Heart Transplantation and Left Ventricular Assist Device Therapy: Two Comparable Options in End‐Stage Heart Failure?

Heart transplantation is the only curative therapy for chronic heart failure, and it plays an important role in the treatment of chronic heart failure with a survival rate of approximately 50% of all patients after 10 years. This has to be kept in mind when alternative therapies enter into our daily routine in treating this patient population. However, the shortage of appropriate donor organs and the expanding pool of patients waiting for heart transplantation have led to growing interest in alternative strategies, particularly in left ventricular assist device (LVAD) therapy. With growing clinical experience and continued technical advances, continuous‐flow pumps are evolving as a bridge to transplantation or as a destination therapy for advanced heart failure. Nevertheless, the importance of this new indication of chronic cardiac support compared to heart transplantation is still completely open and the object of controversial ongoing discussion. This review (1) describes the clinical use and long‐term outcome of a currently available miniaturized LVAD in the context to the standard of care—heart transplantation, (2) provides an outlook of the ongoing process of further optimization of LVADs, and (3) comments on the challenges with assist devices as alternatives to transplantation with a 5‐year outlook.     

Patient Selection for Long-Term Mechanical Circulatory Support: Is It Ever too Early for the NYHA Class III Patient?

Heart failure is a common condition with significant morbidity and mortality. Pharmacologic and device therapies have resulted in substantial improvements in heart failure outcomes. Despite optimal therapy, 10 % of patients progress to advanced HF, characterized by progressive symptoms, poor quality of life, and poor prognosis. The “gold-standard” treatment of advanced heart failure remains cardiac transplantation. However, the number of patients with advanced heart failure far exceeds available donor organs. Left ventricular assist devices (LVADs) were initially developed to bridge patients with hemodynamic collapse to transplantation. Their use resulted in marked improvements in survival and quality of life in select patients giving rise to increased and expanded overall implantation. Despite these improvements, patient selection and timing for LVAD therapy is still evolving. In this article, we will review a brief history of LVADs, examine patient selection, and explore the currently debated expansion of LVADs to “less sick” patients.     

Ventricular Assist Device Therapy

Ventricular assist devices are an important therapeutic option for advanced congestive heart failure. A left ventricular assist device (LVAD) can be implanted as a bridge to transplantation or for the purpose of destination therapy. LVADs improve end‐organ function and reduce morbidity and mortality in appropriately selected patients. The development of axial flow pumps has overcome many of the limitations of the first‐generation pulsatile flow LVADs. However, many complications of LVAD therapy remain. Treating these complications requires an understanding of LVAD physiology. Ongoing research is directed at reducing the incidence of many of these complications and may allow for wider use of LVADs.     

To ventricular assist devices or not: When is implantation of a ventricular assist device appropriate in advanced ambulatory heart failure?

Advanced heart failure has been traditionally treated via either heart transplantation,continuous inotropes,consideration for hospice and more recently via left ventricular assist devices(LVAD).Heart transplantation has been limited by organ availability and the futility of other options has thrust LVAD therapy into the mainstream of therapy for end stage heart failure.Improvements in technology and survival combined with improvements in the quality of life have made LVADs a viable option for many patients suffering from heart failure.The question of when to implant these devices in those patients with advanced,yet still ambulatory heart failure remains a controversial topic.We discuss the current state of LVAD therapy and the risk vs benefit of these devices in the treatment of heart failure.     

Right Ventricle-Sparing Left Ventricular Resection and Replacement with a Continuous-Flow Rotary Blood Pump: An In Vivo Experiment

Despite recent advances in left ventricular assist device and total artificial heart technologies, these devices are still so large that they pose a significant problem in small patients with refractory heart failure. Excising the left ventricle while preserving the right ventricle—and then replacing the left ventricle with a mechanical pump—has been proposed as an alternative approach to this problem. We conducted a pilot study to evaluate possible surgical techniques and the hemodynamic effects of right ventricle-sparing left ventricular resection and replacement with a continuous-flow rotary blood pump in a healthy bovine model.Key words: Animals, blood pump, centrifugal, heart, artificial, heart-assist devices, heart failure, congestive, heart transplantation, heart ventricles, prosthesis fitting, prosthesis implantationLeft ventricular assist devices (LVADs) have proved useful both in supporting patients who have chronic refractory heart failure until an appropriate donor heart can be obtained and in enabling patients who manifest acute decompensation to become, over time, better candidates for cardiac transplantation.¹ Similarly, the pneumatically actuated total artificial heart has been shown to benefit these same patients.¹ More recently, LVADs have been implanted as permanent, or destination, therapy in patients who were deemed not to be transplantation candidates. Despite substantial advances in LVAD and total artificial heart technology over the past several years, these devices are still so large that they pose a significant problem in small patients with refractory heart failure.^1-4 Surgically excising the left ventricle (LV) and placing an LVAD-like pump in the left atrial-to-aortic position might mitigate some of the difficulties associated with size constraints by removing the markedly enlarged LV and, as an added benefit, might eliminate a potential source of emboli and right ventricular (RV) dysrhythmias.In our previous studies,^2,3 we demonstrated in a bovine model the feasibility of long-term LV replacement with a pulsatile, pneumatically actuated volume-displacement pump. After LV excision and replacement, the calf maintained normal RV function and systemic hemodynamics for 4 days. In the current pilot study, we attempted to repeat this experiment with a continuous-flow rotary pump. By exploiting some of the advantages of the newer rotary pumps, namely smaller size and better wear resistance, we hoped to demonstrate the viability of a potentially beneficial treatment option for some patients with end-stage heart failure.     

Evolving trends in mechanical circulatory support: Clinical development of a fully magnetically levitated durable ventricular assist device

Early generation left ventricular assist devices (LVAD) for treatment of refractory heart failure attempted to mimic the pulsatility of a native heart and were bulky and less durable due to valves within the inflow and outflow pathways. The next disruption came with the introduction of continuous flow pumps characterized by a low-pulse pressure circulation. Since the mechanism of action did not involve displacement of blood, these pumps were much smaller and less noisy in part due to fewer moving parts. Such devices include the HeartMate II axial-flow pathway pump which is implanted thoraco-abdominally and the HVAD, a centrifugal-flow pathway pump which is smaller and is implanted entirely within the thoracic cavity and uses a combination of hydrodynamic and magnetic levitation of the internal rotor. These pumps improved survival compared with the early generation LVADs and in a trial, the HVAD demonstrated non-inferiority compared with the HeartMate II but with an increase in ischemic and hemorrhagic strokes. The HeartMate 3 LVAD is an intrapericardial centrifugal-flow pathway pump with a full magnetically levitated, frictionless rotor with a fixed intrinsic pulse. In a randomized trial, the HeartMate 3 “hybrid” pump was associated with near-elimination of pump thrombosis, a reduction in strokes of any type or severity and lower mucosal bleeding rates. Despite improvements in hemocompatibility, right heart failure and infections contribute to significant morbidity, and devices designed to be internally contained with a wireless power source and physiological flow characteristics are still required despite great strides in the field.     

Current state of ventricular assist devices

Left ventricular assist device (LVAD) support is an accepted treatment of patients with end-stage heart failure. The increased applicability and excellent results with LVADs have revolutionized the treatment options available for such patients. Success with LVADs as bridge-to-transplant therapy has led to their successful use as an alternate to a transplant (ie, as destination therapy [DT]). The use of these devices as DT represents a relatively newer but growing indication. Until recently, most patients who have undergone LVAD implantation have been supported by pulsatile devices. Newer continuous-flow (CF) pumps have resulted in superior outcomes, including significantly reduced complication rates with improved durability over first-generation pulsatile design pumps. However, as with all new technology, the newer LVADs have introduced management challenges that were either unimportant or absent with pulsatile LVADs. This article reviews the current state of left ventricular devices, focusing on the CF pumps that currently dominate the field, including clinical outcomes, the physiologic and pathologic effects that are associated with CF pumps, and their unique management issues and complications.     

Echocardiography and cardiac assist devices

Mechanical circulatory support is, nowadays, a well established treatment modality for end stage heart failure. Patients candidate for cardiac transplantation who decompensate while awaiting graft can be supported by long-term left ventricular assist devices (long-term LVAD). These devices are intracorporeal pumps, expensive and complicated to install, but offer the advantages of a high cardiac output and a good patient mobility. Echocardiography is usually applied to any kind of LVAD to accomplish: preoperative evaluation to exclude contraindications, intraoperative when circulatory support starts to assess left ventricular (LV) filling and unloading, postoperative evaluation during intensive care unit course to prevent hypovolemia, cardiac tamponade and right ventricular failure, controls during assistance for suspected device malfunction. Short-term devices are utilized as acute support after the initial resuscitation of the patient. These devices are bedside extracorporeal pumps, less expensive and less complicated to install. They provide a brief but sufficient time to wait patient recovery ('bridge to recovery') or to evaluate further therapies ('bridge to long-term device' or 'bridge to transplantation'). Echocardiography has an important role during implantation to guide cannulae positioning, to prevent insufficient LV unloading, to detect echo contrast enhancement with blood stagnation and intracardiac clot formation, to titrate pharmacologic support, and to assess myocardial recovery.     

Chronic mechanical circulatory support for inotrope-dependent heart failure patients who are not transplant candidates: results of the INTrEPID Trial.

OBJECTIVES: This study evaluated the impact of left ventricular assist device (LVAD) support on survival and quality of life in inotrope-dependent heart failure patients ineligible for cardiac transplantation. BACKGROUND: The role for LVADs as a bridge to cardiac transplantation has been established, but data supporting their role as permanent therapy in nontransplant candidates are limited. METHODS: The INTrEPID (Investigation of Nontransplant-Eligible Patients Who Are Inotrope Dependent) trial was a prospective, nonrandomized clinical trial comparing LVAD with optimal medical therapy (OMT). Fifty-five patients with New York Heart Association functional class IV symptoms who failed weaning from inotropic support were offered a Novacor LVAD. Eighteen of these patients did not receive an LVAD owing to patient preference (n = 14) or unavailability of the device (n = 4) but consented to follow-up and constitute a contemporaneous control group. RESULTS: The LVAD and OMT patients were well matched for demographic and disease severity measures, except OMT patients had a lower mean serum sodium (128 mg/dl vs. 134 mg/dl; p = 0.001) and a higher mean blood urea nitrogen concentration (59 vs. 40; p = 0.02). The LVAD-treated patients had superior survival rates at 6 months (46% vs. 22%; p = 0.03) and 12 months (27% vs. 11%; p = 0.02). Adverse event rates were higher in the OMT group. Eighty-five percent of the LVAD-treated patients had minimal or no heart failure symptoms. Five LVAD patients and 1 OMT patient improved sufficiently while on therapy to qualify for cardiac transplantation. CONCLUSIONS: Inotrope-dependent heart failure patients who are ineligible for transplantation have a high short-term mortality rate and derive a significant survival advantage from "destination" mechanical circulatory support.     

Medical Management of Left Ventricular Assist Device Patients: A Practical Guide for the Nonexpert Clinician

Left ventricular assist devices (LVADs) provide short- or long-term circulatory support to improve survival and reduce morbidity in selected patients with advanced heart failure. LVADs are being used increasingly and now have expanded indications. Health care providers across specialties will therefore not only encounter LVAD patients but play an integral role in their care. To accomplish that, they need to understand the elements of LVAD function, physiology and clinical use. This article provides a concise overview of the medical management of LVAD patients for nonexpert clinicians. Our presentation includes the basics of LVAD physiology, design, and operation, patient selection and assessment, medical management, adverse event identification and management, multidisciplinary care, and management of special circumstances, such as noncardiac surgery, cardiac arrest, and end-of-life care. The clinical examination of LVAD patients is unique in terms of blood pressure and heart rate assessment, LVAD “hum” auscultation, driveline and insertion site inspection, and device parameter recording. Important potential device-related adverse events include stroke, gastrointestinal bleeding, hematologic disorders, device infection, LVAD dysfunction, arrhythmias, and heart failure. Special considerations include the approach to the unconscious or pulseless patient, noncardiac surgery, and palliative care. An understanding of the principles presented in this paper will enable the nonexpert clinician to be effective in collaborating with an LVAD center in the assessment, medical management, and follow-up of LVAD patients. Future opportunities and challenges include the improvement of device designs, greater application of minimally invasive surgical implantation techniques, and management of health economics in cost-constrained systems like those of Canada and many other jurisdictions.     

Mechanical circulatory assistance: established (IABP) and evolving (LVAD). A narrative summary

Comparisons of the physiologic bases of intraaortic balloon and extracorporeal or implantable left ventricular assist device or partial artificial heart pumping in experimental and clinical setting are made. The concepts and first principles common and unique to both of these forms of mechanical circulatory support are presented with emphasis on the similarities and important differences. Intraaortic balloon counterpulsation is examined as an intravascular, volume displacement device in series with the systemic circulations. Left ventricular assist devices are analyzed as extravascular in-series or parallel volume-capturing/ejecting devices and as true blood pumps which can be implanted. The interrelated mechanisms of synchronous, diversion/counterpulsation/diastolic augmentation are discussed in relation to quantitative indices of myocardial ischemia, myocardial oxygen supply/demand ratios, the Sarnoff theorem and the Laplace relationship, vis à vis ventricular unloading/impedance reductions. Some of the many clinical settings of IABP are mentioned, along with hydraulic considerations which allow non-invasive determination of stroke volume during clinical IABP mechanical circulatory support. Cardiogenic shock/left ventricular failure/low cardiac output are defined in terms of failure to generate pressure and displace volume and deficits of ejection fraction and stroke volume. Vasodilator therapy (nitroprusside), IABP, and LVAD are then viewed as escalating methods of reversing these deficits. Finally, pressure volume loops of the human left ventricle are compared with those of LVADs, experimentally and clinically, to indicate that LVADs can function and support the circulation during all low output states including ventricular fibrillation and standstill. Representative hemodynamic traces (Fig. 5 and 6) obtained during clinical LVAD trials in man are included to illustrate these theoretical and practical considerations. The use of LVADs in any instance of IABP inadequacy is implicit and inferred.     

Early mobilization of LVAD recipients who require prolonged mechanical ventilation

Early mobilization and aggressive physical therapy are essential in patients who receive left ventricular assist devices (LVADs) due to long-term, end-stage heart failure. Some of these patients remain ventilator dependent for quite some time after device implantation. We report our regimen of mobilization with the aid of a portable ventilator, in patients with cardiac cachexia and LVAD implantation. Further, we describe the specific physical therapy interventions used in an LVAD patient who required prolonged mechanical ventilation after device implantation. The patient was critically ill for 5 weeks before the surgery and was ventilator dependent for 48 days postoperatively. There were significant functional gains during the period of prolonged mechanical ventilation. The patient was able to walk up to 600 feet by the time he was weaned from the ventilator and transferred out of the intensive care unit. He underwent successful heart transplantation 6 weeks after being weaned from the ventilator We believe that improving the mobility of LVAD patients who require mechanical ventilation has the potential both to facilitate ventilator weaning and to improve the outcomes of transplantation.     

Comment--the REMATCH trial: Long-term use of a left ventricular assist device for end-stage heart failure

BACKGROUND: Implantable left ventricular assist devices (LVADs) have been used primarily as bridges to cardiac transplantation, although some patients have been maintained long term on these devices and a few have recovered enough to be weaned. This trial was designed to evaluate their suitability as long-term myocardial replacement therapy in patients who are ineligible for cardiac transplantation. METHODS AND RESULTS: One hundred twenty-nine patients with end-stage heart failure who were ineligible for cardiac transplantation were randomly assigned to receive an LVAD (Thoratec HeartMate; Thoratec, Pleasanton, CA) or optimal medical therapy, with a primary end point of all-cause mortality. To be eligible, patients had to have New York Heart Association (NYHA) class IV heart failure for at least 90 days despite attempted therapy with an angiotensin-converting enzyme inhibitor, diuretics, and digoxin; an ejection fraction 相似文献   

LVAD destination therapy: applying what we know about psychiatric evaluation and management from cardiac failure and transplant

Left ventricular assist devices (LVADs) have evolved into long-term use as destination therapy for those with severe end-stage heart failure due to other medical risks. Success with LVAD depends on adherence to a complicated mechanical regimen, and acceptance of a life that is far from normal. Patients with LVADs share characteristics with other end-stage cardiac failure patients and those waiting for or receiving heart transplants. Understanding the more thoroughly studied issues of psychiatric disorders, adherence, and behavioral correlates of success in heart failure and transplantation may identify feasible strategies for optimizing care of LVAD patients and suggest directions for future research. Depression and distress complicate post-transplant care. Psychiatric morbidity is associated with poor outcomes, including graft rejection, non-adherence, hospitalizations, infection, and death. With a high risk of embolic neurological events, patients’ ability for self-care may be compromised. Psychiatric symptoms are underdiagnosed and undertreated, which may impact overall survival and quality of life.     

Left ventricular assist device therapy in advanced heart failure: patient selection and outcomes

Despite improvements in pharmacological therapy and pacing, prognosis in advanced heart failure (HF) remains poor, with a 1‐year mortality of 25–50%. While heart transplantation provides excellent survival and quality of life for eligible patients, only a few can be offered this treatment due to shortage of donor organs. Implantable left ventricular assist device (LVAD) technology has improved considerably, and the currently used continuous flow devices may last >10 years in a patient. LVADs are being used increasingly both as bridge‐to‐transplantation and as destination therapy. Current studies report 1‐ and 2‐year survival after LVAD implantation of 80% and 70%, respectively. Outcome after LVAD implantation in stable patients is superior to that of ‘crash and burn’ patients or patients sliding on inotropes, favouring early referral and implantation. This review summarizes factors to consider when deciding on LVAD implantation such as age, co‐morbidity, and cardiac pathophysiology. Complications to LVAD therapy are reviewed. It is concluded that while complications with LVAD therapy are not uncommon, most are manageable, and current outcomes clearly justify use of LVADs in advanced HF.     

A call for guidance in the use of left ventricular assist devices in older adults

Left ventricular assist devices (LVADs) are approved as "destination therapy" (permanent use without plans for transplantation) in individuals with advanced heart failure who are not candidates for a cardiac transplant; as such, these devices are increasingly being used in older adults. Although LVADs have been shown to increase quality of life and survival, the associated treatment burdens and complications deserve careful consideration. The current study illustrates myriad clinical challenges that can arise during long-term mechanical support using an older adult case history. Current data on LVAD use in older adults is reviewed, and a discussion of relevant points to consider before LVAD implantation in older adults, including advance care planning, assessment of gait and cognition, and the potential for substantial caregiver burden, is undertaken.     

Destination therapy with ventricular assist devices

Despite extensive research and great strides over the past 40 years, the ideal permanent mechanical assist device remains elusive. The incidence of heart failure is increasing, and the number of heart transplants has remained constant. The HeartMate and Novacor are two pulsatile, long-term ventricular assist devices (VADs) commonly used as a bridge to transplantation. Randomized Evaluation of Mechanical Assistance in the Treatment of Congestive Heart Failure is a randomized study of device therapy in heart failure with treatment either with device (HeartMate) therapy or maximal medical therapy which was recently completed and demonstrated a Kaplan-Meier survival rate at 1 year of 52% for the device group compared to 25% in the medical therapy group. The TCI HeartMate is the only device approved for destination therapy, while others such as the Novacor device are in the process of evaluation. Most of these devices are still plagued by mechanical problems, bleeding, thromboembolism and infection. Other promising new devices include smaller VADs using impeller pump technology, such as the Arrow LionHeart, Micromed Debakey pump and Jarvik 2000 pump. The CardioVAD is an interesting chronically implantable balloon pump inserted into the descending thoracic aorta. While experience with the newer implantable pumps is growing, most of them require some manipulation of the heart perioperatively, in addition to anticoagulation postoperatively and careful monitoring for complications and infection.     

Dealing with surgical left ventricular assist device complications

Left ventricular assist devices (LVAD) will undoubtedly have an increasing role due to the aging population, anticipated concomitant increase in the prevalence of end-stage heart failure, and improvements in LVAD technology and outcomes. As with any surgical procedure, LVAD implantation is associated with an adverse event profile. Such complications of LVAD therapy include bleeding, infection, pump thrombosis, right heart failure, device malfunction, and stroke. Although each has a unique management, early recognition and diagnosis of these complications is uniformly paramount. In this review, we provide an overview of managing surgical complications of LVADs.     

Symptomatic relief: left ventricular assist devices versus resynchronization therapy

In patients who have end-stage heart failure, medical therapy is of limited use, and heart transplantation is frequently not an option because of the shortage of donor hearts. Two new treatment options, left ventricular assist devices (LVADs) and implantable cardiac resynchronization therapy (CRT) devices, can improve survival and quality of life in patients who have heart failure. Both types of devices are easy to implant. However, LVADs carry the risk of infection and mechanical failure, and CRT is ineffective in a substantial proportion of patients who have heart failure. Therefore, methods must be devised to identify patients who have heart failure who are likely to benefit from these devices. Data suggest that early LVAD implantation, before end-stage heart failure develops, is critical to slowing or reversing disease progression. Similarly, in indicated patients who have less advanced disease, CRT may be particularly beneficial.     

Late sequelae of left ventricular assist device infection presenting after heart transplant

The long‐term use of left ventricular assist devices (LVADs) is becoming more common among the end‐stage heart failure population. At the time of heart transplantation, most of the LVAD is removed, but some of its components might be retained. Retained LVAD prosthetic material can lead to serious infection post heart transplant. We report 4 such cases. Our goal is to highlight the importance of complete prosthetic material removal at the time of cardiac transplant to prevent late‐onset infection, especially in patients with preceding infection, but also in patients without evidence of LVAD infection prior to orthotopic heart transplantation.