bluuebunny/crossref_metadata_2025 huggingface dataset:
Off-label underdosed apixaban use in Asian patients with non-valvular atrial fibrillation
Authors: Lee SR , Choi EK , Park SH , Jung JH , Han KD , Lip GYH
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

In Asian patients with atrial fibrillation (AF), off-label underdosed prescriptions of direct oral anticoagulants (DOACs) are common

Purpose

We aimed to compare the effectiveness and safety of off-label underdosed apixaban with on-label standard dose apixaban in Asian patients with AF.

Methods

Using the Korean nationwide claims database, we identified patients who prescribed apixaban and did not fulfill the dose reduction criteria of apixaban between January 2015 and December 2017. Multivariable Cox hazard regression model was performed and hazard ratios (HRs) for ischemic stroke, major bleeding (MB), all-cause death, and the composite clinical outcome were analyzed.

Results

Compared to patients prescribed on-label standard dose apixaban (n = 4,194), patients prescribed off-label underdosed apixaban (n = 2,890) were associated with higher risks of ischemic stroke (adjusted HR [aHR] 1.38, 95% confidence interval [CI] 1.06-1.81), all-cause death (aHR 1.19, 95% CI 1.01-1.39) and the composite clinical outcome (aHR 1.17, 95% CI 1.03-1.34), but with no significant differences in MB between the two groups (Figure). In patients without any dose reduction criteria, off-label underdosed apixaban use was associated with a significantly higher risk of ischemic stroke than on-label standard dose apixaban use (aHR 1.85, 95% 1.25-2.73); however, in patients who had single dose reduction criteria (age ≥80 years, serum creatinine ≥1.5mg/dL, or bodyweight ≤60 kg), off-label underdosed apixaban use did not show a significant overall benefit in the composite clinical outcome compared with on-label standard dose apixaban, but was associated with a higher risk of all-cause death (aHR 1.32, 95% CI 1.07-1.64).

Conclusion

Off-label underdosed apixaban use was associated with higher risks of ischemic stroke, all-cause death, and composite clinical outcome and comparable risk of MB compared with on-label standard dose apixaban use. Label-adherence of apixaban dosing should be emphasized to achieve the best clinical outcome for Asian patients with non-valvular AF, especially in those without any dose reduction criteria. Abstract Figure.
Assessing atrial fibrillation ablation priority during COVID-19 -does use of patient questionnaires help in stratification above physician assessment?
Authors: Pius C , Ahmad H , Snowdon R , Ashrafi R , Waktare J , Borbas Z , Luther V , Mahida S , Modi S , Hall M , Gupta D , Todd D
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Catheter ablation for atrial fibrillation (AF) is largely offered for symptomatic relief. The ORBIT registry has shown that patients with a higher EHRA class and lower quality of life (QoL) scores (AFEQT score <65.7) are more likely to suffer emergency hospital admissions. To help prevent unplanned AF admissions and to best utilise the reduced capacity for elective work during the COVID-19 pandemic, it has become even more important to prioritise the most symptomatic AF patients for ablation. Purpose: To evaluate the accuracy of a subjective symptom-based clinician prioritisation schema compared to objective patient-completed quality of life (QoL) scores. Methods: In July 2020, all elective cases awaiting AF ablation at our institution were categorised by their cardiologist as either category 1 (C1-urgent), category 2 (C2–priority, procedure to be done during the ongoing COVID-19 pandemic) or category 3 (C3–routine, procedure may be delayed until post pandemic). This categorisation was based on review of clinic letters where EHRA AF symptom class or PROMS are not routinely recorded.  All patients in C2 and C3 were then posted an AF specific (AFEQT) and a generic (EQ5D) QoL questionnaire to complete. Physicians were blinded to patient responses on the QoL questionnaires. Results: Details of physician prioritisation and completed questionnaires were available for 85 patients (62 ± 10 years, PAF in 61%, males 66%). The 18 patients that had been categorised in C2 (priority) group were found to have a significantly lower AFEQT score (30.4, IQR 17.2-51.9) compared to the 67 patients classed in C3 (routine) group (56.5, IQR 32.1-74.1; p < 0.01)(Figure 1a). EQ5D scores also tended to be lower in the C2 patients (0.7, IQR 0.4-0.8) compared to C3 (0.8, IQR 0.6-0.9; p = 0.056) (Figure 1c). 16 (89%) patients in C2 had significant AF-related impact on QoL (as defined as AFEQT score <65.7) compared to 42 (63%) of patients in C3.  However, there was significant overlap between groups (Figure 1b). 4 patients in C3 had unplanned AF related hospital admissions while awaiting ablation, as compared to none in C2. The median AFEQT score of these 4 patients was 23.3, indicating that they were highly symptomatic despite being classified in C3 by their cardiologist. Conclusion : Physician assessments are moderately accurate in prioritising patients awaiting AF ablation. The addition of formal patient-completed QoL assessment such as with AFEQT, helps to identify the most symptomatic patients at risk of emergency hospital admission, and physicians should consider using these as part of routine assessment, especially during the COVID pandemic. Abstract Figure 1
Oral anticoagulant therapy at hospital admission associates with lower mortality in older COVID-19 patients with atrial fibrillation. An insight from the Covid Registry
Authors: Fumagalli S , Trevisan C , Del Signore S , Pelagalli G , Volpato S , Gareri P , Mossello E , Malara A , Monzani F , Coin A , Bellelli G , Zia G , Antonelli Incalzi R
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

OnBehalf

the GeroCovid Investigators

Introduction. Atrial fibrillation (AF), the arrhythmia most frequently diagnosed in older patients, associates with serious, thrombo-embolic, complications and high mortality. COVID-19 severely affects aged subjects, determining an important prothrombotic status.

Purpose. Aim of this study was to evaluate mortality-related factors in older AF patients with COVID-19. 

Methods. We included 806 in-hospital COVID-19 patients aged 60 years or more hospitalized between March 1st and June 6th 2020 and enrolled in a multicenter observational study.

Results. The prevalence of AF was 21.8%. In-hospital mortality was higher in the AF group (36.9 vs. 27.5%; p = 0.015). Among AF patients, those who survived were younger (81 ± 8 vs. 84 ± 7 years; p = 0.002), had a lower CHA2DS2-VASc score (3.9 ± 1.6 vs. 4.4 ± 1.3; p = 0.02) and were more frequently treated with oral anticoagulants at admission (63.1 vs. 32.3%; p < 0.001) than those who died in hospital. At multivariable logistic regression analysis, lower age (p = 0.042), a better functional profile (p = 0.007), less severe COVID-19 manifestations at admission (p = 0.001), and the use of Vitamin K antagonists (OR = 0.16, 95%CI: 0.03-0.84; p = 0.031) or DOACs (OR = 0.22, 95%CI: 0.08-0.56; p = 0.002), compared to antiplatelet therapy or no treatment at all, were associated with a lower chance of in-hospital death.

Conclusions. AF is a prevalent condition and a severity factor in older COVID-19 patients. Advanced age, dependency and severe clinical manifestations of disease characterized older AF subjects with a worse prognosis. Interestingly, pre-admission anticoagulant therapy correlated positively with in-hospital survival.
Supraventricular arrhythmia in tetralogy of Fallot repair
Authors: Vincze V , Kardos A , Kornyei L , Balint H
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): Gottsegen National Cardiovascular Center

BACKGROUND

With aging morbidity related to arrhythmias in adult patients with Tetralogy of Fallot repair (TOFr) is increasing.

OBJECTIVE

We aimed to analyze the prevalence of supraventricular tachycardia in these patients using our prospective database.

METHODS

TOFr data were collected from our prospective database conducted since 2010. Supraventricular arrhythmias (intraatrial reentrant tachycardia (IART), atrial fibrillation, AFib) related complications and therapies were documented.

RESULTS

Among those with TOFr (n = 296, mean age 34 ± 11) supraventricular tachyarrhythmias (SVT) were present in 41 patients (14%), as following: n = 12 AFib, and n = 29 IART. At the univariate analysis predictors of atrial fibrillation and IART were: age at last follow-up (p < 0,0001), age at first repair (p < 0,0001), number of surgeries (p = 0,014), and tricuspid regurgitation (p = 0,013). Supraventricular tachycardia was a strong predictor of death (OR 3.0). 

Twenty-five patients had radiofrequency ablation, and after a mean follow-up of 61 ± 56 months, the rate of recurrence for SVT was 32 %. In the non-ablated cohort (treated with amiodarone) 73 % recurrence was detected.

CONCLUSION

Supraventricular arrhythmias are common in TOFr patients and are associated with increased mortality risk, but arrhythmia control with catheter ablation is superior to anti-arrhythmic drug therapy in this patient population.
First Vs Recurrent Syncope In Patients With Structural Heart Disease Or Bundle Branch Block
Authors: Francisco Pascual J , Rivas Gandara N , Santos Ortega A , Perez Rodon J , Benito B , Roca I , Cantalapiedra Romero J , Maldonado J , Jordan Marchite P , Herrador Galindo L , Ferreira Gonzalez I
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): Hospital Universitari Vall d"Hebron - Vall d"Hebron Institut de Recerca. CIBERCV

BACKGROUND

Patients with structural heart disease (SHD) or bundle branch block (BBB) are at high risk of having an arrhythmic syncope (AS).  In patients with recurrent syncope episodes (RSE)  complete work-up including electrophysiological study (EPS) and/or implantation of a loop recorder (ILR) is recommended, however patients with their first episode may also be at risk of an AS.

AIM

To determinate if the patients with SHD or BBB with a single syncope episode (SSE) are at high risk of having an AS and compare it with patients with recurrent episodes (RSE).

METHODS Cohort study carried out in a tertiary hospital that is a reference centre for syncope. From January 2008 to August 2020 patients with SHD or BBB with syncope of unknown origin after the initial evaluation and without direct indication of an ICD were included. They were managed according the current ESC guidelines.

RESULTS

417patients were included  (74 ±11 y. o; 39% female). Mean follow up was 2.5 ±1 y. 223 patients were diagnosed from an AS [113 (53%) in SSE group and 110 (54%) in RSE group, p = 0.9], 210 were due to bradyarrhythmia (AV block or sinus arrest). No differences in baseline characteristics where found comparing both groups, except that BBB was slightly more prevalent in patients with RSE (81% vs 90%, p = 0.01) (FIGURE- PANEL A). Risk of AS was 53% in patients with SE and 54% (p = 0.9). RSE were not associated with an increased risk of AS in univariate analyses (OR 1.01 IC95% 0.7-1.5) neither in the multivariate (FIGURE- PANEL B). EPS and ILR diagnostic yield was 45% / 32% respectively in SSE group and 44% / 33% in RSE group (p = 0.8) (FIGURE - PANEL C).  After appropriate treatment, recurrence syncope rate was 10% in SSE group and 9% in RSE group (p = 0.8). No significant differences in mortality rate were found.

CONCLUSIONS

Patients with SHD or BBB and single syncope episode are at a high risk of having AS, and similar to those with RSE. EPS and ILR offer a similar diagnostic yield in both groups. Complete syncope work-up must be recommended in these patients despite having had only a single episode. Abstract Figure
Ventricular repolarization homogeneity in transthyretin cardiac amyloidosis
Authors: Kochav S , Coromilas E , Lavelle M , Bohnen MS , Maurer MS , Yarmohammadi H , Dizon J
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Non-sustained ventricular tachycardia is frequently observed in patients with transthyretin cardiac amyloidosis (TTR-CA); however, the incidence of sudden tachyarrhythmic death is low. Homogeneity of amyloid fibril deposition within the myocardium and conduction system may mitigate against sustained ventricular tachyarrhythmias. In contrast, myocardial scar heterogeneity is an established predictor of sudden cardiac death in conditions such as hypertrophic cardiomyopathy (HCM), as evidenced by increased myocardial dispersion of repolarization. Whether such indices of arrhythmogenesis are evident in TTR-CA has not been established.

Purpose

To compare ventricular repolarization indices in TTR-CA to HCM and controls without known cardiovascular disease.

Methods

We identified TTR-CA and HCM patients from our single center respective registries, and control patients from our clinical ECG database. Only patients in normal sinus rhythm without bundle branch block, cardiac pacing or artifact were included for analysis. Demographic and clinical data were abstracted. ECGs were analyzed at 25 mm/s paper speed and 10 mm/mV amplitude. ECG parameters included QT interval, QT dispersion, and T peak to T end (TpTe) using the tangent method. All measurements were performed by two blinded independent cardiologists.

Results

A total of 112 patients (45 TTR-CA, 32 HCM, and 35 controls) were studied. Despite a longer QTc in TTR-CA (468.4 ms in TTR-CA vs. 424.6 in controls; p < 0.001), patients with TTR-CA demonstrated similar repolarization indices as controls, including TpTE (93.0 ± 13.5 ms in TTR-CA vs 86.4 ± 12.2 ms in controls, p = 0.24), and TpTe/QTc (0.20 ± 0.03 in TTR-CA vs 0.2 ± 0.03 in controls, p = 0.99). In contrast, HCM patients demonstrated greater TpTe and TpTe/QTc compared with controls (Figure). and a trend toward increased QT dispersion in HCM vs. TTR-CA (p = 0.06).

Conclusion

Unlike HCM, patients with TTR-CA demonstrate a relative lack of myocardial repolarization heterogeneity compared with controls. This finding correlates with  homogeneous distribution of myocardial amyloid fibrils and may explain the low observed incidence of sudden cardiac death in this population. Abstract Figure
Impact of high density mapping using a grid shaped catheter with orthogonal signal analysis on ventricular tachycardia ablation strategy
Authors: Roca I , Lorgat F , Haqqani H , Lacotte J , Roithinger F , Fiedler L , Miller A , Steven D
Published: May 2021

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Abbott

Background

Ventricular tachycardia (VT) in patients with structural heart disease (SHD) is related to scar and slow conduction areas. Substrate-based ablation has become the gold standard treatment in patients with SHD-related refractory VT. A new high-density grid shaped catheter that allows simultaneous analysis of adjacent orthogonal bipolar signals can allow better understanding of these slow conduction areas with the potential to improve ablation results.

Purpose

This was a prospective, multicenter observational study to characterize the utility of electroanatomical mapping with a high density grid-style mapping catheter (HD Grid) in subjects undergoing catheter ablation for ventricular tachycardia (VT) in real-world clinical settings.

Methods

During the study period, patients who underwent VT ablation using the HD Grid catheter as the primary mapping catheter were included. Comparisons both during the procedure and retrospectively were performed between conventional electrode configuration maps and simultaneous orthogonal bipole electrode configuration maps. The influence of these different configurations on ablation strategy was analyzed.

Results

  During study period (January 2019 – April 2020) 57 maps were performed in 34 VT subjects (average age: 64.3yr, male: 85.3%, ischemic cardiomyopathy: 70.6%). The left ventricle was mapped in 94.1% of subjects, including left ventricular outflow tract and papillary muscles in 20.6% and 8.8% respectively, reporting minimal or no ectopic beats in 97.1% of the subjects. The total number of mapping points collected was 14172.0 ± 15174.8 in 24.3 ± 17.9 min per map.

Simultaneous orthogonal bipole mapping identified differences in 67.6% of maps compared to linear along-the-spline electrode configurations. The differences consisted mainly in the surface area (92%) and location of low voltage (40%). When compared during the procedure, simultaneous orthogonal bipole mapping was used to identify ablation strategy in 100% of cases. When compared to a standard along-the-spline configuration retrospectively, the ablation strategy identified with simultaneous orthogonal bipoles was different in 30.1% of cases.  The ablation strategy used in these subjects was mainly substrate ablation (late potentials and low voltage areas in scar regions) with an acute success rate of 97.1%.

Conclusions

The use of the HD Grid catheter with the ability to analyze orthogonal signals is feasible and has the potential to change the ablation strategy in one third of VT patients with a high acute success rate.
Frequency of ventricular tachyarrhythmias in patients with different risk scores for sudden cardiac death in hypertrophic cardiomyopathy and cardioverter defibrilators implanted in primary prevention
Authors: Brankovic N , Radovanovic NN , Vujadinovic N , Kircanski B , Sajic V , Milasinovic A , Zivkovic M , Bisenic V , Pavlovic SU , Milasinovic G
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

The European Society of Cardiology’s (ESC) risk calculator for sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathies (HCM) is currently a tool that facilitates the decision to implant a cardioverter defibrillator (ICD) in primary prevention, but doubts still exist in everyday clinical practice.

Purpose

We aimed to determine the incidence of life-threatening ventricular arrhythmias

during long-term follow-up in patients with different ESC HCM risk scores for SCD

calculated on ICD implantation in primary prevention.

Methods

This retrospective, observational study was conducted in a tertiary center among

adult patients with HCM and ICD devices (ICD-VR, ICD-DR and CRT-ICD) implanted in

primary prevention from January 2008 to December 2019. The patients followed up for less than one year were excluded from the analysis. Study group was divided into three subgroups, according to the ESC 5 years risk score of SCD and based on it the estimated need for ICD implantation: group A

with risk < 4%, where ICD is generally not indicated; group B with risk 4-6%, where ICD

may be considered; group C with risk ≥6%, where ICD should be considered. Regularly, ICD

was interrogated twice a year, while emergency controls were performed after delivering of

ICD therapy. Follow-up data including information about sustained ventricular tachicardia

(VT) and ventricular fibrillation (VF) episodes were collected from patients medical records.

Results

In the observed period, ICD devices were implanted in 60 adult patients with HCM.

Ten of them had history of sustained ventricular arrhythmias and 3 were lost to follow-up. Therefore, we analysed 47 patients (55.3% male, mean age 51.0 ± 15.7 years), 13 from group

A, 12 from group B and 22 from group C. Mean follow-up period was 80.6 ± 37.9 months.

During the follow-up period ventricular tachyarrhythmias (VT and VF, either in monitoring or

therapy zone) were recorded in one patient from group A (7.7%), in two patients from group

B (16.7%) and in 7 patients from group C (31.8%). Using Kruskal-Wallis analysis of

variance, we did not find a statistically significant difference in the occurrence of ventricular

tachyarrhythmias among the observed groups (p = 0.225).

Conclusions

Patients with HCM and a 5-year risk of SCD ≥ 6% calculated on ICD

implantation had more frequent life-threatening ventricular arrhythmias during long-term

follow-up, but not statistically significant. There should be an individual

approach when deciding on the need for device implantation in all patients with HCM.
Comparison of QRSarea and left ventricular activation time during left bundle branch pacing and left ventricular septal pacing
Authors: Heckman LIB , Luermans JGK , Curila K , Van Stipdonk AMW , Westra S , Prinzen FW , Vernooy K
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Left bundle branch area pacing (LBBAP) has recently been introduced as a novel physiological pacing strategy. Within LBBAP, distinction is made between left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP, no left bundle capture).

Objective

To compare acute electrocardiographic (ECG) and vectorcardiographic (VCG) effects of LBBP and LVSP as compared to intrinsic conduction.

Methods

In 50 patients with normal cardiac function and pacemaker indication for bradycardia, ECG characteristics of LBBP and LVSP were evaluated during RVSP and pacing at various depths in the septum: starting at the RV side of the septum: the last position with QS morphology, the first position with r’ morphology, LVSP and – in patients where LBB capture was achieved – LBBP. From the ECG’s QRS duration and QRS morphology in V1, and the stimulus-LVAT interval were measured. After conversion of the ECG into VCG (Kors conversion matrix), QRS area was calculated.

Results

In LVSP, QRS area significantly decreased from 82 ± 29 µVs during RVSP to 46 ± 12 µVs during LVSP. In patients where LBB capture was achieved QRS area significantly decreased from 78 ± 23 µVs to 38 ± 15 µVs in LBBP. In patients with LBB capture, QRS area was significantly smaller during LBBP compared to LVSP (figure A), but LVAT was not significantly different (figure B, p = 0.138).

In patients with normal ventricular activation where LBBP was achieved (n = 20), QRS area was significantly larger during LVSP (48 ± 17) compared to LBBP (37 ± 16), the latter being not significantly different from normal intrinsic ventricular activation (35 ± 19 µVs).

Conclusions

ECG and VCG indices demonstrate that ventricular dyssynchrony is comparable but slightly more synchronous during LBBP compared to LVSP. Abstract Figure. QRS area and S-LVAT in LVSP and LBBP
Anatomical predictors of high grade atrioventricular conduction disorders in patients with specific pacemaker implanted after TAVI
Authors: Frey P , Brochier A , Nezzouhairi N , Irles D
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

OnBehalf

STIM TAVI-MS study

Background

 The evolution of atrioventricular conduction disorders after transcatheter aortic valve implantation (TAVI) remains poorly understood. Recent studies have identified short membranous septum (MS) length, deep implantation depth (ID) or their relation as anatomic risk of high-grade AV block and permanent pacemaker implantation.

Purpose : We sought to examine whether the atrioventricular (AV) membranous septum (MS) measured by computed tomography (CT) and the depth of valve implantation measured from the final aortic angiogram could predict high-grade atrioventricular block (HG AVB) after TAVI, based on specific pacemaker memory data.

Methods

STIM-TAVI-MS was a prospective, multicentre observational study that enrolled patients implanted with a specific dual chamber pacemaker after TAVI, with the SafeR algorithm activated, allowing continuous monitoring of atrioventricular conduction. The primary endpoint was the occurrence of late (after Day 7) high-grade atrioventricular block(s) during the year after TAVI. We measured on CT scans the coronal MS lenght, infra-annular MS lenght and the quantification of calcifications, on the final angiogram after TAVI we measured the implant depth (ID) to identifie ΔID-MS corresponding to the difference between implant depth and MS length. The variables were compared with the occurrence of late HG-AVB on PM memory data.

Results : Among 82 patients, (mean age 84,5 years ± 4,8, self-expending valve n = 24, 29,3%), n = 47 (57.3%) had ≥1 late high-grade atrioventricular block. Mean coronal MS length was 8,1 ± 2,5 mm, mean infra annular MS was 3,4 ± 3.1 mm, mean calcification volume was 93.0 ± 88, 85,5± 104 and 141,5 ± 137,5 mm3 for the noncoronary, right coronary and left coronary cusp respectively. Mean implant depth was 7,3 ± 3,3mm, and mean ΔID-MS = -0,7 ± 4,1mm. There were no association between MS length (OR = 1,06; CI 0,91 to 1,24), ID (OR = 1,6; CI 0,85 to 2,9), nor ΔID-MS (OR = 0,67; CI 0,37 to 1,23) and late HG AVB. Calcification volume were not associated with late HG AVB.

Conclusion

In an high risk high grade AV block population after TAVI, anatomical analysis of MS length, degree of calcification, implant depth and ΔID-MS did not predict occurrence of late (> day 7 after TAVI ) high grade AV Blocks. Abstract Figure. CT scan A : aortic plane, B : MS lenght
Assessment of the SyncAV fusion pacing algorithm on exercise capacity in patients with cardiac resynchronisation therapy device
Authors: Green PG , Holdsworth D , Monteiro C , Betts T , Herring N
Published: May 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): British Heart Foundation (BHF) and Local Departmental Research Funding

Background

Fusion pacing as part of cardiac resynchronization therapy (CRT) requires correct timing of left ventricular pacing to right ventricular activation.  The SyncAV algorithm, available in Quadra Allure and Assura CRT devices, is designed to allow optimal fusion pacing by dynamic reassessment of intrinsic atrio-ventricular (AV) conduction to adjust the paced/sensed AV delay. However, it is unclear whether AV optimisation continues to maintain resynchronisation during exercise, or whether potential loss of fusion pacing with changes in intrinsic AV conduction could lead to decreased exercise capacity. Cardio-pulmonary exercise testing (CPET) is the gold standard method for assessing exercise performance.

Purpose

To assess exercise capacity using the SyncAV algorithm for fusion pacing, compared with conventional biventricular pacing with fixed AV delays (AVD) for CRT.

Methods

 Patients at least 6 months post-CRT implant were recruited in a prospective single-centre randomized single-blind crossover study.  Patients performed 2 CPET tests at least 1 week apart, with randomization to either SyncAV with fusion pacing or conventional biventricular pacing with a fixed AVD of 120ms. All other programming was optimised to produce the narrowest QRS duration possible at rest in each case.

Results

Nine patients (5 male, age 70 ± 10 years, mean ± standard deviation) were recruited, with both ischaemic and non-ischaemic aetiology of heart failure.  All had clinical or echocardiographic response to CRT.  There was no difference in peak oxygen consumption (V̇O2max) between programming (1.47 ± 0.57 vs 1.50 ± 0.65 l/min for fixed AVD and SyncAV groups respectively, p = 0.59), or oxygen consumption at anaerobic threshold (VT1) (0.72 ± 0.20 vs 0.74 ± 0.25 l/min, p = 0.57). There was no difference in oxygen pulse (V̇O2/heart rate - a surrogate of stroke volume) at peak (12.3 ± 3.8 vs 13 ± 5.0 ml/beat , p = 0.28) or VT1 (8.4 ± 2.2 vs 8.7 ± 2.1 ml/beat, p = 0.67) and also no change in time to V̇O2max (1400 ± 491 vs 1367 ± 543 seconds, p = 0.38) or VT1 (518 ± 211 vs 534 ± 200 seconds, p = 0.75).  Average heart rate at the median stage of exercise showed no difference between programming (96 ± 18 vs 93 ± 15 bpm respectively, p = 0.32).  There was no difference in BORG Rating of Perceived Exertion (BORG-RPE) score at either peak exercise (median 19 [interquartile range (IQR) 2] vs 17 [IQR 2], p = 0.23) or at the median stage of exercise (median 13 [IQR 1] vs 13 [IQR 2], p = 0.30). 

Conclusion

Fusion pacing using the SyncAV algorithm does not appear to improve exercise capacity compared to optimised conventional biventricular pacing with fixed AVD.
Outcome of catheter ablation of arrhythmias in adult congenital heart disease with high density multi-electrode mapping with automatic annotation algorithm
Authors: Gomes J , Saeed Y , Kawada S , Benson L , Downar E , Nair K
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Arrhythmias are frequently encountered in adult congenital heart disease (ACHD) and respond poorly to pharmacological therapies. Catheter ablation is challenging due to anatomical variation and complexity of the arrhythmia substrate. High density multi electrode mapping (MEM) with automatic annotation of activation time may aid mapping of arrhythmia, decrease procedure time and improve the accuracy of targeting of ablation therapy.

Purpose

To compare the acute and long term outcomes and procedural characteristics of catheter ablation in ACHD patients with and without automatic annotation of activation with MEM.

Methods

Retrospective analysis of the acute and long term outcomes of ACHD patients in a single centre undergoing ablation procedures from 1 Jan 2014 to 18 August 2017 was undertaken. 2 groups were identified.

Group 1 included patients who had arrhythmia mapping performed with the CARTO 3D electroanatomic mapping system without the use of automatic signal annotation. Most patients in this group had sequential mapping performed with the ablation catheter (78%), the rest had multi-electrode mapping with the PentaRay 20 pole catheter.

Group 2 included patients who had arrhythmia mapping performed with the CARTO 3D electroanatomic mapping system using the automated CONFIDENSE mapping algorithm.

Results

Group 1: n = 27, mean age 44.6 +/-3 years. Male 46.6%. Group 2: n = 38, mean age 44.0 +/- 1.9 years. Male 56.7%. All patients had CHD of at least moderate complexity. 25% of patients in group 1 and 45% in group 2 were repeat ablations. 45 arrhythmias were induced in group 1 of which 29 were targeted and 74 arrhythmias were induced in group 2 of which 46 were targeted. Acute success rates (after attempts at reinduction) were 96.3% in group 1 and 94.7% in group 2. Recurrences of arrhythmia occurred significantly less in patients in group 2 compared to group 1  (44.7% and 70.4% respectively,  p < 0.05) after a follow up duration of 17.3+/-0.43 months in group 2 and 45.3 +/-1.19 months in group 1. Fluoroscopy time, procedure time and ablation time were not significantly different between groups.

Conclusions

The use of multi-electrode mapping with an automatic annotation algorithm was associated with a significantly lower risk of recurrence during the follow up period of this study.
Hypertension burden and the risk of new-onset atrial fibrillation: a nationwide population-based study
Authors: Lee SR , Park CS , Choi EK , Ahn HJ , Han KD , Oh S , Lip GYH
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

The association between the cumulative hypertension burden and the development of atrial fibrillation (AF) is unclear.

Purpose

We aimed to investigate the relationship between hypertension burden and the development of incident AF.

Methods and Results: Using the Korean National Health Insurance Service database, we identified 3,726,172 subjects who underwent four consecutive annual health checkups between 2009 and 2013, with no history of AF. During the median follow-up of 5.2 years, AF was newly diagnosed in 22,012 patients (0.59% of the total study population, 1.168 per 1,000 person-years). Using the BP values at each health checkup, we determined the burden of hypertension (systolic blood pressure [SBP] ≥130 mmHg or diastolic blood pressure [DBP] ≥80 mmHg), stratified as 0 to 4 per the hypertension criteria. The subjects were grouped according to hypertension burden scale 1 to 4: 20% (n = 742,806), 19% (n = 704,623), 19% (n = 713,258), 21% (n = 766,204), and 21% (n = 799,281). Compared to normal people, subjects with hypertension burdens of 1, 2, 3, and 4 were associated with an 8%, 18%, 26%, and 27% increased risk of incident AF, respectively. On semi-quantitative analyses with further stratification of stage 1 (SBP 130-139 mmHg or DBP 80-89 mmHg) and stage 2 (SBP ≥140 mmHg or DBP ≥90 mmHg) hypertension, the risk of AF increased with the hypertension burden by up to 71%.

Conclusions

Both a sustained exposure and the degree of increased blood pressure were associated with an increased risk of incident AF. Tailored blood pressure management should be emphasized to reduce the risk of AF. Abstract Figure.
Evaluation of the device independent nature of a photoplethysmography-deriving smartphone app
Authors: Gruwez H , Evens S , Proesmans T , Smeets C , Haemers P , Pison L , Vandervoort P
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Smartphone apps using photoplethysmography (PPG) technology enable digital heart rhythm monitoring through their built-in camera, without the need for additional, specific, or costly hardware. This may positively impact the availability and scalability of remote monitoring. However, the diversity of smartphone specifications on the consumer market may raise concerns regarding the robustness of AF detection algorithms between various devices.

Purpose

To study the device independency of AF detection performance by a PPG-based smartphone application.

Methods

Patients from the cardiology department were consecutively enrolled. Patients were handed 7 iOS models and 1 Android model and were asked to consecutively perform one PPG measurement per device. A 12-lead electrocardiogram (ECG) was collected during the same consultation and interpreted by a cardiologist as reference diagnosis. To allow an objective comparison across the devices, patients who failed to perform one successful measurement on each device were excluded. Additional exclusions were atrial flutter rhythms and insufficient quality results. Sensitivity, specificity and accuracy were calculated with respect to the reference diagnosis. McNemar’s analysis was used for the head-to-head comparison of the sensitivity and specificity of the proprietary algorithm on the different smartphone devices.

Results

A total of 150 patients participated in the study with a median CHA2DS2-VASc score of 3 (interquartile range: 1-5). The median age of the study population was 70 (interquartile range: 56-79) years. In total, 54.7% of the population was male and the AF-prevalence was 35.3%. After the exclusion of patients with atrial flutter (n = 14) and patients who did not successfully perform a PPG measurement on each device (n = 5), diagnostic-grade results of 131 patients were used to calculate the performance of the proprietary algorithm. The sensitivity and specificity of the AF detection algorithm ranged from 90.9% (95% CI 75.7-98.1) to 100.0% (95% CI 91.0-100) and 94.5% (95% CI 86.6-98.5) to 100.0% (95% CI 94.6-100), respectively. The overall accuracy across the devices ranged from 94.4% (95% CI 88.3-97.9) to 99.0% (95% CI 94.6-100). Head-to-head comparisons of the results did not reveal significant differences in sensitivity (P = 0.125-1.000) or specificity (P = 0.375-1.000) of the proprietary AF detection algorithm among the different devices.

Conclusion

This study demonstrated the device-independent nature of the PPG-deriving smartphone application with respect to 12-lead ECG diagnosis.
PDE4B and PDE4D differentially regulate cardiac pacemaker activity
Authors: Pereira De Vasconcelos WPV , Gomez AMG , Fischmeister RF , Vandecasteele GV , Mika DM
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Agence Nationale de la Recherche (ANR)

Background Heart rate (HR) is generated by spontaneous electrical activity in the sinoatrial node (SAN) and is modulated by the autonomic nervous system. During sympathetic stimulation, the activation of β-adrenergic receptors (βAR) increases cAMP levels, leading to positive chronotropic effect. Among the 6 cardiac cAMP-PDE families, PDE4 is critical for controlling excitation-contraction coupling (ECC) during β-stimulation in atrial and ventricular myocytes. PDE4 may also be important for automaticity. 3 genes encode for PDE4 in the heart (pde4a, 4b, 4d). We propose to investigate their respective contribution to the regulation of pacemaker activity. 

Methods Total PDE activity in mouse SAN was determined as the cAMP-hydrolytic activity measured in the absence of PDE inhibitor and the fraction corresponding to PDE4 activity was assessed by including the PDE4 inhibitor Ro-20-1724. The in vitro pacemaker activity was assessed by measuring spontaneous Ca2+ transients in Fluo4-loaded-SAN tissue from wild-type (WT) and PDE4KO mice. Images were obtained using confocal microscopy. Telemetry EKG was recorded in conscious mice in control (CTRL) conditions, after pharmacological denervation with atropine (1 mg/kg) and propranolol (2 mg/kg) and after β-stimulation with isoproterenol (ISO, 1.5 mg/kg). HR variability was evaluated by calculating the SDNN (standard deviation of RR intervals) parameter.

Results Ro-20-1724 (10 µM) increased beating rate of intact SAN and increased PKA-phosphorylation of key ECC actors (ryanodine receptor, phospholamban and contractile proteins). PDE4 activity was found to account for 60% of total cAMP-PDE activity in SAN. PDE4A, 4B and 4D isoforms were found to be expressed in mouse SAN. In PDE4BKO SAN, the effect of ISO on SAN beating rate was higher than in WT. Ablation of PDE4D induced decreased beating rate in CTRL and ISO conditions and increased Ca2+ spark frequency compared to WT SAN. In vivo, PDE4BKO and PDE4DKO mice displayed increased resting HR during day and night. HR variability was decreased in PDE4BKO, but not in PDE4DKO mice during the day, and decreased in both genotypes at night compared to WT mice. After atropine + propranolol denervation, the rhythmic phenotype was only maintained in PDE4BKO but not in PDE4DKO mice. The response to β-AR stimulation with ISO was higher in PDE4BKO than in PDE4DKO. In addition, under ISO we observed an increased number of premature beats and atrioventricular blocks in PDE4DKO, but not in PDE4BKO mice.

Conclusion PDE4B and PDE4D differentially regulate cardiac pacemaker activity. While PDE4B clearly controls intrinsic SAN automaticity, PDE4D might be important for ANS-mediated regulation of HR and conduction.
Post myocardial infarction ionic remodelling promotes repolarisation dispersions and abnormalities in acute and chronic stages
Authors: Zhou X , Wang Z , Tomek J , Wang L , Rodriguez B
Published: May 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): Wellcome Trust

Background

Sudden cardiac death after a myocardial infarction (MI) was reported in both the acute stage and the chronic stage with the development of heart failure (HF). Around 50% of these deaths were due to ventricular tachyarrhythmia which is related to the temporal dispersion of repolarisation caused by the post-MI remodelling of ionic currents. While variable extent of ionic current changes was observed in multiple animal species in different post-MI phases, the proarrhythmic effects of such remodelling in post infarction human hearts is not fully explored.

Purpose

The goal of this study is to explore the proarrhythmic effects of post-MI ionic remodelling in human ventricular myocyte models of electrophysiology for both the acute and the chronic stages.

Methods

The ToR-ORd human ventricular cellular model was used as the baseline model, and a new formulation of the calcium activated potassium current was implemented. We constructed and calibrated a population of 253 human ventricular cell models (POM) to represent electrophysiological variability of normal zone (NZ) myocytes. For the acute phase, three types of border zone (BZ) remodelling (Acute BZ1-3) were introduced based on dog experimental data collected within one week after infarction. For the chronic phase with the development of HF, BZ (Chronic BZ) and one type of remote zone (RZ) remodelling (Chronic RZ1) were introduced based on minipig data collected 5 months post-MI. Another type of RZ remodelling (Chronic RZ2) was introduced based on experimental data from failing human hearts. The cellular models were paced at cycle lengths of 1000ms, 500ms, 400ms and 300ms for 500 beats before the analysis of repolarization abnormalities.

Results

For both the acute and the chronic stages post-MI, the extent of repolarisation dispersion between BZ and the corresponding NZ and RZ varied from 2ms up to 120ms, and largely depended on the level of potassium current remodelling. A weaker calcium transient was always observed in the BZ. Early after depolarisations (EADs) and repolarisation failure (RF) were observed in the chronic stages, caused by the reactivation of L-type calcium current due to the augmentation of late sodium current and the inhibition of hERG current. Beat-to-beat repolarization alternans was observed in both the acute and the chronic stages, with the key ionic mechanisms being the inhibition of SERCA activity and the slower calcium release due to enhanced CaMKII.

Conclusions

Post-MI ionic remodelling of the acute and chronic stages can cause a substantial dispersion of repolarisation in human hearts by inducing the prolongation of action potential durations, EADs, RFs, and alternans, providing substrates for the generation and maintenance of lethal reentrant waves. Abstract Figure. BZ and RZ ionic current remodelling
Glucagon-like peptide-1 directly increases heart rate and shortens atrial refractoriness: an in vivo and ex vivo study in pigs
Authors: Lubberding AF , Veedfald S , Sattler SM , Linz BM , Eggertsen CHE , Lilleoer TMB , Qazi S , Moeller C , Tfelt-Hansen J , Holst JJ , Jespersen T
Published: May 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation Synergy program Novo Nordisk Foundation Center for Basic Metabolic Research

Background

 Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes not only reduces hyperglycaemia, but also improves cardiovascular outcomes. However, GLP-1 RA treatment also increases heart rate: an apparent paradox.

Purpose

 Whether the heart rate increase is a direct effect, and whether GLP-1 affects other aspects of cardiac electrophysiology, remain unclear. To answer these questions we investigated the effect of GLP-1 infusion on cardiac electrophysiology in vivo and ex vivo in pigs and pig hearts, respectively, during sinus rhythm and pacing.

Methods

 Anaesthetised pigs (n = 8) received infusions of GLP-1 (10 pmol/kg/min). Electrocardiogram, atrial monophasic action potentials and atrial conduction velocity data were collected and atrial and ventricular effective refractory periods (ERP) were measured. For the ex vivo studies, pig hearts (n = 7) were excised, retrogradely perfused and exposed to consecutive bolus perfusions of 2 and 4 nmol GLP-1, 100 nmol of the GLP-1 receptor antagonist exendin-9-39 and a final 4 nmol bolus of GLP-1. The same electrophysiological parameters were measured.

Results

 In anaesthetised pigs, GLP-1 increased heart rate, cardiac output and diastolic pressure, while systemic vascular resistance was decreased. Infusion of GLP-1 decreased PQ interval in sinus rhythm (P = 0.019, n = 8) and during atrial pacing (P = 0.027, n = 6) with 8 ± 3 % and 12 ± 3 %, respectively. Additionally, GLP-1 decreased atrial ERP at all pacing cycle lengths (P = 0.04, n = 7), while ventricular ERP was unaffected (P = 0.29, n = 7). In the isolated perfused heart, GLP-1 increased heart rate with 13 ± 2 bpm (P = 0.001, n = 7). This increase in heart rate was completely abolished by pre-administration of exendin-9-39. Atrial ERP shortened after GLP-1 perfusion (P = 0.01, n = 7) comparable to the in vivo studies, with an average decrease of 11 ± 2 %. This effect was also abolished by exendin-9-39.

Conclusion

 GLP-1 increases heart rate through activation of the GLP-1 receptor in the isolated perfused heart, suggesting a direct effect of GLP-1 rather than activation through the central nervous system. Additionally, GLP-1 affects atrial electrophysiology, but not ventricular electrophysiology, in vivo and ex vivo independent of the increase in heart rate.
Piezo1 and BKCa channels in human atrial fibroblasts: interplay and remodelling in atrial fibrillation
Authors: Jakob D , Klesen A , Allegrini B , Darkow E , Aria D , Emig D , Guizouarn H , Schmidt C , Kohl P , Ravens U , Peyronnet R
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Science, Research and Arts Baden-Württemberg (MWK-BW Sonderlinie Medizin)

Atrial Fibrillation (AF) is an arrhythmia of increasing prevalence. One of the important indicators for AF is sustained atrial dilatation, highlighting the importance of mechanical overload in the pathophysiology of AF. The mechanisms by which atrial cells, including fibroblasts, sense and react to such changing mechanical forces, are not fully elucidated. Here, we characterise stretch-activated ion channels (SAC) in human atrial fibroblasts and changes in their expression and activity associated with AF.

Using primary cultures of human atrial fibroblasts, isolated from patients in sinus rhythm or with sustained AF, we combine electrophysiological, molecular and pharmacological tools to identify SAC. Two electrophysiological SAC-signatures were detected, indicative of cation-nonselective and potassium-selective channels. Using siRNA-mediated knockdown, we identified the nonselective SAC as Piezo1. Biophysical properties of the potassium-selective channel and its pharmacology indicated presence of ‘big potassium channels’, BKCa. In cells from AF patients, Piezo1 activity and mRNA expression levels were higher than in cells from sinus rhythm patients, while BKCa activity (but not expression) was downregulated. Both Piezo1-knockdown and removal of extracellular calcium from the patch pipette resulted in a significant reduction of stretch-induced BKCa current. No co-immunoprecipitation of Piezo1 and BKCa was detected.

Human atrial fibroblasts express functional Piezo1 and BKCa channels. While Piezo1 is directly stretch-activated, the increase in BKCa activity during mechanical stimulation appears to be mainly secondary to calcium influx via SAC such as Piezo1. During sustained AF, Piezo1 is increased, while BKCa activity is reduced, highlighting differential regulation of both channels. Our data show the presence and activity of Piezo1 and BKCa in human atrial fibroblasts and suggest an interplay between the two in the absence of direct physical interactions.
Innate immune response: ally or enemy in cutaneous leishmaniasis?
Authors: Serrano-Coll Héctor , Cardona-Castro Nora , Ramos Ana Pilar , Llanos-Cuentas Alejandro
Published: May 2021

Cutaneous leishmaniasis (CL) is an infectious and neglected disease caused by parasites of the genus Leishmania, which produces a wide spectrum of cutaneous manifestations. CL research has shown that the innate immune activity of cells such as neutrophils, natural killers, macrophages, dendritic cells and the complement system are capable of controlling this infection. However, Leishmania can also modulate the immune activity of these cells to promote its own survival and proliferation at the intracellular level. This review discusses the role of the innate immune response in the control and spread of this infection.