Multicenter bridge to transplantation with the HeartMate assist device: evaluation from another perspective. A rebuttal.
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Bias↗
Biomedical subjects
O H Frazier
Publications and source records attributed to O H Frazier.
Diagnosis and management of bacterial endocarditis in 2003.
The diagnosis of infective endocarditis has been notoriously difficult. Over the last decade, the modified Duke criteria have assumed an increasingly important role in the early detection of this often occult disease. Echocardiography has assumed increasing importance. Transesophageal echocardiography is recognized as more sensitive and specific than transthoracic echocardiography at detecting vegetations less than 10 mm in diameter. Vegetations greater than 10 mm in diameter are thought to be at increased risk of embolizing. Combined medical and surgical medical management result in the lowest mortality for those patients with hemodynamic compromise.
Anti-Bacterial Agents↗
Left ventricular assist devices: an alternative to medical therapy for end-stage heart failure.
Although aggressive medical therapy and ultimately cardiac transplantation have long been the therapeutic mainstays for patients with end-stage heart failure, the left ventricular assist device (LVAD), which was originally used clinically as a bridge to transplantation, may also be used as destination therapy. LVAD therapy for selected patients has been shown in the REMATCH trial to be superior to medical therapy in ameliorating symptoms and improving outcome in patients with terminal heart failure. LVAD therapy has also proved useful in improving native heart function by neuroendocrine modulation and reverse remodeling. Furthermore, current evidence suggests that when LVAD therapy is utilized to improve ventricular function, it may be further enhanced when combined with aggressive medical therapy.
Clinical Trials as Topic↗
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.
OBJECTIVE: To evaluate the Jarvik 2000 axial flow left ventricular assist system (LVAS) as a bridge to transplant and as destination therapy. SUMMARY BACKGROUND DATA: The 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. METHODS: The 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. RESULTS: Of 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%. CONCLUSIONS: The 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.
Adult↗
Mechanical unloading of the failing human heart fails to activate the protein kinase B/Akt/glycogen synthase kinase-3beta survival pathway.
BACKGROUND: Left ventricular assist device (LVAD) support of the failing human heart improves myocyte function and increases cell survival. One potential mechanism underlying this phenomenon is activation of the protein kinase B (PKB)/Akt/glycogen synthase kinase-3beta (GSK-3beta) survival pathway. METHODS AND RESULTS: Left ventricular tissue was obtained both at the time of implantation and explantation of the LVAD (n = 11). Six patients were diagnosed with idiopathic dilated cardiomyopathy, 4 patients with ischemic cardiomyopathy and 1 patient with peripartum cardiomyopathy. The mean duration of LVAD support was 205 +/- 35 days. Myocyte diameter and phosphorylation of ERK were used as indices for reverse remodeling. Transcript levels of genes required for the activation of PKB/Akt (insulin-like growth factor-1, insulin receptor substrate-1) were measured by quantitative RT-PCR. In addition, we measured the relative activity of PKB/Akt and GSK-3beta, and assayed for molecular and histological indices of PKB/Akt activation (cyclooxygenase mRNA levels and glycogen levels). Myocyte diameter and phosphorylation of ERK decreased with LVAD support. In contrast, none of the components of the PKB/Akt/GSK-3beta pathway changed significantly with mechanical unloading. CONCLUSION: The PKB/Akt/GSK-3beta pathway is not activated during LVAD support. Other signaling pathways must be responsible for the improvement of cellular function and cell survival during LVAD support.
Actins↗
Anesthetic management for implantation of the Jarvik 2000 left ventricular assist system.
UNLABELLED: The Jarvik 2000 Heart(TM) is a left ventricular assist device that produces continuous nonpulsatile axial flow by means of a single, rotating, vaned impeller. Anesthetic and perioperative considerations of the Jarvik 2000 Heart(TM) differ from those of conventional assist devices. The Jarvik 2000 is implanted within the left ventricle through a left thoracotomy, which is aided by left lung isolation. A brief period of cardiopulmonary bypass and induced ventricular fibrillation facilitate implantation. Transesophageal echocardiography is essential to assure proper intraventricular positioning of the device and aortic outflow, confirmed by observation of aortic valve opening in the presence of adequate left ventricular volume. Because continuous flow devices function best in the presence of lower systemic and pulmonary vascular resistance, milrinone was preferentially used as an inotropic drug. In the first group of 10 patients to receive the Jarvik 2000, the pump provided a cardiac output of up to 8 L/min, depending on preload, afterload, and pump speed. There were no early perioperative deaths. The average support duration was 81.2 days; the range was 13-214 days. Seven of the 10 patients survived to transplantation. Survivors underwent complete physical rehabilitation during pump support. IMPLICATIONS: The Jarvik 2000 is a left ventricular assist device that produces continuous nonpulsatile axial flow by means of a rotating, vaned impeller. Because the anesthetic considerations differ from those of conventional left ventricular assist devices, we report the perioperative management of the first 10 patients who participated in a bridge-to-transplantation feasibility study of the Jarvik 2000.
Aged↗
Off-pump coronary artery bypass grafting and transmyocardial laser revascularization via a left thoracotomy.
Off-pump coronary artery bypass grafting may be combined with adjunctive transmyocardial laser revascularization to optimize revascularization. This approach may be advantageous for high-risk patients, particularly those having undergone previous sternotomies. From October 2000 through May 2001, 17 patients (9 women and 8 men) underwent off-pump coronary artery bypass grafting and transmyocardial laser revascularization via a left thoracotomy. The patients had a mean age of 63 years and a mean ejection fraction of 0.33. All but 1 patient had undergone previous coronary surgery. In each patient, the heart was approached via a left thoracotomy through the 5th intercostal space, and 37 transmural channels, 1 mm in diameter, were each created with a single pulse of the carbon dioxide laser. Coronary artery bypass grafting was then performed with left internal thoracic artery or saphenous vein grafts. The follow-up period ranged from 2.1 to 9.3 months (mean, 6.2 months). The patients received 28 bypass grafts (mean, 1.6 grafts). Postoperatively, 2 patients required inotropic support. On day 8, 1 patient died of ventricular fibrillation. After a mean hospitalization of 7.7 days, the remaining patients were discharged, free of angina. At follow-up examination after a mean of 6 months (range, 2-9 months), 15 patients remained free of angina and one had mild angina. None had required further hospitalization. Performed via a left thoracotomy, off-pump coronary artery bypass grafting plus transmyocardial laser revascularization yielded an acceptable mortality rate, no major morbidity, and substantial angina relief in this carefully selected group of challenging, high-risk patients.
Adult↗
Ex vivo resuscitation of adult pig hearts.
One possible way to expand the human heart donor pool is to include non-heart-beating human donors. To begin validating this approach, we developed an ex vivo cardiac perfusion circuit to support large mammalian hearts in Langendorff mode and beating-ejecting mode and to assess and improve their ischemic tolerance. In vivo hemodynamic data and heparinized blood (4.0 +/- 0.5 L) were collected from 6 anesthetized pigs. Hearts were isolated and connected to a recirculating perfusion circuit primed with autologous buffered blood (pH, 7.40). After retrograde aortic perfusion in Langendorff mode, the left atrium was gravity-filled at 10-20 mmHg, and the left ventricle began to eject against a compliance chamber in series with a systemic reservoir set to a hydraulic afterload of 100-120 mmHg. Left ventricular function was restored and maintained in all 6 hearts for 30 min. Cardiac output, myocardial oxygen consumption, stroke work, aortic pressure, left atrial pressure, and heart rate were measured. The mean myocardial oxygen consumption was 4.8 +/- 2.7 mL/min/100 g (95.8% of in vivo value); and mean stroke work, 5.3 +/- 1.1 g x m/100 g (58.95% of in vivo value). One resuscitated heart was exposed to 30 min of normothermic ischemic arrest, then flushed with Celsior and re-resuscitated. The ex vivo perfusion method described herein restored left ventricular ejection function and allowed assessment of ischemic tolerance in large mammalian hearts, potentially a 1st step toward including non-heart-beating human donors in the human donor pool.
Animals↗
Metabolically controlled reperfusion in acute myocardial infarction: should the polarizing solution be given subselectively?
BACKGROUND: In working rat hearts, metabolic support of injured tissue enhances recovery after acute myocardial infarction. Clinical experience with a systemic "polarizing solution" supports this claim. OBJECTIVES: In a dog model of ischemia/reperfusion, we tested the feasibility of subselectively supplying adapted metabolic substrates before instituting blood reperfusion. METHODS: Thirty-five dogs underwent ligation of the proximal left anterior descending artery and collaterals for 90 minutes. The animals were randomly assigned to receive direct blood reperfusion (Group I), intracoronary glucose, insulin, and potassium (Group II), or intracoronary glucose, insulin, and potassium plus propionyl-L-carnitine (PLC) (Group III). After 30 minutes of artificial reperfusion, prograde blood flow was resumed in groups II and III. A routine necropsy was performed 3 to 5 days later. Primary endpoints were severe arrhythmias, death, markers of infarct size, and specific histologic features. RESULTS: We excluded 4 dogs for technical reasons and 2 others for preexisting cardiomyopathy. In the remaining 29 animals, large apical infarctions were documented ventriculographically during arterial ligation. One dog died of irreversible ventricular fibrillation during the initial ischemic period, and 9/28 dogs (32.1%) died during early reperfusion. Ventricular fibrillation was more common with 10% (versus 5%) dextrose concentrations and was eliminated by PLC. Irreversibly injured (versus jeopardized) areas of myocardium were more common in Group III (85.9 19.3%) than in Groups I and II (16.9 10.8%). CONCLUSION: Subselective infusion of metabolically supportive solutions during acute myocardial infarction is technically feasible. To prevent osmotic endothelial damage, the perfusate must have a low (< 5%) dextrose content.
Animals↗
Surgical management of metastatic melanoma to the ventricle.
The treatment of patients who have cardiac tumors can be challenging, because these tumors occur infrequently and in variable locations, and surgical resection is often technically difficult. We report the cases of 2 patients, each of whom underwent successful surgical excision of large melanomas that had metastasized to the right cardiac ventricle. Although the presence of widespread disease and a limited life expectancy usually prevent surgical therapy for patients who have metastatic cardiac tumors, removal of such masses greatly facilitated subsequent medical management of these 2 patients and improved their quality of life.
Adult↗
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.
Adult↗
Circulatory support for long-term treatment of heart failure: experience with an intraventricular continuous flow pump.
BACKGROUND: A lifetime mechanical solution for advanced heart failure must be reliable, with a low risk of life-threatening complications. After extensive laboratory testing, we began clinical trials with an axial flow pump for long-term treatment of New York Heart Association class IV, transplant-ineligible patients. METHODS AND RESULTS: The Jarvik 2000 is a continuous flow device that is implanted in the apex of the left ventricle with offloading to the descending thoracic aorta. Skull-based percutaneous power delivery was derived from cochlear implant technology. We used this system in 4 patients with end-stage dilated cardiomyopathy. Exercise capacity, quality of life, device parameters, and native heart function were monitored serially. One patient died from right heart failure at 3 months. The other patients were discharged from hospital between 3 and 8 weeks postoperatively and are currently New York Heart Association I or II. Follow-up lasted between 9 and 20 months. There has been no device failure or hemolysis. Native heart function and quality of life were markedly improved. CONCLUSIONS: The Jarvik 2000 is a true assist (rather than replacement) device that functions synergistically with the native left ventricle and provides excellent quality of life. Adverse events are infrequent. This blood pump may provide a mechanical solution for end-stage heart failure in the community.
Adrenergic beta-Antagonists↗
Implant technique for the Jarvik 2000 Heart.
The Jarvik 2000 Heart is a silent compact axial flow impeller pump which is now undergoing clinical trials for both bridge to transplantation and permanent mechanical circulatory support. The pump is implanted into the apex of the failing left ventricle by left thoracotomy. A vascular graft offloads to the descending thoracic aorta so that only the left pleural cavity is opened. Power supply is through an abdominal drive line or postauricular titanium pedestal according to the treatment strategy.
Heart, Artificial↗
Use of autologous auricular chondrocytes for lining artificial surfaces: a feasibility study.
BACKGROUND: Auricular elastic cartilage is a potential source of autologous cells for lining the luminal surfaces of cardiovascular prostheses. We tested this potential in vitro and in vivo using a left ventricular assist device (LVAD) and a calf model. METHODS: In vitro, auricular cartilage was harvested from the anesthetized ear of a calf, isolated, and cultured on tissue culture dishes. Primary chondrocytes were typed by immunocytochemistry, transferred into culture media, passaged twice, and seeded onto the blood-contacting luminal surfaces of four LVADs (HeartMate; Thoratec Corporation, Woburn, MA). Seeded cell linings were preconditioned under simulated flow conditions to promote cell adhesion to luminal surfaces. Seeding efficiency and cumulative cell loss under flow conditions were quantitated. In vivo, one of the four autologous chondrocyte-lined and preconditioned LVADs was implanted into the tissue-donor calf; run for 7 days; explanted; and evaluated grossly, by scanning electron microscopy, and by transmission electron microscopy. RESULTS: The efficiency of seeding chondrocytes onto the luminal surfaces of the four LVADs was 95.11% +/- 4.23% (n = 4). Cumulative cell loss during preconditioning under flow conditions in vitro did not exceed 12% (n = 4). After 7 days of in vivo implantation, the luminal surfaces of the implanted LVAD demonstrated an intact, strongly adherent cellular lining. CONCLUSIONS: Auricular elastic cartilage is a ready and easily accessible source of chondrocytes whose ability to produce collagen II and other important extracellular matrix constituents allows them to adhere strongly to the luminal surfaces of LVADs. The simple method of isolating and expanding auricular chondrocytes presented here could be used to provide strongly adherent autologous cell linings for LVADs and other cardiovascular devices. If and when chondrocytes can be genetically engineered to produce antithrombogenic factors and then used to line the luminal surfaces of LVADs or other cardiovascular prostheses, they may be able to improve the hemocompatibility of the blood-biomaterial interface in such devices. Our successful feasibility study in a calf model warrants further studies of this concept in vivo.
Animals↗
Cytomegalovirus cholecystitis in a heart transplant recipient.
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Antiviral Agents↗
Implantation of the permanent Jarvik-2000 left-ventricular-assist-device: surgical technique.
The Jarvik-2000 is an axial-flow left-ventricular-assist-device (LVAD) designed for permanent use. The power supply is provided by a cable plugged into a skull-pedestal mounted in the retro-auricular area. We describe the surgical technique and discuss potential and encountered problems.
Heart-Assist Devices↗
The Jarvik 2000 Heart. Clinical validation of the intraventricular position.
OBJECTIVE: Heart failure is now a public health epidemic. Donor hearts are severely restricted in availability. Permanent mechanical circulatory support or bridge to myocardial recovery are emerging alternatives. After extensive laboratory experience we sought to evaluate the intraventricular Jarvik 2000 Heart in patients with endstage heart failure. METHODS: The Jarvik 2000 Heart is a novel thumb-sized left ventricular assist device (LVAD) which is fitted within the apex of the native left ventricle. A vascular graft off loads this to the descending thoracic aorta. The pump rotor spins at between 8000 and 12,000 rpm providing 5-6 litres blood flow per minute. We have used the device with skull-mounted power delivery for seven permanent implants and trans-abdominal drive line for ten bridge-to-transplant patients. RESULTS: All patients survived the operation. Three died from non-device related complications. Survivors had early resolution of heart failure with return to NYHA I/II. All had pulsatile circulation. The device was user-friendly and imperceptible to the patient. Both the pump and native left ventricle contributed to the cardiac output during exercise. Seven patients have been transplanted successfully. All explanted devices were free from thrombus formation. Two permanent implant patients left hospital as early as 3 weeks postoperatively. CONCLUSIONS: The Jarvik 2000 is an effective user-friendly LVAD which allows early discharge from hospital. The intraventricular position has distinct advantages especially through absence of an inflow cannula. Synergy develops between the LVAD and native left ventricle. Early experience suggests that this may be a realistic LVAD to treat heart failure routinely in the outpatient setting.
Adult↗
Mechanical circulatory support: new advances, new pumps, new ideas.
Mechanical circulatory support (MCS) is a viable therapy for severe end-stage heart disease. Most obstacles to long-term MCS therapy have been overcome, and a number of clinical trials, including the recent REMATCH trial, have shown a clear benefit in terms of survival and improved quality of life. MCS should therefore no longer be considered as simply a temporary bridge to other therapies, but also a destination therapy whose potential should continue to expand through the development and use of newer, more innovative devices such as continuous flow pumps, next-generation centrifugal pumps, and total artificial hearts. The homebound heart failure patient and the patient facing imminent death from massive myocardial infarction receive little statistical benefit from current therapies, and the new and evolving MCS technologies offer the potential for effective therapy to these desperately ill patients.
Assisted Circulation↗