Molecular Drivers of Aortic Remodeling After Left Ventricular Assist Device.

Over the last 2 decades, numerous advancements in medical therapies have improved patient outcomes in heart failure (HF). However, a significant number of patients still progress to end-stage HF, in which treatment options are largely limited to cardiac transplantation. As patient demands for transplant continue to exceed the supply of available organs, mechanical assist devices—specifically, the left ventricular assist device (LVAD)—were initially introduced as a bridge to cardiac transplantation. LVADs have 2 important beneficial effects. First, LVADs are placed in parallel to the native left ventricle (LV), causing pressure and volume unloading of the LV. Second, LVADs restore cardiac output and subsequent perfusion to the organs. As a result of these 2 effects, it became evident that some patients had actual improvement in LV function after LVAD placement. The term reverse remodeling was used to describe the improvement in myocardial function that was observed in patients with a seemingly end-stage disease. With reverse remodeling, a new hope for the treatment of HF was born—using LVADs as a bridge to recovery; however, to date, this promise has largely been unrealized. This probably is reflective of the fact that the sequela of mechanical ventricular unloading are quite complex and appear to involve the engagement of competing biological pathways including regression of cardiomyocyte hypertrophy as well as progressive cell atrophy. Although the promise of ventricular recovery still persists, its actualization will await a more comprehensive dissection of these competing biological processes. This review will discuss the beneficial clinical effects of LVAD support as well as review what is known about the cellular and molecular response to mechanical unloading and mechanisms of reverse remodeling. Key research findings have been summarized in the Table. View this table: Table. Summary of Research of LVAD Support on Clinical Effects and the Cellular and Molecular Changes That May Contribute to Reverse …

The success of left ventricular assist device (LVAD) therapy is hampered by complications such as thrombosis and bleeding. Understanding blood flow interactions between the heart and the LVAD might help optimize treatment and decrease complication rates. We hypothesized that LVADs modify shear stresses and blood transit in the left ventricle (LV) by changing flow patterns and that these changes can be characterized using 2D echo color Doppler velocimetry (echo-CDV). We used echo-CDV and custom postprocessing methods to map blood flow inside the LV in patients with ongoing LVAD support (Heartmate II, N = 7). We compared it to healthy controls (N = 20) and patients with dilated cardiomyopathy (DCM, N = 20). We also analyzed intraventricular flow changes during LVAD ramp tests (baseline ± 400 rpm). LVAD support reversed the increase in blood stasis associated with DCM, but it did not reduce intraventricular shear exposure. Within the narrow range studied, the ventricular flow was mostly insensitive to changes in pump speed. Patients with significant aortic insufficiency showed abnormalities in blood stasis and shear indices. Overall, this study suggests that noninvasive flow imaging could potentially be used in combination with standard clinical methods for adjusting LVAD settings to optimize flow transport and minimize stasis on an individual basis.

MECHANICAL support of the cardiovascular system is an important therapeutic modality for a growing number of patients with congestive heart failure.Certain patients with refractory end-stage failure who will likely succumb to their disease before a potential heart transplant may be effectively "bridged to transplant" by a left ventricular assist device (LVAD).Three such devices are currently approved by the US Food and Drug Administration for this indication.Several ongoing multicenter clinical trials are also evaluating LVAD therapy as an alternative to transplantation ("destination therapy").Preliminary data from the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure Trial indicate that an implantable LVAD prolongs survival and enhances quality of life in patients with end-stage heart failure. 1 The efficacy of destination therapy will undoubtedly lead to an expansion in the number of LVADsupported patients in future years.Some of these patients will require operations for noncardiac, non-LVAD problems.Anesthesiologists should therefore be familiar with the unique considerations related to these patients and their devices.Accordingly, this review presents important features of the commonly used devices, describes the effects of LVAD therapy on the pathophysiology of heart failure, and discusses the major perioperative considerations for patients who come to the operating room with an implanted LVAD.The discussion focuses on the patient with a chronically implanted device, not on the implantation procedure itself, which involves a different set of physiologic challenges and anesthetic considerations.

Second INTERMACS annual report: More than 1,000 primary left ventricular assist device implants

Systolic Nonclosure of the Mitral Valve: Two Left Ventricular Assist Device Patients with Pan-Cardiac Cycle Mitral Valve Opening During Shock States

Axial-flow LVADs have become an integral tool in the management of end-stage heart failure. Consequently, nonsurgical bleeding has emerged as a major source of morbidity and mortality in this fragile population. The mechanisms responsible for these adverse events include acquired von Willebrand disease, GI tract angiodysplasia formation, impaired platelet aggregation, and overuse of anticoagulation therapy. Because of ongoing concerns for pump thrombosis and thromboembolic events, the thrombotic/bleeding paradigm has led to a difficult clinical dilemma for those managing patients treated with axial flow LVADs. As the field progresses, advances in the understanding of the pathological mechanisms underlying bleeding/thrombosis risk, careful risk stratification, and potential use of novel anticoagulants will all play a role in the management of the LVAD patient.

Nurses must target interventions toward reducing the uncertainty associated with living with a ventricular assist device.Edgar Allan Poe wrote the timeless short story "The Pit and the Pendulum" nearly 20 years before the Civil War (see Box for synopsis). Certainly, at that time, he could not even have imagined the medical technology now available to patients with heart failure, most notably, ventricular assist devices (VADs). Yet, in many ways, his story captures many of the same feelings experienced by VAD patients today. Frank (a pseudonym), a 58-year-old man we interviewed about his experience of living with a VAD, stated the following:Although the comparison of the experience of living with a VAD to the experience of the narrator in "The Pit and the Pendulum" who was sentenced to death and confined to prison does not provide an easy image for nurses who care for patients who have VADs, the diagnosis of heart failure can be a sentence: a sentence to an uncertain future, physical decline, and even death.According to the American Heart Association,2 more than 5 million adults live with the diagnosis of heart failure. Despite the national trend toward improving outcomes in cardiovascular diseases in general, 1 of every 8 deaths in the United States is in some way attributable to heart failure. About 20% of all patients with heart failure die within 1 year of diagnosis.2 Once a patient's illness has progressed to advanced heart failure, 1-year mortality is greater than 30%.3 In fact, only about 40% to 60% of heart failure patients survive 5 years after diagnosis.4–6 Even with proper medical care, diminishing functional status can result in confinement physically (eg, through multiple hospitalizations or becoming increasingly homebound) or emotionally (eg, through progressing depression or social isolation).In addition to high mortality, patients with advanced heart failure often experience physical and psychological signs and symptoms that may remain unrelieved until the time of death. Dyspnea, fatigue, edema, anxiety, depression, and even pain are just a few of the common signs and symptoms.7–12 Experts7,13–16 in the care of patients with heart failure assert that pharmacological treatment according to heart failure guidelines is the foundation of all strategies for managing symptoms. Nevertheless, some heart failure is refractory to pharmacological treatment.3,17For patients with intractable signs and symptoms, a heart transplant, the reference standard for cardiac replacement,18,19 is the only established surgical approach.13 In the United States, however, the number of patients awaiting heart transplantation is much greater than the number of available donors. As of September 11, 2009, a total of 2874 patients were on the national heart transplant waiting list.20 The number of donors available between 2001 and 2007 ranged from 2015 to 2209, indicating a deficit in the number of available hearts each year. Even when patients receive a heart transplant, the waiting time for a heart donor is long, approximately 50 to 503 days, depending on a patient's transplant status.20As a result of the disparity between the number of patients needing transplants and the number of hearts available, mechanical circulatory assist devices are being used with increasing frequency as a bridge to transplant.21 Since 2002, implantable assist devices have been considered destination therapy (ie, rather than as a bridge to transplant) for patients who are not eligible for transplant21 and whose estimated 1-year mortality is greater than 50% with medical therapy.13,22,23 According to Grady and Shinn,21 by the end of 2006, nearly 13000 VADs had been implanted. Nearly 12000 patients are currently included in registries associated with VADs.24VADs are typically used to stabilize patients' clinical states while improving cardiac output via support of the ailing ventricle.25 Improved cardiac output then results in increased end-organ perfusion and, ideally, improves activity tolerance to the extent that patients who would be symptomatic with minimal exertion can be discharged to home. Device therapies are not problem-free; postoperative mortality associated with multiple organ failure, stroke, infection, hemorrhage, and even device malfunction remains high.21,25–28 Survival rates for patients who receive VADs as destination therapy are varied and depending on associated risk factors, range between 11% (very high risk) and 81% (low risk).26,29,30Examples of commonly used VADs include the HeartMate VE and XVE and HeartMate II. All are implantable (typically in the right upper part of the abdomen) and electronically driven. In general, VADs consist of a pump, a control system, and a power supply (see FigureF1). An inflow tube is placed in the apex of the left ventricle; blood flows through the pump (maintained by the power supply) and then is pumped through an outflow tube into the aorta. The pump may be either pulsatile or nonpulsatile,25 but both kinds essentially supplement left ventricular function. Tubing from the pump exits the body to the pump's outside power unit, which provides information on the function of the VAD and can be attached to a battery system to provide increased mobility when the patient wishes. The battery pack can be worn in a vest or a waist pack, or the patient can plug the unit into a wall socket when needed.Each VAD has specific features,21 but all VADs have general features related to patients' experiences in and out of the hospital. Before discharge, each patient and his or her family members must undergo extensive education to prepare them for the challenges they face. Typically they learn about the VAD itself (eg, function, components, warning lights), how to maintain the device (eg, system checks, maintenance and cleaning, how to order supplies), and what to do if problems occur (eg, troubleshooting and emergency responses).21 Then they must learn how to care for the external driveline, including proper dressing changes to minimize the risk of infection. Patients also may require anticoagulants to decrease the risk of thromboembolism. Even activities such as travel in a car may need to be altered because deployment of air bags may cause damage to the VAD or bleeding.21In a qualitative study31 conducted in the acute care setting, registered nurses thought that patients with VADs were in a unique situation compared with other chronically ill patients. According to these nurses, the hospitalized VAD patients and the patients' families required extensive emotional support during adjustment to the device and while waiting for transplantation. On the basis of their own clinical experience, the nurses reported that the VAD patients often experienced marked fear, anxiety, boredom, and depression, necessitating additional psychological support beyond that required by other hospitalized chronically ill patients.Although patients' psychological experiences related to VADs were the focus of a few early studies,32,33 exploration of such experiences in the acute care setting and in the community is still needed. Our study was designed to gain a better understanding of the experience of living with a VAD.Principles of naturalistic inquiry guided the study.34,35 Participants were recruited from the transplant center of a 442-bed acute care, university-affiliated hospital located in the southeast. Patients were selected if they had advanced heart failure and had had a VAD implanted within the preceding 12 months, were age 18 years or older, spoke English, were able to give consent for participation in the study, and lived within 3 hours' travel by car from the study site. Patients were excluded if they had a coexisting terminal illness such as cancer or primary organ failure (eg, renal or liver failure).Approval from the appropriate institutional review board was obtained before the study began. Potential participants were identified through review of transplant center records. Patients who met the inclusion criteria received letters from the nurse researcher at the transplant center that explained the study and the nature of the requested participation. Interested patients returned an enclosed postcard, and they were contacted to confirm their appropriateness for inclusion and to arrange a time and location for the interview. The underlying assumption was that patients who were willing to talk about their experiences of living with a VAD thought that they had important information to share.Qualitative interviewing was used. In order to facilitate data collection, a semistructured interview guide was developed on the basis of previous research,31 review of the literature, and consultation with VAD program staff. Examples of questions include the following: "Tell me what it was like to live with a VAD," "Tell me how your daily life has changed since you received the device," and "Tell me what else about having a VAD is important to talk about." Probing questions were asked to assist participants in clarifying content and to increase the descriptiveness of the responses.Basic sociodemographic data (including age, sex, living situation, and ethnicity) were also collected during the interview. Each patient was interviewed at his or her home; the interviews were 45 to 90 minutes long. Field notes were written and/or dictated after the conclusion of each interview.Interviews were tape-recorded and were transcribed verbatim. Data were analyzed on an ongoing basis; qualitative content analysis36 was used to generate major conceptual categories. A key patient was interviewed a second time to verify the emerging themes. Further, a consultant (C.P.) from the Department of English, Bellarmine University, Louisville, Kentucky, with expertise in literature provided additional analysis of "The Pit and the Pendulum" as the short story was related to each theme.In total, 18 patients received either an initial or a follow-up letter from the transplant center. Of these, 2 men and 4 women, 42 to 76 years old (mean, 59; SD, 11.3) volunteered to participate in the study. Both men and 2 of the women were white; the other 2 women were African American. One man was married; the other lived alone but had a significant other who visited him regularly. Three of the women were married; the fourth lived with other family. At the time of the interviews, 5 of the 6 patients had received heart transplants. The duration of use of a VAD varied widely (mean, 181 days; SD, 147; range, 28–407). One woman decided to accept the VAD as destination therapy rather than undergo transplantation.During the interviews, a patient articulated his experience of choosing and ultimately living with a VAD via an analogy with "The Pit and the Pendulum." As the patient described the themes of his experience, we realized that the language of the other patients in the study corresponded closely with several themes of the short story. Four critical themes emerged: facing the unknown, feeling confined, living with fear, and hope for the future.Upon awakening in the darkness of his prison cell, the narrator in "The Pit and the Pendulum" reaches out his hand, striving "to imagine where and what I could be."1(p157) He realizes he is not dead, but he also wonders whether he has "been remanded to my dungeon, to await the next sacrifice."1(p158) His relief at being alive is mitigated, however, by the unknown circumstances confronting him. He gives voice to his fear of his unknown future: "Was I left to perish of starvation in this subterranean world of darkness; or what fate, perhaps even more fearful, awaited me?"1(p159) Exploration of the darkness in the cell reveals the pit, which lies directly in his path, a chasm bathed in the unknown, and he admits that he has narrowly avoided succumbing to his death. As the story unfolds, the narrator travels blindly, confused, disoriented by his surroundings, and enveloped in fear at what awaits him, both in the long- and the short-term.Like Poe's character, our patients (identified by pseudonyms) discussed their constant reminder of facing the unknown while living with a VAD. In discussing the period when he was waiting for a transplant, Frank, a 58-year-old man who lived with his wife of many years, said, "I had no idea how long I was going to be on the VAD; we're talking about years at a time. I thought [it was overwhelming]." These comments call to mind Poe's narrator, who is regularly overcome by "the agony of suspense"1(p158) and the "terrors"1(p162) of his situation.The narrator drifts in and out of consciousness, struggling with bouts of swooning and irrationality due to such visceral fear. Similarly, Joe, a 61-year-old man living alone at the time of the interview, talked about times when his mind played tricks on him: "My biggest problem was thinking about what if it ever stopped. My mind plays tricks on me, puts stupid things in my head, and that was one of them, you know, what would happen if I got stopped by the police." Joe clarified that he thought he might get arrested with the device, that police would think the holster with the battery pack was a holster with a gun.Feelings of fear of the unknown also were related to how confident patients were about the functioning of the VAD. This fear could adversely affect their lifestyle. Mary, a 42-year-old African American single mother, described her transition from being adventurous to being frightened with the VAD: "I was just that adventurous. Now it's like, okay, I'm scared to do anything because I never know what's going to happen." This fear denoted how the patients believe that the VAD is keeping them alive.The fear of not knowing how the device would perform was voiced several times, indicating how critically the patients viewed the reliable functioning of the device. Joe discussed his fear of troubleshooting the VAD when out with friends: "If I break down in the middle of the expressway and get stuck for three hours with no battery, . . . I don't want to cause an emergency. I want to get home to change my batteries." In summary, the patients described fear at many levels, as does Poe's narrator, and they also expressed a sense of isolation, another theme in "The Pit and the Pendulum."In "The Pit and the Pendulum," the narrator is confined to a prison cell, which he initially assumes is a tomb. At first, he faces complete darkness, totally dependent on others for light, food, and water. He experiences the loss of freedom physically through confinement, that is, the boundaries he remains unaware of, and emotionally because he has no interaction with others except through the knowledge that they exist because food is provided. The patients in the study also discussed feeling confined physically and emotionally. For example, Mary talked at length about her stay in the hospital, particularly the hospital room:Several patients talked about the loss of choices in the hospital, even feeling like a prisoner. For example, Mary stated:Mary also recalled the experience of waking up with the device in the intensive care unit: "When I was coming out of it, I remember they must have tied me down. . . . I was trying to get loose . . . and I didn't like that." This comment bears an eerie similarity to those made by Poe's narrator, who at one point awakens to the realization "that my personal condition had been greatly changed. I now lay on my back, and at full length . . . securely bound by a long strap."1(p163) The narrator is terrified and overwhelmed by his sense of helplessness; he has been completely dependent on others for what little food and water he has been his and he now realizes that his in the of of our patients on the need to be by another to be a African American woman who lived with her and stated that even physically better with more "The only that I didn't like about it is that I do I had to on to be with me at all . . . I do or to the was with me at all a spoke at length of the feelings of on others in to patients talked of feeling when being in the outside world with the VAD. Frank spoke as of these experiences to those of Poe's narrator In "The Pit and the Pendulum," the situation has been by and he has been even for the food and water that while he As the story his is to this ongoing on for it is only through outside that his death sentence might be His sense of is and is his in the the narrator narrowly into the and gives voice to the fear and pain that him for the duration of the story. he are with not was the of death with physical or death with most the narrator experiences both physical and psychological the psychological is the most as he awaits what he to be He admits at this point that long my had been and also in every His is one of ongoing fear. that is within his His is as and as the death sentence patients also expressed a fear that it their Frank discussed the fear that his life after the VAD feeling of described by Poe was not in VAD the comments by several of our patients the psychological described by For example, Mary stated the also that they were living with fear because they that their life was in a described the fear had when made the to receive the VAD: "I didn't have I was I at that point I I was scared you know, I going to described her family as as didn't want to happen and they even thinking about the transplant it was this his agony and like our the narrator in "The Pit and the Pendulum" to I a of it within my to my mind a thought of . . . as I a . . . I that it was of hope . . He to think of to as the and toward his was hope that the to to was hope that on the to the even in the of the patients described their hope for the as a for through the VAD As Joe "When you get right down to the you to it's not the of but I'm not with it Frank, who lived with a VAD for about 4 months, made the while struggling with their symptoms and the device VAD talked about they were for the For example, Frank patients that the they had they would through it all Mary Frank talked about to the device, he was to get used but when when you the like, it's like what you up with for the a woman was asked if would undergo me I would do that life and . . . theme the unknown, feeling confined, living with fear, and hope for the that in the study to a understanding of the experience of living with a VAD. "The Pit and the Pendulum" provides an analogy that can the understanding of the experience for patients and provide for interventions to the experience beyond the challenges patients in acute care and as facing the unknown, has in of patients with other As expressed by our the uncertainty of living with a VAD into many of life and daily and like the uncertainty that in of information to the more is a constant In on patients with heart failure who were waiting for donor uncertainty was the primary theme for both patients and the patients' Similarly, our patients' about what would happen next was by about the of the VAD and the patients' to if also were about how other would to the to when information to a or of an the may be as and may result in increased emotional and of These that with care can uncertainty is particularly important as patients and their families to gain in their to the for patients with implanted VADs to with or VAD may the a that can guide them through the One of our Frank, who had the to with a man who had lived with a VAD for a time, the of being able to talk with the man about the As Frank patients with heart failure, support can patients' and and symptoms, the on outcomes The of and support in patients with VADs also study, particularly as rates to in their study of patients' experiences of acute care we that feeling confined was a key theme as patients from VAD a confinement expressed through such as of feelings of personal and physical Further, fear and a sense of from others to the sense of several of their patients confined in the intensive care unit than in the these to a greater in the intensive care unit, a situation that patients' fear and feelings of our patients in that reported the of being and made to being in a prison or of confinement are also problems for patients. For example, in a of patients in an acute unit, confinement to was associated with increased and physical and with use of the of confinement on in a a of loss of personal and even power between and boundaries are altered because patients have little control their own and the they have is being on by and In our study, use of feeling dependent on and the of patients' to the sense of Nurses must be of the need to provide to the sense of confinement, particularly in acute care The results of the of nurses in improving the for theme of living with fear has been reported in several on cardiovascular in general and on of VAD patients focus that fear was a of the associated with of life in patients with heart failure. For some fear was associated with the nature of the of heart failure. patients being a to their families as the signs and symptoms of heart failure This fear of becoming a was with the of and In their several patients experienced fear of family members as as fear of the to the hospital, and fear of In on patients with heart failure, that patients and experienced fear of the and death. these not include patients with VADs, this device does not associated with heart failure. Nurses must be willing to and patients are and to interventions to patients those the of in their study of patients with hope for the was a common theme the patients in our study. a that hope to patients' and was considered As in our study, patients used a sense of hope to with and the uncertainty that in their for the is also an in patients with cardiovascular For a of patients having the use of hope as a the uncertainty of the of this a total of patients to questions about the patients' of their before and after heart The patients described a need to that hope was important in them overcome problems they in a of hospitalized heart failure patients had hope than control On the other hand, in a of qualitative of adults with heart failure by was a primary of and many hope in patients with heart patients in our study that hope was by having a One of their was associated with their spoke of their and how much their them, by them hope for the An additional of was the of the One patient stated how important it was that the nurses not be by how he it when the nurses would his and him how his would nurses not their own VAD key in hope for the was the patients' significant from and other VAD our patients overcome Nurses need to to support VAD and to strategies to support the emotional status of the a such as that by may be in interventions to patients and patients' families to the challenges of heart failure, including living with The in to the need to life to patients with and heart failure to provide of and of such as and social support may of care is to the important as the use of the is, wrote that the of hope and are in the to conceptual to guide interventions that may increase patients' whether for increasing time, improving of or a of VAD was in of age, and duration of VAD Yet, the of the themes the in a we not data on of VADs, technology in mechanical circulatory assist devices to and must be considered in the significant physical associated with VADs, our the marked psychological challenges experienced by patients not in the acute care Our patients experienced feelings of isolation, and fear in addition to the hope that them to their and them of the of the device to their of the experience of living with a VAD to the of Poe's narrator in "The Pit and the Pendulum" provides a analogy that the and of the VAD patients' The analogy can be an in patient care and provide nurses an to the challenges beyond physical and to interventions to better patients' psychological

For a man with end-stage heart failure, a left ventricular assist device prolongs life but brings dire complications.

Left Ventricular Assist Devices and Renal Ramifications.

Nonpulsatile left ventricular assist devices (LVADs) are increasingly used for treatment of refractory heart failure. A majority of such patients have implanted cardiac devices, namely implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy-pacemaker (CRT-P) or cardiac resynchronization therapy-defibrillator (CRT-D) devices. However, potential interactions between LVADs and cardiac devices in this category of patients remain unknown. We reviewed case records and device logs of 15 patients with ICDs or CRT-P or CRT-D devices who subsequently had implantation of a VentrAssist LVAD (Ventracor Ltd., Chatswood, Australia) as destination therapy or bridge to heart transplantation. Pacemaker and ICD lead parameters before and after LVAD implant were compared. In addition, ventricular tachyarrhythmia event logs and potential electromagnetic interference reports were evaluated. Right ventricular (RV) sensing decreased in the first 6 months post-LVAD. Mean R-wave amplitude preimplant was 10.9 +/- 5.25 mV compared with 7.2 +/- 3.4 mV during follow-up (P = 0.02). RV impedance also decreased from 642 +/- 240 ohms at baseline to 580 +/- 212 ohms at follow-up (P = 0.007). There was a significant increase in RV stimulation threshold following implantation of the LVAD from 0.8 +/- 0.6 V at baseline to 1.4 +/- 1.0 V in the first 6 months postimplant (P = 0.01). A marked increase in ventricular tachyarrhythmia burden was observed in three patients. One patient displayed electromagnetic interference between the LVAD and defibrillator, resulting in inappropriate defibrillation therapy. LVADs have a definite impact on cardiac devices in respect with alteration of lead parameters, ventricular tachyarrhythmias, and electromagnetic interference.

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

In this issue of Circulation, Birks et al 1 report their recent experience using the combination of continuous-flow (CF) circulatory support and pharmacological therapy to treat advanced heart failure in patients requiring left ventricular assist device (LVAD) support. Thirty-three patients underwent HeartMate II (HMII) LVAD implantation at Harefield hospital during the 3-year study period. Twenty-three patients (70%) with nonischemic cardiomyopathy were considered appropriate for the recovery protocol at the time of HMII LVAD implantation, and 20 patients (61%) who survived LVAD implantation formed the study cohort. With their strategy of aggressive neurohormonal blockade (phase I) followed by high-dose clenbuterol (phase II), 12 (60%) of the study cohort met criteria for LVAD explantation, and all 10 (50%) who survived the perioperative period demonstrated sustained recovery over 56 to 1112 days of follow-up. Therefore, 30% of all patients and 43% of all nonischemic patients undergoing HMII implantation could be managed to long-lasting recovery. In an era in which transplant waiting times have blurred the distinction between bridge-totransplant and destination therapy for some patients, this single-center experience is intriguing and offers hope for a new strategy for select patients supported with CF LVADs. Article see p 381 Reports in the literature regarding rates of cardiac recovery during pulsatile LVAD support are quite varied (Table 1). The Columbia University group reported a 1% rate of sustained cardiac recovery in 111 patients with both ischemic and nonischemic etiology of heart failure. 2 In contrast, the German Heart Institute reported that 13% of patients with nonischemic heart failure demonstrated sustained recovery (minimum follow-up of 36 months) after LVAD explantation. 3 The LVAD Working Group was the first multicenter, prospective initiative to study recovery.4 Sixty-seven LVAD patients (only 1 CF LVAD) with both ischemic and nonischemic causes underwent serial echocardiograms at reduced flow to seek recovery. Six percent of the whole cohort and 7% of all nonischemic patients could undergo LVAD explantation. None of these reports described the consistent use of pharmacological therapy during LVAD support, and it was not until the first Harefield recovery study 5 that data regarding combined pharmacological and mechanical support were available. In the first Harefield study, 15 LVAD patients (1 CF LVAD) received maximal doses of heart failure medications, followed by high-dose clenbuterol. All patients had a nonischemic etiology, and most (80%) had heart failure for 6 months. The authors reported that 75% of patients receiving clenbuterol could undergo LVAD explantation and 46% of all patients with nonischemic heart failure presenting for LVAD could be managed successfully to recovery in this way. These data from Harefield represented the most successful reported recovery strategy to date, and prompted a multicenter study in the United States (to replicate the Harefield recovery protocol) called the Harefield Recovery Protocol Study (HARPS). HARPS has now completed enrollment of 17 patients with the HMI pulsatile LVAD, 13 of whom received both maximal neurohormonal blockade and high-dose clenbuterol. Results from the US HARPS study will be presented in the near future. With the approval of the HMII LVAD for both bridge-to

Intraoperative Use of Vascular Ultrasound to Localize Thrombus in Left Ventricular Assist Device Exchange.

Right Ventricular Systolic and Diastolic Function as Assessed by Speckle-Tracking Echocardiography Improve with Long-Term Left Ventricular Assist Device Support

The field of cardiac mechanical assist devices has achieved a number of striking technical breakthroughs over the past 40 years.1 Emblematic of the type of important technical accomplishments that have been achieved in this field has been the development of the portable, battery-driven left ventricular assist device (LVAD) for patients with intractable cardiac failure. Although LVADs have been used primarily as a “bridge to transplantation,” a number of centers have now begun to implant LVADs as an alternative to transplantation.2 Indeed, as the technology in this field improves, it is entirely conceivable that LVADs will evolve into small, unobtrusive devices that will run on small, portable, long-lasting battery supplies that will not require external connection to the outside. This, in turn, will allow LVADs to serve as a very reliable alternative to transplantation for many patients with advanced heart failure who cannot receive transplants or who cannot be weaned from LVAD support. Thus far, the clinical experience with LVADs as a bridge to transplantation has consistently shown dramatic improvements in cardiac output3 4 and New York Heart Association functional class.4 5 Importantly, these clinical changes have been attended by concomitant decreases in levels of neurohormones6 7 and cytokines,8 suggesting that LVAD support may alter the heart failure “milieu.” In an effort to explain these salutary changes in clinical status, investigators have turned to more basic studies and begun to examine myocardial ultrastructure before and after LVAD implantation. These latter studies have shown decreased myocyte necrosis9 10 and apoptosis,11 decreased myocytolysis,3 and improved myocyte contractility.12 The beneficial changes in the biology of the failing myocardium after LVAD support have also been …