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Background Physician visual assessment (PVA) in invasive coronary angiography (ICA) is the current clinical method to determine stenosis severity and guide percutaneous coronary intervention. This study sought to evaluate the effect of sex differences in assessing coronary stenosis severity between PVA and quantitative coronary angiography (QCA). Methods 209 patients with coronary artery disease (288 coronary lesions) underwent ICA and fractional flow reserve (FFR). ICA image processing including PVA and QCA was used to quantify diameter stenosis (DS). The difference of DS (ΔDS) between PVA and QCA was defined as DSPVA-DSQCA. DS ≥50% was considered anatomically obstructive. FFR ≤0.8 was defined as myocardial ischemia. Results Mean ± SD age was 63 ± 9 years. There were no significant differences in DSPVA (61.1 ± 16.3% vs 60.1 ± 18.9%) and DSQCA (53.1 ± 12.1% vs 55.4 ± 14.3%) between females and males. However, ΔDS between PVA and QCA was higher in females (8.0 ± 10.9%) than in males (4.7 ± 10.9%) (P = 0.03). Thirty-four of 72 vessels (47.2%) in female patients and 75 of 216 vessels (34.7%) in male patients were classified differently by at least one grade using PVA compared to QCA assessment. DSPVA and DSQCA were negatively correlated with FFR in females (rPVA = −0.397, rQCA = −0.448) with an even stronger negative correlation in males (rPVA = −0.607, rQCA = −0.607). ROC analysis demonstrated that DSQCA myocardial ischemia (FFR ≤ 0.80) discrimination capability was superior to DSPVA in both sexes (P Conclusions A systematic bias was found in PVA (QCA reference) for overestimating severity of coronary artery disease in females compared to males.

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.

Circadian patterns in ST-segment elevation myocardial infarction (STEMI) patients have been previously reported, but little is known about the impact of time dependence of symptom onset on long-term prognosis. Our study population consisted of 11,731 STEMI patients treated by primary percutaneous coronary intervention (PPCI), enrolled in the Singapore Myocardial Infarction Registry (SMIR). Analysis of STEMI incidence trends over the 24-hour period showed the highest rate of symptom onset in the morning, with the peak incidence at 09:00 am . Patients with symptom onset in between 00:00 am -5:59 am showed the highest prevalence of diabetes (P = .010) and anterior STEMI (P pm -11:59 pm and 00:00 am -05:59 am having an estimated 30% to 50% higher risk of rehospitalization for HF at 1 year. Moreover, symptom onset remained a predictor of worse prognosis only in the subgroup of patients with symptoms lasting longer than 120 minutes. The results of this study demonstrate for the first time that rehospitalization for HF in STEMI patients treated with PPCI has a dependence on the time of onset of symptoms, with prolonged ischemia time playing a pivotal role. This may be an additional risk factor to identify those who warrant closer monitoring and more rigorous optimization of their treatment at follow-up, to improve their outcomes.

Introduction: Early reperfusion of ST-segment elevation myocardial infarction (STEMI) results in better outcomes. Interventions that have resulted in shorter door-to-balloon (DTB) time include prehospital cardiovascular laboratory activation and prehospital electrocardiogram (ECG) transmission, which are only available for patients who arrive via emergency ambulances. We assessed the impact of mode of transport on DTB time in a single tertiary institution and evaluated the factors that affected various components of DTB time. Methods: We conducted a retrospective cohort study using registry data of patients diagnosed with STEMI in the emergency department (ED) who underwent primary percutaneous coronary intervention. We compared patients who arrived by emergency ambulances with those who came via their own transport. The primary study end point was DTB, defined as the earliest time a patient arrived in the ED to balloon inflation. As deidentified data was used, ethics review was waived. Results: A total of 321 patients were included for analysis after excluding 7 with missing data. The mean age was 61.4±11.4 years old with 49 (15.3%) females. Ninety-nine (30.8%) patients arrived by emergency ambulance. The median DTB time was shorter for patients arriving by ambulance versus own transport (52min, interquartile range [IQR] 45–61 vs 67min, IQR 59–74; P

We aimed to identify independent predictors of cardiac mortality and hospitalization for heart failure (HHF) from a real-world, multi-ethnic Asian registry [the Singapore Myocardial Infarction Registry] of ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention. 11,546 eligible STEMI patients between 2008 and 2015 were identified. In-hospital, 30-day and 1-year cardiac mortality and 1-year HHF rates were 6.4%, 6.8%, 8.3% and 5.2%, respectively. From the derivation cohort (70% of patients), age, Killip class and cardiac arrest, creatinine, hemoglobin and troponin on admission and left ventricular ejection fraction (LVEF) during hospitalization were predictors of in-hospital, 30-day and 1-year cardiac mortality. Previous ischemic heart disease (IHD) was a predictor of in-hospital and 30-day cardiac mortality only, whereas diabetes was a predictor of 1-year cardiac mortality only. Age, previous IHD and diabetes, Killip class, creatinine, hemoglobin and troponin on admission, symptom-to-balloon-time and LVEF were predictors of 1-year HHF. The c-statistics were 0.921, 0.901, 0.881, 0.869, respectively. Applying these models to the validation cohort (30% of patients) showed good fit and discrimination (c-statistic 0.922, 0.913, 0.903 and 0.855 respectively; misclassification rate 14.0%, 14.7%, 16.2% and 24.0% respectively). These predictors could be incorporated into specific risk scores to stratify reperfused STEMI patients by their risk level for targeted intervention.

To assess the clinical and angiographic outcomes of coronary intravascular lithotripsy (IVL) use in an all-comers population with moderate-to-severely calcified coronary lesions.IVL has been shown to modify coronary calcific plaques with minimal vascular complications.This was a retrospective, observational study of patients treated with IVL. The primary endpoint was in-hospital major adverse cardiovascular event (MACE), which included cardiac death, myocardial infarction (MI), and target-vessel revascularization (TVR). Secondary endpoints were clinical success (stent expansion with30% in-stent residual stenosis and no in-hospital MACE) and angiographic success.Between August 2019 and December 2019, a total of 50 calcified lesions were treated in 45 patients using the Shockwave C2 IVL catheter (Shockwave Medical). They were further studied in 3 treatment subgroups: (1) primary IVL group with de novo lesions (n = 23 lesions); (2) secondary IVL group in which non-compliant balloon dilation failed (n = 15 lesions); and (3) tertiary IVL group with IVL to underexpanded stents (n = 12 lesions). The mean diameter stenosis of calcified lesions was 63.2 ± 10.2% at baseline, and decreased to 33.5 ± 10.9% immediately post IVL (P.001) and 15 ± 7.1% post stenting (P.001). Mean minimal lumen diameter was 1.1 ± 0.3 mm at baseline, and increased to 1.90 ± 0.5 mm post IVL (P.001) and 2.80 ± 0.50 mm post stenting (P.001). In-hospital and 30-day MACE occurred in 3 and 4 patients, respectively. Overall, clinical success and angiographic success were achieved in 90% and 94% of cases, respectively.IVL appears to be a safe, effective, and feasible strategy for calcium modification in an all-comers cohort with high success rate, minimal procedural complications, and low MACE rates.

Introduction: We report two cases of recurrent ventricular tachycardia (VT) successfully treated by intra-coronary Gelatin sponge embolization where initial endocardial ablation was unsuccessful and epicardial approaches were unfavourable. Case Histories: (1) A 75-year-old male with Inferior STEMI who underwent PCI to oRPDA developed VT storm that required DCCV 11 times. The VT was hemodynamically unstable, hence only substrate modification was performed. He still had recurrent episodes of VT and a second ablation attempt localised VT circuit breakout to the infero-apical septum, but ablation was unsuccessful due to a deep intramural circuit. Epicardial ablation was not attempted due to a 1cm pericardial effusion after the first procedure. Unipolar signals from selective wiring of the distal rPDA with a percutaneous coronary intervention guidewire and microcatheter showed early local electrograms. 5ml of Gelatin sponge injection was injected after a 5x2mm coil failed to occlude the distal rPDA. Post occlusion, VT was not inducible with double ventricular extra-stimuli. He has been VT free for 5 months (2) A 41-year-old female with dilated cardiomyopathy, previous left ventricular assist device and revision was admitted for VT storm. The VT map identified earliest activation with far-field pre-systolic potentials at the baso-lateral LV segment. Pre-systolic far field ventricular EGMs were also seen in the adjacent coronary sinus, consistent with a likely epicardial exit site of the VT. Endocardial ablation failed, and epicardial access was not feasible due to adhesions. Coronary angiography revealed a small calibre non dominant left circumflex artery supplying the VT exit site. Cold saline injection down the mLCX terminated the VT and the vessel was occluded with 5 ml of Gelatin sponge. VT was subsequently not inducible. Discussion & Conclusion: Critical portions of VT circuits may course epicardially or intramurally 3 , limiting successful endocardial catheter ablation. Epicardial access was risky. Coronary vessel embolization using coils 4 and ethanol 5 have been performed. Use of absorbable Gelatin sponge has been described in managing coronary perforation 6 , but to the best of our knowledge these are the first cases of its use in VT ablation.

Owing to the COVID-19 outbreak in Lombardy, Italy) there is an urgent need to manage cardiovascular emergencies, including acute coronary syndrome (ACS), with appropriate standards of care and dedicated preventive measures and pathways against the risk of SARS-CoV-2 infection. For this reason, the Government of Lombardy decided to centralize the treatment of ACS patients in a limited number of centers, including our university cardiology institute, which in the past 4 weeks became a cardiovascular emergency referral center in a regional hub-and-spoke system. Therefore, we rapidly developed a customized pathway to allocate patients to the appropriate hospital ward, and treat them according to ACS severity and risk of suspected SARS-CoV-2 infection. We present here the protocol dedicated to ACS patients adopted in our center since March 13, 2020, and our initial experience in the management of ACS patients during the first 4 weeks of its use. Certainly, the protocol has room for further improvement as everyone's experience grows, but we hope that it could be a starting point, adaptable to different realities and local resources.

Background In ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI), current oral P2Y12 platelet inhibitors do not provide maximal platelet inhibition at the time of reperfusion. Furthermore, administration of cangrelor prior to reperfusion has been shown in pre-clinical studies to reduce myocardial infarct (MI) size. Therefore, we hypothesize that cangrelor administered prior to reperfusion in STEMI patients will reduce the incidence of microvascular obstruction (MVO) and limit MI size in STEMI patients treated with PPCI. Methods The platelet inhibition to target reperfusion injury (PITRI) trial, is a phase 2A, multi-center, double-blinded, randomized controlled trial, in which 210 STEMI patients will be randomized to receive either an intravenous (IV) bolus of cangrelor (30 μg/kg) followed by a 120-minute infusion (4 μg/kg/min) or matching saline placebo, initiated prior to reperfusion (NCT03102723). Results The study started in October 2017 and the anticipated end date would be July 2020. The primary end-point will be MI size quantified by cardiovascular magnetic resonance (CMR) on day 3 post-PPCI. Secondary endpoints will include markers of reperfusion, incidence of MVO, MI size, and adverse left ventricular remodeling at 6 months, and major adverse cardiac and cerebrovascular events. Summary The aim of the PITRI trial is to assess whether cangrelor administered prior to reperfusion would reduce acute MI size and MVO, as assessed by CMR.

Background To evaluate the combined diagnostic accuracy of coronary computed tomography angiography (CCTA) and computed tomography derived fractional flow reserve (FFRct) in patients with suspected or known coronary artery disease (CAD). Methods PubMed, The Cochrane library, Embase and OpenGray were searched to identify studies comparing diagnostic accuracy of CCTA and FFRct. Diagnostic test measurements of FFRct were either extracted directly from the published papers or calculated from provided information. Bivariate models were conducted to synthesize the diagnostic performance of combined CCTA and FFRct at both "per-vessel" and "per-patient" levels. Results 7 articles were included for analysis. The combined diagnostic outcomes from "both positive" strategy, i.e. a subject was considered as "positive" only when both CCTA and FFRct were "positive", demonstrated relative high specificity (per-vessel: 0.91; per-patient: 0.81), high positive likelihood ratio (LR+, per-vessel: 7.93; per-patient: 4.26), high negative likelihood ratio (LR−, per-vessel: 0.30; per patient: 0.24) and high accuracy (per-vessel: 0.91; per-patient: 0.81) while "either positive" strategy, i.e. a subject was considered as "positive" when either CCTA or FFRct was "positive", demonstrated relative high sensitivity (per-vessel: 0.97; per-patient: 0.98), low LR+ (per-vessel: 1.50; per-patient: 1.17), low LR− (per-vessel: 0.07; per-patient: 0.09) and low accuracy (per-vessel: 0.57; per-patient: 0.54). Conclusion "Both positive" strategy showed better diagnostic performance to rule in patients with non-significant stenosis compared to "either positive" strategy, as it efficiently reduces the proportion of testing false positive subjects.

Background: Targeted temperature management (TTM) is an important component of post-cardiac arrest care. Studies have suggested that cooling is associated with better outcomes. The aim of this study was to evaluate the cooling efficacy of a protocol including a novel cooling device in the Emergency Department. Methods: This was a single-center, pre-post cohort study of post-cardiac arrest patients with return of spontaneous circulation (ROSC), for whom TTM was initiated at a tertiary hospital between April 2010 and December 2017. A surface cooling device which uses a graphite cooling material in an insulating suit was introduced in July 2015. The target temperature was 34.0 °C with TTM continued in the ICUs. The primary outcome was time from ROSC to target temperature (TT). Results: Of 124 patients included, 40 were in the intervention period and 84 in the control period. Time from ROSC to TT was significantly lower in the intervention period at 119 [interquartile range (IQR), 65–250] minutes versus 482 (IQR, 356–596) minutes (P Conclusions: Use of a novel cooling device in the ED resulted in a shorter time to target temperature. As it is reusable and does not require a power source, it has potential to be an affordable solution for pre- hospital and transport cooling.

Despite timely reperfusion by primary percutaneous coronary intervention (PPCI), microvascular obstruction (MVO) occurs in up to 50% of patients with ST-segment elevation myocardial infarction (STEMI) [(1)][1]. Its presence is associated with adverse left ventricular remodeling and worse clinical

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.

A 55-year-old woman with a history of CAD with prior CABG presented with unstable angina. Her other comorbidities include hypertension and hyperlipidaemia. The CABG was performed 10 years ago with LIMA to LAD and SVG to obtuse marginal. At this most recent presentation, her ECG showed T wave inversions anteriorly, and echocardiography showed mildly impaired left ventricular function with LVEF 40–45%.

Area stenosis (AS) is emerging as new index to assess the severity of coronary artery disease (CAD). Coronary artery lumen area and its derived area stenosis can be obtained noninvasively from computed tomography angiographic (CTA) images. In this study, we developed a novel approach with 3D centerline-centric straightening method, which consisted of original segmentation, smoothing, fast marching (FM) method and central cutting, to quantify coronary lumen area. We tested the differences of area stenosis in a human patient with suspected CAD by varying the combination of methods (Group 2: original segmentation + no smoothing + FM +central cutting; Group 3: Original segmentation + smoothing + thinning + central cutting; Group 4: denser segmentation + smoothing +FM + central cutting; Group 5: original segmentation + smoothing + FM + one-sided cutting). The data with our method demonstrated patient had area stenosis of 37.5% with low intra-observer variability (1.1%). Group 2 to Group 4 underestimated the area stenosis (AS = 32.3%, 36.8% and 32.0%, respectively), however, Group 5 overestimated the area stenosis (AS = 45.6%). All groups 2 to 5 had much higher intra-observer variability than our method. The computational time per data set is approximately 25 minutes, which demonstrates our methods clinical potential as a real-time cardiac assessment tool.

Invasive fractional flow reserve (FFR) is the gold standard to assess the functional coronary stenosis. The non-invasive assessment of diameter stenosis (DS) using coronary computed tomography angiography (CTA) has high false positive rate in contrast to FFR. Combining CTA with computational fluid dynamics (CFD), recent studies have shown promising predictions of FFRCT for superior assessment of lesion severity over CTA alone. The CFD models tend to be computationally expensive, however, and require several hours for completing analysis. Here, we introduce simplified models to predict noninvasive FFR at substantially less computational time. In this retrospective pilot study, 21 patients received coronary CTA. Subsequently a total of 32 vessels underwent invasive FFR measurement. For each vessel, FFR based on steady-state and analytical models (FFRSS and FFRAM, respectively) were calculated non-invasively based on CTA and compared with FFR. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 90.6% (87.5%), 80.0% (80.0%), 95.5% (90.9%), 88.9% (80.0%) and 91.3% (90.9%) respectively for FFRSS (and FFRAM) on a per-vessel basis, and were 75.0%, 50.0%, 86.4%, 62.5% and 79.2% respectively for DS. The area under the receiver operating characteristic curve (AUC) was 0.963, 0.954 and 0.741 for FFRSS, FFRAM and DS respectively, on a per-patient level. The results suggest that the CTA-derived FFRSS performed well in contrast to invasive FFR and they had better diagnostic performance than DS from CTA in the identification of functionally significant lesions. In contrast to FFRCT, FFRSS requires much less computational time.

Sudden cardiac arrest constitutes a major public health burden in both developed and developing countries. In those successfully resuscitated from cardiac arrest, subsequent mortality is still high (∼75%) and is due to a combination of ischaemia and reperfusion injury. The purpose of this review is to describe the experimental and clinical evidence supporting therapeutic hypothermia in survivors of sudden cardiac arrest. We also discuss controversies and unresolved issues in therapeutic hypothermia, including the optimum target temperature for therapeutic hypothermia, and the role of pre-hospital induction of hypothermia. We conclude with a perspective on therapeutic hypothermia as it applies to the Singapore context.

We thank Berry and colleagues for their letter regarding our recent study [(1)][1], suggesting we used incomplete data, because we did not include studies reporting median index microvascular resistance (IMR). Although different methods are available to accommodate median values in a meta-analysis

Local hemodynamic parameters, such as wall shear stress (WSS), oscillatory shear index and relative resident time (RRT), have been linked to coronary plaque initiation and progression. In this study, a left coronary artery tree model was reconstructed from computed tomography angiography images of a patient with multiple stenoses. The geometry of the coronary artery tree model was virtually restored by eliminating the lesions, essentially re-creating the virtually healthy artery anatomy. Using numerical simulations, flow characteristics and hemodynamic parameter distributions in the stenosed and virtually healthy models were investigated. In the virtually healthy artery model, disturbed flows were found at four locations, prone to initialization of plaque formation. Low WSS and high RRT were exhibited in three of the four locations, and high WSS and low RRT were exhibited in the fourth. These findings suggest that coronary plaque is more likely to form in locations with disturbed flow conditions characterized by low WSS and high RRT or high WSS and low RRT. In addition, clinical index of fractional flow reserve was found to significantly correlate with blood flow rate, rather than anatomic parameters, such as diameter stenosis, which implied the importance of hemodynamic environment in stenosis formation.