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Research Article *Corresponding author
Silvia Gelás Lage, Instituto do Coração, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Impact of Intra-Aortic Balloon Universidade de Sao Paulo, Sao Paulo, SP, Brazil, Av. Dr. Enéas de Carvalho Aguiar, 44, 05403-000 - São Support on Endothelial Paulo, SP, Brazil, Tel: (55-11) 26615302; Email: Submitted: 12 September 2018 Accepted: 03 October 2018 Function and Tissue Perfusion Published: 05 October 2018 Copyright Markers in Severe Heart © 2018 Lage et al. OPEN ACCESS Failure Keywords • Intra-aortic balloon pump; Severe heart failure; Antônio A. P. Fagundes Júnior, Liliane Kopel, Claudia Bernoche, Endothelial function; Central venous oxygen saturation; Arteriovenous carbon dioxide gradient; Milena F. Macatrão-Costa, Leonardo N. Lopes, Antonio P. B-type natriuretic peptide Mansur, and Silvia Gelás Lage* Heart Institute, Hospital das Clinicas HCFMUSP, Brazil
Abstract Background: The intra-aortic balloon pump (IABP) is a common therapy available for ventricular support in critical cardiac patients. The aim of this study
was to characterize the effect of IABP on endothelial function, on serum B-type natriuretic peptide (BNP) levels and on central venous oxygen saturation (ScVO2)
and arteriovenous carbon dioxide gradient (∆PCO2) as perfusion tissue markers. Methods and results: Twenty-three patients with severe heart failure, mean age 50±13 years, left ventricular ejection fraction of 22±8% were included. All were on IABP support and the protocol considered 3 conditions: 1) IABP ratio 1:1, 2) IABP ratio 1:3 and 3) IAPB ratio 1:1. The period of time between conditions was 20 minutes. In the three conditions the endothelial-dependent flow-mediated vasodilatation (FMD) was measured by ultrasound method. Blood
was sampled to determine ScVO2, ∆PCO2 and BNP. FMD was impaired, ∆PCO2 and BNP were high, compatible with severe heart failure, but did not change
with IABP variation. ScVO2 (%) was 68.3±10.2 and 61.3±12.5, p<0.002 (condition 1 vs. 2). The values were also significant considering the condition 2vs . 3
when ScVO2 was 61.3±12.5 and 64.8±9.7, p=0.035 respectively.
Conclusions: The FMD, ∆PCO2 and BNP were abnormal secondary to decompensated heart failure but did not change with the variation of IABP support.
The ScVO2 proved to be a sensitive tissue perfusion marker to evaluate the response of mechanical support even in short periods of time. The ScVO2 may represent an excellent clinical monitoring tool for patients on IABP as well as assistance to their weaning.
ABBREVIATIONS
2 Some evidence has made its benefits controversial [4-6]. However, the cardiac disease etiology and the indication of IABP ∆PCO : Arteriovenous Carbon Dioxide Gradient; BNP: B-Type should be considered. A recent clinical study showed that IABP Natriuretic Peptide; CI: Cardiac Index; Dmax B: Is Brachial Artery was useful for nonischemic cardiomyopathy critical patients, Maximum Diameter before Reactive Hyperemia; Dmax RH: Is especially as a bridge for cardiac transplantation [7]. Brachial Artery Maximum Diameter after Reactive Hyperemia; vo2 FMD: Flow-Mediated Vasodilatation; IABP: Intra-Aortic Balloon Endothelial dysfunction is a pathological condition mainly c Pump; LVEF: Left Ventricular Dysfunction; S : Central Venous characterized by an altered proportion between vasodilator, OxygenINTRODUCTION Saturation antimitogenic, and anti-thrombogenic agents (endothelium- derived relaxing factors) [8] and vasoconstrictor, prothrombotic, and proliferative agents (endothelium-derived constricting The treatment of critical decompensated heart failure is factors) [9]. In individuals with heart failure, the behavior of the based on the use of vasoactive agents for hemodynamic support endothelial function is already known from the literature [10]. and frequently on the necessity to implement circulatory assist devices [1,2]. Although new devices have brought considerable A recent study demonstrated that the impairment of the improvements in the clinical setting [3]), the intra-aortic endothelial glycocalyx in cardiogenic shock, particularly on balloon pump (IABP) is a useful therapy available for temporary circulating levels of syndecan-1 and glycosaminoglycan heparin ventricular support. sulfate have prognostic relevance, even in patients supported by Cite this article: Fagundes Júnior AAP, Kopel L, Bernoche C, Macatrão-Costa MF, Lopes LN, et al. (2018) Impact of Intra-Aortic Balloon Support on Endothe- lial Function and Tissue Perfusion Markers in Severe Heart Failure. J Cardiol Clin Res 6(4): 1142. Lage et al. (2018) Email:
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IABP [11]. However, the endothelial behavior in patients with ∆%The FMD ∆% of =FMD wasDmax calculated RH – using Dmax the Bformula:X100 IABP support demands complementary studies. Dmax B Several biomarkers associated with heart failure are well known, especially B-type natriuretic peptide (BNP). They are where: Dmax RH is brachial artery maximum associated with the diagnosis and prognosis of the disease [12], diameter after reactive hyperemia; Dmax B is brachial artery however, the impact on acute therapeutic interventions is not maximumStatistical diameter analysis before reactive hyperemia clear. In addition, the evaluation of markers sensitive to low 2 2 peripheral perfusion, such as central venous oxygen saturation c (S VO ) and arteriovenous carbon dioxide gradient (∆PCO ) have For categorical variables, the absolute and relative frequencies long been studied [13-18]. There is much discrepancy in results were calculated. Continuous variables were summarizedvs. asvs. the and conclusions in view of the great heterogeneity of protocols meanvs. and standard deviation values. The paired Student’s t test applied in the studies, particularly in those with short-term was used for comparisons between the conditions (1 2; 2 3; interventions. 1 Software3). The level 9.0 versionof significanceSAS Institute., was set Cary,at p<0.05 NC [23]. Statistical This study aimed to assess the effect of IABP support on the analyses were performed by an independent statistician using 2 2 RESULTS endothelial function and to evaluate the impact of the device on SAS ( ). serum BNP levels and on ScVO and ΔPCO as tissue perfusion markers.MATERIALS AND METHODS The age of the patients included in the study ranged from 19 to 70 years, with a mean of 50±13 years. Among the This experimental and prospective study was performed at patients, 17 (74%) were men, whereas 6 (26%) were women. the intensive care unit of the Heart Institute (InCor-HC-FMUSP). Regarding the etiology of heart failure, 8 patients (34%) The study was designed in accordance with the Human Research presented with idiopathic dilated cardiomyopathy; 9 (39%), Guidelines and Standards (Resolution 196/1996 of the National ischemic cardiomyopathy; 4 (17%) cardiomyopathy induced Health Council) and approved by the ethics committee of the by Chagas disease; and 2 (8%) valve heart disease. The LVEF, Hospital das Clínicas of the University of São Paulo. We evaluated estimated through an echocardiogram performed during patient a cohort of patients hospitalized for heart failure receiving hospitalization, ranged from 14% to 40%, with a mean of 22±8%. ventricular IABP support. The patients included in the study Regarding the use of cardiovascular medications, dobutamine were aged >18 years and had left ventricular dysfunction (LVEF was administered to 21 patients (91%) at a mean dose of <45%), as detected on an echocardiogram through the Teichholz 13.0±7.6 mcg/kg/min; sodium nitroprusside to 12 patients method. All the patients received IABP (Datascope System 98XT, (52%) at 1.9±1.6 mcg/kg/min; milrinone to 1 patient (4%) at 0.6 NJ, USA). Meanwhile, we considered the following parameters as mcg/kg/min; noradrenaline to 2 patients (8%) at 0.5±0.4 mcg/ exclusion criteria: clinical instability of the patient that did not kg/min; nitroglycerin to 1 patient (4%) at 0.79 mcg/kg/min; allow to change the IABP support; clinical signs of severe sepsis captopril to 3 patients (13%) at 70±31 mg/day; hydralazine to 2 and/or septic shock according to the criteria of the American patients (8%) at 93±79.54 mg/day; and isosorbide mononitrate College of Chest Physicians/Society of Critical Care Medicine to 1 patient (4%) at 120 mg/day. There was no modification to [19]; the necessity to modify the dose of vasoactive drugs in the the dose of vasoactive drugs during the protocol. Nine patients course of the study; technical impossibility to obtain images of (39%) were on the waiting list for a heart transplant at the time the brachial artery; cardiac arrhythmias at the time of protocol of inclusion in our study. Out of 8 patients (34%) who were using implementation; and previous brachial artery surgery. antibiotics, none had any signs of severe sepsis or septic shock, which was an exclusion criterion. Urea and creatinine serum Once included in the study, the patients received a 1:1 IABP levels were 54.1±34.2 mg/dL and 1.46±0.86 mg/dL, respectively. support with maximum inflation (condition 1), which was then changed to the ratio 1:3 with minimum inflation with helium gas Considering the laboratory analysis 22 patients were 2 (condition 2) for a period of 20 min. Then, the IABP device was set evaluated and technical problems occurred for one patient. The c to 1:1 with maximum inflation (condition 3). In the 3 periods of results of the S VO (%) reveal a statistically significant difference the study, venous blood was collected from all the patients using between condition 1 and 2 (68.3±10.2 and 61.3±12.5); p<0.002 a central venous catheter to obtain blood gas and serum BNP. The respectively. Difference was also observed between condition arterial blood gas levels were determined at the 3-time points 2 to 3 (the last 64.8±9.7; p=0.035). There was no statistical 2 via an arterial line in the IABP (Figure 1). To assess endothelial difference (p=0.064) between conditions 1 and 3 (Figure 3). The function, a brachial artery ultrasound was performed during analysis of ∆PCO (mmHg) in conditions 1, 2 and 3 (whose values reactive hyperemia to evaluate endothelial-dependent flow- were respectively: 7.01±4.08, 8.07±3.40 and 6.54±4.07) was mediated vasodilatation (FMD) according to previous guideline not statistically significant. In addition, the results of BNP (pg/ [20] (Figure 2). ml) conditions 1, 2 and 3 were also not statistically significant TM Cypress , considering their respective values: 1077±791, 1228 ± 1068 and The measurement of brachial artery diameter and blood flow Siemens Medic al Solutions USA, Inc. CA 1125±929. The mean of FMD (%) was 9.21±12.81 in condition velocity was performed with an ultrasound device ( 1, 4.32±7.15 in condition 2 and 4.14±7.11 in condition 3. Then, ) using a linear high- there was no statistical significance between the conditions resolution transducers (10 Mhz) and a software developed at the (Figure 4). Heart Institute [21, 22]. J Cardiol Clin Res 6(4): 1142 (2018) 2/6 Lage et al. (2018) Email:
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Figure 1
Study design, IABP: intra-aortic balloon; condition 1 and 3: ratio 1:1; condition 2: ratio 1:3; BNP: B-type natriuretic peptide; US: ultrasound.
Figure 2
Flow velocity curves of brachial artery - A: Double pulse using the IABP support at baseline; B: double pulse using the IABP support after reactive hyperemia (HR).
Figure 3 2
Variation of central venous oxygen saturation (SVcO %) between condition 1, condition 2 and condition 3, paired t-Student test, mean ± standard error, significance p<0.05. J Cardiol Clin Res 6(4): 1142 (2018) 3/6 Lage et al. (2018) Email:
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Figure 4
Delta percentual of brachial artery flow-mediated dilatation (∆% FMD) in condition 1, condition 2 and condition 3, paired t-Student test, mean ± standard. DISCUSSION Endothelial dysfunction may induce heart failure progression, which may cause peripheral and central effects. Increased arterial The patients included in this study were hospitalized for stiffness and reduced compliance increase the ventricular decompensated heart failure. They had a severe myocardial afterload and left ventricular end-diastolic stress, which leads to damage and despite the optimized pharmacological support, heart dilatation and failure [27-29]. mechanical devices to control the low cardiac output were necessary. This is the first study that analyzed the endothelial function in critical cardiac patients, receiving ventricular IABP support, It is important to note that the sample of this study did being excluded AMI patients. not include patients with circulatory collapse secondary to acute coronary insufficiency. It included patients with chronic In our study, although patients had full IABP support, we cardiomyopathy whose mechanical support was necessary observed that FMD was diminished since the condition 1, to overcome acute decompensation or as a bridge for cardiac in accordance with with previous findings in the literature transplantation. Thus, as we have seen in previous studies [7], considering patients with heart failure [30]. Considering the perspectives for IABP benefit are quite different from studies condition 2, there was a reduction in FMD, which remained evaluating acute myocardial infarction [4] and surgical patients unrecovered after the IABP was in condition 3 (Figure 3). [6]. This trend was not statistically significant but showed severe endothelial dysfunction, with mean FMD values of less than 10%, Considering this perspective of benefit, our purpose was to which did not recover following the return of full IABP support. It evaluate possible markers of improvement of the peripheral flow is possible that the 20-minute interval between condition 2 and provided by the mechanical support. condition 3 was not enough to restore endothelial function to In this cohort we evaluated the effect of the IABP support on basalBiomarkers levels, which was already quite impaired. 2 2 endothelial function, its influence on BNP serum levels and on tissueEndothelial perfusion dysfunction markers (ScVO and ∆PCO ). BNP can be considered a marker of the severity of ventricular dysfunction. The literature shows that plasma levels of BNP have Heart failure alters the endothelial function of large a possible correlation with LVEF and glomerular filtration [31]. conductance and small resistance arteries [24]. The specific In our study, we observed high levels of plasma BNP, mechanisms that modulate endothelial function include confirming the severity of ventricular dysfunction in the sample decreased peripheral blood flow, cytokine activation, increased of patients included. Under the conditions of the protocol, there activity of the angiotensin-converting enzyme, increased were fluctuations of BNP levels without significant modification oxidative stress, and enhanced endothelin production [10, 25]. at constant high values. These factors contribute to the decreased synthesis and release of nitric oxide and its increased inactivation because of the The literature demonstrates that BNP and other serum generation of oxygen free radicals. Moreover, the vascular tone biomarkers in cardiogenic shock can be reduced with mechanical increases with the endothelin production, which competes with circulatory support; however, with a longer period (7 days) of nitric oxide vasodilation [26]. patients’ observation [32]. J Cardiol Clin Res 6(4): 1142 (2018) 4/6 Lage et al. (2018) Email:
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2 This research did not receive any specific grant from funding agenciesREFERENCES in the public, commercial, or not-for-profit sectors. The ∆PCO measurements reflect the adequacy of cardiac 2 index (CI) to oxygen demand. It has an inverse relationship with CI, which means an elevated ∆PCO may be a marker of low 1. Marik PE, Flemmer M. Narrative review: the management of acute cardiac index [33, 34].2 decompensated heart failure. J Intensive Care Med. 2012; 27: 343-353. In fact, the ∆PCO values observed in our study were high, 2. Brown JR, Gottlieb SS. Acute decompensated heart failure. Cardiol consistent with low cardiac output. They oscillated consistently Clin. 2012; 30: 665-671. with the IABP intervention, however the value trend was not 3. 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Cite this article Fagundes Júnior AAP, Kopel L, Bernoche C, Macatrão-Costa MF, Lopes LN, et al. (2018) Impact of Intra-Aortic Balloon Support on Endothelial Function and Tissue Perfusion Markers in Severe Heart Failure. J Cardiol Clin Res 6(4): 1142.
J Cardiol Clin Res 6(4): 1142 (2018) 6/6