bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with silent cerebral events during catheter ablation for atrial fibrillation in the era of uninterrupted oral anticoagulation therapy
Authors: Harada M , Nomura Y , Nishimura A , Motoike Y , Koshikawa M , Watanabe E , Izawa H , Ozaki Y
Published: November 2020

Background

A silent cerebral event (SCE), detected by brain magnetic resonance imaging (MRI), is defined as an acute new brain lesion without clinically apparent neurological deficit, and is frequently observed after catheter ablation in atrial fibrillation (AF) patients. Although the small number of SCEs does not cause neurocognitive dysfunction, the greater volume and/or larger number of SCE lesions are reportedly related to neuropsychological decline; SCE incidence may be a surrogate marker for the potential thromboembolic risk. Thus, strategies to reduce SCEs would be beneficial. Uninterrupted oral anticoagulation strategy for peri-procedural period reportedly reduced the risk of SCEs, but the incidence hovers at 10% to 30%. We sought factors associated with SCEs during catheter ablation for AF in patients with peri-procedural uninterrupted oral anticoagulation (OAC) therapy.

Methods

AF patients undergoing catheter ablation were eligible (n=255). All patients took non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonist (VKA) for peri-procedural OAC (>4 weeks) without interruption during the procedure. Brain MRI was performed within 2 days after the procedure to detect SCEs. Clinical characteristics and procedure-related parameters were compared between patients with and without SCEs.

Results

SCEs were detected in 59 patients (23%, SCE[+]) but not in 196 patients (77%, SCE[-]). Average age was higher in SCE[+] than SCE[-] (66±10 years vs. 62±12 years, p<0.05). Persistent AF prevalence, CHADS2/CHA2DS2-VASc scores, and serum NT-ProBNP levels increased in SCE[+] vs. SCE[-]. In transthoracic/transesophageal echocardiography, left-atrial dimension (LAD) was larger and AF rhythm/spontaneous echo contrast were more frequently observed in SCE[+] than SCE[-]. SCE[+] had lower initial activated clotting time (ACT) before unfractionated heparin (UFH) injection and longer time to reach optimal ACT (>300 sec) before trans-septal puncture than SCE [-]. In multivariate analysis, LAD, initial ACT before UFH injection, and time to reach optimal ACT were predictors for SCEs.

Conclusions

LAD and intra-procedural ACT kinetics affect SCEs during the procedure in patients with uninterrupted OAC for AF ablation. Shortening time to achieve optimal ACT during the procedure may reduce the risk of SCEs.

Funding Acknowledgement

Type of funding source: None
Cryoballoon pulmonary-vein isolation for atrial fibrillation with heart failure: results from a single-center cohort
Authors: Boehmer A , Rothe M , Jaqubi S , Summ A , Soether C , Abboud J , Ringwald V , Dobre B , Kaess B , Ehrlich J
Published: November 2020

Background

Atrial fibrillation (AF) and heart failure (HF) are of growing prevalence and increasing mortality. Radiofrequency ablation is safe and effective for patients with AF and HF. Prognosis might be improved in patients treated. However, there is no prospective trial investigating efficacy and safety of cryoballon ablation in patients with AF and HF.

Objective

To prospectively compare cryoballoon ablation in patients with and without HF (defined as LVEF ≤40%) in terms of safety and efficacy.

Methods

Ongoing POLAR-HF trial is a prospective, investigator-initiated, single-center, non-inferiority, open-label study. We analyzed 244 consecutive patients who underwent cryoballoon ablation. Of these 217 had normal LVEF (age 68.1±9.6 years, CHA2DS2-VASc Score 2.5±1.3, 55.3% male) while 27 patients (11%) suffered from HF (age 70.4±8.6 years, CHA2DS2-VASc Score 3±1.2, 70.4% male). Follow-up was performed at 3, 6 and 12 months after ablation. Kaplan-Meier method was used to calculate 12-month event-rate estimates. Log-Rank Test to estimate hazard ratios in the primary analysis. Endpoints were: symptomatic AF relapse for efficacy and bleeding, stroke or death for safety.

Results

Analysis showed no difference in AF-free survival rate between patients with and without HF (81% vs. 76.3%, Log-Rank-Test P=0.81, Figure). Primary safety end point occurred in 5 patients with normal LVEF (2.3%) and none in the HF-group. No deaths were observed.

Conclusion

Results of POLAR-HF indicate that cryoballoon ablation is an effective ablation method for patients suffering from AF and HF.

Event-Free Survival (Efficacy Endpoint)

Funding Acknowledgement

Type of funding source: None
Risk scoring by CHADS2 and CHA2DS2-VASc as predictors for long-term outcomes after surgical ablation for atrial fibrillation
Authors: Lauritzen D , Vodstrup H.J , Christensen T.D , Onat M , Christensen R , Heiberg J
Published: November 2020

Background

Following catheter ablation for atrial fibrillation (AF), CHADS2 and CHA2DS2-VASc have utility in predicting long-term outcomes. However, it is currently unknown if the same holds for patients undergoing surgical ablation.

Purpose

To determine whether CHADS2 and CHA2DS2-VASc predict long-term outcomes after surgical ablation in concomitance with other cardiac surgery.

Methods

In this prospective, follow-up study, we included patients who underwent biatrial ablation - or pulmonary vein isolation procedure concomitantly with other cardiac surgery between 2004 and 2018. CHADS2 and CHA2DS2-VASc scores were assessed prior to surgery and categorized in groups as 0–1, 2–4 or ≥5. Outcomes were death, AF, and AF-related death. Follow-up was ended in April 2019.

Results

A total of 587 patients with a mean age of 68.7±0.4 years were included. Both CHADS2 and CHA2DS2-VASc scores were predictors of survival p=0.005 and p<0.001, respectively (Figure). For CHADS2, mean survival times were 5.9±3.7 years for scores 0–1, 5.0±3.0 years for scores 2–4 and 4.3±2.6 years for scores ≥5. For CHA2DS2-VASc mean survival times were 7.3±4.0 years for scores 0–1, 5.6±2.9 years for scores 2–4 and 4.8±2.1 years for scores ≥5. The incidence of death was 20.1% for CHADS2 0–1, 24.8% for CHADS2 2–4, and 35.3% for CHADS2 ≥5, p=0.186. The incidence of AF was 50.2% for CHADS2 0–1, 47.9% for CHADS2 2–4, and 76.5% for CHADS2 ≥5, p=0.073. The incidence of AF related death was 13.0% for CHADS2 0–1, 16.8% for CHADS2 2–4, and 35.3% for CHADS2 ≥5, p=0.031. The incidence of death was 16.8% for CHA2DS2-VASc 0–1, 26.2% for CHA2DS2-VASc 2–4, and 45.0% for CHA2DS2-VASc ≥5, p=0.001. The incidence of AF was 49.6% for CHA2DS2-VASc 0–1, 52.5% for CHA2DS2-VASc 2–4, and 72.5% for CHA2DS2-VASc ≥5, p=0.035. The incidence of AF related death was 12.2% for CHA2DS2-VASc 0–1, 16.0% for CHA2DS2-VASc 2–4, and 42.5% for CHA2DS2-VASc ≥5, p<0.001.

Conclusion

Both CHADS2 and CHA2DS2-VASc scores predict long-term outcomes after surgical ablation for AF. However, CHA2DS2-VASc was superior in predicting death, AF, and AF-related death.

Survival curves

Funding Acknowledgement

Type of funding source: None
Impact of antithrombotic therapy in the prognosis of atrial fibrillation patients with advanced chronic kidney disease
Authors: Andreu Cayuelas J.M , Raposeiras-Roubin S , Fortuny Frau E , Garcia Del Egido A , Seller-Moya J , Ortiz Cortes C , Camacho Freire S.J , Alonso Fernandez P , Jorge-Perez P , Lopez-Pais J , Bravo-Marques R , Palacios-Rubio J , Benezet-Mazuecos J , Cosin-Sales J
Published: November 2020

Introduction

Chronic kidney disease (CKD) is associated with an elevated thromboembolic and bleeding risk in atrial fibrillation (AF) patients, so the decision of antithrombotic therapy is a challenge.

Purpose

To analyze mortality, embolic and bleeding events in patients with advanced CKD and AF.

Methods

Multicentric retrospective registry on patients with AF and advanced CKD (CKD-EPI <30 mL/min/1.73 m2). For death, multivariable Cox regression analysis was developed. For embolic and bleeding events, competing-risks regression based on Fine and Gray's proportional subhazards model was performed, being death the competing event

Results

We analysed 405 patients with advanced CKD and newly diagnosed AF. 57 patients were not treated with antithrombotic therapy (14.1%), 80 only with antiplatelet/s (19.8%), 211 only with anticoagulation (52.1%), and 57 with anticoagulant plus antiplatelet/s (14.1%). During a follow-up of 4.6±2.5 years, 205 died (50.6%), 34 had embolic events (8.4%) and 85 had bleeding outcomes (21.0%). Bleeding event rate was significantly lower in patients without antithrombotic therapy (Figure). After multivariate analysis, anticoagulant treatment was associated with higher bleeding rates, without differences in mortality or embolic events (Table).

Conclusion

Anticoagulation therapy was associated with a significant increase in bleeding events in patients with advanced CKD and newly diagnosed AF. None of the antithrombotic therapy regimens resulted in lower embolic events rate neither benefit in mortality.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): This study was supported by an unconditional grant from BMS-Pfizer
Recommended and non-recommended edoxaban dosing in patients with atrial fibrillation (AF): one-year clinical events from the Global ETNA-AF non-interventional study (NIS)
Authors: Chao T.F , Kirchhof P , Koretsune Y , Yamashita T , Unverdorben M , Reimitz P , Chen C , De Caterina R
Published: November 2020

Background

In AF patients on direct oral anticoagulants (DOAC), safety and effectiveness vary with dose. This might impact treatment decisions.

Purpose

To investigate the effects of dosing of the DOAC edoxaban in AF patients on safety and effectiveness during 1-year observation in a real-world setting.

Methods

The Global ETNA-AF NIS included 26,823 patients. Baseline data by edoxaban dosing (60mg/30mg) and their influences on the safety (major bleeding [MB], clinically relevant non-major bleeding [CRNMB]), and effectiveness (stroke, systemic embolism, myocardial infarction [MI], death) were investigated (Table).

Results

Figure shows the breakdown by dose (60mg vs 30mg) and recommended (rec) vs non-recommended (non-rec) dosing. Patients on non-rec 30mg vs on rec 60mg edoxaban were older (mean ± SD: 74±9 vs 70±9 y); had lower creatinine clearance (72.2±20.6 vs 85.8±26.8 mL/min); and had more comorbidities, history of MB (2.1% vs 1.1%), and strokes (11.0% vs 8.6%). Non-rec 60mg vs rec 30mg patients were younger (75±9 vs 78±9 y), had fewer comorbidities, history of MB (1.2% vs 2.6%), and strokes (10.2% vs 16.4%). In non-rec 30mg vs rec 60mg, MB was not lower and ischaemic events were not higher. In non-rec 60mg vs rec 30mg, no increase in MB, CRNMB or ischaemic events was seen.

Conclusion

Edoxaban was prescribed at the label recommended dose in the vast majority of patients. Non-rec 30mg patients were sicker than rec 60mg patients while non-rec 60mg patients were less sick than rec 30mg patients. Overall event rates were low, and ischaemic event rates of non-rec 30mg and bleeding event rates of non-rec 60mg were not numerically higher than that of corresponding rec dosing groups.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Daiichi Sankyo
Early-onset and recurrent reflex syncope is associated with left ventricular diastolic filling and left atrial function properties
Authors: Roumelis P , Antoniadis A , Sotiriadou M , Pagkourelias E , Konstantinidis P , Meletidou M , Bakogiannis C , Toumpourleka M , Mpoulmpou A , Kyriakou P , Papadopoulos C , Fragakis N , Vassilikos V
Published: November 2020

Background/Introduction

The effects of the left atrial and ventricular function in the pathophysiology of reflex syncope remain elusive. Head-up tilt table test (HUTT) is frequently used in the diagnostic workup of patients with syncope, but the outcomes of HUTT have not been attributed to any anatomical or functional cardiac characteristics.

Purpose

We sought to assess the effects of anatomical and functional echocardiographic features of the left atrium and the left ventricle at rest in the clinical presentation of syncope and the outcomes of HUTT.

Methods

We investigated patients with a history of syncope and symptoms suggestive of reflex syncope who underwent HUTT. Specific echocardiographic indices of left cardiac morphology and function were assessed at rest. The patients were divided into two groups, those who presented with syncopal episodes at age <35 years (group A) and those who presented with syncopal episodes at age >35 years (group B).

Results

In 119 patients (age 46.75±21.17 years, 69 women), patients in group A exhibited a higher chance for numerous (>3) syncopal episodes (odds ratio [OR] 3.4, 95% Confidence Interval [CI] 1.41 to 7.93, p<0.05). Group A showed also a trend for positive HUTT (OR 1.99, 95% CI 0.97 to 4.23, p=0.08). In patients with positive HUTT, Group A had higher E-wave velocity (0.83 vs 0.65 m/sec, p<0.05), lower A-wave velocity (0.60 vs 0.75 m/sec, p<0.05), higher E/A ratio (1.54 vs 1.00, p<0.05), higher e' wave velocity (0.16 vs 0.10 m/sec, p<0.05) and lower E/e' (5.64 vs 7.85, p<0.05). Also, patients in group A exhibited lower left atrial volumes (min 9.88 vs 16.21 ml, p<0.05, max 30.42 vs 44.89 ml, p<0.05), higher left atrial strain reservoir (40.56 vs 32.42%, p<0.05) and higher left atrial strain booster (25.94 vs 18.06%, p<0.05).

Conclusion(s)

Patients with a younger age of onset and recurrent syncopal episodes manifest smaller dimensions of the left atrium with distinct patterns of diastolic performance and better reservoir and booster function. These findings may indicate a more pronounced susceptibility of this group of patients to preload reduction, thereby triggering the mechanism of reflex syncope.

Funding Acknowledgement

Type of funding source: None
Validation of the FAINT risk score in a large prospective international multicenter study
Authors: Du Fay De Lavallaz J , Zimmermann T , Badertscher P , Flores D , Widmer V , Walter J , Belkin M , Boeddinghaus J , Nestelberger T , Reichlin T , Kuehne M , Christ M , Miro O , Martin-Sanchez J , Mueller C
Published: November 2020

Background

Risk stratification of older patients presenting to the Emergency Department (ED) with syncope remains an unmet clinical need. The FAINT Score was derived in a large American cohort in an attempt to predict 30-day serious cardiac outcomes in patients >60y.o. While a FAINT score of 0 showed high sensitivity to exclude death and serious outcomes at 30 days in the derivation cohort, it remains unvalidated.

Methods

We validated the FAINT score (History of heart failure, history of arrhythmia, initial ECG result abnormal, elevate NT-proBNP, elevated hs-troponin T) in a large prospective international multicenter study recruiting patients 40 years presenting to the ED with syncope within the last 12 hours in eight countries on three continents. Main outcome measure was 30-day serious cardiac events or mortality. We assessed the performance and calibration of the FAINT score for validation and compared it to the OESIL score (Age >64y, cardiovascular disease history, syncope without prodromes, abnormal ECG).

Results

1885 patients were eligible for this validation analysis. 169 (8.9%) patients experienced 30-day serious adverse events.

A FAINT score of 0 was present for 378 patients (20% of the cohort) and allowed for a sensitivity of 0.97 to rule out adverse events and death at 30-days. A FAINT score of 0 or 1 was present for 626 patients (33% of the cohort) and allowed for a sensitivity of 0.92.

The area under the receiver operating characteristic curve (AUC) for the FAINT score was 0.75 (95%, Confidence Interval (CI) 0.72–0.79), which was comparable to the performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) or high-sensitivity Troponin T (hs-cTnT) alone, which are two biomarkers used in the FAINT score. The score did not outperform the OESIL score.

A calibration curve showed that the score was extremely well calibrated for low-risk patients.

Conclusion

This is the first validation of the FAINT score in a large international syncope cohort. The safety of a FAINT score of 0 or 1 was good and comparable to the results obtained in the derivation cohort. While the score is suitable to highlight low-risk patients and calibrates well in an external cohort, its discrimination for higher risk patients is not better than biomarkers alone or an older, less complex risk score.

Figure 1. Area under the Receiver Operating Curve (ROC) for the FAINT score and for NT-proBNP and hs-cTnT as continuous markers as well as for the OESIL score. CI = Confidence Interval.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): University Hospital Basel, Switzerland
Implications of pacemaker implantation after TAVR: insights from the Nationwide Readmissions Database
Authors: Sharma E , Sheikh W , Parulkar A , Lima F , Wu M , Chu A
Published: November 2020

Introduction

Conduction disturbances after transcatheter aortic valve replacement (TAVR) requiring permanent pacemaker (PPM) implantation are a well-known procedural complication. Data on the effect of post-TAVR PPM implantation on 30-day readmissions is scarce.

Methods

The Nationwide Readmissions Database (NRD) is a nationally representative sample of all US hospitalizations, representing over 35 million discharges. The 2016 NRD was used to identify patients who underwent TAVR and PPM implantation from January to November 2016. Propensity matching was used to balance baseline clinical characteristics.

Results

Of the 44,607 patients who underwent TAVR, 4,878 (10.9%) required permanent pacemaker implantation during their index hospitalization. Patients requiring PPM during their index admission for TAVR had a higher crude median length of stay (LOS) (5d vs. 3d, p<0.001), median cost of index admission ($61,604 vs. $45,513, p<0.001) and rate of 30-day readmission (14.5% vs 11.2%, p<0.001). After 2:1 propensity matching, PPM patients still had a higher median LOS (5d vs. 3d, p<0.001), median cost of index admission ($61,902 vs. $41,162, p<0.001), and rate of 30-day readmission (13.8% vs 11.1%, p=0.003). Patients who received PPM were more likely to be older (81.1 vs 80.3, OR 1.01, CI 1.01–1.02), diabetic (OR 1.27, 1.13–1.44), obese (OR 1.22, 1.05–1.43), and have right (OR 4.35, 3.72–5.09) or left (OR 1.80, 1.51–2.15) bundle branch blocks on multivariate analysis. Causes of readmission in patients with and without PPM were predominantly non-cardiac (62.9% vs 68.0%). Heart failure was the most common cause of readmission for both groups (18.4% vs 14.6%). Median cost of readmissions ($8716 vs $8250, p=0.34) and LOS (4d vs 4d, p=1) were not significantly different during readmissions.

Conclusions

Based on a nationally representative sample, 10.9% of patients undergoing TAVR required PPM implantation during the index hospitalization. Age, diabetes, obesity, and right or left bundle branch blocks were significant predictors of PPM implantation. PPM implantation resulted in significantly higher LOS, costs, and 30-day readmissions on propensity-matched analysis.

Funding Acknowledgement

Type of funding source: None
Clinical impact of acquired risk factors in TTN-mediated dilated cardiomyopathy
Authors: Giudicessi J , Ackerman M , Pereira N
Published: November 2020

Background/Introduction

Truncating variants in TTN-encoded titin (TTNtvs) underlie ∼25% of familial dilated cardiomyopathy (DCM) cases. In addition, TTNtvs are over-represented in alcoholic, peripartum, and chemotherapy-induced CM suggesting that risk factors may play a substantive role in the penetrance and expressivity of TTN-mediated DCM.

Purpose

To determine the prevalence and clinical impact of risk factors for TTN-mediated DCM within a single center cohort of unrelated patients with pathogenic (P)/likely pathogenic (LP) TTNtvs.

Methods

In this retrospective study, an institutionally developed natural language processing algorithm was used to identify all TTNtv-positive patients evaluated clinically between 01/2012 and 12/2019. Each TTNtv was then mapped to the TTN reference sequence (NM_133378.4) and classified according to a strict interpretation of the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. After exclusion of individuals with complex congenital heart disease, ischemic heart disease, and those without ACMG P/LP TTNtvs, available medical records were reviewed for risk factors such as long-term heavy alcohol consumption (>80 grams/day), cardiotoxic chemotherapy exposure, morbid obesity (body mass index >40), biopsy/imaging-confirmed myocarditis, peripartum/tachycardia-mediated CM, and valvular heart disease.

Results

Overall, 33 ACMG P/LP TTNtv-positive patients were identified (40% female; mean age at presentation 45±16 years; mean LVEF at presentation 38%±17%). Of note, 17/33 (52%) presented with heart failure (HF) and 4/33 (12%) presented with sustained ventricular arrhythmias (VAs). The remaining 12 (36%) TTNtv-positive patients presented with incidentally detected asymptomatic left ventricular systolic dysfunction (n=9) or as a result of genetic cascade screening (n=3). In comparison to TTNtv-positive patients with non-HF presentations, those with HF had worse left ventricular function (mean LVEF: 26% ± 11% vs 51% ±12%; p<0.001) and were more likely to have ≥1 risk factor [11/17 (65%) vs 4/16 (25%); p=0.04]. Unexpectedly, the 7 TTNtv-positive patients that presented with (n=4) or subsequently developed (n=3) sustained VAs were younger at the time of presentation (34±13 years vs 48±15 years; p=0.04) and displayed a similar degree of left ventricular dysfunction to those without sustained VAs (mean LVEF: 42% ± 17% vs 36% ± 17%; p=ns). Interestingly, the only risk factor over-represented amongst those with sustained VAs was bileaflet mitral valve prolapse [3/7 (43%) vs 0/26 (0%); p=0.006].

Conclusion

The majority of TTNtv-positive patients (14/23; 61%) with a history of HF and/or sustained VAs possessed ≥1 acquired risk factor providing further evidence that gene-environment interaction(s) exert a crucial role in the manifestation of TTN-mediated disease.

Funding Acknowledgement

Type of funding source: None
Novel risk factor for fatal arrhythmia in Brugada syndrome
Authors: Nishinarita R , Niwano S , Ishizue N , Satoh T , Matsuura G , Arakawa Y , Kobayashi S , Shirakawa Y , Horiguchi A , Nakamura H , Oikawa J , Kishihara J , Fukaya H , Niwano H , Ako J
Published: November 2020

Background

Brugada syndrome (BrS) is a genetic disease associated with increased risk of ventricular fibrillation (VF)/ventricular tachycardia (VT). The VF/VT in BrS occurs more frequently during a night time or at a rest with parasympathetic nerve activation. Some risk factors of VF/VT occurrence in BrS have been elucidated, however, it remains controversial about risk stratification. Salusin-β is an endogenous bioactive peptide that systemically exerts rapid and profound hypotensive and bradycardic activities and parasympathomimetic hemodynamic actions in vivo. Previous reports suggested that salusin-β is suppressed following physiological parasympathetic stimulation and appears to constitute a negative feedback relationship with the parasympathetic nervous system.

Purpose

We hypothesized that salusin-β is associated with the occurrence of VF/VT in BrS.

Methods

The study population consisted of 26 BrS patients with newly implantation of implantable cardioverter defibrillator (ICD) during 2003–2008. In all patients, salusin-β was measured in supine position after 20 minute rest. The date of salusin-β sampling was set as the registration point for this study. The VF/VT was defined as any episode of fatal ventricular tachyarrhythmia or any appropriate shock. In accordance with the presence or absence of VF/VT events within 5 years, all patients were divided into VF/VT group (n=6) and non-VF/VT group (n=20).Various clinical parameters were compared between the two groups. For analysis of autonomic nervous function, heart rate variability (HRV) and pupil function were evaluated.

Results

The mean age was 54±17 years old. There is no differences between the two groups in clinical parameters. In analysis of HRV, the high-frequency component (0.15–0.40 Hz; HF), low frequency component (0.04–0.15 Hz; LF) and the LF/HF ratio were analyzed over 24 h. LF/HF ratio was significantly lower over 24h in VF/VT groups in comparison with non-VF/VT groups [day-time; 1.8 (1.2–5.6) vs. 5.2 (3.4–8.8), p=0.048, night-time; 1.2 (1.1–1.3) vs. 3.9 (2.5–8.7), p=0.003]. Furthermore, in analysis of pupil function, right/left miosis ratio was higher in VT/VF groups in comparison with non-VT/VF groups [right pupil; 0.39 (0.37–0.59) vs. 0.34 (0.28–0.38), p=0.035, left pupil; 0.43 (0.36–0.50) vs. 0.33 (0.28–0.40), p=0.049]. In plasma total salusin-β levels, the VF/VT groups exhibited significantly lower than non-VF/VT groups (55.2±14.6 vs. 73.2±22.2, p=0.039, Figure).

Conclusions

Salusin-β was associated with the occurrence of VF/VT in Brugada syndrome. Salusin-β might be useful to identify high-risk patients for the occurrence of VT/VF events in Brugada syndrome.

Funding Acknowledgement

Type of funding source: None
Two novel variants in the SLC4A3 gene in two families with Short QT Syndrome: the role of cascade screening
Authors: Kovacs B , Graf U , Magyar I , Baehr L , Maspoli A , Duru F , Berger W , Saguner A.M
Published: November 2020

Background

Short QT syndrome (SQTS) is a rare, autosomal dominant disease causing sudden cardiac death (SCD). Genetic testing is recommended according to current guidelines. Variants in KCNQ1, KCNH2, KCNJ2 and SLC4A3 genes have been reported in SQTS.

Purpose

We report implications of genetic testing and cascade screening (CS) in two families with phenotypical presentation of SQTS and novel genetic variants of unknown significance.

Methods

We performed a thorough clinical and electrophysiological work-up of the index patients of both families. In addition, genetic screening was conducted. Subsequently, segregation analysis of potentially pathogenic variants was carried out in available relatives.

Results

Index patient 1 presented with a history of recurrent syncope. His ECG showed a shortened QTc of 340ms. Family history was unremarkable. Structural heart disease was excluded by cardiac MRI and coronary angiography. Genetic testing detected a rare heterozygous missense variant in the KCNH2 gene (p.(Arg328Cys), frequency 0.053%), predicted to be pathogenic according to various prediction algorithms (Polyphen, SIFT, Align GVGD, mutation taster). CS of relatives did not confirm this variant as the causative mutation. Reanalysis of whole-exome sequencing data revealed a novel heterozygous missense variant, p.(Arg370Cys) in the recently identified SLC4A3 gene. A variant at the same position has previously been associated with SQTS. CS suggested disease association. The second index patient had a SCD at the age of 17. A previously registered ECG showed a shortened QTc of 340ms. Autopsy revealed no structural heart disease. Post-mortem genetic testing revealed variants in the LDB3, MYH7 and a novel heterozygous missense variant, p.(Ser1039Arg) also in the SLC4A3 gene. Family history was positive for SCD in three 2° relatives. The index patient's father had a positive phenotype with a QTc of 365ms. CS again suggested disease association of the variant in the SLC4A3 gene only.

Conclusion

Genetic testing revealed two novel variants in the SLC4A3 gene, which was recently implicated in the pathogenesis of the SQTS. Predictive bioinformatic algorithms to assess the pathogenicity of missense variants are of limited relevance, but genetic analysis of additional unaffected and affected family members may be instrumental to identify pathogenic DNA sequence variations.

Family tree index patients 1 and 2

Funding Acknowledgement

Type of funding source: None
Mutation site-specific risk profile in patients with Type 1 Long QT Syndrome
Authors: Trancuccio A , Mazzanti A , Kukavica D , Marino M , Monteforte N , Bloise R , Braghieri L , Memmi M , Morini M , Napolitano C , Priori S.G
Published: November 2020

Background

Type 1 Long QT Syndrome (LQT1) is an arrhythmogenic disorder, caused by loss-of-function mutations on KCNQ1 gene, coding for Kv7.1 potassium channel. Although LQT1 is described as the most benign form of LQTS, patients still experience arrhythmic events and there is an unmet need for personalized risk stratification. Attempts have been made to correlate the location of mutations with outcome, but the results are unequivocal.

Purpose

We provide in the present study a new mutation site-specific risk profile obtained from a large cohort of LQT1 patients.

Methods

We gathered data on 963 patients with the diagnosis of LQT1 and divided the Kv7.1 channel into 5 functional regions: the N-terminus (NT), the voltage sensor (VS, including transmembrane segments S1 to S4), the cytoplasmic loops (CL), the pore (PO, including the transmembrane segments S5, S6 and the S5-S6 extracellular linker), the C-terminus (CT).

Results

We studied 963 LQT1 patients: 518 (54%) females; average age 20±17 years; mean QTc at baseline ECG 465±38ms. During a mean follow-up of 8±7 years, 172 (18%) patients experienced arrhythmic events: 31 (3%) experienced one or more cardiac arrests, while 141 (15%) experienced one or more syncopal spells. We identified 188 different variants in the KCNQ1 gene, with the following distribution: 15 (8%) in the NT, 33 (18%) in the VS, 27 (14%) in the CL, 43 (23%) in the PO, 70 (37%) in the CT. The frequency of pathogenic variants per number of amino acids (a.a.) was higher in the CL region, as compared to the other domains (1 mutation every 1.4 a.a.). The duration of QTc interval was significantly longer for patients with mutations in the PO region (473±40 ms) and in the CL region (468±38 ms) as compared to the other regions (p<0.01).

Importantly, in a multivariate analysis PO and CL regions were associated with a higher probability of experiencing arrhythmic events (OR 2.89, 95% CI 1.95–4.29, p=0.019 and OR 1.61, 95% CI 1.0–2.49, p=0.05, respectively. Figure) than the other regions. Interestingly, the risk was independent from QTc interval duration.

Conclusions

Mutations affecting the PO and the CL region of the Kv7.1. channel are associated with a higher probability of experiencing arrhythmic events. This finding is clinically relevant, because it will allow for a more personalized, mutation site-specific risk stratification.

Mutation site and arrhythmic events

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Research and University Dipartimenti di Eccellenza 2018–2022 grant to the Molecular Medicine Department (University of Pavia)
Sex-specific differences in risk stratification of ventricular arrhythmias among implantable cardioverter defibrillator patients: do women differ from men?
Authors: Van Der Lingen A.C.J , Theuns D.A.M.J , Becker M.A.J , Van Rossum A.C , Van Halm V.P , Kemme M.J.B , Rijnierse M.T , Yap S.C , Allaart C.P
Published: November 2020

Background

Implantable cardioverter defibrillator (ICD) guidelines and risk stratification models of sudden cardiac death (SCD) are applied without differentiation between men and women, based on the assumption that the incidence of ventricular arrhythmias and risk factors of SCD are similar in both sexes. Sex-specific risk factors of SCD may influence studies evaluating the benefit of ICD therapy, for both men and women.

Purpose

Aim of the study is to assess sex-specific differences in occurrence and predictors of appropriate device therapy (ADT) for ventricular arrhythmias.

Methods

A multicenter retrospective cohort of 2300 consecutive patients was evaluated, including patients referred for ICD implantation between the years 2009–2018 (age 62±13 years, LVEF 32±12%, 53% ischemic cardiomyopathy [CMP], 28% resynchronization therapy, 65% primary prevention). Exclusion criteria were: (1) patients with hypertrophic CMP, arrhythmogenic right ventricular CMP, systemic infiltrative cardiac disease or channelopathy; (2) lost to follow-up immediately after ICD implantation. Primary endpoint was ADT, defined as anti-tachycardia pacing or shock for ventricular tachyarrhythmia. Secondary endpoints were mortality and inappropriate ICD therapy. Univariable and multivariable Cox regression analyses, stratified by sex, were performed to assess predictors of ADT.

Results

The cohort primarily consisted of men (75%). After a mean follow-up of 4.8±3.0 years, men experienced more ADT compared to women (25% versus 16%, HR 1.71, p<0.001) and men displayed a higher mortality compared to women (25% versus 19%, HR 1.37, p<0.01). No difference in inappropriate ICD therapy was observed (9% versus 10%, HR 1.01, p=0.94). In the total study cohort, male sex (HR 1.55, p<0.001), higher age (HR 1.15 per 10 years, p<0.0019), left bundle branch block (LBBB, HR 0.74, p=0.01) and secondary prevention indication (HR 1.89, p<0.001) were independently associated with ADT. In male patients, independent predictors of ADT were comparable with the total study cohort: higher age (HR 1.20 per 10 years, p<0.001), LBBB (HR 0.72, p=0.01) and secondary prevention therapy (HR 1.80, p<0.001). In contrast, age (p=0.54) or LBBB (p=0.29) were not associated with ADT in women. In women, only paroxysmal atrial fibrillation (HR 1.76, p=0.03) and secondary prevention therapy (HR 1.78, p<0.01) were independently associated with ADT.

Conclusion

This study showed that men were at higher risk of ADT compared to women and that risk factors associated with SCD differ between both sexes. The results strongly suggests that SCD risk stratification models are primarily driven by male patients and sex-specific risk models of SCD are needed to identify those women at high risk of SCD.

Figure 1

Funding Acknowledgement

Type of funding source: None
Efficacy of deep sedation for patients with intractable electrical storm refractory to anti-arrhythmic drugs
Authors: Martins R , Urien J.M , Barbarot N , Sellal J.M , Clementy N , Guenancia C , Gandjbakhch E , Duchateau J , Hamon D , Champ-Rigot L , Marijon E , Garcia R , De Chillou C , Sacher F , Galand V
Published: November 2020

Background

Sympathetic overactivity is implicated in the initiation and maintenance of electrical storm (ES). Deep sedation has empirically been considered as an efficient therapeutic option to blunt sympathetic tone and control ES.

Purpose

The aim of this multicenter study was to determine the efficacy of deep sedation in patients presenting intractable ES refractory to anti-arrhythmic drugs.

Methods

Patients requiring deep sedation for refractory ES from January 1st 2007 to July 31st 2018 were retrospectively included in 13 centers. The primary endpoint was the rate of acute response to sedation, defined as ES termination within 15 minutes after deep sedation.

Results

Among the 116 patients, 55 (47.4%) had ES termination within 15 minutes and were considered “acute responders” to deep sedation. Clinical signs of congestive heart failure before deep sedation (OR=3.31, 95% CI:1.001–10.97, p=0.049) was the only independent predictor of non-acute response. Twenty-one non-acute responders (34.4%) had an extracorporeal membrane oxygenation (ECMO) implanted. Non-acute responders had a significantly lower in-hospital survival (Log-rank, p=0.010). ECMO implantation did not influence survival in non-acute responders to sedation. Acute response to deep sedation was an independent protector of in-hospital mortality, decreasing by 73% the risk of death (OR 0.27; 95% CI:0.10–0.70, p=0.008).

Conclusion

To the best of our knowledge, this multicenter study is the first analysis of the efficacy of deep sedation in patients with intractable ES refractory to anti-arrhythmic drugs, and demonstrating the positive impact of “acute response” on in-hospital survival.

Funding Acknowledgement

Type of funding source: None
Impact of an adaptive CRT optimization algorithm on the risk of life-threatening ventricular arrythmias of heart failure patients
Authors: Briongos Figuero S , Estevez A , Perez M.L , Martinez-Ferrer J.B , Alvarez L , Anguera I , Garcia E , Perez-Lorente F , Porres M , Villacastin J , Munoz-Aguilera R
Published: November 2020

Introduction

Adaptive cardiac resynchronization therapy (aCRT) algorithm provides ambulatory CRT optimization and synchronized left-ventricular pacing instead of conventional biventricular pacing.

Purpose

To analyze the impact of aCRT on the risk of life-threatening ventricular arrythmia (VA) in patients with concomitant defibrillator therapy.

Methods

Symptomatic HF patients, in sinus rhythm, with LVEF ≤35% and QRS complex ≥130 ms undergoing first CRT-defibrillator (CRT-D) implant were collected from the multicentre, prospective and nationwide UMBRELLA study (2012–2017). All device information was automatically stored and collected through the remote monitoring system. An experts committee analysed in a blinded manner all electrograms. The endpoint was first appropriate therapy (AT) delivered within ventricular fibrillation zone at 12-months follow-up.

Results

206 patients were collected (66.1±8.7 years; 73.3% male). Fifty nine patients composed the aCRT group and 147 composed the non-aCRT group. At implant, LBBB was present in 93% of patients, functional class III or IV in 69.9%, non-ischemic HF in 63.1% of patients and mean LVEF was 26.5±5.6%. Optimal medical treatment was achieved in a majority (B-blockers in 92%; RAASi in 89% and MRA in 72.2%).

The percentage of ventricular pacing through 12 months was 96.1±9.4% in non-aCRT patients and 97.5±2.7% in aCRT patients (p=0.261). At 1-year of follow-up, 16 patients were delivered an AT (event rate: 7.8%). Most of these episodes (n=14) were due to sustained monomorphic ventricular tachycardia while the rest were caused by sustained polymorphic ventricular tachycardia/VF. A lower incidence of AT was observed in aCRT patients (3.4%) compared to non-aCRT patients (9.5%) but with no statistical differences (OR=0.33, CI 0.07–1.51, p=0.155).

Conclusions

In patients undergoing CRT provided by aCRT algorithm the risk of malign VA after 1-year of follow-up was low. Randomized studies are needed to clarify the impact of this dynamic algorithm on the arrhythmic risk of HF patients.

Funding Acknowledgement

Type of funding source: None
Non-selective para-hisian stimulation used for QRS normalization guided by non-invasive electrical synchrony method in patients with electrical conduction disorders
Authors: Logarzo E , Ortega D , Barja L , Paolucci A , Revollo G , Aboy J , Mangani N
Published: November 2020

Introduction

Para-hisian stimulation produces a physiological cardiac activation through normal conduction system. Frequently it is used in patients with no electrical conduction disorders. We developed an implant technique guided by non-invasive electrical synchrony using conventional screw-in leads. Non-selective para-hisian stimulation can normalize electrical conduction disorders. Synchromax is a novel device used to evaluate non-invasive cardiac electrical synchrony. It is easy to understand, fast to obtain, non-invasive and reproducible. Synchromax was analyzed in previous studies and correlated with other methods.

Objective

Evaluate usefulness and safety of non-selective para-hisian stimulation guided by non-invasive cardiac electrical synchrony method using conventional screw-in leads to normalize electrical conduction disorders.

Materials and methods

421 patients with para-hisian stimulation were analyzed retrospectively. 139 patients had different intraventricular and auriculo-ventricular electrical disorders. Non-selective para-hisian stimulation guided by no-invasive electrical synchrony method (Synchromax) was performed in all cases. Synchrony index and curves were analyzed according curves chart. Type 2 curve and index between 0,1 and 0,4 were considered synchronous. Type 8 curve and index more than 0.7 were considered dyssynchronous.

Results

Mean age 71 years (±7 years). 65,4% males. 30,9% had 2° and 3° grade AV block associated. Patients were divided in 5 groups:

1-Right bundle branch block (RBBB): 43 patients

2-Left bundle branch block (LBBB): 33 patients

3-Brugada Syndrome: 8 patients

4-Left anterior hemi-block (LAHB) 30 patients.

5-RBBB associated with LAHB: 25 patients.

QRS normalization was achieved in 87% of the cases using non-selective para-hisian stimulation guided by Synchromax with conventional screw in leads. A ventricular approach was performed during implantation. Electrical synchrony was not solved in 13% of patients mostly in LBBB and RBBB associated with LAHB. Two dislodgments were evidenced.

Conclusions

Non-selective para-hisian stimulation guided by Synchromax method using conventional screw in leads solved most of intraventricular electrical disorders. It is also safe to use in patients with auriculo-ventricular electrical disorder.

Funding Acknowledgement

Type of funding source: None
Long-term follow-up of patients with tetralogy of Fallot and implantable cardioverter defibrillator
Authors: Waldmann V , Bouzeman A , Duthoit G , Koutbi R , Bessiere F , Labombarda F , Marquie C , Gourraud J.B , Ladouceur M , Mondoly P , Sacher F , Iserin L , Thambo J.B , Combes N , Marijon E
Published: November 2020

Background

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce.

Purpose

We aimed to describe long-term follow-up of patients with TOF and ICD through a large nationwide registry.

Methods

Nationwide Registry including all TOF patients with an ICD initiated in 2010. The primary outcome was the first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee. Cox proportional hazard models were used to identify predictors of appropriate ICD therapies and ICD-related complications.

Results

A total of 165 patients (mean age 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (IQR) follow-up of 6.8 (2.5–11.4) years, 78 (47.3%) patients received at least one appropriate ICD therapy, giving an annual incidence of 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively, p=0.03). Overall, 71 (43.0%) patients presented with at least one complication, including inappropriate ICD shocks in 42 (25.5%) patients and lead/generator dysfunction in 36 (21.8%) patients. Among 61 (37.0%) primary prevention patients, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with respectively no, one, two, or ≥ three guideline-recommended risk factors. In our cohort, QRS fragmentation was the only independent predictor of appropriate ICD therapies (HR 4.34, 95% CI 1.42–13.23), and its integration in a model with current criteria increased the area under the curve from 0.61 to 0.72 (p=0.006). No patient with left ventricular ejection fraction (LVEF) ≤35% without at least one other risk factor had appropriate ICD therapy. Patients with congestive heart failure and/or reduced LVEF had a higher risk of non-sudden death or heart transplantation (HR=11.01, 95% CI: 2.96–40.95).

Conclusions

Our findings demonstrate high rates of appropriate therapies in TOF patients with an ICD, including in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria might improve risk stratification beyond low LVEF.

Freedom from appropriate ICD therapy

Funding Acknowledgement

Type of funding source: None
Optimal programming of cardiac resynchronisation therapy with His bundle pacing based on aortic velocity time integral in patients with congestive heart failure and permanent atrial fibrillation
Authors: Boczar K , Zabek A , Slawuta A , Debski M , Gajek J , Lelakowski J , Malecka B
Published: November 2020

Background

Cardiac resynchronisation therapy (CRT) in patients with permanent atrial fibrillation (AF) is usually less effective than in sinus rhythm patients. Recent evidence has shown that His bundle pacing (HBP) might be a valuable alternative to conventional pacing systems resulting in more physiologic electrical activation of the heart. Currently, there is a need to identify the optimal way of CRT + HBP programming in patients with congestive heart failure (CHF) and permanent AF to achieve high cardiac output and improve physical capacity and survival.

Purpose

The aim of this study was to evaluate the impact of CRT + HBP programming on cardiac output in the early post-operative measurements.

Methods

We included consecutive patients with: 1. permanent AF, 2. CHF in NYHA class III-IV, 3. bundle branch block with QRS >130 ms or QRS <130 ms and high expected requirement of ventricular pacing, 4. severely reduced left ventricular ejection fraction (LVEF) ≤35%, 5. CHF refractory to optimal medical therapy, 6. implanted CRT + HBP. All patients gave informed consent for CRT + HBP implantation and optimization of device programming.

During the early post-operative phase, we aimed to optimize CRT + HBP settings in order to achieve the highest cardiac output assessed by repeated echocardiographic measurements of aortic velocity time integral at various pacing programs (Table 1). Then, we selected the optimal pacing settings of CRT + HBP for each individual patient.

Results

Study included 17 consecutive patients aged 71.5±6.3 years, 12 were male. Mean LVEF was 24% and median NYHA class was III. The most efficacious method of pacing in terms of aortic VTI was HBP combined with left ventricular pacing (LV) which resulted in median VTI of 22.5. HBP + LV was superior to right ventricular pacing (RV): VTI of 22.5 vs 18.5, P=0.003 and outperformed biventricular pacing: VTI 22.5 vs 18.7, P=0.019. Detailed results are shown in Figure 1.

Conclusion

His bundle pacing coupled with LV pacing proved to be the most advantageous pacing program setting with regard to cardiac output and it performed significantly better than RV pacing only or biventricular pacing. Our observation supports the use of His bundle pacing in CRT systems in patients with CHF and permanent AF.

Figure 1

Funding Acknowledgement

Type of funding source: None