Association between recipient’s preexisting antibodies and allograft vasculopathy and mortality in heart transplant patients

Objectives: To evaluate the role of preexisting Angiotensin II receptor type I antibodies (AT1RAb) and anti-HLA antibodies in predicting mortality and cardiac allograft vasculopathy (CAV) among heart transplant patients. Methods: In this retrospective cohort study, we included 114 adults who received heart transplant from January 1st, 2007 to December 31, 2014 and were followed up at Nebraska Medicine. 48 hours pre-transplant sera sample were used to detect antibodies. A cutoff of 10UL/ml was used for AT1RAb positive and mean fluorescence intensity of 3,000 and 1,500 were used for anti HLA class I and class II, respectively. Patients were positive for composite antibodies if they were positive for anti-HLA, or AT1R antibodies. Survival analysis was conducted to compare the risk for mortality or CAV between antibody positive and negative groups. Result: Participants who had positive composite antibodies had higher probability of having CAV (p=0.05). Participants who were negative for AT1RAb trended toward a lower risk of mortality or developing CAV compared to AT1RAb positive counterparts. Conclusion: Positive status for any of anti-HLA or AT1RAb increased the risk of CAV. AT1RAb positivity is possibly linked with higher risk of death or developing CAV. Future study can focus on verifying these trends and the potential interaction effect between anti-HLA and AT1R antibodies

Exploring Body Mass Index Changes in Left Ventricular Assist Device Patients

Background: Current treatment options for end-stage heart failure, such as transplantation, can be limited by obesity guidelines. Mechanical devices such as Left Ventricular Assistive Devices (LVAD) can bridge heart failure patients to transplantation, however, after implantation; some patients may experience weight gain that precludes them from transplantation. Therefore, the objective of this study was to evaluate weight changes after the implantation of an LVAD. Methods: A retrospective review of 130 patients receiving an LVAD were divided into two groups based on BMI at the time of implantation: obese (\u3e30 kg/m2) and non-obese (/m2). Patients were evaluated at three time points post LVAD implantation: 3, 6, and 12 months for changes in weight and BMI. Results: The mean BMI of the overall cohort at the time of LVAD implantation was 30.3 kg/m2. Patients who were not classified as obese at the time of LVAD implementation had a significant increase in BMI (2.1 kg/m2, p\u3c0.001) Conclusion: Weight gain after LVAD implementation is more likely in patients who are non-obese at the time of LVAD evaluation; however, obese subjects remained unlikely to lose weight one year post implantation

Damaging Cardiac and Cancer Genetic Variants in the LVAD Population

Background: Next generation sequencing technology, coupled with population genetic databases, have made broad genetic evaluation relatively inexpensive and widely available. Our objective was to assess the prevalence of potentially damaging cancer and cardiac gene variants in advanced non-ischemic cardiomyopathy patients. Methods: Explanted human heart tissue procured at LVAD placement was obtained from the University of Nebraska Medical Center Heart Tissue Bank. Genomic DNA was isolated from tissues and amplified by PCR using targeted ampliseq primer pools from an inherited disease panel. Individual libraries were amplified by emulsion PCR on Ion Sphere particles and sequencing was performed on a PGM sequencer (Ion torrent) using the Ion 316 chip. The Ion Torrent browser suite was used to map the reads and call the variants. The identified single nucleotide polymorphisms, insertions, and deletions were then annotated and characterized with ANNOVAR. Non-synonymous mutations with a population frequency of less than or equal to 1% were identified and analyzed utilizing an open source integrative genomics viewer. Amino acid substitution effects on protein function were determined by a bioinformatics algorithm. Myocardial recovery was defined as an improvement in EF to greater than 45% at three months post implant. Results: Our sample population included 12 males and 2 females with an average age of 49 and an average EF at presentation of 17%. Damaging cardiac gene variants were present in 11/14 patients. Only 1 of the 11 patients with damaging cardiac gene variants improved their ejection fraction to greater than 45% post LVAD. Two of the 2 patients without mutations improved their ejection fraction to greater than 45%, p-value=.04. Nine of the 14 patients in this population had damaging oncogene mutations. Conclusions: Damaging variants in cancer and cardiac genes are common in end-stage non-ischemic cardiomyopathy patients undergoing LVAD placement. Genetic variation likely contributes to disease progression and cancer risk

International Geomagnetic Reference Field: the 12th generation

The 12th generation of the International Geomagnetic Reference Field (IGRF) was adopted in December 2014 by the Working Group V-MOD appointed by the International Association of Geomagnetism and Aeronomy (IAGA). It updates the previous IGRF generation with a definitive main field model for epoch 2010.0, a main field model for epoch 2015.0, and a linear annual predictive secular variation model for 2015.0-2020.0. Here, we present the equations defining the IGRF model, provide the spherical harmonic coefficients, and provide maps of the magnetic declination, inclination, and total intensity for epoch 2015.0 and their predicted rates of change for 2015.0-2020.0. We also update the magnetic pole positions and discuss briefly the latest changes and possible future trends of the Earth’s magnetic fiel

Commentary Myocardial protection in sepsis

Sepsis with myocardial dysfunction is seen commonly. Betablockers have been used successfully to treat chronic heart failure based on the premise that chronically elevated adrenergic drive is detrimental to the myocardium. However, recent reports on the acute use of beta-blockers in situations with potential hemodynamic compromise have shown the risks associated with this approach. In critical situations, the main effect of adrenergic activation is to support cardiovascular function. Caution should be exercised in designing studies to assess beta-blockers in septic patients. Can β-blockers improve outcomes in septic patients with myocardial depression? In the previous issue of Critical Care, Schmittinger and colleagues [1] discuss the results of treating myocardial depression in septic shock patients with the combination of milrinone and metoprolol. They report on

Tetrahydrobiopterin Concentrations in Normal and Coronary Artery Diseased Heart Tissue

Tetrahydrobiopterin (BH4) is an essential cofactor that controls the enzymatic activity of aromatic amino acid hydroxylases as well as all forms of nitric oxide synthase (NOS), which include endothelial (eNOS), neuronal (nNOS) and inducible (iNOS) isoforms [1]. In coronary arteries, reduced availability of BH4 in the endothelium causes decreased production of nitric oxide and an increase in eNOSderived production of reactive oxygen species including superoxide anion and hydrogen peroxide [2,3]. Studies have demonstrated that oxidative stress causes uncoupling of eNOS and endothelial dysfunction, which is associated with chemical inactivation of BH4 and its oxidation to dihydrobiopterin (BH2) [4]. There is mounting evidence that this mechanism plays a particularly important role in coronary artery disease (CAD). For instance, low BH4 and BH4/BH2 ratio have been found to be decreased in plasma of patients with CAD and in blood vessel wall [5]. BH4 levels are reported to be reduced in heart tissue from rodent models of cardiac ischemia that results in NOS decoupling [6-8].</p