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Background Diminished respiratory muscle strength and endurance have been demonstrated in patients with heart failure. This may contribute to exertional dyspnea and reduced exercise capacity in these patients. The purpose of this study was to investigate whether selective respiratory muscle training could alleviate dyspnea and improve exercise performance in patients with chronic congestive heart failure. Methods and Results Fourteen patients with chronic heart failure (left ventricular ejection fraction, 22±9%) were enrolled in a supervised respiratory muscle training program. This consisted of three weekly sessions of isocapnic hyperpnea at maximal sustainable ventilatory capacity, resistive breathing, and strength training. Maximum sustainable ventilatory capacity, maximum voluntary ventilation, maximal inspiratory and expiratory pressures, peak V̇ o 2 , and the 6-minute walk test were measured before (pre) and after (post) 3 months of training. Eight patients completed the training program. Respiratory muscle endurance was improved with training, as evidenced by increases in maximal sustainable ventilatory capacity (pre, 48.6±10.7 versus post, 76.9±14.5 L/min; P P 2 O; P 2 O; P P o 2 (pre, 11.4±3.3 versus post, 13.3±2.7 mL · kg −1 · min −1 ; P o 2 was observed in the 6 patients who did not complete the training program. Conclusions Selective respiratory muscle training improves respiratory muscle endurance and strength, with an enhancement of submaximal and maximal exercise capacity in patients with heart failure. Dyspnea during activities of daily living was subjectively improved in the majority of trained patients.

Severe right ventricular failure often is considered a contraindication for left ventricular assist device (LVAD) therapy and necessitates use of biventricular assist devices (BiVADs). Available options for BiVADs are limited, and comparative outcomes are largely unknown.Heart transplant candidates who were registered on the United Network for Organ Sharing waitlist and underwent long-term contemporary LVAD (n = 3195) or BiVAD (n = 408) implantation, from January 2010 through June 2014, were retrospectively analyzed. We evaluated clinical characteristics and outcomes of patients requiring a BiVAD, as well as regional differences in utilization of this technology.Patients requiring a BiVAD were younger (48.9 vs 53.3 years), had a higher proportion of nonischemic disease (69.1% vs 58.2%), a higher bilirubin level (0.9 vs 0.7 mg/dL), and a lower 6-month survival rate (68.1% vs 92.7%) after device implantation (all P.05). Postimplantation and posttransplantation survival was comparable for commonly used BiVAD configurations, including total artificial heart, continuous flow BiVAD, a continuous-flow LVAD coupled with a right-sided device, and pulsatile flow. Significant variation was found in regional utilization of these devices, regardless of differences in transplantation waitlist times. A large body surface area was an independent predictor of mortality on a BiVAD (hazard ratio = 2.12, P = .017).Outcomes of patients requiring a BiVAD remain poor in the contemporary device era, regardless of the configuration used. Among other clinical factors, body surface area should be incorporated into decision making for device selection in these patients.

Objectives This study aimed to investigate the utility of serial tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) for monitoring right ventricular failure (RVF) after left ventricular assist device (LVAD) surgery. Background RVF post-LVAD is a devastating adverse event. Methods The authors prospectively studied 68 patients undergoing elective LVAD surgery. Echocardiograms were performed within 72 h before and 72 h after surgery. RVF was pre-specified as: 1) the need for salvage right ventricular assist device (RVAD); or 2) persistent need for inotrope and/or pulmonary vasodilator therapy 14 days after surgery. Patients were classified as Group RVF or Group Non-RVF. Results A total of 24 patients (35.3%) met criteria for RVF. Preoperative TDI-derived S’ was lower and RV E/E’ ratio was higher (3.7 ± 0.6 cm/s vs. 4.7 ± 0.9 cm/s, 12.0 ± 2.3 vs. 10.0 ± 2.5, both p l 0.001, respectively), and the absolute value of RV longitudinal strain (RV-strain) obtained from STE was lower (–12.6 ± 3.3% vs. –16.2 ± 4.3%, p l 0.001) in Group RVF vs. Group Non-RVF. Echo parameters within 72 h after surgery showed higher RV-E/E’, (13.9 ± 4.6 vs. 10.1 ± 3.0, p l 0.001) and lower RV-strain (–11.8 ± 3.5% vs. –16.7 ± 4.4%, p l 0.001) in Group RVF vs. Group Non-RVF. Preoperative S’l4.4 cm/s, RV-E/E’>10 and RV-strain l –14% discriminated patients who developed RVF at day 14 with a predictive accuracy of 76.5%. When we included postoperative RV-E/E’ and RV-strain, the predictive accuracy increased to 80.9%, with a sensitivity of 66.7% and a specificity of 88.7%. Conclusions Serial echocardiograms using TDI and STE before and soon after LVAD surgery may aid in identifying need to initiate targeted RVF specific therapy in this population.

We thank Haufe et al for their insightful comments on our study of adipose tissue inflammation and adiponectin resistance in patients with advanced heart failure (HF) and the impact of mechanical unloading.1 We appreciate the observation that incorrect homeostasis model of insulin resistance (HOMA-IR) values were listed in Table 3. Upon recalculation using the HOMA-IR formula, the correct values were found to be 1.0±0.6 for controls, 7.6±7.7 in advanced HF ( P =0.02 versus controls) and 4.5±3.6 after left ventricular assist device (LVAD) support ( P =0.01 versus HF). This supports the conclusion …

Aims Abnormal bone metabolism and progressive demineralization have been described in patients with heart failure (HF). We hypothesized that mechanical unloading through implantation of a ventricular assist device (VAD) with subsequent haemodynamic improvement would correct abnormal bone metabolism in patients with advanced HF. Methods and results Serum was collected from 14 controls, 20 patients with moderate HF, 34 patients with advanced HF undergoing VAD implantation, and 34 patients at the time of VAD explantation (mean duration: 169 ± 125 days). Bone metabolism markers were measured using enzyme-linked immunosorption assay (ELISA) or chemiluminescence immunoassay (CLIA). Compared with controls, HF patients showed increased parathyroid hormone (PTH: 42 ± 19 vs. 117 ± 117 pg/mL in HF; P < 0.02) with decreased 25-hydroxyvitamin D [25(OH)D: 29 ± 14 vs. 21 ± 11 ng/mL in HF; P = 0.05]. While procollagen-1 N-terminal peptide (P1NP) and osteocalcin were similar, cross-linked C- and N-telopeptides of type I collagen (CTX and NTX) were both higher in HF (NTX: 14 ± 6 vs. 20 ± 11 ng/mL; P < 0.05; CTX: 0.35 ± 0.13 vs. 1.05 ± 0.78 ng/mL; P < 0.01 for controls and HF, respectively). P1NP increased markedly after VAD implantation (49 ± 37 vs. 121 ± 62 ng/mL; P < 0.0001), with a mild decrease in CTX and NTX levels indicating a shift towards anabolic bone formation. Serum PTH correlated with estimated glomerular filtration rate (r = –0.245, P < 0.05). Conclusion Patients with advanced HF are characterized by increased levels of biochemical markers of bone resorption potentially as a result of secondary hyperparathyroidism and uncoupling of bone remodelling. Haemodynamic improvement and mechanical unloading after VAD implantation lead to correction of bone metabolism and increased levels of anabolic bone formation markers.

BACKGROUND Chronic heart failure is associated with higher risk for developing diabetes mellitus. Secretory products from adipocytes may contribute to the deterioration in glycemic control and increased insulin resistance (IR). Retinol binding protein 4 (RBP4) is an adipose tissue-derived protein with pro-diabetogenic effects. The aim of the present study was to investigate the relationship of RBP4 in patients with heart failure. METHODS AND RESULTS Serum levels of RBP4, insulin, and fasting glucose were assessed in 58 patients with severe heart failure at the time of left ventricular assist device (LVAD) implantation and in 44 patients at the time of explantation, as well as in 10 normal control subjects. Serum RBP4 levels were measured by specific enzyme-linked immunosorbent assay, and IR was assessed using the homeostatic model of IR (HOMA-IR). Fasting glucose, insulin and HOMA-IR were significantly higher in patients at the time of LVAD implantation compared to controls (all P

Background Mortality for refractory cardiogenic shock (RCS) remains high. However, with improving mechanical circulatory support device (MCSD) technology, the treatment options for RCS patients are expanding. We report on a recent 5-year single-center experience with MCSD for treatment of RCS. Methods This study was a retrospective review of adult patients who required an MCSD due to RCS in the past 5 years. We excluded those patients with post-cardiotomy shock and post-transplant cardiac graft dysfunction. In the setting of RCS, a short-term ventricular assist device (VAD) was inserted as a bridge-to-decision device. Veno-arterial extracorporeal membrane oxygenation (VA ECMO) was chosen in cases of unknown neurologic status, complete hemodynamic collapse or severe coagulopathy. Results From January 2007 through January 2012, 90 patients received an MCSD for RCS, 21 (23%) of whom had active cardiopulmonary resuscitation (CPR). The etiology of RCS included acute myocardial infarction in 49% and acute decompensated heart failure in 27%. Mean age was 53±14 years, 71% were male, and 60% had an intra-aortic balloon pump. The initial approach utilized was short-term VAD in 49% and VA ECMO in 51%. Median length of support was 8 days (IQR 4 to 18 days). Exchange to implantable VAD was performed in 26% of patients. Other destinations included myocardial recovery in 18% and heart transplantation in 11%. Survival to hospital discharge was 49%. Multivariate analysis showed ongoing CPR to be an independent risk factor for mortality (OR = 5.79, 95% CI 1.285 to 26.08, p = 0.022). Conclusions In the current era, roughly half of the patients who need an MCSD for RCS survive, and roughly half of these survivors require an implantable VAD. Ongoing CPR is predictive of in-hospital mortality.

Since 1977, the cardiac transplantation program at Columbia has performed 2143 heart transplant operations with a current 1-year survival rate of approximately 87% and a 5-year survival rate of approximately 76%, representing the largest single-institution experience in North America. Over three decades of experience in the selection of donors and recipients has permitted us to expand eligibility limits and relax conventional exclusion criteria, allowing us to transplant high-risk donors and medically complex recipients with excellent results. Increasing use of mechanical support is being seen to bridge candidates to cardiac transplantation. Recipient characteristics, rather than those of the donor, substantially impact outcome following OHT and use of extended-criteria donors helps to alleviate the ongoing donor shortage; but this scarcity of donor hearts remains the major obstacle to the growth of transplantation. During the last decade, substantial improvements have been made in the areas of immunosuppression, treatment of rejection, and handling of sensitized recipients. Frequent causes of late mortality such as graft rejection, infection and TCAD, have been significantly diminished in the modern area of immune manipulation but remain major causes of death and barriers to long-term survival.

Cardiac allograft vasculopathy (CAV) is an important cause of morbidity and mortality among cardiac transplant recipients. CAV occurs in approximately 30% of patients by 5 years and 50% by 10 years, and is a major cause of graft loss and death. Early detection of CAV is important because it may allow alterations in medical therapy before progression to the stage that revascularization is required. This has led to routine screening for CAV in transplant recipients, traditionally by invasive coronary angiography (ICA). Recent advances in imaging technology, specifically intravascular ultrasound, now also permit detection of subangiographic CAV. Noninvasive stress testing and multislice coronary computed tomography angiography have been investigated as noninvasive alternatives to routine ICA. However, currently available noninvasive tests remain limited with respect to their sensitivity and specificity for CAV. Given the multiple available diagnostic modalities, no consensus definition for the classification of CAV has been widely accepted, although new guidelines that rely heavily on ICA have recently been published by the International Society of Heart and Lung Transplantation. This review summarizes imaging modalities that are utilized in the diagnosis and surveillance of CAV and explores newer imaging techniques that may play a future role.

This study sought to develop a novel approach to optimizing continuous-flow left ventricular assist device (CF-LVAD) function and diagnosing device malfunctions.In CF-LVAD patients, the dynamic interaction of device speed, left and right ventricular decompression, and valve function can be assessed during an echocardiography-monitored speed ramp test.We devised a unique ramp test protocol to be routinely used at the time of discharge for speed optimization and/or if device malfunction was suspected. The patient's left ventricular end-diastolic dimension, frequency of aortic valve opening, valvular insufficiency, blood pressure, and CF-LVAD parameters were recorded in increments of 400 rpm from 8,000 rpm to 12,000 rpm. The results of the speed designations were plotted, and linear function slopes for left ventricular end-diastolic dimension, pulsatility index, and power were calculated.Fifty-two ramp tests for 39 patients were prospectively collected and analyzed. Twenty-eight ramp tests were performed for speed optimization, and speed was changed in 17 (61%) with a mean absolute value adjustment of 424 ± 211 rpm. Seventeen patients had ramp tests performed for suspected device thrombosis, and 10 tests were suspicious for device thrombosis; these patients were then treated with intensified anticoagulation and/or device exchange/emergent transplantation. Device thrombosis was confirmed in 8 of 10 cases at the time of emergent device exchange or transplantation. All patients with device thrombosis, but none of the remaining patients had a left ventricular end-diastolic dimension slope-0.16.Ramp tests facilitate optimal speed changes and device malfunction detection and may be used to monitor the effects of therapeutic interventions and need for surgical intervention in CF-LVAD patients.

Shared decision making for advanced heart failure has become both more challenging and more crucial as duration of disease and treatment options have increased. High-quality decisions are chosen from medically reasonable options and are aligned with values, goals, and preferences of an informed patient. The top 10 things to know about decision making in advanced heart failure care are listed in Table 1. View this table: Table 1. Top Ten Things to Know Providers have an ethical and legal mandate to involve patients in medical decisions. Shared decision making recognizes that there are complex trade-offs in the choice of medical care.1 Shared decision making also addresses the ethical need to fully inform patients about the risks and benefits of treatments.2 In the setting of multiple reasonable options for medical care, shared decision making involves clinicians working with patients to ensure that patients' values, goals, and preferences guide informed decisions that are right for each individual patient. Grounded in the ethical principle of autonomy,3 judicial decisions (eg, Cruzan v Missouri Department of Health 4) and legislative actions (eg, the Patient Self-Determination Act5) have repeatedly affirmed the rights of patients or duly appointed surrogates to choose their medical therapy from among reasonable options.6 The formal process of informed consent before procedural interventions is an embodiment of this concept in that it underscores the clinician's obligation to ensure that the patient has the opportunity to be informed.3 An informed patient is one who is aware of the diagnosis and prognosis, the nature of the proposed intervention, the risks and benefits of that intervention, and all reasonable alternatives and their associated risks and benefits.7 A major purpose of a high-functioning healthcare system is to provide the resources with which an activated, informed patient can engage in productive discussions with a proactive, …

Objectives. We sought to investigate whether reduced respiratory muscle endurance contributes to increased dyspnea and decreased exercise capacity in patients with chronic heart failure.Background. In patients with heart failure, the sensation of dyspnea may be related to abnormalities of respiratory muscle function, such as diminished strength or endurance, or both.Methods. Respiratory muscle endurance was assessed by measuring maximal sustainable ventilatory capacity in 15 patients with congestive heart failure and 8 normal subjects using progressive isocapnic hyperpnea. Near-infrared spectroscopy of an accessory respiratory muscle, Borg scale recordings of perceived dyspnea, time in inspiration, time per breath and minute ventilation were measured. Exercise testing with measurement of oxygen consumption was also performed.Results. Maximal voluntary ventilation (normal subjects 167 ± 40, heart failure group 89 ± 31 liters/min) and maximal sustainable ventilatory capacity (normal subjects 90 ± 23, heart failure group 53 ± 22 liters/min) were significantly reduced in patients with heart failure (both p < 0.05). No significant accessory respiratory muscle deoxygenation was observed in either group. Borg scale recordings at maximal sustainable ventilatory capacity were comparable in both groups. At rest, the inspiratory duty cycle (i.e., time in inspiration divided by the time per breath) was comparable in the two groups (normal subjects 0.34 ± 0.09, heart failure group 0.37 ± 0.12, p = NS). However at maximal sustainable ventilatory capacity, only normal subjects had a significant increase in the inspiratory duty cycle (normal subjects 0.49 ± 0.04, heart failure group 0.36 ± 0.10, p < 0.05). This finding suggests obstruction to airflow in patients with congestive heart failure. Values for peak exercise minute ventilation did not differ significantly from values in maximal sustainable ventilatory capacity in either group and were significantly correlated (r = 0.84, p < 0.0001).Conclusion. Respiratory muscle endurance as assessed by maximal sustainable ventiiatory capacity is reduced in patients with heart failure.

The present priority scheme for the allocation of donor hearts based on patient acuity and waiting time contributes to the escalating costs of heart transplantation, ignores the potential outcome advantages of prospective tissue matching, and is vulnerable to manipulation. Costs have trebled in recent years, as recipients frequently spend weeks before transplantation as inpatients in intensive care units and become more susceptible to nosocomial complications. The findings from an international cooperative study suggest that patient survival is correlated with the level of histocompatibility (ie, human lymphocyte antigen [HLA]) matching. We observed a similar inverse association between retrospective fortuitous HLA matching and the risk of rejection in 39 patients undergoing heart transplantation over a 29-month period (p = 0.03 by nonparametric analysis). These observations prompted us to consider the feasibility of donor heart allocation based on the degree of HLA matching and waiting time alone. Current methods permit the accurate determination of HLA type in a matter of hours using donor peripheral blood alone. Human lymphocyte antigen typing, therefore, could be performed locally before organ harvesting, making issues of donor heart preservation irrelevant. We evaluated the extent of HLA matching that might be achieved practically. Forty-seven patients on our waiting list during calendar year 1991 were tested retrospectively for HLA matching with all geographically accessible 1991 heart donors identified by the United Network for Organ Sharing for all donors from hospitals east of the Mississippi River.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND Skeletal muscle metabolic abnormalities have been described in patients with heart failure that are independent of total limb perfusion, histochemical changes, and muscle mass. However, these skeletal muscle metabolic abnormalities may result from tissue hypoxia caused by maldistribution of flow. Myoglobin is an O2 binding protein that can indirectly assess tissue hypoxia. METHODS AND RESULTS In vivo measurement of deoxymyoglobin was performed by use of proton (1H) magnetic resonance spectroscopy in 16 heart failure (HF) (left ventricular ejection fraction = 20 +/- 6%; VO2 = 14.5 +/- 5.1 mL/kg per minute) and 7 healthy (Nl) subjects. Simultaneous phosphorus (31P) magnetic resonance spectroscopy and near-infrared spectroscopy also were obtained to examine muscle metabolism and oxygenation. Supine calf plantarflexion was performed every 4 seconds. Incremental steady-state work was performed. A second exercise protocol studied rapid incremental (RAMP) exercise with plantarflexion every 2 seconds. Arterial occlusion at end exercise provided physiological calibration for myoglobin and hemoglobin signals. With steady-state exercise, the work slope, ie, inorganic phosphorus to phosphocreatine ratios versus work, was significantly greater in patients with heart failure (Nl: 0.18 +/- 0.08; HF: 0.40 +/- 0.32 W-1; P < .05). Intracellular pH was reduced significantly at end exercise in patients but not healthy subjects. Despite these metabolic abnormalities, muscle oxygenation derived from 760- to 850-nm absorption was comparable in both groups throughout exercise. The relation of inorganic phosphorus/phosphocreatine (P1/PCr) ratio and muscle oxygenation was shifted upward in patients with heart failure such that at the same muscle oxygenation, Pi/PCr ratio in these patients was increased. No deoxymyoglobin signals were observed at rest. At maximal exercise, 4 of the healthy subjects and 3 of the patients exhibited deoxymyoglobin (P = NS). With RAMP exercise, the work slope was again significantly greater in patients with heart failure (Nl: 0.21 +/- 0.10; HF: 0.57 +/- 0.32 W-1; P < .05). Intracellular pH again was significantly decreased at end exercise in patients but not healthy subjects. Five of the healthy subjects and 3 of the heart failure patients had deoxymyoglobin signal (P = NS). With arterial occlusion, deoxymyoglobin was seen in all subjects. CONCLUSION Abnormal skeletal muscle metabolism in patients with heart failure usually occurs in the absence of myoglobin deoxygenation, suggesting that the abnormalities are not a result of cellular hypoxia during exercise with minimal cardiovascular stress.

To evaluate the incidence and etiology of osteopenia and pathologic fractures in cardiac transplant recipients.Thirty-one adult male cardiac transplant recipients and 14 adult men with congestive heart failure (CHF) awaiting cardiac transplantation.Assessment of indices of bone and mineral metabolism and of bone mineral density (BMD) by dual-energy x-ray absorptiometry.BMD in the proximal femur was below normal in both groups compared to that in age-matched control subjects, whereas BMD in the lumbar spine was normal. There was no significant difference in BMD at any site between the two groups. No clinical parameter predicted BMD. In all patients, laboratory indices of bone mineral metabolism, except parathyroid hormone (PTH) levels, were normal and not statistically different between the two groups. CHF patients had a trend toward elevations of PTH, 1,25-dihydroxyvitamin D, and urinary calcium excretion compared to transplant patients. Eight of 31 transplant patients and 2 of 14 CHF patients had vertebral compression fractures (c2 = 11.8, p0.0006). Transplant recipients with fractures had twice as many rejection episodes as did transplant patients without fractures, but did not differ in cumulative dose of steroids. Two patients developed avascular necrosis of the femoral head following transplantation.Cardiac transplant recipients and patients with CHF awaiting transplantation had decreased hip BMD, but normal spine BMD. Although immunosuppressive therapy did not appear to influence bone mass, loop diuretics prior to transplantation may have stimulated a mild secondary increase in PTH that could have differentially caused loss of bone density at the hip in both groups. Pulse corticosteroids used in treating rejection may have contributed to the increased incidence of vertebral fractures in transplant patients. These data suggest that severe CHF with its associated diuretic use and decreased activity are primary contributors to osteopenia in these patients.

Right ventricular failure (RVF) after left ventricular assist device (LVAD) placement is associated with increased morbidity and mortality. Echocardiography is a primary imaging method in the assessment of cardiac function; however, visualization of the right-sided heart is often technically difficult in patients with heart failure. We aimed to create a simple and generally applicable scoring system based on "left-sided echocardiographic parameters" to provide complementary information for predicting RVF after LVAD surgery. We reviewed 111 consecutive patients undergoing LVAD surgery from 2007 through 2010. Echocardiograms within 5 days before surgery were analyzed. RVF was defined as an unexpected RV assist devices requirement, nitric oxide inhalation48 hours, and/or inotropic support14 days. Thirty-five patients (32%) developed RVF. LV end-diastolic dimension (LVEDD) was smaller, LV ejection fraction was greater, and the left atrial diameter/LVEDD ratio was greater (p0.05 for all comparisons) in patients with RVF than in those without RVF. An RVF score (LV echocardiographic RVF score) was determined as a sum of points based on receiver operator characteristics analysis: LVEDD78, 79 to 70, and70 mm; LV ejection fraction ≤19%, 19% to 33%, and33%; and left atrial diameter/LVEDD0.63, 0.63 to 0.68, and0.68; each variable was associated with 0 and 1 point and 2 points, respectively. LV echocardiographic RVF score ≥3 was associated with RVF with a sensitivity of 88.6% and score ≥5 with a specificity of 80.3%. In conclusion, patients with relatively small LV size, preserved LV contraction, and dilated left atrium were at higher risk for RVF after LVAD surgery. In conclusion, LV echocardiographic RVF score provides a novel tool to predict RVF after LVAD surgery, which does not involve invasive or technically complicated procedures.

Percutaneous coronary intervention with stent placement for the treatment of patients with cardiac allograft vasculopathy is common, but data regarding stent behavior in this setting is lacking.We investigated mechanisms and potential differences in stent expansion among transplant patients vs. patients with native coronary artery atherosclerotic disease ("controls").We compared pre- and poststent intravascular ultrasound in 12 transplant patients (17 lesions) and 33 control patients (34 lesions) matched according to age (60.1 ± 9.2 years), diabetes mellitus, and lesion location. Planar and volumetric analysis was conducted for every 1 mm at the lesion site as well as the first 5 mm proximal and distal to the stent edge. Focal stent expansion was defined as minimum stent area (MSA) divided by mean reference lumen area. Diffuse stent expansion was defined as mean stent area divided by mean reference lumen area.Transplant patients had more plaque than "controls" prestenting, but similar MSA and focal and diffuse stent expansion afterwards. The increase in mean lumen area correlated with the increase in mean vessel area in both groups, transplant (R = 0.64, P = 0.008) and controls (R = 0.70, P0.0001), but correlated inversely with changes in mean plaque area only in the transplant group (R = 0.55, P = 0.027). There were no differences in calcification between the two groups and no axial plaque distribution from the lesion into the reference segments in either group.The mechanism of stent expansion in transplant vasculopathy appears to be similar to de novo atherosclerosis-i.e., mainly vessel expansion to achieve similar acute results.

Background Selection criteria guidelines list mental retardation as a relative contraindication to heart transplantation, but not to kidney transplantation. Objective The authors present a case series of adults with mental retardation or comparable acquired intellectual disability who underwent heart transplantation. They discuss the literature on heart and kidney transplantation in people with mental retardation and the ethical reasoning that guides how recipients of solid organ grafts are chosen. Method Literature review and retrospective review of long-term outcomes for five adult patients with mental retardation or comparable disability who received heart transplants. Results Among these cases, survival times to date ranged from 4 to 16 years, with a median survival of greater than 12 years. Medical non-adherence was a significant factor in only 1 of the 5 cases. In that case, the patient's medical non-adherence was due to a functional decline in the primary caretaker. Conclusion People with mental retardation can receive long-term benefit from heart transplantation when they have the cognitive and social support necessary to ensure adherence to post-transplant regimens. There is no ethical or medical reason for guidelines to consider mental retardation, in and of itself, a contraindication to heart transplantation. The totality of the individual patient's circumstances should be considered in assessing transplant candidacy.

Exertional intolerance is a major clinical problem in ambulatory patients with chronic heart failure and is associated with both muscle fatigue and dyspnea. The increased muscle fatigability is most likely caused by a combination of muscle underperfusion and muscle deconditioning; patients frequently exhibit skeletal muscle atrophy, altered muscle metabolism and reduced mitochondrial-based enzyme levels, consistent with deconditioning. The muscle underperfusion is largely due to impaired arteriolar vasodilation within exercising muscle. Exertional dyspnea appears to be due to increased respiratory muscle work mediated by excessive ventilation and decreased lung compliance. Both excessive carbon dioxide production, secondary to increased muscle lactate release, and increased lung dead space contribute to the excessive ventilation. Decreased lung compliance is caused by chronic pulmonary congestion and fibrosis. Optimal management of exercise intolerance in patients with heart failure requires an understanding of the role of these multiple potential contributors to exertional fatigue and dyspnea.

Hypoalbuminemia has been recognized as a marker of poor outcomes in patients with chronic diseases including those with advanced heart failure. We recently reported that pre-operative hypoalbuminemia is associated with poor prognosis following LVAD surgery, although post-operative normalization of albumin level would improve their survival [1]. We also reported that pre-transplant serum albumin concentration is a strong prognostic marker for 1-year post-transplant survival in heart transplant (HTx) recipients [2]. However, an association between pre-transplant serum albumin and long-term outcome in HTx recipients has not yet been fully elucidated. In the present investigation, we aimed to create a post-transplant survival probability equation based on a preoperative albumin level using parametric survival model to estimate survival reflecting multiple factors such as nutrition, inflammation, hepatic function and overall catabolic state. We reviewed a total of 822 consecutive patients undergoing HTx at Columbia University Medical Center between 1999 and 2010. Pre-transplant clinical data including serum albumin concentration were obtained. For patients with multiple laboratory measurements prior to the transplants, the results obtained at the closest date to the surgery were used for the analysis. A parametric model of survival using an arbitrary value of albumin was analyzed and a formula to estimate survival provability based on pre-transplant albumin value was created. We also analyzed an available data from the United Network of Organ Sharing (UNOS). Patients with available albumin levels before HTx were selected for the current study (n=13,671). In the same manner, a parametric survival estimation formula was created based on the UNOS data. Survival probability of S(t) and the moment mortality of λ were determined by a parametric analysis as follows; S(t)=exp(−λt); λ=exp(β0+Σβjxj) β0, constant number; βj, partial regression coefficient of covariable xj. Univariate parametric analysis for post-transplant mortality based on our institutional data revealed that an serum albumin value before transplant (mg/dL) was associated with a hazard ratio (HR) of 0.559 with 95% confidence interval (CI) ranged from 0.453 to 0.689. Multivariate analysis including pre-and peri-operative parameters revealed the strongest association between pre-operative albumin level and post-transplant mortality (HR 0.540, 95%CI 0.421–0.693, p

Historically, advanced heart failure therapies were considered inappropriate for patients infected with human immunodeficiency virus (HIV). As HIV has become a chronic illness with the advent of highly active anti-retroviral therapy (HAART), cardiac transplantation has been used for selected HIV patients with end-stage heart failure. We present a case series describing the clinical outcomes with left ventricular assist device (LVAD) use in 4 patients with HIV. Three of the patients are alive: 1 after a successful bridge to transplant and the other 2 on continued device support at 18 and 13 months after implantation. No infectious complications occurred in 3 patients, and no opportunistic infections occurred in the fourth patient. De novo allosensitization did not occur in our patients after LVAD implantation. With the ongoing donor shortage, implantation of an LVAD in advanced heart failure patients with HIV with controlled viremia on HAART represents a viable option.

Patients with heart failure frequently exhibit an excessive ventilatory response to exercise, which is acutely unaltered by therapeutic interventions. To investigate whether these ventilatory responses resolve after cardiac transplantation, 15 ambulatory patients with severe heart failure underwent exercise testing with measurement of respiratory gases before and 1.4 +/- 0.6 years [corrected] after transplantation. Ventilatory response was also measured in 7 age-matched, sedentary control subjects. Left ventricular ejection fraction at rest and hemodynamic measurements were obtained before and after transplantation in all patients. After transplantation, ejection fraction at rest increased from 16 +/- 6 to 56 +/- 10%, pulmonary capillary wedge pressure declined from 26 +/- 8 to 12 +/- 5 mm Hg, and cardiac index increased from 1.7 +/- 0.5 to 2.8 +/- 0.5 liters/min/m2 (all p less than 0.001). Peak oxygen consumption increased from 11.8 +/- 1.9 to 19.2 +/- 3.1 ml/kg/min (p less than 0.001), but remained significantly lower than that in control subjects (33.4 +/- 6.9 ml/kg/min; p less than 0.01). Minute ventilation (VE) was significantly reduced after transplantation, but excessive compared with normal values. Ventilation at a carbon dioxide production of 1 liter/min decreased significantly after cardiac transplantation (52.1 +/- 7.9 to 38.8 +/- 3.8 liters; p less than 0.01), but remained elevated when contrasted to that in control subjects (31.4 +/- 3.4 liters; p less than 0.05). Ventilatory response to exercise is significantly improved after cardiac transplantation; however, VE remains excessive. This may reflect an attenuated cardiac output response to exercise, abnormal intrapulmonary pressures or persistent deconditioning.

Background —Incomplete suppression of the renin-angiotensin system during long-term ACE inhibition may contribute to symptomatic deterioration in patients with severe congestive heart failure (CHF). Combined angiotensin II type I (AT 1 ) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT 1 receptor blockade with losartan improves exercise capacity in patients with severe CHF already treated with ACE inhibitors is unknown. Methods and Results —Thirty-three patients with severe CHF despite treatment with maximally recommended or tolerated doses of ACE inhibitors were randomized 1:1 to receive 50 mg/d losartan or placebo for 6 months in addition to standard therapy in a multicenter, double-blind trial. Peak aerobic capacity (V̇ o 2 ) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V̇ o 2 at baseline and after 3 and 6 months were 13.5±0.6, 15.1±1.0, and 15.7±1.1 mL · kg −1 · min −1 , respectively, in patients receiving losartan and 14.1±0.6, 14.3±0.9, and 13.6±1.1 mL · kg −1 · min −1 , respectively, in patients receiving placebo ( P Conclusions —Losartan enhances peak exercise capacity and alleviates symptoms in patients with CHF who are severely symptomatic despite treatment with maximally recommended or tolerated doses of ACE inhibitors.

Background Cardiac retransplantation is the definitive treatment for allograft failure despite decreased long-term survival in these patients. The cause of the poorer outcomes in cardiac retransplant patients is unclear. Methods This study was a retrospective analysis of 859 adult cardiac transplant patients. Of these, 45 (5.7%) underwent cardiac retransplantation at 8.2 ± 5.3 (mean ± SD) years after the first transplant, primarily for severe transplant vasculopathy ( n = 42). Results One-year survival for retransplant patients was significantly lower compared with de novo transplant patients (75% vs 87%; p n = 8), infection ( n = 6), rejection ( n = 3), sudden death ( n = 2), recurrent transplant coronary artery disease ( n = 2) or post-operative bleeding ( n = 1). Conclusion Although cardiac retransplantation has immediate life-saving benefits, survival is lower compared with de novo cardiac transplantation due to higher rates of malignancy and infection.

Transplant allograft vasculopathy (TAV) was a leading cause of death in cardiac transplant recipients after the first year of transplantation. Whether drug-eluting stents (DESs) performed better than bare-metal stents (BMSs) for the treatment of patients with discrete epicardial stenosis was unknown. The aim was to determine the safety and efficacy of DESs compared with BMSs in the treatment of patients with TAV. Outcomes of 32 patients sequentially treated using DESs for TAV were retrospectively reviewed and compared with a historic cohort of 35 patients treated sequentially with BMSs for TAV. Patients treated with DESs were also compared with age- and gender-matched cardiac transplant controls to determine differences in survival. After adjustment for baseline risk factors, there was no difference in 1-year survival between patients treated with DESs or BMSs for TAV. Restenosis rates at 1 year were 49% in lesions treated using BMSs and 19% in those treated using DESs. Compared with an age- and gender-matched control group of cardiac transplant patients who did not have discrete obstructive epicardial TAV, patients who required treatment with DESs for epicardial obstructive disease had significantly worse survival. In conclusion, treatment of patients with TAV with DESs did not seem to alter the natural deleterious history of this disease process.

Anemia is a significant co-morbidity in patients with heart failure (HF) irrespective of the ejection fraction and is routinely quantified by hemoglobin concentration. Hemodilution as a cause of anemia has been described in systolic HF. The aim of this study was to further investigate the effects of plasma volume in patients with HF by (1) assessing the prevalence of dilutional anemia in patients with anemia and preserved ejection fractions and (2) exploring the relation between hemoglobin and red cell volume in these patients. Forty-six patients with anemia (as determined by standard hemoglobin measurement), 22 with HF and low ejection fractions (HFLEF) and 24 with HF and preserved ejection fractions (HFPEF), all underwent plasma volume measurement with iodine-131-labeled albumin. Hemoglobin values did not differ between subjects with HFLEF and those with HFPEF (10.8 +/- 1.0 vs 11.0 +/- 1.0 g/dl, p = 0.55), but a red cell deficit was found in 88% of patients with HFPEF compared with 59% of those with HFLEF (p = 0.04). This was the result of a higher prevalence of an expansion of plasma volume in patients with HFLEF (100%) compared with those with HFPEF (71%). Among all patients, no correlation was found between hemoglobin and red cell volume (r = 0.09, p = 0.54), but a correlation did exist in patients with normal blood volumes (r = 0.55, p = 0.02). In conclusion, dilutional anemia caused by an expansion in plasma volume without a red cell deficit occurs more commonly in patients with HFLEF than those with HFPEF, and hemoglobin does not correlate with red cell volume in patients with anemia and HF.

Purpose: Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation. CAV is associated with intragraft B cell infiltrates in or around coronary arteries with evidence of intimal thickening. However, the phenotype, specificity and function of these infiltrating B cells are currently unknown. Our objective was to study the composition of such B cell infiltrates. Methods: Our experiments used 4 cardiac allografts with CAV explanted at time of re-transplantation. B cell infiltrates were visualized by immunohistochemistry. The immunoglobulin heavy chain variable region repertoire was analyzed in different tissue fragments of the 4 specimens and in the patients’ blood by next generation sequencing. Lastly, we isolated B cells directly from two of the specimens and immortalized them by EBV infection. We used the monoclonal immunoglobulins produced in vitro by the clones to assess their reactivity towards HLA, apoptotic cells and autoantigens by Luminex, flow cytometry and ELISA respectively. Results: CD20+ B cells were detected in the perivascular area of the epicardium as well as in the tissue adjacent to the coronary arteries in 4 of 4 specimens. Deep sequencing results showed robust B cell clonal expansion in the graft but not in the blood. Several expanded B cell clones characterized by the sequence of their uniquely rearranged complementarity determining region 3 were detected in different locations in the graft, revealing the breadth of the immune infiltration. Twenty six and thirty four clones were generated from these two grafts respectively. While none of the clones reacted to HLA, 57% reacted to multiple generic self-antigens, displaying a pattern of polyreactivity. Using protein microarrays, we further characterized the reactivity profile of 1 polyreactive clone that was found to be expanded in situ. This clone strongly reacted to immunoglobulin Fc fragment, suggesting that it corresponded to a rheumatoid factor (RF) B cell. Conclusion: Our studies characterize for the first time the clonal composition of B cell infiltrates in human cardiac allografts with CAV and demonstrate the prevalence of polyreactive cells in situ. Moreover, the local expansion of an RF B cell clone suggests that cells with such reactivity may actively contribute to the pathophysiology of CAV through a mechanism that needs to be identified.

Purpose Sponsor: TransMedics, Inc.; Completion Date of Trial: 2013. Methods and Materials The PROCEED Trial is an international, FDA pivotal trial to assess the clinical efficacy and safety of the OCS™ Heart technology for heart transplantation. Results PROCEED is a prospective, multicenter, international trial comparing OCS™ technology to cold storage (CS) to preserve donor hearts for transplantation. A total of 128 heart transplant recipient will be randomized into the trial. Donor inclusion criteria: age 60 mmHg, satisfactory ECHO assessment. Donor exclusion criteria: abnormal coronary angiogram, unstable hemodynamic requiring high-inotropic support & body weight ration 4 sternotomies, renal failure, ventilator dependency, PRA >40% with + ve cross match, presence of VAD line sepsis, IC hemorrhage, or HIT, & the use of another investigational drug/device. Primary endpoint: 30-day patient and graft survival; Secondary endpoints: Incidences of cardiac SAEs, grade 2R/3R rejection and ICU time. Conclusions To-date 92 patients were transplanted in the trial. We expect the trial enrollment to be completed in early 2013. We will report our interim results at the ISHLT late breaking session.

This study investigates the outcomes of cardiac transplantation using older donors.Despite high mortality rates on waiting lists, transplanting hearts from older donors remains a relative contraindication.We retrospectively reviewed data on 479 adult heart transplant recipients, 352 status I patients, and 534 status II patients enrolled on a waiting list between 1992 and 1999. The Cox proportional hazards model was used for statistical analysis.Of all donors, 20% were 40 to 50 years old and 8% wereor =50 years old. The risk of six-month mortality on the waiting list for patients who were not transplanted (status I: relative risk [RR] 8.5; status II: RR 3.7) significantly outweighed the risk of transplanting patients with a heart from donors40 years old (status I: RR 1.6; status II: RR 2.1). Recipients of cardiac allografts from donors40 years old had a one-month mortality rate of 5%, in contrast to 13% and 22% in those receiving allografts from donors 40 to 50 years old andor =50 years old, respectively. Donor age did not influence long-term survival or frequency of rejections; however, it did correlate with the early presence of transplant-related coronary artery disease (TCAD). By the first annual angiogram, only 17% of recipients with donors20 years old developed TCAD, in contrast to 26% to 30% and 34% of recipients who received allografts from donors age 20 to 40 years and40 years, respectively.Despite a strong association between older donor age and increased post-operative mortality and TCAD, it is more beneficial in terms of patient survival to receive an allograft from a donor40 years old than to remain on the waiting list.

Purpose Neurological complications (NC) are a major adverse event following left ventricular assist device (LVAD) surgery. Pre- and post-operative factors associated with NC were investigated. Methods and Materials We reviewed 287 consecutive patients who underwent LVAD surgery [167 Heart Mate (HM) I and 121 HM II] at Columbia University Medical Center between November 2000 and June 2010. Clinical characteristics, hemodynamic and laboratory indexes were analyzed. The NC was defined according to the INTERMACS definition of neurological dysfunction including transient ischemic attack (TIA) and ischemic or hemorrhagic stroke. Results In total, 43 (15.0%) patients developed NC at 145±218 days after surgery, including 28 infarcts, 5 hemorrhages, and 14 TIAs. Six patients developed multiple events. The type of NC was not different between HM I and HM II patients. Preoperative factors that were different between patients with and without NC included: serum albumin (pre-alb, 3.3±0.6 vs. 3.5±0.5 mg/dL; p=0.015); sodium (pre-Na, 127±9 vs. 132±8 mg/dL, p=0.001), and the history of stroke (pre-stroke, 37.2% vs. 17.1%, p=0.003). Postoperative factors associated with NC again included lower albumin (post-alb, 3.4±0.7 vs. 3.9±0.7 mg/dL, p=0.001); sodium (post-Na, 128±8 vs. 132±7 mg/dL, p=0.003) and hematocrit (post-Hct, 31.8±6.1 vs. 35.3±6.6 %, p=0.001). The incidence of LVAD-related infection (post-Inf) was higher (39.5% vs. 20.8%, p=0.008) in patients with NC than without NC. Multiple regression analysis revealed that pre-stroke [odds ratio (OR) 3.0, 95% confidential interval (CI), 1.2-7.3, p=0.002], post-Na (OR, 0.9, 95%CI, 0.90-0.99, p=0.002), and post-Infect (OR, 2.9, 95%CI, 1.24-6.67, p=0.001) were highly associated with NC development. The combination of pre-Alb, pre-stroke, post-Alb, post-Na, post-Hct and post-Inf could predict NC with a probability of 76.4%. Conclusions Persistent malnutrition, severity of heart failure, previous stroke and post LVAD infections were the key factors associated with NC development post LVAD.