Validation of scoring system predicting permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with severe aortic stenosis. Despite newer generation valves, atrioventricular (AV) conduction disturbance is a common complication, necessitating permanent pacemaker (PPM) implantation in about 10% of patients. Hence, it is imperative to improve periprocedural risk stratification to predict PPM implantation after TAVR. The objective of this study was to externally validate a novel risk-stratification model derived from the National Inpatient Sample (NIS) database that predicts risk of PPM from TAVR. METHODS: Components of the score included pre-TAVR left and right bundle branch block, sinus bradycardia, second-degree AV block, and transfemoral approach. The scoring system was applied to 917 patients undergoing TAVR at our institution from November 2011 to February 2017. We assessed its predictive accuracy by looking at two components: discrimination using the C-statistic and calibration using the Hosmer-Lemeshow goodness of fit test. RESULTS: Ninety patients (9.8%) required PPM. The scoring system showed good discrimination with C-statistic score of 0.6743 (95% CI: 0.618-0.729). Higher scores suggested increased PPM risk, that is, 7.3% with score ⩽3, 19.23% with score 4-6, and 37.50% with score ≥7. Patients requiring PPM were older (81.4 versus 78.7 years, P = .002). Length of stay and in-hospital mortality was significantly higher in PPM group. CONCLUSIONS: The NIS database derived PPM risk prediction model was successfully validated in our database with acceptable discriminative and gradation capacity. It is a simple but valuable tool for patient counseling pre-TAVR and in identifying high-risk patients.

Radiotherapy-Induced Malfunction in Contemporary Cardiovascular Implantable Electronic Devices: Clinical Incidence and Predictors.

IMPORTANCE: Risk stratification and management paradigms for patients with cardiovascular implantable electronic devices (CIEDs) requiring radiotherapy (RT) vary widely and are based on limited clinical data. OBJECTIVE: To identify the incidence and predictors of CIED malfunction and describe associated clinical consequences in a large cohort of patients treated with photon- and electron-based RT. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of all patients with a functioning CIED who underwent RT between August 2005 and January 2014 with CIED interrogation data following RT at an academic cancer center. We identified 249 courses of photon- and electron-based RT in 215 patients (123 pacemakers [57%]; 92 implantable cardioverter-defibrillators [43%]). Substantial neutron production was generated in 71 courses (29%). EXPOSURE: Implantation of CIED with subsequent therapeutic radiation treatment (neutron producing with 15- or 18-MV photons and non-neutron producing with electrons, GammaKnife, or 6-MV photons). MAIN OUTCOMES AND MEASURES: Malfunction of CIED, characterized as single-event upset (data loss, parameter resets, unrecoverable resets), and delayed effects including signal interference, pacing threshold changes, and premature battery depletion. RESULTS: Malfunction of CIED attributable to RT occurred during 18 courses (7%), with 15 CIEDs experiencing single-event upsets, and 3, transient signal interference. All single-event upsets occurred during neutron-producing RT, at a rate of 21%, 10%, and 34% per neutron-producing course for CIEDs, pacemakers, and implantable cardioverter-defibrillators, respectively. No single-event upsets were found among 178 courses of non-neutron-producing RT. Incident CIED dose did not correlate with device malfunction. Patients treated to the abdomen and pelvis region were more likely to undergo a single-event upset (hazard ratio, 5.2 [95% CI, 1.2-22.6]; P = .03). Six patients with a CIED parameter reset developed clinical symptoms: 3 experienced hypotension and/or bradycardia, 2 experienced abnormal chest ticking consistent with pacemaker syndrome, and 1 developed congestive heart failure. The 3 episodes of signal interference did not result in clinical effects. No delayed malfunctions were directly attributed to RT. CONCLUSIONS AND RELEVANCE: In a cohort of contemporary CIEDs, all cases of single-event upset malfunction occurred in the setting of notable neutron production, at a rate of 21% for neutron-producing RT and 0% for non-neutron-producing RT. Where clinically feasible, the use of non-neutron-producing RT is recommended. Given the lack of correlation between CIED malfunction and incident dose observed up to 5.4 Gy, invasive CIED relocation procedures in these settings can be minimized.

Biomarkers for the development of new medications for cocaine dependence.

There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as biomarkers. In cancer treatment research, biomarkers have permitted a more accurate pathophysiological characterization of an individual patient, and have enabled practitioners to target mechanistically the right drug, to the right patient, at the right time. Similar to cancer, patients with substance use disorders (SUDs) present clinically with heterogeneous symptomatology and respond variably to therapeutic interventions. If comparable biomarkers could be identified and developed for SUDs, significant diagnostic and therapeutic advances could be made. In this review, we highlight current opportunities and difficulties pertaining to the identification and development of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine dependence are discussed across a range of methodological approaches. A possible cocaine-dependent clinical outcome assessment (COA)--another type of defined DDT--is also discussed. At present, biomarkers for cocaine dependence are in their infancy. Much additional research will be needed to identify, validate, and qualify these putative tools prior to their potential use for medications development and/or application to clinical practice. However, with a large unmet medical need and an estimated market size of several hundred million dollars per year, if developed, biomarkers for cocaine dependence will hold tremendous value to both industry and public health.

Malfunctions of implantable cardiac devices in patients receiving proton beam therapy: incidence and predictors.

PURPOSE: Photon therapy has been reported to induce resets of implanted cardiac devices, but the clinical sequelae of treating patients with such devices with proton beam therapy (PBT) are not well known. We reviewed the incidence of device malfunctions among patients undergoing PBT. METHODS AND MATERIALS: From March 2009 through July 2012, 42 patients with implanted cardiac implantable electronic devices (CIED; 28 pacemakers and 14 cardioverter-defibrillators) underwent 42 courses of PBT for thoracic (23, 55%), prostate (15, 36%), liver (3, 7%), or base of skull (1, 2%) tumors at a single institution. The median prescribed dose was 74 Gy (relative biological effectiveness; range 46.8-87.5 Gy), and the median distance from the treatment field to the CIED was 10 cm (range 0.8-40 cm). Maximum proton and neutron doses were estimated for each treatment course. All CIEDs were checked before radiation delivery and monitored throughout treatment. RESULTS: Median estimated peak proton and neutron doses to the CIED in all patients were 0.8 Gy (range 0.13-21 Gy) and 346 Sv (range 11-1100 mSv). Six CIED malfunctions occurred in 5 patients (2 pacemakers and 3 defibrillators). Five of these malfunctions were CIED resets, and 1 patient with a defibrillator (in a patient with a liver tumor) had an elective replacement indicator after therapy that was not influenced by radiation. The mean distance from the proton beam to the CIED among devices that reset was 7.0 cm (range 0.9-8 cm), and the mean maximum neutron dose was 655 mSv (range 330-1100 mSv). All resets occurred in patients receiving thoracic PBT and were corrected without clinical incident. The generator for the defibrillator with the elective replacement indicator message was replaced uneventfully after treatment. CONCLUSIONS: The incidence of CIED resets was about 20% among patients receiving PBT to the thorax. We recommend that PBT be avoided in pacing-dependent patients and that patients with any type of CIED receiving thoracic PBT be followed closely.

Recurrent syncope in a cancer patient: a case report and review of the literature.

A 59-year-old male with invasive squamous cell carcinoma of the left preauricular region, treated with several chemotherapy regimens and radiation therapy, was admitted for recurrent syncopal episodes. He was found to be suffering from neurocardiogenic reflex-mediated syncope secondary to mechanical compression of the carotid baroreceptors and glossopharyngeal nerve by the tumor. We discuss the pathophysiology of this case and the available treatment options.

Noncompacted ventricular myocardium: is syncope the only warning sign?

We present a case of a 14-year-old young boy with ventricular noncompaction and coexistent Wolff-Parkinson-White syndrome who presented with syncope. Detailed testing was performed, and an ablation was successful for Wolff-Parkinson-White syndrome; however, because of patient/family desires, an implantable cardiodefibrillator was placed. A careful review of the literature highlights the complex decision making involved with this condition.

Multiple shocks after upgrade of an implantable cardioverter-defibrillator to a cardiac resynchronization therapy-defibrillator device.

Inappropriate shocks from implantable cardioverter-defibrillators (ICDs) may occur for many reasons. Inappropriate shocks are not simply painful inconveniences for patients; they also may result in the need for further operative procedures, and sometimes even death. Herein, we report the case of a patient who after upgrade of an ICD to a cardiac resynchronization therapy-defibrillator device (CRT-D), returned with multiple shocks due to altered sensing and defibrillation polarities that resulted from actual physical reversal of the distal (-) and proximal (+) lead terminals in the header of the device.

Arrhythmogenic right ventricular cardiomyopathy with implantable cardioverter defibrillator placement in pregnancy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder that predominantly affects the right side of the heart and causes ventricular arrhythmias. In many patients the disease is familial. ARVC may account for as many as 5% of unexpected sudden deaths. We report a case of ARVC diagnosed at 21 weeks gestation treated with an implantable cardiac defibrillator. The remainder of her pregnancy was uneventful and the patient underwent induction of labor at 39 weeks gestation with a passive second stage forceps-assisted delivery resulting in delivery of a normal infant. In the gravida with cardiac arrhythmias, defibrillator placement may offer a safe, life-preserving treatment and should be considered.