Creation and Validation of an Algorithm for Predicting the Recurrence of Atrial Fibrillation Following Pulmonary Vein Isolation by Utilizing Real-World Data and Ensemble Modeling Techniques.

Introduction Catheter ablation (CA) of atrial fibrillation (AF) represents a mainstay in the treatment of this increasingly prevalent arrhythmia. Prospective clinical trials investigating the efficacy of CA may poorly represent real-world patient populations. However, many real-world clinical datasets possess missing data, which may impede their applicability in research. Thus, we sought to use ensemble modeling to address missing data and develop a model to estimate the probability of AF recurrence following CA. Methods We retrospectively analyzed clinical variables in 476 patients who underwent an initial CA of AF. Univariate and multivariate logistic regression was performed to determine those variables predictive of AF recurrence. A multivariate logistic model was created to estimate the probability of AF recurrence after CA. Missing data were addressed using ensemble modeling, and variable selection was performed using the aggregate of multiple models. Results After analysis, six variables remained in the model: AF during the post-procedural blanking period, coexistence of atrial flutter, end-stage renal disease, reduced left ventricular ejection fraction, prior failure of anti-arrhythmic drugs, and valvular heart disease. Predictive modeling was performed using these variables for 1000 randomly partitioned datasets (80% training, 20% testing) and 1000 random imputations for each partitioned dataset. The model predicted AF recurrence with an accuracy of 74.34 ± 3.99% (recall: 54.03 ± 8.15%; precision: 89.30 ± 4.21%; F1 score: 81.08 ± 3.65%).  Conclusion We successfully identified six clinical variables that, when modeled, predicted AF recurrence following CA with a high degree of classification accuracy. Application of this model to patients undergoing CA of AF may help identify those at risk of post-procedural AF recurrence.

Validity of 1% Hormonal Receptor Positivity Cutoff by the ASCO/College of American Pathologists Guidelines at the Georgia Cancer Center.

PURPOSE: Treatment of breast cancer (BC) with borderline or low (1%-9%) estrogen and progesterone expression remains controversial, with recent data disputing ASCO/College of American Pathologists 2010 guidelines that lowered the threshold of receptor positivity from 10% to 1%. The objective of this retrospective study was to validate these guidelines at the Georgia Cancer Center with a high percentage of Black race. METHODS: All female patients with invasive BC diagnosed between 2005 and 2010 at the Georgia Cancer Center were chart reviewed up to an 11-year follow-up with data cutoff at 2016. We used Cox regression to explore survival among three hormonal status (HS) groups (< 1%, 1%-9%, and ≥ 10%) adjusting for all known BC clinicopathologic variables. Fisher's exact test was used to evaluate response to endocrine therapy (ET). RESULTS: Among 431 patients with mean age 59 years, 24.75% had HS < 1%, 17.5% HS 1%-9%, and 57.75% HS ≥ 10%. Race was 43.75% Black and 54% White. Disease stages were early (I-IIIA) in 84.4% and advanced (IIIB-IV) in 15.56%. Mortality in HS < 1% was significantly higher than that in HS ≥ 10% (hazard ratio [HR]: 1.8; 95% CI, 1.07 to 3.02), whereas no significant mortality difference between HS 1%-9% and HS ≥ 10% (HR: 1.05; 95% CI, 0.48 to 2.30) was observed. ET was protective, and treated patients had higher predicted survival than untreated patients in the 1%-9% group (HR: 0.10; 95% CI, 0.01 to 0.85). There was no significant mortality difference between ET-treated HS 1%-9% and ≥ 10% groups. CONCLUSION: One percent cutoff predicted superior survival on treatment with ET compared with the other groups, and HS as low as 1%-9% was equiprognostic to HS ≥ 10%. Whether other factors such as lymphovascular invasion, grade, and other parameters change the behavior of the 1%-9% HS group remains to be explored.

Development of Tg(UAS:SEC-Hsa.ANXA5-YFP,myl7:RFP); Casper(roy-/-,nacre-/-) Transparent Transgenic In Vivo Zebrafish Model to Study the Cardiomyocyte Function.

The zebrafish provided an excellent platform to study the genetic and molecular approach of cellular phenotype-based cardiac research. We designed a novel protocol to develop the transparent transgenic zebrafish model to study annexin-5 activity in the cardiovascular function by generating homozygous transparent skin Casper(roy-/-,nacre-/-); myl7:RFP; annexin-5:YFP transgenic zebrafish. The skin pigmentation background of any vertebrate model organism is a major obstruction for in vivo confocal imaging to study the transgenic cellular phenotype-based study. By developing Casper(roy-/-,nacre-/-); myl7; annexin-5 transparent transgenic zebrafish strain, we established time-lapse in vivo confocal microscopy to study cellular phenotype/pathologies of cardiomyocytes over time to quantify changes in cardiomyocyte morphology and function over time, comparing control and cardiac injury and cardio-oncology. Casper contributes to the study by integrating a transparent characteristic in adult zebrafish that allows for simpler transparent visualization and observation. The Casper(roy-/-,nacre-/-) transgenic progenies developed through cross-breeding with the transgenic strain of Tg(UAS:SEC-Hsa.ANXA5-YFP,myl7:RFP). Confocal and fluorescent microscopy were being used to obtain accurate, precise imaging and to determine fluorescent protein being activated. This study protocol was conducted under two sections; 1.1: Generation of homozygous Tg(UAS:SEC-Hsa.ANXA5-YFP,myl7:RFP); Casper(roy-/-,nacre-/-) zebrafish (generation F01-F06) and 1.2: Screening and sorting the transparent transgenic progeny and in vivo imaging to validate cardiac morphology through in vivo confocal imaging. We coined the newly developed strain as Tg(UAS:SEC-Hsa.ANXA5-YFP,myl7:RFP); Casper(roy-/-,nacre-/-)gmc1. Thus, the newly developed strain maintains transparency of the skin throughout the entire life of zebrafish and is capable of application of a non-invasive in vivo imaging process. These novel results provide an in vivo whole organism-based platform to design high-throughput screening and establish a new horizon for drug discovery in cardiac cell death and cardio-oncology therapeutics and treatment.

Safety of Phosphodiesterase-5 Inhibitors in Valvular Heart Disease.

ABSTRACT: Erectile dysfunction is a common entity in clinical practice. Primary erectile dysfunction, not related to vasculopathy or psychiatric disorder, can be readily treated with phosphodiesterase inhibitors. These drugs have many physiologic effects that can alter a patient's hemodynamic profile considerably, especially in the presence of concomitant structural heart disease, specifically valvular heart disease. Although some contraindications to the use of PDE5 inhibitors in patients with cardiovascular disease are defined, the effect of these drugs in the presence of valvular heart disease is not well documented. The purpose of this review is to analyze the data regarding the safety of PDE5 inhibitors in patients with valvular heart disease.

Efficacy of Implantable Cardioverter-defibrillators for Secondary Prevention of Sudden Cardiac Death in Patients with End-stage Renal Disease.

End-stage renal disease (ESRD) constitutes a major burden on the health-care system in the United States, with more than 300,000 patients nationwide being treated with renal replacement therapy. Very few studies to date have evaluated the benefit of implantable cardioverter-defibrillator (ICD) implantation for secondary prevention in patients with ESRD. In this study, we evaluated the efficacy of secondary-prevention ICDs in reducing all-cause mortality in patients on dialysis using the United States Renal Data System (USRDS) database. We queried the USRDS for relevant data between 2004 and 2010. Patients with diagnoses of ventricular fibrillation (VF), ventricular tachycardia (VT), or sudden cardiac arrest (SCA) were included in the study. Patients were excluded from the analysis if they were younger than 18 years; had missing age, sex, or race/ethnicity information; had experienced myocardial infarction; or had an ICD in situ at the time of VF, VT, or SCA diagnosis. The primary endpoint of this study was to determine the efficacy of secondary-prevention ICDs in reducing all-cause mortality in patients on dialysis. A total of 1,442 patients (3.4%) with ESRD had ICD insertion. Patients who received an ICD were predominantly younger, white males with lower Charlson Comorbidity Index and with fewer cardiovascular events. Survival at two years was 53% among those with an ICD relative to 27% among those without an ICD. In this study, we observed a substantial decrease in mortality in patients receiving an ICD for secondary prevention when compared with a cohort of similar patients with a history of VF, VT, or SCA.