Heart rate informed artificial pancreas system enhances glycemic control during exercise in adolescents with T1D.

OBJECTIVE: To evaluate the safety and performance of using a heart rate (HR) monitor to inform an artificial pancreas (AP) system during exercise among adolescents with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized, cross-over trial, adolescents with T1D age 13 - 18 years were enrolled to receive on separate days either the unmodified UVa AP (stdAP) or an AP system connected to a portable HR monitor (AP-HR) that triggered an exercise algorithm for blood glucose (BG) control. During admissions participants underwent a structured exercise regimen. Hypoglycemic events and CGM tracings were compared between the two admissions, during exercise and for the full 24-hour period. RESULTS: Eighteen participants completed the trial. While number of hypoglycemic events during exercise and rest was not different between visits (0.39 AP-HR vs 0.50 stdAP), time below 70 mg dL -1 was lower on AP-HR compared to stdAP, 0.5±2.1% vs 7.4±12.5% (P = 0.028). Time with BG within 70-180 mg dL -1 was higher for the AP-HR admission vs stdAP during the exercise portion and overall (96% vs 87%, and 77% vs 74%), but these did not reach statistical significance (P = 0.075 and P = 0.366). CONCLUSIONS: Heart rate signals can safely and efficaciously be integrated in a wireless AP system to inform of physical activity. While exercise contributes to hypoglycemia among adolescents, even when using an AP system, informing the system of exercise via a HR monitor improved time <70 mg dL -1 . Nonetheless, it did not significantly reduce the total number of hypoglycemic events, which were low in both groups.

Safety of using real-time sensor glucose values for treatment decisions in adolescents with poorly controlled type 1 diabetes mellitus: a pilot study.

BACKGROUND: This study explored the safety of using real-time sensor glucose (SG) data for treatment decisions in adolescents with poorly controlled type 1 diabetes. METHODS: Ten adolescents with type 1 diabetes, HbA1c ≥9% on insulin pumps were admitted to the clinical research center and a continuous glucose sensor was inserted. Plasma glucose was measured at least hourly using Yellow Springs Instrument's (YSI) glucose analyzer. Starting at dinner, SG rather than YSI was used for treatment decisions unless YSI was <70 mg/dL (<3.9 mmol/L) or specific criteria indicating SG and YSI were very discordant were met. Participants were discharged after lunch the next day. RESULTS: Ten participants (seven males; 15.2-17.8 year old) completed the study. The range of differences between high glucose correction doses using SG vs YSI for calculations was -2 (SG < YSI dose) to +1 (SG > YSI dose); this difference was two units in only 2 of 23 correction doses given (all SG < YSI dose). There were five episodes of mild hypoglycemia in two patients, two of which occurred after using SG for dose calculations. There was no severe hypoglycemia and no YSI glucose >350 mg/dL (19.4 mmol/L). Mean (±SE) pre- and postmeal YSI glucose were 163 ± 11 and 183 ± 12 mg/dL (9.1 ± 0.6 and 10.2 ± 0.7 mmol/L), respectively. CONCLUSION: Use of real-time continuous glucose monitoring for treatment decisions was safe and did not result in significant over- or undertreatment. Use of SG for treatment decisions under supervised inpatient conditions is a suitable alternative to repeated fingerstick glucose monitoring. Outpatient studies using SG in real-time are needed.

24 Versus 48-hour bravo pH monitoring.

BACKGROUND: Historical ambulatory pH monitoring systems for the evaluation of gastroesophageal reflux disease have been catheter based and uncomfortable for patients, commonly limiting both their diet and activities. Catheter-based studies have also been reported to underestimate the amount of reflux a patient may have in a normal, routine day. Compared with conventional catheter-based pH monitoring systems, wireless (Bravo) pH monitoring is better tolerated by patients and allows for an increased duration of pH recording. Currently, there is lack of data regarding the optimal duration of wireless studies and concern that day 1 results are not typical of a patient's routine lifestyle, given the effects of sedation. Few studies have evaluated the merits of 24 versus 48-hour wireless pH monitoring. AIMS: The aims of this study were (1) to identify differences in reflux parameters between 24 versus 48-hour testing as measured by wireless pH monitoring and (2) to assess the effect of 48-hour studies on the number of reflux episodes and symptom correlation as compared with 24-hour studies. METHODS: A retrospective chart review of 124 consecutive patients who underwent 48-hour wireless esophageal pH monitoring studies was prepared. All patients underwent esophagogastroduodenoscopy using intravenous conscious sedation before wireless capsule placement. Acid reflux variables (including total reflux time, number of reflux episodes, and total percent time of pH<4) and symptom-association probability (SAP) scores were compared for day 1 versus day 2 versus total. RESULTS: Forty-eight-hour SAP scores were significantly higher when compared with the first 24 hours for all reported primary symptoms. SAP scores were calculated at 24 and 48 hours, respectively for heartburn (56 vs. 65, P<0.0001), regurgitation (65 vs. 80, P<0.0001), chest pain (59 vs. 78, P=0.0009), and cough (55 vs. 64, P=0.0027). In addition, the percentage of SAP scores >95 was significantly higher for both heartburn and regurgitation (34% vs. 48%, P=0.003 and 38% vs. 62%, P=0.005). As expected, 48-hour testing also captured a significantly higher number of reflux episodes as compared with day 1 results alone (97 vs. 47, P<0.0001). There were no statistical differences noted between the 2 days for total percent time of pH <4. CONCLUSIONS: Forty-eight-hour wireless (Bravo) pH monitoring strengthens symptom correlation as compared with 24-hour results alone and yields a greater percentage of SAP scores >95 for typical symptoms of gastroesophageal reflux disease. Prolonged recording of patient symptoms and/or sedation effects may account for the better symptom correlation. Although there were no statistical differences seen in this study between 24 and 48-hour studies for total percent time pH <4, 48-hour studies captured significantly more reflux episodes as compared with 24 hours of monitoring alone. These results suggest that patients undergoing wireless pH monitoring should have 48-hour studies performed as a standard of practice.

Ambulatory monitoring of central arterial pressure, wave reflections, and arterial stiffness in patients at cardiovascular risk.

This paper reviews current 24 h ambulatory noninvasive technologies for pulse wave analysis (PWA) providing central arterial pressure, pulse wave velocity, and augmentation index and the scientific evidence supporting their use in the clinical management of patients with arterial hypertension or at risk for cardiovascular complications.The most outstanding value of these techniques lies in the fact that they are user-friendly, mostly operator independent, and enable the evaluation of vascular function during daily-life conditions, allowing to obtain repeated measurements in different out-of-office circumstances, less artificial than those of the laboratory or doctor's office.Studies performed so far suggest that 24 h PWA may represent a potentially promising tool for evaluating vascular function, structure, and damage in daily-life conditions and promoting early screening in subjects at risk. The current evidence in favor of such an approach in the clinical practice is still limited and does not recommend its routine use. In particular, at the moment, there is a shortage of long-term prognostic studies able to support the predictive value of 24 h PWA. Finally, the accuracy of the measures is strongly dependent on the type of technology and device employed with lack of interoperability among the devices that deeply affects comparability of results among studies using different technologies. It is thus mandatory in the near future to promote proper validation studies, for instance using the ARTERY protocol, and to plan well-designed long-term longitudinal studies that may prove the accuracy and high predictive value of PWA in ambulatory conditions.

Bluetooth Wireless Technology Cybersecurity and Diabetes Technology Devices.

Medical devices have transitioned from hospital into the home and consumer environments and have been shown to provide for mobility and quality-of-life improvements for chronic conditions such as diabetes. It is important to collect sensor and usage data while remotely connected in real time. The protection of these data is commonly called "cybersecurity." Bluetooth® wireless technology (Bluetooth is a registered trademark of the Bluetooth Special Interest Group, Inc.) is commonly used for low-cost medical devices to provide connections to other medical devices as well as compute and display devices such as smartphones. This paper provides a review of its use with respect to diabetes devices with a particular focus on cybersecurity.

Continuous glucose monitoring in non-insulin-using individuals with type 2 diabetes: acceptability, feasibility, and teaching opportunities.

BACKGROUND: Continuous glucose monitoring (CGM) has the potential to provide useful data for behavioral interventions targeting non-insulin-using, sedentary individuals with type 2 diabetes mellitus (T2DM). The aims of this study were to describe CGM in terms of (1) feasibility and acceptability and (2) dietary- and exercise-teaching events. METHODS: Cross-sectional data were analyzed from 27 non-insulin-using adults with T2DM who wore CGM for 72 h as part of a larger study on using CGM for exercise counseling in this population. Feasibility data included accuracy of entering daily self-monitored blood glucose (SMBG) readings and events (e.g., meals, exercise), sensor failures, alarms, optimal accuracy of glucose data, and download failures. Acceptability data included CGM satisfaction and wearing difficulties. Dietary- and exercise-teaching events were identified from CGM and activity monitor data. RESULTS: CGM graphs showed 141 dietary- and 71 exercise-teaching events. About half the participants (52%) reported difficulty remembering to enter events into CGM monitors, but most (82%) kept an accurate paper log of events. Insufficient SMBG entries resulted in 32 CGM graphs with "use clinical judgment" warnings. Eighty-three percent of missed SMBG entries were from 18 participants 55-77 years old. Missing correlation coefficients resulted from glucose concentrations varying <100 mg/dL. A majority of participants (n = 19) were willing to wear CGM again despite reporting minor discomfort at sensor site and with wearing the monitor. CONCLUSIONS: CGM data provided several teaching opportunities in non-insulin-using adults with T2DM. Overall, CGM was acceptable and feasible. Some identified problems may be eliminated by newer technology.

EEG Electrode-induced Skin Injury among Adult Patients Undergoing Ambulatory EEG Monitoring.

Introduction: Ambulatory electroencephalography technology has improved in the last 40 years. Many clinicians believe that some skin injury is an unavoidable complication of prolonged EEG monitoring. In this study, we examined potential risk factors associated with electrode-induced skin injury in adult patients with AEEG monitoring. Methods: A cross-sectional observational study was conducted from December 2017 to October 2018, in the outpatient clinic at a teaching hospital in Sydney, Australia. Patients were included if they were older than 16 years of age and had been referred for AEEG monitoring of two to five days duration. Trained neurophysiology nurses completed a pre-application skin assessment before they applied the EEG electrodes. Daily assessments of the skin condition were conducted. The patients completed a questionnaire to assess comfort levels at the completion of the testing. Results: A total of 251 patients participated in this study. Two groups were established - those who were monitored for 2-3 days (Group 1; n = 92) and those who were monitored for 4-5 days (Group 2; n = 159). There was a significant acceleration in inflammation which occurred between day 2 and day 4/5. Cross-sectional analyses of patient characteristics showed that increasing age, fair skin color, dry skin texture and fine hair texture were the prevailing risk factors for greater inflammation scores. Conclusion: The patient discomfort and inflammatory burden associated with this procedure were high. Inflammation was shown to increase with the duration of electrode application.

Continuous glucose monitoring in children with type 1 diabetes.

OBJECTIVE: To examine the feasibility of daily use of a continuous glucose monitor, the FreeStyle Navigator Continuous Glucose Monitoring System ("Navigator"), in children with type 1 diabetes (T1D). STUDY DESIGN: After a masked Navigator was used for 4 to 7 days to establish a baseline level of glycemic control, 30 insulin pump users with T1D (average age 11.2 years) were asked to use the Navigator daily for 13 weeks. RESULTS: Subjects averaged 149 h/wk of Navigator use during the first 4 weeks, which decreased slightly to 134 h/wk during weeks 9 to 13 (P = .006). Mean hemoglobin A1c improved from 7.1% at baseline to 6.8% at 13 weeks (P = .02), and the percentage of glucose values between 71 and 180 mg/dL increased from 52% to 60% (P = .01). Subjects and parents reported high satisfaction with the Navigator on the Continuous Glucose Monitor Satisfaction Scale. Two subjects had severe skin reactions related to sensor mount adhesive. CONCLUSION: This study indicates that incorporating real-time continuous glucose monitoring into the daily treatment of children with T1D is feasible. The results provide a compelling rationale for conducting a randomized trial of daily use of a continuous glucose monitor in children with T1D.

Oesophageal pH monitoring using the Bravo catheter-free radio capsule.

OBJECTIVES: Oesophageal pH monitoring is the current standard for the diagnosis of gastro-oesophageal reflux disease. The Bravo capsule allows 48-h monitoring without the need for a naso-oesophageal catheter. Our aim was to assess the Bravo capsule in terms of patient discomfort and interference with daily activities, and to determine if 48-h Bravo pH studies facilitate the diagnosis of gastro-oesophageal reflux disease. METHODS: Ambulatory pH studies were performed at two hospitals using either the Bravo capsule (n=100) or a conventional naso-oesophageal catheter (n=100). Participants were selected either for investigation of symptoms suggestive of gastro-oesophageal reflux disease, or to follow-up antireflux surgery. All participants completed questionnaires to assess discomfort and interference with daily activities. RESULTS: Eighty-nine Bravo studies recorded at least 48 h of data, and 95 were diagnostic. Bravo participants reported significantly less discomfort during insertion (P<0.0001) and monitoring (P<0.0001), and less interference with daily activities (P<0.0001), eating (P<0.005), sleeping (P<0.0001) and work (P<0.0001). No significant difference was observed between day 1 and 2 median total time pH<4 (4.0 and 4.3%, P=0.64), erect time pH<4 (5.0 and 5.0%, P=0.56), supine time pH<4 (0.5 and 0.5%, P=0.23), and Johnson-DeMeester scores (15.9 and 16.2, P=0.90). Ten Bravo participants (10%) were diagnosed with gastro-oesophageal reflux disease using day 2 data after a normal day 1. CONCLUSIONS: The Bravo capsule significantly reduces the patient discomfort and interference with normal daily activities during pH monitoring associated with a naso-oesophageal catheter. Moreover, 48-h Bravo studies offer an advantage over conventional 24-h studies in diagnosing gastro-oesophageal reflux disease.

Accuracy and tolerability of the Bravo catheter-free pH capsule in patients between the ages of 4 and 18 years.

OBJECTIVE: The aim of this study was to determine if the Bravo pH capsule is comparable to the nasally placed pH catheter in terms of pH-metry, safety, and tolerability in children. METHODS: Ten patients each in the age ranges of 4 to 6 years, 7 to 10 years, and >10 years were tested simultaneously with the catheter and the capsule. Six each were tested with the catheter alone or the capsule alone. Subjects recorded adverse events and graded tolerance (in terms of activity, appetite, and satisfaction) on a scale of 1 to 5, with a score of 5 indicating that the device was well tolerated. A 24-hour reflux index and 24- and 48-hour reflux indices were generated from the catheter and capsule, respectively. Student t test, Mann-Whitney U test, and Fisher exact test were used to compare reflux index, tolerability, and adverse events between the catheter and capsule. RESULTS: Sixty-six patients 4 to 16 years of age (mean, 9.4 years) were enrolled. There was no statistically significant difference between the mean reflux indices (RIs) obtained simultaneously with the catheter and capsule in all patients combined on day 1 (P = 0.0665). There was a significant difference between day 2 and days 1 and 2 combined with the capsule versus the catheter (P = 0.007 and P = 0.0107); however, a discordant result of normal RI on day 1 and pathological RI on day 2 was seen in only 1 patient. The capsule was better tolerated than the catheter in terms of appetite (P = 0.029), activity (P = 0.001), and satisfaction (P = 0.003). There were no significant complications. CONCLUSIONS: The Bravo pH capsule was as accurate and safe and better tolerated than the conventional pH catheter in children 4 years of age and older.

Do patients need to stay in bed all day in the Epilepsy Monitoring Unit? Safety data from a non-restrictive setting.

PURPOSE: To assess whether injuries occur more often in an Epilepsy Monitoring Unit (EMU) where portable EEG amplifiers are used, and where patients can freely move within a large area during the monitoring. METHODS: Patients were monitored at the Danish Epilepsy Center, in an EMU specifically designed for this purpose, and they were under continuous surveillance by personnel dedicated to the EMU. Adverse events (AEs) - including injuries, were prospectively noted, as part of the safety policy of the hospital. Other data were retrospectively extracted from the electronic database, for a 5-year period (January 2012-December 2016). RESULTS: 976 patients were admitted to the EMU. Falls occurred in 19 patients (1.9%) but none of them resulted in injury. Only one serious AE occurred: a patient had a convulsive status epilepticus, which did not respond to first-line treatment in the EMU and was transferred to the intensive care unit. The rate of AEs were similar or lower than previously reported by other centers, where the mobility of the patients had been restricted during monitoring. CONCLUSION: In an EMU specially designed for this purpose, where patients are under continuous surveillance by personnel dedicated to the EMU, injuries can be avoided even when the mobility of the patients is not restricted.

Consensus-based guidelines for Video EEG monitoring in the pre-surgical evaluation of children with epilepsy in the UK.

PURPOSE: Paediatric Epilepsy surgery in the UK has recently been centralised in order to improve expertise and quality of service available to children. Video EEG monitoring or telemetry is a highly specialised and a crucial component of the pre-surgical evaluation. Although many Epilepsy Monitoring Units work to certain standards, there is no national or international guideline for paediatric video telemetry. METHODS: Due to lack of evidence we used a modified Delphi process utilizing the clinical and academic expertise of the clinical neurophysiology sub-specialty group of Children's Epilepsy Surgical Service (CESS) centres in England and Wales. This process consisted of the following stages I: Identification of the consensus working group, II: Identification of key areas for guidelines, III: Consensus practice points and IV: Final review. Statements that gained consensus (median score of either 4 or 5 using a five-point Likerttype scale) were included in the guideline. RESULTS: Two rounds of feedback and amendments were undertaken. The consensus guidelines includes the following topics: referral pathways, neurophysiological equipment standards, standards of recording techniques, with specific emphasis on safety of video EEG monitoring both with and without drug withdrawal, a protocol for testing patient's behaviours, data storage and guidelines for writing factual reports and conclusions. All statements developed received a median score of 5 and were adopted by the group. CONCLUSION: Using a modified Delphi process we were able to develop universally-accepted video EEG guidelines for the UK CESS. Although these recommendations have been specifically developed for the pre-surgical evaluation of children with epilepsy, it is assumed that most components are transferable to any paediatric video EEG monitoring setting.

Evaluation of a Predictive Low-Glucose Management System In-Clinic.

BACKGROUND: Predictions based on continuous glucose monitoring (CGM) data are the basis for automatic suspension and resumption of insulin delivery by a predictive low-glucose management feature termed "suspend before low," which is part of the Medtronic MiniMed® 640G combined insulin pump and CGM system. This study assessed the safety and performance characteristics of the system in an in-clinic setting at eight sites. MATERIALS AND METHODS: In-clinic standardized increases in basal insulin delivery rates were used to induce nocturnal hypoglycemia in subjects (14-75 years) with type 1 diabetes wearing the MiniMed 640G system. The "suspend before low" feature was set at 65 mg/dL, and as a result, the predictive algorithm suspended insulin delivery when the forecasted glucose was predicted to be ≤85 mg/dL in 30 min (a 20 mg/dL safety buffer). Reference plasma glucose values (Yellow Springs Instruments [YSI], Yellow Springs, OH) were used to establish hypoglycemia and were defined as ≥2 consecutive values ≤65 mg/dL. RESULTS: Eighty subjects were screened. Among the 69 successful completers, 27 experienced a hypoglycemic event and 42 did not, a prevention rate of 60%. The mean (±standard deviation) YSI value at the time of pump suspension was 101 ± 18.5 mg/dL, and the mean duration of the 68 "suspend before low" events was 105 ± 27 min. At 120 min after the start of the pump suspension events, the mean YSI value was 102 ± 34.6 mg/dL. CONCLUSION: The MiniMed 640G "suspend before low" feature prevented 60% of induced predicted hypoglycemic events without significant rebound hyperglycemia.

Effectiveness of SmartGuard Technology in the Prevention of Nocturnal Hypoglycemia After Prolonged Physical Activity.

BACKGROUND: The prevention of postexercise nocturnal hypoglycemia after prolonged physical activity using sensor-augmented pump (SAP) therapy with predictive low-glucose management (PLGM) has not been well studied. We conducted a study at a pediatric diabetes camp to determine whether a SAP with PLGM reduces the frequency of nocturnal hypoglycemia after prolonged physical activity more effectively than a SAP with a carbohydrate intake algorithm. METHODS: During a 1-week sport camp, 20 children (aged 10-13 years) with type 1 diabetes (T1D) managed by SAP therapy either with (n = 7) or without PLGM (n = 13) were studied. The hypoglycemia management strategy and the continuous glucose monitoring (CGM)/PLGM settings were standardized. The incidence, severity, and duration of hypoglycemia and carbohydrate intake were documented and compared. RESULTS: The PLGM system was activated on 78% of all nights (once per night on average). No difference was found between the SAP and PLGM groups in the mean overnight glucose curve or mean morning glucose (7.8 ± 2 mmol/L vs. 7.4 ± 3 mmol/L). There was no difference in the frequency and severity of hypoglycemia. However, the SAP group consumed significantly more carbohydrates to prevent and treat hypoglycemia than those in the PLGM group; the values were 10 ± 2 and 1 ± 2 gS (P < 0.0001) in the SAP and PLGM groups, respectively. Moreover, the SAP group spent a significantly longer time in hypoglycemia (64 ± 2 min vs. 38 ± 2 min, P < 0.05). We observed a difference in the time distribution of nocturnal hypoglycemia (10 to 12 p.m. in the PLGM group and 3 to 7 a.m. in the SAP group, P < 0.05). CONCLUSION: With PLGM system, euglycemia after prolonged physical activity was largely maintained with a minimal carbohydrate intake.

Fear of hypoglycemia: Influence on glycemic variability and self-management behavior in young adults with type 1 diabetes.

PURPOSE: The purpose of this study was to examine how fear of hypoglycemia (FOH) is associated with glycemic variability (GV) and self-management behavior in young adults (aged 18-35) with type 1 diabetes (T1DM). PROCEDURES: Using a prospective repeated-measures design, in 35 young adults, within- and between-person and temporal associations of FOH, specific self-management behaviors, and GV were measured. The data were collected using questionnaires and real-time measures using daily diaries, insulin pump downloads, actigraphy, and continuous glucose monitoring. FINDINGS: FOH was associated with greater glycemic variability. Significant temporal associations emerged. Concurrent day (glucose SD, p=.011) and previous-evening fear levels were associated with GV (glucose SD, p=.007). FOH was also associated with greater calorie intake (r=.492, p=.003) and less physical activity (light activity, r=-.341, p=.045). CONCLUSIONS: The significant associations of FOH with GV, dietary patterns, and physical activity provide evidence for FOH as an important psychological factor associated with diabetes care.

[Metabolic/glycemic control accuracy, effect and complications of the continuous glucose monitoring system in diabetic patients]. / Impacto do sistema de monitorização contínua da glicose em pacientes diabéticos.

OBJECTIVE: To evaluate the accuracy, safety and complications of the continuous glucose monitoring system (CGMS) in diabetic patients (DM). The impact of this system on metabolic/glycemic control is still under discussion. METHODS: The 53 patients studied (47.2% male / 52.8% female), average age: 29.74+/-16.38 years, DM1 prevalence (86.8%) were submitted to 72h CGMS (Medtronic; Northridge, CA). Capillary glycemia (CG) and mean CGMS sensor's glycaemic value; correlation coefficient, glycemic excursions (CGMS vs. CG), postprandial hyperglycemia, unrecognized hypoglycemia, complications and therapeutic management after CGMS were analyzed. A1c levels were measured at baseline (1 month before) and after 3 months of the study. RESULTS: The mean capillary glucose values were 191.3+/-45.6 vs. 192.5+/-43.9 mg/dl by CGMS sensor, with significant correlation (p=0.001). The correlation coefficient was 0.87+/-0.16 (VR>0.79). The CGMS was significantly more efficient in the detection of glycemic excursion related to capillary glycemia (p=0.001). Postprandial hyperglycemia was identified in 77.3% of diabetic patients and nocturnal unrecognized hypoglycemia was detected in 54%. Data showed a significantly decreased A1c level, three months after the CGMS (p=0.001). No complications were registered in 89.8% of patients. CONCLUSION: The CGMS was confirmed to be a very safe method, with high accuracy in glycemic values and to have a low complication rate. It is a good method to identify glucose excursion, postprandial hyperglycemia and asymptomatic hypoglycemia, with a significant impact on the A1c levels of diabetic patients.

The AngelMed Guardian system: Is there a role for implantable devices for early detection of coronary artery occlusion?

The AngelMed Guardian System is an implantable device similar to a single chamber pacemaker that continuously monitors the intracardiac electrogram for evidence of ST segment shift indicating acute coronary artery occlusion. The system aims to reduce time to presentation by alerting patients to present to a medical facility whether symptoms are present or not. In March 2016, the US Food and Drug Administration (FDA) assembled a meeting of the Circulatory System Devices Panel to review the results of the AngelMed for Early Recognition and Treatment of STEMI (ALERTS) pivotal trial and the accompanying premarket approval (PMA) application for regulatory approval of the AngelMed Guardian System in the US. In this review, we examine the ALERTS trial methodology and results, and describe the FDA panel's deliberations and recommendations.

Do we need to monitor the percentage of biventricular pacing day by day?

BACKGROUND: Incidence and clinical significance of transient, daily fluctuations of biventricular pacing percentage (CRT%) remain unknown. We assessed the value of daily remote monitoring in identifying prognostically critical burden of low CRT%. METHODS AND RESULTS: Prospective, single-centre registry encompassed 304 consecutive heart failure patients with cardiac resynchronization therapy defibrillators (CRT-D). Patients with 24-h episodes of CRT% loss<95% were assigned to quartiles depending on cumulative time spent in low CRT%: quartile 1 (1-8days), 2 (9-20days), 3 (21-60days) and quartile 4 (>60days). During median follow-up of 35months 51,826 transmissions were analysed, including 15,029 in 208 (68.4%) patients with episodes of low CRT%. Overall, mean CRT%≥95% vs. <95% resulted in a 4-fold lower mortality (17.3 vs. 68.2%; p<0.001). Fifty-four percent of patients experienced episodes of CRT% loss, despite 85.6% having mean CRT%≥95%. Mortality was lowest in quartile 1 (7.7%), while longer periods of CRT% loss resulted in significantly higher death rates (25.0 vs. 34.6 vs. 57.7%; quartiles 2-4 respectively, p<0.001), despite mean CRT% still being ≥95% in quartiles 1-3. Cumulative low CRT% burden was the independent risk factor for death (HR 1.013; 95% CI 1.006-1.021; p<0.001). Mortality rose by 1.3 and 49% with every additional day and quartile of CRT% loss, respectively. CONCLUSIONS: Daily remote monitoring allows one to detect 24-h episodes of CRT% loss<95% in over two-thirds of CRT-D recipients during median observation of 3years. Cumulative low CRT% burden (in days) independently predicts mortality before mean CRT% drop.