C. Mussap

Varying Definitions for Periprocedural Myocardial Infarction Alter Event Rates and Prognostic Implications

Background Periprocedural myocardial infarction (PMI) has had several definitions in the last decade, including the Society for Cardiovascular Angiography and Interventions (SCAI) definition, that requires marked biomarker elevations congruent with surgical PMI criteria. Methods and Results The aim of this study was to examine the definition‐based frequencies of PMI and whether they influenced the reported association between PMI and increased rates of late death/ myocardial infarction (MI). We studied 742 patients; 492 (66%) had normal troponin T (TnT) levels and 250 (34%) had elevated, but stable or falling, TnT levels. PMI, using the 2007 and the 2012 universal definition, occurred in 172 (23.2%) and in 99 (13.3%) patients, respectively, whereas 19 (2.6%) met the SCAI PMI definition (P<0.0001). Among patients with PMI using the 2012 definition, occlusion of a side branch ≤1 mm occurred in 48 patients (48.5%) and was the most common angiographic finding for PMI. The rates of death/MI at 2 years in patients with, compared to those without, PMI was 14.7% versus 10.1% (P=0.087) based on the 2007 definition, 16.9% versus 10.3% (P=0.059) based on the 2012 definition, and 29.4% versus 10.7% (P=0.015) based on the SCAI definition. Conclusion In this study, PMI, according to the SCAI definition, was associated with more‐frequent late death/MI, with ≈20% of all patients, who had PMI using the 2007 universal MI definition, not having SCAI‐defined PMI. Categorizing these latter patients as SCAI‐defined no PMI did not alter the rate of death/MI among no‐PMI patients.

Outcomes of Coronary Revascularization (Percutaneous or Bypass) in Patients With Diabetes Mellitus and Multivessel Coronary Disease

Clinical outcomes in patients with diabetes mellitus and multivessel disease (MVD) undergoing coronary revascularization have not been extensively evaluated, we sought to examine outcomes in a diabetic cohort of 195 consecutive patients with MVD characterized by SYNTAX scores (SSs) undergoing nonrandomized revascularization, 102 (52%) by percutaneous intervention (PCI) and 93 (48%) by coronary artery bypass grafting (CABG) at Liverpool Hospital (Sydney, Australia) from June 2006 to March 2010. Clinical outcomes were assessed at a median term of 14 months. The overall median SS was 44, with significantly higher SSs in CABG- than PCI-treated patients (48 vs 39, p <0.0001). There was a similar incidence of all-cause death, nonfatal myocardial infarction and stroke in PCI- and CABG-treated patients (6.1% vs 8.3%, p = 0.383; 12% vs 4.9%, p = 0.152; 3.1% vs 3.5%, p = 0.680 respectively). However, the rates of target vessel revascularization and major adverse coronary and cerebral event were significantly higher in PCI-treated patients than in those undergoing CABG (20% vs 1.2%, p <0.0001; 29% vs 15%, p = 0.034). Despite a much higher SS, patients who underwent PCI achieved comparable outcomes at 1 year to those with diabetes mellitus and a SS ≥ 33 as reported in the SYNTAX trial. In conclusion, in this single-center nonrandomized observational study, coronary revascularization by PCI is associated with increased major adverse coronary and cerebral events at 1-year follow-up, predominantly driven by a high rate of target vessel revascularization. Thus, CABG should remain the revascularization procedure of choice for diabetic patients with MVD and high SSs.

Carotid stenting and bivalirudin with and without vascular closure: 3-year analysis of procedural outcomes.

Objectives: The purpose of this study was to examine the outcome of carotid stenting using bivalirudin and the influence of vascular closure devices (VCD) on the incidence and severity of peri‐procedural hypotension. Background: Bivalirudin, a short‐acting direct thrombin inhibitor, has been shown to be an effective anticoagulant in coronary interventions, with less risk of bleeding compared with heparin. Routine use of VCD has become the standard of care, facilitating patient ambulation after percutaneous carotid and coronary interventions. The combined use of these two therapies (bivalirudin and VCD) may improve outcomes in carotid interventions where prolonged patient immobilization may exacerbate hypotension following stenting. Methods: A total of 514 patients underwent 536 carotid stenting procedures in the 3‐year period from September 2004 to September 2007. All patients received adjunctive bivalirudin, with and without VCD. This cohort was analyzed for peri‐procedural and 30‐day clinical outcomes and length of hospitalization. Results: Thirty‐day stroke and death rate was 1.7%. A total of 83 patients (15.4%) experienced intra‐ or post‐procedural hypotension (systolic BP < 80 mm Hg). There were four (0.7%) major bleeding complications requiring transfusion, and length of stay was delayed more than 24 hr in five patients (0.93%), all of whom were in the manual compression group. Conclusions: This was a negative study, with no significant difference on prolonged hypotensive events in patients with vascular closure device and bivalirudin, compared with those with manual compression and bivalirudin. Vascular closure devices were safe and effective with a low incidence of complications. In carotid artery stenting, bivalirudin is safe with low incidence of major bleeding and acceptable 30‐day adverse event rates (stroke and death).

The autoradiographic distribution of substance P binding sites in guinea-pig vas deferens is altered by capsaicin pretreatment

The distribution of binding sites for [125I]Bolton-Hunter substance P (BHSP) was investigated in vasa deferentia from normal, capsaicin-pretreated and vehicle-pretreated guinea-pigs, using qualitative and quantitative autoradiography. Dense binding of BHSP was seen over the outer longitudinal muscle with less over the inner longitudinal muscle. Very low specific binding occurred to the circular muscle and was absent in the mucosa. Characterization in slide-mounted sections showed that binding was saturable and of high affinity, with equilibrium dissociation constant (KD) 91 +/- 15 pM. BHSP was displaced by substance P greater than neurokinin A greater than neurokinin B, suggesting binding to NK-1 receptors. Capsaicin pretreatment had no effect on the lengthwise distribution of binding sites but significantly altered their relative distribution between the different smooth muscle layers. There was a very marked increase in BHSP binding over the inner longitudinal muscle and the inner part of the circular muscle layer, whereas binding was virtually abolished over the outer longitudinal muscle, compared with vehicle control. Capsaicin-sensitive binding sites over the outer longitudinal muscle may be located presynaptically on capsaicin-susceptible primary afferent sensory neurons. In contrast, the increase in number of binding sites associated with the inner longitudinal muscle may be due to receptor upregulation resulting from loss of sensory innervation, and suggests that these binding sites are postsynaptic.

Management of Acute Coronary Syndromes in Patients with Diabetes: Implications of the FREEDOM Trial

BACKGROUND Diabetes mellitus (DM) is a powerful independent risk factor for multivessel, diffuse coronary artery disease (CAD). The optimal coronary revascularization strategy in DM is not clearly defined, but past trials have suggested an advantage for coronary artery bypass grafting (CABG). Recently, the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial found patients randomized to CABG had lower rates of death and myocardial infarction (MI) compared with those randomized to percutaneous coronary intervention (PCI). OBJECTIVE This article reviews the contemporary management of patients with DM presenting with acute coronary syndromes, particularly ST-elevation MI, in the post-FREEDOM era. METHODS We undertook a comprehensive review of published literature addressing trials in this field performed to address current knowledge both in the pre- and post-FREEDOM era. RESULTS The implications of FREEDOM for patients with acute coronary syndrome are that CABG provides a significant benefit, compared with PCI with drug-eluting stents, to patients with DM and multivessel coronary artery disease; and that patients similar to those enrolled in FREEDOM should receive CABG in preference to PCI. The relevance of FREEDOMs findings to the large proportion of patients who would not meet inclusion criteria-including patients with an acute coronary syndrome undergoing an early or emergent invasive strategy, remains uncertain. DISCUSSION FREEDOMs outcomes have generated uncertainty regarding best practice once thrombolysis in myocardial infarction grade 3 flow is re-established in patients with DM and multivessel disease. Current interventional guidelines recommend optimally treating the culprit artery; however, decisions made at the time of revascularization influence future revascularization strategies, particularly stent choice and resultant P2Y12 receptor antagonist therapy. The preferred method for future revascularization may be questioned if the patients residual coronary stenoses do not, post-PCI, meet the FREEDOM inclusion criteria, or where the left anterior descending artery is the infarct-related artery, and after left anterior descending artery PCI the patient would not receive an internal mammary graft. The management of residual disease and the preferred (further) revascularization strategy needs to be tested in an appropriately powered randomized trial. CONCLUSIONS The optimal revascularization strategy in patients with acute coronary syndrome, diabetes, and multivessel disease, in particular those with ST elevation, is unclear, and not guided by level A (or B) evidence. Currently CABG is favored over PCI, and an individually tailored, collaborative approach, guided by a multidisciplinary heart team, should be employed.

Safety and Efficacy of Same-Day Discharge Following Elective Percutaneous Coronary Intervention, Including Evaluation of Next Day Troponin T Levels

BACKGROUND As patients are increasingly undergoing elective percutaneous coronary intervention (PCI) with same-day discharge (SDD), and as post-PCI troponin T (TnT) elevations are associated with increased rates of death/myocardial infarction (MI) following elective PCI, we examined late outcomes with respect to post-PCI TnT elevations in patients undergoing SDD. METHODS AND RESULTS We studied 303 patients (mean age 62±9years, 89% male) who underwent elective-PCI between October 2007 and September 2012, of whom 149 had SDD and 154 stayed overnight (ON) who were age-and sex-matched. Eligibility for SDD excluded patients with: multi-vessel PCI, proximal LAD lesions, chronic total occlusions, side branch occlusions, or access site complications. Femoral access rates were 72% and 96% among SDD and ON patients respectively. Post-PCI, SDD patients left at 4.40[4.13-5.30]hours, and ON patients left at 23.44[21.50-25.41]hours (p<0.001). Overall 8.45% met the 2012 universal MI definition. No patients were re-hospitalised within 48hours. At 30-days, unplanned cardiac re-hospitalisation rates were 3.4% and 0.7% among SDD and ON patients (p=0.118); the only event was MI in an SDD patient. At 16[9-32] months, rates of death, MI, target vessel revascularisation, stroke, were 1.3%,1.3%,2.7% and 1% respectively; the composite rate was 6%(6.1% SDD; 6% ON; p=0.965). Late death/MI rates among patients with, and without, post-PCI TnT levels≥5xURL were 3.4% and 2.8% respectively (p=0.588). CONCLUSION SDD following elective PCI among low risk patients appears to be safe and ≥5 fold post-PCI TnT elevations did not appear to confer incremental short and long term risk. A larger cohort is required to confirm this observation.

Practical experience with ticagrelor: an Australian and New Zealand perspective

Abstract Objective: Ticagrelor is recommended in local and international guidelines as first-line therapy in combination with aspirin in patients presenting with acute coronary syndromes (ACS). The purpose of this article is to provide practical guidance regarding the use of ticagrelor in this setting. Methods and results: Ticagrelor, a direct-acting, reversible P2Y12 receptor antagonist, has a faster onset, and a more potent and predictable antiplatelet effect compared with clopidogrel. The authors recommend considering the use of ticagrelor in moderate-to-high risk ACS patients treated with an invasive approach and those managed non-invasively who have elevated troponin levels. Consistent with outcomes observed in the PLATO trial overall, ticagrelor was superior to clopidogrel treatment in patients with chronic kidney disease, a history of stroke or transient ischemic attack, the elderly, and patients requiring surgical revascularization. Conclusions: When switching from clopidogrel to ticagrelor, patients established on clopidogrel therapy can be switched directly without loading; patients not loaded with clopidogrel and not taking maintenance dose clopidogrel for at least 5 days should first be loaded with ticagrelor. Guidelines recommend discontinuing ticagrelor 5 days before surgery if antiplatelet effects are not desired and recommencing therapy as soon as safe following surgery. Ticagrelor should be avoided in individuals with a history of intracranial hemorrhage, moderate-to-severe hepatic impairment, high bleeding risk, within 24 hours of thrombolytic therapy, and in those treated with oral anticoagulants. Local, real-world experience suggests low bleeding rates with ticagrelor therapy. Dyspnoea is a common symptom in patients with ACS and is also a side-effect of ticagrelor therapy. Discontinuation of ticagrelor due to dyspnoea has been uncommon in clinical trials. However, local registry data suggest higher discontinuation rates (2–9%) related to dyspnoea in the real-world setting, indicating that clinicians may need to consider other potential causes of dyspnoea before discontinuing ticagrelor.

Stent sizing by coronary computed tomographic angiography: comparison with conventional coronary angiography in an experienced setting.

The goal was to compare stent sizing by coronary computed tomographic angiography (CCTA) with that deployed in an experienced setting based upon conventional coronary angiography (CA).

Binding sites for [125I]-Bolton-Hunter scyliorhinin II in guinea-pig ileum: a radioligand binding, functional and autoradiographic study

Binding of the tachykinin NK-3 receptor-preferring radioligand [125I] -Bolton-Hunter scyliorhinin II (BHSCYII) was investigated in membranes from guinea-pig ileum muscularis externa with myenteric plexus (MMP). Specific binding for BHSCYII was saturable and reversible. Curvilinear Scatchard plots and biphasic competition data indicate binding to two classes of sites (0.8 nM, 8% of sites; 340 nM, 92% of sites). Competition-binding data was ambiguous with the rank order of potency neuropeptide K (NPK) > substance P (SP) ∼ [Sar9,Met(O2)11]-SP ∼ [pGlu6,Pro9]SP(6–11) (septide) > neuropeptide γ (NPγ) > kassinin ∼ physalaemin > neurokinin A (NKA) > SCYII > neurokinin B (NKB). Senktide, eledoisin, [Lys5,MeLeu9,Nle10]-NKA(4–10), CP 96345, RP 67580, MDL 29913, SR 48968 and Gpp[NH]p were ineffective competitors, suggesting a lack of binding to conventional NK-1, NK-2 or NK-3 receptors. Competition curves for 5 agonists could be resolved into two sites, with no competitor showing outstanding affinity. Autoradiographic studies revealed moderate BHSCYII binding to myenteric plexus ganglia, unaffected by co-incubation with CP 96345 or with senktide. These data suggest a component of BHSCYII binding at unusual NPK/SP-preferring sites on ganglia. [Sar9,Met(O2)11]-SP was the most potent contractile agonist of the isolated ileum, followed by SCYII, NPy, senktide and NPγ, with [Lys5,MeLeu9,Nle10]-NKA(4–10) least potent. Contractions elicited by senktide were entirely neurogenic. Responses to SCYII were partly sensitive to tetrodotoxin, atropine and CP 96345, indicative of action at both neuronal receptors and smooth muscle NK-1 receptors. The NK-2 antagonist SR 48968 did not alter responses to SCYII, [Sar9,Met(O2)11]-SP or senktide.

The contribution of cardiovascular mortality to long term outcomes in a relatively young demographic following acute pulmonary embolism: A validation study

BACKGROUND Long-term studies following acute pulmonary embolism (PE) remain limited in the current era. A recent study from our collaborative group, in a contemporary adult population, showed substantially increased cardiovascular mortality following PE. We sought to evaluate the contribution of cardiovascular mortality to long-term outcomes in a different demographic that comprised of a significantly younger PE cohort. METHODS AND RESULTS Demographic and clinical characteristics were retrospectively collected for this cohort, and similar methods and outcome measures were applied as detailed in the original study. We compared a population from a different metropolitan area (LH: Liverpool Hospital) to that from the original study (CRGH: Concord Hospital) over a similar time period. A total of 815 patients comprised this cohort with mean 5.3±3.8year follow-up. There were similar demographics between the two cohorts, though the mean age was significantly younger in LH group (60 vs 68years, p<0.001). Prior history of cardiovascular disease in the LH group was half of that present in the CRGH cohort. The overall mortality was 7.4% per patient-year. Patients with underlying cardiovascular disease when presenting with an acute PE had a 2.3-fold increased risk of death during follow-up compared to those without. Multivariate analysis showed that older age, male gender, malignancy, diabetes, cardiovascular disease and chronic pulmonary disease were independent predictors of post-discharge mortality. CONCLUSIONS Despite our cohort being significantly younger with a lower incidence of pre-existing cardiovascular disease, cardiovascular disease was still a significant contributor to long-term outcomes and an important predictor of mortality following acute PE.