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Background Increased body mass index (BMI) is a major risk factor for heart failure with preserved ejection fraction (HFpEF), and HFpEF is more prevalent in elderly females than males. We hypothesized that there may be gender differences in the association between BMI and echocardiographic left ventricular (LV) diastolic parameters. Methods We enrolled 456 subjects (243 males) without overt cardiac diseases, all of whom underwent a health checkup. Early (E) and late (A) diastolic transmitral flow velocity, early diastolic mitral annular velocity (e'), and left atrial (LA) volume index were measured by echocardiography to assess LV diastolic function. To examine gender differences in the association between BMI and LV diastolic function, we analyzed the interaction effects of gender on the association between BMI and echocardiographic LV diastolic parameters. Results Although there were significant gender differences in the association between BMI and E/A and e' in the crude model (interaction effect 0.037 and 0.173, respectively; P = .006 and .022, respectively), these differences were not statistically significant after adjustment for factors related to LV diastolic function. On the other hand, there were significant associations between BMI and LV diastolic parameters in each gender, even after adjustment. Conclusions Our findings suggest there is no gender difference in the association between BMI and echocardiographic LV diastolic parameters. However, the association between BMI and LV diastolic parameters was significant in both genders. Controlling body weight might be beneficial for both women and men to prevent progression of LV diastolic dysfunction and development of HFpEF.

Right ventricular (RV) function has recently gained attention as a prognostic predictor of outcome even in patients who have left-sided heart failure. Since several conventional echocardiographic parameters of RV systolic function have been proposed, our aim was to determine if any of these parameters (tricuspid annular plane systolic excursion: TAPSE, tissue Doppler derived systolic tricuspid annular motion velocity: S', fractional area change: FAC) are associated with outcome in advanced heart failure patients with dilated cardiomyopathy (DCM).We retrospectively enrolled 68 DCM patients, who were New York Heart Association (NYHA) Class III or IV and had a left ventricular (LV) ejection fraction35%. All patients were undergoing evaluation for heart transplantation or management of heart failure. Primary outcomes were defined as LV assist device implantation or cardiac death within one year.Thirty-nine events occurred (5 deaths, 32 LV assist devices implanted). Univariate analysis showed that age, systolic blood pressure, heart rate, NYHA functional class IV, plasma brain natriuretic peptide concentration, intravenous inotrope use, left atrial volume index, and FAC were associated with outcome, whereas TAPSE and S' were not. Receiver-operating characteristic curve analysis showed that the optimal FAC cut-off value to identify patients with an event was26.7% (area under the curve=0.74). The event-free rate determined by Kaplan-Meier analysis was significantly higher in patients with FAC≥26.7% than in those with FAC26.7% (log-lank, p=0.0003). Moreover, the addition of FAC26.7% improved the prognostic utility of a model containing clinical variables and conventional echocardiographic indexes.FAC may provide better prognostic information than TAPSE or S' in advanced heart failure patients with DCM.

BACKGROUND Ultrasound measurements of the inferior vena cava (IVC) diameter (IVCD), together with its respiratory variation, provide a noninvasive estimate of right atrial pressure (RAP). However, there is a paucity of studies that have compared this technique with simultaneous catheterization. We explored the best cut-off values of IVC parameters for elevated RAP in comparison with RAP measured by catheterization.Methods and Results:We prospectively enrolled 120 East Asian patients who were scheduled for catheterization. The IVCD and IVC collapsibility index (IVCCI) were measured according to the current guidelines. The optimal maximum IVCD (IVCDmax) and IVCCI cut-offs for detecting elevated RAP (RAP ≥10 mmHg) were 17 mm and 40%, respectively. When we combined both in proportion to the guidelines, the sensitivity and specificity for detecting elevated RAP were 75% and 94%, respectively. When the cut-off values from the current guidelines (>21 mm and

Noninvasive hemodynamic assessments in patients with heart failure (HF) are essential for appropriate diagnosis and establishment of the best treatment strategies. Recently, the impact of pulmonary circulation and right ventricular function on prognosis in HF patients has drawn increasing attention. In this article, we explore the usefulness of cardiac imaging for hemodynamic assessments, mainly focusing on echocardiographic evaluation. The reliability of Doppler echocardiography as a noninvasive alternative to Swan-Ganz catheterization has been well investigated with higher than 80% accuracy for estimating pulmonary artery pressure. Strain measurement and three-dimensional echocardiography are useful for evaluating right ventricular function together with pulmonary circulation. The accuracy of analyzing left and right ventricular functions by cardiac computed tomography and cardiac magnetic resonate imaging has also been established. These modalities can provide myocardial tissue information and allow calculation of the extracellular volume fraction as well. According to the rapid improvement of technologies, cardiac imaging has become an essential tool for hemodynamic evaluation in HF management.

We evaluated the association between visceral adiposity and left ventricular (LV) diastolic function in association with plasma adiponectin levels in 213 subjects without overt cardiac diseases. Abdominal visceral fat area was quantified by computed tomography. Excessive visceral fat was significantly associated with impaired diastolic parameters including E/A, E′ and E/E′. Although serum adiponectin levels decreased with increased visceral adiposity, there was no independent association between serum adiponectin levels and diastolic parameters, which suggest that the role of adiponectin in this association might be indirect.

Background Left ventricular assist devices are increasingly being used in patients with advanced heart failure as both destination therapy and bridge to transplant. We aimed to identify histomorphometric, structural and inflammatory changes after pulsatile- and continuous-flow left ventricular assist device placement. Methods Clinical and echocardiographic data were collected from medical records. Aortic wall diameter, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at left ventricular assist device placement and at explantation during heart transplantation. Expression of adhesion molecules was quantified by Western blot. Results Decellularization of the aortic tunica media was observed in patients receiving continuous-flow support. Both device types showed an increased inflammatory response after left ventricular assist device placement with variable T-cell and macrophage accumulations and increased expression of vascular E-selectin, ICAM and VCAM in the aortic wall. Conclusions Left ventricular assist device implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on continuous-flow left ventricular assist and associated with aortic media decellularization. The present findings help to explain the progressive aortic root dilation and vascular dysfunction in patients after continuous-flow device placement.

According to recent advances in operative techniques, an increasing number of patients with liver dysfunction have been subjected to cardiac surgery. Model of End-Stage Liver Disease (MELD and MELD-XI) scores allow risk stratification of patients undergoing cardiac and non-cardiac surgeries.We retrospectively analyzed 1856 consecutive patients (69.3% male, mean 66.8 ± 12.2 years) undergoing cardiac surgery between 2008 and 2013 at our institution.The mean values of MELD/MELD-XI scores obtained from the total cohort were 9.7 ± 4.6/11.9 ± 4.8. Patients with high MELD/MELD-XI scores (12) were older, more anemic, and had lower left ventricular ejection fraction than those with low scores (all p0.0001). High scores were associated with longer hospitalization (36.8 ± 33.0 vs. 23.6 ± 21.5 days for MELD, 36.7 ± 34.0 vs. 23.5 ± 21.0 days for MELD-XI, both p0.0001) and higher in-hospital all-cause mortality (6.6% vs. 1.0% for MELD, 7.7% vs. 0.7% for MELD-XI). Atrial fibrillation occurred more frequently in the high MELD group, but this difference was not found for MELD-XI. MELD/MELD-XI could predict mortality with a sensitivity of 64.3%/60.0% and specificity of 79.1%/85.3%. Comparison of AUC values among MELD scores, individual MELD components, and Child-Turcotte-Pugh (CTP) classification showed that the predictive strength of MELD scores for mortality was stronger than individual parameters or CTP classification (AUC: 0.7702 for MELD, 0.7655 for MELD-XI, 0.5799 for CTP classification with pairwise p0.0001 and p=0.0002 vs. MELD and MELD-XI, respectively).Assessment of liver dysfunction using the MELD scores can be useful for predicting postoperative morbidity and mortality, which may allow additional risk stratification in patients undergoing cardiac surgery.

Background— Skeletal muscle dysfunction and exercise intolerance are clinical hallmarks of patients with heart failure. These have been linked to a progressive catabolic state, skeletal muscle inflammation, and impaired oxidative metabolism. Previous studies suggest beneficial effects of ω-3 polyunsaturated fatty acids and glutamine on exercise performance and muscle protein balance. Methods and Results— In a randomized double-blind, placebo-controlled trial, 31 patients with heart failure were randomized to either l -alanyl- l -glutamine (8 g/d) and polyunsaturated fatty acid (6.5 g/d) or placebo (safflower oil and milk powder) for 3 months. Cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, 6-minute walk test, hand grip strength, functional muscle testing, echocardiography, and quality of life and lateral quadriceps muscle biopsy were performed at baseline and at follow-up. Oxidative capacity and metabolic gene expression were analyzed on muscle biopsies. No differences in muscle function, echocardiography, 6-minute walk test, or hand grip strength and a nonsignificant increase in peak V O 2 in the treatment group were found. Lean body mass increased and quality of life improved in the active treatment group. Molecular analysis revealed no differences in muscle fiber composition, fiber cross-sectional area, gene expression of metabolic marker genes (PGC1α, CPT1, PDK4, and GLUT4), and skeletal muscle oxidative capacity. Conclusions— The combined supplementation of l -alanyl- l -glutamine and polyunsaturated fatty acid did not improve exercise performance or muscle function but increased lean body mass and quality of life in patients with chronic stable heart failure. These findings suggest potentially beneficial effects of high-dose nutritional polyunsaturated fatty acids and amino acid supplementations in patients with chronic stable heart failure. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01534663.

Impaired cardiac function is considered a contraindication for lung transplantation (LT). Because right ventricular (RV) function is expected to improve after LT, poor left ventricular (LV) function is often the determinant for LT eligibility. However, the changes in cardiac function before and after LT have not yet been elucidated. Therefore, we reviewed echocardiograms obtained from 67 recipients before and after LT. In a subset of 49 patients, both RV and LV longitudinal strains based on 2-dimensional speckle tracking echocardiography were analyzed. The cardiopulmonary exercise tests were also reviewed. All patients showed significant improvements in their exercise capacity after LT. RV echo parameters improved in all patients after LT (RV fractional area change: 36.7 ± 5.6% to 41.5 ± 2.7%, RV strain: -15.5 ± 2.9% to -18.0 ± 2.1%, RV E/E': 8.4 ± 1.8 to 7.7 ± 1.8; all p0.05). Overall, the left ventricular ejection fraction (LVEF) did not change (58.7 ± 6.0% to 57.5 ± 9.7%, p = 0.385); however, 20 patients (30%) showed10% decrease in LVEF after LT (61.5 ± 6.1% to 47.3 ± 4.2%, p0.001) and an increase in LV E/E' (11.8 ± 1.8 to 12.9 ± 2.2, p = 0.049). Multivariate logistic regression analysis revealed that pre-LT LV E/E' was associated with decrease in LVEF after LT (odds ratio 1.381, 95% confidence interval 1.010 to 1.947, p = 0.043). Furthermore, patients with strain data showed that lower pre-LT LV strain was independently associated with LVEF decrease after LT (odds ratio 1.293, 95% confidence interval 1.088 to 1.614, p = 0.002). Although RV function improves after LT, LV systolic and diastolic functions deteriorate in a sizable proportion of patients. Impaired LV diastolic function before transplant appears to increase the risk of LVEF deterioration after LT.

Renal dysfunction is a major adverse event after cardiovascular surgery. Therefore, the preoperative prediction of which patients will require renal replacement therapy (RRT) after cardiac surgery is an important issue. In the present study, 1,822 consecutive patients who underwent cardiovascular surgery from 2008 and 2013 at a single institution were reviewed. Patients who were already receiving long-term hemodialysis before surgery (n = 134) were excluded. The remaining 1,688 patients were separated into 2 groups: those requiring postoperative RRT and those without RRT requirement. A total of 128 patients (7.6%) required RRT. Patients requiring RRT had greater perioperative blood loss, longer intubation time, and longer hospital stays (p0.0001 for all). Multivariate analysis revealed that cardiopulmonary bypass use, preoperative body surface area, the left ventricular ejection fraction, serum albumin, and creatinine were independent risk factors for postoperative RRT (odds ratios 2.435, 0.204, 0.976, 0.556, and 5.394, 95% confidence intervals 1.471 to 4.140, 0.054 to 0.841, 0.962 to 1.025, 0.363 to 0.860, and 3.671 to 8.223, respectively, p0.05 for all). A subgroup of patients with relatively preserved renal function before surgery (creatinine1.12 mg/dl, a cut-off value for RRT requirement obtained from receiver-operating characteristic curve analysis [area under the curve 0.74748, sensitivity 60.2%, specificity 85.0%]) showed that preoperative serum albumin concentration was most significantly associated with postoperative RRT requirement (odds ratio 0.048, 95% confidence interval 0.023 to 0.095, p0.0001). In conclusion, cardiopulmonary bypass use, preoperative renal impairment as reflected by elevated creatinine level, small body size, a low left ventricular ejection fraction, and hypoalbuminemia were associated with a requirement for postoperative RRT. In patients with preserved renal function, hypoalbuminemia was most significantly related to requirement for RRT.

Functional and structural liver abnormalities may be found in patients with advanced heart failure (HF). The Model of End-Stage Liver Disease Excluding INR (MELD-XI) score allows functional risk stratification of HF patients on and off anti-coagulation awaiting heart transplantation (HTx), but these scores may improve or worsen depending on bridging therapies and during time on the waiting list. Liver biopsy is sometimes performed to assess for severity of fibrosis. Uncertainty remains whether biopsy in addition to MELD-XI improves prediction of adverse outcomes in patients evaluated for HTx.Sixty-eight patients suspected of advanced liver disease underwent liver biopsy as part of their HTx evaluation. A liver risk score (fibrosis-on-biopsy + 1) × MELD-XI was generated for each patient.Fifty-two patients were listed, of whom 14 had mechanical circulatory support (MCS). Thirty-six patients underwent transplantation and 27 patients survived ≥1 year post-HTx (74%, as compared with 88% average 1-year survival in HTx patients without suspected liver disease; p0.01). Survivors had a lower liver risk score at evaluation for HTx (31.0 ± 20.4 vs 65.2 ± 28.6, p0.01). A cut-point of 45 for liver risk score was identified by receiver-operating-characteristic (ROC) analysis. In the analysis using Cox proportional hazards models, a liver risk score ≥45 at evaluation for HTx was associated with greater risk of death at 1 year post-HTx compared with a score of45 in both univariable (HR 3.94, 95% CI 1.77-8.79, p0.001) and multivariable (HR 4.35, 95% CI 1.77-8.79, p0.001) analyses. Patients who died1 year post-HTx had an increased frequency of acute graft dysfunction (44.4% vs 3.7%, p = 0.009), longer ventilation times (55.6% vs 11.1%, p = 0.013) and severe bleeding events (44.4% vs 11.1%, p = 0.049). The liver risk score at evaluation for HTx also predicted 1-year mortality after HTx listing (p0.001).Patients with HF and advanced liver dysfunction are high-risk HTx candidates. Liver biopsy in addition to MELD-XI improves risk stratification of patients with advanced HF and suspected irreversible liver dysfunction.

Induction therapy with interleukin-2 receptor antagonists has been established as an effective immunosuppressive strategy in the management of heart transplant (HTx) recipients. We compared outcomes following HTx in patients receiving basiliximab, daclizumab, or no induction therapy.We investigated post-transplant prognosis of patients receiving basiliximab (n=67), daclizumab (n=98) or no induction therapy (n=70). Patients treated with daclizumab (50.3 ± 14.7 years) were younger than those receiving basiliximab (55.8 ± 11.2 years) or no induction therapy (54.9 ± 14.1 years; both P0.05). Patients receiving either induction therapy showed better survival 1 year after HTx (95%) than those without induction therapy (82%; P0.001). Survival was similar between patients receiving basiliximab and daclizumab. The incidence of acute cellular or antibody-mediated rejections did not differ among the groups. The main reason that patients did not receive induction therapy was ongoing infection (65.7%), which was more common in patients on ventricular assist device (VAD) support than those without VAD (76.1% vs. 45.8%; P=0.004). The VAD-related infection rate in the entire study cohort was 29.7% (35/118 VAD recipients).Survival following HTx was worse in patients not receiving induction therapy. No differences were noted in survival or the incidence of rejection between the daclizumab- and basiliximab-treated groups. Induction therapy was less used in patients with infection, which was related to prior VAD support.

Heart failure (HF) is associated with the derangement of muscle structure and metabolism, contributing to exercise intolerance, frailty, and mortality. Reduced handgrip strength is associated with increased patient frailty and higher morbidity and mortality. We evaluated handgrip strength as a marker of muscle function and frailty for prediction of clinical outcomes after ventricular assist device (VAD) implantation in patients with advanced HF.Handgrip strength was measured in 72 patients with advanced HF before VAD implantation (2.3 ± 4.9 days pre-VAD). We analyzed dynamics in handgrip strength, laboratory values, postoperative complications, and mortality. Handgrip strength correlated with serum albumin levels (r = 0.334, P = .004). Compared with baseline, handgrip strength increased post-VAD implantation by 18.2 ± 5.6% at 3 months (n = 29) and 45.5 ± 23.9% at 6 months (n = 27). Patients with a handgrip strength25% of body weight had an increased risk of mortality, increased postoperative complications, and lower survival after VAD implantation.Patients with advanced HF show impaired handgrip strength indicating a global myopathy. Handgrip strength25% of body weight is associated with higher postoperative complication rates and increased mortality after VAD implantation. Thus, the addition of measures of skeletal muscle function underlying the frailty phenotype to traditional risk markers might have incremental prognostic value in patients undergoing evaluation for VAD placement.

Hypoalbuminemia has been recognized as a prognostic indicator in patients with heart failure. We aimed to investigate the association of hypoalbuminemia with postoperative mortality in patients undergoing left ventricular assist device (LVAD) implantation. We studied 272 consecutive patients undergoing LVAD implantation from 2000 to 2010 at our institution. Preoperative clinical characteristics and laboratory variables associated with mortality were analyzed. Postoperative survival of patients with preoperative hypoalbuminemia (

Background Previous studies have shown remarkable decrease in size of the left ventricle after left ventricular assist device (LVAD) implantation due to mechanical unloading. However, a certain number of patients continue to have significant mitral regurgitation (MR) under LVAD support. We investigated pre-operative echocardiographic features associated with persistent MR after LVAD implantation. Methods We retrospectively reviewed 82 consecutive patients undergoing continuous-flow LVAD implantation between 2007 and 2010. We obtained echocardiograms performed within 2 weeks before and 1 week after surgery. We investigated the pre-operative echocardiographic findings associated with significant MR post-LVAD and compared 1-year mortality after LVAD surgery between patients with and without significant MR post-LVAD. Results MR was significant in 43 patients (52.4%) before LVAD surgery. Among those, 5 underwent concomitant mitral valve repair (MVr) at the time of LVAD implantation. Of the remaining 38 patients, 25 (65.8%) showed improvement of MR, whereas 13 patients (34.2%) continued to have significant MR post-LVAD. Multivariate analysis revealed that posterior displacement of the coaptation point of mitral leaflets was significantly associated with significant MR post-LVAD (hazard ratio, 1.335; 95% confidence interval, 1.035–1.721; p = 0.026) even after adjusting for the amount of pre-operative MR flow. Post-LVAD 1-year survival of patients with and without significant MR post-LVAD was not significantly different (92.3% vs 89.1%, p = 0.826). Conclusions Pre-LVAD posterior displacement of mitral leaflets may be indicative of post-operative significant MR, which would help identify echocardiographic features of functional MR refractory to simple volume reduction of the ventricle.

Background Studies have shown that patients with poor pre-lung transplant (LTx) right ventricular (RV) function have prolonged post-operative ventilation time and intensive care stay as well as a higher risk of in-hospital death. RV stroke work index (RVSWI) calculates RV workload and contractility. We hypothesized that patients with higher RV workload capacity, indicated by higher RVSWI, would have better outcomes after LTx. Methods A retrospective record review was performed on all LTx patients between 2005 and 2011 who had right heart catheterizations (RHC) 1-year before LTx. In addition, results for echocardiograms and cardiopulmonary exercise testing within 1-year of RHCs were gathered. Results Mean RVSWI was 9.36 ± 3.59 for 115 patients. There was a significant relation between mean pulmonary artery pressure (mPAP), RVSWI, RV end-diastolic diameter (RVEDd), left atrial dimension (LAD), peak and resting pressure of end-tidal carbon dioxide, minute ventilation /volume of carbon dioxide production , and 1-year mortality after LTx. Contrary to our hypothesis, those who survived had lower RVSWI than those who died within 1 year (8.99 ± 3.38 vs 11.6 ± 4.1, p = 0.026). Hospital length of stay significantly correlated with mPAP, RVSWI, left ventricular ejection fraction, percentage of fractional shortening, RVEDd, RV fractional area change, LAD, and RV wall thickness in diastole. Intensive care length of stay also significantly correlated with these variables and with body mass index. RVSWI was significantly different between groups of different RV function, indicating that increased RVSWI is associated with impairment of RV structure and function in patients undergoing LTx evaluation. Conclusions This study demonstrates an association between 1-year mortality, initial hospital and intensive care length of stay, and pre-LTx RVSWI. Increased mPAP is a known risk for outcomes in LTx patients. Our findings support this fact and also show increased mortality with elevation of RVSWI, demonstrating the value of RV function in the assessment of risk for pre-LTx patients.

Background— Alternate waiting list strategies expand listing criteria for patients awaiting heart transplantation (HTx). We retrospectively analyzed clinical events and outcome of patients listed as high-risk recipients for HTx. Methods and Results— We analyzed 822 adult patients who underwent HTx of whom 111 patients met high-risk criteria. Clinical data were collected from medical records and outcome factors calculated for 61 characteristics. Significant factors were summarized in a prognostic score. Age >65 years (67%) and amyloidosis (19%) were the most common reasons for alternate listing. High-risk recipients were older (63.2±10.2 versus 51.4±11.8 years; P P =0.0005). Prior cerebral vascular accident, albumin 2 prior sternotomies were associated with poor survival after HTx. A prognostic risk score (CARRS [CVA, albumin, re-HTx, renal dysfunction, and sternotomies]) derived from these factors stratified survival post-HTx in high-risk (3+ points) versus low-risk (0–2 points) patients (87.9% versus 52.9% at 1-year; 65.9% versus 28.4% at 5-year post-HTx; P P =0.46). Conclusions— High-risk patients had reduced survival compared with regular patients post-HTx. Among patients previously accepted for alternate donor listing, application of the CARRS score identifies patients with unacceptably high mortality after HTx and those with a survival similar to regularly listed patients.

Risk stratification of ambulatory heart failure (HF) patients has relied on peak VO(2)14 ml/kg/min. We investigated whether additional clinical variables might further specify risk of death, ventricular assist device (VAD) implantation (INTERMACS4) or heart transplantation (HTx, Status 1A or 1B) within 1 year after HTx evaluation. We hypothesized that right ventricular stroke work index (RVSWI), pulmonary capillary wedge pressure (PCWP) and the model for end-stage liver disease-albumin score (MELD-A) would be additive prognostic predictors.We retrospectively collected data on 151 ambulatory patients undergoing HTx evaluation. Primary outcomes were defined as HTx, LVAD or death within 1 year after evaluation.Average age in our cohort was 55 ± 11.1 years, 79.1% were male and 39% had an ischemic etiology (LVEF 21 ± 10.5% and peak VO(2) 12.6 ± 3.5 ml/kg/min). Fifty outcomes (33.1%) were observed (27 HTxs, 15 VADs and 8 deaths). Univariate logistic regression showed a significant association of RVSWI (OR 0.47, p = 0.036), PCWP (OR 2.65, p = 0.007) and MELD-A (OR 2.73, p = 0.006) with 1-year events. Stepwise regression showed an independent correlation of RVSWI5gm-m(2)/beat (OR 6.70, p0.01), PCWP20 mm Hg (OR 5.48, p0.01), MELD-A14 (OR 3.72, p0.01) and peak VO(2)14 ml/kg/min (OR 3.36, p = 0.024) with 1-year events. A scoring system was developed: MELD-A14 and peak VO(2)14-1 point each; and PCWP20 and RVSWI5-2 points each. A cut-off at≥4 demonstrated a 54% sensitivity and 88% specificity for 1-year events.Ambulatory HF patients have significant 1-year event rates. Risk stratification based on exercise performance, left-sided congestion, right ventricular dysfunction and liver congestion allows prediction of 1-year prognosis. Our findings support early and timely referral for VAD and/or transplant.

Background Controversy exists whether heart transplantation (HTx) is an appropriate treatment option for patients with cardiac sarcoidosis due to its potential recurrence and multi-organ involvement. Recent data from the United Network for Organ Sharing dataset suggest that the clinical outcome of cardiac sarcoidosis patients is equivalent or even better than that of the general HTx population. Methods We retrospectively reviewed the clinical course of 14 patients with cardiac sarcoidosis among a total of 825 patients who underwent HTx at Columbia University Medical Center between 1997 and 2010. Post-transplant survival of patients with sarcoidosis was compared with that of non-sarcoidosis patients. Results More than half of cardiac sarcoidosis patients were initially diagnosed after HTx by tissue analysis of the explanted heart. While only 2/14 cases showed recurrence of cardiac sarcoidosis, the clinical outcome of sarcoid patients showed a trend toward higher mortality than that of non-sarcoidosis patients following HTx (1- and 5-year survival, 78.5 versus 87.2%, 52.4 versus 76.2%, respectively, p = 0.09). Conclusions Although this is a single-center, retrospective analysis of a small number of cardiac sarcoidosis patients who underwent HTx, a concerning trend toward a higher mortality of patients with cardiac sarcoidosis was noted. A careful candidate selection in patients with known cardiac sarcoidosis should be discussed.

Adequate fluid management is an important component of patient care following cardiac surgery. Our aim in this study was to determine the benefits of tolvaptan, an oral selective vasopressin-2 receptor antagonist that causes electrolyte-free water diuresis, in postoperative fluid management. We prospectively examined the effect of tolvaptan on renal excretion of electrolytes and urea nitrogen in cardiac surgery patients. Patients undergoing coronary artery bypass surgery were randomized to receive conventional loop diuretics (Group C, n = 30) or conventional loop diuretic therapy plus tolvaptan (Group T, n = 27). Fractional excretions of sodium (FENA), potassium (FEK) and urea nitrogen (FEUN) were measured in both groups during post-surgical hospitalization. Urine output was greater with tolvaptan (Group T) than without it (Group C), and some patients in Group C required intravenous as well as oral loop diuretics. Serum sodium concentrations decreased after surgery in Group C, but were unchanged in Group T (postoperative day [POD] 3, 139.8 ± 3.5 vs. 142.3 ± 2.6 mEq/L, p = 0.006). However, postoperative FENA values in Group C did not decrease, and the values were similar in both groups. Serum potassium levels remained lower and FEK values remained higher than the preoperative values, but only in Group C (all p

Effective therapeutic options for advanced hepatocellular carcinoma are limited. Hematopoietic stem cell transplantation may offer a graft-versus-tumor effect. Combined liver and hematopoietic stem cell transplantation from the same donor with preparatory conditioning may promote tolerogenicity to the liver allograft and offers the potential for immunosuppression withdrawal. We report our experience with the use of this approach in a pediatric patient with invasive hepatocellular carcinoma and pulmonary metastases who underwent a living-donor liver transplantation followed by reduced-toxicity myeloablative conditioning and hematopoietic stem cell transplant from the same parental donor. Neutrophil engraftment and full donor chimerism was achieved without liver allograft dysfunction. Despite normal liver function and marrow engraftment, the patient succumbed to multisystem organ failure from disseminated toxoplasmosis. At autopsy, there was no histologic evidence of tumor recurrence. No pulmonary nodules were found. Regardless of the unfortunate overall result, this case demonstrates preliminary feasibility of sequential living-donor liver transplantation and hematopoietic stem cell transplantation for unresectable and metastasized hepatic tumors. Future studies in select pediatric patients require evaluation of the optimal conditioning regimen and prevention strategies for opportunistic infections to determine both graft-versus-tumor effect on hepatic tumors and durability of tolerogenicity and possible immunosuppression withdrawal.

Background Obesity has been found to be associated with future development of diastolic heart failure. Other evidence has indicated that the effect of obesity on left ventricular (LV) mass varies among ethnicities. However, there are few data on the relationship between body mass index (BMI) and LV diastolic dysfunction in the Japanese population. Methods and results We performed echocardiography in 788 subjects without valvular disease or LV systolic dysfunction. They were divided into 3 groups by BMI: normal weight, overweight, and obese. We used multivariable linear regression analysis to assess the clinical variables associated with diastolic parameters, including BMI. We also assessed the risk of diastolic dysfunction associated with BMI using multivariable logistic models. Overweight and obese subjects had significantly worse LV diastolic function and greater LV mass than normal weight subjects. In the multivariable analysis, BMI was independently associated with diastolic parameters. Furthermore, after adjusting for clinical factors, the increased risks of diastolic dysfunction in overweight subjects (adjusted odds ratio: 2.02, 95% confidence interval 1.21-3.36) and obese subjects (4.85, 3.36-16.27) were greater than those previously observed in Western populations. Conclusions The Japanese population might be more susceptible than Western subjects to the effect of BMI on LV diastolic function. Differences between ethnicities should be taken into consideration in strategies for the prevention of diastolic heart failure. (Circ J 2016; 80: 1951-1956).

Background Galectin-3 is a marker of myocardial inflammation and fibrosis shown to correlate with morbidity and mortality in heart failure (HF). We examined the utility of galectin-3 as a marker of the severity of HF, the response of galectin-3 levels to ventricular assist device (LVAD) implantation or heart transplantation (HTx), and its use as a prognostic indicator. Methods Plasma galectin-3 was measured using a commercially available ELISA assay in patients with stable HF (n = 55), severe HF (n = 63), at 3 (n = 17) and 6 (n = 14) months post-LVAD and at LVAD explantation (n = 23), patients following HTx (n = 85) and healthy controls (n = 30). Results Galectin-3 levels increase with the severity of HF (severe HF: 28.2 ± 14, stable HF: 19.7 ± 13, p = 0.001; controls: 13.2 ± 9 ng/ml, p = 0.02 versus stable HF). Following LVAD implantation, galectin-3 levels are initially lower (3 months: 23.7 ± 9, 6 months: 21.7 ± 9 versus 29.2 ± 14 ng/ml implantation; p = NS) but are higher at explantation (40.4 ± 19 ng/ml; p = 0.005 versus pre-LVAD). Galectin-3 levels >30 ng/ml are associated with lower survival post-LVAD placement (76.5 % versus 95.0 % at 2 years, p = 0.009). After HTx, galectin-3 levels are lower (17.8 ± 7.1 ng/ml post-HTx versus 28.2 ± 14 pre-HTx; p

Cardiopulmonary bypass usage provokes a systemic inflammatory response resulting in deterioration of renal function. However, risk factors for requiring renal replacement therapy (RRT) following off-pump coronary artery bypass graft surgery (CABG) have not yet been fully elucidated. We reviewed 718 consecutive patients undergoing elective off-pump CABG at our institution, excluding patients on chronic hemodialysis preoperatively. Sub-analysis of patients with preserved renal function, defined as a creatinine level below a cut-off value of 1.12 mg/dL (obtained by receiver operating characteristic curve), was also performed. Of the 718 patients, 41 (5.7 %) required RRT. There were 556 patients (77.4 %) with preserved renal function preoperatively, and 13 (2.4 %) of these required postoperative RRT. Multivariate analysis revealed that age (years) and preoperative serum creatinine (mg/dL) and brain natriuretic peptide (BNP) levels (pg/dL) were associated with RRT [odds ratios (OR) 1.052, 95 % confidence interval (CI) 9.064 and 1.001, respectively, all p

Cardiac transplantation is a treatment option for patients with hypertrophic cardiomyopathy (HC) who developed refractory heart failure and/or intractable arrhythmia. However, the pretransplant characteristics and post-transplant prognosis for patients with nondilated idiopathic HC has not yet fully elucidated. Therefore, we retrospectively reviewed 813 consecutive transplant recipients undergoing cardiac transplantation at Columbia University Medical Center from 1999 to 2010 and compared the clinical course of 41 patients with idiopathic HC with that of 373 patients with ischemic heart disease and 398 patients with other heart disease. The patients with HC were younger than those with ischemic heart disease (47.8 ± 14.0 vs 57.1 ± 9.4 years; p0.0001). The proportion of patients undergoing ventricular assist devise surgery for bridge-to-transplant was lower in patients with HC than in those with ischemic heart disease or other heart disease (14.6% vs 31.1% vs 35.7%, all p0.01). The post-transplant survival of those with HC was better than that for those with ischemic heart disease (90.1% vs 85.8% and 83.9% vs 67.1% at 1 and 5 years, respectively; p = 0.0359), although it was not significantly different from those with other heart disease. Proportional hazards analysis revealed that the subjects with HC had reduced post-transplant mortality (hazard ratio 0.4760, 95% confidential interval 0.1889 to 0.9762; p = 0.042) on univariate, but not multivariate, analysis. Most patients with HC had nondilated left ventricles (left ventricular end-diastolic dimension ≤ 55 mm; n = 27), and post-transplant survival did not differ from that for those with dilated left ventricles (left ventricular end-diastolic dimension55 mm; n = 14). In conclusion, the post-transplant survival of those with HC did not differ from those of the subjects who underwent transplant for other non-HC indications.

Cardiac extracellular matrix (ECM) is a dynamic and metabolically active collagenous network that responds to mechanical strain. The association between ECM turnover and right ventricular failure (RVF) development after left ventricular assist device (LVAD) implantation in patients with advanced heart failure (HF) was investigated.Circulating levels of osteopontin, metalloproteinases (MMP)-2 and MPP-9, and tissue inhibitor of MMP (TIMP)-1 and TIMP-4 were measured in 61 patients at LVAD implantation and explantation and in 10 control subjects. RVF was defined as the need for RVAD, nitric oxide inhalation48 hours and/or inotropic support14 days.All ECM markers were elevated in patients with HF compared with controls (all p0.05). RVF developed in 23 patients (37.7%) on LVAD support. All ECM markers decreased on LVAD support in patients without RVF (all p0.05), but serum MMP-2, TIMP-1, TIMP-4, and osteopontin remained elevated in RVF patients. Multivariate analysis identified that right ventricular stroke work index (RVSWI), circulating B-type natriuretic peptide, and osteopontin were associated with RVF (all p0.05). Osteopontin correlated inversely with RVSWI (r = -0.44, p0.001). Osteopontin levels260 ng/ml discriminate patients who develop RVF from those without RVF (sensitivity, 83%; specificity, 82%).Marked elevation of osteopontin levels before LVAD placement is associated with RVF development. Persistent elevation of circulating ECM markers after LVAD implantation characterizes patients who develop RVF. These novel biomarkers would have a potential role in the prediction of RVF development in patients undergoing LVAD implantation.

BACKGROUND Off-pump coronary artery bypass grafting (OPCAB) has evolved into a standard technique in coronary artery bypass grafting. However, a detailed investigation in Japanese population undergoing OPCAB has not yet been fully elucidated. METHODS A total of 1109 consecutive patients undergoing isolated OPCAB between 2006 and 2013 at Juntendo University were reviewed. The data was evaluated in the light of previously published OPCAB-associated reports. RESULTS There were 904 male (81.5%) and a mean was 67.5 ± 9.8 years. Eight patients (0.5%) died within 30 days postoperatively or before discharge, which was equivalent to or rather better than the previously reported mortality rates, including the European System for Cardiac Operation Risk Evaluation II (2.1 ± 2.1) data. A morbidity analysis revealed that prolonged intubation (>24 h) occurred in 43 patients (3.6%), surgical site infections in 18 (1.9%), neurological complications in 13 (1.3%). A reduced preoperative left ventricular ejection fraction (less than 40%) was found to be a risk factor for early postoperative death (odds ratio 10.58, respectively, p

Background Increased left atrial volume (LAV) predicts a higher incidence of cardiovascular events and is widely recognized as a major surrogate marker of left ventricular (LV) diastolic dysfunction (DD). Although the pathophysiology of LA enlargement is probably multifactorial, few studies have examined comprehensively the clinical factors that lead to LA enlargement in the absence of valvular disease or LV systolic dysfunction. Therefore, we investigated associations between LAV and several clinical and echocardiographic parameters including DD. Methods We enrolled 557 subjects without significant valve disease or LV systolic dysfunction from the health check-up clinic retrospectively. We performed univariable and multivariable linear regression using ln LAV index as the dependent variable and the following independent variables: gender, age, smoking status, drinking habit, hypertension, diabetes, body mass index (BMI), LV ejection fraction, DD, LV mass index, hemoglobin, serum creatinine, serum total cholesterol, serum uric acid, serum sodium, and serum iron. Results In multivariable analysis, LAV index was independently associated with BMI, lower hemoglobin, and moderate and severe DD compared with normal diastolic function (p Conclusions LA enlargement was independently associated with moderate and severe DD, but not with mild DD. Furthermore, obesity and lower hemoglobin were associated with LAV independently of DD.

Background Renal failure is a serious complication after cardiac surgery, which can be caused by long-term intravenous (IV) loop diuretic use. Tolvaptan is an oral selective vasopressin-2 receptor antagonist used in patients irresponsive to loop diuretics. We investigated their renal perfusion changes using the resistive index (RI) postoperatively. Methods Serial renal RI, echocardiography, and laboratory examinations from 14 patients requiring continuous postoperative IV loop diuretics were reviewed. Eight patients received tolvaptan (Group T) and six received oral loop diuretics before the discontinuation of IV loop diuretics (Group L). The 1st data were obtained between postoperative day 0 and 2, the 2nd when patients were still under IV loop diuretic treatment, the 3rd after the initiation of tolvaptan or oral loop diuretic, and the 4th after the discontinuation of IV diuretics. Results The 2nd RI value was higher in Group T than Group L (0.77 ± 0.09 vs. 0.69 ± 0.01, p = 0.049) but significantly decreased after tolvaptan administration [0.77 ± 0.09 to 0.65 ± 0.05 (2nd to 3rd), to 0.62 ± 0.04 (to 4th), both p = 0.006], while no such changes were seen in Group L. The serum sodium and albumin levels, and echo-derived tricuspid annular plane systolic excursion increased only in Group T (134.1 ± 1.5 to 138.8 ± 3.2 mEq/L, 3.3 ± 0.3 to 3.7 ± 0.5 g/dL, 16.4 ± 3.6 to 19.7 ± 4.2 mm, all p

BACKGROUND Cerebrovascular accidents (CVA) are a major adverse event following cardiac surgery, for which atrial fibrillation (AF) is considered as a risk factor. We have recently performed left atrial appendage (LAA) surgical closure or amputation (LAAC/A), which is the main source of emboli, during open-heart surgery. METHODS AND RESULTS A prospective observational study of 1,831 consecutive patients (69.2% male, aged 66.8±12.2 years) undergoing cardiac surgery between 2009 and 2013 was performed. The incidence of postoperative CVA within 6 months in patients with and without LAAC/A was compared. We further stratified patients according to their risk of CVA using CHA2DS2-VASc score; dichotomizing low-risk (score

The aim of the present study was to investigate the relationship between rejections and gene expression of Ca(2+)-handling proteins in heart transplant recipients. Thirty-seven heart transplant recipients underwent routine endomyocardial biopsy. Levels of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) and ryanodine receptor-2 mRNAs in endomyocardial tissue were quantified by a real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) method. Rejections were diagnosed according to the conventional International Society for Heart and Lung Transplantation criteria. Patients were classified as follows; group AR(+) (n = 9) with rejection grade of 2 or higher versus group AR(-) (n = 28) with rejection grade of 0, 1a or 1b at the time of biopsy, and group Rec-AR(+) (n = 6) with a history of more than 4 episodes of treatment required rejection versus group Rec-AR(-) (n = 31) without history of recurrent rejection. The mRNA levels of the SERCA2/GAPDH ratio and ryanodine receptor-2/GAPDH ratio were not different between group AR(+) and group AR(-); however, they were reduced in group Rec-AR(+) more than in group Rec-AR(-) (0.83 +/- 0.07 versus 0.90 +/- 0.07, P = 0.034, 0.74 +/- 0.06 versus 0.84 +/- 0.10, P = 0.027, respectively). A single episode of on-going rejection would not affect myocardial Ca(2+)-handling proteins; however, cumulative rejection episodes might alter the gene expression of myocardial Ca(2+)-handling proteins in heart transplant recipients.

Thermal therapy for heart failure is recognized to improve clinical symptoms. We describe our experience with appendicular thermal therapy applied to a patient fitted with an extracorporeal left ventricular assist device (LVAD) who was wait-listed for a heart transplant. A 21-year-old male with end-stage heart failure due to dilated cardiomyopathy was fitted with a LVAD. His general condition stabilized after LVAD placement and the status of his heart failure has remained at NYHA class II for the past 13 months. However, his cardiac function did not sufficiently recover to discontinue LVAD support. We conducted appendicular thermal therapy using a steam foot bath and heated gloves for 2 weeks. Immediately after thermal therapy, his average sublingual temperature increased from 36.3 to 37.0°C and the grade of mitral regurgitation, as well as LV ejection fraction and endothelial function improved. Furthermore, levels of oxidative and anti-oxidative stress markers decreased and increased, respectively, after 2 weeks of therapy. No complications developed. We conclude that appendicular thermal therapy was safe in this patient waiting for a heart transplant and who had an extracorporeal LVAD, and that the procedure might be beneficial for others with end-stage heart failure.

Objectives We performed dobutamine stress testing for evaluation of myocardial contractile reserve in asymptomatic or mildly symptomatic patients with dilated cardiomyopathy (DCM). Background Catecholamine sensitivity is reduced in failing hearts as a result of myocardial abnormalities in the beta-adrenergic receptor signaling pathway. However, little is known about adrenergic myocardial contractile reserve in asymptomatic or mildly symptomatic patients with DCM. Methods The maximal first derivative of left ventricular pressure (LV dP/dtmax) was determined during infusion of dobutamine (10 μg kg−1 min−1) in 46 asymptomatic or mildly symptomatic (New York Heart Association functional class I or II) patients with DCM. The expression of messenger ribonucleic acid (mRNA) for contractile regulatory proteins in endomyocardial biopsy specimens was quantified by reverse transcription and real-time polymerase chain reaction analysis. Plasma norepinephrine levels were measured in all patients and [123I]metaiodobenzylguanidine (MIBG) scintigraphy performed. Results Patients were classified into 3 groups based on the percentage increase in LV dP/dtmax induced by dobutamine (ΔLV dP/dtmax) and on LV ejection fraction (LVEF) at baseline: group I (n = 18): ΔLV dP/dtmax >100% and LVEF >25%; group IIa (n = 17): ΔLV dP/dtmax ≤100% and LVEF > 25%; and group IIb (n = 11): ΔLV dP/dtmax ≤100% and LVEF ≤25%. The amounts of beta1-adrenergic receptor, sarcoplasmic reticulum Ca2+-adenosine triphosphatase, and phospholamban mRNA were significantly smaller in groups IIa and IIb than in group I. The plasma norepinephrine level was increased and the delayed heart/mediastinum count ratio in MIBG scintigraphy was decreased in both groups IIa and IIb. Conclusions Dobutamine stress testing is a useful diagnostic tool for identifying reduced adrenergic myocardial contractile reserve related to altered myocardial expression of beta1-adrenergic receptor, sarcoplasmic reticulum Ca2+-adenosine triphosphatase, and phospholamban genes even in asymptomatic or mildly symptomatic patients with DCM.

Background The purpose of the study was to characterize the pharmacokinetics of mycophenolic acid (MPA) in Japanese heart transplant recipients and to find the time point that has the best correlation with the MPA area under the plasma concentration curve (AUC). Methods and Results Twenty-two Japanese recipients treated with mycophenolate mofetil were evaluated in the study. Approximately 9 months after transplantation, the area under the MPA serum concentration-time curve from 0 to 12 h (AUC0-12 h) was evaluated. The MPA AUC0-12 h h values in the cyclosporine (CsA) and tacrolimus (FK) groups ranged from 13.11 to 50.98 μg · h/ml and from 39.19 to 93.18 μg · h/ml, respectively. Fourteen models were developed and analyzed for their ability to estimate the MPA AUC0-12 h based on a limited number of samples in the CsA group. Sixteen models were developed in the FK group. The best model for predicting the full MPA AUC0-12 h in the CsA group was a 3-time-point model that included C0 h, C1 h and C2 h (r2, 0.96; mean prediction error, 0.15±7.85%); a 2-time-point model that included C0 h, and C2 h (r2, 0.94; mean prediction error, 0.495±10.35%) was also reliable. In the FK group, a 3-time-point model that included C1 h, C2 h and C4h (r2, 0.73; mean prediction error, 2.73±17.09%) was the best model for predicting the full MPA AUC0-12 h, but it was not reliable in clinical practice. Conclusion A 3-(C0 h, C1 h and C2 h) and a 2-time-point model (C0 h and C2 h) are useful for predicting the full MPA AUC0-12 h in Japanese heart transplant recipients treated with CsA but not with FK. (Circ J 2007; 71: 1022 - 1028)

Background The prevalence of left ventricular diastolic dysfunction (LVDD) sharply increases in women after their 50s and may contribute to the high prevalence of diastolic heart failure in elderly women. A decrease in estrogen levels after menopause is postulated to be one of the mechanisms responsible for this phenomenon. However, there is a paucity of data on the relationship between the timing of menopause and the progression of LVDD in the clinical setting; thus, we investigated this relationship in healthy postmenopausal women. Methods We enrolled 115 women and divided them into two groups according to median menopause age: 61 who experienced menopause at ≤50 years (early menopause group), and 54 who experienced menopause at >50 years (late menopause group). We compared the echocardiographic and clinical characteristics between the two groups. Results There were no significant differences in LV diastolic parameters (mitral E/A, p = 0.561; e’, p = 0.052; E/e’, p = 0.081; DCT, p = 0.082; prevalence of LVDD class, p = 0.801), as well as other echocardiographic parameters and clinical characteristics between the two groups. Multivariate linear regression analysis showed that the independent determinants of LVDD were age and body mass index, but not the timing of menopause. Conclusions Early menopause did not influence the progression of LVDD in postmenopausal women. The sharp progression of LVDD in elderly women is complex and probably influenced by multiple factors.

Background The aim of our study was to examine and compare the predictive value of operative mortality of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, the Society of Thoracic surgeons (STS) score, the Ambler score, and the Japan score in patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS). Methods A total of 406 patients undergoing AVR with or without coronary artery bypass grafting (CABG, n = 139) at our institution from August 2002 to December 2013 were enrolled in this cohort study. Accuracy of calibration and discrimination performance of four risk scores was assessed in the overall patient population and quartiles of each risk score. Results Operative mortality was 3.4% ( n = 14). The mean EuroSCORE II, STS score, Ambler score, and the Japan score were 3.1%, 4.9%, 5.7%, and 3.2%, respectively, giving observed-to-expected (O/E) ratio of 1.09, 0.69, 0.59, and 1.06. The C -statistics for operative mortality were 0.704 (EuroSCORE II), 0.781 (STS score), 0.709 (Ambler score), and 0.771 (Japan score). In the last quartile, the EuroSCORE II demonstrated excellent calibration (O/E ratio = 0.97) and discrimination ( C -statistic = 0.904), and the STS score (O/E ratio = 0.86, C -statistic = 0.779) and the Japan score (O/E ratio = 1.14, C -statistic = 0.80) showed reasonable correlation. However, the risk calibration by the Ambler score in the last quartile was unacceptable (O/E ratio = 0.60). Conclusions The EuroSCORE II and the Japan score showed superior ability of calibration, but the STS score and the Ambler score overestimated the risk. However, the discrimination power was similar among the four risk scores. In the last quartile of risk, the EuroSCORE II gave an excellent predictive performance.

Epicardial adipose tissue is a source of pro-inflammatory cytokines and has been linked to the development of coronary artery disease. No study has systematically assessed the relationship between local epicardial fat volume (EFV) and myocardial perfusion defects. We analyzed EFV in patients undergoing SPECT myocardial perfusion imaging combined with computed tomography (CT) for attenuation correction. Low-dose CT without contrast was performed in 396 consecutive patients undergoing SPECT imaging for evaluation of coronary artery disease. Regional thickness, cross-sectional areas, and total EFV were assessed. 295 patients had normal myocardial perfusion scans and 101 had abnormal perfusion scans. Mean EFVs in normal, ischemic, and infarcted hearts were 99.8 ± 82.3 cm(3), 156.4 ± 121.9 cm(3), and 96.3 ± 102.1 cm(3), respectively (P 0.001). Reversible perfusion defects were associated with increased local EFV compared to normal perfusion in the distribution of the right (69.2 ± 51.5 vs 46.6 ± 32.0 cm(3); P = 0.03) and left anterior descending coronary artery (87.1 ± 76.4 vs 46.7 ± 40.6 cm(3); P = 0.005). Our results demonstrate increased regional epicardial fat in patients with active myocardial ischemia compared to patients with myocardial scar or normal perfusion on nuclear perfusion scans. Our results suggest a potential role for cardiac CT to improve risk stratification in patients with suspected coronary artery disease.

Background— The differentiation of hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) on the basis of morphological information obtained by conventional echocardiography is occasionally problematic. We investigated whether strain rate (SR) imaging derived from tissue Doppler imaging (TDI) is able to discriminate HCM from H-LVH. Methods and Results— Conventional echocardiography and TDI were performed with 34 patients with LVH and 16 reference subjects. Mean values of systolic strain (ε sys ), peak systolic SR, and early diastolic SR obtained from 8 left ventricular (LV) segments were calculated. LV pressures were recorded simultaneously in the patients. Patients were diagnosed with HCM (n=20) or H-LVH (n=14) on the basis of conventional echocardiography and endomyocardial biopsy findings. Multivariate analysis revealed that septum/posterior wall thickness ratio ( P =0.00013) and ε sys ( P sys cutoff value of −10.6% discriminated between HCM and H-LVH with a sensitivity of 85.0%, specificity of 100.0%, and predictive accuracy of 91.2%. The combination of the septum/posterior wall thickness ratio and ε sys discriminated HCM from H-LVH with a predictive accuracy of 96.1%. The ε sys parameter was significantly correlated with pulmonary arterial wedge pressure, LV end-diastolic pressure, the peak positive first derivative of LV pressure, and the time constant of LV pressure decay. Conclusions— SR imaging is able to discriminate HCM from H-LVH, with ε sys reflecting myocardial contractile and lusitropic properties.

Background and Purpose— Stroke is a major adverse event after left ventricular assist device (LVAD) surgery. The purpose of this study was to describe differences in hemispheric distribution of stroke in LVAD patients. Methods— We reviewed 317 consecutive patients who underwent LVAD surgery between November 2000 and July 2011. Stroke during LVAD support was analyzed. Results— In total, 46 strokes occurred at 76.0±96.8 days postoperatively. Among the 46 strokes, 27 events (58.7%) occurred in right hemisphere, 13 events (28.2%) in the left hemisphere, 3 events (8.7%) occurred bilaterally, and 2 events (4.3%) were vertebrobasilar lesions. The right hemispheric stroke was significantly more common in patients with postoperative infection compared with left hemispheric events. Conclusions— Stroke after LVAD implantation has a right hemispheric predominance. This finding suggests LVAD-related thrombus in the setting of infection and/or the anatomic configuration of LVAD outflow cannula-ascending aorta anastomosis to be highly associated with stroke after LVAD surgery.

Peripheral vascular disease (PVD) portends increased morbidity and mortality in patients with heart failure. In those with advanced heart failure, heart transplantation (HT) is the only causative therapy to increase survival. However, little is known about the impact of symptomatic PVD on survival of HT recipients in large multicenter cohorts. The aim of this study was to investigate an association between recipient symptomatic PVD and survival after HT. We analyzed 20,297 patients from the United Network of Organ Sharing data set. Survival analysis using a control cohort established by propensity matching was performed. There was an increased prevalence of traditional cardiovascular risk factors in 711 patients with symptomatic PVD compared with 19,586 patients without PVD. Patients with pre-transplant symptomatic PVD had increased post-transplant mortality compared with those without PVD (1-, 5- and 10-year survival rate 91.5% vs 94.9%, 74.8% vs 82.6%, 48.6% vs 54.7%, respectively, log-rank p

Progressive renal dysfunction develops in patients with advanced HF. We evaluated neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C compared with established markers of renal function in patients with heart failure (HF) because they might improve prognostic assessment of patients with HF.Serum samples were collected from 40 patients with stable HF (age: 58 ± 8 years, body mass index [BMI]: 28.4 ± 6.4 kg/m(2)), 40 HF patients undergoing ventricular assist device (VAD) implantation (age: 53 ± 11 years, BMI: 26.8 ± 5.5 kg/m(2)), 40 patients undergoing VAD removal at cardiac transplantation, and 24 controls (age: 48 ± 7 years, BMI: 29.4 ± 4.2 kg/m(2)). Clinical data were collected from institutional medical records. NGAL and cystatin C levels were measured by enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease formula.Patients with stable HF showed elevated NGAL and cystatin C levels compared with controls (NGAL: 114.9 ± 48.3 ng/mL vs 72.0 ± 36.6 ng/mL, p0.0001; cystatin C: 1490.4 ± 576.1 ng/mL vs 954.7 ± 414.2 ng/mL, p = 0.0026). Unlike cystatin C, NGAL increased in advanced HF patients requiring VAD implantation (158.7 ± 74.8 ng/mL, p0.001). On VAD support, NGAL levels decreased (127.1 ± 80.4 ng/mL, p = 0.034). NGAL was higher in patients who developed right ventricular failure (187.8 ± 66.0 vs 130.9 ± 67.0 ng/mL, p = 0.03) and irreversible renal dysfunction (190.0 ± 73.8 ng/mL vs 133.8 ± 54.2 ng/mL, p0.05), whereas cystatin C, creatinine, and eGFR were not different. NGAL correlated with eGFR (r = -0.2188, p = 0.01).NGAL levels correlate with HF severity and hemodynamic improvement after VAD placement. Our findings suggest a role of this novel biomarker as a marker of severity and prognosis in patients with HF.

Thrombus formation inside of the pump is a major cause for device malfunction following the left ventricular assist device (LVAD) implantation. We recently established a novel ramp test protocol facilitating continuous bedside echo monitoring to optimize LVAD function and diagnosing device malfunctions. We describe a case of 29-year-old woman undergoing HeartMate II LVAD implantation, in whom serial ramp studies were used to diagnose intra-device thrombus after device implantation. The 1st ramp study at postoperative day (POD) 26 revealed adequate reduction in ventricular size according to the increase in LVAD speed (left ventricular end-diastolic diameter [LVEDD] at minimum and maximum speeds, 68 and 37 mm, respectively). The patient was discharged home and received routine anticoagulation maintenance therapy. However, a 2nd ramp test was performed on POD 56 due to increased lactase dehydrogenase and brain natriuretic peptide levels and showed marked increase in left ventricle (LV) chamber size without adequate response to the LVAD speed changes (LVEDD at minimum and maximum speeds, 88 and 76 mm, respectively). Given the suspicion for partial pump thrombosis, the patient was immediately hospitalized and received intravenous heparin infusion. After the optimization of the intensive anticoagulation therapy, the patient underwent a 3rd ramp study, which showed a remarkable improvement of the adequate response to LVAD speed changes. The patients eventually underwent cardiac transplant successfully, and the partial clot was found inside of the pump. This case demonstrates the usefulness of serial ramp studies in patients who are suspected to have device thrombosis.

A noninvasive detection of allograft rejection is one of the major objectives in the management of heart transplant recipients. Endomyocardial biopsy still remains the gold standard for diagnosing rejection; however, it is invasive, expensive, and subject to sampling error and interobserver variability. Advances in echocardiographic techniques provide an important role for the reliable detection of rejection. This article reviews recently developed echocardiographic modalities and their clinical utility for rejection monitoring in transplant recipients.Conventional two-dimentional (2D)-echocardiographic and Doppler echocardiographic parameters can be useful to detect an increase in left ventricular (LV) mass and diastolic and/or systolic dysfunction associated with acute rejection; however, these parameters are not sufficiently reliable to guide the treatment strategy of asymptomatic, clinically stable patients. Tissue-Doppler Imaging (TDI), which is now widely used, has been reported to detect rejection more accurately than conventional parameters. More recently, 2D speckle-tracking echocardiography (2D-STE)-derived LV torsion and strain parameters, which are calculated by off-line using conventional 2D images, are expected to detect subclinical rejection.Considering the advantages of TDI and 2D-STE over conventional echocardiograms, including pre-load and after-load independency, angle-independency and simple-offline calculation, such newly developed echocardiographic modalities will emerge as useful follow-up tools for monitoring rejection in transplant recipients.

Background Noninvasive detection of rejection is a major objective in the management of heart transplant recipients. Methods and Results To investigate the utility of 2-dimensional speckle-tracking echocardiography (2D-STE), we retrospectively evaluated 160 sets of endomyocardial biopsies and echocardiograms from 59 asymptomatic heart transplant recipients. Conventional International Society for Heart and Lung Transplantation grade 1B or higher rejection was considered as treatment-requiring rejection (group R), whereas International Society for Heart and Lung Transplantation grade 0 or 1A was classified as group Non-R. Left ventricular global longitudinal strain (GLS), global circumferential strain, and global radial strain were assessed by 2D-STE. Twenty-five specimens were classified into group R. GLS was significantly associated with treatment-requiring rejection, whereas neither global radial strain nor global circumferential strain were. Lower GLS remained significantly associated with an increased risk of treatment-requiring rejection (odds ratio, 1.15 [95% CI, 1.01-1.30]; P=0.03) even in multivariate analysis. GLS with the absolute value of less than 14.8% showed sensitivity and specificity of 64% and 63%, respectively, for detection of treatment-requiring rejection. Conclusion The 2D-STE–derived left ventricular GLS was associated with treatment-requiring rejection. Two-dimensional STE might be useful as a noninvasive supplemental tool for monitoring heart transplant recipients for possible treatment-requiring rejection.

Background— Serum albumin concentration has been recognized as a marker of nutrition, severity of inflammation, and hepatic function in patients with various chronic diseases. The purpose of this study was to investigate the impact of pretransplant serum albumin concentration on post-transplant outcome in heart transplant recipients. Methods and Results— Preoperative laboratory variables, including albumin concentration and donor-related information, were obtained from 822 consecutive patients undergoing heart transplant at Columbia University Medical Center between 1999 and 2010. The association between pretransplant albumin concentration and post-transplant 1-year survival was analyzed. Available data from the United Network for Organ Sharing (n=13 671) were also analyzed to evaluate the impact of preoperative albumin levels on post-transplant outcome. In our cohort, multivariable analysis revealed that preoperative albumin (mg/dL; hazard ratio, 0.46; P P =0.0002) were associated with post-transplant 1-year mortality. This implied that for every 1 mg/dL increase in albumin concentration, the post-transplant 1-year mortality rate decreased by 54%. The Kaplan–Meier analysis based on our patients cohort and the United Network for Organ Sharing dataset showed lower survival rate at 1-year post-transplant in patients with albumin levels ≤3.5 mg/dL compared with those with >3.5 mg/dL (our patients, 91.3 versus 72.4%; P P Conclusions— Pretransplant serum albumin concentration is a strong prognostic marker for post-transplant survival in heart transplant recipients.

We thank Bandera et al for their insightful comments on our recent publication demonstrating synergistic effects of exercise parameters and cardiac biomarkers, such as brain natriuretic peptide, for risk prediction in ambulatory and euvolemic patients with advanced heart failure.1 We agree with the assumption that levels of brain natriuretic peptide in this cohort might reflect different degrees of myocardial load and associated wall stress …