1 Acute Kidney Injury Following Coronary Artery Bypass Surgery and Long-term Risk of Heart Failure Olsson et al: Kidney Injury, CABG and Heart Failure Daniel Olsson BS; Ulrik Sartipy MD, PhD; Frieder Braunschweig, MD, PhD; Martin J. Holzmann MD, PhD From the Departments of Emergency Medicine (D.O., M.J.H.); Cardiothoracic Surgery and Anesthesiology (U.S.); and Cardiology (F.B.), all at Karolinska University Hospital, and Departments of Medicine (D.O., F.B., M.J.H) and Molecular Medicine and Surgery (U.S.) at the Karolinska Institutet, all in Stockholm, Sweden. Correspondence to Martin Holzmann, Department of Emergency Medicine Karolinska University Hospital 17176 Stockholm Sweden E-mail: [email protected]Telephone: +46 851770000 Fax: +46 851771111 DOI: 10.1161/CIRCHEARTFAILURE.112.971705 Journal Subject Codes: 7, 8, 10, 36, 110 M M M M M M M d d ed d d ed dic ic ic ic ic ic icin in in in in in ine e e e e e e an an an an an an and d d d d d d Su Su Su Su Su Su Surg rg rg rg rg rg rg nstitutet all in Stockholm, Sweden. e n m nsti i i i itu tu tu tu tute te te te tet, t, t, t, t, a a a a all l l l l i i i i in Stockholm, Swede de de de en. n n n n e to n, m merge nc nc nc nc ncy y y y y Me Me Me Me Medi di di di dici ci ci ci cine ne ne ne ne by guest on April 28, 2018 http://circheartfailure.ahajournals.org/ Downloaded from by guest on April 28, 2018 http://circheartfailure.ahajournals.org/ Downloaded from by guest on April 28, 2018 http://circheartfailure.ahajournals.org/ Downloaded from
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Acute Kidney Injury Following Coronary Artery Bypass Surgery and
Long-term Risk of Heart Failure
Olsson et al: Kidney Injury, CABG and Heart Failure
Daniel Olsson BS; Ulrik Sartipy MD, PhD;
Frieder Braunschweig, MD, PhD; Martin J. Holzmann MD, PhD
From the Departments of Emergency Medicine (D.O., M.J.H.); Cardiothoracic Surgery and
Anesthesiology (U.S.); and Cardiology (F.B.), all at Karolinska University Hospital, and
Departments of Medicine (D.O., F.B., M.J.H) and Molecular Medicine and Surgery (U.S.) at
the Karolinska Institutet, all in Stockholm, Sweden.
Correspondence to Martin Holzmann, Department of Emergency Medicine Karolinska University Hospital 17176 Stockholm Sweden E-mail: [email protected] Telephone: +46 851770000 Fax: +46 851771111
DOI: 10.1161/CIRCHEARTFAILURE.112.971705
Journal Subject Codes: 7, 8, 10, 36, 110
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o ed AKI. Duri a mean follow-u of 4.1 ears there were 132
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Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure, and
an effective method of relieving angina and improving the prognosis for selected patients with
ischemic heart disease.1 Despite a gradual decline over the past decade, more than 1000
patients per million population still undergo CABG in the United States each year.2 Acute
kidney injury (AKI) is a frequent complication after CABG with an incidence between 8 and
15%3,4 and has been associated with an increased risk of postoperative complications as well
as increased short- and long-term mortality.4–7 A minor elevation of postoperative serum
creatinine by 0.5 mg/dL has been found to be associated with an almost threefold increase in
30-day mortality.6
Heart failure (HF) is a highly prevalent syndrome with a poor prognosis, resulting in
substantial morbidity and reduced quality of life despite recent advances in treatment.8 Also,
HF is the most common cause of hospital admission in the United States and Europe9,10 and
HF hospitalization per se is linked to adverse outcome and high treatment costs.11 Heart
failure is closely interrelated with kidney dysfunction. Both conditions share risk factors such
as hypertension, diabetes mellitus and ischemic heart disease and may promote the
progression of the other. The co-existence of kidney and heart disease is known as the
“cardiorenal syndrome”.12 Five different subtypes of cardiorenal syndrome have been
described based on the different modes of pathological interaction between the kidney and
heart where acute or chronic dysfunction in one organ results in acute or chronic dysfunction
in the other.12
While the general relationship between chronic kidney disease (CKD) and chronic HF has
received considerable attention in the literature13 studies investigating the impact of AKI on
the development of HF are scarce, and in the context of cardiac surgery has never been
examined. This study aimed to describe the risk of first hospitalization for HF in relation to
AKI in a large nationwide cohort of patients who underwent a first isolated CABG.
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ommon cause of hospital admission in the United States and E r
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interrelated with kidney dysfunction. Both conditions share risk
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defined as an increase of < 0.3 mg/dL (< 26 μmol/L) or a decrease in postoperative SCr. The
classification has been used in a recently published study5 and is based on AKIN criteria15 and
traditional definitions.5
Glomerular filtration rates were estimated using the simplified Modification of Diet in
Renal Disease (MDRD) study equation.16 Diagnosis of hypertension, hyperlipidemia, chronic
obstructive pulmonary disease and diabetes mellitus were made on the basis of patients´
ongoing pharmacological treatment for these illnesses. Peripheral vascular disease was
defined as previous surgery to the abdominal aorta, iliac artery or carotid artery or the
presence of claudication. Left ventricular function was assessed by echocardiography prior to
surgery and categorized as normal (ejection fraction > 50%), reduced (ejection fraction 30 to
50%) or severely reduced (ejection fraction < 30%).
Outcome
The primary study outcome was first hospitalization for HF defined as a primary discharge
diagnosis of HF in the Swedish National Inpatient Register, where patients hospitalized in
Sweden have been registered since 1964. This register covers the whole country since 1987.17
This register was also used to ascertain information about illnesses prior to surgery. The
validity of the diagnosis “heart failure” in this register has been shown to be 95% if it is the
principal cause of hospitalization.17,18 A secondary outcome was a composite of first
hospitalization for HF or death from any cause. The date of death was obtained from the
Swedish Cause-of-Death register, where all deaths of persons residing in Sweden are
registered.
Data from SWEDEHEART, the Inpatient Register and the Cause-of-Death Register were
linked by the National Board of Health and Welfare, using the unique personal identification
number that is assigned to each permanent resident of Sweden. Follow-up began 30 days
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dy ouououououtctctctct oooomo e ee waawawass fififfifirsttt tt hooohohospitititititalalalalalizizizizizatatatioioioii nnn n fofofofoforrr rr HFHFHFHFHF dddddefefefefefininini ededededed aaaaass sss aaaa a prppprp imimmimmarararyyy
analysis. Some data were missing in the study dataset and multiple imputation by chained
equations was used to impute missing values. All multivariable analyses were performed on
the imputed dataset. We assumed that the missing values were missing at random. The
frequency of missing values in the variables included in the final multivariable analysis, with
24 018 patients were none for age, sex, eGFR, and myocardial infarction before surgery or
during follow-up; 8% for left ventricular ejection fraction; and 29% for diabetes mellitus. One
hundred datasets were imputed and estimates from these datasets were combined using
standard methods. The proportionality assumption of the primary analysis was tested by
formal and graphical test and no indication of a violation was found. We also performed a
complete-case analysis where only observations without missing values for model covariates
were included (n = 16 002). Sex- and eGFR-specific analyses were performed to estimate the
risk for incident HF in these subgroups. STATA version 12.1 (StataCorp LP, College Station,
TX, USA) was used for data analysis.
Results
The study population consisted of 24 018 patients with a mean age of 66.8 ±9.2 years and
21% were women. Patients’ characteristics are presented in Table 1. The overall incidence of
AKI was 12% and did not vary significantly between 2000 to 2004 compared with 2004 to
2008. Patients with AKI were more likely to be: older; have hypertension, peripheral vascular
disease, diabetes mellitus, and a reduced GFR; have had a prior myocardial infarction, a
previous stroke or severely reduced left ventricular ejection fraction, compared with patients
without AKI. The median duration of hospital stay in the department of cardio-thoracic
surgery was 6, 7, 7 and 9 days for patients with no kidney injury, AKI stage 1, 2, and 3
respectively.
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Kidney Injury Network (AKIN) classification of AKI (Table 1, s
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s st a harmful effect of AKI on the heart, which is consiste t
rome type 3. This syndrome describes the connection between c
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failure. Even though we could adjust for left ventricular systolic dysfunction we did not have
information about diastolic function. Thus, there may have been residual confounding that we
could not control for which may have affected our results.
Conclusions
Acute kidney injury after coronary artery bypass grafting was associated with increased long-
term risk of first hospitalization for HF. This was true for patients with or without pre-existing
chronic kidney disease, and for both sexes. Patients with AKI after CABG should be followed
closely in order to detect early changes in cardiac function. Our results should be interpreted
with caution since we could not control for medication or anemia before or after surgery.
Acknowledgments
The authors are thankful to the steering committee of SWEDEHEART for making their
register available for the purpose of this study.
Disclosures
None.
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G, Zamperetti N, Ponikowski P. Cardio-renal syndromes: rep trence of the acute dialysis quality initiative Eur Heart J 2010;
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Cardiothorac Surg. 2011; 40:715-721. 37. Saxena A, Dinh D, Smith JA, Shardey G, Reid CM, Newcomb AE. Sex differences in outcomes following isolated coronary artery bypass graft surgery in Australian patients: analysis of the Australasian Society of Cardiac and Thoracic Surgeons cardiac surgery database. Eur J Cardiothorac Surg. 2012; 41:755-762.
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* AKI; Acute kidney injury classified according to absolute raise in serum creatinine values. Stage 1; 0.3-0.5 mg/dL, stage
2&3; > 0.5 mg/dL. CI; confidence interval, HF; heart failure, HR; hazard ratio. † Multivariable adjustment was made for; age,
sex, diabetes mellitus, left ventricular ejection fraction, pre- and postoperative myocardial infarction.
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is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation: Heart Failure published online December 10, 2012;Circ Heart Fail.
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