First Experiences With the HeartWare Ventricular Assist System in Children

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First Experiences With the HeartWare Ventricular Assist System in Children Oliver Miera, MD, Evgenij V. Potapov, MD, PhD, Matthias Redlin, MD, Alexander Stepanenko, MD, Felix Berger, MD, PhD, Roland Hetzer, MD, PhD, and Michael Hübler, MD Departments of Pediatric Cardiology, Thoracic and Cardiovascular Surgery, and Anesthesiology, Deutsches Herzzentrum Berlin, Germany

Purpose. The purpose of this study is to describe initial experience with a new continuous flow, ventricular assist system in the pediatric population. Description. Seven children (aged 6 to 16 years) received implantation of a novel third-generation, continuous flow, ventricular assist device (HeartWare, HeartWare Inc, Miami Lakes, FL) as a bridge to cardiac transplantation. NEW TECHNOLOGY

Evaluation. All children were in terminal heart failure despite inotropic support, and signs of renal or hepatic impairment developed. Six children had dilatative cardiomyopathy and 1 had congenital heart disease (hypoplastic left heart, total cavopulmonary connections with extracardiac conduit). Six patients have been successfully bridged to transplantation. Median support time was 75 days (range, 1 to 136 days). One child is still under continuous mechanical support. None of the patients suffered a thromboembolic event or an infection. Conclusions. The HeartWare assist system can be successfully used as a bridge to transplantation in children and adolescents with end-stage heart failure. (Ann Thorac Surg 2011;91:1256 – 60) © 2011 by The Society of Thoracic Surgeons

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reatment of terminal heart failure with ventricular assist devices (VAD) is a well-established therapy in adult patients. With the development of implantable continuous flow VADs of the third generation, survival and quality of life have improved [1]. Because implantable VAD systems that are suitable for adult patients are too large for application in pediatric patients, paracorporeal systems are routinely used in children [2]. Shortage of donor hearts and increasing application of VADs may lead to increased waiting times on the transplant list, which poses new challenges in the treatment of children with terminal heart failure. There is an urgent need for VAD systems that allow long-term support with low morbidity and minimal restrictions of the daily activities of patients. This report describes the first pediatric experience with HeartWare (HeartWare Inc, Miami Lakes, FL), a small continuous-flow VAD, which is implanted in the pericardial space. Written informed consent was obtained from the parents of all patients prior to implantation. The study was conducted according to the Declaration of Helsinki and in adherence to good clinical practice

Accepted for publication Dec 9, 2010. Address correspondence to Dr Hübler, Department of Thoracic and Cardiovascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin 13353, Germany; e-mail: [email protected].

© 2011 by The Society of Thoracic Surgeons Published by Elsevier Inc

guidelines. Local Ethics Committee approved the protocol.

Technology The HeartWare System has been previously described in detail [3]. It consists of a centrifugal blood pump (HVAD pump), integrated inflow cannula, an outflow graft, and a percutaneous driveline, which is connected to a controller (Fig 1). The small pump has a displacement volume of 50 cc and weighs 140 g. It has one moving part, which is an impeller that spins blood to generate 1 to 10 L/min of flow at 1,800 to 4,000 rpm. A short integrated inflow cannula is inserted into the ventricle, and the outflow graft connects the pump to the aorta. A sewing ring attaches to the myocardium and allows pump orientation adjustments intraoperatively. The device size and short inflow cannula allow pericardial placement, which eliminates the need for device pockets.

Technique After median sternotomy, the patients were placed on cardiopulmonary bypass. The insertion site for the inflow cannula in patients with normal anatomy was slightly anterior to the left ventricular apex. In 1 patient with a univentricular heart of right ventricular morphology, the pump 0003-4975/$36.00 doi:10.1016/j.athoracsur.2010.12.013

Fig 1. Picture of the HVAD pump (HeartWare Inc, Miami Lakes, FL). The diameter of the pump is 49 mm, the total height of pump and integrated inflow cannula of 58 mm. The inflow cannula has a diameter of 20.5 mm and a length of 25 mm. The outflow graft has a diameter of 10 mm, and the percutaneous driveline a diameter of 4.2 mm.

was inserted through the diaphragmatic surface of the single ventricle 3 cm from the tricuspid valve toward the apex. Prior to implantation, the pump was completely submerged in sterile dextrose, and the outflow graft was clamped. After sewing of the ring to the myocardium and coring of the ventricular wall of the HVAD pump, an inflow cannula was inserted into the ventricle. The outflow graft was anastomosed to the ascending aorta using partial clamping. The driveline was then tunneled to the right upper quadrant and was connected to the controller. Anticoagulation was begun, once bleeding had subsided, on postoperative day 1 with unfractionated heparin and a target activated partial thromboplastin time of 50 to 60 seconds. As patients tolerated oral nutrition, anticoagulation was switched to warfarin (target international normalized ratio, 2 to 3) plus platelet inhibition with acetylsalicylic acid and dipyridamole. Required doses were in the range of 0.5 to 1 mg/kg/day acetylsalicylic acid and 3 to 4 mg/kg/day dipyridamole. Dose of anticoagulation and platelet inhibition was monitored with thromboelastography and platelet aggregometry (target inhibition of 30%).

Clinical Experience Patient characteristics (n ⫽ 7), indications for mechanical support, and outcome data are given in Table 1. Repre-

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sentative preoperative and postoperative roentgenograms appear in Figure 2. Six of seven children described here had dilatative cardiomyopathy, which had been proven in myocardial biopsy. After implantation of the HeartWare System, organ function of all patients promptly recovered. After a maximum time of mechanical support of 136 days, 6 patients underwent successful heart transplantation, and 1 child is still under continuous mechanical support. The clinical course with the LVAD was uneventful in 6 patients, and 1 patient had an acquired von Willebrand factor deficit, leading to hemorrhagic pericardial effusion in the first week that needed surgical drainage. In this patient, the activated partial thromboplastin time was slightly prolonged (40 to 45 seconds) with therapy of unfractionated heparin; values for prothrombin time (⬎ 85%) and platelet count (220,000 to 297,000/␮L) were normal. Analysis of von Willebrand factor revealed a normal antigen (220%) with reduced activity (119%) and reduced levels of large multimers. Of the patients described herein, 1 of 7 had terminal failure of his univentricular heart with Fontan hemodynamics. Because of the predominant ventricular failure with low transpulmonary gradient it was decided to implant a HeartWare system as a ventricular support system without modifying the cavopulmonary connections (Fig 3). The initial postoperative data showed excellent performance of the VAD. The boy did not need inotropic support but a low dose of the vasopressor norepinephrine (0.03 ␮g/kg/min). To improve pulmonary perfusion inhalative nitric oxide was necessary. In the first 12 hours, urine output was 4 mL/kg/hour, central venous saturation was 42%, and pulmonary artery pressure was 14 mm Hg. In postoperative hour 12, a donor organ became available, and the boy underwent successful heart transplantation.

Comment We believe that this is the first report on the application of the HeartWare assist system in the pediatric population. The HeartWare system is a novel third generation, implantable VAD, which creates continuous flow to support even children in end-stage cardiac failure. The patients described (aged 6 to 16 years) were all in multiorgan failure under inotropic support. One is still on VAD, and 6 children were successfully bridged to cardiac transplantation. Not only was the outcome good, but the morbidity during circulatory support was low. During a total of more than 480 days of support, no patient suffered from an infection or thromboembolism. The only relevant complication was a re-thoracotomy due to pericardial hemorrhagic effusion in 1 patient. Development of a secondary von Willebrand syndrome may be explained by injury of the large protein multimers by turbulent flow through the pump. The role of the continuous flow pumps in the depletion of von Willebrand factor has been discussed [4, 5], and the axial flow pump Heartmate II (Thoratec, Pleasanton, CA) has been shown to cause acquired von Willebrand factor

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Baseline Characteristics Age Gender Weight (kg) Body surface area (m2) Diagnosis Left ventricular diameter (mm) Ejection fraction (%)a Inotropic support Secondary organ dysfunctionb Outcome data Extubation (postoperative day) Pump speed (rpm, median) Pump flow (L/min, median) Days of VAD support Complications Outcome

Patient 1

Patient 2

16 Male

12 Male

79 2.0 DCM 77 20 Epinephrine/ Milrinone Renal

0 2,700 5.8

Patient 3 14 Male

29 1.1 HLHS, TCPC 79 25 Dobutamine/ Milrinone Renal, hepatic c

2,700 2.1

75

1c

Transplantation

Transplantation

36 1.2 DCM 63 27 Epinephrine/ Milrinone Hepatic

Patient 4 14 Female 49 1.5 DCM 64 25 Dobutamine/ Milrinone Gastrointestinal

Patient 5

Patient 6

15 Male

9 Male

72 1.9 DCM

20 0.9 DCM

71 20 Dobutamine/ Milrinone Renal

60 19 Epinephrine/ Milrinone Renal, hepatic

Patient 7 6 Female 17 0.7 DCM 45 11 Epinephrine/ Milrinone Hepatic

5

2

1

1

4

2,500

2,600

2,700

2,800

2,400

4.5 57 Pericardial tamponade Transplantation

4.5

4.2

29

80

Transplantation

Transplantation

3.0 111

Transplantation

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Table 1. Baseline Characteristics and Outcome Data

2.3 136

Under continuous mechanical support

a b Measured while on inotropic support. Secondary organ dysfunction is defined as follows: hepatic, elevation of transaminases ⬎ three-fold of upper normal limit or bilirubin level ⬎ 1 mg/dL; renal, c Cardiac transplantation 12 hours after implantation of VAD. oliguria (⬍ 1 mL/kg/hr) or creatinine ⬎ normal limit; gastrointestinal, intolerance of enteral nutrition.

DCM ⫽ dilatative cardiomyopathy;

HLHS ⫽ hypoplastic left heart syndrome;

TCPC ⫽ total cavopulmonary connection;

VAD ⫽ ventricular assist device. Ann Thorac Surg 2011;91:1256 – 60

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deficit [6]. The impact of the centrifugal pump HeartWare HVAD on the development of acquired von Willebrand syndrome remains uncertain. In our patient, no further signs of bleeding appeared during 57 days of support under the previously mentioned standard anticoagulation protocol. However, patients placed on continuous flow devices may be at higher risk for the development of platelet dysfunction [6] and should be screened for acquired von Willebrand syndrome. Of special interest is our second patient who suffered from failing Fontan hemodynamics with end-stage heart failure. We were able to show the feasibility of the HeartWare assist system in a Fontan patient using a

modified implantation location (Fig 3). This patient group deserves particular attention in the future, because the number of children with univentricular heart successfully operated on and reaching adolescence and adulthood is growing. So far there is no well-established treatment strategy for bridging the failing univentricular heart to transplantation. There are only two existing reports of the application of implantable continuous flow devices in children [7, 8]. The first report, published by Fraser and colleagues [7], describes preliminary experience with the DeBakey VAD child in 6 children (aged 6 to 14 years). In 3 of the children, cardiac transplantation was successful; however, the other 3 children died during support. This device received regulatory approval by the Food and Drug Administration in 2004. Ruygrok and colleagues [8] reports the application of an implantable continuous flow device (ie, the VentrAssist system) in 3 children [8]. One of the alternatives to the HeartWare VAD is the paracorporeal pulsatile pediatric BerlinHeart Excor (Berlin Heart AG, Berlin, Germany). This device may be applied, even in small infants with a body weight of less than 3 kg, whereas for the HeartWare VAD, 17 to 20 kg seems to be the lowest range due to the limitation of flow to a minimum of 2 L/minutes. Given our initial experience and long waiting time for heart transplantation in Europe, the HeartWare assist system offers an attractive alternative to paracorporeal systems for larger children and adolescents with endstage heart failure. In newborns and small children, the pediatric BerlinHeart Excor remains the only reliable option.

Disclosures and Freedom of Investigation

Fig 3. Chest roentgenogram of patient with univentricular heart. The pump was implanted in the diaphragmatic surface of the pericardial space. The inflow cannula penetrates the right ventricle 3-cm apical of the tricuspid valve.

The authors of this article had full control of the design of the study, methods used, outcome measurements, analysis of data, and production of the written report. HeartWare Inc had no role in this study or access to the information obtained. We thank Anne Gale, medical editor, for her editorial assistance.

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Fig 2. Chest roentgenogram of patient 3 (A) pre-implantation and (B) post-implantation.

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References 1. Slaughter MS, Rogers JG, Carmelo AM, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. New Engl J Med 2009;361:2241–51. 2. Potapov EV, Stiller B, Hetzer R. Ventricular assist devices in children: current achievements and future perspectives. Pediatr Transplant 2007;11:241–55. 3. LaRose JA, Tamez D, Ashenuga M, Reyes C. Design concepts and principle of operation of the heartware ventricular assist device. ASAIO J 2010;56:285–9. 4. Letsou GV, Shah N, Gregoric ID, Myers TJ, Delgado R, Frazier OH. Gastrointestinal bleeding from arteriovenous malformations in patients supported by the Jarvik 2000 axial-flow left ventricular assist device. J Heart Lung Transplant 2005; 24:105–9. 5. Hayes HM, Dembo LG, Larbalestier R, O’Driscoll G. Management options to treat gastrointestinal bleeding in patients supported on rotary left ventricular assist devices: a singlecenter experience. Artif Organs 2010;34:703– 6.

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6. Malehsa D, Meyer AL, Bara C, Strüber M. Acquired von Willebrand syndrome after exchange of the HeartMate XVE to the HeartMate II ventricular assist device. Eur J Cardiothorac Surg 2009;35:1091–3. 7. Fraser CD, Carberry KE, Owens WR, et al. Preliminary experience with the MicroMed DeBakey pediatric ventricular assist device. Semin Thorac Cardiovasc Surg Pediatr Card Surg Ann 2006;9:109 –14. 8. Ruygrok PN, Esmore DS, Alison PM, et al. Pediatric experience with the VentrAssist LVAD. Ann Thorac Surg 2008;86: 622– 6.

Disclaimer The Society of Thoracic Surgeons, the Southern Thoracic Surgical Association, and The Annals of Thoracic Surgery neither endorse nor discourage use of the new technology described in this article.

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