Clinical Research in Cardiology https://doi.org/10.1007/s00392-018-1266-7
ORIGINAL PAPER
Association between central venous pressure as assessed by echocardiography, left ventricular function and acute cardio-renal syndrome in patients with ST segment elevation myocardial infarction Shafik Khoury1 · Arie Steinvil1 · Amir Gal‑Oz2 · Gilad Margolis1 · Aviram Hochstatd1 · Yan Topilsky1 · Gad Keren1 · Yacov Shacham1 Received: 11 February 2018 / Accepted: 30 April 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract Background Recent reports have demonstrated the adverse effects of venous congestion on renal function in patients with heart failure. None of these trials, however, has evaluated the effect of acute myocardial ischemia on the occurrence of acute kidney injury (AKI). Methods We conducted a retrospective study of 1336 ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) between June 2012 and June 2016. Comprehensive echocardiographic examination was performed within 72 h of hospital admission. Non-invasive evaluation of central venous pressure (CVP) was estimated from measurements of inferior vena cava diameter and its collapsibility. Intermediate-high CVP was defined as ≥ 8 mm/Hg. Patients were stratified according to left ventricular ejection fraction (LVEF) and CVP and assessed for AKI. Results Intermediate-high CVP was associated with AKI both in patients with LVEF greater than 45% and those with 45% or lower. Patients having LVEF ≤ 45% and intermediate-high CVP had a 10-fold increase in the incidence of AKI compared to patients with LVEF > 45% and normal CVP (39 vs. 4%). In a multivariable logistic regression model, intermediate-high CVP was independently associated with AKI (OR = 2.73, 95% CI 1.54–4.87; p = 0.001). Other variables associated with AKI included LVEF ≤ 45% (OR = 2.37, 95%CI 1.25–4.51; p = 0.008), time to reperfusion, mechanical ventilation and chronic kidney disease. Conclusions Among STEMI patients undergoing PCI, the utilization of simple echocardiographic measurements (LVEF and CVP) may be useful for early identification of those at high risk for AKI. Keywords Acute kidney injury · ST elevation myocardial infarction · Central venous pressure · Cardiorenal syndrome
Introduction The occurrence of acute kidney injury (AKI) following myocardial infarction has complex and multifactorial pathogenesis [1–5]. Among this specific patient population, AKI may Shafik Khoury and Arie Steinvil contributed equally to this paper. * Yacov Shacham
[email protected] 1
Department of Cardiology, Tel-Aviv Sourasky Medical Center affiliated to the Sackler Faculty of Medicine, TelAviv University, Tel Aviv, Israel
Department of Intensive Care, Tel-Aviv Sourasky Medical Center affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel‑Aviv, Israel
2
represent type I cardiorenal syndrome (CRS) [6, 7]. The acute reduction in left ventricular (LV) systolic function often results in decreased cardiac output leading to reduced renal perfusion [6, 8]. Recently published studies on heart failure patients suggested the role of venous congestion in renal dysfunction and pointed out the importance of elevated central venous pressure (CVP) rather than low cardiac output as the main predictor for worsening renal function [9, 10]. However, no data are currently available on the relation between CVP and the occurrence of CRS in patients with acute myocardial infarction. We aimed to evaluate the possible interactions between reduced LV systolic function, elevated CVP and the development of type I CRS in a large population of ST elevation myocardial infarction (STEMI) patients undergoing reperfusion with primary percutaneous coronary intervention (PCI).
13
Vol.:(0123456789)
Materials and methods We performed a retrospective, single center observational study at the Tel-Aviv Sourasky Medical Center, a tertiary referral hospital with a 24/7 primary PCI service as previously described [11, 12]. All 1524 patients admitted between June 2012 and June 2016 to the Cardiac Intensive Care Unit (CICU) with the diagnosis of acute STEMI were included. We excluded patients who were treated either conservatively or by thrombolysis (n = 11) and those who were discharged with a diagnosis other than STEMI (e.g., myocarditis, Takotsubo cardiomyopathy; n = 34). We also excluded patients on chronic peritoneal dialysis or hemodialysis treatment (n = 4) and those who died within 24 h of admission (n = 26), since we presumed there was insufficient time for AKI to occur. Finally, patients whose echocardiographic assessment failed to demonstrate adequate imaging of the inferior vena cava flow (n = 113) were also excluded. In those patients, demonstration of the inferior vena cava was technically difficult and inadequate so that any assessment of pressure could not have been performed. Few cases contained only “frozen” images or very short video clips (< 2 s) that failed to demonstrate respiratory changes in diameter. The final study population included 1336 patients whose baseline demographics, cardiovascular history, clinical risk factors, treatment characteristics, echocardiographic and laboratory results were all retrieved from the hospital electronic medical records. Diagnosis of STEMI was established in accordance with the published guidelines including a typical chest pain history, diagnostic electrocardiographic changes, and serial elevation of cardiac biomarkers [13]. Data collection and assessment of co-morbidities were taken from discharge letters. Data were collected by S.K, G. M and Y. S. Quality control was available by comparing the co-morbidities list from the letters’ chronic problem list and thorough review of the discharge letters free text for verification and was performed for all patients included. The study protocol was approved by the local institutional ethics committee. Primary PCI was performed on patients with symptoms ≤ 12 h in duration as well as in patients with symptoms lasting 12–24 h in duration if the symptoms persisted at the time of admission. Time to coronary reperfusion was defined as the time from symptom onset (usually chest pain or discomfort), recorded upon admission, to the restoration of thrombolysis in myocardial infarction (TIMI) grade 3 flow in the infarct artery, as reported in the catheterization laboratory report. Following coronary interventional procedures, physiologic (0.9%) saline was given intravenously at a rate of 1 ml/ kg/h for 12 h after contrast exposure. In patients with overt
13
Clinical Research in Cardiology
heart failure, the hydration rate was reduced at the discretion of the attending physician. The contrast medium used in procedures was iodixanol (Visipaque, GE healthcare, Ireland) or iohexol (Omnipaque, GE healthcare, Ireland). The serum creatinine level was determined upon hospital admission, prior to primary PCI, and at least once a day during the CICU and/or step down unit stay until hospital discharge, and was available for all analyzed patients. The estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and chronic kidney disease (CKD) was categorized as admission eGFR of ≤ 60 ml/ min/1.73 m2 [14]. AKI was determined using the KDIGO criteria [15] and was defined as an increase in serum creatinine ≥ 0.3 mg/dl within 48 h of admission or an increase in serum creatinine ≥ 1.5 times baseline, which was known or presumed to have occurred within the prior 7 days. Mortality was assessed over a median period of 1271 ± 405 days up to December 1st, 2017. Assessment of survival following hospital discharge was determined from computerized records of the population registry bureau.
Echocardiography All patients underwent a screening echocardiographic examination within 3 days of admission. Relevant data were collected from the clinical echocardiographic exam reports. Echocardiography was performed by Philips IE-33 equipped with S5-1 transducers (Philips Healthcare, Andover, MA, USA), and GE Vivid 7 model equipped with M4S transducer. LV ejection fraction was calculated by the Biplane method of disks (modified Simpson’s rule). Central venous pressure was estimated by the inferior vena cava (IVC) diameter as well as its response to inspiration [16]. The performance of this technique is reviewed and presented annually during routine training sessions to all the echocardiographic technicians and physicians performing the exams in our institution. Briefly, expiratory and inspiratory IVC diameters and percentage collapse were measured using 2D images in subcostal views, with the patient in the supine position at 1–2 cm from the junction with the right atrium, using the long axis view. IVC diameter < 2.1 cm that collapsed > 50% with a sniff suggested normal CVP pressure of 3 mm Hg (range 0–5 mm Hg), whereas an IVC diameter > 2.1 cm that collapsed < 50% with a sniff suggested high CVP pressure of 15 mm Hg (range 10–20 mm Hg). In scenarios in which IVC diameter and collapse did not fit this paradigm, hepatic flow patterns were used to assess CVP [17]. Systolic predominance in hepatic vein flow (i.e., velocity of the systolic wave greater than the velocity of the diastolic wave) was suggestive of normal CVP (3 mm Hg, range 0–5). If systolic predominance was lost, such that the hepatic vein systolic filling fraction (velocity of the systolic
Clinical Research in Cardiology
wave/ velocity of the diastolic wave) was lower than 55%, high CVP was assumed (15 mm Hg, range 10–20) [17]. If uncertainty remained, CVP pressure was left as intermediate value of 8 mm Hg (range, 6–10). Forward stroke volume was calculated by multiplying the LV outflow tract area at rest by the LV outflow tract velocity–time integral measured by pulsed wave with subsequent calculation of cardiac output and index. LV outflow tract area was calculated based on the formula: LVOT outflow diameter2 × 0.785. To ascertain the accuracy of the Doppler-echocardiographic measurements of stroke volume we used the clearest on-axis image of the LVOT providing the largest LVOT diameter and measured the LVOT diameter inner-edge-to-inner-edge from the base of the right coronary cusp anteriorly to the commissure posteriorly. Cardiac output (l/min) was determined by multiplication of the stroke volume by the pulse. Early transmitral flow velocity (E) was measured in the apical 4-chamber view to provide an estimate of LV diastolic function [18]. Early diastolic mitral annular velocity (e′) was measured using spectral tissue Doppler imaging in both septal and lateral positions. The ratio of peak E to peak e′ was calculated (E/e′ ratio) from the average of at least 3 cardiac cycles. In patients with atrial fibrillation, we have used the average measured from 5 to 7 cardiac cycles. Prior data demonstrated that an E/e′ ratio > 15 was independently associated with AKI in STEMI patients [19]. Accordingly, this cutoff was used for the analysis.
Statistical analysis All data were summarized and displayed as mean ± standard deviation for continuous variables and as number (percentage) for categorical variables. The p values for the categorical variables were calculated with the chi square test. Continuous variables were compared using the independent sample t test or the Mann–Whitney U test. A two-tailed p value of < 0.05 was considered significant for all analyses. The influence of intermediate-high CVP and LV ejection fraction on the risk for AKI was evaluated using multivariable binary logistic regression models at the enter mode, adjusted for age, gender, hypertension, diabetes mellitus, familial history of ischemic heart disease, smoking, coronary artery disease severity, admission Killip class ≥ 2, presence of chronic kidney disease, mechanical ventilation, time to reperfusion (1 h increment), peak CPK levels, admission C-reactive protein, E/e′ ratio ≥ 15, intermediate high CVP and LV ejection fraction ≤ 45%. To elucidate the effect of mechanical ventilation and chronic kidney disease, separate regression models were performed to patients not mechanically ventilated (model 2) and without chronic kidney disease (model 3). Inter-observer variability was assessed by independent blinded observers who reviewed the stored video clips of the echocardiographic exams in 190 randomly
selected patients and assessed CVP and LV ejection fraction from those stored clips. Inter-observer variability was assessed using a Pearson’s correlation test, a paired Wilcoxon test and a within-subject coefficient of variation. The within-subject coefficient of variation (calculated using the root mean square of the measurements delta/mean ratio) provides a scale-free, unit-less estimate of variation expressed as a percentage. We measured inter-observer reproducibility for CVP and LV ejection fraction and expressed it using the coefficient of variation. All analyses were performed with the SPSS software (SPSS Inc., Chicago, IL).
Results A total of 1336 patients were included in the study. The mean age of the study population was 61 ± 11 years and most of them, 657 (81%), were males. 152/1336 patients (11%) developed AKI. Patients with AKI were of older age, more likely to be females, and had multiple co-morbidities, greater extent of coronary artery disease, longer time to culprit vessel reperfusion, higher Killip class and higher levels of C-reactive protein on admission (Table 1). Patients with AKI demonstrated lower LV ejection fraction (42% ± 9 vs. 47% ± 7, p < 0.001), higher CVP (9.5 ± 5.4 vs. 6.1 ± 3.2 mm/hg, p < 0.001) and were more likely to have intermediate-high CVP and lower cardiac output (4.6 ± 1.1 vs. 5.1 ± 1.2 l/min, p = 0.002) (Table 2). A sub-analysis for non-ventilated patients (n = 1273) yielded similar results to those found in the entire cohort.
Interaction between LV systolic function, CVP and AKI Intermediate-high CVP was associated with AKI both in patients with LV ejection fraction greater than 45% and those with 45% or lower (Fig. 1). Patients having both LV ejection fraction ≤ 45% and intermediate-high CVP had a 10-fold higher incidence of AKI compared to patients with LV ejection fraction > 45% and normal CVP (39% vs. 4%). Intermediate-high CVP was also associated with higher maximal in-hospital serum creatinine change (Fig. 2). In multivariable binary logistic regression model for the entire cohort (model 1, Table 3), intermediate-high CVP was independently associated with AKI (OR = 2.73, 95% CI 1.54–4.87; p = 0.001). Other variables associated with AKI included LV ejection fraction ≤ 45% (OR = 2.37, 95%CI 1.25–4.51; p = 0.008), time to reperfusion, mechanical ventilation and chronic kidney disease. The effect of an intermediate-high CVP was maintained among non-ventilated patients (model 2, Table 3) and patients without CKD (model 3, Table 3).
13
Table 1 Baseline characteristics
Clinical Research in Cardiology Variables
Acute kidney injury
Age (years) Male Systolic blood pressure (mm/Hg) Diastolic blood pressure (mm/Hg) Diabetes mellitus Dyslipidemia Hypertension Smoking history Family history of CAD Prior MI Time to reperfusiom (min) Admission Killip class ≥ 2 Mechanical ventilation Coronary artery disease severity: 1 2/3 Chronic kidney disease Peak CPK (Units/l) Contrast volume (ml) Admission C-reactive protein (mg/l) Duration of hospitalization (days)
No (n = 1184)
Yes (n = 152)
p value
60 ± 13 967 (82%) 136 ± 19 81 ± 13 268 (23%) 535 (45%) 489 (41%) 637 (54%) 285 (24%) 185 (16%) 379 ± 479 97 (8%) 28 (2%) 514 (43%) 670 (57%) 213 (18%) 1302 ± 1529 145 ± 56 11.5 ± 25.9 5.4 ± 2.8
70 ± 13 112 (74%) 133 ± 25 78 ± 14 51 (34%) 80 (53%) 99 (65%) 56 (37%) 18 (12%) 27 (18%) 599 ± 654 54 (35%) 35 (23%) 48 (31%) 104 (69%) 78 (52%) 1859 ± 1767 140 ± 51 23.8 ± 44.1 9.8 ± 8.2
< 0.001 0.01 0.214 0.584 < 0.01 0.08 < 0.001 < 0.001 < 0.001 0.49 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 0.328 < 0.001 < 0.001
CAD coronary artery disease, MI myocardial infarction, CPK creatine phosphokinase
Table 2 Key echocardiographic parameters according to acute kidney injury status
Variable
Acute kidney injury
Left ventricle ejection fraction (%) Left ventricle ejection fraction ≤ 45% E/e′ ratio E/e′ ratio ≥ 15 Central venous pressure (mm/Hg) Intermediate-high central venous pressure Cardiac output (l/min) Cardiac index (l/min/m2)
No (n = 1184)
Yes (n = 152)
p value
47 ± 7 640 (54%) 12.2 ± 5 213 (18%) 6.1 ± 3.2 151 (13%) 5.1 ± 1.2 2.7 ± 0.6
42 ± 9 121 (79%) 16.3 ± 7 68 (45%) 9.5 ± 5.4 78 (51%) 4.6 ± 1.1 2.3 ± 0.5
< 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 0.002 < 0.001
Long‑term outcomes
Discussion
Over a mean period of 3.5 ± 1.4 years, 115/1336 patients (8.6%) died. Mortality was significantly higher among those with AKI (44/152, 29%) following STEMI than those without AKI (71/1184, 6%; p < 0.001). The hazard ratio for all-cause mortality associated with AKI was 12.6 (95% CI 7.47–21.56, p < 0.001).
This is the first study to date suggesting the possible interaction between LV systolic function, CVP and the occurrence of AKI following STEMI. We have now demonstrated that among this patient population, the combination of reduced LV systolic function and elevated CVP was associated with a 10-fold increase in the incidence of AKI.
13
Clinical Research in Cardiology Fig. 1 Incidence of AKI in patients with normal (blue boxes) and intermediate-high (red boxes) CVP according to left ventricular ejection fraction (EF) above and ≤ 45%
Fig. 2 Maximal in-hospital serum creatinine change in patients with normal and intermediate-high CVP
Acute (or type I) CRS described to date in patients with acutely decompensated heart failure is characterized by a rapid worsening of cardiac function leading to AKI [20]. Renal dysfunction in CRS type I is attributed to a combination of low cardiac output, which consequently causes reduction in blood flow and renal perfusion pressure, and/or venous congestion. Reduced LV systolic function is a known risk factor for the development of AKI following STEMI [8]. The sudden myocardial insult in STEMI results in an acute reduction of cardiac output and reduced effective renal blood flow leading to hypoxic changes and the synthesis of reactive oxygen species [21]. Following the resumption of coronary flow and the improvement of left ventricular function, as
well as the resolution of arrhythmias, hemodynamic impairment often resolves while renal function may still remain impaired or lag in recovery. Recent studies on heart failure patients have highlighted the role of venous congestion on renal dysfunction and suggested that central venous pressure and right atrial pressure, rather than cardiac output, are the main predictors for worsening renal function [9, 10]. Recent sub-analysis of the ESCAPE trial has also suggested that renal impairment was related to CVP [9]. Venous congestion was the most important hemodynamic factor driving worsening of renal function in decompensated patients with advanced heart failure [22]. In a large cohort of patients with advanced heart failure, venous congestion was associated with decreased renal function. Moreover, the extent of congestion was also associated with the severity of renal impairment [23]. Venous congestion characterized by an increased right atrial pressure was also related to reduced renal blood flow and lower eGFR [24]. Increased venous congestion causes an increase in renal interstitial pressure and hypoxia to the renal parenchyma [25]. Increased oxidative stress and inflammation in the tubule-interstitium following venous congestion may also play a role in renal dysfunction [26]. Only limited data are present to date on the possible relation of echocardiographic parameters of elevated CVP and renal impairment among patients with acute ischemia. Tandon et al. evaluated the relation between right ventricular function and the development of CRS in patients presenting with inferior wall STEMI and right ventricular involvement [7]. They demonstrated that the presence of echocardiographic markers of reduced right ventricular function was associated with higher risk for the occurrence of type I CRS.
13
Clinical Research in Cardiology
Table 3 Multivariable binary logistic regression models for predicting acute kidney injury Correlates
Model 1 entire cohort adjusted OR (95% CI)
Age Male gender Hypertension Smoker Family history CAD severity Time to reperfusion (1 h increment) Killip class ≥ 2 Mechanical ventilation Peak CPK levels Diabetes mellitus C-reactive protein Chronic kidney disease LVEF ≤ 45% E/e′ ratio ≥ 15 Intermediate-high CVP
1.01 (0.98–1.04) 1.02 (0.52–2.02) 1.71 (0.97–3.03) 0.71 (0.4–1.24) 1.02 (0.49–2.12) 1.18 (0.85–1.63) 1.03 (1.00-1.05) 1.48 (0.74–2.93) 8.01 (3.11–20.06) 1.01 (1.00–1.01) 1.28 (0.72–2.31) 1.00 (0.97–1.01) 2.94 (1.49–5.78) 2.37 (1.25–4.51) 1.07 (0.56–2.03) 2.73 (1.53–4.87)
Model 2 non-ventilated patients adjusted OR (95% CI)
p value
Model 3 non-CKD patients p value adjusted OR (95% CI)
0.476 0.951 0.06 0.231 0.95 0.334 0.04
1.01 (0.97–1.03) 1.24 (0.61–2.56) 1.85 (1.01–3.38) 0.56 (0.31–1.01) 0.96 (0.44–2.11) 1.19 (0.84–1.69) 1.02 (0.99–1.05)
0.942 0.552 0.04 0.07 0.922 0.322 0.193
1.02 (0.98–1.05) 0.64 (0.22–1.85) 2.04 (0.91–4.59) 0.63 (0.29–1.37) 0.98 (0.41–2.37) 1.35 (0.85–2.16) 1.03 (1.00-1.07)
0.459 0.414 0.084 0.248 0.969 0.203 0.085
0.266 < 0.001 0.151 0.411 0.229 0.002 0.008 0.831 0.001
1.79 (0.87–3.66) – 1.01 (1.00–1.01) 1.14 (0.61–2.12) 1.00 (0.98–1.02) 3.19 (1.51–6.71) 2.15 (1.07–4.33) 1.22 (0.62–2.4) 3.11 (1.69–5.72)
0.113 – 0.07 0.684 0.215 0.002 0.03 0.551 < 0.001
1.63 (0.58–4.68) 12.2 (3.01–49.6) 1.01 (1.00-1.01) 0.76 (0.29–1.96) 1.00 (0.97–1.01) – 1.64 (0.69–3.91) 1.06 (0.38–2.93) 3.61 (1.62–8.08)
0.360 < 0.001 0.829 0.569 0.763 – 0.260 0.909 0.002
p value
CKD chronic kidney disease, CAD coronary artery disease, LVEF left ventricle ejection fraction, CVP central venous pressure, OR odds ratio
This report, however, included a small number of patients and only 10% of them underwent primary PCI. In our cohort, the combination of reduced LV systolic function and elevated CVP was associated with the highest risk for AKI. The finding that patients with AKI had both reduced LV ejection fraction and elevated CVP may point out the importance of combined systolic and diastolic dysfunction resulting in elevated right heart and central venous pressures. This finding may support a plausible explanation for a pathomechanism in which the worsening of renal function in STEMI patients is related to a combination of pump failure and reduced perfusion as well as venous congestion, thus fulfilling the criteria for type I CRS. Contrast material is still considered the major reason for AKI development in STEMI patients undergoing primary PCI. Contrast-induced AKI is a prevalent and deleterious complication of coronary angiography and reported to be the third most common cause of hospital acquired renal failure [27]. Unlike previous reports in which the risk of contrastinduced AKI in patients undergoing PCI was directly associated with increasing contrast media volume, we did not find in our study a significant difference in contrast media volume between patients with and without AKI. Furthermore, we have previously demonstrated that contrast media volume did not predict AKI in this patient population [6, 8, 12]. This finding suggests that factors other than contrast media volume may contribute to AKI development in the setting of STEMI. These include mainly hemodynamic
13
parameters which make the kidneys more susceptible to contrast-induced AKI. Our findings may bear some clinical implications. While various clinical factors and biomarkers have been studied in STEMI patients who develop AKI, only few studies focused on the relation between echocardiographic parameters and the occurrence of AKI [7, 8, 28]. As the treatment of AKI in STEMI patients following primary PCI is rather limited, the main strategy is early identification of those at risk for developing this complication and thus offering a better opportunity to apply appropriate preventive measures. The addition of simple and early echocardiographic measurements (LV ejection fraction and CVP) to other established clinical risk factors may be useful for early identification of those at high risk for post-PCI AKI. In these patients, physicians may consider daily assessment of serum creatinine. In addition, novel biomarkers offer the opportunity to diagnose early tubular injury and may help in early detection of cellular injury in response to various renal toxins, including contrast-induced nephropathy [29, 30].
Limitations We acknowledge several important limitations of our study. This is a single center retrospective and non-randomized observational study and, therefore, might have been subject to bias, although we included consecutive
Clinical Research in Cardiology
patients and attempted to adjust for confounding factors using the multivariate regression model. The data from echocardiographic reports were analyzed retrospectively. Echocardiography is highly operator dependent and our data were collected and recorded by different sonographers. We tried to adjust for this limitation by the assessment of inter-observer variability using independent blinded observers who reviewed the stored video clips of the echocardiographic exams and assessed CVP and LV ejection fraction. Comparison of inter-observer parameters showed good agreement, with statistically significant, yet clinically insignificant differences. No information was present on the concomitant medications patients were receiving (e.g., renin–angiotensin blockers, beta blockers and diuretics) upon hospital admission, throughout hospitalization and upon discharge; thus, their effect on the occurrence of AKI and long-term outcomes could not have been assessed. Patients having AKI were older, had greater coronary artery disease, longer time to culprit vessel reperfusion, more likely to have heart failure and had higher C-reactive protein levels on admission. In addition, they had larger infarct sizes. It is possible that the development of AKI in this group was not related to elevated CVP and may simply be reflective of a higher degree of underlying pathology. Patients with AKI were significantly more likely to be mechanically ventilated. Mechanical ventilation may result in decreased IVC collapsibility and increased pulmonary resistance and thus may lead to overestimation of CVP. We performed, however, a sub-analysis of data in non-ventilated patients yielding similar echocardiographic findings and adjusted the regression model also for non-ventilated patients. No information was present on patients with right ventricular dysfunction; thus, its relation to CVP could not have been assessed. Intravenous fluids have complex interaction effects on renal function. While fluids enhance forward flow and renal perfusion, with possible reduction of AKI, it may also cause venous congestion resulting in potential increase in AKI. No information was present regarding the amount of intravenous fluid administrated to patients throughout their CICU stay and, thus, their potential effect on renal function could not be assessed. The routine use of pulmonary artery catheter and/or pulse index continuous cardiac output is not a common practice in our CICU; thus, we could not correlate or confirm the CVP as assessed by echocardiography. Finally, worsening of renal function might have occurred following hospital discharge in some patients; thus, the true incidence of AKI described in our study might have been underestimated.
Conclusions Among STEMI patients undergoing primary PCI, the utilization of simple echocardiographic measurements (LV ejection fraction and CVP) may be useful for early identification of those at high risk for AKI.
Compliance with ethical standards Conflict of interest The authors declare that they have no conflict of interest.
References 1. Shacham Y, Leshem-Rubinow E, Steinvil A, Assa EB, Keren G, Roth A, Arbel Y (2014) Renal impairment according to acute kidney injury network criteria among ST elevation myocardial infarction patients undergoing primary percutaneous intervention: a retrospective observational study. Clin Res Cardiol 103(7):525–532. https://doi.org/10.1007/s00392-014-0680-8 2. Marenzi G, Assanelli E, Campodonico J, De Metrio M, Lauri G, Marana I, Moltrasio M, Rubino M, Veglia F, Montorsi P, Bartorelli AL (2010) Acute kidney injury in ST-segment elevation acute myocardial infarction complicated by cardiogenic shock at admission. Crit Care Med 38(2):438–444. https://doi. org/10.1097/CCM.0b013e3181b9eb3b 3. Goldberg A, Hammerman H, Petcherski S, Zdorovyak A, Yalonetsky S, Kapeliovich M, Agmon Y, Markiewicz W, Aronson D (2005) Inhospital and 1-year mortality of patients who develop worsening renal function following acute ST-elevation myocardial infarction. Am Heart J 150(2):330–337. https: //doi. org/10.1016/j.ahj.2004.09.055 4. Parikh CR, Coca SG, Wang Y, Masoudi FA, Krumholz HM (2008) Long-term prognosis of acute kidney injury after acute myocardial infarction. Arch Intern Med 168(9):987–995. https ://doi.org/10.1001/archinte.168.9.987 5. Amin AP, Spertus JA, Reid KJ, Lan X, Buchanan DM, Decker C, Masoudi FA (2010) The prognostic importance of worsening renal function during an acute myocardial infarction on longterm mortality. Am Heart J 160(6):1065–1071. https: //doi. org/10.1016/j.ahj.2010.08.007 6. Shacham Y, Leshem-Rubinow E, Gal-Oz A, Arbel Y, Keren G, Roth A, Steinvil A (2015) Acute cardio-renal syndrome as a cause for renal deterioration among myocardial infarction patients treated with primary percutaneous intervention. Can J Cardiol 31(10):1240–1244. https: //doi.org/10.1016/j. cjca.2015.03.031 7. Tandon R, Mohan B, Chhabra ST, Aslam N, Wander GS (2013) Clinical and echocardiographic predictors of cardiorenal syndrome type I in patients with acute ischemic right ventricular dysfunction. Cardiorenal Med 3(4):239–245. https: //doi. org/10.1159/000355524 8. Schroten NF, Damman K, Valente MA, Smilde TD, van Veldhuisen DJ, Navis G, Gaillard CA, Voors AA, Hillege HL (2016) Long-term changes in renal function and perfusion in heart failure patients with reduced ejection fraction. Clin Res Cardiol 105(1):10–16. https://doi.org/10.1007/s00392-015-0881-9 9. Nohria A, Hasselblad V, Stebbins A, Pauly DF, Fonarow GC, Shah M, Yancy CW, Califf RM, Stevenson LW, Hill JA (2008) Cardiorenal interactions: insights from the ESCAPE trial. J
13
10.
11.
12.
13.
14.
15. 16.
17.
18.
Clinical Research in Cardiology Am Coll Cardiol 51(13):1268–1274. https://doi.org/10.1016/j. jacc.2007.08.072 Testani JM, Khera AV, St John Sutton MG, Keane MG, Wiegers SE, Shannon RP, Kirkpatrick JN (2010) Effect of right ventricular function and venous congestion on cardiorenal interactions during the treatment of decompensated heart failure. Am J Cardiol 105(4):511–516. https://doi.org/10.1016/j.amjcard.2009.10.020 Khoury S, Carmon S, Margolis G, Keren G, Shacham Y (2017) Incidence and outcomes of early left ventricular thrombus following ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Clin Res Cardiol 106(9):695– 701. https://doi.org/10.1007/s00392-017-1111-4 Shacham Y, Leshem-Rubinow E, Gal-Oz A, Arbel Y, Keren G, Roth A, Steinvil A (2014) Relation of time to coronary reperfusion and the development of acute kidney injury after ST-segment elevation myocardial infarction. Am J Cardiol 114(8):1131–1135. https://doi.org/10.1016/j.amjcard.2014.07.032 American College of Emergency P, Society for Cardiovascular A, Interventions, O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX, Anderson JL, Jacobs AK, Halperin JL, Albert NM, Brindis RG, Creager MA, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Kushner FG, Ohman EM, Stevenson WG, Yancy CW (2013) 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 61(4):e78–e140. https:// doi.org/10.1016/j.jacc.2012.11.019 Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF III, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Ckd EPI (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612 Summary of Recommendation Statements (2012) Kidney Int Suppl (2011) 2(1):8–12. https://doi.org/10.1038/kisup.2012.7 Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ, Chamber Quantification Writing G, American Society of Echocardiography’s G, Standards C, European Association of E (2005) Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18(12):1440–1463. https://doi.org/10.1016/j.echo.2005.10.005 Nagueh SF, Kopelen HA, Zoghbi WA (1996) Relation of mean right atrial pressure to echocardiographic and Doppler parameters of right atrial and right ventricular function. Circulation 93(6):1160–1169 Nagueh SF, Smiseth OA, Appleton CP, Byrd BF III, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Popescu BA, Waggoner AD (2016) Recommendations for the evaluation of left ventricular diastolic
13
19.
20. 21. 22.
23.
24.
25.
26.
27.
28.
29.
30.
function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 29(4):277–314. https://doi.org/10.1016/j.echo.2016.01.011 Flint N, Kaufman N, Gal-Oz A, Margolis G, Topilsky Y, Keren G, Shacham Y (2017) Echocardiographic correlates of left ventricular filling pressures and acute cardio-renal syndrome in ST segment elevation myocardial infarction patients. Clin Res Cardiol 106(2):120–126. https://doi.org/10.1007/s00392-016-1031-8 Ronco C, Haapio M, House AA, Anavekar N, Bellomo R (2008) Cardiorenal syndrome. J Am Coll Cardiol 52(19):1527–1539. https://doi.org/10.1016/j.jacc.2008.07.051 Hori M, Nishida K (2009) Oxidative stress and left ventricular remodelling after myocardial infarction. Cardiovasc Res 81(3):457–464. https://doi.org/10.1093/cvr/cvn335 Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, Young JB, Tang WH (2009) Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol 53(7):589–596. https://doi. org/10.1016/j.jacc.2008.05.068 Damman K, Voors AA, Hillege HL, Navis G, Lechat P, van Veldhuisen DJ, Dargie HJ, Investigators C-, Committees (2010) Congestion in chronic systolic heart failure is related to renal dysfunction and increased mortality. Eur J Heart Fail 12(9):974–982. https://doi.org/10.1093/eurjhf/hfq118 Maeder MT, Holst DP, Kaye DM (2008) Tricuspid regurgitation contributes to renal dysfunction in patients with heart failure. J Card Fail 14(10):824–830. https://doi.org/10.1016/j.cardf ail.2008.07.236 Hamza SM, Kaufman S (2007) Effect of mesenteric vascular congestion on reflex control of renal blood flow. Am J Physiol Regul Integr Comp Physiol 293(5):R1917–R1922. https://doi. org/10.1152/ajpregu.00180.2007 Tanaka M, Yoshida H, Furuhashi M, Togashi N, Koyama M, Yamamoto S, Yamashita T, Okazaki Y, Ishimura S, Ota H, Hasegawa T, Miura T (2011) Deterioration of renal function by chronic heart failure is associated with congestion and oxidative stress in the tubulointerstitium. Intern Med 50(23):2877–2887 James MT, Samuel SM, Manning MA, Tonelli M, Ghali WA, Faris P, Knudtson ML, Pannu N, Hemmelgarn BR (2013) Contrast-induced acute kidney injury and risk of adverse clinical outcomes after coronary angiography: a systematic review and meta-analysis. Circ Cardiovasc Interv 6(1):37–43. https://doi. org/10.1161/CIRCINTERVENTIONS.112.974493 Shacham Y, Gal-Oz A, Topilsky Y, Keren G, Arbel Y (2016) Relation of pulmonary artery pressure and renal impairment in ST segment elevation myocardial infarction patients. Echocardiography 33(7):956–961. https://doi.org/10.1111/echo.13206 Coca SG, Yalavarthy R, Concato J, Parikh CR (2008) Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review. Kidney Int 73(9):1008–1016. https://doi. org/10.1038/sj.ki.5002729 Koyner JL, Parikh CR (2013) Clinical utility of biomarkers of AKI in cardiac surgery and critical illness. Clin J Am Soc Nephrol 8(6):1034–1042. https://doi.org/10.2215/CJN.05150512