Evaluation of an adaptive, rule-based dosing algorithm to maintain therapeutic anticoagulation during atrial fibrillation ablation.

Background: Cerebral thromboembolism during atrial fibrillation (AF) ablation is an infrequent (0.17%) complication in part owing to strict adherence to intraprocedural anticoagulation. Failure to maintain therapeutic anticoagulation can lead to an increase in events, including silent cerebral ischemia. Objective: To evaluate a computerized, clinical decision support system (CDSS) to dose intraprocedural anticoagulation and determine if it leads to improved intraprocedural anticoagulation outcomes during AF ablation. Methods: The Digital Intern dosing algorithm is an adaptive, rule-based CDSS for heparin dosing. The initial dose is calculated from the patient's weight, baseline activated clotting time (ACT), and outpatient anticoagulant. Subsequent recommendations adapt based on individual patient ACT changes. Outcomes from 50 cases prior to algorithm introduction were compared to 139 cases using the algorithm. Results: Procedures using the dosing algorithm reached goal ACT (over 300 seconds) faster (17.6 ± 11.1 minutes vs 33.3 ± 23.6 minutes pre-algorithm, P < .001). ACTs fell below goal while in the LA (odds ratio 0.20 [0.10-0.39], P < .001) and rose above 400 seconds less frequently (odds ratio 0.21 [0.07-0.59], P = .003). System Usability Scale scores were excellent (96 ± 5, n = 7, score >80.3 excellent). Preprocedure anticoagulant, weight, baseline ACT, age, sex, and renal function were potential predictors of heparin dose to achieve ACT >300 seconds and final infusion rate. Conclusion: A heparin dosing CDSS based on rules and adaptation to individual patient response improved maintenance of therapeutic ACT during AF ablation and was rated highly by nurses for usability.

Into a Fluoroless Future: an Appraisal of Fluoroscopy-Free Techniques in Clinical Cardiac Electrophysiology.

PURPOSE OF REVIEW: There are risks to both patients and electrophysiology providers from radiation exposure from fluoroscopic imaging, and there is increased interest in fluoroscopic reduction. We review the imaging tools, their applications, and current uses to eliminate fluoroscopy. RECENT FINDINGS: Multiple recent studies provide supporting evidence for the transition to fluoroscopy-free techniques for both ablations and device implantation. The most frequently used alternative imaging approaches include intracardiac echocardiography, cardiac MRI guidance, and 3D electroanatomic mapping systems. Electroanatomic mapping and intracardiac echocardiography originally used to augment fluoroscopy imaging are now replacing the older imaging technique. The data supports that the future of electrophysiology can be fluoroscopy-free or very low fluoroscopy for the vast majority of cases. As provider and institution experience grows with these techniques, many EP labs may choose to completely forego the use of fluoroscopy. Trainees will benefit from early experience with these techniques.

Outcomes During Intended Fluoroscopy-free Ablation in Adults and Children.

Electroanatomic mapping (EAM) systems facilitate the elimination of fluoroscopy during electrophysiologic (EP) studies and ablations. The rate and predictors of fluoroscopy requirements while attempting fluoroscopy-free (FF) ablations are unclear. This study aimed (1) to investigate the rates of fluoroscopic use and acute success in patients initially referred for FF ablation and (2) to identify procedural characteristics associated with fluoroscopic use in patients in whom FF ablation was initially planned (IFF). We performed a retrospective review of all patients who underwent IFF EP study or ablation between 2010 and 2013. Patient and procedural characteristics were compared between those with successful FF procedures and those who subsequently required fluoroscopy during their procedure. An FF EP study with or without ablation was performed in 124 patients during 138 procedures for either supraventricular or idiopathic ventricular arrhythmias. Of the 138 procedures, 105 of them were performed without fluoroscopy. In the remaining 33 cases, fluoroscopy was used for an average of 1.21 minutes ± 1.18 minutes. Acute procedural success was achieved in 97% of both FF and fluoroscopy procedures. The primary reason for fluoroscopy use was as a guide for transseptal puncture. There were no significant differences between FF and fluoroscopy procedures with respect to catheter placement time or complication rate. In conclusion, in this single-center study of IFF procedures, despite careful case selection for IFF ablation, 24% of IFF cases ultimately required minimal fluoroscopy. Fluoroscopy and FF procedures had similar rates of procedural success and complications. Additional large prospective studies are required to further investigate the safety and efficacy of FF ablations.

P-Wave Amplitude and PR Changes in Patients With Inappropriate Sinus Tachycardia: Findings Supportive of a Central Mechanism.

BACKGROUND: The mechanism of inappropriate sinus tachycardia (IST) remains incompletely understood. METHODS AND RESULTS: We prospectively compared 3 patient groups: 11 patients with IST (IST Group), 9 control patients administered isoproterenol (Isuprel Group), and 15 patients with cristae terminalis atrial tachycardia (AT Group). P-wave amplitude in lead II and PR interval were measured at a lower and higher heart rate (HR1 and HR2, respectively). P-wave amplitude increased significantly with the increase in HR in the IST Group (0.16±0.07 mV at HR1=97±12 beats per minute versus 0.21±0.08 mV at HR2=135±21 beats per minute, P=0.001). The average increase in P-wave amplitude in the IST Group was similar to the Isuprel Group (P=0.26). PR interval significantly shortened with the increases in HR in the IST Group (146±15 ms at HR1 versus 128±16 ms at HR2, P<0.001). A similar decrease in the PR interval was noted in the Isuprel Group (P=0.6). In contrast, patients in the atrial tachycardia Group experienced PR lengthening during atrial tachycardia when compared with baseline normal sinus rhythm (153±25 ms at HR1=78±17 beats per minute versus 179±29 ms at HR2=140±28 beats per minute, P<0.01). CONCLUSIONS: We have shown that HR increases in patients with IST were associated with an increase in P-wave amplitude in lead II and PR shortening similar to what is seen in healthy controls following isoproterenol infusion. The increase in P-wave amplitude and absence of PR lengthening in IST support an extrinsic mechanism consistent with a state of sympatho-excitation with cephalic shift in sinus node activation and enhanced atrioventricular nodal conduction.

Machine Learning Algorithm Predicts Cardiac Resynchronization Therapy Outcomes: Lessons From the COMPANION Trial.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in heart failure patients with reduced left ventricular function and intraventricular conduction delay. However, individual outcomes vary significantly. This study sought to use a machine learning algorithm to develop a model to predict outcomes after CRT. METHODS AND RESULTS: Models were developed with machine learning algorithms to predict all-cause mortality or heart failure hospitalization at 12 months post-CRT in the COMPANION trial (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure). The best performing model was developed with the random forest algorithm. The ability of this model to predict all-cause mortality or heart failure hospitalization and all-cause mortality alone was compared with discrimination obtained using a combination of bundle branch block morphology and QRS duration. In the 595 patients with CRT-defibrillator in the COMPANION trial, 105 deaths occurred (median follow-up, 15.7 months). The survival difference across subgroups differentiated by bundle branch block morphology and QRS duration did not reach significance (P=0.08). The random forest model produced quartiles of patients with an 8-fold difference in survival between those with the highest and lowest predicted probability for events (hazard ratio, 7.96; P<0.0001). The model also discriminated the risk of the composite end point of all-cause mortality or heart failure hospitalization better than subgroups based on bundle branch block morphology and QRS duration. CONCLUSIONS: In the COMPANION trial, a machine learning algorithm produced a model that predicted clinical outcomes after CRT. Applied before device implant, this model may better differentiate outcomes over current clinical discriminators and improve shared decision-making with patients.

Concealed Accessory Pathways with a Single Ventricular and Two Discrete Atrial Insertion Sites.

BACKGROUND: Atrioventricular reciprocating tachycardia (AVRT) utilizing a concealed accessory pathway is common. It is well appreciated that some patients may have multiple accessory pathways with separate atrial and ventricular insertion sites. METHODS: We present three cases of AVRT utilizing concealed pathways with evidence that each utilizing a single ventricular insertion and two discrete atrial insertion sites. RESULTS: In case one, two discrete atrial insertion sites were mapped in two separate procedures, and only during the second ablation was the Kent potential identified. Ablation of the Kent potential at this site remote from the two atrial insertion sites resulted in the termination of the retrograde conduction in both pathways. Case two presented with supraventricular tachycardia (SVT) with alternating eccentric atrial activation patterns without alteration in the tachycardia cycle length. The two distinct atrial insertion sites during orthodromic AVRT and ventricular pacing were targeted and each of the two atrial insertion sites were successfully mapped and ablated. In case three, retrograde decremental conduction utilizing both atrial insertion sites was identified prior to ablation. After mapping and ablation of the first discrete atrial insertion site, tachycardia persisted utilizing the second atrial insertion site. Only after ablation of the second atrial insertion site was SVT noninducible, and VA conduction was no longer present. CONCLUSIONS: Concealed retrograde accessory pathways with discrete atrial insertion sites may have a common ventricular insertion site. Identification and ablation of the ventricular insertion site or the separate discrete atrial insertion sites result in successful treatment.

Survival After Secondary Prevention Implantable Cardioverter-Defibrillator Placement: An Analysis From the NCDR ICD Registry.

OBJECTIVES: This study sought to define the characteristics and risks of death of patients receiving a physician-designated secondary prevention implantable cardioverter-defibrillator (ICD) in contemporary clinical practice. BACKGROUND: Data on utilization and outcomes of ICDs for the secondary prevention of sudden cardiac death (SCD) are limited. METHODS: Patients enrolled in the National Cardiovascular Data Registry's (NCDR) ICD Registry from 2006 to 2009 with a physician-designated secondary prevention indication for ICD implantation were identified and linked to the Social Security Death Master File. Those patients with a history either of tachycardic arrest or sustained ventricular tachycardia (SCD/VT) or of syncope without SCD/VT were included. Kaplan-Meier survival analysis was used to assess mortality. Cox proportional hazards survival modeling was used to assess the risk of death in these groups, adjusting for patient characteristics. RESULTS: In the study cohort of 46,685 patients (mean age 66 ± 14 years, 73.5% male, 85% white), 78% had SCD/VT and 22% had syncope. Overall mortality was 10.4% at 1 year and 16.4% at 2 years. Compared with patients having SCD/VT, the adjusted hazard of death at 1 year was lower in the patients having syncope (hazard ratio: 0.89; 95% confidence interval: 0.83 to 0.96) but was not significantly different by 2 years (hazard ratio: 0.96; 95% confidence interval: 0.90 to 1.01). CONCLUSIONS: Nearly 9 of 10 patients receiving a secondary prevention ICD in clinical practice are alive 1 year after implantation. The risk of death varies by indication and is highest among patients who survive SCD or sustained VT in the first year after device implantation.

Immunotherapy for prostate cancer - recent progress in clinical trials.

Prostate cancer is the most common malignancy affecting men in the United States. Traditional therapy with radical prostatectomy or radiation therapy can be curative for localized disease, but metastatic prostate cancer is currently incurable. The only treatments known to prolong survival in patients with metastatic disease are androgen-deprivation therapy and chemotherapy, both of which have significant side effects. Immunotherapy approaches offer hope in providing new treatments to delay disease progression, ideally with fewer side effects. The results from nearly all early immunotherapy clinical trials for prostate cancer conducted to date have shown minimal toxicity, and many have suggested clinical benefit in terms of delaying disease progression. Several phase III clinical trials are currently under way in patients with metastatic, androgen-independent prostate cancer. The current article reviews recent trials evaluating immune-modulating agents, antigen-specific active immunotherapy, and combination therapies in clinical development for the treatment of prostate cancer.

Chemical inhibition of the TFIIH-associated kinase Cdk7/Kin28 does not impair global mRNA synthesis.

The process of gene transcription requires the recruitment of a hypophosphorylated form of RNA polymerase II (Pol II) to a gene promoter. The TFIIH-associated kinase Cdk7/Kin28 hyperphosphorylates the promoter-bound polymerase; this event is thought to play a crucial role in transcription initiation and promoter clearance. Studies using temperature-sensitive mutants of Kin28 have provided the most compelling evidence for an essential role of its kinase activity in global mRNA synthesis. In contrast, using a small molecule inhibitor that specifically inhibits Kin28 in vivo, we find that the kinase activity is not essential for global transcription. Unlike the temperature-sensitive alleles, the small-molecule inhibitor does not perturb protein-protein interactions nor does it provoke the disassociation of TFIIH from gene promoters. These results lead us to conclude that other functions of TFIIH, rather than the kinase activity, are critical for global gene transcription.