Divya Ratan Verma

Left ventricular assist device unloading effects on myocardial structure and function: current status of the field and call for action.

Purpose of review Myocardial remodeling driven by excess pressure and volume load is believed to be responsible for the vicious cycle of progressive myocardial dysfunction in chronic heart failure. Left ventricular assist devices (LVADs), by providing significant volume and pressure unloading, allow a reversal of stress-related compensatory responses of the overloaded myocardium. Herein, we summarize and integrate insights from studies which investigated how LVAD unloading influences the structure and function of the failing human heart. Recent findings Recent investigations have described the impact of LVAD unloading on key structural features of cardiac remodeling – cardiomyocyte hypertrophy, fibrosis, microvasculature changes, adrenergic pathways and sympathetic innervation. The effects of LVAD unloading on myocardial function, electrophysiologic properties and arrhythmias have also been generating significant interest. We also review information describing the extent and sustainability of the LVAD-induced myocardial recovery, the important advances in understanding of the pathophysiology of heart failure derived from such studies, and the implications of these findings for the development of new therapeutic strategies. Special emphasis is given to the great variety of fundamental questions at the basic, translational and clinical levels that remain unanswered and to specific investigational strategies aimed at advancing the field. Summary Structural and functional reverse remodeling associated with LVADs continues to inspire innovative research. The ultimate goal of these investigations is to achieve sustained recovery of the failing human heart.

Characterization of diffuse fibrosis in the failing human heart via diffusion tensor imaging and quantitative histological validation

Non‐invasive imaging techniques are highly desirable as an alternative to conventional biopsy for the characterization of the remodeling of tissues associated with disease progression, including end‐stage heart failure. Cardiac diffusion tensor imaging (DTI) has become an established method for the characterization of myocardial microstructure. However, the relationships between diffuse myocardial fibrosis, which is a key biomarker for staging and treatment planning of the failing heart, and measured DTI parameters have yet to be investigated systematically. In this study, DTI was performed on left ventricular specimens collected from patients with chronic end‐stage heart failure as a result of idiopathic dilated cardiomyopathy (n = 14) and from normal donors (n = 5). Scalar DTI parameters, including fractional anisotropy (FA) and mean (MD), primary (D1), secondary (D2) and tertiary (D3) diffusivities, were correlated with collagen content measured by digital microscopy. Compared with hearts from normal subjects, the FA in failing hearts decreased by 22%, whereas the MD, D2 and D3 increased by 12%, 14% and 24%, respectively (P < 0.01). No significant change was detected for D1 between the two groups. Furthermore, significant correlation was observed between the DTI scalar indices and quantitative histological measurements of collagen (i.e. fibrosis). Pearsons correlation coefficients (r) between collagen content and FA, MD, D2 and D3 were –0.51, 0.59, 0.56 and 0.62 (P < 0.05), respectively. The correlation between D1 and collagen content was not significant (r = 0.46, P = 0.05). Computational modeling analysis indicated that the behaviors of the DTI parameters as a function of the degree of fibrosis were well explained by compartmental exchange between myocardial and collagenous tissues. Combined, these findings suggest that scalar DTI parameters can be used as metrics for the non‐invasive assessment of diffuse fibrosis in failing hearts. Copyright

Clinical and Hemodynamic Effects of Renin–Angiotensin System Blockade in Cardiac Transplant Recipients

Chronic kidney disease continues to be a major limiting factor for long-term survival of heart transplant recipients. Little is known about the early use of renin-angiotensin system (RAS) blocking agents and their impact on renal function and hemodynamics in heart transplant recipients. In this cohort study all eligible recipients of orthotopic heart transplants at the UTAH cardiac transplantation program from 2001 through 2007 were divided into 2 groups-patients who were started on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers within the first 4 weeks of transplantation and continued on these for ≥4 weeks during the first 3 months (RAS blockade group, n = 75) and those who were not (non-RAS blockade group, n = 52). All patients were followed for 1 year after transplantation. There were no significant differences at baseline between the 2 groups. Estimated glomerular filtration rate at 12 months was significantly higher in the RAS blockade group compared to the non-RAS blockade group (mean ± SD, 56.3 ± 22.4 vs 47.3 ± 18.1 ml/min/1.73 m(2), p = 0.036). At 12 months pulmonary artery systolic pressure was significantly lower in the RAS blockade group compared to the non-RAS blockade group (30.2 ± 7.4 vs 32.9 ± 9.3 mm Hg, p = 0.023). Left ventricular ejection fraction and pulmonary capillary wedge pressure were similar between the 2 groups. In conclusion, early RAS blockade after heart transplantation is safe, well tolerated, and associated with better renal function and hemodynamic profile at 1 year after transplantation.

Effect of Blood Product Transfusion-Induced Tolerance on Incidence of Cardiac Allograft Rejection

BACKGROUND Blood product transfusion has been successfully used in solid-organ transplantation to induce tolerance. Whether a similar protective effect of blood product transfusion exists in heart transplantation is controversial. OBJECTIVE To investigate the effect of cellular blood product transfusion within 2 weeks posttransplantation on the incidence of cellular and antibody-mediated rejection. PATIENTS AND METHODS Patients were grouped on the basis of number of blood transfusions; group 1 received no transfusions, and groups 2, 3, and 4 each received an incremental number of transfusion units. All endomyocardial biopsy samples were routinely studied using immunofluorescence in the first 12 weeks posttransplantation. RESULTS Baseline characteristics including age, sex, body mass index, history of diabetes, donor characteristics, and pretransplantation laboratory values were similar except that group 4 had a higher rate of previous sternotomy and longer ischemic time during transplantation. Approximately 9200 endomyocardial biopsy samples composed the data. Short- and long-term freedom from the International Society for Heart & Lung Transplantation grade 3A or higher cellular rejection and from antibody-mediated rejection were comparable between groups. CONCLUSIONS Blood transfusions within the first 2 weeks post-transplantation do not seem to confer any protective effect against posttransplantation cellular rejection or antibody- mediated rejection. Whether other unmeasured confounding factors mask their effect requires further prospective studies.

INHIBITION OF ANGIOTENSIN SIGNALING REDUCES INCIDENCE OF ANTIBODY MEDIATED ALLOGRAFT REJECTION.

Methods: Among consecutive patients transplanted in our program between 2002 and 2007 we identified those who were started on ACE-I or ARB within 30 days of transplant and those who were not. We evaluated the incidence of cellular and antibody mediated rejection (AMR) in the first year after transplant in the two groups. AMR episode was defined as deposits of complement (C3d or C4d) and immunoglobulin detected by immunofluorescence on 3 endomyocardial biopsies.

EVALUATION OF DYSPNEA DUE TO PULMONARY HYPERTENSION, HFPEF AND MITRAL STENOSIS

Evaluation of dyspnea in the setting of pulmonary hypertension (PHT), heart failure with preserved ejection fraction (HFpEF) and mitral valve (MV) disease is often challenging. Correct diagnosis is critical for selecting appropriate management strategy. 76 year old man with h/o sick sinus syndrome

COMPARING TEE WITH ANGIOGRAPHIC SIZING OF WATCHMAN DEVICE FOR LEFT ATRIAL APPENDAGE CLOSURE

Background: There are significant limitations to using TEE as imaging modality for selecting the size of WATCHMAN device as frequently changing device size is needed which adds cost and risk of complications. We compared TEE with angiography sizing for WATCHMAN device Methods: TEE and angiographic

Volume-outcome relationships for transcatheter aortic valve replacement-risk-adjusted and volume stratified analysis of TAVR outcomes

Objectives This purpose of the study was to evaluate TAVR outcomes at low, intermediate and high volume institutions. Background For the care of complex patients, volume-outcome effect is well described. The initial US TAVR experience was limited to a few centers of excellence. The impact of institutional volume on outcomes after TAVR has not been systematically studied. Methods Within the Banner Health system, TAVR is performed at 3 institutions-a low volume, an intermediate volume and a high volume institution. 181 consecutive patients undergoing TAVR within these 3 institutions were the study cohort. To adjust for bias and confounders between the 3 groups, risk-adjusted multivariate logistic regression and propensity score analysis was performed. The primary endpoint was a composite of mortality, dialysis-dependent renal failure, cerebrovascular accident, need for new permanent pacemaker and readmission within 30 days. Results The primary endpoint was reached in 38.8% of patients at the high volume institution and 76.2% of patients at the low volume institution (p < 0.01). Having a TAVR procedure at a larger volume institution was an independent predictor of having improved outcomes (OR 0.33, 95% CI 0.16–0.68; p = 0.003). These improved outcomes after the TAVR procedure noted at the large volume institution were seen in the most complex patients: age ≥80 years, BMI >30, diabetes, hypertension, prior CAD, CKD and NYHA class III/IV heart failure. Conclusions High-risk patients undergoing TAVR at a large volume institution have better 30-day outcomes compared to outcomes at intermediate and low volume centers.

Transcatheter aortic valve replacement using the transaortic approach

This is a frail 73-year-old male with symptomatic critical aortic stenosis (AS). He has suffered a significant functional decline with associated shortness of breath and chest discomfort. His past medical history is significant for coronary artery disease with prior bypass grafting, porcelain aorta, chronic kidney disease-stage III, diabetes mellitus, hypertension, hyperlipidemia, and peripheral arterial disease. Echocardiography demonstrates tri-leaflet, calcific AS with an aortic valve area of 0.7 cm, a jet velocity of 5.0 m/s, and a mean gradient of 60 mmHg. Cardiac catheterization reveals a widely patent LIMA-to-LAD with patent vein grafts and limited native coronary flow.

TCT-623 Predictors of MACE with the WATCHMAN device: An Intention-to-Treat Analysis in a Real World Experience

nos: 626 646 TCT-626 Validating a prediction modeling tool for LVOT obstruction after transcatheter mitral valve replacement Dee Dee Wang, Marvin Eng, Adam Greenbaum, Mayra Guerrero, William O’Neill