Assessment of left atrial fibrosis progression in canines following rapid ventricular pacing using 3D late gadolinium enhanced CMR images.

BACKGROUND: Atrial fibrillation (AF) is associated with extracellular matrix (ECM) remodelling and often coexists with myocardial fibrosis (MF); however, the causality of these conditions is not well established. OBJECTIVE: We aim to corroborate AF to MF causality by quantifying left atrial (LA) fibrosis in cardiac magnetic resonance (CMR) images after persistent rapid ventricular pacing and subsequent AF using a canine model and histopathological validation. METHODS: Twelve canines (9 experimental, 3 control) underwent baseline 3D LGE-CMR imaging at 3T followed by insertion of a pacing device and 5 weeks of rapid ventricular pacing to induce AF (experimental) or no pacing (control). Following the 5 weeks, pacing devices were removed to permit CMR imaging followed by excision of the hearts and histopathological imaging. LA myocardial segmentation was performed manually at baseline and post-pacing to permit volumetric %MF quantification using the image intensity ratio (IIR) technique, wherein fibrosis was defined as pixels > mean LA myocardium intensity + 2SD. RESULTS: Volumetric %MF increased by an average of 2.11 ± 0.88% post-pacing in 7 of 9 experimental dogs. While there was a significant difference between paired %MF measurements from baseline to post-pacing in experimental dogs (P = 0.019), there was no significant change in control dogs (P = 0.019 and P = 0.5, Wilcoxon signed rank tests). The median %MF for paced animals was significantly greater than that of non-paced dogs at the 5-week post-insertion time point (P = 0.009, Mann Whitney U test). Histopathological imaging yielded an average %MF of 19.42 ± 4.80% (mean ± SD) for paced dogs compared to 1.85% in one control dog. CONCLUSION: Persistent rapid ventricular pacing and subsequent AF leads to an increase in LA fibrosis volumes measured by the IIR technique; however, quantification is limited by inherent image acquisition parameters and observer variability.

Atrial flutter and atrial fibrillation ablation - sequential or combined? A cost-benefit and risk analysis of primary prevention pulmonary vein ablation.

BACKGROUND: Recent studies have tested the hypothesis that preventive pulmonary vein isolation (PVI) at time of atrial flutter ablation in patients who have not had atrial fibrillation (AF) will reduce future incidence of AF. OBJECTIVE: To model relative procedural costs, risks, and benefits of sequential versus combined ablation strategies. METHODS: The decision model compares a sequential ablation strategy of atrial flutter ablation, followed by future PVI if necessary, with an initial combined flutter and preventive PVI ablation strategy. Assumptions are AF incidence 20% per year, PVI success rate 70%, PVI complication rate 4%, atrial flutter complication rate 1%, and costs $13,056 for PVI and $8,466 for atrial flutter ablation. RESULTS: The sequential ablation strategy is less expensive, at 1.4 vs 1.6 expected flutter ablation equivalents (FAE) ($11,852 vs $13,545) per patient, and entails less average risk, at 2% vs 4%. A combined ablation strategy is more expensive if the relative cost of PVI is more than 24.6% higher than atrial flutter ablation. A combined ablation strategy has higher total risk if PVI procedural risk is 24.6% more than atrial flutter ablation. CONCLUSIONS: Under base case assumptions of relative cost of PVI to flutter ablation 1.5 and relative risk 4, a sequential ablation approach has less total expected cost and less expected risk. There appears to be no compelling reason to adopt a combined ablation approach into standard practice. Nomograms are presented to allow the reader to assess which strategy is preferred according to local relative costs and risk.

A detailed description and assessment of outcomes of patients with hospital recorded QTc prolongation.

Corrected QT (QTc) interval prolongation has been shown to be an independent predictor of mortality in many clinical settings and is a common finding in hospitalized patients. The causes and outcomes of patients with extreme QTc interval prolongation during a hospital admission are poorly described. The aim of this study was to prospectively identify patients with automated readings of QTc intervals >550 ms at 1 academic tertiary hospital. One hundred seventy-two patients with dramatic QTc interval prolongation (574 ± 53 ms) were identified (mean age 67.6 ± 15.1 years, 48% women). Most patients had underlying heart disease (60%), predominantly ischemic cardiomyopathy (43%). At lease 1 credible and presumed reversible cause associated with QTc interval prolongation was identified in 98% of patients. The most common culprits were QTc interval-prolonging medications, which were deemed most responsible in 48% of patients, with 25% of these patients taking ≥2 offending drugs. Two patients were diagnosed with congenital long-QT syndrome. Patients with electrocardiograms available before and after hospital admission demonstrated significantly lower preadmission and postdischarge QTc intervals compared with the QTc intervals recorded in the hospital. In conclusion, in-hospital mortality was high in the study population (29%), with only 4% of patients experiencing arrhythmic deaths, all of which were attributed to secondary causes.

Impact of routine transoesophageal echocardiography on safety, outcomes, and cost of pulmonary vein ablation: inferences drawn from a decision analysis model.

AIMS: The practice of routine vs. selective transoesophageal echocardiography (TEE) surveillance for left atrial appendage or intracavitary thrombus prior to pulmonary vein isolation (PVI) varies widely as evidence to guide this decision in terms of important clinical outcomes is lacking. METHODS AND RESULTS: We constructed a decision analysis model to compare the cost-effectiveness of routine TEE for detection of left atrial thrombus vs. no TEE. The model incorporated health outcomes and costs. Markov methodology was used to follow patients as they transition through varying health states. We examined a hypothetical cohort of patients with symptomatic atrial fibrillation suitable for PVI, and expected outcomes were modelled over a period of 2 years. Simulated patients (SPs) undergoing a strategy of a routine TEE experienced significantly fewer transient ischemic attacks (TIAs) [OR 0.28 (0.22-0.37)], and debilitating strokes [OR 0.23 (0.15-0.33)]. Routine TEE led to an absolute risk reduction for stroke of 1.2% [number needed to treat (NNT) 84 (79-100)] and 1.9% for TIA [NNT 53 (48-59)]. The incremental cost-effectiveness ratio (ICER) for TEE was $226,608 per quality-adjusted life year (QALY). The ICER for TEE among high-risk SPs, with pre-existing clot in the left atrium, was $2232 per QALY. CONCLUSION: Decision analysis and microsimulation suggest that routine use of TEE in an unselected population prior to PVI lowers the incidence of cerebral thrombo-embolic events but with considerable cost per QALY.

Systematic assessment of patients with unexplained cardiac arrest: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER).

BACKGROUND: Cardiac arrest without evident cardiac disease may be caused by subclinical genetic conditions. Provocative testing to unmask a phenotype is often necessary to detect primary electrical disease, direct genetic testing, and perform family screening. METHODS AND RESULTS: Patients with apparently unexplained cardiac arrest and no evident cardiac disease (normal cardiac function on echocardiogram, no evidence of coronary artery disease, and a normal ECG) underwent systematic evaluation that included cardiac magnetic resonance imaging, signal-averaged ECG, exercise testing, drug challenge, and selective electrophysiological testing. Diagnostic criteria were based on accepted criteria or provocation of the characteristic clinical features for long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization, arrhythmogenic right ventricular cardiomyopathy, coronary spasm, and myocarditis. Sixty-three patients in 9 centers were enrolled (age 43.0+/-13.4 years, 29 women). A diagnosis was obtained in 35 patients (56%): Long-QT syndrome in 8, catecholaminergic polymorphic ventricular tachycardia in 8, arrhythmogenic right ventricular cardiomyopathy in 6, early repolarization in 5, coronary spasm in 4, Brugada syndrome in 3, and myocarditis in 1. Targeted genetic testing demonstrated evidence of causative mutations in 9 (47%) of 19 patients. Screening of 64 family members of these patients identified 15 affected individuals who were treated (24%). The remaining 28 patients (44%) were considered to have idiopathic ventricular fibrillation. CONCLUSIONS: Systematic clinical testing, including drug provocation and advanced imaging, results in unmasking of the cause of apparently unexplained cardiac arrest in >50% of patients. This approach assists in directing genetic testing to diagnose genetically mediated arrhythmia syndromes, which results in successful family screening.

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.

Ejection fraction assessment and survival: an analysis of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).

BACKGROUND: Ejection fraction (EF) is an important method of mortality prediction among cardiac patients, and has been used to identify the highest risk patients for enrollment in the defibrillator primary prevention trials. Evidence suggests that measures of EF by different imaging modalities may not be equivalent. In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), the type of imaging modality for EF assessment was not mandated. METHODS: Baseline assessment of EF was performed using either echocardiography, radionuclide angiography (RNA), or contrast angiography. Multivariable analysis using a Cox proportional hazards model was used to examine whether the modality of assessing EF affected the likelihood of survival. RESULTS: Among the 2,521 patients enrolled in SCD-HeFT, EF was measured by RNA in 616 (24%), echocardiography in 1,469 (58%), and contrast angiography in 436 (17%). Mean EF as measured by RNA was 25.1% +/- 6.9%; by echocardiography, 23.8 +/- 6.9%; and by angiography, 21.9 +/- 6.9%. These measures were significantly different (P < .001), and each pairwise comparison differed significantly (P < .001 for each). Multivariable analysis showed no significant difference in survival between patients enrolled based on RNA versus echocardiography (HR 1.06, 95% CI 0.88-1.28), RNA versus angiography (HR 1.25, 95% CI 0.97-1.62), or echocardiography versus angiography (HR 1.18, 95% CI 0.94-1.48). CONCLUSIONS: Among patients enrolled in SCD-HeFT, the distribution of ejection fractions measured by radionuclide angiography differed from those measured by echocardiography or contrast angiograms. Survival did not differ according to modality of EF assessment.

Cost of preimplantation cardiac imaging in patients referred for a primary-prevention implantable cardioverter-defibrillator.

Recent guidelines have focused on ejection fraction cut-off values to determine eligibility for primary-prevention implantable cardioverter-defibrillators (ICDs). Clinical trials that led to the guidelines used varying techniques for ejection fraction assessment, including echocardiography and multigated acquisition (MUGA) scan. A prospective cohort study to determine the economic attractiveness of repeated echocardiography and MUGA scanning during the evaluation process of patients referred for consideration of a primary-prevention ICD was undertaken. From January 2005 to December 2006, data were collected for patients aged >18 years with ejection fraction <30% referred for a primary-prevention ICD based on referral assessment of heart function in any form. Costs based on the 2006 Ontario Health Insurance Plan fee schedule were determined for clinical assessment, echocardiography, MUGA scanning, and ICD implantation in patients who remained eligible based on MUGA ejection fraction. The 100 patients (age 61.1 +/- 10.2 years; 78 men) assessed for primary-prevention ICD implantation had an ejection fraction of 28.9 +/- 12.3% using MUGA scan. Thirty-one of 100 patients (31%) had an ejection fraction >30% and were no longer eligible for an ICD. Although imaging increased preimplantation cost from dollars 130 to dollars 536 per patient, averted inappropriate ICDs decreased the overall per-patient cost from dollars 20,914 to dollars 14,877. Despite an additional testing cost of dollars 40,599, the overall cost savings was dollars 603,722 in the 100 patients, with a cost savings of dollars 6,037 per patient. In conclusion, verification of ejection fraction identified a significant proportion of patients who were not eligible for an ICD.

Is defibrillation testing still necessary? A decision analysis and Markov model.

OBJECTIVE: To assess the impact of defibrillation threshold (DFT) testing of implanted cardioverter-defibrillators (ICDs) on survival. BACKGROUND: DFT testing is generally performed during implantation of ICDs to assess sensing and termination of ventricular fibrillation. It is common clinical practice to defibrillate ventricular fibrillation twice at an output at least 10 J below the maximum output of the device, providing a 10 J safety margin. However, there are few data regarding impact of DFT testing on outcomes. METHODS: Decision analysis and Monte Carlo simulation were used to assess expected outcomes of DFT testing. Survival of a hypothetical cohort of patients was assessed according to two strategies-routine DFT testing at time of ICD implant versus no DFT testing. Assumptions in the model were varied over a range of reasonable values to assess outcomes under a variety of scenarios. RESULTS: Five-year survival with DFT and no-DFT strategies were similar at 59.72% and 59.36%, respectively. The results were not sensitive to changing risk estimates for arrhythmia incidence and safety margin. Results of the Monte Carlo simulation were qualitatively similar to the base case scenario and consistent with a small and nonsignificant survival advantage with routine DFT testing. CONCLUSIONS: The impact of DFT testing on 5-year survival in ICD patients, if it exists, is small. Survival appears higher with DFT testing as long as annual risk of lethal arrhythmia or the risk of a narrow safety margin is at least 5%, although the incremental benefit is marginal and 95% confidence intervals cross zero. A prospective randomized study of DFT testing in modern devices is warranted.

When should we recommend catheter ablation for patients with the Wolff-Parkinson-White syndrome?

PURPOSE OF REVIEW: Catheter ablation has been proven as very effective and safe therapy for patients with symptomatic Wolff-Parkinson-White (WPW) syndrome. Its application in asymptomatic individuals with WPW pattern remains controversial. This review will elaborate on the role of catheter ablation in symptomatic and asymptomatic patients with WPW pattern on ECG. RECENT FINDINGS: Several recent prospective studies evaluated invasive risk stratification followed by prophylactic catheter ablation in asymptomatic patients with WPW pattern. Inducibility of arrhythmias in these patients during invasive electrophysiological study was shown to predict the development of future symptomatic arrhythmias. Although ablation of accessory pathways performed in 'inducible' patients decreased the incidence of subsequent symptomatic arrhythmias, the studies were not powered to detect a reduction in life-threatening arrhythmias. SUMMARY: Radiofrequency catheter ablation remains the first-line therapy for patients with symptomatic WPW syndrome. Invasive electrophysiological study and possible ablation of accessory pathway may be offered to well informed asymptomatic individuals with WPW if they are willing to trade the very small risk of subsequent sudden death or incapacity for a small immediate procedural risk of serious complications or death. Asymptomatic patients may require invasive risk stratification and possible catheter ablation for important social or professional reasons.

Noninvasive assessment of atrial substrate change after wide area circumferential ablation: a comparison with segmental pulmonary vein isolation.

BACKGROUND: The wide area circumferential ablation (WACA) approach to atrial fibrillation is thought to result in 'substrate modification' perhaps related to autonomic denervation. We examined this prospectively by comparing WACA and segmental pulmonary vein isolation (PVI) using noninvasive surrogate markers. METHODS: Heart rate variability (HRV) and signal averaged P wave (SAPW) data were derived from high-resolution (HR) recordings ('SpiderView' ELA Medical) made in sinus rhythm immediately before and 24 hours after ablation. RESULTS: Forty patients recruited (20 WACA; 20 PVI); cohorts were comparable. WACA caused marked SAPW change: P wave duration (PWD) (149[4.6] ms to 160[5.9] ms; P = 0.003), root mean square (RMS) (4.4[0.4]microV to 2.8[0.4]; P = 0.001) and energy content (30-150 Hz; 20.4 [3.6]microV(2)/s to 13.7[2.4]; P = 0.001). No significant change was seen after PVI. Heart rate increased after WACA and PVI (61.4 to 73.5 [P = 0.001]; 69.5 to 75.0 [P = 0.07], respectively). HRV was significantly influenced after WACA: low frequency power (LF) 5.7(0.4) to 3.6(0.4); P = 0.001), high-frequency power (HF) 4.6(0.4)-3.4(0.3); P = 0.024, and after PVI: LF 5.4(0.3) to 4.3(0.3); P = 0.024. HF: 4.4(0.4) to 3.0(0.4); P = 0.018). CONCLUSIONS: HR recordings exhibit change in HRV after WACA and PVI. Marked change in both HRV and SAPW is observed after WACA. SAPW variables provide a measure of atrial substrate change after WACA unrelated to autonomic denervation.

Cost comparison of catheter ablation and medical therapy in atrial fibrillation.

INTRODUCTION: There is emerging evidence for clinical superiority of catheter ablation over rate and rhythm control strategies in paroxysmal atrial fibrillation (PAF). The objective of this study was to compare costs related to medical therapy versus catheter ablation for PAF in Ontario (Canada). METHODS: Costs related to medical therapy in the analysis included the cost of anticoagulation, rate and rhythm control medications, noninvasive testing, physician follow-up visits, and hospital admissions, as well as the cost of complications related to this management strategy. Costs related to catheter ablation were assumed to include the cost of the ablation tools (electroanatomic mapping or intracardiac echocardiography-guided pulmonary vein ablation), hospital and physician billings, and costs related to periprocedural medical care and complications. Costs related to these various elements were obtained from the Canadian Registry of Atrial Fibrillation (CARAF), government fee schedules, and published data. Sensitivity analyses looking at a range of initial success rates (50-75%) and late attrition rates (1-5%), prevalence of congestive heart failure (CHF) (20-60%), as well as discounting varying from 3% to 5% per year were performed. RESULTS: The cost of catheter ablation ranged from $16,278 to $21,294, with an annual cost of $1,597 to $2,132. The annual cost of medical therapy ranged from $4,176 to $5,060. Costs of ongoing medical therapy and catheter ablation for PAF equalized at 3.2-8.4 years of follow-up. CONCLUSION: Catheter ablation is a fiscally sensible alternative to medical therapy in PAF with cost equivalence after 4 years.

Utility and cost effectiveness of temporary pacing using active fixation leads and an externally placed reusable permanent pacemaker.

Active-fixation leads and externally placed permanent pacemakers for temporary pacing may be beneficial because they allow for greater patient mobility and comfort and increased reliability of lead placement. The relative cost of this form of pacing may be prohibitive unless markedly prolonged pacing is required. Twenty patients (63 +/- 15 years of age, 15 men) underwent external "temporary permanent" pacing. Pacing duration and associated complications were recorded. Cost models were then constructed using data from the London Health Sciences Center business unit to compare the cost of traditional temporary pacing and this technique using a Medtronic KSR903 pacemaker and 5,076 leads. Direct costs were calculated based on the 2005 Ontario Health Insurance Plan fee schedule, combined with calculation of labor and materials. Pacing was undertaken for a median of 2 days (range 2 to 83). There were no complications during implantation or pacing or after system removal. Sensing was lost in only 1 instance, which was reprogrammed uneventfully. Cost comparison showed that, although active-fixation lead placement was initially more costly ($798.71 vs $471.91), the added reliability of the permanent system allowed ward telemetry instead of cardiac care unit monitoring. This resulted in cost equivalence after only 18 hours and conferred a cost savings of $456 per 24-hour period thereafter. As a result, a savings of $585.20 is projected for a modeled patient after 48 hours of temporary pacing. In conclusion, temporary pacing using this technique is a reliable and comfortable alternative to traditional temporary pacing and appears to be a cost-effective temporary pacing option after 18 hours.

Is ambulatory monitoring for "community-acquired" syncope economically attractive? A cost-effectiveness analysis of a randomized trial of external loop recorders versus Holter monitoring.

BACKGROUND: Out patient ambulatory monitoring is often performed in patients with syncope that present in the primary care setting to include or exclude an arrhythmia. The cost-effectiveness of 2 monitoring strategies was assessed in a prospective randomized trial. METHODS: One hundred patients referred for ambulatory monitoring with syncope or presyncope were randomized to a 1-month external loop recorder (n = 49) or 48-hour Holter monitor (n = 51). Patients were offered crossover if there was failed activation or no symptom recurrence. The primary end point was symptom-rhythm correlation during monitoring. Direct costs were calculated based on the 2003 Ontario Health Insurance Plan fee schedule, combined with calculation of labor, materials, service, and overhead for diagnostic testing and related equipment. RESULTS: Before enrollment, the cost of all previous health care resource use was USD 472 +/- USD 397 (range USD 21-USD 1965). In the loop recorder group, 63% of patients had symptom recurrence and successful activation, compared with 24% in the Holter group (P < .0001). The cost per Holter was USD 177.64, and per loop recorder, USD 533.56, with a similar cost per diagnosis with the 2 techniques. The incremental cost-effectiveness ratio of the loop recorder was USD 901.74 per extra successful diagnosis. A strategy of Holter followed by offered loop recorder trended toward lower cost than initial loop recorder followed by Holter (USD 481 +/- USD 267 vs USD 551 +/- USD 83, P = .08), but was associated with a lower overall diagnostic yield (49% vs 63%) and a resultant higher cost per diagnosis (USD 982 vs USD 871, P = .08). Bootstrapping suggested that 90% of incremental cost-effectiveness ratios were less than USD 1250. CONCLUSION: Despite the increased upfront cost of external loop recorders, the marked improvement in diagnostic yield offsets the cost. External loop recorders are an economically attractive alternative. First-line use of external loop recorders in patients with "community-acquired" syncope and presyncope should be considered to optimize diagnostic yield given its value.

Cost implications of testing strategy in patients with syncope: randomized assessment of syncope trial.

OBJECTIVES: We sought to assess the cost implications of two investigation strategies in patients with unexplained syncope. BACKGROUND: Establishing a diagnosis in patients with unexplained syncope is complicated by infrequent and unpredictable events. The cost-effectiveness of immediate, prolonged monitoring as an alternative to conventional diagnostic strategies has not been studied. METHODS: Sixty patients (age 66 +/- 14 years; 33 males) with unexplained syncope and LV ejection fraction >35% were randomized to conventional testing with an external loop recorder, tilt and electrophysiologic (EP) testing, or prolonged monitoring with an implantable loop recorder with one-year monitoring. If patients remained undiagnosed after their assigned strategy, they were offered a crossover to the alternate strategy. Cost analysis of the two testing strategies was performed. RESULTS: Fourteen of 30 patients who were being monitored were diagnosed at a cost of 2,731 Canadian dollars +/- 285 Canadian dollars per patient and 5,852 Canadian dollars +/- 610 Canadian dollars per diagnosis. In contrast, only six of 30 conventional patients were diagnosed (20% vs. 47%, p = 0.029), at a cost of 1,683 Canadian dollars +/- 505 Canadian dollars per patient (p < 0.0001) and 8,414 Canadian dollars +/- 2,527 Canadian dollars per diagnosis (p < 0.0001). After crossover, a diagnosis was obtained in 1 of 5 patients undergoing conventional testing, compared with 8 of 21 patients who completed monitoring (20% vs. 38%, p = 0.44). Overall, a strategy of monitoring followed by tilt and EP testing was associated with a diagnostic yield of 50%, at a cost of 2,937 Canadian dollars +/- 579 Canadian dollars per patient and 5,875 Canadian dollars +/- 1,159 Canadian dollars per diagnosis. Conventional testing followed by monitoring was associated with a diagnostic yield of 47%, at a greater cost of 3,683 Canadian dollars +/- 1,490 Canadian dollars per patient (p = 0.013) and a greater cost per diagnosis (7,891 Canadian dollars +/- 3,193 Canadian dollars, p = 0.002). CONCLUSIONS: A strategy of primary monitoring is more cost-effective than conventional testing in establishing a diagnosis in recurrent unexplained syncope.