Bend-insensitive fiber optic ultrasonic tracking probe for cardiovascular interventions.

BACKGROUND: Transesophageal echocardiography (TEE) is widely used to guide medical device placement in minimally invasive cardiovascular procedures. However, visualization of the device tip with TEE can be challenging. Ultrasonic tracking, enabled by an integrated fiber optic ultrasound sensor (FOUS) that receives transmissions from the TEE probe, is very well suited to improving device localization in this context. The problem addressed in this study is that tight deflections of devices such as a steerable guide catheter can result in bending of the FOUS beyond its specifications and a corresponding loss of ultrasound sensitivity. PURPOSE: A bend-insensitive FOUS was developed, and its utility with ultrasonic tracking of a steerable tip during TEE-based image guidance was demonstrated. METHODS: Fiberoptic ultrasound sensors were fabricated using both standard and bend insensitive single mode fibers and subjected to static bending at the distal end. The interference transfer function and ultrasound sensitivities were compared for both types of FOUS. The bend-insensitive FOUS was integrated within a steerable guide catheter, which served as an exemplar device; the signal-to-noise ratio (SNR) of tracking signals from the catheter tip with a straight and a fully deflected distal end were measured in a cardiac ultrasound phantom for over 100 frames. RESULTS: With tight bending at the distal end (bend radius < 10 mm), the standard FOUS experienced a complete loss of US sensitivity due to high attenuation in the fiber, whereas the bend-insensitive FOUS had largely unchanged performance, with a SNR of 47.7 for straight fiber and a SNR of 36.8 at a bend radius of 3.0 mm. When integrated into the steerable guide catheter, the mean SNRs of the ultrasonic tracking signals recorded with the catheter in a cardiac phantom were similar for straight and fully deflected distal ends: 195 and 163. CONCLUSION: The FOUS fabricated from bend-insensitive fiber overcomes the bend restrictions associated with the FOUS fabricated from standard single mode fiber, thereby enabling its use in ultrasonic tracking in a wide range of cardiovascular devices.

Treatment Strategies and Outcomes of Emergency Left Main Percutaneous Coronary Intervention.

Emergency percutaneous coronary intervention of the left main (LM ePCI) coronary artery necessitated by acute coronary syndrome is associated with a high risk of mortality. However, optimal treatment strategies and related outcomes remain undefined in this group. We undertook a multi-center, retrospective, observational cohort study of consecutive patients requiring LM ePCI between 2011 and 2018 and reported the coronary anatomy, treatment strategies, outcomes, and predictors of mortality. A total of 116 consecutive cases were included. Patients were predominantly male (85%) with a median age of 68.0 years; 12 patients (10%) had previous coronary artery bypass grafting. ST-elevation was noted in 76 (66%); 30 (26%) presented with an out-of-hospital cardiac arrest (OOHCA) and 47 (41%) with cardiogenic shock. The most frequent pattern of disease was Medina 1,1,1, seen in 59 patients (51%). The commonest revascularization strategy was provisional stenting (95 cases, 82%) with improved or thrombolysis in myocardial infarction 3 flow seen in 85 cases (73%). All-cause mortality was 35% at 30 days, rising to 58% at 5 years. Adverse predictors of 30-day mortality included presentation with cardiogenic shock (p = 0.018) and OOHCA (p = 0.020), whereas improved flow and/or thrombolysis in myocardial infarction 3 flow in both circumflex and left anterior descending artery afforded a better prognosis (p = 0.028). In conclusion, patients who underwent LM ePCI are a high-risk subgroup and commonly present with cardiogenic shock and OOHCA. Provisional stenting appears to be the preferred option with the successful restoration of coronary flow in most cases despite complex anatomy. High 30-day mortality is driven by the presence of cardiogenic shock, OOHCA, and failure to restore or improve coronary flow.

Morphological and Physiological Characteristics of Ruptured Plaques in Native Arteries and Neoatherosclerotic Segments: An OCT-Based and Computational Fluid Dynamics Study.

Background: Intravascular imaging has been used to assess the morphology of lesions causing an acute coronary syndrome (ACS) in native vessels (NV) and identify differences between plaques that ruptured (PR) and caused an event and those that ruptured without clinical manifestations. However, there is no data about the morphological and physiological characteristics of neoatherosclerotic plaques that ruptured (PR-NA) which constitute a common cause of stent failure. Methods: We retrospectively analyzed data from patients admitted with an acute myocardial infarction that had optical coherence tomography (OCT) imaging of the culprit vessel before balloon pre-dilation. OCT pullbacks showing PR were segmented at every 0.4 mm. The extent of the formed cavity, lipid and calcific tissue, thrombus, and macrophages were measured, and the fibrous cap thickness (FCT) and the incidence of micro-channels and cholesterol crystals were reported. These data were used to reconstruct a representative model of the native and neoatherosclerotic lesion geometry that was processed with computational fluid dynamics (CFD) techniques to estimate the distribution of the endothelial shear stress and plaque structural stress. Result: Eighty patients were included in the present analysis: 56 had PR in NV (PR-NV group) and 24 in NA segments (PR-NA group). The PR-NV group had a larger minimum lumen area (2.93 ± 2.03 vs. 2.00 ± 1.26 mm2, p = 0.015) but similar lesion length and area stenosis compared to PR-NA group. The mean FCT (186 ± 65 vs. 232 ± 80 µm, p = 0.009) and the lipid index was smaller (16.7 ± 13.8 vs. 25.9 ± 14.1, p = 0.008) while the of calcific index (8.3 ± 9.5 vs. 2.2 ± 1.6%, p = 0.002) and the incidence of micro-channels (41.4 vs. 12.5%, p = 0.013) was higher in the PR-NV group. Conversely, there was no difference in the incidence of cholesterol crystals, thrombus burden or the location of the rupture site between groups. CFD analysis revealed higher maximum endothelial shear stress (19.1 vs. 11.0 Pa) and lower maximum plaque structural stress (38.8 vs. 95.1 kPa) in the PR-NA compared to the PR-NV model. Conclusion: We reported significant morphological and physiological differences between culprit ruptured plaques in native and stented segments. Further research is needed to better understand the causes of these differences and the mechanisms regulating neoatherosclerotic lesion destabilization.

A patient-specific multi-modality abdominal aortic aneurysm imaging phantom.

PURPOSE: Multimodality imaging of the vascular system is a rapidly growing area of innovation and research, which is increasing with awareness of the dangers of ionizing radiation. Phantom models that are applicable across multiple imaging modalities facilitate testing and comparisons in pre-clinical studies of new devices. Additionally, phantom models are of benefit to surgical trainees for gaining experience with new techniques. We propose a temperature-stable, high-fidelity method for creating complex abdominal aortic aneurysm phantoms that are compatible with both radiation-based, and ultrasound-based imaging modalities, using low cost materials. METHODS: Volumetric CT data of an abdominal aortic aneurysm were acquired. Regions of interest were segmented to form a model compatible with 3D printing. The novel phantom fabrication method comprised a hybrid approach of using 3D printing of water-soluble materials to create wall-less, patient-derived vascular structures embedded within tailored tissue-mimicking materials to create realistic surrounding tissues. A non-soluble 3-D printed spine was included to provide a radiological landmark. RESULTS: The phantom was found to provide realistic appearances with intravascular ultrasound, computed tomography and transcutaneous ultrasound. Furthermore, the utility of this phantom as a training model was demonstrated during a simulated endovascular aneurysm repair procedure with image fusion. CONCLUSION: With the hybrid fabrication method demonstrated here, complex multimodality imaging patient-derived vascular phantoms can be successfully fabricated. These have potential roles in the benchtop development of emerging imaging technologies, refinement of novel minimally invasive surgical techniques and as clinical training tools.

Impact of COVID-19 pandemic on the management of nonculprit lesions in patients presenting with ST-elevation myocardial infarction: Outcomes from the pan-London heart attack centers.

BACKGROUND: The impact of COVID-19 on the diagnosis and management of nonculprit lesions remains unclear. OBJECTIVES: This study sought to evaluate the management and outcomes of patients with nonculprit lesions during the COVID-19 pandemic. METHODS: We conducted a retrospective observational analysis of consecutive primary percutaneous coronary intervention (PPCI) pathway activations across the heart attack center network in London, UK. Data from the study period in 2020 were compared with prepandemic data in 2019. The primary outcome was the rate of nonculprit lesion percutaneous coronary intervention (PCI) and secondary outcomes included major adverse cardiovascular events. RESULTS: A total of 788 patients undergoing PPCI were identified, 209 (60%) in 2020 cohort and 263 (60%) in 2019 cohort had nonculprit lesions (p = .89). There was less functional assessment of the significance of nonculprit lesions in the 2020 cohort compared to 2019 cohort; in 8% 2020 cohort versus 15% 2019 cohort (p = .01). There was no difference in rates of PCI for nonculprit disease in the 2019 and 2020 cohorts (31% vs 30%, p = .11). Patients in 2020 cohort underwent nonculprit lesion PCI sooner than the 2019 cohort (p < .001). At 6 months there was higher rates of unplanned revascularization (4% vs. 2%, p = .05) and repeat myocardial infarction (4% vs. 1%, p = .02) in the 2019 cohort compared to 2020 cohort. CONCLUSION: Changes to clinical practice during the COVID-19 pandemic were associated with reduced rates of unplanned revascularization and myocardial infarction at 6-months follow-up, and despite the pandemic, there was no difference in mortality, suggesting that it is not only safe but maybe more efficacious.

Challenges of antithrombotic therapy in the management of cardiovascular disease in patients with inherited bleeding disorders: A single-centre experience.

INTRODUCTION: Cardiovascular events in patients with inherited bleeding disorders are challenging to manage. The risk of bleeding secondary to antithrombotic treatment must be balanced against the risk of thrombosis secondary to haemostatic therapy. METHODS: Patients with inherited bleeding disorders with coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) or atrial fibrillation (AF) from a single centre (2010-2018) are included. RESULTS: A total of 11 patients undergoing CABG (n = 3), PCI (n = 5) or with AF (n = 3) and a diagnosis of haemophilia A (n = 8), haemophilia B (n = 1), factor XI deficiency (n = 1) and von Willebrand disease (n = 1) managed by a multidisciplinary team are reported. In patients undergoing CABG, factor levels were normalized for 7-10 days with trough levels of 70-80% with severe patients continuing high-dose factor prophylaxis (trough 20-30%) three weeks post-operatively with daily aspirin. In a patient with mild haemophilia A and an inhibitor, recombinant factor VIIa dosing was monitored with thromboelastometry. For PCI, a 3rd-generation drug-eluting stent with one month of dual antiplatelet therapy in addition to high-dose prophylaxis as needed was preferred. Patients with AF and severe haemophilia did not receive antithrombotic treatment, and a thrombin generation assay was used to guide heparin dosing in mild haemophilia. CONCLUSION: Our experience demonstrates the importance of interdisciplinary communication to identify strategies that decrease the risk of bleeding and thrombosis. The use of extended, increased intensity prophylaxis facilitated antiplatelet therapy. Global assays may help balance the intensity of haemostatic and antithrombotic treatment.

Wall shear stress estimated by 3D-QCA can predict cardiovascular events in lesions with borderline negative fractional flow reserve.

BACKGROUND AND AIMS: There is some evidence of the implications of wall shear stress (WSS) derived from three-dimensional quantitative coronary angiography (3D-QCA) models in predicting adverse cardiovascular events. This study investigates the efficacy of 3D-QCA-derived WSS in detecting lesions with a borderline negative fractional flow reserve (FFR: 0.81-0.85) that progressed and caused events. METHODS: In this retrospective cohort study, we identified 548 patients who had at least one lesion with an FFR 0.81-0.85 and complete follow-up data; 293 lesions (286 patients) with suitable angiographic characteristics were reconstructed using a dedicated 3D-QCA software and included in the analysis. In the reconstructed models blood flow simulation was performed and the value of 3D-QCA variables and WSS distribution in predicting events was examined. The primary endpoint of the study was the composite of cardiac death, target lesion related myocardial infarction or clinically indicated target lesion revascularization. RESULTS: During a median follow-up of 49.4 months, 37 events were reported. Culprit lesions had a greater area stenosis [(AS), 66.1% (59.5-72.3) vs 54.8% (46.5-63.2), p<0.001], smaller minimum lumen area [(MLA), 1.66 mm2 (1.45-2.30) vs 2.10 mm2 (1.69-2.70), p=0.011] and higher maximum WSS [9.0 Pa (5.10-12.46) vs 5.0 Pa (3.37-7.54), p < 0.001] than those that remained quiescent. In multivariable analysis, AS [hazard ratio (HR): 1.06, 95% confidence interval (CI): 1.03-1.10, p=0.001] and maximum WSS (HR: 1.08, 95% CI: 1.02-1.14, p=0.012) were the only independent predictors of the primary endpoint. Lesions with an increased AS (≥58.6%) that were exposed to high WSS (≥7.69Pa) were more likely to progress and cause events (27.8%) than those with a low AS exposed to high WSS (7.4%) or those exposed to low WSS that had increased (12.8%) or low AS (2.7%, p<0.001). CONCLUSIONS: This study for the first time highlights the potential value of 3D-QCA-derived WSS in detecting, among lesions with a borderline negative FFR, those that cause cardiovascular events.

Flexible and directional fibre optic ultrasound transmitters using photostable dyes.

All-optical ultrasound transducers are well-suited for use in imaging during minimally invasive surgical procedures. This requires highly miniaturised and flexible devices. Here we present optical ultrasound transmitters for imaging applications based on modified optical fibre distal tips which allow for larger transmitter element sizes, whilst maintaining small diameter proximal optical fibre. Three optical ultrasound transmitter configurations were compared; a 400 µm core optical fibre, a 200 µm core optical fibre with a 400 µm core optical fibre distal tip, and a 200 µm core optical fibre with a 400 µm core capillary distal tip. All the transmitters used a polydimethylsiloxane-dye composite material for ultrasound generation. The material comprised a photostable infra-red absorbing dye to provide optical absorption for the ultrasound transduction. The generated ultrasound beam profile for the three transmitters was compared, demonstrating similar results, with lateral beam widths <1.7 mm at a depth of 10 mm. The composite material demonstrates a promising alternative to previously reported materials, generating ultrasound pressures exceeding 2 MPa, with corresponding bandwidths ca. 30 MHz. These highly flexible ultrasound transmitters can be readily incorporated into medical devices with small lateral dimensions.

Optically Generated Ultrasound for Intracoronary Imaging.

Conventional intravascular ultrasound (IVUS) devices use piezoelectric transducers to electrically generate and receive US. With this paradigm, there are numerous challenges that restrict improvements in image quality. First, with miniaturization of the transducers to reduce device size, it can be challenging to achieve the sensitivities and bandwidths required for large tissue penetration depths and high spatial resolution. Second, complexities associated with manufacturing miniaturized electronic transducers can have significant cost implications. Third, with increasing interest in molecular characterization of tissue in-vivo, it has been challenging to incorporate optical elements for multimodality imaging with photoacoustics (PA) or near-infrared spectroscopy (NIRS) whilst maintaining the lateral dimensions suitable for intracoronary imaging. Optical Ultrasound (OpUS) is a new paradigm for intracoronary imaging. US is generated at the surface of a fiber optic transducer via the photoacoustic effect. Pulsed or modulated light is absorbed in an engineered coating on the fiber surface and converted to thermal energy. The subsequent temperature rise leads to a pressure rise within the coating, which results in a propagating ultrasound wave. US reflections from imaged structures are received with optical interferometry. With OpUS, high bandwidths (31.5 MHz) and pressures (21.5 MPa) have enabled imaging with axial resolutions better than 50 µm and at depths >20 mm. These values challenge those of conventional 40 MHz IVUS technology and show great potential for future clinical application. Recently developed nanocomposite coating materials, that are highly transmissive at light wavelengths used for PA and NIRS light, can facilitate multimodality imaging, thereby enabling molecular characterization.

COVID-19 pandemic and STEMI: pathway activation and outcomes from the pan-London heart attack group.

OBJECTIVES: To understand the impact of COVID-19 on delivery and outcomes of primary percutaneous coronary intervention (PPCI). Furthermore, to compare clinical presentation and outcomes of patients with ST-segment elevation myocardial infarction (STEMI) with active COVID-19 against those without COVID-19. METHODS: We systematically analysed 348 STEMI cases presenting to the PPCI programme in London during the peak of the pandemic (1 March to 30 April 2020) and compared with 440 cases from the same period in 2019. Outcomes of interest included ambulance response times, timeliness of revascularisation, angiographic and procedural characteristics, and in-hospital clinical outcomes RESULTS: There was a 21% reduction in STEMI admissions and longer ambulance response times (87 (62-118) min in 2020 vs 75 (57-95) min in 2019, p<0.001), but that this was not associated with a delays in achieving revascularisation once in hospital (48 (34-65) min in 2020 vs 48 (35-70) min in 2019, p=0.35) or increased mortality (10.9% (38) in 2020 vs 8.6% (38) in 2019, p=0.28). 46 patients with active COVID-19 were more thrombotic and more likely to have intensive care unit admissions (32.6% (15) vs 9.3% (28), OR 5.74 (95%CI 2.24 to 9.89), p<0.001). They also had increased length of stay (4 (3-9) days vs 3 (2-4) days, p<0.001) and a higher mortality (21.7% (10) vs 9.3% (28), OR 2.72 (95% CI 1.25 to 5.82), p=0.012) compared with patients having PPCI without COVID-19. CONCLUSION: These findings suggest that PPCI pathways can be maintained during unprecedented healthcare emergencies but confirms the high mortality of STEMI in the context of concomitant COVID-19 infection characterised by a heightened state of thrombogenicity.

Hydroxychloroquine use in COVID-19: is the risk of cardiovascular toxicity justified?

The outbreak of COVID-19 in Wuhan, China and its declaration as a global pandemic by WHO has left the medical community under significant pressure to rapidly identify effective therapeutic and preventative strategies. Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were found to be efficacious against SARS-CoV-2 when investigated in preliminary in vitro experiments. Reports of success in early clinical studies were widely publicised by news outlets, politicians and on social media. These results led several countries to approve the use of these drugs for the treatment of patients with COVID-19. Despite having reasonable safety profiles in the treatment of malaria and certain autoimmune conditions, both drugs are known to have potential cardiotoxic side effects. There is a high incidence of myocardial injury and arrhythmia reported with COVID-19 infection, and as such this population may be more susceptible to this side-effect profile. Studies to date have now demonstrated that in patients with COVID-19, these drugs are associated with significant QTc prolongation, as well as reports of ventricular arrhythmias. Furthermore, subsequent studies have failed to demonstrate clinical benefit from either drug. Indeed, clinical trials have also been stopped early due to safety concerns over HCQ. There is an urgent need for credible solutions to the global pandemic, but we argue that in the absence of high-quality evidence, there needs to be greater caution over the routine use or authorisation of drugs for which efficacy and safety is unproven.

All-Optical Rotational Ultrasound Imaging.

Miniaturised high-resolution imaging devices are valuable for guiding minimally invasive procedures such as vascular stent placements. Here, we present all-optical rotational B-mode pulse-echo ultrasound imaging. With this device, ultrasound transmission and reception are performed with light. The all-optical transducer in the probe comprised an optical fibre that delivered pulsed excitation light to an optical head at the distal end with a multi-walled carbon nanotube and polydimethylsiloxane composite coating. This coating was photoacoustically excited to generate a highly directional ultrasound beam perpendicular to the optical fibre axis. A concave Fabry-Pérot cavity at the distal end of an optical fibre, which was interrogated with a tuneable continuous-wave laser, served as an omnidirectional ultrasound receiver. The transmitted ultrasound had a -6 dB bandwidth of 31.3 MHz and a peak-to-peak pressure of 1.87 MPa, as measured at 1.5 mm from the probe. The receiver had a noise equivalent pressure <100 Pa over a 20 MHz bandwidth. With a maximum outer probe diameter of 1.25 mm, the probe provided imaging with an axial resolution better than 50 µm, and a real-time imaging rate of 5 frames per second. To investigate the capabilities of the probe, intraluminal imaging was performed in healthy swine carotid arteries. The results demonstrate that the all-optical probe is viable for clinical rotational ultrasound imaging.

Micron resolution, high-fidelity three-dimensional vascular optical imaging phantoms.

Microscopic and mesoscale optical imaging techniques allow for three-dimensional (3-D) imaging of biological tissue across millimeter-scale regions, and imaging phantom models are invaluable for system characterization and clinical training. Phantom models that replicate complex 3-D geometries with both structural and molecular contrast, with resolution and lateral dimensions equivalent to those of imaging techniques (<20 µm), have proven elusive. We present a method for fabricating phantom models using a combination of two-photon polymerization (2PP) to print scaffolds, and microinjection of tailored tissue-mimicking materials to simulate healthy and diseased tissue. We provide a first demonstration of the capabilities of this method with intravascular optical coherence tomography, an imaging technique widely used in clinical practice. We describe the design, fabrication, and validation of three types of phantom models: a first with subresolution wires (5- to 34-µm diameter) arranged circumferentially, a second with a vessel side-branch, and a third containing a lipid inclusion within a vessel. Silicone hybrid materials and lipids, microinjected within a resin framework created with 2PP, served as tissue-mimicking materials that provided realistic optical scattering and absorption. We demonstrate that optical phantom models made with 2PP and microinjected tissue-mimicking materials can simulate complex anatomy and pathology with exquisite detail.

All-optical dual photoacoustic and optical coherence tomography intravascular probe.

Intravascular imaging in percutaneous coronary interventions can be an invaluable tool in the treatment of coronary artery disease. It is of significant interest to provide molecular imaging contrast that is complementary to structural contrast provided by optical coherence tomography (OCT) and intravascular ultrasound imaging (IVUS). In this study, we developed a dual-modality intravascular imaging probe comprising a commercial OCT catheter and a high sensitivity fiber optic ultrasound sensor, to provide both photoacoustic (PA) and OCT imaging. With PA imaging, the lateral resolution varied from 18 µm to 40 µm; the axial resolution was consistently in the vicinity of 45 µm. We demonstrated the clinical potential of the probe with 2-D circumferential PA and OCT imaging, and with multispectral PA imaging.