A multi-variate predictability framework to assess invasive cardiac activity and interactions during atrial fibrillation

Objective: This study introduces a predictability framework based on the concept of Granger causality (GC), in order to analyze the activity and interactions between different intracardiac sites during atrial fibrillation (AF). Methods: GC-based interactions were studied using a three-electrode analysis scheme with multi-variate autoregressive models of the involved preprocessed intracardiac signals. The method was evaluated in different scenarios covering simulations of complex atrial activity as well as endocardial signals acquired from patients. Results: The results illustrate the ability of the method to determine atrial rhythm complexity and to track and map propagation during AF. Conclusion: The proposed framework provides information on the underlying activation and regularity, does not require activation detection or postprocessing algorithms and is applicable for the analysis of any multielectrode catheter. Significance: The proposed framework can potentially help to guide catheter ablation interventions of AF

Selection of reference genes is critical for miRNA expression analysis in human cardiac tissue. A focus on atrial fibrillation

MicroRNAs (miRNAs) are emerging as key regulators of complex biological processes in several cardiovascular diseases, including atrial fibrillation (AF). Reverse transcription-quantitative polymerase chain reaction is a powerful technique to quantitatively assess miRNA expression profile, but reliable results depend on proper data normalization by suitable reference genes. Despite the increasing number of studies assessing miRNAs in cardiac disease, no consensus on the best reference genes has been reached. This work aims to assess reference genes stability in human cardiac tissue with a focus on AF investigation. We evaluated the stability of five reference genes (U6, SNORD48, SNORD44, miR-16, and 5S) in atrial tissue samples from eighteen cardiac-surgery patients in sinus rhythm and AF. Stability was quantified by combining BestKeeper, delta-Cq, GeNorm, and NormFinder statistical tools. All methods assessed SNORD48 as the best and U6 as the worst reference gene. Applications of different normalization strategies significantly impacted miRNA expression profiles in the study population. Our results point out the necessity of a consensus on data normalization in AF studies to avoid the emergence of divergent biological conclusions

Monitoring steam penetration in channeled instruments: an evidence-based worst-case for practical situations

Steam sterilization of channeled medical devices requires steam penetration into narrow channels. However, a quantitative characterization of this phenomenon in practical situations is lacking. This study evaluates the effect of load, loading pattern, and wrapping system on steam penetration into channels. We tested the hypothesis that a 70 cm tube with one closed end could be representative of the worst case for steam penetration in wrapped channeled instruments in practical conditions. A validated sterilization process was run in a sterilizer equipped with infrared sensors for the measurement of water vapor fraction (WVF). WVF values collected at the closed end of an unwrapped 70 cm reference tube were compared to those obtained at the closed end of wrapped 50 cm test tubes, representative for channeled devices in the clinical practice. The open ends of the test tubes were placed inside packs, testing the effects of different combinations of wrappings, load amounts, and pack positions. The worst case for steam penetration was experimentally defined as the condition showing the lowest WVF value during the exposure phase. WVF values at the closed end of 50 cm long tubes were affected by load amount, wrapping, and pack position. Steam penetration was higher for heavier loads in rigid containers, but lower for heavier loads in soft wrappings (pouch, non-woven fabric, and crepe). In all the tested combinations of load/wrappings related to the clinical practice the 70 cm reference tube displayed lower WVF values than the wrapped 50 cm test tubes, indicating worse steam penetration in the reference than test tubes. Our findings provide experimental evidence that a 70 cm is the worst case in all practical combinations of load and wrapping encountered in the field. The 70 cm tube is a representative for a wrapped 50 cm channel with one end closed and for a wrapped 100 cm channel with both ends open. A measuring system integrating the WVF sensor on a 70 cm tube may provide a physics-based, quantitative steam penetration test for real-time monitoring of the steam sterilization process of channeled instruments

Declining clinical benefit of ICD in heart failure patients: Temporal trend of mortality outcomes from randomized controlled trials

The risk of sudden cardiac death in patients with heart failure has declined over time thanks to the sequential introduction of new treatments. However, current guidelines recommendations for implantable cardioverter-defibrillator (ICD) are based on randomized controlled trials (RCTs) carried out in the past three decades and their meta-analyses. To highlight potential changes over time in ICD clinical benefit in primary prevention of sudden cardiac death, we analyzed the temporal trends of RCT risk of mortality outcomes in this time frame

Ventricular tachycardia-inducibility predicts arrhythmic events in post-myocardial infarction patients with low ejection fraction. A systematic review and meta-analysis

Background: Inducibility of ventricular arrhythmias at electrophysiological study (EPS) has long been suggested as predictive for subsequent arrhythmic events. Nevertheless, the usefulness of EPS in the clinical practice is still unclear. We performed a systematic review and meta-analysis to assess the predictive power of EPS in primary prevention of ventricular arrhythmias in post-myocardial infarction (MI) patients with left ventricular dysfunction. Methods: MEDLINE and the Cochrane Library databases were systematically searched to identify studies, which analyzed EPS predictive value in post-MI patients with mean EF < 40% for the composite arrhythmic endpoint defined by: sudden cardiac death (SCD), aborted SCD, ventricular tachycardia (VT), ventricular fibrillation (VF), appropriate implantable cardioverter-defibrillator (ICD) interventions. Results: Nine studies, evaluating 3959 patients with 647 arrhythmic events, were included in the meta-analyses. EPS showed a strong predictive power for the arrhythmic endpoint with a pooled odds ratio (OR) of 4.00 (95% confidence interval [CI]: 2.30–6.96) in the whole set of studies, albeit a high level of heterogeneity among studies. EPS predictive power was higher in studies where VT-inducibility was tested (OR 6.52; 95% CI: 2.30–18.44; sensitivity 0.65, specificity 0.78, and negative predictive value 0.94), versus those assessing VT/VF-inducibility (OR 2.09; 95% CI: 1.34–3.26). VT-inducibility was predictive even when assessed within one month after MI (OR 7.85; 95% CI: 3.67–16.80). Conclusions: Inducibility of ventricular arrhythmias at EPS is a strong predictor of the arrhythmic endpoint in post-MI patients with impaired EF, particularly when VT-inducibility is tested. EPS could help selecting the patients who can mostly benefit from ICD therapy. Keywords: Arrhythmia inducibility, Clinical electrophysiology, Implantable cardioverter-defibrillator, Left ventricular dysfunction, Myocardial infarction, Sudden cardiac deat