Altering Metabolic Profiles of Drugs by Precision Deuteration 2: Discovery of a Deuterated Analog of Ivacaftor with Differentiated Pharmacokinetics for Clinical Development.

Ivacaftor is currently used for the treatment of cystic fibrosis as both monotherapy (Kalydeco; Vertex Pharmaceuticals, Boston, MA) and combination therapy with lumacaftor (Orkambi; Vertex Pharmaceuticals). Each therapy targets specific patient populations: Kalydeco treats patients carrying one of nine gating mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, whereas Orkambi treats patients homozygous for the F508del CFTR mutation. In this study, we explored the pharmacological and metabolic effects of precision deuteration chemistry on ivacaftor by synthesizing two novel deuterated ivacaftor analogs, CTP-656 (-ivacaftor) and -ivacaftor.

Outcomes after repeat ablation of ventricular tachycardia in structural heart disease: An analysis from the International VT Ablation Center Collaborative Group.

Background: Data evaluating repeat radiofrequency ablation (>1RFA) of ventricular tachycardia (VT) are limited.

Objective: The purpose of this study was to determine the safety and outcomes of VT >1RFA in patients with structural heart disease.

Methods: Patients with structural heart disease undergoing VT RFA at 12 centers with data on prior RFA history were included.

Early Mortality After Catheter Ablation of Ventricular Tachycardia in Patients With Structural Heart Disease.

Background: In patients referred for radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in the setting of structural heart disease, early post-procedural mortality (EM) has not been previously investigated.

Objectives: The purpose of this study was to evaluate EM after catheter ablation of scar-related VT.

Methods: Associations between clinical and procedural variables and EM (within 31 days of the procedure) were tested in patients with structural heart disease undergoing RFCA of VT at 12 international centers.

Development of Asymmetric Facial Depigmentation in a Patient Treated with Dasatinib with New-Onset Hypovitaminosis D: Case Report and Review of the Literature.

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) used to treat imatinib-resistant chronic myelogenous leukemia (CML), as well as other Philadelphia chromosome-positive lymphoproliferative disorders. While the most commonly reported cutaneous side effects with this therapy include a morbilliform eruption, skin exfoliation, and skin irritation, pigmentary abnormalities have also been observed, albeit much more rarely. We present the case of a 72-year-old South Asian male with CML who presented with new-onset hypopigmentation of his face and scalp three years after a dose increase of dasatinib therapy, in the setting of newly discovered borderline hypovitaminosis D.

Permanent His-bundle pacing for cardiac resynchronization therapy: Initial feasibility study in lieu of left ventricular lead.

Background: Permanent His-bundle pacing (HBP) has the potential to physiologically normalize wide QRS duration in patients with bundle branch block and cardiomyopathy.

Objective: The purpose of this study was to assess the feasibility of incorporating a His-bundle lead for cardiac resynchronization therapy (CRT) in lieu of a coronary sinus lead.

Methods: Patients with an indication for CRT (n = 21) underwent attempted implantation of an HBP placed into the left ventricular (LV) lead port.

Atrial Arrhythmias and Electroanatomical Remodeling in Patients With Left Ventricular Assist Devices.

Background: The incidence, predictors, and impact of atrial arrhythmias along with left atrial structural changes in patients with left ventricular assist devices (LVADs) remain undetermined.

Methods And Results: All patients who underwent LVAD implantation from 2008 to 2015 at the University of Chicago Medical Center were included. Electronic medical records, electrocardiograms, echocardiograms, and cardiac electrical device interrogations were reviewed.

Processing Adipose-Rich Mohs Samples: A Comparative Study of Effectiveness of Pretreatment With Liquid Nitrogen Versus Flash Freezing Spray.

Processing of adipose-rich Mohs micrographic surgery (MMS) specimens poses challenges that may preclude complete margin evaluation. In this setting, the value of additional freezing methods using various cooling agents has not been previously investigated. The aim of this study is to compare the frozen section quality of high-adipose Mohs specimens processed without additional cooling treatments versus those pretreated with 1,1,1,2-tetrafluoroethane (TFE) or liquid nitrogen (LN2).

Ventricular Tachycardia Ablation in Severe Heart Failure: An International Ventricular Tachycardia Ablation Center Collaboration Analysis.

Background: Ventricular tachycardia (VT) radiofrequency ablation has been associated with reduced VT recurrence and mortality, although it is typically not considered among New York Heart Association class IV (NYHA IV) heart failure patients. We compared characteristics and VT radiofrequency ablation outcomes of those with and without NYHA IV in the International VT Ablation Center Collaboration.

Methods And Results: NYHA II-IV patients undergoing VT radiofrequency ablation at 12 international centers were included.

MAGNETIC VT study: a prospective, multicenter, post-market randomized controlled trial comparing VT ablation outcomes using remote magnetic navigation-guided substrate mapping and ablation versus manual approach in a low LVEF population.

Purpose: Patients with ischemic cardiomyopathy (ICM) are prone to scar-related ventricular tachycardia (VT). The success of VT ablation depends on accurate arrhythmogenic substrate localization, followed by optimal delivery of energy provided by constant electrode-tissue contact. Current manual and remote magnetic navigation (RMN)-guided ablation strategies aim to identify a reentry circuit and to target a critical isthmus through activation and entrainment mapping during ongoing tachycardia.

Localization of premature ventricular contractions from the papillary muscles using the standard 12-lead electrocardiogram: a feasibility study using a novel cardiac isochrone positioning system.

Aims: The precise localization of the site of origin of a premature ventricular contraction (PVC) prior to ablation can facilitate the planning and execution of the electrophysiological procedure. In clinical practice, the targeted ablation site is estimated from the standard 12-lead ECG. The accuracy of this qualitative estimation has limitations, particularly in the localization of PVCs originating from the papillary muscles.

Selective versus non-selective his bundle pacing for cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) has an established role in the device-based therapy for patients with systolic dysfunction and intraventricular conduction delay, particularly left bundle branch block (LBBB). Recently, His bundle pacing (HBP) has emerged as a viable alternative for resynchronization which can successfully narrow surface QRS and improve mechanical dyssynchrony. The role of selective (i.

Characterization of the epicardial substrate for catheter ablation of Brugada syndrome.

Background: Catheter ablation in the right ventricular outflow tract (RVOT) may modify the electrophysiologic substrate for recurrent ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with Brugada syndrome (BrS).

Objective: The purpose of this study was to investigate the mechanism and arrhythmogenic substrate of VT/VF and to evaluate the long-term outcomes of catheter ablation in patients with BrS.

Methods: Eleven consecutive patients with BrS referred to 2 academic medical centers underwent combined epicardial-endocardial electroanatomic mapping.

Sex and Catheter Ablation for Ventricular Tachycardia: An International Ventricular Tachycardia Ablation Center Collaborative Group Study.

Importance: Significant differences have been described between women and men regarding presentation, mechanism, and treatment outcome of certain arrhythmias. Previous studies of ventricular tachycardia (VT) ablation have not included sufficient women for meaningful comparison.

Objective: To compare outcomes between women and men with structural heart disease undergoing VT ablation.

Sustained Ventricular Tachycardia in Apparently Normal Hearts: Ablation Should Be the First Step in Management.

Patients without structural heart disease tend to have fewer morphologies of ventricular tachycardia, with automaticity and triggered activity a more common mechanism than re-entry associated with extremely low risk of sudden death. Ablation can be curative in patients with a single morphology of ventricular tachycardia that is focal in origin, particularly in patients without overt structural heart disease. There are limited data in secondary prevention implantable cardioverter defibrillator literature to support the routine implementation of implantable cardioverter defibrillator in normal hearts.

Directional Influences of Ventricular Activation on Myocardial Scar Characterization: Voltage Mapping With Multiple Wavefronts During Ventricular Tachycardia Ablation.

Background: The effects of varying the wavefront of activation on ventricular scar characterization has not been systematically assessed.

Methods And Results: Patients referred for ablation of scar-related ventricular tachycardia underwent voltage maps during a minimum of 2 wavefronts of activation. The bipolar and unipolar low-voltage areas were compared, and direct electrogram analysis was performed in regions where discrepancies were seen.