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A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload
IJCA-24932; No of Pages 5 International Journal of Cardiology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload☆ Marco Morpurgo a, Mario Pasqualini b, Maria Cristiana Brunazzi b, Gabriele Vianello c, Roberto Valle c, Loris Roncon d, Fulvio Fiorini d, Nadia Aspromonte e, Mario Barbiero f, Marco Goldoni g, Giancarlo Marenzi a,⁎ a
Centro Cardiologico Monzino, I.R.C.C.S., Milan, Italy Pieve di Coriano Hospital, Italy Chioggia Hospital, Chioggia, Italy d Santa Maria della Misericordia Hospital, Rovigo, Italy e San Filippo Neri Hospital, Rome, Italy f Mater Salutis Hospital, Legnago, Italy g Haemotronic, S.p.A., Mirandola, Italy b c
a r t i c l e
i n f o
Article history: Received 21 October 2016 Received in revised form 13 March 2017 Accepted 24 April 2017 Available online xxxx Keywords: Ultrafiltration Acute heart failure Congestive heart failure Feasibility study
a b s t r a c t Objectives: The need for a central venous catheter has limited the widespread use of ultrafiltration in daily clinical practice for the treatment of acute heart failure (AHF) with overt fluid overload. We evaluated the feasibility of a new ultrafiltration device, the CHIARA (Congestive Heart Impairment Advanced Removal Approach) system, that utilizes a single-lumen cannula (17G, multi-hole) inserted in a peripheral vein of the arm. Methods: In this multicenter, prospective, feasibility study, consecutive ultrafiltration treatments (lasting ≥ 6 hours and with an ultrafiltration rate ≥100 ml/h) with the CHIARA device and a single peripheral venous approach were performed at 6 Italian hospitals. For each session, we evaluated the performance of the venous access, the ultrafiltrate volume removed, and the cause of its interruption. Results: One-hundred-three ultrafiltration sessions were performed in 55 patients with AHF (average 1.9 ± 1.7 treatment/patient). The overall median length of ultrafiltration treatment was 14 h (interquartile range 7–21) with removal of 3266 ± 3088 ml of fluid (183 ± 30 ml/hour). The treatment was successfully completed in 92 (89%) sessions and in 80% of patients. The mean suction flow rate from the vein was 70 ± 20 ml/min, while the mean re-injection flow rate was 98 ± 26 ml/min. There were no clinically relevant complications related to the venous access and/or to the anticoagulant therapy with heparin. Conclusions: The study demonstrated that the CHIARA system satisfies clinical applicability and efficacy criteria in the treatment of AHF, in terms of adequate fluid removal through a single peripheral venous access. © 2017 Elsevier B.V. All rights reserved.
1. Introduction Extracorporeal ultrafiltration has been proposed for the treatment of patients with acute heart failure (AHF) and overt fluid overload not fully responsive to diuretics and as an alternative to high-dose diuretic therapy, with the aim to obtain more decongestion and less neurohormonal activation [1–5]. Although it represents a rapid and physiologic method of fluid removal, the need for a double-lumen central venous catheter (CVC) and for admission to the Intensive Care Unit (ICU) has limited its widespread use in daily clinical practice. These limitations can possibly be overcome by the recent development of a new dedicated device for ultrafiltration, the CHIARA (Congestive Heart Impairment Advanced
Removal Approach) system that uses a single-lumen cannula inserted in a peripheral vein of the arm. This system is based on a push-pull syringe pump, a ball with an inner silicone membrane for blood and saline separation, and two check valves that drive the blood from and to the same peripheral vein through alternate flows, which can be adjusted separately (Fig. 1). The CHIARA system has never been used in the clinical setting thus far, and we have no information about its operative performance. Therefore, we designed a multicenter study to evaluate the feasibility of this innovative “minimal invasive” ultrafiltration approach for the treatment of AHF. 2. Methods
☆ All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author at: Centro Cardiologico Monzino, Via Parea 4, 20138 Milan, Italy. E-mail address: [email protected] (G. Marenzi).
2.1. Study population Patients with AHF and overt fluid overload were consecutively enrolled from January 31st, 2013 to December 31st, 2015, at 6 Italian hospitals.
http://dx.doi.org/10.1016/j.ijcard.2017.04.088 0167-5273/© 2017 Elsevier B.V. All rights reserved.
Please cite this article as: M. Morpurgo, et al., A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.04.088
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M. Morpurgo et al. / International Journal of Cardiology xxx (2017) xxx–xxx
Fig. 1. Left = the CHIARA system; right = scheme of ultrafiltration using the CHIARA system, based on an alternating axial piston pump, constituted by a syringe, a blood/saline separation ball (pump chamber) and two unidirectional valves, that draws and re-injects the blood from and to the same peripheral vein of the arm. BD = blood detector; BLD = blood leakage detector in the ultrafiltrate line; HTC = hematocrit sensor.
Inclusion criteria were: AHF with age N 18 years, New York Heart Association (NYHA) functional class III or IV, systolic and/or diastolic dysfunction, estimated weight gain due to peripheral fluid overload ≥4 kg in the preceding 2 months (estimation of reference body weight was based on body weight referred by the patient as their normal weight), poor response to intravenous diuretics at discretion of the treating physician, and an adequate peripheral venous access allowing a withdrawal flow rate ≥ 60 ml/min (suitable peripheral access). Exclusion criteria were: contraindications to anticoagulation, severe renal insufficiency (serum creatinine ≥ 3.0 mg/dl), acute pulmonary edema, cardiogenic shock, and presence of acute or chronic clinical conditions considered by the clinicians as potential contraindications to ultrafiltration. The investigation conforms with the principles outlined in the Declaration of Helsinki. The Ethical Committees of all the institutions approved the research protocol, and all subjects gave written informed consent to participate in the study.
Patients without adequate withdrawal flow rate through the peripheral cannula were excluded from the study; in these patients, the decision to use a CVC, as an alternative approach for ultrafiltration, was left to the discretion of the physician.
2.4. Anticoagulation protocol The following anticoagulation protocol was recommended during ultrafiltration: a loading bolus of 3000–5000 IU heparin (2000 IU for patients with an international normalized ratio value ≥ 2) was directly administered into the circuit, upstream the filter; then, a continuous heparin infusion rate of 500–800 UI/h was maintained during the entire ultrafiltration session. Lower heparin bolus and infusion rates were allowed if clinically indicated. Due to the short duration of each ultrafiltration session, no measurement of anticoagulation parameters for adjustment of heparin dose was required.
2.2. Study protocol This study was designed as a prospective, open-label, observational, multicenter study. A complete clinical and laboratory evaluation was made, with particular attention to body weight and fluid balance, renal function (serum creatinine concentration, estimated glomerular filtration rate [eGFR]), and plasma electrolytes, all of which were evaluated before and 24 h after ultrafiltration. All eligible patients were then treated with a single or multiple session(s) of ultrafiltration. Ultrafiltration sessions were performed only during the hours of the day (maximal length allowed for each single session 12 h); this was planned in order to avoid nurse work overload during the night shift. If required, a new session was performed the following morning after a temporary treatment withdrawal during the nighttime. The same peripheral venous cannula was maintained during the overall ultrafiltration treatment. All ultrafiltration treatments were performed with the CHIARA system (MediCon Ingegneria S.r.l., Budrio [Bologna], Italy) and a dedicated circuit (CHIARAKIT, Haemotronic®, S.p.A., Mirandola [Modena], Italy). The initial ultrafiltration rate, as well as its possible adjustment during the procedure, was left to the discretion of the physician in charge of the patients. Cumulative fluid removal (ultrafiltration plus urine output) was recommended not to exceed 75% of the estimated initial body weight increase to reduce the risk of hypovolemia-induced acute kidney injury associated with excessive dehydration [6]. Achievement of this target was defined as end of treatment. Moreover, hematocrit changes (%) were automatically and continuously monitored inside the extracorporeal circuit by a dedicated integrated sensor in order to guide physicians for ultrafiltration rate adjustments (reduction of ultrafiltration rate in case of hematocrit increase), and thus prevent hypovolemia during ultrafiltration [3]. Additional pharmacologic therapy was left to the discretion of the cardiologist in charge of the patient. Specifically, diuretic therapy withdrawal was not required and continuation of diuretic therapy at unchanged doses recommended during ultrafiltration sessions. 2.3. Peripheral venous access In order to increase the success rate and avoid premature circuit failure and/or filter clotting, accurate preliminary selection and evaluation of the peripheral vein access were performed. The choice of venous access followed this sequence: antecubital veins, cephalic veins, and basilic veins. A single-lumen cannula (17 gauge, single-lumen, multihole, 25–32 mm long catheter) was inserted in the best approachable vessel; the withdrawal flow rate was manually estimated by a syringe and a dedicated device (Haemocatch®, Haemotronic®, S.p.A., Mirandola [Modena], Italy). In patients in whom a withdrawal flow rate ≥ 10 ml/10 s was confirmed, ultrafiltration treatment was started.
Fig. 2. Diagram showing the flow of participants through each stage of the study. CVC = central venous catheter.
Please cite this article as: M. Morpurgo, et al., A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.04.088
M. Morpurgo et al. / International Journal of Cardiology xxx (2017) xxx–xxx 2.5. Study end points and statistical analysis The primary end point of the study was defined as the ability of the CHIARA system to perform an ultrafiltration session of ≥6 h, with an ultrafiltration rate ≥ 100 ml/h. Any complications related to the insertion of the cannula and to the anticoagulation treatment were also evaluated as secondary safety end points. One-hundred ultrafiltration sessions were planned; such a sample size should allow to estimate a rate of ultrafiltration treatment failure of 5%, with 95% confidence intervals ranging from 1.6% to 11% (estimated by binomial confidence limits). Paired t test was used to compare laboratory variables before and after ultrafiltration. Data are expressed as mean ± standard deviation or as median and interquartile range (IQR), as appropriate, or as actual numbers and percentages.
3. Results During the study period, a total of 72 patients were initially screened (Fig. 2). Seventeen of them were excluded. Among excluded patients, the CHIARA treatment was still performed for clinical reasons, via a CVC, in 13 patients (in 7 patients a CVC was already inserted and the physicians chose to use it for the ultrafiltration treatment, while in 6 patients a peripheral venous access with a ≥ 60 ml/min withdrawal flow rate was not found and a CVC was then positioned). Fifty-five subjects were therefore included in the study and underwent a total of 103 treatments (average 1.9 ± 1.7 sessions/patient). The baseline (before ultrafiltration) clinical characteristics of the study population are summarized in Table 1. The average estimated baseline fluid overload was 8.2 ± 4.5 kg (range 4–30 kg). Of the 103 treatments performed, 92 (89%) were successfully completed, with a cumulative median length of treatment of 14 (IQR 7–21) hours, a mean ultrafiltration rate of 183 ± 30 ml per hour, a cumulative ultrafiltration volume of 3266 ± 3088 ml, and a total weight loss of 5.8 ± 4.1 kg. The mean suction flow rate from the vein was 70 ± 20 ml/min, while the mean re-injection flow rate was Table 1 Baseline characteristics of the study patients. Clinical characteristics N Age, years Men, n (%) Diabetes mellitus, n (%) Systemic hypertension, n (%) COPD, n (%) NYHA class III, n (%) NYHA class IV, n (%) Chronic atrial fibrillation, n (%) PM/ICD/CRT, n (%) LVEF, % Heart rate, beats/min Systolic blood pressure, mm Hg
55 74 ± 9 29 (52%) 17 (30%) 9 (16%) 7 (12%) 22 (40%) 33 (60%) 23 (41%) 14 (25%) 39 ± 11 75 ± 15 114 ± 15
Heart failure cause Ischemic CMP, n (%) Valvular heart disease Post-myocarditis CMP other CMP, n (%)
25 (46%) 18 (32%) 1 (0.5%) 11 (21%)
Medications ACE-inhibitors or ARB, n (%) Intravenous furosemide dose, mg/day Beta-blockers, n (%) Aldosterone antagonists, n (%)
19 (34%) 193 ± 150 28 (50%) 21 (38%)
Laboratory measures Urea, mg/dl Serum creatinine, mg/dl eGFR, ml/min/1.73 m2 Sodium, mEq/l Potassium, mEq/l
103 ± 40 1.6 ± 0.5 52 ± 30 137 ± 4 3.7 ± 0.6
ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; CMP = cardiomyopathy; COPD = chronic obstructive pulmonary disease; CRT = cardiac resynchronization therapy; eGFR = estimated glomerular filtration rate; HF = heart failure; ICD = implantable cardioverter-defibrillator; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; PM = pacemaker.
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98 ± 26 ml/min. The duration of each ultrafiltration session was 8 (IQR 7–8) hours. When patients, and not ultrafiltration sessions, were considered, a 20% rate of treatment failure occurred (11/55 patients). Table 2 shows the procedural details of ultrafiltration in each treated patient. No patient experienced complications related to the insertion of the cannula and to the ultrafiltration procedure. In one case, asymptomatic, transient heparin-induced thrombocytopenia was observed at the end of the treatment. No serious adverse clinical event was recorded during the study. Laboratory data measured before and 24 h after ultrafiltration treatment are shown in Table 3. 4. Discussion The results of this prospective, multicenter feasibility study on ultrafiltration in patients with AHF and severe fluid overload demonstrated that short-term treatment with a single-lumen peripheral access and with the CHIARA device is feasible and safe. Indeed, ultrafiltration was successfully completed in 80% of treated patients and in almost 90% of sessions, without adverse events. Some previous studies have pointed towards possible benefits of ultrafiltration, when compared to diuretic therapy, in removing fluid overload without eliciting neurohormonal compensatory mechanisms [3,4,7,8]. In these studies, most of the reported serious adverse effects of this kind of treatment were related to the insertion of a CVC, to its management, and to the anti-coagulation protocol utilized [5,9]. The new CHIARA device, by utilizing a low-volume extracorporeal circuit and a single-lumen peripheral venous access, may overcome most of the abovementioned procedural risks, and have some potential advantages, when compared to standard ultrafiltration systems. The first advantage is the reduction of adverse events related to central venous catheterization. In fact, inserting a small (17 gauge) cannula in a peripheral vein of the arm is less traumatic and dangerous for the patient than positioning a multi-lumen cannula in a central vein. Contemporary ultrafiltration devices that enable a peripheral approach may sometimes require two venous accesses – one for blood withdrawal and one for its restitution – which are not easily available in fluid overloaded patients. Moreover, a continuous withdrawal blood flow through the veins of the arm, like that used in these ultrafiltration devices, is particularly problematic in AHF patients, resulting in frequent premature failure of the treatment. Conversely, the alternate flow utilized by the CHIARA system, which includes two different phases (withdrawal and return), allows differentiating the speed of blood suction from and return into the vein. This step flow behavior, combined with a dedicated algorithm, may reduce the vein collapse. Another important advantage is that the reduced volume of blood inside the extracorporeal circuit, when compared to conventional renal replacement therapy modalities (50 ml vs. about 200–300 ml) implies a reduced risk of blood loss in the case of clotting of the circuit. Furthermore, due to the reduced contact surface between blood and tubing set and the air-free system, the heparin dose required to prevent the clotting of the system could be lower than that usually utilized in conventional treatments, as well as in the present study, thus diminishing the risk of bleeding or other complications related to anticoagulants (i.e. thrombocytopenia). Indeed, during ultrafiltration, the interface between air and blood and the turbulences in the bubble traps are known inductors of the coagulation cascade [10]. Finally, CHIARA does not necessarily require the admission of the patient to the ICU. While conventional ultrafiltration treatments are often performed in an ICU setting, or on specific wards, like a heart failure or cardiac telemetry units, or dialysis department, treatments with this new device can be managed in a normal ward or even in the emergency department, thanks to its minimally invasive approach, its reduced procedural risk, and its lower nurse surveillance requirement. In contrast to patients admitted to an ICU who remain confined to bed for many days
Please cite this article as: M. Morpurgo, et al., A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.04.088
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M. Morpurgo et al. / International Journal of Cardiology xxx (2017) xxx–xxx
Table 2 Procedural characteristics of ultrafiltration sessions. Pt
sessions (n)
Catheter venous site
Estimated fluid overload (kg)
Overall UF volume (ml)
Average UF rate (ml/hour)
Heparin bolus (IU)
Heparin infusion (IU/hour)
withdrawal/ return flow rate (ml/min)
Reason for stopping UF
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55
1 1 1 1 3 1 4 1 1 2 1 2 1 2 2 2 1 1 1 1 1 1 1 2 1 8 1 1 3 2 2 2 2 2 1 1 3 4 3 10 1 1 1 3 1 1 1 1 1 1 1 3 4 1 1
antecub. antecub. basilic cephalic antecub. antecub. antecub. median basilic cephalic antecub. basilic antecub. antecub. antecub. basilic antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. basilic antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. basilic antecub. basilic antecub. antecub.
8 8 10 4 10 5 11 10 10 6 4 8 4 5 7 30 5 10 7 6 6 8 12 5 7 20 9 7 9 4 5 6 5 6 8 10 8 10 10 18 7 4 10 15 12 7 4 6 8 5 4 10 6 8 5
1990 1000 850 1200 4500 1150 5500 1300 830 2250 1455 2315 1500 3400 3230 2480 1260 2000 1970 3600 494 5650 1650 10805 4300 1970 3150 2880 2650 2400 1650 1700 4315 4000 3870 17866 1050 6150 2700 1500 1500 1500 1100 3760 4760 -
248 166 212 192 187 165 172 162 138 161 181 158 187 212 202 160 210 210 195 156 70 182 206 200 215 151 197 206 165 170 206 170 180 129 155 200 175 207 190 230 250 176 183 209 194 -
5000 2500 3000 2500 4000 4000 2000 3000 2000 2000 4000 2000 2000 2000 2000 5000 2000 1600 2000 1000 1000 3000 6000 3500 3000 3000 2000 2000 2000 2500 2000 3500 4000 2500 4000 5000 3000 2000 6000 2000 2000 2000 3500 3500 5000 2000 2000 4000 4000 2000 4000 1400 4000 2000 2000
1000 550 1000 600 600 800 400 600 750 800 600 600 600 600 600 1600 800 600 500 500 1200 800 750 750 500 700 500 800 1000 650 900 500 700 700 1500 800 800 800 1250 1000 1000 800 500 400 600 -
80/120 45/140 62/125 50/142 77/85 60/100 30/100 60/110 45/45 40/90 50/120 50/50 60/100 40/90 60/80 50/40 80/120 70/100 80/100 80/110 35/120 50/50 80/80 50/70 100/120 80/120 97/115 72/120 90/130 75/120 78/105 115/115 70/90 70/90 65/70 80/80 70/90 80/90 90/65 98/116 100/145 54/100 70/110 100/100 70/70 -
end of treatment end of treatment kinking of the cannula end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment failure b 1 hour end of treatment failure b 1hour end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment failure b 1 hour failure b 1 hour end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment failure b 1 hour failure b 1 hour end of treatment end of treatment end of treatment failure b 1 hour failure b 1 hour end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment failure b 1 hour failure b 1 hour
Antecub. = antecubital vein; UF = ultrafiltration.
Table 3 Laboratory parameters before and after ultrafiltration treatment.
BNP, pg/ml Urea, mg/dl Serum creatinine, mg/dl eGFR, ml/min/1.73 m2 Sodium, mEq/l Potassium, mEq/l
Before ultrafiltration
After ultrafiltration
P value
1580 ± 1194 103 ± 40 1.6 ± 0.5 52 ± 30 137 ± 4 3.9 ± 0.6
1421 ± 1092 102 ± 50 1.5 ± 0.5 58 ± 34 137 ± 5 4.1 ± 0.7
0.46 0.91 0.29 0.32 1.00 0.11
BNP = brain natriuretic peptide; eGFR = estimated glomerular filtration rate (MDRD formula); UF = ultrafiltration.
during ultrafiltration therapy, those treated with the CHIARA system can easily be mobilized between two consecutive ultrafiltration sessions. Specifically, we designed this study protocol, characterized by a relatively short treatment period (daily sessions of 6–12 h), in order to investigate the potential applicability of the CHIARA system in this specific clinical scenario. Indeed, our study confirms that 89% of treatments can be successfully carried out during this pre-defined treatment period. In our study, the feasibility of the treatment and its success were strictly related to the selection of the venous access. An appropriate peripheral vein allowing a withdrawal flow rate of at least 10 ml in 10 s, and the use of a dedicated cannula (17 gauge, single-lumen, multihole catheter) were crucial to achieve a good performance of the system
Please cite this article as: M. Morpurgo, et al., A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.04.088
M. Morpurgo et al. / International Journal of Cardiology xxx (2017) xxx–xxx
for the entire duration of the treatment, and to avoid troublesome, expensive premature circuit losses. We suggest that an accurate preliminary evaluation of the peripheral access should be performed before starting an ultrafiltration treatment with CHIARA. Notably, in our study, the treatment was started with a blood flow ≥ 60 ml/min and was then lowered during the session up to a minimum of 30 ml/min in two patients; this suggests that the limit of withdrawal flow rate we chose to include patients in the present study could possibly be lowered. The results of any medical device feasibility study, such as this one, must be interpreted with caution. Firstly, since there was no control group undergoing procedures without the CHIARA system in this study, there can be no formal assessment of the clinical impact, if any, of this kind of treatment. Secondly, the economic impact of ultrafiltration was not evaluated in our trial, and should be a matter of dedicated investigation. Indeed, at the time the study was designed, the CHIARA system was not commercially available, and the costs of the procedure were unknown. Thirdly, we planned to perform only shortterm (≥ 6 h) sessions. Therefore, the feasibility of a single, longerlasting continuous treatment with CHIARA remains unexplored. However, in patients in whom a CVC was used, much longer treatments, up to 48 h, were performed. This suggests that prolonged continuous sessions can be performed if needed, and that, although the device was specifically designed for a peripheral venous approach, it can also be used with traditional approaches. Indeed, in cases in which we either failed to find a suitable peripheral approach or the physicians chose to directly shift to a CVC, the treatment with the CHIARA device resulted to be as effective and as safe as treatments performed with the peripheral approach. Finally, physicians having a long experience with ultrafiltration treated all patients, and this aspect may have significantly impacted the results of our study. Therefore, the overall applicability of our findings remains to be confirmed. The Global rEgistry on decongestioN Therapy using Less invasivE UltraFiltration (GENTLE-UF; clinicaltrials.gov Identifier: NCT02769351), which was started in December 2015, intends to investigate the impact of the CHIARA system in a real-world AHF population. It is expected that it could confirm our preliminary results and more precisely identify the clinical characteristics of patients who may benefit most from this therapeutic approach. 5. Conclusions The results of our study demonstrated that treating AHF with the CHIARA system satisfies safety and performance criteria, in terms of
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adequate fluid removal through a single peripheral venous access. Based on these encouraging preliminary results and on their potential benefits, larger studies are warranted to ultimately prove its efficacy and to define its clinical role in the treatment of AHF with overt fluid overload. Conflict of interest None. Funding source This work was supported by the Amici del Cuore “Maria Sandrini” Association, Legnago, Verona, Italy. The funding source had no role in study design, data collection, analysis, interpretation, or reporting. Disclosure Dr. Marco Goldoni is an employee of Haemotronic. None of the other authors declared a conflict of interest related to this work. References [1] M.E. Silverstein, C.A. Ford, M.J. Lysaght, L.W. Henderson, Treatment of severe fluid overload by ultrafiltration, N. Engl. J. Med. 291 (1974) 747–751. [2] B. Canaud, M. Leblanc, H. Leray-Moragues, S. Delmas, K. Klouche, J.J. Beraud, Slow continuous and daily ultrafiltration for refractory congestive heart failure, Nephrol. Dial. Transplant. 13 (Suppl. 4) (1998) 51–55. [3] G. Marenzi, G. Lauri, M. Grazi, E. Assanelli, J. Campodonico, P. Agostoni, Circulatory response to fluid overload removal by extracorporeal ultrafiltration in refractory congestive heart failure, J. Am. Coll. Cardiol. 38 (2001) 963–968. [4] G. Marenzi, S. Grazi, F. Giraldi, et al., Interrelation of humoral factors, hemodynamics, and fluid and salt metabolism in congestive heart failure: effects of extracorporeal ultrafiltration, Am. J. Med. 941 (1993) 49–56. [5] G. Marenzi, M. Morpurgo, P. Agostoni, Continuous ultrafiltration in acute decompensated heart failure: current issues and future directions, Am. J. Cardiovasc. Drugs 15 (2015) 103–112. [6] G. Marenzi, M. Muratori, E.R. Cosentino, et al., Continuous ultrafiltration for congestive heart failure. The CUORE trial, J. Card. Fail. 20 (2014) 9–17. [7] M.R. Costanzo, M.E. Guglin, M.T. Saltzberg, et al., Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure, J. Am. Coll. Cardiol. 49 (2007) 675–683. [8] M.R. Costanzo, D. Negoianu, B.E. Jaski, et al., Aquapheresis versus intravenous diuretics and hospitalizations for heart failure, JACC Heart Fail. 4 (2016) 95–105. [9] B.A. Bart, S.R. Goldsmith, K.L. Lee, et al., Ultrafiltration in decompensated heart failure with cardiorenal syndrome, N. Engl. J. Med. 367 (2012) 2296–2304. [10] K.G. Fisher, Essentials of anticoagulation in hemodialysis, Hemodial. Int. 11 (2007) 178–189.
Please cite this article as: M. Morpurgo, et al., A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.04.088
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload☆ Marco Morpurgo a, Mario Pasqualini b, Maria Cristiana Brunazzi b, Gabriele Vianello c, Roberto Valle c, Loris Roncon d, Fulvio Fiorini d, Nadia Aspromonte e, Mario Barbiero f, Marco Goldoni g, Giancarlo Marenzi a,⁎ a
Centro Cardiologico Monzino, I.R.C.C.S., Milan, Italy Pieve di Coriano Hospital, Italy Chioggia Hospital, Chioggia, Italy d Santa Maria della Misericordia Hospital, Rovigo, Italy e San Filippo Neri Hospital, Rome, Italy f Mater Salutis Hospital, Legnago, Italy g Haemotronic, S.p.A., Mirandola, Italy b c
a r t i c l e
i n f o
Article history: Received 21 October 2016 Received in revised form 13 March 2017 Accepted 24 April 2017 Available online xxxx Keywords: Ultrafiltration Acute heart failure Congestive heart failure Feasibility study
a b s t r a c t Objectives: The need for a central venous catheter has limited the widespread use of ultrafiltration in daily clinical practice for the treatment of acute heart failure (AHF) with overt fluid overload. We evaluated the feasibility of a new ultrafiltration device, the CHIARA (Congestive Heart Impairment Advanced Removal Approach) system, that utilizes a single-lumen cannula (17G, multi-hole) inserted in a peripheral vein of the arm. Methods: In this multicenter, prospective, feasibility study, consecutive ultrafiltration treatments (lasting ≥ 6 hours and with an ultrafiltration rate ≥100 ml/h) with the CHIARA device and a single peripheral venous approach were performed at 6 Italian hospitals. For each session, we evaluated the performance of the venous access, the ultrafiltrate volume removed, and the cause of its interruption. Results: One-hundred-three ultrafiltration sessions were performed in 55 patients with AHF (average 1.9 ± 1.7 treatment/patient). The overall median length of ultrafiltration treatment was 14 h (interquartile range 7–21) with removal of 3266 ± 3088 ml of fluid (183 ± 30 ml/hour). The treatment was successfully completed in 92 (89%) sessions and in 80% of patients. The mean suction flow rate from the vein was 70 ± 20 ml/min, while the mean re-injection flow rate was 98 ± 26 ml/min. There were no clinically relevant complications related to the venous access and/or to the anticoagulant therapy with heparin. Conclusions: The study demonstrated that the CHIARA system satisfies clinical applicability and efficacy criteria in the treatment of AHF, in terms of adequate fluid removal through a single peripheral venous access. © 2017 Elsevier B.V. All rights reserved.
1. Introduction Extracorporeal ultrafiltration has been proposed for the treatment of patients with acute heart failure (AHF) and overt fluid overload not fully responsive to diuretics and as an alternative to high-dose diuretic therapy, with the aim to obtain more decongestion and less neurohormonal activation [1–5]. Although it represents a rapid and physiologic method of fluid removal, the need for a double-lumen central venous catheter (CVC) and for admission to the Intensive Care Unit (ICU) has limited its widespread use in daily clinical practice. These limitations can possibly be overcome by the recent development of a new dedicated device for ultrafiltration, the CHIARA (Congestive Heart Impairment Advanced
Removal Approach) system that uses a single-lumen cannula inserted in a peripheral vein of the arm. This system is based on a push-pull syringe pump, a ball with an inner silicone membrane for blood and saline separation, and two check valves that drive the blood from and to the same peripheral vein through alternate flows, which can be adjusted separately (Fig. 1). The CHIARA system has never been used in the clinical setting thus far, and we have no information about its operative performance. Therefore, we designed a multicenter study to evaluate the feasibility of this innovative “minimal invasive” ultrafiltration approach for the treatment of AHF. 2. Methods
☆ All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author at: Centro Cardiologico Monzino, Via Parea 4, 20138 Milan, Italy. E-mail address: [email protected] (G. Marenzi).
2.1. Study population Patients with AHF and overt fluid overload were consecutively enrolled from January 31st, 2013 to December 31st, 2015, at 6 Italian hospitals.
http://dx.doi.org/10.1016/j.ijcard.2017.04.088 0167-5273/© 2017 Elsevier B.V. All rights reserved.
Please cite this article as: M. Morpurgo, et al., A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.04.088
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M. Morpurgo et al. / International Journal of Cardiology xxx (2017) xxx–xxx
Fig. 1. Left = the CHIARA system; right = scheme of ultrafiltration using the CHIARA system, based on an alternating axial piston pump, constituted by a syringe, a blood/saline separation ball (pump chamber) and two unidirectional valves, that draws and re-injects the blood from and to the same peripheral vein of the arm. BD = blood detector; BLD = blood leakage detector in the ultrafiltrate line; HTC = hematocrit sensor.
Inclusion criteria were: AHF with age N 18 years, New York Heart Association (NYHA) functional class III or IV, systolic and/or diastolic dysfunction, estimated weight gain due to peripheral fluid overload ≥4 kg in the preceding 2 months (estimation of reference body weight was based on body weight referred by the patient as their normal weight), poor response to intravenous diuretics at discretion of the treating physician, and an adequate peripheral venous access allowing a withdrawal flow rate ≥ 60 ml/min (suitable peripheral access). Exclusion criteria were: contraindications to anticoagulation, severe renal insufficiency (serum creatinine ≥ 3.0 mg/dl), acute pulmonary edema, cardiogenic shock, and presence of acute or chronic clinical conditions considered by the clinicians as potential contraindications to ultrafiltration. The investigation conforms with the principles outlined in the Declaration of Helsinki. The Ethical Committees of all the institutions approved the research protocol, and all subjects gave written informed consent to participate in the study.
Patients without adequate withdrawal flow rate through the peripheral cannula were excluded from the study; in these patients, the decision to use a CVC, as an alternative approach for ultrafiltration, was left to the discretion of the physician.
2.4. Anticoagulation protocol The following anticoagulation protocol was recommended during ultrafiltration: a loading bolus of 3000–5000 IU heparin (2000 IU for patients with an international normalized ratio value ≥ 2) was directly administered into the circuit, upstream the filter; then, a continuous heparin infusion rate of 500–800 UI/h was maintained during the entire ultrafiltration session. Lower heparin bolus and infusion rates were allowed if clinically indicated. Due to the short duration of each ultrafiltration session, no measurement of anticoagulation parameters for adjustment of heparin dose was required.
2.2. Study protocol This study was designed as a prospective, open-label, observational, multicenter study. A complete clinical and laboratory evaluation was made, with particular attention to body weight and fluid balance, renal function (serum creatinine concentration, estimated glomerular filtration rate [eGFR]), and plasma electrolytes, all of which were evaluated before and 24 h after ultrafiltration. All eligible patients were then treated with a single or multiple session(s) of ultrafiltration. Ultrafiltration sessions were performed only during the hours of the day (maximal length allowed for each single session 12 h); this was planned in order to avoid nurse work overload during the night shift. If required, a new session was performed the following morning after a temporary treatment withdrawal during the nighttime. The same peripheral venous cannula was maintained during the overall ultrafiltration treatment. All ultrafiltration treatments were performed with the CHIARA system (MediCon Ingegneria S.r.l., Budrio [Bologna], Italy) and a dedicated circuit (CHIARAKIT, Haemotronic®, S.p.A., Mirandola [Modena], Italy). The initial ultrafiltration rate, as well as its possible adjustment during the procedure, was left to the discretion of the physician in charge of the patients. Cumulative fluid removal (ultrafiltration plus urine output) was recommended not to exceed 75% of the estimated initial body weight increase to reduce the risk of hypovolemia-induced acute kidney injury associated with excessive dehydration [6]. Achievement of this target was defined as end of treatment. Moreover, hematocrit changes (%) were automatically and continuously monitored inside the extracorporeal circuit by a dedicated integrated sensor in order to guide physicians for ultrafiltration rate adjustments (reduction of ultrafiltration rate in case of hematocrit increase), and thus prevent hypovolemia during ultrafiltration [3]. Additional pharmacologic therapy was left to the discretion of the cardiologist in charge of the patient. Specifically, diuretic therapy withdrawal was not required and continuation of diuretic therapy at unchanged doses recommended during ultrafiltration sessions. 2.3. Peripheral venous access In order to increase the success rate and avoid premature circuit failure and/or filter clotting, accurate preliminary selection and evaluation of the peripheral vein access were performed. The choice of venous access followed this sequence: antecubital veins, cephalic veins, and basilic veins. A single-lumen cannula (17 gauge, single-lumen, multihole, 25–32 mm long catheter) was inserted in the best approachable vessel; the withdrawal flow rate was manually estimated by a syringe and a dedicated device (Haemocatch®, Haemotronic®, S.p.A., Mirandola [Modena], Italy). In patients in whom a withdrawal flow rate ≥ 10 ml/10 s was confirmed, ultrafiltration treatment was started.
Fig. 2. Diagram showing the flow of participants through each stage of the study. CVC = central venous catheter.
Please cite this article as: M. Morpurgo, et al., A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.04.088
M. Morpurgo et al. / International Journal of Cardiology xxx (2017) xxx–xxx 2.5. Study end points and statistical analysis The primary end point of the study was defined as the ability of the CHIARA system to perform an ultrafiltration session of ≥6 h, with an ultrafiltration rate ≥ 100 ml/h. Any complications related to the insertion of the cannula and to the anticoagulation treatment were also evaluated as secondary safety end points. One-hundred ultrafiltration sessions were planned; such a sample size should allow to estimate a rate of ultrafiltration treatment failure of 5%, with 95% confidence intervals ranging from 1.6% to 11% (estimated by binomial confidence limits). Paired t test was used to compare laboratory variables before and after ultrafiltration. Data are expressed as mean ± standard deviation or as median and interquartile range (IQR), as appropriate, or as actual numbers and percentages.
3. Results During the study period, a total of 72 patients were initially screened (Fig. 2). Seventeen of them were excluded. Among excluded patients, the CHIARA treatment was still performed for clinical reasons, via a CVC, in 13 patients (in 7 patients a CVC was already inserted and the physicians chose to use it for the ultrafiltration treatment, while in 6 patients a peripheral venous access with a ≥ 60 ml/min withdrawal flow rate was not found and a CVC was then positioned). Fifty-five subjects were therefore included in the study and underwent a total of 103 treatments (average 1.9 ± 1.7 sessions/patient). The baseline (before ultrafiltration) clinical characteristics of the study population are summarized in Table 1. The average estimated baseline fluid overload was 8.2 ± 4.5 kg (range 4–30 kg). Of the 103 treatments performed, 92 (89%) were successfully completed, with a cumulative median length of treatment of 14 (IQR 7–21) hours, a mean ultrafiltration rate of 183 ± 30 ml per hour, a cumulative ultrafiltration volume of 3266 ± 3088 ml, and a total weight loss of 5.8 ± 4.1 kg. The mean suction flow rate from the vein was 70 ± 20 ml/min, while the mean re-injection flow rate was Table 1 Baseline characteristics of the study patients. Clinical characteristics N Age, years Men, n (%) Diabetes mellitus, n (%) Systemic hypertension, n (%) COPD, n (%) NYHA class III, n (%) NYHA class IV, n (%) Chronic atrial fibrillation, n (%) PM/ICD/CRT, n (%) LVEF, % Heart rate, beats/min Systolic blood pressure, mm Hg
55 74 ± 9 29 (52%) 17 (30%) 9 (16%) 7 (12%) 22 (40%) 33 (60%) 23 (41%) 14 (25%) 39 ± 11 75 ± 15 114 ± 15
Heart failure cause Ischemic CMP, n (%) Valvular heart disease Post-myocarditis CMP other CMP, n (%)
25 (46%) 18 (32%) 1 (0.5%) 11 (21%)
Medications ACE-inhibitors or ARB, n (%) Intravenous furosemide dose, mg/day Beta-blockers, n (%) Aldosterone antagonists, n (%)
19 (34%) 193 ± 150 28 (50%) 21 (38%)
Laboratory measures Urea, mg/dl Serum creatinine, mg/dl eGFR, ml/min/1.73 m2 Sodium, mEq/l Potassium, mEq/l
103 ± 40 1.6 ± 0.5 52 ± 30 137 ± 4 3.7 ± 0.6
ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; CMP = cardiomyopathy; COPD = chronic obstructive pulmonary disease; CRT = cardiac resynchronization therapy; eGFR = estimated glomerular filtration rate; HF = heart failure; ICD = implantable cardioverter-defibrillator; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; PM = pacemaker.
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98 ± 26 ml/min. The duration of each ultrafiltration session was 8 (IQR 7–8) hours. When patients, and not ultrafiltration sessions, were considered, a 20% rate of treatment failure occurred (11/55 patients). Table 2 shows the procedural details of ultrafiltration in each treated patient. No patient experienced complications related to the insertion of the cannula and to the ultrafiltration procedure. In one case, asymptomatic, transient heparin-induced thrombocytopenia was observed at the end of the treatment. No serious adverse clinical event was recorded during the study. Laboratory data measured before and 24 h after ultrafiltration treatment are shown in Table 3. 4. Discussion The results of this prospective, multicenter feasibility study on ultrafiltration in patients with AHF and severe fluid overload demonstrated that short-term treatment with a single-lumen peripheral access and with the CHIARA device is feasible and safe. Indeed, ultrafiltration was successfully completed in 80% of treated patients and in almost 90% of sessions, without adverse events. Some previous studies have pointed towards possible benefits of ultrafiltration, when compared to diuretic therapy, in removing fluid overload without eliciting neurohormonal compensatory mechanisms [3,4,7,8]. In these studies, most of the reported serious adverse effects of this kind of treatment were related to the insertion of a CVC, to its management, and to the anti-coagulation protocol utilized [5,9]. The new CHIARA device, by utilizing a low-volume extracorporeal circuit and a single-lumen peripheral venous access, may overcome most of the abovementioned procedural risks, and have some potential advantages, when compared to standard ultrafiltration systems. The first advantage is the reduction of adverse events related to central venous catheterization. In fact, inserting a small (17 gauge) cannula in a peripheral vein of the arm is less traumatic and dangerous for the patient than positioning a multi-lumen cannula in a central vein. Contemporary ultrafiltration devices that enable a peripheral approach may sometimes require two venous accesses – one for blood withdrawal and one for its restitution – which are not easily available in fluid overloaded patients. Moreover, a continuous withdrawal blood flow through the veins of the arm, like that used in these ultrafiltration devices, is particularly problematic in AHF patients, resulting in frequent premature failure of the treatment. Conversely, the alternate flow utilized by the CHIARA system, which includes two different phases (withdrawal and return), allows differentiating the speed of blood suction from and return into the vein. This step flow behavior, combined with a dedicated algorithm, may reduce the vein collapse. Another important advantage is that the reduced volume of blood inside the extracorporeal circuit, when compared to conventional renal replacement therapy modalities (50 ml vs. about 200–300 ml) implies a reduced risk of blood loss in the case of clotting of the circuit. Furthermore, due to the reduced contact surface between blood and tubing set and the air-free system, the heparin dose required to prevent the clotting of the system could be lower than that usually utilized in conventional treatments, as well as in the present study, thus diminishing the risk of bleeding or other complications related to anticoagulants (i.e. thrombocytopenia). Indeed, during ultrafiltration, the interface between air and blood and the turbulences in the bubble traps are known inductors of the coagulation cascade [10]. Finally, CHIARA does not necessarily require the admission of the patient to the ICU. While conventional ultrafiltration treatments are often performed in an ICU setting, or on specific wards, like a heart failure or cardiac telemetry units, or dialysis department, treatments with this new device can be managed in a normal ward or even in the emergency department, thanks to its minimally invasive approach, its reduced procedural risk, and its lower nurse surveillance requirement. In contrast to patients admitted to an ICU who remain confined to bed for many days
Please cite this article as: M. Morpurgo, et al., A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.04.088
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Table 2 Procedural characteristics of ultrafiltration sessions. Pt
sessions (n)
Catheter venous site
Estimated fluid overload (kg)
Overall UF volume (ml)
Average UF rate (ml/hour)
Heparin bolus (IU)
Heparin infusion (IU/hour)
withdrawal/ return flow rate (ml/min)
Reason for stopping UF
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55
1 1 1 1 3 1 4 1 1 2 1 2 1 2 2 2 1 1 1 1 1 1 1 2 1 8 1 1 3 2 2 2 2 2 1 1 3 4 3 10 1 1 1 3 1 1 1 1 1 1 1 3 4 1 1
antecub. antecub. basilic cephalic antecub. antecub. antecub. median basilic cephalic antecub. basilic antecub. antecub. antecub. basilic antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. basilic antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. antecub. basilic antecub. basilic antecub. antecub.
8 8 10 4 10 5 11 10 10 6 4 8 4 5 7 30 5 10 7 6 6 8 12 5 7 20 9 7 9 4 5 6 5 6 8 10 8 10 10 18 7 4 10 15 12 7 4 6 8 5 4 10 6 8 5
1990 1000 850 1200 4500 1150 5500 1300 830 2250 1455 2315 1500 3400 3230 2480 1260 2000 1970 3600 494 5650 1650 10805 4300 1970 3150 2880 2650 2400 1650 1700 4315 4000 3870 17866 1050 6150 2700 1500 1500 1500 1100 3760 4760 -
248 166 212 192 187 165 172 162 138 161 181 158 187 212 202 160 210 210 195 156 70 182 206 200 215 151 197 206 165 170 206 170 180 129 155 200 175 207 190 230 250 176 183 209 194 -
5000 2500 3000 2500 4000 4000 2000 3000 2000 2000 4000 2000 2000 2000 2000 5000 2000 1600 2000 1000 1000 3000 6000 3500 3000 3000 2000 2000 2000 2500 2000 3500 4000 2500 4000 5000 3000 2000 6000 2000 2000 2000 3500 3500 5000 2000 2000 4000 4000 2000 4000 1400 4000 2000 2000
1000 550 1000 600 600 800 400 600 750 800 600 600 600 600 600 1600 800 600 500 500 1200 800 750 750 500 700 500 800 1000 650 900 500 700 700 1500 800 800 800 1250 1000 1000 800 500 400 600 -
80/120 45/140 62/125 50/142 77/85 60/100 30/100 60/110 45/45 40/90 50/120 50/50 60/100 40/90 60/80 50/40 80/120 70/100 80/100 80/110 35/120 50/50 80/80 50/70 100/120 80/120 97/115 72/120 90/130 75/120 78/105 115/115 70/90 70/90 65/70 80/80 70/90 80/90 90/65 98/116 100/145 54/100 70/110 100/100 70/70 -
end of treatment end of treatment kinking of the cannula end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment failure b 1 hour end of treatment failure b 1hour end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment failure b 1 hour failure b 1 hour end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment failure b 1 hour failure b 1 hour end of treatment end of treatment end of treatment failure b 1 hour failure b 1 hour end of treatment end of treatment end of treatment end of treatment end of treatment end of treatment failure b 1 hour failure b 1 hour
Antecub. = antecubital vein; UF = ultrafiltration.
Table 3 Laboratory parameters before and after ultrafiltration treatment.
BNP, pg/ml Urea, mg/dl Serum creatinine, mg/dl eGFR, ml/min/1.73 m2 Sodium, mEq/l Potassium, mEq/l
Before ultrafiltration
After ultrafiltration
P value
1580 ± 1194 103 ± 40 1.6 ± 0.5 52 ± 30 137 ± 4 3.9 ± 0.6
1421 ± 1092 102 ± 50 1.5 ± 0.5 58 ± 34 137 ± 5 4.1 ± 0.7
0.46 0.91 0.29 0.32 1.00 0.11
BNP = brain natriuretic peptide; eGFR = estimated glomerular filtration rate (MDRD formula); UF = ultrafiltration.
during ultrafiltration therapy, those treated with the CHIARA system can easily be mobilized between two consecutive ultrafiltration sessions. Specifically, we designed this study protocol, characterized by a relatively short treatment period (daily sessions of 6–12 h), in order to investigate the potential applicability of the CHIARA system in this specific clinical scenario. Indeed, our study confirms that 89% of treatments can be successfully carried out during this pre-defined treatment period. In our study, the feasibility of the treatment and its success were strictly related to the selection of the venous access. An appropriate peripheral vein allowing a withdrawal flow rate of at least 10 ml in 10 s, and the use of a dedicated cannula (17 gauge, single-lumen, multihole catheter) were crucial to achieve a good performance of the system
Please cite this article as: M. Morpurgo, et al., A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.04.088
M. Morpurgo et al. / International Journal of Cardiology xxx (2017) xxx–xxx
for the entire duration of the treatment, and to avoid troublesome, expensive premature circuit losses. We suggest that an accurate preliminary evaluation of the peripheral access should be performed before starting an ultrafiltration treatment with CHIARA. Notably, in our study, the treatment was started with a blood flow ≥ 60 ml/min and was then lowered during the session up to a minimum of 30 ml/min in two patients; this suggests that the limit of withdrawal flow rate we chose to include patients in the present study could possibly be lowered. The results of any medical device feasibility study, such as this one, must be interpreted with caution. Firstly, since there was no control group undergoing procedures without the CHIARA system in this study, there can be no formal assessment of the clinical impact, if any, of this kind of treatment. Secondly, the economic impact of ultrafiltration was not evaluated in our trial, and should be a matter of dedicated investigation. Indeed, at the time the study was designed, the CHIARA system was not commercially available, and the costs of the procedure were unknown. Thirdly, we planned to perform only shortterm (≥ 6 h) sessions. Therefore, the feasibility of a single, longerlasting continuous treatment with CHIARA remains unexplored. However, in patients in whom a CVC was used, much longer treatments, up to 48 h, were performed. This suggests that prolonged continuous sessions can be performed if needed, and that, although the device was specifically designed for a peripheral venous approach, it can also be used with traditional approaches. Indeed, in cases in which we either failed to find a suitable peripheral approach or the physicians chose to directly shift to a CVC, the treatment with the CHIARA device resulted to be as effective and as safe as treatments performed with the peripheral approach. Finally, physicians having a long experience with ultrafiltration treated all patients, and this aspect may have significantly impacted the results of our study. Therefore, the overall applicability of our findings remains to be confirmed. The Global rEgistry on decongestioN Therapy using Less invasivE UltraFiltration (GENTLE-UF; clinicaltrials.gov Identifier: NCT02769351), which was started in December 2015, intends to investigate the impact of the CHIARA system in a real-world AHF population. It is expected that it could confirm our preliminary results and more precisely identify the clinical characteristics of patients who may benefit most from this therapeutic approach. 5. Conclusions The results of our study demonstrated that treating AHF with the CHIARA system satisfies safety and performance criteria, in terms of
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adequate fluid removal through a single peripheral venous access. Based on these encouraging preliminary results and on their potential benefits, larger studies are warranted to ultimately prove its efficacy and to define its clinical role in the treatment of AHF with overt fluid overload. Conflict of interest None. Funding source This work was supported by the Amici del Cuore “Maria Sandrini” Association, Legnago, Verona, Italy. The funding source had no role in study design, data collection, analysis, interpretation, or reporting. Disclosure Dr. Marco Goldoni is an employee of Haemotronic. None of the other authors declared a conflict of interest related to this work. References [1] M.E. Silverstein, C.A. Ford, M.J. Lysaght, L.W. Henderson, Treatment of severe fluid overload by ultrafiltration, N. Engl. J. Med. 291 (1974) 747–751. [2] B. Canaud, M. Leblanc, H. Leray-Moragues, S. Delmas, K. Klouche, J.J. Beraud, Slow continuous and daily ultrafiltration for refractory congestive heart failure, Nephrol. Dial. Transplant. 13 (Suppl. 4) (1998) 51–55. [3] G. Marenzi, G. Lauri, M. Grazi, E. Assanelli, J. Campodonico, P. Agostoni, Circulatory response to fluid overload removal by extracorporeal ultrafiltration in refractory congestive heart failure, J. Am. Coll. Cardiol. 38 (2001) 963–968. [4] G. Marenzi, S. Grazi, F. Giraldi, et al., Interrelation of humoral factors, hemodynamics, and fluid and salt metabolism in congestive heart failure: effects of extracorporeal ultrafiltration, Am. J. Med. 941 (1993) 49–56. [5] G. Marenzi, M. Morpurgo, P. Agostoni, Continuous ultrafiltration in acute decompensated heart failure: current issues and future directions, Am. J. Cardiovasc. Drugs 15 (2015) 103–112. [6] G. Marenzi, M. Muratori, E.R. Cosentino, et al., Continuous ultrafiltration for congestive heart failure. The CUORE trial, J. Card. Fail. 20 (2014) 9–17. [7] M.R. Costanzo, M.E. Guglin, M.T. Saltzberg, et al., Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure, J. Am. Coll. Cardiol. 49 (2007) 675–683. [8] M.R. Costanzo, D. Negoianu, B.E. Jaski, et al., Aquapheresis versus intravenous diuretics and hospitalizations for heart failure, JACC Heart Fail. 4 (2016) 95–105. [9] B.A. Bart, S.R. Goldsmith, K.L. Lee, et al., Ultrafiltration in decompensated heart failure with cardiorenal syndrome, N. Engl. J. Med. 367 (2012) 2296–2304. [10] K.G. Fisher, Essentials of anticoagulation in hemodialysis, Hemodial. Int. 11 (2007) 178–189.
Please cite this article as: M. Morpurgo, et al., A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.04.088