Safety of ventricular arrhythmia radiofrequency ablation with half-normal saline irrigation.

AIMS: Failure of radiofrequency (RF) ablation of ventricular arrhythmias is often due to inadequate lesion size. Irrigated RF ablation with half-normal saline (HNS) has the potential to increase lesion size and reduce sodium delivery to the patient if the same volume of RF irrigant were used for normal saline (NS) and HNS but could increase risks related to steam pops and lesion size. This study aims to assess periprocedural complications and acute ablation outcome of ventricular arrhythmias ablation with HNS. METHODS AND RESULTS: Prospective assessment of outcomes was performed in 1024 endocardial and/or epicardial RF ablation procedures in 935 consecutive patients (median age 64 years, 71.2% men, 73.4% cardiomyopathy, 47.2% sustained ventricular tachycardia). Half-normal saline was selected at the discretion of the treating physician. Radiofrequency ablation power was generally titrated to a ≤15â€…Ω impedance fall with intracardiac echocardiography monitoring. Half-normal saline was used in 900 (87.9%) and NS in 124 (12.1%) procedures. Any adverse event within 30 days occurred in 13.0% of patients treated with HNS RF ablation including 4 (0.4%) strokes/transient ischaemic attacks and 34 (3.8%) pericardial effusions requiring treatment (mostly related to epicardial access). Two steam pops with perforation required surgical repair (0.2%). Patients who received NS irrigation had less severe disease and arrhythmias. In multivariable models, adverse events and acute success of the procedure were not related to the type of irrigation. CONCLUSION: Half-normal saline irrigation RF ablation with power guided by impedance fall and intracardiac echocardiography has an acceptable rate of complications and acute ablation success while administering half of the saline load expected for NS irrigation.

Efficacy of a Bio-Absorbable Antibacterial Envelope to Prevent Cardiac Implantable Electronic Device Infections in High-Risk Subjects.

INTRODUCTION: Cardiac implantable electronic device (CIED) infections are potentially preventable complications associated with high morbidity, mortality, and cost. A recently developed bio-absorbable antibacterial envelope (TYRX™-A) might prevent CIED infections in high-risk subjects. However, data regarding safety and efficacy have not been published. METHODS AND RESULTS: In a single-center retrospective cohort study, we compared the prevalence of CIED infections among subjects with ≥2 risk factors treated with the TYRX™-A envelope (N = 135), the nonabsorbable TYRX™ envelope (N = 353), and controls who did not receive an envelope (N = 636). Infection was ascertained by individual chart review. The mean (95% confidence interval) number of risk factors was 3.08 (2.84-3.32) for TYRX™-A, 3.20 (3.07-3.34) for TYRX™, and 3.09 (2.99-3.20) for controls, P = 0.3. After a minimum 300 days follow-up, the prevalence of CIED infection was 0 (0%) for TYRX™-A, 1 (0.3%) for TYRX™, and 20 (3.1%) for controls (P = 1 for TYRX™-A vs. TYRX™, P = 0.03 for TYRX™-A vs. controls, and P = 0.002 for TYRX™ vs. controls). In a propensity score-matched cohort of 316 recipients of either envelope and 316 controls, the prevalence of infection was 0 (0%) and 9 (2.8%), respectively, P = 0.004. When limited to 122 TYRX™-A recipients and 122 propensity-matched controls, the prevalence of CIED infections was 0 (0%) and 5 (4.1%), respectively, P = 0.024. CONCLUSIONS: Among high-risk subjects, the TYRX™-A bio-absorbable envelope was associated with a very low prevalence of CIED related infections that was comparable to that seen with the nonabsorbable envelope.

Stroke and Bleeding Risks of Endocardial Ablation for Ventricular Arrhythmias.

BACKGROUND: Risks of radiofrequency catheter ablation for ventricular arrhythmias include emboli and bleeding complications but data on antithrombotic regimens are limited and guidelines do not specify a systematic approach. OBJECTIVES: This study sought to assess embolic and bleeding complications in relation to pre-periprocedure and post-periprocedure antithrombotic regimens. METHODS: Prospective assessment for complications was performed for 663 endocardial radiofrequency catheter ablation procedures in 616 consecutive patients (median age 64 years [Q1-Q3: 54-73 years], 70.3% men, 71.6% with cardiomyopathy, 44.5% with sustained ventricular tachycardia). RESULTS: There were 2 strokes (0.3%; 95% CI: 0.0%-0.8%), 1 transient ischemic attack (0.15%), and 2 pulmonary emboli (0.3%). There were 39 bleeding complications (5.9%) including 11 pericardial effusions (1.7%), and 28 related to vascular access (4.2%). Consistent with the prevalence of coronary artery disease (47.5%), atrial fibrillation (30.0%), and prior stroke (10.6%), preprocedure, 464 patients (70.0%) were taking antithrombotic agents including 220 (33.2%) taking aspirin alone (ASA), and 163 (24.6%) taking warfarin or a direct acting oral anticoagulant (DOAC). Preprocedure non-ASA antiplatelet use (OR: 2.846; P = 0.011) and DOAC use (OR: 2.585; P = 0.032) were associated with risk of bleeding complications. Following ablation, 49.8% of patients were treated with ASA 325 mg/d and 30.3% received DOACs or warfarin. New DOAC or warfarin administration was initiated in only 6.6% of patients. Overall, 39.7% of patients continued the same preprocedure antithrombotic regimen. CONCLUSIONS: Stroke is a rare complication of radiofrequency catheter ablation for ventricular arrhythmia using ASA 325 mg/d as a minimal postprocedure regimen with more potent regimens for selected patients.

Can Intracardiac Echocardiography Reduce Steam Pops During Half-Normal Saline Irrigated Radiofrequency Ablation?

BACKGROUND: Irrigated radiofrequency ablation with half-normal saline can potentially increase lesion size but may increase the risk of steam pops with the risk of emboli or perforation. We hypothesized that pops would be preceded by intracardiac echocardiography (ICE) findings as well as a large impedance fall. METHODS: In 100 consecutive patients undergoing endocardial ventricular arrhythmia radiofrequency ablation with half-normal saline, we attempted to observe the ablation site with ICE. Radiofrequency ablation power was titrated to a 15 to 20 Ohm impedance fall and could be adjusted for tissue whitening and increasing bubble formation on ICE. Steam pops were defined as audible or a sudden explosion of microbubbles on ICE. RESULTS: Of 2190 ablation applications in 100 patients (82% cardiomyopathy, 50% sustained ventricular tachycardia), pops occurred during 43 (2.0%) applications. Sites with pops had greater impedance decreases of 18 [14, 21]% versus 13 [10, 17]% (P<0.001). ICE visualized 1308 (59.7%) radiofrequency sites, and fewer pops occurred when ICE visualized the radiofrequency ablation site (1.4%) compared with without ICE visualization (2.8%; P=0.016). Of the 18 ICE-visible pops, 7 (39%) were silent but recognized as an explosion of bubbles on ICE. With ICE, 89% of pops were preceded by either tissue whitening or a sudden increase in bubbles. In a multivariable model, tissue whitening and a sudden increase in bubbles were associated with steam pops (odds ratio, 7.186; P=0.004, and odds ratio, 29.93; P<0.001, respectively), independent of impedance fall and power. There were no pericardial effusions or embolic events with steam pops. CONCLUSIONS: Steam pops occurred in 2% of half-normal saline radiofrequency applications titrated to an impedance fall and are likely under-recognized without ICE. On ICE, steam pops are usually preceded by tissue whitening or a sudden increase in bubble formation, which can potentially be used to adjust radiofrequency application to help reduce pops.

Effects of Zilpaterol Hydrochloride with a Combination of Vitamin D3 on Feedlot Lambs: Growth Performance, Dietary Energetics, Carcass Traits, and Meat Quality.

This study evaluated the impact of supplementing ZH in combination with D3 on the growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. Thirty-two Dorper × Katahdin cross lambs (37.3 ± 5.72 kg) were utilized in a 29 d experiment in a completely randomized block design with a 2 × 2 factorial structure consisting of two levels of ZH for 26 d (0 and 0.20 mg/kg PV-1) and two levels of D3 for 7 d (0 and 1.5 × 106 IU/d-1). ZH improved (p ≤ 0.05) the average daily gain (ADG) and feed efficiency by 9.9% and 17.8%, respectively, as well as hot carcass weight (HCW) and dressing carcass by 4.3% and 2.6%, respectively. (p ≤ 0.03). However, ZH increased (p < 0.01) muscle pH and Warner-Bratzler shear force (WBSF) (2.5 and 23.0%, respectively). D3 supplementation negatively affected (p ≤ 0.02) dry matter intake (DMI) (last 7 d) and ADG by 15.7% and 18.1%. On the other hand, D3 improved the pH of the longissimus thoracis muscle by 1.7% (p = 0.03) without affecting WBSF. When D3 was supplemented in combination with ZH, it was observed that meat quality was improved by reducing muscle pH compared to lambs treated only with ZH. However, D3 did not improve the meat tenderness negatively affected by ZH supplementation.

Pulmonary Vein Myocardial Sleeve Length and its Association With Sex and 4q25/PITX2 Genotype.

BACKGROUND: Experimental evidence suggests genetic variation in 4q25/PITX2 modulates pulmonary vein (PV) myocardial sleeve length. Although PV sleeves are the main target of atrial fibrillation (AF) ablation, little is known about the association between different PV sleeve characteristics with ablation outcomes. OBJECTIVES: This study sought to evaluate the association between clinical and genetic (4q25) risk factors with PV sleeve length in humans, and to evaluate the association between PV sleeve length and recurrence after AF ablation. METHODS: In a prospective, observational study of patients undergoing de novo AF ablation, PV sleeve length was measured using electroanatomic voltage mapping before ablation. The sentinel 4q25 AF susceptibility single nucleotide polymorphism, rs2200733, was genotyped. The primary analysis tested the association between clinical and genetic (4q25) risk factors with PV sleeve length using a multivariable linear regression model. Covariates included age, sex, body mass index, height, and persistent AF. The association between PV sleeve length and atrial arrhythmia recurrence (>30 seconds) was tested using a multivariable Cox proportional hazards model. RESULTS: Between 2014 and 2019, 197 participants were enrolled (median age 63 years [IQR: 55 to 70 years], 133 male [67.5%]). In multivariable modeling, men were found to have PV sleeves 2.94 mm longer than women (95% CI: 0.99-4.90 mm; P < 0.001). Sixty participants (30.5%) had one 4q25 risk allele and 6 (3.1%) had 2 alleles. There was no association between 4q25 genotype and PV sleeve length. Forty-six participants (23.4%) experienced arrhythmia recurrence within 3 to 12 months, but there was no association between recurrence and PV sleeve length. CONCLUSIONS: Common genetic variation at 4q25 was not associated with PV sleeve length and PV sleeve length was not associated with ablation outcomes. Men did have longer PV sleeves than women, but more research is needed to define the potential clinical significance of this observation.

A Mechanistic Clinical Trial Using (R)- Versus (S)-Propafenone to Test RyR2 (Ryanodine Receptor) Inhibition for the Prevention of Atrial Fibrillation Induction.

BACKGROUND: Experimental data suggest ryanodine receptor-mediated intracellular calcium leak is a mechanism for atrial fibrillation (AF), but evidence in humans is still needed. Propafenone is composed of two enantiomers that are equally potent sodium-channel blockers; however, (R)-propafenone is an ryanodine receptor inhibitor whereas (S)-propafenone is not. This study tested the hypothesis that ryanodine receptor inhibition with (R)-propafenone prevents induction of AF compared to (S)-propafenone or placebo in patients referred for AF ablation. METHODS: Participants were randomized 4:4:1 to a one-time intravenous dose of (R)-propafenone, (S)-propafenone, or placebo. The study drug was given at the start of the procedure and an AF induction protocol using rapid atrial pacing was performed before ablation. The primary endpoint was 30 s of AF or atrial flutter. RESULTS: A total of 193 participants were enrolled and 165 (85%) completed the study protocol (median age: 63 years, 58% male, 95% paroxysmal AF). Sustained AF and/or atrial flutter was induced in 60 participants (84.5%) receiving (R)-propafenone, 60 (80.0%) receiving (S)-propafenone group, and 12 (63.2%) receiving placebo. Atrial flutter occurred significantly more often in the (R)-propafenone (N=23, 32.4%) and (S)-propafenone (N=26, 34.7%) groups compared to placebo (N=1, 5.3%, P=0.029). There was no significant difference between (R)-propafenone and (S)-propafenone for the primary outcome of AF and/or atrial flutter induction in univariable (P=0.522) or multivariable analysis (P=0.199, adjusted for age and serum drug level). CONCLUSIONS: There is no difference in AF inducibility between (R)-propafenone and (S)-propafenone at clinically relevant concentrations. These results are confounded by a high rate of inducible atrial flutter due to sodium-channel blockade. REGISTRATION: https://clinicaltrials.gov; Unique Identifier: NCT02710669.

Increase in mitochondrial biogenesis, oxidative stress, and glycolysis in murine lymphomas.

Lymphomas adapt to their environment by undergoing a complex series of biochemical changes that are currently not well understood. To better define these changes, we examined the gene expression and gene ontology profiles of thymic lymphomas from a commonly used model of carcinogenesis, the p53(-/-) mouse. These tumors show a highly significant upregulation of mitochondrial biogenesis, mitochondrial protein translation, mtDNA copy number, reactive oxygen species, antioxidant defenses, proton transport, ATP synthesis, hypoxia response, and glycolysis, indicating a fundamental change in the bioenergetic profile of the transformed T cell. Our results suggest that T cell tumorigenesis involves a simultaneous upregulation of mitochondrial biogenesis, mitochondrial respiration, and glycolytic activity. These processes would allow cells to adapt to the stressful tumor environment by facilitating energy production and thereby promote tumor growth. Understanding these adaptations is likely to result in improved therapeutic strategies for this tumor type.

Enhanced external counterpulsation treatment improves arterial wall properties and wave reflection characteristics in patients with refractory angina.

OBJECTIVES: To determine if arterial properties and wave reflection characteristics are favorably altered after enhanced external counterpulsation (EECP) treatment in patients with refractory angina. BACKGROUND: Early return of reflected waves from the lower body, resulting from increased arterial stiffness, augments central aortic pressure and increases left ventricular (LV) afterload and myocardial oxygen demand. EECP acutely enhances coronary perfusion (supply) and reduces LV afterload (demand). However, the mechanisms responsible for the sustained beneficial effects of EECP treatment are unclear. METHODS: Radial artery pressure waveforms were recorded by applanation tonometry and central aortic pressure waveforms generated using a mathematical transfer function in 20 patients with stable refractory angina. Data were collected before and after 34 1-h EECP sessions. Augmentation index (AI(a)) and timing of the reflected pressure wave were calculated from the aortic waveform. RESULTS: EECP treatment caused a decline in AI(a) and an increase in reflected wave travel time. These modifications in wave reflection characteristics caused a decrease in aortic systolic pressure and wasted LV pressure energy. The average number of angina episodes and Canadian Cardiovascular Society (CCS) class, both decreased in concordance with the physiologic changes due to EECP treatment. CONCLUSIONS: EECP treatment reduces arterial stiffness and improves wave reflection characteristics in patients with refractory angina. These changes decrease LV afterload and myocardial oxygen demand and reduce the number of angina episodes, therefore enabling patients to participate in continuous exercise programs which in turn may provide long-term benefits and sustained improved quality of life.