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.

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.

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.

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.

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.

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.

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'.

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.

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.

Percutaneous brachial artery access for coronary artery procedures: Feasible and safe in the current era.

BACKGROUND: Percutaneous vascular access for coronary intervention is currently achieved predominately via the radial route, the femoral route acting as a backup. Percutaneous trans-brachial access is no longer commonly used due to concerns about vascular complications. This study aimed to investigate the safety and feasibility of percutaneous brachial access when femoral and radial access was not possible. METHODS: This is a retrospective data analysis of patients who attended a single tertiary cardiology centre in the UK between 2005 and 2014 and had a coronary intervention (coronary angiogram or PCI) via the brachial route. The primary endpoints were procedural success and the occurrence of vascular complications. RESULTS: During the study period 26602 patients had a procedure (15655 underwent PCI and 10947 diagnostic angiography). Of these, 117 (0.44% of total) had their procedure performed via the brachial route. The procedure was successful in 96% (112/117) of cases. 13 (11%) patients experienced post procedural complications, of which 2 (1.7%) were serious. There were no deaths. CONCLUSION: Percutaneous trans-brachial arterial access is feasible with a high success rate and without evidence of high complication rate in a rare group of patients in whom femoral or sometimes radial attempts have failed.

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.

Smoking is associated with adverse clinical outcomes in patients undergoing revascularization with PCI or CABG: the SYNTAX trial at 5-year follow-up.

BACKGROUND: Cigarette smoking is a well-known risk factor for development of coronary artery disease (CAD). However, some studies have suggested a "smoker's paradox," meaning neutral or favorable outcomes in smokers who have developed CAD, especially myocardial infarction (MI). OBJECTIVES: The study aimed to examine the association of smoking status with clinical outcomes in the randomized controlled SYNTAX (SYNergy Between PCI With TAXUS and Cardiac Surgery) trial at 5-year follow-up. METHODS: Detailed smoking history was collected at baseline, 6-month, 1-year, 3-year, and 5-year follow-up. The composite endpoints included death/MI/stroke (primary endpoint) plus major adverse cardiac and cerebrovascular events (MACCE) (combination of death/MI/stroke and target lesion revascularization) according to patient smoking status. The comparison of 5-year clinical outcomes between the groups according to smoking status was performed with Cox regression using smoking status at baseline or smoking as a time-dependent covariate. RESULTS: A sizeable proportion (n = 322, 17.9%) of patients had changing smoking status during 5-year follow-up. One in 5 patients with complex CAD was smoking at baseline. However, 60% stopped after revascularization while others continued to smoke. Smokers had worse clinical outcomes due to a higher incidence of recurrent MI in both revascularization arms. Smoking was an independent predictor of the composite endpoint of death/MI/stroke (hazard ratio [HR]: 1.8; 95% confidence interval [CI]: 1.3 to 2.5; p = 0.001) and MACCE (HR: 1.4; 95% CI: 1.1 to 1.7; p = 0.02). CONCLUSIONS: Smoking is associated with poor clinical outcomes after revascularization in patients with complex CAD. This places further emphasis on efforts at smoking cessation to improve revascularization benefits. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972).

Incidence and predictors of stent thrombosis: a single-centre study of 5,833 consecutive patients undergoing coronary artery stenting.

AIMS: Stent thrombosis (ST) is an infrequent but potentially fatal complication of PCI. The reported incidence of ST varies from 0-5%, due to differences in definition of ST, inclusion/exclusion criteria, and the type of stent and dual antiplatelet therapy used. We aimed to examine the incidence of ST and associated risk factors in this "real-world, all-comers" study. METHODS AND RESULTS: All patients undergoing PCI at South Yorkshire Cardiothoracic Centre (UK) between 2007 and 2010 were included, with no exclusion criteria. ST cases were divided into definite and probable ST, according to the ARC criteria. Univariate predictors were identified using Student's t-test and chi-square test, and entered into a Cox proportional hazards model to identify factors independently associated with ST. For 5,833 PCI patients followed up for two years, the incidence of definite and probable ST together was 1.9% (n=109); of these 73% were early, 11% late and 16% very late ST. Cardiogenic shock, ST-elevation myocardial infarction (STEMI), lack of dual antiplatelet treatment, diabetes mellitus, stent length and stent diameter were the independent predictors of ST. CONCLUSIONS: The incidence of definite/probable ST in this "real-world" registry is 1.9%. Cardiogenic shock, often excluded in clinical trials, is the strongest independent predictor of ST.

Symptomatic hypertrophic obstructive cardiomyopathy: semi-supine bicycle ergometry as a useful provocative manoeuvre to elicit latent gradient.

We report the case of a 58-year-old Caucasian woman with severe symptoms attributable to hypertrophic obstructive cardiomyopathy (HOCM). When supine there was no significant left ventricular outflow tract (LVOT) gradient on echocardiography or cardiac catheter measurements-despite provocation with supine leg exercise and right ventricular pacing. However, semi-supine bicycle exercise induced a marked increase in the LVOT gradient, which helped guide successful percutaneous alcohol septal ablation. This case report demonstrates the usefulness of bicycle exercise echocardiography in diagnosing HOCM with latent LVOT obstruction.