RHYTHM-AF: design of an international registry on cardioversion of atrial fibrillation and characteristics of participating centers.

BACKGROUND: Atrial fibrillation is a serious public health problem posing a considerable burden to not only patients, but the healthcare environment due to high rates of morbidity, mortality, and medical resource utilization. There are limited data on the variation in treatment practice patterns across different countries, healthcare settings and the associated health outcomes. METHODS/DESIGN: RHYTHM-AF was a prospective observational multinational study of management of recent onset atrial fibrillation patients considered for cardioversion designed to collect data on international treatment patterns and short term outcomes related to cardioversion. We present data collected in 10 countries between May 2010 and June 2011. Enrollment was ongoing in Italy and Brazil at the time of data analysis. Data were collected at the time of atrial fibrillation episode in all countries (Australia, Brazil, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom), and cumulative follow-up data were collected at day 60 (±10) in all but Spain. Information on center characteristics, enrollment data, patient demographics, detail of atrial fibrillation episode, medical history, diagnostic procedures, acute treatment of atrial fibrillation, discharge information and the follow-up data on major events and rehospitalizations up to day 60 were collected. DISCUSSION: A total of 3940 patients were enrolled from 175 acute care centers. 70.5% of the centers were either academic (44%) or teaching (26%) hospitals with an overall median capacity of 510 beds. The sites were mostly specialized with anticoagulation clinics (65.9%), heart failure (75.1%) and hypertension clinics (60.1%) available. The RHYTHM-AF registry will provide insight into regional variability of antiarrhythmic and antithrombotic treatment of atrial fibrillation, the appropriateness of such treatments with respect to outcomes, and their cost-efficacy. Observations will help inform strategies to improve cardiovascular outcomes in patients with atrial fibrillation. TRIAL REGISTRATION: Clinical trials NCT01119716.

Relationship between a validated molecular cardiac transplant rejection classifier and routine organ function parameters.

BACKGROUND: As acute cellular cardiac allograft rejection is a systemic process affecting the entire organism, we hypothesized that scores of a peripheral blood mononuclear cell gene expression profiling (GEP) test developed and validated to rule out International Society of Heart and Lung Transplantation (ISHLT) grade > or = 3A/2R acute cellular cardiac allograft rejection also reflects biologically plausible changes of the routinely assessed clinical parameters. METHODS: We retrospectively analyzed 76 patients who underwent GEP testing, at the time of their routine clinical follow-up in our Institution between February 1, 2006 and January 31, 2007. Data were analyzed with t-test, nonparametric tests, bivariate Spearman's correlation, and multivariate linear regression modeling. RESULTS: More activated GEP-score correlated with longer corrected QT (QTc)-interval (r = 0.377, p = 0.001, n = 63), longer QRS duration (r = 0.231, p = 0.03, n = 66), higher heart rate (r = 0.221, p = 0.037, n = 66), higher serum creatinine (r = 0.26, p = 0.01, n = 75), higher gamma-glutamyl transferase (GGT) GGT (r = 0.266, p = 0.037, n = 46), lower pulmonary artery oxygen saturation (r = -0.313, p = 0.003, n = 76), lower platelet count (r = -0.372, p = 0.001, n = 74), lower monocyte count (r = -0.208, p = 0.040, n = 72), and lower high-density lipoprotein (HDL) HDL level (r = -0.242, p = 0.041, n = 53). Multivariate analysis showed a significant amount of variance in the GEP score independently explained by the variability of QTc-interval (beta = 1.998, p = 0.001) and platelet count (beta = -1.540, p = 0.017). Post hoc analysis of the 11 individual GEP-classifier genes showed WDRA40 (p = 0.02) and ras homolog gene family, member U (RHOU) RHOU (p = 0.01) independently related to mixed venous O(2)Sat%. CONCLUSION: A GEP test developed and validated to detect the absence of cardiac rejection correlates with electrocardiographic and hemodynamic cardiac parameters as well as renal, hepatic, bone marrow, and lipid metabolism parameters suggesting a complex relationship between rejection, leukocytes, and organ function within the continuum between alloimmunological quiescence and rejection.

Evaluation of blood pressure reduction response and responder characteristics to fixed-dose combination treatment of amlodipine and losartan: a post hoc analysis of pooled clinical trials.

Data from four clinical trials compared reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) among patients treated with amlodipine/losartan 5/50 mg vs 5/100 mg and amlodipine/losartan 5/50 mg vs amlodipine 5 mg and 10 mg. Response rate was assessed as reduction in SBP or DBP (>20/10 mm Hg) and proportion of patients achieving SBP <140 mm Hg or DBP <90 mm Hg. Patients were grouped into quartiles based on baseline SBP and DBP. Mean SBP and DBP were reduced in amlodipine/losartan 5/50 mg (n=182) and amlodipine/losartan 5/100 mg (n=95) users across all baseline quartiles. Patients using amlodipine/losartan 5/50 mg had significantly greater SBP and DBP reductions vs amlodipine 5 mg (P=.001 and P=.02, respectively). Amlodipine/losartan 5/50 mg users had significantly greater SBP reduction vs amlodipine 10 mg (SBP P=.02; DBP P=not significant). The odds of responding to therapy were significantly greater with amlodipine/losartan 5/50 mg vs amlodipine 5 mg (odds ratio, 5.33; 95% confidence interval, 1.42-25.5) and were similar vs amlodipine 10 mg (odds ratio, 0.67; 95% confidence interval, 0.017-9.51). These results support the use of combination therapy early in the treatment of hypertension.

Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy.

Background. Cardiac allograft vasculopathy (CAV) is a major cause of graft loss and death after heart transplantation. Currently, no diagnostic methods are available during the early post-transplant period to accurately identify patients at risk of CAV. We hypothesized that PBMC gene expression profiles (GEP) can identify patients at risk of CAV. Methods. We retrospectively analyzed a limited set of whole-genome PBMC microarrays from 10 post-transplant patients who did (n = 3) or did not (n = 7) develop advanced grade CAV during their long-term follow-up. We used significance analysis of microarrays to identify differentially expressed genes and High-Throughput GoMiner to assess gene ontology (GO) categories. We corroborated our findings by retrospective analysis of PBMC real-time PCR data from 33 patients. Results. Over 300 genes were differentially expressed (FDR < 5%), and 18 GO-categories including "macrophage activation", "Interleukin-6 pathway", "NF-KappaB cascade", and "response to virus" were enriched by these genes (FDR < 5%). Out of 8 transcripts available for RT-PCR analysis, we confirmed 6 transcripts (75.0%) including FPRL1, S100A9, CXCL10, PRO1073, and MMP9 (P < .05). Conclusion. Our pilot data suggest that GEP of PBMC may become a valuable tool in the evaluation of patients at risk of CAV. Larger prospectively designed studies are needed to corroborate our hypothesis.