Success of pacemaker remote monitoring using app-based technology: Does patient age matter?

BACKGROUND: Remote monitoring (RM) improves patient outcomes. App-based RM is a novel technology that enables transmission of implantable device data using smart devices. Limited data exist on the impact of age and sex on the use of app-based RM. OBJECTIVE: To examine the impact of age and sex on the proportion of pacemaker patients who activated app-based RM, time from order to activation, and patient follow-up transmission adherence per guidelines. METHODS: A retrospective analysis was performed using deidentified data from U.S. pacemaker patients enrolled in the Medtronic CareLink database with an app-based monitor (MyCareLink Smart™). Activation was defined as first RM transmission and was considered early if it occurred < 90 days from order. Adherence analysis was limited to patients with ≥12 months' follow-up from activation and excluded transmissions < 90 days from activation. RESULTS: Of 48,016 patients assigned app-based RM, 40,511 (84.4%) activated their device; of these, 31,640 (65.9%) activated their device early. Among 14,232 activated patients (with 12 months' follow-up), 12,743 (89.5%) were considered adherent to guidelines by transmitting at least once more within 3-12 months following their activation transmission. While there were statistical differences in activation, early activation, and adherence among age and sex groups due to large sample sizes, the differences were not clinically significant and the majority of older patients were able to successfully use app-based RM. CONCLUSIONS: Most patients in this large and first-of-its kind reported cohort used smart devices to successfully activate app-based RM technology and remained adherent per guidelines irrespective of age or sex.

Limited utility of exercise-stress testing to prevent T-wave oversensing in pediatric internal cardioverter defibrillator recipients.

BACKGROUND: Inappropriate internal cardioverter defibrillator (ICD) therapies may result from T-wave oversensing (TWOS) during exertion in children. The aim of this study was to evaluate the utility of an exercise treadmill test to predict inappropriate ICD therapies secondary to TWOS. METHODS: Eligible pediatric ICD recipients underwent exercise-stress testing with concomitant evaluation of all intracardiac electrograms. Double counting at a programmed sensitivity of 0.3 mV was considered indicative of TWOS. Patients were prospectively followed for 2 years and censored at either the development of an inappropriate ICD therapy secondary to TWOS or at the time of ICD revision. RESULTS: Nineteen patients (age: 13.8 ± 3.2 years) underwent exercise testing (median time from ICD implant: 1.5 years, range 2-4.3 years). Two patients were identified with TWOS during the stress test and had a clinically inappropriate ICD discharge within 2 weeks despite a sensitivity adjustment to 0.6 mV. One individual had an inappropriate ICD discharge from TWOS 11 months following an initial uneventful exercise-stress test. CONCLUSIONS: Inappropriate ICD therapies from TWOS relate to a reduction in the intrinsic R wave or augmentation of the T wave during exertion. While intracardiac electrogram assessment during stress testing may aid in the early recognition of TWOS, it did not absolutely translate to a reduction in the incidence of inappropriate ICD shocks.

Exploring New Endpoints for Patients With Heart Failure With Preserved Ejection Fraction.

The epidemiological, clinical, and societal implications of the heart failure (HF) epidemic cannot be overemphasized. Approximately half of all HF patients have HF with preserved ejection fraction (HFpEF). HFpEF is largely a syndrome of the elderly, and with aging of the population, the proportion of patients with HFpEF is expected to grow. Currently, there is no drug known to improve mortality or hospitalization risk for these patients. Besides mortality and hospitalization, it is imperative to realize that patients with HFpEF have significant impairment in their functional capacity and their quality of life on a daily basis, underscoring the need for these parameters to ideally be incorporated within a regulatory pathway for drug approval. Although attempts should continue to explore therapies to reduce the risk of mortality or hospitalization for these patients, efforts should also be directed to improve other patient-centric concerns, such as functional capacity and quality of life. To initiate a dialogue about the compelling need for and the challenges in developing such alternative endpoints for patients with HFpEF, the US Food and Drug Administration on November 12, 2015, facilitated a meeting represented by clinicians, academia, industry, and regulatory agencies. This document summarizes the discussion from this meeting.

Tachycardia-induced heart failure does not alter myocardial P-glycoprotein expression.

STUDY OBJECTIVE: To determine the effects of tachycardia-induced heart failure on myocardial P-glycoprotein (P-gp) expression. DESIGN: Nonblinded, parallel, sham-controlled, animal model study. SETTING: University laboratory. ANIMALS: Thirty mongrel dogs. INTERVENTION: Heart failure was induced by rapid ventricular pacing over 4 weeks; sham procedures were performed for the control group. MEASUREMENTS AND MAIN RESULTS: Myocardial biopsies were taken from the left ventricular lateral wall and prepared for P-gp quantification by laser-induced fluorescence. The relative amount of P-gp messenger RNA (mRNA) was assessed by reverse transcriptase polymerase chain reaction. Rapid ventricular pacing produced heart failure and reduced the area ejection fraction from 48% +/- 6% to 21% +/- 6% (p<0.05 vs baseline). However, heart failure did not alter the quantity of myocardial P-gp (0.20 +/- 0.02 microg/ml for the control group vs 0.23 +/- 0.02 microg/ml for the intervention group, p=0.4). Furthermore, heart failure did not alter P-gp expression significantly. CONCLUSION: Myocardial P-gp does not change in response to tachycardia-induced heart failure. Thus, there is a low likelihood for P-gp-related drug resistance during a syndrome similar to tachycardia-induced heart failure.

Pharmacy students' retention of knowledge and skills following training in automated external defibrillator use.

OBJECTIVES: To assess pharmacy students' retention of knowledge about appropriate automated external defibrillator use and counseling points following didactic training and simulated experience. DESIGN: Following a lecture on sudden cardiac arrest and automated external defibrillator use, second-year doctor of pharmacy (PharmD) students were assessed on their ability to perform basic life support and deliver a shock at baseline, 3 weeks, and 4 months. Students completed a questionnaire to evaluate recall of counseling points for laypeople/the public. ASSESSMENT: Mean time to shock delivery at baseline was 74 ± 25 seconds, which improved significantly at 3 weeks (50 ± 17 seconds, p < 0.001) and was maintained at 4 months (47 ± 18 seconds, p < 0.001). Recall of all signs and symptoms of sudden cardiac arrest and automated external defibrillator counseling points was diminished after 4 months. CONCLUSION: Pharmacy students can use automated external defibrillators to quickly deliver a shock and are able to retain this ability after 4 months. Refresher training/courses will be required to improve students' retention of automated external defibrillator counseling points to ensure their ability to deliver appropriate patient education.

Influence of intermittent hypoxia on myocardial and hepatic P-glycoprotein expression in a rodent model.

STUDY OBJECTIVE: Patients with obstructive sleep apnea who receive drug therapy for cardiovascular disease may experience resistant hypertension, arrhythmias, or more severe heart failure, and many of the drugs used to treat these conditions are substrates for P-glycoprotein (P-gp) transporters. Therefore, we sought to determine if intermittent hypoxia, which mimics obstructive sleep apnea, would upregulate myocardial and hepatic P-gp expression and Abcb1a and Abcb1b messenger RNA (mRNA) expression (genes that encode for P-gp) in an animal model. DESIGN: Prospective, randomized, blinded, parallel-design animal study. SETTING: University research laboratory. ANIMALS: Thirty adult, male Sprague-Dawley rats. INTERVENTION: Rats were assigned to either 2 weeks of intermittent hypoxia exposure similar to sleep apnea (12 rats) or no hypoxia exposure (controls, 18 rats). MEASUREMENTS AND MAIN RESULTS: After intermittent hypoxia or normoxia exposure, the rats were anesthetized. Heart and liver were harvested, and small samples were taken from the left ventricle (heart) and the liver for analysis. Expression of P-gp was measured by Western blotting, whereas Abcb1a and Abcb1b mRNA expression was assessed by real-time polymerase chain reaction. Band density of myocardial (but not hepatic) P-gp expression (standardized by beta-actin) was significantly higher in hypoxic rats than in control rats (p=0.03). Quantitative polymerase chain reaction revealed that myocardial and hepatic Abcb1a and myocardial Abcb1b mRNA expression were significantly increased in hypoxic rats compared with controls (p<0.05). CONCLUSION: Myocardial P-gp expression and myocardial and hepatic Abcb1a mRNA expression were significantly increased after 2 weeks of intermittent hypoxia. Hypoxia-induced increases in P-gp expression may partially explain drug-resistant cardiovascular disease in patients with obstructive sleep apnea.

Allopurinol as a cardioprotectant during coronary artery bypass graft surgery.

OBJECTIVE: To examine the role of allopurinol as a cardioprotectant during coronary artery bypass graft (CABG) surgery. DATA SOURCES: A search of MEDLINE (1966-October 2002) was performed using the following terms: allopurinol, xanthine oxidase, oxygen free radical, and coronary artery bypass. References evaluated were limited to English-language and human studies, yielding 41 citations, 13 of which were found suitable. The 5 largest studies are discussed. DATA SYNTHESIS: Multiple studies with various doses have evaluated the effects of allopurinol on outcomes in CABG patients. These studies found that allopurinol can reduce in hospital mortality, improve cardiac performance, reduce incidence of arrhythmias, reduce markers of ischemia and free-radical generation, and reduce the need for inotropic support. However, these findings were not consistent between all studies. CONCLUSIONS: Allopurinol may reduce the incidence of CABG complications. Although the optimal dose has not been determined, reviewed literature suggests that patients should receive at least 600 mg one day prior to surgery, as well as at least 600 mg on the day of surgery.

Electrical heterogeneity and arrhythmogenesis: importance of conduction velocity dispersion.

An experimental model of conduction velocity (CV) and refractory period dispersion was established to determine which variable is a determinant of myocardial vulnerability. Anesthetized swine were instrumented with a left anterior descending coronary artery catheter for regional infusion of lidocaine (n = 6), low-dose d-sotalol (n = 4), high-dose d-sotalol (n = 6), or saline (n = 6), to create dispersion in CV (lidocaine), refractoriness (d-sotalol), or neither (saline). Ventricular fibrillation thresholds (VFTs) and refractory periods were determined at five sites (one drug perfused, four non-drug perfused). CV was determined in one drug-perfused area (left ventricular epicardial apex) and one non-drug perfused area (right ventricular epicardial base). Lidocaine and low- and high-dose d-sotalol increased VFT when stimuli were delivered in the drug-perfused area. However, lidocaine decreased VFT when stimuli were delivered at non-drug perfused areas by an average of 52%. Neither d-sotalol dose affected VFT when stimuli were delivered in non-drug perfused areas. Lidocaine increased CV dispersion by 18-26 cm/s but did not alter refractoriness. Both d-sotalol doses increased dispersion in refractoriness by 15-27 ms but did not alter CV. Saline did not affect either variable. Regional lidocaine had profibrillatory effects when stimuli were delivered in non-drug perfused areas, whereas regional d-sotalol did not. Hence, CV dispersion is a more likely determinant of myocardial vulnerability than refractoriness.

Regional gap junction inhibition increases defibrillation thresholds.

It is clear that ischemia inhibits successful defibrillation by altering regional electro-physiology. However, the exact mechanisms are unclear. This study investigated whether regional gap junction inhibition increases biphasic shock defibrillation thresholds (DFT). Sixteen swine were instrumented with a mid-left anterior descending (LAD) perfusion catheter for regional infusion of 0.5 mM/h heptanol (n = 8) or saline (n = 8). DFT values and effective refractory periods (ERP) at five myocardial sites were determined. Regional conduction velocity (CV) was determined in an LAD drug-perfused and nondrug-perfused region in an additional seven swine. Regional heptanol infusion increased 50% DFT values by 33% (P = 0.01) and slowed CV by 42-59% (P < 0.01) but did not affect ERP. Regional heptanol also increased CV dispersion by approximately 270% (P < 0.05) but did not change ERP dispersion. Regional placebo did not alter any of these parameters. Furthermore, regional heptanol infusion induced spontaneous ventricular fibrillation in eight of eight animals. Increasing spatial conduction velocity dispersion by impairing regional gap junction conductance increased DFT values. Dispersion in conduction velocity slowing during regional ischemia may be an important determinant of defibrillation efficacy.