Outcomes With Ventricular Assist Device Versus Extracorporeal Membrane Oxygenation as a Bridge to Pediatric Heart Transplantation

Extracorporeal membrane oxygenation (ECMO) has long been the sole means of mechanical support for pediatric patients with end‐stage cardiac failure, but has a high waitlist mortality and a reported survival to hospital discharge of less than 50%. The purpose of this study was to compare waitlist mortality and survival for ECMO versus ventricular assist device (VAD) support. A review was conducted of all patients listed for heart transplantation (HTx) since 2002 and requiring mechanical support. VAD support has been available from 2004 (Berlin Heart Excor Pediatrics). Competing risks analysis was used to model survival to one of four outcomes (HTx, death on waitlist, delisting, improvement). Thirty‐six patients were on mechanical support while awaiting HTx (21 ECMO, 12 VAD, three both). Median age at listing was 1.2 years (birth–16.6 years) for ECMO and 11.3 years (0.3–14.6 years) for VAD. Diagnosis was cardiomyopathy in 33% for ECMO and 93% for VAD. Median time to HTx was 37 days (1–930) overall, 20 days (1–85) for ECMO, and 39 days (5–108) for VAD. Mechanical support was associated with increased odds of HTx (hazard ratio [HR] 2.4 [1.7–3.3], P < 0.0001) but also delisting or death waiting (HR 3.0 [1.1–7.8], P = 0.03). Waitlist mortality of 38% on ECMO was reduced to 13% with VAD use. Survival post‐HTx to hospital discharge was better in the group on VAD support (92 vs. 80%). Pediatric patients requiring mechanical support as a bridge to HTx have short wait times but high waitlist mortality. Those patients who survived to be put on the Berlin Heart Excor Pediatric device based on individualized clinical decision making then had a lower waitlist mortality, a longer duration of support, and a higher survival to transplantation and hospital discharge.     

The Present and Future of Cardiac Assist Devices

This article describes the status of development of an implantable electrically powered ventricular assist device designed for a minimum of a 2-year operation in patients with advanced heart failure. While these devices are envisioned for chronic support of the failing circulation, air-driven blood pumps have been used to provide life support to patients with acute ventricular dysfunction produced by a reversible myocardial injury of unknown origin. The physical and hemodynamic characteristics of the mechanical circulatory support devices are detailed. Clinical indications and results are provided on patients treated with temporary ventricular assist devices. Long-term follow-up of some patients has demonstrated sustained improved cardiac function for up to 5 years after treatment. Reperfusion injury and postischemic myocardial depression are discussed as two possible etiologies of acute ventricular dysfunction. In the summer of 1984, investigators began a collaborative program to test the engineering reliability of implantable devices as well as their performance in animals. This 3-year Device Readiness Program had a goal of demonstrating an 80% reliability with a confidence interval of 70%. In the future, the implantable device will be evaluated clinically in selected patients to investigate its ability to support circulatory functions and the results of host-device interactions. These devices have potential both as experimental tools in studies of heart and vascular disease and in the treatment of patients with intractable heart failure.     

Design, Manufacturing, and Testing of a Paracorporeal Pulsatile Ventricular Assist Device: S˜o Paulo Heart Institute VAD

Abstract: This paper describes the design of a ventricular assist device (VAD), its manufacturing, and testing. The VAD presented is pulsatile, with a free-floating membrane, smooth internal surfaces, and pericardial valves. It comprehends also a pneumatic driving unit capable of operating in the "full to empty," EKG synchronized or asynchronous modes. In vitro tests were performed to assess its mechanical durability, hydrodynamic performance, and hemolysis. To optimize cannulas and implant techniques, we performed in vivo tests in 22 sheep and 8 calves. In these tests, we also evaluated hemolysis and the device's capacity to normalize hemodynamic parameters during induced cardiac failure. The VAD worked for 4,000 h without failure in a mock circulatory loop. In full to empty mode, it displayed a rate-mediated "Starling-like" performance. Optimum output was achieved with a systole duration of 40% of the cycle. The in vitro hemolysis index (IH) was 6.7 ±2.1. Hemolysis in animal experiments was clinically nonsignificant. In calves with induced cardiac failure, the VAD was able to normalize hemodynamic parameters within 120 min.     

新型主动脉旁与主动脉内球囊反搏对羊重度急性心力衰竭辅助的实验研究

目的比较新型主动脉旁反搏装置（paraaortic counterpulsation device,PACD）与主动脉内球囊反搏（intraaortic balloon pump,IABP）装置对羊重度急性心力衰竭的辅助效果。方法选成年小尾寒羊8只,将自制PACD（每搏量为55 ml）的无瓣人工血管吻合于降主动脉,同时于降主动脉内植入IABP（每搏量为40 ml）进行反搏辅助。结扎冠状动脉分支建立重度急性心力衰竭动物模型,观察PACD和IABP辅助对重度急性心力衰竭辅助后的血流动力学变化;实验结束后观察PACD辅助和羊主要器官的变化。结果成功建立了8只羊心力衰竭模型,心力衰竭后心排血量（CO）、肺毛细血管楔压（PCWP）、平均动脉压（MAP）和左心室舒张期末压（LVEDP）与基础值比较差异均有统计学意义（t=-8.466,34.083,25.767,-5.219,P=0.000）。应用IABP和PACD辅助后,平均动脉舒张压（MADP）较辅助前不明显或明显增高（38.34±7.13 mm Hg vs.38.42±6.81 mm Hg,P=0.418;38.34±7.13 mmHg vs.54.14±10.13 mm Hg,P=0.001）,IABP与PACD比较差异有统计学意义（P=0.010）;而LVEDP较辅助前无明显降低（7.43±2.54 mm Hg vs.7.32±2.14 mm Hg,P=0.498;7.43±2.54 mm Hg vs.6.53±1.91 mm Hg,P=0.821）,IABP与PACD比较差异无统计学意义（P=0.651）;冠状窦血流量（CSF）较辅助前不明显或明显增加（86.63±7.71 ml/min vs.87.04±6.53 ml/min,P=0.981;86.63±7.71 ml/min vs.110.52±11.03 ml/min,P=0.000）,IABP与PACD比较差异有统计学意义（P=0.000）;IABP辅助后,左侧颈动脉流量（LCAF）较辅助前无明显降低（131.07±21.26 ml/min vs.128.36±20.38 ml/min,P=0.689）,而PACD辅助后较辅助前增加（131.07±21.26 ml/min vs.151.29±18.37 ml/min,P=0.008）,IABP与PACD比较差异有统计学意义（P=0.002）。PACD后血囊、人工血管内及动物心脏、肝、肾、肺等器官未见血栓、栓塞和缺血坏死;病理切片在光学显微镜下观察未见明显异常。结论 IABP对羊重度急性心力衰竭无辅助作用,而PACD辅助明显提高了MADP,增加了冠状窦血流量,改善了脑灌注流量,对重度心力衰竭具有良好的循环辅助效果。     

Management of single-ventricle patients with Berlin Heart EXCOR Ventricular Assist Device: single-center experience

There are minimal data regarding chronic management of single‐ventricle ventricular assist device (VAD) patients. This study aims to describe our center's multidisciplinary team management of single‐ventricle patients supported long term with the Berlin Heart EXCOR Pediatric VAD. Patient #1 was a 4‐year‐old with double‐outlet right ventricle with aortic atresia, L‐looped ventricles, and heart block who developed heart failure 1 year after Fontan. She initially required extracorporeal membrane oxygenation support and was transitioned to Berlin Heart systemic VAD. She was supported for 363 days (cardiac intensive care unit [CICU] 335 days, floor 28 days). The postoperative course was complicated by intermittent infection including methicillin‐resistant Staphylococcus aureus, intermittent hepatic and renal insufficiencies, and transient antithrombin, protein C, and protein S deficiencies resulting in multiple thrombi. She had a total of five pump changes over 10 months. Long‐term medical management included anticoagulation with enoxaparin, platelet inhibition with aspirin and dipyridamole, and antibiotic prophylaxis using trimethoprim/sulfamethoxazole. She developed sepsis of unknown etiology and subsequently died from multiorgan failure. Patient #2 was a 4‐year‐old with hypoplastic left heart syndrome who developed heart failure 2 years after bidirectional Glenn shunt. At systemic VAD implantation, he was intubated with renal insufficiency. Post‐VAD implantation, his renal insufficiency resolved, and he was successfully extubated to daytime nasal cannula and biphasic positive airway pressure at night. He was supported for 270 days (CICU 143 days, floor 127 days). The pump was upsized to a 50‐mL pump in May 2011 for increased central venous pressures (29 mm Hg). Long‐term medical management included anticoagulation with warfarin and single‐agent platelet inhibition using dipyridamole due to aspirin resistance. He developed increased work of breathing requiring intubation, significant anasarca, and bleeding from the endotracheal tube. The family elected to withdraw support. Although both patients died prior to heart transplantation, a consistent specialized multidisciplinary team approach to the medical care of our VAD patients, consisting of cardiothoracic surgeons, heart transplant team, hematologists, pharmacists, infectious disease physicians, psychiatrists, specialty trained bedside nursing, and nurse practitioners, allowed us to manage these patients long term while awaiting heart transplantation.     

Risk Factor Screening Scale to Optimize Treatment for Potential Heart Transplant Candidates under Extracorporeal Membrane Oxygenation

We developed a risk factor-scaling score (RFSS) to select which patients supported by extracorporeal membrane oxygenation (ECMO) were suitable for ventricular assist device (VAD) implantation or heart transplantation (HTx). A total of 78 patients supported with ECMO for more than 48 h due to cardiac origin were included in this study. Patients were categorized into two groups based on the outcomes: the poor outcome group (n = 33) consisted of for those who later died or were later excluded from VAD or HTx; the favorable outcome group (n = 45) consisted of those who were weaned off ECMO finally and survived or were deemed suitable candidates for VAD or HTx. Seven risk factors were significant according to univariate analyses. Based on the regression coefficients of multivariate analysis, the RFSS was developed: (lung dysfunction x 7) + (systemic infection x 3) + (peak lactate > 3 mmole/L x 3) + (kidney dysfunction x 2) + (creatine kinase > 10,000 U/L x 1). Patients with an RFSS of 7 or more were be allocated to the poor outcome group. The RFSS was validated by another group of 30 patients with good correlation. The RFSS provides a way to predict which ECMO-supported patients are suitable candidates for VAD implantation or HTx.     

Survival Predictors in Ventricular Assist Device Patients With Prior Extracorporeal Life Support: Selecting Appropriate Candidates

Several centers turn patients down for long‐term ventricular assist devices (VADs) once they have received extracorporeal life support (ECLS) due to the expected poor outcome in these patients. The aim of this study was to identify survival predictors in this cohort of patients. Data of patients undergoing VAD support between January 2010 and November 2013 were retrospectively reviewed. Patients on ECLS support before implantation were considered eligible for inclusion. Outcome in survivors following long‐term VAD support was compared with outcomes in nonsurvivors. Student's t‐test and χ²‐test were used as applicable. A total of 65 long‐term VADs were implanted. The inclusion criteria were met by 24 patients. Eight patients did not survive the first 30 days. All preoperative characteristics were comparable between the two groups except for statistically higher Model for End‐stage Liver Disease (MELD) score, bilirubin, white blood cell count, and blood urea nitrogen in nonsurvivors (P = 0.002, 0.01, 0.01, and 0.003, respectively). Stepwise discriminant analysis revealed MELD score as the most important survival predictor. Based on this analysis, an outcome predictor formula was generated. The 30‐day and 1‐year survival rates were 67% and 54%, respectively. In this study, we were able to determine survival predictors in VAD patients with prior ECLS support. The outcome in these patients is limited and associated with higher postoperative complications, particularly right ventricular and respiratory failure. The pre‐VAD MELD score is an important predictor of poor outcome.     

Extracorporeal Life Support Bridge to Ventricular Assist Device: The Double Bridge Strategy

In patients requiring left ventricular assist device (LVAD) support, it can be difficult to ascertain suitability for long‐term mechanical support with LVAD and eventual transplantation. LVAD implantation in a shocked patient is associated with increased morbidity and mortality. Interest is growing in the utilization of extracorporeal life support (ECLS) as a bridge‐to‐bridge support for these critically unwell patients. Here, we reviewed our experience with ECLS double bridging. We hypothesized that ECLS double bridging would stabilize end‐organ dysfunction and reduce ventricular assist device (VAD) implant perioperative mortality. We conducted a retrospective review of prospectively collected data for 58 consecutive patients implanted with a continuous‐flow LVAD between January 2010 and December 2013 at The Alfred Hospital, Melbourne, Victoria, Australia. Twenty‐three patients required ECLS support pre‐LVAD while 35 patients underwent LVAD implantation without an ECLS bridge. Preoperative morbidity in the ECLS bridge group was reflected by increased postoperative intensive care duration, blood loss, blood product use, and postoperative renal failure, but without negative impact upon survival when compared with the no ECLS group. ECLS stabilization improved end‐organ function pre‐VAD implant with significant improvements in hepatic and renal dysfunction. This series demonstrates that the use of ECLS bridge to VAD stabilizes end‐organ dysfunction and reduces VAD implant perioperative mortality from that traditionally reported in these “crash and burn” patients.     

Out-of-center extracorporeal membrane oxygenation for adult cardiogenic shock patients

Patients with cardiogenic shock refractory to conventional management require advanced mechanical circulatory support such as extracorporeal membrane oxygenation (ECMO). In hospitals lacking ECMO facilities, interhospital transportation is necessary for further patient management. Thirty-one adult cardiac patients, who were transported to our hospital by our ECMO transport team between January 1998 and July 2004, were enrolled in this study. The median transportation distance was 200 km (range: 3-300 km). During transportation, the ECMO circuit per se and the patients did not have complications. Of the 31 patients, 20 (64.2%) were weaned off ECMO or bridged to ventricular assist devices and 10 patients (32.1%) survived to discharge. Delayed transfer (>2 days) and high organ dysfunction score were associated with poor outcomes. The survival rate was similar to that of our in-hospital group (survival rate: 32.8%, n = 64). In conclusion, adult cardiogenic shock patients requiring interhospital ECMO transport had a reasonable chance of survival.     

ECMO在临床心脏移植领域的应用

目的 总结体外膜肺氧合(ECMO)技术在临床心脏移植领域的应用效果.方法 19例行双腔法同种异体原位心脏移植病人于术中或术后应用ECMO支持.年龄33-6l岁,平均(42.5±9.6岁;体重61.92 kg,平均(73.6士15.2)kg.其中扩张型心肌病16例、瓣膜病2例、冠心病1例;术前心Z能均为NYIIAⅢ~IV级.术后采用环孢素A+霉芬酸酯+强的松三联免疫抑制和巴利昔单抗免疫诱导方案.结果 1O例术中并术后应用ECMO者供体冷缺血(7.5±1.3)h;ECMO术中转机流量为(3.9±0.8)L/min;术后辅助流量为(2.2±0.3)L/min;辅助(62±35)h;9例生存,1例移植物衰竭死亡.9例心脏移植术后发生移植物衰竭者,供体冷缺血(4.5±1.0)h;开始应用ECIVlO进行辅助支持为术后停体外循环即刻至术后12h,平均(5.4±3.5)h;ECMO辅助流量为(2.7.4-0.5)L/min,辅助(88±24)h;2例分别死于感染、多器官功能衰竭,ECMO辅助分别为112 h、78 h,撤机后3 d、14 d死亡.生存16例无严重并发症,病理活检未见急性排斥反应,心功能I~Ⅱ级出院.现生存3个月至2年,未发现明确与ECI~IO相关的,发症.结论 ECMO术中转机并术后辅助治疗策略有利于长时间缺血供心的功能恢复,从而扩大边缘性供体心脏的使用范围;ECMO辅助支持有利促进移植物衰竭病人的恢复.     

Test Controller Design, Implementation, and Performance for a Magnetic Suspension Continuous Flow Ventricular Assist Device

A new continuous flow ventricular assist device using full magnetic suspension has been designed, constructed, and tested. The magnetic suspension centers the centrifugal pump impeller within the clearance passages in the pump, thus avoiding any form of contact. The noncontact operation is designed to give very high expected mechanical reliability, large clearances, low hemolysis, and a relatively small size compared to current pulsatile devices. A unique configuration of magnetic actuators on the inlet side and exit sides of the impeller provides full 5 axis control and suspension of the impeller. The bearing system is divided into segments which allow for 3 displacement axes and 2 angular control axes. The controller chosen for the first suspension tests consists of a decentralized set of 5 proportional integral derivative (PID) controllers. This document describes both the controller and an overview of some results pertaining to the magnetic bearing performance. The pump has been successfully operated in both water and blood under design conditions suitable for use as a ventricular assist device.     

Chronic Survival of Calves Implanted with the DeBakey Ventricular Assist Device

The DeBakey ventricular assist device (VAD) is a miniaturized, electromagnetically driven axial flow pump capable of generating in excess of 10 L/min output. The VAD was evaluated in 19 calves during experiments designed to test iterative modifications in the system and to determine the safety of the DeBakey VAD for intermediate to long-term implant. Five of the animals died or were euthanized during the perioperative period (i.e., Days 1-5) due to complications associated with bleeding (n = 3), sudden cardiac arrest (n = 1), or pump occlusion due to a muscle remnant associated with coring (n = 1). The remaining 14 animals survived from 7-145 days. Ten of the 14 animals survived 30 or more days, and 2 animals survived 93 and 145 days before elective euthanasia. Pump function was evaluated in the 14 calves that survived beyond the perioperative period. Pump output at implantation averaged 3 L/min while output at 100 days (n = 2) averaged 4.22 L/min. The electrical current did not change across time during the study, indicating normal operation of the bearings. Pumps consumed less than 10.5 W of power for all support durations. Hemolysis did not occur; the average daily plasma free hemoglobin varied from 2.0 to 8.0 mg/dl. Evaluation of serum biochemical data showed that implantation of the DeBakey VAD in calves with normal hearts did not impair end organ function; BUN, creatinine, and total bilirubin varied minimally within the normal range. The white blood cell count of implanted animals remained within the normal range throughout the study.     

Impact of Pump Replacement on Outcome in Advanced Heart Failure Patients With Left Ventricular Assist System

Pump thrombosis is one of the major adverse events associated with the use of a left ventricular assist system (LVAS) in patients with advanced heart failure. We investigated the clinical implication of pump replacement because of thrombus formation. This study included 87 patients who underwent implantation of a Nipro (Toyobo) pulsatile extracorporeal LVAS intended as a bridge to transplantation and were alive more than 3 months after implantation. The pump of this device is translucent, and daily evaluation for signs of thrombus formation was performed. Pump replacement was performed for significant thrombus formation that became visible. Data collection including demographics as well as hematologic values were performed 1 day before (baseline) and 3 months after implantation, and all patients were followed for 2 years or until death. At 3 months after LVAS implantation, 41 patients (47.1%) had undergone pump replacement because of pump thrombus. Baseline body surface area <1.63 m² was a significant predictor of pump replacement (hazard ratio [HR] 2.15, P = 0.04). At 3 months after implantation, there was a significantly higher incidence of stroke (P < 0.05) as well as a significantly greater decrease in body weight (F = 4.92, P = 0.03) in patients who underwent pump replacement as compared to those without. The 2‐year mortality after implantation was 26.4%. Multivariate Cox regression analysis showed that pump replacement within 3 months after implantation was an independent predictor of mortality (HR 2.50, P = 0.03). In conclusion, pump replacement for thrombus formation may have a strong association with worse outcome. Our results reconfirm the clinical importance of device thrombus in the management of LVAS.     

Feasibility of a tiny centrifugal blood pump (TinyPump) for pediatric extracorporeal circulatory support

Abstract: In this study, the performances of the TinyPump (priming volume 5 mL) system including the pediatric cannulae (Stöckert Pediatric Arterial Cannulae 2.6, 3.0, and 4.0 mm, Stöckert Instruments GmbH, Munich, Germany; Polystan 20‐Fr Venous Catheter, MAQUET GmbH, Rastatt, Germany) and an oxygenator (Terumo Capiox RX05 Baby‐RX, Terumo Cardiovascular Systems Co., Tokyo, Japan) were studied in vitro followed with preliminary ex vivo studies in 20‐kg piglets. In vitro results revealed that the TinyPump system met the requirements for pump speed, pump flow, and pressure drop as extracorporeal circulatory support during open heart surgery and extracorporeal membrane oxygenation (ECMO) in pediatric patients. In 2‐h ex vivo studies using 20‐kg piglets where the blood contacting surface of the TinyPump was coated with a biocompatible phospholipid polymer, the plasma‐free hemoglobin levels remained less than 5.0 mg/dL and no thrombus formation was observed inside the pump. The TinyPump system including the oxygenator and connecting circuits resulted in an overall priming volume of 68 mL, the smallest ever reported. The TinyPump can be a safe option for pediatric circulatory support during open heart surgery and ECMO without requiring blood transfusion.     

Left Ventricular Assist for Pediatric Patients With Dilated Cardiomyopathy Using the Medos Vad Cannula and a Centrifugal Pump

Ventricular assist devices for small pediatric patients are expensive and commercially unavailable in Taiwan. We used the Medos ventricular assist device cannula (Medos, Aachen, Germany) and a centrifugal pump to support pediatric patients with dilated cardiomyopathy and decompensated heart failure. From January 2007 to December 2008, three pediatric patients with dilated cardiomyopathy were supported using a centrifugal pump as the left ventricular assist device. The Medos arterial cannula was sutured to the ascending aorta, and the Apex cannula was fixed into the left ventricular apex. When the patient was weaned off of cardiopulmonary bypass, the left ventricular assist device pump was started. The pump flow was gradually titrated according to the filling status of the left ventricle. All the left ventricular assist devices were successfully implanted and functioned well. Two patients on extracorporeal membrane oxygenation had severe lung edema before left ventricular assist device implantation. Both patients required extracorporeal membrane oxygenation for the postoperative period until the pulmonary edema was resolved. Among the three patients, two successfully bridged to heart transplantation after support for 6 and 11 days, respectively. The first patient (10 kg) expired due to systemic emboli 30 days after left ventricular assist device support. In summary, these results suggest that the Medos ventricular assist device cannula and a centrifugal pump is an option for temporary left ventricular assist device support in patients with intractable heart failure and as a bridge to heart transplantation.     

边缘性供心移植术中采用体外膜肺氧合技术四例

目的 研究体外膜肺氧合(ECMO)技术用于边缘性供心移植的临床效果.方法 4例患者心脏移植时采用ECMO技术,其供心的冷缺血时间长达4.8～8.0 h.术中采用ECMO技术代替体外循环,全流量控制在4.5～5.0 L/min,术后流量降到1/2左右时,改为经典的ECMO心脏辅助管路的连接方式,带ECMO辅助回到重症监护室,随后在合适的时机撤除ECMO的辅助.结果 4例手术均顺利完成,主动脉开放后心脏自动复跳.术中阻断时间为(90±3)min,转机(136±14)min,转流时的主动脉流量为50～70 ml·kg-1·min-1,氧流量为2～4 L/min.4例患者均于术后第2天撤除ECMO,术后ECMO辅助时间为(16±4)h.2例术后出现出血,1例右下肢出现淋巴漏和神经过敏,经过积极治疗后好转,无右心衰竭和三尖瓣明显返流现象.4例患者恢复顺利,出院时左心室舒张末径为37～43 mm,左心室射血分数为56 %～64 %,三尖瓣无返流或仅有轻度返流,心功能均为Ⅱ级.结论 以ECMO代替体外循环技术可以有效地保护供心,有利于经历长时间缺血的供心恢复功能.     

Primary extracorporeal membrane oxygenation versus primary ventricular assist device implantation in low cardiac output syndrome following cardiac operation

Mechanical support is often the only therapeutic option in low cardiac output (LCO) following cardiac operation using extracorporeal circulation (ECC). However, the question whether primary ventricular assist device (VAD) or primary extracorporeal membrane oxygenation (ECMO) followed by secondary VAD implantation is superior remains unclear. We analyzed the outcome of 183 patients with LCO following ECC. Primary VAD implantation (VAD) was performed on 20 patients and 163 patients underwent ECMO implantation (ECMO). Out of this group, 13 patients received a secondary VAD (ECMO-VAD). Age was significantly lower in the VAD group, while gender and type of operation were similarly distributed. Thirty-day mortalities were 50, 75, and 46% (VAD, ECMO, and ECMO-VAD, respectively; P < 0.05 ECMO vs. VAD and ECMO-VAD). Survival was best with VAD implantation 1.2 +/- 1.2 days following LCO. In conclusion, the outcome of LCO following ECC remains poor. Early VAD support provides best survival. Primary or secondary VAD implantation has no impact on survival.