Pushing the Isotopic Envelope: When carrier channels pollute their neighbors' signals.

Individual cells are the foundational unit of biology, and understanding their functions and interactions is critical to advancing our understanding of health and disease. Single cell proteomics has seen intense interest from mass spectrometrists, with a goal of quantifying the proteome of single cells by adapting current techniques used in bulk samples. To date, most method optimizations research has worked towards increasing the proteome coverage of single cells. One prominent technique multiplexes many individual cells into a single data acquisition event using isobaric labels. Accompanying the single cells, one label is typically used for a mixed set of many cells, called a carrier or boost channel. Although this improves peptide identification rates, several groups have examined the impact on quantitative accuracy as more cells are included in the carrier channel, e.g. 100x or 500x. This manuscript explores how impurities in the multiplexing reagent can lead to inaccurate quantification observed as a measurable signal in the wrong channel. We discover that the severe abundance differential between carrier and single cell, combined with the reagent impurities, can overshadow several channels typically used for single cells. For carrier amounts 100x and above, this contamination can be as abundant as true signal from a single cell. Therefore, we suggest limiting the carrier channel to a minimal amount and balance the goals of identification and quantification.

Risk of malignant ventricular arrhythmias in patients with mildly to moderately reduced ejection fraction after permanent pacemaker implantation.

BACKGROUND: Many patients with mildly to moderately reduced left ventricular ejection fraction (LVEF) who require permanent pacemaker (PPM) implantation do not have a concurrent indication for implantable cardioverter-defibrillator (ICD) therapy. However, the risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in this population is unknown. OBJECTIVE: The aim of this study was to describe the risk of VT/VF after PPM implantation in patients with mildly to moderately reduced LVEF. METHODS: Retrospective analysis was performed of 243 patients with LVEF between 35% and 49% who underwent PPM placement and did not meet indications for an ICD. The primary end point was occurrence of sustained VT/VF. Competing risks regression was performed to calculate subhazard ratios for the primary end point. RESULTS: Median follow-up was 27 months; 73% of patients were male, average age was 79 ± 10 years, average LVEF was 42% ± 4%, and 70% were New York Heart Association class II or above. Most PPMs were implanted for sick sinus syndrome (34%) or atrioventricular block (50%). Of 243 total patients, 11 (4.5%) met the primary end point of VT/VF. Multivessel coronary artery disease (CAD) was associated with significantly higher rates of VT/VF, with a subhazard ratio of 5.4 (95% CI, 1.5-20.1; P = .01). Of patients with multivessel CAD, 8 of 82 (9.8%) patients met the primary end point for an annualized risk of 4.3% per year. CONCLUSION: Patients with mildly to moderately reduced LVEF and multivessel CAD undergoing PPM implantation are at increased risk for the development of malignant ventricular arrhythmias. Patients in this population may benefit from additional risk stratification for VT/VF and consideration for upfront ICD implantation.

Conduction velocity is reduced in the posterior wall of hypertrophic cardiomyopathy patients with normal bipolar voltage undergoing ablation for paroxysmal atrial fibrillation.

OBJECTIVES: We investigated characteristics of left atrial conduction in patients with HCM, paroxysmal AF and normal bipolar voltage. BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) exhibit abnormal cardiac tissue arrangement. The incidence of atrial fibrillation (AF) is increased fourfold in patients with HCM and confers a fourfold increased risk of death. Catheter ablation is less effective in HCM, with twofold increased risk of AF recurrence. The mechanisms of AF perpetuation in HCM are poorly understood. METHODS: We analyzed 20 patients with HCM and 20 controls presenting for radiofrequency ablation of paroxysmal AF normal left atrial voltage(> 0.5 mV). Intracardiac electrograms were extracted from the CARTO mapping system and analyzed using Matlab/Python code interfacing with Core OpenEP software. Conduction velocity maps were calculated using local activation time gradients. RESULTS: There were no differences in baseline demographics, atrial size, or valvular disease between HCM and control patients. Patients with HCM had significantly reduced atrial conduction velocity compared to controls (0.44 ± 0.17 vs 0.56 ± 0.10 m/s, p = 0.01), despite no significant differences in bipolar voltage amplitude (1.23 ± 0.38 vs 1.20 ± 0.41 mV, p = 0.76). There was a statistically significant reduction in conduction velocity in the posterior left atrium in HCM patients relative to controls (0.43 ± 0.18 vs 0.58 ± 0.10 m/s, p = 0.003), but not in the anterior left atrium (0.46 ± 0.17 vs 0.55 ± 0.10 m/s, p = 0.05). There was a significant association between conduction velocity and interventricular septal thickness (slope = -0.013, R2 = 0.13, p = 0.03). CONCLUSIONS: Atrial conduction velocity is significantly reduced in patients with HCM and paroxysmal AF, possibly contributing to arrhythmia persistence after catheter ablation.

Outcomes of posterior wall isolation with pulmonary vein isolation for paroxysmal atrial fibrillation.

INTRODUCTION: Prior studies have shown that addition of posterior wall isolation (PWI) may reduce atrial fibrillation recurrence in patients with persistent atrial fibrillation. No data on PWI in paroxysmal AF (pAF) patients with normal left atrial voltage is available, to date. OBJECTIVE: This study sought to evaluate the efficacy of PWI in addition to pulmonary vein isolation (PVI) in patients presenting with pAF and normal left atrial voltage. METHODS: Consecutive patient registry analysis was performed on all patients with pAF and normal left atrial voltage undergoing initial radiofrequency ablation from November 1, 2018 to November 15, 2019. Primary endpoint was recurrence of atrial arrhythmia including AF, atrial tachycardia (AT), or atrial flutter (AFL). RESULTS: A total of 321 patients were studied, 214 in the PVI group and 107 in the PWI + PVI group. Recurrence of any atrial arrhythmia occurred in 18.2% of patients in the PVI group and 16.8% in the PVI + PWI cohort (p = 0.58). At 1 year, recurrence was 14.0% in the PVI group and 15.0% in the PWI + PVI group (p = 0.96). There was a lower AT/AFL recurrence in the PVI + PWI group, not reaching significance (3.7% in the PWI + PVI group vs. 7.9% in PVI group, p = 0.31). Need for carina lesions predicted recurrence in the PVI-only group. CONCLUSIONS: Addition of PWI to PVI in pAF patients undergoing their first ablation did not reduce the frequency of atrial arrhythmia recurrence. This warrants further study in a prospective trial.

QT interval dynamics and triggers for QT prolongation immediately following cardiac arrest.

BACKGROUND: The prolongation in QT interval typically observed following cardiac arrest is considered to be multifactorial and induced by external triggers such as hypothermia therapy and exposure to antiarrhythmic medications. OBJECTIVE: To evaluate the corrected QT interval (QTc) dynamics in the first 10 days following cardiac arrest with respect to the etiology of arrest, hypothermia and QT prolonging medications. METHODS: We enrolled 104 adult survivors of cardiac arrest, where daily ECG was available for at least 3 days. We followed their QT and QRS intervals for the first 10 days of hospitalization. We used both Bazett and Fridericia formulas to correct for heart rate. For patients with QRS < 120 we analyzed the QTc interval (n = 90) and for patients with QRS > 120 ms we analyzed the JTc (n = 104) vs. including only the narrow QRS samples (n = 89). We stratified patients by 3 groups: (1) presence of ischemic heart disease (IHD) (2) treatment with hypothermia protocol, and (3) treatment with QTc prolonging medications. Additionally, genetic information obtained during hospitalization was analyzed. RESULTS: QTc and JTc intervals were significantly prolonged in the first 6 days. Maximal QTc/JTc prolongation was observed in day 2 (QTcB = 497 ± 55). There were no differences in daily QTc/JTc and QRS intervals in the first 2 days post arrest between patients with or without hypothermia induction but such difference was found with QT prolonging medications. All subgroups demonstrated significantly prolonged QTc/JTc interval regardless of the presence of IHD, hypothermia protocol or QTc prolonging medication exposure. Our results were consistent for both Bazetts' and Frediricia correction and for any QRS duration. Prolongation of the JTcB beyond 382 ms after day 3 predicted sustained QTc/JTc prolongation beyond day 6 with an ROC of 0.78. CONCLUSIONS: QTc/JTc interval is significantly and independently prolonged post SCA, regardless of known QT prolonging triggers. Normalization of the QTc post cardiac arrest should be expected only after day 6 of hospitalization. Assessment of the QTc for adjudication of the etiology of arrest or for monitoring the effect of QT prolonging medications may be unreliable.

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.