Estimating the real world daily usage and cost for exenatide twice daily and liraglutide in Germany, the Netherlands, and the UK based on volumes dispensed by pharmacies.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are indicated for improvement of glycemic control in adults with type 2 diabetes. Cost is one aspect of treatment to be considered, in addition to clinical benefits, when selecting optimal therapy for a patient. The objective of this study was to estimate the average dose usage and real world daily cost of the GLP-1 receptor agonists, exenatide twice daily and liraglutide once daily, in Germany, the Netherlands, and the UK. METHODS: Administrative databases were used to source the data from longitudinal records of dispensed prescriptions. Data were extracted from the IMS Longitudinal Prescription database which captures details of prescriptions dispensed in pharmacies. Information on the dispensed quantity of each product was used to estimate average daily usage per patient. Daily dose usage was multiplied by the public price per unit to estimate daily cost. RESULTS: The dispensed volume in Germany corresponded to a mean dispensed daily dose of 16.81 µg for exenatide twice daily and 1.37 mg for liraglutide (mean daily cost €4.02 and €4.54, respectively). In the Netherlands, average dispensed daily doses of 17.07 µg and 1.49 mg were observed for exenatide twice daily and liraglutide (mean daily cost €3.05 and €3.97, respectively). In the UK, the mean dispensed volume corresponded to a daily usage of 20.49 µg for exenatide twice daily and 1.50 mg for liraglutide (mean daily cost £2.53 and £3.28, respectively). CONCLUSION: Estimates of average daily dispensed doses of GLP-1 receptor agonists derived from pharmacy data in real world settings corresponded to the dosing recommendation of the summaries of product characteristics. Nevertheless, the mean daily cost of exenatide twice daily was lower than that of liraglutide in Germany, the Netherlands, and the UK. Such estimates can be used to inform health care decision-makers on the real world usage and cost of medications effective in achieving glycemic control in patients with type 2 diabetes.

Dark regions of no-reflow on late gadolinium enhancement magnetic resonance imaging result in scar formation after atrial fibrillation ablation.

OBJECTIVES: The aim of this study was to assess acute ablation injuries seen on late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) immediately post-ablation (IPA) and the association with permanent scar 3 months post-ablation (3moPA). BACKGROUND: Success rates for atrial fibrillation catheter ablation vary significantly, in part because of limited information about the location, extent, and permanence of ablation injury at the time of procedure. Although the amount of scar on LGE MRI months after ablation correlates with procedure outcomes, early imaging predictors of scar remain elusive. METHODS: Thirty-seven patients presenting for atrial fibrillation ablation underwent high-resolution MRI with a 3-dimensional LGE sequence before ablation, IPA, and 3moPA using a 3-T scanner. The acute left atrial wall injuries on IPA scans were categorized as hyperenhancing (HE) or nonenhancing (NE) and compared with scar 3moPA. RESULTS: Heterogeneous injuries with HE and NE regions were identified in all patients. Dark NE regions in the left atrial wall on LGE MRI demonstrate findings similar to the "no-reflow" phenomenon. Although the left atrial wall showed similar amounts of HE, NE, and normal tissue IPA (37.7 ± 13%, 34.3 ± 14%, and 28.0 ± 11%, respectively; p = NS), registration of IPA injuries with 3moPA scarring demonstrated that 59.0 ± 19% of scar resulted from NE tissue, 30.6 ± 15% from HE tissue, and 10.4 ± 5% from tissue identified as normal. Paired t-test comparisons were all statistically significant among NE, HE, and normal tissue types (p < 0.001). Arrhythmia recurrence at 1-year follow-up correlated with the degree of wall enhancement 3moPA (p = 0.02). CONCLUSIONS: Radiofrequency ablation results in heterogeneous injury on LGE MRI with both HE and NE wall lesions. The NE lesions demonstrate no-reflow characteristics and reveal a better predictor of final scar at 3 months. Scar correlates with procedure outcomes, further highlighting the importance of early scar prediction.

Atrial fibrosis helps select the appropriate patient and strategy in catheter ablation of atrial fibrillation: a DE-MRI guided approach.

UNLABELLED: MRI for AF Patient Selection and Ablation Approach. INTRODUCTION: Left atrial (LA) fibrosis and ablation related scarring are major predictors of success in rhythm control of atrial fibrillation (AF). We used delayed enhancement MRI (DE-MRI) to stratify AF patients based on pre-ablation fibrosis and also to evaluate ablation-induced scarring in order to identify predictors of a successful ablation. METHODS AND RESULTS: One hundred and forty-four patients were staged by percent of fibrosis quantified with DE-MRI, relative to the LA wall volume: minimal or Utah stage 1; <5%, mild or Utah stage 2; 5-20%, moderate or Utah stage 3; 20-35%, and extensive or Utah stage 4; >35%. All patients underwent pulmonary vein (PV) isolation and posterior wall and septal debulking. Overall, LA scarring was quantified and PV antra were evaluated for circumferential scarring 3 months post ablation. LA scarring post ablation was comparable across the 4 stages. Most patients had either no (36.8%) or 1 PV (32.6%) antrum circumferentially scarred. Forty-two patients (29%) had recurrent AF over 283 ± 167 days. No recurrences were noted in Utah stage 1. Recurrence was 28% in Utah stage 2, 35% in Utah stage 3, and 56% in Utah stage 4. Recurrence was predicted by circumferential PV scarring in Utah stage 2 and by overall LA wall scarring in Utah stage 3. No recurrence predictors were identified in Utah stage 4. CONCLUSIONS: Circumferential PV antral scarring predicts ablation success in mild LA fibrosis, while posterior wall and septal scarring is needed for moderate fibrosis. This may help select the proper candidate and strategy in catheter ablation of AF.

Echocardiographic left atrial reverse remodeling after catheter ablation of atrial fibrillation is predicted by preablation delayed enhancement of left atrium by magnetic resonance imaging.

BACKGROUND: Atrial fibrosis is a hallmark of atrial structural remodeling (SRM) and leads to structural and functional impairment of left atrial (LA) and persistence of atrial fibrillation (AF). This study was conducted to assess LA reverse remodeling after catheter ablation of AF in mild and moderate-severe LA SRM. METHODS: Catheter ablation was performed in 68 patients (age 62 ± 14 years, 68% males) with paroxysmal (n = 26) and persistent (n = 42) AF. The patients were divided into group 1 with mild LA SRM (<10%, n = 31) and group 2 with moderate-severe LA SRM (>10%, n = 37) by delayed enhancement magnetic resonance imaging (DEMRI). Two-dimensional echocardiography, LA strain, and strain rate during left ventricular systole by velocity vector imaging were performed pre and at 6 ± 3 months postablation. The long-term outcome was monitored for 12 months. RESULTS: Patients in group 1 were younger (57 ± 15 vs 66 ± 13 years, P = .009) with a male predominance (80% vs 57%, P < .05) as compared to group 2. Postablation, group 1 had significant increase in average LA strain (Δ↑: 14% vs 4%, P < .05) and strain rate (Δ↑: 0.5 vs 0.1 cm/s, P < .05) as compared to group 2. There was a trend toward more patients with persistent AF in group 2 (68% vs 55%, P = .2), but it was not statistically significant. Group 2 had more AF recurrences (41% vs 16%, P = .02) at 12 months after ablation. CONCLUSION: Mild preablation LA SRM by DEMRI predicts favorable LA structural and functional reverse remodeling and long-term success after catheter ablation of AF, irrespective of the paroxysmal or persistent nature of AF.

Evaluation of the left atrial substrate in patients with lone atrial fibrillation using delayed-enhanced MRI: implications for disease progression and response to catheter ablation.

BACKGROUND: Lone atrial fibrillation (AF) is thought to be a benign type or an early stage of the disease. OBJECTIVE: This study sought to compare the left atrium (LA) substrate using delayed-enhanced magnetic resonance imaging (DE-MRI) in patients with lone AF versus those with comorbidities. METHODS: Forty of 333 included patients met criteria for lone AF. All patients underwent DE-MRI to quantify atrial fibrosis as a marker for structural remodeling (SRM) and underwent catheter ablation. Based on the degree of SRM, patients were staged into 4 groups: Utah I (≤5% LA wall enhancement), Utah II (>5% to ≤20%), Utah III (>20% to ≤35%), or Utah IV (>35%). RESULTS: Distribution in Utah I to IV was comparable in patients with lone AF and non-lone AF. In both groups, a number of patients showed extensive SRM. Mean enhancement (14.08 ± 8.94 vs. 16.94 ± 11.37) was not significantly different between the 2 groups (P = .0721). In the lone AF group, catheter ablation was successful in suppressing AF in all of Utah I, 81.82% of Utah II, 62.5% of Utah III, and none of Utah IV patients. Similar results were achieved in the non-lone AF group. Outcome after ablation was significantly dependent on the SRM of the LA (P < .001). CONCLUSION: The degree of LA structural remodeling as detected using DE-MRI is independent of AF type and associated comorbidities. Selecting appropriate treatment candidates based on the quality and quantity of atrial fibrosis using DE-MRI would improve procedural outcome and avoid unnecessary intervention.

Evaluation of left atrial lesions after initial and repeat atrial fibrillation ablation: lessons learned from delayed-enhancement MRI in repeat ablation procedures.

BACKGROUND: We evaluated scar lesions after initial and repeat catheter ablation of atrial fibrillation (AF) and correlated these regions to low-voltage tissue on repeat electroanatomic mapping. We also identified gaps in lesion sets that could be targeted and closed during repeat procedures. METHODS AND RESULTS: One hundred forty-four patients underwent AF ablation and received a delayed-enhancement MRI at 3 months after ablation. The number of pulmonary veins (PV) with circumferential lesions were assessed and correlated with procedural outcome. Eighteen patients with AF recurrence underwent repeat ablation. MRI scar regions were compared with electroanatomic maps during the repeat procedure. Regions of incomplete scar around the PVs were then identified and targeted during repeat ablation to ensure complete circumferential lesions. After the initial procedure, complete circumferential scarring of all 4 PV antrum (PVA) was achieved in only 7% of patients, with the majority of patients (69%) having <2 completely scarred PVA. After the first procedure, the number of PVs with complete circumferential scarring and total left atrial wall (LA) scar burden was associated with better clinical outcome. Patients with successful AF termination had higher average total left atrial wall scar of 16.4%+/-9.8 (P=0.004) and percent PVA scar of 66.2+/-25.4 (P=0.01) compared with patients with AF recurrence who had an average total LA wall scar 11.3%+/-8.1 and PVA percent scar 50.0+/-24.7. In patients who underwent repeat ablation, the PVA scar percentage was 56.1%+/-21.4 after the first procedure compared with 77.2%+/-19.5 after the second procedure. The average total LA scar after the first ablation was 11.0%+/-4.1, whereas the average total LA scar after second ablation was 21.2%+/-7.4. All patients had an increased number of completely scarred pulmonary vein antra after the second procedure. MRI scar after the first procedure and low-voltage regions on electroanatomic mapping obtained during repeat ablation demonstrated a positive quantitative correlation of R(2)=0.57. CONCLUSIONS: Complete circumferential PV scarring difficult to achieve but is associated with better clinical outcome. Delayed-enhancement MRI can accurately define scar lesions after AF ablation and can be used to target breaks in lesion sets during repeat ablation.