Longitudinal Trends in Cardiovascular Risk Factor Profiles and Complications Among Patients Hospitalized for COVID-19 Infection: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry.

BACKGROUND: The COVID-19 pandemic has evolved through multiple phases characterized by new viral variants, vaccine development, and changes in therapies. It is unknown whether rates of cardiovascular disease (CVD) risk factor profiles and complications have changed over time. METHODS: We analyzed the American Heart Association COVID-19 CVD registry, a national multicenter registry of hospitalized adults with active COVID-19 infection. The time period from April 2020 to December 2021 was divided into 3-month epochs, with March 2020 analyzed separately as a potential outlier. Participating centers varied over the study period. Trends in all-cause in-hospital mortality, CVD risk factors, and in-hospital CVD outcomes, including a composite primary outcome of cardiovascular death, cardiogenic shock, new heart failure, stroke, and myocardial infarction, were evaluated across time epochs. Risk-adjusted analyses were performed using generalized linear mixed-effects models. RESULTS: A total of 46 007 patient admissions from 134 hospitals were included (mean patient age 61.8 years, 53% male, 22% Black race). Patients admitted later in the pandemic were younger, more likely obese, and less likely to have existing CVD (Ptrend ≤0.001 for each). The incidence of the primary outcome increased from 7.0% in March 2020 to 9.8% in October to December 2021 (risk-adjusted Ptrend=0.006). This was driven by an increase in the diagnosis of myocardial infarction and stroke (Ptrend<0.0001 for each). The overall rate of in-hospital mortality was 14.2%, which declined over time (20.8% in March 2020 versus 10.8% in the last epoch; adjusted Ptrend<0.0001). When the analysis was restricted to July 2020 to December 2021, no temporal change in all-cause mortality was seen (adjusted Ptrend=0.63). CONCLUSIONS: Despite a shifting risk factor profile toward a younger population with lower rates of established CVD, the incidence of diagnosed cardiovascular complications of COVID increased from the onset of the pandemic through December 2021. All-cause mortality decreased during the initial months of the pandemic and thereafter remained consistently high through December 2021.

Clinical Trial Participation and COVID-19: a Descriptive Analysis from the American Heart Association's Get With The Guidelines Registry.

As COVID-19 cases begin to decrease in the USA, learning from the pandemic experience will provide insights regarding disparities of care delivery. We sought to determine if specific populations hospitalized with COVID-19 are equally likely to be enrolled in clinical trials. We examined patients hospitalized with COVID-19 at centers participating in the American Heart Association's COVID-19 CVD Registry. The primary outcome was odds of enrollment in a clinical trial, according to sex, race, and ethnicity. Among 14,397 adults hospitalized with COVID-19, 9.5% (n = 1,377) were enrolled in a clinical trial. The proportion of enrolled patients was the lowest for Black patients (8%); in multivariable analysis, female and Black patients were less likely to be enrolled in a clinical trial related to COVID-19 compared to men and other racial groups, respectively. Determination of specific reasons for the disparities in trial participation related to COVID-19 in these populations should be further investigated.

Enriching the American Heart Association COVID-19 Cardiovascular Disease Registry Through Linkage With External Data Sources: Rationale and Design.

Background The AHA Registry (American Heart Association COVID-19 Cardiovascular Disease Registry) captures detailed information on hospitalized patients with COVID-19. The registry, however, does not capture information on social determinants of health or long-term outcomes. Here we describe the linkage of the AHA Registry with external data sources, including fee-for-service (FFS) Medicare claims, to fill these gaps and assess the representativeness of linked registry patients to the broader Medicare FFS population hospitalized with COVID-19. Methods and Results We linked AHA Registry records of adults ≥65 years from March 2020 to September 2021 with Medicare FFS claims using a deterministic linkage algorithm and with the American Hospital Association Annual Survey, Rural Urban Commuting Area codes, and the Social Vulnerability Index using hospital and geographic identifiers. We compared linked individuals with unlinked FFS beneficiaries hospitalized with COVID-19 to assess the representativeness of the AHA Registry. A total of 10 010 (47.0%) records in the AHA Registry were successfully linked to FFS Medicare claims. Linked and unlinked FFS beneficiaries were similar with respect to mean age (78.1 versus 77.9, absolute standardized difference [ASD] 0.03); female sex (48.3% versus 50.2%, ASD 0.04); Black race (15.1% versus 12.0%, ASD 0.09); dual-eligibility status (26.1% versus 23.2%, ASD 0.07); and comorbidity burden. Linked patients were more likely to live in the northeastern United States (35.7% versus 18.2%, ASD 0.40) and urban/metropolitan areas (83.9% versus 76.8%, ASD 0.18). There were also differences in hospital-level characteristics between cohorts. However, in-hospital outcomes were similar (mortality, 23.3% versus 20.1%, ASD 0.08; home discharge, 45.5% versus 50.7%, ASD 0.10; skilled nursing facility discharge, 24.4% versus 22.2%, ASD 0.05). Conclusions Linkage of the AHA Registry with external data sources such as Medicare FFS claims creates a unique and generalizable resource to evaluate long-term health outcomes after COVID-19 hospitalization.

New-Onset Atrial Fibrillation in Patients Hospitalized With COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Registry.

BACKGROUND: New-onset atrial fibrillation (AF) in patients hospitalized with COVID-19 has been reported and associated with poor clinical outcomes. We aimed to understand the incidence of and outcomes associated with new-onset AF in a diverse and representative US cohort of patients hospitalized with COVID-19. METHODS: We used data from the American Heart Association COVID-19 Cardiovascular Disease Registry. Patients were stratified by the presence versus absence of new-onset AF. The primary and secondary outcomes were in-hospital mortality and major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, stroke, cardiogenic shock, and heart failure). The association of new-onset AF and the primary and secondary outcomes was evaluated using Cox proportional-hazards models for the primary time to event analyses. RESULTS: Of the first 30 999 patients from 120 institutions across the United States hospitalized with COVID-19, 27 851 had no history of AF. One thousand five hundred seventeen (5.4%) developed new-onset AF during their index hospitalization. New-onset AF was associated with higher rates of death (45.2% versus 11.9%) and MACE (23.8% versus 6.5%). The unadjusted hazard ratio for mortality was 1.99 (95% CI, 1.81-2.18) and for MACE was 2.23 (95% CI, 1.98-2.53) for patients with versus without new-onset AF. After adjusting for demographics, clinical comorbidities, and severity of disease, the associations with death (hazard ratio, 1.10 [95% CI, 0.99-1.23]) fully attenuated and MACE (hazard ratio, 1.31 [95% CI, 1.14-1.50]) partially attenuated. CONCLUSIONS: New-onset AF was common (5.4%) among patients hospitalized with COVID-19. Almost half of patients with new-onset AF died during their index hospitalization. After multivariable adjustment for comorbidities and disease severity, new-onset AF was not statistically significantly associated with death, suggesting that new-onset AF in these patients may primarily be a marker of other adverse clinical factors rather than an independent driver of mortality. Causality between the MACE composites and AF needs to be further evaluated.

Association of COVID-19 Hospitalization Volume and Case Growth at US Hospitals with Patient Outcomes.

BACKGROUND: Whether the volume of coronavirus disease 2019 (COVID-19) hospitalizations is associated with outcomes has important implications for the organization of hospital care both during this pandemic and future novel and rapidly evolving high-volume conditions. METHODS: We identified COVID-19 hospitalizations at US hospitals in the American Heart Association COVID-19 Cardiovascular Disease Registry with ≥10 cases between January and August 2020. We evaluated the association of COVID-19 hospitalization volume and weekly case growth indexed to hospital bed capacity, with hospital risk-standardized in-hospital case-fatality rate (rsCFR). RESULTS: There were 85 hospitals with 15,329 COVID-19 hospitalizations, with a median hospital case volume was 118 (interquartile range, 57, 252) and median growth rate of 2 cases per 100 beds per week but varied widely (interquartile range: 0.9 to 4.5). There was no significant association between overall hospital COVID-19 case volume and rsCFR (rho, 0.18, P = .09). However, hospitals with more rapid COVID-19 case-growth had higher rsCFR (rho, 0.22, P = 0.047), increasing across case growth quartiles (P trend = .03). Although there were no differences in medical treatments or intensive care unit therapies (mechanical ventilation, vasopressors), the highest case growth quartile had 4-fold higher odds of above median rsCFR, compared with the lowest quartile (odds ratio, 4.00; 1.15 to 13.8, P = .03). CONCLUSIONS: An accelerated case growth trajectory is a marker of hospitals at risk of poor COVID-19 outcomes, identifying sites that may be targets for influx of additional resources or triage strategies. Early identification of such hospital signatures is essential as our health system prepares for future health challenges.

Racial and Ethnic Differences in Presentation and Outcomes for Patients Hospitalized With COVID-19: Findings From the American Heart Association's COVID-19 Cardiovascular Disease Registry.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has exposed longstanding racial and ethnic inequities in health risks and outcomes in the United States. We aimed to identify racial and ethnic differences in presentation and outcomes for patients hospitalized with COVID-19. METHODS: The American Heart Association COVID-19 Cardiovascular Disease Registry is a retrospective observational registry capturing consecutive patients hospitalized with COVID-19. We present data on the first 7868 patients by race/ethnicity treated at 88 hospitals across the United States between January 17, 2020, and July 22, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events (death, myocardial infarction, stroke, heart failure) and COVID-19 cardiorespiratory ordinal severity score (worst to best: death, cardiac arrest, mechanical ventilation with mechanical circulatory support, mechanical ventilation with vasopressors/inotrope support, mechanical ventilation without hemodynamic support, and hospitalization alone. Multivariable logistic regression analyses were performed to assess the relationship between race/ethnicity and each outcome adjusting for differences in sociodemographic, clinical, and presentation features, and accounting for clustering by hospital. RESULTS: Among 7868 patients hospitalized with COVID-19, 33.0% were Hispanic, 25.5% were non-Hispanic Black, 6.3% were Asian, and 35.2% were non-Hispanic White. Hispanic and Black patients were younger than non-Hispanic White and Asian patients and were more likely to be uninsured. Black patients had the highest prevalence of obesity, hypertension, and diabetes. Black patients also had the highest rates of mechanical ventilation (23.2%) and renal replacement therapy (6.6%) but the lowest rates of remdesivir use (6.1%). Overall mortality was 18.4% with 53% of all deaths occurring in Black and Hispanic patients. The adjusted odds ratios for mortality were 0.93 (95% CI, 0.76-1.14) for Black patients, 0.90 (95% CI, 0.73-1.11) for Hispanic patients, and 1.31 (95% CI, 0.96-1.80) for Asian patients compared with non-Hispanic White patients. The median odds ratio across hospitals was 1.99 (95% CI, 1.74-2.48). Results were similar for major adverse cardiovascular events. Asian patients had the highest COVID-19 cardiorespiratory severity at presentation (adjusted odds ratio, 1.48 [95% CI, 1.16-1.90]). CONCLUSIONS: Although in-hospital mortality and major adverse cardiovascular events did not differ by race/ethnicity after adjustment, Black and Hispanic patients bore a greater burden of mortality and morbidity because of their disproportionate representation among COVID-19 hospitalizations.

Association of Kidney Disease With Outcomes in COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry.

Background Emerging evidence links acute kidney injury (AKI) in patients with COVID-19 with higher mortality and respiratory morbidity, but the relationship of AKI with cardiovascular disease outcomes has not been reported in this population. We sought to evaluate associations between chronic kidney disease (CKD), AKI, and mortality and cardiovascular outcomes in patients hospitalized with COVID-19. Methods and Results In a large multicenter registry including 8574 patients with COVID-19 from 88 US hospitals, data were collected on baseline characteristics and serial laboratory data during index hospitalization. Primary exposure variables were CKD (categorized as no CKD, CKD, and end-stage kidney disease) and AKI (classified into no AKI or stages 1, 2, or 3 using a modification of the Kidney Disease Improving Global Outcomes guideline definition). The primary outcome was all-cause mortality. The key secondary outcome was major adverse cardiac events, defined as cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, new-onset nonfatal heart failure, and nonfatal cardiogenic shock. CKD and end-stage kidney disease were not associated with mortality or major adverse cardiac events after multivariate adjustment. In contrast, AKI was significantly associated with mortality (stage 1 hazard ratio [HR], 1.72 [95% CI, 1.46-2.03]; stage 2 HR, 1.83 [95% CI, 1.52-2.20]; stage 3 HR, 1.69 [95% CI, 1.44-1.98]; versus no AKI) and major adverse cardiac events (stage 1 HR, 2.17 [95% CI, 1.74-2.71]; stage 2 HR, 2.70 [95% CI, 2.07-3.51]; stage 3 HR, 3.06 [95% CI, 2.52-3.72]; versus no AKI). Conclusions This large study demonstrates a significant association between AKI and all-cause mortality and, for the first time, major adverse cardiovascular events in patients hospitalized with COVID-19.

Trends in Patient Characteristics and COVID-19 In-Hospital Mortality in the United States During the COVID-19 Pandemic.

Importance: In-hospital mortality rates from COVID-19 are high but appear to be decreasing for selected locations in the United States. It is not known whether this is because of changes in the characteristics of patients being admitted. Objective: To describe changing in-hospital mortality rates over time after accounting for individual patient characteristics. Design, Setting, and Participants: This was a retrospective cohort study of 20 736 adults with a diagnosis of COVID-19 who were included in the US American Heart Association COVID-19 Cardiovascular Disease Registry and admitted to 107 acute care hospitals in 31 states from March through November 2020. A multiple mixed-effects logistic regression was then used to estimate the odds of in-hospital death adjusted for patient age, sex, body mass index, and medical history as well as vital signs, use of supplemental oxygen, presence of pulmonary infiltrates at admission, and hospital site. Main Outcomes and Measures: In-hospital death adjusted for exposures for 4 periods in 2020. Results: The registry included 20 736 patients hospitalized with COVID-19 from March through November 2020 (9524 women [45.9%]; mean [SD] age, 61.2 [17.9] years); 3271 patients (15.8%) died in the hospital. Mortality rates were 19.1% in March and April, 11.9% in May and June, 11.0% in July and August, and 10.8% in September through November. Compared with March and April, the adjusted odds ratios for in-hospital death were significantly lower in May and June (odds ratio, 0.66; 95% CI, 0.58-0.76; P < .001), July and August (odds ratio, 0.58; 95% CI, 0.49-0.69; P < .001), and September through November (odds ratio, 0.59; 95% CI, 0.47-0.73). Conclusions and Relevance: In this cohort study, high rates of in-hospital COVID-19 mortality among registry patients in March and April 2020 decreased by more than one-third by June and remained near that rate through November. This difference in mortality rates between the months of March and April and later months persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity and did not appear to be associated with changes in the characteristics of patients being admitted.

Association of Body Mass Index and Age With Morbidity and Mortality in Patients Hospitalized With COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry.

BACKGROUND: Obesity may contribute to adverse outcomes in coronavirus disease 2019 (COVID-19). However, studies of large, broadly generalizable patient populations are lacking, and the effect of body mass index (BMI) on COVID-19 outcomes- particularly in younger adults-remains uncertain. METHODS: We analyzed data from patients hospitalized with COVID-19 at 88 US hospitals enrolled in the American Heart Association's COVID-19 Cardiovascular Disease Registry with data collection through July 22, 2020. BMI was stratified by World Health Organization obesity class, with normal weight prespecified as the reference group. RESULTS: Obesity, and, in particular, class III obesity, was overrepresented in the registry in comparison with the US population, with the largest differences among adults ≤50 years. Among 7606 patients, in-hospital death or mechanical ventilation occurred in 2109 (27.7%), in-hospital death in 1302 (17.1%), and mechanical ventilation in 1602 (21.1%). After multivariable adjustment, classes I to III obesity were associated with higher risks of in-hospital death or mechanical ventilation (odds ratio, 1.28 [95% CI, 1.09-1.51], 1.57 [1.29-1.91], 1.80 [1.47-2.20], respectively), and class III obesity was associated with a higher risk of in-hospital death (hazard ratio, 1.26 [95% CI, 1.00-1.58]). Overweight and class I to III obese individuals were at higher risk for mechanical ventilation (odds ratio, 1.28 [95% CI, 1.09-1.51], 1.54 [1.29-1.84], 1.88 [1.52-2.32], and 2.08 [1.68-2.58], respectively). Significant BMI by age interactions were seen for all primary end points (P-interaction<0.05 for each), such that the association of BMI with death or mechanical ventilation was strongest in adults ≤50 years, intermediate in adults 51 to 70 years, and weakest in adults >70 years. Severe obesity (BMI ≥40 kg/m2) was associated with an increased risk of in-hospital death only in those ≤50 years (hazard ratio, 1.36 [1.01-1.84]). In adjusted analyses, higher BMI was associated with dialysis initiation and with venous thromboembolism but not with major adverse cardiac events. CONCLUSIONS: Obese patients are more likely to be hospitalized with COVID-19, and are at higher risk of in-hospital death or mechanical ventilation, in particular, if young (age ≤50 years). Obese patients are also at higher risk for venous thromboembolism and dialysis. These observations support clear public health messaging and rigorous adherence to COVID-19 prevention strategies in all obese individuals regardless of age.

American Heart Association COVID-19 CVD Registry Powered by Get With The Guidelines.

BACKGROUND: In response to the public health emergency created by the coronavirus disease 2019 (COVID-19) pandemic, American Heart Association volunteers and staff aimed to rapidly develop and launch a resource for the medical and research community to expedite scientific advancement through shared learning, quality improvement, and research. In <4 weeks after it was first announced on April 3, 2020, AHA's COVID-19 CVD Registry powered by Get With The Guidelines received its first clinical records. METHODS AND RESULTS: Participating hospitals are enrolling consecutive hospitalized patients with active COVID-19 disease, regardless of CVD status. This hospital quality improvement program will allow participating hospitals and health systems to evaluate patient-level data including mortality rates, intensive care unit bed days, and ventilator days from individual review of electronic medical records of sequential adult patients with active COVID-19 infection. Participating sites can leverage these data for onsite, rapid quality improvement, and benchmarking versus other institutions. After 9 weeks, >130 sites have enrolled in the program and >4000 records have been abstracted in the national dataset. Additionally, the aggregate dataset will be a valuable data resource for the medical research community. CONCLUSIONS: The AHA COVID-19 CVD Registry will support greater understanding of the impact of COVID-19 on cardiovascular disease and will inform best practices for evaluation and management of patients with COVID-19.