Effect of remote ischaemic conditioning on infarct size and remodelling in ST-segment elevation myocardial infarction patients: the CONDI-2/ERIC-PPCI CMR substudy.

The effect of limb remote ischaemic conditioning (RIC) on myocardial infarct (MI) size and left ventricular ejection fraction (LVEF) was investigated in a pre-planned cardiovascular magnetic resonance (CMR) substudy of the CONDI-2/ERIC-PPCI trial. This single-blind multi-centre trial (7 sites in UK and Denmark) included 169 ST-segment elevation myocardial infarction (STEMI) patients who were already randomised to either control (n = 89) or limb RIC (n = 80) (4 × 5 min cycles of arm cuff inflations/deflations) prior to primary percutaneous coronary intervention. CMR was performed acutely and at 6 months. The primary endpoint was MI size on the 6 month CMR scan, expressed as median and interquartile range. In 110 patients with 6-month CMR data, limb RIC did not reduce MI size [RIC: 13.0 (5.1-17.1)% of LV mass; control: 11.1 (7.0-17.8)% of LV mass, P = 0.39], or LVEF, when compared to control. In 162 patients with acute CMR data, limb RIC had no effect on acute MI size, microvascular obstruction and LVEF when compared to control. In a subgroup of anterior STEMI patients, RIC was associated with lower incidence of microvascular obstruction and higher LVEF on the acute scan when compared with control, but this was not associated with an improvement in LVEF at 6 months. In summary, in this pre-planned CMR substudy of the CONDI-2/ERIC-PPCI trial, there was no evidence that limb RIC reduced MI size or improved LVEF at 6 months by CMR, findings which are consistent with the neutral effects of limb RIC on clinical outcomes reported in the main CONDI-2/ERIC-PPCI trial.

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.

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Duration of type 2 diabetes mellitus and systolic blood pressure as determinants of severity of coronary stenosis and adverse events in an asymptomatic diabetic population: PROCEED study.

BACKGROUND: Evidence from imaging studies suggests a high prevalence of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, there are no criteria for initiating screening for CAD in this population. The current study investigated whether clinical and demographic characteristics can be used to predict significant CAD in patients with T2DM. METHODS: Computed tomography coronary angiography (CTCA) and laboratory assessments were performed in 259 patients diagnosed with T2DM attending clinics in Northwest London, UK. Coronary artery calcium (CAC) was calculated during CTCA. Significant plaque was defined as one causing more than 50% luminal stenosis. Associations between groups and variables were evaluated using Student's t test, Chi-square tests and univariate and multivariate regression analysis. P < 0.05 was considered statistically significant. RESULTS: Among patients with a median duration of T2DM of 13 years and a mean age of 62.0 years, median CAC score was 105.91 Agatston Units. In a multivariate analyses, duration of diabetes, CAC score and the presence and number of coronary artery plaques and presence of significant plaque were significant predictors of cardiovascular adverse events. Systolic blood pressure (SBP) had borderline significance as a predictor of cardiovascular events (p = 0.05). In a receiver operating characteristic curve (ROC) analysis, duration of diabetes of > 10.5 years predicted significant CAD (sensitivity, 75.3%; specificity 48.2%). Area under the ROC curve was 0.67 when combining duration of T2DM > 10.5 years and SBP of > 139 mm Hg. Adverse cardiovascular events after a median follow-up of 22.8 months were also significantly higher in those with duration of T2DM > 10.5 years and SBP > 140 mm Hg (log rank p = 0.02 and 0.009, respectively). CONCLUSIONS: Routine screening for CAD using CTCA should be considered for patients with a diagnosis of T2DM for > 10.5 years and SBP > 140 mm Hg. Trial registration Clinicaltrials.gov identifier: NCT02109835, 10 April 2014 (retrospectively registered).

Prospective comparison of novel dark blood late gadolinium enhancement with conventional bright blood imaging for the detection of scar.

BACKGROUND: Conventional bright blood late gadolinium enhancement (bright blood LGE) imaging is a routine cardiovascular magnetic resonance (CMR) technique offering excellent contrast between areas of LGE and normal myocardium. However, contrast between LGE and blood is frequently poor. Dark blood LGE (DB LGE) employs an inversion recovery T2 preparation to suppress the blood pool, thereby increasing the contrast between the endocardium and blood. The objective of this study is to compare the diagnostic utility of a novel DB phase sensitive inversion recovery (PSIR) LGE CMR sequence to standard bright blood PSIR LGE. METHODS: One hundred seventy-two patients referred for clinical CMR were scanned. A full left ventricle short axis stack was performed using both techniques, varying which was performed first in a 1:1 ratio. Two experienced observers analyzed all bright blood LGE and DB LGE stacks, which were randomized and anonymized. A scoring system was devised to quantify the presence and extent of gadolinium enhancement and the confidence with which the diagnosis could be made. RESULTS: A total of 2752 LV segments were analyzed. There was very good inter-observer correlation for quantifying LGE. DB LGE analysis found 41.5% more segments that exhibited hyperenhancement in comparison to bright blood LGE (248/2752 segments (9.0%) positive for LGE with bright blood; 351/2752 segments (12.8%) positive for LGE with DB; p < 0.05). DB LGE also allowed observers to be more confident when diagnosing LGE (bright blood LGE high confidence in 154/248 regions (62.1%); DB LGE in 275/324 (84.9%) regions (p < 0.05)). Eighteen patients with no bright blood LGE were found to have had DB LGE, 15 of whom had no known history of myocardial infarction. CONCLUSIONS: DB LGE significantly increases LGE detection compared to standard bright blood LGE. It also increases observer confidence, particularly for subendocardial LGE, which may have important clinical implications.

Agreement of wall shear stress distribution between two core laboratories using three-dimensional quantitative coronary angiography.

Wall shear stress (WSS) estimated in models reconstructed from intravascular imaging and 3-dimensional-quantitative coronary angiography (3D-QCA) data provides important prognostic information and enables identification of high-risk lesions. However, these analyses are time-consuming and require expertise, limiting WSS adoption in clinical practice. Recently, a novel software has been developed for real-time computation of time-averaged WSS (TAWSS) and multidirectional WSS distribution. This study aims to examine its inter-corelab reproducibility. Sixty lesions (20 coronary bifurcations) with a borderline negative fractional flow reserve were processed using the CAAS Workstation WSS prototype to estimate WSS and multi-directional WSS values. Analysis was performed by two corelabs and their estimations for the WSS in 3 mm segments across each reconstructed vessel was extracted and compared. In total 700 segments (256 located in bifurcated vessels) were included in the analysis. A high intra-class correlation was noted for all the 3D-QCA and TAWSS metrics between the estimations of the two corelabs irrespective of the presence (range: 0.90-0.92) or absence (range: 0.89-0.90) of a coronary bifurcation, while the ICC was good-moderate for the multidirectional WSS (range: 0.72-0.86). Lesion level analysis demonstrated a high agreement of the two corelabls for detecting lesions exposed to an unfavourable haemodynamic environment (WSS > 8.24 Pa, κ = 0.77) that had a high-risk morphology (area stenosis > 61.3%, κ = 0.71) and were prone to progress and cause events. The CAAS Workstation WSS enables reproducible 3D-QCA reconstruction and computation of WSS metrics. Further research is needed to explore its value in detecting high-risk lesions.

Superior outcome with direct catheter laboratory access vs ED-activated primary percutaneous coronary intervention.

AIMS: Admitting patients directly to a heart attack center (HAC) catheter laboratory for primary percutaneous coronary intervention (PPCI) bypassing the emergency department (ED) might be beneficial in delivering treatment of ST-elevation myocardial infarction with superior outcome. METHODS: In this analysis, the clinical outcome of service redesign of the PPCI pathway from ED triggered to a direct catheter laboratory HAC access was assessed in 361 consecutive patients with ST-elevation myocardial infarction treated with a PPCI. RESULTS: A total of 200 patients were admitted via the ED, and 161 were admitted directly to the HAC. Door-to-balloon times and call-to-balloon times were significantly better in the HAC group (median [interquartile range] door-to-balloon times and call-to-balloon times were 39 [26, 53] and 106 [91, 132] minutes, respectively) in comparison with the ED group (82 [49,120; P < .0001] and 130 [103, 164] minutes, respectively [P = .0005]). A nonsignificant trend to a lower 30-day (5% in the HAC group and 6% in the ED group) and 17-month (8% in HAC group and 11% in ED group) mortality was seen in the HAC group (P = .63). Composite end point analysis of left ventricular ejection fraction less than 50%, thrombolysis in myocardial infarction grades 0 and 1, and myocardial blush scores 0 and 1 showed that a significantly higher number of patients in the ED group experienced at least 1 of the composite events in comparison with the patients in the HAC group (P = .01). CONCLUSION: A direct-access catheter laboratory (HAC) model of PPCI bypassing the ED should be the favored approach to service delivery with superior outcome.

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.

Apical hypertrophic cardiomyopathy associated with circumflex to left ventricular fistulae: a case report of two rare subtypes of rare conditions occurring together.

BACKGROUND: Coronary arterial fistulae are rare yet have been associated with hypertrophic cardiomyopathy (HCM). We present a patient who was found to have a left circumflex (LCx) to left ventricular (LV) fistula in combination with apical HCM. CASE SUMMARY: A 72-year-old female presented with syncope after exercise. She sustained facial injuries including fracture of her nasal bones. There were no previous episodes, no cardiac history, and she denied chest pain or anginal symptoms. Electrocardiogram showed sinus rhythm with T-wave inversion throughout the chest leads. Echocardiography suggested apical HCM with hypertrophy of the LV apex but good systolic function. This was confirmed on cardiac magnetic resonance imaging with a characteristically spade-shaped LV cavity. Coronary angiography demonstrated a distal LCx to LV fistula from the apical hypertrophy but no coronary artery disease. She was started on beta-blockers and has had no further episodes, remaining well. DISCUSSION: Coronary fistulae are present in 0.002% of the population but clinical outcomes are poorly understood. The majority are asymptomatic but anginal chest pains can occur through the 'coronary steal' phenomenon. Apical HCM is a subtype of HCM characterized by spade-shaped LV cavity obliteration. It is unclear whether the association between fistulae and HCM occur because of the increased vascularization and fibrosis associated with HCM or whether congenital malformation leads to hypertrophy. Both can produce a constellation of cardiac symptoms. Our patient has the previously unreported combination of apical HCM and an LCx fistula; two rarer subtypes of rare conditions appearing together.

Association of Epicardial Fat Volume With the Extent of Coronary Atherosclerosis and Cardiovascular Adverse Events in Asymptomatic Patients With Diabetes.

Epicardial adipose tissue has a paracrine effect, enhancing coronary artery atherosclerotic plaque development. This study evaluated epicardial fat volume (EFV), adipokines, coronary atherosclerosis, and adverse cardiovascular events in a cohort of asymptomatic patients with type 2 diabetes mellitus (T2DM). Epicardial fat volume was calculated using data from computed tomography coronary angiograms. Adipokines and inflammatory cytokines were also assayed and correlated with EFV. Epicardial fat volume was also assessed as a predictor of coronary artery calcium (CAC) score, number of coronary artery plaques, and significant plaque (>50% luminal stenosis). Data from the EFV analysis were available for 221 (85.7%) participants. Median EFV was 97.4 cm3, mean body mass index was 28.1 kg/m2, and mean duration of T2DM was 13 years. Statistically significant, but weak, correlations were observed between several adipokines, inflammatory cytokines, and EFV. Epicardial fat volume was a significant univariate (P = .01), but not multivariate, predictor of the number of coronary plaques, but not of CAC score or significant plaque. After a mean follow-up of 22.8 months, 12 adverse cardiovascular events were reported, exclusively in participants with EFV >97.4 cm3. Epicardial fat volume has limited utility as a marker of coronary artery plaque in patients with T2DM and is weakly correlated with adipokine expression.

Risks and benefits of percutaneous coronary intervention in spontaneous coronary artery dissection.

OBJECTIVE: To investigate percutaneous coronary intervention (PCI) practice in an international cohort of patients with spontaneous coronary artery dissection (SCAD). To explore factors associated with complications and study angiographic and longer term outcomes. METHODS: SCAD patients (n=215, 94% female) who underwent PCI from three national cohort studies were investigated and compared with a matched cohort of conservatively managed SCAD patients (n=221). RESULTS: SCAD-PCI patients were high risk at presentation with only 8.8% undergoing PCI outside the context of ST-elevation myocardial infarction/cardiac arrest, thrombolysis in myocardial infarction (TIMI) 0/1 flow or proximal dissections. PCI complications occurred in 38.6% (83/215), with 13.0% (28/215) serious complications. PCI-related complications were associated with more extensive dissections (multiple vs single American Heart Association coronary segments, OR 1.9 (95% CI: 1.06-3.39),p=0.030), more proximal dissections (proximal diameter per mm, OR 2.25 (1.38-3.67), p=0.001) and dissections with no contrast penetration of the false lumen (Yip-Saw 2 versus 1, OR 2.89 (1.12-7.43), p=0.028). SCAD-PCI involved long lengths of stent (median 46mm, IQR: 29-61mm). Despite these risks, SCAD-PCI led to angiographic improvements in those with reduced TIMI flow in 84.3% (118/140). Worsening TIMI flow was only seen in 7.0% (15/215) of SCAD-PCI patients. Post-PCI major adverse cardiovascular and cerebrovascular events (MACCE) and left ventricular function outcomes were favourable. CONCLUSION: While a conservative approach to revascularisation is favoured, SCAD cases with higher risk presentations may require PCI. SCAD-PCI is associated with longer stent lengths and a higher risk of complications but leads to overall improvements in coronary flow and good medium-term outcomes in patients.

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.

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.

Acute changes in cardiac structural and tissue characterisation parameters following haemodialysis measured using cardiovascular magnetic resonance.

In patients with chronic kidney disease (CKD), reverse left ventricular (LV) remodelling, including reduction in LV mass, can be observed following long-term haemodialysis (HD) and has been attributed to regression of LV hypertrophy. However, LV mass can vary in response to changes in myocyte volume, edema, or fibrosis. The aims of this study were to investigate the acute changes in structural (myocardial mass and biventricular volumes) and tissue characterization parameters (native T1 and T2) following HD using cardiovascular magnetic resonance (CMR). Twenty-five stable HD patients underwent non-contrast CMR including volumetric assessment and native T1 and T2 mapping immediately pre- and post-HD. The mean time between the first and second scan was 9.1 ± 1.1 hours and mean time from completion of dialysis to the second scan was 3.5 ± 1.3 hours. Post-HD, there was reduction in LV mass (pre-dialysis 98.9 ± 36.9 g/m2 vs post-dialysis 93.3 ± 35.8 g/m2, p = 0.003), which correlated with change in body weight (r = 0.717, p < 0.001). Both native T1 and T2 reduced significantly following HD (Native T1: pre-dialysis 1085 ± 43 ms, post-dialysis 1072 ± 43 ms; T2: pre-dialysis 53.3 ± 3.0 ms, post-dialysis 51.8 ± 3.1 ms, both p < 0.05). These changes presumably reflect acute reduction in myocardial water content rather than regression of LV hypertrophy. CMR with multiparametric mapping is a promising tool to assess the cardiac changes associated with HD.

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.

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.

Myocardial Edema and Prognosis in Amyloidosis.

BACKGROUND: Prognosis in light-chain (AL) and transthyretin (ATTR) amyloidosis is influenced by cardiac involvement. ATTR amyloidosis has better prognosis than AL amyloidosis despite more amyloid infiltration, suggesting additional mechanisms of damage in AL amyloidosis. OBJECTIVES: The aim of the study was to assess the presence and prognostic significance of myocardial edema in patients with amyloidosis. METHODS: The study recruited 286 patients: 100 with systemic AL amyloidosis, 163 with cardiac ATTR amyloidosis, 12 with suspected cardiac ATTR amyloidosis (grade 1 on 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid), 11 asymptomatic individuals with amyloidogenic TTR gene mutations, and 30 healthy volunteers. All subjects underwent cardiovascular magnetic resonance with T1 and T2 mapping and 16 underwent endomyocardial biopsy. RESULTS: Myocardial T2 was increased in amyloidosis with the degree of elevation being highest in untreated AL patients (untreated AL amyloidosis 56.6 ± 5.1 ms; treated AL amyloidosis 53.6 ± 3.9 ms; ATTR amyloidosis 54.2 ± 4.1 ms; each p < 0.01 compared with control subjects: 48.9 ± 2.0 ms). Left ventricular (LV) mass and extracellular volume fraction were higher in ATTR amyloidosis compared with AL amyloidosis while LV ejection fraction was lower (p < 0.001). Histological evidence of edema was present in 87.5% of biopsy samples ranging from 5% to 40% myocardial involvement. Using Cox regression models, myocardial T2 predicted death in AL amyloidosis (hazard ratio: 1.48; 95% confidence interval: 1.20 to 1.82) and remained significant after adjusting for extracellular volume fraction and N-terminal pro-B-type natriuretic peptide (hazard ratio: 1.32; 95% confidence interval: 1.05 to 1.67). CONCLUSIONS: Myocardial edema is present in cardiac amyloidosis by histology and cardiovascular magnetic resonance T2 mapping. T2 is higher in untreated AL amyloidosis compared with treated AL and ATTR amyloidosis, and is a predictor of prognosis in AL amyloidosis. This suggests mechanisms additional to amyloid infiltration contributing to mortality in amyloidosis.

Superior long term outcome associated with native vessel versus graft vessel PCI following secondary PCI in patients with prior CABG.

BACKGROUND: Secondary percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass graft surgery is increasingly common. Graft vessel PCI has higher rates of adverse events compared with native coronary vessel PCI. AIM: To investigate the clinical outcomes of patients with prior CABG who underwent secondary PCI of either a graft vessel (GV), a native coronary vessel (NV) or both graft and native (NG) vessels. METHODS: 220 patients (84% male) who underwent PCI in our institution to either GV (n=89), NV (n=103) or both GV and NV (NG group) (n=28) were studied. The study population underwent 378 procedures (GV group; n=126, NV group; n=164 and NG group; n=88). Median follow up was for 36months [range 2-75months]. RESULTS: Target vessel revascularisation (TVR) occurred in 12.5% of the GV group and 3.6% in the NV group [p=0.0004], and was predominantly due to in-stent restenosis. Patients who had PCI due to TVR were more likely to suffer from diabetes and peripheral vascular disease. History of chronic renal failure was associated with higher risk (HR 2.21, p=0.005) whereas preserved left ventricular ejection fraction (LVEF) with lower risk (HR 0.17, p=0.0007) of death. The median survival (interval between CABG and end of follow-up period) was lower in the GV compared with the NV group (315 vs 372months p=0.005). CONCLUSION: This registry demonstrates inferior long term outcome for patients undergoing secondary PCI of GV versus NV. Where possible, a strategy of NV rather than GV target PCI should be considered in patients with prior CABG. CONDENSED ABSTRACT: Secondary PCI in patients with prior CABG surgery is increasingly common. Graft vessel PCI has inferior outcomes with high rates of restenosis and occlusion compared with native coronary vessel PCI. We studied the clinical outcomes of 220 patients with prior CABG who underwent secondary PCI to either a graft vessel (GV), a native coronary vessel (NV) or both graft and native (NG) vessels. Target vessel revascularisation was 5 times higher in the GV compared with the NV group. History of CRF and impaired left ventricular function were associated with higher risk of death. We also found that the median survival (interval between CABG and end of follow-up period) was better in the NV group compared with GV group. This registry study demonstrates inferior long term outcome for patients undergoing secondary PCI of GV. A strategy of NV rather than GV target PCI should be considered in patients with prior CABG.

Microparticles and their role in coronary artery disease.

Despite significant advances in prevention, medical and interventional management, coronary artery disease (CAD) remains the leading cause of death worldwide. Although the number of people being diagnosed with CAD has plateaued in the western world, it is projected to increase significantly in the developing world reaching epidemic proportions, particularly in South Asia. To better stratify the risk of developing and suffering a cardiovascular event due to CAD, not only plasma biomarkers relating to disease burden but also disease activity in CAD are needed; this will allow targeting of appropriate management to high-risk patients for acute events. Over the last twenty years, data have emerged showing the role of sub-micron vesicles called microparticles (MPs) in the pathogenesis of formation and evolution of atherosclerotic plaques causing either stable angina (SA) or acute coronary syndromes (ACS). Herein we provide an overview of our current knowledge of MP formation, composition and possible mechanisms through which they could be contributing to CAD. We also reviewed currently available methods and their limitations in quantifying MPs and in determining their functional aspects. Role of various treatments ranging from dietary substitutes to oral medicines and intravenous medications to mechanistic procedures such as hemofiltration are elaborated. Although evidence implicating the role of MPs in CAD are mounting large scale prospective studies are still lacking and are the need of the hour prior to establishing the use of MPs as biomarkers for the early detection of CAD and its progression.

Microparticles in acute coronary syndrome.

BACKGROUND: Emerging evidence supports the role of cell-derived microparticles (MPs) in the pathophysiology of acute coronary syndrome (ACS). OBJECTIVES: To explore the relationship between coronary and systemic MP levels, investigate the correlation between MPs, inflammatory markers and Troponin T in patients with ACS. METHODS: Thirty seven patients with ACS scheduled for percutaneous coronary interventions (PCI) were studied. Eleven patients with stable angina (SA) were included as a control group. AnnexinV+MPs (AnV+MPs) and activated platelet-monocyte aggregates (PMA) from right atrium (RA) and culprit coronary artery (CO) distal to culprit lesion were measured using flow cytometry. High sensitivity C-reactive protein (CRP), Interleukin - 6 (IL-6), tumour necrosis factor - α (TNF-α), serum amyloid A (SAA) and Troponin T were assayed. RESULTS: Total and cell specific AnV+MP expression were higher in the ACS group in both the CO and RA, with greater levels detected in the CO. Platelet activation showed positive correlation with Troponin-T and platelet MP in both CO and RA of the ACS group (r=0.4 for both; p=0.04 & p=0.03 respectively). Inflammatory markers levels did not differ between the ACS and SA patients. CONCLUSIONS: Elevated coronary and systemic MP levels and positive correlation of platelet activation with Troponin-T and platelet MPs suggest a pathogenic role for MPs in ACS.