In the REMATCH trial, infection and me- chanical failure of the device contributed impor- tantly to the low 2-year survival rate of 23%. The device employeddthe HeartMate XVEdrequires a large percutaneous line, which can become a conduit for bacterial and fungal infection. Malnutrition was identified in these patients as a predisposing factor to infection and other complications. Factors contributing to postoper- ative malnutrition include early satiety, nausea, or both from the bulk of the implanted device; chronic inflammation associated with HF and the device; and severe and often-underdiagnosed preoperative debilitation [15]. Because these pumps are large, a substantial pump pocket must be formed around them, and the blood that collects in this pump pocket can be a culture medium for bacteria. The axial flow devices, on the other hand, are much smaller than conventional LVADs. Furthermore, the Jarvik 2000 is implanted within the left ventricle, elimi- nating the need for a pump pocket altogether. One study has shown that the Jarvik 2000 is associated with a lower infection rate than a conventional LVAD [7]. Additionally, the 26 patients in the authors’ previously published clinical study experi- enced no significant device-related infections [10]. Because infections can reduce QOL by interfering with daily activities, requiring patients to take additional medications or necessitating a return to the hospital, the reduced infection rate associ- ated with the Jarvik 2000 may enable the device to enhance QOL to a greater extent than conven- tional LVADs. Mechanical failure of the LVAD was the second most frequent cause of death in the REMATCH trial’s device group. The findings of inflow-valve failure and late erosions of the outflow graft resulting from kinking have already led to modifi- cations in the device’s design. Malfunction of the mechanical parts, such as rupture of the lining, motor failure, and wear on the bearings, also limits the durability of the device. Device failure limited use of the HeartMate XVE to 2 years or less. New devices have longer life spans, however; the Jarvik 2000 is expected to last 5 years. One study suggests that patients survive longer after heart transplantation if they were supported by HeartMate XVE LVADs than if they did not have LVAD support during the waiting period [16]. However, patients supported by conventional LVADs also have greater cognitive impairment and are more likely to be unemployed 1 year after heart transplantation [17]. The authors recently evaluated the ease of use and reliability of the Jarvik device and the frequency of medical problems in outpatients with these pumps. There were no readmissions for technical reasons, and the pump never failed. QOL improved and was not adversely affected by the need to monitor or maintain the LVAS [18]. Cardiac support with an LVAD can signifi- cantly improve symptoms of HF and, in some cases, lead to complete recovery [19–22]. Signs of improvement in LVAD-supported patients in- clude decreased levels of epinephrine, norepineph- rine, angiotensin II, and arginine vasopressin, as well as interleukin-6, interleukin-8, and tissue necrosis factor-alpha [23–25]. Additionally, long- term LVAD support reduces collagen content and myocyte size in the myocardium and im- proves contractility and response to b-adrenergic stimulation, suggesting that prolonged cardiac unloading with the LVAD promotes reverse re- modeling [26,27]. However, patient selection is important be- cause LVAD support does not produce complete recovery in all patients who have HF [28]. The degree of irreversible myocardial damage at the time of LVAD implantation as well as the quality of medical management after implantation are important determinants of outcome after LVAD implantation [29]. Symptomatic relief with cardiac resynchronization therapy placement In patients who have advanced HF and a pro- longed QRS interval, CRT has been shown to improve symptoms and hemodynamics, increase exercise tolerance, and decrease the risk of death from any cause [30–33]. In the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study, CRT resulted in clinical improvement in patients who had moderate-to-severe HF (LVEF !35%) and an intraventricular conduction delay (QRS interval O130 msec) [33]. After 6 months, the 228 CRT patients could walk farther in 6 min- utes and had greater endurance on the treadmill during exercise testing than the 225 patients in the control group. The CRT patients also had a greater decrease in LVEF, less need for hospital- ization and intravenous medications, and greater improvement in NYHA class and QOL. However, 4 of the CRT patients had refractory hypotension, bradycardia, or asystole, and 2 of them died during implantation. Two other patients had 261SYMPTOMATIC RELIEF Should Patients who have Persistent Severe Symptoms Receive a Left Ventricular Assist Device or Cardiac Resynchronization Therapy as the Next Step? John Cleland, MD, FESC, FACC * , Ahmed Tageldien, MSc, MD, Olga Khaleva, MD, Neil Hobson, MBBS, Andrew L. Clark, MD University of Hull, Castle Hill Hospital, Kingston-upon-Hull, UK Many patients who have heart failure experi- ence severe recurrent or persistent symptoms despite standard pharmacologic treatment with diuretics, ACE inhibitors or angiotensin receptor blockers, aldosterone antagonists, and beta- blockers [1–3]. Careful review of standard medica- tion may identify that the dose of one or more components is not optimal and can be adjusted for greater effect. Finding the optimal dose and combination of diuretics may be particularly diffi- cult. Excessive doses will cause hypotension, renal dysfunction, and worsening symptoms. Insuffi- cient doses will also lead to worsening symptoms. Digoxin probably still has a role for the manage- ment of advanced symptoms, especially when the patient has atrial fibrillation, because beta- blockers often do not adequately control ventric- ular rate [4]. Correction of anemia with iron supplements when it is due to iron deficiency or erythropoietin-stimulating peptides when not due to specific haematinic deficiency may also improve symptoms, although the data are not robust [5]. Withdrawal of nonsteroidal anti-inflammatory drugs, including aspirin, also seems to reduce the need for hospitalization for worsening heart fail- ure [6,7]. However, when standard pharmacologic therapy has failed, surgical and device options should be considered. Two substantial studies are underway to assess the benefits of revascularization with or without the benefits of surgical left ventricular remodeling [8–10]. Currently there is no evidence that revas- cularization of patients who have heart failure and LVSD is safe or effective, even when a large amount of viable but hibernating myocardium is present. We should obtain the first results of trials in 2007. Revascularization is not discussed further in this manuscript. The initial enthusiasm for skeletal myoblast and stem cell transplantation into the failing myocardium has been tempered by experience. There is now considerable uncertainty whether this approach provides worthwhile benefits [11,12]. Hopefully, refinements in the technologic approach might improve results. The two surgical technologies that have shown benefit on symptoms and survival are left ventricular assist devices (LVADs) and cardiac resynchronization therapy (CRT), with or without a defibrillator function [3,13–15]. The purpose of this manuscript is to describe the benefits of CRT and the gaps in our knowledge that are an impediment to clinical practice and may be ex- ploited by further research and then to compare that to what we know about LVADs. However, it should be clear from the outset that there is a role for both in the management of advanced heart failure. Cardiac dyssynchrony Cardiac dyssynchrony is conceptually simple but rather difficult to define and measure on an individual patient basis [13]. Indeed, it may not be * Corresponding author. University of Hull, Castle Hill Hospital, Kingston-upon-Hull, HU 16 5JQ, UK. E-mail address: j.g.cleland@hull.ac.uk (J. Cleland). 1551-7136/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.hfc.2007.05.005 heartfailure.theclinics.com Heart Failure Clin 3 (2007) 267–273 Does Myectomy Convey Survival Benefit in Hypertrophic Cardiomyopathy? Anna Woo, MD, SM, FRCPC, FACC * , Harry Rakowski, MD, FRCPC, FACC University of Toronto, Toronto, ON, Canada Hypertrophic cardiomyopathy (HCM) is a complex disorder and concepts regarding this condition have evolved considerably since its modern description in the 1950s [1,2]. Although once perceived as a rare disease causing sudden cardiac death (SCD) in young adults [2], HCM is now recognized as a relatively common genetic disorder affecting 1 in 500 individuals and charac- terized by a wide spectrum of clinical manifesta- tions [3,4]. Dynamic left ventricular outflow tract (LVOT) obstruction has been a prominent aspect of HCM and, in the early years of the disease’s recognition, its presence was inextricably linked to the diagnosis of this condition [5,6]. Patients who have the obstructive form of HCM have unique and distinguishing clinical and hemody- namic features [4–6]. The dynamic LVOT obstruction of HCM has generated much interest and controversy; its existence, cause, diagnosis, treatment, and prog- nosis have all provoked debate [3,4]. Aside from its hemodynamic effects, some investigators had questioned the importance of obstruction and re- garded it as a secondary finding in this disease [7,8]. Multiple echocardiographic and hemody- namic studies support the view that LVOT ob- struction is caused by systolic anterior motion (SAM) of the anterior mitral leaflet, contact of the mitral leaflet with the hypertrophied interven- tricular septum, and consequent obstruction to blood flow in the outflow tract during systole [3,4,9]. LVOT obstruction is accompanied by mi- tral regurgitation [10,11], and these lesions are largely responsible for the disabling symptoms (eg, dyspnea, angina, presyncope, syncope) and hemodynamic abnormalities associated with obstructive HCM [3,4,6]. The presence of an LVOT gradient measuring at least 30 mm Hg is generally accepted as the definition for obstructive HCM [3]. At the present time there is a general consensus that patients who have symptoms attributable to LVOT obstruction should receive treatment to diminish or abolish the LVOT gradient [3]. Treat- ment options include medications (negative ino- tropic agents), dual chamber (DDD) permanent pacing, septal ethanol ablation (SEA), or surgical myectomy. All of these therapies have variable ef- fects on reducing symptoms and on controlling the LVOT gradient [3,4]. The longest experience has been with surgery, which was first performed in this condition in the late 1950s [5]. Because myectomy has consistently improved symptoms and LVOT obstruction, many investigators regard this procedure as the optimum treatment of ob- structive HCM [3,12]. Myectomy remains contro- versial, however, because it is unclear if there is a survival advantage with myectomy compared with conservative management or compared with other available therapies [3,8]. Because recent studies demonstrate that LVOT obstruction is associated with a worsened prog- nosis [13,14] and because there are different treat- ment options for obstructive HCM, it is important to evaluate the risks and benefits of myectomy, especially in its impact on survival. In this article we review the clinical course of * Corresponding author. Division of Cardiology, Toronto General Hospital, University of Toronto, 200 Elizabeth Street, 4N 504, Toronto, ON M5G 2C4, Canada. E-mail address: anna.woo@uhn.on.ca (A. Woo). 1551-7136/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.hfc.2007.04.010 heartfailure.theclinics.com Heart Failure Clin 3 (2007) 275–288 . of the mechanical parts, such as rupture of the lining, motor failure, and wear on the bearings, also limits the durability of the device. Device failure limited use of the HeartMate XVE to 2. cause of death in the REMATCH trial’s device group. The findings of in ow-valve failure and late erosions of the outflow graft resulting from kinking have already led to modi - cations in the device’s. and, in some cases, lead to complete recovery [19 22 ]. Signs of improvement in LVAD-supported patients in- clude decreased levels of epinephrine, norepineph- rine, angiotensin II, and arginine