Study of Two Dose Regimens of Ticagrelor Compared With Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention for Stable Coronary Artery Disease.

BACKGROUND: Ticagrelor has superior efficacy to clopidogrel in the management of acute coronary syndromes but has not been assessed in patients undergoing percutaneous coronary intervention for stable coronary artery disease. We compared the pharmacodynamic effects of ticagrelor and clopidogrel in this stable population. METHODS: One hundred eighty aspirin-treated stable coronary artery disease patients, who were planned to undergo elective percutaneous coronary intervention in a single center, were randomized 1:1:1 to either a standard clopidogrel regimen or 1 of 2 regimens of ticagrelor, either 90 mg (T90) or 60 mg twice daily (T60), both with a 180 mg loading dose. Cellular adenosine uptake was assessed, at the time of the procedure and pre- and postdose at 1 month, by adding adenosine 1 µmol/L to aliquots of anticoagulated whole blood and mixing with a stop solution at 0, 15, 30, and 60 seconds, then measuring residual plasma adenosine concentration by high-performance liquid chromatography. Systemic plasma adenosine concentration and platelet reactivity were assessed at the same timepoints. High-sensitivity troponin T was measured pre- and 18 to 24 hours postpercutaneous coronary intervention. RESULTS: One hundred seventy-four patients underwent an invasive procedure, of whom 162 received percutaneous coronary intervention (mean age 65 years, 18% female, 21% with diabetes mellitus). No effect on in vitro adenosine uptake was seen postdose at 1 month for either ticagrelor dose compared with clopidogrel (residual adenosine at 15 seconds, mean±SD: clopidogrel 0.274±0.101 µmol/L; T90 0.278±0.134 µmol/L; T60 0.288±0.149 µmol/L; P=0.37). Similarly, no effect of ticagrelor on in vitro adenosine uptake was seen at other timepoints, nor was plasma adenosine concentration affected (all P>0.1). Both maintenance doses of ticagrelor achieved more potent and consistent platelet inhibition than clopidogrel (VerifyNow P2Y12 reaction units, 1 month, mean±SD: predose, T60: 62±47, T90: 40±38, clopidogrel 181±44; postdose, T60: 34±30, T90: 24±21, clopidogrel 159±57; all P<0.0001 for ticagrelor versus clopidogrel). High platelet reactivity was markedly less with both T60 and T90 compared with clopidogrel (VerifyNow P2Y12 reaction units>208, 1 month postdose: 0%, 0%, and 21%, respectively). Median (interquartile range) high-sensitivity troponin T increased 16.9 (6.5-46.9) ng/L for clopidogrel, 22.4 (5.5-53.8) ng/L for T60, and 17.7 (8.1-43.5) ng/L for T90 (P=0.95). There was a trend toward less dyspnea with T60 versus T90 (7.1% versus 19.0%; P=0.09). CONCLUSIONS: Maintenance therapy with T60 or T90 had no detectable effect on cellular adenosine uptake at 1 month, nor was there any effect on systemic plasma adenosine levels. Both regimens of ticagrelor achieved greater and more consistent platelet inhibition than clopidogrel but did not appear to affect troponin release after percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02327624.

Initial experience of a large, self-expanding, and fully recapturable transcatheter aortic valve: The UK & Ireland Implanters' registry.

OBJECTIVES: The UK & Ireland Implanters' registry is a multicenter registry which reports on real-world experience with novel transcatheter heart valves. BACKGROUND: The 34 mm Evolut R transcatheter aortic valve is a self-expanding and fully recapturable transcatheter aortic valve, designed to treat patients with a large aortic annulus. METHODS: Between January 2017 and April 2018, clinical, procedural and 30-day outcome data were prospectively collected from all patients receiving the 34 mm Evolut R valve across 17 participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2(VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days. RESULTS: A total of 217 patients underwent attempted implant. Mean age was 79.5 ± 8.8 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.2% ± 3.4%. Iliofemoral access was used in 91.2% of patients. Device success was 79.7%. Mean gradient was 7.0 ± 4.6 mmHg and effective orifice area 2.0 ± 0.6 cm2 . Paravalvular regurgitation was more than mild in 7.2%. A new permanent pacemaker was implanted in 15.7%. Early safety was demonstrated in 91.2%. At 30 days, all-cause mortality was 3.2%, stroke 3.7%, and major vascular complication 2.3%. CONCLUSIONS: Real-world experience of the 34 mm Evolut R transcatheter aortic valve demonstrated acceptable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation.

The impact of smoking on mortality after acute ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: a retrospective cohort outcome study at 3 years.

The "smoker's paradox", where smokers have improved survival post-myocardial infarction, was predominantly observed in the thrombolytic era. However, evidence for the smoker's paradox in the current era of PCI therapy is both limited and inconsistent. We aimed to examine the effect of smoking status on survival in unselected ST-elevation myocardial infarction (STEMI) patients managed by primary percutaneous coronary intervention (PCI). Data were collected for all patients with acute STEMI undergoing primary PCI at The South Yorkshire Cardiothoracic Centre, UK over a 5-year period between 2009 and 2014. Differences in survival by smoking status were assessed before and after adjustment for differences in baseline variables using a Kaplan-Meier curve and a Cox regression analysis, respectively. A total of 3133 STEMI patients were included in the study. After adjustment for differences in baseline variables, smoking was associated with a significantly increased mortality (hazard ratio 1.35 (95% CI 1.04-1.74)) compared to never smokers after 3 years. The risk for ex-smokers (hazard ratio 0.99 (0.76-1.28)) was similar to never smokers. There were no significant differences in survival by smoking status at 30 days and 1 year. In this large registry of STEMI patients managed by primary PCI, smokers had a significantly higher 3-year mortality than non-smokers. This study is the first to not only dispel the existence of the smoker's paradox, but to highlight a high-risk subgroup who may warrant tailored secondary prevention treatment, including smoking cessation.

Comparison of P2Y12 inhibitors for mortality and stent thrombosis in patients with acute coronary syndromes: Single center study of 10 793 consecutive 'real-world' patients.

Three oral platelet P2Y12 inhibitors, clopidogrel, prasugrel, and ticagrelor, are available for reducing the risk of cardiovascular death and stent thrombosis in patients with acute coronary syndromes (ACS). We sought to compare the efficacy of these antiplatelet drugs in contemporary practice. Data were collected for 10 793 consecutive ACS patients undergoing coronary angiography at Sheffield, UK (2009-2015). Since prasugrel use was mostly restricted to the STEMI subgroup, clopidogrel and ticagrelor were compared for all ACS patients, and all three agents were compared in the STEMI subgroup. Differences in outcomes were evaluated at 12 months by KM curves and log-rank test after adjustment for independent risk factors. Of 10 793 patients with ACS (36% STEMI), 43% (4653) received clopidogrel, 11% (1223) prasugrel and 46% (4917) ticagrelor, with aspirin for all. In the overall group, ticagrelor was associated with lower all-cause mortality compared with clopidogrel (adjusted hazard ratio (adjHR) 0.82, 95% confidence intervals (CI) 0.71-0.96, p = 0.01). In the STEMI subgroup, both prasugrel and ticagrelor were associated with a lower mortality compared with clopidogrel (prasugrel vs. clopidogrel: adjHR 0.65, CI 0.48-0.89, p = 0.007; ticagrelor vs. clopidogrel: adjHR 0.70, CI 0.61-0.99, p = 0.05). Of the 7595 patients who underwent PCI, 78 (1.0%) had definite stent thrombosis by 12 months. Patients treated with ticagrelor had a lower incidence of definite stent thrombosis compared with clopidogrel (0.6% vs. 1.1%; adjHR 0.51, CI 0.29-0.89, p = 0.03). In the STEMI subgroup, there was no significant difference between the three groups (ticagrelor 1.0%, clopidogrel = 1.5%, prasugrel = 1.6%; p = 0.29). In conclusion, ticagrelor was superior to clopidogrel for reduction in both mortality and stent thrombosis in unselected invasively managed ACS patients. In STEMI patients, both ticagrelor and prasugrel were associated with lower mortality compared with clopidogrel, but there was no significant difference in the incidence of stent thrombosis.

A retrospective cohort study of the association between smoking and mortality after acute ST-segment elevation myocardial infarction.

BACKGROUND: Several studies have shown a 'smoker's paradox', where following an acute myocardial infarction, smokers have a paradoxically lower mortality than non-smokers. To date, no large study has investigated this paradox in unselected patients with acute ST-segment elevation myocardial infarction (STEMI) managed by primary percutaneous coronary intervention (PCI) alone. OBJECTIVES: We aimed to examine the association of smoking status and 1-year mortality in patients who had STEMI managed by primary PCI. METHODS: This retrospective study included all patients admitted with acute STEMI undergoing primary PCI in a single UK centre from January 2009 to April 2012. The survival status for all patients post-STEMI was obtained. Differences in survival by smoking status were assessed using a Kaplan-Meier curve, and after adjustment for age, gender and additional cardiovascular risk factors using a Cox regression analysis. RESULTS: The 1-year mortality for patients with STEMI was 149/1796 (8.3%). There were 846/1796 (47.1%) current smokers, 476/1796 (26.5%) ex-smokers and 417/1796 (23.2%) never smokers. Current smokers were approximately 10 years younger than ex-smokers and never smokers (p=0.001). A multivariate Cox proportional hazards model found no evidence of an association between mortality and smoking status after adjustment; p=0.23. Compared with never smokers, the HR (95% CI) for 1-year mortality for current smokers was 1.47 (0.90 to 2.39) and 1.08 (0.66 to 1.77) for ex-smokers. CONCLUSIONS: In this retrospective cohort study, we found no evidence of an association between mortality and smoking status in patients with acute STEMI treated with PCI, and thus no evidence of a 'smoker's paradox'.

A retrospective cross-sectional study on the association between tobacco smoking and incidence of ST-segment elevation myocardial infarction and cardiovascular risk factors.

BACKGROUND: Cigarette smoking is a well-established risk factor for the development of coronary heart disease. However, the relationship between smoking and acute ST-segment elevation myocardial infarction (STEMI) is less well described. OBJECTIVE: To determine the relative risk of acute STEMI in smokers and ex-smokers, compared with individuals who had never smoked. METHODS: This observational study studied all patients with STEMI undergoing percutaneous coronary intervention (PCI) in South Yorkshire, UK from 1 January 2009 to 6 April 2012. Additional contemporary demographical data for the South Yorkshire population, supplied by the Office for National Statistics, allowed derivation of the incidence rate of STEMI in South Yorkshire-both overall and stratified by smoking status. Incidence rate ratios and population attributable risk (PAR) were calculated to quantify STEMI risk. RESULTS: There were 1715 STEMIs in 1680 patients during the study period. Smoking status was obtained in 96.2% patients. The prevalence of smoking was 47.3% in patients with STEMI and 22.0% in the general population. In patients with STEMI, smokers were ∼10 years younger, mean (SD) 57.2 (11.1) years, than never-smokers, 66.4 (12.1) years, and ex-smokers, 67.9 (11.9) years. The age-standardised incident rate ratio of STEMI was 5.2 (4.5-6.1) for current smokers and 1.1 (1.0-1.3) for ex-smokers, with the reference group being never-smokers for both. Almost 50% of STEMIs were attributable to smoking (PAR=48.3%). CONCLUSION: Cigarette smoking is associated with a fivefold increased risk of STEMI. Smoking cessation reduced this risk to a level similar to never-smokers.

Modelled impact of virtual fractional flow reserve in patients undergoing coronary angiography (VIRTU-4).

BACKGROUND: The practical application of 'virtual' (computed) fractional flow reserve (vFFR) based on invasive coronary angiogram (ICA) images is unknown. The objective of this cohort study was to investigate the potential of vFFR to guide the management of unselected patients undergoing ICA. The hypothesis was that it changes management in >10% of cases. METHODS: vFFR was computed using the Sheffield VIRTUheart system, at five hospitals in the North of England, on 'all-comers' undergoing ICA for non-ST-elevation myocardial infarction acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). The cardiologists' management plan (optimal medical therapy, percutaneous coronary intervention (PCI), coronary artery bypass surgery or 'more information required') and confidence level were recorded after ICA, and again after vFFR disclosure. RESULTS: 517 patients were screened; 320 were recruited: 208 with ACS and 112 with CCS. The median vFFR was 0.82 (0.70-0.91). vFFR disclosure did not change the mean number of significantly stenosed vessels per patient (1.16 (±0.96) visually and 1.18 (±0.92) with vFFR (p=0.79)). A change in intended management following vFFR disclosure occurred in 22% of all patients; in the ACS cohort, there was a 62% increase in the number planned for medical management, and in the CCS cohort, there was a 31% increase in the number planned for PCI. In all patients, vFFR disclosure increased physician confidence from 8 of 10 (7.33-9) to 9 of 10 (8-10) (p<0.001). CONCLUSION: The addition of vFFR to ICA changed intended management strategy in 22% of patients, provided a detailed and specific 'all-in-one' anatomical and physiological assessment of coronary artery disease, and was accompanied by augmentation of the operator's confidence in the treatment strategy.

When Blades broke my heart.

Takotsubo cardiomyopathy (TCM) was first described about 30 years ago. It has been attributed to the sudden catecholamine surge in relation to severe stress, which can cause multi-vessel coronary spasms and myocardial apical ballooning. Football supporters are prone to develop severe stress due to sudden changes in match results. This case presents a football supporter of Sheffield United (the Blades) who was admitted to the hospital with cardiac sounding chest pain following a last minute goal by the opposing team. The necessary investigations were carried out including coronary angiogram and echocardiogram. He was diagnosed with TCM following a left ventricular angiogram demonstrating the typical appearance of the octopus pot.

Left ventricular blood flow kinetic energy is associated with the six-minute walk test and left ventricular remodelling post valvular intervention in aortic stenosis.

BACKGROUND: Left ventricular (LV) kinetic energy (KE) assessment by four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) may offer incremental value over routine assessment in aortic stenosis (AS). The main objective of this study is to investigate the LV KE in patients with AS before and after the valve intervention. In addition, this study aimed to investigate if LV KE offers incremental value for its association to the six-minute walk test (6MWT) or LV remodelling post-intervention. METHODS: We recruited 18 patients with severe AS. All patients underwent transthoracic echocardiography for mean pressure gradient (mPG), CMR including 4D flow and 6MWT. Patients were invited for post-valve intervention follow-up CMR at 3 months and twelve patients returned for follow-up CMR. KE assessment of LV blood flow and the components (direct, delayed, retained and residual) were carried out for all cases. LV KE parameters were normalised to LV end-diastolic volume (LVEDV). RESULTS: For LV blood flow KE assessment, the metrics including time delay (TD) for peak E-wave from base to mid-ventricle (14±48 vs. 2.5±9.75 ms, P=0.04), direct (4.91±5.07 vs. 1.86±1.72 µJ, P=0.01) and delayed (2.46±3.13 vs. 1.38±1.15 µJ, P=0.03) components of LV blood flow demonstrated a significant change between pre- and post-valve intervention. Only LV KEiEDV (r=-0.53, P<0.01), diastolic KEiEDV (r=-0.53, P<0.01) and Ewave KEiEDV (r=-0.38, P=0.04) demonstrated association to the 6MWT. However, Pre-operative LV KEiEDV (r=0.67, P=0.02) demonstrated association to LV remodelling post valve intervention. CONCLUSIONS: LV blood flow KE is associated with 6MWT and LV remodelling in patients with AS. LV KE assessment provides incremental value over routine LV function and pressure gradient (PG) assessment in AS.

Standard and emerging CMR methods for mitral regurgitation quantification.

BACKGROUND: There are several methods to quantify mitral regurgitation (MR) by cardiovascular magnetic resonance (CMR). The interoperability of these methods and their reproducibility remains undetermined. OBJECTIVE: To determine the agreement and reproducibility of different MR quantification methods by CMR across all aetiologies. METHODS: Thirty-five patients with MR were recruited (primary MR = 12, secondary MR = 10 and MVR = 13). Patients underwent CMR, including cines and four-dimensional flow (4D flow). Four methods were evaluated: MRStandard (left ventricular stroke volume - aortic forward flow by phase contrast), MRLVRV (left ventricular stroke volume - right ventricular stroke volume), MRJet (direct jet quantification by 4D flow) and MRMVAV (mitral forward flow by 4D flow - aortic forward flow by 4D flow). For all cases and MR types, 520 MR volumes were recorded by these 4 methods for intra-/inter-observer tests. RESULTS: In primary MR, MRMVAV and MRLVRV were comparable to MRStandard (P > 0.05). MRJet resulted in significantly higher MR volumes when compared to MRStandard (P < 0.05) In secondary MR and MVR cases, all methods were comparable. In intra-observer tests, MRMVAV demonstrated least bias with best limits of agreement (bias = -0.1 ml, -8 ml to 7.8 ml, P = 0.9) and best concordance correlation coefficient (CCC = 0.96, P < 0.01). In inter-observer tests, for primary MR and MVR, least bias and highest CCC were observed for MRMVAV. For secondary MR, bias was lowest for MRJet (-0.1 ml, PNS). CONCLUSION: CMR methods of MR quantification demonstrate agreement in secondary MR and MVR. In primary MR, this was not observed. Across all types of MR, MRMVAV quantification demonstrated the highest reproducibility and consistency.

Effect of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) on infarct size in anterior STEMI: PiCSO in ACS study.

BACKGROUND: The aim of this clinical research was to investigate the effects of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) on infarct size at 5 days after primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: This comparative study was carried out in four UK hospitals. Forty-five patients with anterior STEMI presenting within 12 h of symptom onset received pPCI plus PiCSO (initiated after reperfusion; n = 45) and were compared with a propensity score-matched control cohort from INFUSE-AMI (n = 80). Infarct size (% of LV mass, median [interquartile range]) measured by cardiac magnetic resonance (CMR) at day 5 was significantly lower in the PiCSO group (14.3% [95% CI 9.2-19.4%] vs. 21.2% [95% CI 18.0-24.4%]; p = 0.023). There were no major adverse cardiac events (MACE) related to the PiCSO intervention. CONCLUSIONS: PiCSO, as an adjunct to pPCI, was associated with a lower infarct size at 5 days after anterior STEMI in a propensity score-matched population.

Validation of four-dimensional flow cardiovascular magnetic resonance for aortic stenosis assessment.

The management of patients with aortic stenosis (AS) crucially depends on accurate diagnosis. The main aim of this study were to validate the four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR) methods for AS assessment. Eighteen patients with clinically severe AS were recruited. All patients had pre-valve intervention 6MWT, echocardiography and CMR with 4D flow. Of these, ten patients had a surgical valve replacement, and eight patients had successful transcatheter aortic valve implantation (TAVI). TAVI patients had invasive pressure gradient assessments. A repeat assessment was performed at 3-4 months to assess the remodelling response. The peak pressure gradient by 4D flow was comparable to an invasive pressure gradient (54 ± 26 mmHG vs 50 ± 34 mmHg, P = 0.67). However, Doppler yielded significantly higher pressure gradient compared to invasive assessment (61 ± 32 mmHG vs 50 ± 34 mmHg, P = 0.0002). 6MWT was associated with 4D flow CMR derived pressure gradient (r = -0.45, P = 0.01) and EOA (r = 0.54, P < 0.01) but only with Doppler EOA (r = 0.45, P = 0.01). Left ventricular mass regression was better associated with 4D flow derived pressure gradient change (r = 0.64, P = 0.04). 4D flow CMR offers an alternative method for non-invasive assessment of AS. In addition, 4D flow derived valve metrics have a superior association to prognostically relevant 6MWT and LV mass regression than echocardiography.

Impact of socioeconomic status on survival following ST-elevation myocardial infarction in a universal healthcare system.

BACKGROUND: Lower socioeconomic status (SES) has been associated with worse outcomes after acute myocardial infarction. Data for survival after ST-elevation myocardial infarction (STEMI) by SES in the current era of primary percutaneous coronary intervention (PCI) is more limited. METHODS: Data was collected for all patients with acute STEMI undergoing primary PCI at The South Yorkshire Cardiothoracic Centre, UK between 2009 and 2014. A Cox regression analysis was used to assess differences in survival by SES quartile (using an area-level measure). RESULTS: Of the 3126 STEMI patients, 2655 (84.9%) were first presentations of STEMI. Lower SES groups generally had a less favourable baseline cardiovascular risk factor profile, with higher rates of smoking (p = 0.001), diabetes (p = 0.007) and previous coronary heart disease (p = 0.025). With the exception of beta-blockers, the use of secondary preventative medications was similar between SES quartiles. Adjusting for age and gender, the most disadvantaged SES quartile trended to a non-significant increased mortality at 30 days (hazard ratio 1.35 (0.79-2.33)), 1 year (1.12 (0.76-1.65)), or 3 years (1.22 (0.88-1.70)) compared to the least disadvantaged SES quartile, but this was attenuated by adjusting for additional cardiovascular risk factors and medication use on discharge. CONCLUSIONS: In this large study of unselected STEMI patients managed by primary PCI, we did not find any significant differences in survival by SES at 30 days, 1 year, or 3 years.

Differential Risk of ST-Segment Elevation Myocardial Infarction in Male and Female Smokers.

BACKGROUND: Smoking is a well-documented risk for acute ST-segment elevation myocardial infarction (STEMI). The differential effect between sexes has yet to be quantified. OBJECTIVES: The purpose of this study was to differentiate the effect of smoking on increased risk of STEMI between sexes. METHODS: For this retrospective ecological cohort study, all patients at a U.K. tertiary cardiothoracic center who presented between 2009 and 2014 with acute STEMI were combined with population data to generate incidence rates of STEMI. Age-standardized incidence rate ratios (IRRs) using the Poisson distribution were calculated comparing STEMI rates between smokers and nonsmokers stratified by sex and 3 age groups (18 to 49, 50 to 64, and >65 years). RESULTS: A total of 3,343 patients presented over 5,639,328 person-years. Peak STEMI rate for current smokers was in the 70 to 79 years age range for women (235 per 100,000 patient-years) and 50 to 59 years (425 per 100,000 patient-years) in men. Smoking was associated with a significantly greater increase in STEMI rate for women than men (IRR: 6.62; 95% confidence interval [CI]: 5.98 to 7.31, vs. 4.40; 95% CI: 4.15 to 4.67). The greatest increased risk was in women age 18 to 49 (IRR: 13.22; 95% CI: 10.33 to 16.66, vs. 8.60; 95% CI: 7.70 to 9.59 in men). The greatest risk difference was in the age 50 to 64 years group, with IRR of 9.66 (95% CI: 8.30 to 11.18) in women and 4.47 (95% CI: 4.10 to 4.86) in men. CONCLUSIONS: This study quantifies the differential effect of smoking between sexes, with women having a significantly increased risk of STEMI than men. This information encourages continued efforts to prevent smoking uptake and promote cessation.

Non-Hodgkin's lymphoma causing extrinsic pulmonary artery compression.

Acquired pulmonary stenosis in adults is rare and is usually caused by extrinsic compression from a mediastinal tumour. We present the case of a patient with high grade non-Hodgkin's lymphoma who presented with progressive exertional dyspnoea. Compression of the right pulmonary artery was diagnosed by transthoracic echocardiography.

Early invasive versus conservative treatment in patients with failed fibrinolysis--no late survival benefit: the final analysis of the Middlesbrough Early Revascularisation to Limit Infarction (MERLIN) randomized trial.

BACKGROUND: Early (30 days) and midterm (6 months) clinical outcomes in trials comparing rescue angioplasty (rescue percutaneous coronary intervention [rPCI]) with conservative treatment of failed fibrinolysis complicating ST-segment elevation myocardial infarction have shown variable results. Whether early rPCI confers late (up to 3 years) clinical benefits is not known. METHODS: The MERLIN trial compared rPCI and a conservative strategy in patients with failed fibrinolysis complicating ST-segment elevation myocardial infarction. Three hundred seven patients with electrocardiographic evidence of failure to reperfuse at 60 minutes were included. Patients in cardiogenic shock were excluded. Thirty-day and 1-year results have been reported. Results of 3 years of follow-up are presented. RESULTS: Three-year mortality in the conservative arm and rPCI, respectively, was 16.9% versus 17.6% (P = .9, relative difference [RD] -0.8, 95% CI [-9.3 to 7.8]). Death rates were similar (3.9% vs 3.2%) between 1- and 3-year follow-up, respectively. The incidence of the composite secondary end point of death, reinfarction, stroke, unplanned revascularization, or heart failure was significantly higher in the conservative arm (64.3% vs 49%, P = .01, RD 15.3, 95% CI [4.2-26]). There was no significant difference in the rate of reinfarction (0.7% vs 0.7%) or heart failure (1.3% vs 2.7%) between 1 and 3 years between the conservative and rPCI arms, respectively. The incidence of subsequent unplanned revascularization at 3 years was significantly higher in the conservative arm (33.8% vs 14.4%, P < .01, RD 19.4, 95% CI [10-28.7]), most of which occurred within 1 year; the rates between 1 and 3 years were 3.9% in the conservative arm versus 2% in the rPCI arm. There was a trend toward fewer strokes in the conservative arm at 3 years (conservative arm 2.6% vs rPCI 6.5%, P = .1, RD -3.9%, 95% CI [-9.4 to 0.8]), with similar stroke rates (1.3% vs 1.3%) between 1- and 3-year follow-up. CONCLUSIONS: Rescue angioplasty did not confer a late survival advantage at 3 years. The composite end point occurred less often in the rPCI arm mainly because of fewer unplanned revascularization procedures in the early phase of follow-up. The highest risk of clinical events in patients with failed reperfusion is in the first year, beyond which the rate of clinical events is low.

Pronounced increase in risk of acute ST-segment elevation myocardial infarction in younger smokers.

OBJECTIVES: Previous studies have shown that smokers presented with ST-segment elevation myocardial infarction (STEMI) a decade earlier than non-smokers. However, no account has been made for population smoking trends, an important deficit addressed by this study. METHODS: The combination of admission data on patients with acute STEMI undergoing percutaneous coronary intervention and demographic data supplied by the Office for National Statistics for the South Yorkshire population between 2009-2012 were analysed to generate incidence rates and rate ratios (RR) to quantify the relative risk of STEMI from smoking, overall and by age group. RESULTS: There were 1795 STEMI patients included of which 72.9% were male. 68 patients were excluded as they had no smoking status recorded, leaving 48.5% of the remaining population as current smokers, 27.2% ex-smokers and 24.3% never smokers. Smokers were over-represented with overall smoking prevalence in South Yorkshire calculated at 22.4%. The incidence of STEMI in smokers aged under 50, 50-65 and over 65 years was 59.7, 316.9 and 331.0 per 100 000 patient years at risk compared to 7.0, 60.9 and 106.8 for the combined group of ex- and never smokers. This gave smokers under the age of 50 years an 8.47 (95% CI 6.80 to 10.54) increase in rate compared to non-smokers of the same age, with the 50-65 and over 65 age groups having RRs of 5.20 (95% CI 4.76 to 5.69) and 3.10 (95% CI 2.67 to 3.60), respectively. CONCLUSIONS: Smoking was associated with an eightfold increased risk of acute STEMI in younger smokers, when compared to ex- and never smokers. Further efforts to reduce smoking in the youngest are needed.

A randomized trial of rescue angioplasty versus a conservative approach for failed fibrinolysis in ST-segment elevation myocardial infarction: the Middlesbrough Early Revascularization to Limit INfarction (MERLIN) trial.

OBJECTIVES: We sought to compare emergency coronary angiography with or without rescue percutaneous coronary intervention (PCI) with conservative treatment in patients with failed fibrinolysis complicating ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Most patients with STEMI receive fibrinolytic therapy and aspirin. The management of failed fibrinolysis is unclear. METHODS: A total of 307 patients with STEMI and failed fibrinolysis were randomized to emergency coronary angiography with or without rescue PCI or conservative treatment. RESULTS: Thirty-day all-cause mortality was similar in the rescue and conservative groups (9.8% vs. 11%, p = 0.7, risk difference [RD] 1.2%, 95% confidence interval [CI] -5.8 to 8.3). The composite secondary end point of death/re-infarction/stroke/subsequent revascularization/heart failure occurred less frequently in the rescue group (37.3% vs. 50%, p = 0.02, RD 12.7%, 95% CI 1.6 to 23.5), driven by less subsequent revascularization (6.5% vs. 20.1%, p < 0.01, RD 13.6%, 95% CI 6.2 to 21.4). Re-infarction and clinical heart failure were less common in the rescue group (7.2% vs. 10.4%, p = 0.3, RD 3.2%, 95% CI -3.3 to 9.9; and 24.2% vs. 29.2%, p = 0.3, RD 5.7%, 95% CI -4.3 to 15.6, respectively). Strokes and transfusions were more common in the rescue group (4.6% vs. 0.6%, p = 0.03, RD 3.9%, 95% CI 0.5 to 8.6; and 11.1% vs. 1.3%, p < 0.001, RD 9.8%, 95% CI 4.9 to 19.9, respectively). Left ventricular function at 30 days was the same in the two groups. CONCLUSIONS: Rescue angioplasty did not improve survival by 30 days, but improved event-free survival, almost completely due to a reduction in subsequent revascularization. Rescue angioplasty was associated with more strokes and more transfusions and did not result in preservation of left ventricular systolic function at 30 days.