Performance of Anatomically Designed Quadripolar Left Ventricular Leads: Results from the NAVIGATE X4 Clinical Trial.

INTRODUCTION: The safety and efficacy of a novel family of quadripolar left ventricular (LV) pacing leads designed to pace from nonapical regions of the LV with low pacing capture thresholds was studied in patients undergoing implantation of a cardiac resynchronization therapy defibrillator (CRT-D). METHODS AND RESULTS: Patients receiving a CRT-D were implanted with 1 of 3 ACUITY X4 leads (Spiral Long, Spiral Short, or Straight), designed to address coronary venous anatomical variability. Electrical performance and LV lead related complications were evaluated 3 and 6 months post implantation, respectively. 764 patients (68 ± 11 years, 66% male) were enrolled; 738 (97%) successfully implanted with an ACUITY X4 lead (Spiral L, n = 239, 31%; Spiral S, n = 281, 37%; Straight, n = 218, 29%). A targeted threshold ≤2.5 V was achieved in 644 (94%) patients. The median threshold from the best proximal electrode was lower than the tip electrode (0.9 V [IQR 0.7, 1.3] vs. 1.3 V [IQR 0.7, 2.5], p< 0.001) on Spiral leads. Irrespective of lead implanted, one of the proximal electrodes was the programmed cathode in most patients. The overall LV complication-free rate was 98%. LV lead dislodgment occurred in 8 (1%) patients. PNS occurred in 58 (8%) patients, but only 3 (0.4%) patients required surgical intervention. CONCLUSION: The ACUITY X4 LV leads had low pacing thresholds particularly from proximal electrodes, a high incidence of pacing from the nondistal electrode, and low likelihood of dislodgment or PNS requiring surgical intervention. (ClinicalTrials.gov Identifier: NCT02071173).

Usefulness of Multisite Ventricular Pacing in Nonresponders to Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients with myocardial dysfunction and delayed ventricular activation, but approximately 25% to 40% of patients do not respond to CRT. Left ventricular (LV) multisite pacing (MSP) has been proposed as a tool to improve CRT response. The goal of this study is to examine the safety and efficacy of LV MSP in CRT nonresponders. Between January 2018, and September 2019, the Strategic Management to Improve CRT Using Multi-Site Pacing trial prospectively enrolled 584 CRT-defibrillator recipients for established indications at 52 sites across the United States and evaluated their response at 6 months using the clinical composite score (CCS). Of the nonresponders, 102 patients had the LV MSP feature turned on and 78 patients completed the 12-month CCS evaluation. The LV MSP feature-related complication-free rate was 99.0% with a lower 95% confidence interval limit of 94.9%, which was higher than the performance goal of 90%. The proportion of nonresponders with an improved CCS from 6 to 12 months was 51.3% with a lower 95% confidence interval limit of 41.4%, which was higher than the performance goal of 5%. The estimated mean reduction in battery longevity with the LV MSP feature was about 3.6 months (estimated battery longevity of 8.87 ± 2.08 years at 6 months and 8.07 ± 2.23 years at 12 months). In conclusion, in CRT nonresponders, the use of the LV MSP feature is safe and associated with a ∼50% conversion rate with a small projected reduction in CRT-defibrillator battery longevity. LV MSP should be considered in the management of CRT nonresponders.

Implantable Cardiac Alert System for Early Recognition of ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Symptoms remain a poor prompt for acute coronary syndromes (ACS). Timely restoration of perfusion in ST-segment elevation myocardial infarction is associated with improved left ventricular function and survival. OBJECTIVES: This report details the results of ALERTS (AngelMed for Early Recognition and Treatment of STEMI), a multicenter, randomized trial of an implantable cardiac monitor that alerts patients with rapidly progressive ST-segment deviation. METHODS: High-risk ACS subjects (N = 907) were randomized to a control (alarms deactivated) or treatment group for 6 months, after which alarms were activated in all subjects. The primary safety endpoint was absence of system-related complications (>90%). The composite primary efficacy endpoint was cardiac/unexplained death, new Q-wave myocardial infarction, or detection to presentation time >2 h. RESULTS: Safety was met with 96.7% freedom from system-related complications (n = 30). The efficacy endpoint for a confirmed occlusive event within 7 days was not significantly reduced in the treatment compared with control group (16 of 423 [3.8%] vs. 21 of 428 [4.9%], posterior probability = 0.786). Within a 90-day window, alarms significantly decreased detection to arrival time at a medical facility (51 min vs. 30.6 h; Pr [pt < pc] >0.999). In an expanded analysis using data after the randomized period, positive predictive value was higher (25.8% vs. 18.2%) and false positive rate significantly lower in the ALARMS ON group (0.164 vs. 0.678 false positives per patient-year; p < 0.001). CONCLUSIONS: The implantable cardiac system detects early ST-segment deviation and alerts patients of a potential occlusive event. Although the trial did not meet its pre-specified primary efficacy endpoint, results suggest that the device may be beneficial among high-risk subjects in potentially identifying asymptomatic events. (AngelMed for Early Recognition and Treatment of STEMI [ALERTS]; NCT00781118).

Implanted Monitor Alerting to Reduce Treatment Delay in Patients With Acute Coronary Syndrome Events.

BACKGROUND: Increased pre-hospital delay during acute coronary syndrome (ACS) events contributes to worse outcome. OBJECTIVES: The purpose of this study was to assess the effectiveness of an implanted cardiac monitor with real-time alarms for abnormal ST-segment shifts to reduce pre-hospital delay during ACS events. METHODS: In the ALERTS (AngeLmed Early Recognition and Treatment of STEMI) pivotal study, subjects at high risk for recurrent ACS events (n = 907) were randomized to control (Alarms OFF) or treatment groups for 6 months, after which alarms were activated in all subjects (Alarms ON). Emergency department (ED) visits with standard-of-care cardiac test results were independently adjudicated as true- or false-positive ACS events. Alarm-to-door (A2D) and symptom-to-door (S2D) times were calculated for true-positive ACS ED visits triggered by 3 possible prompts: alarm only, alarms + symptoms, or symptoms only. RESULTS: The Alarms ON group showed reduced delays, with 55% (95% confidence interval [CI]: 46% to 63%) of ED visits for ACS events <2 h compared with 10% (95% CI: 2% to 27%) in the Alarms OFF group (p < 0.0001). Results were similar when restricted to myocardial infarction (MI) events. Median pre-hospital delay for MI was 12.7 h for Alarms OFF and 1.6 h in Alarms ON subjects (p < 0.0089). Median A2D delay was 1.4 h for asymptomatic MI. Median S2D delay for symptoms-only MI (no alarm) in Alarms ON was 4.3 h. CONCLUSIONS: Intracardiac monitoring with real-time alarms for ST-segment shift that exceeds a subject's self-normative ischemia threshold level significantly reduced the proportion of pre-hospital delays >2 h for ACS events, including asymptomatic MI, compared with symptoms-only ED visits in Alarms OFF. (AngeLmed for Early Recognition and Treatment of STEMI [ALERTS]; NCT00781118).

Image Quality of Cardiac Magnetic Resonance Imaging in Patients With an Implantable Cardioverter Defibrillator System Designed for the Magnetic Resonance Imaging Environment.

BACKGROUND: Recently, magnetic resonance (MR)-conditional implantable cardioverter defibrillator (ICD) systems have become available. However, associated cardiac MR image (MRI) quality is unknown. The goal was to evaluate the image quality performance of various cardiac MR sequences in a multicenter trial of patients implanted with an MR-conditional ICD system. METHODS AND RESULTS: The Evera-MRI trial enrolled 275 patients in 42 centers worldwide. There were 263 patients implanted with an Evera-MRI single- or dual-chamber ICD and randomized to controls (n=88) and MRI (n=175), 156 of whom underwent a protocol-required MRI (9-12 weeks post implant). Steady-state-free-precession (SSFP) and fast-gradient-echo (FGE) sequences were acquired in short-axis and horizontal long-axis orientations. Qualitative and quantitative assessment of image quality was performed by using a 7-point scale (grades 1-3: good quality, grades 6-7: nondiagnostic) and measuring ICD- and lead-related artifact size. Good to moderate image quality (grades 1-5) was obtained in 53% and 74% of SSFP and FGE acquisitions, respectively, covering the left ventricle, and in 69% and 84%, respectively, covering the right ventricle. Odds for better image quality were greater for right ventricle versus left ventricle (odds ratio, 1.8; 95% confidence interval, 1.5-2.2; P<0.0001) and greater for FGE versus SSFP (odds ratio, 3.5; 95% confidence interval, 2.5-4.8; P<0.0001). Compared with SSFP, ICD-related artifacts on FGE were smaller (141±65 versus 75±57 mm, respectively; P<0.0001). Lead artifacts were much smaller than ICD artifacts (P<0.0001). CONCLUSIONS: FGE yields good to moderate quality in 74% of left ventricle and 84% of right ventricle acquisitions and performs better than SSFP in patients with an MRI-conditional ICD system. In these patients, cardiac MRI can offer diagnostic information in most cases. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02117414.

Full-Body MRI in Patients With an Implantable Cardioverter-Defibrillator: Primary Results of a Randomized Study.

BACKGROUND: Magnetic resonance imaging (MRI) of patients with conventional implantable cardioverter-defibrillators (ICD) is contraindicated. OBJECTIVES: This multicenter, randomized trial evaluated safety and efficacy of a novel ICD system specially designed for full-body MRI without restrictions on heart rate or pacing dependency. The primary safety objective was >90% freedom from MRI-related events composite endpoint within 30 days post-MRI. The primary efficacy endpoints were ventricular pacing capture threshold and ventricular sensing amplitude. METHODS: Subjects received either a single- or dual-chamber ICD. In a 2:1 randomization, subjects either underwent MRI at 1.5-T of the chest, cervical, and head regions to maximize radiofrequency exposure up to 2 W/kg specific absorption rate and gradient field exposure to 200 T/m/s per axis (MRI group, n = 175), or they underwent a 1-h waiting period without MRI (control group, n = 88). A subset of MRI patients underwent ventricular fibrillation induction testing post-MRI to characterize defibrillation function. RESULTS: In 42 centers, 275 patients were enrolled (76% male, age 60.4 ± 13.8 years). The safety endpoint was met with 100% freedom from the composite endpoint (p < 0.0001). Both efficacy endpoints were met with minimal differences in the proportion of MRI and control patients who demonstrated a ≤0.5 V increase in ventricular pacing capture threshold (100% MRI vs. 98.8% control, noninferiority p < 0.0001) or a ≤50% decrease in R-wave amplitude (99.3% MRI vs. 98.8% control, noninferiority p = 0.0001). A total of 34 ventricular tachyarrhythmia/ventricular fibrillation episodes (20 induced; 14 spontaneous) occurred in 24 subjects post-MRI, with no observed effect on sensing, detection, or treatment. CONCLUSIONS: This is the first randomized clinical study of an ICD system designed for full-body MRI at 1.5-T. These data support that the system is safe and the MRI scan does not adversely affect electrical performance or efficacy. (Confirmatory Clinical Trial of the Evera MRI System for Conditionally-Safe MRI Access; NCT02117414).