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Clinical Outcomes–Devices

Pulsatile Paracorporeal Assist Devices in Children and Adolescents with Biventricular Failure

Sharma, Mahesh S.; Webber, Steven A.; Gandhi, Sanjiv K.; Morell, Victor O.; Winowich, Steven; Buchanan, Julianne R.; Kormos, Robert L.

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doi: 10.1097/01.mat.0000177679.55397.e2
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Abstract

Children with heart failure who are unresponsive to maximal medical management have limited options for survival. Over the last two decades, mechanical circulatory support has assumed an expanding role in the care of these patients by providing support to the failing myocardium. Options for the pediatric population include miniaturized intraaortic balloon pumps,1 extracorporeal membrane oxygenation (ECMO),2 centrifugal ventricular assist devices (VADs),3 and more recently pulsatile VADs.4 The use of intraaortic balloon pumps in children has been unrealistic because of technical constraints such as vessel diameter, increased aortic compliance in children, and synchronization to a rapid heart rate.1 Centrifugal VADs and ECMO are efficacious for immediate support of the failing heart. However, both have limitations for long-term use including the need for systemic heparinization, lack of pulsatile blood flow, and immobilization of the patient. Pulsatile paracorporeal biventricular assist devices (BVADs) provide complete support of the heart during the bridge to transplant or myocardial recovery period while allowing for maximum patient rehabilitation. However, in many patients their cardiomyopathy can result in substantial right ventricular as well as left ventricular dysfunction. In patients with severely decompensated heart failure with signs of significant right ventricular failure, an LVAD alone may not provide adequate circulatory support, and so a strategy of planned BVAD implantation would be more effective. Unfortunately, in most published series, the mortality in patients requiring BVAD as a bridge to transplantation has been reported to be over 40%, in contrast to the 25% mortality of patients bridged on a left VAD.5,6 This disparity in survival between BVADs and left VADs, in addition to the perceived technical challenges to placement of a BVAD, has led some to question the rationale for use of a BVAD for morbid congestive heart failure. This is especially so for the pediatric population.

Herein we report our experience with biventricular support with the Thoratec VAD (Thoratec Corporation, Pleasanton, CA) in children and adolescents with refractory cardiogenic shock.

Materials and Methods

Data

Demographic and clinical outcome data including adverse events and information regarding pump performance and device malfunction was collected prospectively on all VAD recipients at the time of device implantation or upon listing for transplantation. Patient data was prospectively collected into the Web-based Transplant Patient Management System (TPMS). This database was designed to function as both a clinical database and a research registry and operates under protocols for these purposes that are approved by the University of Pittsburgh Institutional Review Board for the use of patient management, quality assurance reports, and clinical research. It interfaces between multiple electronic databases within the University of Pittsburgh Medical Center and automatically insures that all laboratory work, tests, and procedures related to the assist device are recorded in the database.

In addition to all qualitative data on laboratory values (including hematology, blood chemistry, and microbiology), qualitative reports, progress notes, device-related complications, and demographic data are entered directly by the ventricular assist device coordinators, bioengineers, and physicians. Integrity of the database and quality assurance of the data is maintained by one of the investigators (JRB) who performs the aggregate reports for this study as the honest broker in a de-identified format. Access to the TPMS database is password protected and conforms to HIPPA requirements.

Patients

The prospectively collected data from the TPMS was evaluated retrospectively in patients under the age of 21 who underwent insertion of a BVAD at the University of Pittsburgh Medical Center between February 1995 and July 2004. Data points are summarized in tabular format and expressed as a mean value with range where appropriate. The median value is reported when statistically relevant.

Children and adolescents with intractable heart failure with evidence of end-organ dysfunction were included in this study. All patients were evaluated for transplant eligibility according to our program guidelines and met the criteria for heart transplantation. The study included eight boys and four girls with mean age of 15 (range 7–20) years. Body surface area ranged from 1.1 to 1.9 (mean 1.7) m2. Indications for support (Figure 1) included end-stage cardiomyopathy (idiopathic-6, viral-2, peripartum-2), myocarditis in one child, and one patient who underwent repair of recurrent supravalvular aortic stenosis at another institution requiring postoperative ECMO. He was transferred to our institution and subsequently had BVAD placement. Preimplant conditions are summarized in Table 1. Six patients (50%) required use of two or more inotropes. Six children required mechanical ventilation while on BVAD supported period for a mean of 4.2 days. Organ recovery while on VAD was determined by evaluation of hemodynamic parameters, echocardiographic determination of myocardial function, and improvement in laboratory values. The mean duration of support was 64.5 (range 2–175) days, with a median support time of 35 days.

Figure 1.
Figure 1.:
The etiology of heart failure for all patients included in this study. The majority of patients (n = 10) had end-stage cardiomyopathy.
Table 1
Table 1:
Preimplantation Characteristics

Device

Our preferred device was the Thoratec paracorporeal pneumatic VAD because it has the flexibility of providing left, right, or biventricular support. This device consists of three components: a blood pump, which has a 65 ml stroke volume and can deliver pulsatile flows of 1.3 to 7.1 l/min; cannulae, which connect the blood pump to the heart; and a drive console that powers the blood pump pneumatically. The VADs were placed in a paracorporeal position on the anterior abdominal wall. The left VAD cannulation was performed via left ventricular apex (inflow) with return to ascending aorta (outflow). We exclusively use left ventricular apical cannulation in all twelve patients. The right VAD was cannulated via the right atrium with return to the pulmonary artery. All children and adolescents were run exclusively in volume mode.

The anticoagulation protocol consisted of full systemic heparinization during insertion on cardiopulmonary bypass. Aprotinin was used at implant and removal. Postoperative anticoagulation was started with Dextran 40% at 25 ml/h 6 hours after admission to the intensive care unit if bleeding was < 100 ml/h. Subsequently, heparin was started when postoperative bleeding from the chest tubes was < 50 ml/h over 3 consecutive hours. The goal for partial thromboplastin time was 40–51 seconds for at least the first 72 hours or until the risk of bleeding from more aggressive anticoagulation was felt to be acceptable. Heparin was then increased to maintain a partial thromboplastin time of 42–62 seconds. Coumadin was introduced at postoperative day 10 to keep the INR between 2.5 and 3.5. Heparin was discontinued after obtaining an INR of at least 2.5. The philosophy of anticoagulation was to maintain heparin until the patient demonstrated a low risk for bleeding complications and after there had been a period of stable gastrointestinal tract function and diet. This usually was found to occur around 10 to 14 days after implantation.

In general, we did not add aspirin unless there was a specific concern about thromboembolism. After discharge, the INR was assessed at a minimum of two times per week for stable patients. To prevent infection from the exit site and kinking of the conduits, the VADs were restrained with an elastic dressing after implantation.

Results

Ten of the 12 patients (83%) who received VADs survived the period of circulatory support. Outcomes based on the etiology of end-stage heart failure are depicted in Figure 2. One patient with postpartum cardiomyopathy demonstrated full myocardial recovery and underwent explantation of her device. Two deaths occurred during the period of support, and both were attributable to multisystem organ failure.

Figure 2.
Figure 2.:
Outcome for each of the etiologies of end-stage heart failure reflecting excellent survival in those patients with end-stage cardiomyopathy.

Adverse events during VAD support are indicated in Table 2. Device malfunction occurred in one patient in which the Thoratec right VAD pump fill sensor was defective. This occurred in an early version of the device that is no longer available. Bleeding requiring reoperation occurred in 3 (25%) patients. Hemolysis, as measured by plasma free hemoglobin (fHb), occurred in three patients. Embolic or ischemic cerebrovascular accidents occurred in 8% (one patient). Infectious complications (any positive culture) occurred in 50% of patients and were divided into class I through III (nonbloodstream, bloodstream, and VAD cannula site).7 No patients suffered blood-borne infections, but four children experienced minor infections. Driveline-site infections occurred in two patients.

Table 2
Table 2:
Adverse Events during VAD Support

Eight of the VAD survivors (67%) were completely ambulatory, and four of the 12 children discharged from hospital were supported as outpatients before explantation or orthotopic heart transplantation. Overall, 9 patients (75%) were successfully bridged to transplant. All nine patients were discharged from hospital alive and 1-year survival posttransplant survival was 100%, excluding one patient who is 8 months post orthotopic heart transplantation. Six of the nine transplanted patients are alive and well with a mean follow-up of 39 months (range 8 months to 8 years).

Discussion

Historically, ECMO has been used as the mainstay of pediatric circulatory support.8 In contrast to adults, true cardiorespiratory support is more often required in children because of the contributions of hypoxemia, pulmonary hypertension, and right ventricular failure to the pathophysiology necessitating support.9 The survival rate for use of ECMO for postoperative cardiac assistance has been from 30% to 70%.10–12 Although ECMO can be used in adolescents and small children, its main limitations are the inability to provide safe, long-term extracorporeal support13 and the lack of patient mobility leading to prolonged immobilization and subsequent deconditioning.14

Early efforts for postcardiotomy support in children and adolescents began in 1966, when DeBakey reported the first successful use of a LVAD in a 16-year-old girl who was supported for 10 days after mitral valve repair.15 Initial successes were met with subsequent poor outcomes limiting the application of VAD technology in pediatric patients.10 Nonetheless, a limited number of centers continued to develop this important technology over the next several decades bringing them to clinical fruition.16–19 Because of federal regulations in the United States, however, suitable VAD systems for smaller children are unavailable. Without alternatives for long-term pulsatile support, surgeons have relied on adult-size devices in the support of such patients.20–22 Use of BVADs have been shown to be efficacious in adults with profound cardiogenic shock, with survival rates of nearly 60%.23

Multicenter trials using the Thoratec VAD have shown the feasibility of using this adult-size device in children and adolescents for univentricular and biventricular support.24,25 In addition, these studies have elucidated specific complications related to using “oversized” VADs in pediatric patients including large stroke volumes, which may lead to systolic hypertension and subsequent intracranial hemorrhage; stasis in the device that can cause thromboembolic complications; and the obligatory use of four adult-size cannulae in a limited pericardial space. Although we were able to run all of the patients in the volume mode of the device, it is conceivable that in smaller patients, where the pump does not fill at a rate of at least 55 to 65 beats per minute, it may be better to run it in the fixed mode. In this case we recommend running the device at a fixed rate of at least 65 to 75 beats per minute with an eject time that could be reduced to at least 200 milliseconds. This reduces the risk of thromboembolic complications with low pump rates.

In this series, 83% of children and adolescents who received a BVAD survived the period of circulatory support. Our experience highlights that patient selection and timing of device implantation are crucial for obtaining acceptable results when using this expensive technology. Two children died while on circulatory support, both of whom developed multisystem organ failure. The first death was early in our experience and was directly attributable to a delay in initiation of mechanical circulatory support. The second death was in a patient who suffered postcardiotomy biventricular failure after attempted repair of a congenital heart lesion. The child was transferred to our facility on ECMO and died 2 days after BVAD implantation. It is known that postcardiotomy failure after congenital heart surgery is a risk factor for death.24

Reinhartz et al.25 reported results using the Thoratec VAD in children with body surface areas < 1.3 m2. A subgroup analysis of the 19 patients included in this study revealed that 10 patients underwent BVAD implantation. Overall survival was 30% in this group. When examining the data more closely, those patients who suffered heart failure after the repair of congenital heart defect had a significantly worse prognosis. The survival in this group was 25% compared with 50% in those patients with myocarditis or dilated cardiomyopathy. The cause of death in half the patients in this report was secondary to ischemic stroke or intercerebral hemorrhage. Although the majority of these patients had left ventricular apical inflow cannulation, the incidence of neurologic events was significantly higher than in our report. A possible explanation for this discrepancy includes a higher proportion of patients in their report undergoing BVAD implantation for postcardiotomy heart failure. Moreover, the mean body surface area in their report was lower than in our study, supporting the notion that adult-size devices in patients with smaller body surfaces areas may lead to higher rates of neurological events and death.

Hetzer et al.26 reported their experience from the Deutshes Herzzentrum using the Berlin Heart VAD in 28 patients. In their study, 19 children were supported with a BVAD with an overall survival of 63%. Interestingly, the rate of neurologic complications was only 5%. This may have been a reflection of appropriate patient-to-device size match and device design including the use of polyurethane valves instead of mechanical valves, which are noted to be less thrombogenic, and the transparency of the blood chambers and ports allowing for visual control of filling and emptying and transillumination for protection from thrombotic deposits. Goldman et al.27 reported their experience using the Medos HIA BVAD in nine children. The Medos system is a pneumatically driven miniaturized VAD with biomaterial and valve properties similar to the Berlin Heart. Overall mortality in this series was 33%, with four out nine patients experiencing a neurologic complication. The rates of neurologic complications were higher in this report, which is most likely attributable to the majority of patients in this group undergoing left atrial inflow cannulation, which was shown to be a statistically significant risk factor for developing neurologic events.24

The use of pediatric-size pulsatile paracorporeal VADs has been a clinical reality in centers in Europe and Asia. However, because of federal regulations in the United States, the use of such technology has not yet been approved. Our limited experience using miniaturized VAD technology is promising. Recently, our center has successfully supported two children with heart failure with the Berlin Heart who were ultimately bridged to transplantation. Neither of these children had device-related complications while on VAD, raising the question of limiting the availability of this technology in our country.

The willingness of cardiac surgeons to repair even the most complex congenital cardiac lesions had led to an expanded role for postcardiotomy circulatory support. Moreover, there is an increasing population of patients with a failing Fontan circulation, who may ultimately be candidates for long-term VAD. Our results and those of others21,24,25 have shown that the Thoratec BVAD can be successfully used to support children and adolescents with heart failure. However, there is uncertainty whether these adult-size devices when applied to smaller individuals have the same efficacy and safety. The use of miniaturized pulsatile paracorporeal ventricular devices in Europe and Asia has been a clinical reality for almost a decade. Long-term cardiac support may be achieved in these patients with the possibility of discharge home and the resumption of normal activities while awaiting transplantation. With the next generation of pediatric mechanical cardiac assist devices on the horizon, care providers for children with heart failure must demand that these technologies be available for use in this country.

Conclusion

The Thoratec paracorporeal assist device functions effectively in the pediatric population with severe end-stage congestive heart failure as a bridge to transplantation or as a means to promote myocardial recovery. Both left and biventricular support is feasible with excellent survival and acceptable morbidity.

References

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