Modification of a Transvalvular Microaxial Flow Pump for Instantaneous Determination of Native Cardiac Output and Volume.

BACKGROUND: The current Impella cardiopulmonary (CP) pump, used for mechanical circulatory support in patients with cardiogenic shock (CS), cannot assess native cardiac output (CO) and left ventricular (LV) volumes. These data are valuable in facilitating device management and weaning. Admittance technology allows for accurate assessment of cardiac chamber volumes. OBJECTIVES: This study tested the ability to engineer admittance electrodes onto an existing Impella CP pump to assess total and native CO as well as LV chamber volumes in an instantaneous manner. METHODS: Impella CP pumps were fitted with 4 admittance electrodes and were placed in the LVs of adult swine (n = 9) that were subjected to 3 different hemodynamic conditions, including Impella CP speed adjustments, administration of escalating doses of dobutamine and microsphere injections into the left main artery to result in cardiac injury. CO, according to admittance electrodes, was calculated from LV volumes and heart rate. In addition, CO was calculated in each instance via thermodilution, continuous CO measurement, the Fick principle, and aortic velocity-time integral by means of echocardiography. RESULTS: Modified Impella CP pumps were placed in swine LVs successfully. CO, as determined by admittance electrodes, was similar by trend to other methods of CO assessment. It was corrected for pump speed to calculate native CO, and calculated LV chamber volumes trended as expected in each experimental protocol. CONCLUSIONS: We report, for the first time, that an Impella CP pump can be fitted with admittance electrodes and used to determine total and native CO in various hemodynamic situations. CONDENSED ABSTRACT: Transvalvular mechanical circulatory support devices such as the Impella CP do not have the ability to provide real-time information on native cardiac output (CO) and left ventricular (LV) volumes. This information is critical in device management and in weaning in patients with cardiogenic shock. We demonstrate, for the first time, that Impella CP pumps coupled with admittance electrodes are able to determine native CO and LV chamber volumes in multiple hemodynamic situations such as Impella pump speed adjustments, escalating dobutamine administration and cardiac injury from microsphere injection.

A Comprehensive Review of Calcineurin Inhibitors Used for Immunosuppression in Cardiac Transplantation.

Calcineurin inhibitors (CNIs) have been the foundation of immunosuppression in solid organ transplantation since the 1980s. Cyclosporine A (CSA), the first in class, was identified as the metabolite of the soil fungus Tolypocladium inflatum Gams as part of a larger program of screening for naturally occurring fungal metabolites with biologic activity in the 1970s. Significant immunosuppressive effects were discovered and consequently CSA was trialed as an immunosuppressant in renal transplantation. This initial success led to its widespread study and adoption in solid organ transplantation. This novel agent yielded significant improvements in both 1 year and longer-term allograft and patient survival. Subsequently, a similar and more potent CNI, tacrolimus was developed. Today, it is the principal CNI used for prevention of allograft rejection. Like all other immunosuppressives, the benefits of CNIs are counterbalanced by side effects and complications resulting from drug toxicity. This chapter comprehensively reviews the clinical use of CNIs in cardiac transplantation.

Between-center variation in high-priority listing status under the new heart allocation policy.

Under the new US heart allocation policy, transplant centers listed significantly more candidates at high priority statuses (Status 1 and 2) with mechanical circulatory support devices than expected. We determined whether the practice change was widespread or concentrated among certain transplant centers. Using data from the Scientific Registry of Transplant Recipients, we used mixed-effect logistic regression to compare the observed listings of adult, heart-alone transplant candidates post-policy (December 2018 to February 2020) to seasonally matched pre-policy cohort (December 2016 to February 2018). US transplant centers (N = 96) listed similar number of candidates in each policy period (4472 vs. 4498) but listed significantly more at high priority status (25.5% vs. 7.0%, p < .001) than expected. Adjusted for candidate characteristics, 91 of 96 (94.8%) centers listed significantly more candidates at high-priority status than expected, with the unexpected increase varying from 4.8% to 50.4% (interquartile range [IQR]: 14.0%-23.3%). Centers in OPOs with highest Status 1A transplant rate pre-policy were significantly more likely to utilize high-priority status under the new policy (OR: 9.73, p = .01). The new heart allocation policy was associated with widespread and significantly variable changes in transplant center practice that may undermine the effectiveness of the new system.

Cardiac transplantation outcomes in patients with amyloid cardiomyopathy.

OBJECTIVE: Amyloid cardiomyopathy (ACM) is a progressive and life-threatening disease caused by abnormal protein deposits within cardiac tissue. The most common forms of ACM are caused by immunoglobulin derived light chains (AL) and transthyretin (TTR). Orthotopic heart transplantation (OHT) remains the definitive treatment for patients with end stage heart failure. In this study, we perform a contemporary multicenter analysis evaluating post OHT survival in patients with ACM. METHODS: We conducted a multicenter analysis of 40,044 adult OHT recipients captured in the United Network for Organ Sharing (UNOS) registry from 1987-2018. Patients were characterized as ACM or non-ACM. Baseline characteristics were obtained, and summary characteristics were calculated. Outcomes of interest included post-transplant survival, infection, treated rejection, and the ability to return to work. Racial differences in OHT survival were also analyzed. Unadjusted associations between ACM and non-ACM survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. RESULTS: Three hundred ninety-eight patients with a diagnosis of ACM were identified of which 313 underwent heart only OHT. ACM patients were older (61 vs 53; P < .0001) and had a higher proportion of African Americans (30.7% vs 17.6%; P < .0001). Median survival for ACM was 10.2 years vs 12.5 years in non-ACM (P = .01). After adjusting for confounding, ACM patients had a higher likelihood of death post-OHT (HR 1.39 CI: 1.14, 1.70; P = .001). African American ACM patients had a higher likelihood of survival compared to White ACM patients (HR 0.51 CI 0.31-0.85; P = .01). No difference was observed in episodes of treated rejection (OR 0.63 CI 0.23, 1.78; P = .39), hospitalizations for infections (OR 1.24 CI: 0.85, 1.81; P = .26), or likelihood of returning to work for income (OR 1.23 CI: 0.84, 1.80; P = .30). CONCLUSIONS: In this analysis of OHT in ACM, ACM was associated with a higher likelihood of post-OHT mortality. Racial differences in post-OHT were observed with African American patients with ACM having higher likelihood of survival compared to White patients with ACM. No differences were observed in episodes of treated rejection, hospitalization for infection, or likelihood to return to work for income.

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 .).

COVID-19 and the cardiovascular system: A review of current data, summary of best practices, outline of controversies, and illustrative case reports.

As the severe acute respiratory syndrome coronavirus 2 virus pandemic continues to grow globally, an association is apparent between patients with underlying cardiovascular disease comorbidities and the risk of developing severe COVID-19. Furthermore, there are potential cardiac manifestations of severe acute respiratory syndrome coronavirus 2 including myocyte injury, ventricular dysfunction, coagulopathy, and electrophysiologic abnormalities. Balancing management of the infection and treatment of underlying cardiovascular disease requires further study. Addressing the increasing reports of health care worker exposure and deaths remains paramount. This review summarizes the most contemporary literature on the relationship of the cardiovascular system and COVID-19 and society statements with relevance to protection of health care workers, and provides illustrative case reports in this context.

Evaluating Biventricular Myocardial Velocity and Interventricular Dyssynchrony in Adult Patients During the First Year After Heart Transplantation.

BACKGROUND: Magnetic resonance tissue phase mapping (TPM) measures three-directional myocardial velocities of the left and right ventricle (LV, RV). This noninvasive technique may supplement endomyocardial biopsy (EMB) in monitoring grafts post-heart transplantation (HTx). PURPOSE: To assess biventricular myocardial velocity alterations in grafts and investigate the relationship between velocities and acute cellular rejection (ACR) episodes. STUDY TYPE: Prospective. SUBJECTS: Twenty-seven patients within 1 year post-HTx (49 ± 13 years, 19 M) and 18 age-matched controls (49 ± 15 years, 12 M). FIELD STRENGTH/SEQUENCE: 1.5T, 2D balanced steady-state free precession, and TPM. ASSESSMENT: Ventricular function: end-diastolic and end-systolic volumes, stroke volumes, ejection fraction (EF), and myocardial mass. TPM velocities: peak-systolic and peak-diastolic velocities, cardiac twist, and interventricular dyssynchrony. ACR rejection episodes: International Society for Heart and Lung Transplantation grading of EMB specimens. STATISTICAL TESTS: The Lilliefors test for normality, unpaired t-tests, and Wilcoxon rank-sum tests for normally and nonnormally distributed data, respectively, were used, as well as multivariate regression for confounding variables and Pearson's correlation for associations between TPM velocities and global function. RESULTS: Compared to controls, HTx patients demonstrated reduced biventricular systolic longitudinal velocities (LV: 5.2 ± 2.1 vs. 4.0 ± 1.5 cm/s, P < 0.05; RV: 4.2 ± 1.3 vs. 3.1 ± 1.2 cm/s, P < 0.01). Correlation analysis revealed significant positive relationships for biventricular EF with radial peak velocities of the same ventricle in both systole and diastole (LV systole: r = 0.48, P < 0.01; LV diastole: r = 0.28, P < 0.05; RV systole: r = 0.35, P < 0.01; RV diastole: r = 0.36, P < 0.01). Segmentally, longitudinal velocities were impaired in 7/16 LV segments and 5/10 RV segments in systole and 7/10 RV segments in diastole. TPM analysis in studies with >4 preceding ACR episodes showed globally reduced RV and LV systolic radial velocity, and segmentally reduced radial and longitudinal systolic velocities. DATA CONCLUSION: Biventricular global and segmental velocities were reduced in HTx patients. Patients with >4 rejection episodes showed reduced myocardial velocities. The TPM sequence may add functional information for monitoring graft dysfunction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:920-929.

Mineralocorticoid Receptor Antagonists: a Comprehensive Review of Finerenone.

PURPOSE OF REVIEW: We aim to review the mechanism of action and safety profile of mineralocorticoid receptor antagonists (MRAs) and discuss the differences between selective and non-selective MRAs. More specifically, finerenone is a new medication that is currently under investigation for its promising cardiovascular and nephrological effects. RECENT FINDINGS: MRAs are well known for their utility in treating heart failure, refractory hypertension, and diverse nephropathies, namely, diabetic nephropathy. As their name denotes, MRAs inhibit the action of aldosterone at the mineralocorticoid receptor, preventing receptor activation. This prevents remodeling, decreases inflammation, and improves proteinuria. There are not significant differences in outcomes between selective and non-selective MRAs. A new selective MRA named finerenone (originally BAY 94-8862) has shown promising results in several trials (ARTS-HF and ARTS-DN) and smaller studies. Finerenone may have a dose-dependent benefit over older MRAs, decreasing rates of albuminuria and levels of BNP and NT-ProBNP without causing a significant increase in serum potassium levels. This medication is not yet approved as it is still in phase 3 clinical trials (FIGARO-DKD and FIDELIO-DKD trials). MRAs are beneficial in several disease states. Newer medications, such as finerenone, should be considered in patients with heart failure and diabetic nephropathy who may benefit from a reduction in albuminuria and BNP/NT-ProBNP. Data surrounding finerenone are limited to date. However, results from ongoing clinical trials, as well as new trials to evaluate use in other pathologies, could validate the implementation of this medication in daily practice.

Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB.

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the aggressive coronavirus disease (COVID-19) pandemic. Recently, investigators have stipulated that COVID-19 patients receiving angiotensin-converting-enzyme inhibitors (ACEI) may be subject to poorer outcomes. This editorial presents the available evidence to guide treatment practices during this pandemic. RECENT FINDINGS: Recent studies from Wuhan cohorts provide valuable information about COVID-19. A cohort with 52 critically ill patients revealed cardiac injury in 12% of patients. Worse outcomes appear to be more prevalent in patients with hypertension and diabetes mellitus (DM), possibly due to overexpression of angiotensin-converting enzyme 2 (ACE2) receptor in airway alveolar epithelial cells. Investigators suspect that SARS-CoV-2 uses the ACE2 receptor to enter the lungs in a mechanism similar to SARS-CoV. Several hypotheses have been proposed to date regarding the net effect of ACEI/ARB on COVID-19 infections. Positive effects include ACE2 receptor blockade, disabling viral entry into the heart and lungs, and an overall decrease in inflammation secondary to ACEI/ARB. Negative effects include a possible retrograde feedback mechanism, by which ACE2 receptors are upregulated. Even though physiological models of SARS-CoV infection show a theoretical benefit of ACEI/ARB, these findings cannot be extrapolated to SARS-CoV-2 causing COVID-19. Major cardiology scientific associations, including ACC, HFSA, AHA, and ESC Hypertension Council, have rejected these correlation hypotheses. After an extensive literature review, we conclude that there is no significant evidence to support an association for now, but given the rapid evolvement of this pandemic, findings may change.

The Role of Anticoagulation in COVID-19-Induced Hypercoagulability.

PURPOSE OF REVIEW: We aim to provide a comprehensive analysis of hypercoagulability in individuals affected by COVID-19. Our goal is to describe the hypercoagulable state related to the infection and provide guidance regarding the possible benefits of anti-coagulation with the support of evidence from current literature. RECENT FINDINGS: The incidence of thrombotic disease in individuals affected by COVID-19 is reported as high as 31%. A significant mortality benefit has been observed with the use of therapeutic anticoagulation in high-risk individuals. Literature supports the use of scoring systems, such as the sepsis-induced coagulopathy score, to risk-stratify individuals who might benefit from anticoagulation. COVID-19-induced hypercoagulability has been demonstrated to play a significant role in overall COVID-19 outcomes. Current literature shows promising evidence with the use of therapeutic anticoagulation in high-risk individuals. Further studies are needed to better analyze the risks and benefits of anticoagulation in this specific patient population.

Anatomic Dissection and CT Imaging of the Anterior Cruciate and Medial Collateral Ligament Footprint Anatomy in Skeletally Immature Cadaver Knees.

BACKGROUND: Anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injuries in skeletally immature patients are increasingly recognized and surgically treated. However, the relationship between the footprint anatomy and the physes are not clearly defined. The purpose of this study was to identify the origin and insertion of the ACL and MCL, and define the footprint anatomy in relation to the physes in skeletally immature knees. METHODS: Twenty-nine skeletally immature knees from 16 human cadaver specimens were dissected and divided into 2 groups: group A (aged 2 to 5 y), and group B (aged 7 to 11 y). Metallic markers were placed to mark the femoral and tibial attachments of the ACL and MCL. Computed tomography scans were obtained for each specimen used to measure the distance from the center of the ligament footprints to the respective distal femoral and proximal tibial physes. RESULTS: The median distance from the ACL femoral epiphyseal origin to the distal femoral physis was 0.30 cm (interquartile range, 0.20 to 0.50 cm) and 0.70 cm (interquartile range, 0.45 to 0.90 cm) for groups A and B, respectively. The median distance from the ACL epiphyseal tibial insertion to the proximal tibial physis for groups A and B were 1.50 cm (interquartile range, 1.40 to 1.60 cm) and 1.80 cm (interquartile range, 1.60 to 1.85 cm), respectively. The median distance from the MCL femoral origin on the epiphysis to the distal femoral physis was 1.20 cm (interquartile range, 1.00 to 1.20 cm) and 0.85 cm (interquartile range, 0.63 to 1.00 cm) for groups A and B, respectively. The median distance from the MCL insertion on the tibial metaphysis to the tibial physis was 3.05 cm (interquartile range, 2.63 to 3.30 cm) and 4.80 cm (interquartile range, 3.90 to 5.10 cm) for groups A and B, respectively. CONCLUSION: Surgical reconstruction is a common treatment for ACL injury. Computed tomography scanning of pediatric tissue clearly defines the location of the ACL and MCL with respect to the femoral and tibial physes, and may guide surgeons for physeal respecting procedures. CLINICAL RELEVANCE: In addition to ACL reconstruction, recent basic science and clinical research suggest that ACL repair may be more commonly performed in the future. MCL repair and reconstruction is also occasionally required in skeletally immature patients. This information may be useful to help surgeons avoid or minimize physeal injury during ACL/MCL reconstructions and/or repair in skeletally immature patients.

Pediatric Heart Transplantation: Transitioning to Adult Care (TRANSIT): Feasibility of a Pilot Randomized Controlled Trial.

BACKGROUND: Young-adult heart transplant recipients transferring to adult care are at risk for poor health outcomes. We conducted a pilot randomized controlled trial to determine the feasibility of and to test a transition intervention for young adults who underwent heart transplantation as children and then transferred to adult care. METHODS: Participants were randomized to the transition intervention (4 months long, focused on heart-transplant knowledge, self-care, self-advocacy, and social support) or usual care. Self-report questionnaires and medical records data were collected at baseline and 3 and 6 months after the initial adult clinic visit. Longitudinal analyses comparing outcomes over time were performed using generalized estimating equations and linear mixed models. RESULTS: Transfer to adult care was successful and feasible (ie, excellent participation rates). The average patient standard deviation of mean tacrolimus levels was similar over time in both study arms and < 2.5, indicating adequate adherence. There were no between-group or within-group differences in percentage of tacrolimus bioassays within target range (> 50%). Average overall adherence to treatment was similarly good in both groups. Rates of appointment keeping through 6 months after transfer declined over time in both groups. CONCLUSIONS: The feasibility of the study was demonstrated. Our transition intervention did not improve outcomes.

Cardiac Structure-Function MRI in Patients After Heart Transplantation.

BACKGROUND: Following heart transplantation (Tx), recipients are closely monitored using endomyocardial biopsy, which is limited by cost and invasiveness, and echocardiography, which is limited regarding detailed structural and functional evaluation. PURPOSE: To test the feasibility of comprehensive structure-function cardiac MRI as a noninvasive modality to assess changes in myocardial structure and function. STUDY TYPE: Prospective. SUBJECTS: MR was performed in 61 heart transplant recipients (age 47.9 ± 16.3 years, 39% female) and 14 age-matched healthy controls (age 47.7 ± 16.7 years, 36% female). FIELD STRENGTH/SEQUENCE: 1.5T; 2D CINE steady state free precession (SSF)P imaging, T2 -mapping, pre- and postgadolinium contrast T1 -mapping, and tissue-phase mapping (TPM). ASSESSMENT: Quantification of myocardial T2 (as a measure of edema), pre- and post-Gd T1 (allowing calculation of extracellular volume (ECV) to estimate interstitial expansion), and TPM-based assessment of peak regional left ventricular (LV) velocities, dyssynchrony, and twist. STATISTICAL TESTS: Comparisons between transplant recipients and controls were performed using independent samples t-tests. Relationships between structural (T2 , T1 , ECV) and functional measures (myocardial velocities, dyssynchrony, twist) were assessed using Pearson correlation analysis. RESULTS: T2 and T1 were significantly elevated in transplant recipients compared to controls (global T2 : 50.5 ± 3.4 msec vs. 45.2 ± 2.3 msec, P < 0.01; global T1 : 1037.8 ± 48.0 msec vs. 993.8 ± 34.1 msec, P < 0.01). Systolic longitudinal function was impaired in transplant recipients compared to controls (reduced peak systolic longitudinal velocities, 2.9 ± 1.1 cm/s vs. 5.1 ± 1.2 cm/s, P < 0.01; elevated systolic longitudinal dyssynchrony, 60.2 ± 30.2 msec vs. 32.1 ± 25.1 msec, P < 0.01). Correlation analysis revealed a significant positive relationship between T2 and ECV (r = 0.45,P < 0.01). In addition, peak systolic longitudinal velocities demonstrated a significant inverse relationship with T2 (global r = -0.29, P = 0.02), and systolic radial dyssynchrony was positively associated with peak T2 and peak T1 (r = 0.26,P = 0.04; r = 0.27,P = 0.03). DATA CONCLUSION: MR techniques are sensitive to structural and functional differences in transplant recipients compared to controls. Structural (T2 , T1 ) and functional (peak myocardial velocities, dyssynchrony) measures were significantly associated, suggesting a structure-function relationship of cardiac abnormalities following heart transplant. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:678-687.

Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial.

RATIONALE: Potential benefits of mesenchymal stem cell (MSC) therapy in heart failure may be related to paracrine properties and systemic effects, including anti-inflammatory activities. If this hypothesis is valid, intravenous administration of MSCs should improve outcomes in heart failure, an entity in which excessive chronic inflammation may play a pivotal role. OBJECTIVE: To assess the safety and preliminary efficacy of intravenously administered ischemia-tolerant MSCs (itMSCs) in patients with nonischemic cardiomyopathy. METHODS AND RESULTS: This was a single-blind, placebo-controlled, crossover, randomized phase II-a trial of nonischemic cardiomyopathy patients with left ventricular ejection fraction ≤40% and absent hyperenhancement on cardiac magnetic resonance imaging. Patients were randomized to intravenously administered itMSCs (1.5×106 cells/kg) or placebo; at 90 days, each group received the alternative treatment. Overall, 22 patients were randomized to itMSC (n=10) and placebo (n=12) at baseline. After crossover, data were available for 22 itMSC patients. No major differences in death, hospitalization, or serious adverse events were noted between the 2 treatments. Change from baseline in left ventricular ejection fraction and ventricular volumes was not significantly different between therapies. Compared with placebo, itMSC therapy increased 6-minute walk distance (+36.47 m, 95% confidence interval 5.98-66.97; P=0.02) and improved Kansas City Cardiomyopathy clinical summary (+5.22, 95% confidence interval 0.70-9.74; P=0.02) and functional status scores (+5.65, 95% confidence interval -0.11 to 11.41; P=0.06). The data demonstrated MSC-induced immunomodulatory effects, the magnitude of which correlated with improvement in left ventricular ejection fraction. CONCLUSIONS: In this pilot study of patients with nonischemic cardiomyopathy, itMSC therapy was safe, caused immunomodulatory effects, and was associated with improvements in health status and functional capacity. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02467387.

Bridge to Transplantation With Long-Term Mechanical Assist Devices in Adults With Transposition of the Great Arteries.

Prior to the widespread adoption of the arterial switch operation, patients with transposition of the great arteries (TGA) commonly underwent atrial switch operation (Mustard or Senning). It is not uncommon for these patients to progress to end stage heart failure and increasingly ventricular assist devices (VADs) are used to support these patients as a bridge to transplantation, though there is limited experience with this worldwide. A retrospective review of our institution's VAD database was undertaken and revealed seven adult patients with a history of TGA and subsequent systemic ventricular failure were implanted with a VAD: four of whom received the VAD as a bridge to transplantation (BTT) at the time of implantation, two who were initially designated as destination therapy secondary to severe pulmonary hypertension, and one who was designated as destination therapy secondary to a high risk of life-threatening non-compliance. Seven patient cases who received a VAD for severe systemic ventricular failure were included in this study. The mean age of the patients was 40 years and the majority of patients were male (6/7, 85%). Five of the patients (71.4%) had previously undergone an atrial switch operation and all of these were Mustard procedures. Two of the seven patients (28.5%) had congenitally corrected transposition of the great arteries (CC-TGA). Two of the seven patients (28.5%) had supra-systemic pulmonary pressures before VAD implantation and were designated as destination therapy (DT). One of these patients was later designated as BTT as an improvement in his pulmonary vascular resistance was observed, and subsequently underwent heart transplantation. Because of anatomic considerations, four of the patients (57%) underwent redo-sternotomy with outflow cannula anastomosis to the ascending aorta, one patient underwent VAD implantation via a left subcostal incision with anastomosis of the outflow graft to the descending thoracic aorta, and two patients (28.5%) underwent VAD implantation via a left thoracotomy and anastomosis of the outflow cannula to the descending thoracic aorta. Six of the seven patients had a HeartWare HVAD VAD implanted; one received a Thoratec Heartmate II VAD. Two patients underwent VAD explant and orthotopic heart transplant, 222 days and 444 days after VAD implant, respectively. One patient died on postoperative day 17 after complications from recurrent VAD thrombosis despite multiple pump exchanges. Four patients remain on VAD support, three of these patients are awaiting transplantation at last follow-up (mean days on support, 513 days). Bridge to transplantation with a durable VAD is technically feasible and relatively safe in patients with TGA. Multiple redo-sternotomies can be avoided with a left posterior thoracotomy approach and outflow graft anastomosis to the descending thoracic aorta after careful anatomic considerations.

Association of Transplant Center With Survival Benefit Among Adults Undergoing Heart Transplant in the United States.

Importance: In the United States, the number of deceased donor hearts available for transplant is limited. As a proxy for medical urgency, the US heart allocation system ranks heart transplant candidates largely according to the supportive therapy prescribed by transplant centers. Objective: To determine if there is a significant association between transplant center and survival benefit in the US heart allocation system. Design, Setting, and Participants: Observational study of 29 199 adult candidates for heart transplant listed on the national transplant registry from January 2006 through December 2015 with follow-up complete through August 2018. Exposures: Transplant center. Main Outcomes and Measures: The survival benefit associated with heart transplant as defined by the difference between survival after heart transplant and waiting list survival without transplant at 5 years. Each transplant center's mean survival benefit was estimated using a mixed-effects proportional hazards model with transplant as a time-dependent covariate, adjusted for year of transplant, donor quality, ischemic time, and candidate status. Results: Of 29 199 candidates (mean age, 52 years; 26% women) on the transplant waiting list at 113 centers, 19 815 (68%) underwent heart transplant. Among heart transplant recipients, 5389 (27%) died or underwent another transplant operation during the study period. Of the 9384 candidates who did not undergo heart transplant, 5669 (60%) died (2644 while on the waiting list and 3025 after being delisted). Estimated 5-year survival was 77% (interquartile range [IQR], 74% to 80%) among transplant recipients and 33% (IQR, 17% to 51%) among those who did not undergo heart transplant, which is a survival benefit of 44% (IQR, 27% to 59%). Survival benefit ranged from 30% to 55% across centers and 31 centers (27%) had significantly higher survival benefit than the mean and 30 centers (27%) had significantly lower survival benefit than the mean. Compared with low survival benefit centers, high survival benefit centers performed heart transplant for patients with lower estimated expected waiting list survival without transplant (29% at high survival benefit centers vs 39% at low survival benefit centers; survival difference, -10% [95% CI, -12% to -8.1%]), although the adjusted 5-year survival after transplant was not significantly different between high and low survival benefit centers (77.6% vs 77.1%, respectively; survival difference, 0.5% [95% CI, -1.3% to 2.3%]). Overall, for every 10% decrease in estimated transplant candidate waiting list survival at a given center, there was an increase of 6.2% (95% CI, 5.2% to 7.3%) in the 5-year survival benefit associated with heart transplant. Conclusions and Relevance: In this registry-based study of US heart transplant candidates, transplant center was associated with the survival benefit of transplant. Although the adjusted 5-year survival after transplant was not significantly different between high and low survival benefit centers, compared with centers with survival benefit significantly below the mean, centers with survival benefit significantly above the mean performed heart transplant for recipients who had significantly lower estimated expected 5-year waiting list survival without transplant.

A Prospective Pilot Study of Pocket-Carried Ultrasound Pre- and Postdischarge Inferior Vena Cava Assessment for Prediction of Heart Failure Rehospitalization.

BACKGROUND: Rehospitalization for heart failure (HF) is common, and subclinical congestion may be present at discharge. Larger inferior vena cava (IVC) size and lower collapsibility at discharge assessed via bedside ultrasound are predictive of rehospitalization; however, the utility of IVC assessment with the use of pocket-carried ultrasound (PCUS) during the transition from discharge to the posthospitalization follow-up visit (FU) has not been investigated. METHODS AND RESULTS: IVCmax and IVCmin were measured with the use of PCUS, and the collapsibility index (IVCCI = [IVCmax - IVCmin]/IVCmax) was determined. The primary outcome was 90-day rehospitalization or death. We prospectively enrolled 49 adults (71 ± 13 years of age, 51% male, 47% black, 43% preserved ejection fraction) hospitalized for HF. Nineteen patients (39%) experienced the outcome. Within the rehospitalized group, discharge and FU mean IVCmax were both >2.1 cm (2.2 ± 0.5 and 2.2 ± 0.7) and IVCCIs <50% (44 ± 20% and 45 ± 24%). Within those not rehospitalized, FU IVCmax was ≤2.1 cm (2.1 ± 0.6 and 1.9 ± 0.6; P = .038) and IVCCI >50% at both time points (55 ± 25% and 62 ± 19%; P = NS). FU IVCCI below an optimal cutoff of 42% had modest discrimination alone (c-statistic = 0.73). FU IVCCI <42% was associated with a greater hazard of the outcome independent of admission log B-type natriuretic peptide (adjusted hazard ratio = 6.8; 95% confidence interval 2.4-19.0; P < .001). CONCLUSIONS: Posthospitalization IVCCI assessment with PCUS predicts HF rehospitalization and may identify patients in need of intervention.

Cytomegalovirus infection in heart transplantation: A single center experience.

BACKGROUND: Cytomegalovirus (CMV) infection remains a major complication after heart transplantation with varying prophylaxis strategies employed. We sought to determine the impact of valganciclovir (VGC) duration on the epidemiology of CMV infections after heart transplantation. METHODS: We performed a prospective cohort study of CMV donor (D) or recipient (R) seropositive heart transplant recipients from 2005 to 2012 who completed VGC prophylaxis, ranging from 3 to 12 months according to serostatus and induction immunosuppression. Univariate and multivariate logistic regression was performed. RESULTS: Among 159 heart transplant recipients during the study period, 130 (82%) were eligible for VGC prophylaxis. CMV D/R serostatus was as follows: 24% D+/R-, 30% D+/R+, and 29% D-/R+. 65% and 21% received basiliximab and thymoglobulin induction, respectively, followed by maintenance tacrolimus, mycophenolate mofetil, and prednisone. Twenty-one (16%) recipients suffered CMV infection. There was no association with comorbidities including diabetes mellitus, chronic kidney disease, or mechanical assist devices, nor were there associations with rejection, treatments of rejection, or mortality. When VGC prophylaxis duration was stratified by ≤6 vs ≥12 months, time from heart transplantation to CMV infection was delayed (median 247 vs 452 days, P = .002) but there was no difference in days from VGC discontinuation to onset of CMV infection (median 72 vs 83 days, P = .31). CMV infection occurred most frequently within 6-16 weeks of VGC cessation, and 95% of infections occurred during the 6 months post-prophylaxis period. CONCLUSIONS: Relative to ≤6 months, ≥12 months of VGC did not reduce incidence of CMV infection and only delayed time to onset. 95% of CMV infection occurs within 6 months after cessation of VGC.

2018 International Olympic Committee consensus statement on prevention, diagnosis and management of paediatric anterior cruciate ligament (ACL) injuries.

In October 2017, the International Olympic Committee hosted an international expert group of physiotherapists and orthopaedic surgeons who specialise in treating and researching paediatric ACL injuries. Representatives from the American Orthopaedic Society for Sports Medicine, European Paediatric Orthopaedic Society, European Society for Sports Traumatology, Knee Surgery & Arthroscopy, International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine, Pediatric Orthopaedic Society of North America and Sociedad Latinoamericana de Artroscopia, Rodilla y Deporte attended. Physiotherapists and orthopaedic surgeons with clinical and research experience in the field, and an ethics expert with substantial experience in the area of sports injuries also participated. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision-making with children and the potential long-term ramifications of the injury. This consensus statement addresses six fundamental clinical questions regarding the prevention, diagnosis and management of paediatric ACL injuries. The aim of this consensus statement is to provide a comprehensive, evidence-informed summary to support the clinician, and help children with ACL injury and their parents/guardians make the best possible decisions.

All-Epiphyseal Anterior Cruciate Ligament Femoral Tunnel Drilling: Avoiding Injury to the Physis, Lateral Collateral Ligament, Anterolateral Ligament, and Popliteus-A 3-Dimensional Computed Tomography Study.

PURPOSE: To investigate the relation of the at-risk structures (distal femoral physis, lateral collateral ligament, anterolateral ligament, popliteus, and articular cartilage) during all-epiphyseal femoral tunnel drilling. A second purpose was 2-fold: (1) to develop recommendations for tunnel placement and orientation that anatomically reconstruct the anterior cruciate ligament (ACL) while minimizing the risk of injury to these at-risk structures, and (2) to allow for maximal tunnel length to increase the amount of graft in the socket to facilitate healing. METHODS: Three-dimensional models of 6 skeletally immature knees (aged 7-11 years) were reconstructed from computed tomography and used to simulate all-epiphyseal femoral tunnels. Tunnels began within the ACL footprint and were directed laterally or anterolaterally, with the goal of avoiding injury to at-risk structures. The spatial relation between the ideal tunnel and these structures was evaluated. Full-length tunnels and partial length condyle sockets were simulated in the models using the same trajectories. RESULTS: An anterolateral tunnel could be placed to avoid direct injury to lateral structures. The safe zone on the anterolateral aspect of the femur was larger than that of a tunnel with a direct lateral trajectory (median 127 mm2 vs 83 mm2, P = .028). Anterolateral tunnels were longer than direct lateral tunnels (median 30 mm vs 24 mm, P = .041). Safe angles for anterolateral tunnels were 34° to 40° from the posterior condylar axis; direct lateral tunnels were drilled 4° to 9° from the posterior condylar axis. Sockets could be placed without direct injury to structures at risk with either orientation. CONCLUSIONS: An all-epiphyseal ACL femoral tunnel can be placed without causing direct injury to at-risk structures. A tunnel angled anterolaterally from the ACL origin is longer and has a larger safe zone compared with the direct lateral tunnel. CLINICAL RELEVANCE: The largest safe zone for femoral all-epiphyseal ACL drilling was (1) anterior to the lateral collateral ligament origin, (2) distal to the femoral physis, and (3) proximal to the popliteus tendon origin. A direct lateral tunnel may also be used, but has a smaller safe zone. Sockets or partial length tunnels may have a lower risk of injury to at-risk structures.