Head-to-head comparison of two angiography-derived fractional flow reserve techniques in patients with high-risk acute coronary syndrome: A multicenter prospective study.

FFRangio and QFR are angiography-based technologies that have been validated in patients with stable coronary artery disease. No head-to-head comparison to invasive fractional flow reserve (FFR) has been reported to date in patients with acute coronary syndromes (ACS). This study is a subset of a larger prospective multicenter, single-arm study that involved patients diagnosed with high-risk ACS in whom 30-70% stenosis was evaluated by FFR. FFRangio and QFR - both calculated offline by 2 different and blinded operators - were calculated and compared to FFR. The two co-primary endpoints were the comparison of the Pearson correlation coefficient between FFRangio and QFR with FFR and the comparison of their inter-observer variability. Among 134 high-risk ACS screened patients, 59 patients with 84 vessels underwent FFR measurements and were included in this study. The mean FFR value was 0.82 ± 0.40 with 32 (38%) being ≤0.80. The mean FFRangio was 0.82 ± 0.20 and the mean QFR was 0.82 ± 0.30, with 27 (32%) and 25 (29%) being ≤0.80, respectively. The Pearson correlation coefficient was significantly better for FFRangio compared to QFR, with R values of 0.76 and 0.61, respectively (p = 0.01). The inter-observer agreement was also significantly better for FFRangio compared to QFR (0.86 vs 0.79, p < 0.05). FFRangio had 91% sensitivity, 100% specificity, and 96.8% accuracy, while QFR exhibited 86.4% sensitivity, 98.4% specificity, and 93.7% accuracy. In patients with high-risk ACS, FFRangio and QFR demonstrated excellent diagnostic performance. FFRangio seems to have better correlation to invasive FFR compared to QFR but further larger validation studies are required

Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro.

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells

Under-reporting bicycle accidents to police in the COST TU1101 international survey: Cross-country comparisons and associated factors

Police crash reports are often the main source for official data in many countries. However, with the exception of fatal crashes, crashes are often underreported in a biased manner. Consequently, the countermeasures adopted according to them may be inefficient. In the case of bicycle crashes, this bias is most acute and it probably varies across countries, with some of them being more prone to reporting accidents to police than others. Assessing if this bias occurs and the size of it can be of great importance for evaluating the risks associated with bicycling. This study utilized data collected in the COST TU1101 action “Towards safer bicycling through optimization of bicycle helmets and usage”. The data came from an online survey that included questions related to bicyclists' attitudes, behaviour, cycling habits, accidents, and patterns of use of helmets. The survey was filled by 8655 bicyclists from 30 different countries. After applying various exclusion factors, 7015 questionnaires filled by adult cyclists from 17 countries, each with at least 100 valid responses, remained in our sample. The results showed that across all countries, an average of only 10% of all crashes were reported to the police, with a wide range among countries: from a minimum of 0.0% (Israel) and 2.6% (Croatia) to a maximum of a 35.0% (Germany). Some factors associated with the reporting levels were type of crash, type of vehicle involved, and injury severity. No relation was found between the likelihood of reporting and the cyclist's gender, age, educational level, marital status, being a parent, use of helmet, and type of bicycle. The significant under-reporting – including injury crashes that do not lead to hospitalization – justifies the use of self-report survey data for assessment of bicycling crash patterns as they relate to (1) crash risk issues such as location, infrastructure, cyclists' characteristics, and use of helmet and (2) strategic approaches to bicycle crash prevention and injury reduction.Fil: Shinar, D.. Ben Gurion University of the Negev; IsraelFil: Valero Mora, Pedro. Universidad de Valencia; EspañaFil: van Strijp Houtenbos, M.. Institute For Road Safety Research; Países BajosFil: Haworth, N.. Queensland University of Technology; AustraliaFil: Schramm, A.. Queensland University of Technology; AustraliaFil: de Bruyne, G.. Universiteit Antwerp; BélgicaFil: Cavallo, V.. No especifíca;Fil: Chliaoutakis, J.. No especifíca;Fil: Pereira Dias, Joao. Instituto Superior Tecnico; PortugalFil: Ferraro, Ottavia Eleonora. Universita Degli Studi Di Pavia; ItaliaFil: Fyhri, Aslak. No especifíca;Fil: Sajatovic, Anika Hursa. No especifíca;Fil: Kuklane, Kalev. Lund University; SueciaFil: Ledesma, Ruben Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Psicología Básica, Aplicada y Tecnología. Universidad Nacional de Mar del Plata. Facultad de Psicología. Instituto de Psicología Básica, Aplicada y Tecnología.; ArgentinaFil: Calvé Mascarell, Oscar. Ben Gurion University of the Negev; IsraelFil: Morandi, A.. Universita Degli Studi Di Pavia; ItaliaFil: Muser, Markus. No especifíca;Fil: Otte, Diettmar. No especifíca;Fil: Papadakaki, M.. No especifíca;Fil: Sanmartín, J.. Universidad de Valencia; EspañaFil: Dulf, D.. No especifíca;Fil: Saplioglu, M.. No especifíca;Fil: Tzamalouka, Georgia. No especifíca

Validation of coronary angiography-derived vessel fractional flow reserve in heart transplant patients with suspected graft vasculopathy

Cardiac transplant-related vasculopathy remains a leading cause of morbidity and mortality in heart transplant (HTx) recipients. Recently, coronary angiography-derived vessel fractional flow reserve (vFFR) has emerged as a new diagnostic computational tool to functionally evaluate the severity of coronary artery disease. Although vFFR estimates have been shown to perform well against invasive FFR in atherosclerotic coronary artery disease, data on the use of vFFR in heart transplant recipients suffering from cardiac transplant-related arteriopathy are lacking. The aim of the presented study was to validate coronary angiography-derived vessel fractional flow reserve to calculate fractional flow reserve in HTx patients with and without cardiac transplant-related vasculopathy. A prospective, single center study of HTx patients referred for annual check-up, undergoing surveillance coronarography was conducted. Invasive FFR was measured using a motorized device at the speed of 1.0 mm/s in all three major coronary arteries. Angiography-derived pullback FFR was derived from the angiogram and compared with invasive FFR pullback curve. Overall, 18,059 FFR values were extracted from the FFR pullback curves from 23 HTx patients. The mean age was 59.3 ± 9.7 years, the mean time after transplantation was 5.24 years [IQR 1.20, 11.25]. A total of 39 vessels from 23 patients (24 LAD, 11 LCX, 4 RCA) were analyzed. Mean distal vFFR was 0.87 ± 0.14 whereas invasive distal FFR was 0.88 ± 0.17. An excellent correlation was found between invasive distal FFR and vFFR (r = 0.92; p < 0.001). The correlation of the pullback tracing was high, with a correlation coefficient between vFFR and invasive FFR pullback values of 0.72 (95% CI 0.71 to 0.73, p < 0.001). The mean difference between vFFR and invasive FFR pullback values was −0.01 with 0.06 of SD (limits of agreements −0.12 to 0.13). In HTx patients, coronary angiography-derived FFR correlates excellently with invasively measured wire-derived FFR. Therefore, angiography derived FFR could be used as a novel diagnostic tool to quantify the functional severity of graft vasculopathy

Simplified Assessment of the Index of Microvascular Resistance

Background. To validate a simplified invasive method for the calculation of the index of microvascular resistance (IMR). Methods. This is a prospective, single-center study of patients with chronic coronary syndromes presenting with nonobstructive coronary artery disease. IMR was obtained using both intravenous (IV) adenosine and intracoronary (IC) papaverine. Each IMR measurement was obtained in duplicate. The primary objective was the agreement between IMR acquired using adenosine and papaverine. Secondary objectives include reproducibility of IMR and time required for the IMR measurement. Results. One hundred and sixteen IMR measurements were performed in 29 patients. The mean age was 68.8 ± 7.24 years, and 27.6% was diabetics. IMR values were similar between papaverine and adenosine (17.7 ± 7.26 and 20.1 ± 8.6, p=0.25; Passing-Bablok coefficient A 0.58, 95% CI -2.42 to 3.53; coefficient B 0.90, 95% CI -0.74 to 1.07). The reproducibility of IMR was excellent with both adenosine and papaverine (ICC 0.78, 95% CI 0.63 to 0.88 and ICC 0.93, 95% CI 0.87 to 0.97). The time needed for microvascular assessment was significantly shortened by the use of IC papaverine (3.23 (2.84, 3.78) mins vs. 5.48 (4.94, 7.09) mins, p<0.0001). Conclusion. IMR can be reliably measured using IC papaverine with similar results compared to intravenous infusion of adenosine with increased reproducibility and reduced procedural time. This approach simplifies the invasive assessment of the coronary microcirculation in the catheterization laboratory

The Disrupt CAD II Study

BACKGROUND: The feasibility of intravascular lithotripsy (IVL) for modification of severe coronary artery calcification (CAC) was demonstrated in the Disrupt CAD I study (Disrupt Coronary Artery Disease). We next sought to confirm the safety and effectiveness of IVL for these lesions. METHODS: The Disrupt CAD II study was a prospective multicenter, single-arm post-approval study conducted at 15 hospitals in 9 countries. Patients with severe CAC with a clinical indication for revascularization underwent vessel preparation for stent implantation with IVL. The primary end point was in-hospital major adverse cardiac events (cardiac death, myocardial infarction, or target vessel revascularization). An optical coherence tomography substudy was performed to evaluate the mechanism of action of IVL, quantifying CAC characteristics and calcium plaque fracture. Independent core laboratories adjudicated angiography and optical coherence tomography, and an independent clinical events committee adjudicated major adverse cardiac events. RESULTS: Between May 2018 and March 2019, 120 patients were enrolled. Severe CAC was present in 94.2% of lesions. Successful delivery and use of the IVL catheter was achieved in all patients. The post-IVL angiographic acute luminal gain was 0.83±0.47 mm, and residual stenosis was 32.7±10.4%, which further decreased to 7.8±7.1% after drug-eluting stent implantation. The primary end point occurred in 5.8% of patients, consisting of 7 non-Q-wave myocardial infarctions. There was no procedural abrupt closure, slow or no reflow, or perforations. In 47 patients with post-percutaneous coronary intervention optical coherence tomography, calcium fracture was identified in 78.7% of lesions with 3.4±2.6 fractures per lesion, measuring 5.5±5.0 mm in length. CONCLUSIONS: In patients with severe CAC who require coronary revascularization, IVL was safely performed with high procedural success and minimal complications and resulted in substantial calcific plaque fracture in most lesions. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03328949

Microvascular Resistance Reserve for Assessment of Coronary Microvascular Function: JACC Technology Corner

The need for a quantitative and operator-independent assessment of coronary microvascular function is increasingly recognized. We propose the theoretical framework of microvascular resistance reserve (MRR) as an index specific for the microvasculature, independent of autoregulation and myocardial mass, and based on operator-independent measurements of absolute values of coronary flow and pressure. In its general form, MRR equals coronary flow reserve (CFR) divided by fractional flow reserve (FFR) corrected for driving pressures. In 30 arteries, pressure, temperature, and flow velocity measurements were obtained simultaneously at baseline (BL), during infusion of saline at 10 mL/min (rest) and 20 mL/min (hyperemia). A strong correlation was found between continuous thermodilution-derived MRR and Doppler MRR (r = 0.88; 95% confidence interval: 0.72-0.93; P < 0.001). MRR was independent from the epicardial resistance, the lower the FFR value, the greater the difference between MRR and CFR. Therefore, MRR is proposed as a specific, quantitative, and operator-independent metric to quantify coronary microvascular dysfunction