Reducing Quantitative Uncertainty Caused by Data Processing in Untargeted Metabolomics.

Processing liquid chromatography-mass spectrometry-based metabolomics data using computational programs often introduces additional quantitative uncertainty, termed computational variation in a previous work. This work develops a computational solution to automatically recognize metabolic features with computational variation in a metabolomics data set. This tool, AVIR (short for "Accurate eValuation of alIgnment and integRation"), is a support vector machine-based machine learning strategy (https://github.com/HuanLab/AVIR). The rationale is that metabolic features with computational variation have a poor correlation between chromatographic peak area and peak height-based quantifications across the samples in a study. AVIR was trained on a set of 696 manually curated metabolic features and achieved an accuracy of 94% in a 10-fold cross-validation. When tested on various external data sets from public metabolomics repositories, AVIR demonstrated an accuracy range of 84%-97%. Finally, tested on a large-scale metabolomics study, AVIR clearly indicated features with computational variation and thus guided us to manually correct them. Our results show that 75.3% of the samples with computational variation had a relative intensity difference of over 20% after correction. This demonstrates the critical role of AVIR in reducing computational variation to improve quantitative certainty in untargeted metabolomics analysis.

Angiographic characteristics of patients with STEMI and COVID-19: Insights from NACMI registry.

BACKGROUND: To date, there has been no independent core lab angiographic analysis of patients with COVID-19 and STEMI. The study characterized the angiographic parameters of patients with COVID-19 and STEMI. METHODS: Angiograms of patients with COVID-19 and STEMI from the North American COVID-19 Myocardial Infarction (NACMI) Registry were sent to a Core Laboratory in Vancouver, Canada. Culprit lesion(s), Thrombolysis In Myocardial Infarction (TIMI) flow, Thrombus Grade Burden (TGB), and percutaneous coronary intervention (PCI) outcome were assessed. RESULTS: From 234 patients, 74% had one culprit lesion, 14% had multiple culprits and 12% had no culprit identified. Multivessel thrombotic disease and multivessel CAD were found in 27% and 53% of patients, respectively. Stent thrombosis accounted for 12% of the presentations and occurred in 55% of patients with previous coronary stents. Of the 182 who underwent PCI, 60 (33%) had unsuccessful PCI due to post-PCI TIMI flow <3 (43/60), residual high thrombus burden (41/60) and/or thrombus related complications (27/60). In-hospital mortality for successful, partially successful, and unsuccessful PCI was 14%, 13%, and 27%, respectively. Unsuccessful PCI was associated with increased risk of in-hospital mortality (risk ratio [RR] 1.96; 95% CI: 1.05-3.66, P = .03); in the adjusted model this estimate was attenuated (RR: 1.24; 95% CI: 0.65-2.34, P = .51). CONCLUSION: In patients with COVID-19 and STEMI, thrombus burden was pervasive with notable rates of multivessel thrombotic disease and stent thrombosis. Post-PCI, persistent thrombus and sub-optimal TIMI 3 flow rates led to one-third of the PCI's being unsuccessful, which decreased over time but remained an important predictor of in-hospital mortality.

A Review of ST-Elevation Myocardial Infarction in Patients with COVID-19.

The Coronavirus disease 2019 (COVID-19) pandemic has led to a significant increase in worldwide morbidity and mortality. Patients with COVID-19 are at risk for developing a variety of cardiovascular conditions including acute coronary syndromes, stress-induced cardiomyopathy, and myocarditis. Patients with COVID-19 who develop ST-elevation myocardial infarction (STEMI) are at a higher risk of morbidity and mortality when compared with their age- and sex-matched STEMI patients without COVID-19. We review current knowledge on the pathophysiology of STEMI in patients with COVID-19, clinical presentation, outcomes, and the effect of the COVID-19 pandemic on overall STEMI care.

Novel multi-marker proteomics in phenotypically matched patients with ST-segment myocardial infarction: association with clinical outcomes.

Early prediction of significant morbidity or mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) represents an unmet clinical need. In phenotypically matched population of 139 STEMI patients (72 cases, 67 controls) treated with primary percutaneous coronary intervention, we explored associations between a 24-h relative change from baseline in the concentration of 91 novel biomarkers and the composite outcome of death, heart failure, or shock within 90 days. Additionally, we used random forest models to predict the 90-day outcomes. After adjustment for false discovery rate, the 90-day composite was significantly associated with concentration changes in 14 biomarkers involved in various pathophysiologic processes including: myocardial fibrosis/remodeling (collagen alpha-1, cathepsin Z, metalloproteinase inhibitor 4, protein tyrosine phosphatase subunits), inflammation, angiogenesis and signaling (interleukin 1 and 2 subunits, growth differentiation factor 15, galectin 4, trefoil factor 3), bone/mineral metabolism (osteoprotegerin, matrix extracellular phosphoglycoprotein and tartrate-resistant acid phosphatase), thrombosis (tissue factor pathway inhibitor) and cholesterol metabolism (LDL-receptor). Random forest models suggested an independent association when inflammatory markers are included in models predicting the outcomes within 90 days. Substantial heterogeneity is apparent in the early proteomic responses among patients with acutely reperfused STEMI patients who develop death, heart failure or shock within 90 days. These findings suggest the need to consider synergistic multi-biomarker strategies for risk stratification and to inform future development of novel post-myocardial infarction therapies.

Statins and atherosclerotic cardiovascular outcomes in patients on incident dialysis and with atherosclerotic heart disease.

Statins failed to reduce cardiovascular (CV) events in trials of patients on dialysis. However, trial populations used criteria that often excluded those with atherosclerotic heart disease (ASHD), in whom statins have the greatest benefit, and included outcome composites with high rates of nonatherosclerotic CV events that may not be modified by statins. Here, we study whether statin use associates with lower atherosclerotic CV risk among patients with known ASHD on dialysis, including in those likely to receive a kidney transplant, a group excluded within trials but with lower competing mortality risks. METHODS: Using data from the United States Renal Data System including Medicare claims, we identified adults initiating dialysis with ASHD. We matched statin users 1:1 to statin nonusers with propensity scores incorporating hard matches for age and kidney transplant listing status. Using Cox models, we evaluated associations of statin use with the primary composite of fatal/nonfatal myocardial infarction and stroke (including within prespecified subgroups of younger age [<50 years] and waitlisting status); secondary outcomes included all-cause mortality and the composite of all-cause mortality, nonfatal myocardial infarction, or stroke. RESULTS: Of 197,716 patients with ASHD, 47,562 (24%) were consistent statin users from which we created 46,186 matched pairs. Over a median 662 days, statin users had similar risk of fatal/nonfatal myocardial infarction or stroke overall (hazard ratio [HR] 1.00, 95% CI 0.97-1.02), or in subgroups (age< 50 years [HR = 1.05, 95% CI 0.95-1.17]; waitlisted for kidney transplant [HR 0.99, 95% CI 0.97-1.02]). Statin use was modestly associated with lower all-cause mortality (HR 0.96, 95% CI 0.94-0.98; E value = 1.21) and, similarly, a modest lower composite risk of all-cause mortality, nonfatal myocardial infarction, or stroke over the first 2 years (HR 0.90, 95% CI 0.88-0.91) but attenuated thereafter (HR 0.98, 95% CI 0.96-1.01). CONCLUSIONS: Our large observational analyses are consistent with trials in more selected populations and suggest that statins may not meaningfully reduce atherosclerotic CV events even among incident dialysis patients with established ASHD and those likely to receive kidney transplants.

High-throughput targeted proteomics discovery approach and spontaneous reperfusion in ST-segment elevation myocardial infarction.

BACKGROUND: Although spontaneous reperfusion (SR) prior to primary percutaneous coronary intervention (pPCI) is associated with improved outcomes, its pathophysiology remains unclear. The objective of the study was to explore associations between SR in ST-segment elevation myocardial infarction (STEMI) using a multimarker cardiovascular proteins strategy METHODS: We evaluated STEMI patients from the Assessment of Pexelizumab in Acute Myocardial Infarction trial treated with pPCI within 6 hours from symptom onset. SR was core laboratory-defined as pre-PCI Thrombolysis in Myocardial Infarction flow 2 or 3. Ninety-one cardiovascular disease-related serum biomarkers drawn prior to PCI were analyzed using a high-throughput "targeted discovery" panel. Expression levels for individual biomarkers were compared between patients with/without SR. A hierarchical clustering method of biomarkers identified clusters of biomarkers that differentiated the 2 groups. Associations between individual biomarkers and clusters with SR were further evaluated by multivariable logistic regression. RESULTS: Of 683 patients studied, 290 had spontaneous reperfusion; those with compared to without SR were more likely noninferior STEMI and had lower clinical acuity and lower baseline levels of troponin and creatine kinase. SR was associated with a lower occurrence of 90-day composite of death, heart failure, or cardiogenic shock. Fifty-two of 91 individual biomarkers were significantly univariably associated with SR. Forty-five remained significant with adjustment for false discovery rate. Using cluster analysis, 26 biomarkers clusters were identified, explaining 72% of total covariance, and 13 biomarker clusters were significantly associated with SR after multivariable adjustment. SR was associated with higher mean expression levels of proteins in all 13 clusters. The cluster most strongly associated with SR consisted of novel proteins across various distinct, yet interlinked, pathobiological processes (kallikrein-6, matrix extracellular phosphoglycoprotein, matrix mettaloproteinaise-3, and elafin). CONCLUSIONS: Spontaneous reperfusion prior to pPCI in STEMI was associated with a lower risk of adverse clinical events. These exploratory data from a targeted discovery proteomics platform identifies novel proteins across diverse, yet complementary, pathobiological axes that show promise in providing mechanistic insights into spontaneous reperfusion in STEMI. CONDENSED ABSTRACT: Spontaneous reperfusion has been established with improved STEMI outcomes, yet its pathobiology is unclear and appears to involve diverse physiological processes. Using a 91-biomarker high-throughput proteomics platform, we studied 683 STEMI patients in the APEX AMI trial (290 had core laboratory-adjudicated pre-PCI TIMI 2/3 flow) and identified 52 proteins that univariably associate with spontaneous reperfusion. Cluster analysis identified 26 biomarker clusters (explaining 72% of total variance), 13 of which, after multivariable adjustment, were significantly associated with spontaneous reperfusion. Four proteins (kallikrein-6, matrix extracellular phosphoglycoprotein, matrix mettaloproteinaise-3, and elafin) across diverse, yet complementary, pathways appear to be associated most strongly with spontaneous reperfusion.

Associations between ß-blocker therapy and cardiovascular outcomes in patients with diabetes and established cardiovascular disease.

BACKGROUND: The effects of ß-blocker therapy in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) are unclear. We sought to evaluate associations between ß-blocker use in T2D with ASCVD and cardiovascular (CV) outcomes. METHODS: In patients with T2D and ASCVD enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), an inverse probability of treatment-weighted Cox proportional hazards model was used to examine the association between baseline ß-blocker therapy (at randomization) and the primary CV composite (defined as CV death, non-fatal myocardial infarction [MI], non-fatal stroke, or hospitalization for unstable angina), including in subgroups with prior MI and heart failure (HF); other outcomes evaluated included individual components of the primary composite, hospitalization for HF, and severe hypoglycemic events. RESULTS: Of the 14,671 patients randomized, 9322 (64%) were on a ß-blocker at baseline; these patients were more likely to have prior MI or HF. Over a median 3.0 (25th, 75th percentile: 2.2, 3.6) years, the risk of the primary CV composite was significantly higher with baseline ß-blocker use versus no ß-blocker use (4.5 vs. 3.4 events/100-patient years, adjusted hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05-1.29); no significant interaction was noted for patients with versus without prior MI or HF. Baseline ß-blocker use was not associated with risks for severe hypoglycemic events (HR 1.14, 95% CI 0.88-1.48). CONCLUSIONS: In this observational analysis of T2D and ASCVD, baseline ß-blocker use was not associated with risks for severe hypoglycemia yet also was not associated with CV risk reduction over 3 years of follow-up, supporting a randomized examination of chronic ß-blocker therapy in this patient population. (TECOS ClinicalTrials.gov number, NCT00790205).

Secondary mitral regurgitation: percutaneous edge-to-edge repair on the cutting edge?

PURPOSE OF REVIEW: Secondary mitral regurgitation commonly complicates heart failure. Although the evidence for its management is most robust for treating the underlying cardiomyopathy, treatment aimed at additionally reducing the severity of mitral regurgitation with a percutaneous edge-to-edge device, MitraClip, has recently emerged. RECENT FINDINGS: Despite the use of contemporary evidence-based heart failure therapies, patients with secondary mitral regurgitation and heart failure continue to remain at high risk for adverse clinical events; in both the MITRA-FR and COAPT trials, an extremely high event rate was evident in the medically managed arms over the respective 12-24-month follow-up. Data supporting the use of MitraClip to mitigate adverse outcomes in secondary mitral regurgitation is, however, conflicting. In MITRA-FR no difference was noted between MitraClip compared with the medically managed arm for the composite of all-cause death or heart failure hospitalization at 12 months. However, in COAPT, a significant reduction in the rate of heart failure re-hospitalization over 2 years was evident with MitraClip compared with medical therapy alone. SUMMARY: Recommendations exist for the use of MitraClip in patients with primary mitral regurgitation and prohibitive surgical risk. However, with the divergent results of two recent high-quality randomized trials, its role in patients with secondary mitral regurgitation remains controversial.

Determination of fasiglifam-induced liver toxicity: Insights from the data monitoring committee of the fasiglifam clinical trials program.

BACKGROUND: Different approaches to safety event collection influence the determination of liver toxicity within drug development programs. Herein, a description of how fasiglifam-induced liver injury was detected is provided. METHODS: This eight-trial drug development program was intended to evaluate fasiglifam (25 mg, 50 mg) against placebo or active comparators (glimepiride, sitagliptin) in approximately 11,000 suboptimally controlled patients with type 2 diabetes (terminated Dec 2013 due to liver toxicity). Liver safety had been pre-identified as a concern, and within the phase 3 trials, was measured through (1) adverse event reporting, (2) central predefined liver monitoring schedule with various thresholds for potential drug-induced liver injury, and (3) blinded adjudication of serious liver toxicity by a panel of experts in drug-induced liver injury. A single data monitoring committee provided safety oversight across all trials within the program. FINDINGS: Prior to program termination, 7595 of 7602 (99.9%) randomized participants across the eight trials received at least one dose of the study drug (fasiglifam, placebo, or active control). No concerning trends were noted in adverse or serious adverse event frequency, suspected unexpected serious adverse reaction, alanine or aspartate transaminase elevations, or hepatobiliary or gastrointestinal adverse events as reported by local site investigators. However, the predefined central liver safety measurements revealed a greater frequency of possible Hy's Law cases (5 vs 2) and a 3- to 7-fold greater relative risk in alanine or aspartate transaminase elevation (with respect to upper limit of normal) within fasiglifam recipients compared with placebo/active control: alanine or aspartate transaminase > 3×: relative risk 3.34 (95% confidence interval 2.29-4.90), alanine or aspartate transaminase > 5×: relative risk 6.60 (95% confidence interval 3.03-14.38), alanine or aspartate transaminase > 8×: relative risk 6.14 (95% confidence interval 2.18-17.27), and alanine or aspartate transaminase > 10×: relative risk 6.74 (95% confidence interval 2.05, 22.14). All elevations resolved on study drug discontinuation. Drug-induced liver injury was adjudicated as highly likely or probably related in 0.64% of fasiglifam-treated versus 0.06% placebo or active control-treated patients. CONCLUSION: In spite of clear liver toxicity detected with a systematic surveillance program, liver safety signals were not identified from investigator adverse event reporting alone. By integrating key safety monitoring processes within the randomized design of adequately sized clinical trials, the rare but serious liver toxicity signal became clear, leading to timely program termination.

Comprehensive electrocardiogram-to-device time for primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: A report from the American Heart Association mission: Lifeline program.

BACKGROUND: Assessing hospital-related network-level primary percutaneous coronary intervention (PCI) performance for ST-segment elevation myocardial infarction (STEMI) is challenging due to differential time-to-treatment metrics based on location of diagnostic electrocardiogram (ECG) for STEMI. METHODS: STEMI patients undergoing primary PCI at 588 PCI-capable hospitals in AHA Mission: Lifeline (2008-2013) were categorized by initial STEMI identification location: PCI-capable hospitals (Group 1); pre-hospital setting (Group 2); and non-PCI-capable hospitals (Group 3). Patient-specific time-to-treatment categories were converted to minutes ahead of or behind their group-specific mean; average time-to-treatment difference for all patients at a given hospital was termed comprehensive ECG-to-device time. Hospitals were then stratified into tertiles based on their comprehensive ECG-to-device times with negative values below the mean representing shorter (faster) time intervals. RESULTS: Of 117,857 patients, the proportion in Groups 1, 2, and 3 were 42%, 33%, and 25%, respectively. Lower rates of heart failure and cardiac arrest at presentation are noted within patients presenting to high-performing hospitals. Median comprehensive ECG-to-device time was shortest at -9 minutes (25th, 75th percentiles: -13, -6) for the high-performing hospital tertile, 1 minute (-1, 3) for middle-performing, and 11 minutes (7, 16) for low-performing. Unadjusted rates of in-hospital mortality were 2.3%, 2.6%, and 2.7%, respectively, but the adjusted risk of in-hospital mortality was similar across tertiles. CONCLUSIONS: Comprehensive ECG-to-device time provides an integrated hospital-related network-level assessment of reperfusion timing metrics for primary PCI, regardless of the location for STEMI identification; further validation will delineate how this metric can be used to facilitate STEMI care improvements.

Contemporary Outcomes of Acute Coronary Syndromes in Indigenous Compared With Non-Indigenous Patients: A Northern Saskatchewan Perspective.

BACKGROUND: In patients presenting with an acute coronary syndrome (ACS), the impact of efforts to bridge historical care gaps between Indigenous and non-Indigenous patients remains limited. METHODS: For consecutive ACS presentations (ST-segment elevation myocardial infarction [STEMI] and non-ST-segment elevation myocardial infarction [NSTEMI]/unstable angina [UA], respectively) at the Royal University Hospital, Saskatoon, we compared self-identified Indigenous and non-Indigenous patients' demographics, treatments, and all-cause mortality (in-hospital and within 3 years). We used propensity score inverse probability weighting to mitigate confounding and Cox regression models to estimate the adjusted hazard ratio (aHR) for all-cause mortality. RESULTS: Of 3946 ACS patients, 37.2% (n = 1468) were STEMI, of whom 11.3% (n = 166) were Indigenous. Of the NSTEMI/UA (n = 2478), 12.6% (n = 311), were Indigenous. Overall, Indigenous compared with non-Indigenous patients were likely to be younger, female, have higher risk burden, and live more remotely; Indigenous STEMI patients triaged to primary percutaneous coronary intervention had longer times from first medical contact to device, and Indigenous NSTEMI/UA patients more likely to present with heart failure, cardiac arrest, and cardiogenic shock. No significant differences were noted for in-hospital mortality (STEMI 8.4% vs 5.7% [P = 0.16], NSTEMI/UA 1.9% vs 1.6% [P = 0.68]), although in follow-up, Indigenous STEMI patients were associated with a higher all-cause mortality risk (aHR 1.98, 95% CI 1.19-3.31; P = 0.009) with no between-group differences evident for NSTEMI/UA (aHR 1.03, 95% CI 0.63 1.69; P = 0.91). CONCLUSIONS: Indigenous compared with non-Indigenous patients presenting with an ACS had higher cardiovascular risk profiles and consequent residual mortality risk. Improving primary care and intensifying secondary risk reduction, particularly for Indigenous patients, will substantially modify ACS outcomes in Saskatchewan.

Catheter-Induced Postextrasystolic Potentiation in the Assessment of Severity of Low-Gradient Aortic Valve Stenosis.

BACKGROUND: Deciphering which patients with low-gradient aortic valve disease have severe stenosis can be difficult. We aimed to correlate the postextrasystolic potentiation (PESP) with dobutamine stress echocardiography and multidetector computed tomography in patients with low-gradient aortic valve stenosis. METHODS: Patients with an aortic valve area ≤1 cm2 and a mean gradient <40 mm Hg were included. Aortic valve stenosis severity was assessed by a core lab with dobutamine stress echocardiography, followed by a multidetector computed tomography aortic valve score if indeterminate. A premature ventricular contraction was induced by intentional catheter contact with the myocardium within the left ventricle. PESP was calculated as a percent change of pre-to-post mean gradient. Multidetector computed tomography was used to measure the aortic valve calcification score, and subsequently, aortic valve calcification density. RESULTS: Twenty-eight patients (age, 77±10 years; 19 female) were included. Dobutamine stress echocardiography increased mean gradient from baseline of 25±7 mm Hg to 36±11 mm Hg; pre-premature ventricular contraction mean gradient was 25±7 mm Hg and increased to post-premature ventricular contraction mean gradient of 32±10 mm Hg, representing a PESP of 24±11%. A ≥20% in PESP resulted in 100% sensitivity, 77% specificity, 83% positive predictive value, and 100% negative predictive value for diagnosing severe aortic valve stenosis. There was a significant correlation between PESP and projected aortic valve area and aortic valve calcification density (R=-0.64, P=0.0003; R=0.057, P=0.014, respectively). CONCLUSIONS: In patients with low-gradient aortic valve stenosis, catheter-induced premature ventricular contractions during cardiac catheterization causing ≥20% PESP has a 100% sensitivity for severe aortic valve stenosis. Validation of this 20% cutoff in larger groups with correlation to clinical end points is required.

Comparative Analysis of Patients With STEMI and COVID-19 Between Canada and the United States.

Background: Important health care differences exist between the United States (US) and Canada, which may have been exacerbated during the pandemic. We compared clinical characteristics, treatment strategies, and clinical outcomes of patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19 (STEMI-COVID) treated in the US and Canada. Methods: The North American COVID-19 Myocardial Infarction registry is a prospective, investigator-initiated study enrolling patients with STEMI with confirmed or suspected COVID-19 in the US and Canada. The primary end point was in-hospital mortality. Additionally, we explored associations between vaccination and clinical outcomes. Results: Of 853 patients with STEMI-COVID, 112 (13%) were enrolled in Canada, and compared with the US, patients in Canada were more likely to present with chest pain and less likely to have a history of heart failure, stroke/transient ischemic attack, pulmonary infiltrates or renal failure. In both countries, the primary percutaneous coronary intervention was the dominant reperfusion strategy, with no difference in door-to-balloon times; fibrinolysis was used less frequently in the US than in Canada. The adjusted in-hospital mortality was not different between the 2 countries (relative risk [RR], 1.0; 95% CI, 0.46-2.72; P = 1.0). However, the risk of in-hospital mortality was significantly higher in unvaccinated compared with vaccinated patients with STEMI-COVID (RR, 4.7; 95% CI, 1.7-11.53; P = .015). Conclusions: Notable differences in morbidities and reperfusion strategies were evident between patients with STEMI-COVID in the US compared with Canada. No differences were noted for in-hospital mortality. Vaccination, regardless of region, appeared to associate with a lower risk of in-hospital mortality strongly.

Mechanical Circulatory Support in Patients With COVID-19 Presenting With Myocardial Infarction.

ST-segment elevation myocardial infarction (STEMI) complicating COVID-19 is associated with an increased risk of cardiogenic shock and mortality. However, little is known about the frequency of use and clinical impact of mechanical circulatory support (MCS) in these patients. We sought to define patterns of MCS utilization, patient characteristics, and outcomes in patients with COVID-19 with STEMI. The NACMI (North American COVID-19 Myocardial Infarction) is an ongoing prospective, observational registry of patients with COVID-19 positive (COVID-19+) with STEMI with a contemporary control group of persons under investigation who subsequently tested negative for COVID-19 (COVID-19-). We compared the baseline characteristics and in-hospital outcomes of COVID-19+ and patients with COVID-19- according to the use of MCS. The primary outcome was a composite of in-hospital mortality, stroke, recurrent MI, and repeat unplanned revascularization. A total of 1,379 patients (586 COVID-19+ and 793 COVID-19-) enrolled in the NACMI registry between January 2020 and November 2021 were included in this analysis; overall, MCS use was 12.3% (12.1% [n = 71] COVID-19+/MCS positive [MCS+] vs 12.4% [n = 98] COVID-19-/MCS+). Baseline characteristics were similar between the 2 groups. The use of percutaneous coronary intervention was similar between the groups (84% vs 78%; p = 0.404). Intra-aortic balloon pump was the most frequently used MCS device in both groups (53% in COVID-19+/MCS+ and 75% in COVID-19-/MCS+). The primary outcome was significantly higher in COVID-19+/MCS+ patients (60% vs 30%; p = 0.001) because of very high in-hospital mortality (59% vs 28%; p = 0.001). In conclusion, patients with COVID-19+ with STEMI requiring MCS have very high in-hospital mortality, likely related to the significantly higher pulmonary involvement compared with patients with COVID-19- with STEMI requiring MCS.

A Review of ST-Elevation Myocardial Infarction in Patients with COVID-19.

The Coronavirus disease 2019 (COVID-19) pandemic has led to a significant increase in worldwide morbidity and mortality. Patients with COVID-19 are at risk for developing a variety of cardiovascular conditions including acute coronary syndromes, stress-induced cardiomyopathy, and myocarditis. Patients with COVID-19 who develop ST-elevation myocardial infarction (STEMI) are at a higher risk of morbidity and mortality when compared with their age- and sex-matched STEMI patients without COVID-19. We review current knowledge on the pathophysiology of STEMI in patients with COVID-19, clinical presentation, outcomes, and the effect of the COVID-19 pandemic on overall STEMI care.

Incidence and Predictors of Adverse Events Among Initially Stable ST-Elevation Myocardial Infarction Patients Following Primary Percutaneous Coronary Intervention.

Background Cardiac intensive care units were originally created in the prerevascularization era for the early recognition of ventricular arrhythmias following a myocardial infarction. Many patients with stable ST-segment-elevation myocardial infarction (STEMI) are still routinely triaged to cardiac intensive care units after a primary percutaneous coronary intervention (pPCI), independent of clinical risk or the provision of critical care therapies. The aim of this study was to determine factors associated with in-hospital adverse events in a hemodynamically stable, postreperfusion population of patients with STEMI. Methods and Results Between April 2012 and November 2019, 2101 consecutive patients with STEMI who received pPCI in the Vancouver Coastal Health Authority were evaluated. Patients were stratified into those with and without subsequent adverse events, which were defined as cardiogenic shock, in-hospital cardiac arrest, stroke, re-infarction, and death. Multivariable logistic regression models were used to determine predictors of adverse events. After excluding patients presenting with cardiac arrest, cardiogenic shock, or heart failure, the final analysis cohort comprised 1770 stable patients with STEMI who had received pPCI. A total of 94 (5.3%) patients developed at least one adverse event: cardiogenic shock 55 (3.1%), in-hospital cardiac arrest 42 (2.4%), death 28 (1.6%), stroke 21 (1.2%), and re-infarction 5 (0.3%). Univariable predictors of adverse events were older age, female sex, prior stroke, chronic kidney disease, and atrial fibrillation. There was no significant difference in reperfusion times between those with and without adverse events. Following multivariable adjustment, moderate to severe chronic kidney disease (creatinine clearance <44 mL/min; 13% of cohort) was associated with adverse events (odds ratio 2.24 [95% CI, 1.12-4.48]) independent of reperfusion time, age, sex, smoking status, hypertension, diabetes, and prior myocardial infarction/PCI/coronary artery bypass grafting. Conclusions Only 1 in 20 initially stable patients with STEMI receiving pPCI developed an in-hospital adverse event. Moderate to severe chronic kidney disease independently predicted the risk of future adverse events. These results indicate that the majority of patients with STEMI who receive pPCI may not require routine admission to a cardiac intensive care unit following reperfusion.

North American COVID-19 Myocardial Infarction (NACMI) Risk Score for Prediction of In-Hospital Mortality.

Background: In-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is higher in those with COVID-19 than in those without COVID-19. The factors that predispose to this mortality rate and their relative contribution are poorly understood. This study developed a risk score inclusive of clinical variables to predict in-hospital mortality in patients with COVID-19 and STEMI. Methods: Baseline demographic, clinical, and procedural data from patients in the North American COVID-19 Myocardial Infarction registry were extracted. Univariable logistic regression was performed using candidate predictor variables, and multivariable logistic regression was performed using backward stepwise selection to identify independent predictors of in-hospital mortality. Independent predictors were assigned a weighted integer, with the sum of the integers yielding the total risk score for each patient. Results: In-hospital mortality occurred in 118 of 425 (28%) patients. Eight variables present at the time of STEMI diagnosis (respiratory rate of >35 breaths/min, cardiogenic shock, oxygen saturation of <93%, age of >55 â€‹years, infiltrates on chest x-ray, kidney disease, diabetes, and dyspnea) were assigned a weighted integer. In-hospital mortality increased exponentially with increasing integer risk score (Cochran-Armitage χ2, P â€‹< â€‹.001), and the model demonstrated good discriminative power (c-statistic â€‹= â€‹0.81) and calibration (Hosmer-Lemeshow, P â€‹= â€‹.40). The increasing risk score was strongly associated with in-hospital mortality (3.6%-60% mortality for low-risk and very high-risk score categories, respectively). Conclusions: The risk of in-hospital mortality in patients with COVID-19 and STEMI can be accurately predicted and discriminated using readily available clinical information.

Ticagrelor or clopidogrel dual antiplatelet therapy following a pharmacoinvasive strategy in ST-segment elevation myocardial infarction.

OBJECTIVES: To describe and evaluate outcomes in STEMI patients sustained on clopidogrel compared to those switched to ticagrelor following fibrinolysis. BACKGROUND: World-wide, many STEMI patients cannot achieve timely PCI and therefore require fibrinolysis. Although comparable 30-day and 1-year safety was shown with clopidogrel or ticagrelor in the TREAT study, there is paucity of long-term outcomes in pharmacoinvasive treated STEMI. METHODS: We conducted an observational cohort study evaluating consecutive pharmacoinvasive STEMI patients treated in a network, comparing those switched to ticagrelor to those sustained on clopidogrel. The primary efficacy composite was one-year all-cause death, recurrent myocardial infarction, and stroke with major bleeding and intracranial hemorrhage (ICH) as the safety outcomes. Multivariable Cox regression model was used to examine the association between P2Y12 inhibitor and outcomes with inverse probability weighting. RESULTS: Of 1426 pharmacoinvasive STEMI patients, 28% (n = 396) were converted to ticagrelor at a mean of 9.9 h after fibrinolysis with comparable GRACE Risk Scores (median; 158 vs 157, p0.352). The primary composite occurred in 3.5% of ticagrelor and 7.0% of clopidogrel treated patients (p0.014). Following adjustment, ticagrelor was associated with a 54% lower composite outcome (adjusted HR 0.46, 95% confidence interval 0.26-0.84). Major bleeding 6.3% vs 6.1% (NS) and ICH 0.0% vs 0.2% (NS) were similar. CONCLUSIONS: In a prospective STEMI cohort, switching to ticagrelor compared with sustaining clopidogrel following fibrinolysis pharmacoinvasive reperfusion reduced recurrent ischemic events at 1-year with no differences in major bleeding or ICH. Aligned with randomized data, these findings provide support to switch pharmaco-invasively treated STEMI patients.

Novel Biomarkers, ST-Elevation Resolution, and Clinical Outcomes Following Primary Percutaneous Coronary Intervention.

Background Despite restoration of epicardial flow following primary percutaneous coronary intervention (PPCI), microvascular reperfusion as reflected by ST-elevation resolution (ST-ER) resolution remains variable and its pathophysiology remains unclear. Methods and Results Using principal component analyses, we explored associations between 91 serum biomarkers drawn before PPCI clustered into 14 pathobiologic processes (including NT-proBNP [N-terminal pro-B-type natriuretic peptide] as an independent cluster), and (1) ST-ER resolution ≥50% versus <50%; and (2) 90-day composite of death, shock, and heart failure. Network analyses were performed to understand interbiomarker relationships between the ST-ER groups. Among the 1160 patients studied, 861 (74%) had ST-ER ≥50% at a median 40 (interquartile range, 23-70) minutes following PPCI, yet both groups had comparable post-PPCI TIMI (Thrombolysis in Myocardial Infarction) grade 3 flow (86.6% versus 82.9%; P=0.25). ST-ER ≥50% was associated with significantly lower pre-PPCI concentrations of platelet activation cluster (particularly P-selectin, von Willebrand factor, and platelet-derived growth factor A) and NT-proBNP, including after risk adjustment. Across both ST-ER groups, strong interbiomarker relationships were noted between pathways indicative of myocardial stretch, platelet activation, and inflammation, whereas with ST-ER <50% correlations between iron homeostasis and inflammation were observed. Of all 14 biomarker clusters, only NT-proBNP was significantly associated with the 90-day clinical composite. Conclusions Suboptimal ST-ER is common despite achieving post-PPCI TIMI grade 3 flow. The cluster of platelet activation proteins and NT-proBNP were strongly correlated with suboptimal ST-ER and NT-proBNP was independently associated with 90-day outcomes. This analysis provides insights into the pathophysiology of microvascular reperfusion in ST-segment-elevation myocardial infarction and suggests novel pre-PPCI risk targets potentially amenable to enhancing tissue-level reperfusion following PPCI.