Objectives: Organ shortages and increased numbers of nontransplant older patients have necessitated a search for alternatives to heart transplants. The Jarvik 2000 assist device (Jarvik Heart, Inc., Manhattan, NY, USA), as a small long-term axial flow pump, offers many advantages, such as retroauricular power supply, which minimizes driveline infection risks. When implanted biventricularly, the device may offer support for patients with biventricular heart failure, especially for nontransplant patients as a destination therapy.

Materials and Methods: We implanted biventricular Jarvik 2000 systems into 3 men (aged, 65.3 ± 5.0 y; ejection fraction, 24.7% ± 1.5% for left ventricle and 17.7% ± 5.0% for right ventricle). These were the first patients worldwide to receive a biventricular Jarvik 2000 device with retroauricular power supply via a median sternotomy and with additional cardiac surgical procedures.

Results: No technical problems were noted during biventricular assist device implant. Mean support time on the device was 224 ± 198 days. All 3 patients showed sufficient cardiac support; 2 patients died from noncardiac complications. Patient 1 died on day 3 as a result of postoperative hepatic failure after preo­perative reanimation, and patient 3 died as a result of an ileus and colon perforation after 50 days. Patient 2 died of ventricular fibrillation (after 1.5 y), which occurred 1 year after right ventricular pump shutdown, although significant improvement of right ventricle fun­ction was shown (ejection fraction increased by 48%).

Conclusions: Our 3 patients were old, had multiple comorbidities, and needed further cardiac surgery. None of the patients died as a result of technical failure of the device but because of complications accompanying their morbidities. If complication rates can be reduced, a biventricular assist device implant could and should be considered as a potential alternative for nontransplant patients.

Key words : Alternative to transplant, Biventricular assist device, Destination therapy

Introduction

Organ shortages have resulted in many patients with terminal heart failure waiting for heart transplants. In addition, patient populations are increasingly older and have more comorbidities and thus are often considered inoperable because of low cardiac output or because they are not qualified for heart transplant. As an alternative solution to help these patients, the use of left ventricular assist devices (LVADs), such as the Jarvik 2000 (Jarvik Heart Inc., Manhattan, NY, USA), is becoming more important as an alternative to heart transplant. Although primarily used as a bridge to transplant, the Jarvik 2000 LVAD is now used as a destination therapy, showing very good results for up to 7.5 years, and could be seen as an option with satisfying quality of life.¹

The advantages of the Jarvik 2000 system are clear. It is one of the smallest (90 g/25 mL)² intraventricularly positioned pumps currently available on the market, there is no need for the creation of a pump pocket, and it can be implanted fairly quickly. The intermittent low-speed mode, which reduces the motor speed every 1 minute for 8 seconds, provides a partial pulsatility and “washing out” of the aortic valve, reducing thromboembolic events caused by a closed aortic valve.³ Furthermore, the patient’s own ventricle is still working as a backup but has the chance to recover (bridge-to-recovery concept). In contrast to the abdominal driveline connection version in all other systems, the behind-the-ear connector improves the quality of life and reduces the driveline infection rate almost to zero (unpublished data).

To treat patients with terminal biventricular heart insufficiency, we implanted the biventricular Jarvik 2000 system with 2 retroauricular power supply connectors via a median sternotomy. This was the first time for this type of implant in Germany and worldwide. We describe our methods and results for 3 patients who received the biventricular Jarvik 2000 assist device.

Materials and Methods

The protocol, conducted according to the guidelines of the Declaration of Helsinki, was approved by our institutional ethics committee, and written informed consent was obtained from the patients.

We implanted the Jarvik 2000 biventricular assist device into 3 male patients with multiple morbidities (age, 65.3 ± 5.0 y, ejection fraction of 24.7% ± 1.5% for the left ventricle and 17.7% ± 5.0% for the right ventricle). All 3 patients had already received maximum conservative therapy and had shown progressive biventricular heart failure with low ejection fractions. Baseline characteristics and follow-up of the patients are shown in Table 1.

Patient 1
Patient 1 was a 67-year-old man who presented with hemodynamic instability and numerous diagnoses, including severe coronary artery 3-vessel disease, myocardial infarction (recorded in 1998, with percutaneous transluminal coronary angioplasties in 1998 and 1999), reduced LVAD pump function (ejection fraction of 27%), right heart insufficiency (ejection fraction of 20%) combined with pulmonary hypertension, New York Heart Association class 3, chronic atrial fibrillation, mitral valve insufficiency grade 2, and renal insufficiency due to diabetic nephropathy and hepatomegaly. Cardiovascular risk factors were hypertension, type 2 diabetes mellitus, hyperlipoproteinemia, and nicotine abuse. In sum­mary, this patient had severe multiple morbidities, who initially was resuscitated the evening before a planned coronary artery bypass operation and received an intra-aortic balloon pump, with hemodynamic measurements also showing severe right heart failure. Therefore, the indication for a biventricular assist device was given (Figures 1 and 2). Because of increasing high doses of inotropic catecholamines, as final therapy, the decision was made to implant a left and right ventricular Jarvik 2000 assist device as a destination therapy.

Because an additional coronary artery bypass procedure (left internal mammary artery to the left anterior descending) was necessary, we switched from our standard implant procedure (via a left posterolateral thoracotomy) to a median sternotomy4 and modified it for biventricular implant (modified Munich technique) with 2 retroauricular connectors. The patient was positioned in similar way as for a left anterolateral thoracotomy, and the head was turned to the right side to expose the retroauricular area. After the sternotomy, the power cables were tunneled via 2 help incisions from the jugulum to the left retroauricular area (Figure 3). The coronary artery bypass revascularization was then carried out by using extracorporeal circulation and cardioplegia. Before reperfusion, 2 Jarvik sewing rings were attached: the first to the apex of the left ventricle and the second to the apical posterior wall of the right ventricle with single-stich technique. The outflow conduits were first anastomosed for the right ventricular assist device (RVAD) with the pulmonary trunk and then for the LVAD with the ascending aorta after adjusting the length of the Dacron outflow graft (Figure 4). First, the pump of the LVAD was inserted after incision with a ring knife into the left ventricular apex, and then the pump of the RVAD was inserted in the same way into the right ventricular apex. The power controller was primarily set on level 4 for the LVAD pump and 3 for the RVAD pump.

Patient 2
Patient 2 was a 56-year-old man who presented with severe leg edema and respiratory distress after global cardiac decompensation and multiple hospital­izations. Further diagnoses were dilative ischemic cardiomyopathy (left ventricular and right ventricular ejection fractions of 22% and 25%), status after mechanic aortic valve replacement (documented in 1995), coronary artery 3-vessel disease with coronary bypass revascularizations (documented in 2002 and 2010), intermittent absolute arrhythmia, chronic renal insufficiency grade 2, implantable cardioverter defib­rillator (in 2002), acute urinary tract infection, and clostridium difficile-associated colitis. Numerous cardiovascular risk factors were found, including essential hypertension, type 2 diabetes mellitus, and hypercholesterinemia.

The indication for a biventricular assist device was primarily given, and we once again chose the modified Munich technique as the surgical pro­cedure because it was necessary to replace the mechanical aortic valve as a redo procedure by a biologic prosthesis (C-E Perimount magna Ease Aortic, 23 mm; [C-E Perimount, Irvine, CA, USA]) because of thromboembolic causes. This was the first patient who received the new, so-called blue controller for the right ventricle. Although the normal LVAD controller uses intermittent low-speed mode, which allows the heart to eject by itself for 8 seconds every 1 minute, when the pump slows down to 6000 rounds/min, we found that this mode in the RVAD causes insufficient unloading to the right ventricle. The blue controller, however, has no intermittent low-speed mode and thus provides a continuous flow and right ventricle unloading. Because the patient had severe fixed pulmonary hypertension, the power mode for both ventricles was primarily set on level 4.

Patient 3
Patient 3 was a 73-year-old man with severe biventricular heart failure after chronic dilative cardiomyopathy (left and right ventricular ejection fractions of 25% and 8%; Figure 5). Other diagnoses included chronic renal insufficiency grade 3, pulmonary hypertension (systolic pulmonary artery pressure of 85 mm Hg), mitral valve insufficiency grade 2, tricuspidal valve insufficiency grade 3 (Figure 5), atrial fibrillation, hypoxia (PO₂ = 52 mm Hg, P_CO2 = 42 mm Hg), symptomatic epilepsy, and obstructive sleep apnea syndrome requiring continuous positive airway pressure home therapy. The patient’s history included middle cerebral infarction in 2002 and 2004, a biventricular implantable cardioverter defibrillator with several cardioversions (2005), a struma resection, and a spinal channel stenosis operation in 2010. Additional cardiovascular risk factors were type 2 diabetes mellitus, hypertension, and hypercholesteremia.

Profoundly limited biventricular pump function led to the indication for a biventricular Jarvik 2000 implant via a median sternotomy, which had a total surgical procedure time of 407 minutes without complications. Again, the new blue controller was used for the RVAD pump. The power controller was set on level 4 for the left ventricle and on level 3 for the right ventricle.

Results

All biventricular assist devices were implanted without technical complications. Mean support time on the device was 224 ± 198 days. All patients showed sufficient cardiac support, and 2 patients died as a result of noncardiac complications.

Patient 1
After implant, the correct position of the pumps was checked with a radiograph (Figure 6). During follow-up, administration of the initial high catecholamines doses was reduced. No bleeding was reported; however, transfusions of fresh frozen plasma were necessary due to a lack of coagulation factors. No focal neurologic deficits were found at a ventilation of fraction of inspired oxygen of 35% and positive end-expiratory pressure of PEEP of 10 mbar, but a continuous hemofiltration was necessary because of renal insufficiency. After ventricular tachycardia and defibrillation, the patient also developed metabolic acidosis and sepsis. Because of the resulting hypotension, we used a high-speed controller in power mode 7 with 14 000 revolutions/minute. Nevertheless, a delayed hepatic failure occurred, primarily caused by the preoperative reanimation, with led to exitus letalis 3 days after implant.

Patient 2
During postoperative follow-up, we could not detect any bleeding or neurologic deficits, and ventilation was stopped on day 3, and continued with continuous positive airway pressure training until day 17. Both catecholamine administration and hemofiltration ended on day 7. On day 17, the patient was discharged from the intensive care unit. Because of gastrointestinal bleeding, he received balloon endoscopy, with administration of agents for gastro­intestinal protection.

After 7 weeks, the patient was discharged for rehabilitation, and right ventricular ejection fraction improved to 37% (Figures 7, 8, and 9). Further diagnostics (radiograph, computed tomography scan) were suddenly necessary after 3 months because of a right ventricel pump alarm, which showed a dislocation of the RVAD pump by 18 degrees, suction to the septum wall, and thrombosis of the outflow graft conduit. The RVAD was left in position but shut down. The patient was hemodynamically stable, could be mobilized, and was in good physical condition with a recovered right ventricle in echocardiography and with the LVAD as destination therapy (Figure 10). Eleven months after implant, the measured right ventricular ejection fraction increased to ~50%, even after the RVAD pump had been shut down. After > 20 months (620 d) of pump support, the patient died due to ventricular fibrillation because the patient had not previously received a defibrillator implant.

Patient 3
After implant, ventilation was stopped on day 1 and the patient quickly recovered and was sitting in a chair on postoperative day 3 (Figure 11 On day 8, several transfusions were necessary after bleeding and a pericardial tamponade forced us to perform 2 resternotomies. After coumarin anticoagulation (International Normalized Ratio of 2.5-3.5), a severe gastrointestinal bleeding occurred and the antico­agulation had to be paused. A colonoscopy showed large blood clots, and the patient’s cardiovascular and pulmonary situation worsened, leading to need for higher doses of catecholamines (3.0 mg/h norpinephrine, 3.0 IE/h vasopressin) and pressure-controlled ventilation. Abdominal sonography showed subdiaphragmatic free air on the right side. We assumed that the patient had a perforation of hollow organs, probably caused by the previous colonoscopy. With the combined multiorgan failure consisting of septic, pulmonary, nephrologic, and gastrointestinal failure, we decided that no recovery would be possible and stopped the assist device support on postoperative day 50. An autopsy revealed multiorgan failure and a 3.5-cm defect of the colon ascendens after ileus.

For all 3 patients, it was an ultima ratio decision to implant the biventricular assist devices. In general, because further cardiovascular surgery was necessary, this was the first in the world-documented implant of a Jarvik 2000 device with retroauricular power supply via a median sternotomy (Figure 12). From the technical side, this procedure could be done quite quickly (time of 550 ± 68 min). Catecholamines could be reduced within 7 days in all of our patients. Two patients received the new blue controller for the right ventricle, which does not use the intermitted low speed function, thus protecting the right ventricle by continuous unloading. Two of 3 patients died from noncardiac complications (hepatic failure after shock and colon perforation after colonoscopy). One patient died after 620 days as a result of ventricular fibrillation, which could have been prevented by an early implant of a defibrillator. In this patient, the RVAD pump was shut down after 2 months after a dislocation and suction of the RVAD pump to the septum. However, during these 2 months, he showed a clear recovery of the right ventricle function (in the beginning, the patient had an EF = 25%; after our therapy, he had an EF = 37%; this is an increase of 48%). No infections could be found postoperatively. No thromboembolic events or neurologic compli­cations occurred. Mean support time was 224 ± 198 days.

Discussion

The LVAD Jarvik 2000 is already well established for temporary bridge-to-transplant treatment and recently as destination therapy as well. Relief of symptoms and good survival rates have been shown by Westaby and associates⁵ and Frazier and associates.¹

Here, we tried to use this successful system to help patients with biventricular terminal heart failure. Because most of these patients often have severe multiple morbidities and have numerous cardiovascular risk factors (see Table 1), further cardiac surgical procedures, such as valve replace­ment, are often needed. To perform all of these steps in 1 operation, we deviated from our more frequently used surgical technique of posterolateral thoracotomy and used our modified Munich technique, published here for the first time, via median sternotomy and retroauricular power supply. This technique was described for LVAD implant by Siegenthaler and associates.⁴ We were able to show that this method for Jarvik 2000 biventricular device implant works hemodynamically quite well and is convenient to perform (procedure time of 550 ± 68 min). None of our patients died directly as a result of surgical complications but from other com­plications, often caused by progressive multiorgan failure after lengthy cardiac decompensation. Consequently, a future aim is to implant the biventricular assist device not as an ultima ratio procedure but earlier. This could offer a therapeutic option for patients who had biventricular heart failure as a destination therapy for older patients or as a bridge-to-transplant therapy. For patients who do not need further surgical intervention such as valve replacement, it is possible to implant both pumps via a left-sided posterolateral thoracotomy, which was first published by Pitsis and associates.⁶ This procedure could also be a possible solution for patients who require a redo procedure, that is, those who have already received multiple median sternotomies and therefore have a higher risk of adhesions and bleeding.

There are different types of biventricular assist devices being implanted. The BerlinHeart EXCOR (Berlin Heart GmbH, Berlin, Germany) has shown creditable results, especially with bridge-to-transplant patients due to its huge output volume. Complications are mainly the result of the paracorporeal placement, with an increasing number of driveline infections and thrombosis of the very huge pumps.^7,8 The HeartWare pump (HeartWare, Framingham, MA, USA) also can be successfully implanted into both ventricles.⁹ Problems with this pump, as with LVAD systems, are gastrointestinal bleeding (13%), bleeding that requires reoperation in 15% of the cases, and driveline infections due to the abdominal exit (17% in 1 y).10 A survival rate of 79% in LVAD support shows the liability of this system.¹¹ However, the HeartWare system does show a problem coming along with most biventricular assists: because the pulmonary vascular resistance is much smaller than the total peripheral resistance, it is necessary to narrow the RVAD outflow conduit from 10 to 5 mm to avoid overloading the pulmonary circulation.^12,13 In addition, the biventricular HeartWare needs 4 batteries and 2 controllers simultaneously, which increases the inconvenience for the patient.¹² Therefore, there are several reasons why we preferred the Jarvik 2000 system. In contrast to the HeartWare system,⁹ the Jarvik 2000 uses a retroauricular power supply, minimizing driveline infection rates due to excellent blood circulation in this area and allowing a better quality of life without abdominal cable drivelines. The liability of the mechanical pump and connection parts has been shown by Siegenthaler and associates.¹⁴ Implant practicality and quality of life increase because of the small pump size, the small controller size, and the need for only 1 battery.

Development of the new blue controller has improved the Jarvik 2000 system, providing conti­nuous flow instead of an intermittent low-speed mode and protecting the right ventricle by continuously unloading it. An advantage of the intermittent low-speed mode is it can prevent thromboembolic events at the aortic valve by purging the aortic bulb missing for the pulmonary valve.3 Nevertheless, a challenge for the future will be to integrate the separate RVAD and LVAD systems into 1 more user-friendly controller device. This could be achieved by combining the 2 connectors and controllers into 1 system. One step in this direction has already been taken by connecting both cont­rollers to 1 battery via a cross-cable.

Another challenge will be to develop a technique for a better coordination of the RVAD and LVAD pumps. Normally, the middle pulmonary arterial pressure is much lower than the middle arterial blood pressure; therefore, we adjusted semiquantitatively the RVAD on power mode 3 while setting the LVAD on power mode 4. Because we had 1 patient with fixed pulmonary hypertension, we tried to compensate this by setting both pumps on the same level semi­quantitatively. This worked quite well; nevertheless, we admit that we were not able to measure the exact flow and to adjust the speed level to the patients’ needs because a Swan-Ganz catheter is not suitable for cardiac output measurement during a running RVAD pump. In addition, heart motility is modified by the preload and afterloads (Frank-Starling mechanism), which is a continuously changing system that also influences both pumps. Therefore, continuous flow measurement of the LVAD and RVAD devices and pressure transducers in both atria and ventricle should be considered as an additional feature in the next pump generation. For example, the Data Sciences International system (Data Sciences International [DSI], St. Paul, MN, USA), presently used for pressure sensing in animal research and which can transmit 2 pressure measurements and 1 electrocardiogram wirelessly, could be modified for the clinical setting and could be potentially combined with an external remote control to coordinate both biventricular assist device pumps.

Although we already have data regarding LVAD implants, proven criteria regarding when to implant a biventricular device are controversial. From our experience, it was important that the right ventricle had an ejection fraction of < 40% and for the patient to have a higher tricuspid insufficiency of at least grade 2 and pulmonary hypertension.

Furthermore, we were able to show that, even after pump shutdown of a few weeks, the device had an enormous effect on the right ventricle ejection fraction (increased by 48% to 37%) by remodeling and decreasing the diameter of the right ventricle, which we view as a therapeutic success. Eleven months after implant, the measured right ventricular ejection fraction even increased after the RVAD pump was shut down to ~50%, leading us to hypothesize that further recovery of the ventricle would be possible after initial support therapy by a ventricular assist device followed by a pump shutdown. It is important to emphasize that we could show, for the first time, the successful possibility of an intracardiac remaining pump after pump shutdown for RVAD. Thereby we could avoid an explant operation. However, in patients with multiple morbidities, an explant as an additional surgery would mean extra adhesions and additional trauma and stress of the vulnerable myocardium with possible intra- or postoperative complications. The fact that the right ventricle is able to partially recover offers us additional therapy concepts (bridge-to-recovery of RVAD). One option would be to monitor recovery of the right ventricle and, if desired, shut down the RVAD under control without the pump being explanted.

In general, we can state that biventricular use of the Jarvik 2000 system is reasonable and could be used, besides as bridge to transplant, as a potential destination therapy plan when transplant is not possible (eg, because of organ shortage or other excluding factors like high age or multiple morbi­dities). Therefore, it is important to continuously improve the mechanical system and to examine whether a biventricular assist device implant can be not only an ultima ratio therapy for patients with multiple morbidities but also as a therapeutic alternative when implanted earlier.

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