Influence of automatic frequent pace-timing adjustments on effective left ventricular pacing during cardiac resynchronization therapy.

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.

Charge Transport and Conductance Switching of Redox-Active Azulene Derivatives.

Azulene (Az) is a non-alternating, aromatic hydrocarbon composed of a five-membered, electron-rich and a seven-membered, electron-poor ring; an electron distribution that provides intrinsic redox activity. By varying the attachment points of the two electrode-bridging substituents to the Az center, the influence of the redox functionality on charge transport is evaluated. The conductance of the 1,3 Az derivative is at least one order of magnitude lower than those of the 2,6 Az and 4,7 Az derivatives, in agreement with density functional theory (DFT) calculations. In addition, only 1,3 Az exhibits pronounced nonlinear current-voltage characteristics with hysteresis, indicating a bias-dependent conductance switching. DFT identifies the LUMO to be nearest to the Fermi energy of the electrodes, but to be an active transport channel only in the case of the 2,6 and the 4,7 Az derivatives, whereas the 1,3 Az derivative uses the HOMO at low and the LUMO+1 at high bias. In return, the localized, weakly coupled LUMO of 1,3 Az creates a slow electron-hopping channel responsible for the voltage-induced switching due to the occupation of a single molecular orbital (MO).

Automated detection of effective left-ventricular pacing: going beyond percentage pacing counters.

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.

High-conductive organometallic molecular wires with delocalized electron systems strongly coupled to metal electrodes.

Besides active, functional molecular building blocks such as diodes or switches, passive components, for example, molecular wires, are required to realize molecular-scale electronics. Incorporating metal centers in the molecular backbone enables the molecular energy levels to be tuned in respect to the Fermi energy of the electrodes. Furthermore, by using more than one metal center and sp-bridging ligands, a strongly delocalized electron system is formed between these metallic "dopants", facilitating transport along the molecular backbone. Here, we study the influence of molecule-metal coupling on charge transport of dinuclear X(PP)2FeC4Fe(PP)2X molecular wires (PP = Et2PCH2CH2PEt2); X = CN (1), NCS (2), NCSe (3), C4SnMe3 (4), and C2SnMe3 (5) under ultrahigh vacuum and variable temperature conditions. In contrast to 1, which showed unstable junctions at very low conductance (8.1 × 10(-7) G0), 4 formed a Au-C4FeC4FeC4-Au junction 4' after SnMe3 extrusion, which revealed a conductance of 8.9 × 10(-3) G0, 3 orders of magnitude higher than for 2 (7.9 × 10(-6) G0) and 2 orders of magnitude higher than for 3 (3.8 × 10(-4) G0). Density functional theory (DFT) confirmed the experimental trend in the conductance for the various anchoring motifs. The strong hybridization of molecular and metal states found in the C-Au coupling case enables the delocalized electronic system of the organometallic Fe2 backbone to be extended over the molecule-metal interfaces to the metal electrodes to establish high-conductive molecular wires.

Tachycardia detection performance of implantable loop recorders: results from a large 'real-life' patient cohort and patients with induced ventricular arrhythmias.

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%.

Prolonged PR interval and incidence of atrial fibrillation, heart failure admissions, and mortality in patients with implanted cardiac devices: A real-world survey.

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.

First-in-human noninvasive left ventricular ultrasound pacing: A potential screening tool for cardiac resynchronization therapy.

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.

Electrical Synchrony Optimization for Left Bundle Branch Area Pacing in Patients With Bradycardia and Heart Failure.

Left bundle branch area pacing (LBBAP) has emerged as a promising physiological pacing modality. This study was designed to investigate the acute impact of the atrioventricular delay (AVD) on cardiac electrical characteristics and identify an optimal range of AVDs for LBBAP to achieve electrical atrioventricular and interventricular synchrony. Patients indicated for ventricular or biventricular pacing were studied during routine follow-ups at least 3 months after LBBAP implantation. Patients were excluded if they had a complete AV block or persistent atrial fibrillation. AVD was programed from 40 to 240 ms or until intrinsic conduction occurred. Optimal AVD was determined by the electrocardiography criteria, including QRS duration, reduced R-wave in lead V1, reduced notching or slurring in lateral leads, and more desirable precordial QRS transition. A total of 38 patients (age 68.7 ± 10.3 years; 16 male (42%); 18 dual-chamber pacemakers and 20 cardiac resynchronization therapy devices; average follow-up period 15.1 ± 10.2 months) were included. The fusion of LBBAP and intrinsic right ventricular conduction occurred in 21 patients with corresponding optimal AVD determined. A great proportion (∼85%) of the optimal AVDs ranged from 50% to 80% of the observed atrium-to-left bundle branch-sensing (A-LBBS) intervals. The linear correlation between the optimal AVD and corresponding A-LBBS interval (optimal AVD = 0.84 × [A-LBSs interval] - 36 ms) produced R = 0.86 and p <0.0001. In conclusion, AVD selection during LBBAP greatly impacted the ventricular electrical characteristics and the optimal AVD was linearly correlated with the corresponding A-LBBS interval.

Noninvasive Electrical Mapping Compared with the Paced QRS Complex for Optimizing CRT Programmed Settings and Predicting Multidimensional Response.

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.

Electron transfer through a single barrier inside a molecule: from strong to weak coupling.

In all theoretical treatments of electron transport through single molecules between two metal electrodes, a clear distinction has to be made between a coherent transport regime with a strong coupling throughout the junction and a Coulomb blockade regime in which the molecule is only weakly coupled to both leads. The former case where the tunnelling barrier is considered to be delocalized across the system can be well described with common mean-field techniques based on density functional theory (DFT), while the latter case with its two distinct barriers localized at the interfaces usually requires a multideterminant description. There is a third scenario with just one barrier localized inside the molecule, which we investigate here using a variety of quantum-chemical methods by studying partial charge shifts in biphenyl radical ions induced by an electric field at different angles to modulate the coupling and thereby the barrier within the π-system. We find steps rounded off at the edges in the charge versus field curves for weak and intermediate coupling, whose accurate description requires a correct treatment of both exchange and dynamical correlation effects is essential. We establish that DFT standard functionals fail to reproduce this feature, while a long range corrected hybrid functional fares much better, which makes it a reasonable choice for a proper DFT-based transport description of such single barrier systems.

Validation of Intrinsic Left Ventricular Assist Device Data Tracking Algorithm for Early Recognition of Centrifugal Flow Pump Thrombosis.

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.

A Sensorless Modular Multiobjective Control Algorithm for Left Ventricular Assist Devices: A Clinical Pilot Study.

Background: Contemporary Left Ventricular Assist Devices (LVADs) mainly operate at a constant speed, only insufficiently adapting to changes in patient demand. Automatic physiological speed control promises tighter integration of the LVAD into patient physiology, increasing the level of support during activity and decreasing support when it is excessive. Methods: A sensorless modular control algorithm was developed for a centrifugal LVAD (HVAD, Medtronic plc, MN, USA). It consists of a heart rate-, a pulsatility-, a suction reaction-and a supervisor module. These modules were embedded into a safe testing environment and investigated in a single-center, blinded, crossover, clinical pilot trial (clinicaltrials.gov, NCT04786236). Patients completed a protocol consisting of orthostatic changes, Valsalva maneuver and submaximal bicycle ergometry in constant speed and physiological control mode in randomized sequence. Endpoints for the study were reduction of suction burden, adequate pump speed and flowrate adaptations of the control algorithm for each protocol item and no necessity for intervention via the hardware safety systems. Results: A total of six patients (median age 53.5, 100% male) completed 13 tests in the intermediate care unit or in an outpatient setting, without necessity for intervention during control mode operation. Physiological control reduced speed and flowrate during patient rest, in sitting by a median of -75 [Interquartile Range (IQR): -137, 65] rpm and in supine position by -130 [-150, 30] rpm, thereby reducing suction burden in scenarios prone to overpumping in most tests [0 [-10, 2] Suction events/minute] in orthostatic upwards transitions and by -2 [-6, 0] Suction events/min in Valsalva maneuver. During submaximal ergometry speed was increased by 86 [31, 193] rpm compared to constant speed for a median flow increase of 0.2 [0.1, 0.8] L/min. In 3 tests speed could not be increased above constant set speed due to recurring suction and in 3 tests speed could be increased by up to 500 rpm with a pump flowrate increase of up to 0.9 L/min. Conclusion: In this pilot study, safety, short-term efficacy, and physiological responsiveness of a sensorless automated speed control system for a centrifugal LVAD was established. Long term studies are needed to show improved clinical outcomes. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04786236.

Graphical prediction of quantum interference-induced transmission nodes in functionalized organic molecules.

Quantum interference (QI) in molecular transport junctions can lead to dramatic reductions of the electron transmission at certain energies. In a recent work [Markussen et al., Nano Lett., 2010, 10, 4260] we showed how the presence of such transmission nodes near the Fermi energy can be predicted solely from the structure of a conjugated molecule when the energies of the atomic p(z) orbitals do not vary too much. Here we relax the assumption of equal on-site energies and generalize the graphical scheme to molecules containing different atomic species. We use this diagrammatic scheme together with tight-binding and density functional theory calculations to investigate QI in linear molecular chains and aromatic molecules with different side groups. For the molecular chains we find a linear relation between the position of the transmission nodes and the side group π orbital energy. In contrast, the transmission functions of functionalized aromatic molecules generally display a rather complex nodal structure due to the interplay between molecular topology and the energy of the side group orbital.

Controlling the transmission line shape of molecular t-stubs and potential thermoelectric applications.

Asymmetric line shapes can occur in the transmission function describing electron transport in the vicinity of a minimum caused by quantum interference effects. Such asymmetry can be used to increase the thermoelectric efficiency of molecular junctions. So far, however, asymmetric line shapes have been only empirically found for just a few rather complex organic molecules where the origins of the line shapes relation to molecular structure were not resolved. In the present, work we introduce a method to analyze the structure dependence of the asymmetry of interference dips from simple two site tight-binding models, where one site corresponds to a molecular π orbital of the wire and the other to an atomic p(z) orbital of a side group, which allows us to characterize analytically the peak shape in terms of just two parameters. We assess our scheme with first-principles electron transport calculations for a variety of t-stub molecules and also address their suitability for thermoelectric applications.

The relation between structure and quantum interference in single molecule junctions.

Quantum interference (QI) of electron pathways has recently attracted increased interest as an enabling tool for single-molecule electronic devices. Although various molecular systems have been shown to exhibit QI effects and a number of methods have been proposed for its analysis, simple guidelines linking the molecular structure to QI effects in the phase-coherent transport regime have until now been lacking. In the present work we demonstrate that QI in aromatic molecules is intimately related to the topology of the molecule's π system and establish a simple graphical scheme to predict the existence of QI-induced transmission antiresonances. The generality of the scheme, which is exact for a certain class of tight-binding models, is proved by a comparison to first-principles transport calculations for 10 different configurations of anthraquinone as well as a set of cross-conjugated molecular wires.

Electrode effects on the observability of destructive quantum interference in single-molecule junctions.

Destructive quantum interference (QI) has been a source of interest as a new paradigm for molecular electronics as the electronic conductance is widely dependent on the occurrence or absence of destructive QI effects. In order to interpret experimentally observed transmission features, it is necessary to understand the effects of all components of the junction on electron transport. We perform non-equilibrium Green's function calculations within the framework of density functional theory to assess the structure-function relationship of transport through pyrene molecular junctions with distinct QI properties. The chemical nature of the anchor groups and the electrodes controls the Fermi level alignment, which determines the observability of destructive QI. A thorough analysis allows to disentangle the transmission features arising from the molecule and the electrodes. Interestingly, graphene electrodes introduce features in the low-bias regime, which can either mask or be misinterpreted as QI effects, while instead originating from the topological properties of the edges. Thus, this first principles analysis provides clear indications to guide the interpretation of experimental studies, which cannot be obtained from simple Hückel model calculations.

Long-lived charged states of single porphyrin-tape junctions under ambient conditions.

The ability to control the charge state of individual molecules wired in two-terminal single-molecule junctions is a key challenge in molecular electronics, particularly in relation to the development of molecular memory and other computational componentry. Here we demonstrate that single porphyrin molecular junctions can be reversibly charged and discharged at elevated biases under ambient conditions due to the presence of a localised molecular eigenstate close to the Fermi edge of the electrodes. In particular, we can observe long-lived charge-states with lifetimes upwards of 1-10 seconds after returning to low bias and large changes in conductance, in excess of 100-fold at low bias. Our theoretical analysis finds charge-state lifetimes within the same time range as the experiments. The ambient operation demonstrates that special conditions such as low temperatures or ultra-high vacuum are not essential to observe hysteresis and stable charged molecular junctions.

A Power Tracking Algorithm for Early Detection of Centrifugal Flow Pump Thrombosis.

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.

Downloadable algorithm to reduce inappropriate shocks caused by fractures of implantable cardioverter-defibrillator leads.

BACKGROUND: The primary method for monitoring implantable cardioverter-defibrillator lead integrity is periodic measurement of impedance. Sprint Fidelis leads are prone to pace-sense lead fractures, which commonly present as inappropriate shocks caused by oversensing. METHODS AND RESULTS: We developed and tested an algorithm to enhance early identification of lead fractures and to reduce inappropriate shocks. This lead-integrity algorithm, which can be downloaded into presently implanted implantable cardioverter-defibrillators, alerts the patient and/or physician when triggered by either oversensing or excessive increases in impedance. To reduce inappropriate shocks, the lead-integrity algorithm increases the number of intervals to detect (NID) ventricular fibrillation when triggered. The lead-integrity algorithm was tested on data from 15 970 patients with Fidelis leads (including 121 with clinically diagnosed fractures) and 95 other fractured leads confirmed by analysis of returned product. The effect of the NID on inappropriate shocks was tested in 92 patients with 927 shocks caused by lead fracture. Increasing the NID reduced inappropriate shocks (P<0.0001). The lead-integrity algorithm provided at least a 3-day warning of inappropriate shocks in 76% (95% CI, 66 to 84) of patients versus 55% (95% CI, 43 to 64) for optimal impedance monitoring (P=0.007). Its positive predictive value was 72% for lead fractures and 81% for lead fractures or header-connector problems requiring surgical intervention. The false-positive rate was 1 per 372 patient-years of monitoring. CONCLUSIONS: A lead-integrity algorithm developed for download into existing implantable cardioverter-defibrillators increases short-term warning of inappropriate shocks in patients with lead fractures and reduces the likelihood of inappropriate shocks. It is the first downloadable RAMware to enhance the performance of nominally functioning implantable cardioverter-defibrillators and the first implantable cardioverter-defibrillator monitoring feature that triggers real-time changes in ventricular fibrillation detection parameters to reduce inappropriate shocks.