Acute, Severe Noncardiac Conditions in Patients with Acute Myocardial Infarction

Article Outline

• Abstract
• Methods
• Variables
  • Life-Threatening and Severe Noncardiac and Cardiac Conditions at Presentation
  • Statistical Analyses
• Results
• Discussion
• References
• Copyright

Abstract 

Purpose

The study’s purpose was to determine the prevalence and prognostic importance of acute, severe, noncardiac conditions present at the time of an acute myocardial infarction (AMI).

Methods

We identified consecutive patients with AMI who were discharged from Yale-New Haven Hospital between January 1, 1997, and June 30, 2000. Acute, noncardiac conditions that were present at admission were abstracted from patient records and graded by severity (imminent threat to life; other significant condition that would warrant admission). We examined the prognostic importance of these conditions on hospital mortality in multivariable logistic models. The study included 1145 patients with AMI, of whom 8.5% (n=97) presented with an acute, life-threatening, noncardiac condition at admission and 19.5% (n=223) presented with another significant noncardiac condition.

Results

Hospital mortality was 25.8% and 9.0%, respectively, for patients who presented with life-threatening and other significant noncardiac conditions, compared with 4.6% for patients without either of these conditions. In multivariable analysis, life-threatening noncardiac conditions were associated with increased hospital mortality after adjusting for demographic factors, medical history, clinical presentation, cardiac severity, and initial therapy (odds ratio 2.5; 95% confidence interval [CI], 1.2-5.2). No increased hospital mortality risk was found for other significant noncardiac conditions in the risk-adjusted analyses (odds ratio 1.0; 95% CI, 0.5-1.7).

Conclusions

A subgroup of patients with AMI presented with a life-threatening noncardiac condition, which was associated with a marked increase in the risk of death during the hospitalization. Despite the excessive mortality risk associated with concomitant noncardiac conditions, this subset of patients with AMI are poorly described in current literature.

Keywords: Acute myocardial infarction, Mortality, Risk factors

Although research, guidelines, and textbooks commonly consider acute myocardial infarction (AMI) in isolation, it often occurs concomitantly with other acute conditions. Many studies have extensively documented the importance of chronic comorbidity in prognosis,¹, ², ³, ⁴, ⁵, ⁶ but studies have not addressed patients who present with an AMI and also have a severe, coexisting clinical condition that would merit admission in its own right. There is a need for information about how often these patients present, what conditions they have, how they are treated, and their outcomes.

Accordingly, we conducted a retrospective study of patients presenting to the hospital with an AMI to determine the prevalence of acute, concomitant, noncardiac conditions. Specifically, we identified acute, noncardiac conditions present at admission and graded them in terms of their severity (acute, life-threatening conditions that posed an imminent risk of death; significant though not life-threatening noncardiac conditions that would warrant admission) to carefully examine the prognostic importance of each classification of conditions on hospital mortality. We hypothesize that acute concomitant conditions are present among a substantial subset of patients with AMI; however, the gradient of severity is a more important prognostic factor than the presence of an acute, noncardiac condition at the time of admission. Furthermore, we anticipate that the most severe conditions, although less common among patients with AMI, actually account for a disproportionate percentage of hospital deaths. The recognition of these complex patients as an important subgroup of patients with AMI may lead to new approaches to their care.

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Methods 

We identified consecutive patients with AMI who were discharged from Yale New Haven Hospital between January 1997 and June 2000 from our local National Registry of Myocardial Infarction (NRMI) database. The NRMI is a voluntary registry of cross-sectional data on hospitalized patients to identify those with a confirmed AMI (CK or CK-MB ≥ twice the upper limit of normal; electrocardiogram evidence of AMI; alternative biomarker, scintigraphic, echocardiographic, or autopsy evidence indicative of AMI). We excluded patients who were transferred into the hospital or did not have their AMI diagnosed within 48 hours after admission. The institutional review board of the Yale University School of Medicine approved the study.

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Variables 

Life-Threatening and Severe Noncardiac and Cardiac Conditions at Presentation 

We characterized the presentation of active, acute, noncardiac conditions at admission to the hospital. Clinical information was abstracted from hospital discharge summaries by reviewers who were blinded to physician identifiers. They used a standardized data entry form to collect detailed clinical information that was used to categorize the severity of these noncardiac events as life threatening (immediate threat to life) or severe (demanded urgent treatment, but not immediately life threatening). Life-threatening and other significant noncardiac conditions are listed in Table 1. We also identified acute, life-threatening cardiac conditions at admission. These conditions included cardiogenic shock, heart failure requiring intubation, tamponade, myocardial rupture (within 2 days of admission), cardiac arrest (within 2 days of admission), and VT/VF resuscitation (within 2 days of admission). These acute, cardiac conditions were included in risk-adjusted analyses.

Table 1. Life-threatening and Other Significant Noncardiac Conditions at Presentation

	N	(%)
Life-threatening conditions at admission⁎	97	8.5
Active bleeding (not associated with therapy)	25	2.2
Pneumonia (requiring intubation)	17	1.5
Major stroke	14	1.2
Exacerbated COPD (requiring intubation)	11	1.0
Cancer (end-stage/metastatic)	10	0.9
Coma	5	0.4
Septic shock	8	0.7
Acute renal failure requiring dialysis	7	0.6
Ischemic bowel	2	0.2
Intracerebral hemorrhage	1	0.1
Pneumothorax (tension)	0	0.0
Abdominal aortic aneurysm rupture	0	0.0
Acute psychosis	1	0.1
Hepatic failure	0	0.0
Major trauma	0	0.0
Other significant conditions at admission⁎	223	19.5
Pneumonia	65	5.7
Delirium/disorientation/confusion	68	5.9
Acute renal failure without dialysis	45	3.9
Metabolic derangements	41	3.6
GI bleed (not requiring transfusion)	26	2.3
COPD (exacerbated without intubation)	15	1.3
Cancer (active, non–end-stage)	9	0.8
Transient ischemic attack/minor stroke	6	0.5
Decubitus ulcer	6	0.5
Pneumothorax (not tension)	0	0.0
Hepatitis	0	0.0

COPD = Chronic obstructive pulmonary disease; GI = gastrointestinal.

To assess the accuracy of data abstracted from discharge summaries, we conducted a full medical record review for a small subset of the study sample (N=19). Agreement between discharge summary and full medical record review was consistently high for each of the acute presentation categories: life-threatening cardiac (agreement for 18/19), life-threatening noncardiac (18/19), severe cardiac (17/19,) and severe noncardiac conditions (17/19).

We obtained additional patient characteristics including demographic, medical history (Table 2), and clinical presentation factors (Table 3) from the NRMI database. In-hospital treatments and procedures during admission are detailed in Table 4, while in-hospital events are in Table 5. The primary outcome variable was hospital mortality defined as the proportion of study participants who died during the hospitalization.

Table 2. Baseline Demographic and Clinical History by Acute, Noncardiac Condition at Hospital Presentation

Characteristic	Life-threatening NonncardiacConditions (N=97)	Other Significant Noncardiac Conditions (N=223)	Neither (N=825)	P value
Age (mean)	74.8±10.7	73.5±14.2	65.7±14.3	<.001
Female (%)	46.4	46.6	38.8	.06
Non-white race (%)	20.6	17.5	17.2	.71
Medical history
Myocardial infarction (%)	37.1	35.9	31.3	.27
Angina (%)	50.5	48.9	52.0	.70
Heart failure (%)	21.7	30.9	13.7	<.001
CABG (%)	16.5	12.6	12.6	.55
PCI (%)	7.2	7.2	14.7	.003
Stroke (%)	17.5	17.5	8.5	<.001
Diabetes (%)	41.2	41.3	30.6	.003
Hypertension (%)	63.9	65.9	65.5	.94
Current smoking (%)	14.4	16.6	23.5	.018
Hypercholesterolemia (%)	18.6	26.5	47.4	<.001

CABG = coronary artery bypass graft surgery; PCI = percutaneous coronary intervention.

Table 3. Clinical Presentation by Acute, Noncardiac Condition at Hospital Presentation

Characteristic	Life-threatening Noncardiac Conditions (N=97)	Other Significant Noncardiac Conditions (N=223)	Neither (N=825)	P value
Diagnosis on admission
Myocardial infarction (%)	25.0	29.4	49.9	<.001
Rule out myocardial infarction (%)	8.3	16.3	16.2
Unstable angina (%)	2.1	3.6	20.9
Other (%)	64.6	50.7	12.9
Clinical characteristics on admission
Chest pain present (%)	25.3	33.8	72.1	<.001
Systolic BP <100 mm Hg (%)	14.4	13.9	5.3	<.001
Pulse >100 beats/min (%)	44.3	27.4	19.4	<.001
Findings on ECG
ST elevation (%)	16.5	19.3	37.8	<.001
ST depression (%)	43.3	36.3	45.3	.06
Q-wave (%)	6.2	12.6	18.9	.001
Left bundle branch block (%)	13.4	9.4	5.1	.001
Right bundle branch block (%)	8.3	5.4	3.2	.028
Infarct location
Anterior (%)	24.7	26.5	29.6	<.001
Inferior (%)	16.5	16.1	33.6
Other (%)	58.8	57.4	36.9
Other clinical data
Ejection fraction determined (%)	30.9	32.3	27.2	.27
Ejection fraction (mean)	42.4±14.6	41.3±15.2	45.2±13.7	<.001
Time to presentation
<2 h (%)	10.3	12.1	27.3	<.001
2-6 h (%)	6.2	7.2	17.3
>6 h (%)	3.1	6.3	13.2
Unknown (%)	80.4	74.4	42.2

BP = Blood pressure; ECG = electrocardiogram.

Table 4. In-Hospital Treatment and Events by Acute, Noncardiac Condition at Hospital Presentation

ACE =Angiotensin-converting enzyme; ASA = aspirin; CABG = coronary artery bypass graft surgery; PCI = percutaneous coronary intervention.

Table 5. In-Hospital Events by Acute, Noncardiac Condition at Hospital Presentation

Characteristic	Life-threatening Noncardiac Conditions (N = 97)	Other Significant Noncardiac Conditions (N = 223)	Neither (N = 825)	P value
Angina (%)	14.4	19.7	35.2	<.001
Recurrent AMI (%)	5.2	0.9	2.9	.08
Heart failure (%)	58.8	50.2	27.9	<.001
Hypotension (%)	51.6	29.6	25.8	<.001
Shock (%)	8.3	7.6	4.7	.12
Cardiac rupture (%)	4.1	1.8	1.2	.09
V-tac/V-fib (%)	8.3	4.5	5.8	.41
Unexpected cardiac arrest (%)	7.2	0.9	0.7	<.001
Length of stay (mean days)	9.4±6.6	8.6±6.5	5.8±4.2	<.001
Hospital mortality rate (%)	25.8	9.0	4.6	<.001

AMI = Acute myocardial infarction.

Statistical Analyses 

We performed bivariate analyses to examine the relationship between the acute, noncardiac conditions and demographic and clinical factors. We used the chi-square test for categoric variables and the t test for continuous variables. To examine the association between active, noncardiac conditions and hospital mortality, we used generalized estimating equation methods. This statistical technique allowed us to control for correlations between patients treated by the same physician. The initial model examined the relationship between the active, noncardiac conditions and hospital mortality. Groups of variables were sequentially added to the model (patient demographics, clinical factors, life-threatening cardiac conditions at admission, and treatment therapies within the first 48 hours) to determine the independent association between the noncardiac conditions and outcome while controlling for these additional factors. We performed all calculations with the software program PC-SAS 8.02 (SAS Corporation, Cary, NC).

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Results 

Of the 1145 hospitalized patients with AMI in the study sample, approximately 8.5% (97/1145) presented to the hospital with an acute, life-threatening noncardiac condition, and 19.5% (223/1145) presented with another acute, significant noncardiac condition (Table 1). Patients who presented to the hospital with an acute, noncardiac condition of either severity tended to be older (P<.001) and female (P=.056) (Table 2). A greater percentage of these patients had a documented history of diabetes (P=.003) and heart failure (P<.001) than patients without these conditions.

The clinical presentation of the AMI differed for patients admitted with acute, life-threatening or other significant noncardiac conditions compared with patients who did not present with either category of these concurrent conditions (Table 3). Patients with an acute, noncardiac condition (life-threatening or severe classification) at admission were less likely to have documented chest pain present at the time of admission (P<.001) and had higher rates of hypotension (P<.001) and elevated pulse rates (P<.001) than patients without these conditions. Time from symptom onset to hospital presentation was recorded less frequently for patients with acute, noncardiac conditions, but for those with time to presentation information, patients with concurrent noncardiac conditions presented less quickly to the hospital than patients without these conditions (P<.001).

Treatment patterns varied among the groups. Patients with life-threatening or other significant acute, noncardiac conditions had lower use rates of angiotensin-converting enzyme inhibitors (P<.001; Table 4), any antiplatelet agents (P<.001), intravenous heparin (P<.001), intravenous nitroglycerin (P<.001), and any beta-blockers within the first 24 hours (P<.001). Patients with acute, noncardiac conditions had lower rates of cardiac catheterization (P<.001), percutaneous coronary intervention (P<.001), coronary artery bypass graft surgery (P=.020), and use of intra-aortic balloon pump (P=.009).

In-hospital adverse clinical events occurred more frequently for patients who presented with life-threatening or other significant noncardiac conditions at admission compared with patients who did not have these conditions (Table 4). Heart failure (P<.001), hypotension (P<.001), cardiac rupture (P=.089), and unexpected cardiac arrest (P<.001) rates were higher for patients with noncardiac conditions but were especially marked for those who presented with life-threatening noncardiac conditions (Table 5). The mean length of stay was longer for patients who presented with life-threatening noncardiac conditions compared with patients who presented with other significant noncardiac conditions, or patients without these conditions at admission (P<.001). The hospital mortality was highest for patients who presented with life-threatening noncardiac conditions (25.8%), compared with patients who presented with severe noncardiac conditions (9.0%) and with patients without these noncardiac conditions present on admission (4.6%; P<.001).

A sequence of risk-adjusted models was developed to examine the independent association of acute, noncardiac conditions at admission with hospital mortality, while controlling for demographic, clinical, and therapeutic differences among patients (Figure 1, Figure 2). In an unadjusted model, the odds of hospital mortality were more than seven times greater for patients who presented with a life-threatening noncardiac condition at admission, compared with patients who did not have any acute, noncardiac conditions (odds ratio [OR] 7.2, 95% confidence interval [CI], 4.1-12.6). The association was attenuated, but not eliminated, by the sequential inclusion of demographic characteristics (OR 5.2, CI, 2.9-9.3), medical history (OR 4.3, CI, 2.4-7.7), clinical presentation (OR 4.5, CI, 2.3-8.8), cardiac severity at admission (OR 3.0, CI, 1.5-6.3), and initial therapy (OR 2.5, CI, 1.2-5.2) variables in the model. Similarly, the unadjusted risk of hospital mortality was higher for patients who presented with other significant noncardiac conditions at admission (OR 2.1, CI, 1.2-3.6) compared with patients who did not have these conditions. However, the increased risk was not evident after sequential adjustment for the selected covariates in the model (OR 1.0, CI, 0.5-1.7).

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• Figure 1. 

  Odds ratios (ORs) for in-hospital mortality in patients with life-threatening noncardiac conditions at presentation versus those without.

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• Figure 2. 

  Odds ratios (ORs) for in-hospital mortality in patients with other significant noncardiac conditions at presentation versus those without. ASA, aspirin; BP, blood pressure; CABG, coronary artery bypass graft surgery; CHF, congestive heart failure; CI, confidence interval; IV, intravenous; LBBB, left bundle branch block; MI, myocardial infarction; RBBB, right bundle branch block; PTCA, percutaneous transluminal coronary angioplasty.

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Discussion 

Our principal finding was that approximately 30% of patients with AMI also have another acute, noncardiac condition that would warrant hospital admission. In fact, almost 1 in 12 patients with AMI presented to the hospital with an acute, life-threatening noncardiac condition, and 1 in 5 patients presented with another significant condition. When graded by the severity of conditions at admission, patients who presented with a life-threatening noncardiac condition had a crude hospital mortality rate of 25.8%, compared with 9.0% for patients with the dual presentation of another significant noncardiac condition, and 4.6% for patients with AMI without these additional concomitant conditions. Although approximately one third of patients present with an active, noncardiac condition, it is the smaller subset of patients with AMI with the most severe conditions who account for a large portion of the observed hospital mortality. Physicians treating these high-risk patients with AMI are faced with managing at least two complicated conditions, including decision-making about interventions that could help one condition while worsening another. Several recent articles have noted the limitations of disease-specific guidelines that tend to focus on a specific condition, providing little guidance for clinicians treating patients with multiple comorbid diseases.⁷, ⁸ For example, the effectiveness of multiple medications among patients with complex disease, whose response to therapies may be altered by the presence of coexisting conditions, remains largely untested in randomized, controlled trials. This extremely high-risk subset of patients with AMI has not previously been described within the larger population of patients with AMI, even though their clinical presentation and course are distinct. Despite how commonly patients with AMI present with these concomitant conditions, textbooks, guidelines, and risk models have generally not acknowledged the special considerations that the care of these patients demands.

Several decades ago the term “comorbidity” was introduced, and there was recognition that concomitant chronic conditions had an important effect on the care and outcomes of patients.⁹, ¹⁰ In studies of hospitalized patients, and in clinical trials of therapy, there is a tendency to focus on a single condition (eg, AMI) and comorbid conditions directly related to the disease (eg, heart failure). In the present study, we were interested in describing a broad range of serious, acute, noncardiac conditions that could be present at admission and potentially warrant admission independently from the AMI. The specific chronology of events within this acute phase (ie, differentiating the cause and effect of concomitant conditions during the acute presentation of the AMI) was less important than describing the prevalence, frequency, and severity of these acute, noncardiac conditions, because the clinical focus would be on treating these dual conditions during the initial hospitalization period. Our results demonstrate that these types of serious, acute, noncardiac conditions occur frequently, but it is the smaller subset of patients with AMI who present with a potentially life-threatening noncardiac condition who represent a disproportionate number of deaths. To fully characterize the condition of patients with AMI, given our findings, it is imperative to describe both the presence and severity of these other conditions.

Current studies that have examined the role of comorbid conditions on mortality outcomes among patients with AMI have not addressed the acuity or severity of the conditions described in this study. These acute, noncardiac conditions have been omitted for several potential reasons. Many have been used as exclusion criteria for clinical trials.¹, ⁴, ¹¹, ¹², ¹³, ¹⁴, ¹⁵ The exclusion of these high-risk patients with AMI has limited our understanding of the full-spectrum of acute conditions that can be present among patients with AMI, as well as their prognostic importance of predicting mortality outcomes.

The role of noncardiac conditions on mortality outcomes for patients with AMI has been described in nonclinical trial studies, including cohort studies, registries, or clinically enriched datasets. However, these studies have not described the conditions in terms of their acute presentation or severity at the time of the AMI.², ⁴, ¹¹, ¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰ Many of these data resources have the advantage of chart-abstracted data, covering a broad range of noncardiac conditions; however, results derived from these datasets have not reported the severity or presence of these conditions at the time of the hospitalization.², ³, ⁵, ⁶, ²⁰ Even studies that included disease severity summary scores such as the Charlson Comorbidity Index or Greenfield Index of Coexistent Disease have been limited by the identification of events from retrospective medical record review that cannot provide adequate detail to discriminate between acute and chronic conditions during the presentation of the AMI.², ¹⁸

Our study reports that hospital mortality is markedly increased for patients with AMI with acute, life-threatening conditions, even after adjustment for demographic, clinical, and initial therapeutic factors. These findings demonstrate the prognostic importance of these conditions. The finding that patients with severe comorbid conditions did not sustain the same elevated risk underscores the importance of considering the severity of acute, noncardiac conditions within the context of the AMI. Prognostic risk scores have been developed to aid physicians in making decisions for patients with AMI. Failure to include acute, noncardiac conditions in currently available risk-adjustment models calls into question the use of “risk-adjusted mortality” to estimate the risk of outcomes, or compare outcomes across institutions. For example, an increase in the proportion of patients with AMI with acute, noncardiac conditions at any one hospital could result in an increase in mortality that could not be “risk adjusted” using typical methods. Similarly, comparing outcomes across hospitals may be invalid if some hospitals care for a greater number of these patients than other hospitals.

There are several issues to consider in the interpretation of this study. We conducted a detailed review of discharge summaries within a single academic center. The specific prevalence of life-threatening noncardiac conditions we report may not be the same at other institutions; however, we believe the high prevalence of these conditions and independent risk on mortality is generalizable to other institutions. We validated the accuracy of data derived from discharge summaries with full medical record reviews to classify acute, life-threatening, and significant other noncardiac events at presentation to the hospital, but cannot account for conditions that were not recorded in the medical record. We believe this concern is minimal for acute, life-threatening conditions, because they were likely to be significant contributors to the hospitalization for the patient and are unlikely to go unmentioned. Because our identification of acute presentation depended on retrospective medical record review, there is the potential that complications during the hospitalization could be misinterpreted as acute events at the time of presentation. We minimized this risk by establishing clear a priori criteria for identifying events that were present at presentation to the hospital. In our efforts to avoid this potential bias, we may have underestimated the actual prevalence of acute presentation events in our study. Additional work is needed to replicate these findings in more diverse, multicenter samples.

Our findings reveal an important subgroup of patients with AMI who present with an acute, life-threatening noncardiac condition that is associated with a disproportionately high hospital mortality risk. Despite the excessive mortality risk for patients who present with competing acute conditions, they are poorly described in current literature. In fact, current guidelines do not describe this population or address the associated mortality risk, recommend treatment, or suggest strategies to balance the immediate health priorities of these patients. We found that this group differed from other patients with AMI in terms of clinical presentation, use of traditional cardiovascular therapies, and in-hospital outcomes. Current prognostic indicators do not include these patients in risk scores. Given the disproportionate mortality associated with the dual presentation of an acute AMI and a concomitant noncardiac condition, future efforts to define risk may benefit from including consideration of noncardiac life-threatening conditions.

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