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The expectation of ventricular assist device (VAD) therapy has shifted from patient survival to adequate quality of life (QoL). The use of intracorporeal left ventricular assist device (LVAD) in adults with subsequent discharge home has become routine; however, options for children with a body surface area (BSA) <1.2 m2 are still limited. Progress in the VAD technology leading to miniaturization of LVADs offers new perspectives for children.
Harmful cardiotoxic side effects of anthracyclines may lead to inotropic heart failure, necessitating VAD therapy to salvage the patient’s life. Recovery of cardiac function if at all may take months, and therapeutic strategies are limited. We report on a child experiencing chemotherapy-induced cardiomyopathy (CMP) provided with an intracorporeal LVAD and present our institutional algorithm for such cases.
An 8-year-old girl (BSA 0.97 m2) was diagnosed with a bone sarcoma of the left tibia. The tumor was treated by surgical resection and triple drug chemotherapy according to the EURAMOS 1 trial, including methotrexate, doxorubicin, and adriamycin. Ten days after the last chemotherapy course, inotropic-dependent heart failure occurred and the patient was transferred to our institution. At admission, transthoracic echocardiography revealed reduced biventricular contractility with an estimated LV ejection fraction of 20%, a dilated left ventricle (Figure 1A), and moderate tricuspid and mitral regurgitation. Despite maximal medical therapy (adrenalin, milrinone, and levosimendan) and artificial ventilation, clinical condition of the patient worsened acutely (oliguria and anuria, leg edema, lung edema) and mechanical circulatory support (MCS) was indicated. A HeartWare ventricular assist device (HVAD) (HeartWare Inc., Framingham, MA) intracorporeal LVAD was implanted via median sternotomy (Figure 1B). During a short phase of induced fibrillation, the left ventricular cavity was inspected to rule out thrombus. No cardioplegia was given and the aorta was not cross-clamped. For right ventricular (RV) support, inhaled nitric oxide (iNO) ventilation, nitrate, milrinone, and catecholamine support (adrenaline) were given. The patient could be weaned from cardiopulmonary bypass (time 61 minutes) without any complications. Anticoagulation with intravenous heparin was started 8 hours postoperatively, with a target antifactor Xa level of 0.5–0.8 IU/ml. Right ventricular support with iNO was necessary for another 6 days, and milrinone was continued until the 14th postoperative day. Extubation was realized on postoperative day 7. After the removal of mediastinal drainage tubes and pacing wires, oral anticoagulation with coumadin was initiated. The target international normalized ratio was set at 2.5–3.0. Additional platelet inhibition with acetylsalicylic acid (0.5 mg/kg per day) and dipyridamole (0.3 mg/kg per day) was applied. Weaning from adrenalin was possible after 12 days; the patient was fully mobilized and transferred to the normal ward (postoperative day 28). Left ventricular assist device settings were 2,080 revolutions per minute and calculated flow 2.1 L/minute and 1.9 W. After 90 days, the child was discharged home (Figure 2). Frequent outpatient visits are assigned and pump settings are set according to the echocardiographic findings at the outpatient visits (opening of the aortic valve, size of the right and the left ventricles); for hemolysis monitoring, laboratory values (lactate dehydrogenase, free hemoglobin, and platelet count) and clinical signs (urine) are controlled. Histologic examination confirmed an anthracycline-induced CMP (myocardial interstitial fibrosis, scattered vacuolated cardiomyocytes, distention of the sarcoplasmic reticulum, and partial loss of myofibrils).
In many inotropic-dependent anthracycline-induced CMP patients, recovery of cardiac function and time to recovery are uncertain and treatment strategies are limited. In children experiencing anthracycline-induced CMP, reports of MCS with an extracorporeal assist device have been published.1 Nevertheless, extracorporeal LVADs are associated with inferior QoL and higher complication rates compared with intracorporeal LVADs. In this case, we estimated that the support time until candidacy for heart transplantation (HTx) will be too long for short-term MCS, and fast myocardial recovery is unlikely. For children with a BSA <1.2 m2, only a small number of VADs are available; the HeartMate II was applied in a small number of patients in small BSA and was reported to be applicable in patients with a BSA of 1.0 m2 (Slaughter, 2009, #1729). The HVAD (HeartWare Inc.) is a third-generation rotary blood pump, with magnetically levitated rotor initially designed for left ventricular support.2 In Europe, the HVAD is accredited for patients with a BSA >1.2 cm2; due to its small size, it is also applicable in children. The Berlin group published their experience with the HVAD in seven pediatric patients with a median support time of 75 days and a success rate of 86% for bridging to HTx.3 This group also reported the youngest patient provided with an HVAD, a 6-year-old girl weighing 16 kg and a BSA of 0.6 m2 at the time of implantation. Regardless of the type of device, the size of the left ventricle in children (Figure 1A) is critical to the feasibility of implanting an intracorporeal VAD. A relative oversized inflow cannula placed in a small left ventricle can induce inlet occlusion.
Our established institutional MCS algorithm distinguishes between pathologies where early recovery is likely (i.e., acute myocarditis or postcardiotomy failure) versus those where it is unlikely; if recovery is expected to take >2 weeks, VAD implantation is considered, when no absolute contraindications exist. The BSA and the RV function are important variables that factor into the decision-making process. In general, with a BSA >0.6 m2 and a moderate RV function, an HVAD is preferred, whereas for a BSA <0.6 m2 or severe biventricular failure a Berlin Heart Excor biventricular assist device is considered. If RV function is questionable, a HeartWare LVAD can be implanted with a short-term RV centrifugal pump support (Levitronix Centrimag; Thoratec Corporation, Pleasanton, CA).
Complications such as infections, thromboemboli, or bleeding events during long-term LVAD support may still arise; therefore, an individual decision about how long the patient should be supported with LVAD before necessary freedom from tumor recurrence can be postulated, and the patient may then be listed for HTx. Myocardial recovery in patients experiencing chronic anthracycline-induced CMP supported with LVAD has been reported, ranging from 135 days to >16 months.4–6
In conclusion, the current case outlines that in children with a BSA ≥0.6 m2 when long-term MCS is aimed, an intracorporeal LVAD using the HVAD results in saving the patient’s life, discharging the child home, and offering adequate QoL during support. Myocardial recovery may be still possible after months on support. Close follow-up focusing on tumor recurrence will be essential.
1. Potapov EV, Weng Y, Jurmann M, Lehmkuhl H, Hetzer R. Bridging to transplantability with a ventricular assist device. J Thorac Cardiovasc Surg. 2005;130:930
2. Wieselthaler GM, O Driscoll G, Jansz P, Khaghani A, Strueber MHVAD Clinical Investigators. . Initial clinical experience with a novel left ventricular assist device with a magnetically levitated rotor in a multi-institutional trial. J Heart Lung Transplant. 2010;29:1218–1225
3. Miera O, Potapov EV, Redlin M, et al. First experiences with the HeartWare ventricular assist system in children. Ann Thorac Surg. 2011;91:1256–1260
4. Khan N, Husain SA, Husain SI, et al. Remission of chronic anthracycline-induced heart failure with support from a continuous-flow left ventricular assist device. Tex Heart Inst J. 2012;39:554–556
5. Castells E, Roca J, Miralles A, et al. Recovery of ventricular function with a left ventricular axial pump in a patient with end-stage toxic cardiomyopathy not a candidate for heart transplantation: First experience in Spain. Transplant Proc. 2009;41:2237–2239
6. Freilich M, Stub D, Esmore D, et al. Recovery from anthracycline cardiomyopathy after long-term support with a continuous flow left ventricular assist device. J Heart Lung Transplant. 2009;28:101–103
Keywords:Copyright © 2013 by the American Society for Artificial Internal Organs
chemotherapy-induced cardiomyopathy; intracorporeal ventricular assist device; child; bridge to candidacy