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Background and Aim: Diabetes has been shown in last decades to be associated with a significantly higher mortality among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary PCI (PPCI). Therefore, the aim of current study was to evaluate the impact of diabetes on times delays, reperfusion and mortality in a contemporary STEMI population undergoing PPCI, including treatment during the COVID pandemic., Methods and Results: The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry involving PPCI centers from Europe, Latin America, South-East Asia and North-Africa, including patients treated from 1st of March until June 30, 2019 and 2020. Primary study endpoint of this analysis was in-hospital mortality. Secondary endpoints were postprocedural TIMI 0-2 flow and 30-day mortality. Our population is represented by 16083 STEMI patients. A total of 3812 (23,7 %) patients suffered from diabetes. They were older, more often males as compared to non-diabetes. Diabetic patients were less often active smokers and had less often a positive family history of CAD, but they were more often affected by hypertension and hypercholesterolemia, with higher prevalence of previous STEMI and previous CABG. Diabetic patients had longer ischemia time, had more often anterior MI, cardiogenic shock, rescue PCI and multivessel disease. They had less often out-of-hospital cardiac arrest and in-stent thrombosis, received more often a mechanical support, received less often a coronary stent and DES. Diabetes was associated with a significantly impaired postprocedural TIMI flow (TIMI 0-2: 9.8 % vs 7.2 %, adjusted OR [95 % CI] = 1.17 [1.02-1.38], p = 0.024) and higher mortality (in-hospital: 9.1 % vs 4.8 %, Adjusted OR [95 % CI] = 1.70 [1.43-2.02], p < 0.001; 30-day mortality: 10.8 % vs 6 %, Adjusted HR [95 % CI] = 1.46 [1.26-1.68], p < 0.001) as compared to non-diabetes, particularly during the pandemic., Conclusions: Our study showed that in a contemporary STEMI population undergoing PPCI, diabetes is significantly associated with impaired epicardial reperfusion that translates into higher in-hospital and 30-day mortality, particularly during the pandemic., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Hypertension is the most prevalent cardiovascular risk factor, with several detrimental effects on the cardiovascular system. Contrasting results have been reported so far on its prognostic role in patients admitted for ST-segment elevation myocardial infarction (STEMI). Therefore, we investigated the impact of hypertension on short-term mortality in a large multicenter contemporary registry of STEMI patients, including patients treated during COVID-19 pandemic., Methods: The ISACS-STEMI COVID-19 was a retrospective registry that included STEMI patients treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 in 109 high-volume primary PCI centers from 4 continents. We collected data on baseline, clinical and procedural characteristics, in-hospital outcome and 30-day mortality. For this analysis patients were grouped according to history of hypertension at admission., Results: A total of 16083 patients were assessed, including 8813 (54.8%) with history of hypertension. These patients were more often elderly, with a worse cardiovascular risk profile, but were less frequently active smoker. Some procedural differences were observed between the two groups, including lower rate of thrombectomy and use of glycoprotein IIb/IIIa inhibitors or cangrelor but more extensive coronary disease in patients with hypertension. Between patients with and without hypertension, there was no significant difference in SARS-CoV-2 positivity. Hypertensive patients had a significantly higher in-hospital and 30-day mortality, similarly observed in both pre-COVID-19 and COVID-19 era, and confirmed after adjustment for main baseline differences and propensity score (in-hospital mortality: adjusted odds ratio (OR) [95% confidence interval (CI)] =1.673 [1.389-2.014], P < 0.001; 30-day mortality: adjusted hazard ratio (HR) [95% CI] = 1.418 [1.230-1.636], P < 0.001)., Conclusion: This is one of the largest and contemporary study assessing the impact of hypertension in STEMI patients undergoing primary angioplasty, including also the COVID-19 pandemic period. Hypertension was independently associated with significantly higher rates of in-hospital and 30-day mortality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

SARS-Cov-2 has been suggested to promote thrombotic complications and higher mortality. The aim of the present study was to evaluate the impact of SARS-CoV-2 positivity on in-hospital outcome and 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the International Survey on Acute Coronary Syndromes ST-segment elevation Myocardial Infarction (ISACS-STEMI COVID-19 registry. The 109 SARS-CoV-2 positive patients were compared with 2005 SARS-CoV-2 negative patients. Positive patients were older ( P = .002), less often active smokers ( P = .002), and hypercholesterolemic ( P = .006), they presented more often later than 12 h ( P = .037), more often to the hub and were more often in cardiogenic shock ( P = .02), or requiring rescue percutaneous coronary intervention after failed thrombolysis (P < .0001). Lower postprocedural Thrombolysis in Myocardial Infarction 3 flow ( P = .029) and more thrombectomy ( P = .046) were observed. SARS-CoV-2 was associated with a significantly higher in-hospital mortality (25.7 vs 7%, adjusted Odds Ratio (OR) [95% Confidence Interval] = 3.2 [1.71-5.99], P < .001) in-hospital definite in-stent thrombosis (6.4 vs 1.1%, adjusted Odds Ratio [95% CI] = 6.26 [2.41-16.25], P < .001) and 30-day mortality (34.4 vs 8.5%, adjusted Hazard Ratio [95% CI] = 2.16 [1.45-3.23], P < .001), confirming that SARS-CoV-2 positivity is associated with impaired reperfusion, with negative prognostic consequences., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19., Methods: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March-June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality., Results: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825-0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24-1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05-1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic., Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic.

Background: Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry., Methods: This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March-June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality., Results: We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825-0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31-2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96-1.34], p = 0.12)., Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females. Trial registration number: NCT 04412655.

The so-called “smoking paradox”, conditioning lower mortality in smokers among STEMI patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS−STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality, reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic. Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization (p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with non-smokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day (p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in our population, active smoking was significantly associated with improved epicardial recanalization and lower in-hospital and 30-day mortality compared with previous and non-smoking history.

Background: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study., Methods: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents., Results: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups., Conclusion: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity., Trial Registration Number: NCT04412655 (2nd June 2020)., (© 2022. The Author(s).)

Background: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment., Methods: The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients., Results: Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, p  = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, p  < 0.0001), consistently both in 2019 and in 2010., Conclusions: This is first study to investigate the impact of RASI therapy on prognosis and SARS-CoV2 infection of diabetic patients experiencing STEMI and undergoing PPCI during the COVID-19 pandemic. Both pre-admission chronic RASI therapy and in-hospital RASI did not negatively affected patients' survival during the hospitalization, neither increased the risk of SARS-CoV2 infection., Trial Registration Number: NCT04412655., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Masson SAS.)

Background and Aims: SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI)., Methods: We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure., Results: Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and a significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29% vs 5.5%, p < 0.001), definite in-stent thrombosis (8.1% vs 1.6%, p = 0.004) and heart failure (22.6% vs 10.6%, p = 0.001) that was confirmed after adjustment for confounding factors., Conclusions: Our study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Concerns have been raised on a potential interaction between renin-angiotensin system inhibitors (RASI) and the susceptibility to coronavirus disease 2019 (COVID-19). No data have been so far reported on the prognostic impact of RASI in patients suffering from ST-elevation myocardial infarction (STEMI) during COVID-19 pandemic, which was the aim of the present study., Methods: STEMI patients treated with primary percutaneous coronary intervention (PPCI) and enrolled in the ISACS-STEMI COVID-19 registry were included in the present sub-analysis and divided according to RASI therapy at admission., Results: Our population is represented by 6095 patients, of whom 3654 admitted in 2019 and 2441 in 2020. No difference in the prevalence of SARSCoV2 infection was observed according to RASI therapy at admission (2.5% vs 2.1%, p = 0.5), which was associated with a significantly lower mortality (adjusted OR [95% CI]=0.68 [0.51-0.90], P = 0.006), confirmed in the analysis restricted to 2020 (adjusted OR [95% CI]=0.5[0.33-0.74], P = 0.001). Among the 5388 patients in whom data on in-hospital medication were available, in-hospital RASI therapy was associated with a significantly lower mortality (2.1% vs 16.7%, OR [95% CI]=0.11 [0.084-0.14], p < 0.0001), confirmed after adjustment in both periods. Among the 62 SARSCoV-2 positive patients, RASI therapy, both at admission or in-hospital, showed no prognostic effect., Conclusions: This is the first study to investigate the impact of RASI therapy on the prognosis and SARSCoV2 infection of STEMI patients undergoing PPCI during the COVID-19 pandemic. Both pre-admission and in-hospital RASI were associated with lower mortality. Among SARSCoV2-positive patients, both chronic and in-hospital RASI therapy showed no impact on survival., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19., Methods: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality., Results: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73-0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients., Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic., Trial Registration Number: NCT04412655.

Background: Failure of a small surgical aortic bioprosthesis represents a challenging clinical scenario with valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) often resulting in patient-prosthesis mismatch. Bioprosthetic valve fracture (BVF) performed as a part of the ViV TAVI has recently emerged as an alternative approach with certain types of surgical bioprostheses., Case Summary: An 81-year-old woman with a history of three surgical aortic valve procedures presented with heart failure. Aortic bioprosthesis degeneration with severe stenosis and moderate regurgitation was found. The patient was deemed a high-risk surgical candidate and the heart team decided that ViV TAVI was the preferred treatment option. Due to the very small 19 mm stented surgical aortic bioprosthesis Mitroflow 19 mm (Sorin Group, Italy) we decided to perform BVF as a part of ViV TAVI to prevent patient-prosthesis mismatch. Since this was the first BVF procedure in our centre, an ex vivo BVF of the same kind of bioprosthetic valve was performed first. Subsequently, successful BVF with implantation of Evolut R 23 mm (Medtronic, USA) self-expandable transcatheter valve was performed. Excellent haemodynamic result was achieved and no periprocedural complications were present. The patient had an immediate major improvement in clinical status and remains asymptomatic after 6 months., Discussion: Bioprosthetic valve fracture together with ViV TAVI is a safe and effective emerging technique for treatment of small surgical aortic bioprosthesis failure. Bioprosthetic valve fracture allows marked oversizing of implanted self-expandable transcatheter aortic valves, leading to excellent haemodynamic and clinical results. An ex vivo BVF can serve as an important preparatory step when introducing the new method., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality., Objectives: The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of "at-risk" patient cohorts for failure to present or delays to treatment., Methods: This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality., Results: A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001). The heterogeneity among centers was not related to the incidence of death due to COVID-19. A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019. Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic., Conclusions: The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic. (Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655)., Competing Interests: Author Relationship With Industry This study was promoted by the Eastern Piedmont University, Novara, Italy, without any financial support. Dr. Cortese has been funded by PRIN2017 (20178S4EK9). All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to prospectively assess the impact of routine invasive physiology at the time of angiography on reclassification of therapeutic management of multivessel disease (MVD) patients, and to assess how implementation of instantaneous wave-free ratio (iFR) alters the process., Background: Routine invasive physiology in intermediate coronary lesions at the time of diagnostic angiography, primarily in patients with single-vessel disease and using fractional flow reserve (FFR), reclassifies coronary revascularization management in 26% to 44% of patients. The role of invasive physiology in patients with MVD is unclear., Methods: In 18 centers, 484 patients undergoing diagnostic angiography disclosing MVD with lesions >40% by visual assessment were included. Investigators were asked to prospectively define their initial management strategy based on angiography and clinical information. Invasive physiology (FFR or iFR driven) was then performed and final strategy defined. Initial and final vessel, patient, procedural, and overall management were described. Reclassification was defined as the difference between initial and final strategy., Results: The majority of patients were clinically stable (82.2%). Two- and 3-vessel disease was present in 73.3% and 26.7% of patients, respectively. Lesions investigated were "intermediate" with median percent stenosis, median FFR, and median iFR at 60% (interquartile range [IQR]: 50% to 70%), 0.84 (IQR: 0.78 to 0.90), and 0.92 (IQR: 0.85 to 0.96), respectively. Vessel management was reclassified by physiology in 30.0% (249 of 828) of vessels. Patient and overall management were reclassified in 26.9% (130 of 484) and 45.7% (211 of 484) of patients, respectively. Reclassification rates were high irrespective of initial management (optimal medical therapy, percutaneous coronary intervention, or coronary artery bypass grafting), and performance and results of pre-procedural noninvasive tests. Reclassification of overall management in particular increased with the number of vessels investigated (1 vessel: 37.3%; 2 vessels: 45.0%; 3 vessels: 66.7%; p = 0.002). Incorporating iFR in the decision process was associated with investigation of more vessels (p = 0.04) and higher reclassification (p = 0.0001)., Conclusions: In patients with MVD and intermediate coronary lesions, invasive physiology at time of angiography reclassifies revascularization strategy in a large proportion of cases (26.9%) and investigation of more vessels is associated with higher reclassification rates., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cigarette smoke is associated with increased carotid intimal thickening or stroke. Preliminary work showed that exposure to smoke resulted in a 4.5-fold reduction of heat shock protein-70 (HSP70) expression in spleens of mice using gene microarray analysis. In the current study, we investigated the role of extracellular HSP70 in carotid intimal thickening of mice exposed to cigarette smoke. Intimal thickening was induced by placement of a cuff around the right carotid artery of mice. Cuff injury resulted in increased HSP70 mRNA expression in carotid arteries that persisted for 21 days. Cigarette smoke exposure decreased arterial HSP70 expression and significantly increased intimal thickening compared with mice exposed to air. Treatment of mice exposed to cigarette smoke with intravenous recombinant HSP70 attenuated intimal thickening through reduced phosphorylated extracellular signal-regulated kinase (pERK) expression in the arterial wall. In vitro experiments with rat aortic smooth muscle cells confirmed that recombinant HSP70 decreases pERK and proliferating cell nuclear antigen (PCNA) expression in cells exposed to cigarette smoke extract and H(2)O(2). Our study suggests that decreased expression of arterial HSP70 is an important mechanism by which exposure to cigarette smoke augments intimal thickening. The effects of recombinant HSP70 suggest a role for extracellular HSP70.

Interleukin 15 (IL-15) is a pro-inflammatory cytokine that modulates T cell recruitment and activation, independent of antigen. It has been detected in human atherosclerotic plaques and atherosclerotic plaques of apoE-/- mice. IL-15 regulates fractalkine (FKN)-CX3CR1 chemokine signaling which is involved in atherogenesis and promotes SMC proliferation. We investigated the role of IL-15 in intimal thickening after arterial injury. Treatment of serum-stimulated SMC with IL-15 in vitro attenuated proliferation and suppressed CX3CR1 and FKN mRNA expression. The role of endogenous IL-15 in vivo was investigated in injured carotid arteries of mice. Periadventitial arterial injury resulted in increased IL-15 expression in the media and neointima, paralleled by increased IL-15 receptor alpha expression. Blockade of endogenous IL-15 increased intimal thickening. FKN and CX3CR1 expression increased after injury and were further augmented after IL-15 blockade. These data suggest that endogenous IL-15 attenuated intimal thickening after arterial injury. The potential mechanism of action is suppression of CX3CR1 signaling.

An experimental investigation is presented on oscillations excited by the dynamics of an anode double layer or fireball in a double plasma (DP) machine. The fireball is created by additional ionization processes in front of a small circular anode, which is inserted into the diffusive DP plasma and biased positively. An annular (ring) electrode, usually biased negatively, surrounds the anode. The extension of the ion sheath in front of this ring controls the anode current by varying the effective diameter of the anode during the fireball oscillations. The ring voltage affects not only the oscillation frequency of the anode current but also other characteristics of the instability. Related phenomena consisting of ion-acoustic waves and almost synchronous oscillations of the plasma potential in the chamber where the fireball is formed are also presented.

Alkaptonuria is a rare genetic disorder of tyrosine metabolism in which a bluish pigment accumulates in the connective tissues throughout the body, and causes degenerative changes. The most common clinical manifestation of ochronosis is arthropathy. Heart valves may also be affected, though cardiac involvement is rare. The present patient has cardiac ochronosis, and has several family members diagnosed with ochronosis and aortic valve stenosis.

New prognosticators are needed for breast cancer patients after the initial surgical treatment to make therapeutic decisions that ultimately will affect their DFS. These consist of specific proteolytic enzymes including lysosomal endopeptidases. In this study, the activity and protein concentrations of cathepsins (Cats) D, B, and L were measured in 282 invasive breast tumor cytosols. These potential biological prognostic indicators were compared with other histopathological parameters, such as tumor size, lymph node involvement, tumor-node-metastasis stage, histological grade, DNA analysis, and steroid receptors. CatD protein concentration correlated with lymph node involvement. CatB and CatL levels correlated significantly with Scarf-Bloom-Richardson histological grade and were also higher in estrogen-negative tumors, and CatB was higher in larger tumors. As prognostic markers, CatB concentration was significant for increased risk for recurrence in the entire patient population and specifically also in lymph node-negative patients as follows: high CatB concentration (above 371 micrograms/g) in tumor cytosols was significant (P < 0.00) for high risk of recurrence but was of only borderline prognostic significance (P < 0.06) for overall survival of all patients. In lymph node-negative patients, CatB (above 240 micrograms/g, P < 0.003) was highly significant for recurrence-free survival, followed by CatL (above 20 micrograms/g, P < 0.049) and CatD (above 45 nmol/g, P < 0.044) concentrations. For overall survival of node-negative patients, only CatB was a significant (P < 0.014) prognosticator. We conclude that CatB is useful as a prognostic indicator in lymph node-negative patients. This suggests that selective adjuvant therapy should be applied in this lower risk group of patients when high levels of CatB are determined.