6.3% (CI 5.6–6.9%). This corresponded to 9.3 cases of new onset AF/1000 patient days at risk. New onset AF was independently associated with 90 day mortality [adjusted hazard ratio (HR) 1.81; 95% CI 1.06–3.09; P = 0.029] after accounting for baseline covariates and in-hospital procedures and complications. New onset AF was associated with shock (adjusted HR 3.81; 95% CI 1.88–7.70; P = 0.0002), congestive heart failure (adjusted HR 2.66; 95% CI 1.74–4.06; P < 0.0001), and stroke (adjusted HR 2.98; 95% CI 1.47–6.04; P = 0.0024) in models accounting for baseline covariates. Of AF patients, 55% did not receive oral anticoagulation therapy at discharge. Among patients with coronary stents, 5.1% were discharged on triple therapy. Patients at highest risk of stroke (CHADS2 score ≥2) were least likely to receive oral anticoagulation at discharge (39%). Warfarin use in patients with AF at discharge (43.4%) was associated with lower rates of 90 day mortality and stroke.

Conclusion

Atrial fibrillation prevalence at baseline and at discharge was 4.8 and 2.5%, respectively. The proportion of patients who developed new onset AF was 6.3%. New onset AF was independently associated with 90 day mortality and was a marker of adverse outcomes in patients undergoing primary PCI.

The matricellular protein SPARC (secreted protein, acidic and rich in cysteine, also known as osteonectin) mediates cell–matrix interactions during wound healing and regulates the production and/or assembly of the extracellular matrix (ECM). This study investigated whether SPARC functions in infarct healing and ECM maturation after myocardial infarction (MI). In comparison with wild-type (WT) mice, animals with a targeted inactivation of SPARC exhibited a fourfold increase in mortality that resulted from an increased incidence of cardiac rupture and failure after MI. SPARC-null infarcts had a disorganized granulation tissue and immature collagenous ECM. In contrast, adenoviral overexpression of SPARC in WT mice improved the collagen maturation and prevented cardiac dilatation and dysfunction after MI. In cardiac fibroblasts in vitro, reduction of SPARC by short hairpin RNA attenuated transforming growth factor β (TGF)–mediated increase of Smad2 phosphorylation, whereas addition of recombinant SPARC increased Smad2 phosphorylation concordant with increased Smad2 phosphorylation in SPARC-treated mice. Importantly, infusion of TGF-β rescued cardiac rupture in SPARC-null mice but did not significantly alter infarct healing in WT mice. These findings indicate that local production of SPARC is essential for maintenance of the integrity of cardiac ECM after MI. The protective effects of SPARC emphasize the potential therapeutic applications of this protein to prevent cardiac dilatation and dysfunction after MI.

The authors discuss how to stratify risk in patients with chest pain and a normal coronary angiogram.

Objective To develop a clinical risk prediction tool for estimating the cumulative six month risk of death and death or myocardial infarction to facilitate triage and management of patients with acute coronary syndrome.

Design Prospective multinational observational study in which we used multivariable regression to develop a final predictive model, with prospective and external validation.

Setting Ninety four hospitals in 14 countries in Europe, North and South America, Australia, and New Zealand.

Population 43 810 patients (21 688 in derivation set; 22 122 in validation set) presenting with acute coronary syndrome with or without ST segment elevation enrolled in the global registry of acute coronary events (GRACE) study between April 1999 and September 2005.

Main outcome measures Death and myocardial infarction.

Results 1989 patients died in hospital, 1466 died between discharge and six month follow-up, and 2793 sustained a new non-fatal myocardial infarction. Nine factors independently predicted death and the combined end point of death or myocardial infarction in the period from admission to six months after discharge: age, development (or history) of heart failure, peripheral vascular disease, systolic blood pressure, Killip class, initial serum creatinine concentration, elevated initial cardiac markers, cardiac arrest on admission, and ST segment deviation. The simplified model was robust, with prospectively validated C-statistics of 0.81 for predicting death and 0.73 for death or myocardial infarction from admission to six months after discharge. The external applicability of the model was validated in the dataset from GUSTO IIb (global use of strategies to open occluded coronary arteries).

Conclusions This risk prediction tool uses readily identifiable variables to provide robust prediction of the cumulative six month risk of death or myocardial infarction. It is a rapid and widely applicable method for assessing cardiovascular risk to complement clinical assessment and can guide patient triage and management across the spectrum of patients with acute coronary syndrome.

Background

The optimal antithrombotic therapy to accompany tenecteplase in cases of acute ST-segment elevation myocardial infarction (STEMI) remains unclear. We undertook a prespecified pooled analysis of data from the ASSENT-3 and ASSENT-3 PLUS trials.

Methods

We created a combined database of the 2040 and 818 patients who received enoxaparin in ASSENT-3 and ASSENT-3 PLUS, respectively, and compared them with the 2038 and 821 patients who received unfractionated heparin.

Results

The primary efficacy end point, a composite of 30-day mortality, reinfarction or refractory ischemia, was 16.0% with enoxaparin versus 12.2% with unfractionated heparin (p < 0.001); the efficacy plus safety (intracranial hemorrhage [ICH] or major systemic bleeding) end point, 18.0% versus 15.0% (p = 0.003). The 1049 patients urgently revascularized had greater benefit from enoxaparin (15.4% v. 10.1%, p = 0.013), yet the excess in major systemic bleeding evident with enoxaparin (3.3% v. 2.4%, p = 0.01) was largely confined to the 3492 patients without or before revascularization. Although ICH rates in the groups were similar (1.3% v. 0.9%, p = 0.26), an excess of ICH occurred among those administered enoxaparin during the ASSENT-3 PLUS trial (6.7% v. 0.8%, p = 0.013), especially among women over 75 years of age.

Interpretation

These data demonstrated the benefit of enoxaparin used in conjunction with tenecteplase, but raised caution about its prehospital use to treat STEMI in elderly women.

Objective To investigate the relation between access to a cardiac catheterisation laboratory and clinical outcomes in patients admitted to hospital with suspected acute coronary syndrome.

Design Prospective, multinational, observational registry.

Setting Patients enrolled in 106 hospitals in 14 countries between April 1999 and March 2003.

Participants 28 825 patients aged ≥ 18 years.

Main outcome measures Use of percutaneous coronary intervention or coronary artery bypass graft surgery, death, infarction after discharge, stroke, or major bleeding.

Results Most patients (77%) across all regions (United States, Europe, Argentina and Brazil, Australia, New Zealand, and Canada) were admitted to hospitals with catheterisation facilities. As expected, the availability of a catheterisation laboratory was associated with more frequent use of percutaneous coronary intervention (41% v 3.9%, P < 0.001) and coronary artery bypass graft (7.1% v 0.7%, P < 0.001). After adjustment for baseline characteristics, medical history, and geographical region there were no significant differences in the risk of early death between patients in hospitals with or without catheterisation facilities (odds ratio 1.13, 95% confidence interval 0.98 to 1.30, for death in hospital; hazard ratio 1.05, 0.93 to 1.18, for death at 30 days). The risk of death at six months was significantly higher in patients first admitted to hospitals with catheterisation facilities (hazard ratio 1.14, 1.03 to 1.26), as was the risk of bleeding complications in hospital (odds ratio 1.94, 1.57 to 2.39) and stroke (odds ratio 1.53, 1.10 to 2.14).

Conclusions These findings support the current strategy of directing patients with suspected acute coronary syndrome to the nearest hospital with acute care facilities, irrespective of the availability of a catheterisation laboratory, and argue against early routine transfer of these patients to tertiary care hospitals with interventional facilities.

Objective

Recognition of learning curves in medical skill acquisition has enhanced patient safety through improved training techniques. Clinical trials research has not been similarly scrutinized. We retrospectively evaluated VALIANT, a large multinational, pragmatic, randomized, double-blind, multicenter trial, for evidence of research conduct consistent with a performance “learning curve.”

Design

Records provided protocol departure (deviations/violations) and documentation query data. For each site, analysis included patient order (e.g., first, second), recruitment rate, and first enrollment relative to study start date.

Setting

Computerized data from a trial coordinated by an academic research organization collaborating with 10 academic and two commercial research organizations and an industry sponsor.

Interventions

931 sites enrolled 14,703 patients. Departures were restricted to the first year. Exclusions included: patient’s death or loss to follow-up within twelve months and subjects 80th or higher at a site. Departures were assessed for variance with higher patient rank, more frequent recruitment, and later start date.

Methods and Results

12,367 patients at 931 sites were analyzed. Departures were more common for patients enrolled earlier at a site (P<0.0001). For example, compared to the 30th patient the first had 47% more departures. Departures were also more common with slower enrollment and site start closer to the trial start date (P<0.0001). Similar patterns existed for queries.

Conclusions

Research performance improved during VALIANT consistent with a “learning curve.” Although effects were not related to a change in outcome (mortality), learning curves in clinical research may have important safety, ethical, research quality, and economic implications for trial conduct.