In Hospital Outcomes for High-Risk Percutaneous Coronary Intervention (PCI) in Patients Referred From a Rural Centre to Metropolitan Sites.

BACKGROUND: Cardiac Society of Australia and New Zealand (CSANZ) guidelines recommend elective high-risk percutaneous coronary intervention (PCI) is not performed in sites greater than 1 hour from cardiac surgery. METHODS: In hospital outcomes for all patients from Orange Health Service (OHS) from January 2017 to January 2020 who were transferred electively to tertiary centres in Sydney for high risk PCI were examined. RESULTS: One hundred and fourteen (114) patients were identified, with 1,259 PCIs performed at OHS over the same period without transfer. The mean age of these 114 patients was 71 years, with 74.6% male. Receiving hospitals were Royal Prince Alfred Hospital, Sydney, NSW (66.7%), Concord Repatriation General Hospital, Concord, NSW (19.3%) and Strathfield Private Hospital, Strathfield, NSW (14%). The definition of high risk and indication for transfer included at least one of: moderate or greater calcification of the target lesion or proximal segment (34%), single or multiple target lesions that in aggregate jeopardised over 50% of remaining viable myocardium (27%), degenerated saphenous vein grafts (14.8%), chronic total occlusions (7.0%) and severe left ventricular (LV) impairment (3.9%). American Heart Society/American College of Cardiology (AHA/ACC) lesion types were A (1%), B1 (4.2%), B2 (40.2%), and C (54.6%). PCI was performed via the femoral route in 96.2%. The mean procedure duration was 72 minutes, mean combined fluoroscopy time was 19 minutes and mean radiation dose as defined by Reference Air Kerma was 1,630 mGy. Complications occurred in 13 patients and were: acute vessel dissection requiring stenting (4), perforation (2), acute vessel closure (4), puncture site related (1), and life-threatening arrhythmia (2). There were no cases of emergent coronary artery bypass graft (CABG) or death. CONCLUSION: This contemporary cohort of high-risk patients transferred electively from a regional PCI centre to a tertiary cardiac unit underwent lengthy PCI procedures, with high radiation doses, and a modest rate of peri-procedural complications, but had otherwise excellent procedural and clinical outcomes.

Long-Term Outcomes Following Rapid Access Chest Pain Clinic Assessment: First Australian Data.

Australian guidelines recommend prompt evaluation of patients presenting to emergency departments with chest pain, found to be low risk for acute coronary syndromes, and cardiologist-led Rapid Access Chest Pain Clinics (RACPC) have been proposed as a model to provide such care. Initial Australian experience of RACPCs suggests excellent short-term outcomes, and that they are cost-beneficial, though little data exists examining longer-term outcomes. The present study therefore examines such longer-term outcomes to beyond 5 years following presentation to an RACPC in an Australian tertiary metropolitan centre.

Aspirin hypersensitivity in patients with coronary artery disease: linking pathophysiology to clinical practice.

Dual antiplatelet therapy, consisting of aspirin and a P2Y12 receptor antagonist, has been the cornerstone of management in those undergoing percutaneous coronary intervention, reducing stent thromboses and cardiovascular events. Given the pivotal role of aspirin in cardiovascular disease management, patients with aspirin hypersensitivity pose complex clinical challenges. Allergy to aspirin is reported in 1.5-2.6% of patients presenting with cardiac disease. Identification of the subtype of aspirin hypersensitivity will determine suitability for aspirin desensitization, dictate choice of desensitization protocol and inform risk management. Aspirin desensitization is an effective and viable clinical strategy, although it remains underutilised in clinical practice. Collaboration between cardiologists and immunologists should be strongly encouraged to facilitate optimal management of such patients. This review describes the complexity of managing patients with aspirin hypersensitivity in cardiac disease, the indications and risks of aspirin desensitization, and the approach to management of the minority of patients who are unsuitable for desensitization.

A Rapid Access Chest Pain Clinic (RACPC): Initial Australian Experience.

BACKGROUND: Chest pain is the second most common presenting symptom to emergency departments (ED) in Australia, although up to 85% of these patients do not have an acute coronary syndrome (ACS). Cardiologist-led rapid access chest pain clinics (RACPC) have been proposed overseas to assist in the management of such patients, with prompt outpatient assessment if patients are deemed low risk and discharged from the ED. The use of RACPCs in Australia has been only recently proposed; we therefore sought to examine one such RACPC in an Australian context. METHODS AND RESULTS: 1133 consecutive patients were seen at a metropolitan RACPC, between August 2008 and February 2017. There was a high preponderance of cardiovascular risk factors. Exercise stress testing (EST) was the default investigation upon discharge from ED, with a total of 1038 ESTs performed in 1113 patients (93%), with low numbers of other functional tests, and a small, but increasing number of coronary computed tomography (CT) scans performed over this period. Eighteen patients subsequently underwent revascularisation (1.6% of the total cohort), and none of these patients were readmitted at any time with an ACS between the interval of their index ED presentation to these investigations or treatments. Five (0.4%) patients represented to ED within 48hours, none due to a cardiovascular cause. A total of 24 (2.1%) patients represented between 2 and 28 days, with none of these due to an ACS. CONCLUSIONS: Following ED assessment of acute chest pain as low risk-with direct ED referral for exercising testing followed by RACPC review-results in very low readmission rates at 48hours and at 28 days. Moreover, these readmissions were almost always not of cardiovascular aetiology, and occurred despite relatively longer waiting periods for both EST (8 days) and between EST and RACPC review (11 days), than the prespecified 72 to 96hours as defined by the clinic protocol. Further investigation into this model of care in Australia is suggested.

Intravascular blood sampling using the Thrombuster II catheter does not cause artifactual platelet activation.

Platelets and leukocytes play an important role in atherosclerotic plaque progression. Determining the activation state of both the platelet and leukocyte population at the lesion site has become increasingly of interest. A novel thrombus aspiration catheter, the Thrombuster II (Kaneka Medical Products, Osaka, Japan), has recently been introduced into clinical practice, and is finding rapidly increasing use. This catheter is capable of local blood collection within the coronary tree, but to our knowledge has not previously been validated to demonstrate lack of platelet activation. This study therefore aims to establish whether or not blood sampling via the Thrombuster II results in artefactual platelet activation. Duplicate blood samples were obtained from the descending aorta using both the Thrombuster II and a femoral arterial sheath (control). The samples were collected into CTAD (to minimize ex vivo activation) blood collection tubes and processed for flow cytometry analysis. Platelet activation was assessed based on the expression of CD62P, PAC-1 binding and platelet CD147 expression. Platelet-leukocyte aggregates were also examined. No significant difference was noted between the sheath samples and the Thrombuster II catheter. The Thrombuster II catheter is a novel thrombus aspiration device capable of providing the assessment of platelet activation and platelet-leukocyte aggregates in coronary arteries.

Intracoronary shear-related up-regulation of platelet P-selectin and platelet-monocyte aggregation despite the use of aspirin and clopidogrel.

Recent in vitro studies have shown that shear stress can cause platelet activation by agonist-independent pathways. However, no studies have assessed the extent of shear-induced platelet activation within human coronary arteries. We sampled blood from the coronary arteries proximal and distal to coronary lesions and from the coronary sinus in humans with stable coronary disease who were taking both aspirin and clopidogrel. A novel, computationally based technique for estimating shear stress from 3-dimensional coronary angiographic images of these arteries was developed, and the effect of stenosis severity and calculated shear stress on in vivo platelet and related leukocyte activation pathways were determined. We provide evidence of intracoronary up-regulation of platelet P-selectin, platelet-monocyte aggregation, and monocyte CD11b without platelet glycoprotein IIb-IIIa activation or soluble P-selectin up-regulation. This correlates with intracoronary stenosis severity and calculated shear stress and occurs despite the concurrent use of aspirin and clopidogrel. Our results show for the first time shear-related platelet and monocyte activation in human coronary arteries and suggest this as a potential therapeutic target that is resistant to conventional antiplatelet agents.

Intracoronary delivery of DNAzymes targeting human EGR-1 reduces infarct size following myocardial ischaemia reperfusion.

Despite improvements in treatment, myocardial infarction (MI) remains an important cause of morbidity and mortality. Inflammation arising from ischaemic and reperfusion injury is a key mechanism which underpins myocardial damage and impairment of cardiac function. Early growth response-1 (Egr-1) is an early immediate gene and a master regulator that has been implicated in the pathogenesis of ischaemia-reperfusion (IR) injury. This study sought to examine the effect of selective inhibition of Egr-1 using catalytic deoxyribonucleic acid molecules (DNAzymes, DZs) delivered via the clinically relevant coronary route in a large animal model of myocardial IR. It was hypothesized that Egr-1 inhibition with intracoronary DZ would reduce infarction size by modulating its downstream effector molecules. Egr-1 DZs inhibited the adherence of THP-1 monocytes to IL-1ß-activated endothelial cells in vitro and retained its catalytic activity up to 225 min after in vivo administration. In a porcine model of myocardial IR (45 min ischaemia/3 h reperfusion), DZ was taken up in the cytoplasm and nuclei of cardiomyocytes and endothelial cells in the myocardium after intracoronary delivery. Egr-1 DZs reduced infarct size and improved cardiac functional recovery following intracoronary delivery at the initiation of IR in this large animal model of MI. This was associated with inhibition of pro-inflammatory Egr-1 and ICAM-1 expression, and the reduced expression of TNF-α, PAI-1, TF, and myocardial MPO activity in tissue derived from the border zone of the infarct. Taken together, these data suggest that strategies targeting Egr-1 via the intracoronary route after IR injury in pigs have potential therapeutic implications in human MI.

Three-dimensional and two-dimensional quantitative coronary angiography, and their prediction of reduced fractional flow reserve.

AIMS: We investigated whether three-dimensional (3D) and two-dimensional quantitative coronary angiography (2D-QCA) measurements differed in their accuracy in predicting reduced fractional flow reserve (FFR), and how this varied with stenosis severity and the FFR cut-off used. METHODS AND RESULTS: Three-dimensional and 2D-QCA were compared in their measurements of minimum luminal area (MLA), percentage area stenosis, lesion length, minimum luminal diameter (MLD) and percentage diameter stenosis, and in their prediction of functionally significant FFR. In total, 63 target lesions were interrogated in 63 patients undergoing elective percutaneous coronary intervention. Of all measurements of lesion severity obtained by 3D-QCA, MLA best correlated with FFR (R = 0.63, P < 0.001), and was the most accurate predictor of FFR < 0.75 (C statistic 0.86, P < 0.001). Of 2D-QCA measurements, MLD correlated best with FFR (R = 0.58, P < 0.001), and best predicted FFR < 0.75 (C statistic 0.80, P < 0.001). Overall, 3D-QCA showed a non-significant trend towards more accurate prediction of FFR than 2D-QCA, especially in intermediate lesions. The relationship between FFR and apparent stenosis severity was found to be curvilinear. Both 3D- and 2D-QCA were less accurate in intermediate lesions, and in predicting FFR ≤ 0.80 than in predicting FFR <0.75. CONCLUSIONS: The accuracy of QCA in predicting functionally significant FFR is limited and is dependent on FFR cut-off used and lesion severity. Where FFR is not available or contraindicated, 3D-QCA may assist in the evaluation of coronary lesions of intermediate severity.

c-Jun DNAzymes inhibit myocardial inflammation, ROS generation, infarct size, and improve cardiac function after ischemia-reperfusion injury.

OBJECTIVE: Coronary reperfusion has been the mainstay therapy for reduced infarct size after a heart attack. However, this intervention also results in myocardial injury by initiating a marked inflammatory reaction, and new treatments are keenly sought. METHODS AND RESULTS: The basic-region leucine zipper protein, c-Jun is poorly expressed in the normal myocardium and is induced within 24 hours after myocardial ischemia-reperfusion injury. Synthetic catalytic DNA molecules (DNAzymes) targeting c-Jun (Dz13) reduce infarct size in the area-at-risk (AAR) regardless of whether it is delivered intramyocardially at the initiation of ischemia or at the time of reperfusion. Dz13 attenuates neutrophil infiltration, c-Jun and ICAM-1 expression in vascular endothelium, cardiomyocyte apoptosis, and the generation of reactive oxygen species in the reperfused myocardium. It inhibits infiltration into the AAR of complement 3 (C3), C3a receptor (C3aR), membrane attack complex-1 (Mac-1), or matrix metalloproteinase-2 (MMP-2) positive inflammatory cells. Dz13 also improves cardiac function without influencing myocardial vascularity or fibrosis. CONCLUSIONS: These findings demonstrate the regulatory role of c-Jun in the pathogenesis of myocardial inflammation and infarction following ischemia-reperfusion injury, and inhibition of this process using catalytic DNA.

The intracoronary electrocardiogram in percutaneous coronary intervention.

The technique of obtaining an epicardial electrocardiogram trace by connecting the guidewire during coronary angioplasty to an electrocardiogram lead has been used since 1985. The intracoronary electrocardiogram appears to be more sensitive than the surface electrocardiogram in detecting transient ischemia, particularly in the territory of the left anterior descending and left circumflex coronary arteries. Importantly, recent studies have shown the intracoronary electrocardiogram to be particularly useful in demonstrating pre- and postconditioning during interventional procedures, predicting periprocedural myocardial damage, and in the determination of regional viability in the catheterization laboratory. Barriers to the use of the intracoronary electrocardiogram in the clinical setting include the lack of standardized methods for acquiring and analyzing the intracoronary electrocardiogram, and the lack of commercially available continuous intracoronary monitoring systems to permit analysis while performing coronary interventions. Facilitating these relatively simple technical developments may permit optimal integration of the intracoronary electrocardiogram into the catheterization laboratory.

Lumen loss in the first year in saphenous vein grafts is predominantly a result of negative remodeling of the whole vessel rather than a result of changes in wall thickness.

BACKGROUND: The use of saphenous vein grafts (SVG) in coronary artery bypass surgery is established but little is known of SVG remodeling during the first year in vivo. METHODS AND RESULTS: The feasibility of measuring total vessel diameter (lumen plus wall), lumen diameter, and wall thickness by a novel computed tomography (CT) method was established in phantom model tubes (r=0.98 for lumen diameter and r=0.98 for wall thickness) and in an initial clinical study of 14 patients correlating CT and intravascular ultrasound measurements of SVG (r=0.88 for total vessel diameter, r=0.85 for lumen diameter and r=0.89 for wall thickness). In a separate group of 42 patients (aged 66+/-10 years; 36 male, 6 female) undergoing coronary artery bypass grafting, SVG total vessel diameter, lumen diameter, and wall thickness were determined prospectively with multi-slice CT angiography at 1 and 12 months postoperatively. Mean total vessel diameter decreased from 5.95+/-0.83 mm to 5.39+/-0.87 mm, P<0.001 (range, -39% to +8% change). Twenty-six patients (62%) had a decrease of SVG vessel diameter (negative remodeling) >5%. Mean lumen diameter decreased from 3.69+/-0.66 mm to 3.36+/-0.68 mm, P<0.001, (range, -40 to +11% change). Surprisingly, mean wall thickness decreased from 1.14+/-0.27 mm to 1.01+/-0.21 mm (P<0.001; range, -48 to +33% change). CONCLUSIONS: Lumen loss in SVG between postoperative months 1 and 12 is predominantly caused by negative remodeling of the whole vessel rather than to changes in wall thickness. Therapies targeting negative remodeling may be required for optimal maintenance of SVG lumen in the first postoperative year.

Immediate Thrombolysis Followed by PCI for Left-Main Stem STEMI if Presenting Out of Hours: Should We Go "Back to the Future"?

A case of left-main stem STEMI presenting "out of hours" is discussed, wherein an excellent result was achieved with acute thrombolysis.

A Time to Act and a Time to Watch: Severe Guide-Catheter Induced Proximal Coronary Dissection With Extensive Ascending Aorta and Arch Dissection, Managed by Immediate Coronary Stenting and Watchful Waiting.

In this case, prompt stenting of the dissection entry flap allowed for stabilization and eventual healing of a severe catheter-induced aortic dissection, without resort to surgical intervention.

Revascularisation compared with initial medical therapy for non-ST-elevation acute coronary syndromes in the elderly: a meta-analysis.

OBJECTIVE: Whether revascularisation is superior to medical therapy in older populations presenting with non-ST-elevation acute coronary syndromes (NSTEACS) remains contentious, with inconclusive evidence from randomised trials. We aimed to compare routine invasive therapy with initial medical management in the elderly presenting with NSTEACS. METHODS: MEDLINE, EMBASE and Cochrane Controlled Trial Register were searched for studies comparing routine invasive therapy with initial medical management in patients ≥75 years old presenting with NSTEACS. Endpoints included long-term mortality, myocardial infarction (MI), revascularisation, rehospitalisation, stroke and major bleeding reported as ORs. RESULTS: Four randomised trials and three observational studies met inclusion criteria, enrolling a total of 20 540 patients followed up from 6 months to 5 years. Routine invasive therapy reduced mortality (OR 0.67, CI 0.61 to 0.74), MI (OR 0.56, CI 0.45 to 0.70) and stroke (OR 0.53, CI 0.30 to 0.95). Analyses restricted to randomised controlled trials (RCTs) confirmed a reduction in MI (OR 0.51, CI 0.40 to 0.66), revascularisation (OR 0.27, CI 0.13 to 0.56) and a trend to reduced mortality (OR 0.84, CI 0.66 to 1.06) at the expense of major bleeding (OR 2.19, CI 1.12 to 4.28). Differences in major bleeding were unapparent in more recent studies. CONCLUSION: Routine invasive therapy reduces MI and repeat revascularisation and may reduce mortality at the expense of major bleeding in elderly patients with NSTEACS. Our findings highlight the need for further RCTs to better determine the effect on mortality and contemporary bleeding risk.

Distal protection in cardiovascular medicine: current status.

Iatrogenic and spontaneous downstream microembolization of atheromatous material is increasingly recognized as a source of cardiovascular morbidity and mortality. Devising ways of reducing this distal embolization using a variety of mechanical means--distal protection--is currently under intense and diverse investigation. This review therefore summarizes the present status of distal protection. It examines the problem of distal embolization, describes the available distal protection devices, reviews those areas of cardiovascular medicine where distal protection devices are being investigated, and discusses potential future developments.