Influence of Pathophysiological Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

BACKGROUND: Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. RESULTS: 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). CONCLUSIONS: Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

Protocol Variation in Functional Coronary Angiography Among Patients With Suspected Angina With Non-Obstructive Coronary Arteries: A Nationwide Snapshot of Current Practice Within Australia and New Zealand.

BACKGROUND: Functional coronary angiography (FCA) for endotype characterisation (vasospastic angina [VSA], coronary microvascular disease [CMD], or mixed) is recommended among patients with angina with non-obstructive coronary arteries. Whilst clear diagnostic criteria for VSA and CMD exist, there is no standardised FCA protocol. Variations in testing protocol may limit the widespread uptake of testing, generalisability of results, and expansion of collaborative research. At present, there are no data describing protocol variation across an entire geographic region. Therefore, we aimed to capture current practice variations in the approach to FCA to improve access and standardisation for diagnosis of coronary vasomotor disorders in Australia and New Zealand. METHOD: Between July 2022 and July 2023, we conducted a national survey across all centres in Australia and New Zealand with an active FCA program. The survey captured attitudes towards FCA and protocols used for diagnosis of coronary vasomotor disorders at 33 hospitals across Australia and New Zealand. RESULTS: Survey responses were received from 39 clinicians from 33 centres, with representation from centres within all Australian states and territories and both North and South Islands of New Zealand. A total of 21 centres were identified as having an active FCA program. In general, respondents agreed that comprehensive physiology testing helped inform clinical management. Barriers to program expansion included cost, additional catheter laboratory time, and the absence of an agreed-upon national protocol. Across the clinical sites, there were significant variations in testing protocol, including the technique used (Doppler vs thermodilution), order of testing (hyperaemia resistance indices first vs vasomotor function testing first), rate and dose of acetylcholine administration, routine use of temporary pacing wire, and routine single vs multivessel testing. Overall, testing was performed relatively infrequently, with very little follow-on FCA performed, despite nearly all respondents believing this would be clinically useful. CONCLUSIONS: This survey demonstrates, for the first time, variations in FCA protocol among testing centres across two entire countries. Furthermore, whilst FCA was deemed clinically important, testing was performed relatively infrequently with little or no follow-on testing. Development and adoption of a standardised national FCA protocol may help improve patient access to testing and facilitate further collaborative research within Australia and New Zealand.

Prevalence of Coronary Vasomotor Disorders in Patients With Angina and Nonobstructive Coronary Arteries: A Sydney Experience.

BACKGROUND: Patients with angina and non-obstructive coronary arteries (ANOCA) frequently have coronary vasomotor disorders (CVaD), characterised by transient pathological vasoconstriction and/or impaired microvascular vasodilatation. Functional coronary angiography is the gold standard for diagnosing CVaD. Despite recommendations, testing is only available at a limited number of Australian and New Zealand centres. This study aimed to determine the prevalence of CVaDs in an Australian ANOCA population and identify predictive factors associated with specific endotypes. METHOD: Functional coronary angiography was performed in patients with suspected ANOCA. Vasoreactivity testing was performed using intracoronary acetylcholine provocation. A pressure-temperature sensor guidewire was used for coronary physiology assessment. Comprehensive clinical data on patient characteristics, cardiac risk factors, and symptom profiles was collected before testing. RESULTS: This prospective observational study at Royal Prince Alfred and Concord Repatriation General Hospital included 110 patients (58±13 years with 63.6% women), with 81.8% (90/110) having a CVaD. Regarding specific ANOCA endotypes, microvascular angina (MVA) occurred in 31.8% (35/110) of cases, vasospastic angina (VSA) in 25.5% (28/110) and a mixed presentation of MVA and VSA in 24.5% (27/110) of patients. Patients with CVaD were found to be older (59±11 vs 51±15, p=0.024), overweight (61.1% vs 15.0%, p<0.001) and had a worse quality of life (EuroQol 5 Dimensions-5 Levels; 0.61 vs 0.67, p=0.043). MVA was associated with being overweight (odds ratio [OR] 4.2 [95% confidence interval [CI] 1.9-9.3]; p=0.015) and ischaemia on stress testing (OR 2.4 [95% CI 1.1-4.3]; p=0.028), while VSA was associated with smoking (OR 9.1 [95% CI 2.21-39.3]; p=0.007). CONCLUSIONS: Coronary vasomotor disorders are highly prevalent among ANOCA patients. This study highlights the importance of increasing national awareness and the use of functional coronary angiography to evaluate and manage this unique cohort.

Rationale and design of the pullback pressure gradient (PPG) global registry.

INTRODUCTION: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum. AIM: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR. METHODS: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events. RESULTS: Recruitment is ongoing and is expected to be completed in the second half of 2023. CONCLUSION: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes.

Variability in Contemporary Heparin Prescription and Activated Clotting Time Monitoring During Percutaneous Coronary Intervention: Call for Up-To-Date Evidence-Based Guidelines.

BACKGROUND: Unfractionated heparin (UFH) is the preferred anticoagulant agent in percutaneous coronary intervention (PCI) procedures for minimising the risk of thrombotic complications. Because of the narrow therapeutic range of UFH, some society guidelines have advocated the use of the activated clotting time (ACT) test to monitor anticoagulation intensity during PCI to reduce thrombotic and bleeding complications. We aimed to assess the current practice of UFH prescription and its monitoring in Australia and New Zealand (ANZ). METHOD: We conducted an anonymous voluntary cross-sectional survey of interventional cardiologists (ICs) who were members of the Cardiac Society of Australia and New Zealand in 2022. The survey included 10 questions pertaining to the current practice of anticoagulation during PCI. RESULTS: Of 430 ICs surveyed, 148 responded (response rate, 34.4%). Most ICs (84.4%) prescribed 70-100 IU/kg of UFH for PCI. Over half of ICs (58.7%) routinely measured ACT during PCI, whereas only 22.2% routinely measured ACT after PCI to guide additional UFH prescription. Among ICs who prescribed additional UFH, approximately half (48%) aimed for ACT ≥250 seconds. Factors that influenced post-PCI UFH prescription included vascular access site and concomitant antiplatelet or anticoagulant therapy. CONCLUSIONS: The contemporary practice of UFH prescription during PCI and ACT monitoring in ANZ is variable and based on outdated evidence preceding current drug-eluting stents, antiplatelet therapies, and radial-first practice. Current society guideline recommendations lack clarity and agreement, reflecting the quality of the available evidence. Up-to-date clinical trials evaluating UFH prescription and ACT monitoring are needed to optimise clinical outcomes in contemporary PCI procedures.

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.

Colchicine in Patients With Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial.

BACKGROUND: Inflammation plays a crucial role in clinical manifestations and complications of acute coronary syndromes (ACS). Colchicine, a commonly used treatment for gout, has recently emerged as a novel therapeutic option in cardiovascular medicine owing to its anti-inflammatory properties. We sought to determine the potential usefulness of colchicine treatment in patients with ACS. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial involving 17 hospitals in Australia that provide acute cardiac care service. Eligible participants were adults (18-85 years) who presented with ACS and had evidence of coronary artery disease on coronary angiography managed with either percutaneous coronary intervention or medical therapy. Patients were assigned to receive either colchicine (0.5 mg twice daily for the first month, then 0.5 mg daily for 11 months) or placebo, in addition to standard secondary prevention pharmacotherapy, and were followed up for a minimum of 12 months. The primary outcome was a composite of all-cause mortality, ACS, ischemia-driven (unplanned) urgent revascularization, and noncardioembolic ischemic stroke in a time to event analysis. RESULTS: A total of 795 patients were recruited between December 2015 and September 2018 (mean age, 59.8±10.3 years; 21% female), with 396 assigned to the colchicine group and 399 to the placebo group. Over the 12-month follow-up, there were 24 events in the colchicine group compared with 38 events in the placebo group (P=0.09, log-rank). There was a higher rate of total death (8 versus 1; P=0.017, log-rank) and, in particular, noncardiovascular death in the colchicine group (5 versus 0; P=0.024, log-rank). The rates of reported adverse effects were not different (colchicine 23.0% versus placebo 24.3%), and they were predominantly gastrointestinal symptoms (colchicine, 23.0% versus placebo, 20.8%). CONCLUSIONS: The addition of colchicine to standard medical therapy did not significantly affect cardiovascular outcomes at 12 months in patients with ACS and was associated with a higher rate of mortality. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615000861550.

Outcomes of 1,098 Patients Following Transcatheter Aortic Valve Implantation: A Statewide Population-Linkage Cohort Study.

BACKGROUND: The increasing implementation of transcatheter aortic valve implantation (TAVI) in Australia warrants real-world data on the prevalence and outcomes of these patients. The aim of this study is to describe trends in case-volumes of TAVI in New South Wales (NSW), Australia and associated mortality outcomes. METHODS: From the Centre of Health Record Linkage registry, all NSW residents who underwent TAVI between 5 June 2013 and 30 June 2018 were identified. Cause-specific mortality was tracked from the statewide death registry. Temporal trends in case-volumes between 2013 and 2018 were assessed by linear regression. Binary logistic regression was used to compare differences in in-hospital and 30-day mortality, while Cox proportional hazards regression was used to compare mortality beyond 30 days. RESULTS: Case-volumes increased from 30 in 2013 to 345 by 2017. The cohort comprised 1,098 persons (mean[±SD] age: 83.3±7.7 yrs). Cumulative in-hospital, 180-day and at end-of-study (mean: 1.8±1.2 yrs) all-cause mortality were 1.3% (n=14), 4.9% (n=54) and 20.3% (n=224) respectively. Heart failure (14.3%, n=2), myocardial infarction (14.3%, n=2), and sepsis (14.3%, n=2) were the primary causes of in-hospital death. Post-discharge, sepsis (25.2%, n=53) was the main cause-specific death, while combined cardiovascular deaths accounted for 46% (n=97), mostly from heart failure (n=35). Heart failure, chronic kidney disease, and requirement for ventilation post-TAVI were independent predictors of in-hospital death and at 180 days. TAVI procedure in low-volume public centres was a predictor of mortality at 180 days. CONCLUSION: The number of TAVI procedures increased 10-fold between 2013 and 2017 state-wide, with mortality rates comparable to international cohorts at short and medium-term follow-up. Pre-existing comorbidities and site-specific caseloads may be important determinants of outcome, emphasising the importance of appropriate patient selection and treating centre.

Cardiac Complications in Patients Hospitalised With COVID-19 in Australia.

OBJECTIVES: Describe the incidence of cardiac complications in patients admitted to hospital with COVID-19 in Australia. DESIGN: Observational cohort study. SETTING: Twenty-one (21) Australian hospitals. PARTICIPANTS: Consecutive patients aged ≥18 years admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MAIN OUTCOME MEASURES: Incidence of cardiac complications. RESULTS: Six-hundred-and-forty-four (644) hospitalised patients (62.5±20.1 yo, 51.1% male) with COVID-19 were enrolled in the study. Overall in-hospital mortality was 14.3%. Twenty (20) (3.6%) patients developed new atrial fibrillation or flutter during admission and 9 (1.6%) patients were diagnosed with new heart failure or cardiomyopathy. Three (3) (0.5%) patients developed high grade atrioventricular (AV) block. Two (2) (0.3%) patients were clinically diagnosed with pericarditis or myopericarditis. Among the 295 (45.8%) patients with at least one troponin measurement, 99 (33.6%) had a peak troponin above the upper limit of normal (ULN). In-hospital mortality was higher in patients with raised troponin (32.3% vs 6.1%, p<0.001). New onset atrial fibrillation or flutter (6.4% vs 1.0%, p=0.001) and troponin elevation above the ULN (50.3% vs 16.4%, p<0.001) were more common in patients 65 years and older. There was no significant difference in the rate of cardiac complications between males and females. CONCLUSIONS: Among patients with COVID-19 requiring hospitalisation in Australia, troponin elevation was common but clinical cardiac sequelae were uncommon. The incidence of atrial arrhythmias and troponin elevation was greatest in patients 65 years and older.

Development of a Computational Fluid Dynamics Model for Myocardial Bridging.

Computational fluid dynamics (CFD) modeling of myocardial bridging (MB) remains challenging due to its dynamic and phasic nature. This study aims to develop a patient-specific CFD model of MB. There were two parts to this study. The first part consisted of developing an in silico model of the left anterior descending (LAD) coronary artery of a patient with MB. In this regard, a moving-boundary CFD algorithm was developed to simulate the patient-specific muscle compression caused by MB. A second simulation was also performed with the bridge artificially removed to determine the hemodynamics in the same vessel in the absence of MB. The second part of the study consisted of hemodynamic analysis of three patients with mild and moderate and severe MB in their LAD by means of the developed in silico model in the first part. The average shear stress in the proximal and bridge segments for model with MB were significantly different from those for model without MB (proximal segment: 0.32 ± 0.14 Pa (with MB) versus 0.97 ± 0.39 Pa (without MB), P < 0.0001 - bridge segment: 2.60 ± 0.94 Pa (with MB) versus 1.50 ± 0.64 Pa (without MB), P < 0.0001). When all three patients were evaluated, increasing the degree of vessel compression shear stress in the proximal segment decreased, whereas the shear stress in the bridge segment increased. The presence of MB resulted in hemodynamic abnormalities in the proximal segment, whereas segments within the bridge exhibited hemodynamic patterns which tend to discourage atheroma development.

A Practical Guide for Fractional Flow Reserve Guided Revascularisation.

The presence and extent of myocardial ischaemia is a major determinant of prognosis and benefit from revascularisation in patients with stable coronary artery disease. Fractional Flow Reserve (FFR) is accepted as the reference standard for invasive assessment of ischaemia. Its ability to detect lesion specific ischaemia makes it a useful test in a wide range of patient and lesion subsets, with FFR guided intervention improving clinical outcomes and reducing health care costs compared to assessment with coronary angiography alone. This article will review the basic principles in FFR, practical tips in FFR guided revascularisation and the role of emerging non-hyperaemic indices of ischaemia.

Cardiac Remote Ischaemic Preconditioning: Mechanistic and Clinical Considerations.

Brief, non-harmful ischaemic insults to an organ remote from the heart, remote ischaemic preconditioning (RIPC), has been proposed to confer protection to the heart against ischaemia-reperfusion injury. While most clinical trials of RIPC during coronary interventions (PCI) suggest benefit, recent large, multicentre trials in coronary artery bypass surgery suggest a lack of efficacy. Mechanistically, RIPC most likely promotes the release of circulating factors which modulate multiple cellular pathways in the heart, promoting cell survival. This review explores potential mechanisms underlying RIPC and includes a contemporary evaluation of clinical studies in PCI and cardiac surgery, highlighting methodological differences which may explain discrepant findings between these two clinical groups.

Invasive evaluation of patients with angina in the absence of obstructive coronary artery disease.

BACKGROUND: More than 20% of patients presenting to the cardiac catheterization laboratory with angina have no angiographic evidence of coronary artery disease. Despite a "normal" angiogram, these patients often have persistent symptoms, recurrent hospitalizations, a poor functional status, and adverse cardiovascular outcomes, without a clear diagnosis. METHODS AND RESULTS: In 139 patients with angina in the absence of obstructive coronary artery disease (no diameter stenosis >50%), endothelial function was assessed; the index of microcirculatory resistance, coronary flow reserve, and fractional flow reserve were measured; and intravascular ultrasound was performed. There were no complications. The average age was 54.0±11.4 years, and 107 (77%) were women. All patients had at least some evidence of atherosclerosis based on an intravascular ultrasound examination of the left anterior descending artery. Endothelial dysfunction (a decrease in luminal diameter of >20% after intracoronary acetylcholine) was present in 61 patients (44%). Microvascular impairment (an index of microcirculatory resistance ≥25) was present in 29 patients (21%). Seven patients (5%) had a fractional flow reserve ≤0.80. A myocardial bridge was present in 70 patients (58%). Overall, only 32 patients (23%) had no coronary explanation for their angina, with normal endothelial function, normal coronary physiological assessment, and no myocardial bridging. CONCLUSIONS: The majority of patients with angina in the absence of obstructive coronary artery disease have occult coronary abnormalities. A comprehensive invasive assessment of these patients at the time of coronary angiography can be performed safely and provides important diagnostic information that may affect treatment and outcomes.

Impact of Age on the Functional Significance of Intermediate Epicardial Artery Disease.

BACKGROUND: The functional significance of an intermediate coronary lesion is crucial for determining the treatment strategy, but age-related changes in cardiovascular function could affect the functional significance of an epicardial stenosis. The aim of this study was therefore to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease (CAD). METHODS AND RESULTS: Intracoronary pressure measurements and intravascular ultrasound (IVUS) were performed in 178 left anterior descending coronary arteries with intermediate stenosis. The morphological characteristics and FFR of 91 lesions in patients <65 years old were compared with those of 87 patients ≥65 years old. There was no difference in lesion location, diameter stenosis, minimum lumen area, plaque burden, or lesion length between the 2 age groups. Elderly patients had higher FFR (0.81±0.06 vs. 0.79±0.06, P=0.004) and lower ∆FFR, defined as the difference between resting Pd/Pa and FFR (0.13±0.05 vs. 0.15±0.05, P=0.014). Age, along with the location and degree of stenosis, was independently associated with FFR and ∆FFR (ß=0.162, P=0.008; ß=-0.131, P=0.043, respectively). CONCLUSIONS: Elderly patients with intermediate CAD are more likely to have higher FFR and lower ∆FFR, despite a similar degree of epicardial stenosis, compared with younger patients. (Circ J 2016; 80: 1583-1589).

Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention.

BACKGROUND: Most methods for assessing microvascular function are not readily available in the cardiac catheterization laboratory. The aim of this study is to determine whether the Index of Microcirculatory Resistance (IMR), measured at the time of primary percutaneous coronary intervention, is predictive of death and rehospitalization for heart failure. METHODS AND RESULTS: IMR was measured immediately after primary percutaneous coronary intervention in 253 patients from 3 institutions with the use of a pressure-temperature sensor wire. The primary end point was the rate of death or rehospitalization for heart failure. The prognostic value of IMR was compared with coronary flow reserve, TIMI myocardial perfusion grade, and clinical variables. The mean IMR was 40.3±32.5. Patients with an IMR >40 had a higher rate of the primary end point at 1 year than patients with an IMR ≤40 (17.1% versus 6.6%; P=0.027). During a median follow-up period of 2.8 years, 13.8% experienced the primary end point and 4.3% died. An IMR >40 was associated with an increased risk of death or rehospitalization for heart failure (hazard ratio [HR], 2.1; P=0.034) and of death alone (HR, 3.95; P=0.028). On multivariable analysis, independent predictors of death or rehospitalization for heart failure included IMR >40 (HR, 2.2; P=0.026), fractional flow reserve ≤0.8 (HR, 3.24; P=0.008), and diabetes mellitus (HR, 4.4; P<0.001). An IMR >40 was the only independent predictor of death alone (HR, 4.3; P=0.02). CONCLUSIONS: An elevated IMR at the time of primary percutaneous coronary intervention predicts poor long-term outcomes.

Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels.

Ligand-induced ectodomain shedding of glycoprotein VI (GPVI) is a metalloproteinase-dependent event. We examined whether shear force, in the absence of GPVI ligand, was sufficient to induce shedding of GPVI. Human-citrated platelet-rich plasma or washed platelets were subjected to increasing shear rates in a cone-plate viscometer, and levels of intact and cleaved GPVI were examined by Western blot and ELISA. Pathophysiologic shear rates (3000-10 000 seconds(-1)) induced platelet aggregation and metalloproteinase-dependent appearance of soluble GPVI ectodomain, and GPVI platelet remnant. Shedding of GPVI continued after transient exposure to shear. Blockade of α(IIb)ß(3), GPIbα, or intracellular signaling inhibited shear-induced platelet aggregation but minimally affected shear-induced shedding of GPVI. Shear-induced GPVI shedding also occurred in platelet-rich plasma or washed platelets isolated from a von Willebrand disease type 3 patient with no detectable VWF, implying that shear-induced activation of platelet metalloproteinases can occur in the absence of GPVI and GPIbα ligands. Significantly elevated levels of sGPVI were observed in 10 patients with stable angina pectoris, with well-defined single vessel coronary artery disease and mean intracoronary shear estimates at 2935 seconds(-1) (peak shear, 19 224 seconds(-1)). Loss of GPVI in platelets exposed to shear has potential implications for the stability of a forming thrombus at arterial shear rates.

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.

Insights into the invasive diagnostic challenges of coronary artery vasospasm - A systematic review.

Coronary provocation testing is an essential diagnostic procedure when evaluating vasospastic angina. Invasive methods using acetylcholine or ergonovine are considered the current gold standard. Despite efforts from global cardiovascular institutions, current protocols vary in dosage, administration time, and procedural approach. In addition, concerns over the specificity of findings and potential complications have limited routine uptake of this procedure in clinical practice. This systematic review evaluates current diagnostic protocols, focusing on invasive provocation testing. We included studies using intracoronary provocation testing with acetylcholine or ergonovine for the assessment of coronary artery vasospasm that detailed specific elements of the procedure (dosage, administration time, etc.) and included ≥50 patients. A total of 28 articles met strict inclusion criteria. Our review highlights the heterogeneity between current diagnostic protocols for invasive provocation testing. We believe standardization of a diagnostic protocol will encourage both current and future cardiologists to incorporate such procedures in the evaluation of variant angina.

Comparison of cuff inflation and cuff deflation brachial sphygmomanometry with intra-arterial blood pressure as reference.

Conventional sphygmomanometry with cuff deflation is used to calibrate all noninvasive BP (NIBP) instruments and the International Standard makes no mention of calibrating methods specifically for NIBP instruments, which estimate systolic and diastolic pressure during cuff inflation rather than cuff deflation. There is however increasing interest in inflation-based NIBP (iNIBP) instruments on the basis of shorter measurement time, reduction in maximal inflation pressure and improvement in patient comfort and outcomes. However, we have previously demonstrated that SBP estimates based on the occurrence of the first K1 Korotkoff sounds during cuff deflation can underestimate intra-arterial SBP (IA-SBP) by an average of 14 ±â€Š10 mmHg. In this study, we compare the dynamics of intra-arterial blood pressure (IABP) measurements with sequential measurement of Korotkoff sounds during both cuff inflation and cuff deflation in the same individual. In 40 individuals aged 64.1 ±â€Š9.6 years (range 36-86 years), the overall dynamic responses below the cuff were similar, but the underestimation error was significantly larger during inflation than deflation, increasing from 14 ±â€Š10 to 19 ±â€Š12 mmHg ( P  < 0.0001). No statistical models were found which could compensate for this error as were found for cuff deflation. The statistically significant BP differences between inflation and deflation protocols reported in this study suggest different behaviour of the arterial and venous vasculature between arterial opening and closing which warrant further investigation, particularly for iNIBP devices reporting estimates during cuff inflation. In addition, measuring Korotkoff sounds during cuff inflation represents significant technical difficulties because of increasing pump motor noise.