Feasibility of long-term continuous flow total heart replacement in calves.

INTRODUCTION: Implementation of continuous flow (CF) technology in modern ventricular assist devices (VAD) has afforded a wealth of engineering and design advantages in the development of a total artificial heart (TAH). However, clinical application of CF has created a unique physiologic state, the consequences of which remain largely unknown. We sought to evaluate clinical and biochemical markers of end-organ function in calves supported with biventricular CF VADs for more than 30 days. METHODS: Eight calves survived longer than 30 days following biventriculectomy and implantation of dual CF VADs. Four types of CF pumps were utilized for the study. Serial hematologic and biochemical profiles were drawn as markers for end-organ function, and hemodynamic data-including pump flows and intravascular pressures-were continuously monitored. RESULTS: The eight calves survived an average of 58.8 days (range 30-92 days). Two of the calves were electively terminated at the conclusion of the study period, while the remaining animals were euthanized as a result of respiratory distress (n = 2) or impaired pump flows (n = 4). In each case, serial biochemical and hematologic values were suggestive of preserved end-organ function. Six animals successfully participated in treadmill exercise evaluations. No evidence of end-organ damage was encountered upon necropsy or histologic tissue analysis. CONCLUSION: Biventricular CF VAD implantation permits a viable bovine CFTAH model capable of demonstrating long-term survival. After 30 days of completely nonpulsatile flow, cumulative hemodynamic, clinical, biochemical, and histological analyses were consistent with preserved end-organ function, suggesting previously unreported long-term feasibility of a CFTAH design.

Tolerance of Sustained Ventricular Fibrillation During Continuous-Flow Left Ventricular Assist Device Support.

The widespread use of continuous-flow left ventricular assist devices for mechanical circulatory support has shown that long-term hemodynamic support is possible, even when a clinical "pulse" cannot be detected. We present the incidental discovery of ventricular fibrillation in 6 alert, hemodynamically stable patients supported only by a continuous-flow device (HeartMate II, n=5; Jarvik 2000, n=1). Ventricular fibrillation was found in 3 patients during routine outpatient follow-up visits and in 3 awaiting discharge from the hospital after device placement. Diagnosis was confirmed by electrocardiographic and echocardiographic studies. The average duration of mechanical circulatory support before ventricular fibrillation occurred was 221 ± 362 days (range, 5-864 d). All patients were conscious and ambulatory at the time of the arrhythmia. Three patients reported symptoms-primarily fatigue, nausea, and exertional dyspnea-that prompted evaluation. Serum chemistry analysis of blood drawn immediately after diagnosis showed no changes that suggested end-organ dysfunction. Three patients died of unrelated complications an average of 3.9 yr (range, 360-2,270 d) after the event. Two of the remaining 3 patients eventually underwent successful pump explantation, and one is on ongoing support. Our experience shows that it is possible for patients with continuous-flow left ventricular assist devices to remain hemodynamically stable while in ventricular fibrillation. Additional investigation is needed to determine whether defibrillator settings for these patients should be adjusted to limit delivery of shock therapy.

Location and density of alpha- and beta-adrenoreceptor sub-types in myocardium after mechanical left ventricular unloading.

BACKGROUND: We hypothesized that not all subtypes of alpha- and beta-adrenoreceptors undergo similar upregulation and redistribution in human myocardium after mechanical unloading with an assist device. METHODS: We obtained core biopsy samples of the left ventricle in 19 patients before and after removal of a Jarvik or Thoratec left ventricular assist device (LVAD) to study the effect of mechanical unloading on the distribution of alpha- and beta-adrenoreceptors. Fresh, embedded tissue sections were incubated with receptor blockers and antibodies before the fluorescent labeling of receptors. Images were obtained by fluorescence deconvolution microscopy, and composite tissue renditions were made from the stacked images. Multiple adrenoreceptor subtypes were studied. RESULTS: We saw a reversal of myocyte hypertrophy in all patients, but the upregulation of receptors was not seen in all post-LVAD tissue samples. Furthermore, we noted receptor relocalization from an initial punctate/clumped pattern to a normal homogeneous distribution in many patients. Significant differences were seen in the distribution of beta(2)- and alpha(1)-receptors and in alpha(1A) subtypes. CONCLUSIONS: In this study we show not only the expected reversal of myocyte hypertrophy and the increase in adrenoreceptors after ventricular unloading, but also the relocalization of specific receptor subtypes.

A less invasive approach to axial flow pump insertion.

BACKGROUND: Implantation of a HeartMate II or a Jarvik 2000 FlowMaker left ventricular assist system (LVAS) usually involves a mid-line sternotomy and the use of cardiopulmonary bypass (CPB). In patients with numerous co-morbid conditions, however, surgical trauma may be minimized by implanting the LVAS via a minimally invasive approach, preferably without CPB. METHODS: In 6 patients with end-stage heart failure and other serious co-morbidities, we implanted a HeartMate II (n = 3) or a Jarvik 2000 FlowMaker (n = 3) LVAS via a right mini-thoracotomy and a left sub-costal incision. Patients included 3 men and 3 women with a mean age of 41 years. In 3 cases, the LVAS was implanted without CPB. RESULTS: After a mean follow-up period of 6 months, 5 patients are alive and well and on the transplant waiting list. Seven months after LVAS implantation, the remaining patient developed a hemorrhagic stroke necessitating Jarvik 2000 replacement with a new pump of the same type. CONCLUSIONS: In this small series, the combined sub-costal and mini-thoracotomy incision proved safe and technically feasible. It may be useful for other LVAS candidates who have serious co-morbidities that preclude traditional implant operations.

Initial clinical experience with the HeartMate II axial-flow left ventricular assist device.

The redesigned HeartMate II, an axial-flow left ventricular assist device, is simpler, smaller, and easier to operate than are pulsatile pumps. These design characteristics should make the HeartMate II more reliable and durable and broaden the eligible population base. We implanted the HeartMate II in 43 patients (average age, 42 yr). The indication for use was bridge-to-heart transplantation in 26 patients and destination therapy in 17. The average duration of device support was 258 days (range, 1-761 days), and cumulative duration, more than 31 patient-years. Hemodynamic function improved in all patients during support. By 48 hours after implantation, the mean cardiac index had increased from 1.9+/-0.27 L/(min.m(2)) (baseline) to 3.5+/-0.8 L/(min.m(2)), and the pulmonary capillary wedge pressure had decreased from 24.8+/-11 mmHg to 18.5+/-5.3 mmHg. Of the 43 patients, 35 were discharged from the hospital. Support is ongoing in 27 patients (longest duration, >700 days). Nine patients died during support. Four patients had sufficient heart recovery to undergo pump explantation. Three patients underwent transplantation. One patient underwent device replacement after the pump driveline was fractured in a skateboarding accident; the device was removed in another patient because of a pump-pocket infection after 749 days of support. Of the 10 patients in whom the HeartMate II replaced a failed HeartMate I, 8 were discharged from the hospital. We have seen excellent results with use of the HeartMate II. Functional status and quality of life have greatly improved in patients who survived the perioperative period.

Urgent pump exchange for stroke resulting from a distorted HeartMate XVE inflow conduit.

Long-term left ventricular assist device (LVAD) implantation is associated with an inherent risk of transient ischemic attacks (TIAs). When TIAs occur in patients who have undergone placement of a HeartMate XVE LVAD, the pump must be assumed to be the likely source of the TIA. The HeartMate XVE is unique in that it has a pumping surface of flocked Biomer and a pump housing and inlet cannula coated with sintered titanium. This design facilitates coating of the surfaces with the patient's own cells, usually within 48 hours of implantation, effectively eliminating the pumping surface as a source of thromboemboli. Similarly, neither the outflow conduit nor the porcine outflow valve have been shown to be sources of thromboemboli, as they are both subjected to the wash-out of pulsatile systolic pressure. In our experience, the only components vulnerable to pannus formation are the inflow conduit and its associated valve, and then only when the inflow conduit is distorted at implantation. We describe an illustrative case of a patient supported with a HeartMate XVE LVAD who suffered a device-related stroke that was attributed to the inflow conduit, which was distorted during implantation to configure the pump for the patient's narrow body habitus. The resultant disruption in laminar flow was the most likely cause of the TIAs and stroke. Therefore, documented TIAs in patients with an implanted HeartMate XVE are an indication for urgent pump replacement, even if pump performance is otherwise normal. In this case, the pump was exchanged for a smaller, continuous-flow HeartMate II LVAD.

Management of air embolism during HeartMate XVE exchange.

Air embolism is a rare and usually fatal complication of major cardiac surgery. We present a case in which a 45-year-old man supported by a HeartMate(R) XVE left ventricular assist device required a pump exchange due to failure of the device motor. During pump dissection, a massive amount of air entered the systemic circulation. Urgent cannulation for cardiopulmonary bypass was performed, and cardiopulmonary bypass was initiated, followed by profound hypothermia, circulatory arrest, retrograde cerebral perfusion, retrograde coronary sinus perfusion, and then barbiturate coma and steroid therapy. The HeartMate XVE left ventricular assist device was removed, and a HeartMate II was implanted. After 5 days, the patient awoke with left hemiparesis, which nearly resolved with aggressive physical therapy. Forty-four days after the pump exchange operation, the patient was discharged from the hospital with only mild left hemiparesis. Exposure of the left ventricular assist device or its external components requires careful monitoring, because air can enter the pump-particularly in a hypovolemic patient. Rapid response after massive air entry into the left ventricular assist device system, as in our patient, can result in a successful outcome.

Mechanical circulatory support for the pediatric patient.

In adult patients, mechanical circulatory support (MCS) devices are part of the standard of care for heart failure. There are several options available that clinicians may use to provide support for their patients and thus the choice of devices can be tailored to their individual needs. Unfortunately, this is not the case for pediatric patients with heart failure, where the options for MCS modalities are far more limited because of size constraints and regulatory hurdles. Furthermore, the pathophysiology of heart failure in children is not identical to that of adults; thus, the device selection and configuration require different considerations. Management of pediatric patients on MCS requires a highly specialized team of pediatric professionals. The nurse caring for a child on MCS is an active participant in all aspects of the patient's care and must have an in-depth understanding of the patient's underlying physiology, the circulatory physiology of the MCS system, the reason for mechanical support, and the goal of support.

In vivo evaluation of the HeartWare centrifugal ventricular assist device.

In this study, long-term (90-day) hemocompatibility and end-organ effects of a centrifugal left ventricular assist device (the Heartware HVAD) were evaluated in 6 healthy sheep. The device was implanted into the left ventricular apex on beating hearts. The outflow graft of each device was anastomosed to the descending aorta. None of the sheep received anticoagulation or antiaggregation medication during the study. Hematologic and biochemical tests of liver and kidney function were performed pre-operatively (baseline) and throughout the study. Data associated with pump function were collected continuously until 90 +/- 1 days of support, at which time the sheep were humanely killed, and the end-organs were examined macroscopically and histopathologically. Hematologic and biochemical test results were within normal limits during the study period. There were no significant complications. Postmortem examination of the explanted organs revealed no evidence of ischemia or infarction, except in 2 sheep, in which small foci of infarction were detected in each of their left kidneys. There was no significant device failure. In all sheep, the pump's inflow and outflow conduits were free of thrombus. During the 90-day study, the HeartWare HVAD showed exceptional hemocompatibility and reliability, both of which are crucial to the clinical success of any implantable left ventricular assist device.

Clinical experience with the TandemHeart percutaneous ventricular assist device.

The TandemHeart percutaneous ventricular assist device can be used to support patients in cardiogenic shock (until cardiac recovery occurs or as a bridge to definitive therapy) or as a temporary application during high-risk coronary interventions. The TandemHeart is a left atrial-to-femoral artery bypass system comprising a transseptal cannula, arterial cannulae, and a centrifugal blood pump. The pump can deliver flow rates up to 4.0 L/min at a maximum speed of 7500 rpm. From May 2003 through May 2005, the TandemHeart was used to support 18 patients (11 in cardiogenic shock and 7 undergoing high-risk percutaneous transluminal coronary angioplasty). The patients in cardiogenic shock were supported for a mean of 88.8 +/- 74.3 hours (range, 4-264 hr) at a mean pump flow rate of 2.87 +/- 0.56 L/min (range, 1.8-3.5 L/min). The mean cardiac index improved from 1.57 +/- 0.31 L/min/m2 before support to 2.60 +/- 0.34 L/min/m2 during support. The mean duration of support for the high-risk percutaneous transluminal coronary angioplasty patients was 5.5 +/- 8.3 hours (range, 1-24 hr). The mean flow rate was 2.42 +/- 0.55 L/min (range, 1.5-3.0 L/ min). The overall 30-day survival rate was 61%. In our experience, the TandemHeart device was easy to insert and provided a means either to cardiac recovery or to continued support with an implantable left ventricular assist device.

Use of the TandemHeart Percutaneous Ventricular Assist Device to Support Patients Undergoing High-Risk Percutaneous Coronary Intervention.

OBJECTIVES: We describe our experience in using the TandemHeart percutaneous ventricular assist device (pVAD) during high-risk percutaneous coronary intervention (PCI). BACKGROUND: Coronary artery bypass grafting (CABG) is the preferred treatment for disease in an unprotected left main coronary artery or left main equivalent. However, severe comorbidities may preclude surgery in some patients. In these cases, PCI is also often a high-risk procedure. The pVAD is designed to provide circulatory support during high-risk PCI. METHODS AND RESULTS: We used the pVAD for hemodynamic support during PCI in 5 consecutive patients who were ineligible for CABG because of severe comorbidities. In all 5 cases, the device was inserted and support initiated without complications. Percutaneous revascularization was successfully performed with pVAD support (approximately 3 L/minute). Four patients were supported for an average of 107 minutes, the pVAD being withdrawn shortly after PCI; all 4 patients recovered uneventfully. The fifth patient required support for 48 more hours after the procedure because of poor ventricular function. He died of heart failure and severe mitral regurgitation 10 days after pVAD withdrawal. CONCLUSIONS: The pVAD may provide sufficient circulatory support for hemodynamic protection during high-risk PCI, thus improving morbidity and mortality and broadening the therapeutic options for high-risk patients. Further investigation of this device is warranted.

Use of the TandemHeart percutaneous ventricular assist device to support patients undergoing high-risk percutaneous coronary intervention.

OBJECTIVES: We describe our experience in using the TandemHeart percutaneous ventricular assist device (pVAD) during high-risk percutaneous coronary intervention (PCI). BACKGROUND: Coronary artery bypass grafting (CABG) is the preferred treatment for disease in an unprotected left main coronary artery or left main equivalent. However, severe comorbidities may preclude surgery in some patients. In these cases, PCI is also often a high-risk procedure. The pVAD is designed to provide circulatory support during high-risk PCI. METHODS AND RESULTS: We used the pVAD for hemodynamic support during PCI in 5 consecutive patients who were ineligible for CABG because of severe comorbidities. In all 5 cases, the device was inserted and support initiated without complications. Percutaneous revascularization was successfully performed with pVAD support (approximately 3 L per minute). Four patients were supported for an average of 107 minutes, the pVAD being withdrawn shortly after PCI; all 4 patients recovered uneventfully. The fifth patient required support for 48 more hours after the procedure because of poor ventricular function. He died of heart failure and severe mitral regurgitation 10 days after pVAD withdrawal. CONCLUSIONS: The pVAD may provide sufficient circulatory support for hemodynamic protection during high-risk PCI, thus improving morbidity and mortality and broadening the therapeutic options for high-risk patients. Further investigation of this device is warranted.

Thirty-five years of mechanical circulatory support at the Texas Heart Institute: an updated overview.

Since the 1960s, the Texas Heart Institute has been intimately involved in the development of mechanical circulatory support devices (for example, ventricular assist devices, aortic counterpulsation pumps, and total artificial hearts) for both short- and long-term use. Here, we review the varied clinical experience with these technologies at the Texas Heart Institute over the last 35 years.

Hemodynamic support with a percutaneous left ventricular assist device during stenting of an unprotected left main coronary artery.

Coronary artery bypass grafting prolongs survival in patients with left main coronary artery stenosis. However, this benefit is denied to patients who refuse the procedure or who are poor surgical candidates due to comorbid conditions. We describe a novel technique for the percutaneous revascularization of stenosis in an unprotected left main coronary artery in high-risk patients. The TandemHeart, a percutaneously inserted left ventricular assist device, was used to provide periprocedural hemodynamic support during angioplasty and stenting of an unprotected left main coronary artery for stenosis in a 70-year-old woman. The device was removed immediately after the procedure, and the patient was discharged from the hospital on the 2nd postprocedural day. The potential advantages of angioplasty with the support of percutaneous left ventricular assist devices in high-risk patients are discussed.