Low Utilization of Lead Extraction Among Patients With Infective Endocarditis and Implanted Cardiac Electronic Devices.

BACKGROUND: Cardiac implantable electronic device (CIED)-associated infections are associated with substantial morbidity, mortality, and costs. Guidelines have cited endocarditis as a Class I indication for transvenous lead removal/extraction (TLE) among patients with CIEDs. OBJECTIVES: The authors sought to study utilization of TLE among hospital admissions with infective endocarditis using a nationally representative database. METHODS: Using the Nationwide Readmissions Database (NRD), 25,303 admissions for patients with CIEDs and endocarditis between 2016 and 2019 were evaluated on the basis of International Classification of Diseases-10th Revision, Clinical-Modification (ICD-10-CM) codes. RESULTS: Among admissions for patients with CIEDs and endocarditis, 11.5% were managed with TLE. The proportion undergoing TLE increased significantly from 2016 to 2019 (7.6% vs 14.9%; P trend < 0.001). Procedural complications were identified in 2.7%. Index mortality was significantly lower among patients managed with TLE (6.0% vs 9.5%; P < 0.001). Presence of Staphylococcus aureus infection, implantable cardioverter-defibrillator, and large hospital size were independently associated with TLE management. TLE management was less likely with older age, female sex, dementia, and kidney disease. After adjustment for comorbidities, TLE was independently associated with significantly lower odds of mortality (adjusted OR: 0.47; 95% CI: 0.37-0.60 by multivariable logistic regression, and adjusted OR: 0.51; 95% CI: 0.40-0.66 by propensity score matching). CONCLUSIONS: Utilization of lead extraction among patients with CIEDs and endocarditis is low, even in the presence of low rates of procedural complications. Lead extraction management is associated with significantly lower mortality, and its use has trended upward between 2016 and 2019. Barriers to TLE for patients with CIEDs and endocarditis require investigation.

Early Stroke and Mortality After Percutaneous Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation.

BACKGROUND: Percutaneous endocardial left atrial appendage occlusion (LAAO) is an alternative therapy for stroke prevention in patients with atrial fibrillation who are poor candidates for oral anticoagulants. Oral anticoagulation is generally discontinued 45 days following successful LAAO. Real-world data on early stroke and mortality following LAAO are lacking. METHODS: Using International Classification of Diseases, Tenth Revision, Clinical-Modification codes, we performed a retrospective observational registry analysis to examine the rates and predictors of stroke, mortality, and procedural complications during index hospitalization and 90-day readmission among 42 114 admissions in the Nationwide Readmissions Database for LAAO between 2016 and 2019. Early stroke and mortality were defined as events occurring during index admission or 90-day readmission. Data on timing of early strokes post-LAAO were collected. Multivariable logistic regression modeling was used to ascertain predictors of early stroke and major adverse events. RESULTS: LAAO was associated with low rates of early stroke (0.63%), early mortality (0.53%), and procedural complications (2.59%). Among patients who had readmissions with strokes after LAAO, the median time from implant to readmission was 35 days (interquartile range, 9-57 days); 67% of readmissions with strokes occurred <45 days postimplant. Between 2016 and 2019, the rates of early stroke after LAAO significantly decreased (0.64% versus 0.46% P-for-trend <0.001), while early mortality and major adverse event rates were unchanged. Peripheral vascular disease and a history of prior stroke were independently associated with early stroke after LAAO. Early post-LAAO stroke rates were similar between low, medium, and high LAAO volume tertile centers. CONCLUSIONS: In this contemporary real-world analysis, the early stroke rate after LAAO was low, with the majority occurring within 45 days of device implantation. Despite an increase in LAAO procedures between 2016 and 2019, there with a significant decline in early strokes after LAAO during that period.

Electrocardiographic Risk Stratification in COVID-19 Patients.

Background: The COVID-19 pandemic has resulted in worldwide morbidity at unprecedented scale. Troponin elevation is a frequent laboratory finding in hospitalized patients with the disease, and may reflect direct vascular injury or non-specific supply-demand imbalance. In this work, we assessed the correlation between different ranges of Troponin elevation, Electrocardiographic (ECG) abnormalities, and mortality. Methods: We retrospectively studied 204 consecutive patients hospitalized at NYU Langone Health with COVID-19. Serial ECG tracings were evaluated in conjunction with laboratory data including Troponin. Mortality was analyzed in respect to the degree of Troponin elevation and the presence of ECG changes including ST elevation, ST depression or T wave inversion. Results: Mortality increased in parallel with increase in Troponin elevation groups and reached 60% when Troponin was >1 ng/ml. In patients with mild Troponin rise (0.05-1.00 ng/ml) the presence of ECG abnormality and particularly T wave inversions resulted in significantly greater mortality. Conclusion: ECG repolarization abnormalities may represent a marker of clinical severity in patients with mild elevation in Troponin values. This finding can be used to enhance risk stratification in patients hospitalized with COVID-19.

Comparison of the Effect of Atrial Fibrillation Detection Algorithms in Patients With Cryptogenic Stroke Using Implantable Loop Recorders.

Occult atrial fibrillation (AF) can be the underlying cause for cryptogenic stroke (CS). Implantable loop recorders (ILRs) have become an important tool for long-term arrhythmia monitoring in CS patients. Office-based ILR implantation by nonelectrophysiologist physicians is increasingly common. To report the real world diagnostic yield and accuracy of remote ILR monitoring in high risk CS patients, we retrospectively analyzed 145 consecutive patients with CS who underwent ILR implantation between October 2014 and October 2018 at New York University Langone Health. A certified device technician and an electrophysiologist adjudicated all transmissions. The yield and accuracy of Reveal LINQ Intra Cardiac Monitor (ICM), a fourth generation device, was compared to that of TruRhythm Detection algorithm (fifth generation device). AF was diagnosed in 17 patients (12%) over a mean follow-up of 28 ± 12 months. The median time to diagnosis was 7.4 ± 21.3 months. A total of 1,637 remote transmissions (scheduled- and auto-triggered alerts: 756; patient-triggered: 881) were adjudicated. The positive predictive value for AF episodes in the scheduled interrogations increased from 4% in the Reveal LINQ ICM to 16% in the TruRhythm LINQ. Of 881 patient-triggered transmissions, none were found to be true positive. In the Reveal LINQ ICM, for scheduled transmissions, primary causes of false positive (FP) were atrial ventricular premature complexes (80%). In the TruRhythm LINQ, for scheduled transmissions, primary cause of FP were T-wave over-sensing (87%). In conclusion, the real world diagnostic yield of ILR for patients with CS remains suboptimal, with at least 84% of AF alerts being FP. Patient-riggered events did not correlate with arrhythmia and the necessity of patient triggering in this population should be questioned. Expert interpretation of recordings is critical to assure accurate diagnosis.

QT interval prolongation and torsade de pointes in patients with COVID-19 treated with hydroxychloroquine/azithromycin.

Background: There is no known effective therapy for patients with coronavirus disease 2019 (COVID-19). Initial reports suggesting the potential benefit of hydroxychloroquine/azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT interval prolongation and induction of torsade de pointes (TdP). Objective: The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ. Methods: This is a retrospective study of 251 patients from 2 centers who were diagnosed with COVID-19 and treated with HY/AZ. We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality. Results: The QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc interval prolongation to >500 ms, a known marker of high risk of TdP, had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal. Conclusion: The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19. This prolongation may be responsible for life-threatening arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy. Strict QTc interval monitoring should be performed if the regimen is given.

Esophageal temperature dynamics during high-power short-duration posterior wall ablation.

BACKGROUND: Increased peak luminal esophageal temperature (LET) is associated with increased risk of esophageal injury after left atrial posterior wall (LAPW) ablation. The magnitude, distribution, and risk factors of LET increase with high-power short-duration (HPSD) LAPW ablation are not well understood. OBJECTIVE: The purpose of this study was to describe the spatial and temporal characteristics of LET changes associated with HPSD LAPW radiofrequency (RF) ablation. METHODS: LET was sampled at 20 Hz using a 12-point esophageal temperature monitor (CIRCA S-CATH; Circa Scientific, Inc) in 16 patients undergoing LAPW ablation. Esophageal temperature sensor position and lesion locations were recorded using an electroanatomic mapping system with fluoroscopic integration (CARTO 3, CARTOUNIVU; Biosense Webster, Inc). Point-by-point LAPW ablation was performed at 50 W for 6 seconds. The first 20 LAPW lesions were individually analyzed in each patient. RESULTS: LET increase ≥4°C (8 lesions: max LET 5.8°C), 2°-4°C (34 lesions), and 1°-2°C (58 lesions) occurred at 9 ± 2 mm, 8 ± 2 mm, and 13 ± 2 mm from sensors, respectively. Lesions placed >20 mm from a temperature sensor did not result in an LET increase ≥2°C. Temperature resolution to within 1°C of baseline occurred ∼60 seconds after cessation of RF application. Consecutive lesions resulting in additive heating of at least 1°C occurred in 17 lesion pairs with an interlesion distance of 9 ± 4 mm and interlesion time of 21 ± 4 seconds. CONCLUSION: HPSD LAPW ablation can result in severe esophageal temperature increases. Significant LET increase will be undetected when lesions are >20 mm away from a temperature sensor. Additive LET increase was observed with consecutive lesions placed <20 mm apart within 60 seconds.

Ablation in Atrial Fibrillation with Ventricular Pacing Results in Similar Spatial Catheter Stability as Compared to Ablation in Sinus Rhythm with Atrial Pacing.

BACKGROUND: Improved catheter stability is associated with decreased arrhythmia recurrence after atrial fibrillation (AF) ablation. Recently, atrial voltage mapping in AF was demonstrated to correlate better with scar as compared to mapping in sinus rhythm (SR). However, it is unknown whether ablation of persistent AF in sinus rhythm with atrial pacing or in atrial fibrillation with ventricular pacing results in differences in catheter stability or arrhythmia recurrence. METHODS: We analyzed 53 consecutive patients undergoing first-time persistent AF ablation with pulmonary vein and posterior wall isolation: 27 were cardioverted, mapped, and ablated in sinus rhythm with atrial pacing, and 26 were mapped and ablated in AF with ventricular pacing. Ablation data was extracted from the mapping system and analyzed using custom MATLAB software to determine high-frequency (60Hz) catheter excursion as a novel metric for catheter spatial stability. RESULTS: There was no difference in catheter stability as assessed by maximal catheter excursion, mean catheter excursion, or contact force variability between the atrial-paced and ventricular-paced patients. Ventricular-paced patients had significantly greater mean contact force as compared to atrial-paced patients. Contact-force variability demonstrated poor correlation with catheter excursion. One year arrhythmia-free survival was similar between the atrial paced and ventricular paced patients. CONCLUSIONS: For patients with persistent AF, ablation in AF with ventricular pacing results in similar catheter stability and arrhythmia recurrence as compared to cardioversion and ablation in sinus rhythm with atrial pacing. Given the improved fidelity of mapping in AF, mapping and ablating during AF with ventricular pacing may be preferred.

Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes.

Converting lead compounds into drug candidates is a crucial step in drug development, requiring early assessment of potency, selectivity, and off-target effects. We have utilized activity-based chemical proteomics to determine the potency and selectivity of deubiquitylating enzyme (DUB) inhibitors in cell culture models. Importantly, we characterized the small molecule PR-619 as a broad-range DUB inhibitor, and P22077 as a USP7 inhibitor with potential for further development as a chemotherapeutic agent in cancer therapy. A striking accumulation of polyubiquitylated proteins was observed after both selective and general inhibition of cellular DUB activity without direct impairment of proteasomal proteolysis. The repertoire of ubiquitylated substrates was analyzed by tandem mass spectrometry, identifying distinct subsets for general or specific inhibition of DUBs. This enabled identification of previously unknown functional links between USP7 and enzymes involved in DNA repair.