bluuebunny/crossref_metadata_2025 huggingface dataset:
Different renal function estimation formulae and implications for dosing and clinical outcomes when prescribing non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation
Authors: Chao T.F , Chan Y.H , Kuo C.T , Chen S.A
Published: November 2020

Background

Pivotal randomized trials of non-vitamin K antagonist oral anticoagulants (NOACs) adopted Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of NOACs. However, Modified Diet in Renal Disease (MDRD]) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae are commonly used in clinical practice. In the present study, we investigated the agreements/disagreements of eGFRs calculated using different equations in Asian AF patients. Second, we studied the impacts of using different equations on the dosages of NOACs used, and finally, clinical outcomes compared to warfarin were assessed.

Methods

This retrospective study used medical data from a multicenter healthcare provider in Taiwan which included 39,239 AF patients whose data about body weight (BWs) and serum Creatinine (sCr) were available. Among these patients, there were 11,185 and 2,323 AF patients treated with NOACs and warfarin, respectively.

Results

At the cutoff values of eGFR of <15 mL/min, 15–50 mL/min and >50 mL/min, the agreements were 78% between MDRD and CG, and 81% between CKD-EPI and CG. The disagreements between different equations were largely due to over-estimations (21% for MDRD and 17% for CKD-EPI), especially for patients aged >75 years and BWs <50kg (58.8% for MDRD and 50.9% for CKD-EPI). For patients treated with NOACs, around 7.6% (MDRD) and 6.5% (CKD-EPI) had dosages of NOACs that were discordant compared to using the CG equation, with the highest percentages for rivaroxaban (11–13%) and lowest for edoxaban (1%).

Among patients receiving NOACs whose dosages were defined as “on-label” based on MDRD or CKD-EPI, only those whose dosages were “truly on-label” based on CG were associated with a lower risk of ischemic stroke/systemic embolism (IS/SE) (adjusted hazard ratio [aHR] 0.78, 95% CI 0.61–1.00), major bleeding (aHR 0.34, 95% CI 0.26–0.45) and IS/SE or major bleeding (aHR 0.55, 95% CI 0.46–0.66) compared to warfarin (Figure). The risk of IS/SE (aHR 0.82, 95% CI 0.39–1.72), major bleeding (aHR 0.57, 95% CI 0.25–1.32) and IS/SE or major bleeding (aHR 0.69, 95% CI 0.40–1.19) were similar between warfarin and patients treated with NOACs whose dosages were disconcordant between eGFRs calculated using MDRD and CG (Figure).

Conclusions

The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of NOACs (mainly overdosing) which would attenuate the advantages of NOACs compared to warfarin. Therefore, the CG equation should be used as the “gold standard” for the calculations of eGFRs to guide the NOAC dosages.

Funding Acknowledgement

Type of funding source: None
Risk factors of major bleeding in elderly atrial fibrillation patients from the ANAFIE registry
Authors: Inoue H , Yamashita T
Published: November 2020

Background

Bleeding is associated with shorter life expectancy during anticoagulant treatment in atrial fibrillation (AF) patients. Prior studies showed bleeding during anticoagulant treatment occurred more frequently in elderly AF patients than in younger AF patients. HAS-BLED score is a risk assessment tool for bleeding. However, since it was developed from the database of patients with warfarin, it has not been clarified whether this score is applicable in the era of direct oral anticoagulant (DOACs), especially for elderly AF patients.

Purpose

All Nippon AF In the Elderly (ANAFIE) registry was designed to obtain real-world information regarding patients with non-valvular AF (NVAF) aged ≥75 years, including current status of anticoagulant therapy and prognosis. The present study aimed to determine factors that associate with major bleeding for elderly NVAF patients using the dataset of ANAFIE registry conducted in Japan.

Methods

Total of 32,099 patients aged ≥75 years with NVAF were enrolled in ANAFIE registry, and followed for 2 years. Incidence rates of major bleeding for total population, <85 years old group and ≥85 years old group were estimated using Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of major bleeding. The factors included in the model were selected by backward elimination procedure.

Results

Mean age was 81.5 years. 23,738 (74.0%) was <85 years old and 8,361 (26.0%) was ≥85 years old. 92.5% of whole population used anticoagulants including warfarin (27.6%) or DOACs (72.3%). Major bleeding occurred in 279 patients at 12 months with 189 in <85 years and 90 in ≥85 years old group. The cumulative incidence rate of major bleeding at 12 months by Kaplan-Meier method was 0.9% in whole patients, and was slightly higher in ≥85 years than in <85 years old group (1.1% vs 0.8%). In multivariate analysis of the whole patients, history of major bleeding (hazard ratio [HR]: 2.17), severe hepatic dysfunction (HR: 3.62), malignancy (HR: 1.52), falling within a year (HR: 2.07), antiplatelet use (HR: 1.37) and warfarin use (HR: 1.81) emerged as independent predictors of major bleeding. Severe hepatic dysfunction (HR: 9.17), HbA1c <6.0% (HR: 2.19) and dementia (HR: 2.00) were associated with major bleeding in patients only in aged ≥85 years. On the other hand, proton pump inhibitor use (HR: 1.36), creatinine clearance <30 mL/min (HR: 1.53) and polypharmacy (HR: 1.61) were associated with major bleeding only in those aged <85 years.

Conclusion

Among elderly (≥75 years old) Japanese NVAF patients in the era of DOACs, prior major bleeding, severe hepatic dysfunction, malignancy, falling within a year, antiplatelet use and warfarin use were identified as independent predictors of major bleeding. Impact of some predictors differed between the 2 age groups (<85 years vs ≥85 years).

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.
Comparison of warfarin, dabigatran, rivaroxaban and apixaban for effectiveness and safety among elderly patients with atrial fibrillation: a nationwide cohort study
Authors: Rutherford O.C.W , Jonasson C , Ghanima W , Soderdahl F , Halvorsen S
Published: November 2020

Introduction

Age is a strong independent risk factor for stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). Reducing risk of stroke/SE with oral anticoagulation (OAC) in elderly patients involves a correspondingly greater risk of bleeding than in younger patients. Non-vitamin K antagonist oral anticoagulants (NOACs) are associated with a net clinical benefit over vitamin K antagonists in the elderly population, but knowledge is lacking about the comparative effectiveness and safety between specific oral anticoagulants in these patients.

Purpose

The aim of this study was to compare the rates of stroke/SE and major bleeding between new users of warfarin, dabigatran, rivaroxaban, and apixaban, in a nationwide cohort of AF patients over 75 years.

Methods

From Norwegian national registries we identified all anticoagulant naïve initiators of warfarin, dabigatran, rivaroxaban and apixaban over 75 years of age between January 2013 and December 2017. During follow-up, patients were censored upon switching OAC, discontinuation of OAC, death, or end of study period. Multivariate competing risk regression was used to evaluate association between treatment and the outcomes stroke/se and major bleeding, treating death as a competing risk.

Results

A total of 30 401 patients were identified; 6 650 starting warfarin, 3 857 starting dabigatran, 6 108 starting rivaroxaban, and 13 786 starting apixaban. The median age was 82 years. Dabigatran-users had less comorbidity than all other OAC-users; the greatest difference was seen in the proportion of patients with chronic kidney disease (4.3% in the dabigatran-group versus 7.0%, 10.5%, and 16.5% in the rivaroxaban, apixaban, and warfarin groups, respectively). The median follow-up time was 15 months, during which time 1 386 (4.6%) patients suffered a stroke/SE; 1 277 (4.2%) patients had a major bleeding episode; and 3 270 (10.8%) died. Adjusted subhazard ratios for stroke/SE and major bleeding are presented in the figure.

Conclusion

Comparing NOACs with warfarin, we found no significant differences in risk of stroke/SE, while apixaban was associated with lower risk of major bleeding than warfarin. Comparing NOACs with each other; dabigatran was associated with a significantly lower risk of stroke/SE compared with rivaroxaban and apixaban, while both dabigatran and apixaban were associated with significantly lower risks of major bleeding compared with rivaroxaban.

Incidence rates and subhazard ratios

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): South-Eastern Norway regional Health Authority
Edoxaban treatment of elderly patients with atrial fibrillation in routine clinical practice: 1-year results of the non-interventional Global ETNA-AF program
Authors: Yamashita T , Wang C.C , Kim Y.-H , De Caterina R , Kirchhof P , Reimitz P , Chen C , Unverdorben M , Koretsune Y
Published: November 2020

Background

The prevalence of atrial fibrillation (AF) and the need for appropriate anticoagulation increase with age. The benefit/risk profile of direct oral anticoagulants such as edoxaban in elderly population with AF in regular clinical practice is therefore of particular interest.

Purpose

Analyses of Global ETNA-AF data were performed to report patient characteristics, edoxaban treatment, and 1-year clinical events by age subgroups.

Methods

Global ETNA-AF is a multicentre, prospective, noninterventional program conducted in Europe, Japan, Korea, Taiwan, and other Asian countries. Demographics, baseline characteristics, and 1-year clinical event data were analysed in four age subgroups.

Results

Of 26,823 patients included in this analysis, 50.4% were ≥75 years old and 11.6% were ≥85 years. Increase in age was generally associated with lower body weight, lower creatinine clearance, higher CHA2DS2-VASc and HAS-BLED scores, and a higher percentage of patients receiving the reduced dose of 30 mg daily edoxaban. At 1-year, rates of ISTH major bleeding and ischaemic stroke were generally low across all age subgroups. The proportion of intracranial haemorrhage within major bleeding events was similar across age groups. All-cause mortality increased with age more than cardiovascular mortality.

Conclusion

Data from Global ETNA-AF support the safety and effectiveness of edoxaban in elderly AF patients (including ≥85 years) in routine clinical care with only a small increase in intracranial haemorrhage. The higher all-cause mortality with increasing age is not driven by cardiovascular causes.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Daiichi Sankyo
Contemporary procedural trends of Watchman percutaneous left atrial appendage occlusion in the United States: insight from the National Inpatient Sample
Authors: Munir M.B , Khan M.Z , Han F.T , Reeves R , Hsu J.C
Published: November 2020

Background/Introduction

Left atrial appendage occlusion with the Watchman device has emerged as a viable therapy for stroke risk mitigation in atrial fibrillation (AF) patients.

Purpose

To determine trends in real-world utilization and in-hospital adverse events from Watchman implantation since its approval by the Food and Drug Administration (FDA) in 2015.

Methods

This was a retrospective cohort study utilizing data from National Inpatient Sample for calendar years 2015–2017. Watchman procedures were identified using ICD-9-CM and ICD-10-CM codes of 37.90 and 02L73DK, respectively. The outcomes assessed were associated complications and in-hospital mortality. Trends analysis were performed using analysis of variance.

Results

A total of 17,700 patients underwent Watchman implantation during the study period. There was a significantly increased trend in the number of Watchman procedures performed over the study years (from 1,195 in 2015 to 11,165 devices in 2017, p<0.01). A significant decline in the rate of complications (from 26.4% in 2015 to 7.9% in 2017, p<0.01) and inpatient mortality (from 1.3% in 2015 to 0.1% in 2017, p<0.01) were noted.

Conclusion

Since its introduction, the Watchman procedure appears to be increasingly more common and safe in the management of stroke risk in patients with AF.

Trends in mortality over years

Funding Acknowledgement

Type of funding source: None
A pro-thrombotic left atrial haemodynamic profile is present in older individuals with cardiovascular risk factors even without atrial fibrillation
Authors: Spartera M , Stracquadanio A , Pessao-Amorim G , Von Ende A , Ferreira V , Hess A.T , Neubauer S , Wijesurendra R.S , Casadei B
Published: November 2020

Background

Atrial fibrillation (AF), by inducing left atrial (LA) stasis and thrombus formation, is a major cause of ischaemic embolic stroke. However, up to 25% of embolic strokes occur in the absence of AF or any other identifiable mechanism. We hypothesised that exposure to risk factors leads to a prothrombotic LA haemodynamic profile, with a consequent risk of thrombus formation and embolic stroke even in sinus rhythm (SR).

Purpose

To quantify the relative effects of AF and risk factors on LA function and haemodynamics in three groups: (1) patients with persistent AF before and after cardioversion, (2) patients in SR with no history of AF who were matched to AF patients for stroke risk, and (3) healthy controls.

Methods

Ninety-five participants were recruited: 37 AF patients scheduled for cardioversion [median CHA2DS2-VASc = 2 (1.5–3.5); median age 69 years], 35 matched non-AF patients [median CHA2DS2-VASc 3 (2.0–4.0); median age 69 years], and 23 healthy subjects [median CHA2DS2-VASc 0 (0–0); median age 33 years]. Advanced cardiovascular MRI was used to assess LA function and 4D flow.

Results

Patients with persistent AF displayed significantly lower LA emptying fraction (LAEF), reservoir strain, and peak blood flow velocities compared to both control groups in SR, as well as profound alterations in atrial blood flow patterns and vortex volume ratio (all p<0.001 vs both control groups). In the 65% of patients who were in SR at ≥4 weeks post cardioversion, all LA parameters were significantly improved (all paired p<0.001 vs baseline scan in AF; red vs blue in Figure 1), but LA haemodynamics were now no longer different from those in matched non-AF patients (all p=ns; blue vs green in Figure 1 C-D). However, both AF patients cardioverted to SR and matched non-AF patients had significantly impaired LA function (LA EF and LA reservoir strain) and LA haemodynamics (lower peak velocity and higher vortex volume ratio), compared to heathy controls (all p<0.01; blue/green vs grey in Figure 1).

Conclusions

We found evidence of a gradient of LA haemodynamic dysfunction, where the most marked phenotype was seen in patients scanned in AF, but with significant abnormalities remaining after restoration of SR in AF patients, and intriguingly, also present to a similar degree in matched non-AF patients. Advanced atrial imaging offers the potential to select patients with an adverse pathophysiological substrate directly predisposing to LA thrombus formation for future clinical trials of anticoagulation in SR.

Figure 1

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): NIHR Oxford Biomedical Research Centre
Prognostic impact of renal function trajectories and temporal variability amongst anticoagulated atrial fibrillation patients: a subgroup analysis of the SPORTIF III and V trials
Authors: Proietti M , Gumprecht J , Romiti G.F , Lip G.Y.H
Published: November 2020

Background

Renal function is a major determinant of major adverse outcomes in patients with atrial fibrillation (AF). Scarce data are available about the impact of renal function trajectories and creatinine clearance (CrCl) temporal variability, on prognosis.

Aim

To evaluate the progression and impact of renal function impairment and variability on outcomes over a long-term follow-up observation in a cohort of anticoagulated AF patients.

Methods

We included warfarin-treated AF patients in SPORTIF trials with available creatinine clearance (according to Cockroft-Gault) at baseline and at least 4 evaluations throughout their follow-up. Patients with a BMI ≥45 kg/m2 were excluded from the analysis. Average successive variability (ASV) was used as measure of variability.

Results

Among 3665 original patients, 3366 (91.8%) were included in this analysis. Median [IQR] CHA2DS2-VASc score was 3 [2–4] and HAS-BLED was 3 [2–4]. At baseline, 876 (26.0%) patients had CKD (CrCl <60 mL/min), with 14 (0.4%) patients having severe CKD (<30 mL/min), with a mean (SD) CrCl of 86.7 (47.4) mL/min. Over a mean (SD) 577.1 (122.1) days of follow-up, a total of 521 new CKD cases were found with an overall incidence of 13.1 per 100 patient-years, with 91 new severe CKD cases (1.71 per 100 patient-years). Across follow-up, prevalence of CKD and severe CKD increased progressively (both p<0.001) [Figure]. Mean (SD) AVS was −0.567 (±2.803) mL/min. According to AVS, patients were divided into quartiles: i) Q1: +34.012/+0.450; ii) Q2: +0.449/−0.443; iii) Q3: −0.443/−1.503; Q4: −1.505/−19.750. While no difference was found in stroke/systemic embolism, rate of major bleeding was higher in Q4 (4.5%) and Q1 (4.0%) than in other quartiles (Q2 2.5%, Q3 2.0%; p=0.009) as well as all-cause death (Q4: 6.7%; p=0.003 compared to other quartiles). A Cox multivariate adjusted model documented that AVS Q1 and Q4 were independently associated with a higher risk of major bleeding, while Q4 was associated with a higher risk of all-cause death (Table).

Conclusion

In a cohort of AF patients treated with warfarin, characterized by a progressive increase in the proportion with CKD and severe CKD, the largest reduction in CrCl throughout follow-up was associated to an increased risk of major bleeding and all-cause death.

Renal Function Trajectories

Funding Acknowledgement

Type of funding source: None
Downregulation of growth hormone in postural orthostatic tachycardia syndrome: insights from the SYSTEMA cohort
Authors: Johansson M , Schulte J , Ricci F , Persson M , Sutton R , Hamrefors V , Fedorowski A
Published: November 2020

Background

Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder occurring predominantly in young women. POTS is characterized by an excessive heart rate increase when assuming upright posture accompanied by symptoms of orthostatic intolerance. The pathophysiology of POTS has not been fully established and is believed to be multifactorial.

Purpose

We aimed to investigate the alterations in circulating growth hormone level in POTS.

Methods

We conducted an age-matched case-control study enrolling 42 patients with POTS (age 31±9 years; 36 women) verified by positive head-up tilt testing and cardiovascular autonomic tests, and 46 controls (32±9 years; 35 women) with negative active standing test and no history of syncope, orthostatic intolerance and endocrine disease. We measured plasma levels of growth hormone using a high-sensitivity chemiluminescence immunoassay in relation to presence of POTS diagnosis. All study participants completed the validated Orthostatic Hypotension Questionnaire (OHQ), consisting of two components: the symptoms assessment scale (OHSA) and daily activity scale (OHDAS) to evaluate the burden of symptoms. We applied standard statistical tests for group differences. Growth hormone values were log-transformed and standardized before the group comparison.

Results

POTS patients had significantly lower plasma levels of growth hormone (ng/mL) (median=0.53, IQR, 0.10–2.83 vs. median=2.33, IQR, 0.26–7.2, p=0.04) than controls. Levels of growth hormone were reversely related to OHDAS (p=0.049) among POTS patients. Supine heart rate was significantly higher in POTS patients (69.0±11.1 beats/min vs. 63.3±10.8 beats/min, p=0.02), as well as diastolic blood pressure (72.9±9.1 mmHg vs. 69.0±8.5 mmHg, p=0.04). We observed no significant difference in supine systolic blood pressure (116.6±13.3 mmHg vs. 115.2±10.0 mmHg, p=0.60). POTS patients had a significantly higher composite OHQ score than controls (60.0±18.6 vs. 4.2±7.5, p<0.001), as well as OHSA (36.2±10.0 vs. 3.6±6.4, p<0.001) and OHDAS (23.8±9.7 vs. 0.6±1.3, p<0.001).

Conclusion(s)

Our study shows that patients with POTS have significantly reduced plasma levels of circulating growth hormone. Lower growth hormone levels among POTS patients are associated with increased impairment of daily life activities. Further studies are necessary to confirm our findings in the independent populations and explain the mechanisms behind this alteration.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Crafoord Foundation, Swedish Heart and Lung Foundation
The prevalence of familial form of atrioventricular nodal reentry tachycardia in south-eastern regions of Poland
Authors: Deutsch K.J , Ciurzynski M.C , Zienciuk-Krajka A.Z.K , Sledz J.S , Mazij M.M , Ludwik B.L , Lewandowski Z.L , Stec S.M.S
Published: November 2020

Introduction

Atrioventricular nodal reentry tachycardia (AVNRT) is one of the most common regular supraventricular arrhythmia referred for catheter ablation (CA). Although, several families with familial form of AVNRT (FAVNRT) in Subcarpathia province (SP, Poland), the comparison or prevalence of FAVNRT and comparison of their incidence in other provinces in Poland were not prospectively validated.

Methods

Data was derived from prospective multicenter registry of CA (ELEKTRO- ELMedica Network). Between year 2010 to 2018, the clinical data of 1544 patients with invasively documented AVNRT were verify for family history of FAVNRT. From December 2016 to March 2019 each patient with AVNRT were consulted with detailed family history and family residence origin with up to three-generation pedigree. Families with substantiate form of FAVNRT (at least two persons from the family after invasive validation of AVNRT and CA) divided into three groups according to their origin.

Results

From 1544 recruited patients 932 had origin in south-eastern provinces (SEP) of Poland [n=379, from SP; n=34, from Lubelskie; n=214, from Lesser Poland; and n=305 from Holy Cross]. The rest of the group (n=612) consisted of patients from other, not SEP parts of the country – other part of Poland (RPP). Finally, 45 (2,91%) patients from 24 families had diagnosed FAVNRT. The incidence of FAVNRT was significantly higher in SEP than RPP (4.02% vs 1.17%). Moreover, patients from SP has the highest prevalence of FAVNRT (6.33%) as compared to other provinces of SEP (2.47%). In SP and in bordering SEP provinces as well as the RPP appropriate risk (according to previous region) of FAVNRT was respectively 2.67 (95% CI: 1.36–5.23; P<0.004), 2.14 (95% CI: 0.86–5.34; P<0.10) according to reference RPP were observed.

Conclusion

Based on Hill's Criteria for Causality observed biological monotonic risk gradient of FAVNRT is proving geographical cause of increased prevalence of FAVNT. The closer they are the higher they is to the most endangered provinces in Poland- SP that also adjoined to Ucraine and Slovakia. Further, international, trans-border cooperation and genetic testing are required to validate genetic impact of FAVNRT in past Galicia region of Central Europe.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Study is funding by the research grant DI2015 021945 from budget resources in 2015 to 2017, as a research project in “Diamentowy Grant” program from “Narodowe Centrum Badan i Rozwoju (PL)”.
MAPping with fragmentation analysis in patients with atypical atrial FLUtter using the RHYthmia navigation system (MAP-FLURHY study)
Authors: Franco E , Lozano Granero C , Matia R , Hernandez-Madrid A , Sanchez-Perez I , Zamorano J.L , Moreno J
Published: November 2020

Background

Atypical atrial flutter (AAFL) circuits use areas of slow conduction which can be visualized as fragmented electrograms (fEGMs).

Purpose

To test an ablation strategy based on the identification and ablation of spots with fEGMs in AAFL.

Methods

The MAP-FLURHY study prospectively included all AAFL ablations with Rhythmia in our Center from June 2016 to June 2019. Patients with non-mappable AAFL, frequent conversion to atrial fibrillation, or cavotricuspid isthmus-dependent flutters were excluded from analysis. The IntellaMap ORION catheter was used to detect fragmentation areas, arbitrarily defined as fEGMs >70ms. Entrainment was used to check if these areas belonged to the AAFL circuit. Ablation targeted the longest fEGM within the circuit (return cycle <30ms): focal ablation for microreentries, and lines including the fEGMs for macroreentries. Ablation success was defined as conversion to sinus rhythm or another flutter. Procedural success was defined as successful ablation of all inducible flutters. Follow-up included visits with 24h Holter ECG at 3–6-12 months.

Results

50 Patients received ablation (Figure). 27 Patients (70.6±13.1 years; 10 females; LVEF 57%±13%) with 44 mappable AAFLs were included in the analysis (Table). All AAFLs showed areas with fEGMs (106 areas; 2.4 areas per flutter). 42/44 AAFLs had fEGMs within the circuit, which were target of ablation. Ablation success: 34/36 AAFLs (94%); success could not be assessed in 6 circuits, due to mechanical conversion to sinus rhythm onto the target fEGM. Fragmented areas within the AAFL circuits (n=51) were longer (110±30 vs 90±15 ms, p<0.001) but had similar voltage (0.34±0.25 vs 0.36±0.26 mV) than areas outside the circuits (n=45). A fEGM duration >100ms/>40% of the cycle length predicted to be a successful site for ablation with 72.3%/73.8% specificity. Procedural success was achieved in 24/27 patients (89%). Excluding a 2-month blanking period, mean survival free from atrial arrhythmias was 19 (95% CI: 12.6–25.5) months. 57% of the patients were free from atrial arrhythmias at 1 year.

Conclusions

Most AAFLs had detectable fEGMs which could be target of ablation with high efficacy.

Figure 1

Funding Acknowledgement

Type of funding source: None
The use of half normal saline during catheter ablation of typical atrial flutter has no impact on the time to achieve bidirectional block
Authors: Alhammad N.J.H , Redfearn D.R , Enriquez A.E , Chacko S.C , Hong K.H , Glover B.M.G
Published: November 2020

Background

Achieving bidirectional block (BB) is generally considered to be the endpoint in the ablation of typical atrial flutter (AFL), however acute reconnection is common. Recent data suggest that deeper ablation lesions may be created by decreasing the irrigant ionic concentration using half normal saline (HNS) delivered through an open irrigated ablation catheter compared with normal saline (NS). We sought to assess whether the use of HNS was associated with a more rapid achievement of BB and less reconnections compared with NS.

Methods

Patients were randomly allocated to catheter ablation with either NS or HNS using a 4-mm irrigated catheter at a power setting of 30 W. Ablation approach employing either a maximum voltage guided (MVG) or empiric cavo-tricuspid isthmus (CTI) line was performed aiming for BB that was confirmed by double potentials separated by an isoelectric line measuring ≥110 ms and evidence of conduction block using differential pacing. Study was powered to an endpoint of acute reconnection within 30 mins.

Results

A total of 60 patients underwent catheter ablation for typical AFL with either HNS (n=30) or NS (n=30). There were no significant differences between the two groups in terms of patient age (68±7 yrs HNS vs. 68±10 yrs NS) and BMI (31±7 HNS vs 31±5 NS). BB was achieved in all patients. The MVG approach was employed in 28/60 patients. Acute reconnection was observed in 11 patients (18%); 4 in HNS vs 7 in NS group (ns). The mean RF time to achieve BB was 386±262 seconds in HNS vs 456±270 seconds in NS (p=0.21). The approach to CTI ablation showed a significant difference in time to BB: Time to block in MVG cases was 264±143 seconds vs 567±273 in empiric CTI line cases. Figure 1 demonstrates the time to block in both approaches with the choice of irrigant not appearing to impact the time to BB. There were 4 steam pops in the HNS arm and 0 steam pops observed in the NS arm. There were no significant complications in either arm.

Conclusion

Irrigation with HNS resulted in no statistically significant reduction in duration of RF time or improvement in acute outcomes over NS in the atrial flutter population. Reduction in duration of RF time was driven by MVG approach. However, acute reconnections were higher in NS group, all 4 steam pops occurred in HNS arm.

Figure 1

Funding Acknowledgement

Type of funding source: None
Comparison catheter ablation versus permanent pacemaker implantation in patients with tachycardia-bradycardia syndrome: prospective, randomized trial
Authors: Choi K.J , Nam G.B , Zo J.H , Lee J.H , Cho M.S , Kim J , Kim Y.H
Published: November 2020

Background

Clinical outcomes after catheter ablation (CA) or pacemaker (PM) implantation for tachycardia-bradycardia syndrome (TBS) has not been well evaluated.

Purpose

This randomized controlled study compared the efficacy and safety outcomes of CA and PM implantation as an initial treatment for TBS with paroxysmal atrial fibrillation (AF).

Methods

A total of 70 patients with paroxysmal AF and TBS (mean 64 years, 64.3% male) underwent randomization, and received CA (CA group, n=35) or PM (PM group, n=35) as an initial treatment. The primary outcome was unexpected emergency room visit or hospitalization from any cardiovascular causes.

Results

The two groups were well-balanced with respect to the baseline characteristics except for difference in age (61.0±8.0 vs. 66.2±7.2, P=0.005). In the intention-to-treatment analysis, the rate of primary outcome was not significantly different between two groups at 2-years of follow-up (19.8% vs. 24.2%; HR 1.25, 95% CI 0.42–3.73, P=0.684). The same trend was noted when the result was adjusted for age (HR 1.16 95% CI 0.26–2.89, P=0.807). The rate of recurrent AF was significantly lower in CA group compared to PM group (24.0% vs. 100% at 2-yreas, P<0.001). Four patients (11.4%) in CA group finally received PM implantation after CA due to syncope. The rate of major or minor procedure related complications was not significantly different between two groups (14.3% vs. 14.3%, P>0.99).

Conclusion

In this randomized controlled study, CA was associated with a similar efficacy and safety with higher rate of sinus rhythm maintenance. CA could be considered a preferable treatment option over PM implantation in patients with paroxysmal AF and TBS.

Funding Acknowledgement

Type of funding source: None
Pacemaker implantation after balloon- or self-expandable transcatheter aortic valve replacement in patients with aortic stenosis
Authors: Bodin A , Bisson A , Herbert J , Lacour T , Saint Etienne C , Pierre B , Deharo P , Babuty D , Clementy N , Fauchier L
Published: November 2020

Background

The incidence of conduction abnormalities requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with different devices available in recent years remains a matter of debate.

Methods

Based on the administrative hospital-discharge database, we collected information for all patients treated with TAVR between 2010 and 2019 in France. We compared the incidence of PPI after TAVR according to the type and generation of valve implanted.

Results

A total of 49,201 patients with aortic stenosis treated with transcatheter aortic valve replacement (TAVR) using the balloon-expandable (BE) Edwards SAPIEN valve or the self-expanding (SE) Medtronic CoreValve were found in the database. Patients treated with early BE or SE valves had higher Charlson comorbidity and frailty indexes than those treated with later BE or SE valves, and slightly higher EuroSCORE II. Patients treated with SE valves had higher rates of previous pacemaker or defibrillator than those treated with BE valves. Mean (SD) follow-up was 1.2 (1.5 years) (median [interquartile range] 0.6 [0.1–2.0] years). PPI after the procedure was reported in 13,289 patients, among whom 11,010 (22.4%) had implantation during the first 30 days (figure 1). In multivariable analysis, using early BE TAVR as reference, adjusted OR (95% CI) for PPI during the first 30 days was 0.88 (0.81–0.95) for latest BE TAVR, 1.40 (1.27–1.55) for early SE TAVR and 1.17 (1.07–1.27) for latest SE TAVR. Compared to early BE TAVR, adjusted HR for PPI during the whole follow-up was 1.01 (0.95–1.08) for latest BE TAVR, 1.30 (1.21–1.40) for early SE TAVR and 1.25 (1.18–1.34) for latest SE TAVR.

Conclusion

In patients with aortic stenosis treated with TAVR, our systematic analysis at a nationwide level found higher rates of PPI than previously reported. BE technology was independently associated with lower incidence rates of PPI both at the acute and chronic phases than SE technology. However, this was less apparent than previously reported in this large analysis of unselected patients seen in “real life” practice. Recent generations of TAVR were not independently associated with different rates of PPI than early generations during the overall follow-up.

Funding Acknowledgement

Type of funding source: None
Outcomes of permanent pacemaker implantation following transcatheter aortic valve replacement
Authors: Fauchier L , Bodin A , Bisson A , Herbert J , Lacour T , Saint Etienne C , Clerc J.M , Quilliet L , Semaan K , Ivanes F , Pierre B , Deharo P , Babuty D , Clementy N
Published: November 2020

Background

Conduction abnormalities leading to permanent pacemaker (PPM) implantation are common complications following transcatheter aortic valve replacement (TAVR). Whether PPM implantation placement is associated with adverse outcomes is unclear. The purpose of this study was to evaluate the incidence, predictors, and clinical outcomes of PPI following TAVR.

Methods

Based on the administrative hospital-discharge database, we collected information for all patients treated with TAVR between 2010 and 2019 in France.

Results

A total of 49,201 patients with aortic stenosis treated with transcatheter aortic valve replacement (TAVR) using the balloon-expandable (BE) Edwards SAPIEN valve or the self-expanding (SE) Medtronic CoreValve were found in the database. Among them, 10,019 (20.4%) had prior PPM implantation, including 476 (4.8%) treated with cardiac resynchronization therapy (CRT). New PPM implantation was required within 30 days of TAVR in 11,010 patients (22.4%), which varied among those receiving self-expanding valves (24.7%) versus balloon-expanding valves (20.9%). There were 349/10,010 patients (3.1%) treated with cardiac resynchronization therapy (CRT) within 30 days following TAVR. In a multivariable analysis comprising 38 variables (including among others underlying conduction disorders, Euroscore 2, Charlson comorbidity index, frailty score and type of implanted valve), prior PPM implantation was associated with an increased risk of all-cause death (adjusted hazard ratio [HR]: 1.10 95% CI 1.04–1.16). New PPM implantation was associated with even higher risk of mortality (adjusted HR: 1.21 95% CI 1.15–1.28). By contrast, previous CRT was associated with a lower risk of death during follow-up (adjusted HR: 0.78 95% CI 0.63–0.96), while PPM with CRT within 30 days of TAVR was not associated with a different risk of death (adjusted HR: 1.00 95% CI 0.80–1.24). Prior PPM and new PPM implantation were also associated with an increased risk of rehospitalization for heart failure (adjusted HR: 1.26 95% CI 1.19–1.32 and 1.18 95% CI 1.12–1.24, respectively). Previous CRT was associated with a non-significant lower risk of rehospitalization for heart failure (adjusted HR: 0.92 95% CI 0.77–1.09).

Conclusions

Both previous PPM and early PPM implantation following TAVR are commonly seen in patients treated with TAVR, and they are associated with a higher risk of death and rehospitalisation for heart failure when compared to patients with no PPM. The fact that CRT when implanted before TAVR was associated with a better survival may deserve consideration when elaborating future optimal approaches for management of conduction disturbances in patients treated with TAVR.

Funding Acknowledgement

Type of funding source: None
Incidence of sudden cardiac death after heart transplantation
Authors: Bonnet G , Coutance G , Waldmann V , Aubert O , Asselin A , Raynaud M , Racape M , Bories M.C , Varnous S , Rouvier P , Bruneval P , Leprince P , Marijon E , Loupy A , Jouven X
Published: November 2020

Background

Sudden cardiac death (SCD) is a major contributor to the rate of mortality after heart transplantation. However, little is known about the incidence of SCD in heart recipients.

Objective

To assess the incidence of SCD after heart transplantation.

Methods

We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centers. We defined 7 main groups of causes of deaths: SCD, cardiovascular (including Cardiac allograft vasculopathy), infection, primary graft dysfunction, graft failure (including late graft dysfunction, rejection), malignancy and others. Causes of deaths were independently adjudicated by two senior cardiologists based on the analysis of death certificates and medical records. Discrepancies were resolved by discussion until a consensus was made. SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms.

Results

A total of 1,363 patients were included. The median follow-up post-transplant was 3.99 years (IQR=0.49–7.49). 450 patients (33%) deceased during the first year. The leading cumulative causes of death in the first year after transplantation were infection, primary graft failure, multiple organ failure during the period in intensiv car unit. Beyond the post-operativ high-risk period of the first year, the leading cumulative cause of death was SCD: among the 213 deaths that occurred beyond the first year, 44 patients (21%) died from SCD. In this period, the incidence rate of SCD reached 0,82 per 100 person-year (95% CI: 0.51–2.05).

Conclusion

In a large multicentric and highly phenotyped cohort of heart transplant recipients, the leading cumulative cause of death beyond the first-year post transplant was sudden cardiac death. Our results open discussion on management of heart recipient, such as the implementation of cardioverter-defibrillators.

Figure 1. Cumulative incidence of causes of death in heart transplant recipients beyond the first year (n=913).

Funding Acknowledgement

Type of funding source: None
Left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy
Authors: Parashar N , Sinha M , Sharma S , Ramakrishnan S
Published: November 2020

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is not an isolated RV disease. Left ventricular (LV) or biventricular involvement is being increasingly diagnosed in such patients. There is available research to show that the LV peak strain calculated from feature tracking (FT) cardiac MRI is impaired even before the impairment of function. If present, such involvement is an adverse prognostic marker.

Purpose

The aim of this study is to calculate LV involvement in patients with ARVC using FT cardiac MRI.

Methods

27 patients of ARVC who underwent cardiac MRI with late gadolinium enhancement (LGE) in our department were identified. 10 healthy volunteers (controls) were also assessed using non-contrast cardiac MRI. LV strain analysis was performed using Cvi42 Circle cardiovascular imaging software; and global LV peak radial, circumferential and longitudinal strain values were calculated. Patients were divided into two sub groups: those with preserved LV ejection fraction (LVEF) and those with reduced LVEF. Peak LV strain values were compared between the two groups of ARVC patients; and between ARVC patients with preserved LVEF and healthy volunteers.

Results

The LV peak global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) were −17.7±2.47, −18.16±2.65, 31.04±6.07 respectively in healthy volunteers. LV global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were significantly impaired in ARVC/D patients (GLS: −11.97±4.34%, GCS: −14.35±4.32%, GRS: 22.1±7.39%). ARVC patients were divided into 2 subgroups: the preserved LV ejection fraction (LVEF) group (LVEF ≥55%, n=9) and the reduced LVEF group (LVEF <55%, n=18). In ARVC patients with reduced LVEF, the peak GLS was −9.99±3.94, GCS was −12.88±4.08 and GRS was 19.57±7.56. With preserved LVEF these values were −15.1±3.02, −17.3±3.3 and 27.1±3.67 respectively. In ARVC patients with preserved LVEF, the peak LV strain were impaired when compared with healthy volunteers with significant difference in peak GLS in between the two groups (p=0.05).

Conclusion

In patients with ARVC, cardiac MRI feature tracking can detect early LV dysfunction and thus adverse prognostic marker. Even in patients with normal LVEF, GLS was found to be significantly impaired as compared to healthy controls.

Calculation of longitudinal strain

Funding Acknowledgement

Type of funding source: None
A novel SCN5A gene mutation causing LQT3 with unique phenotype in a large canadian kindred
Authors: MacIntyre C.J , Gray C.J , Newman V , Crowley A , Dyack S , Gardner M.J
Published: November 2020

Background

SCN5A gene mutations are associated with diverse clinical phenotypes including Long QT (LQT) Syndrome, Brugada Syndrome, progressive conduction system disease and cardiomyopathy.

Objective

We identified a novel SCN5A variant (T731I) in a pedigree affected by QT prolongation and ventricular arrhythmia. Clinical phenotype and co-segregation with genotype within the pedigree were characterized.

Methods

Family members were invited to attend clinics held in their indigenous community. All subjects underwent a history, physical exam, 12 lead ECG and had blood samples collected for genetic testing. Patients were assessed by an adult or pediatric cardiologist and genetic counselors over a six year period. There were 86 females and 69 males ranging in age from 1 to 82 years (mean 36 years) at the time of first assessment. ECG analysis was performed by a cardiac electrophysiologist blinded to patient identity and genotype. The QTc was calculated using Bazett's formula.

Results

One hundred and fifty five family members were evaluated (86 (55%) female; mean age 36 years (range 1 to 82 years). Mean QTc was 461 + 21 ms for the gene positive group and 419 + 22 ms for the gene negative group (P<0.001) (Figure). There was no significant difference in age or sex between the gene positive and gene negative groups.

Gene positive family members were also noted to have low right atrial p waves and frequent unifocal ventricular ectopy and non-sustained monomorphic ventricular tachycardia. One gene positive individual developed dilated cardiomyopathy with high burden ventricular tachycardia and required cardiac transplantation.

Conclusion

This novel SCN5A variant co-segregated with an abnormal phenotype consisting of significant QTc prolongation, low atrial rhythm, and ventricular arrhythmia. This pedigree highlights the phenotypic heterogeneity of SCN5A gene mutations and the importance of cascade family screening to identify at risk family members.

Figure 1. QTc intervals

Funding Acknowledgement

Type of funding source: None
Usefulness of subcutaneous Implantable Loop Recorder in Brugada Syndrome. A single UK centre experience
Authors: Scrocco C , Ben-Haim Y , Tome-Esteban M , Papadakis M , Sharma S , Behr E.R
Published: November 2020

Background

Experience with implantable loop recorder (ILR) in Brugada Syndrome (BrS) is limited.

Purpose

We sought to evaluate the usefulness of continuous monitoring in BrS patients in a UK based Inherited Cardiac Conditions centre.

Methods

Subjects with BrS were consecutively recruited and demographic, clinical, device and follow-up data acquired.

Results

Of 452 subjects with BrS recruited in our centre, 41 (9%) received an ILR. Twenty-one (51%) were males. Twenty-four subjects (59%) had a high probability of BrS based on the Shanghai score. Mean age at implantation was 45.3±15.5 years. The indications for the implantation were: syncope or pre-syncope in 28 subjects (68%), palpitations in 12 (29%), family history of SADS in 1 case. Sixteen subjects presented with a spontaneous type 1 pattern, of whom 12 (75%) underwent an electrophysiological study for risk stratification which was negative. During a mean follow-up of 82±46 months (range 4.0–182), 5 new diagnoses of atrial fibrillation (AF) or supraventricular tachycardia were made; 3 subjects had symptomatic pathological pauses (in one case associated with fast AF) and underwent permanent pacemaker or ICD implantation; one subject experienced an asymptomatic episode of fast, non-sustained monomorphic ventricular tachycardia. In 2 cases the device was explanted prematurely due to site infection. Patients who received an ECG diagnosis following interrogation of the ILR were older (mean age 55±11 vs 43±16m p=0.04), although there were no differences in sex or Shanghai score.

Conclusions

In a large UK cohort of BrS patients, the use of ILR was low. However, continuous subcutaneous monitoring yielded a diagnosis of tachy- or brady-arrhythmic episodes in 22% of cases, and therefore can be helpful in guiding the management of low/intermediate risk BrS patients.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Robert Lancaster Memorial Fund
Novel insights on Andersen-Tawil syndrome type 1
Authors: Mazzanti A , Guz D , Trancuccio A , Pagan E , Chargeishvili T , Biernacka E.K , Sacilotto L , Zorio E , Brugada G , Nof E , Anastasakis A , Sansone V , Jimenez-Jaimez J , Cruz F , Priori S.G
Published: November 2020

Background

Andersen-Tawil Syndrome type 1 (ATS1) in a rare arrhythmogenic disease caused by loss-of-function mutations in the KCNJ2 gene and characterized by ventricular arrhythmias, dysmorphic features and episodes of periodic paralysis. Although the prognosis of ATS1 patients is typically considered benign, definitive outcome data are lacking.

Purpose

We aimed to: 1) define the risk of life-threatening arrhythmic events (LAEs); 2) identify risk factors for such events; 3) assess the efficacy of anti-arrhythmic drugs in preventing LAEs.

Methods

We included 118 ATS1 patients from 57 families with confirmed pathogenic or likely pathogenic KCNJ2 mutations. Clinical and genetical data were acquired by investigators from 23 centers in 9 countries.

Results

Baseline characteristics of the population are presented in the Table. Over a follow-up of 6.2 years, 17/118 (14%) patients experienced a first LAE, with a 5-year cumulative probability of 7.9% (Figure). Cox multivariable analysis demonstrated that a previous history of syncope (HR 4.5, p=0.02), the documentation of sustained VT (HR 9.3, p=0.001) and the administration of amiodarone (HR 268, p<0.001) were associated with an increased risk of LAE. The baseline rate of LAE was not reduced by beta-blockers alone (1.37 per 100 py; p=1), or in combination with class Ic antiarrhythmic drugs (1.46 per 100 py, p=1).

Conclusions

Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope, and documentation of sustained ventricular tachycardia are independently associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in ATS1 patients.

ATS1: Diagnosis, Outcome, Risk Factors

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): ERN Guard-Heart European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart