bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of catheter ablation of AF without pre- or periprocedural imaging for the detection of LA thrombus
Authors: Vlachos K , Bazoukis G , Prappa E , Megarisiotou A , Dragasis S , Mililis P , Saplaouras A , Efremidis T , Sideris A , Efremidis M , Letsas K
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

The need for pre- or peri-procedural imaging to rule out the presence of left atrial thrombus in patients undergoing catheter ablation of atrial fibrillation (AF) is unclear in the era of uninterrupted direct oral anticoagulant (DOAC) regimen. We sought to examine the safety of catheter ablation in appropriately selected patients with paroxysmal AF without performing screening for left atrial thrombus.

Methods

Consecutive patients planned for radiofrequency AF catheter ablation between January 2016 and June 2020 were enrolled, and prospectively studied. All subjects were receiving uninterrupted anticoagulation with DOACs for at least 4 weeks before the procedure. All subjects were in sinus rhythm the day of the procedure. The primary outcome of the study was ischemic stroke or transient ischemic attack (TIA) during at 30 days.

Results

A total of 451 patients (age 59.7 ± 10.2 years, 289 males) with paroxysmal AF were included in the study. The mean CHA2DS2-VASc score was 1.4 ± 1.2. The mean left ventricular ejection fraction and left atrial diameter were 60 ± 5% and 39.3 ± 4 mm, respectively. Regarding the anticoagulation regimen, apixaban was used in 197 (43.6%) patients, rivaroxaban in 148 (32.8%) patients, and dabigatran in 106 (23.5%) patients. None of the patients developed clinical ischemic stroke or TIA during the 30-day post-discharged period.

Conclusions

Catheter ablation can be safely performed in low-risk patients with paroxysmal AF without imaging for the detection of left atrial thrombus in the era of uninterrupted DOAC anticoagulation.
Prevalence and predictor factors of persistent pulmonary vein isolation in redo AF ablation procedure
Authors: Ribeiro Da Silva M , Santos Silva G , Ribeiro Queiros P , Teixeira R , Almeida J , Fonseca P , Oliveira M , Goncalves H , Rodrigues A , Primo J , Fontes Carvalho R
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Atrial fibrillation (AF) catheter ablation is a well-established procedure for the treatment of AF. The cornerstone of AF ablation is the complete isolation of pulmonary veins (PV). However, persistent PV isolation (PVI) is difficult to accomplish, with PV reconnection rates of > 70%. The factors associated with persistent PVI are still uncertain.

Purpose

To assess the PVI status in patients (pts) undergoing a redo ablation and to determinate the predictors associated with persistent PVI.

Methods

Consecutive pts who underwent a redo ablation between 2016 and 2020 were identified in a single-centre retrospective study. PVI status was assessed during electrophysiologic study with electroanatomic mapping system. Index procedures included second generation cryoballoon (CB), conventional radiofrequency (RF) before 2018 and CLOSE protocol guided RF ablation after 2018. Persistent PVI was defined by the absence of reconnection of all pulmonary veins.

Results

We included 83 pts with a mean age of 55,9 ± 11,9 years; 71,1% (n = 59) were male with a mean CHA2DS2-VASc score of 1,14 ±1,0. Seventy-five percent had paroxysmal AF and undergone a redo 35,0 months (±30,9) after the index PVI.

Seventeen pts (20,5%) had persistent PVI whereas 66 pts (79,5%) had at least one PV reconnected after the index procedure, with a reconnection rate of 51,8% for right superior and inferior PV, 47,0% for left superior PV and 36,1% for left inferior PV.

No statistically significant differences were noticed between pts with persistent and non-persistent PVI in baseline (clinical and echocardiographic) characteristics.

Regarding index ablation procedure, persistent PVI occurred more frequently in patients who underwent a "CLOSE" protocol-guided index PVI compared to RF pre-2018 and CB (45,5% vs 16,7%; p = 0,043).

Twenty-nine percent of pts with persistent PVI had a "CLOSE" protocol-guided index PVI whereas only 9,1% of non-persistent PVI pts had a "CLOSE" protocol-guided index PVI (p = 0,043).

In this cohort, "CLOSE" protocol-guided index PVI was the only predictor of persistent PVI (odds ratio 4.2, 95% confidence interval 1.1-15.9; p = 0.037).

Conclusions

In patients undergoing redo AF ablation procedures, only 20,5% had persistent PVI. "CLOSE" protocol-guided index PVI presented significantly higher rates of persistent PVI.  "CLOSE" protocol-guided index PVI was the only predictor for persistent PVI in patients with AF recurrence requiring a redo procedure.
Risk factors for the development of arrhythmias after the fontan surgery
Authors: Fernandez Domenech J , Ortiz-Solis WA , Cueva-Parra A , Gomez-Flores JR , Nava-Townsend S
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Fontan surgery or total cavopulmonary connection is a palliative procedure for complex congenital heart disease with univentricular physiology, without the possibility of biventricular surgical correction. This surgery has a high mortality rate (70%), with heart failure and arrhythmias being the main causes of death.

Objective

Identify the pre, intra and post-surgical factors that may predispose to arrhythmias in patients undergoing to Fontan surgery.

Methods

We conducted a retrospective review of the patients who underwent a total cavopulmonary connection from January 2003 to December 2018. We performed an analysis employing the Chi-square test to determine which variables were associated with the development of arrhythmias.

Results

During the mentioned period, 115 patients underwent to Fontan surgery, of which 51.3% were women, the average age at the time of surgery was 8 years. The most frequent diagnosis was tricuspid atresia in 44 patients (38.2%), followed by pulmonary atresia in 18 patients (15.7%) and double outlet right ventricle in 14 patients (12.2%).

Regarding the type of the procedures performed, 93.9% (n = 108) were total extracardiac cavopulmonary connection and 6.1% (n = 7) were intracardiac. Also, 8.6% (n = 10) were taken to fenestration, the mean size of the fenestration was 7 mm (7 ± 3 mm)

After Fontan surgery, there was a high incidence of arrhythmias which was 38% (n = 44). 22 patients (50%) presented them in the late postoperative period, being this, the most frequent time for the appearance of arrhythmias.

We found that the intracardiac surgery presented an OR of 4.423 (95% CI 0.819 - 23.879, p> 0.05), being not statistically significant. Instead, the bidirectional cavopulmonary shunt previous to the Fontan surgery presented an OR of 0.255 (95% CI 0.081 - 0.806, p <0.05) and on the other hand the QRS duration > 120 ms was significantly associated with the appearance of arrythmias with an OR 2.99 (95% CI 1.2-4.2, p <0.05).

Conclusions

In patients undergoing to Fontan surgery, the previous bidirectional cavopulmonary bypass is a protective factor for the development of arrhythmias. And an QRS duration > 120 ms is a parameter that predicts the apparence of arrhythmias. Abstract Figure. QRS INTERVAL POST FONTAN SURGERY
Impact of guideline-based medical therapy on malignant arrhythmias and mortality among heart failure patients implanted with a primary prevention ICD/CRTD
Authors: Rav Acha M , Farkash R , Davarashvili I , Glikson M , Hasin T
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

In contrast with the well-established impact of heart failure (HF) medical treatment reducing HF hospitalizations and improving survival, its impact on ventricular arrhythmia (VA) is based mainly on circumstantial evidence.

Aim

To evaluate prevalence of HF medical treatment and its impact on VA and overall survival among HF patients implanted with primary prevention ICD/CRTD.

Methods

Single center retrospective analysis of all HF patients implanted with ICD/CRTD as primary prevention. Patients" indication for implant according to guidelines was confirmed by a senior EP physician. Thereafter, the association of HF medications and dose (% guideline recommended target dose) of beta-blockers (BB), Angiotensin-antagonists (AgA), Mineralocorticoid-antagonsits (MRA), and Anti-Arrhythmic Drugs (AAD) with VA episodes and overall mortality was analyzed, based on patients" medical records and device clinic regular interrogations.

Results

186 HF patients qualifying for primary prevention ICD/CRTD implant according to HF and device guidelines, were included. Their mean ± SD age 66.4 ± 12 years, 15.1% female, 79 (42.5%) implanted with an ICD and 107 (57.5%) with CRTD. During 3.8 [2.1;6.7] (median[IQR]) years; 52 (28%) had VA and 77 (41.4%) died. Treatment (medication, % of patients) included: BB (83%), AgA (87%), MRA (59%), and AAD (43.5%). Doses were 25[12.5;50]% of target for BB or AgA and 25[0;50]% of target for MRA. Treatment with >25% target dose of BB was associated with significantly reduced VA incidence. In a multivariable model including age, gender, diabetes, heart rate, and medication doses, increased BB dose was significantly and independently associated with reduced VA (HR 0.443 95%CI 0.222-0.885; p = 0.021). Kapkan-Myer analysis for survival without VA according to each medication group dose, supported reduced VA among patients receiving > median dose of BB (Figure 1). Multivariable model for overall mortality including age, gender, renal disease, VA, and medical treatment; VA was associated with increased mortality (HR 2.672; 95% CI 1.429-4.999; p = 0.002) while AgA treatment was significantly and independently associated with reduced mortality (HR 0.515; 95% CI 0.285-0.929; p = 0.028).

Conclusions

In this cohort of real-life HF patients discharged after primary prevention ICD/CRTD implant, most of the patients were prescribed with guideline-based HF medications albeit with low doses. Higher BB dose was associated with reduced VA, while treatment with AgA was associated with improved survival. Abstract Figure. Survival without VA according to HF medi
Increasing adiposity and metabolic dysfunction prolong QTc interval and increase risk of ventricular arrhythmias: results from the UK Biobank
Authors: Patel K , Li X , Xu X , Sun L , Ardissino M , Punjabi P , Purkayastha S , Peters N , Ware J , Ng FS
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): National Institute for Health Research

Background/purpose: Small-scale studies have associated obesity and metabolic ill-health with QTc interval prolongation. Whether these associations are modulated by an underlying genetic predilection and translate into higher risks of ventricular arrhythmias (VA) is unknown.

Methods

 Using the UK Biobank and adjusted multivariate regression analysis, we studied the associations between QTc and clinical measures of adiposity and metabolic ill-health. A polygenic risk score was used to determine whether these associations are modulated by a genetic predilection for QTc prolongation. We compared QTc between four clinical phenotypes defined according to presence (+) or absence (-) of obesity (Ob), and metabolic ill-health (MU). Logistic regression was used to calculate odds ratios (OR) for VA amongst these groups.

Results

 23,683 individuals (11,563 male, mean age 61.0 + 7.5years) had ECG and clinical data available. QTc prolongs with increasing body mass index (0.76ms/kg/m2, 95%CI: 0.68-0.83ms/kg/m2), body fat (0.45ms/%, 95%CI:0.39-0.50ms/%), hip girth (0.35ms/cm, 95%CI:0.31-0.39ms/cm) and waist girth (0.32ms/cm, 95%CI:0.29-0.35ms/cm); all p < 0.001. Genetically determined repolarisation reserve has no significant modulatory effect on the QTc-prolonging effects of increasing adiposity. Referenced to Ob-MU-, Ob + MU- and Ob-MU+ independently prolong QTc to a comparable extent, and Ob + MU+ has an additive effect on QTc prolongation. With reference to Ob-MU-, OR for VA in Ob-MU+ males and females were 5.96 (95%CI:4.70-7.55) and 5.10 (95%CI:3.34-7.80), respectively. OR for Ob + MU+ were 6.99 (95%CI:5.72-8.54) and 3.56 (95%CI:2.66-4.77) in males and females, respectively, (all p < 0.001, see Table).

Conclusion

 Adiposity and metabolic perturbation prolong QTc to a similar extent, and their co-existence exerts an additive effect. These effects are independent of genetically determined repolarisation reserve. Despite their comparable QTc prolonging effects, metabolic ill-health is associated with higher OR for VA than obesity. VA in obesity and metabolic dysfunctionReference phenotypeOb + MU-Ob-MU+Ob + MU+Ob-MU+male1.10(0.87-1.39)ns5.96 (4.70-7.55)***6.99(5.72-8.54)***female0.87(0.64-1.18)ns5.10(3.34-7.80)***3.56(2.66-4.77)***Ob + MU-male--6.01(4.98-7.26)***female--5.61(4.18-7.52)***Ob + MU+male--1.25(1.05-1.49)*female--1.16(0.80-1.68)nsOb, obese; MU, metabolically unhealthy; +, presence; -, absence; ns, non-significant; *p < 0.05; ***p < 0.001. Abstract Figure. QTc in obesity and metabolic dysfunction
Global cardiac sympathetic denervation is associated with diffuse myocardial fibrosis in non-ischemic cardiomyopathy
Authors: Chen HS , Jungen C , Kimura Y , Dibbets-Schneider P , Piers SRD , Androulakis AFA , Van Der Geest RJ , Lamb HJ , Scholte AJHA , De Geus-Oei LF , Jongbloed MRM , Zeppenfeld K
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

 

Occurrence of ventricular tachycardias (VT) has been related to changes in sympathetic innervation and myocardial tissue in ischemic cardiomyopathy. In non-ischemic cardiomyopathy (NICM) patients with VT, the relation between global cardiac sympathetic innervation and non-ischemic fibrosis is less clear. The current gold standard in electrophysiology to identify non-ischemic fibrosis relies on unipolar endocardial voltage mapping.

Objective

To establish the relationship between global cardiac sympathetic innervation and global fibrosis.

Methods

29 patients (93% male, 58 ± 14 years, mean LVEF 38%±13) from the ‘Leiden Nonischemic Cardiomyopathy Study’ undergoing VT ablation between 2011-2018 were included. Endocardial voltage mapping was performed and the mean endocardial unipolar voltage (UV) was taken as a surrogate for global fibrosis. Global cardiac sympathetic innervation was analyzed by 123-I-MIBG imaging using heart-to-mediastinum ratio (HMR). A cut-off of 1.8 was used to delineate between normal (>1.8) and denervated (<1.8). HMR was correlated with mean UV.

Results

For patients with global cardiac sympathetic denervation a linear relationship was present between HMR and mean UV (R = 0.5278, P = 0.0431. There was no significant linear relationship for patients with normal cardiac sympathetic innervation between HMR and mean UV (R=-0.1696, P = 0.5795).

Conclusion

Global cardiac sympathetic denervation is related to myocardial fibrosis in patients with NICM and VT. The data support an interplay between denervation and fibrosis which may contribute to arrhythmogeneity, as observed in ICM. Abstract Figure.
Identification of novel biomarkers for predicting atrial fibrillation outcomes in patients with cardiovascular risk factors
Authors: Khashaba A , Brady P , Nehaj F , Schnabel RB , Kirchhof P , Fabritz L , Chua W
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): CATCH ME European Commission H2020 grant (no. 633196)

Background

Several novel blood biomarkers were recently found to reflect underlying pathophysiology implicated in atrial fibrillation (AF). These biomarkers could be used for stratifying patients at risk of developing AF or AF-related adverse events.

Purpose

We combined 9 clinical risk factors and 12 biomarkers to model composite outcomes of 1) incident AF, hospitalisation for arrhythmias, and cardiovascular death in sinus rhythm patients at risk of AF, and 2) recurrent AF, hospitalisation for arrhythmias, and cardiovascular death in patients with AF.

Methods

1455 patients presenting acutely to hospital with either diagnosed AF (n = 648) or sinus rhythm and ≥2 CHA2DS2-VASc risk factors (n = 807, silent AF ruled out by 7-day ECG monitoring) were followed up for two years. Outcomes were collected from linked hospital episode statistics (HES) and Office of National Statistics (ONS) data from NHS Digital. We univariately evaluated 12 cardiovascular biomarkers quantified from EDTA plasma collected at baseline (ANG2, BMP10, CA125, CRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NTproBNP, Troponin T). Two predictive models combining clinical characteristics and biomarkers were developed for each patient group, using Cox regression with backward elimination and considering non-cardiovascular death as a competing risk.

Results

In sinus rhythm patients (n = 117/807 with outcome), elevated BMP10, ANG2, CA125, IGFBP7, NTproBNP univariately predicted the composite outcome (adjusted for age, sex, body mass index (BMI), eGFR, heart failure, stroke/TIA, hypertension, diabetes, coronary artery disease – see Figure part A). In the combined model, age, prior stroke/TIA, coronary artery disease, ANG2, IGFBP7 and NTproBNP predicted the outcome (C-statistic [95% confidence interval (CI)] 0.733 [0.683, 0.784]).

In patients with AF (n = 193/648 with outcome), elevated BMP10, ANG2, CA125, troponin T, GDF15, IGFBP7, NTproBNP univariately predicted the composite outcome (adjusted for same variables as above – see Figure part B). In the combined model, high BMI, low eGFR, hypertension, IGFBP7, NTproBNP and troponin T were predictive of the composite outcome (C-statistic [95% CI]: 0.643 [0.596, 0.689]).

Conclusion

Combinations of clinical risk factors and biomarkers were predictive of two-year AF-related adverse events in sinus rhythm patients at risk of AF and in patients with AF. These markers could be used to identify patients for more intensive follow-up or therapy. IGFBP7 and NTproBNP were present in both models, implicating pathways involved with cardiac overload, inflammation, and oxidative stress. These findings call for external validation of these markers and prospective evaluation in at-risk populations. Abstract Figure. Biomarkers predicting 2-year AF outcomes
Application of recurrence plot analysis to characterise whole chamber propagation of atrial fibrillation
Authors: Pope M , Kuklik P , Briosa E Gala A , Leo M , Paisey J , Mahmoudi M , Betts TIMOTH
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): Oxford Biomedical Research Centre

Introduction

Non-contact charge density mapping allows visualisation of whole chamber propagation during atrial fibrillation (AF). The identification of regions with repetitive or, conversely, more complex patterns of wavefront propagation may provide clues to mechanisms responsible for AF maintenance and lead to improved outcomes from catheter ablation. Our novel mapping approach based on signal recurrence plots has never been applied to whole chamber, bi-atrial recording of atrial fibrillation.

Purpose

To apply recurrence analysis to characterise whole chamber bi-atrial AF propagation.

Methods

Non-contact dipole signals from left and right atrial maps were obtained during simultaneous bi-atrial charge density mapping of AF. Signals were converted to phase and mean phase coherence calculated for the generation of recurrence distance matrices for the whole chamber and each anatomical region (6x LA and 4x RA) over the 30-second recording duration, where a value of 1 (purple, see figure panel A) represents uniform repetitive conduction, and 0 (red), irregular, non-repetitive activity. Whole chamber and regional mean recurrence values were calculated and correlated with the frequency of wavefronts of localised irregular activation patterns.

Results

Maps were obtained prior to ablation in 21 patients (5 paroxysmal (pAF), 16 persistent AF (persAF)) undergoing de-novo catheter ablation procedures. Whole chamber recurrence was higher in patients with pAF (0.40 ± 0.08) than persAF (0.34 ± 0.05), p < 0.0005. There was an inverse correlation between regional recurrence values and the number of localised irregular activations detected (-0.7021, p < 0.0005, figure panel B) with the lateral LA and anterior RA demonstrating the highest recurrence values in each chamber (figure panel C).

Conclusion

Use of recurrence distance matrices characterises global AF propagation phenotypes. Regional values are inversely correlated with the frequency of localised irregular activation patterns identified demonstrating an anatomic dependence in the level of AF propagation complexity, greatest in the anterior LA and septal RA. Comparison of strategies targeting regions with maximal vs. minimal values during catheter ablation may define an optimal approach to treatment of persistent AF. Abstract Figure. Recurrence abstract figure
Factors predicting adverse cardiovascular outcomes in patients with atrial fibrillation and heart failure with preserved ejection fraction
Authors: Saksena S , Slee APRIL , Lakkireddy D , Shah DIPEN , Di Biase LUIGI , Lewalter T , Natale A
Published: May 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): Electrophysiology Research Foundation

Introduction

Atrial fibrillation (AF) is known to impact cardiovascular(CV) mortality in heart failure (HF) patients (pts) with preserved ejection fraction (pEF) but its exact causes are unknown.

Methods

 We analyzed demographic, clinical, ECG and AF presentation as predictors of CV mortality, sudden death( SCD) and pump failure death(PFD) in HFpEF pts in the TOPCAT AMERICAS trial. We analyzed two AF presentations 1. Pts in sinus rhythm (SR, n = 1319) compared to AF  on ECG (n = 446) at entry or 2. Pts with no AF event by history or ECG ( n = 1007 ) to those with any AF event (n = 760 ).

Results (Table): 5 year (yr) CV mortality was higher in pts with AF on ECG (30%) than SR (18%, p = 0.014) but 5 yr SCD was (10% in AF on ECG & 7% in any AF) & comparable to SR (7% & 9% respectively, p = ns). 5 yr PFD was higher in AF on ECG  (13%) than SR (5%, p = 0.007) 

Conclusions

: 1. CV death risk in HFpEF pts increased with AF on ECG.. 2. SCD was not more frequent with both AF presentations 3. PFD in HFpEF increased with age, ECG recorded AF & elevated heart rate. 4. The recording of AF on ECG was more strongly associated with CV death & PFD, possibly due to greater AF burden . Predictors of adverse outcomes in HFpEF AF on ECG* Any AF* Endpoint Covariate HR (95% CI) p-value HR (95% CI) p-value Time to cardiovascular death Atrial Fibrillation* 1.44 (1.08, 1.92) 0.014 1.15 (0.87, 1.51) 0.338 Age (years) 1.03 (1.02, 1.05) <.001 1.03 (1.02, 1.05) <.001 Black/AA (vs. White) 0.97 (0.65, 1.46) 0.002 0.96 (0.64, 1.44) 0.004 Other race (vs. White) 2.41 (1.46, 3.99) 2.32 (1.41, 3.83) Smoking 2.62 (1.63, 4.20) <.001 2.60 (1.62, 4.17) <.001 Diabetes 1.47 (1.12, 1.94) 0.006 1.45 (1.10, 1.91) 0.009 Systolic BP (mmHg) 0.99 (0.98, 1.00) 0.022 0.99 (0.98, 1.00) 0.014 Heart rate (bpm) 1.02 (1.00, 1.03) 0.012 1.02 (1.01, 1.03) 0.006 Time to Any sudden cardiac death Atrial Fibrillation* 1.17 (0.69, 1.96) 0.563 0.85 (0.53, 1.35) 0.484 Female (vs. Male) 0.46 (0.28, 0.75) 0.002 0.46 (0.28, 0.74) 0.002 Black/AA (vs. White) 1.57 (0.87, 2.82) 0.194 1.49 (0.83, 2.69) <.001 Other race (vs. White) 1.76 (0.70, 4.41) 1.70 (0.68, 4.25) Diabetes 1.70 (1.07, 2.70) 0.024 1.65 (1.04, 2.62) 0.033 Time to pump failure death Atrial Fibrillation* 2.04 (1.22, 3.42) 0.007 1.62 (0.96, 2.75) 0.074 Age (years) 1.06 (1.03, 1.10) <.001 1.06 (1.03, 1.10) <.001 Heart rate (bpm) 1.03 (1.00, 1.05) 0.034 1.03 (1.01, 1.05) 0.015 Cox model of covariates associated with outcomes adjusted for baseline imbalances
The onset of paroxysmal non-valvular atrial fibrillation in men with hypertension is associated with an increase in blood levels of transforming growth factor beta 1
Authors: Koval S , Reznik LA , Starchenko TG , Mysnychenko OV , Penkova M YU
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background. Patients with essential hypertension (H), primarily men, are characterized by early formation of left ventricular hypertrophy (LVH) followed by left atrial (LA) enlargement, which significantly increases the risk of development non-valvular atrial fibrillation (nAF). The most important pathogenic factor in the development of nAF is fibrosis of the LA myocardium. One of the key profibrogenic factors is transforming growth factor beta 1(TGF-beta1).

Purpose. To evaluate the blood levels of TGF-beta1 in hypertensive men with paroxysmal nAF and without AF.

Methods.The study included 57 men with H grade 2–3 and with LVH (age 48 ± 4 years), of those 26 with paroxysmal nAF and 31 without AF. Controls were 26 practically healthy men. All patients with paroxysmal nAF had an at least one episode of paroxysmal AF attack with spontaneous return to normal sinus rhythm and were in sinus rhythm at the time of the assessment. Patients with valvular heart disease, heart failure, ischemic heart disease, cardiomyopathy, cardiac surgery, thyroid disease, diabetes mellitus, obesity, anemia, infectious or pulmonary diseases were not included. The examination of patients include standard methods as well as echocardiography. Levels of TGF-beta1 in blood serum were measured by immune enzyme assay. All patients included in the study received standard antihypertensive therapy.

Results. It was found that the blood levels of TGF-beta1 in whole group of men with H were significantly higher (13,2 [5,3;22,5] ng/mL, р=0,034 ) than in practically healthy men (7,3 [2,3;16,5] ng/mL ). The highest blood levels of TGF-beta1 were found in hypertensive men with paroxysmal nAF (18,4 [9,2;31,8] ng/mL ) and significantly exceeded (р=0,018) those in hypertensive men without AF ( 11,6 [ 4,5;19,7] ng/mL ). The following positive correlations were found in whole group of men with H between TGF-beta1 blood levels and a number of echocardiographic parameters: LA size (LA volume/height2 ) (r = 0,510, р=0,012), LV mass index ( LV mass/BSA (g/m2) ( r = 0,411, р=0,027) and E/e′ (averaged) ratio (r = 0,357, р=0,036).

Conclusion. The data obtained indicate that TGF-beta1 can play an important role, both in the pathogenesis of pathological remodeling of the LV and LA in men with H, and in the development of AF in these patients.
Atrial fibrillation substrate mapping with decrement evoked potential mapping
Authors: Salvador-Montanes O , Fitzgerald J , Jackson N , Haldar S , Cotton J , Gizurarson S , Nanthakumar K , Porta-Sanchez A
Published: May 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): Sociedad Española de Cardiologia.

OnBehalf

DEFINE-AF

Background

Identifying and targeting atrial substrate zones that are vulnerable to unidirectional block and slow conduction may be critical to improve the outcomes of atrial fibrillation (AF) ablation. Functional mapping of the atrial substrate with Decrement Evoked Potential (DeEP) and a single extrastimulus in this population could potentially lead to novel therapeutic strategies.

Aim

1) To systematically analyze whether the DEEP are present in the atrial tissue and their locations after pulmonary vein isolation. 2) To assess their relationship with the underlying voltage.  3) To assess the presence of DEEP as a function of the subtype of AF.

Methods

Consecutive patients with AF undergoing ablation were prospectively enrolled at 3 institutions. A biatrial voltage map was created and after pulmonary vein isolation (PVI). A drive train and an extrastimulus (atrial refractory period + 20ms) was delivered from an epicardial site (proximal CS) and an endocardial site (left atrial appendage (LAA). A multipolar mapping catheter was sequentially placed at 8 left atrial sites and 5 right atrial sites. Electrograms (EGMs) that showed a local delay of >10ms in activation with the extrastimulus were identified as DEEPs. Patients were followed for a mean of 11 ± 5 months

Results

74 patients, 63 pers AF (85%), mean age 62 ± 8, mean LA size 41 ±12 mm were enrolled. Of 19240 EGMs analyzed, 8.2% showed DEEPs (54.6% with CS pacing and 45.4% with LAA pacing, p = 0.0001). The mean local decrement seen was 39 ms. Most DEEPs (76.2%) were identified in sites with a normal EGM at baseline with preserved voltages. DEEPs were differentially distributed within the regions mapped, more frequently in LA than RA (9.2% vs 6.6%, p < 0.0001). Patients with persistent AF had a higher proportion of DEEPs than patients with paroxysmal AF (9.7% vs 5.1%, p < 0.001).

Conclusions

Atrial DEEPs are: 1) More often identified when pacing endocardially. 2) More common in patients with persistent AF. 3) More frequent in the LA than in the RA. 4) Mostly located in regions with normal voltages at baseline. All those findings suggest the importance of the functional substrate mapping in the atrium and could lead to novel therapeutic targets. Abstract Figure. Example of atrial DEEP
Season of birth and cardiovascular mortality in atrial fibrillation: a population-based cohort study
Authors: Fauchier L , Bisson A , Bodin A , Spiesser P , Pierre B , Clementy N , Babuty D
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background. Month and season of birth may be indicators for a variety of prenatal and early postnatal exposures and they have been associated with life expectancy in adulthood. It is suggested that people born in the autumn on the northern hemisphere live longer than those born during the spring or summer, who may have an increase in cardiovascular disease specific mortality. Only few studies have followed populations longitudinally and no study has investigated the relation between season of birth and mortality in patients with established cardiac conditions.

Methods. All patients with atrial fibrillation (AF) seen in an academic institution were identified in a database. We examined the clinical course of 8962 consecutive patients with AF seen over a 10-year period. The adverse outcomes were investigated during follow-up and we identified the causes of death. The relation between season of birth (autumn, winter, spring and summer) and mortality risk was assessed using Cox proportional hazard regression models using autumn as the reference. Analyses were also made separately for men and women. 

Results. In these 8962 patients (age 70 ± 10 years, CHA2DS2VASc score 3.1 ± 1.7), 1253 deaths were recorded during a follow-up of 2.5 ± 3.0 years (median 1.2, interquartile 4.3 years, yearly rate of death 5.5%) and 97% of causes of death were identified. Cardiovascular deaths accounted for 54% and 43% for non-cardiovascular. The three main causes of death were heart failure (29%), infection (18%) and cancer (12%). 

Season of birth was a significant predictor of cardiovascular mortality (overall p = 0.0006). The lowest mortality was seen for people born in autumn or winter and the highest mortality in those born in spring and summer. This was mainly related to a higher cardiovascular mortality in males (hazard ratio [HR] 1.46, 95%CI 1.10-1.93, p = 0.009 for males born in spring and HR 1.44, 95%CI 1.08-1.91, p = 0.01 for those born in summer when compared to males born in autumn as the reference) while this effect was not seen in women. In a model adjusted for age, CHA2DS2VASc score, HASBLED score, cardiovascular risk factors, other comorbidities, AF pattern, antithrombotic use and other cardiovascular drugs use, a higher cardiovascular mortality was still seen in males born in spring (adjusted HR 1.43, 95%CI 1.05-1.96, p = 0.03) or in summer (adjusted HR 1.46, 95%CI 1.07-1.99, p = 0.02) when compared to those born in autumn while this was not seen in women.

Conclusion. Birth in spring or summer is associated with a higher risk of cardiovascular mortality in male AF patients. Further studies should aim at clarifying the mechanisms behind this association, which would support the so-called fetal origins hypothesis.
Pregnancy-related complications and incidence of atrial fibrillation: a systematic review and meta-analysis
Authors: Al Bahhawi T , Aqeeli A , L Harrison S , A Lane D , Buchan I , Skjoth F , Sharp A , Lip GYH
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Pregnancy-related complications have been previously associated with incident cardiovascular disease. However, data are scarce on the association between pregnancy-related complications and incident atrial fibrillation (AF). This systematic review examines associations between pregnancy-related complications and incident AF.

Methods

A systematic search of the literature utilising MEDLINE and EMBASE (Ovid) was conducted from 1990 to 6 April 2020. Observational studies examining the association between pregnancy-related complications including hypertensive disorders of pregnancy (HDP), gestational diabetes, placental abruption, preterm birth, low birth weight, small-for-gestational-age and stillbirth, and incidence of AF were included. Screening and data extraction were conducted independently by two reviewers. Inverse-variance random-effects models were used to pool hazard ratios.

Results: Six observational studies met the inclusion criteria

one case-control study and five retrospective cohort studies, with four studies eligible for meta-analysis.  Sample sizes ranged from 1,839-1,303,365. Mean/median follow-up for the cohort studies ranged from 7-36 years. Most studies reported an increased risk of incident AF associated with pregnancy-related complications. The pooled summary statistic from four studies reflected a greater risk of incident AF for HDP (hazard ratio (HR) 1.47, 95% confidence intervals (CI) 1.18-1.84; I2 = 84%) and from three studies for pre-eclampsia (HR 1.71, 95% CI 1.41-2.06; I2 = 64%; Figure).

Conclusions

The results of this review suggest that pregnancy-related complications particularly pre-eclampsia appear to be associated with higher risk of incident AF. The small number of included studies and the significant heterogeneity in the pooled results suggest further large-scale prospective studies are required to confirm the association between pregnancy-related complications and AF. Abstract Figure.
Subclinical thyroid dysfunction and incident atrial fibrillation - a systematic review and meta-analysis
Authors: Singh H , Shahid MZ , Harrison SL , Lane DA , Lip GYH , Logantha SJRJ
Published: May 2021

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): This project was supported by the MRes programme in the Institute of Life Course and Medical Sciences at The University of Liverpool.

Thyroid hormones can act directly and indirectly on the cardiovascular system and studies have demonstrated associations between overt and subclinical thyroid dysfunction and adverse cardiovascular outcomes including heart failure, myocardial infarction, and coronary heart disease. The aim of this study was to assess the association between subclinical thyroid dysfunction and atrial fibrillation (AF). 

The protocol was registered on PROSPERO (CRD42020221565). MEDLINE and Scopus were searched from inception to 13th November 2020 for studies investigating subclinical thyroid dysfunction and incident AF. Risk of bias was assessed using the Risk of Bias Assessment Tool (RoBANS). The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Subgroup analysis was performed for post-operative and non-post-operative AF.

5413 records were identified. Nine cohort studies were suitable for inclusion in the systematic review, of which seven studies were included in the meta-analysis. The meta-analysis comprised 595,058 patients. Subclinical hyperthyroidism was associated with a 99% increase in the risk of incident AF (Risk ratio (RR): 1.99; 95% confidence intervals (CI); 1.43 to 2.77; p < 0.0001; I² = 67%). Subclinical hypothyroidism was also associated with a greater risk of AF (RR: 1.24; 95% CI; 1.05 to 1.47; p = 0.01; I² = 65%). Subgroup analysis demonstrated a 76% increase in the risk of post-operative AF in patients with subclinical hypothyroidism compared to euthyroid post-operative patients (RR: 1.76; 95% CI; 1.36 to 2.28; p < 0.0001; I² = 0%). Six studies were rated as low risk of bias and three as medium risk of bias according to the RoBANS tool. The quality of evidence for AF in subclinical hyper- and hypothyroid patients was low.

Subclinical hyperthyroidism and subclinical hypothyroidism were associated with a higher risk of incident AF and post-operative AF, respectively. The quality of the current evidence is low and ideally a randomised controlled trial should be conducted to confirm these associations and assess impacts of treatments. Abstract Figure.
Different implication in dementia between patients with atrial flutter and atrial fibrillation: a national cohort study
Authors: Chen YL
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Importance

Atrial fibrillation (AF) has been reported with increasing the risk of stroke and dementia. Atrial flutter (AFL) is also a risk of stroke with different discrepancies in clinical outcome. Little is known about the difference in the risk of dementia between AF and AFL.

Objective

To investigate if the risk of dementia is difference between AF and AFL.

Methods

The patients with newly diagnosed AF and AFL during 2001–2013 was retrieved from Taiwan’s National Health Insurance Research Database. Patients with missing information, aged <20 years, history of valvular surgery, rheumatic heart disease, hyperthyroidism, and history of dementia were excluded. Propensity score matching (PSM) between AF and AFL was performed, which included patient comorbidities, past medical history, medications, and index date stratified by age. Primary outcome was defined as dementia at follow-up.

Results

A total of 232,425 AF and 7,569 AFL were eligible for analysis. After 4:1 PSM, we included 30,276 AF (aged 67.3 ± 15.7 years) and 100,065 AFL (aged 67.4 ± 16.0 years) for analysis. The risk of dementia was higher in AF patients compared with AFL patients (subdistribution HR (SHR)=1.52, 95% CI 1.39 - 1.66; p <0.0001) before PSM and still higher in AF patients (SHR = 1.14, 95% CI 1.04 to 1.25; p = 0.0064). The risk was higher in AF patients without previous stroke after PSM and there was no difference between AF and AFL patients with previous stroke history.

Conclusions and relevance

Our finding supports that risk of dementia is higher in AF patients than AFL patients. However, the risk of dementia between patients with AF and AFL varies depending on whether there is a previous stroke history.
Performance of automated single-lead ECG atrial fibrillation screening is associated with patient characteristics
Authors: Zink MD , Freedman B , Mischke K , Keszei A , Rummey C , Marx N
Published: May 2021

Funding Acknowledgements

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The investigators received and unrestricted research grant by Pfizer/BMS. Pfizer/BMS was not involved in the planning, conduction, analysis, or interpretation of the data.

Introduction

Screening for atrial fibrillation (AF) with a single-lead electrocardiogram device is on the rise. However, little is known about influence of automated AF screening performance related to patient characteristics.

Aim

We tested the accuracy of automated AF detection of a single-lead ECG device and identified factors associated with diagnostic performance.

Methods

In 6482 subjects of community-pharmacies a single-time point AF screening was performed. All ECGs were analyzed by blinded human overread and compared to the automated results in context of patient characteristics.

Results

Automated screening showed good prediction of AF with an area under the receiver operating curve of 0.89; sensitivity 80%; specificity 98%; positive predictive value 71%; negative predictive value 99%. Good ECG signal quality was highly associated with correct measurement, while low signal quality leads to incorrect measurements. In a multivariate model we determined factors associated with excellent signal quality and as counterexample incorrect automatic AF identification. The Odds’ ratio (OR) for excellent signal quality was strongly associated with female sex, lower age, lower height, and higher body weight index (table).

Conclusion

The performance of automated AF screening is influenced by sex, age, height and body mass index. Potential target population groups, with high AF prevalence, have a higher chance of incorrect automatic measurement. We recommend an expert over-read, at least for all AF positive ECG recordings. Table 1 Excellent signal quality Incorrect measurement Univariate analysis Multivariate analysis Univariate analysis Multivariate analysis Parameter OR 95% CI P OR 95% CI P OR 95% CI P OR 95% CI P Sex [Female] 2.33 1.97-2.75 <0.001 1.92 1.53-2.41 <0.001 0.64 0.49-0.84 0.001 0.57 0.43-0.76 <0.001 Age [years] 0.97 0.96-0.98 <0.001 0.97 0.96-0.98 <0.001 1.07 1.04-1.09 <0.001 1.06 1.04-1.09 <0.001 Height [cm] 0.96 0.95-0.97 <0.001 0.98 0.97-0.99 0.003 1.01 0.99-1.03 0.068 Weight [kg] 0.99 0.99-1.00 0.418 0.99 0.98-0.99 0.003 BMI [kg/cm2] 1.04 1.03-1.06 <0.001 1.04 1.03-1.06 <0.001 0.91 0.88-0.95 <0.001 0.91 0.87-0.94 <0.001 CHADSVASC 1 0.95-1.06 0.912 1.06 0.97-1.17 0.205 Heart failure 0.62 0.41-0.93 0.022 1.86 1.13-3.05 0.015 Hypertension 0.96 0.83-1.11 0.58 1.06 0.80-1.39 0.689 Diabetes mellitus 0.85 0.68-1.07 0.159 0.82 0.54-1.25 0.359 Stroke / TIA 0.82 0.66-1.01 0.066 1.19 0.83-1.69 0.341 Vascular disease 0.89 0.75-1.07 0.213 1.31 0.98-1.77 0.70 OR – odd’s ratio, CI – confidence interval
Prediction of left atrial thrombus in patients with nonvalvular atrial fibrillation referred to catheter ablation or cardioversion: comparison of different risk scores
Authors: Zaigraev IA , Yavelov IS , Drapkina OM , Bazaeva EV
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background. Left atrial thrombus (LAT) is the main source of cardiac emboly in patients with non-valvular atrial fibrillation (NAF). Several risk scores – mostly modified CHADS2 and CHA2DS2-VASc – were offered to predict LAT in patients with NAF. However, their relative predictive value requires further evaluation.

Purpose. Compare the ability of different risk scores to predict LAT before catheter ablation or cardioversion in patients with NAF.

Methods. In a retrospective single-center study, medical records of 1994 patients with NAF who underwent transesophageal echocardiography before catheter ablation or cardioversion were analyzed. LAT was identified in 33 (1.6%) of them. For the control group 167 patients without LAT were randomly selected from this database. Logistic regression analysis and C-statistic were used for evaluation and comparison of predictive values of CHADS2, R2CHADS2, CHA2DS2-VASc, R-CHA2DS2-VASc, R2CHA2DS2-VASc, CHA2DS2-VASc-RAF, mCHA2DS2-VASc and CHA2DS2-VASc-AFR scores.

Results. The mean age of studied patients was 60.3 ± 10.9 years, 110 (55%) of them were males. The mean CHA2DS2-VASc score was 2.54 ± 1.79.

Results of univariate analysis and C-statistic for above mentioned risk scores are presented in the table. Each of them was associated with LAT. In comparison with a CHA2DS2-VASc score C-statistic was significantly higher for CHA2DS2-VASc-RAF and CHA2DS2-VASc-AFR scores (p values 0.03 and 0.001 respectively).

In multivariate analysis only CHA2DS2-VASc-RAF score was associated with LAT (OR 1.37; 95% CI 1.21-1.55, p < 0.0001). OR for LАT in patients with CHA2DS2-VASc-RAF >3 was 12.8 (95% CI 3.75-43.9; p < 0.0001) with sensitivity, specificity, positive and negative predictive values 90.6%, 57.1%, 33.3% and 58.9% respectively.

Conclusion. In a group of patients with NAF and relatively low incidence of LAT all studied scores were associated with LAT and CHA2DS2-VASc-RAF score has appeared the most informative. Predictors of LAT in patients with NAF Risk stratification models OR (95% CI) p-value C-statistic (95% CI) CHADS2 2.12 (1.55-2.91) <0.0001 0.77 (0.68-0.85) R2CHADS2 2.00 (1.53-2.62) <0.0001 0.78 (0.69-0.87) CHA2DS2-VASc 1.65 (1.36-2.05) <0.0001 0.74 (0.65-0.84) R-CHA2DS2-VASc 1.64 (1.34-2.03) <0.0001 0.76 (0.66-0.85) R2CHA2DS2-VASc 1.59 (1.32-1.92) <0.0001 0.76 (0.66-0.85) CHA2DS2-VASc- RAF 1.35 (1.27-1.52) <0.0001 0.84 (0.76-0.91) mCHA2DS2-VASc 1.83 (1.42-2.35) <0.0001 0.75 (0.65-0.85) CHA2DS2-VASc-AFR 1.75 (1.41-2.17) <0.0001 0.80 (0.71-0.88)
Sex-related differences in self-reported treatment burden in patients with atrial fibrillation
Authors: Mihajlovic M , Simic J , Marinkovic M , Kovacevic V , Kocijancic A , Mujovic N , Potpara T
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

 Treatment burden (TB) is defined as the patient’s workload of health care and its impact on patient functioning and well-being. High TB can lead to nonadherence, higher risk of adverse outcomes and lower quality of life. We have previously reported a higher TB in patients with atrial fibrillation (AF) vs. those with other chronic conditions. In this analysis, we explored sex-related differences in self-reported TB in AF patients.

Methods

 A single-centre, prospective study included consecutive patients with AF under drug treatment for at least six months before enrolment from April to June 2019. Patients were asked to voluntarily and anonymously answer Treatment Burden Questionnaire (TBQ). All patients signed the written consent for participation.

Results

 Of 331 patients (mean age 65.4 ±10.3 years, mean total AF history 6.41 ±6.62 years), 127 (38.4%) were females. The mean TB was significantly higher in females compared to males (53.7 vs. 42.6 out of 170 points, p < 0.001), also females more frequently reported TB ≥59 points than males (37.8% vs 20.6%, p = 0.001). Item-specific sex-related differences in self-reported TB questionnaire are showed in Figure. Sex-related differences in TB on multivariable regression analyses of the highest TB quartile (≥59 points) are showed in Table.

Conclusion

 Our study was first to explore the sex-specific determinants of TB in AF patients. Females had significantly higher TB compared with males. Approximately 2 in 5 females and 1 in 5 males reported TB ≥59 points, previously shown to be an unacceptable burden of treatment for patients. Using a NOAC rather than VKA in females and a rhythm control strategy in males could decrease TB to acceptable values. Table.Multivariable Logistic Regression analysis of the highest TB quartile (TB ≥59)VariableOR95% CIP valueFemalePPI therapy5.3541.97-14.560.001NOAC0.3190.12-0.830.019Diuretic therapy0.3180.13-0.760.010CHA2DS2-VASc score0.7000.49-0.990.045MaleAblation and/or ECV0.3830.18-0.810.012Supraventricular arrhythmias0.2220.05-0.980.047VKA Vitamin K antagonist; ECV: electrical cardioversion; AF: Atrial fibrillation; PPI: Proton pump inhibitor; PCI: Percutaneous coronary intervention; NOAC: Non-vitamin k antagonist oral anticoagulant.Abstract Figure.