We were interested to read Olesen et al.'s1 recent article, which describes the dose-dependent relationship between post-operative serum C-reactive protein (CRP) levels and development of post-operative atrial fibrillation (POAF) in patients who underwent coronary artery bypass graft surgery. Results showed a statistically significant difference (P < 0.0001) between the proportion of patients with POAF in the first serum CRP quartile (24.5% in CRP ≤90 mg/L) and fourth quartile (35.1% in CRP >175 mg/L). We commend the authors for their efforts and would like to draw a few useful comparisons between their study and similar studies that add additional weight to their findings. In Tanaka et al.'s2 prospective case–control study, an elevated serum CRP level in patients at baseline was found to correlate with an increased risk of developing AF. The crude incidence rate of AF per 1000 person-years increased from 0.6 for the lowest CRP...
Intravascular (IV) imaging in percutaneous coronary interventions can be invaluable to treat coronary artery disease, to facilitate decision making and to guide stent placement. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are both established IV imaging modalities. However, achieving contrast for specific structures such as lipid plaques can be challenging; with OCT, visualisation is typically limited to tissue depths less than 2 mm. Photoacoustic (PA) imaging provides contrast that is complementary to those of IVUS and OCT, and with previous demonstrations, visualisation of lipid plaques at depths greater than 4 mm has been achieved. In this study, we developed an intravascular PA probe that comprises a commercial OCT catheter and a high sensitivity miniature fibre optic ultrasound sensor with a Fabry-Pérot cavity. This probe, which can provide both PA imaging and OCT, had a maximum width of 1.2 mm. The PA excitation sources included both pulsed and modulated lasers at different wavelengths. The omni-directionality of the US sensor allowed for three-dimensional PA images. The PA-OCT probe was characterised using a series of resolution phantoms, including fine carbon fibres. It was found that with PA imaging, the probe can provide a lateral resolution better than 25 µm and an axial resolution better than 100 µm at the optical focus. Co-registered PA and OCT images of blood vessels ex-vivo with stents and lipid injections were acquired. We conclude that PA imaging with OCT catheters is viable and that it has strong potential to guide clinical interventions.
We report the development and characterisation of highly miniaturised fibre-optic sensors for simultaneous pressure and temperature measurement, and a compact interrogation system with a high sampling rate. The sensors, which have a maximum diameter of 250 µm, are based on multiple low-finesse optical cavities formed from polydimethylsiloxane (PDMS), positioned at the distal ends of optical fibres, and interrogated using phase-resolved low-coherence interferometry. At acquisition rates of 250 Hz, temperature and pressure changes of 0.0021 °C and 0.22 mmHg are detectable. An in vivo experiment demonstrated that the sensors had sufficient speed and sensitivity for monitoring dynamic physiological pressure waveforms. These sensors are ideally suited to various applications in minimally invasive surgery, where diminutive lateral dimensions, high sensitivity and low manufacturing complexities are particularly valuable.
Assessment of hyperaemia during adenosine stress CMR remains a clinical challenge with lack of a gold standard marker of adequate stress. Multiple parameters including the splenic switch off (SSO) sign, heart rate response (HRR) and blood pressure response (BPR) are used in clinical practice. Perfusion mapping provides a pixelwise representation of myocardial blood flow (MBF), allowing for measurement of MBF at a regional level. This may provide an alternative tool for assessment of hyperaemia.
Objectives
To validate the use of stress MBF for assessment of hyperaemic response and compare this to currently used clinical markers.
Methods
In total, 216 subjects were recruited. This included 3 cohorts: 1) Derivation cohort (22 healthy volunteers) to identify a stress MBF threshold value representative of the normal minimum response to adenosine; 2) Validation cohort (37 patients with suspected coronary disease) who underwent stress CMR and invasive coronary physiological assessment on the same day, to validate the stress MBF threshold value against invasive markers of hyperaemia; 3) Clinical cohort (159 patients undergoing clinically-indicated adenosine stress CMR) to assess the presence of stress MBF-defined hyperaemia and other physiological markers of hyperaemia (SSO, HHR and BPR).
Results
From the derivation cohort, maximum stress MBF (SMBFmax) >1.43 ml/g/min was derived as the threshold value of hyperaemia (defined as 1.96 standard deviations below the sample mean of lowest stress MBF values). This threshold was tested in the validation cohort: 100% of patients with invasive evidence of hyperaemia demonstrated SMBFmax >1.43 ml/g/min, 81% had SSO and 81% had HRR >10 bpm. Of the clinical cohort, 93% had hyperaemia defined by SMBFmax compared to 71% using SSO and 81% using HRR. SMBFmax was no different in those with or without SSO (2.58±0.89 ml/g/min vs 2.54±1.04 ml/g/min, p=0.84) but those with HRR had significantly higher SMBFmax (2.69 ml/g/min vs 1.95 ml/g/min, p<0.001). HRR >16 bpm was able to predict SMBFmax >1.43 ml/g/min with sensitivity 63% and specificity 91% (AUC 0.87, p<0.001) and performed better than SSO (AUC 0.62, p<0.001 for comparison of methods).
Conclusion
Adenosine-induced increase in MBF measured using perfusion mapping is accurate for the confirmation of hyperaemia during stress CMR studies and is superior to traditional, clinically used markers of adequate stress.
Abstract Background Antiretroviral therapy (ART) has dramatically improved the prognosis in PLWH with survival nearing that of HIV negative people. PLWH may develop significant comorbidities as they age including cardiovascular disease (CVD) such as myocardial infarction, sudden cardiac death, heart failure, as well as subclinical evidence of myocardial inflammation. Overall, ART treated patients are at an increased CVD risk with some studies quoting a 2.2 fold relative risk. Aim To assess the incidence of functional, structural and tissue characterisation changes in PLWH using CMR with multiparametric mapping Methods 39 PLWH (34 men, mean age 55.8±10.9, mean duration of HIV 17.8±9.29 years) and 29 healthy volunteers (20 men, mean age 45.1±8.3) underwent CMR with late gadolinium enhancement (LGE) imaging, T1 and T2 mapping. Results Of PLWH, only 7 scans (18%) were normal. LV ejection fraction was significantly lower and LV mass significantly higher compared to controls. Native T1, a marker of diffuse fibrosis or increased myocardial water content was no different between the groups. T2, a more specific marker of myocardial oedema, was elevated in PLWH. Sixteen PLWH (41%) had evidence of LGE including 8 with an ischaemic pattern (7 sub-endocardial and one transmural) and 8 with a non-ischaemic pattern (5 with mid-wall enhancement and 3 with RV insertion point LGE. No controls had evidence of LGE. Student t-Test: PLWH versus controls PLWH (n=39) Control (n=29) P-value LVEF (%) 59±15 67±5 <0.01 iLVM 79±24 56±13 <0.01 Native T1 (ms) 1021±52 1001±41 0.116 T2 (ms) 48±2 46±2 <0.05 LGE 16 (41%) 0 (0%) <0.001 LVEF (%) = Left Ventricular Ejection Fraction; iLVM = Indexed Left Ventricular Mass (g/m2); LGE = Late Gadolinium Enhancement. Conclusion This study identifies a number of cardiac changes associated with HIV and prolonged treatment with ART. The elevated LV mass may be associated with hypertension, commonly found in PLWH. The elevated myocardial T2 compared to controls may be due to chronic inflammation associated to prolonged HIV exposure. There was no evidence of diffuse fibrosis but focal areas of non-ischaemic scar were a common finding which may relate to previous myocarditis or HIV-related cardiomyopathy. A fifth of PLWH also had evidence of previous myocardial infarction. We propose to image asymptomatic PLWH to further classify, diagnose and treat a vulnerable group of patients who are now described as having a normal life expectancy.
Human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) was traditionally associated with severe heart failure, pulmonary hypertension and myocarditis but this is rarely seen following the advent of antiretroviral therapy (ART). Previous studies in asymptomatic people living with HIV (PLWH) have revealed a high burden of cardiovascular disease (CVD), and subclinical myocardial inflammation as detected by cardiac magnetic resonance imaging (CMR). The H-ART to Heart study was designed to assess the prevalence of CVD in PLWH. In this sub-study, we aim to assess bio-markers, structural and functional cardiac changes associated with HIV using CMR.
Methods
In this cross-sectional study, we recruited asymptomatic Caucasian men who have sex with men (MSM) diagnosed with HIV > 10yrs ago, aged 35-55 years, with undetectable viral loads on ART. They were compared to HIV-negative age and ethnicity MSM matched controls. Those with Q-Risk3 CVD risk factors (hypertension, hyperlipidaemia, diabetes, smoking, inflammatory arthritis, depression, severe mental illness) or hepatitis co-infection were excluded. Assessments included blood pressure (BP); bloods for inflammation; transthoracic echocardiography for all participants and stress perfusion CMR with multiparametric mapping for PLWH. We compared CMR results with a previously selected control group of healthy volunteers with no cardiovascular risk factors.
Results
45 participants were recruited (26 MLWH; 19 HIV- MSM), mean results for MLWH were as follows: duration of HIV 17.8±6.4yrs, duration on ART 10.7±5.2yrs, nadir CD4 count 318±145 cells/μL, current CD4 count 610±150 cells/μL and current viral load <40 copies/mL . There were no significant differences in baseline data (Table 1). Although not significant, detectable inflammatory markers were more prevalent and median levels higher in MLWH. Echocardiogram parameters were similar between groups. Of those who had a Left Ventricular Ejection Fraction (LVEF) <55% (Simpson's Biplane) all 3 (15%) were MLWH (range 47.5-53.1%). CMR data for LVEF was comparable to that reported by echocardiography, most parameters were similar between the groups aside from statistically significant higher T2 (46.2±1.6 v 44.4±2.5ms; P<0.05) and LGE (76.5 v 14.3%; P<0.001) in MLWH (Table 2). There was no evidence of ischaemia or myocarditis in either group.
Conclusion
From our small study of well treated asymptomatic MLWH with low CVD risk profiles, we were able to detect subtle differences in inflammatory biomarkers compared to controls, However this did not translate to evidence of detectable myocardial pathology classically associated with HIV (cardiomyopathy, myocarditis). There was no difference in LVEF%, LV Mass-I or native T1, a marker of diffuse fibrosis, which is different to previous published data, perhaps due to our strict inclusion criteria. However T2, a more specific marker of myocardial oedema, and more non-specific LGE were detected in MLWH. This may indicate an early signal of myocardial inflammation in well treated MLWH.
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.
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