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Background: Left bundle branch area pacing (LBBAP) may be an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). We sought to compare the acute hemodynamic and ECG effects of LBBAP, BVP, and left bundle-optimized therapy CRT (LOT-CRT) in CRT candidates with advanced conduction disease., Methods: In this multicenter study, 48 patients with either nonspecific interventricular conduction delay (n=29) or left bundle branch block (n=19) underwent acute hemodynamic testing to determine the change in left ventricular pressure maximal first derivative (LV d P /d t max ) from baseline atrial pacing to BVP, LBBAP, or LOT-CRT., Results: Atrioventricular-optimized increases in LV d P /d t max for LOT-CRT (mean, 25.8% [95% CI, 20.9%-30.7%]) and BVP (26.4% [95% CI, 20.2%-32.6%]) were greater than unipolar LBBAP (19.3% [95% CI, 15.0%-23.7%]) or bipolar LBBAP (16.4% [95% CI, 12.7%-20.0%]; P ≤0.005). QRS shortening was greater in LOT-CRT (29.5 [95% CI, 23.4-35.6] ms) than unipolar LBBAP (11.9 [95% CI, 6.1-17.7] ms), bipolar LBBAP (11.7 ms [95% CI, 6.4-17.0]), or BVP (18.5 [95% CI, 11.0-25.9] ms), all P ≤0.005. Compared with patients with left bundle branch block, patients with interventricular conduction delay experienced less QRS reduction ( P =0.026) but similar improvements in LV d P /d t max ( P =0.29). Bipolar LBBAP caused anodal capture in 54% of patients and resulted in less LV d P /d t max improvement than unipolar LBBAP (18.6% versus 23.7%; P <0.001). Subclassification of LBBAP capture (European Heart Rhythm Association criteria) indicated LBBAP or LV septal pacing in 27 patients (56%) and deep septal pacing in 21 patients (44%). The hemodynamic benefit of adding left ventricular coronary vein pacing to LBBAP depended on baseline QRS duration ( P =0.031) and success of LBBAP ( P <0.004): LOT-CRT provided 14.5% (5.0%-24.1%) greater LV d P /d t max improvement and 20.8 (12.8-28.8) ms greater QRS shortening than LBBAP in subjects with QRS ≥171 ms and deep septal pacing capture type., Conclusions: In a CRT cohort with advanced conduction disease, LOT-CRT and BVP provided greater acute hemodynamic benefit than LBBAP. Subjects with wider QRS or deep septal pacing are more likely to benefit from the addition of a left ventricular coronary vein lead to implement LOT-CRT., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04905290., Competing Interests: Dr Jastrzębski: speaker/consultant honoraria from Abbott, Biotronik, Boston Scientific, and Medtronic. Dr Foley: consultant to Medtronic, proctor for Medtronic. Dr Chandrasekaran: honoraria, consultancy fees and funding support from Medtronic, Biotronik, and Abbot. Dr Whinnett: speaker honoraria, consulting fees, and institutional fellowship/research support from Abbot, Boston Scientific, and Medtronic. Dr Vijayaraman: Medtronic: honoraria, consultant, research and fellowship support Abbott: honoraria, consultant Boston Scientific/Biotronik: honoraria; patent: HBP delivery tool. Dr Upadhyay: consulting and speaker honoraria from Abbott, Biotronik, Boston Scientific, GE Healthcare, Medtronic, Philips, Rhythm Science, and Zoll Medical. R.D. Schaller: speaking honoraria for Medtronic. Dr Richardson: consulting and speaking honoraria from Medtronic, Inc. Dr Herweg: fellowship support from Medtronic, speaker for Medtronic and Abbott. Dr Stadler, D. Kudlik, R. Waxman, Dr Zimmerman, J. Burrell, and Dr Cornelussen are Medtronic employees. The other authors report no conflicts

Background: Delivery of cardiac resynchronization therapy (CRT) requires left ventricular myocardial capture to achieve clinical benefits., Objective: We sought to determine whether ineffective pacing affects survival., Methods: Ineffective ventricular pacing (VP) was defined as the difference between the percentage of delivered CRT (%VP) and the percentage of effective CRT in CRT devices. Using the Optum de-identified electronic health record data set and Medtronic CareLink data warehouse, we identified patients implanted with applicable devices with at least 30 days of follow-up. Kaplan-Meier and Cox proportional hazards models assessed the impact of %VP and % ineffective VP on survival., Results: Among 7987 patients with 2.1 ± 1.0 years of follow-up, increasing ineffective VP was associated with decreasing survival: the highest observed survival was in the quartile with <0.08% ineffective VP and the lowest survival was in the quartile with >1.47% ineffective VP (85.1% vs 75.7% at 3 years; P < .001). As expected, patients with more than the median %VP of 97.7% had better survival than did patients with <97.7% VP (84.2% vs 77.8%; P < .001). However, patients who had >97.7% VP but >2% ineffective VP had similar survival to patients with <97.7% VP but ≤2% ineffective VP (81.6% vs 79.4%; P = .54). A multivariable Cox proportional hazards model demonstrated that <97.7% VP (adjusted hazard ratio 1.29; 95% confidence interval 1.14-1.46; P < .001) and >2% ineffective VP (hazard ratio 1.35; 95% confidence interval 1.18-1.54; P < .001) were both significantly associated with decreased survival., Conclusion: Ineffective VP is associated with decreased survival. In addition to maximizing the percentage of delivered CRT pacing, every effort should be made to minimize ineffective VP., Competing Interests: Disclosures Dr Mittal serves as a consultant to Boston Scientific and Medtronic. Drs Koehler, Stadler, Ghosh, and Klepfer are employees and shareholders of Medtronic. Dr Piccini is supported by R01AG074185 from the National Institutes of Aging. He also receives grants for clinical research from Abbott, the American Heart Association, Boston Scientific, iRhythm, and Philips and serves as a consultant to ABVF, Abbott, AbbVie, Boston Scientific, ElectroPhysiology Frontiers, Kardium, LivaNova, Medtronic, Milestone Pharmaceuticals, Sanofi, Philips, and UpToDate. The rest of the authors report no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The aim was to test the hypothesis that left ventricular (LV) and right ventricular (RV) activation from body surface electrical mapping (CardioInsight 252-electrode vest, Medtronic) identifies optimal cardiac resynchronization therapy (CRT) pacing strategies and outcomes in 30 patients. The LV80, RV80, and BIV80 were defined as the times to 80% LV, RV, or biventricular electrical activation. Smaller differences in the LV80 and RV80 (|LV80-RV80|) with synchronized LV pacing predicted better LV function post-CRT (p = 0.0004) than the LV-paced QRS duration (p = 0.32). Likewise, a lower RV80 was associated with a better pre-CRT RV ejection fraction by CMR (r =  - 0.40, p = 0.04) and predicted post-CRT improvements in myocardial oxygen uptake (p = 0.01) better than the biventricular-paced QRS (p = 0.38), while a lower LV80 with BIV pacing predicted lower post-CRT B-type natriuretic peptide (BNP) (p = 0.02). RV pacing improved LV function with smaller |LV80-RV80| (p = 0.009). In conclusion, 3-D electrical mapping predicted favorable post-CRT outcomes and informed effective pacing strategies., (© 2023. The Author(s).)

Background: Prolongation of the PR interval has long been considered a benign condition, particularly in the setting of nonstructural heart disease., Objective: The purpose of this study was to investigate the effect of PR interval on various well-adjudicated cardiovascular outcomes using a large real-world population data of patients with implanted dual-chamber permanent pacemakers or implantable cardioverter-defibrillators., Methods: PR intervals were measured during remote transmissions in patients with implanted permanent pacemakers or implantable cardioverter-defibrillators. Study endpoints (time to the first occurrence of AF, heart failure hospitalization [HFH], or death) were obtained between January 2007 and June 2019 from the deidentified Optum de-identified Electronic Health Record dataset., Results: A total of 25,752 patients (age 69.3 ± 13.9 years; 58% male) were evaluated. The average intrinsic PR interval was 185 ± 55 ms. In the subset of 16,730 patients with available long-term device diagnostic data, a total of 2555 (15.3%) individuals developed AF during 2.59 ± 2.18 years of follow-up. The incidence of AF was significantly higher (up to 30%) in patients with a longer PR interval (ie, PR interval ≥270 ms; P < .05). Time-to-event survival analysis and multivariable analysis showed that PR interval ≥190 ms was significantly associated with higher incidence of AF, HFH, or HFH or death when compared with shorter PR intervals ( P < .05 for all 3 parameters)., Conclusion: In a large real-world population of patients with implanted devices, PR interval prolongation was significantly associated with increased incidence of AF, HFH, or death., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Background: A screening tool to predict response to cardiac resynchronization therapy (CRT) could improve patient selection and outcomes., Objective: The purpose of this study was to investigate the feasibility and safety of noninvasive CRT via transcutaneous ultrasonic left ventricular (LV) pacing applied as a screening test before CRT implants., Methods: P-wave-triggered ultrasound stimuli were delivered during bolus dosing of an echocardiographic contrast agent to simulate CRT noninvasively. Ultrasound pacing was delivered at a variety of LV locations with a range of atrioventricular delays to achieve fusion with intrinsic ventricular activation. Three-dimensional cardiac activation maps were acquired via the Medtronic CardioInsight 252-electrode mapping vest during baseline, ultrasound pacing, and after CRT implantation. A separate control group received only the CRT implants., Results: Ultrasound pacing was achieved in 10 patients with a mean of 81.2 ± 50.8 ultrasound paced beats per patient and up to 20 consecutive beats of ultrasound pacing. QRS width at baseline (168.2 ± 17.8 ms) decreased significantly to 117.3 ± 21.5 ms ( P  <.001) in the best ultrasound paced beat and to 125.8 ± 13.3 ms ( P <.001) in the best CRT beat. Electrical activation patterns were similar between CRT pacing and ultrasound pacing with stimulation from the same area of the LV. Troponin results were similar between the ultrasound pacing and the control groups ( P = .96), confirming safety., Conclusion: Noninvasive ultrasound pacing before CRT is safe and feasible, and it estimates the degree of electrical resynchronization achievable with CRT. Further study of this promising technique to guide CRT patient selection is warranted., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Advanced stage heart failure patients can benefit from the unloading effects of an implantable left ventricular assist device. Despite best clinical practice, LVADs are associated with adverse events, such as pump thrombosis (PT). An adaptive algorithm alerting when an individual's appropriate levels in pump power uptake are exceeded, such as in the case of PT, can improve therapy of patients implanted with a centrifugal LVAD. We retrospectively studied 75 patients implanted with a centrifugal LVAD in a single center. A previously optimized adaptive pump power-tracking algorithm was compared to clinical best practice and clinically available constant threshold algorithms. Algorithm performances were analyzed in a PT group ( n = 16 patients with 30 PT events) and a thoroughly selected control group ( n = 59 patients, 34.7 patient years of LVAD data). Comparison of the adaptive power-tracking algorithm with the best performing constant threshold algorithm resulted in sensitivity of 83.3% vs. 86.7% and specificity of 98.9% vs. 95.3%, respectively. The power-tracking algorithm produced one false positive detection every 11.6 patient years and early warnings with a median of 3.6 days prior to PT diagnosis. In conclusion, a retrospective single-center validation study with real-world patient data demonstrated advantageous application of a power-tracking algorithm into LVAD systems and clinical practice.

Logfiles from the HeartWare HVAD System provide operational pump trend data to aid in patient management. Pump thrombosis is commonly associated with increases in the logfile power that may precede the clinical presentation. A Power Tracking algorithm was developed to detect significant deviations in pump power that may be associated with pump thrombus (PT). The Power Tracking algorithm was applied retrospectively to logfiles captured in the ENDURANCE, ENDURANCE Supplemental, and LATERAL clinical trials. From a combined dataset of 896 patients, available logfiles with suspected PT (n = 70 events in 60 patients) and available logfiles from patients without adverse events (AEs) (n = 106 patients, consisting of 27.4 patient-years of monitoring) were organized into two cohorts. The Power Tracking algorithm detected PT cases on or before the recorded AE date with a sensitivity of 85.7%, with detection occurring an average of 3.9 days before clinical presentation. The algorithm averaged one false alarm for every 6.85 patient-years of monitoring from logfiles without AEs. The favorable performance of the Power Tracking algorithm may enable earlier detection of pump thrombosis and allow early medical management versus surgical intervention., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Background: The AdaptivCRT algorithm (aCRT) automatically adjusts atrioventricular delays each minute to achieve ventricular fusion through left ventricular (LV) or biventricular (BiV) pacing. aCRT is associated with superior clinical outcomes compared to standard BiV pacing, but the association of aCRT and subsequent atrial fibrillation (AF) in a real-world population has not been fully evaluated., Objective: The purpose of this study was to investigate the incidence of AF ≥48 hours with aCRT vs standard BiV pacing after implant., Methods: Patients implanted with a cardiac resynchronization therapy (CRT) device between 2013 and 2016 were studied via the de-identified Medtronic CareLink database. For univariate and multivariate survival analyses, Kaplan-Meier and Cox proportional hazards were used, respectively., Results: Of 37,450 patients (mean age 69.1 ± 11.0 years; 67.9% male) followed for a mean 15.5 ± 9.1 months, 9.7% (n = 3647) developed ≥48 hours of AF. In univariate analysis, compared with standard BiV pacing, the aCRT BiV and LV mode was associated with a 54% lower risk of ≥48 hours of AF (P <.001) at 2 years, which persisted after multivariate adjustment (hazard ratio 0.53; 95% confidence interval 0.49-0.57; P <.001), even when stratified by sensed PR interval ≤200 ms and >200 ms. Higher percentages of LV-only pacing with aCRT were associated with lower incidence of AF (comparing >92% LV-only pacing vs 0%-5% LV-only pacing: HR 0.05; 95% CI 0.04-0.06; P <.001)., Conclusion: In a large, real-world population of CRT recipients, aCRT pacing compared to standard BiV pacing was associated with a lower incidence of AF in patients with both long and short PR intervals. A higher percentage of LV-only pacing during aCRT was also associated with lower incidence of AF., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac resynchronization therapy (CRT) requires a high percentage of ventricular pacing (%Vp) to maximize its clinical benefits. Atrial fibrillation (AF) has been shown to reduce %Vp in CRT due to competition with irregular intrinsic atrioventricular (AV) conduction. We report the results of a prospective randomized crossover trial evaluating the amount of effective CRT delivered during AF with a novel algorithm (eCRTAF)., Objective: The purpose of this study was to determine whether eCRTAF increases the amount of effective CRT delivered during AF compared to a currently available rate regularization algorithm., Methods: Patients previously implanted with a cardiac resynchronization therapy-defibrillator and with a history of AF and intact AV conduction received up to 4 weeks of control (Conducted AF Response) and up to 4 weeks of eCRTAF in a randomized sequence. The percent effective CRT (%eCRT) pacing, which excludes beats without left ventricular capture, %Vp, and mean heart rate (HR) were recorded during AF and sinus rhythm., Results: The eCRTAF algorithm resulted in a significantly higher %eCRT during AF than control (87.8% ± 7.8% vs 80.8% ± 14.3%; P <.001) and %Vp during AF than control (90.0% ± 5.9% vs 83.2% ± 11.9%; P <.001), with a small but statistically significant increase in mean HR of 2.5 bpm (79.5 ± 9.7 bpm vs 77.0 ± 9.9 bpm; P <.001)., Conclusion: In a cohort of CRT patients with a history of AF, eCRTAF significantly increased %eCRT pacing and %Vp during AF with a small increase in mean HR. This algorithm may represent a novel noninvasive method of significantly increasing effective CRT delivery during AF, potentially improving CRT response., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiac resynchronization therapy (CRT) requires effective left ventricular (LV) pacing (i.e. sufficient energy and appropriate timing to capture). The AdaptivCRT™ (aCRT) algorithm serves to maintain ventricular fusion during LV or biventricular pacing. This function was tested by comparing the morphological consistency of ventricular depolarizations and percentage effective LV pacing in CRT patients randomized to aCRT vs. echo-optimization., Methods and Results: Continuous recordings (≥20 h) of unipolar LV electrograms from aCRT (n = 38) and echo-optimized patients (n = 22) were analysed. Morphological consistency was determined by the correlation coefficient between each beat and a template beat. Effective LV pacing of paced beats was assessed by algorithmic analysis of negative initial EGM deflection in each evoked response. The %CRT pacing delivered, %effective LV pacing (i.e. % of paced beats with effective LV pacing), and overall %effective CRT (i.e. product of %CRT pacing and %effective LV pacing) were compared between aCRT and echo-optimized patients. Demographics were similar between groups. The mean correlation coefficient between individual beats and template was greater for aCRT (0.96 ± 0.03 vs. 0.91 ± 0.13, P = 0.07). Although %CRT pacing was similar for aCRT and echo-optimized (median 97.4 vs. 98.6%, P = 0.14), %effective LV pacing was larger for aCRT [99.6%, (99.1%, 99.9%) vs. 94.3%, (24.3%, 99.8%), P=0.03]. For aCRT vs. echo-optimized groups, the proportions of patients with ≥90% effective LV pacing was 92 vs. 55% (P = 0.002), and with ≥90% effective CRT was 79 vs. 45%, respectively (P = 0.018)., Conclusion: AdaptivCRT™ significantly increased effective LV pacing over echo-optimized CRT., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Aims: Cardiac resynchronization therapy (CRT) devices report percentage pacing as a diagnostic but cannot determine the effectiveness of each paced beat in capturing left-ventricular (LV) myocardium. Reasons for ineffective LV pacing include improper timing (i.e. pseudofusion) or inadequate pacing output. Device-based determination of effective LV pacing may facilitate optimization of CRT response., Methods and Results: Effective capture at the LV cathode results in a negative deflection (QS or QS-r morphology) on a unipolar electrogram (EGM). Morphological features of LV cathode-RV coil EGMs were analysed to develop a device-based automatic algorithm, which classified each paced beat as effective or ineffective LV pacing. The algorithm was validated using acute data from 28 CRT-defibrillator patients. Effective LV pacing and pseudofusion was simulated by pacing at various AV delays. Loss of LV capture was simulated by RV-only pacing. The algorithm always classified LV or biventricular (BV) pacing with AV delays ≤60% of patient's intrinsic AV delay as effective pacing. As AV delays increased, the percentage of beats classified as effective LV pacing decreased. Algorithm results were compared against a classification truth based on correlation coefficients between paced QRS complexes and intrinsic rhythm QRS templates from three surface ECG leads. An average correlation >0.9 defined a classification truth of ineffective pacing. Compared against the classification truth, the algorithm correctly classified 98.2% (3240/3300) effective LV pacing beats, 75.8% (561/740) of pseudofusion beats, and 100% (540/540) of beats with loss of LV capture., Conclusion: A device-based algorithm for beat-by-beat monitoring of effective LV pacing is feasible., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Implantable loop recorders (ILRs) are valuable for diagnosing arrhythmias. We evaluated tachycardia detection performance of the Medtronic Reveal(®) ILR with FullView™ Software., Methods and Results: The rate of occurrence of tachycardia detection [supraventricular tachycardia, ventricular tachycardia (VT), and ventricular fibrillation (VF)] and the percentage of appropriately detected tachycardias were determined from all 2190 ILR patients that transmitted to CareLink over a 4-month period (total follow-up = 135.6 patient-years). All 1909 tachycardia episodes were reviewed. Episodes with actual heart rate above the programmed tachycardia detection rate were classified as appropriate. Sensitivity to detect true ventricular arrhythmias was assessed in another group of 215 patients undergoing implantable cardioverter defibrillator (ICD) implant testing. Skin electrodes represented ILR electrodes. Induced VF (404 episodes) and VT (93 episodes) were processed by an emulation of FullView Software. Generalized estimation equation analysis adjusted for multiple episodes per patient. In the CareLink cohort, 68.7% (63.9% adjusted) of detected episodes had tachycardia above the detection rate. Of 1642 episodes detected in the VT zone (12.1 episodes/patient-year), 78.8% (79.0% adjusted) had tachycardia above the detection rate. Of 267 episodes detected in the fast VT zone (1.9 episodes/patient-year), 6.7% (9.4% adjusted) had tachycardia above the detection rate. Twelve true VT/VF episodes were observed in 10 patients. In the ICD patient cohort, 95.9% (96.5% adjusted) of induced VT/VF segments were correctly detected at nominal rate cutoffs. When VT detection was set to 130 b.p.m. (to include the slowest VT), 99.0% (99.3% adjusted) were correctly detected., Conclusion: The majority (63.9%) of detected tachycardias contained true tachycardia. Sensitivity to detect induced VT/VF was 99.3%.

Introduction: Implantable loop recorders (ILR) have an automatic arrhythmia detection feature that can be compromised by inappropriately detected episodes. This study evaluated a new ILR sensing and detection scheme for automatically detecting asystole, bradyarrhythmia, and tachyarrhythmia events, which is implemented in the next generation device (Reveal DX/XT)., Methods and Results: The new scheme employs an automatically adjusting R-wave sensing threshold, enhanced noise rejection, and algorithms to detect asystole, bradyarrhythmia, and tachyarrhythmia. Performance of the new algorithms was evaluated using 2,613 previously recorded, automatically detected Reveal Plus episodes from 533 patients. A total of 71.9% of episodes were inappropriately detected by the original ILR, and at least 88.6% of patients had one or more inappropriate episodes, with most inappropriate detections due to R-wave amplitude reductions, amplifier saturation, and T-wave oversensing. With the new scheme, inappropriate detections were reduced by 85.2% (P < 0.001), with a small reduction in the detection of appropriate episodes (1.7%, P < 0.001). The new scheme avoided inappropriate detections in 67.4% of patients that had them with the original scheme., Conclusions: The new sensing and detection scheme is expected to substantially reduce the occurrence of inappropriately detected episodes, relative to that of the original ILR.

In patients with heart failure (HF), a convenient and accurate assessment of HF status could enhance titration of medications and possibly reduce hospitalizations for fluid overload. This study examined the feasibility of monitoring HF status by measuring intrathoracic impedance with either an implantable cardioverter-defibrillator or a pacemaker. Six canines were each instrumented with four devices: two capable of measuring intrathoracic impedance between a right ventricular coil electrode and the device case, one custom pacemaker for inducing HF, and an implantable hemodynamic monitor to measure left ventricular end-diastolic pressure as an assessment of HF status. High-rate ventricular pacing for 3-7 weeks induced HF, followed by a 4-week recovery period. During high-rate pacing, left ventricular end-diastolic pressure was inversely correlated with impedance measurements from both systems (median r=-0.66; range r=-0.38 to -0.81). During recovery, the inverse correlation between left ventricular end-diastolic pressure and impedance was enhanced (median r=-0.88; range r=-0.58 to -0.95). The two types of impedance measurements were highly correlated (median r=-0.68 during pacing and r=-0.91 during recovery). These results suggest that various methods of measurement of intrathoracic impedance over time could be used to monitor HF status.

Avoiding inappropriate ICD therapy during supraventricular tachycardia (SVT) while assuring 100% sensitivity for VT/VF remains a challenge. Inappropriate VT/VF therapy during sinus tachycardia (ST) is particularly distressing to the patient because the full sequence of ICD therapies is often delivered. ST or 1:1 atrial tachycardia (AT) with long PR intervals and ST or AT with atrial oversensing of far-field R waves cause the majority of inappropriate therapy in the Medtronic GEM DR (Model 7271) ICD. The goals of the present effort were to define an adaptive interval-based algorithm for withholding VT/VF therapy in dual chamber ICDs during ST and to compare performance of the adaptive algorithm with that of the original ST withholding algorithm in the GEM DR. The adaptive algorithm uses a combination of 1:1 atrial to ventricular conduction pattern, changes in RR intervals and changes in intrinsic PR intervals to establish evidence for or against the presence of ST. Performances of the adaptive and original ST withholding algorithms were compared on 3 databases collected by implanted GEM DR devices. The first database included 684 spontaneous VT/VF episodes. The second database included 216 spontaneous SVT episodes that received inappropriate VT/VF therapy. These databases included up to 2,000 atrial or ventricular sensed or paced events preceding the spontaneous tachycardias. The third database included 320 spontaneous ST/AT episodes for which therapy was appropriately withheld by the GEM DR. Performance of the adaptive algorithm on the third database was predicted rather than directly computed because of record length limitations. VT/VF therapy was classified as "withheld" if evidence of ST remained high for one algorithm (i.e., at least 7 more beats to VT/VF detection) at the point of VT/VF detection by the other algorithm. For the 684 true VT/VF episodes, the original algorithm withheld VT/VF therapy in 5 episodes and the adaptive algorithm withheld VT/VF therapy in 3 episodes. The 95% confidence interval for the difference in VT/VF sensitivity between the adaptive and original algorithms was [-0.5 to + 1.1%]. Twelve of the 320 ST/AT episodes (3.8%) that were appropriately classified by the original algorithm were predicted to receive inappropriate therapy by the adaptive algorithm. However, relative to the original algorithm, the adaptive algorithm appropriately withheld VT/VF therapy for 76 of 216 true SVT episodes (i.e., incremental specificity of 35.2%). For the specific SVT episodes that were the targets for improvement by the adaptive ST algorithm (ST/AT with long PR intervals and ST/AT with intermittent atrial oversensing of far-field R waves), the adaptive algorithm reduced inappropriate therapy by 63.2%.

Introduction: The aim of this study was to compare surface ECGs with electrograms (EGM) that are available from implanted devices for the ability to detect ischemic ST segment changes during normal sinus (NS) and ventricular paced (VP) rhythms., Methods and Results: ECG leads I, II, and V2, right atrial ring to left pectoral patch (representing the can of the device), right ventricular ring to left pectoral patch, and right atrial ring to right ventricular ring EGM were recorded continuously during percutaneous transluminal coronary angioplasty. One balloon inflation (> or = 60 sec) was analyzed from each of 22 NS and 22 VP subjects. The parameter AST was defined as the maximum absolute ST segment deviation (from isoelectric) during the first 60 seconds of inflation, measured relative to the baseline (preinflation) ST segment deviation. For EGM, a normalized deltaST was defined as the AST divided by the ratio of QRS amplitudes of EGM to ECG. During NS, the deltaST for EGM (0.43 mV) was significantly larger than that of ECG (0.09 mV, P = 0.0001) but the normalized deltaST for EGM (0.11 mV) was comparable to that of ECG (0.09 mV, P = 0.45). During VP, the AST for EGM (1.08 mV) was significantly larger than that of ECG (0.17 mV, P = 0.0001), but the normalized AST for EGM (0.11 mV) was significantly smaller than that of ECG (0.17 mV, P = 0.02)., Conclusion: During both NS and VP, ischemic ST segment changes were significantly larger in EGM than in ECG. Much of this difference appears to be related to larger amplitudes of EGM signals. (J

Continuous ST-segment monitoring by implantable devices may lead to clarification of the substrate of arrhythmias, clarification of the origin of nonspecific chest pain, and titration or preventative application of established anti-ischemic therapies. Although ST-segment monitoring algorithms are available for surface electrocardiogram, the computational demand of algorithms for implantable devices must be minimized for considerations of device longevity. The new algorithm first locates a fiducial point (FPT) at the dominant peak of each QRS complex. The ST-segment deviation (measured at 2 rate-adaptive delays after FPT, eg, FPT + 96 ms and FPT + 152 ms at 60 BPM) with respect to the isoelectric level (measured at the minimum slope preceding the QRS) is then measured. The following features are also quantified by simple operations: R-R interval, R-wave slope, R-wave amplitude, ST-segment slope, and noise content during the isoelectric segment. Inconsistencies in these features relative to their adaptive normal ranges are used to reject noisy or ectopic beats and sudden morphology changes. Finally, the ST-segment deviation over time is filtered to reject rates of change that are not likely attributable to human ischemia. Performance of the algorithm was evaluated on the European Society of Cardiology ST-T Database, which contains 180 hours of ambulatory electrocardiogram with 250 expert-annotated ischemic episodes. The sensitivity was 79% [74% 84%] (mean [95% CI]) and positive predictivity was 81% [76% 86%]. This performance is statistically equivalent to that of published electrocardiogram algorithms that were validated on the same dataset. Estimates of computational burden suggest that the algorithm could process two channels of electrogram continuously for more than 5 years with current implanted device technology. In conclusion, we have developed an algorithm for ST-segment monitoring that can be implemented in current implantable devices with sensitivity and positive predictivity that are comparable with the state-of-the-art.

The brachial artery response to flow was assessed non-invasively by ultrasonic measurement of arterial diameter before and 1 min after 5 min of cuff-induced ischemia. It was hypothesized that continuous measurement of arterial diameter and flow velocity would provide a more complete and accurate evaluation of the response to change in blood flow. Therefore, a system to provide this data was developed and its utility in exploring the acute and chronic effects of smoking on arterial function was demonstrated. Brachial artery diameter and flow velocity were measured before, during and for at least 3 min after 5-min of forearm cuff occlusion. Measurements were acquired from 12 habitual smokers (mean 18.3 pack years), after at least 2 h (mean 6.5 h) without smoking ('pre-cigarette') and immediately after smoking one cigarette ('post-cigarette'), as well as from 12 age- and sex-matched lifelong non-smokers. The slope of brachial artery diameter versus time during the occlusion period and the maximum dilation after cuff release relative to the pre-occlusion diameter were significantly decreased in pre-cigarette smokers compared with non-smokers (P < 0.0001 for both comparisons). Importantly, the absolute arterial dilation during the period of increased flow (i.e. reactive hyperemia) was equal for the pre-cigarette smokers and non-smokers (0.31 +/- 0.03 vs. 0.32 +/- 0.04 mm, respectively). Immediately after smoking, the flow response parameters in chronic smokers changed toward non-smoker values (P < 0.001 for post-cigarette vs. pre-cigarette comparisons of the diameter slope during occlusion and the maximum dilation after cuff release relative to pre-occlusion diameter). Thus, continuous diameter measurements in smokers who refrained from smoking demonstrated abnormal constriction of the brachial artery during the low flow period of cuff occlusion, but normal absolute dilation during the period of increased flow. Immediately after smoking, the artery no longer constricted during occlusion. These findings demonstrate the potential value of continuous monitoring of arterial diameter and flow velocity before, during and after application of a vasoactive stimulus.

Hypercholesterolemia is associated with abnormalities in arterial vasoactivity which can be reversed with cholesterol-reducing therapies. Heparin-induced extracorporeal LDL precipitation (HELP), an invasive method for treating refractory hypercholesterolemia, causes regression of both xanthomas and atherosclerosis, but its effect on vasoactivity has not been investigated. We tested the effects of HELP on vasoactivity with an ultrasound system for continuous measurement of arterial flow velocity and end-diastolic diameter. We measured brachial artery vasoactivity before, during, and after a 5 min forearm vascular occlusion. Vasoactivity measurements were acquired from 6 subjects with familial hypercholesterolemia (FH) who had been treated chronically with HELP, immediately before and after each of 4 treatments, and from 12 age- and sex-matched normocholesterolemic subjects (2 matched with each HELP subject). Peak arterial dilation after cuff release, relative to the pre-occlusion diameter, was similar for the pre-treatment, post-treatment, and normocholesterolemic groups (0.29 mm pre-treatment, 0.30 mm post-treatment and 0.33 mm normocholesterolemic, P = NS). The slope of arterial diameter during occlusion was also similar for the three groups (-0.10 microm/s pre-treatment, 0.02 microm/s post-treatment, and 0.06 microm/s normocholesterolemic, P = NS). These two parameters are known to be decreased in hypercholesterolemic subjects to an extent which could be readily detected by the power of this study. Interestingly, one homozygous FH subject consistently demonstrated significant improvement in these two parameters immediately after HELP, suggesting an individual difference in arterial physiology. On average, FH patients treated chronically with HELP have similar vasoactivity to age- and sex-matched subjects with low risk for atherosclerosis. This result, in light of the many studies that have associated hypercholesterolemia with abnormal vasoactivity, suggests that chronic HELP therapy improves vasoactivity in patients with severe hypercholesterolemia.

Measurements of arterial diameter throughout the cardiac cycle (i.e., the arterial distension waveform) are conducted increasingly to study mechanical properties of the arterial wall and changes associated with disease. The distension waveform of peripheral arteries can be measured noninvasively via ultrasonic echo tracking. M-mode imaging, and B-mode imaging. Of these, echo tracking is the most popular method because of its single micrometer resolution during continuous measurements under ideal conditions. However, high resolution within continuous measurements does not imply high reproducibility between measurements. Therefore, we compared repeated measurements of the amplitude of common carotid artery distension in 26 subjects, obtained sequentially in random order by: 1. Off-line echo tracking of digitized radiofrequency ultrasound; 2. M-mode imaging with automated edge detection; and 3. 30-Hz B-mode imaging with automated edge detection and model-based diameter estimation. In each case, the transducer was hand-held and was removed from the neck between repeated measurements. The amplitude of arterial distension was estimated from the serial diameter measurements by maximum likelihood (ML) estimation, by least-squares fit of a Fourier series model, and by application of a cubic smoothing spline. Within continuous measurements, the standard deviation of the ML distension amplitude for neighboring cardiac cycles was significantly smaller (p > 0.05) with echo-tracking (0.023 mm) than with the B-mode (0.036 mm) or M-mode (0.074 mm) methods. However, between discontinuous measurements on the same subject, the standard deviation of the ML distension amplitude was similar for the echo-tracking (0.076 mm) and B-mode (0.073 mm) methods. The Fourier series model and the cubic smoothing spline slightly reduced the standard deviation of the B-mode and M-mode distension amplitudes, but also reduced the mean amplitude estimate. On the basis of this relative comparison of methods, we conclude that, although echo tracking offers high resolution for continuous measurements, the reproducibility of discontinuous measurements of carotid artery distension is no better with echo tracking than can be obtained from 30-Hz B-mode images.

Familial hypercholesterolemia (FH) can cause early disability and death from premature atherosclerotic cardiovascular disease. Patients homozygous for the disease have very high plasma cholesterol, extensive xanthomatosis, and die from atherosclerosis in childhood or early adulthood. Past attempts to improve the prognosis included removal of cholesterol from the circulation by ileal bypass or biliary diversion. Neither treatment was successful. Direct removal by plasmapheresis of low-density lipoprotein (LDL), the primary carrier of cholesterol in plasma, was first performed on an FH homozygous patient in 1966. The treatment was well tolerated and led to rapid diminution of xanthomas. Other experimental treatments included selective LDL apheresis with monoclonal or polyclonal antibody affinity columns. A method for selective LDL apheresis was developed in 1983 by Armstrong, Seidel, and colleagues based on heparin precipitation of LDL at low pH. This method, called HELP, removes all apolipoprotein B-containing lipoproteins including LDL and lipoprotein (a), as well as some fibrinogen. LDL apheresis by HELP is well tolerated; the incidence of side effects is low, and the treatment has been associated with regression of cardiovascular disease. LDL apheresis, rather than liver transplantation, is the treatment of choice for patients with severe, life-threatening hypercholesterolemia which does not respond to diet and drug therapy.

Measurements of endothelium-dependent vasoreactivity and arterial compliance are important metrics of vascular pathophysiology which may be used for the development and evaluation of therapeutic methods. The technique of ultrasonic echo tracking is applicable to measurements of endothelium-dependent vasoreactivity and arterial compliance. To evaluate the application of echo tracking to these measurements, we constructed a system based upon analog-to-digital conversion and storage of the radio frequency (RF) ultrasound signals. Off-line analysis of the RF data with various echo-tracking algorithms demonstrated two potential sources of error: tracking drift and RF transition regions. The tracking drift resulted from the slow accumulation of tracking error. The RF transition regions were associated with disparate motions of neighboring reflectors or the insonation of a new series of tissue layers. As a result of these sources of error, the application of echo tracking to endothelium-dependent vasoreactivity measurements is unlikely to outperform duplex ultrasound methods. The application of echo tracking to arterial compliance measurements via the arterial pressure/diameter relationship may produce variable results due to RF transition regions. Finally, the application of echo tracking to arterial compliance measurements via the pulse wave velocity is relatively insensitive to these sources of error because the pulse-wave velocity measurement depends upon the timing of the peak arterial distension, not on the absolute value of the distension.

Arterial diameter is an important parameter of vascular physiology in vivo. Noninvasive measurements of arterial diameter can be used in the assessment of endothelium-dependent vasoreactivity (EDV) and arterial compliance. Measurements of EDV may serve for assessment of early atherosclerosis. The potential value of EDV measurements with specificity for individual subjects is a strong motivation for improvements in the ultrasonic measurement of arterial diameter. This article presents and evaluates new methods for the measurement and tracking of arterial diameter from B-mode images. B-mode images acquired in planes longitudinal to the vessel and in planes rotated slightly off of the vessel axis ("skew") are considered. The cross-sections of arteries in these planes are modeled as parabola pairs or as ellipses. For the brachial artery, the variance of caliper-based diameter estimates (0.0139 mm2) is twice as large as that of elliptical-model-based diameter estimates (0.0072 mm2) and five times as large as parabolic-model-based diameter estimates (0.0027 mm2). Diameter estimates from the skew and longitudinal planes perform equivalently in limited-motion quantitative comparisons. However, diameter estimates from skew planes are less sensitive to translational motions of the artery. Also, translational motions are unambiguously represented in the skew image, thus facilitating compensatory motions of the transducer. The methods described here are relatively simple to implement and may provide adequate resolution for noninvasive assessment of EDV with individual specificity.

Microphone arrays with fixed (time-invariant) weights are directed at enhancing a desired signal from one direction (straight ahead) while attenuating spatially distributed interference and reverberation. Using the theory of sensitivity-constrained optimal beamforming [Cox et al., IEEE Trans. Acoust. Speech Sig. Process. ASSP-34, 393-398 (1986)], free-field arrays of head-sized extents were studied. The key parameters affecting array design and performance are the set of transfer functions from the target direction to each array microphone [H(f)] and the intermicrophone cross-spectral densities for isotropic noise [Szz(f)]. Design variables included the orientation of the array, the number, and [as motivated by Soede, Ph.D. thesis, Delft University of Technology (1990)] the directionality of the microphones within the array, and the complexity and robustness of the required processing. Performance was characterized by the broadband intelligibility-weighted directivity (gain against isotropic noise) and noise sensitivity (reflecting the array's sensitivity to uncorrelated noise, as well as device tolerances). For broadside orientation, a variety of arrays based on cardioid and hypercardioid microphones gave very similar performance. They can provide directivities of 7-8 dB with easily implemented weights (simple scalars). For endfire orientation, as Soede (1990) recognized, similar directivities result with weights based on analog gains and pure time delays. However, with weightings chosen independently for each frequency, directivities up to approximately 11 dB may be obtained, although the increased noise sensitivities of these arrays require practical evaluation. Because of sound diffraction, placement of arrays onto the head potentially impacts both their design and performance. In-situ measurements of H(f) and Szz(f) as well as simplified theoretical models are suggested to explore the optimization of head-mounted arrays.