Igor Gregoric

Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure.

Background Mechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal‐flow device) against existing technology (a commercially available axial‐flow device) in patients with advanced heart failure who were ineligible for heart transplantation. Methods We conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal‐flow) device or the control (axial‐flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points. Results The intention‐to treat‐population included 297 participants assigned to the study device and 148 participants assigned to the control device. The primary end point was achieved in 164 patients in the study group and 85 patients in the control group. The analysis of the primary end point showed noninferiority of the study device relative to the control device (estimated success rates, 55.4% and 59.1%, respectively, calculated by the Weibull model; absolute difference, 3.7 percentage points; 95% upper confidence limit, 12.56 percentage points; P=0.01 for noninferiority). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups. Conclusions In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal‐flow LVAD was found to be noninferior to an axial‐flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347.)

Morphologic changes in the aortic wall media after support with a continuous-flow left ventricular assist device

BACKGROUNDnContinuous-flow left ventricular assist devices (LVADs) provide durable, reliable, energy-efficient long-term support. However, the biologic effects of continuous flow are not completely known. Therefore, we examined aortic wall morphology in patients with heart failure before and after prolonged circulatory support with a continuous-flow LVAD.nnnMETHODSnAfter applying a partial aortic occlusion vascular clamp in the lower half of the ascending aorta, we removed samples of aortic wall tissue and then attached the outflow graft of the pump. Samples were obtained from 11 patients (9 men and 2 women, mean age 65 ± 7 years) with severe heart failure at the time of LVAD implantation. We obtained matched specimens at explantation after heart transplantation (n = 5) or autopsy (n = 6). These specimens were removed from the distal ascending aorta, remote from the aortic anastomotic site. Tissue sections were stained with hematoxylin and eosin, Movats pentachrome and Massons trichrome. Smooth muscle actin immunohistochemistry was performed on all sections. To evaluate the morphology of the aortic wall media, we quantitatively graded tissue sections for medial thickness, medial degenerative changes, smooth muscle cell (SMC) disorientation and depletion, elastic fiber fragmentation and depletion, medial fibrosis and atherosclerotic changes.nnnRESULTSnThe mean duration of support was 140 ± 136 days (range 87 to 580 days). The histologic evaluation and comparison of specimens obtained before and after LVAD support showed significantly increased foci of medial degeneration, SMC depletion, elastic fiber fragmentation, medial fibrosis and atherosclerotic changes after LVAD support. Mean medial thickness was not significantly different after LVAD support. We observed similar changes between samples obtained at transplantation and those obtained at autopsy.nnnCONCLUSIONSnAfter continuous-flow LVAD support, the morphology of the aortic wall media was altered in all of our patients. The clinical relevance of these findings is unknown.

Salvage of infected left ventricular assist device with antibiotic beads.

Background: The use of left ventricular assist devices has become common for the treatment of end-stage heart failure, both as a bridge to transplantation and as destination therapy. The nature of these devices and the comorbid conditions of the patients in whom the devices are implanted lead to high rates of device infection that are related directly to mortality. Methods: Over 2 years, the senior author (S.A.I.) treated 26 patients with left ventricular assist device infections, ranging from superficial driveline infections to deeper pocket infections and device infections. An algorithm involving the use of repeated débridement and placement of antibiotic beads was used in treatment of these infections. Once cleared of infection, patients were treated with definitive closure or flap coverage of the formerly infected device component. Results: Seventeen of 26 patients with left ventricular assist device–related infections were cleared of their infection using this method. Ten of these patients underwent flap coverage of the device after their infection was cleared. In patients that were cleared of infection, mortality was 29 percent, whereas patients with recalcitrant infections had a mortality of 67 percent over the course of the study. Conclusions: A systematic approach to treating left ventricular assist device–related infections has the potential to treat and clear these infections, with promising overall survival rates. This proposed algorithm led to high infection clearance rates compared with previously published literature. Infection clearance in patients on left ventricular assist device destination therapy may result in mortality rates approaching those of their uninfected peers. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Use of autologous auricular chondrocytes for lining artificial surfaces: a feasibility study

BACKGROUNDnAuricular elastic cartilage is a potential source of autologous cells for lining the luminal surfaces of cardiovascular prostheses. We tested this potential in vitro and in vivo using a left ventricular assist device (LVAD) and a calf model.nnnMETHODSnIn vitro, auricular cartilage was harvested from the anesthetized ear of a calf, isolated, and cultured on tissue culture dishes. Primary chondrocytes were typed by immunocytochemistry, transferred into culture media, passaged twice, and seeded onto the blood-contacting luminal surfaces of four LVADs (HeartMate; Thoratec Corporation, Woburn, MA). Seeded cell linings were preconditioned under simulated flow conditions to promote cell adhesion to luminal surfaces. Seeding efficiency and cumulative cell loss under flow conditions were quantitated. In vivo, one of the four autologous chondrocyte-lined and preconditioned LVADs was implanted into the tissue-donor calf; run for 7 days; explanted; and evaluated grossly, by scanning electron microscopy, and by transmission electron microscopy.nnnRESULTSnThe efficiency of seeding chondrocytes onto the luminal surfaces of the four LVADs was 95.11% +/- 4.23% (n = 4). Cumulative cell loss during preconditioning under flow conditions in vitro did not exceed 12% (n = 4). After 7 days of in vivo implantation, the luminal surfaces of the implanted LVAD demonstrated an intact, strongly adherent cellular lining.nnnCONCLUSIONSnAuricular elastic cartilage is a ready and easily accessible source of chondrocytes whose ability to produce collagen II and other important extracellular matrix constituents allows them to adhere strongly to the luminal surfaces of LVADs. The simple method of isolating and expanding auricular chondrocytes presented here could be used to provide strongly adherent autologous cell linings for LVADs and other cardiovascular devices. If and when chondrocytes can be genetically engineered to produce antithrombogenic factors and then used to line the luminal surfaces of LVADs or other cardiovascular prostheses, they may be able to improve the hemocompatibility of the blood-biomaterial interface in such devices. Our successful feasibility study in a calf model warrants further studies of this concept in vivo.

Ionic Mechanisms Underlying the Effects of Vasoactive Intestinal Polypeptide on Canine Atrial Myocardium

Background— Vasoactive intestinal polypeptide (VIP) is released from intracardiac neurons during vagal stimulation, ischemia, and heart failure, which are associated with increased vulnerability to atrial fibrillation. VIP shortens atrial effective refractory periods in dogs. Endogenous VIP contributes to vagally mediated acceleration of atrial electric remodeling. VIP is also shown to prolong the duration of acetylcholine-induced atrial fibrillation. However, the ionic mechanisms underlying VIP effects are largely unknown. Methods and Results— The effects of VIP on transmembrane ion channels were studied in canine atrial cardiomyocytes using patch-clamp techniques. VIP increased delayed rectifier K+ current and L-type calcium current but decreased the transient outward K+ current and sodium current. Optical mapping technique was used to assess effects of VIP on action potential durations (APDs) in isolated canine left atria. VIP shortened APD and slowed conduction velocity in a dose-dependent manner. Furthermore, VIP increased spatial heterogeneity of APD and conduction velocity, as assessed by the SDs of APD and conduction velocity, and atrial fibrillation inducibility. Conclusions— Through its diverse effects on ion channels, VIP shortens APD with increased APD spatial heterogeneity and decreases intra-atrial conduction velocity, which may play an important role in the pathogenesis of atrial arrhythmias in scenarios where VIP release is increased.

Successful repair of aortic annulus rupture during transcatheter aortic valve replacement using extracorporeal membrane oxygenation support

Aortic annular rupture is a rare and much dreaded complication of transcatheter aortic valve replacement. Device oversizing to prevent post-procedural paravalvular leak is the most commonly identified cause of this complication. However, mechanical stress in a heavily calcified non-compliant vessel can also lead to annular rupture in this older population. We describe a case of aortic annular rupture with involvement of right coronary artery ostium leading to cardiac tamponade and cardiac arrest, successfully managed by extracorporeal membrane oxygenation support, open drainage of the pericardial space, pericardial patching of the defect and bypass of the affected vessel with excellent post-procedural results.

Pathological assessment of end-stage heart failure in explanted hearts in correlation with hemodynamics in patients undergoing orthotopic heart transplantation

BACKGROUNDnTo date, there has been little research, if any, on the pathological correlates of end-stage heart failure in the explanted hearts of orthotopic heart transplant (OHT) recipients in correlation with the patients hemodynamics. We sought to compare the gross and histopathological parameters in hearts explanted-native or previously transplanted-from patients with end-stage heart failure with the clinical hemodynamics parameters at the time of OHT.nnnMETHODSnForty patients undergoing OHT were enrolled in this study and divided into two groups according to whether they suffered from ischemic (ICMP) or nonischemic cardiomyopathy (NICMP). All study patients were treated with OHT for end-stage heart failure at The University of Texas Health Science Center at Houston. The pathological investigations of the hearts were focused on the study of the underlying cause of heart failure leading the patient to OHT; on the quantification of the extent and severity of fibrosis, hypertrophy, and myocytolysis; and on validating a semiquantitative grading scale. Analyses of multiple sections of the explanted hearts were carried out. The heart weights were recorded and compared with the grades of fibrosis, hypertrophy of cardiomyocytes, and myocytolysis. The grades of fibrosis, hypertrophy, and myocytolysis were evaluated in right and left ventricles and atria (with areas of confluent infarction excluded). The pathological parameters were correlated with the patients clinical parameters.nnnRESULTSnTwenty-two patients (20 men, 2 women, mean age±S.E.M., 62.3±2.2 years) suffered from ICMP and 18 patients (9 men, 9 women, mean age±S.E.M., 56.3±2.8 years) from NICMP. All the clinical and pathological measured variables were comparable between the two groups, except for pulmonary vascular resistance, which was higher in the NICMP group of patients, and the grade of myocytolysis, which was significantly higher in the ICMP vs. NICMP group. Most of the clinical and pathological variables were overall linearly correlated.nnnCONCLUSIONSnBoth ICMP and NICMP groups of end-stage heart failure requiring OHT presented high grades of fibrosis, hypertrophy, and myocytolysis. Heart failure is the final common pathway of a variety of primary cardiovascular diseases regardless of the ischemic or nonischemic nature of the cardiomyopathy.

Short-Term Experience with Off-Pump Versus On-Pump Implantation of the HeartWare Left Ventricular Assist Device

Implantation of left ventricular assist devices while avoiding cardiopulmonary bypass (CPB) may decrease bleeding and improve postoperative recovery. To understand the effectiveness of this approach, we reviewed the charts of 26 patients who underwent HeartWare left ventricular assist device (HVAD) implantation without use of CPB (off-CPB group) and 22 patients who had HVAD implanted with CPB (CPB group) with an emphasis on the 30 day postoperative period. Preoperatively, both groups had similar demographic, functional, and hemodynamic characteristics. Off-CPB patients had significantly shorter surgery times than CPB patients, 188.5 (161.5–213.3) min versus 265.0 (247.5–299.5) min, respectively; p < 0.001. Blood transfusion requirements during surgery and within the postoperative 48 hour period were significantly lower in the off-CPB group than in the CPB group (odds ratio: 5.9; 95% confidence interval: 1.1–31.1, p = 0.042). Compared with the CPB group, the off-CPB group patients had a shorter intubation time, 21 (17.4–48.5) hours versus 41 (20.6–258.4) hours; p = 0.042. Intensive care unit stay was 7.0 (4.75–13.5) days for off-CPB versus 10.0 (6.0–19.0) days for CPB (p = 0.256). The off-CPB approach allows HVAD to be implanted quickly with significantly less perioperative bleeding and transfusion requirements and facilitates postoperative rehabilitation.

Mobile Computing Platform With Decision Support Modules for Hemotherapy

OBJECTIVESnWe describe the development of a mobile computing platform (MCP) with a decision support module (DSM) for patients in our coagulation-based hemotherapy service.nnnMETHODSnThe core of our MCP consists of a Microsoft Excel spreadsheet template used to gather and compute data on cardiopulmonary bypass (CPB) patients intraoperatively. The DSM is embedded into the Excel file, where the user would enter in laboratory results, and through our 45 embedded algorithms, recommendations for transfusion products would be displayed in the Excel file.nnnRESULTSnThe DSM has helped decrease the time it takes to come to a transfusion recommendation, helps double-check recommendations, and is an excellent tool for teaching. Furthermore, the problems that occur with a paper system have been eliminated, and we are now able to access this information easily and reliably.nnnCONCLUSIONSnThe development and implementation of our MCP system has greatly increased the productivity and efficiency of our hemotherapy service.

Clinical Factors Implicated in Primary Graft Dysfunction After Heart Transplantation: A Single-center Experience

BACKGROUNDnPrimary graft dysfunction (PGD) is a frequent complication after cardiac transplantation and remains one of the leading causes of mortality in these patients. The objective of this case-control study is to identify donor and surgical procedures factors associated with PGD, and further guide possible strategies to prevent PGD.nnnMETHODSnRetrospective analysis of the medical records of patients who underwent cardiac transplantation at Memorial Hermann Hospital at Texas Medical Center between October 2012 and Februaryxa02015.nnnRESULTSnThe study population included 99 patients, of which 18 developed PGD. Univariate analysis of donor characteristics revealed opioid use (Pxa0= .049) and death owing to anoxia (Pxa0= .021) were associated with PGD. The recipient/donor blood type match AB/A was significantly associated with PGD (Pxa0= .031). Time from brain death to aortic cross clamp (TBDACC) ofxa0≥3 andxa0≥5 days were also found to be associated with PGD (Pxa0= .0011 and .0003, respectively). Multivariate analysis confirmed that patients with a time from brain death to aortic cross clampxa0≥3 andxa0≥5 days had lesser odds of developing PGD (odds ratio, 0.098 [Pxa0= .0026] and OR, 0.092 [Pxa0= .0017], respectively].nnnCONCLUSIONSnOur study showed that a longer time from brain death to aortic cross clamp was associated with lower odds of developing PGD. Therefore, postponing heart procurement for a few days after brain death seems to be beneficial in preventing PGD.