JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 73, NO.

14, 2019

ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

PUBLISHED BY ELSEVIER

Acute Noncardiac Organ Failure in

Acute Myocardial Infarction With
Cardiogenic Shock
Saraschandra Vallabhajosyula, MBBS,a,b Shannon M. Dunlay, MD, MS,a,c Abhiram Prasad, MD,a
Kianoush Kashani, MD, MS,b,d Ankit Sakhuja, MBBS,e Bernard J. Gersh, MBCHB, DPHIL,a Allan S. Jaffe, MD,a
David R. Holmes, JR, MD,a Gregory W. Barsness, MDa

ABSTRACT

BACKGROUND There are limited data on acute noncardiac multiorgan failure in cardiogenic shock complicating acute
myocardial infarction (AMI-CS).

OBJECTIVES The authors sought to evaluate the 15-year national trends, resource utilization, and outcomes of single
and multiple noncardiac organ failures in AMI-CS.

METHODS This was a retrospective cohort study of AMI-CS using the National Inpatient Sample database from 2000 to
2014. Previously validated codes for respiratory, renal, hepatic, hematologic, and neurological failure were used to
identify single or multiorgan ($2 organ systems) noncardiac organ failure. Outcomes of interest were in-hospital
mortality, temporal trends, and resource utilization. The effects of every additional organ failure on in-hospital mortality
and resource utilization were assessed.

RESULTS In 444,253 AMI-CS admissions, noncardiac single or multiorgan failure was noted in 32.4% and 31.9%,
respectively. Multiorgan failure was seen more commonly in admissions with non–ST-segment elevation AMI-CS,
nonwhite race, and higher baseline comorbidity. There was a steady increase in the prevalence of single and multiorgan
failure. Coronary angiography and revascularization were performed less commonly in multiorgan failure. Single-organ
failure (odds ratio: 1.28; 95% confidence interval: 1.26 to 1.30) and multiorgan failure (odds ratio: 2.23; 95% confidence
interval: 2.19 to 2.27) were independently associated with higher in-hospital mortality, greater resource utilization, and
fewer discharges to home. There was a stepwise increase in in-hospital mortality and resource utilization with each
additional organ failure.

CONCLUSIONS There has been a steady increase in the prevalence of multiorgan failure in AMI-CS. Presence
of multiorgan failure was independently associated with higher in-hospital mortality and greater resource utilization.
(J Am Coll Cardiol 2019;73:1781–91) © 2019 by the American College of Cardiology Foundation.

C ardiogenic shock (CS) is defined as a low car-

diac output state due to cardiac dysfunction
that is associated with end-organ hypoper-
fusion (1). CS complicating acute myocardial infarc-
tion (AMI-CS) accounts for nearly 80% of all CS in
developed nations and continues to be associated
with high mortality and morbidity (2). In the contem-
porary era, AMI-CS is still associated with a high in-
hospital mortality of nearly 30% to 45% despite early
revascularization with percutaneous coronary inter-
ventions (PCIs) (3,4). Although the overall mortality
from AMI-CS is lower compared with the early

Listen to this manuscript’s

audio summary by
Editor-in-Chief
Dr. Valentin Fuster on
JACC.org.
From the aDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota; bDivision of Pulmonary and Critical Care
Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota; cDepartment of Health Science Research, Robert D. and
Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota; dDivision of Nephrology and
Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota; and the eDivision of Cardiovascular Critical Care,
Department of Cardiovascular and Thoracic Surgery, West Virginia University School of Medicine, Morgantown, West Virginia. Dr.
Jaffe has been a consultant for Beckman, Abbott, Siemens, ET Healthcare, Sphing6toec, Quidel, and Novartis. All other authors
have reported that they have no relationships relevant to the contents of this paper to disclose.

Manuscript received November 17, 2018; revised manuscript received January 3, 2019, accepted January 8, 2019.

ISSN 0735-1097/$36.00 https://doi.org/10.1016/j.jacc.2019.01.053

1782 Vallabhajosyula et al. JACC VOL. 73, NO. 14, 2019

Acute Organ Failure in AMI With Cardiogenic Shock APRIL 16, 2019:1781–91

ABBREVIATIONS 2000s, it has remained relatively stable in patient demographics, primary payer, hospital char-
AND ACRONYMS the last decade (5–7). Despite shorter door- acteristics, principal diagnosis, up to 24 secondary
to-balloon times and greater use of coronary diagnoses, and procedural diagnoses.
AMI = acute myocardial
infarction
angiography and PCI in recent years, there STUDY POPULATION, VARIABLES, AND OUTCOMES.
appears to be minimal incremental mortality Using the HCUP-NIS data from 2000 to 2014, a retro-
CI = confidence interval
benefit in this population (6). It is, therefore, spective cohort study of admissions with AMI-CS
CS = cardiogenic shock
likely that the post-catheterization hospital were identified. AMI in the primary diagnosis field
HCUP = Healthcare Cost and
Utilization Project
course, including persistent shock and the was identified using International Classification of
development of organ failure, play a signifi- Diseases-9th Revision-Clinical Modification (ICD-9-
ICD-9-CM = International
Classification of Diseases-9th cant role in the outcomes of this population. CM) codes for ST-segment elevation myocardial
Revision-Clinical Modification Furthermore, a “hemometabolic” model for infarction (ICD-9-CM 410.1x-410.6x, 410.8x, 410.9x)
MCS = mechanical circulatory the evolution of AMI-CS has been proposed and non–ST-segment elevation myocardial infarction
support
wherein the initial hemodynamic insult sub- (ICD-9-CM 410.70-410.79) (16). CS was identified
NIS = National/Nationwide sequently evolves into a metabolic insult
Inpatient Sample
using ICD-9-CM code 785.51, which was defined in the
resulting in persistent hypoperfusion and ICD-9-CM as shock resulting from diminution of
OR = odds ratio
multiorgan failure (8). cardiac output in heart disease, shock resulting from
PCI = percutaneous coronary
intervention SEE PAGE 1792 primary failure of the heart in its pumping function,
SOFA = Sequential Organ
as in myocardial infarction, severe cardiomyopathy,
Multiorgan failure has been recognized to
Failure Assessment or mechanical obstruction or compression of the heart
be closely associated with morbidity and
or shock resulting from the failure of the heart to
mortality in unselected medical intensive care unit
maintain adequate output. Validation studies have
and cardiac intensive care unit patients (9,10). The
shown a specificity of 99.3%, a sensitivity of 59.8%, a
Sequential Organ Failure Assessment (SOFA) score
positive predictive value of 78.8%, and a negative
quantifies organ failure in the cardiovascular, neuro-
predictive value of 98.1% for the ICD-9-CM code
logical, respiratory, renal, hepatic, and hematologic
785.51 to identify CS (17). Although the current risk-
domains. Organ failure has shown robust prognostic
scoring systems (including the SOFA score) are well-
implications, resulting in the incorporation of the
validated, they often need detailed physiological
SOFA score into the recent Sepsis-3 criteria for
data that are not available in administrative datasets.
defining septic shock (11,12). It is conceivable that
As an alternative, acute noncardiac organ failure,
independent of the inciting insult, all shock states,
classified into respiratory, renal, hepatic, hemato-
including AMI-CS, progress down the final common
logic, and neurological categories, using validated
pathway of multiorgan failure in patients who die (1).
administrative coding definitions was used in this
Despite prior data demonstrating an increase in acu-
study (Table 1) (18–20). This coding has been previ-
ity of cardiac intensive care unit admissions, there are
ously validated in patients with severe sepsis and
limited data on the burden of multiorgan failure in
septic shock, and has demonstrated a positive pre-
AMI-CS in modern practice (10,13,14).
dictive value of 71%, negative predictive value of
Using a large, nationally representative database,
92%, sensitivity of 50%, and specificity of 96% in
we sought to assess 15-year national trends in multi-
identifying multiorgan failure (21). Noncardiac mul-
organ failure in AMI-CS. We hypothesized that pa-
tiorgan failure was defined as the involvement of $2
tients with AMI-CS have evolved into a more complex
organ systems in addition to cardiovascular
population with greater organ failure and that mul-
dysfunction (present in all admissions due to having
tiorgan failure would be associated with higher in-
CS) using the administrative codes listed in Table 1
hospital mortality.
(9). Prior end-stage renal disease and hemodialysis
METHODS use was excluded in the evaluation of acute kidney
injury. Use of noninvasive ventilation without a
STUDY DATABASE. The National (Nationwide) Inpa- concomitant diagnosis of acute respiratory failure
tient Sample (NIS) is the largest all-payer database of was excluded because this could potentially repre-
hospital inpatient stays in the United States. The NIS sent their use for sleep disorder breathing. De-
contains discharge data from a 20% stratified sample mographic characteristics (age, sex, and race),
of community hospitals and is a part of the Healthcare hospital characteristics (teaching status and location,
Cost and Utilization Project (HCUP), sponsored by the bed size, and region), and primary payer associated
Agency for Healthcare Research and Quality (15). with each discharge were identified from the HCUP-
Information regarding each discharge includes NIS database. The Deyo’s modification of Charlson
JACC VOL. 73, NO. 14, 2019 Vallabhajosyula et al. 1783
APRIL 16, 2019:1781–91 Acute Organ Failure in AMI With Cardiogenic Shock

Comorbidity Index was used to identify the burden of

T A B L E 1 Administrative Codes Used in the Identification of Acute Noncardiac
comorbid diseases (22). Diagnostic coronary angiog- Organ Failure
raphy, PCI, use of mechanical circulatory support
Organ Failure ICD-9-CM Code Description
(MCS), noninvasive and invasive mechanical venti-
Respiratory
lation, and hemodialysis were identified for all ad-
518.81 Acute respiratory failure.
missions (Online Table 1) (6,23).
518.82 Other pulmonary insufficiency, not
The primary outcome was in-hospital mortality elsewhere classified. Includes acute
respiratory distress, acute respiratory
stratified by no organ failure, single-organ failure,
insufficiency, adult respiratory distress
and multiorgan failure in the noncardiac organ sys- syndrome NEC.
tems. Secondary outcomes included the prevalence, 518.85 Acute respiratory distress syndrome after
shock or trauma.
trends, length of stay, costs, and discharge disposi-
786.09 Respiratory distress NOS.
tion in admissions with single and multiorgan failure 799.1 Respiratory arrest.
in AMI-CS compared with patients without noncar- 96.7, 96.70, 96.71, 96.72 Ventilator management.
diac organ failure. Renal
584, 584.5, 584.6, 584.7, Acute kidney injury.
STATISTICAL ANALYSIS. As recommended by HCUP-
584.8, 584.9
NIS, survey procedures using discharge weights pro- Hepatic
vided with HCUP-NIS database were used to generate 570 Acute hepatic failure or necrosis.
national estimates. Trend weights provided by the 572.2 Hepatic encephalopathy.
HCUP-NIS were used to reweight the data to adjust 573.3 Hepatitis unspecified.

for the 2012 HCUP-NIS redesign (24). One-way anal- 573.4 Hepatic infarction.
Hematologic
ysis of variance and Student’s t-tests were used to
286.6 Defibrination syndrome.
compare categorical and continuous variables
286.7 Acquired coagulation factor deficiency.
respectively. The inherent restrictions of the HCUP-
286.9 Other coagulation defect.
NIS database related to research design, data inter- 287.4, 287.5 Thrombocytopenia—secondary or
pretation, and data analysis were reviewed and unspecified.

addressed (24). Unadjusted and adjusted temporal Neurological

293, 293.0, 293.1, 293.8, Transient organic psychotic conditions.
trends of noncardiac acute organ failure and in- 293.81, 293.82, 293.83, 293.84,
hospital mortality stratified by organ failure were 293.89, 293.9
performed. Adjusted temporal trends were calculated 348.1 Anoxic brain injury.

using multivariable hierarchical logistic regression 348.3, 348.30, 348.31, 348.39 Acute encephalopathy.
780.01 Coma.
analysis incorporating age, sex, and comorbidity
780.09 Altered consciousness—unspecified.
(referent year 2000) and presented as odds ratio (OR)
89.14 Electroencephalogram.
with 95% confidence interval (CI) for each year in
comparison to year 2000. For in-hospital mortality, ICD-9-CM ¼ International Classification of Diseases-9th Revision-Clinical Modification; NEC ¼ not elsewhere
classified; NOS ¼ not otherwise specified.
unadjusted and subsequent adjusted analyses were
performed. For the adjusted analysis, a multivariable
hierarchical logistic regression analysis incorporating
to assess for incremental contribution to in-hospital
age, sex, race, admission year, primary payer status,
mortality. Additional analyses were performed for
socioeconomic stratum, hospital characteristics,
temporal trends and unadjusted and adjusted in-
comorbidities, and cardiac procedures was per-
hospital mortality in AMI-CS after excluding
formed. For the multivariable modeling, purposeful
concomitant cardiac arrest. Given the large sample
selection of statistically (p < 0.20) and a priori–selected,
size, all p values are highly significant (i.e., <0.001)
clinically relevant variables was conducted. Multiple
unless otherwise specified. All statistical analyses
additional sensitivity analyses were performed to
were performed using SPSS version 25.0 software
confirm the primary results. To account for the
(IBM Corp., Armonk New York).
nonlinear relationship of age and year of admission
with in-hospital mortality, a supplemental analysis RESULTS
using restricted cubic spline transformations using 5
knots was performed. An a priori–unadjusted and During the period between January 1, 2000, and
adjusted analysis was performed for each additional December 31, 2014, there were w9 million admissions
acute organ failure (numerical number of failed organ with a primary diagnosis of AMI, of which 444,253
systems) and type of organ system failed (i.e., respi- admissions (4.6%) were complicated by CS. Acute
ratory, renal, hepatic, hematologic, and neurological) noncardiac organ failure was noted in 285,761
1784 Vallabhajosyula et al. JACC VOL. 73, NO. 14, 2019

Acute Organ Failure in AMI With Cardiogenic Shock APRIL 16, 2019:1781–91

admissions (64.3%), with multiorgan failure ($2 or-

T A B L E 2 Baseline Characteristics of AMI-CS Stratified by Acute Noncardiac Organ Failure
gan systems) noted in 141,634 admissions (31.9%).
No Organ Failure Single Organ Failure Multiorgan Failure Baseline characteristics of the cohorts with no organ
(n ¼ 158,492) (n ¼ 144,127) (n ¼ 141,634)
failure, single or multiorgan failure are detailed in
AMI type
Table 2. Noncardiac multiorgan failure was seen more
ST-segment elevation AMI 74.8 65.3 63.3
Non–ST-segment elevation AMI 25.2 34.7 36.7 commonly in admissions with non–ST-segment
Age, yrs 68.5  13.7 70.0  12.9 69.1  12.6 elevation–related AMI-CS, nonwhite race, and higher
Female 41.0 41.0 35.2 baseline comorbidity even after adjusting for age and
Race sex. There was a steady increase in multiorgan failure
White 63.4 63.3 62.6 during the study period (15.7% in 2000 to 45.5% in
Black 4.7 5.8 6.8
2014) with a concomitant decline in admissions with
Hispanic 5.4 6.4 7.2
no organ failure or single-organ failure (Figure 1A).
Asian 2.1 2.3 2.9
Native American 0.4 0.5 0.5
There was a steady increase in organ failure rates in
Other 2.9 3.0 3.7 each of the 5 individual organ systems during this
Missing 21.0 18.8 16.2 study period (Figure 1B). Temporal trends adjusted for
Weekend admission 26.6 27.0 27.3 age, sex, and baseline comorbidity showed a modest
Primary payer decrease in single-organ failure with a 4.3-fold higher
Medicare 58.9 64.3 61.7
multiorgan failure in 2014 compared with the referent
Medicaid 5.8 6.2 7.0
year 2000 (Figure 1C). Failure of the respiratory
Private 26.6 22.1 23.2
(43.4%) and renal (35.2%) systems were the most
Uninsured 5.6 4.6 5.1
No charge 0.4 0.4 0.5 commonly noted in this population of AMI-CS. The
Others 2.6 2.4 2.5 increase in multiorgan failure was consistent across
Quartile of median household subgroups stratified by age, sex, and type of AMI
income for zip code
(Online Figure 1). Overall, male sex and nonwhite
0–25th 22.1 23.1 24.7
race admissions were associated with greater multi-
26th–50th 26.9 26.6 26.2
51st–75th 25.2 24.8 24.8
organ failure compared with female sex and white
75th–100th 25.7 25.6 24.3 race (Table 2).
Hospital teaching status and Admissions with organ failure had higher rates of
location cardiac arrest and greater use of invasive hemody-
Rural 10.5 7.1 4.5
namic monitoring and MCS devices (Table 3). Use of
Urban nonteaching 41.8 40.6 39.4
percutaneous MCS and extracorporeal membrane
Urban teaching 47.7 52.4 56.0
Hospital bed size
oxygenation was noted more commonly in admis-
Small 8.4 7.8 7.1 sions with multiorgan failure (Table 3). However,
Medium 22.8 22.0 21.6 coronary angiography and PCI were performed less
Large 68.8 70.2 71.3 frequently in patients with organ failure (Table 3).
Hospital region Despite a steady increase in coronary angiography
Northeast 19.4 19.6 16.5
and PCI use in AMI-CS during the study period,
Midwest 23.1 22.3 23.2
overall rates remained lower in admissions with sin-
South 37.9 38.6 38.4
gle or multiorgan failure (Online Figure 2). In an
West 19.6 19.4 21.9
Charlson Comorbidity Index adjusted analysis incorporating age, sex, race, pri-
0–3 31.1 20.5 20.5 mary payer, socioeconomic status, baseline comor-
4–6 54.0 57.6 54.9 bidity, year of admission, and hospital characteristics,
$7 14.9 21.9 24.6 presence of single-organ failure and multiorgan fail-
Comorbidities ure were independently associated with lower use of
Hypertension 49.9 50.7 50.2
coronary angiography (OR: 0.79; 95% CI: 0.78 to 0.81
Hyperlipidemia 36.0 30.0 28.8
and OR: 0.68; 95% CI: 0.67 to 0.70, respectively) and
Chronic kidney disease 6.7 13.9 20.4
Heart failure 44.9 61.5 61.4
PCI (OR: 0.72; 95% CI: 0.71 to 0.74 and OR: 0.69; 95%
Cancer 7.3 7.0 6.0 CI: 0.68 to 0.71, respectively).

IN-HOSPITAL MORTALITY AND RESOURCE

Values are % or mean  SD. All comparisons were made using 1-way analysis of variance.
AMI ¼ acute myocardial infarction; CS ¼ cardiogenic shock.
UTILIZATION IN AMI-CS. Compared with the cohort
with no organ failure, the primary outcome of
JACC VOL. 73, NO. 14, 2019 Vallabhajosyula et al. 1785
APRIL 16, 2019:1781–91 Acute Organ Failure in AMI With Cardiogenic Shock

F I G U R E 1 Temporal Trends of Acute Noncardiac Organ Failure in AMI-CS

A B
60% 60%
Percentage of Hospital Admissions

Percentage of Hospital Admissions

50% 50%

40% 40%

30% 30%

20% 20%

10% 10%

0% 0%
00

20 1
02

20 3
04

20 5
06

20 7
08
09
10

11
12
13
14

00

20 1
02

20 3
04

20 5
06

20 7
08
09
10
11
12
13
14
0

0
0

0
0

0
0

0
20

20
20

20
20

20
20

20
20

20

20

20
20

20
20

20
20

20
20

20
20

20
No Organ Failure Single Organ Failure
Respiratory Renal Hepatic
Multiorgan Failure
Hematologic Neurologic

C 5.0
4.26
4.5 3.95 3.94
3.71
4.0
Adjusted Odds Ratio

3.31
3.5 3.17

3.0 2.56
2.5 2.15
1.86 1.97
2.0
1.53 1.52 1.61
1.5 1.24
1.00
1.0
1.00 0.97 1.00 1.01 1.05 1.00 1.00 0.92 0.96
0.88 0.86 0.79 0.78 0.80 0.77
0.5
0.0
00

20 1
02
03
04
05
06
07
08
09
10
11
12
13
14
0

20

20
20

20
20

20
20
20

20
20

20

20
20
20

Single Organ Failure Multiorgan Failure

(A) Fifteen-year unadjusted temporal trends of no organ failure, single organ failure, and multiorgan failure; (B) 15-year temporal trends of individual organ system
failure; and (C) age-adjusted, sex-adjusted, and comorbidity-adjusted temporal trends of single and multiorgan failure. AMI ¼ acute myocardial infarction;
CS ¼ cardiogenic shock.

in-hospital mortality was higher in the cohort with nursing facilities as compared with 31% of patients
single (37.6% vs. 30.7%; OR: 1.36; 95% CI: 1.34 to with single-organ failure and 17% of patients without
1.38) and multiorgan failure (48.1% vs. 30.7%; additional organ failure (Table 4). In a multivariate
OR: 2.09; 95% CI: 2.06 to 2.12) (Table 4). Trends of analysis, single (OR: 1.28; 95% CI: 1.26 to 1.30) and
in-hospital mortality for the overall population and multiorgan failure (OR: 2.23; 95% CI: 2.19 to 2.27)
the organ failure cohorts are presented in Figure 2. were independently associated with higher in-
Increasing organ failure was associated with longer hospital mortality in AMI-CS (Online Table 2). This
lengths of stay, higher hospitalization costs, and association remained unchanged in a supplemental
fewer discharges to home (Table 4). Median hospital analysis using restricted cubic spline transformations
length of stay varied between 9 and 11 days, without of age and year of admission using 5 knots to
a clinically significant trend over the 15-year period model the nonlinear relationship with in-hospital
(Online Figure 3). Notably, nearly 45% of admissions mortality (Online Table 3). In a multivariable anal-
with multiorgan failure were dismissed to skilled ysis for in-hospital mortality, adjusted odds ratios
1786 Vallabhajosyula et al. JACC VOL. 73, NO. 14, 2019

Acute Organ Failure in AMI With Cardiogenic Shock APRIL 16, 2019:1781–91

DISCUSSION
T A B L E 3 In-Hospital Course of AMI-CS Stratified by Acute Noncardiac Organ Failure

No Organ Failure Single Organ Failure Multiorgan Failure In this nationally representative population of
(n ¼ 158,492) (n ¼ 144,127) (n ¼ 141,634)
AMI-CS, we noted a 2.9-fold increase in the preva-
Cardiac arrest 11.2 16.6 27.2
lence of noncardiac multiorgan failure between 2000
Coronary angiography 70.2 66.0 66.9
Percutaneous coronary 51.6 43.7 46.1 and 2014 (Central Illustration). Multiorgan failure was
intervention seen more commonly in admissions with non–ST-
Invasive hemodynamic 15.8 21.2 23.3 segment elevation AMI-CS, nonwhite race, and male
assessment*
MCS
sex. The population with multiorgan failure consis-
Total 42.7 44.1 48.7 tently received less frequent coronary angiography
Intra-aortic balloon pump 42.0 43.1 46.4 and PCI despite steady increases in the overall use of
Percutaneous MCS 0.6 1.0 2.5 these procedures during the study period. Single-
Nonpercutaneous MCS 0.3 0.5 0.7 organ failure and multiorgan failure were associated
Extracorporeal membrane 0.2 0.3 1.1
with 1.3- and 2.2-times higher in-hospital mortality
oxygenation
compared with admissions without any organ failure.
Values are %. All comparisons were made using 1-way analysis of variance. *Right heart catheterization or Each additional organ system involvement contrib-
pulmonary artery catheterization.
AMI-CS ¼ acute myocardial infarction with cardiogenic shock; MCS ¼ mechanical circulatory support.
uted to a serial increase in in-hospital mortality and
higher resource utilization.
In patients with AMI-CS, early revascularization
still remains the cornerstone of improving outcomes
for individual organ system failure were as follows:
(2). Early revascularization aids in restoration of
respiratory OR: 1.67 (95% CI: 1.64 to 1.69), renal OR:
normal macrovascular hemodynamics such as blood
1.69 (95% CI: 1.66 to 1.72), hepatic OR: 1.98 (95% CI:
pressure, heart rate, and cardiac index. However,
1.94 to 2.04), hematologic OR: 0.98 (95% CI: 0.96 to
nearly 45% of patients with CS die despite a normal
1.01), and neurological OR: 1.94 (95% CI: 1.90 to
cardiac index, leading to the current thought about
1.99). Each additional organ system failure was
the role of microvascular dysfunction in these pa-
associated with a stepwise increase in the unad-
tients (25,26). Furthermore, inflammatory bio-
justed and adjusted odds of in-hospital mortality as
markers, typically noted in septic shock, have shown
compared with no organ failure (Figure 3). Each
a strong correlation with clinical outcomes in CS (27).
additional failed organ was also associated with a
Acute organ failure in AMI-CS is hypothesized to be
stepwise increase in hospital length of stay, hospi-
due to systemic inflammation and microcirculatory
talization costs, and discharges to care facilities
abnormalities in addition to primary pump failure
(Online Table 4). Additional sensitivity analysis
(1,14,26). Older risk-stratification models in AMI-CS
performed by excluding patients with cardiac arrest
focused primarily on angiographic and hemody-
did not influence the temporal trends or unadjusted
namic parameters (28,29), but more recent models
and adjusted in-hospital mortality during the study
incorporate end-organ assessment into mortality
period (Online Figure 4).
prediction (30,31). Though these scoring systems
incorporate end-organ hypoperfusion based on labo-
T A B L E 4 Clinical Outcomes of AMI-CS Stratified by Acute Noncardiac Organ Failure ratory parameters (lactate, creatinine, etc.), there are
limited assessments of holistic organ system evalua-
No Organ Failure Single Organ Failure Multiorgan Failure
(n ¼ 158,492) (n ¼ 144,127) (n ¼ 141,634) tion. Other investigators have looked at the role of
In-hospital mortality 30.7 37.6 48.1 renal failure, altered mental status, and respiratory
Median length of stay, days 7.1  7.9 10.5  11.7 12.9  10.1 failure in CS and noted worse outcomes with these
Median hospitalization 80,346  91,131 120,173  134,158 183,767  205,582 individual organ failures (32–34). As demonstrated in
costs, U.S.$
this study, we noted an incremental trend in
Discharge disposition
in-hospital mortality with every additional organ
Home 56.3 38.0 26.6
Hospital transfer 11.5 12.1 10.7 system failure. Prior work on multiorgan failure
Skilled nursing facility 17.0 30.9 44.8 assessment has been limited to small single-center
Home with home health care 14.7 18.3 17.1 studies. In 44 patients with AMI-CS, Kellner et al.
Against medical advice 0.4 0.4 0.4 (14) demonstrated established organ failure scores,
including the SOFA score, to prognosticate in-
Values are % or mean  SD. All comparisons were made using 1-way analysis of variance.
AMI-CS ¼ acute myocardial infarction with cardiogenic shock.
hospital mortality accurately. In a population of 68
AMI-CS patients, den Uil et al. (26) demonstrated that
JACC VOL. 73, NO. 14, 2019 Vallabhajosyula et al. 1787
APRIL 16, 2019:1781–91 Acute Organ Failure in AMI With Cardiogenic Shock

F I G U R E 2 15-Year Temporal Trends of In-Hospital Mortality Stratified by Acute Noncardiac Organ Failure in AMI-CS

70%

60%

50%
In-Hospital Mortality

40%

30%

20%

10%

0%
00

01

02

03

04

05

06

07

08

09

10

11

12

13

14
20

20
20

20
20

20
20
20
20

20
20

20

20
20
20

Overall No Organ Failure Single Organ Failure Multiorgan Failure

Abbreviations as in Figure 1.

impaired sublingual microcirculatory flow correlated
with persistent acute organ dysfunction and high
SOFA scores. In unselected patients admitted to the
cardiac intensive care unit, incremental organ failure,
as assessed by the SOFA score, correlated with higher
short-term mortality (10). In a temporal analysis of
French intensive care units during 1997 to 2012,
Puymirat et al. (35) noted a steady increase in multi-
organ failure in unselected patients with CS. How-
ever, only 10% to 14% of these patients were admitted
with AMI-CS (35). They demonstrated multiorgan
failure (assessed by the Simplified Acute Physiology
Score II) to independently correlate with in-hospital
mortality in unselected CS patients. These studies,
and others from non–AMI-CS populations (9,36), note
multiorgan failure to consistently predict worse out-
comes in patients with shock. Our study is of incre-
mental value to these prior works. In this study, we
present 15-year trends and outcomes of acute
noncardiac organ failure from a nationally represen-
tative population. These national trends are impor-
tant in highlighting the
hemometabolic cascade in patients with AMI-CS that
might aid in development of targeted therapies in this
critically ill population.
In this study, we note a steady increase in multi-
organ failure between 2000 and 2014, with a cross-
over around 2008. Incidentally, as noted in Figure 2,
the overall in-hospital mortality trend has held
relatively stable in the AMI-CS population since 2008
despite a steady decline in the prior years. Taken
together, these findings might suggest that any
mortality benefit derived from early revasculariza-
tion might be offset by multiorgan failure in AMI-CS
(1). However, these data need to be interpreted with
caution, given the observational nature of these
findings, and need further evaluation in carefully
designed prospective studies. It is certainly
conceivable that greater recognition of organ
dysfunction/failure and improved coding practices
could have resulted in this observed trend. However,
recent data from other groups have demonstrated an
overall increase in acuity of cardiac intensive care
unit patients, making this less likely in this current
population (10,13). The increase in multiorgan failure
during this study period can be explained by the
increase in overall comorbidity and acuity of pa-
tients presenting with AMI. Due to rapid improve-
ments in care from of ischemic heart disease due to
primary prevention and aggressive revascularization,
it is possible that the spectrum of AMI-CS patients
evolution of the presenting to hospitals has systematically shifted
during this study period. Further dedicated studies
with granular physiological and laboratory data are
needed to confirm this trend. Finally, it is important
to note that a minority of the AMI-CS admissions
may have had creatinine elevations without acute
kidney injury (i.e., no tubular injury) that may have
resulted in misrepresentation of this particular
cohort (37).
1788 Vallabhajosyula et al. JACC VOL. 73, NO. 14, 2019

Acute Organ Failure in AMI With Cardiogenic Shock APRIL 16, 2019:1781–91

F I G U R E 3 In-Hospital Mortality With Acute Noncardiac Organ Failure in AMI-CS

A B
5 6
Odds Ratio for in-Hospital Mortality

Odds Ratio for in-Hospital Mortality

4
5
4 3.72 (3.38-4.09)
3.72 (3.38-4.09)
3 4

3 2.94 (2.82-3.05) 2.94 (2.82-3.05)

3
2 2.42 (2.37-2.48)
2.76 (2.69-2.84)
2 1.87 (1.84-1.90) 2
1.36 (1.34-1.38) 1.93 (1.89-1.96)
1
1 1.29 (1.27-1.31)
1

0 0
0 1 2 3 4 5 0 1 2 3 4 5
Number of Organ Systems with Failure Number of Organ Systems with Failure

Unadjusted odds ratios (A) and adjusted odds ratios* (B) for in-hospital mortality in AMI-CS with every additional organ system failure; represented as odds ratio (95%
confidence interval). *Adjusted for age, sex, race, primary payer, socioeconomic status, hospital location/teaching status, hospital bed size, hospital region,
comorbidity, cardiac arrest, use of coronary angiography, percutaneous coronary intervention, invasive hemodynamic monitoring, and mechanical circulatory support.
Abbreviations as in Figure 1.

In this study, patients with greater comorbidity
consistently underwent less coronary angiography
and revascularization. These findings are consistent
with other studies in AMI-CS patients that demon-
strate decreased use of angiography in sicker pa-
tients (5,38). It is important to note that there is no
reliable way to assess the timing of angiography with
respect to organ failure in this database, and hence
organ failure could both have been a barrier to
angiography or a consequence of the lack of revas-
cularization. The bidirectional relationship between
organ failure and revascularization
the need for a multidisciplinary
decision-making in these patients to improve clinical
outcomes.
STUDY LIMITATIONS. Some of the limitations of this
study are inherent to the analysis of a large admin-
istrative database. The HCUP-NIS attempts to miti-
gate potential errors by using internal and external
quality control measures. The ICD-9-CM codes for
AMI and CS have been previously validated, which
reduces the inherent errors in the study. However,
given the moderate sensitivity of the administrative
code for CS, it is possible that less severe AMI-CS
admissions were missed, which could result in
overestimation of single or multiorgan failure in
AMI-CS. The administrative codes for acute organ
dysfunction/failure have been previously validated
in septic patients and show high specificity and
moderate sensitivity (21). It is conceivable that
particular ICD-9-CM codes are more heavily
weighted than others within a given organ system,
such as invasive or noninvasive mechanical ventila-
tion, use of tracheostomy, or hemodialysis. Further
data are needed on these important aspects of organ
failure to define the variations in the spectrum of
individual organ system. Important factors such as
the timing of organ failure, the presence of organ
failure at admission, and resolution of laboratory
highlights markers of organ injury and dysfunction could not
approach to be reliably identified in this hospital admissions
database. Importantly, change in organ function
during the hospital stay (improvement or decline)
could not be reliably assessed. Prior studies have
noted the serial assessment of organ function to
have important prognostic correlations (9,10). Echo-
cardiographic data and hemodynamic parameters
that aid in vasoactive medication management were
unavailable in this database. Furthermore, despite a
unifying diagnosis of CS, patients exhibit individual
phenotypes such as right ventricular failure, acute
structural complications, and myocardiogenic shock,
which may have different prognoses and clinical
courses. Despite demonstrating an association be-
tween organ failure and lower PCI use, causation
could not be ascertained due to the inability to time
JACC VOL. 73, NO. 14, 2019 Vallabhajosyula et al. 1789
APRIL 16, 2019:1781–91 Acute Organ Failure in AMI With Cardiogenic Shock

C ENTR AL I LL U STRA T I ON Acute Noncardiac Organ Failure in Acute Myocardial Infarction With Cardiogenic Shock

Vallabhajosyula, S. et al. J Am Coll Cardiol. 2019;73(14):1781–91.

Acute myocardial infarction with cardiogenic shock is often associated with respiratory, renal, hepatic, hematologic, and neurological failure that results in
incrementally higher in-hospital mortality.

organ failure. Finally, the reasons for not obtaining outcomes of acute organ failure in AMI-CS over the
cardiac and noncardiac organ support therapies due last 15 years.
to treatment-limiting decisions could not be CONCLUSIONS
assessed in this administrative database. Despite
these limitations, this study addresses an important In this study of 444,253 patients with AMI-CS, we
knowledge gap highlighting the national trends and noted a steady increase in acute organ failure that
1790 Vallabhajosyula et al. JACC VOL. 73, NO. 14, 2019

Acute Organ Failure in AMI With Cardiogenic Shock APRIL 16, 2019:1781–91

demonstrated a strong association with higher PERSPECTIVES

in-hospital mortality. Single-organ failure and
multiorgan failure were independently associated
COMPETENCY IN PATIENT CARE AND
with 1.3-times and 2.2-times higher in-hospital
PROCEDURAL SKILLS: Failure of multiple noncar-
mortality. Dedicated clinical research into patho-
diac organs is an increasingly frequent complication of
physiology and disease-specific factors in AMI-CS is
cardiogenic shock in patients with AMI-CS that is
warranted to prevent and treat multiorgan failure
associated with a poor prognosis.
in an attempt to improve clinical care and
outcomes.
TRANSLATIONAL OUTLOOK: Further research
into the pathophysiology and risk factors for this
ADDRESS FOR CORRESPONDENCE: Dr. Saraschandra
complication of acute myocardial infarction is
Vallabhajosyula, Department of Cardiovascular Med-
necessary to develop effective strategies to prevent
icine, Mayo Clinic, 200 First Street SW, Rochester,
and manage multiorgan failure to improve clinical
Minnesota 55905. E-mail: Vallabhajosyula.
outcomes.
Saraschandra@mayo.edu. Twitter: @SarasVallabhMD,
@MayoClinic, @MayoClinicCV, @MayoPCCM.

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KEY WORDS acute myocardial infarction,
cardiac intensive care unit, cardiogenic
shock, critical care cardiology, National
Inpatient Sample, outcomes research, renal
failure, respiratory failure
A PP END IX For supplemental figures and
tables, please see the online version of
this paper.