COVID-19 Therapeutics for Nonhospitalized Older Adults

This Viewpoint summarizes the factors contributing to increased risk of severe outcomes and hospitalization associated with COVID-19 among older adults, stresses the importance of assessing COVID-19 risk before infection occurs, calls for all immunocompromised older adults to be considered for COVID-19 treatment, and details 3 recommended COVID-19 therapies.

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Novembre 2024

Abstract 4137534: Troponin Can Predict Late Gadolinium Enhancement on Cardiac MRI in COVID-19 Vaccine-Associated Myocarditis

Circulation, Volume 150, Issue Suppl_1, Page A4137534-A4137534, November 12, 2024. Background/Aim:We previously reported that late gadolinium enhancement (LGE) on cardiac MRI (CMR) was as high as 82% in pediatric patients with COVID-19 vaccine-associated myocarditis (C-VAM) despite mild clinical symptoms and normal left ventricular function. As LGE can be a harbinger for future adverse events including arrhythmias, heart failure or sudden cardiac death, we sought to identify predictors for LGE in C-VAM, specifically assessing troponin as a screening marker for C-VAM patients at risk for myocardial scarring who could then be referred for a confirmatory CMR with LGE.Methods:In this longitudinal multicenter retrospective observational study across 38 U.S. member institutions of theMyocarditisAfterCOVIDVaccination (MACiV) study network, 333 patients with C-VAM based on CDC criteria were included from April 2021 to November 2022. Data collected included demographics, laboratory values, clinical and cardiac imaging characteristics and outcomes. Using logistic regression, troponin levels at presentation were assessed as a log transformed continuous variable and categorized into tertiles.Results:The C-VAM patients were predominantly white (67%) adolescent males (91%, 15.7± 2.8 years). There were 216/333 (65%) patients who had both a reported troponin value and had a CMR. On univariate analysis, elevated troponin increased the probability of having LGE (OR=1.29, 95% CI: 1.06, 1.58, p=0.012). Even after controlling for age, race, sex, number of vaccine doses and left ventricular ejection fraction (OR=1.32, 95% CI: 1.06, 1.65, p=0.013). Patients >15 years compared to those ≤15 years of age were 2.94 (95% CI: 1.28, 6.75, p=0.011) times more likely to have LGE at presentation. Patients with troponin levels in the highest tertile compared to lowest tertile were 2.66 times (95% CI: 1.04, 6.83, p=0.042) more likely to have LGE along with a greater involvement > 4 AHA myocardial segments with LGE (p=0.004)Conclusions:Higher troponin values are associated with presence of late gadolinium enhancement on cardiac MRI in patients with COVID-19 vaccine-associated myocarditis. Troponin levels at presentation may facilitate risk stratification and function as a screening tool to identify those C-VAM patients with the greatest likelihood of myocardial scarring, who may benefit from undergoing CMR for tissue characterization.

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Novembre 2024

Abstract 4119613: Evaluation of Gender, Racial and Ethnic Differences in Time to PCI in the Pre and Post Covid-19 Era

Circulation, Volume 150, Issue Suppl_1, Page A4119613-A4119613, November 12, 2024. Introduction:Percutaneous Coronary Intervention (PCI) is recommended for reperfusion of patients presenting with ST-segment myocardial infarction (STEMI) within 90 minutes. In this study, we sought to identify differences in PCI timing based on gender, race and ethnicity in the pre- and post-COVID era.Methods:We collected retrospective data on 760 patients admitted with STEMI at our quaternary academic medical center from 2018-2022. We defined our binary outcome as time to PCI less than 90 minutes, and adjusted for transfers from outside hospitals. We utilized univariate logistic regression analysis to analyze the association of demographic, clinical, and cardiac catheterization details on our outcome. We then utilized multivariate logistic regression analysis to determine the association of our covariates of interests with time to PCI. The logistic regression model was adjusted for collinearity which were deemed not significant.Results:Among our study population, COVID did not significantly impact whether or not a patient had a diagnostic cardiac catheterization on univariate analysis (OR 2.68, 95% CI 0.61-18.40, p=0.23). However, the post-COVID era was significantly associated with a delayed time to PCI on multivariate analysis [OR 1.62, 95% CI 1.04-2.55, p=0.035) [Figure 1]. In addition, females were 1.8x more likely to have a delayed PCI than males on multivariate regression [OR 1.80, 95% CI 1.10-2.95, p= 0.019) [Figure 1]. Interestingly, on multivariate analysis, females were more likely to have delayed reperfusion in the pre-COVID era (OR 2.92, 1.29-6.77,p= 0.01) but not the post-COVID era (OR 1.54, 0.78-3.06,p=0.2134). Patients in the post-COVID era had increased risk of having their culprit coronary not revascularized on multivariate analysis (OR 2.85, 1.2-8.03, p= 0.03).Conclusions:At our center, COVID did not significantly impact cardiac catheterization rates. However, COVID was significantly associated with delayed reperfusion timing and not revascularizing culprit vessels. Females were much more likely to have a delayed PCI than males in the pre-COVID era which was not seen following COVID-19.

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Novembre 2024

Abstract 4126987: A Case of Recurrent Neurocardiogenic Syncope in a COVID-19 Patient

Circulation, Volume 150, Issue Suppl_1, Page A4126987-A4126987, November 12, 2024. Background:COVID-19 infection has been associated with a broad range of clinical manifestations. There are very few reported cases of COVID-19 patients presenting with syncope as an initial symptom. We present an extraordinary case of recurrent neurocardiogenic syncope in a COVID-19 patient.Case:A 66-year-old male presented after experiencing two episodes of syncope. He denied any prodromal or anginal symptoms. His medications included propranolol 10 mg twice daily for essential tremors. He had no family history of unexplained syncope or sudden cardiac death. He was hemodynamically stable and had one episode of fever at 102°F. Telemetry recording showed vagal-mediated sinus arrest and pauses without escape. Blood work showed normal cell counts, electrolytes, thyroid-stimulating hormone, and erythrocyte sedimentation rate, with a slightly elevated C-reactive protein of 22.2 mg/L. He tested positive for COVID-19 and had negative Lyme and Ehrlichia serologies.Decision Making:Due to symptomatic long sinus pauses, propranolol was discontinued, and he received a temporary pacemaker set at 50 beats per minute (bpm). He had another syncopal episode while being paced at 50 bpm, suggesting a neurocardiogenic mechanism, so the pacing rate was increased to 70 bpm. An echocardiogram showed a normal ejection fraction without any significant valvular disease. The syncope was determined to be vasovagal due to autonomic dysfunction in the setting of COVID-19. After 72 hours without further syncope, the temporary pacemaker was removed, and he was discharged home with an implantable loop recorder (ILR). A one-month follow-up showed no syncope, and ILR interrogation showed no bradycardia or pauses.Conclusion:Neurocardiogenic syncope with prolonged asystole and sinus pauses is an uncommon presentation of COVID-19 infection. The clinical course of autonomic dysfunction following COVID-19 is not very clear, and monitoring with an ILR is reasonable before considering permanent pacemaker implantation.

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Novembre 2024

Abstract 4125636: Impaired blood pressure regulation in post-COVID-19 postural orthostatic tachycardia syndrome: novel disease mechanisms beyond sinus tachycardia

Circulation, Volume 150, Issue Suppl_1, Page A4125636-A4125636, November 12, 2024. Background:Postural orthostatic tachycardia syndrome (POTS) is a prevalent cardiovascular disorder after COVID-19 infection. Although POTS is characterized by the presence of sinus tachycardia, other hemodynamic disturbances including blood pressure (BP) regulation, remain largely unexplored.Aims:We investigated BP changes using 24-hour ambulatory-BP-monitoring in patients with new-onset POTS after COVID-19 compared with pre-pandemic healthy controls.Methods:We performed a case-control study in 100 verified COVID-19 patients with new-onset POTS (mean age 40.0±12.9 years, 85% women) diagnosed by positive head-up tilt-testing versus 100 healthy controls (mean age 45.0±14.6 years, 70% women) from a population-based cohort with negative active standing test, no history of syncope, orthostatic intolerance, or endocrine disease. We analyzed 24-hour Systolic BP (SBP) and hypotensive SBP episodes (

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Novembre 2024

Abstract 4140585: Shifting in the settings of stroke fatalities during the COVID-19 pandemic

Circulation, Volume 150, Issue Suppl_1, Page A4140585-A4140585, November 12, 2024. Introduction:Stroke-related mortality poses significant challenges in the US. Increased at-home deaths since COVID-19 pandemic prompted changes in the provision of end-of-life care.Question:What were the settings of stroke deaths in the US during COVID-19 pandemic?Methods:Decedent-level mortality data from death certificates in CDC repository were obtained for the year 2020 (pandemic) and 2019 (comparison). Demographic data include age, sex, race/ethnicity, education, marital status, and place of stroke death, including inpatient, outpatient/emergency room (ER), hospice/nursing facilities (H/NF), and at-home. Multivariable logistic regression models assessed demographic impact on stroke mortality by place-of-death, yielding odds ratios (OR) with significance threshold of p65 years were more likely to die in H/NF (OR 10.05, p

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Novembre 2024

Abstract 4141078: Hearing the Voices of Families: Barriers and Facilitators of Pediatric Cardiac Ambulatory Care During the COVID-19 Pandemic

Circulation, Volume 150, Issue Suppl_1, Page A4141078-A4141078, November 12, 2024. Background:Social determinants of health (SDOH),exacerbated by the COVID-19 pandemic, impact access to medical care.Research Question:Through descriptive qualitative inquiry, we explored barriers and facilitators to pediatric cardiology ambulatory care for patients with complex congenital heart disease (CCHD) during COVID-19.Methods:English- and Spanish-speaking caregivers of children with CCHD who missed at least one clinic visit during the first year of COVID-19 were recruited, with purposeful sampling of Black and Hispanic patients. Semi-structured interviews inquired about the impact of the pandemic, experience with telehealth and communication with providers, effects of SDOH, and perceived impact of their race/ethnicity on care. Content analysis summarized information and identified themes.Results:Interviews (19) were conducted: 14 in English (6 Black, 2 Hispanic, 2 White, 3 mixed race, 1 American Indian), and 5 in Spanish (5 Hispanic). Overarching themes were: Barriers to Care, Facilitators of Returning/Staying in Care, Impact of Diagnosis, and Recommendations for Improvement (Image 1). Despite challenges with finances and transportation, as well as concern for infection risk, the majority of caregivers preferred in-person care over telehealth due to physical exam, diagnostic testing, and interpersonal connection with providers. SDOH challenges including housing, transportation, and employment contributed to missing care. For some families, social vulnerability was exacerbated by their child’s CCHD diagnosis and then again by COVID-19. Universally, caregivers felt their child’s race/ethnicity did not affect the care they received. Spanish-speaking caregivers expressed their primary language as a barrier to care and their desire for more thorough explanations and teach-back from the medical team.Conclusion:While SDOH can hinder access to ambulatory cardiac care, trusting relationships with care teams facilitated engagement. Social vulnerability contributed to dynamic situations for families, especially during COVID-19, highlighting the need for routine SDOH assessment and support. English- and Spanish-speaking caregivers echoed the same challenges. Race/ethnicity was not felt to impact care received.

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Novembre 2024

Abstract 4145299: Myocarditis leading to cardiogenic shock: COVID-19's Cardiac Crisis

Circulation, Volume 150, Issue Suppl_1, Page A4145299-A4145299, November 12, 2024. Background:COVID-19 can present with a wide spectrum of clinical manifestations ranging from asymptomatic to life-threatening. It is often thought of as a primarily pulmonary infection and different systemic presentations are sometimes overlooked. We present a case of COVID-19 induced myocarditis leading to hemodynamic instability and end-organ dysfunction.Case presentation:A 77-year-old male with a history of CKD, paroxysmal atrial fibrillation, and COPD was transferred to our hospital for a higher level of care due to worsening cardiogenic shock. He was cold and wet (Forrester class IV) with a High Sensitivity troponin of 331 and a BNP level of 21,503. EKG showed atrial fibrillation with RVR but no evidence of acute ischemic changes. A TTE was done which revealed an EF of 30-35% and diffuse hypokinesis with regional variation, a significant reduction from an EF of 50-55% just 4 weeks prior. The patient exhibited end-organ dysfunction, as evidenced by deranged liver function tests and a rise in creatinine from a baseline of 2 to 4.6, indicating congestive hepatopathy and cardiorenal syndrome respectively. The patient’s hemodynamics necessitated milrinone and norepinephrine infusions and efforts to wean them off were unsuccessful due to repeated failed fluid bolus challenges. Considering the patient’s clinical picture, there was a strong suspicion of viral-induced cardiomyopathy, and a COVID-19 infection was confirmed by PCR testing; his last COVID-19 booster dose was in 2021. The patient was promptly started on remdesivir and IV steroids. Unfortunately, the patient’s condition continued to deteriorate, and he succumbed to his illness.Discussion:A myriad of cardiovascular manifestations have been implicated with COVID-19, including ACS, myocarditis, and heart failure. Although the exact underlying mechanisms for each of these conditions are unclear, a complex interplay between direct viral injury, systemic inflammation, and cytokine storm has been hypothesized. Our case illustrates the quick progression of heart failure into cardiogenic shock requiring pressor support, with subsequent rapid decompensation rendering CMR, cardiac catheterization, and biopsy timely impractical. It serves as a reminder to explore COVID-19 as a potential cause of biventricular failure in individuals with no evident reason and rapid clinical deterioration, particularly as early initiation of antiviral therapy could improve prognoses.

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Novembre 2024

Abstract 4142129: The Role of Neutrophil to Lymphocyte Ratio and Right Ventricular Dysfunction in Indonesian Patients with COVID-19

Circulation, Volume 150, Issue Suppl_1, Page A4142129-A4142129, November 12, 2024. Background:The clinical impact of neutrophil to lymphocyte ratio (NLR) and right ventricular (RV) dysfunction on clinical outcomes in COVID-19 have not been studied in the often-underrepresented Indonesian population.Aim:To investigate the role of NLR and RV dysfunction in Indonesian patients hospitalized for COVID-19.Methods:A retrospective cohort study was conducted at a COVID-19 referral hospital in Indonesia. We included all adult patients hospitalized with COVID-19 between April 2020 – April 2021 who had transthoracic echocardiography (TTE) during admission. Clinical data were extracted from electronic medical records. TTE variables were defined according to the American Society of Echocardiography criteria. All statistical analyses were conducted using the SPSS software. This study was approved by the IRB at Universitas Indonesia (#2022-01-135).Results:A total of 488 patients were included – 29 with and 459 without RV dysfunction. The mean age of the population was 54.8 (SD ± 13.5), and 42% were females. Receiver operating curve analysis and Youden’s J statistics were used to determine the optimal NLR cut-off (Figure 1). An NLR > 4.79 was considered elevated, and had a sensitivity of 70.6% and a specificity of 80.6% in predicting severe – critical COVID-19. A high NLR (OR: 3.38, P = 0.02) and LV systolic dysfunction (OR: 9.76, P < 0.01) were independently associated with RV dysfunction. In multivariate cox regression analysis, older age (HR: 1.02, P = 0.01), obesity (HR: 1.85, P < 0.01), chronic kidney disease (HR: 1.69, P = 0.01), high NLR (HR: 2.75, P < 0.01), and RV dysfunction (HR: 2.07, P = 0.02) increased the risk of 30-day mortality.Conclusions:In Indonesian patients hospitalized with COVID-19, A high NLR is predictive of severe – critical COVID-19 and is associated with RV dysfunction. A high NLR at admission and RV dysfunction independently increase the risk of 30-day mortality in hospitalized Indonesian adults with COVID-19.

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Novembre 2024

Abstract 4117883: Long noncoding RNAs and machine learning to improve cardiovascular outcomes of COVID-19

Circulation, Volume 150, Issue Suppl_1, Page A4117883-A4117883, November 12, 2024. Introduction/Background:Cardiovascular symptoms appear in a high proportion of patients in the few months following a severe SARS-CoV-2 infection. Non-invasive methods to predict disease severity could help personalizing healthcare and reducing the occurrence of these symptoms.Research Questions/Hypothesis:We hypothesized that blood long noncoding RNAs (lncRNAs) and machine learning (ML) could help predict COVID-19 severity.Goals/Aims:To develop a model based on lncRNAs and ML for predicting COVID-19 severity.Methods/Approach:Expression data of 2906 lncRNAs were obtained by targeted sequencing in plasma samples collected at baseline from four independent cohorts, totaling 564 COVID-19 patients. Patients were aged 18+ and were recruited from 2020 to 2023 in the PrediCOVID cohort (n=162; Luxembourg), the COVID19_OMICS-COVIRNA cohort (n=100, Italy), the TOCOVID cohort (n=233, Spain), and the MiRCOVID cohort (n=69, Germany). The study complied with the Declaration of Helsinki. Cohorts were approved by ethics committees and patients signed an informed consent.Results/Data:After data curation and pre-processing, 463 complete datasets were included in further analysis, representing 101 severe patients (in-hospital death or ICU admission) and 362 stable patients (no hospital admission or hospital admission but not ICU). Feature selection with Boruta, a random forest-based method, identified age and five lncRNAs (LINC01088-201, FGDP-AS1, LINC01088-209, AKAP13, and a novel lncRNA) associated with disease severity, which were used to build predictive models using six ML algorithms. A naïve Bayes model based on age and five lncRNAs predicted disease severity with an AUC of 0.875 [0.868-0.881] and an accuracy of 0.783 [0.775-0.791].Conclusion:We developed a ML model including age and five lncRNAs predicting COVID-19 severity. This model could help improve patients’ management and cardiovascular outcomes.

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Novembre 2024

Abstract 4141333: Predictors of venous thromboembolism in hospitalized patients with COVID-19

Circulation, Volume 150, Issue Suppl_1, Page A4141333-A4141333, November 12, 2024. Background:COVID-19 is a multiorgan disease characterized by a prothrombotic state and increased risk of venous thromboembolism (VTE), especially in hospitalized patients. Although prior studies have attempted to identify predictors of VTE, restricted sample size and use of administrative claims data have limited such analyses. We conducted a multivariable analysis to identify predictors of VTE in hospitalized patients with COVID-19 in a multicenter patient-level registry.Methods:We utilized data from the CORONA-VTE Network, a US multicenter registry of 10,420 adult (≥18 years) patients with PCR-confirmed COVID-19 of whom 3,844 were hospitalized. The primary outcome was time-to-first-event for a composite of adjudicated pulmonary embolism and deep vein thrombosis (e.g. lower extremity, mesenteric, gonadal vein, etc.) during 90-day follow-up. The candidate variables were selected by a priori clinical consensus. The variables with ≥20% missing data were excluded, whereas those with missing data

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Novembre 2024

Abstract 4143186: Prior Statin Therapy Reduces Inflammation and Improves Outcomes in Patients Hospitalized for Covid-19: A Prospective Multicenter Cohort Study

Circulation, Volume 150, Issue Suppl_1, Page A4143186-A4143186, November 12, 2024. Introduction:Statins are lipid-lowering agents with anti-inflammatory effects. Data surrounding the benefits of statins in patients with coronavirus disease 2019 (Covid-19) are conflicting. We sought to better understand the impact of statins in the context of Covid-19-related inflammation.Methods:We leveraged the International Study of Inflammation in Covid-19, a prospective multicenter cohort study of patients hospitalized specifically for Covid-19 between February 1, 2020 and October 30, 2022. Participants underwent systematic assessment of biomarkers of inflammation. We used logistic regression modeling and inverse probability-of-treatment weighting (IPTW) to examine the association between prior statin use and the composite outcome of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy.Results:A total of 4,464 patients were included in the study, of whom 1,364 (27.5%) were taking a statin prior to admission. There were 1,061 primary outcome events, including 540 deaths, 854 mechanical ventilation and 313 renal replacement therapy. Amongst biomarkers of inflammation, statin use was associated solely with lower levels of soluble urokinase plasminogen activator receptor (suPAR) after adjusting for known confounders. In multivariable logistic regression analysis, statin use was associated with lower odds of the composite outcome (adjusted odds ratio (aOR) 0.63, 95%CI[0.53-0.76]) compared to patients not on statins. Findings were consistent with IPTW (aOR 0.92, 95%CI [0.89- 0.95]). The proportion of the effect of statin on the primary outcome mediated by suPAR was estimated at 31.5%.Conclusion:Prior statin use is associated with improved outcomes and lower inflammation as measured by suPAR levels in patients hospitalized for Covid-19.

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Novembre 2024

Abstract 4142935: Circulating endothelial cells and microthrombosis as markers of vascular dysfunction in Long COVID

Circulation, Volume 150, Issue Suppl_1, Page A4142935-A4142935, November 12, 2024. Background.Post-COVID syndrome is related to a multisystem disorder that affects in part the cardiovascular system. This disease involves symptoms, and conditions that continue or develop after acute COVID-19. SARS-CoV-2 infection of immune and endothelial cells are associated with NETosis, microthrombosis and endothelial dysfunction that could persist several weeks after acute phase of infection. Damaged endothelial cells can expose the vessel pro-coagulant area leading to platelet and neutrophil clumps. Increased levels of circulating endothelial cells (CECs) have been described as biomarkers for cardiovascular diseases. Therefore, we hypothesize that CECs and microthrombosis are potential biomarkers of vascular dysfunction in Long COVID.Methods.A cross-sectional study was conducted at the Miami VA long COVID clinic. Long COVID cases and controls were recruited according to WHO definition for long COVID. A total of 23 patients and 7 controls were included in this study. Blood samples were collected in Heparin and Sodium Citrate tubes. Cell immunophenotyping and NETosis markers (MPO) were quantified on a Cytek Aurora spectral flow cytometer system. Microclots (CD62P+PAC-1+) and platelet response were assessed by flow cytometry and response to Adenosine di-phosphate (ADP), respectively. A ttest was used for statistical analysis. Differences were considered significant when p < 0.05.Results.The age and gender were similar between cases and controls while their symptom score was significantly different. There was a significant increase in the number of CECs (CD31+CD309+CD45-CD133-) in Long COVID cases. MPO expression in neutrophils (CD11b+CD66b+CD15+) and classical monocytes (CD14+CD16-) was significantly higher in Long COVID. Microclots were significantly elevated, and the platelet aggregation response was dysregulated in Long COVID.Conclusions.CECs and microthrombosis including NETosis are present in Long COVID and may serve as potential biomarkers or causative mechanisms for vascular dysfunction.

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Novembre 2024

Abstract 4140201: Disparities in Defibrillator Implantations during COVID-19: Insights from the NCDR registry

Circulation, Volume 150, Issue Suppl_1, Page A4140201-A4140201, November 12, 2024. Introduction:While implantable cardiac defibrillators (ICD) decrease sudden cardiac death, disparities in ICD use remain. The COVID-19 pandemic created strains on the US healthcare system that may have exacerbated these disparities.Methods:Using the US NCDR registry of primary and secondary prevention ICD implants, we compared sex, racial and ethnic disparities for 239,014 patients, aged 19-90 years, grouped into three time intervals from 2016 to 2022: Pre-COVID, COVID and Post-COVID. Centers without consistent reporting were excluded, as were patients with incomplete sex, race or ethnicity data. ICD implantation rates were compared using a Poisson regression model with interaction tests for sex, race and ethnicity by time window to see if disparities changed within this period. Implant rates by indication were also assessed.Results:Overall ICD implants decreased over the study period (Figure 1) with an average monthly rate of 3271 in the first three months of 2016 declining to 2334 in the last three months of 2022 (p=0.017). Disparities in ICD implantation for women, racial and ethnic minorities were observed pre-COVID and persisted (Table 1). Average ICD implant rates during these time periods varied by race with predominance in White patients. While gaps in ICD implant persisted, the disparities did not worsen during COVID-19 by sex, race or ethnicity (p-value for interactions were 0.79; 0.47; and 0.095, respectively). There was a more significant decrease in primary prevention ICD compared to secondary prevention ICD (p

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Novembre 2024