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Background Stress cardiovascular magnetic resonance (CMR) offers assessment of ventricular function, myocardial perfusion and viability in a single examination to detect coronary artery disease (CAD). We developed an in-scanner exercise stress CMR (ExCMR) protocol using supine cycle ergometer and aimed to examine the diagnostic value of a multiparametric approach in patients with suspected CAD, compared with invasive fractional flow reserve (FFR) as the reference gold standard. Methods In this single-centre prospective study, patients who had symptoms of angina and at least one cardiovascular disease risk factor underwent both ExCMR and invasive angiography with FFR. Rest-based left ventricular function (ejection fraction, regional wall motion abnormalities), tissue characteristics and exercise stress-derived (perfusion defects, inducible regional wall motion abnormalities and peak exercise cardiac index percentile-rank) CMR parameters were evaluated in the study. Results In the 60 recruited patients with intermediate CAD risk, 50% had haemodynamically significant CAD based on FFR. Of all the CMR parameters assessed, the late gadolinium enhancement, stress-inducible regional wall motion abnormalities, perfusion defects and peak exercise cardiac index percentile-rank were independently associated with FFR-positive CAD. Indeed, this multiparametric approach offered the highest incremental diagnostic value compared to a clinical risk model (χ2 for the diagnosis of FFR-positive increased from 7.6 to 55.9; P Conclusion The study demonstrates the clinical potential of using in-scanner multiparametric ExCMR to accurately diagnose CAD. Trial registration: ClinicalTrials.gov, NCT03217227, Registered 11 July 2017–Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03217227?id=NCT03217227&draw=2&rank=1&load=cart

While brachial mean blood pressure (MBP) and left ventricular mass (LVM) measured from CTCA are the two CFD simulation input parameters, their effects on noninvasive fractional flow reserve (FFRB) have not been systematically investigated. We demonstrate that inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. This is important in the clinical application of noninvasive FFR in coronary artery disease diagnosis.

The aim of this study was to evaluate a new analytical method for calculating non-invasive fractional flow reserve (FFRAM) to diagnose ischemic coronary lesions. Patients with suspected or known coronary artery disease (CAD) who underwent computed tomography coronary angiography (CTCA) and invasive coronary angiography (ICA) with FFR measurements from two sites were prospectively recruited. Obstructive CAD was defined as diameter stenosis (DS) ≥50% on CTCA or ICA. FFRAM was derived from CTCA images and anatomical features using analytical method and was compared with computational fluid dynamics (CFD)-based FFR (FFRB) and invasive ICA-based FFR. FFRAM, FFRB, and invasive FFR ≤ 0.80 defined ischemia. A total of 108 participants (mean age 60, range: 30–83 years, 75% men) with 169 stenosed coronary arteries were analyzed. The per-vessel accuracy, sensitivity, specificity, and positive predictive and negative predictive values were, respectively, 81, 75, 86, 81, and 82% for FFRAM and 87, 88, 86, 83, and 90% for FFRB. The area under the receiver operating characteristics curve for FFRAM (0.89 and 0.87) and FFRB (0.90 and 0.86) were higher than both CTCA- and ICA-derived DS (all p < 0.0001) on per-vessel and per-patient bases for discriminating ischemic lesions. The computational time for FFRAM was much shorter than FFRB (2.2 ± 0.9 min vs. 48 ± 36 min, excluding image acquisition and segmentation). FFRAM calculated from a novel and expeditious non-CFD approach possesses a comparable diagnostic performance to CFD-derived FFRB, with a significantly shorter computational time.

Background: Resident attrition is costly but literature studying the motivations behind it in obstetrics and gynaecology (OBGYN) is lacking. Objectives: We aimed to study the relationship between prior specialty-appropriate work experience and risk of attrition amongst OBGYN residents in Singapore, and identify factors placing residents at greater risk of attrition. Methods: This nationwide mixed methods case control study studied all OBGYN residents in Singapore for the 2011 and 2012 intakes. A pre-piloted questionnaire was used to identify work experience and risk factors related to resident attrition. Structured interviews were conducted with a subgroup of participants chosen for diversity of educational background, work experience, and position towards residency. Results: 28 of 33 (84.8%) eligible residents participated in this study. Female (40.9% vs. 0%), married (50.0% vs. 22.2%) and Singaporean (38.1% vs.14.3%) residents more often considered attrition from training. Those accepted into residency after graduation were 33% less likely to have considered leaving. No statistical difference was observed between residents with prior work experience and those without (38.9% vs. 20.0%, p=0.417). All interviewees believed that prior experience informs expectations and eases initial learning. Low job satisfaction related to mismatched expectations was the most quoted reason for considering attrition. 85.7% of interviewed residents were concerned about competing work and family demands. Conclusions: Lack of specialty-appropriate work experience contributes to misinformed training expectations and increased attrition risk. Residents who have considered attrition may still desire career longevity in their specialty. Reduction in mismatched expectations promises to improve job satisfaction and translate to career longevity.

In-stent restenosis (ISR) is an important cause of drug-eluting stent (DES) failure and target vessel revascularisation. In this study we aimed to evaluate differences between early and late-presenting restenosis in second-generation DES using optical coherence tomography (OCT).Overall, 171 cases of second-generation DES ISR with a follow-up OCT minimum lumen area3.0 mm2 were included: 33.3% of patients (n=57) had early ISR, and 66.7% (n=114) had late ISR (duration from stent implantation1 year). Minimum stent area (MSA)4.0 mm2, neointimal thickness100 µm, and heterogeneous neointimal hyperplasia (NIH) were more prevalent in early ISR, whereas NIH with neoatherosclerosis trended towards being more frequent for late ISR (28.9% vs. 15.8%, p=0.06). Multivariable analysis revealed that duration from implantation2 years, absence of statin use, and NIH50% were independent predictors for neoatherosclerosis (all p0.05).OCT morphological characteristics of second-generation DES ISR differ between early and late presentation. Early ISR was associated with MSA4.0 mm2, while neoatherosclerosis contributed more commonly to late ISR.

Culprit lesion identification in ST elevation myocardial infarction (STEMI) is often guided by electrocardiogram (ECG) changes. However, in the setting of multi-vessel coronary artery occlusion, this can be challenging. We describe an interesting case of dual territory STEMI with unanticipated ECG changes that bring forth the concept of ‘balanced ischaemia’. These seemingly bizarre findings are well explained using the fundamentals of electrocardiography reinstating its relevance in modern day cardiology.

Background/purpose We sought to evaluate the morphological characteristics of nonobstructive coronary lesions in patients with ischemic symptoms and/or signs. Materials/methods We used optical coherence tomography (OCT) to assess the presumed culprit lesion in 142 patients with suspected coronary artery disease in whom coronary angiography showed no lesion with a diameter stenosis ≥50%. Patients with a clinical diagnosis of acute coronary syndrome (ACS, n = 31, including 2 ST-elevation myocardial infarction, 9 non-ST-elevation myocardial infarction, and 20 unstable angina pectoris) were compared to those with stable coronary artery disease (CAD) (n = 111) including 79 patients with stable angina and 32 patients with silent ischemia (positive non-invasive stress test only). Results The overall prevalence of thrombus, plaque rupture, intimal laceration, or calcified nodule in the combined groups was 23.2% (33/142) including 15 thrombus, 12 plaque rupture, 9 calcified nodule, and 8 intimal laceration (not mutually exclusive) without differences between ACS and stable CAD patients. Also the prevalence of thin-cap fibroatheroma was not significantly different between ACS and stable patients (12.9% vs 6.3%, p = 0.22). Minimum lumen area (3.1 mm2 [2.3, 4.1] versus 3.2 mm2 [2.4, 4.7], p = 0.7) and area stenosis (49.9% [37.1, 56.4] versus 48.1% [37.8, 55.8], p = 0.9) were similar between ACS and stable CAD patients. Conclusion In patients presenting with ischemic symptoms and/or signs, but angiographically nonobstructive culprit lesions, approximately 25% had abnormal findings by OCT—whether patients presented with acute/unstable or stable CAD.

Background Computed tomography coronary angiography (CTCA) image analysis enables plaque characterization and non-invasive fractional flow reserve (FFR) calculation. We analyzed various parameters derived from CTCA images and evaluated their associations with ischemia. Methods 49 (61 lesions) patients underwent CTCA and invasive FFR. Lesions with diameter stenosis (DS) ≥ 50% were considered obstructive. CTCA image processing incorporating analytical and numerical methods were used to quantify anatomical parameters of lesion length (LL) and minimum lumen area (MLA); plaque characteristic parameters of plaque volume, low attenuation plaque (LAP) volume, dense calcium volume (DCV), normalized plaque volume (NP Vol), plaque burden, eccentricity index and napkin-ring (NR) sign; and hemodynamic parameters of resistance index, stenosis flow reserve (SFR) and FFR B . Ischemia was defined as FFR ≤ 0.8. Results Plaque burden and plaque volume were inversely related to FFR. Multivariable logistic regression analysis identified the best anatomical, plaque and hemodynamic predictors, respectively, as DS (≥50% vs B (≤0.8 vs >0.8; OR: 44.4; 95% CI: 8.8–224.8). AUC increased from 0.70 with DS as the sole predictor to 0.81 after adding NP Vol and NR Sign; further addition of FFR B increased AUC to 0.93. Conclusion Normalized plaque volume, napkin-ring derived from plaque analysis, and FFR B from numerical simulations on CTCA images substantially improved discrimination of ischemic lesions, compared to assessment by DS alone.

Although reported in bare metal stents (BMS) and first-generation drug-eluting stents (DES), little is known about neoatherosclerosis in second-generation DES. We used optical coherence tomography to evaluate neoatherosclerosis among different stent generations. Overall, 274 in-stent restenosis (ISR) lesions (duration from implantation 56.9 ± 47.2 months) in 274 patients were assessed for the presence of neoatherosclerosis. Neoatherosclerosis was identified in 38.7% of lesions (106/274): 23.0% second-generation DES (38/165), 65.1% first-generation DES (54/83), and 53.8% BMS (14/26). In the neoatherosclerosis cohort (n = 106), more stent underexpansion or fracture/deformation was observed in second-generation DES, whereas thrombus, without plaque rupture, or evagination was more common in first-generation DES. In multivariable analyses, duration from implantation >1 year (OR: 2.44, 95% CI 1.12–5.31; p = 0.03), absence of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (OR 1.95, 95% CI 1.10–3.44; p = 0.02) or statins at the time of ISR (OR 3.12, 95% CI 1.42–6.84; p = 0.01), and first-generation vs first-generation DES (OR 5.32, 95% CI 2.82–10.10; p

Near-infrared spectroscopy (NIRS) has been employed to assess the composition of the atherosclerotic plaques in native coronary arteries. However, little is known about the detection of neoatherosclerosis by NIRS in in-stent restenosis (ISR). The aim of the study was to assess the relationship between the distribution of lipid determined by NIRS and morphology of ISR on optical coherence tomography (OCT).We performed both NIRS and OCT in 39 drug-eluting stents with ISR. Values of lipid-core burden index (LCBI) derived by NIRS were compared with the OCT-derived thickness of the fibrous cap covering neoatherosclerotic lesions. A total of 22 (49%) in-stent neointimas were identified as lipid rich by both NIRS and OCT. There was good agreement between OCT and NIRS in identifying lipid within in-stent neointima (kappa = 0.60, 95% CI: 0.34-0.86). OCT identified thin-cap neoatheromas (TCNA) (65 µm) in 12 stents (23%). The minimal cap thickness of in-stent neoatherosclerotic plaque measured by OCT correlated with the maxLCBI4mm (maximal LCBI per 4 mm) within the stent (r = -0.77, P0.01). Moreover, maxLCBI4mm was able to accurately predict TCNA with a cut-off value of144.NIRS correlates with OCT identification of lipids in stented vessels and is able to predict the presence of thin fibrous cap neoatheroma.

We sought to examine the relation between various degrees of renal function and coronary plaque morphology by grayscale and virtual histology intravascular ultrasound (IVUS). ADAPT-DES was a prospective, multicenter registry of 8,582 consecutive patients treated using coronary drug-eluting stents with a prespecified grayscale and virtual histology-IVUS substudy. A lesion-level analysis of study participants was performed by comparing IVUS parameters of culprit and nonculprit lesions across tertiles of estimated creatinine clearance (CrCl). Preintervention IVUS imaging of 762 patients identified 898 culprit and 752 nonculprit native coronary artery lesions. Patients in the lowest CrCl tertile were older, more often women, and more often presented with stable angina. Compared with the middle and upper tertiles, the lowest tertile was significantly associated with culprit lesion smaller mean external elastic membrane cross-sectional area (12.9 vs 14.2 mm 3 /mm vs 14.9 mm 3 /mm, p 3 /mm vs 5.8 mm 3 /mm vs 6.1 mm 3 /mm, p = 0.002), and more dense calcium volume (11.5% vs 10.2% vs 9.7%, p = 0.02). Similar trends were found in the nonculprit lesions. Plaque rupture was least common in patients in the lowest tertile. On multivariable analysis, independent predictors of greater dense calcium volume were lower CrCl, hyperlipidemia, female gender, and presentation without ST-segment elevation myocardial infarction. In conclusion, in the present large-scale IVUS study diminishing renal function was associated with increased coronary calcification and decreased coronary vessel and lumen sizes, with a graded response according to the reduction in CrCl. In addition, these patients were more likely to present with stable angina versus patients with normal renal function who were more likely to present with an acute coronary syndrome.

Patient initials or identifier number STK ### Relevant clinical history and physical exam A 67-year-old man has experienced recurrent unstable angina pectoris (Canadian Cardiovascular Society angina class IV) in the last six months. He had a 30-year history of smoking twenty cigarettes per

Endothelial dysfunction is associated with traditional and systemic lupus erythematosus (SLE)-specific risk factors, and early data suggest reversibility of endothelial dysfunction with therapy. The clinical relevance of endothelial function assessment has been limited by the lack of studies, demonstrating its prognostic significance and impact on early myocardial function. Therefore, we aimed to determine the association between endothelial and myocardial diastolic function in SLE women. Women with SLE and no coronary artery disease were prospectively recruited and underwent radionuclide myocardial perfusion imaging (MPI) (Jetstream, Philips, the Netherlands) to exclude subclinical myocardial ischemia. Cardiac and vascular functions were assessed in all patients (Alpha 10, Aloka, Tokyo). Diastolic function was assessed using pulse wave early (E) and late mitral blood inflow and myocardial tissue Doppler (mean of medial and lateral annulus e′) velocities. Endothelial function was measured using brachial artery flow-mediated vasodilatation (FMD%). Univariate and multivariate linear regressions were used to assess the association between FMD% and myocardial diastolic function, adjusting for potential confounders. Thirty-eight patients without detectable myocardial ischemia on MPI were studied (mean age 44 ± 10 years; mean disease duration 14 ± 6 years). About 61 % of patients had normal diastolic function (E/e′ ≤ 8), and 5 % of patients had definite diastolic dysfunction with E/e′ > 13 (mean 7.1 ± 2.9). FMD% was associated with E/e′ (regression coefficient β = −0.35; 95 % CI −0.62 to −0.08; p = 0.01) independent of systolic blood pressure, age, and SLICC/ACR Damage Index.

Mechanisms and patterns of in-stent restenosis (ISR) comparing bare metal stents (BMS) and 1st and 2nd generation drug-eluting stent (DES) as evaluated by optical coherence tomography (OCT) have not been well delineated. OCT evaluation of ISR (minimum lumen area

To the Editor:Patients with systemic lupus erythematosus (SLE) are at in-creased risk of premature atherosclerosis, mediated by endothelialdysfunction and increased arterial stiffness[1]. The latter, mostcommonly assessed using carotid-femoralpulse wave velocity, isincreased in patients with SLE and is associated with cardiovascu-lar risk factors[1]. Recently, a more sensitive measure of arterialstiffness (effective arterial elastance; Ea), and ventricular-arterialcoupling (ratio of arterial and end-systolic ventricular elastance;Ea/Ees) demonstrated incremental prognostic value in patientswith chronic heart failure[2]. We aimed to assess the potential ofEa and Ea/Ees as novel biomarkers of cardiovascular risk in SLEwomen without ischemic heart disease.Women whosatisfiedtherevised American College of Rheumatolo-gy classification criteria for SLE were prospectively recruited from therheumatology clinics, as described previously [3]. Patients with recentactive flares, ischemic heart disease (all patients underwent nuclearstress perfusion imaging as part of the study), cardiomyopathies(including myocarditis) and valvular heart disease of≥ moderateseverity were excluded. Cardiovascular risk was defined as historyof hypertension, hyperlipidemia, diabetes mellitus, current tobacco use,cerebrovascularevents,familyhistoryofcoronaryarterydiseaseandsec-ondary anti-phospholipid syndrome. Age-matched control women wererecruited from the community. Left ventricular mass, diastolic functionand systolic ejection fraction were assessed with echocardiography;Ea was estimated as 0.9 x (arm-cuff systolic pressure/Doppler strokevolume) and Ees was calculated by the well-validated approach ofusing arm-cuff pressures, Doppler stroke volumes, ejection fraction,pre-ejection and systolic periods [4,5]. The study was conducted inaccordance with the Declaration of Helsinki and approved by the localresearch ethics committee. Written informed consent was obtainedfrom all participants.Continuousvariableswerepresentedinmean±SDormedian[inter-quartile range] and compared using either the Student t test or Mann-Whitney U test, as appropriate. The mean differences in Ea and Ea/Eeswere adjusted for age,systolic ejection fraction and systolicblood pres-sure. We assessed associations using the Pearson (r) or Spearman (ρ)correlation, as appropriate. All statistical analyses were performedwiththeSPSSversion19(SPSSInc,Chicago,USA).Atwo-sidedP b0.05 was considered statistically significant.Forty-eight patients with SLE (43±9 years old; disease durationof 14±6 years; 1 [0,2] risk factors) and 20 control women (42±9years old) were recruited. There were no differences in left ventricu-lar mass, diastolic function and Ees between SLE and control women(PN0.50 for all;Table 1). Compared to control individuals, patientswithSLEhadlowersystolicejectionfraction,albeitasmalldifference(71±8 versus 75±7%; P=0.04). Despite similar systolic blood pres-sure compared with control women (116±12 versus 119±16mmHg; P=0.52), patients with SLE had increased Ea (1.77±0.56versus 1.37±0.27 mmHg/mL; adjusted mean difference 0.30mmHg/mL, 95% confidence interval [CI] 0.08 to 0.53 mmHg/mL,Pb0.001) and Ea/Ees (0.61±0.18versus 0.50±0.07; adjusted meandifference 0.06, 95% CI 0.01 to 0.12, P=0.04). Furthermore, Ea wasassociated with increasing cardiovascular risk (ρ=0.35; P=0.02),systolic blood pressure (r=0.55, Pb0.001) and duration of predniso-lone use (ρ=0.33, P=0.03).Over 3 years of follow-up (median 31 [17,37] months), 8% ofpatients with SLE developed cardiovascular events (event rate 3.2 per100 person-years; non-fatal myocardial infarction, n=2; stroke, n=1