BACKGROUND: Systemic thromboxane A(2) generation, assessed via measurement of its urinary metabolites, is associated with cardiovascular disease (CVD) risk. Modifiable correlates with thromboxane A(2) generation, including potential nonplatelet sources not readily affected by aspirin, are poorly understood. METHODS: We investigated 2655 FHS (Framingham Heart Study) participants with measurements of urinary thromboxane B-2 metabolites normalized for renal function (TXB2-M-GFR). Life's Essential 8 (LE8) score was constructed from 8 modifiable factors. We additionally examined erythrocyte omega-3 fatty acids and omega-6 fatty acid levels, namely, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid. In a subset of participants, objective measurements of vascular stiffness and adiposity were obtained. We related these factors to TXB2-M-GFR using linear models, adjusting for age, sex, and aspirin use. We also explored the association of LE8 or omega-3 fatty acids with total CVD or heart failure stratified by TXB2-M-GFR. RESULTS: Both total LE8 score (P<0.001) and individual LE8 components (P<0.05 for each), including favorable diet, physical activity, blood glucose, blood pressure, and nonsmoking, were associated with lower TXB2-M-GFR. Higher omega-3 fatty acids (eicosapentaenoic acid+docosahexaenoic acid) and lower arachidonic acid were associated with lower TXB2-M-GFR (P<0.005 for each). Higher TXB2-M-GFR was related to greater waist circumference, computed tomography-measured visceral adipose tissue, and hepatic steatosis (P<0.01 for each), and higher large artery vascular stiffness (P<0.001). Findings were generally consistent across aspirin use status. After median follow-up of 12.9 years (371 CVD and 214 heart failure events), individuals with both high TXB2-M-GFR and low LE8 displayed an over 5-fold higher risk of heart failure (hazard ratio, 5.07 [95% CI, 3.26-7.89]) and 2.5-fold higher risk of CVD (hazard ratio, 2.74 [95% CI, 2.04-3.68]) compared with participants with low TXB2-M-GFR and high LE8. CONCLUSIONS: Our findings suggest several modifiable factors that may impact systemic thromboxane A(2) generation. Higher systemic thromboxane A(2) generation also appears to modulate the association of lifestyle measures (as assessed by LE8 score) with CVD and heart failure.

Background Systemic thromboxane A2 generation, which is readily assessed by quantifying thromboxane B2 metabolites (TXB2-M) in the urine, is associated with impaired cardiac performance and mortality in aspirin (ASA) users with heart failure (HF). Objectives This study sought to determine the association of urinary TXB2-M with the risk of developing HF in individuals without prior history of HF and with normal left ventricular function irrespective of ASA use. Methods Urine TXB2-M were measured by immunoassay and adjusted to urine concentration and renal function (TXB2-MGFR) in 2,611 Framingham Heart Study participants (54.9% women, mean age 65 ± 9 years, 43.8% ASA users) without prior history of HF and with left ventricular ejection fraction (LVEF) ≥55%. The association of TXB2-MGFR with HF risk over a median observation period of 14.8 years (Q1-Q3: 12.6-15.7 years) was modeled using Cox regression. Results HF occurred in 189 participants (7.2%), with 104 of the first events (55.0%) classified as HF with preserved LVEF, 56 (29.6%) as HF with reduced LVEF, and 29 (15.3%) were unclassifiable. TXB2-MGFR levels, above compared to below, of 16.6 and 62.1 filtered prostanoid units for ASA users and nonusers, respectively, were associated with increased risk of developing HF (HR: 1.81; 95% CI: 1.38-2.64; P < 0.0001, adjusted for age, sex, ASA use, and HF risk factors), including both HF subtypes (HF with preserved LVEF: HR: 1.81; 95% CI: 1.17-2.80; P = 0.0081, and HF with reduced LVEF: HR: 2.63; 95% CI: 1.48-4.68; P = 0.0010, adjusted for age, sex, ASA use, and cardiovascular disease). Neither ASA use nor evidence of platelet activation, as measured by plasma P-selectin, were independently associated with HF risk. Conclusions Systemic thromboxane A2 generation as measured by urinary TXB2-MGFR was significantly associated with HF risk and remained so after accounting for traditional risk factors. Urinary TXB2-MGFR is therefore a potentially useful novel biomarker to identify at-risk individuals who might benefit from aggressive primary prevention.

Background: Urinary thromboxane B2 metabolites (TXB 2 ) are biomarkers of systemic thromboxane A2 (TXA 2 ) activity, an eicosanoid synthesized from arachidonic acid (AA) that is recognized to contribute to cardiovascular disease (CVD) independent of its platelet effects. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), produce downstream molecules that can suppress TXA 2 . Whether circulating EPA+DHA or AA may influence TXB 2 levels or modify its association with incident CVD is unknown. Aims: To investigate the relations of circulating EPA, DHA, and AA to urinary TXB 2 and to assess whether these fatty acids may modify the association between TXB 2 and incident CVD. Methods: We studied 2,524 participants in the Framingham Heart Study Offspring/Omni cohorts, who were free of CVD at baseline, with measurements of urinary TXB 2 and circulating EPA, DHA, and AA. Incident CVD included a composite of coronary heart disease, stroke, peripheral artery disease, heart failure, and cardiovascular mortality. Hazard ratio (HR) and 95% confidence interval (CI) of the association between urinary TXB 2 (comparing high vs low using pre-determined cut-offs) and CVD, were calculated using multivariable-adjusted Cox models. We analyzed the cross-sectional relationship between circulating EPA, DHA, and AA with TXB 2 and assessed the relation between a per-1 standard deviation increment in TXB 2 and CVD stratified by tertiles of EPA+DHA or AA. Results: Among non-aspirin users, median TXB 2 decreased across tertiles of EPA (T3 vs T1: 3696 vs 4486 pg/mg creatinine) and DHA (T3 vs T1: 3670 vs 4497) ( P trend <0.0005 for each) ( Table 1 ). On the other hand, TXB 2 increased with higher AA (T3 vs T1: 4378 vs 3857 ( P trend =0.009). Similar trends were seen among aspirin users. After a median 12.9 years of follow-up, 428 incident CVD events occurred. Higher urinary TXB 2 was associated with incident CVD, with HR (95% CI) of 1.61 (1.19, 2.18) for aspirin non-users and 1.36 (1.02, 1.81) for users. Higher EPA+DHA or AA did not appear to modify the association between TXB 2 and incident CVD ( P interaction >0.05 for each). Conclusion: Urinary TXB 2 is associated with incident CVD after accounting for standard CVD risk factors. While circulating EPA and DHA are inversely related to TXB 2 , the association of TXB 2 with incident CVD is consistent across levels of EPA+DHA, suggesting likely separate biological pathways linking TXB 2 and omega-3 fatty acids with CVD development.

Background: Increased risk of thrombotic outcomes has been observed during respiratory infections. This phenomenon likely involves platelet-leukocyte crosstalk via pattern recognition receptors (PRRs), including Toll-like receptors (TLR), Retinoic acid-inducible gene I-like receptors (RLR) and cGAS. Purpose: We studied correlations between PRRs and select pro-thrombotic/procoagulant transcripts (ITGA2B, GP1BA, GP9, GP5, GP6, PF4, PF4V1, F13A1, SELP, SERPING1) in platelets and leukocytes of COVID19 (α-δ variants) patients; and determined if those correlations were present in blood from patients with 3 respiratory infections (COVID19, Influenza, Tuberculosis-TB). Methods: RNA sequencing data of platelets and leukocytes isolated from COVID19 patients (n=10) and non-infected controls (n=15) was generated using AmpliSeq. Whole blood RNAseq was obtained from public databases for COVID19 (GSE217948), influenza (GSE161731), and TB patients (0m-peak infection, GSE181143). Transcripts with significantly greater mean expression in infected patients versus the respective control were assessed for positive correlations with PRRs using Spearman’s correlation coefficients. Data was analyzed in R. Results: Platelets and leukocytes showed distinct patterns of the top five highest expressed PRRs, based on BaseMean (Platelets: TLR9>DDX58>IFIH1>CGAS>TLR4, Leukocytes: TLR4>IFIH1>DDX58>TLR8>TLR2). PRR that were significantly increased in COVID19 platelets versus controls were DDX58 (p=0.017) and IFIH1 (p=0.005); in leukocytes only IFIH1 (p=0.015) showed significant difference. The only overlapping correlation between a PRR and transcript in the two cell populations was TLR1 with F13A1 (platelets, R=0.56, p=0.04; leukocytes, R=0.56, p=0.02). In COVID19 platelets, TLR9 correlated with GP1Ba (R=0.62, p=0.002); DDX58 correlated with GP9 and PF4; and IFIH1 correlated with GP9 and GP6. In COVID19 leukocytes, IFIH1 and DDX58 correlated with SERPING1. In whole blood RNAseq analysis of all 3 infections, only DDX58 and TLR1 uniformly associated with PF4 and F13A1, respectively. Surprisingly, correlations between PRRs and the listed transcripts overlapped predominantly between COVID19 and acute TB, but not with influenza. Conclusion: Platelets and leukocytes show distinct patterns of PRR expression and correlations with pro-thrombotic/procoagulant transcripts. Whole blood correlations between PRRs and thrombotic transcripts in COVID19 infection demonstrate more overlap with TB than influenza.

Objectives:Percutaneous coronary intervention (PCI) via the transradial route has been widely adopted over the transfemoral route, but guide catheter selection remains limited. We present our experience with a novel guide catheter design, the Judkin’s Curve Left- Radial (JCLRAD, Medtronic), which is optimized for transradial PCI to the left coronary system. Methods:Sequential patients who underwent PCI using the JCLRAD catheter over a 3-year period (October 1, 2017 to November 1, 2020) were included in the analysis. Prospectively collected data were extracted from the institutional NCDR CathPCI registry with supplemental medical record review to collect clinical and procedural data. Results:PCI was performed in 2347 patients and 4070 lesions using the JCLRAD guide catheter. The mean age was 65.5 ± 11.7 years, and 72.1% of the population were male; 52.5% of patients presented with acute coronary syndrome. The lesion complexity was high (66.7% Class B2/C by ACCAHA classification) with a 7% use of atherectomy. Procedural success was 99.6% with no identified cases of iatrogenic catheter-induced coronary dissection. Conclusions:In this single-center retrospective study, the use of the JCLRAD was associated with a high success rate and low rates of complications, including no guide catheter-induced dissection in a cohort of patients with complex coronary anatomy. This is the first-reported large clinical experience with this novel radial left coronary system guide catheter.

Background: Systemic thromboxane A(2 )generation, assessed by quantifying the concentration of stable thromboxane B-2 metabolites (TXB2-M) in the urine adjusted for urinary creatinine, is strongly associated with mortality risk. We sought to define optimal TXB2-M cutpoints for aspirin users and nonusers and determine if adjusting TXB2-M for estimated glomerular filtration rate (eGFR) in addition to urinary creatinine improved mortality risk assessment. Methods: Urinary TXB2-M were measured by competitive ELISA in 1363 aspirin users and 1681 nonusers participating in the Framingham Heart Study. Cutpoints were determined for TXB2-M and TXB2-M/eGFR using log-rank statistics and used to assess mortality risk by Cox proportional hazard modeling and restricted mean survival time. Multivariable models were compared using the Akaike Information Criterion (AIC). A cohort of 105 aspirin users with heart failure was used for external validation. Results: Optimized cutpoints of TXB2-M were 1291 and 5609 pg/mg creatinine and of TXB2-M/eGFR were 16.6 and 62.1 filtered prostanoid units (defined as pg center dot min/creatinine center dot mL center dot 1.73 m(2)), for aspirin users and nonusers, respectively. TXB2-M/eGFR cutpoints provided more robust all-cause mortality risk discrimination than TXB2-M cutpoints, with a larger unadjusted hazard ratio (2.88 vs 2.16, AIC P < 0.0001) and greater differences in restricted mean survival time between exposure groups (1.46 vs 1.10 years), findings that were confirmed in the external validation cohort of aspirin users. TXB2-M/eGFR cutpoints also provided better cardiovascular/stroke mortality risk discrimination than TXB2-M cutpoints (unadjusted hazard ratio 3.31 vs 2.13, AIC P < 0.0001). Conclusion: Adjustment for eGFR strengthens the association of urinary TXB2-M with long-term mortality risk irrespective of aspirin use.

We report 4 cases of post myocardial infarction complications due to the delay in presentation during COVID-19 era. We highlighted the need for auscultating the chest for early diagnosis. Through this case series, we urge to raise awareness among cardiac patients to access healthcare despite the fear of COVID-19.

Objective: Destruction of arterial collagen allows monocyte and macrophage infiltration leading to atherosclerotic plaque formation, but it is not clear what role the MMP1 (matrix metalloprotease 1) collagenase plays in this process in vivo. To define the specific contribution of MMP1 to atherosclerotic plaque burden and pathogenesis, we generated ApoE −/− mice deficient in the human MMP1 ortholog, MMP1a. Approach and Results: After 12 to 16 weeks of Western diet, genetic loss of MMP1a resulted in a significant 50% reduction in total aortic plaque burden compared with control ApoE −/− mice. MMP1a deficiency led to significant reductions in plaque monocytes/macrophages, SMCs (smooth muscle cells), and necrosis, with increases in collagen content. Collagen invasion of oxidized-LDL (low-density lipoprotein) activated peripheral blood mononuclear cells from MMP1a-deficient mice was markedly attenuated and was similar to suppressive effects with pharmacological inhibitors of MMP1 and its receptor, PAR1 (protease-activated receptor 1). Patients with coronary artery disease and acute coronary syndrome undergoing cardiac catheterization in the TRIP-PCI trial (Thrombin Receptor Inhibitory Pepducin-Percutaneous Coronary Intervention) were evaluated for circulating levels of all 3 major secreted collagenases, MMP1, MMP8, and MMP13 and total number of coronary lesions with ≥50% stenosis (coronary artery disease burden). MMP1 was significantly ( P <0.001) higher by 19-fold and 5.7-fold relative to MMP13 and MMP8, respectively. MMP1 correlated with stenotic coronary artery disease burden, TNFα (tumor necrosis factor alpha) levels, and was co-expressed with PAR1 on monocytes. Treatment of patients with the PAR1 inhibitor, PZ-128, prevented a drop in monocytes following coronary catheterization, an acute protective effect that was reproduced in mice undergoing cardiac ischemia reperfusion. Conclusions: These data provide evidence for an important role for the MMP1a collagenase in atherosclerotic lesion development and leukocyte behavior and validate MMP1 as a compelling target in patients with coronary artery disease/acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02561000.

BACKGROUND:The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI). OBJECTIVES:The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI. METHODS:A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization. RESULTS:As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p < 0.001 relative to PUIs). COVID+ patients were more likely to present with cardiogenic shock (18%) but were less likely to receive invasive angiography (78%) (all p < 0.001 relative to control patients). Among COVID+ patients who received angiography, 71% received PPCI and 20% received medical therapy (both p < 0.001 relative to control patients). The primary outcome occurred in 36% of COVID+ patients, 13% of PUIs, and 5% of control patients (p < 0.001 relative to control patients). CONCLUSIONS:COVID+ patients with STEMI represent a high-risk group of patients with unique demographic and clinical characteristics. PPCI is feasible and remains the predominant reperfusion strategy, supporting current recommendations.

Rationale: Coronavirus disease 2019 (COVID-19) is characterized by increased incidence of microthrombosis with hyperactive platelets sporadically containing viral RNA. It is unclear if SARS-CoV-2 (severe acute respiratory syndrome, corona virus-2) directly alters platelet activation or if these changes are a reaction to infection-mediated global inflammatory alterations. Importantly, the direct effect of SARS-CoV-2 on platelets has yet to be studied. Objective: To characterize the direct SARS-CoV-2–platelet interactions using in vitro studies with purified infectious virions and samples from infected patients. Methods and Results: Platelet RNA analyzed by ARTIC v3 sequencing for SARS-CoV-2 showed presence of fragmented viral genome in all patients with COVID-19. Immunofluorescent imaging of platelets from patients with COVID-19 confirmed presence of SARS-CoV-2 proteins, whereas there was no detection of viral RNA by real-time quantitative polymerase chain reaction. Transmission electron microscopy of platelets incubated with purified SARS-CoV-2 virions demonstrated rapid internalization and digestion leading to distinct morphological changes and resulted in a release of extracellular vesicles. Interactions between SARS-CoV-2 and platelets occurred with or without ACE (angiotensin-converting enzyme) 2 presence as measured by immunofluorescence. Transmission electron microscopy showed that SARS-CoV-2 virions became internalized when they were attached to microparticles, bypassing the need for ACE2. Enrichment analysis of platelet transcriptome from patients with acute COVID-19, compared with those with clinical thrombosis, suggested upregulation of pathways related to virally mediated cell death, specifically necroptosis and apoptosis. Platelets incubated with infectious virus appeared to undergo cell death in 30 minutes postincubation as assessed by transmission electron microscopy and platelets from patients with COVID-19 showed evidence of increased markers of apoptosis and necroptosis by Western blot. Immunofluorescence confirmed colocalization of SARS-CoV-2 with phospho-MLKL (mixed lineage kinase domain-like pseudokinase) and caspase 3 on nonpermeabilized platelets in vitro and in COVID-19 platelets. Conclusions: Platelets internalize SARS-CoV-2 virions, directly or attached to microparticles, and viral internalization leads to rapid digestion, programmed cell death, and extracellular vesicle release. During COVID-19, platelets mediate a rapid response to SARS-CoV-2 and this response can contribute to dysregulated immunity and thrombosis.

BACKGROUND Persistent systemic thromboxane generation, predominantly from nonplatelet sources, in aspirin (ASA) users with cardiovascular disease (CVD) is a mortality risk factor. OBJECTIVES This study sought to determine the mortality risk associated with systemic thromboxane generation in an unselected population irrespective of ASA use. METHODS Stable thromboxane B2 metabolites (TXB2-M) were measured by enzyme-linked immunosorbent assay in banked urine from 3,044 participants (mean age 66 +/- 9 years, 53.8% women) in the Framingham Heart Study. The association of TXB2-M to survival over a median observation period of 11.9 years (IQR: 10.6-12.7 years) was determined by multivariable modeling. RESULTS In 1,363 (44.8%) participants taking ASA at the index examination, median TXB2-M were lower than in ASA nonusers (1,147 pg/mg creatinine vs 4,179 pg/mg creatinine; P < 0.0001). TXB2-M were significantly associated with all-cause and cardiovascular mortality irrespective of ASA use (HR: 1.96 and 2.41, respectively; P < 0.0001 for both) for TXB2-M in the highest quartile based on ASA use compared with lower quartiles, and remained significant after adjustment for mortality risk factors for similarly aged individuals (HR: 1.49 and 1.82, respectively; P # 0.005 for both). In 2,353 participants without CVD, TXB2-M were associated with cardiovascular mortality in ASA nonusers (adjusted HR: 3.04; 95% CI: 1.29-7.16) but not in ASA users, while ASA use was associated with all-cause mortality in those with low (adjusted HR: 1.46; 95% CI: 1.14-1.87) but not elevated TXB2-M. CONCLUSIONS Systemic thromboxane generation is an independent risk factor for all-cause and cardiovascular mortality irrespective of ASA use, and its measurement may be useful for therapy modification, particularly in those without CVD. (C) 2022 by the American College of Cardiology Foundation.

BACKGROUND:Antiplatelet therapy is paramount to reduce the risk of coronary stent thrombosis after percutaneous coronary intervention (PCI). Newer agents are reliable and have a fast onset of action, but have significantly higher cost, leading to compliance concerns. We adopted and evaluated an acute agent-switching strategy, using prasugrel or ticagrelor for rapid and reliable periprocedural antiplatelet action, followed by a switch to generic clopidogrel. METHODS:This large, single-center study included all patients who underwent PCI between January 1, 2013 and December 31, 2016. Study endpoints were 30- day mortality and bleeding events. RESULTS:A total of 5007 patients met inclusion criteria. Average age was 63.5 ± 12.5 years. Prior to PCI, 54.8% of patients were preloaded with ticagrelor, 8.5% with prasugrel, and 36.7% with clopidogreI. The majority of patients (93%) loaded with ticagrelor and more than half (58%) of those loaded with prasugrel were subsequently switched prior to hospital discharge to clopidogrel for long-term therapy. Patients pretreated with ticagrelor or prasugrel and switched to clopidogrel had overall lowest bleeding rates (0.9% and 0.8%, respectively). The highest rates of bleeding were noted in patients maintained on ticagrelor or clopidogrel throughout (2.5% and 1.7%, respectively). After accounting for additional periprocedural use of intravenous glycoprotein IIb/IIIa inhibitors, the lowest bleeding rates were observed in patients loaded with ticagrelor and switched to clopidogrel (0.75%), with the highest bleeding observed in patients maintained on ticagrelor throughout. There were no events of acute stent thrombosis. CONCLUSIONS:A strategy of using newer, fast-acting, and reliable antiplatelet agents prior to PCI and acutely switching to long-term clopidogrel therapy appears safe and efficacious. Although the superiority of the newer antiplatelet agents for long-term post-PCI dual-antiplatelet therapy in a trial setting is well established, the impact of increased adherence to lower-cost clopidogrel therapy in the real-world setting merits further consideration.

Whether very young patients (≤35-year-old) differ in the prevalence, presentation and prognosis of ACS is not well known. Of 43,446 patients who were referred to a tertiary care cardiac catheterization laboratory between January 1, 2006 and June 30, 2017, 26,545 patients were ACS (defined as ST Elevation MI, Non-ST Elevation MI or unstable angina pectoris). Detailed chart review was performed and characteristics at baseline were compared for ages ≤35 years, ages 36 to 54 years and ages ≥55 years. A total of 291 (1.1%) were ≤35-year-old, 7,649 (28.8) were 36 to 54-year-old and 18,605 (70.1%) were ≥55-year-old. ACS patients aged ≤35-year-old, were more likely to be men, Caucasian white, smoker, obese, and have family history of coronary artery disease and less likely to have comorbidities such as hypertension, diabetes mellitus, and hyperlipidemia compared with older patients. They were also more likely to present with elevated troponin levels than other groups. They also tended to present with late ST elevation myocardial infarction and were more likely to receive bare metal stents than older patients. The prevalence of 2- and 3-vessel disease was lower compared with older patients. They also had higher prevalence of cardiogenic shock. Compared with 36 to 54-year-old patients, ≤35-year-old were at significant higher risk of 30-day mortality in a multivariable adjusted regression model (Odds ratio 5.65, 95% confidence interval 2.49 to 12.82, p <0.001). Very young patients comprised ∼1% of all ACS cases but had much more prevalence of modifiable risk factors and significantly worse mortality. Modifying these risk factors may mitigate the risk in these patients and should be studied in the future.

Objective To evaluate the impact of COVID-19 pandemic migitation measures on of ST-elevation myocardial infarction (STEMI) care. Background We previously reported a 38% decline in cardiac catheterization activations during the early phase of the COVID-19 pandemic mitigation measures. This study extends our early observations using a larger sample of STEMI programs representative of different US regions with the inclusion of more contemporary data. Methods Data from 18 hospitals or healthcare systems in the US from January 2019 to April 2020 were collecting including number activations for STEMI, the number of activations leading to angiography and primary percutaneous coronary intervention (PPCI), and average door to balloon (D2B) times. Two periods, January 2019-February 2020 and March-April 2020, were defined to represent periods before (BC) and after (AC) initiation of pandemic mitigation measures, respectively. A generalized estimating equations approach was used to estimate the change in response variables at AC from BC. Results Compared to BC, the AC period was characterized by a marked reduction in the number of activations for STEMI (29%, 95% CI:18-38,p< .001), number of activations leading to angiography (34%, 95% CI: 12-50,p= .005) and number of activations leading to PPCI (20%, 95% CI: 11-27,p< .001). A decline in STEMI activations drove the reductions in angiography and PPCI volumes. Relative to BC, the D2B times in the AC period increased on average by 20%, 95%CI (-0.2 to 44,p= .05). Conclusions The COVID-19 Pandemic has adversely affected many aspects of STEMI care, including timely access to the cardiac catheterization laboratory for PPCI.

BACKGROUND:Recent studies suggest that primary percutaneous coronary intervention (PCI) and targeted temperature management (TTM) improve outcome in ST-segment elevation myocardial infarction (STEMI) complicated by out-of-hospital cardiac arrest (OHCA). The objective of this study was to evaluate a contemporary series of patients with STEMI and OHCA to characterize treatment approaches and predictors of neurologic outcome. METHODS:From January 2009 through November 2012, a total of 239 patients who underwent emergent coronary angiography at 10 medical centers across the United States were enrolled. All patients suffered OHCA with STEMI on either the prehospital or post-resuscitation electrocardiogram. Neurologic outcome was assessed using the cerebral performance category (CPC) score. Predictors of neurologic outcome were determined using multivariate logistic regression analysis. The primary endpoint was in-hospital survival with good neurologic function (CPC score 1 or 2). RESULTS:Mean age was 60 ± 13 years, 72% were male, and the majority of patients had a history of cardiovascular event. Initial rhythm was ventricular fibrillation in 72%. At hospital presentation, 76% of patients were intubated, 37% were in cardiogenic shock, and 33% were receiving vasopressors. Primary PCI was performed in 74%, with an average door-to-balloon time of 95 ± 77 minutes, and TTM was used in 51%. Forty-four percent of patients had full neurologic recovery (CPC score 1) and 55% had good neurologic function. Overall in-hospital survival rate was 66%. Independent predictors of in-hospital survival with good neurologic function were: receiving bystander cardiopulmonary resuscitation, location of arrest, receiving drug-eluting stents, and not experiencing a recurrent cardiac arrest. CONCLUSIONS:Short-term survival for patients with STEMI and OHCA undergoing emergent coronary angiography and revascularization with TTM in this contemporary, multicenter registry was high and neurologic outcome was good in more than half of patients.

Objective: Arterial thrombosis leading to ischemic injury worsens the prognosis of many patients with cardiovascular disease. PZ-128 is a first-in-class pepducin that reversibly inhibits PAR1 (protease-activated receptor 1) on platelets and other vascular cells by targeting the intracellular surface of the receptor. The TRIP-PCI (Thrombin Receptor Inhibitory Pepducin in Percutaneous Coronary Intervention) trial was conducted to assess the safety and efficacy of PZ-128 in patients undergoing cardiac catheterization with intent to perform percutaneous coronary intervention. Approach and Results: In this randomized, double-blind, placebo-controlled, phase 2 trial, 100 patients were randomly assigned (2:1) to receive PZ-128 (0.3 or 0.5 mg/kg), or placebo in a 2-hour infusion initiated just before the start of cardiac catheterization, on top of standard oral antiplatelet therapy. Rates of the primary end point of bleeding were not different between the combined PZ-128 doses (1.6%, 1/62) and placebo group (0%, 0/35). The secondary end points of major adverse coronary events at 30 and 90 days did not significantly differ but were numerically lower in the PZ-128 groups (0% and 2% in the PZ-128 groups, 6% and 6% with placebo, p=0.13, p=0.29, respectively). In the subgroup of patients with elevated baseline cardiac troponin I, the exploratory end point of 30-day major adverse coronary events + myocardial injury showed 83% events in the placebo group versus 31% events in the combined PZ-128 drug groups, an adjusted relative risk of 0.14 (95% CI, 0.02–0.75); P =0.02. Conclusions: In this first-in-patient experience, PZ-128 added to standard antiplatelet therapy appeared to be safe, well tolerated, and potentially reduced periprocedural myonecrosis, thus providing the basis for further clinical trials. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02561000.