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Background— Mutations in the genes encoding sarcomere proteins have been associated with both hypertrophic and dilated cardiomyopathy. Recently, mutations in myosin heavy chain ( MYH7 ), cardiac actin ( ACTC ), and troponin T ( TNNT2 ) were associated with left ventricular noncompaction, a form of cardiomyopathy characterized with hypertrabeculation that may also include reduced function of the left ventricle. Methods and Results— We used clinically available genetic testing on 3 cases referred for evaluation of left ventricular dysfunction and noncompaction of the left ventricle and found that all 3 individuals carried sarcomere mutations. The first patient presented with neonatal heart failure and was referred for left ventricular noncompaction cardiomyopathy. Genetic testing found 2 different mutations in MYBPC3 in trans . The first mutation, 3776delA, Q1259fs, rendered a frame shift at 1259 of cardiac myosin-binding protein C and the second mutation was L1200P. The frameshift mutation was also found in this mother who displayed mild echocardiographic features of cardiomyopathy, with only subtle increase in trabeculation and an absence of hypertrophy. A second pediatric patient presented with heart failure and was found to carry a de novo MYH7 R369Q mutation. The third case was an adult patient with dilated cardiomyopathy referred for ventricular hypertrabeculation. This patient had a family history of congestive heart failure, including pediatric onset cardiomyopathy where 3 individuals in the family were found to have the MYH7 mutation R1250W. Conclusion— Genetic testing should be considered for cardiomyopathy with hypertrabeculation.

Noninvasive differentiation of ischemic versus nonischemic cardiomyopathy (CM) remains challenging because of the low specificity of imaging-based tests in these patients. We hypothesized that myocardial contrast echocardiography (MCE) and cardiac magnetic resonance (CMR), combined with vasodilator stress, could provide accurate alternatives for determining the cause of CM.To allow side-by-side comparisons between these techniques with coronary angiography as a reference, we studied 16 patients referred for coronary angiography after abnormal nuclear perfusion studies. Both MCE and CMR images were acquired within 48 hours with infusion of adenosine. MCE included flash-echo imaging during intravenous infusion of echocardiographic contrast solution. CMR included gadolinium injections for first-pass perfusion and delayed enhancement imaging. MCE and CMR images were reviewed by experienced investigators, blinded to the findings of the other modality and angiography. For each technique, each myocardial segment was classified as normal or abnormal. Sensitivity and specificity of each technique were calculated against the angiography reference. These calculations were also performed using a perfusion territory as a unit of analysis.Six of 16 patients had normal coronary arteries, and three patients had stenosis50%. By using this threshold for abnormal perfusion, segment-by-segment comparisons with angiography resulted in sensitivity of 0.88, 0.61, and 0.71 and specificity of 0.74, 0.86, and 0.94 for CMR perfusion, delayed enhancement scans, and MCE sequences, respectively. Using stenosis70% as a threshold resulted in a small decrease in both sensitivity and specificity (0.02-0.04) for all three techniques. Analysis of the ability of these techniques to detect an abnormality in at least one perfusion territory yielded sensitivity of 1.00, 1.00, and 0.86 and specificity of 0.78, 0.78, and 0.89, correspondingly, which were threshold-independent.Both CMR and MCE perfusion imaging may be used to differentiate between ischemic and nonischemic CM. These emerging diagnostic tools may prove useful in strategizing treatment in these patients and thus avoiding unnecessary invasive procedures.

Background Peri-operative immunosuppression in cardiac transplantation includes the use of intravenous methylprednisolone. During a national shortage, intravenous dexamethasone was substituted for methylprednisolone at standard equivalencies. Methylprednisolone and dexamethasone are used interchangeably in many clinical settings; however, their equivalency has not been demonstrated. Methods Forty-two consecutive cardiac transplant patients were studied retrospectively. All patients received standard triple immunosuppression. Eighteen patients received dexamethasone and 24 methylprednisolone. Twelve patients were included for comparison after the methylprednisolone shortage resolved. Endomyocardial biopsy (EMB) results graded as ≥1B (ISHLT classification) were considered positive for acute cellular rejection. Results More patients who received dexamethasone as induction had cellular rejection (12/17; (70%) vs. 14/33; (42%); p = 0.05). Four patients were excluded because of deaths unrelated to cardiac function. The increased rate of rejection seen during dexamethasone substitution declined after reinstitution of methylprednisolone ( p = 0.05). Conclusions Peri-operative high-dose dexamethasone in cardiac transplants was associated with higher rates of acute cellular rejection. The equivalencies of dexamethasone and methylprednisolone differ from accepted standards when used in pulse doses. Peri-operative use of glucocorticoids may rely on mechanisms that are different from those considered in the standard equivalency measures. Pulse doses of dexamethasone and methylprednisolone in transplantation may not be interchangeable at standard equivalencies.

Purpose of the review This review discusses the ethical issues raised by the increased use of devices to treat heart failure. Recent findings Recent guidelines and clinical trials describe the benefits of device therapy in advanced heart failure. Other studies and commentaries illustrate the potential for harm, both to the individual patient in the form of reduced quality of life and to society in the form of unbearable costs. Recent reports discuss the specific issues involved with deactivating different devices and document low rates of advanced care planning in relation to device management at the end of life. Summary More research, increased end-of-life education, renewed emphasis on advance directives, and a true multidisciplinary approach are needed to provide optimal care for heart failure patients in relation to device therapy.

Background Despite effective therapies, mortality for many cardiovascular diseases remains higher than for many cancers and is difficult to predict. Guidelines recommend discussing advance directives (AD), including living wills and durable powers of attorney, with heart failure patients. The Patient Self-Determination Act mandates such discussions with all hospitalized patients. Little data are available on AD prevalence in patients with serious cardiac disease. Methods Patients admitted to a cardiac care unit (CCU) were surveyed regarding demographics, medical history, prevalence of AD, and interest in obtaining more information about AD. Histories of life-threatening cardiac diagnoses were tabulated. Prevalence of AD and interest in obtaining more information about AD were obtained via chart review from patients on an oncology (ONC) floor at the same hospital. Results One hundred twelve CCU (average age 58 ± 16 years, 47 women) and 105 ONC (average age 58 ± 14 years, 32 women) patients were enrolled. Prevalence of AD was not different between CCU and ONC patients (26% vs 31%, P = .37). Among CCU patients with prior hospitalizations but no AD, 21 of 64 did not recall being asked about AD. Cardiac care unit patients with heart failure and pulmonary hypertension were more likely to report being asked about AD in the past (39 of 54, P = .03 and 7 of 9, P = .008, respectively), but only heart failure patients were more likely to want more information about AD ( P = .005). Of patients without AD, 83% from CCU and 18% from ONC wanted more information on AD ( P Conclusions Prevalence of AD in the CCU was low, and many patients did not recall prior AD discussions. The CCU patients without AD were more likely to want information about AD than the ONC patients. A renewed emphasis on AD discussions with cardiovascular patients is needed and would be welcomed. Advance directives should be emphasized in cardiovascular training programs.

Background The aim of this study was to evaluate the prognostic performance of novel echocardiographic (transthoracic echocardiography, or TTE) parameters for grading aortic insufficiency (AI) severity in patients with continuous-flow left ventricular assist devices (CF-LVADs). The development of AI after CF-LVAD implantation is common, although the clinical significance remains unclear. We previously described novel TTE parameters that outperformed traditional TTE parameters in grading AI severity in these patients. Methods CF-LVAD patients with varying degrees of AI ( N = 57) underwent Doppler TTE of the LVAD outflow cannula. Patients had AI severity graded by the novel parameters (systolic/diastolic velocity ratio and the diastolic acceleration of the LVAD outflow cannula) and the traditional vena contracta. The prognostic performance of novel and traditional AI parameters was determined by comparing rates of congestive heart failure re-admission, need for aortic valve intervention, urgent transplantation and death (composite end-points) for each parameter. Results Grading AI severity using novel AI parameters led to reclassification of 32% of patients from trace/mild AI to moderate or greater AI ( N = 18). Using traditional AI parameters, there was no difference in the occurrence of the composite end-point between the moderate or greater group and the trace/mild group (1.50 vs 1.18 events/person, p = 0.46). With the novel AI parameters, there were significantly more events in the patients with moderate or greater AI compared to those with trace/mild AI (1.57 vs 0.13 events/person, p = 0.002). Novel parameters also better predicted the need for aortic valve intervention, urgent transplantation or death than traditional methods ( p = 0.024 vs p = 0.343). Conclusions In patients with CF-LVADs, traditional parameters tend to underestimate AI severity and future cardiac events. Novel AI TTE parameters are better able to discriminate AI severity and predict clinically meaningful outcomes.

Background: Echocardiographic assessment of left ventricular assist devices (LVAD) is used as a screening tool to evaluate the integrity and mechanics of the pump and circuit. We aimed to 1) establish the normal range and upper reference limit of peak velocity of the outflow cannula for the modern era of LVADs and 2) assess the performance of the current reference limit and our new reference limit in patients with continuous flow LVADs as a screening tool for cannula malfunction. Methods: LVAD outflow peak velocities were measured with Doppler echocardiography (TTE) in 57 patients with LVADs (HeartMate II (HMII) = 44, HeartWare (HW) = 13). The average velocity and the upper and lower normal reference limits (defined as +/- two standard deviations from the mean) for each LVAD type was then calculated. The upper reference limit was then used as a screening threshold for cannula malfunction. Results: The average outflow cannula peak velocity for the HMII cohort was 1.94 m/sec +/- 0.42 with an upper and lower reference limit of 2.78 m/sec and 1.10 m/sec, respectively. The average outflow cannula peak velocity for the HW cohort was 2.36 +/- 0.53 with an upper and lower reference limit of 3.42 m/sec and 1.3 m/sec, respectively, which was significantly higher than the HMII cohort (p=0.004). Velocities from both cohorts were dramatically higher than the commonly citied upper reference limit velocities of 2 m/sec. Use of the previously cited reference limit poorly discriminated between normal and malfunctioning LVAD cannulas whereas our new reference limit identified all four patients with outlet cannula malfunction (Figure1). Conclusions: In both HeartMate II and HeartWare LVADs, the average peak outflow velocity and reference limit for the normal population as measured by Doppler-TTE was markedly higher than currently cited LVAD reference limits. Patients with peak outflow velocities above our upper reference limit should be evaluated for LVAD outflow cannula malfunction.

Background: The development of aortic insufficiency (AI) following continuous flow left ventricular assist device (CF-LVAD) implantation is common, although the clinical significance remains unclear. We previously described novel echocardiographic (TTE) parameters that outperformed traditional TTE parameters in grading AI severity in these patients. The aim of this study was to evaluate the prognostic performance of these parameters compared to traditional measurements. Methods: CF-LVAD patients with varying degrees of AI (N=57) underwent Doppler TTE of the LVAD outflow cannula. All patients had AI severity graded by our novel parameters (Systolic/Diastolic ratio and the diastolic acceleration of the LVAD outflow cannula) and traditional vena contracta. The prognostic performance of novel and traditional AI parameters was determined by comparing rates of hospital readmission, need for aortic valve intervention and/or urgent transplantation and death (primary endpoints) for each parameter. Results: Grading AI severity using novel AI parameters led to reclassification of 21% of patients from trace/mild AI to moderate or greater AI (N=12). Using traditional AI parameters, there was no difference in the occurrence of the primary endpoint between the trace/mild group and the moderate or greater group (1.08 vs. 0.89 events/person, p=0.39) (Figure 1A). With the novel AI parameters, there were significantly more events in the patients with moderate or greater AI compared to those with trace/mild. (1.11 vs. 0.56 events/person, p=0.02) (Figure 1B). Novel parameters better predicted the need for aortic valve intervention, urgent transplantation or death than traditional methods (p=0.049) (Figure 1C-D). Conclusions: In patients with CF-LVADs, traditional parameters tend to underestimate AI severity and future cardiac events. Novel AI TTE parameters are better able to discriminate AI severity and predict clinically meaningful outcomes.

Introduction: This is a retrospective single-institutional study to investigate safety and efficacy of concomitant valve procedures in patients undergoing left ventricular assist device (LVAD) implantation. Methods: From July 2008 to December 2014, 254 patients underwent LVAD implantation. 165 patients had concomitant valve intervention (aortic valve [A], N=3; mitral valve [M], N=78; tricuspid valve [T], N=131; multiple valve intervention, N=67, A+M=3, A+T=11, M+T=44, A+M+T=9). Patients were divided into two groups: Group D, with residual diseased valve, N=97; and Group C, with no-diseased valve, N=157) (see details in figure) and short-/mid-term outcomes were compared. Results: Intraoperative and postoperative outcomes did not differ in two groups except for significantly more concomitant valve procedures (Group D=54 [56%], Group C=111 [70%], P Conclusions: Concomitant valve procedure during LVAD implantation did not increase operative morbidity and mortality. Aggressive valve intervention during LVAD implantation may contribute to improved mid-term hemodynamics and survival.

Objectives This study tested whether combined invasive hemodynamic and echocardiographic ramp tests can help optimize patient management. Background Guidelines for optimizing speed and medications in continuous flow ventricular assist device (cfLVAD) patients are mainly based on expert opinion. Methods Thirty-five cfLVAD patients (21 HeartMate II [Thoratec, Pleasanton, California] and 14 HVAD [HeartWare International, Framingham, Massachusetts]) underwent ramp tests with right heart catheterization (including central venous pressure [CVP], pulmonary artery pressure, pulmonary capillary wedge pressure [PCWP], and blood pressure) and echocardiography. Data were recorded at up to 9 speed settings. Speed changes were in steps of 400 revolutions per minute (RPM) for HeartMate II (8,000 to 12,000 RPM) and 100 RPM for HVAD (2,300 to 3,200 RPM) patients. Results Only 42.9% of patients had normal CVPs and PCWPs at their original RPM settings. Going from lowest to highest speeds, cardiac output improved by 0.16 ± 0.19 l/min/step (total change 1.28 ± 1.41 l/min) and PCWP decreased by 1.23 ± 0.85 mm Hg/step (total change 9.9 ± 6.5 mm Hg). CVP and systolic blood pressure did not change significantly with RPM. RPM were adjusted based on test results to achieve CVPs and PCWPs as close to normal limits as possible, which was feasible in 56% of patients. For the remainder, results indicated which type of medical management should be pursued. Conclusions Use of combined hemodynamic and echocardiographic ramp tests in patients provides objective means of optimizing RPM, and has the potential to guide medical management. It remains to be tested whether this strategy has a beneficial impact on quality of life or clinical outcomes.

The aim of this study was to develop a technique to measure regurgitant flow throughout the entire cardiac cycle that would more accurately measure aortic insufficiency (AI) severity in patients with continuous-flow left ventricular assist devices (CF-LVADs).AI is a common problem after CF-LVAD implantation. Current echocardiographic evaluation of AI does not take into account the unique flow properties present in patients with CF-LVADs.In this prospective study, patients with LVADs who had varying degrees of AI (N = 20) underwent simultaneous right-sided heart catheterization (RHC) and transthoracic echocardiography (TTE). Regurgitant fraction (RF) across the aortic valve was calculated by subtracting the cardiac output obtained using the Fick method from the total systemic flow measured using the sum of the product of the velocity time integral and the cross-sectional area of the LVAD outflow cannula and aortic valve, respectively. The RFs were then compared with the following: 1) traditional TTE grading parameters; and 2) new TTE parameters unique to LVAD physiology, namely the diastolic flow acceleration and the systolic-to-diastolic peak velocity (S/D) ratio of the LVAD outflow cannula.Patients without evidence of AI had an RF approaching zero (2.4 ± 4.6%). Patients with trace and mild AI had an RF of 31.0 ± 5.4%, whereas patients with moderate or severe AI had an RF of 45.8 ± 3.6%. RF correlated better with pulmonary capillary wedge pressure (PCWP) than with vena contracta (correlation coefficient [R] = 0.73 vs. 0.56). The new TTE parameters (S/D ratio and diastolic acceleration) highly correlated with RF (R = 0.91 and 0.94, respectively) and more strongly correlated with PCWP than did vena contracta (R = 0.82 and 0.65 vs. 0.56).RF measured by simultaneous RHC and TTE better correlates with clinical filling pressures than do traditional TTE parameters and may identify significant AI that could be underestimated using conventional measures. Novel TTE parameters, unique to CF-LVAD physiology, better correlate with RF and filling pressures than do our current TTE measurements.

Accurate assessment of volume status is critical in the management of patients with heart failure (HF). We studied the utility of a pocket-sized ultrasound device in an outpatient cardiology clinic as a tool to guide volume assessment. Inferior vena cava (IVC) size and collapsibility were assessed in 95 patients by residents briefly trained in focused cardiac ultrasound (FCU). Cardiologist assessment of volume status and changes in diuretic medication were also recorded. Patients were followed for occurrence of 30-day events. There was a 94% success rate of obtaining IVC size and collapsibility, and agreement between visual and calculated IVC parameters was excellent. Most patients were euvolemic by both FCU IVC and clinical bedside assessment (51%) and had no change in diuretic dose. Thirty-two percent had discrepant FCU IVC and clinical volume assessments. In clinically hypervolemic patients, the FCU evaluation of the IVC suggested that the wrong diuretic management plan might have been made 46% of the time. At 30 days, 14 events occurred. The incidence of events increased significantly with FCU IVC imaging categorization, from 11% to 23% to 36% in patients with normal, intermediate, and plethoric IVCs. By comparison, when grouped in a binary manner, there was no significant difference in event rates for patients who were deemed to be clinically volume overloaded. Assessment of volume status in an outpatient cardiology clinic using FCU imaging of the IVC is feasible in a high percentage of patients. A group of patients were identified with volume status discordant between FCU IVC and routine clinic assessment, suggesting that IVC parameters may provide a valuable supplement to the in-office physical examination.

Diagnosis of heart failure is being increasingly relied upon on advanced imaging technologies and diagnostic tests. A thorough history and a competent physical examination, followed by an electrocardiogram, basic laboratory studies, and an echocardiogram, remain a sound approach to the initial evaluation of heart failure. Echocardiography is the most useful diagnostic test readily available for the assessment of cardiac structure and function where as cardiac magnetic resonance imaging is the gold standard for the measurement of chamber volume, mass, and thereby ventricular systolic function. Measurement of BNP improves diagnostic accuracy, especially in the acute setting. Evaluation for coronary artery disease is critical. Invasive hemodynamic assessment is not routinely indicated in the diagnosis of heart failure but it is essential in patients being considered for advanced heart failure therapeutic options including cardiac transplantation or left ventricular assist device.

In 2003, 50.8% of applicants and 49.7% of matriculants of U.S. medical schools were women [(1)][1]. This was the first time in our nation's history that women made up more than half of medical school applicants [(2)][2]. Currently, 22.2% of female medical graduates choose an internal medicine

Objective We sought to determine whether physicians with training in echocardiography could successfully use a small echocardiographic device to detect occult cardiovascular disease in patients admitted to a general medical service. Methods In all, 103 consecutive patients had a physician-performed bedside echocardiographic examination with a small portable ultrasound device. Results Of patients, 70% did not have a clinical indication for echocardiography and of these patients, 39% had an abnormal study with the portable ultrasound device. There was a high rate of false-positive examinations, but approximately 17% of patients without a clinical indication for echocardiography had an important cardiac abnormality detected, including 10% with unsuspected left ventricular systolic dysfunction. Conclusions Many patients on a general medical hospital ward have unsuspected, clinically important cardiac findings such as left ventricular dysfunction that can be screened for by physicians with training in echocardiography using small portable ultrasound devices.

We describe a case of cardiac toxoplasmosis diagnosed by routine endomyocardial biopsy in a patient with trimethoprim-sulfamethoxazole (TMP-SMX) intolerance on atovaquone prophylaxis. Data are not available on the efficacy of atovaquone as Toxoplasma gondii prophylaxis after heart transplantation. In heart transplant patients in whom TMP-SMX is not an option, other strategies may be considered, including the addition of pyrimethamine to atovaquone.

Introduction: Left ventricular (LV) assist device (LVAD) has emerged as a valuable option for patients with severe congestive heart failure both as bridge to transplantation or destination therapy. Speed optimization of LVAD is currently based on the position of the inter-ventricular septum, mitral regurgitation severity and aortic valve opening. Hypothesis: We hypothesized that 3D transthoracic echocardiography (3DE) would provide additional information on left and right ventricular (RV) volumes and shape, which could be valuable in determining optimal LVAD speed. Our aim was to assess the feasibility of combined 3D LV and RV analysis during an incremental RAMP study. Methods: Six consecutive patients undergoing a RAMP test were studied. Device speed was increased from 8000 to 12000 rpm in 400-rpm increments for axial-flow pumps (n=2) and from 2300 to 3200 rpm in 100 rpm increments for centrifugal-flow pumps (n=4). Transthoracic 3DE apical full-volume datasets of the LV and the RV were acquired (Philips) at every other step. RV and LV endocardial surfaces were reconstructed using commercial software (TomTec) and used to calculate ventricular volumes. Custom software was used to calculate LV shape indices of sphericity and conicity (a perfectly spherical/conical ventricle would result in 1.0 value). Results: Data acquisition and post-processing was feasible in 5/6 patients. In axial pumps (Figure), increments in LVAD speed were associated with gradually decreasing LV volume, while RV volume initially decreased to a minimum and then increased at higher speeds. These volumetric changes were associated with alterations in LV shape, with the LV becoming less spherical and more conical at higher speeds. With centrifugal pumps, increased speed was associated with similar changes in LV shape but with minimal changes in volumes. Conclusions: Acquisition of 3D datasets during RAMP studies is feasible and could become a valuable aid in optimizing LVAD pump speed.

s S197 technically demanding HTx operation and that longer duration would have a higher incidence of post-operative vasoplegia. Methods: All patients who received a CF-LVAD for BTT at our center from 01/08-09/14 were evaluated (n= 116). Eighty (69%) patients underwent HTx, 12 (10%) died before HTx, and 24 (21%) remain listed for HTx and continue on LVAD support. Of the 80 transplanted patients, 29 (36%) were supported with an LVAD for ≤ 180 days (group 1) and 51 (64%) for > 180 days (group 2). Results: Mean time of LVAD support was 98±41 d for group 1 and 365±193 for group 2. Mean age for group 1 was 52±9 years vs 57±9 for group 2 (p= 0.02). Median operative time (473 vs 523 min), CPB time (205 vs. 219 min), aortic cross clamp time (119 vs 126 min) and intra-operative blood product transfusion (6 vs 6.3 units) did not differ between groups (p> 0.05). While median ICU time (88 vs 92 hrs) and the degree or duration of vasoconstrictor support after HTx were similar, there was a trend for prolonged ventilation (> 24h) in group 2 (24% vs 10%; p= 0.06). Median hospital length of stay was 9 d for both groups. Survival after HTx at 1 and 3 years was 93% for group 1 and 91% and 87% for group 2, respectively (Figure; Log rank p= 0.57). Conclusion: Shorter duration of CF-LVAD support does not appear to increase the technical difficulty of HTx operation and longer duration of support was not associated with a greater incidence of vasoplegia. Both groups had equivalent and excellent long-term survival.

Background: Ventricular assist devices (VADs) are increasingly common, and their surgical implantation predisposes patients to an increased risk of acute kidney injury (AKI). We sought to evaluate the incidence, risk factors and short- and long-term all-cause mortality of patients with AKI following VAD implantation. Methods: We identified all patients who underwent VAD implantation at the University of Chicago between January 1, 2008, and January 31, 2012. We evaluated the incidence of AKI, defined as a ≥50% increase in serum creatinine over the first 7 postoperative days (RIFLE Risk-Creatinine). A logistic regression model was used to identify risk factors for the development of AKI, and a Cox proportional hazards model was used to examine factors associated with 30-day and 365-day all-cause mortality. Results: A total of 157 eligible patients had VAD implantations with 44 (28%) developing postimplantation AKI. In a multivariate analysis, only diabetes mellitus [odds ratio = 2.25 (1.03-4.94), p = 0.04] was identified as a significant predictor of postoperative AKI. Using a multivariable model censored for heart transplantation, only AKI [hazard ratio, HR = 3.01 (1.15-7.92), p = 0.03] and cardiopulmonary bypass time [HR = 1.01 (1.001-1.02), p = 0.02] were independent predictors of 30-day mortality. Preoperative body mass index [HR = 0.95 (0.90-0.99), p = 0.03], preoperative diabetes mellitus [HR = 1.89 (1.07-3.35), p = 0.03] and postimplantation AKI [HR = 1.85 (1.06-3.21), p = 0.03] independently predicted 365-day mortality. Conclusion: AKI is common following VAD implantation and is an independent predictor of 30-day and 1-year all-cause mortality.

Non-surgical bleeding (NSB) is the most common adverse event in patients with Continuous-Flow Left Ventricular Assist Devices (LVADs) and is attributed to the development of arteriovenous malformations (AVMs) a process which may reflect altered angiogenesis. Angiopoietin-2 (Ang-2) is a potent

Advanced glycation end products (AGEs) are chemically heterogeneous structures and include such specific forms as carboxy (methyl)lysine, pentosidine and others, and were previously measured in heart failure patients as serum AGE, skin AGE, and AGE in cardiomyocytes and vascular cells within the heart. The study by Nozynski et al.1 adds to this body of knowledge as it examines AGE expression directly in explanted hearts: 22 with cardiomyopathy (CMP) and diabetes (DM), 114 with CMP without DM, 20 healthy heart donors, and 14 with DM without CMP. One of the main findings in this study was equally increased AGE accumulation in intramyocardial veins, arterioles and venules in diabetic subjects with and without CMP. This is an unexpected finding, since it is believed that AGE may contribute to mechanical (stiffness) as well as molecular (inflammation) changes contributing to myocardial dysfunction. However, we would like to offer a hypothesis for this unexpected result not raised by the authors. The diabetic cohort without CMP consists of patients who died in the first 24 hours after admission to the intensive care unit due to cerebral injury, and therefore represent a very sick cohort. It is well established that trauma is associated with a high burden of systemic inflammation, oxidative stress and for instance serum myeloperoxidase activity is highest in the first 6 hours in non-surviving patients with head trauma2. Moreover, inflammation, reactive oxygen species and myeloperoxidase enzymatic activity promotes protein glycation and AGE formation as rapidly as in 60 minutes3. AGE formation in human tissue is a dynamic process as recently demonstrated by the rapid decline of AGEs in myeloperoxidase-positive inflammatory cells in carotid endarterectomy tissue after treatment with simvastatin prior to surgery4. We speculate that the increased accumulation of AGE in the heart of diabetic subjects without CMP found in the study by Nozynski et al. may be largely explained by the circumstances of this study. The authors cannot exclude the possibility of rapid AGEs formation as a result of enhanced oxidative stress and myeloperoxidase activity associated with lethal trauma in this diabetic control group without CMP. Further studies examining AGE in cardiac tissue are needed to dissect the role of AGE in heart failure. Most importantly, more in-depth analysis of the specific AGEs and their concentrations in these tissues must be performed. Indeed, the concept of the heterogeneous nature of AGEs is underscored in Nyzynski’s study population and design.

Background Patients who receive heart transplants may undergo therapeutic plasma exchange to reduce high levels of HLA antibodies which may increase the risk of allograft rejection. Plasma exchange may predispose to hypocalcemia because of chelation of calcium by sodium citrate, used as an anticoagulant both during the procedure and in thawed fresh frozen plasma often used for replacement. Methods We report three adults with dilated cardiomyopathy who underwent cardiac transplantation and serial plasma exchange for high levels of HLA antibodies. We followed these patients’ pre-exchange serum calcium levels and the quantity of calcium supplementation they received. Further, we examined myocardial tissue sections post-transplantation for calcium deposition. Results Our patients’ serum calcium levels were initially normal, but, despite aggressive calcium repletion, remained low (nadirs for pre-exchange ionized calcium in two patients 4.48 and 3.8 mg/dL, respectively, reference range 4.6–5.4 mg/dL). For patient 3, pre-exchange total calcium on day 2 was 7.9 mg/dL (reference range 8.4–10.2 mg/dL). Two patients had intermittent symptoms of hypocalcemia. Studies of cardiac tissue sections (available only from these two patients) were consistent with the presence of calcium deposition post transplantation. In comparison, six patients who underwent lung transplantation and plasma exchange for high levels of HLA antibodies did not manifest significant hypocalcemia. Conclusions We emphasize the need for prompt and sufficient calcium replacement, monitored by serum ionized calcium levels, in the early post-cardiac transplantation period when plasma exchange is performed with thawed fresh frozen plasma replacement. The persistently low serum calcium levels we observed post heart transplantation were possibly contributed to by increased myocardial calcium influx.

s S75 echocardiography. These findings demonstrate that PAT signals possess inherent signatures which can be extracted by DSP techniques for clinical assessment, one of which is detection of the state of AV in patients with CF-VADs.

Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesu, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2 Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3 Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruna, La Coruna, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium.

Background Myocardial β-adrenergic receptor (β-AR) signaling is severely impaired in chronic heart failure (HF). This study was conducted to determine if left ventricular (LV) β-AR signaling could be restored after continuous-flow LV assist device (LVAD) support. Methods Twelve patients received LVADs as a bridge to transplant. Paired LV biopsy specimens were obtained at the time of LVAD implant (HF group) and transplant (LVAD group). The mean duration of LVAD support was 152 ± 34 days. Myocardial β-AR signaling was assessed by measuring adenylyl cyclase (AC) activity, total β-AR density (B max ), and G protein-coupled receptor kinase-2 (GRK2) expression and activity. LV specimens from 8 non-failing hearts (NF) were used as controls. Results Basal and isoproterenol-stimulated AC activity was significantly lower in HF vs NF, indicative of β-AR uncoupling. Continuous-flow LVAD support restored basal and isoproterenol-stimulated AC activity to levels similar to NF. B max was decreased in HF vs NF and increased to nearly normal in the LVAD group. GRK2 expression was increased 2.6-fold in HF vs NF and was similar to NF after LVAD support. GRK2 activity was 3.2-fold greater in HF vs NF and decreased to NF levels in the LVAD group. Conclusions Myocardial β-AR signaling can be restored to nearly normal after continuous-flow LVAD support. This is similar to previous data for volume-displacement pulsatile LVADs. Decreased GRK2 activity is an important mechanism and indicates that normalization of the neurohormonal milieu associated with HF is similar between continuous-flow and pulsatile LVADs. This may have important implications for myocardial recovery.

Background Antibody-mediated rejection (AMR) is associated with poorer outcomes in cardiac transplantation. The clinical diagnosis of AMR has been confirmed by immunofluorescence for C4d on fresh-frozen cardiac tissue. Immunohistochemistry (IHC) has been suggested as a more practical diagnostic tool because it can be performed on routine paraffin-embedded tissue. There are few published data about hemodynamics and C4d staining. We prospectively performed C4d staining on endomyocardial biopsies (EMBs) and present the pattern of tissue staining and its correlation with intracardiac hemodynamics. Methods EMBs were evaluated by IHC for C4d staining and graded for cellular rejection using ISHLT criteria on hematoxylin-and-eosin–stained sections. Hemodynamic measurements were taken concurrently. Staining for C4d was described as absent, present with serum staining, or present with only tissue staining. The pattern of tissue staining was categorized by location of staining and correlated with intracardiac hemodynamics. Patient demographics, cytomegalovirus status, panel-reactive antibody levels and hemodynamics were analyzed by analysis of variance and chi-square statistics. Results Of the 400 EMBs, 50 had no C4d staining, 330 had tissue and serum staining, whereas 20 had only tissue staining. Forty EMBs had endothelial staining, including 35 with serum and 5 with isolated tissue staining. Endothelial staining correlated with higher intracardiac pressures. Conclusions IHC staining for C4d has been suggested for the diagnosis of AMR. Our data suggest there is a high rate of background C4d staining, but endothelial staining correlates with poorer hemodynamics. Methods for IHC staining and interpretation need to be standardized for widespread use and clinical studies.

We present a 29-year-old male Jehovah's Witness, who underwent a second orthotopic heart transplantation 20 years after his first transplant. After extubation, the patient aspirated and required support with extracorporeal membrane oxygenation (ECMO). During the period of ECMO support, his hemoglobin decreased to 4.7 mg/dl. The patient was ultimately weaned from ECMO and discharged home. To our knowledge, this is the first reported case of 1) heart retransplantation and 2) rescue with ECMO in a Jehovah's Witness patient.

Purpose The HeartMate II® ventricular assist device (HM-VAD) provides continuous flow support and its display monitor reveals an estimate of flow. Whether this flow-estimate predicts cardiac output (CO) in the clinical setting remains unclear. We sought to determine the accuracy and clinical reliability of the estimated flow in determining CO in patients (pts) with an HM-LVAD. Methods and Materials Cardiac catheterization (RHC) was performed in 25 pts with an HM-VAD. Pts with significant aortic insufficiency or presumed HM-VAD thrombosis were excluded. The average of 3 consecutive thermodilution CO measurements was made while simultaneously recording the flow-estimate on the HM-LVAD display monitor. Results The indication for RHC was per clinical protocol (n=19) or right heart failure (n=6). The mean HM-VAD parameters were: speed 9600 rpm, flow 5.7±0.8 l/min, power 6.9±0.7 watts, and pulsatility index 4.8±0.8. A weak correlation was seen between CO and estimated flow (r=0.38; p=0.05) with the poorest correlation seen in those with a lower cardiac index ( figure 1 ] Conclusions Flow estimates correlate poorly with cardiac output and should not be relied upon as a surrogate for CO in HM-VAD pts. A low threshold for invasive CO measurement is warranted particularly in those whose clinical condition is consistent with a low CO state.

Background Accurate determination of left ventricular ejection fraction (LV EF) is of paramount importance in the evaluation of patients with cardiovascular disease. Quantitative techniques for the automated calculation of EF exist however, the robustness of these techniques is dependent on adequate endocardial border definition and therefore are difficult to use in patients with limited images. We sought to combine the endocardial border enhancing effects of contrast echocardiography with an automated border detection technique to provide quantitative and accurate determination of LV EF. Methods Thirty-nine consecutive patients referred to nuclear cardiology for EF determination underwent radionuclide angiography followed by echocardiographic imaging using prototype software that allowed automated border detection during contrast infusion. Results Adequate LV cavity opacification with contrast was possible in 38/39 patients. The mean radionuclide EF was 50±16% (range 19–73). There was no statistically significant difference between the mean nuclear EF and averaged echocardiographically determined EF (51±18%). The mean bias was 0.6 with limits of agreement that were +15 and −14. Conclusion This study demonstrated that prototype software successfully tracked the contrast enhanced endocardial border allowing accurate calculation of LV EF.

Sinus of Valsalva aneurysms are rare congenital anomalies. When they rupture, they can lead to the development of biventricular failure as a result of systemic-pulmonary shunting. Surgical repair has been the traditional treatment for these aneurysms. We present a case of a 54 year old man in whom a ruptured sinus of Valsalva aneurysm was successfully closed using a catheter-based approach with the Amplatzer Duct Occluder.

Introduction: Accurate assessment of volume status is critical in the management of patients with congestive heart failure (CHF). We studied the utility of a pocket sized ultrasound device (Vscan; GE) in an outpatient cardiology clinic as a tool to guide volume assessment and reduce CHF admissions. Hypothesis: Use of pocket ultrasound to assess IVC parameters will help clinicians titrate diuretic medications and decrease hospital admissions. Methods: Inferior vena cava (IVC) maximum size and collapsibility were assessed in 95 patients by two internal medicine residents briefly trained in focused cardiac ultrasound (FCU). Both visual estimation and quantification of IVC size and collapsibility were performed during passive respiration and inspiratory sniff. Patients with IVC size O2cm and collapsibility !50% were deemed volume overloaded. Cardiologist assessment of volume status (blinded to imaging data) and changes in diuretic medication were also recorded. Patients were followed by means of chart review and telephone inquiry for occurrence of 30 day events (ER visit or hospital admission). Results: There was a 95% success rate of obtaining IVC size and collapsibility. Agreement between the visual and calculated IVC assessments of collapsibility and size were excellent, kappa 0.96 (95% CI: 0.89-1.00) and 0.87 (95% CI: 0.745-0.99), respectively, resulting in a 93% concordance for volume status assessment. Comparison of visual IVC and clinician ability to detect volume overload yielded a kappa statistic of 0.25 (95% CI: -0.01 0.51). Most patients were euvolemic by both IVC and clinician assessment (83%); only 2% were overloaded by both techniques. In 14% of patients there was discordance in volume status between visual IVC and clinician assessment, most of whom (11/ 12) were volume overloaded by IVC. In these 11 patients, 10 did not have their diuretic dose increased. At 30 days, 14 events occurred, with volume assessment discordant in 4. Two events were CHF-related and volume assessment was not discordant in either case. Of the other 12 events, half were cardiovascular and half were non-cardiovascular. Conclusion: Assessment of volume status in an outpatient cardiology clinic using FCU imaging of the IVC is feasible in a high percentage of patients. The strong agreement between visually assessed and measured IVC parameters validates FCU as a quick subjective bedside tool. Most patients in this outpatient cohort were euvolemic by both IVC and clinician. A group of patients was identified as volume overloaded by IVC yet euvolemic by clinician, suggesting that FCU in an outpatient setting may be a valuable adjunct to the physical exam. Whether FCU can help prevent hospital admission warrants further study in a larger patient population.