Targeting Wavefront Discontinuity Lines for Scar-Related Ventricular Tachycardia Ablation: A Novel Functional Substrate Ablation Approach.

BACKGROUND: The boundaries of critical isthmuses for re-entrant ventricular tachycardia (VT) are formed by wave-front discontinuities (fixed lines of block, slow propagation, and rotational propagation) seen during baseline rhythm. It is unknown whether wavefront discontinuities can be automatically identified and targeted for ablation using electroanatomic mapping systems. OBJECTIVES: The purpose of this study was to assess the electrophysiologic characteristics of automatically projected wavefront discontinuity lines (WADLs) and outcomes of an ablation strategy targeting WADLs in a mixed cohort of VT patients. METHODS: Late activation substrate maps were analyzed from 1 or more baseline rhythm wavefronts. WADLs were identified using the Carto Extended Early Meets Late module. Number, total length, and distance to critical VT sites were measured. VT recurrence and VT-free survival were followed. RESULTS: In total, 49 patients underwent 52 ablations with 71 unique substrate maps analyzed (18.8% epicardial; 62.0% right ventricular paced, 28.2% sinus rhythm, 9.9% left ventricular paced). A total of 28 VT critical sites were identified in 24 patients. WADLs were present in 49 of 71 (69.0%) maps. WADLs were present regardless of cardiomyopathy etiology, mapping wavefront, or surface. At a WADL threshold of 30%, 73.9% of critical VT sites were in close proximity (≤15 mm) to a WADL. VT-free survival was 62% at 1 year, with a competing risk model estimating a 1-year risk of VT recurrence of 23%. CONCLUSIONS: WADLs can be automatically projected in a majority of patients in a mixed cohort of cardiomyopathy etiology, mapped wavefronts, and myocardial surfaces mapped. Targeting WADLs results in low rate of VT recurrence at 1 year.

Correlation Between Functional Substrate Mapping and Cardiac Computed Tomography-Derived Wall Thinning for Ventricular Tachycardia Ablation.

BACKGROUND: Functional substrate mapping during baseline rhythm can identify arrhythmogenic tissue during ventricular tachycardia (VT) ablation. Wall thinning and wall thickness channels (WTCs) derived from computed tomography angiography have been shown to correlate with low voltage and VT isthmuses. The correlation between functional substrate mapping, wall thinning, and WTCs in patients with infarct- or non-infarct-related cardiomyopathies (ICM and NICM, respectively) has not been previously described. OBJECTIVES: The purpose of this study was to correlate cardiac CTA-derived myocardial wall thinning with functional VT substrate mapping using isochronal late activation mapping. METHODS: In 34 patients with ICM or NICM undergoing VT ablation who had a preprocedure computed tomography angiography, myocardial wall thinning was segmented in layers of 1 to 5 mm. Areas of wall thinning and WTCs were then spatially correlated with deceleration zones (DZs) from registered left ventricular endocardial isochronal late activation maps. RESULTS: In 21 ICM patients and 13 NICM patients, ICM patients had greater surfaces areas of wall thinning (P < 0.001). In ICM patients, 94.1% of primary DZs were located on areas of wall thinning, compared to 20% of DZs in NICM patients overall but 50% if there was any wall thinning present. Fifty-nine percent of DZs in ICM patients and 56% of DZs in NICM patients were located near WTCs. The positive predictive value for WTC in localizing DZs was 22.5% and 37.8% in ICM and NICM patients, respectively. CONCLUSIONS: Wall thinning is highly sensitive for functional substrate in ICM patients. WTCs had modest sensitivity for functional substrate but low positive predictive value for identifying DZs in ICM and NICM patients. These findings suggest that wall thinning may facilitate more efficient mapping in ICM patients, but WTCs are insufficient to localize wavefront discontinuities.

Procedural Adaptations to Avoid Haemodynamic Instability During Catheter Ablation of Scar-related Ventricular Tachycardia.

Classically, catheter ablation for scar-related ventricular tachycardia (VT) relied upon activation and entrainment mapping of induced VT. Advances in post-MI therapies have led to VTs that are faster and haemodynamically less stable, because of more heterogeneous myocardial fibrosis patterns. The PAINESD score is one means of identifying patients at highest risk for haemodynamic decompensation during attempted VT induction, who may, therefore, benefit from alternative ablation strategies. One strategy is to use temporary mechanical circulatory support, although this warrants formal assessment of cost-effectiveness. A second strategy is to minimise or avoid VT induction altogether by employing a family of 'substrate'-based approaches aimed at identifying VT isthmuses during sinus or paced rhythm. Substrate mapping techniques are diverse, and focus on the timing, morphology and amplitude of local ventricular electrograms - sometimes aided by advanced non-invasive cardiac imaging modalities. In this review, the evolution of VT ablation over time is discussed, with an emphasis on procedural adaptations to the challenge of haemodynamic instability.

Epidemiology of heart failure hospitalization in patients with stable atherothrombotic disease: Insights from the TRA 2°P-TIMI 50 trial.

BACKGROUND: Heart failure (HF) is a growing public health problem and ischemic heart disease is an important risk factor. Understanding the epidemiology of HF in patients with atherosclerosis may help identify subgroups at greater risk who have the potential to derive greater benefit from preventive strategies. METHODS AND RESULTS: The TRA 2°P-TIMI 50 trial randomized 26,449 patients with stable atherosclerosis to the antiplatelet agent vorapaxar versus placebo. Hospitalization for HF (HHF) endpoints were adjudicated from serious adverse events by blinded structured review using established definitions. HHF incidence was estimated using Kaplan-Meier analysis. Independent predictors of HHF risk were identified using multivariable logistic regression. The effect of vorapaxar on HHF risk was explored using Cox regression. The estimated incidence of HHF at 3 years was 1.6%. Independent predictors of HHF included prior HF (adjusted odds ratio [adj-OR]: 8.31; 95% confidence interval [CI]: 6.56-10.54), age (adj-OR [per 10 years]: 1.67; 95% CI: 1.47-1.89), type 2 diabetes mellitus (T2DM; adj-OR: 2.55; 95% CI: 2.01-3.24), polyvascular disease (two-territory disease, adj-OR: 1.89; 95% CI: 1.46-2.44; three-territory disease, adj-OR: 2.68; 95% CI: 1.94-3.70), chronic kidney disease (CKD; adj-OR: 1.65; 95% CI: 1.30-2.11), body mass index (BMI; adj-OR [per 5 kg/m2 ]: 1.15; 95% CI: 1.03-1.27), prior myocardial infarction (MI) (adj-OR: 1.35; 95% CI: 1.03-1.78), and hypertension (adj-OR: 1.44; 95% CI: 1.02-2.04). Patients who experienced HHF during follow-up had higher rates of subsequent rehospitalization and death. Vorapaxar did not modify the risk of HHF. CONCLUSIONS: In patients with stable atherosclerosis, prior HF, age, T2DM, polyvascular disease, CKD, BMI, prior MI, and hypertension are important predictors of HHF risk.

Feasibility and safety of same-day discharge and shortened bedrest after atrial fibrillation ablation.

BACKGROUND: While initial studies suggest that same-day discharge or shortened bedrest may be feasible for some patients following atrial fibrillation (AF) ablation, the risks and benefits of this approach remain unclear for patients undergoing hemostasis with figure-of-eight (FO8) suture technique. METHODS: We prospectively evaluated access site bleeding, length of hospitalization, urinary catheterization, and other clinical outcomes in patients undergoing AF ablation with 3 hours of bedrest between April and May 2021, and compared them to a control group that had undergone AF ablation with 6 hours of bedrest from April to July 2019. FO8 sutures were used for hemostasis in all patients. Independent risk factors for bleeding and urinary catheterization were determined using multiple logistic regression. RESULTS: Same-day discharge was achieved in 74% of patients in the 3-hour bedrest group compared to 7% of patients in the 6-hour bedrest group (p < 0.001). There were no differences between 3-hour and 6-hour bedrest groups in the rates of serious adverse events (2% vs. 1%, p = 0.45) or rehospitalizations or ED visits (1% vs. 3%, p = 0.45) within 30 days of ablation. The 3-hour bedrest group showed a non-significant trend toward more access site bleeding (15% vs. 8%, p = 0.10), but had a significant reduction in urinary catheterization (27% vs. 64%, p < 0.001) and opioid analgesia use (20% vs. 33%, p = 0.04). CONCLUSIONS: Same-day discharge after 3 hours of bedrest is safe and feasible following AF ablation and is not associated with higher rates of complications or rehospitalizations at 30 days. Reduced bedrest resulted in decreased opioid analgesia and urinary catheterization.

Cardiovascular Biomarkers and Heart Failure Risk in Stable Patients With Atherothrombotic Disease: A Nested Biomarker Study From TRA 2°P-TIMI 50.

Background Patients with stable atherothrombotic disease vary in their risk of developing heart failure (HF). Circulating cardiovascular biomarkers may improve HF risk assessment and identify patients who may benefit from emerging HF preventive therapies. Methods and Results We measured high-sensitivity cardiac troponin I and BNP (B-type natriuretic peptide) in 15 833 patients with prior myocardial infarction, ischemic stroke, or peripheral artery disease from the TRA 2°P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50) trial, excluding patients with recent myocardial infarction (<30 days). Biomarkers were categorized using a priori cut points. Hospitalization for HF (HHF) end points were adjudicated with blinded structured review of serious adverse events. Associations between biomarkers and HHF outcomes were adjusted for sex and independent clinical risk predictors of HHF in our cohort (age ≥75, prior HF, type 2 diabetes mellitus, polyvascular disease, body mass index, anemia, chronic kidney disease, hypertension). Baseline high-sensitivity cardiac troponin I and BNP each identified a significant graded risk of HHF independent of clinical risk predictors, including in the subgroups of patients with and without type 2 diabetes mellitus and with and without prior HF. Patients with both high-sensitivity cardiac troponin I ≥5 ng/L and BNP ≥100 pg/mL had the highest HHF event rates. When added to a multivariable Cox regression model with clinical risk predictors (C-index 0.88; 95% CI, 0.85-0.90), BNP (C -index 0.92; 95% CI, 0.90-0.93), and high-sensitivity cardiac troponin I (C-index 0.90; 95% CI, 0.88-0.92) each significantly improved the prognostic performance of the model (both PLRT<0.001). Conclusions Biomarkers of myocardial injury and hemodynamic stress are independent predictors of HHF risk in patients with stable atherothrombotic disease, with and without prior HF and/or type 2 diabetes mellitus. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00526474.

Treatment of Overlap Syndromes in Autoimmune Liver Disease: A Systematic Review and Meta-Analysis.

The treatment of overlap syndromes is guided by small observational studies whose data have never been synthesized in a rigorous, quantitative manner. We conducted a systematic review and meta-analysis to evaluate the efficacy of available treatments for these rare and morbid conditions. We searched the literature for studies comparing ≥2 therapies for autoimmune hepatitis (AIH)-primary biliary cholangitis (PBC), AIH-primary sclerosing cholangitis (PSC), PBC-PSC, AIH-PBC-PSC, autoimmune cholangitis (AIC), or autoimmune sclerosing cholangitis (ASC) with respect to various clinical outcomes, including biochemical improvement and transplant-free survival. A total of 28 studies met the inclusion criteria for AIH-PBC, AIH-PSC, AIC, and ASC. AIH-PBC patients tended to experience more biochemical improvement with ursodeoxycholic acid (UDCA) + [corticosteroids and/or antimetabolites], i.e., "combination therapy", than with corticosteroids ± azathioprine (RR = 4.00, 95% CI 0.93-17.18). AIH-PBC patients had higher transplant-free survival with combination therapy than with UDCA, but only when studies with follow-up periods ≤90 months were excluded (RR = 6.50, 95% CI 1.47-28.83). Combination therapy may therefore be superior to both UDCA and corticosteroids ± azathioprine for the treatment of AIH-PBC, but additional studies are needed to show this definitively and to elucidate optimal treatments for other overlap syndromes.

Vision-related quality of life in children with glaucoma.

Although reporting vision-related quality of life (VRQoL) outcomes has become increasingly common in adult glaucoma studies, little is known about the influence of disease severity, medication burden, and surgical experience on the quality of life of children with glaucoma. We tested the feasibility of administering a self-reported VRQoL instrument and describe the VRQoL in children with glaucoma. Better VRQoL was correlated with higher visual acuity in the better-seeing eye but not the number of surgeries the child had undergone or the number of prescribed eyedrops.

Caenorhabditis-in-drop array for monitoring C. elegans quiescent behavior.

STUDY OBJECTIVES: To develop a method, called Caenorhabditis-in-Drop (CiD), encapsulating single worms in aqueous drops, for parallel analysis of behavioral quiescence in C. elegans nematodes. DESIGN: We designed, constructed, and tested a device that houses an array of aqueous droplets laden with individual worms. The droplets are separated and covered by immiscible, biocompatible oil. We modeled gas exchange across the aqueous/oil interface and tested the viability of the encapsulated animals. We studied the behavior of wild-type animals; of animals with a loss of function mutation in the cGMP-dependent protein kinase gene egl-4; of animals with a loss of function mutation in the gene kin-2, which encodes a cAMP-dependent protein kinase A regulatory subunit; of animals with a gain-of-function mutation in the gene acy-1, which encodes an adenylate cyclase; and of animals that express high levels of the EGF protein encoded by lin-3. MEASUREMENTS AND RESULTS: We used CiD to simultaneously monitor the behavior of 24 worms, a nearly 5-fold improvement over the prior best methodology. In support of our gas exchange models, we found that worms remain viable on the chip for 4 days, past the 12-h period needed for observation, but show reduced longevity to that measured on an agar surface. Measurements of duration of lethargus quiescence and total leth-argus quiescence showed reduced amounts as well as reduced variability relative to prior methods. There was reduced lethargus quiescence in animals that were mutant for kin-2 and for acy-1, supporting a wake-promoting effect of PKA in C. elegans, but no change in lethargus quiescence in egl-4 mutants. There was increased quiescence in animals that expressed kin-2 in the nervous system or over-expressed EGF. CONCLUSIONS: CiD is useful for the analysis of behavioral quiescence during lethargus as well as during the adult stage C. elegans. The method is expandable to parallel simultaneous monitoring of hundreds of animals and for other studies of long-term behavior. Using this method, we were successful in measuring, for the first time, quiescence in kin-2(ce179) and in acy-2(ce2) mutants, which are hyperactive. Our observations also highlight the impact of environmental conditions on quiescent behavior and show that longevity is reduced in CiD in comparison to agar surfaces.