Pulmonary embolism (PE) in the setting of COVID-19 is related to the procoagulant state as evidenced by the increased d-dimer levels and in situ thrombosis [1,2] and it usually involves the segmental/subsegmental arteries [2]. Some data have shown that mortality is higher among patients with COVID-19 associated PE compared with non-COVID-19 PE [3]. The COVID-19 pandemic has led to marked reductions in cardiovascular testing in the United States (US) and worldwide [4]. However, the impact of the COVID-19 pandemic on the diagnosis and management of PE is not well studied. To better describe the characteristics and the impact of COVID-19 infection on the management strategies and outcomes among patients with acute PE, we performed a comprehensive analysis of a nationally representative database in the US.
We used the Nationwide Readmissions Database (NRD) for the years 2019 and 2020 to extract the study cohort. All admissions with age 18 years or older with any discharge diagnosis of PE in the years 2019 and 2020 were included. Pregnancy-related PE (n = 2871) and admissions with missing data on mortality (n = 169) were excluded. We examined the differences in all-cause in-hospital mortality, length of stay (LOS), cost, intracranial hemorrhage (ICH), non-ICH bleeding, and 30-day urgent readmission rates between admissions with and without COVID-19 in the year 2020. We also examined the differences in outcomes among admissions with non-COVID-19 PE in 2019 versus 2020. All analyzes were performed according to the Healthcare Cost and Utilization Project (HCUP) regulations. Multivariable logistic regression analyses were used to adjust for the differences in baseline and hospital characteristics, PE severity and different management strategies. Additionally, we performed a subgroup analysis for admissions with high-risk PE (i.e., cardiogenic shock). Statistical analyses were performed using IBM SPSS Statistics for Windows (version 28.0. Armonk, NY: IBM Corp).
A total of 786,963 weighted hospitalizations with acute PE were included in the analysis, 374,122 (47.5%) were admitted in 2019 and 412,842 (52.5%) in 2020. Among those admitted in 2020, 46,825 (11.3%) weighted hospitalizations had concomitant COVID-19 infection. The use of surgical embolectomy, catheter-directed interventions (CDI) and mechanical circulatory support (MCS) devices was less common among admissions with COVID-19 infection. However, vasopressors and mechanical ventilation was higher among admissions with COVID-19 infection. (Table 1 )
Table 1.
Characteristics and outcomes of patients with acute PE admitted in the year 2020.
| PE without COVID-19 (n = 366,017) | PE with COVID-19 (n = 46,825) | P value | |
|---|---|---|---|
| Age, median (IQR) | 66 (54–76) | 66 (55–76) | 0.04 |
| Female | 183,709 (50.2%) | 19,462 (41.6%) | <0.001 |
| Smoking | 85,873 (23.5%) | 10,022 (21.4%) | <0.001 |
| Comorbidities | |||
| Morbid obesity | 46,862 (12.8%) | 6343 (13.5%) | 0.007 |
| Hypertension | 233,817 (63.9%) | 29,628 (63.3%) | 0.118 |
| Diabetes mellitus | 96,420 (26.3%) | 16,634 (35.5%) | <0.001 |
| Anemia | 98,656 (27.0%) | 10,384 (22.2%) | <0.001 |
| Coagulopathy | 49,278 (13.5%) | 8127 (17.4%) | <0.001 |
| Pulmonary hypertension | 41,094 (11.2%) | 2460 (5.3%) | <0.001 |
| Chronic pulmonary disease | 96,833 (26.5%) | 10,084 (21.5%) | <0.001 |
| Atrial fibrillation/flutter | 62,518 (17.1%) | 6857 (14.6%) | <0.001 |
| Heart failure | 87,636 (23.9%) | 7595 (16.2%) | <0.001 |
| Chronic kidney disease | 61,036 (16.7%) | 7431 (15.9%) | 0.008 |
| Chronic liver disease | 4443 (1.2%) | 248 (0.5%) | <0.001 |
| Connective tissue diseases | 13,867 (3.8%) | 1482 (3.2%) | <0.001 |
| CAD | 69,080 (18.9%) | 7197 (15.4%) | <0.001 |
| PAD | 14,340 (3.9%) | 1163 (2.5%) | <0.001 |
| Carotid disease | 3012 (0.8%) | 253 (0.5%) | <0.001 |
| Prior stroke | 30,798 (8.4%) | 3217 (6.9%) | <0.001 |
| Malignancy | 80,199 (21.9%) | 3026 (6.5%) | <0.001 |
| Metastatic | 43,930 (12.0%) | 1005 (2.1%) | <0.001 |
| Presentation and severity | |||
| Saddle PE | 26,195 (7.2%) | 1950 (4.2%) | <0.001 |
| Acute cor pulmonale | 27,267 (7.4%) | 1803 (3.9%) | <0.001 |
| High-risk PE (Cardiogenic shock) | 8647 (2.4%) | 846 (1.8%) | <0.001 |
| Concomitant DVT | 122,654 (33.5%) | 8811 (18.8%) | <0.001 |
| Hospital characteristics | |||
| Large hospital | 202,418 (55.3%) | 24,998 (53.4%) | 0.018 |
| Teaching hospital | 273,508 (74.7%) | 34,137 (72.9%) | 0.003 |
| Medicare | 203,423 (55.6%) | 24,366 (52.0%) | <0.001 |
| Transferred from other hospital | 13,297 (3.6%) | 2203 (4.7%) | <0.001 |
| Treatment modalities | |||
| Systemic thrombolysis | 8687 (2.4%) | 1088 (2.3%) | 0.70 |
| Surgical embolectomy | 596 (0.2%) | 17 (0.04%) | <0.001 |
| CDT | 9549 (2.6%) | 468 (1%) | <0.001 |
| CDE | 410 (1.8%) | 41 (0.8%) | <0.001 |
| IVC filter | 22,557 (6.2%) | 1122 (2.4%) | <0.001 |
| Circulatory and ventilatory support | |||
| Vasopressors | 5628 (1.5%) | 1443 (3.1%) | <0.001 |
| Mechanical ventilation | 31,681 (8.7%) | 9739 (20.8%) | <0.001 |
| Mechanical circulatory support | 1459 (0.4%) | 84 (0.2%) | <0.001 |
| Impella | 392 (0.1%) | 22 (0.0%) | 0.03 |
| ECMO | 702 (0.2%) | 55 (0.1%) | 0.03 |
| IABP | 537 (0.1%) | 10 (0.0%) | <0.001 |
| Outcomes | |||
| In-hospital mortality | 27,240 (7.4%) | 9285 (19.8%) | <0.001 |
| ICH | 5847 (1.6%) | 604 (1.3%) | <0.001 |
| Non-ICH | 39,744 (10.9%) | 5261 (11.2%) | <0.001 |
| Length of stay, days (IQR) | 4 (2–8) | 7 (4–14) | <0.001 |
| Cost of stay, US Dollars (IQR) | 12,462 (7056–25,364) | 17,212 (9079–37,833) | <0.001 |
| 30-day unplanned readmissions* | 46,890/308,437 (15.2%) | 2596/25,967 (10.0%) | <0.001 |
After excluding those who died during the index admissions and those who were admitted in December of each calendar year.
CDI: catheter-directed intervention, PE: pulmonary embolism, IQR: interquartile range, MI: myocardial infarction, PCI: percutaneous coronary intervention, CABG: Coronary artery bypass grafting, DVT: deep venous thrombosis, CDT: catheter-directed thrombolysis, CDE: catheter-directed embolectomy, US: ultrasound, IVC: inferior vena cava, ECMO: extracorporeal membrane oxygenation, IABP: intra-aortic balloon pump, ICH: Intracranial hemorrhage.
The rate of all-cause in-hospital mortality was higher among admissions with COVID-19 (7.4% vs. 19.8%, P < 0.001). The rate of ICH was slightly lower (1.6% vs. 1.3%, P < 0.001) and non-ICH was slightly higher (10.9%. vs. 11.2%, P < 0.001) among admissions with COVID-19. Admissions with COVID-19 had longer LOS and higher cost. (Table 1) On multivariable analysis, COVID-19 infection was independently associated with higher mortality (adjusted odds ratio [aOR] 2.71, 95% confidence interval [CI] 2.56, 2.87, P < 0.001), higher incidence of non-ICH (aOR 1.10, 95% CI 1.05, 1.15, P < 0.001), and lower incidence pf ICH (aOR 0.59, 95% CI 0.51, 0.68, P < 0.001). Among admissions with high-risk PE, in-hospital mortality was higher among those with COVID-19 (36.9% vs. 69.7%, aOR 2.64, 95% CI 2.10, 3.33, P < 0.001).
In the analysis restricted to non-COVID-19 PE admissions, the prevalence of saddle PE (6.2% vs. 7.2%, P < 0.001), cor pulmonale (6.8% vs. 7.4%, P = 0.008), and cardiogenic shock (2.1% vs. 2.4%, P = 0.007) was higher in 2020. There was no difference in the rate of utilization of systemic thrombolysis (2.4% vs. 2.4%, P = 0.76), surgical embolectomy (0.2% vs. 0.2%, P = 0.85), catheter-directed thrombolysis (2.5% vs. 2.6%, P = 0.52), vasopressors (1.3% vs. 1.5%, P = 0.20), and MCS devices (0.4% vs. 0.4%, P = 0.92) between 2019 and 2020. All-cause in-hospital mortality (7.0% vs. 7.4%, P < 0.001) was slightly higher in 2020. However, after adjustment, there was no difference in mortality between both years (2020 vs. 2019: aOR 1.04, 95% CI 0.99, 1.09, P = 0.14).
In this nationwide analysis, we examined the association between COVID-19 infection and the management and outcomes of acute PE during the early wave of the pandemic. The main findings were as follows: (1) Patients with COVID-19 and PE were less likely to receive CDI, surgical embolectomy, and MCS devices, compared with those without COVID-19 infection. (2) COVID-19 infection was independently associated with a higher incidence of all-cause in-hospital mortality, higher costs, and longer LOS compared to patients without COVID-19. (3) In analyses restricted to non-COVID-19 PE, patients admitted in 2020 versus 2019 were sicker but there was no difference in the utilization of advanced therapies and in-hospital mortality.
Similar to prior studies [3], we found that patients with COVID-19 associated PE had fewer comorbidities and risk factors for PE, indicating that COVID-19 itself is a predisposing factor for PE. Also, fewer patients with COVID-19 associated PE had DVT or saddle PE, suggesting that in situ thrombosis plays a role in the pathogenies of COVID-19 associated PE [5]. In the current analysis, COVID-19 infection was associated with a 2.7-fold increase in-hospital mortality among patients with PE. This can be related to severe COVID-19 infection leading to systemic inflammation, shock, multiorgan failure and respiratory failure with involvement of the lung parenchyma [3,6]. Additionally, COVID-19 associated PE is associated with increased incidence of mechanical ventilation and ICU admission [7].
In our analysis, patients with PE and COVID-19 infection during the early wave of the pandemic were less likely to receive surgical embolectomy, CDI, or MCS. This may be attributed to patients' isolation, instability, and difficulties in transferring patients safely to the catheterization laboratory or operating room without exposing the healthcare team. Additionally, patients may have not been offered invasive procedures due to the risk of transmission or poor prognosis.
We found that the care of patients with acute PE was generally not affected during the early wave of the COVID-19 pandemic. We noticed that in 2020, compared with 2019, patients with non-COVID PE were sicker suggesting that only patients with more severe symptoms presented to the emergency departments (ED) or that patients with less severe presentations were discharged directly from the ED. Despite that, there was no decline in the utilization of advanced therapies and no difference in-hospital mortality between 2019 and 2020 for patients without COVID-19, which suggests that care for essential services such as PE was maintained in 2020 despite significant system constraints.
There are some limitations to this study. Being a retrospective observational study, it is prone to selection bias. Given the administrative nature of the NRD, the study is subject to coding errors and data quality at the site of collection, without the ability to adjudicate accuracy. Clinical, laboratory, and imaging data as well as data on prescribed medications including the type and dose of anticoagulation and/or thrombolytic therapy are lacking from the NRD, which may have impacted the clinical outcomes. Long-term outcomes could not be assessed, and we could not also ascertain PE-specific mortality from NRD [8]. Finally, our findings are restricted to the early wave of the pandemic when the therapies for COVID-19 were limited, and widespread vaccines were unavailable.
In this nationwide observational cohort of patients admitted with PE during the early wave of the pandemic, COVID-19 infection was independently associated with a higher risk of all-cause in-hospital mortality. There was no decline in utilization of advanced therapies and no difference in-hospital mortality among patients with acute PE without COVID-19 infection in the year 2019 vs. 2020.
Sources of funding
None.
Declaration of Competing Interest
None.
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