Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High-risk Pulmonary Embolism: The CANARY Randomized Clinical Trial.

Importance: The optimal treatment of intermediate-high-risk pulmonary embolism (PE) remains unknown. Objective: To assess the effect of conventional catheter-directed thrombolysis (cCDT) plus anticoagulation vs anticoagulation monotherapy in improving echocardiographic measures of right ventricle (RV) to left ventricle (LV) ratio in acute intermediate-high-risk PE. Design, Setting, and Participants: The Catheter-Directed Thrombolysis vs Anticoagulation in Patients with Acute Intermediate-High-Risk Pulmonary Embolism (CANARY) trial was an open-label, randomized clinical trial of patients with intermediate-high-risk PE, conducted in 2 large cardiovascular centers in Tehran, Iran, between December 22, 2018, through February 2, 2020. Interventions: Patients were randomly assigned to cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin vs anticoagulation monotherapy. Main Outcomes and Measures: The proportion of patients with a 3-month echocardiographic RV/LV ratio greater than 0.9, assessed by a core laboratory, was the primary outcome. The proportion of patients with an RV/LV ratio greater than 0.9 at 72 hours after randomization and the 3-month all-cause mortality were among secondary outcomes. Major bleeding (Bleeding Academic Research Consortium type 3 or 5) was the main safety outcome. A clinical events committee, masked to the treatment assignment, adjudicated clinical outcomes. Results: The study was prematurely stopped due to the COVID-19 pandemic after recruiting 94 patients (mean [SD] age, 58.4 [2.5] years; 27 women [29%]), of whom 85 patients completed the 3-month echocardiographic follow-up. Overall, 2 of 46 patients (4.3%) in the cCDT group and 5 of 39 patients (12.8%) in the anticoagulation monotherapy group met the primary outcome (odds ratio [OR], 0.31; 95% CI, 0.06-1.69; P = .24). The median (IQR) 3-month RV/LV ratio was significantly lower with cCDT (0.7 [0.6-0.7]) than with anticoagulation (0.8 [0.7-0.9); P = .01). An RV/LV ratio greater than 0.9 at 72 hours after randomization was observed in fewer patients treated with cCDT (13 of 48 [27.0%]) than anticoagulation (24 of 46 [52.1%]; OR, 0.34; 95% CI, 0.14-0.80; P = .01). Fewer patients assigned to cCDT experienced a 3-month composite of death or RV/LV greater than 0.9 (2 of 48 [4.3%] vs 8 of 46 [17.3%]; OR, 0.20; 95% CI, 0.04-1.03; P = .048). One case of nonfatal major gastrointestinal bleeding occurred in the cCDT group. Conclusions and Relevance: This prematurely terminated randomized clinical trial of patients with intermediate-high-risk PE was hypothesis-generating for improvement in some efficacy outcomes and acceptable rate of major bleeding for cCDT compared with anticoagulation monotherapy and provided support for a definitive clinical outcomes trial. Trial Registration: ClinicalTrials.gov Identifier: NCT05172115.

Trends in Clinical Presentation, Management, and Outcomes of STEMI in Patients With COVID-19.

BACKGROUND: We previously reported high in-hospital mortality for ST-segment elevation myocardial infarction (STEMI) patients with COVID-19 treated in the early phase of the pandemic. OBJECTIVES: The purpose of this study was to describe trends of COVID-19 patients with STEMI during the course of the pandemic. METHODS: The NACMI (North American COVID-19 STEMI) registry is a prospective, investigator-initiated, multicenter, observational registry of hospitalized STEMI patients with confirmed or suspected COVID-19 infection in North America. We compared trends in clinical characteristics, management, and outcomes of patients treated in the first year of the pandemic (January 2020 to December 2020) vs those treated in the second year (January 2021 to December 2021). RESULTS: A total of 586 COVID-19-positive patients with STEMI were included in the present analysis; 227 treated in Y2020 and 359 treated in Y2021. Patients' characteristics changed over time. Relative to Y2020, the proportion of Caucasian patients was higher (58% vs 39%; P < 0.001), patients presented more frequently with typical ischemic symptoms (59% vs 51%; P = 0.04), and patients were less likely to have shock pre-PCI (13% vs 18%; P = 0.07) or pulmonary manifestations (33% vs. 47%; P = 0.001) in Y2021. In-hospital mortality decreased from 33% (Y2020) to 23% (Y2021) (P = 0.008). In Y2021, none of the 22 vaccinated patients expired in hospital, whereas in-hospital death was recorded in 37 (22%) unvaccinated patients (P = 0.009). CONCLUSIONS: Significant changes have occurred in the clinical characteristics and outcomes of STEMI patients with COVID-19 infection during the course of the pandemic.

Bleeding risk by intensity of anticoagulation in critically ill patients with COVID-19: A retrospective cohort study.

BACKGROUND: Studies report hypercoagulability in coronavirus disease 2019 (COVID-19), leading many institutions to escalate anticoagulation intensity for thrombosis prophylaxis. OBJECTIVE: To determine the bleeding risk with various intensities of anticoagulation in critically ill patients with COVID-19 compared with other respiratory viral illnesses (ORVI). PATIENTS/METHODS: This retrospective cohort study compared the incidence of major bleeding in patients admitted to an intensive care unit (ICU) within a single health system with COVID-19 versus ORVI. In the COVID-19 cohort, we assessed the effect of anticoagulation intensity received on ICU admission on bleeding risk. We performed a secondary analysis with anticoagulation intensity as a time-varying covariate to reflect dose changes after ICU admission. RESULTS: Four hundred and forty-three and 387 patients were included in the COVID-19 and ORVI cohorts, respectively. The hazard ratio of major bleeding for the COVID-19 cohort relative to the ORVI cohort was 1.26 (95% confidence interval [CI]: 0.86-1.86). In COVID-19 patients, an inverse-probability treatment weighted model found therapeutic-intensity anticoagulation on ICU admission had an adjusted hazard ratio of bleeding of 1.55 (95% CI: 0.88-2.73) compared with standard prophylactic-intensity anticoagulation. However, when anticoagulation was assessed as a time-varying covariate and adjusted for other risk factors for bleeding, the adjusted hazard ratio for bleeding on therapeutic-intensity anticoagulation compared with standard thromboprophylaxis was 2.59 (95% CI: 1.20-5.57). CONCLUSIONS: Critically ill patients with COVID-19 had a similar bleeding risk as ORVI patients. When accounting for changes in anticoagulation that occurred in COVID-19 patients, therapeutic-intensity anticoagulation was associated with a greater risk of major bleeding compared with standard thromboprophylaxis.

Diagnosis and Treatment of Pulmonary Embolism During the Coronavirus Disease 2019 Pandemic: A Position Paper From the National PERT Consortium.

The coexistence of coronavirus disease 2019 (COVID-19) and pulmonary embolism (PE), two life-threatening illnesses, in the same patient presents a unique challenge. Guidelines have delineated how best to diagnose and manage patients with PE. However, the unique aspects of COVID-19 confound both the diagnosis and treatment of PE, and therefore require modification of established algorithms. Important considerations include adjustment of diagnostic modalities, incorporation of the prothrombotic contribution of COVID-19, management of two critical cardiorespiratory illnesses in the same patient, and protecting patients and health-care workers while providing optimal care. The benefits of a team-based approach for decision-making and coordination of care, such as that offered by pulmonary embolism response teams (PERTs), have become more evident in this crisis. The importance of careful follow-up care also is underscored for patients with these two diseases with long-term effects. This position paper from the PERT Consortium specifically addresses issues related to the diagnosis and management of PE in patients with COVID-19.

orth merican OVID-19 ST-Segment-Elevation yocardial nfarction (NACMI) registry: Rationale, design, and implications

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that causes coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. Patients with cardiovascular risk factors or established cardiovascular disease are more likely to experience severe or critical COVID-19 illness and myocardial injury is a key extra-pulmonary manifestation. These patients frequently present with ST-elevation on an electrocardiogram (ECG) due to multiple etiologies including obstructive, non-obstructive, and/or angiographically normal coronary arteries. The incidence of ST-elevation myocardial infarction (STEMI) mimics in COVID-19-positive hospitalized patients, and the association with morbidity and mortality is unknown. Understanding the natural history and appropriate management of COVID-19 patients presenting with ST elevation is essential to inform patient management decisions and protect healthcare workers.Methods: The Society for Cardiovascular Angiography and Interventions (SCAI) and The Canadian Association of Interventional Cardiology (CAIC) in conjunction with the American College of Cardiology Interventional Council have collaborated to create a multi-center observational registry, NACMI. This registry will enroll confirmed COVID-19 patients and persons under investigation (PUI) with new ST-segment elevation or new onset left bundle branch block (LBBB) on the ECG with clinical suspicion of myocardial ischemia. We will compare demographics, clinical findings, outcomes and management of these patients with a historical control group of over 15,000 consecutive STEMI activation patients from the Midwest STEMI Consortium using propensity matching. The primary clinical outcome will be in- hospital major adverse cardiovascular events (MACE) defined as composite of all-cause mortality, stroke, recurrent MI, and repeat unplanned revascularization in COVID-19 confirmed or PUI. Secondary outcomes will include the following: reporting of etiologies of ST Elevation;cardiovascular mortality due to myocardial infarction, cardiac arrest and /or shock;individual components of the primary outcome;composite primary outcome at 1 year;as well as ECG and angiographic characteristics.Conclusion: The multicenter NACMI registry will collect data regarding ST elevation on ECG in COVID-19 patients to determine the etiology and associated clinical outcomes. The collaboration and speed with which this registry has been created, refined, and promoted serves as a template for future research endeavors.

Thrombosis in COVID-19.

Thrombotic complications are frequent in COVID-19 and contribute significantly to mortality and morbidity. We review several mechanisms of hypercoagulability in sepsis that may be upregulated in COVID-19. These include immune-mediated thrombotic mechanisms, complement activation, macrophage activation syndrome, antiphospholipid antibody syndrome, hyperferritinemia, and renin-angiotensin system dysregulation. We highlight biomarkers within each pathway with potential prognostic value in COVID-19. Lastly, recent observational studies have evaluated a role for the expanded use of therapeutic anticoagulation in COVID-19. We review strengths and weaknesses of these studies, and we also discuss the hypothetical benefit and anticipated challenges of fibrinolytic therapy in COVID-19.

Impact of COVID-19 pandemic on STEMI care: An expanded analysis from the United States.

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.

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

Considerations for cardiac catheterization laboratory procedures during the COVID-19 pandemic perspectives from the Society for Cardiovascular Angiography and Interventions Emerging Leader Mentorship (SCAI ELM) Members and Graduates.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly infectious, carries significant morbidity and mortality, and has rapidly resulted in strained health care system and hospital resources. In addition to patient-related care concerns in infected individuals, focus must also relate to diminishing community spread, protection of staff, case selection, and concentration of resources. The current document based on available data and consensus opinion addresses appropriate catheterization laboratory preparedness for treating these patients, including procedure-room readiness to minimize external contamination, safe donning and doffing of personal protective equipment (PPE) to eliminate risk to staff, and staffing algorithms to minimize exposure and maximize team availability. Case selection and management of both emergent and urgent procedures are discussed in detail, including procedures that may be safely deferred or performed bedside.