Pulsed Field vs Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation: Recurrent Atrial Arrhythmia Burden.

BACKGROUND: The ADVENT randomized trial revealed no significant difference in 1-year freedom from atrial arrhythmias (AA) between thermal (radiofrequency/cryoballoon) and pulsed field ablation (PFA). However, recent studies indicate that the postablation AA burden is a better predictor of clinical outcomes than the dichotomous endpoint of 30-second AA recurrence. OBJECTIVES: The goal of this study was to determine: 1) the impact of postablation AA burden on outcomes; and 2) the effect of ablation modality on AA burden. METHODS: In ADVENT, symptomatic drug-refractory patients with paroxysmal atrial fibrillation underwent PFA or thermal ablation. Postablation transtelephonic electrocardiogram monitor recordings were collected weekly or for symptoms, and 72-hour Holters were at 6 and 12 months. AA burden was calculated from percentage AA on Holters and transtelephonic electrocardiogram monitors. Quality-of-life assessments were at baseline and 12 months. RESULTS: From 593 randomized patients (299 PFA, 294 thermal), using aggregate PFA/thermal data, an AA burden exceeding 0.1% was associated with a significantly reduced quality of life and an increase in clinical interventions: redo ablation, cardioversion, and hospitalization. There were more patients with residual AA burden <0.1% with PFA than thermal ablation (OR: 1.5; 95% CI: 1.0-2.3; P = 0.04). Evaluation of outcomes by baseline demographics revealed that patients with prior failed class I/III antiarrhythmic drugs had less residual AA burden after PFA compared to thermal ablation (OR: 2.5; 95% CI: 1.4-4.3; P = 0.002); patients receiving only class II/IV antiarrhythmic drugs pre-ablation had no difference in AA burden between ablation groups. CONCLUSIONS: Compared with thermal ablation, PFA more often resulted in an AA burden less than the clinically significant threshold of 0.1% burden. (The FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation [ADVENT]; NCT04612244).

Autonomic Effects of Pulsed Field vs Thermal Ablation for Treating Atrial Fibrillation: Subanalysis of ADVENT.

BACKGROUND: Autonomic denervation is an ancillary phenomenon during thermal ablation of atrial fibrillation (AF), that may have synergistic effects on symptomatic improvement and long-term freedom from AF. Pulsed field ablation (PFA), a nonthermal ablation modality, was noninferior to thermal ablation in treating AF; however, PFA's relative myocardial selectivity may minimize autonomic effects. OBJECTIVES: This study sought to compare heart rate (HR) and heart rate variability (HRV) metrics as markers of autonomic function after ablation using PFA vs thermal ablation. METHODS: ADVENT (The FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation) was a randomized pivotal study comparing PFA (pentaspline catheter) with thermal ablation (radiofrequency [RF] or cryoballoon [CB]) for treating paroxysmal AF. Baseline HR was acquired from a pre-ablation 12-lead electrocardiogram, whereas follow-up HRs, as well as HRV (standard deviation of all normal to normal RR intervals, standard deviation of 5-minute average RR intervals) metrics, were derived from 72-hour Holter monitors at 6 and 12 months. RESULTS: This study included 379 paroxysmal AF patients undergoing PFA (n = 194) or thermal ablation (n = 185; n = 102 RF, n = 83 CB) completing 6- and 12-month Holter monitoring. Compared with PFA, thermal patients had significantly greater increases in HR from baseline to 6 months (ΔHR; 10.1 vs 5.9 beats/min; P = 0.02) and 12 months (ΔHR; 8.8 vs 5.2 beats/min; P = 0.03). This increase in HR at 6 and 12 months was similar between CB and RF (P = 0.94 and 0.83, respectively). HRV, both standard deviation of all normal to normal RR intervals and standard deviation of 5-minute average RR intervals, were significantly lower at both 6 and 12 months after thermal ablation compared with PFA (P < 0.01). CONCLUSIONS: PFA's effect on the autonomic nervous system was attenuated compared with thermal ablation. Whether this affects long-term freedom from AF or symptomatic bradycardia/pauses after AF ablation requires further study.

Rhythmia zero-fluoroscopy workflow with high-power, short-duration ablation: retrospective analysis of procedural data.

BACKGROUND: Fluoroscopy is commonly used during atrial fibrillation (AF) ablation to guide catheter navigation and placement. Technology improvements have significantly reduced fluoroscopy time, and subsequent radiation dose, necessary to perform successful ablations. However, there is still no amount of radiation exposure known to be completely safe. The aim of this manuscript is to describe a detailed zero-fluoroscopy RHYTHMIA HDx workflow for AF ablation. METHODS: This was an observational, single-center experience to describe the technique, acute procedural success, and safety using a novel zero-fluoroscopy workflow with the RHYTHMIA HDx mapping system and intracardiac echocardiography (ICE). Seventy-two consecutive patients undergoing de novo or redo AF ablation were retrospectively analyzed. Venous access was guided with ultrasound. ICE combined with the mapping system's magnetic tracking and sheath detection was used for precise catheter placement in the coronary sinus, at the transseptal puncture, and in the left atrium. A high-power, short-duration ablation strategy guided by local impedance was used. Pulmonary vein isolation was performed or touched up for all patients with additional lines added at the operator's discretion. RESULTS: Using this zero-fluoroscopy workflow, all patients achieved acute isolation with no significant procedure-related complications. Average procedure time was 73.7 ± 16.2 min, which included persistent (58%) and paroxysmal (42%) AF cases, and no procedures required conversion to fluoroscopy. CONCLUSIONS: In this experience, a zero-fluoroscopy workflow using the RHYTHMIA HDx mapping system combined with ICE was feasible and safe for ablation in a heterogenous AF population. This approach, in the appropriate patient population, can eliminate radiation exposure to patients and staff.

Economic value of insertable cardiac monitors in unexplained syncope in the United States.

INTRODUCTION: Early use of insertable cardiac monitor (ICM) is recommended for patients with unexplained syncope following initial clinical workup, due to its superior ability to establish symptom-rhythm correlation compared with conventional testing (CONV). However, ICMs incur higher upfront costs, and the impact of additional diagnoses and resulting treatment on downstream costs and outcomes is unclear. We aimed to evaluate the cost-effectiveness of ICM compared with CONV for the diagnosis of arrhythmia in patients with unexplained syncope, from a US payer perspective. METHODS: A Markov model was developed to estimate lifetime costs and benefits of arrhythmia diagnosis with ICM versus CONV, considering all related diagnostic and arrhythmia-related treatment costs and consequences. Cohort characteristics and costs were informed by original claims database analyses. Risks of mortality, syncopal recurrence, injury due to syncope and quality of life consequences from syncopal events were identified from the literature. RESULTS: ICM was less costly and more effective than CONV. Most of the observed US$4532 cost savings were attributed to reduced downstream diagnostic testing. For every 1000 patients, ICM was projected to yield an additional 253 arrhythmia diagnoses and lead to treatment in an additional 168 patients. The ICM strategy resulted in overall improved outcomes (0.30 quality-adjusted life years gained), due to a reduction in syncope recurrence and injury resulting from arrhythmia treatment. The results were robust to changes in the base case parameters but sensitive to the model time horizon, underlying probability of syncope recurrence and prevalence of arrhythmias. CONCLUSIONS: Our model projected that early ICM for the diagnosis of unexplained syncope reduced long-term costs, and led to an improvement in overall clinical outcomes by shortening time to arrhythmia treatment. The cost of ICM was outweighed by savings arising from fewer downstream diagnostic episodes, and the increased cost of treatment was counterbalanced by fewer syncope-related event costs.

Cost-effectiveness Analysis of Contralateral Prophylactic Mastectomy Compared to Unilateral Mastectomy with Routine Surveillance for Unilateral, Sporadic Breast Cancer.

BACKGROUND: Contralateral prophylactic mastectomy (CPM) rates in younger women with unilateral breast cancer have more than doubled. Studies of cost and quality of life of the procedure remain inconclusive. METHODS: A cost-effectiveness analysis using a decision-tree model in TreeAge Pro 2015 was used to compare long-term costs and quality of life following unilateral mastectomy (UM) with routine surveillance versus CPM for sporadic breast cancer in women aged 45 years. A 10-year risk period for contralateral breast cancer (CBC), reconstruction, wound complications, cost of routine surveillance, and treatment for CBC were used to estimate accrued costs. In addition, a societal perspective was used to estimate quality-adjusted life years (QALYs) following either treatment for a period of 30 years. Medical costs were obtained from the 2014 Medicare physician fee schedule and event probabilities were taken from recent literature. RESULTS: The mean cost of UM with surveillance was $14,141 and CPM was $20,319. Treatment with CPM resulted in $6178 more in costs but equivalent QALYs (17.93) compared with UM over 30 years of follow-up. Even with worst-case scenario and varying assumptions, CPM is dominated by UM in terms of cost and quality. CONCLUSIONS: From this refined model, UM with routine surveillance costs less and provides an equivalent quality of life. Patients undergoing CPM may eliminate the anxiety of routine surveillance, but they face the burden of higher lifetime medical costs.

The Cardiovascular Intensive Care Unit-An Evolving Model for Health Care Delivery.

Prior to the advent of the coronary care unit (CCU), patients having an acute myocardial infarction (AMI) were managed on the general medicine wards with reported mortality rates of greater than 30%. The first CCUs are believed to be responsible for reducing mortality attributed to AMI by as much as 40%. This drastic improvement can be attributed to both advances in medical technology and in the process of health care delivery. Evolving considerably since the 1960s, the CCU is now more appropriately labeled as a cardiac intensive care unit (CICU) and represents a comprehensive system designed for the care of patients with an array of advanced cardiovascular disease, an entity that reaches far beyond its early association with AMI. Grouping of patients by diagnosis to a common physical space, dedicated teams of health care providers, as well as the development and implementation of evidence-based treatment algorithms have resulted in the delivery of safer, more efficient care, and most importantly better patient outcomes. The CICU serves as a platform for an integrated, team-based patient care delivery system that addresses a broad spectrum of patient needs. Lessons learned from this model can be broadly applied to address the urgent need to improve outcomes and efficiency in a variety of health care settings.

Femoral arterial closure using ProGlide® is more efficacious and cost-effective when ambulating early following cardiac catheterization.

OBJECTIVE: This was a prospective, single-center study evaluating the efficacy and cost-effectiveness of early ambulation (within 30 min) following femoral artery closure with the ProGlide® suture-mediated vascular closure device (PD) in patients undergoing diagnostic cardiac catheterization compared with manual compression. BACKGROUND: It is unclear whether early ambulation with ProGlide is safe or is associated with patient satisfaction and cost savings as compared with manual compression (MC). METHODS AND RESULTS: Inclusion criteria were met in 170 patients (85 PD and 85 MC patients). Patients ambulated 20 ft. within 30 min (PD) or after the requisite 4 h recumbent time (MC) if feasible. Primary endpoint was time-to-ambulation (TTA) following device closure. We also directly compared the safety of closure, times-to-hemostasis (TTH), -ambulation (TTA) and -discharge (TTD) with MC and, using a fully allocated cost model, performed cost analysis for both strategies. Multivariate analysis was used to determine predictors of patient satisfaction. The primary endpoint of safe, early ambulation was achieved following closure (mean of 27.1 ± 14.9 min; 95% confidence interval [CI] 25.2-30.2). Predictors of patient satisfaction in the PD group were absence of pain during closure, decreased TTA, and drastic reductions in TTD; the latter contributed indirectly to significant cost savings in the PD group (1250.3 ± 146.4 vs. 2248.1 ± 910.2 dollars, respectively; P < 0.001) and incremental cost savings by strategy also favored closure over MC ($84,807). CONCLUSIONS: ProGlide is safe and effective for femoral artery closure in patients who ambulate within 30 min after cardiac catheterization; translating into improved patient satisfaction and substantial cost savings.

Impact of cardiac resynchronization therapy on clinical outcomes in patients with continuous-flow left ventricular assist devices.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) can improve survival in left ventricular assist device (LVAD) recipients. However, the impact of cardiac resynchronization therapy (CRT-D) on outcomes in continuous-flow left ventricular assist device (CF-LVAD) patients is not known. We sought to determine if CRT-D improved clinical outcomes in CF-LVAD patients compared with ICDs alone. METHODS AND RESULTS: Sixty-one consecutive CF-LVAD patients with an ICD or CRT-D were evaluated. Impacts of CRT-D on mortality, all-cause hospitalization, and incidence of atrial (AA) and ventricular (VA) arrhythmias after LVAD implantation was compared with patients with ICD alone. Of the 61 LVAD patients, 31 (age 59.8 ± 16 years, 84% male) had CRT-D and 30 (age 57.2 ± 13 years, 74% male) had ICD. Before LVAD implantation, no significant differences were noted between the groups in demographic and clinical characteristics, LVAD indications, and incidence of AA and VA. Over 682 ± 45 days of LVAD support, 8 patients (25.8%) died in the CRT-D arm versus 5 (16.7%) in the ICD arm (P = .35). No differences were noted between the CRT-D and ICD groups in all-cause (96.8 vs 93.3%; P = .63) and HF (19.4 vs 26.7%; P = .78) hospitalizations, left ventricular (LV) end-diastolic diameter (6.4 ± 1.5 vs 6.2 ± 1.1 cm, P = .47), and incidence of AA (35.4% vs 33.3%; P = .80), VA (29% vs 26.6%; P = .86), and ICD shocks (22.6% vs 16.7%; P = .93). Beta-blocker and antiarrhythmic drug use after LVAD implantation was similar in both groups. CONCLUSIONS: In patients with refractory HF who received CF-LVADs, CRT-D, compared with ICD, did not significantly improve mortality, all-cause hospitalization, LV dimensions, and incidence of AA and VA.

Intracardiac transplantation of a mixed population of bone marrow cells improves both regional systolic contractility and diastolic relaxation.

BACKGROUND: Pre-clinical and clinical studies suggest that transplantation of bone marrow-derived stem cells can improve global cardiac function. However, no quantitative assessment of regional systolic contraction and correlation with phenotype has been made. Therefore, we used our model of cryoinfarcted rabbit myocardium for intracardiac transplantation of a mixed population of bone marrow-derived cells and assessed both regional function and myogenic conversion of the cells. METHODS: Nineteen New Zealand white rabbits underwent cryoinjury of the left ventricle. Autologous bone marrow (BM) cells were expanded in vitro. After 2 weeks, either 1 x 10(8) mixed BM-derived progenitor cells (BM group, n = 11) or vehicle (control group, n = 8) were injected into the cryoinjured region. Regional systolic function was measured using micromanometry and sonomicrometry before and 4 weeks after cell injection; cell phenotype was evaluated histologically. RESULTS: All animals in the BM group significantly improved both systolic shortening (0.11 +/- 0.7 vs -0.05 +/- 0.05 mm in the control group, p < 0.05) and regional stroke work when compared with control (9.6 +/- 2.4 vs -1.2 +/- 1.2 mm . mm Hg, p < 0.003). In addition, the BM group had improved global diastolic function, as measured by minimum dP/dt and end-diastolic pressure. On histologic assessment, BM cells differentiated toward a myogenic phenotype. CONCLUSIONS: Transplanting a mixed population of marrow-derived cells that can adopt a myogenic phenotype improves regional contractility and diastolic relaxation after myocardial infarction.

Improved efficacy of stem cell labeling for magnetic resonance imaging studies by the use of cationic liposomes.

Labeling stem cells with FDA-approved superparamagnetic iron oxide particles makes it possible to track cells in vivo with magnetic resonance imaging (MRI), but high intracellular levels of iron can cause free radical formation and cytotoxicity. We hypothesized that the use of cationic liposomes would increase labeling efficiency without toxic effects. Rabbit skeletal myoblasts were labeled with iron oxide by: 1) uptake of iron oxide incorporated into cationic transfection liposomes (group I) or 2) customary endocytosis (group II). In both groups, cell proliferation and differentiation were measured and toxicity was assayed using trypan blue and ratio fluorescence microscopy with BODIPY 581/591 C11. The effects of the intracellular iron oxide on magnetic resonance image intensities were assessed in vitro and in vivo. Both methods resulted in uptake of iron intracellularly, yielding contrast-inducing properties on MRI images. In group II, however, incubation with iron oxide at high concentrations required for endocytosis caused generation of free radicals, a decrease in proliferation, and cell death. Cytotoxic effects in the remaining cells were still visible 24 h after incubation. Conversely, in group I, sufficient intracellular uptake for detection in vivo by MRI could be achieved at 100-fold lower concentrations of iron oxide, which resulted in a high percentage of labeled cells, high retention of the label, and no cytotoxic effects even after stressing the cells with a hypoxia-reoxygenation insult. The use of cationic liposomes for iron oxide stem cell labeling increases labeling efficiency approximately 100-fold without toxic effects. This technique results in high-contrast-inducing properties on MRI images both in vitro and in vivo and could thus be a valuable tool for tracking stem cells noninvasively.