Abstract Background Previous, small studies have found that the effectiveness of catheter ablation among patients with atrial fibrillation (AF) is affected by frailty. However, whether the symptom burden after catheter ablation varies according to frailty remains uncertain. Purpose We aimed to assess whether severity of patient frailty modified the recurrence of AF in the year after first-time catheter ablation for AF including proportion of hospital admissions with AF. Methods We identified patients with a first-time catheter ablation for AF (Jan. 1st 2010-Dec. 31st 2018) from the Danish National Ablation Registry, and eligible for one year of follow-up. Patient comorbidities and concomitant pharmacotherapy were identified using Danish nationwide registries. The patients’ Hospital Frailty Risk Score was calculated using diagnosis codes, and patients were grouped according to cut points of low (<5), intermediate (5-10), and high-risk (>10) frailty. Multivariable Cox proportional-hazards analyses were performed for comparison of associated factors for the risk of recurrence of AF during one year of follow-up after a 3-month blanking period. McNemars test was used for comparison of AF hospital admission rates before and after catheter ablation. Results Among 3,638 patients treated with first-time catheter ablation for AF (median age 62.4 years [Q1,Q3=55.1,68.5 years], 72.8% male), 89.0% had low-risk frailty, 9.4% had intermediate-risk frailty and 1.6% had high-risk frailty. At one year follow-up, 546 (15.0%) patients had recurrence of AF (hospital admission with AF or treatment with electrical cardioversion). Both intermediate-risk frailty patients (HR 1.56, CI: 1.22-2.00, p<0.001) and high-risk frailty patients (HR 2.13, CI: 1.30-3.49, p=0.003) had a significantly increased risk of recurrence of AF during one year of follow-up compared with patients with a low-risk frailty score. All patients across frailty groups had a 5-fold decrease in AF hospital admissions in the year after catheter ablation (15%) compared with the year before (68%) (p<0.001). Patients with high-risk frailty had a more than 3-fold reduction of AF hospital admissions in the year after catheter ablation (28%) compared with the year before (88%) (p<0.001) (Figure 1). During one year follow-up, 35 patients (1.0%) died. Conclusion Patients with high-risk frailty had a 3-fold decrease while all patients across frailty groups had a 5-fold decrease in AF hospital admissions in the year after catheter ablation compared with the year before. Thus, indicating a lower symptom burden after catheter ablation. Nevertheless, intermediate-risk and high-risk frailty was associated with significantly higher recurrence rates of AF one year after first-time catheter ablation for AF compared with low-risk frailty patients. Patient frailty should be considered when selecting patients eligible for ablation in order to improve patient outcomes.

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is the most common clinical arrhythmia. Pulmonary vein isolation (PVI) by catheter ablation has become a cornerstone in the treatment of AF. Serious complications to PVI have been reported to be at an acceptable level and risk of death after AF ablation is low. Purpose In a contemporary nationwide cohort of patients undergoing first-time PVI by catheter ablation, we wanted to investigate the 30-day mortality after ablation, and to examine risk and potential risk factors of PVI-related complications. Methods Population-based cohort study in patients who underwent first-time PVI by catheter ablation between 2011-2018 identified from the National Danish Ablation Registry. Primary outcome was early post-procedural mortality, defined as death of any cause within 30 days of index PVI procedure, or in connection to a hospitalization started within 30 days. Secondary outcomes were all-cause rehospitalization and complication, including postoperative infection, cardiac, vascular, neurological, vascular, and pulmonary complications within 30 days. Data on mortality and complications were collected from national health and administrative registries. Binary regression was used to estimate risk ratio (RR) with 95% confidence intervals (CI) for association between selected predictors and any complication, and adjusted gender, age, BMI, prior ablation, calendar period (ablation from 2011-2013, 2014-2016, and >2016). Results We included 8560 patients. Median age was 62, 66% were men, 12% had a history of heart failure, and median CHA2DS2VASc score was 1 (Interquartile range [IQR]; 1-2). Charlton Comorbidity index (CCI) was none in 66%, moderate in 29% and severe in 5%. A total of 10 (0.12%) patients died within 30 days of ablation, of which 4 patients died during initial hospitalization. Median time to death was 20 (IQR, 12 to 29) days. Patients who died were more likely to have experienced a procedure-related complication (40% vs. 4%, P<0.001). Procedure-related complications occurred in 298 (3.5%), and the risk was 4.4%, 3.0% and 3.3% in the time periods between 2011-2013, 2014-2016 and >2016, respectively. Most common complications were postoperative infection (26%), cardiac complication (26%), and vascular complications (18%). Complication risk was increased in patients with higher age (aRR, 65-74 year; 1.67 [1.32-2.11] and >74 years; 2.48 [1.60-3.84]), moderate CCI (aRR 1.45 [1.14-1.83]), cardiovascular disease (aRR 1.52 [1.09-2.11]) and antithrombotic treatment (aRR 1.41 [1.05-1.89]). After first-time PVI, 1.963 (23%) patients were re-hospitalized within 30 days, and most common primary discharge diagnoses were AF (87%) and direct cardioversion was performed in 765 (39%) patients. Conclusion In a nationwide cohort of patients who underwent first-time PVI, number of deaths within 30 days of ablation was low (0.12%). Risk of complication was low and 23% of the patients were re-hospitalized within 30 days.

Abstract Background Small randomized clinical trials have found that patients with heart failure (HF) and atrial fibrillation (AF) randomized to an ablation strategy for AF experienced improved cardiovascular outcomes. We examined the relation in routine clinical practice. Purpose We aimed to assess if first-time pulmonary vein isolation ablation (PVI) for AF among patients with HF was associated with decrease in HF hospital admissions rates and furosemide dosage in the year after PVI compared with the year before. Methods We identified patients with HF and available left ventricular ejection fraction (LVEF) treated with a first-time PVI using the Danish Ablation Registry, and alive at 1-year follow-up. Patient comorbidities and concomitant pharmacotherapy (including furosemide dosage and HF hospital admissions) were identified utilizing Danish nationwide registries. For inclusion, patients were required to have been diagnosed with HF in an in- or outpatient setting <10 years of first-time PVI or have a LVEF at the time of PVI ≤45%. Patients were grouped according to LVEF at time of PVI: ≤35%, 36–45%, and >45%. For comparison of HF hospital admission and furosemide usage before and after PVI, McNemars test were used. Wilcox signed-rank test were used to test difference in furosemide dosage before and after PVI. Results We identified 668/3450 patients with HF treated with first-time PVI for AF between 2010–2017 (median age 62 years [Q1,Q3=56,69 years], 81% male, and median LVEF 45% [Q1,Q3=40,60%]). Of these, 13 patients (2%) died during one-year follow-up. Overall, 36% of patients with HF had one or more HF hospital admissions the year before PVI compared with 7% in the year after PVI (p<0.0001) (Figure 1). Patients with LVEF ≤35% had the highest proportion of HF hospital admissions the year before PVI (53%) and was reduced more than 4-fold (13%) in the year after first-time PVI, with consistent findings in all LVEF groups (Figure 1). At the time of PVI, 36% of patients with HF were treated with furosemide compared with 30% in the year after PVI (p<0.0001) (Figure 2). Moreover, we identified significant reductions in furosemide dose in the year after PVI compared with the year before (median dose 60 mg [Q1,Q3=30,80 mg] and 20 mg [Q1,Q3=0,60 mg], respectively, p=0.001). Here, reductions in furosemide requirements were consistent across LVEF subgroups. Conclusion Patients with HF treated with a first-time PVI strategy for AF had a 5-fold decrease in HF hospital admissions in the following year compared with the year before PVI. Among patients treated with furosemide at time of PVI, significant reductions in dose one year after PVI was identified but also significant reductions in proportion of patients requiring any furosemide at all. Funding Acknowledgement Type of funding sources: None.

AIMS The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND RESULTS During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. CONCLUSION Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

BackgroundThere are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation.MethodsWe randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis.ResultsThere was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P = 0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P = 0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P = 0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P = 0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation.ConclusionsIn comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.)

BACKGROUND:Fractional Flow Reserve (FFR) is a proven technology for guiding percutaneous coronary intervention (PCI), but is not reimbursed despite the fact that it is frequently used to defer PCI. METHODS:Costs incurred with use of FFR were compared in both the public and private sectors with the costs that would have been incurred if the technology was not available using consecutive cases over a two year period in a public teaching hospital and its co-located private hospital. RESULTS:FFR was performed on 143 lesions in 120 patients. FFR was < 0.80 in 37 lesions in 34 patients and 25 underwent PCI while 11 had CABG. It was estimated that without FFR 78 lesions in 70 patients would have had PCI with 17 patients having CABG with 35 additional functional tests. Despite a cost of $A1200 per wire, FFR actually saved money. Mean savings in the public sector were $1200 per patient while in the private sector the savings were $5000 per patient. CONCLUSIONS:FFR use saves money for the Federal Government in the public sector and for the Private Health Funds in the private sector. These financial benefits are seen in addition to the improved outcomes seen with this technology.

Background: MANTRA-PAF is a large randomized multicenter trial comparing radiofrequency catheter ablation (RFA) and antiarrhythmic drug (AAD) therapy as first line treatment of paroxysmal atrial fibrillation (PAF). Intention-to-treat analysis showed no significant difference in cumulative AF burden, but at 24 months AF burden was significantly lower in the RFA than in the AAD group. In the present on-treatment analysis we compared three groups of patients: those who received only the prescribed treatment (pure RFA and pure AAD groups) and those treated with combination of RFA and AAD (cross-over group). Methods: A total of 294 AAD naïve patients with PAF were randomly assigned to RFA (146 patients) or class IC/III AAD therapy (148 patients). Cumulative and per-visit AF burden (i.e., percentage of time in AF) was evaluated from 7-day Holter recordings at baseline and after 3, 6, 12, 18, and 24 months. The patients were considered free from AF if no AF episodes longer than 60 s were detected. In the AAD group, 54 patients (36%) underwent supplementary ablation and in the RFA group 30 patients (21%) received antiarrhythmic medication after the 3 months blanking period (at 24 months 9% were on AAD). Eight patients were excluded from the analysis because they did not receive the index treatment. Results: At 24 months, AF burden was significantly lower in the pure RFA group (n=110) than in the pure AAD (n=92) and the cross-over (n=84) groups (90th percentile 1% vs. 10% vs. 19%, P=0.007), and more patients in the RFA than in the other groups were free from any AF (89% vs. 73% vs. 74%, P =0.006). The cumulative AF burden was significantly lower in the pure RFA and AAD groups than in the cross-over group (90th percentile 10% vs. 6% vs. 24%, P<0.001). During the 2 year follow-up period 63%, 59% and 21% (P<0.001) of the patients in the pure RFA, pure AAD and the cross-over group had no AF episodes in any Holter recording, respectively. There was no significant difference in the number of severe complications between the groups. Conclusions: These data indicate that RFA is superior to AAD as first line treatment in a large subset of patients with highly symptomatic PAF. The results are pertinent among relatively young and healthy subjects and should not be extrapolated to elderly patients or to those with comorbidities.

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden

Objectives: This randomised trial evaluated if patients with atrial fibrillation (AF) and no history of atrial flutter (AFL) had any benefit of prophylactic cavotricuspid isthmus block (CTIB) in addition to circumferential pulmonary vein ablation (CPVA).Methods: 149 patients with AF (54% paroxysmal) were randomised to CPVA and CTIB (group CTIB+, n=73) or CPVA alone (group CTIB-, n=76). Patients were followed for 12 months with repetitive 7-day Holter monitoring after 3, 6 and 12 months.Results: Six patients (4%) had cardiac tamponade, and one patient had a stroke. No difference was found in the cumulative AFL-free rate between the two treatment groups(CTIB+: 88% vs CTIB-: 84%, hazard ratio (HR) 0.80, 95% CI (0.34 to 1.90), p=0.61). There was no difference in the cumulative AF-free rate between the groups (CTIB+: 34% vs CTIB-: 32%, HR 0.93, 95% CI (0.63 to 1.38), p=0.71). Overall, 33% of the patients were free of AF after a single procedure. Including reprocedures, a complete or partial beneficial effect was noted in 62% of the patients at 12 months. At 12-month follow-up, 24 (50%) patients with documented AF or AFL in the Holter recordings were asymptomatic.Conclusions: It was not possible to demonstrate any beneficial effect of CTIB in addition to CPVA with regard to AFL or AF recurrences during follow-up. Repetitive long-term Holter monitoring demonstrated a 33% rate of freedom from AF during a 1-year follow-up. Including additional CPVA procedures, a clinical effect was noted in 62% of the patients at 12 months. Patients with AF or AFL recurrences were often asymptomatic.

Background Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD.Aim To examine whether YE infection is associated with GD.Design We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD.Methods Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured.Main outcome measures The prevalence of YOP IgA and IgG antibodies.Results Subjects with GD had a higher prevalence of YOP IgA (49% vs. 34%, P = 0.054) and YPO IgG (51% vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49% vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81).Conclusion The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.

BACKGROUND:Atrial fibrillation is common after mitral valve surgery. We do not know the incidence of atrial tachycardia and how it depends on the surgical approach used.METHODS:The subjects of the study were 213 consecutive patients who had surgery for mitral valve disease from January 1, 2001, through January 26, 2004. The surgeons used either the superior transseptal approach (69 patients, group A) or left atrial approach (144 patients, group B). An investigator, blinded for the approach used, analyzed all 12-lead electrocardiograms taken during the admission after the operation. The data were analyzed using the Cox regression analysis as time from the operation until documentation of atrial tachycardia or atrial fibrillation on a 12-lead electrocardiogram. Hazard ratio (95% confidence interval) is reported.RESULTS:The superior transseptal approach (2.0 [1.1 to 3.5], p = 0.023), age 60 years or more (2.3 [1.2 to 4.6], p = 0.015), and male sex (2.6 [1.3 to 5.2], p = 0.007) were independent predictors of atrial tachycardia. Age 60 years or more was the only independent predictor of atrial fibrillation (2.0 [1.2 to 3.3], p = 0.007). Although atrial tachycardia was less frequent than atrial fibrillation in group B (p < 0.001), atrial tachycardia was as common as atrial fibrillation in group A (p = 0.149).CONCLUSIONS:The superior transseptal approach has a higher risk of atrial tachycardia than the left atrial approach. Atrial tachycardia has different predictors than atrial fibrillation and constitutes a significant problem, especially after the superior transseptal approach. These results emphasize the need to distinguish between atrial tachycardia and atrial fibrillation-two entities with different pathophysiology, therapy, and also epidemiology.

BACKGROUND:Tako-tsubo cardiomyopathy (TTC) is an acute reversible cause of segmental myocardial dysfunction that is poorly understood. We have noted a variant of this condition where a tiny segment at the apex retains some contractile function. This paper delineates the frequency of this variant relative to the classical form and the clinical differences between patients suffering from the two forms.METHODS:All cases of TTC (n = 35) were identified from our infarct angiography database and separated on the basis of apical sparing (n = 14) or no apical sparing (n = 21).RESULTS:Compared with the classical form, those with apical sparing were significantly younger (63 +/- 12 vs 72 +/- 13 years) and were more likely premenopausal (5/14 vs 0/21) and had higher ejection fractions (35 +/- 6% vs 32 +/- 4%). There was a trend towards higher recurrence (4/21 vs 0/14). There were no differences in time or season of presentation, precipitant stressor, premorbid drug therapy, haemodynamics at catheterization or acute outcomes.CONCLUSION:The apical sparing variant of TTC is common, accounting for 40% of cases. While the patients are younger and more likely premenopausal, there are no other distinguishing features between the classical and the variant form.

Understanding of the aetiological basis of thyroid autoimmunity may be gained by studying the early stages of the disease process. We aimed to (1) investigate the relationship between thyroid antibody status and Yersinia enterocolitica (YE) infection in euthyroid subjects and (2) explore the relative importance of genetic and environmental risk factors in the acquisition of YE infection. The association between thyroid antibody status and YE infection was explored using a case-control design. Furthermore, thyroid antibody-positive twins were compared with their thyroid antibody-negative co-twin. In 468 twins, IgA and IgG antibodies to virulence-associated outer-membrane proteins (YOPs) of YE were measured. Of these, 147 were thyroid antibody-positive (cases). A total of 147 age- and gender-matched twins were chosen as controls. The prevalence of YOP antibodies was lower among thyroid antibody-positive individuals than among controls. Yersinia infection was not associated with a positive thyroid antibody status: the odds ratio (with 95% CI) for YOP IgA-ab was 0.66 (0.42-1.05), P = 0.078 and for YOP IgG-ab it was 0.95 (0.60-1.50), P = 0.816. Within discordant twin pairs, the thyroid antibody-positive twin did not have an increased risk of Yersinia infection compared to the thyroid antibody-negative co-twin [odds ratio: YOP IgA-Ab: 0.94 (0.49-1.83), P = 0.866, and YOP IgG-Ab: 1.35 (0.72-2.53), P = 0.345]; 41% (95% CI 10-67% of the liability of being YOP antibody-positive was due to genetic effects. In conclusion, Yersinia infection does not confer an increased risk of thyroid antibodies. The genetic contribution in the acquisition of Yersinia infection is modest.