Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing

OBJECTIVES The aim of this study was to provide the spectrum and prevalence of mutations in the 12 Brugada syndrome (BrS)-susceptibility genes discovered to date in a single large cohort of unrelated BrS patients. BACKGROUND BrS is a potentially lethal heritable arrhythmia syndrome diagnosed electrocardiographically by coved-type ST-segment elevation in the right precordial leads (V1 to V3; type 1 Brugada electrocardiographic [ECG] pattern) and the presence of a personal/family history of cardiac events. METHODS Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, comprehensive mutational analysis of BrS1- through BrS12-susceptibility genes was performed in 129 unrelated patients with possible/probable BrS (46 with clinically diagnosed BrS [ECG pattern plus personal/family history of a cardiac event] and 83 with a type 1 BrS ECG pattern only). RESULTS Overall, 27 patients (21%) had a putative pathogenic mutation, absent in 1,400 Caucasian reference alleles, including 21 patients with an SCN5A mutation, 2 with a CACNB2B mutation, and 1 each with a KCNJ8 mutation, a KCND3 mutation, an SCN1Bb mutation, and an HCN4 mutation. The overall mutation yield was 23% in the type 1 BrS ECG pattern-only patients versus 17% in the clinically diagnosed BrS patients and was significantly greater among young men<20 years of age with clinically diagnosed BrS and among patients who had a prolonged PQ interval. CONCLUSIONS We identified putative pathogenic mutations in ∼20% of our BrS cohort, with BrS genes 2 through 12 accounting for <5%. Importantly, the yield was similar between patients with only a type 1 BrS ECG pattern and those with clinically established BrS. The yield approaches 40% for SCN5A-mediated BrS (BrS1) when the PQ interval exceeds 200 ms. Calcium channel-mediated BrS is extremely unlikely in the absence of a short QT interval.

A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na(v)1.5 and K(v)4.3 channel currents.

BACKGROUND Cardiac sodium channel β-subunit mutations have been associated with several inherited cardiac arrhythmia syndromes. OBJECTIVE To identify and characterize variations in SCN1Bb associated with Brugada syndrome (BrS) and sudden infant death syndrome (SIDS). METHODS All known exons and intron borders of the BrS-susceptibility genes were amplified and sequenced in both directions. Wild type (WT) and mutant genes were expressed in TSA201 cells and studied using co-immunoprecipitation and whole-cell patch-clamp techniques. RESULTS Patient 1 was a 44-year-old man with an ajmaline-induced type 1 ST-segment elevation in V1 and V2 supporting the diagnosis of BrS. Patient 2 was a 62-year-old woman displaying a coved-type BrS electrocardiogram who developed cardiac arrest during fever. Patient 3 was a 4-month-old female SIDS case. A R214Q variant was detected in exon 3A of SCN1Bb (Na(v)1B) in all three probands, but not in any other gene previously associated with BrS or SIDS. R214Q was identified in 4 of 807 ethnically-matched healthy controls (0.50%). Co-expression of SCN5A/WT + SCN1Bb/R214Q resulted in peak sodium channel current (I(Na)) 56.5% smaller compared to SCN5A/WT + SCN1Bb/WT (n = 11-12, P<0.05). Co-expression of KCND3/WT + SCN1Bb/R214Q induced a Kv4.3 current (transient outward potassium current, I(to)) 70.6% greater compared with KCND3/WT + SCN1Bb/WT (n = 10-11, P<0.01). Co-immunoprecipitation indicated structural association between Na(v)β1B and Na(v)1.5 and K(v)4.3. CONCLUSION Our results suggest that R214Q variation in SCN1Bb is a functional polymorphism that may serve as a modifier of the substrate responsible for BrS or SIDS phenotypes via a combined loss of function of sodium channel current and gain of function of transient outward potassium current.

Electrocardiographic changes during stress test in a patient with "Brugada syndrome".

We report a 28 year old man with the Brugada syndrome characterised by an electrocardiographic pattern of a right bundle branch block and an ST segment elevation in the right precordial leads as well as syncope. During an exercise test, we observed a normalization of the ST segment in V2+ while in the postexercise phase, the ST segment elevation in the right leads was established. This is the first case reported of the Brugada syndrome in Mexico, with spontaneous changes on the EKG masked during exercise and apparent during postexercise phase.

Neoatherosclerosis as reason for stent failures beyond 5 years after drug-eluting stent implantation

A 69-year-old male (case 1) was admitted due to acute non-ST-segment elevation myocardial infarction (NSTEMI). Eight years earlier, he had previously undergone treatment with a sirolimus-eluting stent (SES). Four years after stent implantation, a follow-up angiography was obtained showing a patent stent without obstructive in-stent restenosis (Panel A). Angiograms obtained at the time of NSTEMI (Panel B) disclosed subtotal occlusion in the middle of the SES (arrowheads). Optical coherence tomography revealed a signal intense luminal layer with an underlying, highly attenuating, diffusely demarcated area, suggestive for an instent fibroatheroma (Panel D) with a minimal cap thickness of 80 µm. Accordingly, ischaemia was caused by the high degree of stenosis (Panel E). Similarly, a 59-year-old male (case 2) was admitted due to STEMI. Nine years before, he had received a paclitaxel-eluting stent (PES). Five years after stent implantation, a follow-up angiography revealed a patent stent (Panel F). Angiograms obtained at the time of STEMI (Panel G) disclosed total occlusion in the proximal of PES (arrowheads). Optical coherence tomography showed a rupture of thin cap fibroatheroma within the stented segment (Panel I). The thin cap fibroatheroma caused a severe stenosis with superimposed thrombus (Panel J). Neoatherosclerosis has been recently described as particular disease entity being responsible for very late stent failures. These two cases illustrate that the presence of a favourable long-term angiographic result years after DES implantation does not exclude a future neoatherosclerosis-related event (restenosis or stent thrombosis). Large observational and long-term intracoronary imaging studies are required to fully elucidate the dynamics and clinical relevance of neoatherosclerosis.

Death by patent foramen ovale in a soccer player

A 34-year-old male patient was referred for primary percutaneous coronary intervention for ST-segment elevation myocardial infarction with cardiogenic shock and was found to have embolic left coronary artery occlusion and subsegmental pulmonary artery emboli as a consequence of venous thrombosis to trauma to the thigh in the presence of a patent foramen ovale.

Sex differences in acute coronary syndrome symptom presentation in young patients

IMPORTANCE Little is known about whether sex differences in acute coronary syndrome (ACS) presentation exist in young patients and what factors determine absence of chest pain in ACS presentation. OBJECTIVES To evaluate sex differences in ACS presentation and to estimate associations between sex, sociodemographic, gender identity, psychosocial and clinical factors, markers of coronary disease severity, and absence of chest pain in young patients with ACS. DESIGN, SETTING, PARTICIPANTS We conducted a prospective cohort study of 1015 patients (30% women) 55 years or younger, hospitalized for ACS and enrolled in the GENESIS PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome) study (January 2009-September 2012). MAIN OUTCOMES AND MEASURES The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered during hospitalization. RESULTS The median age for both sexes was 49 years. Women were more likely to have non-ST-segment elevation myocardial infarction (37.5 vs 30.7; P = .03) and present without chest pain compared with men (19.0% vs 13.7%; P = .03). Patients without chest pain reported fewer symptoms overall and no discernable pattern of non-chest pain symptoms was found. In the multivariate model, being a woman (odds ratio [OR], 1.95 [95% CI, 1.23-3.11]; P = .005) and tachycardia (OR, 2.07 [95% CI, 1.20-3.56]; P = .009) were independently associated with ACS presentation without chest pain. Patients without chest pain did not differ significantly from those with chest pain in terms of ACS type, troponin level elevation, or coronary stenosis. CONCLUSIONS AND RELEVANCE Chest pain was the most common ACS symptom in both sexes. Although women were more likely to present without chest pain than men, absence of chest pain was not associated with markers of coronary disease severity. Strategies that explicitly incorporate assessment of common non-chest pain symptoms need to be evaluated.

Biolimus-Eluting Stents With Biodegradable Polymer Versus Bare-Metal Stents in Acute Myocardial Infarction: Two-Year Clinical Results of the COMFORTABLE AMI Trial

BACKGROUND This study sought to determine whether the 1-year differences in major adverse cardiac event between a stent eluting biolimus from a biodegradable polymer and bare-metal stents (BMSs) in the COMFORTABLE trial (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) were sustained during long-term follow-up. METHODS AND RESULTS A total of 1061 patients were randomly assigned to biolimus-eluting stent (BES) and BMS at 11 centers, and follow-up rates at 2 years were 96.3%. A subgroup of 103 patients underwent angiography at 13 months. At 2 years, differences in the primary end point of cardiac death, target-vessel myocardial infarction, and target lesion revascularization continued to diverge in favor of BES-treated patients (5.8%) compared with BMS-treated patients (11.9%; hazard ratio=0.48; 95% confidence interval, 0.31-0.72; P<0.001) with a significant risk reduction during the second year of follow-up (hazard ratio 1-2 years=0.45; 95% confidence interval, 0.20-1.00; P=0.049). Differences in the primary end point were driven by a reduction in target lesion revascularization (3.1% versus 8.2%; P<0.001) and target-vessel reinfarction (1.3% versus 3.4%; P=0.023). The composite of death, any reinfarction and revascularization (14.5% versus 19.3%; P=0.03), and cardiac death or target-vessel myocardial infarction (4.2% versus 7.2%; P=0.036) were less frequent among BES-treated patients compared with BMS-treated patients. The 13-month angiographic in-stent percent diameter stenosis amounted to 12.0±7.2 in BES- and 39.6±25.2 in BMS-treated lesions (P<0.001). CONCLUSIONS Among patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, BES continued to improve cardiovascular events compared with BMS beyond 1 year.

Function of Natural Internal Mammary-to-Coronary Artery Bypasses and Its Effect on Myocardial Ischemia.

BACKGROUND The function of naturally existing internal mammary (IMA)-to-coronary artery bypasses and their quantitative effect on myocardial ischemia are unknown. METHODS AND RESULTS The primary end point of this study was collateral flow index (CFI) obtained during two 1-minute coronary artery balloon occlusions, the first with and the second without simultaneous distal IMA occlusion. The secondary study end point was the quantitatively determined intracoronary ECG ST-segment elevation. CFI is the ratio of simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. A total of 180 pairs of CFI measurements were performed among 120 patients. With and without IMA occlusion, CFI was 0.110±0.074 and 0.096±0.072, respectively (P<0.0001). The difference of CFI obtained in the presence minus CFI obtained in the absence of IMA occlusion was highest and most consistently positive during left IMA with left anterior descending artery occlusion and during right IMA with right coronary artery occlusion (ipsilateral occlusions): 0.033±0.044 and 0.025±0.027, respectively. This CFI difference was absent during right IMA with left anterior descending artery occlusion and during left IMA with right coronary artery occlusion (contralateral occlusions): -0.007±0.034 and 0.001±0.023, respectively (P=0.0002 versus ipsilateral occlusions). The respective CFI differences during either IMA with left circumflex artery occlusion were inconsistently positive. Intracoronary ECG ST-segment elevations were significantly reduced during ipsilateral IMA occlusions but not during contralateral or left circumflex artery occlusions. CONCLUSION There is a functional, ischemia-reducing extracardiac coronary artery supply via ipsilateral but not via contralateral natural IMA bypasses. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCTO1676207.

Effect of high-intensity statin therapy on atherosclerosis in non-infarct-related coronary arteries (IBIS-4): a serial intravascular ultrasonography study

AIM The effect of long-term high-intensity statin therapy on coronary atherosclerosis among patients with acute ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this study was to quantify the impact of high-intensity statin therapy on plaque burden, composition, and phenotype in non-infarct-related arteries of STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS Between September 2009 and January 2011, 103 STEMI patients underwent intravascular ultrasonography (IVUS) and radiofrequency ultrasonography (RF-IVUS) of the two non-infarct-related epicardial coronary arteries (non-IRA) after successful primary PCI. Patients were treated with high-intensity rosuvastatin (40 mg/day) throughout 13 months and serial intracoronary imaging with the analysis of matched segments was available for 82 patients with 146 non-IRA. The primary IVUS end-point was the change in per cent atheroma volume (PAV). After 13 months, low-density lipoprotein cholesterol (LDL-C) had decreased from a median of 3.29 to 1.89 mmol/L (P < 0.001), and high-density lipoprotein cholesterol (HDL-C) levels had increased from 1.10 to 1.20 mmol/L (P < 0.001). PAV of the non-IRA decreased by -0.9% (95% CI: -1.56 to -0.25, P = 0.007). Patients with regression in at least one non-IRA were more common (74%) than those without (26%). Per cent necrotic core remained unchanged (-0.05%, 95% CI: -1.05 to 0.96%, P = 0.93) as did the number of RF-IVUS defined thin cap fibroatheromas (124 vs. 116, P = 0.15). CONCLUSION High-intensity rosuvastatin therapy over 13 months is associated with regression of coronary atherosclerosis in non-infarct-related arteries without changes in RF-IVUS defined necrotic core or plaque phenotype among STEMI patients.

Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial

BACKGROUND Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent. METHODS We did a randomised, single-blind, non-inferiority trial with minimum exclusion criteria at nine hospitals in Switzerland. We randomly assigned (1:1) patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention to treatment with biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Randomisation was via a central web-based system and stratified by centre and presence of ST segment elevation myocardial infarction. Patients and outcome assessors were masked to treatment allocation, but treating physicians were not. The primary endpoint, target lesion failure, was a composite of cardiac death, target vessel myocardial infarction, and clinically-indicated target lesion revascularisation at 12 months. A margin of 3·5% was defined for non-inferiority of the biodegradable polymer sirolimus-eluting stent compared with the durable polymer everolimus-eluting stent. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01443104. FINDINGS Between Feb 24, 2012, and May 22, 2013, we randomly assigned 2119 patients with 3139 lesions to treatment with sirolimus-eluting stents (1063 patients, 1594 lesions) or everolimus-eluting stents (1056 patients, 1545 lesions). 407 (19%) patients presented with ST-segment elevation myocardial infarction. Target lesion failure with biodegradable polymer sirolimus-eluting stents (69 cases; 6·5%) was non-inferior to durable polymer everolimus-eluting stents (70 cases; 6·6%) at 12 months (absolute risk difference -0·14%, upper limit of one-sided 95% CI 1·97%, p for non-inferiority <0·0004). No significant differences were noted in rates of definite stent thrombosis (9 [0·9%] vs 4 [0·4%], rate ratio [RR] 2·26, 95% CI 0·70-7·33, p=0·16). In pre-specified stratified analyses of the primary endpoint, biodegradable polymer sirolimus-eluting stents were associated with improved outcome compared with durable polymer everolimus-eluting stents in the subgroup of patients with ST-segment elevation myocardial infarction (7 [3·3%] vs 17 [8·7%], RR 0·38, 95% CI 0·16-0·91, p=0·024, p for interaction=0·014). INTERPRETATION In a patient population with minimum exclusion criteria and high adherence to dual antiplatelet therapy, biodegradable polymer sirolimus-eluting stents were non-inferior to durable polymer everolimus-eluting stents for the combined safety and efficacy outcome target lesion failure at 12 months. The noted benefit in the subgroup of patients with ST-segment elevation myocardial infarction needs further study. FUNDING Clinical Trials Unit, University of Bern, and Biotronik, Bülach, Switzerland.

Invasive coronary treatment strategies for out-of-hospital cardiac arrest: a consensus statement from the European association for percutaneous cardiovascular interventions (EAPCI)/stent for life (SFL) groups

Due to significant improvement in the pre-hospital treatment of patients with out-of-hospital cardiac arrest (OHCA), an increasing number of initially resuscitated patients are being admitted to hospitals. Because of the limited data available and lack of clear guideline recommendations, experts from the EAPCI and "Stent for Life" (SFL) groups reviewed existing literature and provided practical guidelines on selection of patients for immediate coronary angiography (CAG), PCI strategy, concomitant antiplatelet/anticoagulation treatment, haemodynamic support and use of therapeutic hypothermia. Conscious survivors of OHCA with suspected acute coronary syndrome (ACS) should be treated according to recommendations for ST-segment elevation myocardial infarction (STEMI) and high-risk non-ST-segment elevation -ACS (NSTE-ACS) without OHCA and should undergo immediate (if STEMI) or rapid (less than two hours if NSTE-ACS) coronary invasive strategy. Comatose survivors of OHCA with ECG criteria for STEMI on the post-resuscitation ECG should be admitted directly to the catheterisation laboratory. For patients without STEMI ECG criteria, a short "emergency department or intensive care unit stop" is advised to exclude non-coronary causes. In the absence of an obvious non-coronary cause, CAG should be performed as soon as possible (less than two hours), in particular in haemodynamically unstable patients. Immediate PCI should be mainly directed towards the culprit lesion if identified. Interventional cardiologists should become an essential part of the "survival chain" for patients with OHCA. There is a need to centralise the care of patients with OHCA to experienced centres.

4-year clinical outcomes and predictors of repeat revascularization in patients treated with new-generation drug-eluting stents: a report from the RESOLUTE All-Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention)

OBJECTIVES The aim of the study was to investigate 4-year outcomes and predictors of repeat revascularization in patients treated with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Minneapolis, Minnesota) and XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Abbott Park, Illinois) in the RESOLUTE (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) All-Comers trial. BACKGROUND Data on long-term outcomes of new-generation drug-eluting stents are limited, and predictors of repeat revascularization due to restenosis and/or progression of disease are largely unknown. METHODS Patients were randomly assigned to treatment with the R-ZES (n = 1,140) or the EES (n = 1,152). We assessed pre-specified safety and efficacy outcomes at 4 years including target lesion failure and stent thrombosis. Predictors of revascularization at 4 years were identified by Cox regression analysis. RESULTS At 4 years, the rates of target lesion failure (15.2% vs. 14.6%, p = 0.68), cardiac death (5.4% vs. 4.7%, p = 0.44), and target vessel myocardial infarction (5.3% vs. 5.4%, p = 1.00), clinically-indicated target lesion revascularization (TLR) (7.0% vs. 6.5%, p = 0.62), and definite/probable stent thrombosis (2.3% vs. 1.6%, p = 0.23) were similar with the R-ZES and EES. Independent predictors of TLR were age, insulin-treated diabetes, SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score, treatment of saphenous vein grafts, ostial lesions, and in-stent restenosis. Independent predictors of any revascularization were age, diabetes, previous percutaneous coronary intervention, absence of ST-segment elevation myocardial infarction, smaller reference vessel diameter, SYNTAX score, and treatment of left anterior descending, right coronary artery, saphenous vein grafts, ostial lesions, or in-stent restenosis. CONCLUSIONS R-ZES and EES demonstrated similar safety and efficacy throughout 4 years. TLR represented less than one-half of all repeat revascularization procedures. Patient- and lesion-related factors predicting the risk of TLR and any revascularization showed considerable overlap. (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention [RESOLUTE-AC]; NCT00617084).

Sex-related differences in access to care among patients with premature acute coronary syndrome

BACKGROUND Access to care may be implicated in disparities between men and women in death after acute coronary syndrome, especially among younger adults. We aimed to assess sex-related differences in access to care among patients with premature acute coronary syndrome and to identify clinical and gender-related determinants of access to care. METHODS We studied 1123 patients (18-55 yr) admitted to hospital for acute coronary syndrome and enrolled in the GENESIS-PRAXY cohort study. Outcome measures were door-to-electrocardiography, door-to-needle and door-to-balloon times, as well as proportions of patients undergoing cardiac catheterization, reperfusion or nonprimary percutaneous coronary intervention. We performed univariable and multivariable logistic regression analyses to identify clinical and gender-related determinants of timely procedures and use of invasive procedures. RESULTS Women were less likely than men to receive care within benchmark times for electrocardiography (≤ 10 min: 29% v. 38%, p = 0.02) or fibrinolysis (≤ 30 min: 32% v. 57%, p = 0.01). Women with ST-segment elevation myocardial infarction (MI) were less likely than men to undergo reperfusion therapy (primary percutaneous coronary intervention or fibrinolysis) (83% v. 91%, p = 0.01), and women with non-ST-segment elevation MI or unstable angina were less likely to undergo nonprimary percutaneous coronary intervention (48% v. 66%, p < 0.001). Clinical determinants of poorer access to care included anxiety, increased number of risk factors and absence of chest pain. Gender-related determinants included feminine traits of personality and responsibility for housework. INTERPRETATION Among younger adults with acute coronary syndrome, women and men had different access to care. Moreover, fewer than half of men and women with ST-segment elevation MI received timely primary coronary intervention. Our results also highlight that men and women with no chest pain and those with anxiety, several traditional risk factors and feminine personality traits were at particularly increased risk of poorer access to care.

Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial.

BACKGROUND It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. METHODS We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. FINDINGS We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). INTERPRETATION In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. FUNDING The Medicines Company and Terumo.

Circulating FABP4 Is a Prognostic Biomarker in Patients With Acute Coronary Syndrome but Not in Asymptomatic Individuals.

OBJECTIVE Blood-borne biomarkers reflecting atherosclerotic plaque burden have great potential to improve clinical management of atherosclerotic coronary artery disease and acute coronary syndrome (ACS). APPROACH AND RESULTS Using data integration from gene expression profiling of coronary thrombi versus peripheral blood mononuclear cells and proteomic analysis of atherosclerotic plaque-derived secretomes versus healthy tissue secretomes, we identified fatty acid-binding protein 4 (FABP4) as a biomarker candidate for coronary artery disease. Its diagnostic and prognostic performance was validated in 3 different clinical settings: (1) in a cross-sectional cohort of patients with stable coronary artery disease, ACS, and healthy individuals (n=820), (2) in a nested case-control cohort of patients with ACS with 30-day follow-up (n=200), and (3) in a population-based nested case-control cohort of asymptomatic individuals with 5-year follow-up (n=414). Circulating FABP4 was marginally higher in patients with ST-segment-elevation myocardial infarction (24.9 ng/mL) compared with controls (23.4 ng/mL; P=0.01). However, elevated FABP4 was associated with adverse secondary cerebrovascular or cardiovascular events during 30-day follow-up after index ACS, independent of age, sex, renal function, and body mass index (odds ratio, 1.7; 95% confidence interval, 1.1-2.5; P=0.02). Circulating FABP4 predicted adverse events with similar prognostic performance as the GRACE in-hospital risk score or N-terminal pro-brain natriuretic peptide. Finally, no significant difference between baseline FABP4 was found in asymptomatic individuals with or without coronary events during 5-year follow-up. CONCLUSIONS Circulating FABP4 may prove useful as a prognostic biomarker in risk stratification of patients with ACS.