Chronic Mechanical Circulatory Support

Introduction

The use of long-term mechanical circulatory support (MCS), predominately in the form of ventricular assist devices (VADs), has undergone a major transformation in the past 15 years. In the early 2000s, device use was uncommon. Support was typically for short duration, in patients with cardiogenic shock, and pediatric-specific device use, especially in the United States, was exceptionally rare. In the initial report on VADs from the Pediatric Heart Transplant Study database, covering children listed for heart transplantation from 1993 to 2003, only 4% of patients were supported with a VAD and only one Berlin Heart EXCOR VAD was used. This is in contrast to the current state where nearly 50% of pediatric patients with dilated cardiomyopathy (DCM) in the International Society for Heart and Lung Transplantation Registry are bridged to transplant with a VAD. In most pediatric transplant centers, VADs would currently be considered a standard part of advanced heart failure management, predominately being used as a bridge to transplant.

Patient Selection

Long-term MCS is generally used when patients have failed medical therapy for severe heart failure. Heart failure in children is not uncommon, with more than 14,000 hospitalizations annually in the United States, with diverse etiologies including congenital heart disease (CHD), cardiomyopathy, and myocarditis. The majority of VADs in children nowadays are used in patients with DCM. Although CHD accounts for 60% to 70% of heart failure–related hospitalizations, only 20% of VADs are implanted in children in CHD. The underlying disease and size of the patient are important considerations for the type of VAD used.

Disease severity is important for consideration and timing of MCS. Many children with less advanced stages of heart failure can be managed on oral therapy as outpatients with few cardiac-related symptoms. Indeed, a substantial minority of children with DCM will have improvement and even normalization of their ventricular function over time. However, heart failure is a severe, progressive disease that carries a high risk of major morbidity and mortality. Many patients will develop symptoms that are refractory to medical therapy, either after a period of long-term medical therapy or during the first presentation of acute heart failure. It is in these patients that placement of a VAD is considered.

Decisions about the timing of VAD placement can be among the most challenging in caring for children with advanced heart failure, but there is growing evidence that earlier placement, before the patients are in shock with multiorgan system failure, leads to improved outcomes. In the most recent annual report from Pedimacs, a large North American registry of pediatric VAD patients, patients who were Pedimacs profile 1 (critical cardiogenic shock) at the time of VAD implant had significantly inferior survival compared with those that were less ill at the time of VAD implant ( Fig. 66.1 ). Additional major morbidities that can complicate heart failure include respiratory failure, renal insufficiency, liver dysfunction, and malnutrition/growth failure. These major morbidities are also associated with outcome after VAD implantation. Data from INTERMACS, a large registry of adult VAD patients, evaluating more than 10,000 adult patients, found that preoperative morbidity, including being on a ventilator and having an elevated bilirubin level, a lower albumin level, and renal insufficiency, are associated with a significantly greater risk of death after VAD implantation. Unfortunately, these morbidities are common in children, with 31% Pedimacs profile 1, nearly 50% intubated, and 35% dependent on total parental nutrition at time of VAD implantation. Fortunately, much of the end-organ dysfunction, growth failure, and debilitated condition of many patients can be reversed after VAD placement and prior to heart transplantation and VAD explant. Indeed, the outcome after transplantation among patients supported with VADs is equivalent to patients who come to transplant on medical therapy alone. This would almost certainly not be the case if patients were transplanted in cardiogenic shock or multiorgan system dysfunction, as is frequently the case for VAD implantation.

There is neither widespread agreement nor evidence-based guidelines on the optimal timing for placement of VADs in children. The International Society for Heart and Lung Transplantation published consensus guidelines for MCS in 2013 and recommended that long-term VADs be considered for patients whose ventricular function is unlikely to recover without long-term support, who are inotrope dependent, too ill to maintain normal hemodynamics and organ function without temporary mechanical support or inotropes, who have the capacity for meaningful recovery of end-organ function and quality of life, and who have a high risk of 1-year mortality without VAD support. These are also reasonable guidelines for children, although clearly more data are needed to help understand the optimal time of VAD placement.

Current Devices for Short-Term Mechanical Circulatory Support in Pediatrics

Extracorporeal membrane oxygenation (ECMO) has been the primary means of short-term MCS for many years due to its familiarity and ease of rapid deployment. Although ECMO is useful in certain circumstances such as the need for emergent support or simultaneous pulmonary support, throughout its 25 years of use we have yet to see significantly more than half the cardiac patients survive to hospital discharge reported in multiinstitutional studies. Furthermore, ECMO as a bridge to transplant is a well-established independent risk factor for posttransplant mortality. For isolated heart failure, other forms of short-term MCS have been developed and are preferred in most situations.

Historically, adult short-term left VADs (LVADs) (e.g., BVS 5000) were occasionally used in larger children, with cannula and device size/output being factors limiting their widespread use. Currently, temporary devices are extracorporeal centrifugal pumps used with cardiopulmonary bypass cannulas, such as the ROTAFLOW (Maquet Cardiovascular) and the CentriMag/PediMag (Abbott). These centrifugal pumps are now found in most pediatric ECMO programs and therefore are familiar and accessible to the vast majority of pediatric heart programs. Another pump, the TandemHeart (Cardiac­Assist), has percutaneously placed cannulas to the left atrium and femoral artery, whereas the Impella (Abiomed) is a percutaneous, rotary heart pump that sits across the aortic valve in the left ventricular outflow tract. Both devices, especially the TandemHeart, require adolescent-sized, if not adult-sized, children. Cannula movement with minimal patient manipulation requiring cannula repositioning makes the use of the TandemHeart in smaller patients quite challenging. Until recently, there was a paucity of pediatric data regarding the outcomes of temporary devices and support, but studies are beginning to accumulate.

The notion of temporary support revolves around a quick and simple cannulation strategy meant to briefly sustain cardiac output (CO) in a patient with a reversible cause of heart failure or in urgent need of MCS. For temporary support, the left atrium can be rapidly cannulated along with the aorta, using bypass cannulas and without the need for cardiopulmonary bypass. This strategy is useful for patients with severe graft rejection or fulminant myocarditis so that perfusion is normalized and end-organ function is supported until the inflamed state of the heart can resolve and function can, hopefully, return. The device can then be removed. However, it can also be used to get a patient out of INTERMACS 1 so they become a better long-term support candidate or in a patient who needs support to allow time to determine etiology of heart failure, neurologic status, genetic issues, and so forth as a bridge to decision.

The PediMag and ROTAFLOW have historically been synonymous with temporary support and were connected to patients with bypass cannulas in a temporary cannulation configuration. However, in the past few years, surgeons have begun connecting the same device pumps to EXCOR cannulas as a bridge to transplantation. This is significantly different because EXCOR cannula placement is a more permanent cannulation technique requiring a more involved surgery and cardiopulmonary bypass. By virtue of using EXCOR cannulas with a pump, these devices are no longer used only as a means of temporary support because it is the cannulas that determine the duration for which support can be provided, not the pump itself. This combination of EXCOR cannulas with CF pumps is being done as a bridge to transplant in smaller children to simplify management of their anticoagulation during their postoperative inflammatory state. Furthermore, centrifugal pumps may require a lower level of anticoagulation, but if they do become thrombosed, they are easier and cheaper to replace. Once the patient stabilizes, the pump can be exchanged for an EXCOR pump to increase patient mobility if desired. A similar strategy is becoming the standard of care for smaller patients (<2 years old) with single ventricle physiology (SVP) and pulmonary artery banding, aortopulmonary collaterals, or a shunted physiology. The ability of the centrifugal pump to accommodate frequent changes in preload and flow at a high output make it a better fit for these single ventricle patients whose pulmonary blood flow can be quite varied, especially soon after surgery. The EXCOR has a set rate and fixed output unless one manipulates the settings, which cannot be done on a minute-to-minute basis. After a single ventricle patient has been supported for some time and is in a steady state (i.e., extubated, on enteral feeds, on stable anticoagulation, and off vasoactive intravenous medications), their preload and CO stabilize and conversion to an EXCOR pump at the bedside is possible. Our current algorithm for determining type of MCS is shown in Fig. 66.2 .

This issue of defining temporary support versus temporary VADs (i.e., centrifugal pumps) was demonstrated in a recent review of the Pedimacs database by Lorts et al. Of the 63 devices implanted under the classification of “temporary” VAD as their first device, 40% were placed with a strategy of bridge to transplant, whereas 60% were more classic temporary strategies (i.e., bridge to candidacy/recovery). Patient median age was 3.7 years, with 41% having CHD and 40% having cardiomyopathy. The median duration of support was 15 days, and 61% of patients received greater than 10 days of support. The median duration of support for transplanted patients was 47 days (interquartile range, 10 to 227), and five patients remained on temporary VAD longer than 5 months. Overall, this multiinstitutional study had a positive result (bridge to transplant/recovery/durable device or alive) in 71% of patients implanted with a temporary device pump.

Several other recent studies have shown good outcomes with longer times on temporary device pumps and as bridge to transplant. A review of the Organ Procurement and Transplantation Network data found that prior to 2011, fewer than three of these devices were used per year as a bridge to transplant, with an explosion in use to 50 of these temporary devices being used as bridge to transplant in 2015. In this review, CentriMag/PediMag was by far the most common, used in 65% of patients, followed by the TandemHeart pump (not system), used in 18%. Importantly, in comparison to the ECMO cohort, a propensity score-matched short-term MCS cohort had longer survival to transplant, as well as longer overall survival. Data have also shown that, if temporary support is used for a chronic heart failure patient with acute cardiogenic failure, the vast majority of these patients will not recover and will require conversion to long-term VAD support.

Current Devices for Long-Term Mechanical Circulatory Support in Children

Berlin Heart EXCOR

The Berlin Heart EXCOR is a paracorporeal pulsatile, pneumatically compressed, volume displacement pump. It is available in 10-, 15-, 25-, 30-, 50-, and 60-mL blood chamber sizes ( Fig. 66.3 ). It is the most studied pediatric VAD, with more than 1800 implants, the only to be FDA approved, and the most commonly used worldwide. Use of customized polyurethane valves has allowed the manufacture of smaller blood pump sizes than are available with “adult” pumps, which have used commercially available mechanical valves. Its first reported successful use as a bridge to transplantation occurred in 1990. The longest known support time has been 877 days to successful transplant. The experience at the Berlin Heart Institute has been extensively reported. A total of 74 pediatric patients were supported there from 1990 to 2006, with a mean age of 7.6 years (range, 2 days to 17 years) and a mean support time of 36 days. Fifteen percent of these patients were weaned from the device, with 43% receiving a heart transplant; 41% of the children died during VAD support. The group notes significant improvement from the year 2000 onward, with a 74% survival rate to transplantation or discharge despite a younger patient population. The authors note that changes in their decision-making process from earlier to later in the experience included earlier implementation of support before the development of significant end-organ failure, improvements in cannula design, apical left ventricle rather than atrial cannulation, fewer biventricular VADs (BiVADs), and a focus on the anticoagulation protocol.

The device was first used in North America in 2000, and by 2004 there was widespread use. The initial EXCOR experience in the United States from 2000 to 2007 ( n = 73) was reported to have a positive outcome in 77% of patients and paved the way for a prospective, multicenter, clinical cohort investigational device exemption (IDE) study. The IDE study enrolled 48 patients from 2007 to 2010 and conclusively demonstrated EXCOR to be superior to ECMO in bridging children to transplantation. The outcomes of all 204 children who underwent EXCOR implantation during the duration of the IDE study was also published and was believed to represent the real-world use of EXCOR in North America. In this study, 75% of patients survived to transplantation or recovery, with lower weight, higher bilirubin values, and BiVAD support predicting early mortality (<2 months). Bilirubin extremes and decreased glomerular filtration rate at implant predicted late mortality (>2 months). The most common cause of death was stroke (33%), most often of thromboembolic origin. Lower weight at implantation and large pump size to body surface area (BSA) have been associated with neurologic injury in other studies. Importantly, only one death in the North American experience was attributed to device malfunction. Recent studies comparing posttransplant survival in those bridged to transplant with EXCOR versus no MCS showed comparable survival between the groups, with 94%, 90%, and 72% survival at 30 days, 1 year, and 5 years, respectively, in the EXCOR group. This was congruent with previous findings, which additionally identified similar 1-year survival between EXCOR patients with and without complications. The latter study also noted a significantly higher incidence of death after transplant in patients with CHD compared with those with cardiomyopathy (26.1% vs. 7.2%).