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Background Many risk models for predicting mortality, hospitalizations, or both in patients with heart failure have been developed but do not have sufficient discriminatory ability. The purpose of this study was to identify predictive biomarkers of hospitalizations in heart failure patients using omics-based technologies applied to blood and electrical monitoring of the heart. Methods Blood samples were collected from 58 heart failure patients during enrollment into this study. Each patient wore a 48-hour Holter monitor that recorded the electrical activity of their heart. The blood samples were profiled for gene expression using microarrays and protein levels using multiple reaction monitoring. Statistical deconvolution was used to estimate cellular frequencies of common blood cells. Classification models were developed using clinical variables, Holter variables, cell types, gene transcripts, and proteins to predict hospitalization status. Results Of the 58 patients recruited, 13 were hospitalized within 3 months after enrollment. These patients had lower diastolic and systolic blood pressures, higher brain natriuretic peptide levels, most had higher blood creatinine levels, and had been diagnosed with heart failure for a longer time period. The best-performing clinical model had an area under the receiver operating characteristic curve of 0.76. An ensemble biomarker panel consisting of Holter variables, cell types, gene transcripts, and proteins had an area under the receiver operating characteristic curve of 0.88. Conclusions Molecular-based analyses as well as sensory data might provide sensitive biomarkers for the prediction of hospitalizations in heart failure patients. These approaches may be combined with traditional clinical models for the development of improved risk prediction models for heart failure.

Background Acute rejection in cardiac transplant patients remains a contributory factor to limited survival of implanted hearts. Currently, there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplant acute cellular rejection. Such a development would be of great value in personalizing immunosuppressive treatment. Methods Recipient age, donor age, cold ischemic time, warm ischemic time, panel-reactive antibody, gender mismatch, blood type mismatch and human leukocyte antigens (HLA-A, -B and -DR) mismatch between recipients and donors were tested in 53 heart transplant patients for their power to predict post-transplant acute cellular rejection. Donor transplant biopsy and recipient pre-transplant blood were also examined for the presence of genomic biomarkers in 7 rejection and 11 non-rejection patients, using non-targeted data mining techniques. Results The biomarker based on the 8 clinical variables had an area under the receiver operating characteristic curve (AUC) of 0.53. The pre-transplant recipient blood gene-based panel did not yield better performance, but the donor heart tissue gene-based panel had an AUC=0.78. A combination of 25 probe sets from the transplant donor biopsy and 18 probe sets from the pre-transplant recipient whole blood had an AUC=0.90. Biologic pathways implicated include VEGF- and EGFR-signaling, and MAPK. Conclusions Based on this study, the best predictive biomarker panel contains genes from recipient whole blood and donor myocardial tissue. This panel provides clinically relevant prediction power and, if validated, may personalize immunosuppressive treatment and rejection monitoring.

Topical recombinant alpha-2 interferon treatment of recurrent genital herpes was studied in a randomized, double-blind, placebo controlled clinical trial. Three hundred and eighty-seven patients were treated at eight study centers with either interferon gel or placebo four times daily for four days. Interferon therapy caused a 26% decrease in the duration of viral shedding. For male patients, there were also significant decreases in the time to crusting (17%) and duration of pain (34%) and itching (21%). For patients with recurrent genital herpes, treatment with topical interferon was found to be effective in decreasing the duration of viral shedding and, for males, pain, itching and time to crusting.

s S139 Canadian Cardiovascular Society (CCS) Highlighted Poster HEART FAILURE HIGHLIGHTED POSTER SESSION Thursday, October 17, 2013 126 BIOMARKERS OF DIASTOLIC AND SYSTOLIC HEART FAILURE Z Hollander, KK Lam, V Chen, JE Wilson-McManus, RT Ng, SJ Tebbutt, BM McManus, A Ignaszewski, T Anderson, J Ezekowitz, GY Oudit, JR Dyck Vancouver, British Columbia BACKGROUND: Heart failure (HF) is a modern day epidemic with a rising prevalence and affects over 23 million global citizens. Methods to identify or diagnose a patient with HF include clinical history, physical exam, imaging and blood tests. The most commonly used blood tests are markers of natriuretic peptides, however, there is a large diagnostic “grey zone” in natriuretic peptides that renders them less useful as a stand-alone HF diagnostic test. In addition, they have not been shown to distinguish between diastolic HF (DHF) and systolic HF (SHF). METHODS: A discovery cohort comprised of 38 DHF patients, 54 SHF patients, and 22 healthy controls (HC) were enrolled in the Alberta HEART initiative. Plasma and PAXgene whole blood samples were analyzed at the PROOF Centre of Excellence with iTRAQ and MRM mass spectrometry and Affymetrix GeneST microarrays, respectively. Samples from a separate replication cohort, again from Alberta Heart (35 DHF, 77 SHF, and 36 HC), were analyzed with MRM mass spectrometry. The PROOF Centre biomarker development pipeline was used to identify novel blood test content by comparing DHF with SHF or comparing HC with HF patients. The computational analysis strategy consisted of prefiltering, univariate and multivariate tests, and classification. The performance of the sets of genes and proteins was assessed in the replication cohort. RESULTS: Proteomic biomarkers of HF were identified in the discovery cohort. When these protein panels were tested in the replication cohort, the area under the receiver operating characteristics curve (AUC) was 0.93. The NT-proBNP cut-off between DHF and HC was determined within the discovery cohort. An analysis combining the cohort-specific NT-proBNP cutoff with a set of novel proteins revealed an increase in performance characteristics (Figure), particularly for the specificity (from 34% to 80%) withNRI of 49%. Panels combining genes and proteins were able to distinguish between DHF and SHF patients. Cross-validation results using the discovery cohort data are promising for differentiating DHF from SHF using a combination of blood-based genes and proteins in women (AUC1⁄40.87) and in men (AUC1⁄4 0.83). CONCLUSION: Novel biomarkers of HF that can improve on the performance characteristics of NT-proBNP have been identified and replicated. Biomarker panels containing genes and proteins have been identified for discriminating between DHF and SHF. All results require further replication and validation in larger cohorts from patients outside of Alberta. 127 DECISION-MAKING ABOUT GOALS OF CARE FOR HOSPITALIZED PATIENTS WITH HEART FAILURE (DECIDE-HF): A PILOT STUDY N Aleksova, C Demers, PH Strachan, J Hoefs, M Yous, J MacIver, J Downar, M Wang, R Fowler, DK Heyland, HJ Ross, J You