Assessing the Impact of Colchicine on Coronary Plaque Phenotype After Myocardial Infarction with Optical Coherence Tomography: Rationale and Design of the COCOMO-ACS Study.

INTRODUCTION: Recurrent event rates after myocardial infarction (MI) remain unacceptably high, in part because of the continued growth and destabilization of residual coronary atherosclerotic plaques, which may occur despite lipid-lowering therapy. Inflammation is an important contributor to this ongoing risk. Recent studies have shown that the broad-acting anti-inflammatory agent, colchicine, may reduce adverse cardiovascular events in patients post-MI, although the mechanistic basis for this remains unclear. Advances in endovascular arterial wall imaging have allowed detailed characterization of the burden and compositional phenotype of coronary plaque, along with its natural history and responsiveness to treatment. One such example has been the use of optical coherence tomography (OCT) to demonstrate the plaque-stabilizing effects of statins on both fibrous cap thickness and the size of lipid pools within plaque. METHODS: The Phase 2, multi-centre, double-blind colchicine for coronary plaque modification in acute coronary syndrome (COCOMO-ACS) study will evaluate the effect of colchicine 0.5 mg daily on coronary plaque features using serial OCT imaging in patients following MI. Recruitment for the trial has been completed with 64 participants with non-ST elevation MI randomized 1:1 to colchicine or placebo in addition to guideline recommended therapies, including high-intensity statins. The primary endpoint is the effect of colchicine on the minimal fibrous cap thickness of non-culprit plaque over an 18-month period. The COCOMO-ACS study will determine whether addition of colchicine 0.5 mg daily to standard post-MI treatment has incremental benefits on high-risk features of coronary artery plaques. If confirmed, this will provide new mechanistic insights into how colchicine may confer clinical benefits in patients with atherosclerotic cardiovascular disease. TRIAL REGISTRATION: ANZCTR trial registration number: ACTRN12618000809235. Date of trial registration: 11th of May 2018.

Telemedicine to Timor-Leste: implementing an international cardiac telehealth service during population dislocation, floods and COVID-19.

BACKGROUND: The East Timor Hearts Fund has provided cardiac services in Timor-Leste since 2010, conducting three clinics yearly. AIM: To develop collaborative telehealth services between Australia and Timor-Leste in the context of international border closures due to the COVID-19 pandemic. METHODS: Scoping discussions identified major challenges (structural, patient related and medical system related). At two pilot clinics, patient history, investigation and management were collated. Clinic metrics were compared with an index face-to-face clinic in February 2019. Post-clinic discussions identified areas of success and shortfall in the conduct of the telehealth clinics. RESULTS: Twenty-three patients were reviewed at the online telehealth clinics held onsite at Timorese medical facilities. Compared with an index 2019 clinic, there were markedly lower numbers of new referrals (2 vs 190 patients; 8.7% vs 59.4%). Patients seen at the online clinic were predominantly female (17/23; 73.9%) and Dili based (18/23; 78.3%), with a mean age of 25.9 ± 7.2 years. The majority (12/23; 52.2%) had isolated rheumatic mitral valve disease. Investigations including electrocardiography, pathology, echocardiography and 6-min walk tests were conducted in select patients. Medication advice was provided for 10 (43.5%) patients. Eleven (47.8%) patients were deemed to require urgent intervention. Post-clinic discussions indicated general satisfaction with telehealth clinics, although frustration at the current inability to provide interventional services was highlighted. CONCLUSION: Our pilot telehealth clinics indicate that capacity-building telemedicine can be rapidly implemented in an emergency setting internationally. Clinic design benefits from careful identification and resolution of challenges to optimise flow. Cardiac patients in Timor-Leste have a significant burden of disease amenable to intervention.

Numerical Study of Incomplete Stent Apposition Caused by Deploying Undersized Stent in Arteries With Elliptical Cross Sections.

Incomplete stent apposition (ISA) is one of the causes leading to poststent complications, which can be found when an undersized or an underexpanded stent is deployed at lesions. The previous research efforts have focused on ISA in idealized coronary arterial geometry with circular cross section. However, arterial cross section eccentricity plays an important role in both location and severity of ISA. Computational fluid dynamics (CFD) simulations are carried out to systematically study the effects of ISA in arteries with elliptical cross section, as such stents are partially embedded on the minor axis sides of the ellipse and malapposed elsewhere. Overall, ISA leads to high time-averaged wall shear stress (TAWSS) at the proximal end of the stent and low TAWSS at the ISA transition region and the distal end. Shear rate depends on both malapposition distance and blood stream locations, which is found to be significantly higher at the inner stent surface than the outer surface. The proximal high shear rate signifies increasing possibility in platelet activation, when coupled with low TAWSS at the transition and distal regions which may indicate a nidus for in-stent thrombosis.

Endothelial shear stress 5 years after implantation of a coronary bioresorbable scaffold.

Aims: As a sine qua non for arterial wall physiology, local hemodynamic forces such as endothelial shear stress (ESS) may influence long-term vessel changes as bioabsorbable scaffolds dissolve. The aim of this study was to perform serial computational fluid dynamic (CFD) simulations to examine immediate and long-term haemodynamic and vascular changes following bioresorbable scaffold placement. Methods and results: Coronary arterial models with long-term serial assessment (baseline and 5 years) were reconstructed through fusion of intravascular optical coherence tomography and angiography. Pulsatile non-Newtonian CFD simulations were performed to calculate the ESS and relative blood viscosity. Time-averaged, systolic, and diastolic results were compared between follow-ups. Seven patients (seven lesions) were included in this analysis. A marked heterogeneity in ESS and localised regions of high blood viscosity were observed post-implantation. Percent vessel area exposed to low averaged ESS (<1 Pa) significantly decreased over 5 years (15.92% vs. 4.99%, P < 0.0001) whereas moderate (1-7 Pa) and high ESS (>7 Pa) did not significantly change (moderate ESS: 76.93% vs. 80.7%, P = 0.546; high ESS: 7.15% vs. 14.31%, P = 0.281), leading to higher ESS at follow-up. A positive correlation was observed between baseline ESS and change in lumen area at 5 years (P < 0.0001). Maximum blood viscosity significantly decreased over 5 years (4.30 ± 1.54 vs. 3.21± 0.57, P = 0.028). Conclusion: Immediately after scaffold implantation, coronary arteries demonstrate an alternans of extremely low and high ESS values and localized areas of high blood viscosity. These initial local haemodynamic disturbances may trigger fibrin deposition and thrombosis. Also, low ESS can promote neointimal hyperplasia, but may also contribute to appropriate scaffold healing with normalisation of ESS and reduction in peak blood viscosity by 5 years.

Elevated Blood Viscosity and Microrecirculation Resulting From Coronary Stent Malapposition.

One particular complexity of coronary artery is the natural tapering of the vessel with proximal segments having larger caliber and distal tapering as the vessel get smaller. The natural tapering of a coronary artery often leads to proximal incomplete stent apposition (ISA). ISA alters coronary hemodynamics and creates pathological path to develop complications such as in-stent restenosis, and more worryingly, stent thrombosis (ST). By employing state-of-the-art computer-aided design software, generic stent hoops were virtually deployed in an idealized tapered coronary artery with decreasing malapposition distance. Pulsatile blood flow simulations were carried out using computational fluid dynamics (CFD) on these computer-aided design models. CFD results reveal unprecedented details in both spatial and temporal development of microrecirculation environments throughout the cardiac cycle (CC). Arterial tapering also introduces secondary microrecirculation. These primary and secondary microrecirculations provoke significant fluctuations in arterial wall shear stress (WSS). There has been a direct correlation with changes in WSS and the development of atherosclerosis. Further, the presence of these microrecirculations influence strongly on the local levels of blood viscosity in the vicinity of the malapposed stent struts. The observation of secondary microrecirculations and changes in blood rheology is believed to complement the wall (-based) shear stress, perhaps providing additional physical explanations for tissue accumulation near ISA detected from high resolution optical coherence tomography (OCT).

Biomechanical stress in coronary atherosclerosis: emerging insights from computational modelling.

Coronary plaque rupture is the most common cause of vessel thrombosis and acute coronary syndrome. The accurate early detection of plaques prone to rupture may allow prospective, preventative treatment; however, current diagnostic methods remain inadequate to detect these lesions. Established imaging features indicating vulnerability do not confer adequate specificity for symptomatic rupture. Similarly, even though experimental and computational studies have underscored the importance of endothelial shear stress in progressive atherosclerosis, the ability of shear stress to predict plaque progression remains incremental. This review examines recent advances in image-based computational modelling that have elucidated possible mechanisms of plaque progression and rupture, and potentially novel features of plaques most prone to symptomatic rupture. With further study and clinical validation, these markers and techniques may improve the specificity of future culprit plaque detection.

Bivalirudin versus unfractionated heparin for residual thrombus burden: a frequency-domain optical coherence tomography study.

OBJECTIVES: This study aimed to compare the effect of bivalirudin and unfractionated heparin (UFH) on residual thrombus burden assessed by frequency-domain optical coherence tomography (FD-OCT), and on angiographic indices of microvascular obstruction (MVO). BACKGROUND: The efficacy of bivalirudin to inhibit thrombus formation inside the stent during percutaneous coronary interventions (PCI) as compared to UFH is unknown. METHODS: Sixty patients with coronary artery disease who underwent post-PCI FD-OCT were studied, including 20 patients treated with bivalirudin and 40 control patients treated with UFH, matched by clinical presentation, stent characteristics, and periprocedural medications. In-stent thrombus volume, thrombus score (number of quadrants with thrombus), and thrombus type (white/red) were assessed by FD-OCT. Thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), and Quantitative Blush Evaluator (QuBE) score were recorded. RESULTS: Patients treated with bivalirudin showed similar thrombus volume (0.14 mm(3) [0.00-0.88] vs. 0.13 mm(3) [0.00-0.63], P = 0.962), thrombus score (10 [0-25] vs. 8 [0-21], P = 0.849) and thrombus length (1.70 mm [0.00-4.10] vs. 1.40 mm [0.00-4.05], P = 0.968], as compared with patients treated with UFH. Patients in the bivalirudin group showed lower proportion of white thrombus (55.5% vs. 78.6%, P = 0.016). There was no significant difference in TIMI flow grade, cTFC, and QuBE score between the two groups. CONCLUSIONS: The present study showed similar residual thrombus burden and angiographic indices of MVO immediately after PCI between patients treated with bivalirudin and those treated with UFH.

A twist in the transradial coronary catheterisation.

The transradial approach for coronary angiography was first described in 1989. With the advent of modern equipment and improved technology it has recently gained significant interest amongst interventional cardiologists. As compared to femoral access, the radial approach has the major advantages of lower access site complication rates, cost-effectiveness, and shorter hospital stays. Further clinical benefits of lower morbidity and cardiac mortality in patients with ST-elevation myocardial infarction have been shown recently. Rare vascular complications may include radial artery spasm, dissection, occlusion, perforation or compartment syndrome. Here, we present two unusual cases of an entrapped catheter in the radial artery and their outcomes.

Radiation exposure with the radial approach for diagnostic coronary angiography in a centre previously performing purely the femoral approach.

INTRODUCTION: Use of the radial approach for coronary angiography and percutaneous coronary intervention (PCI) is known to improve many patient outcome measures. However, there is some concern that it may be associated with increased patient radiation exposure. This study explores radiation exposure with the radial approach compared with the femoral approach in a centre previously performing purely femoral approach. PATIENTS AND METHODS: Data was collected retrospectively for all patients undergoing diagnostic coronary angiography over a six month period. PCIs and procedures with inherent technical difficulty or use of additional techniques (graft studies, optical coherence tomography, fractional flow reserve) were excluded. Dose area product (DAP) and fluoroscopy time (FT) were analysed for all remaining procedures (n=389), comparing radial (n=109) and femoral (n=280) approaches. RESULTS: The overall mean FT for transradial cases (7.45 mins) was significantly higher than for transfemoral cases (4.59 mins; p<0.001). The overall mean DAP for transradial cases (95.64 G Gycm(2)) was significantly higher than for transfemoral cases (70.25 Gycm(2), p<0.05)). Neither the FT nor the DAP decreased over the six month period. CONCLUSION: The radial approach was associated with significantly higher DAP and FT compared to the femoral approach during an initial introductory phase which was likely insufficient to develop radial proficiency. The results of this study are consistent with previous studies and may influence choice of access for non-emergent diagnostic coronary angiography before radial proficiency has been established, particularly for patients more susceptible to radiation risks.

Development of 3D Printed Biodegradable, Entirely X-ray Visible Stents for Rabbit Carotid Artery Implantation.

Biodegradable stents are considered a promising strategy for the endovascular treatment of cerebrovascular diseases. The visualization of biodegradable stents is of significance during the implantation and long-term follow-up. Endowing biodegradable stents with X-ray radiopacity can overcome the weakness of intrinsic radioparency of polymers. Hence, this work focuses on the development of an entirely X-ray visible biodegradable stent (PCL-KIO3) composed of polycaprolactone (PCL) and potassium iodate via physical blending and 3D printing. The in vitro results show that the introduction of potassium iodate makes the 3D-printed PCL stents visualizable under X-ray. So far, there is inadequate study about polymeric stent visualization in vivo. Therefore, PCL-KIO3 stents are implanted into the rabbit carotid artery to evaluate the biosafety and visibility performance. During stent deployment, the visualization of the PCL-KIO3 stent effectively helps to understand the position and dilation status of stents. At 6-month follow-up, the PCL-KIO3 stent could still be observed under X-ray and maintains excellent vessel patency. To sum up, this study demonstrates that PCL-KIO3 stent may provide a robust strategy for biodegradable stent visualization.

Ivabradine in the Prevention, and Reduction in Size, of Perioperative Myocardial Injury in Patients Undergoing Orthopedic Surgery for Acute Fracture.

BACKGROUND: Perioperative myocardial injury is common after major noncardiac surgery and is associated with adverse outcomes. This study investigated the use of ivabradine in patients undergoing urgent surgery for fracture. METHODS AND RESULTS: This was a prospective, double-blind, placebo-controlled, randomized clinical trial. Participants were enrolled 1:1 into ivabradine or placebo arm, and study drug was commenced before operation and continued for 7 days or until discharge. High-sensitivity troponin I was measured daily using Abbott Alinity analyzer and assay, and heart rate data were obtained using continuous Holter monitoring. A total of 199 patients underwent acute orthopedic surgery, 98 in the ivabradine group and 101 in the placebo group. The mean age was 78.7 years (range, 77.5-79.9 years), with 68% women. The average heart rate was 5 to 11 beats per minute lower in the ivabradine group compared with the placebo group at all time points (P<0.001 for all). There was no statistically significant difference between the ivabradine and placebo groups in the number of patients who had perioperative myocardial injury: 28.6% versus 31.6% (P=0.71). In patients with perioperative myocardial injury, average peak troponin was 168.8 ng/L (±431.2 ng/L) in the ivabradine group and 2094.5 ng/L (±7201.9 ng/L) in the placebo group (P=0.16). There was no statistically significant difference between groups in 30-day mortality, blood pressure, stroke, or major adverse cardiovascular event. CONCLUSIONS: Starting ivabradine preoperatively in elderly patients requiring acute surgery for fracture did not result in a statistically significant difference in the incidence of perioperative myocardial injury. There was no statistically significant difference in morbidity, mortality, or adverse events between treatment groups. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12616001634460p.

Angiography and optical coherence tomography derived shear stress: are they equivalent in my opinion?

Advances in image reconstruction using either single or multimodality imaging data provide increasingly accurate three-dimensional (3D) patient's arterial models for shear stress evaluation using computational fluid dynamics (CFD). We aim to evaluate the impacts on endothelial shear stress (ESS) derived from a simple image reconstruction using 3D-quantitative coronary angiography (3D-QCA) versus a multimodality reconstruction method using optical coherence tomography (OCT) in patients' vessels treated with bioresorbable scaffolds. Seven vessels at baseline and five-year follow-up of seven patients from a previous CFD investigation were retrospectively selected for a head-to-head comparison of angiography-derived versus OCT-derived ESS. 3D-QCA significantly underestimated the minimum stent area [MSA] (-2.38mm2) and the stent length (-1.46 mm) compared to OCT-fusion method reconstructions. After carefully co-registering the region of interest for all cases with a sophisticated statistical method, the difference in MSA measurements as well as the inability of angiography to visualise the strut footprint in the lumen surface have translated to higher angiography-derived ESS than OCT-derived ESS (1.76 Pa or 1.52 times for the overlapping segment). The difference in ESS widened with a more restricted region of interest (1.97 Pa or 1.63 times within the scaffold segment). Angiography and OCT offer two distinctive methods of ESS calculation. Angiography-derived ESS tends to overestimate the ESS compared to OCT-derived ESS. Further investigations into ESS analysis resolution play a vital role in adopting OCT-derived ESS.

An optical coherence tomography and endothelial shear stress study of a novel bioresorbable bypass graft.

Endothelial shear stress (ESS) plays a key role in the clinical outcomes in native and stented segments; however, their implications in bypass grafts and especially in a synthetic biorestorative coronary artery bypass graft are yet unclear. This report aims to examine the interplay between ESS and the morphological alterations of a biorestorative coronary bypass graft in an animal model. Computational fluid dynamics (CFD) simulation derived from the fusion of angiography and optical coherence tomography (OCT) imaging was used to reconstruct data on the luminal anatomy of a bioresorbable coronary bypass graft with an endoluminal "flap" identified during OCT acquisition. The "flap" compromised the smooth lumen surface and considerably disturbed the local flow, leading to abnormally low ESS and high oscillatory shear stress (OSI) in the vicinity of the "flap". In the presence of the catheter, the flow is more stable (median OSI 0.02384 versus 0.02635, p < 0.0001; maximum OSI 0.4612 versus 0.4837). Conversely, OSI increased as the catheter was withdrawn which can potentially cause back-and-forth motions of the "flap", triggering tissue fatigue failure. CFD analysis in this report provided sophisticated physiological information that complements the anatomic assessment from imaging enabling a complete understanding of biorestorative graft pathophysiology.

Numerical simulation of the blood flow through the coronary artery stenosis: Effects of varying eccentricity.

Blockages within arteries, called stenoses, are a common cause of coronary artery disease (CAD). Stenosis is a result of atherosclerotic plaque build-up limits blood flow and hence oxygen and nutrient supplies. Past studies on stenosed arterial flows often assumed stenosis to be axisymmetric in shape. However, medical imaging modalities have shown that stenoses in the coronary arteries are often asymmetric. To address it, an asymmetric stenosis is considered in the model which is based on common dimensions of the left anterior descending artery (LAD). The hemodynamic impacts are studied over a range of degrees of eccentricity (DoE) and degree of stenosis (DoS). Blood flow within the artery is analyzed by solving the incompressible Navier-Stokes equations with both resting and hyperemic flow rates. The wall shear stress (WSS), oscillatory shear index (OSI) and fractional flow reserve (FFR) are calculated. The eccentricity makes the flow deflect away from the model's centerline. Behavior of the deflected flow is significantly altered downstream of the stenosis. Transverse dimension of the recirculation zone grows with increasing DoE, while its longitudinal dimension mainly depends on DoS. Eccentricity also contributes to the development of secondary flow distal to the stenosis. Such complex flow behavior contributes to a further pressure loss and hence a significant change in FFR (<0.8). Calculated WSS and OSI indicate that in actual eccentric stenotic LAD the asymmetric remodeling is anticipated. Thus, consideration of the DoE, along with the DoS, could lead to better patient stratification.

Type 2 MI and Myocardial Injury in the Era of High-sensitivity Troponin.

Troponin has been the cornerstone of the definition of MI since its introduction to clinical practice. High-sensitivity troponin has allowed clinicians to detect degrees of myocardial damage at orders of magnitude smaller than previously and is challenging the definitions of MI, with implications for patient management and prognosis. Detection and diagnosis are no doubt enhanced by the greater sensitivity afforded by these markers, but perhaps at the expense of specificity and clarity. This review focuses on the definitions, pathophysiology, prognosis, prevention and management of type 2 MI and myocardial injury. The five types of MI were first defined in 2007 and were recently updated in 2018 in the fourth universal definition of MI. The authors explore how this pathophysiological classification is used in clinical practice, and discuss some of the unanswered questions in this era of availability of high-sensitivity troponin.

Non-Newtonian Endothelial Shear Stress Simulation: Does It Matter?

Patient-specific coronary endothelial shear stress (ESS) calculations using Newtonian and non-Newtonian rheological models were performed to assess whether the common assumption of Newtonian blood behavior offers similar results to a more realistic but computationally expensive non-Newtonian model. 16 coronary arteries (from 16 patients) were reconstructed from optical coherence tomographic (OCT) imaging. Pulsatile CFD simulations using Newtonian and the Quemada non-Newtonian model were performed. Endothelial shear stress (ESS) and other indices were compared. Exploratory indices including local blood viscosity (LBV) were calculated from non-Newtonian simulation data. Compared to the Newtonian results, the non-Newtonian model estimates significantly higher time-averaged ESS (1.69 (IQR 1.36)Pa versus 1.28 (1.16)Pa, p < 0.001) and ESS gradient (0.90 (1.20)Pa/mm versus 0.74 (1.03)Pa/mm, p < 0.001) throughout the cardiac cycle, under-estimating the low ESS (<1Pa) area (37.20 ± 13.57% versus 50.43 ± 14.16%, 95% CI 11.28-15.18, p < 0.001). Similar results were also found in the idealized artery simulations with non-Newtonian median ESS being higher than the Newtonian median ESS (healthy segments: 0.8238Pa versus 0.6618Pa, p < 0.001 proximal; 0.8179Pa versus 0.6610Pa, p < 0.001 distal; stenotic segments: 0.8196Pa versus 0.6611Pa, p < 0.001 proximal; 0.2546Pa versus 0.2245Pa, p < 0.001 distal) On average, the non-Newtonian model has a LBV of 1.45 times above the Newtonian model with an average peak LBV of 40-fold. Non-Newtonian blood model estimates higher quantitative ESS values than the Newtonian model. Incorporation of non-Newtonian blood behavior may improve the accuracy of ESS measurements. The non-Newtonian model also allows calculation of exploratory viscosity-based hemodynamic indices, such as local blood viscosity, which may offer additional information to detect underlying atherosclerosis.