Economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from an English National Health Service perspective.

INTRODUCTION: Three recent randomised controlled trials have demonstrated that pulmonary vein isolation as an initial rhythm control strategy with cryoablation reduces atrial arrhythmia recurrence in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drug (AAD) therapy. The aim of this study was to evaluate the cost-effectiveness of first-line cryoablation compared with first-line AADs for treating symptomatic PAF in an English National Health Service (NHS) setting. METHODS: Individual patient-level data from 703 participants with PAF enrolled into Cryo-FIRST (Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation), STOP AF First (Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation) and EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) were used to derive the parameters applied in the cost-effectiveness model (CEM). The CEM comprised a hybrid decision tree and Markov structure. The decision tree had a 1-year time horizon and was used to inform the initial health state allocation in the first cycle of the Markov model (40-year time horizon; 3-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3.5% per year. Model outcomes were generated using probabilistic sensitivity analysis. RESULTS: The results estimated that cryoablation would yield more QALYs (+0.17) and higher costs (+£641) per patient over a lifetime than AADs. This produced an incremental cost-effectiveness ratio of £3783 per QALY gained. Independent of initial treatment, individuals were expected to receive ~1.2 ablations over a lifetime. There was a 45% relative reduction in time spent in AF health states for those initially treated with cryoablation. DISCUSSION: AF rhythm control with first-line cryoablation is cost effective compared with first-line AADs in an English NHS setting.

The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: The EARLY-AF (NCT02825979), STOP AF First (NCT03118518), and Cryo-FIRST (NCT01803438) randomised controlled trials (RCTs) demonstrated that cryoballoon pulmonary vein isolation reduces atrial fibrillation (AF) recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal atrial fibrillation (PAF). The present study developed a cost-effectiveness model (CEM) of first-line cryoablation compared with first-line AADs for PAF, from the Canadian health care payer's perspective. METHODS: Data from the 3 RCTs were analysed to estimate key CEM parameters. The model structure used a decision tree for the first 12 months and a Markov model with a 3-month cycle length for the remaining lifetime time horizon. Costs were set at 2023 Canadian dollars, health benefits were expressed as quality-adjusted life years (QALYs), and both were discounted 3% annually. Probabilistic sensitivity analysis (PSA) considered parameter uncertainty. RESULTS: The statistical analysis estimated that first-line cryoablation generates a 47% reduction (P < 0.001) in the rate of AF recurrence, a 73% reduction in the rate of subsequent ablation (P < 0.001), and a 4.3% (P = 0.025) increase in health-related quality of life, compared with first-line AADs. The PSA indicates that an individual treated with first-line cryoablation accrues less costs (-$3,862) and more QALYs (0.19) compared with first-line AADs. Cryoablation is cost-saving in 98.4% of PSA iterations and has a 99.9% probability of being cost-effective at a cost-effectiveness threshold of $50,000 per QALY gained. Cost-effectiveness results were robust to changes in key model parameters. CONCLUSIONS: First-line cryoballoon ablation is cost-effective when compared with AADs for patients with symptomatic PAF.

An economic evaluation of first-line cryoballoon ablation vs antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a U.S. Medicare perspective.

Background: Three recent randomized controlled trials have demonstrated that, as an initial rhythm control strategy, first-line cryoballoon ablation (cryoablation) reduces atrial arrhythmia recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal atrial fibrillation (PAF). Objective: The study sought to evaluate the cost-effectiveness of first-line cryoablation compared with first-line AADs for treating symptomatic PAF from a U.S. Medicare payer perspective. Methods: Individual patient-level data from 703 participants with PAF enrolled into the Cryo-FIRST (NCT01803438), STOP AF First (NCT03118518), and EARLY-AF (NCT02825979) trials were used to derive parameters for the cost-effectiveness model. The cost-effectiveness model used a hybrid decision tree and Markov structure. The decision tree had a 1-year time horizon and was used to inform the initial health state allocation in the first cycle of the Markov model. The Markov model used a 40-year time horizon (3-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Results: Cryoablation was estimated to yield higher QALYs (+0.17) and higher costs (+$4274) per patient over a 40-year time horizon than AADs. Ultimately, this produced an average incremental cost-effectiveness ratio of $24,637 per QALY gained. Independent of initial treatment, individuals were expected to receive ∼1.2 ablations over a lifetime. There was a 45% relative reduction in time spent in atrial fibrillation health states for those initially treated with cryoablation compared with AADs. Conclusion: Initial rhythm control with first-line cryoballoon ablation is highly cost-effective compared with first-line AADs from a U.S. Medicare payer perspective.

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Valve Replacement or Repair.

Background We sought to examine outcomes of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation with valve repair/replacement. Methods and Results Two atrial fibrillation cohorts from Medicare were identified from 2015 to 2019. They comprised patients who underwent surgical or transcatheter mitral valve repair (MV repair cohort) and surgical aortic or mitral bioprosthetic or transcatheter aortic valve replacement (bioprosthetic cohort). Each cohort was divided into warfarin and DOACs (apixaban, rivaroxaban, and dabigatran) groups. Study outcomes included mortality, stroke, and major bleeding. Inverse probability weighting was used for adjustment between the 2 groups in each cohort. The MV repair cohort included 1178 patients. After a median of 468 days, DOACs were associated with lower risk of mortality (hazard ratio [HR], 0.67 [95% CI, 0.55-0.82], P<0.001), ischemic stroke (HR, 0.72 [95% CI, 0.52-1.00], P=0.05) and bleeding (HR, 0.79 [95% CI, 0.63-0.99], P=0.04) compared with warfarin. The bioprosthetic cohort included 8089 patients. After a median follow-up of 413 days, DOACs were associated with similar risk of mortality (adjusted HR, 0.93 [95% CI, 0.86-1.01], P=0.08), higher risk of ischemic stroke (adjusted HR, 1.27 [95% CI, 1.13-1.43], P<0.001), and lower risk of bleeding (adjusted HR, 0.86 [95% CI, 0.80-0.93], P<0.001) compared with warfarin. Conclusions In patients with atrial fibrillation, DOACs are associated with similar mortality, lower bleeding, but higher stroke with bioprosthetic valve replacement and lower risk of all 3 outcomes with MV repair compared with warfarin.

Racial and Sex Disparities in Anticoagulation After Electrical Cardioversion for Atrial Fibrillation and Flutter.

Background Anticoagulation is indicated for 4 weeks after cardioversion in patients with atrial fibrillation/flutter. We sought to examine whether there is evidence of sex or racial disparity in anticoagulant prescription following cardioversion, and whether postcardioversion anticoagulation affects outcomes. Methods and Results We identified a representative sample of Medicare patients who underwent elective electric cardioversion in an outpatient setting from 2015 to 2017. We identified patients who had an anticoagulant prescription for 3 months after the cardioversion date. Multivariable logistic regression was used to assess factors associated with a prescription of an anticoagulant after cardioversion. Cox regression analysis was used to test association of anticoagulation with a composite end point of 90-day mortality, ischemic stroke, or arterial embolism. The final study cohort included 7860 patients. Overall, 5510 patients (70.1%) received any anticoagulation following cardioversion, while 2350 (29.9%) did not. Patients who did not receive anticoagulation were younger, with a lower burden of most comorbidities. Patients were less likely to receive anticoagulation if they had dementia or atrial flutter, while patients with valvular heart disease, obesity, heart failure, peripheral vascular or coronary disease, or hypertension were more likely to receive anticoagulation. Female sex (adjusted odds ratio, 0.84; 95% CI, 0.75-0.92; P<0.001), Black and Hispanic race (adjusted odds ratio, 0.50; 95% CI, 0.38-0.65; and odds ratio, 0.56; 95% CI, 0.41-0.75, respectively; P<0.001) were independently associated with lower probability of anticoagulant prescription. Postcardioversion anticoagulation was associated with lower risk of the composite end point (adjusted hazard ratio, 0.38; 95% CI, 0.27-0.52; P<0.001). Conclusions Racial and sex disparities exist in anticoagulant prescription after outpatient elective cardioversion for atrial fibrillation.

Super and Nonresponders to Catheter Ablation for Atrial Fibrillation: A Quality-of-Life Assessment Using Patient Reported Outcomes.

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Predictors of long-term outcomes greater than 10 years after cardiac resynchronization therapy implantation.

BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated in patients with medically refractory heart failure and wide QRS duration. While much is known about predictors of left ventricular (LV) remodeling after CRT implantation and short-term mortality, limited data exist on long-term outcomes after CRT placement. METHODS: We retrospectively reviewed all patients undergoing CRT implantation at our center between 2003 and 2008 and examined mortality using institutional electronic records, social security death index, and online obituary search. We included only patients with preimplant echoes with LV ejection fraction (LVEF) 35% or below. Variable selection was performed using stepwise regression and models were compared using goodness-of-fit criteria. A final model was validated with the bootstrap regression method. RESULTS: Out of the 877 CRT patients undergoing implantation during this time, 287 (32.7%) survived longer than 10 years. Significant (P < .05) predictors of survival in our multivariate model were age, left ventricular diastolic diameter, sex, presence of nonischemic vs ischemic cardiomyopathy, QRS duration, atrial fibrillation, BNP levels, and creatinine levels at the time of CRT implantation. A model using the odds ratios from these variables had a receiver operating curve with an area under the curve score of 0.816 (standard error, 0.019) at predicting survival or freedom from LVAD or heart transplant for longer than 10 years after CRT implantation. The specificity for factors 3 or above and 5 or above was 68% and 77%, respectively. CONCLUSION: A large proportion of patients are still alive 10 years after CRT implantation. Variables at the time of CRT implant can help provide prognostic information to patients and electrophysiologists to determine the long-term benefit and survival of patients after CRT implantation.

Impact of Atrial Fibrillation on Exercise Capacity and Mortality in Heart Failure With Preserved Ejection Fraction: Insights From Cardiopulmonary Stress Testing.

BACKGROUND: Atrial fibrillation (AF) has been objectively associated with exercise intolerance in patients with heart failure with reduced ejection fraction; however, its impact in patients with heart failure with preserved ejection fraction has not been fully scrutinized. METHODS AND RESULTS: We identified 1744 patients with heart failure and ejection fraction ≥50% referred for cardiopulmonary stress testing at the Cleveland Clinic (Cleveland, OH), 239 of whom had AF. We used inverse probability of treatment weighting to balance clinical characteristics between patients with and without AF. A weighted linear regression model, adjusted for unbalanced variables (age, sex, diagnosis, hypertension, and ß-blocker use), was used to compare metabolic stress parameters and 8-year total mortality (social security index) between both groups. Weighted mean ejection fraction was 58±5.9% in the entire population. After adjusting for unbalanced weighted variables, patients with AF versus those without AF had lower mean peak oxygen consumption (18.5±6.2 versus 20.3±7.1 mL/kg per minute), oxygen pulse (12.4±4.3 versus 12.9±4.7 mL/beat), and circulatory power (2877±1402 versus 3351±1788 mm Hg·mL/kg per minute) (P<0.001 for all comparisons) but similar submaximal exercise capacity (oxygen consumption at anaerobic threshold, 12.0±5.1 versus 12.4±6.0mL/kg per minute; P =0.3). Both groups had similar peak heart rate, whereas mean peak systolic blood pressure was lower in the AF group (150±35 versus 160±51 mm Hg; P<0.001). Moreover, AF was associated with higher total mortality. CONCLUSIONS: In the largest study of its kind, we demonstrate that AF is associated with peak exercise intolerance, impaired contractile reserve, and increased mortality in patients with heart failure with preserved ejection fraction. Whether AF is the primary offender in these patients or merely a bystander to worse diastolic function requires further investigation.

Risk factors for 1-year mortality among patients with cardiac implantable electronic device infection undergoing transvenous lead extraction: the impact of the infection type and the presence of vegetation on survival.

AIMS: Infections of cardiac implantable electronic devices (CIEDs) are infrequent but carry significant morbidity and mortality. We aimed to assess risk factors for 1-year mortality among patients with CIED infection and to evaluate if the type of infection and the presence of vegetation affect survival. METHODS AND RESULTS: We reviewed records of all patients with infected CIEDs who underwent transvenous lead extraction at our tertiary care centre between 2002 and 2008. Patients who presented with infection involving the device pocket were classified as 'pocket infection', and those who presented with bacteraemia with or without vegetation and a pocket that looked benign were classified as 'endovascular infection' (EVI). One-year mortality was examined using the social security death index. Five hundred and two patients were identified (68.5 ± 15 years); 289 (58%) had pocket infection and 213 (42%) had EVI. One-year mortality rate was 20%. Using multivariable Cox regression model, EVI was associated with significantly higher 1-year mortality (hazard ratio 2.1, P-value 0.0008). Among patients with EVI, 100 patients had vegetation on transoesophageal echo; however, there was no difference in 1-year mortality between patients with EVI and vegetation compared with patients with EVI and no vegetation (27, 27 vs. 40, 35%; P-value 0.188). Risk factors for 1-year mortality among patients with EVI included renal failure, worse functional class, and bleeding requiring transfusion. The presence of vegetation was not associated with increased 1-year mortality. CONCLUSION: One-year mortality is higher among patients with EVI compared with patients with pocket infection; this increased mortality does not seem to be related to the presence of vegetations.

Outcomes after endocarditis or device infection in patients with left ventricular epicardial leads versus coronary sinus leads.

BACKGROUND: There is scant data about outcomes in patients with left ventricular epicardial (LVE) leads who develop endocarditis or device-related infection. OBJECTIVE: This retrospective study evaluated mortality and recurrence of infection among patients with LVE leads in comparison to patients with endovascular coronary sinus (CS) leads after the development of endocarditis or device-related infection. METHODS: Patients with cardiac resynchronization therapy (CRT) devices who developed endocarditis or pocket infection over 5 years at Cleveland Clinic were included in the study. The groups were all patients with LVE leads versus CRT devices without epicardial leads that developed endocarditis or pocket infection. Mortality was assessed using the Social Security Death Index and re-infection was assessed by reviews of the medical record. RESULTS: Prospective extraction of the CRT device and leads occurred among all 50 patients with CS leads and 8 of the 14 patients with LVE leads. The survival rate was 92.9 versus 92 % and freedom from re-infection rate was 64.3 versus 80 % in the patients with LVE leads versus CS leads, respectively, over 1 year (P value = 0.918 and 0.226, respectively). At 3 years, the survival rate in LVE lead group was 92.9 % and freedom from re-infection rate was 64.3 % in comparison to survival rate of 90 % and freedom from re-infection rate of 68 % in the CS group (P value = 0.751 and 0.798, respectively). CONCLUSION: After development of endocarditis or pocket infection, no statistically significant differences were seen in mortality, or recurrent infection between patients with LVE leads and those with CS leads.

Incidence, management, and outcomes of the arteriovenous fistula complicating transvenous lead extraction.

BACKGROUND: An arteriovenous (AV) fistula is an infrequently reported complication of transvenous lead extraction (TLE), but may be under-recognized. OBJECTIVE: To determine the incidence, management, and outcomes of the AV fistula complicating TLE. METHODS: All TLE procedures from July 2001 to December 2012 were reviewed. RESULTS: Of 2471 patients who underwent TLE, the AV fistula occurred in 8 (0.3%; 6 pacemaker and 2 implantable cardioverter-defibrillator) procedures. Patients who developed an AV fistula had longer lead implant duration (11.8 [interquartile range 7.7] vs 5.2 [interquartile range 7.0] years) and were more likely to have required a powered sheath (8 of 8 [100%] vs 1392 of 2463 [56.5%]) compared to those who did not. Other procedural and demographic details did not discriminate. All patients had a continuous bruit along the anterior chest wall. Catheter angiography was more sensitive (100%) than computed tomography (75%) or ultrasound (25%) for confirming the diagnosis and identifying the vessels involved. One fistula closed spontaneously, while others were closed with covered stents (4) or surgical glue (1). One attempt at closure failed, and one was diagnosed postmortem. Mortality related to the AV fistula was 3 of 8 (37.5%). Patients who died all had structural heart disease. In the 5 patients with normal hearts, the AV fistula was well tolerated for up to 2 years. CONCLUSIONS: An AV fistula is an infrequent, though possibly under-recognized, complication of TLE. It requires a high index of suspicion for early diagnosis, may present late, and may be associated with significant morbidity and mortality in patients with structural heart disease.

Implantable cardioverter-defibrillator FDA safety advisories: Impact on patient mortality and morbidity.

BACKGROUND: A significant proportion of implantable cardioverter-defibrillators (ICDs) have been subject to Food and Drug Administration (FDA) advisories. The impact of device advisories on mortality or patient care is poorly understood. Although estimated risks of ICD generators under advisory are low, dependency on ICD therapies to prevent sudden death justifies the assessment of long-term mortality. OBJECTIVE: To test the association of FDA advisory status with long-term mortality. METHODS: The study was a retrospective, single-center review of clinical outcomes, including device malfunctions, in patients from implantation to either explant or death. Patients with ICDs first implanted at Cleveland Clinic between August 1996 and May 2004 who became subject to FDA advisories on ICD generators were identified. Mortality was determined by using the Social Security Death Index. RESULTS: In 1644 consecutive patients receiving first ICD implants, 704 (43%) became subject to an FDA advisory, of which 172 (10.5%) were class I and 532 (32.3%) were class II. ICDs were explanted before advisory notifications in 14.0% of class I and 10.1% of class II advisories. Among ICDs under advisory, 28 (4.0%) advisory-related and 15 non-advisory- related malfunctions were documented. Over a median follow-up of 70 months, 814 patients died. Kaplan-Meier 5-year survival rate was 65.6% overall, and 64.2, 61.1, and 69.3% in patients with no, class I, and class II advisories, respectively (P = .17). CONCLUSIONS: ICD advisories impacted 43% of the patients. Advisory-related malfunctions affected 4% within the combined advisory group. Based on a conservative management strategy, ICDs under advisory were not associated with increased mortality over a background of significant disease-related mortality.

Assessment of left atrial mechanics in patients with atrial fibrillation: comparison between two-dimensional speckle-based strain and velocity vector imaging.

BACKGROUND: Two-dimensional (2D) speckle tracking-derived left atrial (LA) strain (ε) facilitates comprehensive evaluation of LA contractile, reservoir, and conduit function; however, its dependence on the individual software used for assessment has not been evaluated. The aim of this study was to compare LA ε derived from two different speckle-tracking software technologies, Velocity Vector Imaging (VVI) and 2D speckle-tracking echocardiography (STE). METHODS: VVI-derived and 2D STE-derived global longitudinal LA ε and ε rate (SR) were directly compared in 127 patients (mean age, 62 ± 10 years) with atrial fibrillation. Peak negative, peak positive, and total ε (corresponding to LA contractile, conduit, and reservoir function) were measured during sinus rhythm. Late negative (LA contraction), peak positive (left ventricular systole), and early negative (left ventricular early diastole) SR were also measured. RESULTS: The measurement of LA ε and SR by both software was feasible in high proportions of patients (93% with VVI and 93% with 2D STE). The average analysis of ε(negative) was -7.24 ± 3.87% by VVI and -7.30 ± 3.37% by 2D STE (P = .84). The average analysis of ε(positive) was 14.52 ± 5.82% by VVI and 10.74 ± 4.51% by 2D STE (P < .01). The average analysis of ε(total) was 21.76 ± 7.39% by VVI and 18.04 ± 5.98% by 2D STE (P < .01). VVI-derived and 2D STE-derived ε(positive), ε(negative), and ε(total) had good correlations with one another (R = 0.79, R = 0.75, and R = 0.80), with low mean differences. Late negative, peak positive, and early negative SR were correlated less well (R = 0.78, R = 0.71, and R = 0.67). CONCLUSIONS: LA ε measurement using both VVI and 2D STE is feasible in a large proportion of patients in clinical practice. VVI and 2D STE provide comparable LA ε and SR measurements for LA contractile function.

Cost comparison of ablation versus antiarrhythmic drugs as first-line therapy for atrial fibrillation: an economic evaluation of the RAAFT pilot study.

INTRODUCTION: Radiofrequency ablation (RFA) has become an accepted therapy for atrial fibrillation (AF). The objective of this study was to perform an economic evaluation of RFA versus antiarrhythmic drug therapy (AAD) as first-line treatment of symptomatic paroxysmal AF. METHODS: To estimate and compare the costs of RFA versus AAD, a decision analytic model was developed using data on AF recurrence, hospitalization rates, AAD use, and treatment crossover rates derived directly from the Randomized Trial of RFA versus AAD as First-Line Treatment of Symptomatic Atrial Fibrillation (RAAFT). Resource utilization was modeled to reflect Canadian clinical practice in AF management. Unit costs of healthcare interactions were based on available Canadian government resources and published literature. Costs were assessed based on intention-to-treat. Total expected costs were computed to include initial treatment, hospital stay, physician fees, diagnostic tests, and outpatient visits. Sensitivity analyses were performed to account for the uncertainties. The study was conducted from the third party payer's perspective and costs are reported in 2005 Canadian dollars with 3% discount rate used in the analysis. RESULTS: During the 2-month blanking period following therapy selection, total average costs for RFA and AAD were $10,465 and $2,556, respectively; at 1-year follow-up, these were $12,823 and $6,053; and total 2-year cumulative total average costs were $15,303 and $14,392. Sensitivity analyses did not alter the results, suggesting the model is robust. CONCLUSIONS: RFA as first-line treatment strategy in patients with symptomatic paroxysmal AF was cost neutral 2 years after the initial procedure compared to AAD.

Endoscopic fiberoptic assessment of balloon occlusion of the pulmonary vein ostium in humans: comparison with phased-array intracardiac echocardiography.

BACKGROUND: Anatomic pulmonary vein (PV) variants may affect the ability to position balloon catheter systems at the left atrium (LA)-PV junction with complete circumferential contact, resulting in ineffective PV isolation. OBJECTIVES: This feasibility study was performed to assess the use of the fiberoptic endoscopic light ring balloon catheter (ELRBC) in accessing the PVs and achieving adequate contact at the LA-PV junction, as visualized by phased-array intracardiac echocardiography (ICE). METHODS: We enrolled five men (mean age 59 +/- 8 years) with drug-refractory atrial fibrillation. The ELRBC consisted of a 25-mm balloon catheter with an integral endoscope contained within the balloon and a custom deflectable sheath. At the end of conventional PV isolation, the ELRBC was inserted into the LA in an attempt to position the balloon at each PV ostium. The real position of the ELRBC at this level was assessed by ICE in all patients. RESULTS: All but two PVs (right inferior PVs) (89%) were accessed with the ELRBC in a mean time of 17 +/- 3 minutes, and complete circumferential contact was visualized with the fiberoptic endoscopic component in 15 of 16 PVs accessed (94%). Contact was also confirmed by the absence of color Doppler flow through the balloon-occluded PV, as seen on ICE. On two occasions a gap was seen with the fiberoptic endoscope and visualized by the ICE only after optimization of the echo window. No complications were observed. CONCLUSIONS: The ELRBC is able to access the PV without complications. The endoscope and ICE were complementary for positioning of the balloon at the LA-PV junction and for the definition of circumferential contact.