Timothy J. Myers

Left ventricular assist system as a bridge to myocardial recovery

BACKGROUNDnDespite recent advances in medical therapy, heart transplantation, and mechanical circulatory support, the mortality of patients with congestive heart failure remains high.nnnMETHODSnRetrospective data on 5 patients were obtained from our hospitals medical records. Each patient was supported by a left ventricular assist system (LVAS) because of severe congestive heart failure. The duration of LVAS support averaged 229 days (range, 46 to 447 days). In 3 patients, the LVAS was removed electively after the patient showed recovery of myocardial function. In the other 2, it was removed because of a malfunction.nnnRESULTSnIn response to LVAS support, hemodynamic variables were significantly improved. The mean cardiac index increased from 1.45 to 2.69 L x min(-1) x m(-2) (p < 0.001) and the mean left ventricular ejection fraction increased from 0.144 to 0.288 (p < 0.025). All patients were in New York Heart Association functional class IV at LVAS implantation and class I at its explantation. One patient died of noncardiac-related causes 10 days after LVAS removal. The remaining 4 patients are alive and well 35, 33, 14, and 2 months after LVAS removal.nnnCONCLUSIONSnIn select patients with severe congestive heart failure, mechanical unloading with an LVAS can result in recovery of myocardial function. These patients can return to a normal physical status, thereby avoiding heart transplantation. More research is required to determine optimal modes of LVAS support, to predict which patients are likely to recover, and to assess long-term outcomes.

Initial Clinical Experience With the Jarvik 2000 Implantable Axial-Flow Left Ventricular Assist System

Background—Implantable left ventricular assist systems (LVASs) are used for bridging to transplantation, bridging to myocardial improvement, and for permanent circulatory support. Conventional implantable systems have inherent limitations that increase morbidity during support. In contrast, small, efficient, axial-flow pumps, which have been under development for the past decade, have the potential to improve the length and quality of life in patients with severe heart failure. Methods and Results—To assess the safety and clinical utility of the Jarvik 2000, we implanted this device in 10 transplant candidates (mean age 51.3 years) in New York Heart Association (NYHA) class IV. Implantation was achieved through a left thoracotomy during partial cardiopulmonary bypass. The mean support period was 84 days. Within 48 hours postoperatively, the cardiac index increased 43%, pulmonary capillary wedge pressure decreased 52%, systemic vascular resistance decreased significantly, and inotropic support became unnecessary. Eight patients underwent physical rehabilitation and returned to NYHA class I. Their left ventricular dimensions, cardiothoracic ratios, and pressure-volume loop analyses showed good left ventricular unloading. Seven patients underwent transplantation and 3 died during support. No device thrombosis was observed at explantation. Conclusions—The Jarvik 2000 functions as a true assist device by partially unloading the left ventricle, thereby optimizing the patient’s hemodynamics. Our preliminary results indicate that this LVAS may safely provide circulatory assistance for heart transplant candidates.

First permanent implant of the Jarvik 2000 Heart

BACKGROUNDnHeart failure is a major public-health concern. Quality and duration of life on maximum medical therapy are poor. The availability of donor hearts is severely limited, therefore an alternative approach is necessary. We have explored the use of a new type of left-ventricular assist device intended as a long-term solution to end-stage heart failure.nnnMETHODSnAs part of a prospective clinical trial, we implanted the first permanent Jarvik 2000 Heart--an intraventricular device with an innovative power delivery system--into a 61-year-old man (New York Heart Association functional class IV) with dilated cardiomyopathy. We assessed the effect of this left-ventricular assist device on both native heart function and the symptoms and systemic characteristics of heart failure.nnnFINDINGSnThe Jarvik 2000 Heart sustained the patients circulation, and was practical and user-friendly. After 6 weeks, exercise tolerance, myocardial function, and end-organ function improved. Symptoms of heart failure have resolved, and continuous decreased pulse-pressure perfusion has had no adverse effects in the short term. There has been no significant haemolysis and no device-related complications. The skull-mounted pedestal is unobtrusive and has healed well.nnnCONCLUSIONSnThe initial success of this procedure raises the possibility of a new treatment for end-stage heart failure. In the longer term, its role will be determined by mechanical reliability.

Research and development of an implantable, axial-flow left ventricular assist device: the Jarvik 2000 Heart

Advances in technology and increased clinical need have led to the development of a new type of blood pump. The Jarvik 2000 Heart is an electrically powered, axial-flow left ventricular assist device that has been developed during the past 13 years. Unlike first-generation left ventricular assist devices, which were developed in the 1970s and were designed to totally capture the cardiac output, the Jarvik 2000 is designed to normalize the cardiac output by augmenting the function of the chronically failed heart for extended periods. Design iterations have been tested in 67 animals, and clinical trials have recently begun. Three patients have received the Jarvik 2000 as a bridge to transplantation, and 1 patient is being supported permanently outside the hospital. All 4 patients have improved from New York Heart Association functional class IV to class I, and 2 of them have been discharged from the hospital after heart transplantation. The experimental and clinical results indicate that the Jarvik 2000 can provide physiologic support with minimal complications and is reliable, biocompatible, and easy to implant.

Clinical experience with an implantable, intracardiac, continuous flow circulatory support device: physiologic implications and their relationship to patient selection

BACKGROUNDnWe have been investigating continuous-flow circulatory support devices for 20 years. Unlike pulsatile assist devices, continuous-flow pumps have a simplified pumping mechanism and they do not require compliance chambers or valves. In the 1980s, clinical experience with the Hemopump proved a high-speed, intravascular, continuous-flow pump could safely augment the circulation. Subsequently, a decade of animal experiments with a larger, longer-term continuous-flow pump (the Jarvik 2000) confirmed the safety and efficacy of intraventricular placement, leading to its clinical application.nnnMETHODSnWe analyzed the physiologic and anatomic effect of using the Jarvik 2000 pump for cardiac support in 23 patients in whom the device was applied as a bridge to transplant under the protocol approved by the Food and Drug Administration Investigational Device Exemption. The device was used as a bridge to transplantation in 20 patients and as destination therapy in 3 patients.nnnRESULTSnIn the bridge-to-transplant group, 14 patients underwent transplantation, 5 died during the circulatory support period and 1 is in an ongoing study. The support period lasted an average of 90 days. For the survivors, the follow-up period has averaged 16 months. Within the first 48 postoperative hours, the average cardiac index increased by 65% (from 1.77 +/- 0.24 to 2.92 +/- 0.60 L. min(-1). m(-2), p = 0.00000002), the systemic vascular resistance decreased by 42% (from 1604 +/- 427 to 930 +/- 330 dynes/sec per cm(2), p = 0.00001), and the pulmonary capillary wedge pressure (PCWP) decreased by 41.8% (from 23 +/- 5.1 to 13.4 +/- 6.6 mm Hg, p = 0.00009). Similar results were seen for the patients undergoing destination therapy. Cardiac index increased 89.5% (from 1.9 +/- 0.1 to 3.6 +/- 0.6, p = 0.046) and PCWP decreased by 52.2% (from 23 +/- 10 to 11 +/- 2, p = 0.22). In that group, 1 patient died unexpectedly from an accident 382 days after device implantation. The 2 survivors remain in New York Heart Association (NYHA) functional class I at 700 to 952 days after implantation.nnnCONCLUSIONSnThe Jarvik 2000 can offer effective long-term support for patients with chronic heart failure and NYHA class IV status. However, the new physiology produced by continuous offloading of the heart throughout the cardiac cycle has introduced unique clinical problems. The understanding of the problems generated by this biotechnological interface is essential for obtaining optimal clinical outcomes.

Improved survival after extended bridge to cardiac transplantation.

In the past, left ventricular assist device (LVAD) support was frequently plagued by complications; thus, bridge to transplantation times were kept short. Increasing evidence suggests that extended bridging provides greater benefit due to improved end-organ perfusion and, thus, generally improved physical condition. To assess whether extended bridging translates into improved long-term survival after transplantation, we reviewed our experience with the HeartMate 1000 IP LVAD (Thermo Cardiosystems, Inc, Woburn, MA). Since January 1988, 19 patients (mean age, 45 +/- 9 years) have undergone extended bridging (mean time, 106 +/- 57 days). Their mean weight was 82 +/- 16 kg, and their mean body surface area was 2.0 +/- 0.2 m2. We define extended as the length of support necessary for systemic organ recovery after prolonged heart failure. During support, average pump flow indices ranged from 2.3 to 3.3 L.min-1.m-2, and all patients underwent physical rehabilitation. Between the time of LVAD implantation and explantation, the mean serum creatinine value decreased from 1.63 +/- 0.6 to 1.25 +/- 0.6 mg/dL (p = not significant), and the mean serum total bilirubin value decreased from 2.8 +/- 2.0 to 0.63 +/- 0.11 mg/dL (p < 0.05). All but 1 patient improved from New York Heart Association class IV to class I. Device-related complications were minimal. Twelve control patients (de facto randomized) who did not receive the LVAD also were evaluated: actuarial survival at 1 year was 0% (p < 0.05); 3 (25%) underwent transplantation and died within 2 months; 9 (75%) died before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of the Jarvik 2000 Left Ventricular Assist System as a Bridge to Heart Transplantation or as Destination Therapy for Patients With Chronic Heart Failure

ObjectiveTo evaluate the Jarvik 2000 axial flow left ventricular assist sys-tem (LVAS) as a bridge to transplant and as destination therapy. Summary Background DataThe Jarvik 2000 LVAS was implanted in 22 patients (16 men, 6 women; mean age 53 years) as a bridge to transplant (in the United States) and in 4 patients (all men; mean age 62.8 years) as destination therapy (in the United Kingdom). All patients in both of these initial feasibility studies were in NYHA class 4. MethodsThe pump was implanted through a thoracotomy or median sternotomy incision with the aid of partial cardiopulmonary bypass in bridge-to-transplant patients. A skull-mounted percutaneous power delivery was used for the patients who received the pump as destination therapy. ResultsOf the 22 bridge-to-transplant patients, 13 underwent transplant; 7 died during support; and 2 studies are ongoing. The surviving patients have an average follow-up of 15 months; one died at 2.6 months after transplant, and the remaining patients are all in NYHA class 1. Support averaged 67.1 days. Deaths were due to acute myocardial infarction in two patients and multiorgan failure in five patients. Hemodynamic function improved with LVAS support. The average cardiac index increased 70.6% by 48 hours after implant, pulmonary capillary wedge pressure decreased 44%, systemic vascular resistance decreased significantly, and inotropic support became unnecessary. Similar results have been seen in the patients who received the device as destination therapy. In that series, one patient died of subdural hematoma 380 days after implant. The other two patients are in NYHA class 1, 642 and 889 days after implant. The average cardiac index increased 89.5%, and pulmonary capillary wedge decreased 52.2%. ConclusionsThe Jarvik 2000 axial-flow LVAS can be used safely in selected patients to provide support until transplant or as destination therapy. In this series, the patients who most benefited from this device were those who required true left ventricular assistance rather than total capture of left ventricular output. Current experience indicates that continuous offloading of the ventricle is most effective when there is enough residual myocardial function to maintain pulsatility and aortic root ejection and to maintain, with nonpulsatile pump support, a normal cardiac index as well as reinstitution of the Frank-Starling response to the native ventricle.

Dobutamine stress echocardiography predicts myocardial improvement in patients supported by left ventricular assist devices (LVADs): Hemodynamic and histologic evidence of improvement before LVAD explantation

BACKGROUNDnCardiac function may improve in patients with end-stage heart failure who receive long-term support (>30 days) with left ventricular assist devices (LVADs). Dobutamine stress echocardiography (DSE) has been used to quantitate myocardial recovery in patients with heart failure supported with LVADs. By recording the hemodynamic response with the use of DSE, we evaluated and applied the resulting data to patients receiving LVAD support.nnnMETHODS AND RESULTSnThe study population included 16 patients who underwent LVAD implantation, regained functional capacity on full LVAD support, and tolerated decreased mechanical support with no worsening of dyspnea or fatigue. All 16 patients underwent dobutamine stress with increasing doses of dobutamine (from 5 to 40 mcg/kg/min). Hemodynamics and 2-dimensional (2-D) echocardiography was performed at each dose level. In addition, paired myocardial samples were obtained and analyzed histologically to determine myocyte size and collagen content. Dobutamine stress separated the study population into 2 groups: those who had favorable responses to dobutamine (9/16) and those who had unfavorable responses (i.e., experienced hemodynamic deterioration; 7/16). Favorable dobutamine responses were characterized by improved cardiac index, improved force-frequency relationship in the left ventricle (dP/dt), improved left ventricular ejection fraction, and decreased left ventricular end-diastolic dimension. All 9 favorable responders underwent LVAD explantation, and 6 survived for more than 12 months. In all patients studied, LVAD support resulted in decreased myocyte size (n = 14, 33.9 +/- 0.9 microm before vs 16.6 +/- 0.8 microm after support, p = 0.0001; normal, 5-15 microm) but resulted in no consistent changes in collagen content.nnnCONCLUSIONSnDobutamine stress echocardiography with hemodynamic assessment may be a useful tool in assessing physiologic improvement in myocardial function of patients with end-stage heart failure who receive LVAD support. It may help predict which patients can tolerate LVAD removal. Prospective analysis of cardiac function is now warranted to better define myocardial recovery in patients supported with LVADs.

Assessment of arterial blood pressure during support with an axial flow left ventricular assist device.

BACKGROUNDnAxial-flow left ventricular assist devices (LVADs) have a number of advantages over pulsatile LVADs, including their small size and better durability. Although the design of axial-flow pumps should result in fewer serious complications during support, some adverse events persist. Thus, optimizing patient treatment may minimize complications, allowing broader acceptance of these devices. In this study, we analyzed standard blood pressure measurements obtained by cuff and arterial lines and used these values to help establish guidelines for the safe operation of axial-flow LVADs.nnnMETHODSnThe study included 35 heart failure patients who had received a Jarvik 2000 (Jarvik Heart Inc, New York, NY) axial-flow LVAD as a bridge to cardiac transplantation. Blood pressure and echocardiographic data were collected during speed-change studies.nnnRESULTSnSystolic blood pressure did not change, but diastolic, mean, and pulse pressure values changed significantly with changes in pump speed (p < 0.0001). When blood pressure values obtained from an arterial line were compared with those from an automated cuff machine, the systolic, diastolic, and mean values did not correlate (p < 0.05), but the calculated pulse pressures did (p = 0.33). A pulse pressure calculation of < 15 mm Hg resulted in aortic valve opening 24% of the time, and a pulse pressure > 15 mm Hg was predictive of aortic valve opening 65% of the time.nnnCONCLUSIONSnBecause aortic valve opening minimizes the risk of complications, a safe zone for most patients is a pulse pressure > 15 mm Hg. Arterial blood pressure changes during axial-flow LVAD support can be predicted and may be used as a guide for the proper management of pump speed settings. A calculated pulse pressure from an arterial line or automated cuff may be used to determine a safe zone of Jarvik 2000 operation, leading to fewer complications.

Continuous axial-flow left ventricular assist device (Jarvik 2000) maintains kidney and liver perfusion for up to 6 months

BACKGROUNDnThe Jarvik 2000 axial flow left ventricular assist device (LVAD), under development for the past decade, has the potential to support patients temporarily until cardiac transplantation or as a permanent circulatory support, without the size limitations of other implantable systems.nnnMETHODSnTo assess its ability to perfuse the kidneys and liver, we monitored renal and hepatic function in 10 patients who received the Jarvik 2000 LVAD as a bridge to transplantation. Left ventricular assistance was maintained for up to 214 days (> 6 months), and renal and hepatic function were monitored at least weekly.nnnRESULTSnRenal function before LVAD implantation in these patients was normal in 7 (creatinine, < 1.5) and moderately impaired in 3 (creatinine, 1.2 to 2.0). Hepatic function was normal in 7 patients before LVAD implantation (total bilirubin< 1.2; serum glutamic-oxaloacetic transaminase (SGOT), < 40; serum glutamic-pyruvic transaminase (SGPT), < 50) and normal at the time of transplantation in all 10 patients. Of the 3 patients with abnormal hepatic function before LVAD implantation, 1 patient had also had moderate renal dysfunction.nnnCONCLUSIONSnDespite reduced pulsatility, the Jarvik 2000 LVAD improves or maintains excellent renal and hepatic function during periods of circulatory assistance in patients awaiting transplantation.