Use of enhanced stent visualisation compared to angiography alone to guide percutaneous coronary intervention.

OBJECTIVE: We aimed to assess the use of enhanced stent visualisation (ESV) on outcomes, after PCI with overlapping stents, specifically using CLEARstent technology. BACKGROUND: Stent underexpansion and overlap are both significant risk factors for restenosis and stent thrombosis. Enhanced stent visualisation (e.g. CLEARstent) systems could provide important data to reduce under-expansion and stent overlap. METHODS: This was a cohort study based on this institution's percutaneous coronary intervention (PCI) registry. A total of 2614 patients who had PCI for stable angina or acute coronary syndromes (ACS, excluding cardiogenic shock) with overlapping 2nd generation drug eluting stents (DES) in the same vessel between May 2015 and January 2018 were included in the analysis. Patients were divided into ESV (n = 1354) and no ESV guided intervention (n = 1260). The primary end-point was major adverse cardiovascular events (MACE: target vessel revascularisation, target vessel myocardial infarction and all-cause mortality) recorded at a median follow up of 2.4 years. RESULTS: Groups were comparable for patient characteristics (age, diabetes mellitus, ACS presentation). A significant difference in MACE was observed between patients who underwent ESV-guided PCI (9.5%) compared with patients who underwent Standard PCI (14.4%, p = .018). This difference was mainly driven by reduced rates of target vessel revascularisation and recurrent myocardial infarction. Overall this difference persisted after multivariate Cox analysis (HR 0.86, 95% CI: 0.73-0.98) and propensity matching (HR = 0.88, 95% CI: 0.69-0.99). CONCLUSION: We suggest that routine clinical use of ESV technology during PCI can be useful, and is associated with better medium-term angiographic and clinical outcomes. Further study is required to build on this promising signal.

Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery.

BACKGROUND: Systemic inflammation is pivotal in the pathogenesis of cardiovascular disease. As inflammation can directly cause cardiomyocyte injury, we hypothesised that established systemic inflammation, as reflected by elevated preoperative neutrophil-lymphocyte ratio (NLR) >4, predisposes patients to perioperative myocardial injury. METHODS: We prospectively recruited 1652 patients aged ≥45 yr who underwent non-cardiac surgery in two UK centres. Serum high sensitivity troponin T (hsTnT) concentrations were measured on the first three postoperative days. Clinicians and investigators were blinded to the troponin results. The primary outcome was perioperative myocardial injury, defined as hsTnT≥14 ng L-1 within 3 days after surgery. We assessed whether myocardial injury was associated with preoperative NLR>4, activated reactive oxygen species (ROS) generation in circulating monocytes, or both. Multivariable logistic regression analysis explored associations between age, sex, NLR, Revised Cardiac Risk Index, individual leukocyte subsets, and myocardial injury. Flow cytometric quantification of ROS was done in 21 patients. Data are presented as n (%) or odds ratio (OR) with 95% confidence intervals. RESULTS: Preoperative NLR>4 was present in 239/1652 (14.5%) patients. Myocardial injury occurred in 405/1652 (24.5%) patients and was more common in patients with preoperative NLR>4 [OR: 2.56 (1.92-3.41); P<0.0001]. Myocardial injury was independently associated with lower absolute preoperative lymphocyte count [OR 1.80 (1.50-2.17); P<0.0001] and higher absolute preoperative monocyte count [OR 1.93 (1.12-3.30); P=0.017]. Monocyte ROS generation correlated with NLR (r=0.47; P=0.03). CONCLUSIONS: Preoperative NLR>4 is associated with perioperative myocardial injury, independent of conventional risk factors. Systemic inflammation may contribute to the development of perioperative myocardial injury. CLINICAL TRIAL REGISTRATION: NCT01842568.

Eptifibatide is associated with significant cost savings and similar clinical outcomes to abciximab when used during primary percutaneous coronary intervention for ST-elevation myocardial infarction: An observational cohort study of 3863 patients.

INTRODUCTION: Glycoprotein IIb/IIIa inhibitors are recommended by guidelines in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. There are few studies directly comparing these agents. The aim of this study was to assess whether eptifibatide is a safe and cost-effective alternative to abciximab in the treatment of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. METHODS: This was an observational cohort study of 3863 patients who received a GPIIb/IIIa inhibitor whilst undergoing primary percutaneous coronary intervention from 2007 to 2014. Patients who did not receive a GPIIb/IIIa inhibitor were excluded. Time to first major adverse cardiac event defined as death, non-fatal myocardial infarction, stroke or target vessel revascularization, and total hospital costs were compared between the groups. RESULTS: In all, 1741 patients received abciximab with 2122 receiving eptifibatide. Patients who received eptifibatide had higher rates of previous MI/percutaneous coronary intervention and were more likely to undergo a procedure from the radial route. Unadjusted Kaplan-Meier analysis revealed no significant difference in the 1-year event rates between patients given eptifibatide versus abciximab (p = 0.201). Age-adjusted Cox analysis demonstrated no difference in 1-year outcome between abciximab and eptifibatide (hazard ratio: 0.83; 95% confidence interval: 0.73-1.39), which persisted after multivariate adjustment (hazard ratio: 0.92; 95% confidence interval: 0.79-1.56) including the incorporation of a propensity score (hazard ratio: 0.88; 95% confidence interval: 0.71-1.44). Eptifbatide was associated with significant cost savings being 87% cheaper overall compared to abciximab (on average £650 cheaper per patient and saving approximately £950,000). CONCLUSION: This observational data suggest that eptifibatide is associated with similar outcomes and significant cost savings compared to abciximab when used in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Association between preoperative pulse pressure and perioperative myocardial injury: an international observational cohort study of patients undergoing non-cardiac surgery.

BACKGROUND: The management of elevated blood pressure before non-cardiac surgery remains controversial. Pulse pressure is a stronger predictor of cardiovascular morbidity in the general population than systolic blood pressure alone. We hypothesized that preoperative pulse pressure was associated with perioperative myocardial injury. METHODS: This is a secondary analysis of the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) international cohort study. Participants were aged ≥45 yr and undergoing non-cardiac surgery at 12 hospitals in eight countries. The primary outcome was myocardial injury, defined using serum troponin concentration, within 30 days after surgery. The sample was stratified into quintiles by preoperative pulse pressure. Multivariable logistic regression analysis explored associations between pulse pressure and myocardial injury. We accounted for potential confounding by systolic blood pressure and other co-morbidities known to be associated with postoperative cardiovascular complications. RESULTS: One thousand one hundred and ninety-one of 15 057 (7.9%) patients sustained myocardial injury, which was more frequent amongst patients in the highest two preoperative pulse pressure quintiles {63-75 mm Hg, risk ratio (RR) 1.14 [95% confidence interval (CI): 1.01-1.28], P =0.03; >75 mm Hg, RR 1.15 [95% CI: 1.03-1.29], P =0.02}. After adjustment for systolic blood pressure, preoperative pulse pressure remained the dominant predictor of myocardial injury (63-75 mm Hg, RR 1.20 [95% CI: 1.05-1.37], P <0.01; >75 mm Hg, RR 1.25 [95% CI: 1.06-1.48], P <0.01). Systolic blood pressure >160 mm Hg was not associated with myocardial injury in the absence of pulse pressure >62 mm Hg (RR 0.67 [95% CI: 0.30-1.44], P =0.31). CONCLUSIONS: Preoperative pulse pressure >62 mm Hg was associated with myocardial injury, independent of systolic blood pressure. Elevated pulse pressure may be a useful clinical sign to guide strategies to reduce perioperative myocardial injury.

Preoperative heart rate and myocardial injury after non-cardiac surgery: results of a predefined secondary analysis of the VISION study.

BACKGROUND: Increased baseline heart rate is associated with cardiovascular risk and all-cause mortality in the general population. We hypothesized that elevated preoperative heart rate increases the risk of myocardial injury after non-cardiac surgery (MINS). METHODS: We performed a secondary analysis of a prospective international cohort study of patients aged ≥45 yr undergoing non-cardiac surgery. Preoperative heart rate was defined as the last measurement before induction of anaesthesia. The sample was divided into deciles by heart rate. Multivariable logistic regression models were used to determine relationships between preoperative heart rate and MINS (determined by serum troponin concentration), myocardial infarction (MI), and death within 30 days of surgery. Separate models were used to test the relationship between these outcomes and predefined binary heart rate thresholds. RESULTS: Patients with missing outcomes or heart rate data were excluded from respective analyses. Of 15 087 patients, 1197 (7.9%) sustained MINS, 454 of 16 007 patients (2.8%) sustained MI, and 315 of 16 037 patients (2.0%) died. The highest heart rate decile (>96 beats min(-1)) was independently associated with MINS {odds ratio (OR) 1.48 [1.23-1.77]; P<0.01}, MI (OR 1.71 [1.34-2.18]; P<0.01), and mortality (OR 3.16 [2.45-4.07]; P<0.01). The lowest decile (<60 beats min(-1)) was independently associated with reduced mortality (OR 0.50 [0.29-0.88]; P=0.02), but not MINS or MI. The predefined binary thresholds were also associated with MINS, but more weakly than the highest heart rate decile. CONCLUSIONS: Preoperative heart rate >96 beats min(-1) is associated with MINS, MI, and mortality after non-cardiac surgery. This association persists after accounting for potential confounding factors. CLINICAL TRIAL REGISTRATION: NCT00512109.

Importance of primary percutaneous coronary intervention for reducing mortality in ST-elevation myocardial infarction complicated by out of hospital cardiac arrest.

BACKGROUND: Current recommendations are for primary percutaneous coronary intervention (pPCI) in ST-elevation myocardial infarction (STEMI) complicated by out of hospital cardiac arrest (OHCA). However, information about longer-term outcomes is sparse, particularly among high-risk patients who do not regain consciousness promptly after resuscitation. METHODS AND RESULTS: Of 1836 consecutive patients admitted with STEMI for pPCI between April 2008-October 2011, 132 (7.2%) who had suffered OHCA with recovery of spontaneous circulation (ROSC) form the study population. 101 patients survived to hospital discharge (76.5%) with only one further death in the first year. Prognosis was worse for the 62 patients who were unconscious on arrival and required admission to the intensive therapy unit (ITU), only 54% of whom survived. Every additional minute in the time to ROSC increased the hazard of death by 1.7% while alertness upon ROSC and successful reperfusion in response to pPCI reduced the hazard of death by 90% and 65% respectively. Full neurological recovery was recorded in 85.1% of those who survived to be discharged but in only 30.6% of the 34 survivors who were admitted unconscious and received ITU treatment. Every additional minute in the time to ROSC increased the odds of neurological deficit by 7.0%. CONCLUSIONS: In patients with STEMI who are conscious after OHCA, high rates of survival can be achieved with pPCI, depending in part on the time it takes for ROSC. Prognosis is less good in the subgroup brought to hospital unconscious but even in this high risk group neurologically intact survival can be achieved in about one-third of cases, suggesting the benefit of immediate pPCI in STEMI patients successfully resuscitated after OHCA.

Does a 'direct' transfer protocol reduce time to coronary angiography for patients with non-ST-elevation acute coronary syndromes? A prospective observational study.

OBJECTIVE: National guidelines recommend 'early' coronary angiography within 96 h of presentation for patients with non-ST elevation acute coronary syndromes (NSTE-ACS). Most patients with NSTE-ACS present to their district general hospital (DGH), and await transfer to the regional cardiac centre for angiography. This care model has inherent time delays, and delivery of timely angiography is problematic. The objective of this study was to assess a novel clinical care pathway for the management of NSTE-ACS, known locally as the Heart Attack Centre-Extension or HAC-X, designed to rapidly identify patients with NSTE-ACS while in DGH emergency departments (ED) and facilitate transfer to the regional interventional centre for 'early' coronary angiography. METHODS: This was an observational study of 702 patients divided into two groups; 391 patients treated before the instigation of the HAC-X pathway (Pre-HAC-X), and 311 patients treated via the novel pathway (Post-HAC-X). Our primary study end point was time from ED admission to coronary angiography. We also assessed the length of hospital stay. RESULTS: Median time from ED admission to coronary angiography was 7.2 (IQR 5.1-10.2) days pre-HAC-X compared to 1.0 (IQR 0.7-2.0) day post-HAC-X (p<0.001). Median length of hospital stay was 3.0 (IQR 2.0-6.0) days post-HAC-X v 9.0 (IQR 6.0-14.0) days pre-HAC-X (p<0.0005). This equates to a reduction of six hospital bed days per NSTE-ACS admission. CONCLUSIONS: The introduction of this novel care pathway was associated with significant reductions in time to angiography and in total hospital bed occupancy for patients with NSTE-ACS.

Glycoprotein IIb/IIIa inhibitors use and outcome after percutaneous coronary intervention for non-ST elevation myocardial infarction.

AIMS: We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors on long-term outcomes following percutaneous coronary intervention (PCI) after non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that these agents are associated with improved short-term outcomes. However, many trials were undertaken before the routine use of P2Y12 inhibitors. Recent studies yield conflicting results and registry data have suggested that GP IIb/IIIa inhibitors may cause more bleeding than what trials indicate. METHODS AND RESULTS: This retrospective observational study involves 3047 patients receiving dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all-cause mortality. Major adverse cardiac events (MACE) were a secondary outcome. Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes, multivariate analysis (including propensity scoring) showed no benefit for either survival (P = 0.136) or MACE (P = 0.614). GP IIb/IIIa inhibitor use was associated with an increased risk of major bleeding (P = 0.021). CONCLUSION: Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk. After multivariate adjustment we observed no improvement in MACE or survival and an increased risk of major bleeding.

Case fatality rates for South Asian and Caucasian patients show no difference 2.5 years after percutaneous coronary intervention.

OBJECTIVE: To compare short and medium-term prognosis in South Asian and Caucasian patients undergoing percutaneous coronary intervention (PCI) to determine if there are ethnic differences in case death rates. DESIGN: Retrospective cohort study. SETTING: A cardiology referral centre in east London. PATIENTS: 9771 patients who underwent PCI from October 2003 to December 2007 of whom 7966 (81.5%) were Caucasian and 1805 (18.5%) were South Asian. MAIN OUTCOME MEASURES: In-hospital major adverse cardiac events (MACE; death, myocardial infarction, stroke and target vessel revascularisation), subsequent revascularisation rates (PCI and coronary artery bypass grafting; CABG) and all-cause mortality during a median follow-up of 2.5 years (range 1.5-3.6 years). RESULTS: South Asian patients were younger than Caucasian patients (59.69±0.27 vs 64.69±0.13 years, p<0.0001), and more burdened by cardiovascular risk factors, particularly type II diabetes mellitus (45.9%±1.2% vs 15.7%±0.4%, p<0.0001). The in-hospital rates of MACE were similar for South Asians and Caucasians (3.5% vs 2.8%, p=0.40). South Asians had higher rates of clinically driven PCI for restenosis and subsequent CABG, although Kaplan-Meier estimates of all-cause mortality showed no significant differences; this was regardless of whether PCI was performed post-acute coronary syndrome or as an elective procedure. The adjusted hazard of death for South Asians compared with Caucasians was 1.00 (95% CI 0.81 to 1.23). CONCLUSION: In this large PCI cohort, the in-hospital and longer-term mortality of South Asians appeared no worse than that of Caucasians. South Asians had higher rates of restenosis and CABG during follow-up. Data suggest that the excess coronary mortality for South Asians compared with Caucasians is not explained by differences in case-fatality rates.

Severe orthostatic hypotension in a diabetic patient may not be due to diabetic autonomic neuropathy.

This lesson describes an unusual case of a man who was recently diagnosed with type 1 diabetes and who presented with severe orthostatic hypotension. As his diabetes was recent in onset, well controlled, and he had no other signs of microvascular disease, other causes of orthostatic hypotension were sought. His serum and cerebrospinal fluid were strongly positive for Borrelia burgdorferi IgG, suggesting a diagnosis of Lyme neuroborreliosis. Autonomic instability in Lyme, while rare, has been previously reported.

Modulation of tachyphylaxis to angiotensin II in rabbit isolated aorta by the angiotensin AT1 receptor antagonist, losartan.

In rabbit aortic strip preparations, angiotensin II (AII) concentration-contractile response curves (0.3-100 nM) were highly reproducible. However, tachyphylaxis to the contractile response elicited by AII could be induced by repeated exposure to a supramaximal concentration (10 microM) of the peptide. In contrast, a correspondingly supramaximal concentration of the alpha 1-adrenoceptor agonist, phenylephrine (1 mM), did not cause the tissue to become tachyphylactic to phenylephrine. Furthermore, phenylephrine responses were unaffected in tissues previously made tachyphylactic to AII. When the non-peptide, competitive angiotensin AT1 receptor antagonist, losartan (300 nM), was administered before each supramaximal AII challenge, tachyphylaxis did not subsequently occur. Additionally, in tissues made tachyphylactic to AII, subsequent incubation with losartan (300 nM) reversed the AII tachyphylaxis. Thus, losartan may prevent the loss of contractility by preventing AII from interacting with its receptor in a manner which induces tachyphylaxis. However, since losartan can also completely reverse the loss of contractility, it appears capable of restoring the AT1 receptor to a state which allows subsequently administered AII to fully activate the contractile pathway.