Abstract
Background:
Current cardiac intensive care unit (CICU) practice has seen a rise in patient complexity, including an increase in non-cardiac organ failure, critical care therapies, and comorbidities. We sought to describe the changing epidemiology of non-cardiac multimorbidity in the CICU population.
Methods:
We analyzed consecutive unique patient admissions to two geographically distant tertiary care CICU’s (n=16,390). We assessed for the prevalence of 0, 1, 2, and ≥3 non-cardiac comorbidities (diabetes, chronic lung, liver, and kidney disease, cancer, and stroke/transient ischemic attack) and their associations with hospital and post-discharge one-year mortality using multivariable logistic regression.
Results:
The prevalence of 0, 1, 2, and ≥3 non-cardiac comorbidities was 37.7%, 31.4%, 19.9%, and 11.0%, respectively. Increasing non-cardiac comorbidities were associated with a stepwise increase in mortality, length of stay, non-cardiac indications for ICU admission, and increased utilization of critical care therapies. After multivariable adjustment, compared to those without non-cardiac comorbidities, there was an increased hospital mortality for patients with 1 (odds ratio [OR] 1.30; 95% confidence interval [CI]: 1.10–1.54, p=0.002), 2 (OR 1.47; 95% CI: 1.22–1.77, p<0.001), and ≥3 (OR 1.79; 95% CI: 1.44–2.22, p<0.001) non-cardiac comorbidities. Similar trends for each additional non-cardiac comorbidity were seen for post-discharge one-year mortality (p<0.001, all).
Conclusions:
In two large contemporary CICU populations, we found that non-cardiac multimorbidity was highly prevalent and a strong predictor of short and long-term adverse clinical outcomes. Further study is needed to define the best care pathways for CICU patients with acute cardiac illness complicated by non-cardiac multimorbidity.
Keywords: cardiac intensive care unit, multimorbidity, comorbidity
Introduction
The modern cardiac intensive care unit (CICU) has evolved to care for complicated, critically-ill patients who often develop multiorgan failure and frequently require various non-cardiac critical care therapies.1–3 Non-cardiac illnesses, such as renal failure, sepsis, and respiratory insufficiency, are becoming common reasons for CICU admission.4–6 Potential mechanisms driving this transformation are the aging population and an increase in chronic medical conditions.1, 2 Multimorbidity, defined as the presence of 2 or more chronic conditions,7, 8 offers particular challenges and complexity due to the interaction of conflicting medical conditions. In addition, clinicians carrying for those with multimorbidity are often left extrapolating evidence from trials that largely exclude these patients, resulting in a lack of representation in these trials and subsequent practice guidelines.9, 10
To date, studies assessing the impact of non-cardiac comorbidities in patients with cardiovascular disease have been limited to specific populations, such as those with acute myocardial infarction or heart failure.11–14 However, the increasingly heterogeneous CICU population encompasses a broad array of patients not well represented by these previous studies. In addition, previous studies have generally included a variety of settings while none have focused on the CICU itself. Finally, most of the previous research has focused on the impact of individual comorbidities while very little research has studied the interaction of various comorbidities on clinical outcomes.
Given this gap in the literature, we sought to investigate the prevalence of non-cardiac multimorbidity and its association with utilization of critical care therapies and subsequent clinical outcomes in two contemporary CICU populations. We tested the hypothesis that increasing non-cardiac multimorbidity would be associated with worse short and long-term clinical outcomes.
Methods
Study Design and Study Population
This was a two-center retrospective observational study comprising adult CICU cohorts from Yale New Haven Hospital (New Haven, CT) and Mayo Clinic St. Marys Hospital (Rochester, MN) during overlapping periods. Only unique data from the first CICU admission during the study period were analyzed to avoid systematic bias related to CICU readmissions. This study was approved independently by the Institutional Review Board at each institution.
Yale New Haven Hospital Cohort
Consecutive unique CICU patients admitted to the CICU at Yale New Haven Hospital (YNHH) from 2013 to 2017 were included. YNHH is a 1,541-bed tertiary care center and primary teaching hospital of the Yale School of Medicine. It includes a 14-bed CICU which was an open unit until November 2015, and subsequently transitioned to a closed model. Outcomes, demographics, and clinical variables of interest were extracted electronically from the medical record. Trained abstractors (PEM, AT, YK, FA) reviewed each chart in detail for medical comorbidities and the primary indication for CICU admission.
Mayo Clinic St. Marys Hospital Cohort
Unique adult patients admitted to the CICU at Mayo Clinic Hospital St. Marys Campus between 2007 and 2018 were included.1 The Mayo Clinic CICU is a 16-bed CICU that cares for medical patients with cardiovascular disease. The staffing structure has included a closed model and transitioned to a 24-hour in-house care model in 2015 with hiring of dual-boarded cardiac intensivists. The Charlson Comorbidity Index, individual comorbidities, demographics, and clinical data were extracted from the medical record based on a previously-validated electronic algorithm;1, 15–19 patients without available comorbidity data were excluded from this analysis. Admission diagnoses were defined as all ICD-9/10 diagnosis codes documented within one day before or after CICU admission, and were not mutually-exclusive.18
Variables of Interest
Covariates of interest included patient demographics (age, sex, race), medical comorbidities, CICU admission diagnoses, and procedures. Non-cardiac comorbidities were defined as chronic kidney disease, including end-stage renal disease, diabetes mellitus, transient ischemic attack or stroke, previous or current cancer, chronic lung disease (defined as chronic obstructive lung disease or interstitial lung disease), and chronic liver disease (defined as documented liver fibrosis or cirrhosis). The selection of these comorbidities was based on availability between the two centers, representation of various organ systems, and prior analyses showing clinical relevance in patients with cardiovascular disease.11–13
Outcomes
The primary outcome was all-cause hospital mortality. Secondary outcomes included post-discharge 1-year mortality (assessed among patients with known 1 year vital status), hospital and CICU length of stay (LOS), and extended CICU and hospital LOS defined as 4 and 12 days, respectively, consistent with previous multi-center CICU studies.6
Statistical Analysis
Baseline characteristics are reported for each cohort individually and for the combined cohort stratified by the number of non-cardiac comorbidities (0, 1, 2, or ≥ 3), consistent with previous analyses of multimorbidity.11 Continuous variables were described as means and standard deviation and categorical variables were described as frequencies and percentage. The two cohorts were compared using the t-test for continuous variables and chi-squared test for categorical variables. Trends across comorbidity groups were determined using linear regression in each cohort, with number of comorbidities treated as a continuous variable with a maximum value of 3. Logistic regression was performed to determine associations between comorbidity groups and outcomes of interest. The multivariable model included age, sex, race, cardiac comorbidities (heart failure, coronary artery disease, atrial fibrillation, peripheral vascular disease), CICU admission diagnoses, CICU therapies (continuous renal replacement therapy, central line, arterial line, invasive mechanical ventilation, non-invasive ventilation, intra-aortic balloon pump, right heart catheterization or pulmonary artery catheter, axial flow pump). Post-estimation methods were used to test the final regression model fit for the primary outcome (C-statistic=0.91 [Yale] and 0.88 [Mayo Clinic]). Adjusted results are shown for each cohort as well as a weighted, pooled odds ratio with 95% confidence interval. We performed a subgroup analysis of patients < or ≥65 years of age, using the same multivariable model with the exception of age as a covariate. Finally, we assessed hospital mortality for 4 a prior groups of interest: cardiogenic shock, cardiac arrest, acute myocardial infarction, and heart failure. Analyses were performed with STATA 16.0 (Stata Corp, College Station, TX) in the Yale cohort and with JMP version 14.0 Pro (SAS Institute, Cary, NC) for the Mayo Clinic cohort. Statistical significance was considered at a two-tailed P<0.05.
Results
Baseline Characteristics by Comorbidity Prevalence
Baseline characteristics stratified by the number of non-cardiac comorbidities are shown in Table 1. The prevalence of 0, 1, 2, and ≥3 non-cardiac comorbidities in the combined cohort was: 37.7%, 31.4%, 19.9%, and 11.0%, respectively. Diabetes mellitus (29.6%) was the most common non-cardiac comorbidity, followed by chronic kidney disease (22.1%), cancer (21.4%), and then chronic lung disease (19.3%). The mean age of the combined cohort was 67.9 ± 15.1 years, 62.5% of patients were male and 89.7% of patients were white. As the number of non-cardiac comorbidities increased, patients were older, had more cardiac comorbidities, and had differential patterns of admission diagnoses and CICU procedures (all p<0.05 for trends). Specifically, patients with more comorbidities had a lower prevalence of acute myocardial infarction as an admission diagnosis and a lower use of cardiac procedures. Patients with more non-cardiac comorbidities had more non-cardiac admission diagnoses (e.g. sepsis and respiratory failure) and a higher use of non-cardiac critical care therapies (e.g. ventilator and continuous renal replacement therapy). A comparison of the two study sites as well as baseline characteristics for each center stratified by the number of non-cardiac comorbidities are shown separately in the Supplement.
Table 1.
Baseline patient characteristics from the combined cohort stratified by the number of non-cardiac comorbidities. Data are displayed as number (%) for categorical variables and mean ± standard deviation for continuous variables.
| 0 (n = 6184) | 1 (n = 5150) | 2 (n = 3257) | ≥3 (n = 1799) | |
| Demographics | ||||
| Age (years) | 63.0 ± 16.2 | 69.4 ± 14.5 | 71.9 ± 12.8 | 73.4 ± 11.4 |
| Male | 3957 (64.0) | 3124 (60.7) | 2026 (62.2) | 1130 (62.8) |
| Race | ||||
| White | 5546 (89.7) | 4648 (90.3) | 2897 (88.9) | 1614 (89.7) |
| Black | 189 (3.1) | 161 (3.1) | 140 (4.3) | 88 (4.9) |
| Pre-A dmission Comorbidities | ||||
| Diabetes mellitus | 0 (0.0) | 1588 (30.8) | 1847 (56.7) | 1421 (79.0) |
| Coronary artery disease | 3480 (56.3) | 3035 (58.9) | 2070 (63.6) | 1199 (66.6) |
| Heart Failure | 782 (12.6) | 1302 (25.3) | 1275 (39.1) | 936 (52.0) |
| Chronic kidney disease | 0 (0.0) | 737 (14.3) | 1508 (46.3) | 1370 (76.2) |
| Pulmonary hypertension | 588 (9.5) | 727 (14.1) | 574 (17.6) | 407 (22.6) |
| Cancer | 0 (0.0) | 1279 (24.8) | 1178 (36.2) | 1052 (58.5) |
| Chronic lung disease | 0 (0.0) | 945 (18.3) | 1168 (35.9) | 1058 (58.8) |
| Chronic liver disease | 0 (0.0) | 71 (1.4) | 120 (3.7) | 163 (9.1) |
| Peripheral vascular disease | 212 (3.4) | 473 (9.2) | 548 (16.8) | 423 (23.5) |
| Stroke/Transient ischemic attack | 0 (0.0) | 530 (10.3) | 693 (21.3) | 778 (43.2) |
| Atrial fibrillation | 1603 (25.9) | 1790 (34.8) | 1303 (40.0) | 815 (45.3) |
| Procedures | ||||
| Coronary angiography | 3900 (63.1) | 2659 (51.6) | 1535 (47.1) | 771 (42.9) |
| Percutaneous coronary intervention | 2160 (34.9) | 1575 (30.6) | 955 (29.3) | 547 (30.4) |
| Central line | 1179 (19.1) | 1235 (24.0) | 886 (27.2) | 465 (25.8) |
| Arterial line | 1846 (29.9) | 1503 (29.2) | 911 (28.0) | 509 (28.3) |
| Intra-aortic balloon pump | 534 (8.6) | 440 (8.5) | 249 (7.6) | 118 (6.6) |
| Axial flow pump | 29 (0.5) | 35 (0.7) | 28 (0.9) | 8 (0.4) |
| Right heart catheterization/ Pulmonary artery catheter | 523 (8.5) | 569 (11.0) | 396 (12.2) | 221 (12.3) |
| Non-invasive ventilation | 549 (8.9) | 724 (14.1) | 653 (20.0) | 444 (24.7) |
| Invasive mechanical ventilation | 919 (14.9) | 909 (17.7) | 617 (18.9) | 347 (19.3) |
| Continuous renal replacement therapy | 64 (1.0) | 92 (1.8) | 120 (3.7) | 77 (4.3) |
| Left ventricular assist device | 113 (1.8) | 116(2.3) | 98 (3.0) | 52 (2.9) |
| Orthotopic heart transplant | 85 (1.4) | 75 (1.5) | 39 (1.2) | 18 (1.0) |
| Admission indication* | ||||
| Cardiogenic shock | 645 (10.5) | 596 (11.6) | 357 (11.0) | 170 (9.5) |
| C ardiac arrest | 708 (11.5) | 536 (10.5) | 325 (10.0) | 164 (9.1) |
| Infection/sepsis | 211 (3.4) | 286 (5.6) | 226 (7.0) | 151 (8.4) |
| Respiratory failure | 952 (15.5) | 1086 (21.2) | 808 (24.9) | 544 (30.3) |
| Heart failure | 1874 (30.6) | 2003 (39.1) | 1527 (47.0) | 1020 (56.8) |
| Acute myocardial infarction# | 2774 (45.3) | 1878 (36.7) | 1033 (31.8) | 514 (28.6) |
| ST -elevation myocardial infarction | 1930 (31.2) | 1085 (21.1)) | 490 (15.0) | 219 (12.2) |
| Outcomes | ||||
| CICU LOS (days) | 2.5 ±6.9 | 2.8 ±4.5 | 3.0 ± 5.9 | 3.1 ±4.2 |
| Hospital LOS (days) | 6.6 ± 11.4 | 8.4 ± 12.7 | 10.4 ± 18.8 | 10.1 ± 13.3 |
| Hospital mortality | 389 (6.3) | 498 (9.7) | 400 (12.3) | 263 (14.6) |
| CICU mortality | 271 (4.4) | 331 (6.4) | 260 (8.0) | 160 (8.9) |
| Post-discharge 1-year mortality& | 394 (8.0) | 671 (15.9) | 719 (27.0) | 493 (33.7) |
| 1 -year mortality& | 782 (12.6) | 1169 (22.7) | 1119 (34.4) | 755 (42.0) |
Note, Mayo Clinic admission diagnoses are not mutually exclusive and may sum greater than 1
Includes all Non-ST and ST-segment myocardial infarction
Only patients with known vital status at one year were included in the one-year mortality analysis.
CICU = cardiac intensive care unit; LOS = Length of stay
Hospital and One-year Mortality
A total of 9.5% patients died in the hospital. Hospital mortality for 0, 1, 2, and ≥3 non-cardiac comorbidities was 6.3%, 9.7%, 12.3%, and 14.6%, respectively (all p <0.001) (Figure 1A). After multivariable adjustment, we observed an increased hospital mortality for patients with 1 (odds ratio [OR] 1.30; 95% confidence interval [CI]: 1.10–1.54 p=0.002), 2 (OR 1.47; 95% CI: 1.22–1.77, p<0.001), and ≥3 (OR 1.79; 95% CI: 1.44–2.22, p<0.001) non-cardiac comorbidities compared to patients without non-cardiac comorbidities (Figure 2). The proportion of hospital deaths stratified by each comorbidity group are shown in Figure 3, and for each dyad combination in Supplemental Figure 1. Non-cardiac multimorbidity for each of the four a prior diagnoses of interest are shown in Figure 4.
Figure 1:
Crude (A) hospital mortality and (B) post-discharge 1-year mortality in the combined cohorts as a function of the number of non-cardiac comorbidities.
Figure 2:
Forest plot demonstrating adjusted odds ratio and 95% confidence interval values for hospital mortality for patients with 1, 2 or ≥3 non-cardiac comorbidities compared to patients without non-cardiac comorbidities as referent.
Figure 3:
Proportion of hospital mortality for each comorbidity group in the combined cohort.
Figure 4:
Proportion of hospital mortality for each diagnosis groups of interest.
Excluding patients that died during their index hospitalization (n = 2277), 17.2% of patients with vital status available (n = 13295) died within one year of CICU admission. One-year post-discharge mortality increased from 8.0%, 15.9%, 27.0%, and 33.7% for patients with 0, 1, 2, ≥3 non-cardiac comorbidities, respectively (all p <0.001, Figure 1B). After multivariable adjustment, we similarly found an increased post-discharge 1-year mortality for patients with 1 (OR 1.52; 95% CI: 1.31–1.52 p<0.001), 2 (OR 2.41; 95% CI: 2.08–2.79, p<0.001), and ≥3 (OR 2.79; 95% CI: 2.36–3.30, p<0.001) non-cardiac comorbidities compared to patients without non-cardiac comorbidities (Figure 5).
Figure 5:
Forest plot demonstrating adjusted odds ratio and 95% confidence interval values for one-year mortality for patients with 1, 2 or ≥3 non-cardiac comorbidities compared to patients without non-cardiac comorbidities as referent.
*Only patients whose vital status at one year is known are included.
CICU and Hospital Length of Stay
Mean CICU and hospital LOS were 3.0 ± 6.2 and 8.3 ± 13.9, respectively. After multivariable adjustment, increasing non-cardiac comorbidities were not associated with a prolonged (> 4 days) CICU stay (p>0.05), but were associated with a prolonged (> 12 days) hospital stay (Supplemental Table 4). Compared to those 0 non-cardiac comorbidities, prolonged hospital stay increased for patients with 1 (OR 1.36; 95% CI: 1.21–1.54 p<0.001), 2 (OR 1.71; 95% CI: 1.49–1.95, p<0.001), and ≥3 (OR 1.64; 95% CI: 1.39–1.93, p<0.001) non-cardiac comorbidities.
Subgroup Analysis by Age
Compared to patients ≥65 years of age, those <65 years had fewer comorbidities and lower hospital and one-year mortality (both p<0.05). After multivariable analysis, both patients <65 and ≥65 years of age had higher hospital and one-year post-discharge mortality than patients without non-cardiac comorbidities (all p<0.001) (Table 2A and B). Further, we found the association between non-cardiac comorbidities to be stronger for patients <65 years of age.
Table 2A.
Adjusted Hospital Mortality for Patients Less than 65 Years of Age Stratified by Non-Cardiac Comorbidities. Data are displayed as adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable logistic regression.
| Yale | Mayo Clinic | Combined | ||||
|---|---|---|---|---|---|---|
| Noncardiac comorbidities | OR (95% CI) | P-value | OR (95% CI) | P-value | OR (95% CI) | P-value |
| Hospital Mortality | ||||||
| 0 | Referent | Referent | Referent | |||
| 1 | 1.84 (0.96–3.50) | 0.065 | 1.70 (1.22–2.35) | 0.002 | 1.73 (1.29–2.31) | <0.001 |
| 2 | 2.41 (1.13–5.12) | 0.022 | 1.93 (1.28–2.91) | 0.002 | 2.03 (1.42–2.91) | <0.001 |
| ≥3 | 2.67 (1.00–7.06) | 0.050 | 2.57 (1.51–4.35) | <0.001 | 2.59 (1.63–4.13) | <0.001 |
| 1-Year Mortality | ||||||
| 0 | Referent | Referent | Referent | |||
| 1 | 3.55 (1.99–6.33) | <0.001 | 1.50 (1.12–2.00) | <0.001 | 2.92 (2.21–3.86) | <0.001 |
| 2 | 6.22 (3.29–11.73) | <0.001 | 2.75 (2.00–3.79) | <0.001 | 3.24 (2.44–4.31) | <0.001 |
| ≥3 | 4.37 (1.88–10.18) | 0.001 | 4.08 (2.78–5.99) | <0.001 | 4.13 (2.91–5.85) | <0.001 |
OR = Odds ratio; CI = Confidence interval
Table 2B.
Adjusted Hospital Mortality for Patients Greater than or 65 Years of Age Stratified by Non-Cardiac Comorbidities. Data are displayed as adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable logistic regression.
| Yale | Mayo Clinic | Combined | ||||
|---|---|---|---|---|---|---|
| Noncardiac comorbidities | OR (95% CI) | P-value | OR (95% CI) | P-value | OR (95% CI) | P-value |
| Hospital Mortality | ||||||
| 0 | Referent | Referent | Referent | |||
| 1 | 1.37 (0.88–2.15) | 0.165 | 1.15 (0.92–1.45) | 0.22 | 1.19 (0.97–1.46) | 0.089 |
| 2 | 1.62 (1.00–2.60) | 0.048 | 1.34 (1.05–1.72) | 0.02 | 1.40 (1.12–1.74) | 0.003 |
| ≥3 | 2.00 (1.17–3.41) | 0.011 | 1.63 (1.24–2.17) | <0.001 | 1.70 (1.32–2.17) | <0.001 |
| 1 - Year Mortality | ||||||
| 0 | Referent | Referent | Referent | |||
| 1 | 2.23 (1.53–3.26) | <0.001 | 1.33 (1.10–1.60) | <0.001 | 1.47 (1.24–1.74) | <0.001 |
| 2 | 3.72 (2.53–5.48) | <0.001 | 2.04 (1.67–2.48) | <0.001 | 2.31 (1.94–2.76) | <0.001 |
| ≥3 | 4.84 (3.16–7.40) | <0.001 | 2.20 (1.76–2.74) | <0.001 | 2.60 (2.14–3.17) | <0.001 |
OR = Odds ratio; CI = Confidence interval
Discussion
In two large modern, geographically distant tertiary-care CICU populations totaling more than 16,000 patients, we report several novel findings regarding the prevalence of non-cardiac comorbidities and their association with both hospital and post-charge clinical outcomes. First, the prevalence of non-cardiac multimorbidity in the modern CICU is high, with more than 30% of patients having ≥2 and 11% with ≥3 non-cardiac comorbidities. This is particularly important given the heterogenous mix of patients in the CICU and the limitation of previous studies of non-cardiac comorbidities focusing on specific diagnoses and non-CICU settings. Second, patients with an increasing number of non-cardiac comorbidities were more likely to be admitted for non-cardiac CICU indications and more likely to undergo non-cardiac critical care therapies. Third, a higher number of non-cardiac comorbidities was associated with an increased risk of hospital and post-discharge 1-year mortality. Finally, the association between non-cardiac multimorbidity and adverse outcomes appears to be stronger in those less than 65 years of age, who have a lower overall comorbidity burden at baseline. Our data highlight the substantial burden of non-cardiac illness among contemporary CICU patients, emphasizing that non-cardiac comorbidities contribute substantially to adverse short- and long-term outcomes.
To our knowledge, this is the first study assessing the prevalence and impact of multimorbidity in the CICU. While multimorbidity has been shown to be predictive and important for patients with specific diagnoses,9 multimorbidity may be especially significant for the acutely ill heterogenous mix of patients in the CICU. First, clinical trials and the majority of subsequent practice guidelines generally include patients with fewer comorbid conditions. This forces clinicians when faced with patients with multimorbidity to extrapolate evidence from trials that frequently excluded such patients.20 Second, mounting comorbid conditions are often associated with polypharmacy,21 which can prevent appropriate treatment of the acute cardiovascular problem or exacerbate chronic conditions. Polypharmacy in turn is often associated with serious ICU complications such as delirium and medication errors, which is a potentially harmful complication in the ICU.8, 22 In addition, some medications for chronic conditions (e.g. diabetes mellitus and cancer) may have a negative effect on cardiovascular outcomes.23 Third, significant non-cardiac conditions may potentially delay or even prevent needed therapies due to atypical presentations as well as greater perceived risk and/or lesser perceived benefits of invasive procedures.
In our study, we found that the prevalence of multimorbidity was high, with nearly one-third of patients having ≥2 non-cardiac comorbidities. In a large heart failure registry, Sharma et al. reported approximately 50% of patients had multimorbidity.11 By contrast, in patients with acute myocardial infarction the proportion of non-cardiac multimorbidity has varied widely from 1% to 23% depending on the population and comorbidity definitions.13, 24 Our findings are additive to these previous studies of multimorbidity by focusing on an unselected population of critically ill patients with cardiovascular disease, which may also explain differences in our comorbidity prevalence. An additional strength of our analysis is our assessment of interactions between various comorbidities. Although comparatively rare, chronic liver disease portended a particularly poor prognosis alone or in combination with any of the other comorbidities. In particular, combined chronic liver and kidney disease was associated with an especially poor prognosis (hospital mortality 24.2%).
In addition to highlighting the prevalence of compounded comorbidity in the modern CICU, we found that a greater number of non-cardiac comorbidities was associated with an increased hospital and post-discharge 1-year mortality. These findings identify a particularly vulnerable patient population, whose risk of adverse events starts during the hospitalization and persists for at least one year. This is a notable finding as non-cardiac comorbidities are a dominant driver of post-discharge outcomes. Since multimorbidity is known to increase with age,9 few studies have assessed the impact of multimorbidity in those <65 years. We found that multimorbidity in patients <65 years tended to have a greater relative impact on outcomes than in those ≥65 years. This emphasizes that the clinical implications of non-cardiac multimorbidity are not simply a function of age, but rather an accumulation of complexity and patient risk.
Potential mechanisms for the increased mortality observed in patients with higher comorbid burden include higher illness severity, the increased need for critical care therapies and more frequent non-cardiac indications for CICU admission. Patients with a greater burden of non-cardiac comorbidities were more likely to require critical care therapies, which likely reflects greater severity of illness and multi-organ dysfunction in these patients. Invasive procedures potentially expose patients to the risk of healthcare-associated infections,25 and have been associated with adverse outcomes in prior studies of CICU patients.26, 27 Similarly, admissions for infection or respiratory failure are both known to portend poorer outcomes in patients with cardiovascular disease.28–32 Furthermore, multimorbidity likely contributed to adverse outcomes through a number of additional mechanisms not adequately captured by our data, potentially including concomitant frailty, physician bias, patient goals of care, and decisions by the care team regarding which therapies to offer.8
Limitations
There are several limitations to our study, including being retrospective in nature. Our combined analysis of two geographically distant cohorts is both a strength and a weakness of this analysis. Specifically, we were able to replicate our findings regarding the associations between comorbidities and outcomes using different patient populations. While patient populations vary between hospitals, the patient mix, procedural utilization, and hospital mortality observed in our analyses were similar to a recent multi-center analysis of tertiary care CICUs.6 However, our results may not be applicable to all CICUs, particularly centers that do not provide tertiary care. In addition, our cohort notably included approximately 90% white patients, which may not be representative of other centers. Despite attempting to match non-cardiac comorbidity definitions as accurately as possible, the different methods of comorbidity ascertainment could have influenced the results. We were also unable to assess for each comorbidity’s level of severity or control of each individual comorbidity, both of which are important factors that may influence prognosis. Despite this, the proportions of individual non-cardiac comorbidities were very similar between cohorts. We do not have access to all non-cardiac comorbidities that are known to influence outcomes in patients with cardiovascular disease, such as anemia or depression. Due to different availability of risk score data, we could not adjust our analyses for severity of illness, a relevant potential confounder. Finally, we do not have data on cause of death, medication usage, or care preferences such as “Do-Not-Resuscitate” orders which could have differed based on multimorbidity and affected our outcomes.
Conclusions
Non-cardiac multimorbidity is highly prevalent in patients admitted to tertiary-care CICUs and is strongly associated with mortality, both during the hospitalization and up to 1-year following discharge. Our findings highlight the persistent hazard faced by patients with greater comorbidity, who may survive hospitalization yet remain at substantial risk in the post-hospitalization period. An increasing burden of non-cardiac comorbidities was associated with more “non-traditional” etiologies for CICU admission and more non-cardiac critical care therapies. These findings have important clinical implications as they may represent one mechanism that is driving the increasing complexity in the modern CICU, and emphasize the need for team-based, multidisciplinary approach. Our findings may also identify areas of educational need for clinicians providing acute cardiovascular care, who may need to manage a number of acute and chronic non-cardiac medical problems in the CICU. Future studies are needed to assist clinicians in medical decision-making for CICU patients with non-cardiac multimorbidity, and help determine the risk/benefit profile of common therapies in this understudied population.
Supplementary Material
Clinical Significance.
The prevalence of non-cardiac multimorbidity in the CICU is high, with more than 30% of patients having ≥2 and 11% with ≥3 non-cardiac comorbidities.
Increasing non-cardiac comorbidities are associated with a substantially increased risk of hospital and post-discharge 1-year mortality.
Patient complexity in the CICU due to non-cardiac multimorbidity highlights the need for team-based, multidisciplinary care as well as educational areas of need for clinicians providing acute cardiovascular care.
Funding: Source of Funding:
Dr. Miller reports funding through by the Yale National Clinician Scholars Program and by CTSA Grant Number TL1 TR001864 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.
Footnotes
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Disclosures: None
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