bluuebunny/crossref_metadata_2025 huggingface dataset:
Worsening renal function as an outcome predictor in patients with new onset atrial fibrillation on direct oral anticoagulant
Authors: Bartoli L , Angeli F , Stefanizzi A , Armillotta M , Sansonetti A , Magnani I , Fabrizio M , Paolisso P , Foa' A , Rinaldi A , Galie' N , Pizzi C
Published: October 2021

Background

In patients with atrial fibrillation (AF), baseline kidney function is used to guide oral anticoagulant (OA) selection and dosing, and chronic kidney disease (CKD) is a significant outcome predictor. However, the incidence of worsening renal function (WRF) and its prognostic role during treatment with direct oral anticoagulants (DOACS) has been poorly explored.

Purpose

To assess the prognostic role of WRF in terms of bleedings and major adverse cardiovascular events (MACEs) in a cohort of patients with newly diagnosed non-valvular AF (NVAF) treated with DOACs.

Methods

Between January 2017 and March 2019, we enrolled all the patients with newly diagnosed NVAF and OA indication, treated with DOACs. Renal function was assessed using the mean value of the estimated glomerular filtration rates (eGFR) calculated using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. CHA2DS2-VASc and HAS-BLED scores were used at baseline to estimate the ischemic and hemorrhagic risk, respectively. At follow-up, WRF was identified as a decrease in eGFR of at least 20% while bleedings were classified according to the international society of thrombosis and hemostasis (ISTH) criteria. Finally, we defined AF progression as the transition from paroxysmal to persistent or permanent AF or from persistent to permanent AF.

Results

1009 patients with newly diagnosed NVAF started on DOAC were enrolled. They were followed-up for 21.6±9.5 months. Overall, WRF was observed in 181 cases (18%). Patients with WRF had higher rates of progression of atrial fibrillation (18.5% vs 11.8%, p=0.02), MACEs (20.4% vs 12.9%, p=0.09) and major bleedings (MB) (9,4% vs 4,7%, p=0.013). WRF did not correlate with all bleedings, stroke, or acute coronary syndrome (ACS). However, those who presented WRF using CKD-EPI formula had higher ACS incidence (6.1% vs 2.5%, p=0.015), and generally better-predicted MACEs. At multivariate analysis adjusted for age, hypertension, baseline HAS-BLED score and WRF, the latter emerged as an independent predictor of MB (OR 1.9 95% C.I, 1,059–3,51).

Conclusion

In patients with newly diagnosed NVAF treated with DOACs, WRF is associated with atrial fibrillation progression and MACEs, and emerged as an independent predictor of major bleedings. WRF evaluated with CKD-EPI formula better predicted MACEs.

Funding Acknowledgement

Type of funding sources: None.
Lifetime prevalence of syncope: the HELIUS study
Authors: Brewster L , Van Den Born B.-J , Wieling W , Van Montfrans G
Published: October 2021

Background

Syncope is a common presentation to emergency departments. Cardiovascular risk differs markedly among ancestry groups, but data on syncope are scarce. Fundamental understanding of the determinants of syncope in the population might aid in the risk stratification of syncope in acute settings.

Purpose

To assess lifetime prevalence of syncope and its determinants in the general population.

Methods

We included 14937 adults (18–70 y) randomly sampled in the cross-sectional Healthy Life in an Urban Setting (HELIUS) population study, stratified by White-European, Asian, Turkish, Moroccan, and West-African ancestry. We assessed syncope history, body mass index (BMI), blood pressure (BP), supine stroke volume (SV), cardiac contractility (dP/dt), cardiac output (CO), systemic vascular resistance (SVR), and resting plasma activity of CK, an ATP-generating enzyme that facilitates cardiovascular contractility and sodium retention, counteracting hypotensive susceptibility.

Results

Mean age of the participants (39% men) was 43.3 y (SD 12.9). Lifetime prevalence of syncope was significantly higher in women (31%) vs. men (18%); and in White-European (34%) and other ancestries (25 to 28%), vs. West-African ancestry (19%) (Figure 1). Mean age at first syncope was 24 y (SD 13). Participants without syncope history had higher BP (systolic, +29% SD), BMI (+17% SD), CK (+31% SD) (Figure 1), modestly higher SV, dP/dt, and CO (+6 to 8% SD), and more diabetes (5.2 vs 3.6%). The main protective predictors of syncope were West-African ancestry (0.59 [0.54 to 0.65]), male sex (0.52 [0.48 to 0.57]), and CK (0.56 [0.46 to 0.69]/log CK increase), with high CK in men and West-African ancestry largely explaining the low syncope prevalence in these groups.

Conclusion

To our knowledge the first population study on syncope by ancestry indicates that the lifetime prevalence is high in White-European women, and low in person of African ancestry. The inverse association of syncope with the pressor enzyme CK needs further study.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Syncope by Sex, Ancestry, and CK
Are there sex differences in patients with syncope and bundle branch block?
Authors: Francisco Pascual J , Rivas Gandara N , Badia Molins C , Maymi Ballesteros M , Perez Rodon J , Benito B , Santos Ortega A , Roca Luque I , Bach Oller M , Cantalapiedra Romero J , Maldonado J , Oristrell Santamaria G , Sambola Ayala A , Moya Mitjans A , Ferreira Gonzalez I
Published: October 2021

Background

In the last years a substantial effort has been made to improve the understanding of the sex-differences in cardiovascular disease. However, no studies have examined differences in presentation and outcomes between men and women presenting with syncope and bundle branch block (BBB).

Aim

To determinate if there are sex-specific differences in the characteristics and outcomes of syncope in patients with BBB

Methods

Cohort study carried out in a tertiary hospital that is a reference center for syncope from January 2008 to February 2021. Patients (p.) with BBB and syncope of unknown origin after the initial evaluation without direct indication of an ICD were included. They were managed according to the current ESC guidelines. All patients underwent to an EPS and an ILR was implanted if it was not diagnostic.

Results

374p. were included (75±1 y. o; 135 (36%) female). Mean follow up was 2.3±1.6 y.o. No differences in baseline characteristics where found comparing both groups, except that LBBB was more prevalent in female and RBBB in male (Figure 1A). EPS and ILR diagnostic yield was 44%/44% respectively in females and 50% /40% in males (p=ns). However, basal HV interval in EPS was significant shorter in females (Figure 2A). In the multivariate analyses female sex was associated with a significant lower risk of AV block (Figure 1B), and with a trend of less need of a pacemaker implantation (PM) (53% in females, 60% in males) (Log-rank 0.1) (Figure 2B). No significant differences in recurrences neither in mortality rate were found.

Conclusions

Female patients with syncope and BBB have lower risk of AV block compared to males, and only half of them required a pacemaker implantation. A strategy of direct PM implantation should be avoided, specially in woman.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Utility of telemetry in syncope admissions
Authors: Saha T , Bagel P , Toole J , Coplan N
Published: October 2021

Introduction

Syncope is a major cause of emergency room visits and admission to telemetry units however, prior studies have shown conflicting evidence for the necessity for a telemetry admission. Our current 2017 ACC/AHA/HRS guidelines recommend telemetry admissions for syncope evaluation when cardiac etiology is suspected.

Purpose

The purpose of this study is to investigate whether there are any differences in telemetry events in patients with a cardiac syncope versus non-cardiac/unspecified and to determine any correlation between the number of cardiac risk factors in patients with cardiac syncope versus non-cardiac etiology to predict those who would benefit most from telemetry.

Methods

Our retrospective study included 574 patients admitted to the cardiac telemetry unit between February 2017 and February 2020 at our metropolitan tertiary care centre, further grouped into: cardiac, non-cardiac, or unspecified syncope. Cardiac syncope included aetiologies such as arrhythmias, pulmonary hypertension, Long QTc, device malfunction etc. The non-cardiac syncope group included aetiologies such as orthostatic and reflex mediated. Thirteen cardiac risk factors were summed from the 2009 ESC syncope guidelines. These included HFrEF, elevated BNP, anemia, abnormal ECG, family history of sudden cardiac death or MI, age above 65, male gender, structural heart disease, abnormal vitals on presentation, history of sudden cardiac death, no prodrome prior to syncope and chest pain.

Results

Of the 574 patients, 102 patients (17.7%) had a cardiac etiology, 405 patients (70.5%) had a non-cardiac etiology and 67 patients (11.6%) had unspecified etiology for syncope. Overall, 47% of the cardiac group, 16% of the non-cardiac group, and 12% of the unspecified group had telemetry events. There was a statistically significant difference in the number of patients with telemetry events among the three syncope groups, p<0.0001. The odds of patients with cardiac syncope having telemetry events were 4.0 times greater than those with non-cardiac syncope and 6.3 time higher than those with unspecified syncope.

The average number of risk factors were: 4 (±1.7) (cardiac), 3±1.6 (non-cardiac), and 3±1.7 (unspecified). Linear regression model showed the number of risk factors to be 19% and 15% lower in the non-cardiac and unspecified groups compared to the cardiac group. There was no association between any of the individual risk factors and the presence of telemetry event.

Conclusions

Our study demonstrates that those with cardiac syncope tend to have more cardiac risk factors and more telemetry events relative to their non-cardiac syncope counterparts. While patients with cardiac risk factors have on average a higher cardiac risk factor profile, it is not clinically significant enough to determine who would benefit from telemetry versus who would not.

Funding Acknowledgement

Type of funding sources: None.
Lifelong and mature-onset syncope in older adults may have different mechanisms
Authors: Torabi P , Rivasi G , Hamrefors V , Sutton R , Brignole M , Fedorowski A
Published: October 2021

Background

Syncope is a common clinical problem with a sharp rise in the incidence after 70 years. In older patients, syncope is often a diagnostic challenge. It is unclear whether the age at which patients experience syncope for the first time impacts the results of syncope investigation.

Purpose

To study the influence of early-onset vs. mature-onset syncope on clinical characteristics and final head-up tilt (HUT) diagnosis in a large sample of unexplained syncope patients.

Methods

Consecutive patients (n=1928) with unexplained syncope after initial evaluation examined with a standard HUT protocol in a syncope unit were stratified into age groups below and above 60 years. Clinical characteristics and the final HUT diagnosis were analysed in relation to self-reported age at first syncope and age at investigation. The distribution of age at first syncope was bimodal with peaks at 15 and 70 years (Figure 1). In the present analysis, patients aged >60 years (n=836) with early-onset (<30 years) and mature-onset (>60 years) syncope were compared.

Results

Vasovagal syncope (VVS) was more common in early-onset syncope, 39% vs 19% (p<0.001), (Figure 2). Orthostatic hypotension (OH) was more common in mature-onset syncope, 23% vs 7% (p<0.001), as was hypertension, 59% vs 40% (p=0.001). The frequency of carotid sinus syndrome (CSS) was not affected by age at first syncope in patients aged >60 years.Complex syncope etiology (findings suggesting overlap between VVS, OH and/or CSS) was more common among patients with early-onset syncope, 37% vs 26% (p=0.023). No definite HUT-derived diagnosis was more common in mature-onset syncope, 23% vs 13% (p=0.023). Heart failure, 9% vs 2% (p=0.024) and atrial fibrillation, 20% vs 9% (p=0.013) were more common in mature-onset syncope. Prodromes were less common in mature-onset syncope, 26% vs 52% (p<0.001), however there was no significant difference in reported palpitations preceding syncope and dizziness on standing.

Conclusions

Mature-onset syncope was more often associated with absence of prodromes, orthostatic hypotension, inconclusive HUT findings and presence of heart failure and atrial fibrillation suggesting cardiac syncope to be the likely cause. Early-onset syncope was associated with presence of prodromes, vasovagal reflex mechanism and complex syncope diagnosis. Lifelong and mature-onset unexplained syncope may have different pathophysiological mechanisms in older patients and aetiologies other than vasovagal syncope should be carefully considered in patients with first-ever syncope in later life.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish heart and lung foundationCrafoord foundation
Prognostic impact of percentage of ventricular pacing in patients requiring pacemaker implantation after transcatheter aortic valve replacement
Authors: Dias Ferreira Reis J.P , Mendonca T , Castelo A , Rodrigues I , Fiarresga A , Ramos R , Cacela D , Oliveira M , Cruz Ferreira R
Published: October 2021

Background

Despite the continuous developments of transcatheter aortic valve implantation (TAVI), around 15% of the patients (P) who undergo this procedure require permanent pacemaker (PM). Right ventricular pacing (RVP), particularly with a cumulative percentage of ventricular pacing (CVp) above 40%, has been associated with detrimental effects on ventricular function and an increased risk of cardiovascular events in non-TAVI patients.

Aim

To evaluate the long-term prognostic significance of RVP, regarding overall mortality and the combined endpoint of overall mortality/heart failure hospitalization in P requiring a PM after TAVI.

Methods

We retrospectively examined P who underwent TAVI with a self-expanding valve from 2009 to 2020 at our institution. All P had pre-procedural clinical evaluation, cardiac computed tomographic angiography, transthoracic echocardiography and electrocardiography performed. CVp was determined from stored PM data. P with previous PM were excluded. Post-TAVI PM implantation was defined as a device implantation during hospital stay or during the first month after discharge.

Results

474P, 57% male, mean age 81.7±6.5 years with a mean left ventricular ejection fraction of 51.5±14.6% were analysed. Mean follow-up was 18.7 months. Mean STS score and mean Euroscore II were, respectively, 6.89% and 5.76%. Mean gradient was 51.67 mmHg and mean aortic valve area 0.71 cm2. After TAVI, 104P (21.9%) required PM implantation, with a mean CVp of 65.3±43.4%. Post-TAVI PM was not associated with a worse outcome - overall mortality: HR 1.13, 95% CI 0.72 – 1.78, p=0.57; combined mortality/heart failure hospitalization: HR 1.22, 95% CI 0.87 – 1.70, p=0.24. The follow-up Kaplan-Meier curves according to the need for PM post-TAVI were similar: log rank p=0.24. A CVp cut-off of 40% was not associated with any of the study endpoints - overall mortality: HR 1.72, 95% CI 0.38–7.86, p=0.48; combined mortality/heart failure hospitalization: HR 1.32, 95% CI 0.45–3.91, p=0.61. Also, a CVp cut-off of 40% did not provide an accurate risk stratification as survival free of events was similar between these P and those below this cut-off (log rank p=0.11) and in comparison, with P without PM (log rank p=0.65).

Conclusions

In P submitted to TAVI with a self-expanding valve, the need for PM implantation is common, but not associated with increased risk of total mortality or heart failure hospitalization during a 18 months follow-up period. A CVp cut-off of 40% showed poor discriminative ability regarding long-term events in this population.

Funding Acknowledgement

Type of funding sources: None.
Temporary prolongation of corrected QT interval after cardioneuroablation for functional bradyarrhythmias
Authors: Wichterle D , Jansova H , Stiavnicky P , Stojadinovic P , Peichl P , Cihak R , Kautzner J
Published: October 2021

Background

There are controversial reports on QT interval response to ganglionic plexi ablation that are selectively targeted during cardioneuroablation (CNA) or occurs as collateral lesion during left atrial ablation procedures. Both shortening or prolongation of the heart-rate corrected QT interval (QTc) with therapeutic or safety implications were described.

Purpose

In this retrospective study, we investigated longitudinal changes of QTc after CNA.

Methods

The study included 108 patients (age: 39±12 years, 60% males) who underwent biatrial cardioneuroablation (radiofrequency time: 15.5±6.7 min) for symptomatic functional bradyarrhythmias. Surface ECG examinations were performed on the day before the CNA (N=108), 1 hour after the CNA (N=106), on the 1st post-ablation day (N=50), at the 3-month (N=99), and 1-year (N=63) follow-up visits. Automated measurements of QT interval were employed for the analysis. Four formulas (Bazett, Framingham, Fridericia, and Hodges) were used for the correction of QT interval to instant heart rate.

Results

QTc significantly prolonged immediately after the CNA with rapid return to baseline values (Figure and Table). This was particularly valid for QT correction by Framingham formula (and similarly for Fridericia and Hodges formulas). The QTc by Bazett formula, which is known to overestimate QT at higher heart rates, returned to baseline more slowly and incompletely. Several mechanisms may contribute to observed QTc dynamics: (1) direct effect of autonomic denervation with recovery phenomenon; (2) QT hysteresis with an extremely long time constant; or (3) artifact due to suboptimum QT correction to a substantial change of heart rate.

Conclusions

The study suggests that CNA produces acute prolongation of QTc interval with rapid decay and virtual normalization in 3 months. CNA in otherwise healthy subjects is not likely associated with substantial long-term risk of long-QT-associated arrhythmias. In the same way, we cannot confirm earlier observations of clinically significant QTc shortening effect of ganglionated plexi ablation.

Funding Acknowledgement

Type of funding sources: None. Figure 1Table 1
Repolarization heterogeneity within the myocardial infarction border zone correlates with variability of myocyte remodeling
Authors: Vermoortele D , Amoni M , Ingelaere S , Holemans P , Willems R , Sipido K , Claus P
Published: October 2021

Background

Myocardial infarction (MI) results in a regional scar, with a border zone (BZ) of surviving myocytes interspersed with fibrosis providing an anatomical substrate for re-entry. Heterogeneous repolarization within the BZ may add a functional component aggravating re-entrant arrhythmias.

Purpose

We studied BZ heterogeneity and developed novel methodology for high resolution mapping of local in vivo activation-repolarization intervals (ARI) within the BZ and for studying the relation to cellular action potential (AP) profiles of cells isolated from the BZ.

Methods

Anterior-septal myocardial infarction was induced in 5 domestic pigs by 120-minute occlusion of the left anterior descending artery followed by reperfusion (18.9±4.7% of the left ventricle). After 1-month, electro-anatomical mapping was performed. Contact mapping was used to define the BZ (bipolar voltage 0.5–1.5mV). A non-contact recording of a 64-electrode array was translated to 2048 non-contact electrograms distributed over the LV. The non-contact electrograms were processed to determine the ARIs using a custom-made algorithm, validated against monophasic action potential recordings. After 2–4 days recovery, single cardiomyocytes were enzymatically isolated from the anterior-septal BZs and remote regions. Cardiomyocytes were field stimulated at 1Hz at 37°C and cellular AP duration (APD) was optically recorded (fluorescent voltage-sensitive dye Di-8-Annepps).

Results

In vivo, regional ARIs tended to be longer in the BZs than remote. ARI heterogeneity, quantified as the standard deviation of ARIs in a neighborhood of 1cm radius, was increased in the BZ (anterior BZ: 3.4±1.0 ms, P=0.052, septal BZ: 3.6±1.7 ms, P=0.027 vs remote: 2.0±0.5 ms). Cellular APD was measured in large population samples (>100 cells per region in each pig) and was longer in BZ myocytes compared to the remote region. Cellular APD heterogeneity, measured as the standard deviation within cell population samples pooled by region per animal, was increased in the BZ (anterior BZ: 105.9±17.0 ms, P=0.0010; septal BZ: 98.1±20.8 ms, P=0.0127 vs remote: 73.9±8.6 ms). Cell APD correlated to in vivo ARI (R2=0.34, P=0.021) and cellular heterogeneity correlated strongly with in vivo heterogeneity (R2=0.67, P=0.002).

Conclusion

In the BZ of MI, in vivo regional heterogeneity adds a functional substrate for re-entry that may result from heterogeneous cellular remodeling and increased cell-cell APD variability.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): KU Leuven BOF-C1 “Blood pressure induced premature ventricular beats as triggers for ventricular arrhythmia in ischemic cardiomyopathy”
lncRNA CDKN2B-AS1 associated to ventricular fibrillation during acute myocardial infarction
Authors: Pan-Lizcano R , Nunez L , Pinon P , Flores X , Aldama G , Calvino R , Vazquez-Rodriguez J.M , Hermida M
Published: October 2021

Introduction

Sudden death (SD) due to ventricular fibrillation (VF) during acute myocardial infarction (AMI) is one of the leading causes of death in Western societies. However, the pathophysiology of the disease is not well defined. Recently, it has been proposed that non-coding RNA (ncRNA) may play a determinant role in the genesis of different diseases. In fact, alterations in the expression of long non-coding RNAs (lncRNAs) have been associated with different types of arrhythmias and, also, with acute coronary syndrome. However, little is known about the role of lncRNAs in VF in AMI.

Purpose

The aim of this preliminary study is to identify lncRNAs associated to VF in AMI.

Methods

This preliminary study included 24 patients with AMI, 12 with clinically proven VF and 12 without VF. Expression of 10 lncRNAs (CDKN2B-AS1, KCNQ1OT1, MT-LIPCAR, MALAT1, MIAT, NEAT1, SLC16A1-AS1, LNC-TK-2–4, TNFRSF14-AS1, UCA1) and 2 Housekeeping (ACTB and RPLP0) were analyzed using real-time PCR (qPCR). The Fold Change value with a logarithm transformation [log 2 (2–ΔΔCq)] was calculated. The D'Agostino & Pearson and Shapiro-Wilk test and an unpaired t-test were performed in Graphpad-Prism and Qbase programs.

Results

The lncRNA “cyclin-dependent kinase inhibitor 2B antisense noncoding RNA” (CDKN2B-AS1), also named as ANRIL, showed a significantly lower expression in patients that with VF during AMI (2–ΔΔCq (IQ): Control = 1.099 [0.634–1.583] vs FV=0.507 [0.221–1.022], P=0.018). It is important to note that this lncRNA has been previously associated to myocardial infarction and other cardiovascular diseases as atherosclerosis and hypertension.

Conclusions

Our preliminary results suggest that lncRNA CDKN2B-AS1 could be related to the presence of VF during AMI. Most research must be done to clarify the role of lncRNA in the pathophysiology of VF during AMI.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Sociedad Española de Cardiología
A territory-wide study of arrhythmogenic right ventricular cardiomyopathy patients from Hong Kong
Authors: Lakhani I , Zhou J , Zhang Q , Tse G
Published: October 2021

Background

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a hereditary disease characterised by fibrofatty infiltration of the right ventricular myocardium that predisposes affected patients to malignant ventricular arrhythmias, dual-chamber cardiac failure and sudden cardiac death (SCD).

Methods

This was a territory-wide retrospective cohort study of patients diagnosed with ARVC/D between 1997 and 2019. The primary outcome was incident ventricular tachycardia/ventricular fibrillation (VT/VF). The secondary outcomes were new-onset heart failure with reduced ejection fraction (HFrEF) and all-cause mortality.

Results

This study consisted of 115 ARVC/D patients (median age: 60 [44.1–70.2] years; 58% male). Of these, 51 and 24 patients developed incident VT/VF and new-onset HFrEF, respectively. Five patients underwent cardiac transplantation, and 14 died during follow-up. Multivariate Cox regression identified prolonged QRS duration as a predictor of VT/VF (P<0.05). Female gender, prolonged QTc duration, the presence of epsilon waves and T-wave inversion (TWI) in any lead except aVR/V1 predicted new-onset HFrEF (P<0.05). Female gender, prolonged QTc duration and the presence of epsilon waves, in addition to the parameters of older age at diagnosis of ARVC/D, prolonged QRS duration and worsening ejection fraction predicted all-cause mortality (p<0.05). Clinical scores were also developed to predict new-onset HFrEF (Table 1a-c) and all-cause mortality (Table 2a-c). This was followed by the application of a non-parametric machine learning survival analysis models for outcome prediction. These machine learning algorithms better capture nonlinear and interactive patterns within survival data compared to traditionally used Cox regression models, which assume the existence of a hazard function between survival data and censored outcomes. The present study introduced weighted random survival forests models for the prediction of incident VT/VF, HFrEF and all-cause mortality. Findings indicate that these machine learning wRSF models performed the best in the prediction of all three aforementioned outcomes compared to other analytical methods.

Conclusion

Clinical and electrocardiographic parameters are important for assessing prognosis in ARVC/D patients. Machine learning algorithms appear to be the most optimal tools for event prediction, and as such should potentially be used to aid risk stratification and decision-making in the clinical setting.

Funding Acknowledgement

Type of funding sources: None.
Evaluation of electrocardiographic predictors of brugada type response during flecainide challenge
Authors: Shen X , Zhang A.A , Sia C.H , Tan B.Y , Lim P.C.Y , Chua K.C.M , Ho K.L , Lim E.T.S , Ching C.K , Chong D.T.T
Published: October 2021

Background/Introduction

Brugada syndrome (BrS) is a hereditary channelopathy with an increased risk of sudden cardiac death. Most BrS patients manifest non type 1 Brugada pattern electrocardiography (ECG). Sodium channel blockade is a well-established diagnostic tool for Brugada syndrome. However, intravenous sodium channel blockade is not readily available in all parts of the world. In addition, severe ventricular arrhythmias during drug challenge have an estimated prevalence of 1%. Determining the predictors of a positive test would improve our understanding and facilitate appropriate use of these tests.

Purpose

We aimed to identify ECG predictors of Brugada type response during flecainide challenge and provide an independent assessment of current published ECG criteria predictive of a positive flecainide challenge.

Methods

We analysed the clinical and electrocardiographic data of 526 consecutive individuals referred from a national pre-participation exercise screening program who underwent flecainide challenge for an ECG suspicious of Brugada pattern. ECG recordings included both conventional and high precordial leads (1 and 2 space up ECGs in V1 and V2 – 1V1, 1V2, 2V1, 2V2). Twelve-lead ECGs were evaluated for the width of the β angle, β score, baseline J wave elevation, width of QRS, absence of isoelectric segment in lead II, ST/ QT ratio, presence of S wave in Leads II, III and V5 as well as the presence of R wave in aVR.

Results

Flecainide challenge was positive in 121 (23%) of the 526 cases. Baseline QRS duration was greater in the conventional lead placement [V1 (102.4±20.0 ms vs 97.6±14.0 ms, p=0.003), V2 (111.1±33.5 ms vs 100.9±13.1 ms, p=0.001)] as well as 1 space up [1V1 (108.9±21.0 ms vs 100.6±18.2 ms, p<0.001), 1V2 (117.4±26.6 ms vs 103.2±18.3, p<0.001)] and 2 space up [2V1 (113.6±23.4 ms vs 102.5±19.3 ms, p<0.001), 2V2 (121.6±26.1 ms vs 106.8±19.1 ms, p<0.001)] in cases with a subsequent positive response. A QRS duration of ≥120ms in V2 yielded a sensitivity of 16.5%, specificity of 93.8%, positive predictive value of 44.4% and negative predictive value of 79% for a positive flecainide challenge. Other predictors of positivity included that of a shorter ST duration in lead II (107.0±19.9 ms vs 118.1±24.4, p<0.001) and a shorter ST/ QT ratio (0.30±0.09 vs 0.32±0.07, p=0.006).

Conclusion

In this population, a wider QRS duration, shortened ST segment in lead II and ST/QT ratio were predictors of a positive response to flecainide challenge when BrS was suspected on a baseline ECG. Prior published ECG parameters such as β angle, β score, baseline J wave elevation, presence of S wave in Leads II, III and V5 as well as the presence of R wave in aVR did not perform as well in predicting for a positive response to flecainide challenge in our population.

Funding Acknowledgement

Type of funding sources: None. Baseline CharacteristicsECG Findings
Novel variant of the glycerol-3-phosphate dehydrogenase-1 Like (GPD1-L) gene in Japanese Brugada syndrome patients
Authors: Usuda K , Hayashi K , Ishikawa T , Aizawa Y , Kato T , Kusayama T , Tsuda T , Usui S , Sakata K , Kawashiri M , Mishima H , Yoshiura K , Makita N , Takamura M
Published: October 2021

Background

The incidence of Brugada syndrome (BrS) varies among racial groups. Several studies reported Glycerol-3-Phosphate Dehydrogenase 1-Like (GPD1-L) gene is associated with BrS. However, most of these studies were reported from Western countries, so the evidence about GPD1-L mutation is limited especially among Asian BrS patients. This study aimed to search for rare variants in GPD1-L among Japanese BrS patients and to investigate the pathogenicity.

Method

We performed whole-exome sequencing for patients with Brugada type 1 ECG pattern from Japanese multicenter BrS cohort consisting of SCN5A-negative BrS probands (n=288) and controls (n=372). We conducted patch-clamp study in human embryonic kidney (HEK) 293 cells cotransfected with the wild-type sodium channel (SCN5A) and wild-type or mutant GPD1-L expression plasmid.

Results

We identified a rare variant in GPD1-L, p.D262N (c.784g>a) in 2 of 288 BrS probands, which was not identified in 372 controls. The minor allele frequency of the variant is 0.0014% in the Genome Aggregation Database. One proband was a 49-year-old man and the other was 34-year-old man who both developed a ventricular fibrillation. ECGs of both probands showed Brugada Type 1 pattern after administration of the pilsicainide. In functional study, coexpression of D262N GPD1-L with SCN5A in HEK293 cells significantly reduced inward sodium currents compared with wild-type GPD1-L. Additionally, inward sodium currents with D262N were similar to those with A280V GPD1-L, which was associated with BrS in previous reports (Figure). Also, several pathogenicity prediction programs, such as SIFT (score: 0.031) and PolyPhen2 (score: 0.937) predicted deleterious effects of GPD1-L D262N.

Conclusion

We identified a rare variant in GPD1-L at the rate of 0.7% in Japanese BrS patients without SCN5A mutations. GPD1-L, p.D262N reduces inward sodium currents and may be a novel susceptible variant for BrS in the Japanese population.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Current–voltage curve
Electrophysiologic study for risk stratification in Brugada Syndrome: does it still matters?
Authors: Faia Carvalho Dias G , Oliveira M , Faria B , Von Hafe P , Cardoso F , Pereira T , Tinoco M , Ribeiro S , Sanfins V , Almeida F , Lourenco A
Published: October 2021

Background

The value of eletrophisiologic study (EPS) with programmed ventricular stimulation for risk stratification in patients with Brugada Syndrome (BS) remains controversial.

Purpose

The aim of this study is to determine the clinical and electrocardiographic predictors of positive EPS and to evaluate whether the induction of malignant ventricular dysrhythmias in the EPS is a predictor of events

Methods

A retrospective study was carried out of patients with spontaneous type 1 Brugada pattern followed up in Arrhythmology consultation at our Hospital. From this population, patients who underwent EPS for stratification of dysrhythmic risk were selected. Clinical and electrocardiographic variables were analyzed. Hospital records and monitoring data from cardiac devices were consulted. Statistical analysis was performed using SPSS 20.0.

Results

Fourty nine patients were included, with a mean age at the beginning of follow-up of 45±14 years, 40 (82%) of whom were male. In 16 individuals (33%) the EPS was positive with induction of malignant ventricular dysrhythmias. All patients with positive EPS implanted an implantable cardioverter-defibrillator and of the 32 patients with negative EPS, 10 implanted an implantable event recorder. The group of patients with positive EPS had a higher proportion of male patients (88% vs 78%). The median follow-up time was 31 months.

The family history of sudden death, family history of BS, or identification of a genetic variant classified as pathogenic or probably pathogenic did not present any relationship with EPS positivity. Of the analyzed electrocardiographic markers, PR interval (178±29 vs 171±27) and QRS duration (119±24 vs 113±15) tended to be longer in patients with positive EPS. Additionally, it was found that 74% of patients with a QRS of less than 120 ms had a negative EPS.

In the analysis of the value of EPS in the stratification of dysrhythmic risk, it was found that of all the patients who suffered events (4), 75% had positive EPS. Of the patients with negative EPS, only 3% (1) presented events in the follow-up. However, there was no significant association between these variables.

Conclusion

In this population, the analysed clinical elements did not correlate with the EPS result. Although there was no statistical significance, there was a tendency for patients with narrower QRS to be more likely to have negative EPS. Accordingly with published data, it was found that the EPS result was not a predictor of events during the follow-up period, which highlights the difficulty of risk stratification in patients with BS.

Funding Acknowledgement

Type of funding sources: None.
Direct comparison of adenosine- versus exercise echo-derived distal left anterior descending artery velocity reserve
Authors: Armenis I , Marinou M , Motsi A , Voudris V , Athanassopoulos G.D
Published: October 2021

Introduction

Distal left anterior descending (LAD) velocity reserve (CVR) estimated by vasodilators has been introduced in stress echocardiography as both diagnostic and prognostic parameter. Exercise echocardiography in the form of supine ergometry (Erg) is currently extensively used and provides an alternative means to evaluate CVR.

Aim

Aim of the study was to assess the relationship between the CVR estimated by Erg and the respective one by adenosine (Ad) immediately after Erg recovery.

Methods

Among 73 patients who underwent Erg and were initially screened, 59 (80.8%, age 63±12 years, 45 male, 14 female) with an efficient detection of LAD flow during Erg were studied (19 interrogated for coronary artery disease-CAD, 16 for heart failure with preserved ejection fraction-HFpEF, 7 for asymptomatic aortic stenosis-AS, 17 for mitral regurgitation-MR).

Distal LAD velocity was measured at rest and every 2 min during Erg, provided that a clear envelope was feasible. Time elapsed for the detection of peak velocity and the respective achieved heart rate (Peak V-HR) were measured.

CVR-Ad was estimated blindly by a different operator 30 minutes after Erg recovery. Absolute (dCVR) and % difference (%dCVR) between CVR-Erg and CVR-Ad were calculated.

Results

In 62.7% of cases the maximum CVR-Erg was detected earlier than 3 min during Erg. The respective Peak-V-HR was 81±11% of the maximum HR achieved during Erg.

CVR-Erg was lower than CVR-Ad (2.17±0.61 vs 2.95±0.60, p=0.0001). The underlying substrate did not affect the difference dCVR (CAD: 0.81±0.70, HFpEF: 0.84±0.72, AS: 0.86±0.60, MR: 0.62±0.65, p=0.76).

dCVR and %dCVR were inversely related with the CVR-Erg (r=−0.63, p=0.0001, r=−0.69, p=0.0001 respectively). A greater than 1.7 CVR-Erg had a 100% predictive accuracy for CVR-Ad greater than 2.0.

CVR-Ad was predicted by the CFR-Erg using the following linear regression:

CVR-Ad = 0.258 x CVR − Erg + 2.290

Conclusion

CVR-Erg evaluation is feasible in the majority of patients undergoing Erg for contemporary guidelines indications, even at a relatively low workload, and may be used as a surrogate for CVR-Ad for either diagnostic or prognostic purposes.

The observed metric discrepancies may be explained by the different coronary artery/microvasculature dynamics applied by exercise and vasodilators.

Funding Acknowledgement

Type of funding sources: None. LAD velocity at baselineLAD velocity at peak exercise
Magnetic resonance imaging in the evaluation of idiopathic frequent premature ventricular complexes with normal ventricular function
Authors: Hosseini F , Gulsin G , Murphy D , Hawkins N , Andrade J , Laksman Z , Bennett M , Yeung-Lai-Wah J , Chakrabarti S , Krahn A , Deyell M
Published: October 2021

Background

The role of cardiac magnetic resonance (CMR) imaging in the diagnostic evaluation of patients with frequent premature ventricular complexes (PVCs) and normal left ventricular ejection fraction (LVEF) remains unclear. Existing data has been predominantly derived from highly selected populations, that may overestimate the true prevalence of abnormal findings on CMR in this patient population.

Purpose

The aim of this study was 2-fold: 1) to establish the prevalence of CMR imaging abnormalities in a cohort with normal LVEF and high PVC burden; 2) to identify predictors of CMR imaging abnormalities in patients with frequent PVCs and normal LVEF.

Methods

In this cohort study, 211 patients (age 53.2±19 years; 41% male) with frequent PVCs (≥5%/24 h), of normal LVEF (≥50% by echocardiography) and no known underlying structural heart disease were prospectively enrolled from 2016–2020. Of these, 166 (79%) patients were symptomatic from their PVCs in the form of palpitations, fatigue, chest pain, dizziness, and/or dyspnea. Patients underwent CMR imaging (1.5 Tesla) with a late gadolinium enhancement (LGE) protocol at the time of enrollment for the detection of scarring and/or fibrosis.

Results

Patients had a median baseline echocardiographic LVEF of 60% (± 5%) with 195 (92%) of patients having a normal native QRS morphology. Median PVC burden of the study cohort was 16% (± 14%). CMR LGE abnormalities were found in 19 (9%) patients including 17 scans with non-ischemic LGE and 2 with ischemic LGE. Age >60 (odds ratio [OR]: 3.20, 95% confidence interval [CI]: 1.20–8.51, p=0.020), male sex (OR: 4.67, 95% CI: 1.61–13.50, p=0.004), history of hypertension (OR: 3.43, 95% CI: 1.31–8.97, p=0.012), native QRS duration (OR: 1.03, 95% CI: 1.00–1.05, p=0.031), and history of non-sustained ventricular tachycardia (OR: 2.81, 95% CI: 1.03–7.68, p=0.044) were significantly associated with the presence of imaging abnormalities on CMR. Dominant PVC origin from the left ventricle had a positive trend (OR: 2.60, 95% CI: 0.99–7.66, p=0.083) to association with CMR imaging abnormalities. On multivariate analysis, male sex (OR: 4.10, 95% CI: 1.40–12.04, p=0.010) and history of hypertension (OR: 2.89, 95% CI: 1.08–7.75, p=0.035) remained significantly associated with the presence of CMR abnormalities. There was no association between CMR imaging abnormalities and the burden of PVCs or the number of PVC morphologies.

Conclusion

In this cohort, only 9% of patients with apparently idiopathic frequent PVCs and normal LVEF had concealed myocardial abnormalities on CMR imaging. Male sex and history of hypertension were associated with a higher rate of CMR abnormalities.

Funding Acknowledgement

Type of funding sources: None.
Leadless pacemaker implant in the elderly: a safe and feasible solution
Authors: Barletta V , Parollo M , Mazzocchetti L , Giannotti Santoro M , Canu A , Sbragi S , Di Cori A , De Lucia R , Segreti L , Viani S.M , Zucchelli G , Bongiorni M.G
Published: October 2021

The use of leadless pacing systems could overcome peri-and post-procedural complications related to the presence of transvenous leads and the post-operative recovery, being a favorable option in elderly patients.

The study aimed to investigate feasibility and outcomes of M-TPS implant in a specific patient population, like the elderly, which represent a challenge for conventional cardiac pacing.

Methods

Between May 2014 and March 2021, 138 patients (106 males, 77%, mean age 78) underwent M-TPS implantation in our Centre, targeting a non-apical site of delivery when feasible. A subgroup of 59 patients (43 males, 73%) were older than 80 years. All patients fulfilled standard criteria for pacemaker implantation with specific indication to receive VVI pacing. Study population was divided into two groups according to age (group 1 <80 years vs group 2 ≥80 years). The outcome evaluation included electrical performance (capture threshold, pacing impedance, R wave amplitude) before hospital discharge and then followed at 1, 6, and 12 months and then annually. Major complications were defined as life-threatening events, requiring surgical intervention or any event causing significant hemodynamic instability or resulting in death. High pacing threshold (HPT) was defined as >1.0 V@ 0.24 ms.

Results

In 59/138 cases (43 males, 73%) M-TPS was implanted in patients older than 80 years. There were no statistically significant differences between groups for demographics characteristics, except for age, and PM implant indications. The implant procedure was successful in all cases and no device-related events were registered during follow-up. In particular, no device infection and/or malfunction were reported. Patients were followed-up for an average of 22,19±20,66 months (median 18 months). No differences were observed between groups in procedure duration (44,97±20,24 min vs 45,80±23,27 min; P=0,83), single device delivery (group 1 vs group 2: 63,16% vs 66,07%; P=0,73), fluoroscopy time (11,64±6,22 min vs 12,13±8,67 min; P=0,72) electrical performance at implant [group 1 vs group 2: pacing threshold 0,56±0,37 vs 0,58±0,32, P=0,78; impedance 727,53±170,36 vs 752,88±256,21, P=0,49; R wave amplitude 10,39±4,86 vs 9,26±4,66, P=0,18] and at median follow-up [group 1 vs group 2: pacing threshold 0,63±0,55 vs 0,51±0,1, P=0,40; impedance 535,34±102,53 vs 577,34±69,02, P=0,20; R wave amplitude 12,56±4,56 vs 12,00±5,80, P=0,77]

Conclusions

The demand for cardiac pacing is strongly related to ageing, driving the clinical practice to look for the best solution for a considered fragile population. MTP-S implant is an effective and safe procedure in elderly patients, with similar electrical performance and outcome compared with younger patients at mid-term follow-up.

Funding Acknowledgement

Type of funding sources: None.
Effects of obesity on survival in patients with implantable cardioverter defibrillator
Authors: Polat F , Yalin K , Ikitimur B , Karadag B , Ongen Z
Published: October 2021

Background

Studies have shown that increased body weight and obesity may be associated with an increased risk of arrhythmic events. However, studies conducted in patients with implantable cardioverter-defibrillator (ICD) have found that low body mass index (BMI) is associated with higher mortality. The aim of this study is to evaluate the effect of obesity on the risk of arrhythmic events, hospitalization and death in patients receiving ICD therapy for primary or secondary prevention.

Methods

The study was designed as a single-center prospective and observational. Patients with BMI <30 kg/m2 were classified as non-obese and patients with ≥30 kg/m2 as obese. The primary endpoints were all-cause mortality, cardiac mortality, and cardiac rehospitalization.

Results

Among the total of 340 patients, 78.2% were male, 21.8% were female, and the mean age of the patients was 60.9 years. Among all patients, there were 30.6% normal weight, 47.4% overweight and 22.1% obese patients. AF recording was significantly higher in obese patients compared to the normal weight patient group (p=0.02). Shock, appropriate shock, and liquid load sensing were statistically higher in obese than non-obese patients (p=0.042, p=0.011 and p=0.007). In the primary prevention group, all-cause mortality and cardiac mortality rates were lower in the obesity group (p=0.022, p=0.037).

Conclusion

Our findings showed that although cardiac arrhythmic events are more common in obese patients, mortality and hospitalization events are less common in obese patients. These findings are consistent with the reverse epidemiology that has been demonstrated previously between obesity and mortality

Funding Acknowledgement

Type of funding sources: None. Events obtained from device controlSurvival normal weight and overweight
Mitral and tricuspid annular abnormalities in hypereosinophilic syndrome – a three-dimensional speckle-tracking echocardiographic study
Authors: Nemes A , Kormanyos A , Racz G , Marton I , Borbenyi Z
Published: October 2021

Introduction

Peripheral eosinophilia with absolute eosinophil count more than 1.500 cells/uL and eosinophilic tissue and end-organ damage are typical features in hypereosinophilic syndrome. In the present study it was hypothesized that hypereosinophilic syndrome-related atrial and ventricular abnormalities are associated with changes in size and function of mitral and/or tricuspid annuli.

Methods

The study comprised 17 patients with hypereosinophilic syndrome who were recruited, prospectively, 2 patients had to be excluded due to suboptimal image quality (mean age: 61.7±11.2 years, 10 males). The control group consisted of 24 healthy volunteers (mean age: 55.2±7.9 years, 12 males). Complete two-dimensional Doppler echocardiography was performed, mitral and tricuspid annuli were measured by three-dimensional speckle-tracking echocardiography.

Results

Only interventricular septum proved to be significantly thickened in patients with hypereosinophilic syndrome, other parameters did not differ between the groups examined. Increased end-diastolic and end-systolic mitral annular diameter (2.6±0.3 cm vs. 2.4±0.3 cm, p<0.05 and 2.2±0.2 cm vs. 1.7±0.3 cm, p<0.05, respectively), area (9.5±2.3 cm2 vs. 7.5±1.9 cm2, p<0.05 and 6.7±2.0 cm2 vs. 3.8±1.1 cm2, p<0.05, respectively), and perimeter (11.6±1.7 cm vs. 10.4±1.3 cm, p<0.05 and 9.9±1.9 cm vs. 7.4±1.1 cm, p<0.05, respectively) together with reduced mitral annular fractional area change (29.6±13.0% vs. 47.7±15.8%, p<0.05) and fractional shortening (16.6±11.9% vs. 28.9±12.7%, p<0.05) could be detected in patients with hypereosinophilic syndrome as compared to that of matched controls. From tricuspid annular morphological parameters, only end-diastolic tricuspid annular area (9.1±2.4 cm2 vs. 7.5±1.9 cm2, p<0.05) and end-systolic tricuspid annular perimeter (9.9±1.2 cm vs. 9.3±1.4 cm, p<0.05) proved to be significantly increased in patients with hypereosinophilic syndrome as compared to controls with preserved tricuspid annular functional parameters.

Conclusion

Mitral annular dilation is more pronounced compared to that of tricuspid annulus in hypereosinophilic syndrome. Mitral annular functional impairment is present in hypereosinophilic syndrome.

Funding Acknowledgement

Type of funding sources: None.