bluuebunny/crossref_metadata_2025 huggingface dataset:
Better outcome at lower costs after implementing a CRT-care pathway: a comprehensive evaluation of real-world data
Authors: Van Stipdonk AMW , Schretlen S , Dohmen W , Knackstedt C , Brunner-Larocca HP , Vernooy K
Published: May 2021

Funding Acknowledgements

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Medtronic plc.

Background

Cardiac resynchronization therapy (CRT) requires intensive, complex and multi-disciplinary care to maximize clinical benefit in heart failure patients. In current practice, this is often incomplete due to limitations in time, resources and coordination of care.

Purpose

We evaluated the effect of the introduction of a novel multidisciplinary, standardized CRT care pathway (CRT-CPW) compared with usual care, on clinical outcome and costs.

Methods

The CRT care pathway (CRT-CPW) design, based on an expert consensus of experienced European CRT specialists; focussed on structuring patient selection, implantation and follow-up heart failure treatment and device management. To facilitate and guarantee quality, checklists fitted to each moment in the care pathway were designed, to aid contributors. The CRT-CPW was implemented in the Maastricht University Medical Centre in 2014. Data from patients receiving usual care (2012-2014, 222 patients) and patients receiving care under the CRT-CPW (2015-2018, 241 patients) were compared. Data was extracted from the hospital information system. The primary outcome was the composite of all-cause mortality and heart failure (HF) hospitalization. Hospital-related costs of cardiovascular care after CRT implantation was analysed to address cost-effectiveness.

Results

Patient demographics were comparable in both groups, except that the CRT-CPW group showed more AF and previous myocardial infarction at baseline. The combined endpoint of death from any cause and admission for HF occurred in 127 patients (57.2%) in the usual care group and 64 patients (26.6%) in the CRT- CPW group (adjusted HR 0.68 (95% CI, 0.49 to 0.93), p = 0.015) (Figure 1A). Total costs for cardiology related hospitalizations reduced significantly in the CRT care pathway group (€ 19.177 ± 9.692 vs 20.613 ± 7.066, p< 0.001, Table 4). Bootstrap analyses revealed that 90.7% of samples would show improved outcomes as well as reduction in costs in the CRT-CPW treatment group (Figure 1B).

Conclusion

The introduction of a novel CRT-CPW resulted in improved clinical outcome and reduced costs. Abstract Figure 1 Clinical outcome and costs
Futility risk model for predicting outcome after cardiac resynchronization therapy defibrillator implantation: data from a nationwide analysis
Authors: Maille B , Bodin A , Bisson A , Herbert J , Franceschi F , Koutbi-Franceschi L , Hourdain J , Martinez E , Zabern M , Deharo J-C , Fauchier L
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Objective. Risk-benefit assessment for cardiac resynchronization therapy defibrillator (CRT-D) over a CRT pacemaker (CRT-P) is still a matter of debate. We aimed to identify patients with a bad outcome within one year after CRT-D implantation, and to develop a Futile CRT-D score.

Methods. Based on the administrative hospital-discharge database, all consecutive patients treated with CRT-D implantation in France between 2010 and 2019 were included. A prediction model was derived and validated for one-year all-cause death after CRT-D implantation (considered as futility) by using split-sample validation.

Results. 28,503 patients were included in the analysis (mean age 68 ± 10 years); 2,139 (7.5%) deaths were recorded in the first year. In the derivation cohort (n = 14,252), the final logistic regression model included as main predictors of futility older age, diabetes, mitral regurgitation, history of hospital stay with heart failure, history of pulmonary oedema, atrial fibrillation, renal, pulmonary, liver, or thyroid disease, denutrition and anemia. Based on Futile CRT-D score, 17% of these patients were categorized at high risk (Futile CRT-D score ≥13) and predicted futility at 17%.

Conclusion.  The futility CRT-D score, established from a large nationwide cohort of patients treated with CRT-D may provide a relevant tool for optimizing healthcare decision. Death at one year in patients with CRTD OR (95%CI)pPointsAge (quartile)1.353 (1.266-1.446)<0.00012Diabetes mellitus1.413 (1.225-1.629)<0.00012Heart failure with congestion1.908 (1.501-2.423)<0.00013History of pulmonary edema1.445 (1.194-1.749)<0.00012Mitral regurgitation1.259 (1.074-1.475)0.0042Atrial fibrillation1.601 (1.395-1.838)<0.00012Left BBB0.803 (0.698-0.924)0.002-1Dyslipidemia0.809 (0.696-0.940)0.006-1Denutrition1.709 (1.360-2.147)<0.00012Chronic kidney disease1.574 (1.321-1.875)<0.00012Lung disease1.230 (1.052-1.437)0.0092Sleep apnea syndrome0.740 (0.596-0.919)0.007-1Liver disease1.747 (1.384-2.206)<0.00012Anaemia1.325 (1.105-1.589)0.0022BBB = bundle branch block.; * age quartile: 1 point when age >61, 2 points when age >69, 3 points when age >75.Abstract Figure. AUC and incidences of all-causes death
Duration of the preejection phase is less preload dependent and therefore a better marker of acute response to cardiac resynchronization therapy than maximum pressure rise
Authors: Villegas-Martinez M , Odland HH , Sletten OJ , Khan F , Wajdan A , Elle OJ , Fosse E , Krogh MR , Remme EW
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie

Background

There is no consensus on which haemodynamic marker should be used to quantify acute response to cardiac resynchronization therapy (CRT) during implantation of the device. CRT has been shown to acutely reduce left ventricular (LV) end systolic as well as end-diastolic volume (EDV), precluding the use of preload dependent markers such as LV maximum pressure rise (dP/dtmax).

Purpose

As resynchronization will abolish the uncoordinated regional early systolic contractions of the LV, it will shorten the time to maximal pressure rise and aortic valve opening. For this reason, the purpose of this study was to investigate if duration from the time-point of ventricular pacing to dP/dtmax is less preload dependent and a better marker of acute response to CRT than dP/dtmax by comparing how the 2 markers reflected LV function during different CRT configurations.

Methods

LV pressure by micromanometer and volume by sonomicrometry were measured in 6 anaesthetized canines with left bundle branch block. Transient caval constrictions were performed to vary preload. Preload dependency of the 2 markers was compared by normalizing their values and calculating their relations to EDV. In 4 of the animals, biventricular pacing was performed at 3 different pacing sites with variations in atrioventricular delays that provided a range of response to CRT. To correct for acute

changes in preload by CRT, stroke volume (SV) at identical EDV found from transient caval constrictions, were assessed and used as reference to grade improved LV function. Linear regression analysis was used to assess the correlation of both the duration of the preejection phase and dP/dtmax with SV.

Results

The duration of the preejection phase varied less with changes in preload compared to dP/dtmax: the slopes of their relation to EDV were -0.6 ± 0.7 %/ml and 4.8 ± 2.1 %/ml (p = 0.004), respectively. Turning CRT on, acutely reduced EDV from 74 ± 16 to 69 ± 17 ml (p < 0.001) at the best pacing configuration. For the different pacing sites and settings, there was a consistent relation in all animals where the preejection phase shortened as SV increased (average r2 = 0.75) (Figure A). dP/dtmax showed no clear relation to SV (average r2 = 0.22) and included cases with both negative and positive slopes (Figure B).

Conclusions

The duration of the preejection phase correlated with changes in LV function induced by CRT while dP/dtmax performed poorly as preload was changed. Hence, the novel timing parameter was less preload dependent and may be a better marker for assessing acute response to CRT. Abstract Figure.
A method for accurately and dynamically optimising pacemaker atrio-ventricular delay timing using implantable physiological biomarkers
Authors: Miyazawa AA , Keene D , Johal M , Arnold AD , Peters NS , Kanagaratnam P , Linton NWF , Lim PB , Lefroy DC , Ng FS , Qureshi NA , Koa-Wing M , Whinnett ZI , Francis DP , Shun-Shin MJ
Published: May 2021

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): BRAVO trial: BHF SP/10/002/28189, FS/10/038, FS/11/92/29122, FS/13/44/30291) National Institute for Health Research Imperial Biomedical Research Centre. HOPE-HF trial: British Heart Foundation (CS/15/3/31405, FS/13/44/30291, FS/15/53/31615, FS/14/27/30752, FS/10/038).

Introduction

The optimal atrioventricular (AV) delay for implantable cardiac devices can be derived by echocardiography or  beat-by-beat blood pressure measurements. However, both of these approaches are labour intensive and neither could be incorporated into an implantable cardiac device for frequent repeated optimisations. Laser Doppler perfusion monitoring (LDPM) measures blood flow through tissue. LDPM has been miniaturised ready to be incorporated into future implantable cardiac devices.

Purpose

We studied if LDPM is a clinically reliable alternative method to blood-pressure measurements to determine optimal AV delay.

Methods

Data from  58 patients undergoing 94 clinical AVD optimisations using LDPM and simultaneous non-invasive beat-by-beat blood pressure was obtained. The optimal AV delay for each method and for each optimisation was determined using a curve of haemodynamic response to switching from AAI (reference state) to DDD (test state) at a series of AV delays (40, 80, 120, 160, 200, 240 ms). We then compared the derived optimal AV delays between the two measurement approaches. We also assessed the impact of the paced heart-rate on agreement between laser Doppler and Blood-Pressure derived optimal AV delays.

Results

The AV delay derived using LDPM was not clinically significant different from that derived by blood pressure changes. The median difference was -9ms (IQR -26 to 7, p = 0.05). Variability between the two methods was low (median absolute deviation 17ms). Optimisations performed at higher heart-rates resulted in a non-significant smaller difference between the LDPM and blood-pressure derived AV delays (median absolute deviation 12 vs 22 ms, p = 0.11).

Conclusions

Optimal AVDs derived from non-invasive blood-pressure or laser Doppler perfusion methods are clinically equivalent. The addition of laser Doppler to future implantable cardiac devices may enable devices to dynamically and reliably optimise AV delays. Abstract Figure 1
A multiparametric ICD algorithm for heart failure risk stratification and management: an analysis in clinical practice
Authors: Calo" L , Bianchi V , Ferraioli D , Santini L , Dello Russo A , Carriere C , Santobuono VE , Andreoli C , La Greca C , Arena G , Talarico A , Pisano" E , De Ruvo E , Campari M , D"onofrio A
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

The HeartLogic algorithm combines multiple implantable cardioverter defibrillator (ICD) sensors to identify patients at risk of heart failure (HF) events.

Purpose

We sought to evaluate the risk stratification ability of this algorithm in clinical practice. We also analyzed the alert management strategies adopted in the study group and their association with the occurrence of HF events.

Methods

The HeartLogic feature was activated in 366 ICD and cardiac resynchronization therapy ICD patients at 22 centers. The HeartLogic algorithm automatically calculates a daily HF index and identifies periods IN or OUT of an alert state on the basis of a configurable threshold (in this analysis set to 16).

Results

The HeartLogic index crossed the threshold value 273 times (0.76 alerts/patient-year) in 150 patients over a median follow-up of 11 months [25-75 percentile: 6-16]. Overall, the time IN the alert state was 11% of the total observation period. Patients experienced 36 HF hospitalizations and 8 patients died of HF (rate: 0.12 events/patient-year) during the observation period. Thirty-five events were associated with the IN alert state (0.92 events/patient-year versus 0.03 events/patient-year in the OUT of alert state). The hazard ratio in the IN/OUT of alert state comparison was (HR: 24.53, 95% CI: 8.55-70.38, p < 0.001), after adjustment for baseline clinical confounders. Alerts followed by clinical actions were associated with a lower rate of HF events (HR: 0.37, 95% CI: 0.14-0.99, p = 0.047). No differences in event rates were observed between in-office and remote alert management. By contrast, verification of HF symptoms during post-alert examination was associated with a higher risk of HF events (HR: 5.23, 95% CI: 1.98-13.83, p < 0.001).

Conclusions

This multiparametric ICD algorithm identifies patients during periods of significantly increased risk of HF events. The rate of HF events seemed lower when clinical actions were undertaken in response to alerts. Extra in-office visits did not seem to be required in order to effectively manage HeartLogic alerts, while post-alert verification of symptoms seemed useful in order to better stratify patients at risk of HF events.
Venoplasty to gain venous access during cardiac device implantation is feasible and safe
Authors: Lankveld T , Stipdonk AMW , Brans RJB , Luermans JGLM , De Haan MW , Vernooy K
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Venous obstruction is relatively common after cardiac implantable electronic device (CIED) implantation. After CIED implantation 15% of the patients present with a severe or total occlusion. This poses a problem during lead revisions or upgrades often leading to implantation failure or complex extraction or lead tunneling procedures. Percutaneous balloon venoplasty might be a suitable option but is rarely performed.

Purpose

To identify the feasibility and safety of venoplasty during cardiac device implantation procedures.

Methods

We retrospectively included consecutive cardiac device implantations in which venoplasty was performed during the same procedure from December 2018 until December 2020. The venoplasty was done either planned or ad hoc, by an interventional radiologist.

Results

We included 17 patients, 14 (82%) were male, aged 73 ± 11 years. Fifteen (88%) patients required an upgrade or lead revision and two were de novo implantations. The subclavian vein was the site of occlusion in 13 (76%) patients. In 16 (94%) patients venoplasty was successful and all intended leads could be implanted subsequently. In the patient with the unsuccessful recanalization both an antegrade and retrograde approach via the vena femoralis was attempted. No venoplasty related complications occurred.

The figure shows a succesful upgrade from a single chamber ICD (panel A) to a CRT-D (panel D) after venoplasty for a total occulsion of the vena subclavia (panel B and C). 

Conclusions

Percutaneous balloon venoplasty is a safe and feasible method for patients in whom venous access is an issue during CIED implantation. This method can be performed ad hoc and prevents contralateral lead implantation with tunneling or lead extraction. Abstract Figure. Venoplasty during upgrade.
Submuscular reburial as an alternative to lead extraction in high risk patients
Authors: Llewellyn J , Meda G , Wright DJ , Rao A
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

The Heart Rhythm Society (HRS) and European Heart Rhythm Association (EHRA) consensus states complete extraction is recommended for all patients with definite cardiac implantable electronic device (CIED) infection. Although complete removal of hardware is the best way to manage infections, lead extraction is a complex procedure with significant risk. As age and complexity of patients increase so too does extraction risk. In very high risk cases conservative management is cited, though little is known on outcomes.

Purpose

We are a high volume tertiary centre which serves a population of 2 million. 2 experienced operators perform 65 extraction procedures per year for the past 10 years. We report our experience of device reburial as initial management of CIED pre-erosion and erosion in cases deemed too high risk for extraction.

Method

We retrospectively reviewed all reburial procedures undertaken over 9 years. Patient and lead factors influencing decisions were assessed. Information on number of leads, dwell time, prior procedure, infective status and comorbidity was collated. The outcomes included morbidity, defined by repeat procedure (revision and/or extraction) and mortality. 

Results

86 patients underwent 96 procedures from March 2013 until August 2020. All patients undergoing device reburial were included. 55.8% of patients were male, mean age was 73. 21 patients died, 7 of these deaths occurred within 12 months of the index reburial procedure. The mean follow up period was 39 months (range 5–90). 65.1% of patients had a procedure (de novo implant, upgrade or replacement) within 12 months prior to revision.

We reviewed patients in 2 subgroups based on revision indication – erosion and pre-erosion. Erosion was defined as externalised lead/device. Pre-erosion was defined as superficial device with skin tethering but no exposure. The former is a definite indication for lead extraction, the latter a relative indication. All in the pre-erosion group were systemically well with no infection evident. One patient with erosion had a positive blood culture.

The mean age in the erosion group was 85 years with a Clinical Frailty Score (CFS) 4.98 and lead dwell time 17.87 years compared to age 68 years, CFS 3.98 and dwell time 8.14 years in the pre-erosion group. Patients in this cohort with an eroded device were deemed too high risk to undergo transvenous lead extraction.

A higher proportion of patients presenting with erosion died within 12 months of the index reburial procedure (16.67% vs 4.84%). 21% with an eroded device and 11% with a pre-eroding device undergoing reburial as first line management required future extraction.

Conclusion

Our 9 year data suggests less invasive intervention is a valid option in high risk groups such as older age, frailty, long lead dwell time, with an acceptable incidence of reintervention and/or extraction. This data can help guide informed consent in the future.
Treatment of symptomatic atrial tachycardia in complex anatomic conditions: use and outcome of ablation in patients after damus-kaye-stansel surgery
Authors: Fischer AJ , Ho SY , Ernst S
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Atrial tachycardias (AT) are amongst the most frequent complications in adult patients with congenital heart disease (ACHD). Their incidence mainly depends on age and complexity of underlying defect. AT has a marked impact on morbidity and mortality and is associated with sudden cardiac death particularly in complex ACHD patients. The arrhythmic substrate can be variable from re-entry to multifocal resulting in demanding requirements for electrophysiologic ablation procedures (EP) and thus, relatively high rates of recurrence.

Methods and results

Retrospective analysis of ACHD patients with prior Damus-Kaye-Stansel (DKS) surgery treated at one of the largest specialized tertiary centers for ACHD patients worldwide. Analysis focussed on occurrence of AT, respective treatment and outcome of EP.

Over a median observation time of 15 years, 13 patients with prior DKS surgery and complex congenital heart defects of different types but uniformly Fontan circulation, were identified (median age 22.0 years (IQR 20.5 – 25.5), 76.9% male, 92.3% NYHA Class I, median systemic ventricular ejection fraction 58.5%, 69.2% extracardiac tunnel). Seven patients (53.8%) presented with symptomatic AT (median cyclic length 440 ms (IQR 360.0 – 517.5)). Of these, six patients underwent EP. Median procedure time was 180.5 min (IQR 160.8 – 274.5), median fluoroscopy time 1.56 min (IQR 0.51 – 4.73) and radiofrequency time 851 sec (265.0 -2005.0). Remote magnetic navigation was used to access ablation site through a retrograde access via the aortic as well as the neo-aortic valve.  Three-dimensional image integration aided in mapping and ablation. Throughout the procedure as well as in follow-up visits, no reportable complications were observed. After a mean of 1.5 procedures, all analysed patients stayed complaint-free throughout a median time-interval of 13 months.

Conclusion

AT are frequent in complex univentricular situations after Damus-Kaye-Stansel surgery (53.8%). Although more than one procedure (mean 1.5) was necessary to achieve satisfactory results even in experienced hands, EP appears to be an appropriate treatment strategy in this young and otherwise healthy patient cohort. According to our analysis, EP is feasible and safe in centers with knowledge of specific anatomic characteristics of congenital heart disease and when the appropriate technical infrastructure is present. Access to ablation site was performed by remote magnetic navigation in the majority of procedures. The floppy catheter was navigated through the neo-aortic as well as through the aortic valve without observable peri- or postinterventional complications. Mapping with three-dimensional image integration facilitated EP and led to a relatively low radiation exposure with the known benefits for the patient as well as for the healthcare professionals involved in the procedure. Abstract Figure.
Incidence, risk factors and outcomes of atrial arrhythmias in adult patients with atrioventricular septal defect
Authors: Jacquemart E , Bessiere F , Combes N , Ladouceur M , Iserin L , Gardey K , Henaine R , Chevalier P , Legendre A , Petit J , Di Filippo S , Hascoet S , Marijon E , Waldmann V
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): French Federation of Cardiology

Background

The number of adults with atrioventricular septal defects (AVSD) is growing, with however, very few data regarding the natural history of atrial arrhythmias in this specific population. We aimed to assess the incidence, associated factors and outcomes of atrial arrhythmias among adult patients with AVSD.

Methods

Multicentric retrospective cohort of patients with AVSD from 3 referral centers specialized in adult congenital heart disease. Unbalanced AVSD, univentricular hearts, and Eisenmenger syndromes were excluded. Lifetime cumulative incidences of different types of atrial arrhythmia (>30 seconds) were analyzed (atrial fibrillation [AF] and intra atrial reentrant tachycardia/focal atrial tachycardia [IART/FAT]). Multiple logistic regression models were used to identify risk factors for atrial arrhythmias.

Results

The cohort comprised of 391 patients (61.6% of women) with a mean age of 36.3 ± 16.3 years and 17.3 ± 14.2 years of follow-up after surgical repair in operated patients, including 333 (85.1%) partial/intermediate and 58 (1.0%) complete AVSD. Overall, atrial arrhythmias were documented in 98 patients (25.1%).

The lifetime risks for developing atrial arrhythmia to ages 20, 40, and 60 were 3.7%, 17.6%, and 54.8%. IART/FAT was the leading arrhythmia until the age of 45 then AF surpassed IART/FAT.

Age (OR = 1.4, 95%CI = 1.2-1.6 by 5 years increment), the number of cardiac surgeries (OR = 4.1, 95%CI = 2.5-6.9), left atrial dilatation (OR = 3.1, 95%CI = 1.4-6.8), right atrial dilatation (OR = 4.1, 95%CI = 1.7-10.3), and moderate or severe left AV valve regurgitation (OR = 3.7, 95%CI = 1.2-11.7) were independently associated with a higher risk of atrial arrhythmias. Patients with atrial arrhythmias more frequently had pacemaker implantation (41.8% vs. 8.5%, p < 0.001), heart failure (24.5% vs 1.0%, p < 0.001) and cerebrovascular accidents (11.2% vs 3.4%, p = 0.007).

Conclusions

The lifetime risk of atrial arrhythmias in patients with AVSD is considerable with more than half of patients who will develop an atrial arrhythmia by the age of 60. Atrial arrhythmias are associated with a significant morbidity in this population. Abstract Figure. Central Illustration AVSD
Use of a smartphone ECG to diagnose arrhythmias in athletes: a case series
Authors: Jewson J , Orchard J , Semsarian C , Fitzpatrick J , La Gerche A , Orchard J
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

 While athletes are generally very fit, intense exercise can increase the risk of atrial fibrillation (AF), resulting in distressing symptoms during or after exercise. Moreover, other arrhythmias such as atrial flutter or supraventricular tachycardia (SVT) can also cause troublesome, exercise-related symptoms. Accurate diagnosis is essential to guide appropriate treatment. Given the symptoms are infrequent and/or occur in specific circumstances, traditional monitoring devices are often impractical to use during exercise or too invasive. Recently, smartphone ECGs such as the Alivecor KardiaMobile device (iECG) has been shown to be interpretable by a cardiologist in 95% of cases and may be the portable tool required to help identify arrhythmias in this challenging population. 

Purpose

 This case series was designed to highlight the use of iECG devices in aiding the diagnosis of arrhythmias in exercise-related symptoms.

Methods

 Five cases are reported where the iECG was used to document at least one episode of exercise-related symptoms. Participants were eligible if they were over 18 years of age and had had an iECG trace taken during an episode of exercise-related symptoms (e.g. light-headedness, shortness of breath, palpitations). which could be associated with an arrhythmia All participants were identified by authors from previous clinical experiences (or from clinical colleagues) and provided written, informed consent.

Results

 The cases included one amateur middle-distance runner in his 40s, two amateur ultra-endurance runners in their 30s and two young elite cricketers (Figure 1). In four of the cases, an accurate diagnosis of an arrhythmia (atrial flutter, AF and 2x SVT) was obtained using the iECG device, which helped to guide definitive treatment (e.g. medication or ablation). Two of these cases had been investigated using traditional methods such as stress ECG or Holter monitor over many months without achieving a diagnosis. The final case did not obtain a cardiac diagnosis using the iECG device despite using it on multiple occasions during symptomatic events. This reassured this athlete that the symptoms experienced were not cardiac related and she is now confident to exercise.

Conclusion

 The iECG was able to accurately detect arrhythmias and provide a diagnosis in cases where traditional monitoring had not. The utility of detecting no arrhythmia during symptoms in one case was also highlighted, providing the athlete with the confidence to continue exercising. This reassurance and confidence across all cases is perhaps the most valuable aspect of this device, where clinicians and athletes can be more certain of reaching a diagnosis and undertaking appropriate management. Abstract Figure 1: iECG traces
Machine learning based major complication prediction for patients undergoing transvenous lead extraction
Authors: Mehta VS , O"brien H , Elliott MK , Sidhu BS , Gould J , Razavi R , Niederer S , Rinaldi CA
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

 Relative benefits of transvenous lead extraction (TLE) should be weighed against the risks on an individual basis.  Observational studies have identified disparate risk factors for major adverse events (MAEs), however there are few available tools to aid the clinician risk-stratifying patients.

Purpose

 The purpose of this study was to develop a machine learning (ML)-based risk stratification system to predict risk of MAEs following transvenous lead extraction (TLE).

Methods

 Multiple ML models were derived from a training cohort of 3555 patients undergoing TLE to pre-procedurally identify patients at high and low risk of major adverse events (procedure-related major complication, including procedure-related death). The ML models were then tested on an independent, reference centre cohort of 1171 patients undergoing TLE.  Clinical features were selected based on whether they were available in both datasets without large gaps. For model selection we compared the ML algorithms logistic regression, ridge regression, support vector machines (SVM), gradient boosting classifier and random forest. The best performing of these was then compared to a self-normalising network (SNN).

Results

 In total 3122 cases with the required features were included from the training cohort with 53 MAEs (1.7%), and 998 cases in the test cohort with 24 MAEs (2.4%).  SVM identified lead dwell time, left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), chronic respiratory disease, local infection, heart failure, sepsis and male gender as predictors of MAEs in order of decreasing importance (see figure).  For the training data, the SVM provided a more sensitive result compared with SNN (0.83 vs 0.71) at the cost of specificity (0.63 vs 0.79).  For the test data, the SVM identified MAEs in 12 out of 123 (9.8%) "high risk" patients, 10 out of 552 (1.8%) "medium risk" patients, and 2 out of 323 (0.006%) "low risk" patients.

Conclusion

  Machine learning provided good discriminative capabilities for identifying patients in a "high risk" and "low risk" category for MAEs. Abstract Figure. 8 most important predictors of MAEs
What are patients reading? Assessing the quality of online resources on sudden cardiac arrest in athletes
Authors: Fanous Y , Dorian P
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Patients frequently use the internet as an educational resource and sometimes in complete substitution of an expert physician’s consultation. Sudden cardiac arrests (SCA) in athletes are often sensationalised and attract much online readership. No studies have explored the quality of online content relating to SCA in athletes.

Purpose

To assess the quality of online educational resources on SCA in athletes.

Methods

The first 200 hits of the search "sudden cardiac arrest in athletes" on Google were analyzed. For each website, reading difficulty was evaluated using 5 validated reading indices. Content quality was assessed with point-based scoring systems established by expert opinion.

Results

A total of 115 unique web domains met eligibility criteria, only 2 of which were within the limits of national recommended readability level (≤8th grade). 53.9% were from educational institutions. Mean content accuracy scored only 6.5 ± 3.9 out of 15 (43%), and mean school-grade reading level was 13.3 ± 2.9 years (equivalent to a post-secondary level of education). The majority of websites had poor lay appropriate explanations of concepts; 91.3% failed to adequately explain basic principles of treatment; 68.7% failed to mention over half of common etiologies associated with SCA; only 59.1% correctly cited incidence of SCA amongst young athletes; 24.3% did not explore management options and only 28.7% mentioned treatment options beyond immediate resuscitation. Higher reading difficulty correlated with higher accuracy scores (β 1.1, p < 0.001).

Conclusion

There is a paucity of accurate, lay language appropriate online health information on SCA in athletes. Incomprehensible and incomplete information may lead to inappropriate decisions by patients. A collaborative approach between experts and patients may assist in the creation of resources related to athletes’ health.
The TeleCheck-AF project on remote app-based management of atrial fibrillation during the COVID-19 pandemic: Patient experiences
Authors: Linz D , Pluymaekers N , Duncker D , Manninger M , Van Der Velden R , Hermans A , Verhaert D , Hemels M , Sultan A , Gupta D , Heidbuchel H , Sohaib A , Svennberg E , Crijns H , Hendriks J
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

OnBehalf

TeleCheck-AF Investigators

Aims

TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck®). We describe the characteristics and experiences from recruited patients.

Methods

Self-reported patient characteristics were obtained from the app. A survey exploring patient experiences completed by 826 patients. 

Results

Within 28 weeks, 1930 AF patients were recruited by 38 centers in 14 countries, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). One-third of patients was in the age range 60-69 years. The most common comorbidity was hypertension (42% of all patients). More than 70% of patients were treated with oral anticoagulation. In total 59.858 heart rate and rhythm measurements were recorded. During the one-week FibriCheck® use, patient adherence was high. Patients performed between 2 and 5 recordings a day and the median number of measurements per patient was 21 [15-29]. The highest average number of measurements per patient was seen in patients older than 80years of age. Patients agreed that the FibriCheck® app was easy to use (94%) and easy to install (89%). The app gave patients a safe feeling (74%) due to being in constant heart rate and rhythm control. More than half of the patients (58%) agreed or strongly agreed that they would like to use the FibriCheck® app in the future. They also found the automated reminders useful (64%). 

Conclusions

In the TeleCheck-AF project, mHealth adherence was high, particularly in older patients ≥80 years. The app FibriCheck® is easy to use for 7 days before a scheduled teleconsultation. Patients think that remote rate and rhythm monitoring around teleconsultation by the TeleCheck-AF approach may be an alternative to traditional face-to-face consultations in the future. Abstract Figure.
Does sponsorship of electrophysiology and devices presentations alter conflict of interest disclosures?
Authors: Camm CJF , Crawford W , Bello A , Raouf Z , Schaefer A , Prachee I , Olivarius-Mcallister J , Ginks M , Nicol E
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Interaction with industry is often required for the development of electrophysiology (EP) and devices research. Findings from industry-funded research are often presented at sponsored sessions during international conferences. However, industry interactions produce potential conflict of interests (COIs). Such COIs must be disclosed appropriately when presenting research findings to allow viewers to interpret the results correctly. This is particularly true during sponsored sessions.

Purpose

To assess whether session sponsorship affects the presentation of potential COIs in EP and devices presentations.

Methods

Recorded presentations from the Arrhythmia & Devices section of ESC Annual Congresses 2016-2020 were assessed. Presentations were excluded if the original presentation contained no slides, was a panel discussion, it was a non-scientific presentation, or part of the presentation was missing. Sponsorship information was gathered from presentation meta-data. Chi-squared and Mann-Whitney U tests were used to assess differences between groups for dichotomous and continuous data respectively.

Results

Of 1,153 presentations assessed, 1,017 were suitable for inclusion. Of these 14% (n = 142) were sponsored sessions. COI disclosure slides were more likely to be missing in sponsored sessions (13.4%, n = 19) compared with non-sponsored sessions (6.2%, n = 54), p = 0.002. In those with COI disclosure slides, sponsored presentations contained a greater median number of COIs (12, IQR 6-19) compared with non-sponsored sessions (1, IQR 0-5), p < 0.0001. Conversely, the time-per-word spent on COI disclosures was approximately 50% lower in sponsored sessions (125ms, IQR 76-217ms) compared with non-sponsored sessions (250ms, IQR 125-375ms), p < 0.0001. Furthermore, presenters at sponsored sessions were much less likely than those at non-sponsored sessions to provide sufficient verbal details of their conflicts (0% vs 8.5% respectively, p = 0.0008). These findings were not materially altered when limited to only those presentations with COIs.

Conclusions

Sponsored sessions make up about one seventh of all EP/devices presentations at the ESC annual congress. Presenters at sponsored sessions were less likely to present a COI disclosure slide. Sponsored presentations had a higher number or of potential COIs, yet they were displayed for a far shorter time. This suggests that sponsored sessions have a higher risk of potential bias which viewers are not provided sufficient opportunity to assess.
Anti-desmoglein2 autoantibodies are present in patients with cardiac sarcoidosis and correlate with cardiac inflammation
Authors: Suna G , Kolios A , Chatterjee D , Fatah M , Gasperetti A , Casella M , Sommariva E , Franzen D , Manka R , Pazhenkottil A , Ruschitzka F , Boyman O , Duru F , Hamilton RM , Saguner AM
Published: May 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): The Zurich ACM Program is supported by generous grants from the Georg and Bertha Schwyzer-Winniker Foundation, the Baugarten Foundation, Swiss National Science Foundation, Swiss Heart Foundation and Wild Foundation. This work is also supported by a Canadian Institutes of Health Research grant (FRN: 162402) and the Labatt Heart Centre and Waugh Family Innovation Funds, Caitlin Elizabeth Morris Memorial Fund, Alex Corrance Memorial Foundation and Meredith Cartwright.

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy (ARVC) has several phenocopies such as cardiac sarcoidosis (CS), idiopathic outflow tract ventricular tachycardia (OT-VT) and myocarditis. Differentiation between these entities can be challenging. Recently, we have identified diagnostic anti-desmoglein-2 autoantibodies (anti-DSG2 Abs) in patients with ARVC.

PURPOSE We sought to examine whether anti-DSG2 Abs are also present in clinical phenocopies of ARVC.

METHODS Anti-DSG2 Abs in sera of 25, 19 and 22 patients with sarcoidosis, OT-VT and myocarditis, respectively, were assessed by western blots and ELISA. Clinical and imaging parameters, as well as conventional biomarkers were correlated to detected anti-DSG2 Ab intensity levels.

RESULTS Anti-DSG2 Abs, at various intensities, were identified in 6/25 (24%) patients with sarcoidosis, all presenting with CS, but were absent in patients with OT-VT and myocarditis. Cardiac 18F- fluorodeoxyglucose positron emission tomography (18F-FDG PET) was positive in all sarcoidosis patients with positive anti-DSG2 Abs, corresponding to a median PET maximum standardized uptake value (SUVmax) of 5.65 [IQR: 5.15 – 10.9]. In sarcoidosis patients without anti-DSG2 Abs, the SUVmax values were significantly lower with a median of 0 [IQR: 0 – 4] (p = 0.011). The Pearson correlation coefficient (R) was 0.188 (p = 0.039) indicating a positive correlation between cardiac 18F-FDG uptake and anti-DSG2 Abs. No significant correlation was detected for any of the other clinical parameters and biomarkers.

CONCLUSIONS In addition to being present in ARVC, anti-DSG2 Abs are also found in CS, a common phenocopy of ARVC; conversely, anti-DSG2 Abs are absent in idiopathic OT-VT and myocarditis. Anti-DSG2 Ab levels positively correlate with myocardial disease activity in CS as indicated by cardiac 18F-FDG PET scanning. Abstract Figure. Central illustration
Human-specific desmoglein 2 mutations in mice models of arrythmogenic right ventricular cardiomyopathy reproduce patients" phenotype
Authors: Zankov D , Ohno S
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease that inevitably leads to terminal heart failure and sudden cardiac death due to ventricular arrhythmias. Excessive exercise accelerates the progress of the disease. At present, there is no curative therapy for ARVC. The disease is mostly caused by mutations in genes encoding desmosomal proteins, and Japanese ARVC patients commonly possess missense mutations in DSG2. Although there are animal models with Dsg2-related cardiomyopathy, they do not reﬂect the precise human disease caused by missense mutations in DSG2.

Purpose

We aimed to generate knock-in mouse models of ARVC carrying Dsg2 mutations equivalent to those found in ARVC patients.

Methods

We introduced Dsg2 mutations (R297C, D499A), which were equivalent to most common mutations in Japanese ARVC patients, to mice by CRSPR/Cas9 genome editing system. Echocardiography and treadmill training were performed to evaluate the cardiac phenotype of the mouse models.

Results

There is phenotype inequality between the two lines of Dsg2 knock-in mice. In R297C mice, all the homozygotes died suddenly until the age of 20 weeks, and half of the heterozygotes until the age of 25 weeks. Heart examination of the deceased homozygous mice demonstrated enlarged cavities, predominantly in the right ventricles, and scattered pale patches suggesting ﬁbrotic replacement of the myocardium. Echocardiography of four 9-week-old homozygous mice shows acoustically dense zones (white arrows in the left ﬁgure) and left ventricular dysfunction (ejection fraction (EF) < 35%). Exploration of the hearts of sacriﬁced mice conﬁrmed echocardiographical ﬁndings (red arrow in the right ﬁgure) demonstrating scattered pale regions similar to those in suddenly died mice. In contrast, homozygous and heterozygous D499A mice survived without sudden death. Both mutant mice develop heart failure after the age of 30 weeks. To mimic the effect of exercise, we performed treadmill training for two months started from 11 weeks old in both types of D499A and heterozygous R297C mice. The training signiﬁcantly accelerated cardiac dysfunction: all D499A mice (homo and hetero) and half of heterozygous R297C developed biventricular dysfunction at the age of 19 weeks though no change in WT. EF for R297C heterozygous mice, D499A heterozygous and D499A homozygous mice decreased from 64.4 ± 4.3%, 71.9 ± 1.7% and 73.9 ± 1.1 to 31.2 ± 5.7%, 16.6 ± 2.1% and 12.4%±1.9, respectively. Treadmill training did not alter significantly EF in WT mice: 71.8 ± 2.3% before and 67.5 ± 1.4 at the end of physical challenge.

Conclusion

We generated mouse model of ARVC mutations that mimic the exact gene defect found in the humans. Our experimental work conﬁrms signiﬁcant overlap to the human phenotype. Further investigation will clarify the underlying cellular mechanisms. Abstract Figure. A heart from homozygous R297C mouse
Functional characterization of drug responses in induced pluripotent stem cell-derived cardiomyocytes from a short QT syndrome type 5 patient
Authors: Lee J , Hohn A , Emmenegger V , Ulusan H , Akin I , Saguner AM , Zhou X , Duru F , Hierlemann A , El-Battrawy I
Published: May 2021

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): ETH Zurich Personalized Health and Related Technologies; German Centre for Cardiovascular Research

Introduction

Short QT syndrome (SQTS) and Brugada syndrome (BrS) are rare channelopathies causing sudden cardiac death (SCD). There are only few investigations of effective therapies of SQTS and BrS linked to CACNB2 variants. Since treatment data of SQTS are sparse, we studied drug responses of induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) 2D cultures carrying a mutation in the CACNB2 gene from a SQTS type 5 (SQT5) patient with an established phenotype. We used high-density microelectrode arrays (HD-MEAs), patch clamp, and calcium-transient imaging.

Purpose

To investigate the electrophysiological responses of SQT5 patient-derived iPSC-CMs upon exposure to antiarrhythmic drugs.

Methods

Human iPSCs, derived from a SQT5 patient and a healthy donor, were cultured and differentiated into cardiomyocytes by temporal modulation of the Wnt signaling. For electrophysiological measurements, spontaneously beating cardiomyocytes at day 40-60 were dissociated and plated a) on petri dishes for patch clamp and calcium-transient measurements and b) directly on HD-MEAs. Antiarrhythmic drugs, including sotalol, quinidine, and flecainide, were dosed to the cells after plating as soon as stable activity levels were measured. After baseline measurements, drug doses were sequentially increased from low to high concentrations.

Results

We observed spontaneous and synchronous beating of SQT5 patient- and healthy donor-derived iPSC-CMs. Quinidine, which is known to be effective for treatment of SQTS with possible differences for subtypes, prolonged field-potential duration (FPD) and action-potential duration in SQT5 patient-derived iPSC-CMs. Sotalol slightly increased FPD at 30µM as measured with HD-MEAs, whereas action-potential duration (APD) measured through patch clamp did not exhibit a notable effect at 30 µM. APD became shorter at higher concentrations, which is in line with clinical data of SQTS patients. HD-MEA measurements showed that flecainide shortened the FPD of SQT5 patient-derived CMs at 20µM. For healthy donor-derived iPSC-CMs, quinidine, sotalol, and flecainide prolonged FPDs in HD-MEA measurements. Using calcium-transient imaging, quinidine showed a slight antiarrhythmic effect, whereas sotalol did not have antiarrhythmic effects.

Conclusion

We used HD-MEAs, patch clamp, and calcium-transient imaging to analyze electrophysiological responses of SQT5 patient-derived iPSC-CMs upon dosage of antiarrhythmic drugs. Our preliminary results show that quinidine - but not flecainide - could prolong the repolarization duration in SQT5 patient-derived iPSC-CMs.