Accurate detection of lead malfunction from ECG-derived bipolar pacing stimulus amplitude.

BACKGROUND: One common mode of lead failure is insulation breach, which may result in myopotential noise and device malfunction. "Pseudo-unipolarization" of bipolar pacing stimuli, as observed from a routine 12-lead electrocardiogram (ECG) due to stimulus current leak, has been observed with insulation breaches. OBJECTIVE: We sought to characterize this electrocardiographic finding to detect this type of lead malfunction. METHODS: A total of 138 transvenous leads were analyzed, including 88 with known malfunction and 50 normal leads. The amplitude of a bipolar pacing stimulus on the ECG was recorded and compared with a control data set of newly implanted leads with bipolar stimuli normalized for output. RESULTS: The malfunction group consisted of 61% right atrium and 39% right ventricle leads with mean pacing output of 2.74 V at 0.5 ms. There was a significant difference in ECG bipolar stimulus amplitudes at time of identification of failure (7.89 ± 7.56 mm/V; P < .001) compared with those of normal leads (0.86 ± 0.41 mm/V). Receiver operating characteristic curve for the prediction of lead malfunction based on absolute ECG amplitude displayed an area under the curve of 0.93 (95% CI, 0.891-0.969). When normalized for programmed stimulus output, a cutoff of 5 mm/V demonstrated a sensitivity of 91% and a specificity of 92% (area under the curve, 0.967; 95% CI, 0.938-0.996). CONCLUSION: The maximum amplitude of a bipolar pacing stimulus on the ECG is significantly lower in normal functioning leads compared with those with known malfunction. This simply derived variable demonstrated good accuracy at identifying lead failure due to insulation breach.

Impact of omitting the intravenous heparin bolus on outcomes of leadless pacemaker implantation.

BACKGROUND: Early guidance recommended a bolus of intravenous heparin at the beginning of leadless pacemaker (LP) implantation procedures. However, due to concern about bleeding complications, more recent practice has tended toward omitting the bolus and only running a continuous heparin infusion through the introducer sheath. The impact of omitting the heparin bolus on procedural outcomes is not clear. METHODS: We reviewed all Medtronic Micra LP implants at our institution from 9/2014 to 9/2022. The decision to bolus with heparin was at operator discretion. RESULTS: Among 621 LP implants, 326 received an intravenous heparin bolus, 243 did not, and 52 patients were excluded because heparin bolus status could not be confirmed. There was a trend toward more frequent omission of the heparin bolus with more recent implants. Median follow-up after LP implant was 14.3 (interquartile range [IQR]: 8.4-27.9) months. There was no difference between heparin bolus and no bolus groups in the number of device deployments/recaptures (1.42 ± 0.81 vs. 1.31 ± 0.66, p = .15). Implant-related adverse events were also similar between heparin bolus and no bolus groups: access-site hematoma requiring intervention (7 vs. 5, p = .99), pseudoaneurysm (1 vs. 1, p = .99), cardiac perforation (1 vs. 1, p = .99), intraprocedural device thrombus formation (2 vs. 4, p = .41), 30-day rehospitalization (21 vs. 15, p = .98), and 30-day all-cause mortality (16 vs. 14, p = .70). There was one additional nonfatal cardiac perforation in a patient who was excluded due to unknown heparin bolus status. Regarding device electrical parameters between heparin bolus and no bolus groups, there were no significant differences at the time of implant: pacing capture threshold 0.5 ± 0.4 vs. 0.5 ± 0.3, p = .10; pacing impedance 739.9 ± 226.4 vs. 719.1 ± 215.4, p = .52; R wave sensing 11.7 ± 5.7 vs. 12.0 ± 5.4, p = .34). Long-term device performance was also similar between groups. CONCLUSION: Omission of the systemic heparin bolus at the time of LP implantation appears safe in appropriately selected patients. Heparin bolus may still be considered in long cases requiring multiple device deployments or in patients at high risk for thrombotic complications.

Assessment of Patient-Derived Xenograft Growth and Antitumor Activity: The NCI PDXNet Consensus Recommendations.

Although patient-derived xenografts (PDXs) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and access to a suite of analytical tools will enhance information exchange and facilitate identification of promising novel therapies and biomarkers for guiding cancer therapy.

Outcomes of tricuspid regurgitation after lead extraction.

INTRODUCTION: Transvenous leads have been implicated in tricuspid valve (TV) dysfunction, but limited data are available regarding the effect of extracting leads across the TV on valve regurgitation. The aim of this study is to quantify tricuspid regurgitation (TR) before and after lead extraction and identify predictors of worsening TR. METHODS: We studied 321 patients who had echocardiographic data before and after lead extraction. TR was graded on a scale (0 = none/trivial, 1 = mild, 2 = moderate, 3 = severe). A change of >1 grade following extraction was considered significant. RESULTS: A total of 321 patients underwent extraction of a total of 338 leads across the TV (1.05 ± 0.31 leads across the TV per patient). There was no significant difference on average TR grade pre- and postextraction (1.18 ± 0.91 vs. 1.15 ± 0.87; p = 0.79). TR severity increased after extraction in 84 patients, but was classified as significantly worse (i.e., >1 grade change in severity) in only 8 patients (2.5%). Use of laser lead extraction was associated with a higher rate of worsening TR postextraction (44.0% vs. 31.6%, p = 0.04). CONCLUSION: In our single-center analysis, extraction of leads across the TV did not significantly affect the extent of TR in most patients. Laser lead extraction was associated with a higher rate of worsening TR after extraction.

Evaluation of the in vivo chemical reactivity of a novel copolymer insulation on cardiac leads in a single-center study.

BACKGROUND: Human in vivo data on the chemical stability of different transvenous lead materials, particularly OptimTM leads, are lacking. OBJECTIVES: The purpose of this study was to determine the chemical reactivity of insulation materials by analyzing the molar mass of extracted pacing and defibrillator leads METHODS: We collected extracted leads at Emory University Hospitals and sent the leads with thermoplastic outer insulation material for molar mass analysis, a material characteristic that informs biostability. Leads were separated based on the chemical identity of the outer insulation material, and the molar mass was measured by an independent party. The extent of chemical reaction was compared across leads having different materials: poly(ether)urethane 55D, poly(ether)urethane 80A, and Optim. RESULTS: A total of 70 leads were extracted. The subset of extracted leads having outer insulation materials composed of PEU or Optim were analyzed for molar mass, where implant times ranged from 0.12 to 16.26 years. The rate of chemical degradation was compared by plotting the extent of reaction [Mn(t = 0)/Mn(t)] as a function of implant time. The Optim molar mass decreased to 40% of its initial value at 10 years of implant. No change in the molar mass of the PEU insulations could be resolved over the same 10-year implant time. CONCLUSION: Because the molar mass of a polymer is directly related to its mechanical integrity, the observed decrease in molar mass of Optim likely translates into premature insulation defects and is consistent with the observed increased rate of electrical malfunction/noise in this subset of cardiac leads.

Safety of multi-access site venous closure following catheter ablation of atrial fibrillation and flutter.

BACKGROUND: Following catheter ablation, vascular access management involves potential complications and prolonged recovery. Recently, suture-mediated closure (SMC) devices were approved for venous access procedures. The objective of this study is to evaluate the safety of a commercially available SMC for multiple access site venous closure by duplex ultrasound (DUS) in asymptomatic subjects with non-visible complications. METHODS: Thirty-six subjects (63 ± 10.7 years old, 12 female) were enrolled. Following catheter ablation for atrial fibrillation, all subjects had SMC of every venous access site. Subjects underwent DUS of femoral veins and arteries. DUS was performed at discharge, and again at 30 days. Subjects were evaluated for clinically apparent vascular complications. RESULTS: Mean procedure duration was 138.6 min, and the time to hemostasis was 3.1 min/access site and 9.5 min/subject. Median time to ambulation was 193.5 min, and median time to discharge was 5.95 h, with discharge as early as 2.4 h. A median of 2 sheaths/vein and a median of 2 SMC devices/vein were used. There were no major complications and a 16.7% (6/36) minor complication rate at discharge. All complications resolved at 30 days. The complication rate was not higher in patients with 2 SMC per access site as compared to the patients who just received 1 SMC per access site. CONCLUSIONS: This study demonstrates the safety of multi-access closure using SMC, following catheter ablation procedures, for closure of sites that use sheath sizes from ≤ 8F to ≥ 15F and for those that use 2 or more SMCs per access site.

Long-Term Outcomes of Cardiac Resynchronization Therapy in Patients With Repaired Tetralogy of Fallot: A Multicenter Study.

BACKGROUND: A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot. METHODS: Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Twelve centers contributed baseline and longitudinal data, including vital status, left ventricular ejection fraction (LVEF), QRS duration, and NYHA functional class. Outcomes were analyzed at early (3 months), intermediate (1 year), and late follow-up (≥2 years) after CRT implantation. RESULTS: A total of 44 patients (40.3±19.2 years) with tetralogy of Fallot and CRT were enrolled. Twenty-nine (65.9%) patients had right ventricular pacing before CRT upgrade. The left ventricular ejection fraction improved from 32% [24%-44%] at baseline to 42% [32%-50%] at early follow-up (P<0.001) and remained improved from baseline thereafter (P≤0.002). The QRS duration decreased from 180 [160-205] ms at baseline to 152 [133-182] ms at early follow-up (P<0.001) and remained decreased at intermediate and late follow-up (P≤0.001). Patients with upgraded CRT had consistent improvement in left ventricular ejection fraction and QRS duration at each time point (P≤0.004). Patients had a significantly improved New York Heart Association functional class after CRT implantation at each time point compared with baseline (P≤0.002). The transplant-free survival rates at 3, 5, and 8 years after CRT implantation were 85%, 79%, and 73%. CONCLUSIONS: In patients with tetralogy of Fallot treated with CRT consistent improvement in QRS duration, left ventricular ejection fraction, New York Heart Association functional class, and reasonable long-term survival were observed. The findings from this multicenter study support the consideration of CRT in this unique population.

One-year mortality and causes of death after stereotactic radiation therapy for refractory ventricular arrhythmias: A systematic review and pooled analysis.

Patients treated with cardiac stereotactic body radiation therapy (radioablation) for refractory ventricular arrhythmias are patients with advanced structural heart disease and significant comorbidities. However, data regarding 1-year mortality after the procedure are scarce. This systematic review and pooled analysis aimed at determining 1-year mortality after cardiac radioablation for refractory ventricular arrhythmias and investigating leading causes of death in this population. MEDLINE/EMBASE databases were searched up to January 2023 for studies including patients undergoing cardiac radioablation for the treatment of refractory ventricular arrhythmias. Quality of included trials was assessed using the NIH Tool for Case Series Studies (PROSPERO CRD42022379713). A total of 1,151 references were retrieved and evaluated for relevance. Data were extracted from 16 studies, with a total of 157 patients undergoing cardiac radioablation for refractory ventricular arrhythmias. Pooled 1-year mortality was 32 % (95 %CI: 23-41), with almost half of the deaths occurring within three months after treatment. Among the 157 patients, 46 died within the year following cardiac radioablation. Worsening heart failure appeared to be the leading cause of death (52 %), although non-cardiac mortality remained substantial (41 %) in this population. Age≥70yo was associated with a significantly higher 12-month all-cause mortality (p<0.022). Neither target volume size nor radiotherapy device appeared to be associated with 1-year mortality (p = 0.465 and p = 0.199, respectively). About one-third of patients undergoing cardiac stereotactic body radiation therapy for refractory ventricular arrhythmias die within the first year after the procedure. Worsening heart failure appears to be the leading cause of death in this population.

Cardiac stereotactic radiation therapy for refractory ventricular arrhythmias in patients with left ventricular assist devices.

Left ventricular assist device (LVAD) implantation is an established treatment for patients with advanced heart failure refractory to medical therapy. However, the incidence of ventricular arrhythmias (VAs) is high in this population, both in the acute and delayed phases after implantation. About one-third of patients implanted with an LVAD will experience sustained VAs, predisposing these patients to worse outcomes and complicating patient management. The combination of pre-existing myocardial substrate and complex electrical remodeling after LVAD implantation account for the high incidence of VAs observed in this population. LVAD patients presenting VAs refractory to antiarrhythmic therapy and catheter ablation procedures are not rare. In such patients, treatment options are extremely limited. Stereotactic body radiation therapy (SBRT) is a technique that delivers precise and high doses of radiation to highly defined targets, reducing exposure to adjacent normal tissue. Cardiac SBRT has recently emerged as a promising alternative with a growing number of case series reporting the effectiveness of the technique in reducing the VA burden in patients with arrhythmias refractory to conventional therapies. The safety profile of cardiac SBRT also appears favorable, even though the current clinical experience remains limited. The use of cardiac SBRT for the treatment of refractory VAs in patients implanted with an LVAD are even more scarce. This review summarizes the clinical experience of cardiac SBRT in LVAD patients and describes technical considerations related to the implementation of the SBRT procedure in the presence of an LVAD.

Long-term performance of single-connector (DF4) implantable defibrillator leads.

AIMS: Single-connector (DF4) defibrillator leads have become the predominantly implanted transvenous implantable cardioverter-defibrillator lead. However, data on their long-term performance are derived predominantly from manufacturer product performance reports. METHODS AND RESULTS: We reviewed medical records in 5289 patients with DF4 leads between 2011 and 2023 to determine the frequency of lead-related abnormalities. We defined malfunction as any single or combination of electrical abnormalities requiring revision including a sudden increase (≥2×) in stimulation threshold, a discrete jump in high-voltage impedance, or sensing of non-physiologic intervals or noise. We documented time to failure, predictors of failure, and management strategies. Mean follow-up after implant was 4.15 ± 3.6 years (median = 3.63), with 37% of leads followed for >5 years. A total of 80 (1.5%) leads demonstrated electrical abnormalities requiring revision with an average time to failure of 4 ± 2.8 years (median = 3.5). Of the leads that malfunctioned, 62/80 (78%) were extracted and replaced with a new lead and in the other 18 cases, malfunctioned DF4 leads were abandoned, and a new lead implanted. In multivariable models, younger age at implant (OR 1.03 per year; P < 0.001) and the presence of Abbott/St. Jude leads increased the risk of malfunction. CONCLUSION: DF4 defibrillator leads demonstrate excellent longevity with >98.3% of leads followed for at least 5 years still functioning normally. Younger age at implant and lead manufacturer are associated with an increased risk of DF4 lead malfunction. The differences in lead survival between manufacturers require further investigation.

Complex repolarization dynamics in ex vivo human ventricles are independent of the restitution properties.

AIMS: The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts. METHODS AND RESULTS: We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. CONCLUSION: We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.

Clinical outcomes of automatic algorithms in cardiac resynchronization therapy: Systematic review and meta-analysis.

Background: Algorithms to automatically adjust atrioventricular (AV) and interventricular (VV) intervals in cardiac resynchronization therapy (CRT) devices are common, but their clinical efficacy is unknown. Objective: The purpose of this study was to evaluate automatic CRT algorithms in patients with heart failure for the reduction of mortality, heart failure hospitalizations, and clinical improvement. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) in patients with CRT using automatic algorithms that change AV and VV intervals dynamically without manual input, on a beat-to-beat basis. We performed a subgroup analysis including intracardiac electrogram-based (EGM) algorithms and contractility-based algorithms. Results: Nine RCTs with 8531 participants were included, of whom 4275 (50.1%) were randomized to automatic algorithm. Seven of the 9 trials used EGM-based algorithms, and 2 used contractility sensors. There was no difference in all-cause mortality (10.3% vs 11.3%; odds ratio [OR] 0.90; 95% confidence interval [CI] 0.71-1.03; P = .13; I2 = 0%) or heart failure hospitalizations (15.0% vs 16.1%; OR 0.924; 95% CI 0.81-1.04; P = .194; I2 = 0%) between the automatic algorithm group and the control group. Study-defined clinical improvement was also not significantly different between groups (66.6% vs 63.3%; risk ratio 1.01; 95% CI 0.95-1.06; P = .82; I2 = 50%). In the contractility-based subgroup, there was a trend toward greater clinical improvement with the use of the automatic algorithm (75% vs 68.3%; OR 1.45; 95% CI 0.97-2.18; P = .07; I2 = 40%), which did not reach statistical significance. The overall risk of bias was low. Conclusion: Automatic algorithms that change AV or VV intervals did not improve mortality, heart failure hospitalizations, or cardiovascular symptoms in patients with heart failure and CRT.

Interobserver variability in target definition for stereotactic arrhythmia radioablation.

Background: Stereotactic arrhythmia radioablation (STAR) is a potential new therapy for patients with refractory ventricular tachycardia (VT). The arrhythmogenic substrate (target) is synthesized from clinical and electro-anatomical information. This study was designed to evaluate the baseline interobserver variability in target delineation for STAR. Methods: Delineation software designed for research purposes was used. The study was split into three phases. Firstly, electrophysiologists delineated a well-defined structure in three patients (spinal canal). Secondly, observers delineated the VT-target in three patients based on case descriptions. To evaluate baseline performance, a basic workflow approach was used, no advanced techniques were allowed. Thirdly, observers delineated three predefined segments from the 17-segment model. Interobserver variability was evaluated by assessing volumes, variation in distance to the median volume expressed by the root-mean-square of the standard deviation (RMS-SD) over the target volume, and the Dice-coefficient. Results: Ten electrophysiologists completed the study. For the first phase interobserver variability was low as indicated by low variation in distance to the median volume (RMS-SD range: 0.02-0.02 cm) and high Dice-coefficients (mean: 0.97 ± 0.01). In the second phase distance to the median volume was large (RMS-SD range: 0.52-1.02 cm) and the Dice-coefficients low (mean: 0.40 ± 0.15). In the third phase, similar results were observed (RMS-SD range: 0.51-1.55 cm, Dice-coefficient mean: 0.31 ± 0.21). Conclusions: Interobserver variability is high for manual delineation of the VT-target and ventricular segments. This evaluation of the baseline observer variation shows that there is a need for methods and tools to improve variability and allows for future comparison of interventions aiming to reduce observer variation, for STAR but possibly also for catheter ablation.

Higher-Order Dynamics Beyond Repolarization Alternans in Ex-Vivo Human Ventricles are Independent of the Restitution Properties.

Background: Repolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., periods 4, 6, 8,...) are expected but have minimal experimental evidence. Methods: We studied explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Optical mapping of the transmembrane potential was performed after staining the hearts with voltage-sensitive fluorescent dyes. Hearts were stimulated at an increasing rate until VF was induced. Signals recorded from the right ventricle endocardial surface prior to induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics. Results were correlated to the underlying electrophysiological characteristics as quantified by restitution curves and conduction velocity. Results: A prominent and statistically significant global 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. Discussion: We present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts. We infer from the independence of the period to the underlying restitution properties that the oscillation of the excitation-contraction coupling and calcium cycling mechanisms is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation and may provide targets for substrate-based ablation of VF.

Outcomes of leadless pacemaker implantation after cardiac surgery and transcatheter structural valve interventions.

INTRODUCTION: Permanent pacing indications are common after cardiac surgery and transcatheter structural valve interventions. Leadless pacemakers (LPs) have emerged as a useful alternative to transvenous pacemakers. However, current commercially available LPs are unable to provide atrial pacing or cardiac resynchronization and relatively little is known about LP outcomes after cardiac surgery and transcatheter valve interventions. METHODS: This retrospective study included patients who received a Micra VR (MicraTM MC1VR01) or Micra AV (MicraTM MC1AVR1) (Medtronic) leadless pacemaker following cardiac surgery or transcatheter structural valve intervention between September 2014 and September 2022. Device performance and clinical outcomes, including ventricular pacing burden, ejection fraction, and need for conversion to transvenous pacing systems, were evaluated during follow-up. RESULTS: A total of 78 patients were included, of whom 40 received a Micra VR LP implant, and 38 received a Micra AV LP implant. The mean age of the cohort was 65.9 ± 17.9 years, and 48.1% were females. The follow-up duration for the entire cohort was 1.3 ± 1.1 years: 1.6 ± 1.3 years for the Micra VR group and 0.8 ± 0.5 years for the Micra AV group. Among the cohort, 50 patients had undergone cardiac surgery and 28 underwent transcatheter structural valve interventions. Device electrical performance was excellent during follow-up, with a small but clinically insignificant increase in ventricular pacing threshold and a slight decrease in pacing impedance. The mean right ventricle pacing (RVP) burden significantly decreased over time in the entire cohort (74.3% ± 37.2% postprocedure vs. 47.7% ± 40.6% at last follow-up, p < .001), and left ventricle ejection fraction (LVEF) showed a modest but significant downward trend during follow-up (55.0% ± 10.6% vs. 51.5% ± 11.2% p < .001). Patients with Micra VR implants had significantly reduced LVEF during follow-up (54.1% ± 11.9% vs. 48.8% ± 11.9%, p = .003), whereas LVEF appeared stable in the Micra AV group during follow-up (56.1% ± 9.0% vs. 54.6% ± 9.7%, p = .06). Six patients (7.7%) required conversion to transvenous pacing systems, four who required cardiac resynchronization for drop in LVEF with high RVP burden and two who required dual-chamber pacemakers for symptomatic sinus node dysfunction. CONCLUSION: Leadless pacemakers provide a useful alternative to transvenous pacemakers in appropriately selected patients after cardiac surgery and transcatheter structural valve interventions. Device performance is excellent over medium-term follow-up. However, a significant minority of patients require conversion to transvenous pacing systems for cardiac resynchronization or atrial pacing support, demonstrating the need for close electrophysiologic follow-up in this cohort.