Objective and Aim: The extent of the protection against SARS-CoV-2 conferred by natural infection is unclear. Vitamin D may have a role in the interplay between SARS-CoV-2 infection and the evolving acquired immunity against it. We tested the correlation between baseline 25(OH) D content and both the reinfection rate and the anti-spike protein antibody titer following COVID-19 infection. Methods A retrospective observational survey that included a large convalescent COVID-19 population of subjects insured by the Leumit HMO was recorded between 1 February 2020 and 30 January 2022. Inclusion criteria required at least one available 25(OH)D level prior to enlistment. The association between 25(OH)D levels, the rate of breakthrough infection, and the anti-spike protein antibody titer was evaluated. Results A total of 10,132 COVID-19 convalescent subjects were included, of whom 322 (3.3%) sustained reinfection within a one-year follow-up. In the first 8 months after recovery, the reinfected patients were characterized by a higher incidence of low 25(OH)D levels (<30 ng/mL, 92% vs. 84.8%, p < 0.05), while during the following three months, the incidence of low 25(OH)D levels was non-significantly higher among PCR-negative convalescent subjects compared to those reinfected (86% vs. 81.7, p = 0.15). By multivariate analysis, age > 44 years (OR-0.39, 95% CI: 0.173–0.87, p = 0.02) and anti-spike protein antibody titer > 50 AU/mL (0.49, 95% CI: 0.25–0.96, p = 0.04) were inversely related to reinfection. No consistent correlation with vitamin D levels was observed among the 3351 available anti-spike protein antibody titers of convalescent subjects. However, the median anti-spike protein antibody titers tended to increase over time in the vitamin D-deficient group. Conclusion Higher pre-infection 25(OH)D level correlated with protective COVID-19 immunity during the first 8 months following COVID-19 infection, which could not be explained by anti-spike protein antibody titers. This effect dissipated beyond this period, demonstrating a biphasic 25(OH)D association that warrants future studies.

Risk models to estimate percutaneous coronary intervention (PCI) mortality have limited value in complex high-risk patients. However, it was improved by a recently developed bedside model to predict in-hospital mortality using data from the American College of Cardiology CathPCI Registry that included 706,263 patients. The median risk -standard-ized in-hospital mortality rate was 1.9%. In an attempt to validate this model in patients admitted because of acute coronary ischemia to predict in-hospital, 30-day, and 1-year mortality, we applied the proposed risk score to the study population of the Acute Coro-nary Syndrome Israeli Survey (ACSIS). This study was conducted for 2 months in 2018 and included all patients admitted to 25 coronary care units and cardiology departments in Israel. The ACSIS included 1,155 patients admitted because of acute myocardial infarc-tion and who underwent PCI. In-hospital, 30-day, and 1-year mortality were 2.3%, 3.1%, and 6.2%, respectively. The CathPCI risk score yielded an area under the receiver operat-ing characteristic curve of 0.96 (95% confidence interval [CI] 0.94 to 0.99) for in-hospital mortality; 0.96 (95% CI 0.94 to 0.98) for the 30-day mortality, and 0.88 (95% CI 0.83 to 0.93) for the 1-year mortality. The current model also included frail patients, and those with aortic stenosis, refractory shock, and after cardiac arrest. In conclusion, the CathPCI Registry risk score was validated using data from the ACSIS. Because the ACSIS popula-tion comprised patients with acute ischemia including those with high-risk features this model demonstrates a wider scope of application compared with previous ones. In addi-tion, the model seems to be suitable to predict also the 30-day and 1-year mortality.& COPY; 2023 Elsevier Inc. All rights reserved. (Am J Cardiol 2023;201:268-272)

Background and Aims: Morphine use for patients presenting with NSTE-ACS is associated with excess mortality. However, the role of morphine in STE-ACS is ill characterized. We have recently confirmed direct prothrombotic effect of morphine using murine models. We sought to explore whether morphine use in STE-ACS patients, used to be scheduled for downstream P 2 Y 12 blockers, is negatively associated with procedural and clinical outcomes. Methods: A single-center, observational retrospective analysis enrolling 130 non-randomized stable patients sustaining STE-ACS as their first manifestation of coronary disease, who presented between December 2010 and June 2013. All were managed by early invasive approach. Of study patients, 55 were treated by morphine, and 75 were not. All were administered downstream P 2 Y 12 blockers according to an already abandoned local policy. Outcomes evaluated included TIMI grade flow, thrombus burden, ST-segment resolution, myocardial function by echocardiography, and cardiovascular death. Results: Morphine administration was associated with a significantly higher incidence of impaired final TIMI grade flow (TIMI < 3, 40% vs 4%, P < .05), lower incidence of ST-segment resolution >70% (40.7% vs 76.5%, P < .05), and a higher incidence of moderate or severe systolic dysfunction (48.1% vs 29.1%, P < .05) compared with morphine naive patients. Interestingly, the overall mortality rate was higher in the morphine-treated group (18% vs 5.3%, P < .05). Conclusions and Relevance: Morphine administration combined with the downstream P 2 Y 12 blockers practice signify a group with a higher occurrence of impaired myocardial reperfusion and cardiovascular death despite established on-time primary angioplasty. Keywords morphine , no-reflow , thrombosis , downstream

BACKGROUND AND AIMS:Morphine use for patients presenting with NSTE-ACS is associated with excess mortality. However, the role of morphine in STE-ACS is ill characterized. We have recently confirmed direct prothrombotic effect of morphine using murine models. We sought to explore whether morphine use in STE-ACS patients, used to be scheduled for downstream P2Y12 blockers, is negatively associated with procedural and clinical outcomes. METHODS:A single-center, observational retrospective analysis enrolling 130 non-randomized stable patients sustaining STE-ACS as their first manifestation of coronary disease, who presented between December 2010 and June 2013. All were managed by early invasive approach. Of study patients, 55 were treated by morphine, and 75 were not. All were administered downstream P2Y12 blockers according to an already abandoned local policy. Outcomes evaluated included TIMI grade flow, thrombus burden, ST-segment resolution, myocardial function by echocardiography, and cardiovascular death. RESULTS:Morphine administration was associated with a significantly higher incidence of impaired final TIMI grade flow (TIMI < 3, 40% vs 4%, P < .05), lower incidence of ST-segment resolution >70% (40.7% vs 76.5%, P < .05), and a higher incidence of moderate or severe systolic dysfunction (48.1% vs 29.1%, P < .05) compared with morphine naive patients. Interestingly, the overall mortality rate was higher in the morphine-treated group (18% vs 5.3%, P < .05). CONCLUSIONS AND RELEVANCE:Morphine administration combined with the downstream P2Y12 blockers practice signify a group with a higher occurrence of impaired myocardial reperfusion and cardiovascular death despite established on-time primary angioplasty.

Objective: Vaccines against COVID-19 induce specific antibodies whose titer is perceived as a reliable correlate of protection. Vitamin D confers complex regulatory effects on the innate and adaptive immunity. In this study, we explored a plausible impact of baseline vitamin D content on achieved immunity following COVID-19 vaccination. Methods: A retrospective observational study comprising 73,254 naïve subjects insured by the Leumit Health Service HMO, who were vaccinated between 1 February 2020 and 30 January 2022, with one available vitamin D level prior to vaccination, was performed. The association between 25(OH) vitamin D levels, SARS-CoV-2 antibody titer, and post-vaccination PCR results were evaluated. Results: Of the study population, 5026 (6.9%) tested positive for COVID-19. The proportion of low 25(OH)D levels (<30 ng/mL) was significantly higher in the PCR-positive group (81.5% vs. 79%, p < 0.001). Multivariate analysis showed a higher incidence of breakthrough infection among non-smokers [1.37 (95% CI 1.22–1.54, p < 0.001)] and lower incidences among subjects with sufficient 25(OH)D levels (>30 ng/mL) [0.87 (95% CI 0.79–0.95, p—0.004)], hyperlipidemia [0.84 (95% CI 0.76–0.93, p < 0.001], depression [OR-0.87 (95% CI: 0.79–0.96, p < 0.005], socio-economic status >10 [0.67 (95% CI 0.61–0.73, p < 0.001)], and age >44 years. SARS-CoV-2 antibody titers were available in 3659 vaccinated individuals. The prevalence of antibody titers (<50 AU) among PCR-positive subjects was 42% compared to 28% among PCR-negative subjects (p < 0.001). Baseline 25(OH)D levels showed an inverse relation to total antibody titers. However, no association was found with an antibody titer <50 AU/mL fraction. Conclusion Baseline 25(OH)D levels correlated with the vaccination-associated protective COVID-19 immunity. Antibody titers <50 AU/mL were significantly linked to breakthrough infection but did not correlate with 25(OH)D levels.

BACKGROUND:Movement of the stent delivery system in the coronary bed as a result of the cardiac cycle is a well-known clinical observation that usually is either underestimated or ignored. This effect may potentially jeopardize precise stent deployment. We used a novel technology to objectively measure the relative intracoronary device motion in the different coronary segments throughout the cardiac cycle.METHODS:A total of 193 patients undergoing coronary angiography were enrolled and their studies were analyzed for device movement using the SyncVision System (Philips Volcano). The SyncVision System is an add-on image-processing system with unique enhancement and stabilization capabilities. A new feature, the device-motion indication, can precisely display the predeployment device movement measurement (DMM). The device movements within the three segments of each coronary artery were recorded.RESULTS:We identified 218 branch point sites. Median axial displacement was 2.97 mm at the right coronary artery (RCA), 2.22 mm at the left circumflex, and 1.84 mm at the left anterior descending segments. The most movable segments were mid and distal RCA (P<.05). Both heart rate and cardiac contractility significantly affected DMM.CONCLUSIONS:The study demonstrates an innovative feature of the SyncVision System as a tool to precisely measure relative device displacement. We claim that the relative device movement is an important quality metric to consider for achieving an effective stent implantation process.

Collaterals to occluded coronary arteries have been observed early after the onset of acute myocardial infarction (AMI). The pressure distal to the occluded segment of the culprit coronary artery (P(d)) is generated by collateral flow from the feeding coronary artery supplied by the systemic circulation. The aim of the study was to assess the relation between systemic blood pressure (BP) and P(d). Systemic BP and P(d) were measured simultaneously during intervention of totally occluded coronary arteries in 152 patients admitted for AMI. Patients were divided into groups by time from symptom onset to P(d) measurement. There was a significant positive correlation between P(d) and the systolic, diastolic, and mean BPs measured during the first 3 hours from symptom onset (n = 60; p <0.05, p <0.006, and p <0.005, respectively), from 3 to 12 hours (n = 56; p <0.02 for all), and >12 hours after symptom onset (n = 36; p <0.003 for all). The collateral flow, represented by calculated collateral flow index (mean 0.37 ± 0.14, median 0.36), was correlated with mean BP (p = 0.05) but not with diastolic or systolic BP (p = NS) in the overall study population. A direct relation was established during AMI between systemic BP and P(d) at all time intervals from symptom onset. Collateral flow index correlated with mean BP and was strongly associated with P(d) at all time intervals. In conclusion, the relation between P(d) and systemic BP suggests caution when administering therapy that may lower systemic BP during AMI before restoring flow in the occluded culprit artery, as it may compromise collateral pressure and exacerbate myocardial ischemia.

AIM:Oxidized low-density lipoprotein (oxLDL) interacts with macrophages and is implicated in atherogenesis. Macrophages are also the major source within the atherosclerotic plaque of tissue factor (TF), the membrane-bound glycoprotein receptor that triggers the coagulation cascade in vivo and contributes to plaque thrombogenicity. In this study we tested the hypothesis that oxLDL modulates TF expression in human monocyte-derived macrophages (MDMs).METHODS:Mononuclear cells were isolated from human blood, allowed to differentiate into MDMs during 8 days in cell culture, and then exposed to varying concentrations of oxLDL in the presence or absence of lipopolysaccharide (LPS). TF procoagulant activity (TF-PCA) of MDMs was measured by one-stage recalcification clotting assay using human recombinant TF as standard. TF protein was evaluated by Western blotting, and TF mRNA was determined by Northern blot analysis.RESULTS:OxLDL at 5-10 µg/mL increased TF-PCA, TF protein, and mRNA in MDMs, whereas 20-100 µg/mL oxLDL inhibited TF-PCA, protein expression, and mRNA expression in these cells even in the face of LPS stimulation.CONCLUSIONS:Low concentrations of oxLDL enhance TF expression in MDMs, whereas higher concentrations attenuate TF expression both at baseline as well as following LPS stimulation. Both TF-PCA and TF protein follow this dose-response pattern that is preceded by concordant mRNA changes. Thus, we have demonstrated modulation by oxLDL of TF protein and bioactivity in MDMs.