There are limited contemporary data on the management and outcomes of acute myocardial infarction (AMI) in patients with concomitant acute respiratory infections. Hence, using the National Inpatient Sample from 2000-2017, adult AMI admissions with and without concomitant respiratory infections were identified. We evaluated in-hospital mortality, utilization of cardiac procedures, hospital length of stay, hospitalization costs, and discharge disposition. Among 10,880,856 AMI admissions, respiratory infections were identified in 745,536 (6.9%). Temporal trends revealed a relatively stable tr end with a peak during 2008-2009. Admissions with respiratory infections were on average older (74 vs. 67 years), female (45% vs 39%), with greater comorbidity (mean Charlson comorbidity index 5.9 ± 2.2 vs 4.4 ± 2.3), and had higher rates of non-ST-segment-elevation AMI presentation (71.8% vs. 62.2%) (all p < 0.001). Higher rates of cardiac arrest (8.2% vs 4.8%), cardiogenic shock (10.7% vs 4.4%), and acute organ failure (27.8% vs 8.1%) were seen in AMI admissions with respiratory infections. Coronary angiography (41.4% vs 65.6%, p < 0.001) and percutaneous coronary intervention (20.7% vs 43.5%, p < 0.001) were used less commonly in those with respiratory infections. Admissions with respiratory infections had higher in-hospital mortality (14.5% vs 5.5%; propensity matched analysis: 14.6% vs 12.5%; adjusted odds ratio 1.25 [95% confidence interval 1.24-1.26], p < 0.001), longer hospital stay, higher hospitalization costs, and less frequent discharges to home compared to those without respiratory infections. In conclusion, respiratory infections significantly impact AMI admissions with higher rates of complications, mortality and resource utilization.
The current pandemic of Coronavirus Disease 2019 (COVID-19) has brought attention to the impact of acute respiratory infections on cardiovascular diseases. , The COVID-19 pandemic has identified multiple potential pathogenic mechanisms contributing to myocardial injury, including acute myocardial infarction (AMI) in those with respiratory viral infections. A similar relationship between respiratory infections like influenza and pneumonia and the risk of AMI has been well established over recent years. A six-fold increase in AMI risk during the week after influenza infection was reported in a recent study, while several other reports have shown the heightened risk for acute cardiovascular events, including AMI, and increased short-term mortality in patients with infections such as influenza and pneumonia. , Despite this well-established relationship between respiratory infections and AMI, very little is known regarding the characteristics of AMI patients with concurrent respiratory infections and the impact on the management and outcomes of these patients. As such, we sought to assess the changes in management practices and in-hospital outcomes of AMI admissions in the presence of acute respiratory infections using a large contemporary United States population.
Methods
The National (Nationwide) Inpatient Sample (NIS) is a part of the Healthcare Quality and Utilization Project (HCUP), sponsored by the Agency for Healthcare Research and Quality and contains discharge data from a 20% stratified sample of community hospitals. Information such as patient demographics, primary payer, hospital characteristics, principal diagnosis, up to 39 secondary diagnoses, and procedural diagnoses are available for each discharge. Institutional Review Board approval was not sought due to the publicly available nature of this de-identified database.
We used the HCUP-NIS data from January 1, 2000 through December 31, 2017 to identify a cohort of adult admissions (>18 years) with AMI in the primary diagnosis field (International Classification of Diseases 9.0 Clinical Modification [ICD-9CM] 410.x and ICD-10CM I21.x-22.x). Concomitant respiratory infections including pneumococcal and other bacterial pneumonias, interstitial pneumonia due to organisms like mycoplasma and chlamydia, unspecified pneumonia, influenza due to avian virus, H1N1 and novel influenza A virus were all identified using ICD-9CM 480-488 and ICD-10CM J09-18. We defined the seasons based on the meteorological classification of the Northern Hemisphere as – Spring (March-May), Summer (June-August), Fall (September-November) and Winter (December-February) using admission month provided by HCUP-NIS. Admissions that did not have information on the month of admission were excluded. The burden of co-morbid diseases was identified using the Deyo’s modification of the Charlson Comorbidity Index. Demographic characteristics including age, sex, race, hospital characteristics, acute organ failure, mechanical circulatory support, cardiac procedures, and other non-cardiac organ support use were identified for all admissions using previously used methodologies from our group (Supplementary Table 1). , ,
The primary outcome of interest was in-hospital mortality of AMI admissions among those with and without respiratory infections. The secondary outcomes included evaluating utilization of coronary angiography and percutaneous coronary angiography (PCI), mechanical circulatory support use, hospitalization costs, hospital length of stay, and discharge disposition.
The inherent restrictions of the HCUP-NIS database related to research design, data interpretation, and data analysis were reviewed and addressed. In accordance with HCUP-NIS recommendations, survey procedures using discharge weights provided with the HCUP-NIS database were used to generate national estimates. Samples from 2000-2011 were re-weighted using the trend weights provided by the HCUP-NIS to adjust for the 2012 HCUP-NIS re-design. Chi-square and t-tests were used to compare categorical and continuous variables, respectively. Univariable analysis for trends and outcomes was performed and was represented as odds ratio with 95% confidence interval. Multivariable logistic regression was used to analyze trends over time (referent year 2000). Multivariable logistic regression analysis incorporating demographic and hospital characteristics, comorbidity, admission season and year, acute organ failure, cardiogenic shock, cardiac arrest, cardiac and non-cardiac procedures was performed for assessing temporal trends of in-hospital mortality. Temporal trends in use of coronary angiography and PCI were plotted stratified by the presence of respiratory infections. For the multivariable modeling, regression analysis with purposeful selection of statistically (liberal threshold of p < 0.20 in univariate analysis) and clinically relevant variables was conducted. Sub-group analyses were performed for type of AMI (ST-segment-elevation myocardial infarction [STEMI] vs. non-ST-segment-elevation myocardial infarction [NSTEMI]), age (< or ≥75 years), sex (male/female), admission season (winter/other seasons), type of respiratory infection (pneumonia/influenza), and presence of chronic lung disease.
Additionally, we performed a propensity-matched analysis for age, sex, race, primary payer, socio-economic status estimated by the median household income of residents in the patient’s ZIP Code, comorbidity, AMI type, hospital characteristics, cardiogenic shock, cardiac arrest, acute organ failure, pulmonary artery catheterization, invasive mechanical ventilation, acute hemodialysis, admission season and year between the cohorts with and without respiratory infections. For the propensity matching, due to low missingness rates, records with missing observations were omitted. Using 1:1 nearest neighbor matching, 149,681 matching pairs were developed for further analysis. The propensity score matching balanced covariates such that standardized mean differences for all variables between groups were <0.10 (Supplementary Figure 1). The chi-square test and paired sample t-tests were used to compare categorical and continuous variables respectively in the propensity-matched sample. For all analyses, two-tailed p < 0.05 was considered statistically significant. Propensity score matching was performed using the Match It package (v3.0.2) with the R statistical software suite (v3.5.2). All statistical analyses were performed using SPSS v25.0 (IBM Corp, Armonk NY).
Results
A total of 10,880,856 admissions for AMI were identified between January 1, 2000 to December 31, 2017, of which 745,536 (6.9%) had concomitant acute respiratory infections. Among admissions with respiratory infections, pneumonia was identified in 731,833 (98.2%) and influenza in 13,702 (1.8%). Temporal trends revealed a peak in the prevalence of respiratory infections between years 2008 and 2009 ( Figure 1 ). Respiratory infections were more prevalent in NSTEMI admissions compared to STEMI admissions throughout the study period ( Figure 1 ). Admissions with respiratory infections were on average older, more likely to be female, with greater comorbidity, and more often admitted during winter months compared to AMI admissions without respiratory infections ( Table 1 ). When admissions with respiratory infections were stratified by AMI type, those with NSTEMI were older, more often female, had greater comorbidity, and higher rates of influenza compared to STEMI admissions (Supplementary Table 3)
| Characteristics | Respiratory infections | |||
|---|---|---|---|---|
| YES (N = 745,536) | NO (N = 10,135,321) | p | ||
| Type of acute myocardial infarction | ST-segment elevation | 210,315 (28.2%) | 3,833,590 (37.8%) | <0.001 |
| Non-ST-segment elevation | 535,221 (71.8%) | 6,301,731 (62.2%) | ||
| Age (years) | 74.3 ± 12.8 | 66.9 ± 14.1 | <0.001 | |
| Women | 336,448 (45.1%) | 3,984,915 (39.3%) | <0.001 | |
| White | 478,135 (64.1%) | 6,360,834 (62.8%) | <0.001 | |
| Black | 52,195 (7.0%) | 809,748 (8.0%) | ||
| Other races * | 215,206 (28.9%) | 2,964,739 (29.3%) | ||
| Primary payer | Medicare | 563,659 (75.6%) | 5,666,610 (55.9%) | <0.001 |
| Medicaid | 40,491 (5.4%) | 640,450 (6.3%) | ||
| Private | 105,247 (14.1%) | 2,965,351 (29.3%) | ||
| Others † | 36,138 (4.8%) | 862,909 (8.5%) | ||
| Quartile of median household income for zip code | 0–25 th | 193,530 (26.5%) | 2,406,694 (24.3%) | <0.001 |
| 26 th –50 th | 196,141 (26.9%) | 2,667,884 (26.9%) | ||
| 51 st –75 th | 171,687 (23.5%) | 2,414,603 (24.3%) | ||
| 75 th –100 th | 169,055 (23.1%) | 2,432,428 (24.5%) | ||
| Charlson Comorbidity Index | 0–3 | 101,848 (13.7%) | 4,030,304 (39.8%) | <0.001 |
| 4–6 | 383,169 (51.4%) | 4,423,078 (43.6%) | ||
| ≥7 | 260,518 (34.9%) | 1,681,939 (16.6%) | ||
| Hospital teaching status and location | Rural | 104,919 (14.1%) | 1,156,894 (11.4%) | <0.001 |
| Urban non-teaching | 293,787 (39.4%) | 3,807,928 (37.6%) | ||
| Urban teaching | 346,830 (46.5%) | 5,170,498 (51.0%) | ||
| Hospital bed-size | Small | 100,201 (13.4%) | 1,173,473 (11.6%) | <0.001 |
| Medium | 203,054 (27.2%) | 2,624,629 (25.9%) | ||
| Large | 442,280 (59.3%) | 6,337,218 (62.5%) | ||
| Hospital region | Northeast | 160,202 (21.5%) | 2,119,454 (20.9%) | <0.001 |
| Midwest | 184,364 (24.7%) | 2,472,708 (24.4%) | ||
| South | 262,391 (35.2%) | 3,662,998 (36.1%) | ||
| West | 138,578 (18.6%) | 1,880,160 (18.6%) | ||
| Tertile of admission years | 2000–2005 | 251,485 (33.7%) | 3,627,018 (35.8%) | <0.001 |
| 2006–2011 | 245,539 (32.9%) | 3,063,989 (30.2%) | ||
| 2012–2017 | 248,511 (33.3%) | 3,444,313 (34.0%) | ||
| Admission Season | Summer | 197,984 (26.6%) | 2,628,922 (25.9%) | <0.001 |
| Spring | 149,405 (20.0%) | 2,511,324 (24.8%) | ||
| Fall | 163,282 (21.9%) | 2,414,603 (23.8%) | ||
| Winter | 234,865 (31.5%) | 2,580,472 (25.5%) | ||
| Atrial fibrillation | 200,364 (26.9%) | 1,608,603 (15.9%) | <0.001 | |
| Ventricular tachycardia/fibrillation | 73,601 (9.9%) | 796,798 (7.9%) | <0.001 | |
| Cardiac arrest | 60,900 (8.2%) | 485,434 (4.8%) | <0.001 | |
| Cardiogenic shock | 79,849 (10.7%) | 447,522 (4.4%) | <0.001 | |
| Multiorgan failure | 206,997 (27.8%) | 819,701 (8.1%) | <0.001 | |
| Pulmonary artery catheterization | 17,060 (2.3%) | 97,082 (1.0%) | <0.001 | |
| Invasive mechanical ventilation | 132,088 (17.7%) | 512,436 (5.1%) | <0.001 | |
| Acute hemodialysis | 13,892 (1.9%) | 46,849 (0.5%) | <0.001 | |
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