Use of Ripple mapping to enhance localization and ablation of outflow tract premature ventricular contractions.

INTRODUCTION: Accurate localization of septal outflow tract premature ventricular contractions (PVCs) is often difficult due to frequent mid-myocardial or protected origin. Compared with traditional activation mapping, CARTO Ripple mapping provides visualization of all captured electrogram data without assignment of a specific local activation time and thus may enhance PVC localization. METHODS: Electroanatomic maps for consecutive catheter ablation procedures for septal outflow tract PVCs (July 2018-December 2020) were analyzed. For each PVC, we identified the earliest local activation point (EA), defined by the point of maximal -dV/dt in a simultaneously recorded unipolar electrogram, and the earliest Ripple signal (ERS), defined as the earliest point at which three grouped simultaneous Ripple bars appeared in late diastole. Immediate success was defined as full suppression of the clinical PVC. RESULTS: Fifty-seven unique PVCs in 55 procedures were included. When ERS and EA were in the same chamber (RV, LV, or CS), the odds ratio for the successful procedure was 13.1 (95% confidence interval [CI] 2.2-79.9, p = .005). Discordance between sites was associated with a higher likelihood of needing multi-site ablation (odds ratio [OR] 7.9 [1.4-4.6; p = .020]). Median EA-ERS distance in successful versus unsuccessful cases was 4.6 mm (interquartile range 2.9-8.5) versus 12.5 mm (7.8-18.5); (p = .020). CONCLUSION: Greater EA-ERS concordance was associated with higher odds of single-site PVC suppression and successful septal outflow tract PVC ablation. Visualization of complex signals via automated Ripple mapping may offer rapid localization information complementary to local activation mapping for PVCs of mid-myocardial origin.

Acute echocardiographic and hemodynamic response to his-bundle pacing in patients with first-degree atrioventricular block.

BACKGROUND: Atrial pacing and right ventricular (RV) pacing are both associated with adverse outcomes among patients with first-degree atrioventricular block (1°AVB). His-bundle pacing (HBP) provides physiological activation of the ventricle and may be able to improve both atrioventricular (AV) and inter-ventricular synchrony in 1°AVB patients. This study evaluates the acute echocardiographic and hemodynamic effects of atrial, atrial-His-bundle sequential (AH), and atrial-ventricular (AV) sequential pacing in 1°AVB patients. METHODS: Patients with 1°AVB undergoing atrial fibrillation ablation were included. Following left atrial (LA) catheterization, patients underwent atrial, AH- and AV-sequential pacing. LA/left ventricular (LV) pressure and echocardiographic measurements during the pacing protocols were compared. RESULTS: Thirteen patients with 1°AVB (mean PR 221 ± 26 ms) were included. The PR interval was prolonged with atrial pacing compared to baseline (275 ± 73 ms, p = .005). LV ejection fraction (LVEF) was highest during atrial pacing (62 ± 11%), intermediate with AH-sequential pacing (59 ± 7%), and lowest with AV-sequential pacing (57 ± 12%) though these differences were not statistically significant. No significant differences were found in LA or LV mean pressures or LV dP/dT. LA and LV volumes, isovolumetric times, electromechanical delays, and global longitudinal strains were similar across pacing protocols. CONCLUSION: Despite pronounced PR prolongation, the acute effects of atrial pacing were not significantly different than AH- or AV-sequential pacing. Normalizing atrioventricular and/or inter-ventricular dyssynchrony did not result in acute improvements in cardiac output or loading conditions.

Electrical storm in patients with left ventricular assist devices: Risk factors, incidence, and impact on survival.

BACKGROUND: Ventricular arrhythmias (VAs) and electrical storm (ES) are recognized complications following left ventricular assist device (LVAD) implantation; however, their association with long term-outcomes remains poorly understood. OBJECTIVE: The purpose of this study was to describe the clinical impact of ES in a population of patients undergoing LVAD implantation at a quaternary care center in the United States. METHODS: This was an observational retrospective study of patients undergoing LVAD implantation from 2009 to 2020 at Duke University Hospital. The incidence of ES (≥3 sustained VA episodes over a 24-hour period without an identifiable reversible cause) was determined from patient records. Risk factors for ES were identified using multivariable Cox proportional hazards modeling. RESULTS: Among 730 patients undergoing LVAD implant, 78 (10.7%) developed ES at a median of 269 (interquartile range [IQR] 7-766) days following surgery. Twenty-seven patients (34.6%) developed ES within 30 days, while 51 (65.4%) presented with ES at a median 639 (IQR 281-1017) days after implant. Following ES, 41% of patients died within 1 year. Patients who developed ES were more likely to have a history of VAs, ventricular tachycardia ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support around the time of LVAD implant than patients without ES. CONCLUSION: ES occurs in 1 in 10 patients after LVAD and is associated with higher mortality. Risk factors for ES include a history of VAs, VT ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support. Optimal management of ES surrounding LVAD implant, including escalation of medical therapy, catheter ablation, or adjunctive sympatholytic therapies, remains uncertain.

Stellate Ganglion Blockade: an Intervention for the Management of Ventricular Arrhythmias.

PURPOSE OF REVIEW: To highlight the indications, procedural considerations, and data supporting the use of stellate ganglion blockade (SGB) for management of refractory ventricular arrhythmias. RECENT FINDINGS: In patients with refractory ventricular arrhythmias, unilateral or bilateral SGB can reduce arrhythmia burden and defibrillation events for 24-72 h, allowing time for use of other therapies like catheter ablation, surgical sympathectomy, or heart transplantation. The efficacy of SGB appears to be consistent despite the type (monomorphic vs polymorphic) or etiology (ischemic vs non-ischemic cardiomyopathy) of the ventricular arrhythmia. Ultrasound-guided SGB is safe with low risk for complications, even when performed on anticoagulation. SGB is effective and safe and could be considered for patients with refractory ventricular arrhythmias.

Subcutaneous implantable cardioverter-defibrillator troubleshooting in patients with a left ventricular assist device: A case series and systematic review.

BACKGROUND: There are limited data on the performance of the subcutaneous implantable cardioverter-defibrillator (S-ICD) in patients with a left ventricular assist device (LVAD). OBJECTIVE: The purpose of this study was to describe the clinical course and outcomes of patients with both an S-ICD and an LVAD at our institution and via a systematic review of published studies. METHODS: We performed a retrospective cohort study of all patients who underwent LVAD implantation from 2009 to 2019 at Duke University Hospital. We also performed a systematic review of studies involving patients with an S-ICD and LVAD using the PubMed/Embase databases. RESULTS: Of 588 patients undergoing LVAD implantation with a preexisting implantable cardioverter-defibrillator, 4 had an S-ICD in situ after LVAD implantation. All 4 patients developed electromagnetic interference (EMI) in the primary/secondary vectors after LVAD implantation, resulting in inappropriate implantable cardioverter-defibrillator shocks in 2 patients. Sensing in the alternate vector was adequate immediately postoperatively in 1 patient. Postoperative undersensing was present in the alternate vector in 3 patients but improved at first outpatient follow-up in 2 patients, allowing tachy therapies to be reenabled. Eight studies involving 27 patients were identified in the systematic review. EMI was common and frequently absent in the alternate vector (6 of 7 patients). CONCLUSION: Undersensing and EMI are common after LVAD implantation in patients with an S-ICD in situ, particularly in the primary and secondary sensing vectors. Undersensing in the alternate vector may improve during follow-up, obviating the need for device revision or extraction.

Effectiveness of catheter ablation of atrial fibrillation according to heart failure etiology.

BACKGROUND: Catheter ablation is an important rhythm control therapy in patients with atrial fibrillation (AF) with concomitant heart failure (HF). The objective of this study was to assess the comparative efficacy of AF ablation patients with ischemic vs nonischemic heart failure. METHODS: We conducted a retrospective, observational cohort study of patients with HF who underwent AF ablation. Outcomes were compared based on HF etiology and included in-hospital events, symptoms (Mayo AF Symptom Inventory [MAFSI]), and functional status (New York Heart Association class) and freedom from atrial arrhythmias at 12 months. RESULTS: Among 242 patients (n = 70 [29%] ischemic, n = 172 [71%] nonischemic), patients with nonischemic cardiomyopathy were younger (mean age 64 ± 11.5 vs 69 ± 9.1, P = .002), more often female (36% vs 17%, P = .004), and had higher mean left-ventricular ejection fraction (47% vs 42%, P = .0007). There were no significant differences in periprocedural characteristics, including mean procedure time (243 ± 74.2 vs 259 ± 81.8 minutes, P = .1) and nonleft atrial ablation (17% vs 20%, P = .6). All-cause adverse events were similar in each group (15% vs 17%, P = .7). NYHA and MAFSI scores improved significantly at follow-up and did not differ according to HF etiology (P = .5; P = .10-1.00 after Bonferroni correction). There were no significant differences in freedom from recurrent atrial arrhythmia at 12-months between ischemic (74%) and nonischemic patients (78%): adjusted RR 0.63, 95% confidence interval 0.33-1.19. CONCLUSIONS: Catheter ablation in patients with AF and concomitant heart failure leads to significant improvements in functional and symptom status without significant differences between patients with ischemic vs nonischemic HF etiology.

Catheter ablation of atrial fibrillation in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). Few studies have compared clinical outcomes after catheter ablation between patients with and those without DM. OBJECTIVE: The purpose of this study was to compare AF ablation outcomes in patients with and those without DM. METHODS: We performed a retrospective analysis of 351 consecutive patients who underwent first-time AF ablation. Clinical outcomes included freedom from recurrent atrial arrhythmia, symptom burden (Mayo AF Symptom Inventory score), cardiovascular and all-cause hospitalizations, and periprocedural complications. RESULTS: Patients with DM (n = 65) were older, had a higher body mass index, more persistent AF, more hypertension, and larger left atrial diameter (P <.05 for all). Median (Q1, Q3) total radiofrequency duration [64.0 (43.6, 81.4) minutes vs 54.3 (39.2, 76.4) minutes; P = .132] and periprocedural complications (P = .868) did not differ between patients with and those without DM. After a median follow-up of 29.5 months, arrhythmia recurrence was significantly higher in the DM group compared to the no-DM group after adjustment for baseline differences (adjusted hazard ratio [HR] 2.24; 95% confidence [CI] 1.42-3.55; P = .001). There was a nonsignificant trend toward higher AF recurrence with worse glycemic levels (HR 1.29; 95% CI 0.99-1.69; P = .064). CONCLUSION: Although safety outcomes associated with AF ablation were similar between patients with and those without DM, arrhythmia-free survival was significantly lower among patients with DM. Poor glycemic control seems to an important risk factor for AF recurrence.

Safety and efficacy outcomes of left atrial posterior wall isolation compared to pulmonary vein isolation and pulmonary vein isolation with linear ablation for the treatment of persistent atrial fibrillation.

BACKGROUND: Pulmonary wall isolation (PWI) is increasingly used as an adjunctive lesion set to compliment pulmonary vein isolation (PVI), especially in patients with persistent atrial fibrillation (AF). The objective was to compare outcomes of catheter ablation in patients with persistent AF undergoing PVI with and without adjunctive PWI. METHODS: We performed a retrospective study of 558 patients who underwent de novo and repeat ablation for persistent AF. Subjects were matched using propensity score adjustments. Outcomes were freedom from recurrent atrial arrhythmia and adverse events. RESULTS: Among 558 patients who underwent ablation for persistent AF, 78 (14%) underwent PVI + PWI, 255 (46%) underwent PVI, and 225 (40%) underwent PVI + linear ablation. Stratified logistic regression analysis with propensity matching revealed higher odds of recurrent arrhythmia with PVI + PWI when compared to PVI (odds ratio [OR] 2.25, 95% CI 1.08-4.69, P = .030) and when compared to PVI + linear (OR 2.31, 95% CI 1.01-5.28, P = .048). Within the PVI + PWI group, 57.7% of subjects were in normal sinus rhythm at 6 months compared to 73.9% and 72.2% in PVI and PVI + linear groups, respectively. Adverse events were rare, with 19 events total identified across all groups. CONCLUSIONS: PVI + PWI does not appear to be as effective as PVI or PVI + linear ablation in reducing the recurrence of arrhythmia within 6 months of the index procedure in patients with persistent AF. A prospective, randomized controlled trial comparing these ablation techniques is needed to clarify the role of extensive substrate modification for treatment of persistent AF. CONDENSED ABSTRACT: PWI is increasingly used as an adjunctive lesion set to compliment PVI in patients with persistent AF. We performed a retrospective study of 558 patients who underwent de novo and repeat ablation for persistent AF to compare the outcomes between PVI with and without adjunctive PWI. We found an increased incidence in recurrence of AF and other atrial arrhythmias at 6 months in the PVI + PWI cohort compared to PVI with or without additional linear ablation. A prospective, randomized controlled trial comparing these ablation techniques is needed to clarify the role of extensive substrate modification for treatment of persistent AF.

Predicting atrial fibrillation recurrence after ablation in patients with heart failure: Validity of the APPLE and CAAP-AF risk scoring systems.

BACKGROUND: Compared with medical therapy, catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) improves cardiovascular outcomes. Risk scores (CAAP-AF and APPLE) have been developed to predict the likelihood of AF recurrence after ablation, have not been validated specifically in patients with AF and HF. METHODS: We analyzed baseline characteristics, risk scores, and rates of AF recurrence 12 months postablation in a cohort of 230 consecutive patients with AF and HF undergoing PVI in the Duke Center for Atrial Fibrillation registry from 2009-2013. RESULTS: During a follow-up period of 12 months, 76 of 230 (33%) patients with HF experienced recurrent AF after ablation. The median APPLE and CAAP-AF scores were 1.5 ([Q1, Q3]: [1.0, 2.0]) and 4.0 ([Q1, Q3]: [3.0, 5.0]), respectively and were not different from those patients with and without recurrent AF. Freedom from AF was not different according to APPLE and CAAP-AF scores. Discrimination for recurrent AF with the CAAP-AF score was modest with a C-statistic of 0.60 (95% CI 0.52-0.67). Discrimination with the APPLE score was similarly modest, with a C-statistic of 0.54 (95% CI: 0.47-0.62). CONCLUSIONS: Validated predictive risk scores for recurrent AF after catheter ablation exhibit limited predictive ability in cohorts of AF and HF. Additional tools are needed to facilitate risk stratification and patient selection for AF ablation in patients with concomitant HF.

The Role of the Human Microbiome in Chemical Toxicity.

There is overwhelming evidence that the microbiome must be considered when evaluating the toxicity of chemicals. Disruption of the normal microbial flora is a known effect of toxic exposure, and these disruptions may lead to human health effects. In addition, the biotransformation of numerous compounds has been shown to be dependent on microbial enzymes, with the potential for different host health outcomes resulting from variations in the microbiome. Evidence suggests that such metabolism of environmental chemicals by enzymes from the host's microbiota can affect the toxicity of that chemical to the host. Chemical-microbial interactions can be categorized into two classes: Microbiome Modulation of Toxicity (MMT) and Toxicant Modulation of the Microbiome (TMM). MMT refers to transformation of a chemical by microbial enzymes or metabolites to modify the chemical in a way that makes it more or less toxic. TMM is a change in the microbiota that results from a chemical exposure. These changes span a large magnitude of effects and may vary from microbial gene regulation, to inhibition of a specific enzyme, to the death of the microbes. Certain microbiomes or microbiota may become associated with different health outcomes, such as resistance or susceptibility to exposure to certain toxic chemicals, the ability to recover following a chemical-induced injury, the presence of disease-associated phenotypes, and the effectiveness of immune responses. Future work in toxicology will require an understanding of how the microbiome interacts with toxicants to fully elucidate how a compound will affect a diverse, real-world population.

Utility of Serum miR-122, Liver Enzymes, and Hepatic Histopathology in Response to Hepatotoxicants in Sprague-Dawley Rats.

More than 80,000 chemicals are in commercial use worldwide. Hepatic metabolism to toxic intermediates is often a key mechanism leading to tissue damage and organ dysfunction. Effective treatment requires prompt detection of hepatotoxicity, ideally with rapid, minimally invasive diagnostic assays. In this study, archetypal histologic features of chemically induced hepatic injury were compared with clinical chemistries (including liver enzymes) and serum concentrations of microRNA-122 (miR-122, the processed form miR-122-5p), a biomarker of liver injury. The hepatotoxicants 4,4'-methylenedianiline (4,4'-MDA), allyl alcohol (AA), or carbon tetrachloride (CCl4) were orally administered to male Sprague-Dawley rats for 1, 5, 14, or 28 days to induce liver damage. Formalin-fixed, paraffin-embedded liver sections were evaluated histologically for inflammation, fibrosis, necrosis, and lipid accumulation. Liver enzymes were measured in serum, and serum miR-122 concentrations were assessed by quantitative polymerase chain reaction (qPCR). Histologic features of hepatic injury dose-dependently increased in both severity and frequency. Increases in liver enzymes and bilirubin were more pronounced in response to AA or 4,4'-MDA than to CCl4 at early time points. Elevated serum miR-122 levels in animals administered CCl4, AA, or 4,4'-MDA were more strongly associated with degree of hepatic histopathology than with dosage. Given this sensitive expression pattern postexposure, liver-specific miR-122 may improve the diagnostic accuracy of early hepatic injury.

Comparative Proteomic Analysis of Liver Steatosis and Fibrosis after Oral Hepatotoxicant Administration in Sprague-Dawley Rats.

The past decade has seen an increase in the development and clinical use of biomarkers associated with histological features of liver disease. Here, we conduct a comparative histological and global proteomics analysis to identify coregulated modules of proteins in the progression of hepatic steatosis or fibrosis. We orally administered the reference chemicals bromobenzene (BB) or 4,4'-methylenedianiline (4,4'-MDA) to male Sprague-Dawley rats for either 1 single administration or 5 consecutive daily doses. Livers were preserved for histopathology and global proteomics assessment. Analysis of liver sections confirmed a dose- and time-dependent increase in frequency and severity of histopathological features indicative of lipid accumulation after BB or fibrosis after 4,4'-MDA. BB administration resulted in a dose-dependent increase in the frequency and severity of inflammation and vacuolation. 4,4'-MDA administration resulted in a dose-dependent increase in the frequency and severity of periportal collagen accumulation and inflammation. Pathway analysis identified a time-dependent enrichment of biological processes associated with steatogenic or fibrogenic initiating events, cellular functions, and toxicological states. Differentially expressed protein modules were consistent with the observed histology, placing physiologically linked protein networks into context of the disease process. This study demonstrates the potential for protein modules to provide mechanistic links between initiating events and histopathological outcomes.

Catheter ablation of atrial fibrillation in patients with heart failure and preserved ejection fraction.

BACKGROUND: Few studies have examined outcomes of catheter ablation for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF). OBJECTIVE: The purpose of this study was to compare outcomes of AF ablation in patients with HFpEF vs HF with reduced ejection fraction (HFrEF). METHODS: We performed a retrospective study of 230 patients with HF who underwent AF ablation, including 97 (42.2%) with HFrEF and 133 (57.8%) with HFpEF. Outcomes included adverse events, symptoms (Mayo AF Symptom Inventory [MAFSI]), New York Heart Association (NYHA) functional class, and freedom from recurrent atrial arrhythmia at 12 months. RESULTS: Overall, 150 of 230 patients had nonparoxysmal AF (62.8% HFpEF vs 63.0% HFrEF). Patients with HFpEF had a smaller mean left atrial diameter (4.4 ± 0.8 cm vs 4.7 ± 0.7 cm; P = .013) and were less likely to be taking a beta-blocker at baseline (72.9% vs 85.6%; P = .022). Median (Q1, Q3) procedure times (233 minutes [192, 290] vs 233.5 minutes [193.0, 297.5]; P = .780) and adverse events such as acute HF (3.8% vs 6.2%; P = .395) were similar between HFpEF and HFrEF patients. Freedom from recurrent atrial arrhythmia was not significantly different in HFpEF vs HFrEF patients (33.9% vs 32.6%; adjusted hazard ratio 1.47; 95% confidence interval 0.72-3.01), with similar improvements in NYHA functional class (-0.32 vs -0.19; P = .135) and MAFSI symptom severity (-0.23 vs -0.09; P = .116) after ablation. CONCLUSION: Catheter ablation of AF seems to have similar effectiveness in patients with HF, regardless of presence of systolic dysfunction. There were no significant differences in procedural characteristics, arrhythmia-free recurrence, or functional improvements between patients with HFpEF and those with HFrEF.

Rethinking papillary muscle resection for refractory ventricular tachycardia in the LVAD era. A case report.

We report the case of a 57-year-old man with a history of ischemic cardiomyopathy who presented to the hospital with recurrent episodes of ventricular tachycardia refractory to antiarrhythmic medications. Mapping identified a deep premature ventricular contraction focus in the anterolateral papillary muscle, an area that has been previously identified as difficult to treat with radiofrequency catheter ablation. The hospital course was complicated by cardiogenic shock and VT-storm, and the patient ultimately underwent surgical resection of the anterolateral papillary muscle with left ventricular assist device placement as a successful bridge to cardiac transplantation.