bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient reported symptoms in emergency health care service in patients with complete atrioventricular block
Authors: Sorensen E , Moller A , Lippert F , Kober L , Kragholm K , Folke F , Blomberg S , Christensen H , Torp-Pedersen C , Bang C
Published: October 2022

Aim

To examine initial symptoms in emergency and medical helpline calls of patients prior to hospital admission and pacemaker implantation due to recent onset of complete atrioventricular block.

Methods

In the capital region of Denmark, Copenhagen, citizens who require medical assistance can contact either the regional 24h non-urgent medical helpline 1813 or the emergency number 1–1-2 (equivalent to 9–1–1). In both services, the symptoms/purposes of the calls are registered by health professionals. We identified calls from patients who received a pacemaker due to recent onset complete AV block. Prior to analysis, symptoms were categorized as fainting, dizziness, other CNS symptoms, chest pain, other cardiac symptoms, breathing problems, trauma/exposure, unconsciousness, unclear problems, and other atypical symptoms.

Results

We identified 451 calls (261 emergency calls and 190 non-emergency calls) which included information on symptom presentation prior to hospital admission due to first time diagnosis of complete atrioventricular block, that resulted in pacemaker implantation (Figure). Typical symptoms such as fainting and dizziness accounted for only 12.6% (57/451) and 13.3% (60/451), respectively. Chest pain (13.6%, 61/451) and other cardiac symptoms (5.3%, 24/451) accounted for roughly one in five patient complaints. Across both service types, patients >80 years (median age) was more likely to call for help due to trauma/exposure, while complaints of fainting trended towards younger patients and the 1-1-2 emergency number. Median time from first call to pacemaker implantation was 2–3 days for fainting, dizziness, and chest pain, compared to 6–8 days for other CNS symptoms and other atypical symptoms (Table).

Conclusion

Typical symptoms such as fainting and dizziness accounted for only 13% in patients with complete atrioventricular block. Instead, these patients presented with a wide variety of initial symptoms, including chest pain, breathing problems, unclear problems, or trauma. Finally, symptom presentation seemed to affect the time to pacemaker implantation.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Danish Heart Foundation
Results of permanent lead implantation at the His bundle without the use of an electrophysiological unit
Authors: Israel C , Marinos R , Tribunyan S , Deelawar S , Angleitner A , Kalyani M , Feldmann T , Almahallawi H
Published: October 2022

Background

His bundle pacing (HBP) promises physiological cardiac stimulation using the conduction system for a synchronous ventricular excitation, excluding the risk of pacing-induced cardiomyopathy. In daily practice, HBP is rather rarely used in Germany, in part because it has been recommended to use an electrophysiological unit (EPU) for registration of the His bundle potential and the HV interval. We attempted HBP replacing the EPU by a normal pacing system analyzer (PSA) with high resolution of the electrogram (EGM) which is used during daily clinical routine (Figs. 1 & 2).

Methods

Consecutive patients (pts) with attempted HBP in our department were included in this prospective study. We used a 4,1F and a 7F lead together with specific sheaths to reach the His bundle. Mapping was performed using a conventional PSA (atrial channel, unipolar mode, 20 mm/mV). We recorded the success of the implantation for HBP, selective versus non-selective His bundle capture, parameters of sensing and pacing performance, operation and fluoroscopy times, the number of lead implantation attempts and QRS duration before and after HBP.

Results

Implantation of a system for HBP was attempted in 265 pts (mean age 78±12 years, 102 female, mean left ventricular ejection fraction 55±8%) and was successful in 244 (92%), selective His bundle capture was achieved in 55%, non-selective in 37%. Implantation success rates increased from 86% (earliest quartile) to 98% (latest quartile). Mean operation time was 95±46 min, mean fluoroscopy time 11±10 min; a mean of 6±7 attempts (median: 3) were necessary. Mean R wave amplitude was 5±4 mV, mean threshold 0,7±0,5 V at 1,0 ms. QRS duration before implantation was 111±29 ms, post implantation 88±20 ms.

Conclusions

HBP in daily clinical routine can be successful in >90% of cases without an EPU. Mean operation and fluoroscopy times were similar to those needed for biventricular pacing. An extremely narrow paced QRS could be achieved that indicates extremely good synchronization with HBP.

Funding Acknowledgement

Type of funding sources: None.
CardioneuROablation for reflex syncope: efficacy and effects on autonoMic cArdiac regulatioN. The Roman 1 study
Authors: Piotrowski R , Baran J , Sikorska A , Krynski T , Kulakowski P
Published: October 2022

Purpose

To assess the effects of CNA on syncope recurrences in patients with VVS

Methods

The Roman 1 study was a prospective, randomized, investigator-initiated trial comparing CNA versus optimal standard therapy in patients with asystolic VVS. Patients were included if they had documented symptomatic cardioinhibitory or mixted spontaneous VVS (at least 3 seconds of asystole), frequent and/or severe symptoms (at least one syncope or 3 presyncopal events during preceding 12 months or very severe syncope in the past, leading to injury) and positive atropine test (>30% increase in sinus rate). CNA was performed using RF ablation of the ganlionated plexi from the left and right atrium. Follow-up lasted 2 years. Primary endpoint was time to first syncope recurrence. One of secondary endpoints were changes in quality of life (QoL) assessed using dedicated questionnaire The Impact of Syncope on Quality-of-Life Questionnaire University of Calgary.

Results

48 patients (17 males, mean age 38±10, 24 – CNA group, 24 – control group) entered the study. Baseline demographic and clinical characteristics were similar in both groups. The primary end-point – syncope recurrence, occurred in 2 (8%) patients from the CNA group versus 12 (50%) controls (p=0.00037, see Kaplan-Meier curve). QoL significantly improved in the CNA group (30±10 vs 10±7 points, p=0.0001) whereas remained stable in controls (31±10 vs 30±10 points, p=0.5501).

Conclusion(s)

This is the first randomized study documenting efficacy of CNA in patients with asystolic VVS. Larger studies are needed to confirm these findings.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Centre of Postgraduate Medical Education
Long-term incidence of pacemaker implantations and bradycardia among cross-country skiers
Authors: Svedberg N , Sundstrom J , Hambraeus K , James S , Andersen K
Published: October 2022

Background

Bradycardia is more common among well-trained athletes. The associations of training with pacemaker implantations are less known. We aim to investigate the association of endurance training with incidence of bradycardia and pacemaker implantations in a cohort of endurance athletes. Furthermore, we aim to establish potential sex differences of such associations.

Methods

Swedish skiers (209,072) that completed 1 or more races in the 30 to 90 km cross-country skiing event Vasaloppet (1989–2011) and a matched sample (n=531,949) of nonskiers were followed until first event of bradycardia or pacemaker implantation. The Swedish National Patient Register of in-patient and specialized outpatient care was used to obtain the date of diagnoses. Cox regression was used to investigate associations of number of completed races and finishing time with incidence of bradycardia and pacemaker implantations.

Results

Male skiers had higher incidence of bradycardia (hazard ratio [HR], 1.14; 95% CI, 0.99–1.30) and pacemaker implantations (HR, 1.14; 95% CI, 1.02–1.28) than male nonskiers. Male skiers completing most races or with the fastest finishing times had the highest incidence. The incidence of bradycardia (HR, 0.96; 95% CI, 0.70–1.30) and pacemaker implantations (HR, 0.97; 95% CI, 0.75–1.25) among female skiers in Vasaloppet was not different to that of female nonskiers. There was a trend that female skiers completing most races or with fastest finishing times had lower incidence.

Conclusions

Male skiers had higher incidence of bradycardia and pacemaker implantations. Female skiers in Vasaloppet had non-different incidence of bradycardia and pacemaker implantations. Men with the highest number of races and fastest finishing times had the highest incidence of pacemaker implantations. This indicates that bradycardia associated with training is not always as benign as previously suggested. The response appears to be different between sexes.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Uppsala UniversityCKF Dalarna
Endo- and epicardial mapping of spontaneous ventricular fibrillation during acute myocardial infarction in a porcine model
Authors: Sattler S , Hesselkilde E Z , Orini M , Taggart P , Pehrson S , Jespersen T , Tfelt-Hansen J
Published: October 2022

Introduction

Ventricular fibrillation (VF) during the first minutes of acute myocardial infarction (AMI) is among the most frequent causes of sudden cardiac death. Albeit mechanisms for arrhythmogenesis during ischemia are well understood on a cellular level, little is known in an in-vivo setting.

Aim

Aim of this study was the development and characterization of a porcine model of AMI and spontaneous VF with continuous electrical mapping using a non-contact mapping system (EnSite Array) in the left ventricle (LV) and an electrode sock covering the whole heart. Activation-recovery intervals (ARI), beat-to-beat variation in repolarization (BVR), and ectopic activation were measured.

Methods

Nineteen Danish Landrace pigs (56±4 kg, heart weight 251±20 g) were anaesthetized, equipped with electrophysiological (EP) catheters in the coronary sinus, right and LV as well as a multi electrode array (St. Jude, EnSite Array) catheter in the LV. Thoracotomy was performed and the sock electrode was placed on the pericardium covering the anterior and the posterior surface of the heart. Finally, the mid-left anterior descendent artery was occluded with a percutaneous transluminal coronary angioplasty balloon to induce AMI and kept in place for 45 minutes followed by 20 minutes of reperfusion. Data from both systems were analyzed offline using a custom-made software.

Results

All pigs had stable hemodynamic parameters during the procedure. Spontaneous VF occurred in 8/19 pigs during the occlusion period. Epi- and endocardial mapping showed similar shortening of ARI in the infarcted area (Figure 1A). AMI shortened ARI in the ischemic area to a greater extend in pigs that developed VF (Figure 1B) and caused beat-to-beat variation in repolarization (BVR) in later phases (Figure 1C). Ectopic beats proceeding spontaneous VF varied in activation site and subsequent repolarization (Figure 1D, left). Multiple short-coupled ectopic beats destabilized the electrical substrate further and led to progressive ARI shortening (Figure 1D, last 4 beats).

Conclusion

We present the first whole heart mapping experiments of spontaneous VF during AMI with endo- and epicardial mapping. Pigs with VF had shorter ARI, greater dispersion but similar BVR during AMI compared to those without VF. These findings provide a deeper understanding of arrhythmogenesis during AMI and can help to develop new antiarrhythmic drugs or to assess risk factors of VF.

Funding Acknowledgement

Type of funding sources: None.
Sex differences among patients with tachyarrhythmias and bradyarrhythmias following acute myocardial infarction
Authors: Alnsasra H , Tsaban G , Cooper J , Haim M
Published: October 2022

Background

Acute myocardial infarction (AMI) is commonly complicated by ventricular, supraventricular tachycardias and high-grade atrioventricular block (HAVB) which may result in increased morbidity and mortality.

Purpose

To evaluate the sex differences in tachyarrhythmias and HAVB, and their associated outcomes following AMI.

Methods

Using the Acute Coronary Syndrome Israeli Survey (ACSIS) survey database from 2000–2018, we analyzed the specific incidence rates for arrhythmias including: sustained ventricular tachycardia (VT), ventricular fibrillation (VF), new-onset atrial fibrillation (AF) and HAVB in men and women after AMI. Unadjusted and multivariable-adjusted logistic regression analyses were performed to assess the sex differences of in-hospital arrhythmias after AMI. Multivariate cox proportional hazard models were performed to assess the impact of arrhythmias on 1-year mortality.

Results

In this cohort study of 14280 patients with 3159 (22.1%) women and 11121 (77.9%) men, 316 (2.2%) experienced ventricular arrhythmias (VAs) (sustained VT or secondary VF) with similar rates among men and women (2.3% and 2.2%, respectively, p=0.62). Compared to men, women were less likely to experience primary VF (1.6% vs 2.3%, p=0.034), but more likely to experience AF (8.6% and 5.0%, p<0.001). 372 (2.6%) patients experienced HAVB with higher rates of HAVB in women than men (3.7% and 2.3%, respectively, p<0.001).

After multivariate analyses, the association with primary VF was attenuated (adjusted Odds Ratio (OR) = 0.80, p=0.15) but women remained more likely to experience AF (adjusted OR =1.24, p=0.01) and HAVB (adjusted OR =1.28, p=0.04). The occurrence of VAs was found to be associated with increased mortality in both men (adjusted Hazard Ratio (HR) =3.68, p<0.01) and women (adjusted HR=3.87, p<0.01) without a significant difference between the groups (p for interaction=0.203). The occurrence of AF was found to be associated with increased mortality in both men (adjusted HR=1.64, p<0.001) and women (adjusted HR=1.34, p<0.001) with a significant difference between the groups (p for interaction<0.001). HAVB was found to be associated with increased mortality in both men (adjusted HR=2.31, p<0.001) and women (adjusted HR=2.26, p<0.001) without a significant difference between the groups (p of interaction=0.21).

Conclusions

The incidence rates of VAs after AMI were similar in men and women, except for primary VF, which was more common among men. Women experienced more AF and HAVB than men. VAs, AF and HAVB were found to be associated with increased mortality.

Funding Acknowledgement

Type of funding sources: None.
Correlations between endocardial voltage mapping, diagnosis and genetic in patients with arrhythmogenic right ventricular cardiomyopathy
Authors: Maury P , Delasnerie H , Sauve R , Beneyto M , Domain G , Voglimacci Q , Waintraub X , Mondoly P , Rollin A , Gandjbakhch E
Published: October 2022

Background

The relations between voltage mapping and diagnosis or genetic background of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been investigated so far.

Objective

To investigate if diagnosis or genetic background were linked to voltage mapping in ARVC.

Method

97 patients with proved or suspected ARVC undergoing 3D endocardial mapping and genetic testing have been retrospectively included. Presence, localisation and extension of low voltage areas were correlated to ARVC diagnosis and presence of a culprit mutation.

Results

68 patients (70%) fulfilled ARVC diagnosis according to the Task Force criteria and 43 (44%) had ARVC-causal mutations. 78 (80%) presented with some bipolar or unipolar endocardial scar. 60/ 78 patients with endocardial scar (77%) fulfilled the criteria for a definitive ARVC diagnosis versus 8/19 patients without scar (42%) (p=0.003).

In the 68 patients with a definitive diagnosis of ARVC, the presence of endocardial scar was similar whether an ARVC-causal mutation was present or not (35/40 vs 25/28, p=ns). While there was slightly more infero-lateral scars in patients carrying a pathogenic genetic variant (34/40 vs 18/28, p=0.04), there was no difference for right ventricular outflow tract (24/40 vs 17/28) and apical scars (12/40 vs 11/28) or for multiple scars (26/35 vs 14/25 patients with scars). Scar extension was greater in patients with pathogenic variants (bipolar 12±10 vs 6±10%, p=0.02, and unipolar 22±13 vs 12±15%, p=0.01).

Conclusion

3D endocardial mapping could have an important role for refining ARVC diagnosis. Trends for larger and more infero-lateral scars were observed in mutated patients, without difference according to the mutated genes.

Funding Acknowledgement

Type of funding sources: None.
SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome
Authors: Probst V , Ribouleau G , Geoffroy O , Mabo P , Mansourati J , Pasquie J L , Babuty D , Al Arnaout A , Petit B , Billon O , Thollet A , Sacher F , Gourraud J B
Published: October 2022

Background

Mutations in SCN5A are identified in approximately 20% to 30% of probands affected by Brugada syndrome (BrS). However, in familial studies, the relationship between SCN5A mutations and BrS remains poorly understood. The aim of this study was to investigate the association of SCN5A mutations and BrS in a group of large genotyped families.

Methods

Families were included if at least 3 family members were carriers of the SCN5A mutation, which was identified in the proband. Families were recruited from 12 tertiary centers in France between 1995 and 2020. Type 1 ST elevation was defined by ≥2 mm J-point elevation with coved ST segment and negative T wave.

Results

Forty-nine large families composed of 600 members including 304 mutation carriers (51%) were studied. The signature type I ECG was present in 160 mutation carriers (BrS-ECG+; 53%). In 42 families, we found 33 individuals affected by BrS but with a negative genotype (mutation-negative BrS-ECG+). Among them, 5 patients have an ECG suggestive of BrS but without the complete signature type I ECG. Among these 33 mutation-negative BrS-ECG+ individuals, 3 (9%), belonging to 3 different families, had a spontaneous type I ECG, whereas 28 had a type I ECG only after the administration of sodium channel blockers. Three of these 33 individuals (9%) had also experienced syncope. Mutation carriers had, on average, longer PR (190±36 ms vs 154±29 ms, p<0.0001) and QRS (107±19 vs 92±29 ms, p<0.0001) intervals than noncarriers, demonstrating that these mutations exerted functional effects.

Conclusions

Our results suggest that SCN5A mutations are not directly causal to the occurrence of a BrS-ECG+ and that genetic background may play a powerful role in the pathophysiology of BrS. These findings are consistent with the notion that the pathophysiology of BrS includes various elements beyond mutant sodium channels.

Funding Acknowledgement

Type of funding sources: None.
Calmodulinopathy is a common cause of critical cardiac phenotypes in fetus and infancy
Authors: Fukuyama M , Horie M , Kato K , Ozawa T , Fujii Y , Okuyama Y , Makiyama T , Ohno S , Nakagawa Y
Published: October 2022

Background

Cardiac calmodulinopathy is a life-threatening arrhythmia syndrome which presents several phenotypes of inherited primary arrhythmia syndrome (IPAS), and caused by mutations in calmodulin-encoded genes (CALM1–3). We aimed clarify the frequency and their clinical characteristics of calmodulinopathy in our IPAS cohort.

Methods

By using next generation sequencing, we screened arrhythmia related genes including calmodulin-encoding genes in 322 unrelated symptomatic children (0–12 years) who were suspected as IPAS; they included 40 cases with lethal arrhythmic attacks (LAE) under 6-year-old. After gene screening, we investigated their physiological and clinical characteristics about mutation carriers.

Results

Among 322 children, we identified 6 mutations of calmodulin-encoded genes in 9 probands (2.8%); one CALM1 in 2 probands (N98S), and 5 CALM2 in 7 probands (E46K, D96V, D96G, N98S, E141K). Their clinical diagnoses were long QT syndrome (LQTS, n=4), catecholaminergic polymorphic ventricular tachycardia (CPVT, n=3) and both (n=2). Their age of diagnosis ranges at 0–9 with the median of 5 years. There were three major clinical phenotypes; 1) CALM2-D96V, and E141K: two infants with advanced atrio-ventricular block, significant QTc prolongation, severe heart failure from their fetal period – both of them deceased within 1.5-year-old. Their clinical phenotypes resembled classical Timothy syndrome caused by CACNA1C mutations. 2) CALM1-N98S (n=2), CALM2-N98S (n=2), and CALM2-D96G: four preschoolers with LAEs and one syncope: all of them were 3–5 years old. In addition, a T wave morphology of CALM2-D96G carrier was very similar to LQT1. 3) CALM2-E46K (n=2): two were first diagnosed with neurological and developmental disorders, and showed phenotype of CPVT: their cardiac phenotypes were milder compared with that of 1) or 2). Overall, these phenotypes seemed to be mutation specific (indicated in figure). Their cardiac features were severer, and the onset of LAEs was earlier compared with other genotypes of LQTS/CPVT. As the treatment, β-blocker was effective for control of LAEs.

Conclusion

Cardiac calmodulinopathy presented serious and potentially lethal phenotypes in fetus or infancy. To prevent cardiac death in them, we must correctly diagnose and start the treatment as earlier as possible.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): MEXT KAKENHI from the Ministry of Education, Culture, Sports, Science, and Technology of Japan
Characterization and long-term follow-up of children with brugada syndrome: experience from a tertiary paediatric referral centre
Authors: Fernandes S , Saleiro C , Palma A , Faim D , Dias J , Borges I , Santos I , Andrade H , Martins H , Pires A
Published: October 2022

Introduction

Brugada syndrome (BrS) is an autosomal dominant channelopathy, which typically presents in young adults. It can also be diagnosed in children, but data in this age group is scarce.

Purpose

To describe the clinical features, management and long-term follow-up of children with BrS history followed-up in a tertiary paediatric referral centre.

Methods

Single centre retrospective study of consecutive patients with history of BrS, defined as having a BrS positive phenotype (BrS(+)), or a negative phenotype-positive genotype (BrS(−)). They were all followed up in a paediatric heart rhythm clinic. Clinical and demographical data were collected and analysed according to the phenotype.

Results

30 patients were included, with a median age at diagnosis of 7 years (IQR 1–13) and a mean follow-up time of 7±3 years. Sixteen patients were BrS(+), predominantly male (n=13, 81%). 88% (n=14) performed a genetic test, which was positive in 57% (n=8); the most frequent mutation was SCN5A (n=5). Family history of BrS was present in 56% (n=9) and almost one third had family history of sudden cardiac death (SCD). Most of the patients had a type 1 Brugada ECG pattern (n=14) and 2 patients presented a fever and drug induced pattern, respectively. Fourteen patients were BrS(−), mostly female (n=11, 79%) with a loss-of-function mutation in the SCN5A gene (n=10). They all had family members with BrS, mainly from the paternal side, and 43% (n=6) mentioned SCD history. Although most of the patients were asymptomatic, the prevalence of rhythm or conduction disturbances was not infrequent, particularly in BrS(+) patients (n=12, 75%). Also, in this group and during follow-up, 3 patients had documented supraventricular tachyarrhythmias, and 2 patients had syncope episodes, one of which required an implantable cardioverter-defibrillator. No events were reported in the BrS(−) patients. Nine patients (n=9/30, 30%) were hospitalized, 3 due to an arrhythmic event (all in the BrS(+) group). Overall, no sudden cardiac death event was reported during follow-up.

Conclusion

In our study, although the majority of the patients were asymptomatic, the occurrence of arrhythmic events was not negligible, especially in the BrS(+) patients. Despite the significant family history, patients with BrS(−) had no events reported during follow-up. Nevertheless, the management of these patients is not clear cut, and a personalized therapeutic strategy with close follow-up is essential.

Funding Acknowledgement

Type of funding sources: None.
Clinical features of drug-induced long QT syndrome in a large prospective cohort
Authors: Campos Garcia B , Hernandez-Ontiveros H , Avila-Parcet A , Garcia-Hernando V , Carceller-Sindreu M , Salazar-Blanco J , Rodriguez-Santiago B , Juanes-Borrego A , Alonso-Martin C , Rodriguez-Font E , Moreno-Weidmann Z , Mendez-Zurita F , Vinolas-Prat X , Guerra Ramos J M
Published: October 2022

Introduction

Drug-induced long QT syndrome (DI-LQTS) is a clinical entity with prevalence and arrhythmic risk not well defined.

Purpose

To determine the clinical characteristics of patients with DI-LQTS diagnosed in the setting of a tertiary hospital center.

Methods

Prospective observational study with consecutive inclusion of patients with the diagnosis of DI-LQTS as per standard criteria, in a tertiary hospital, between 2018 and 2022.

Results

Eighty-five patients were included (age 65±15 years, 59% male). The mean corrected QT interval (QTc) of the entire cohort was 545±56 ms. The drugs responsible for QTc prolongation were: psychotropic drugs 51%, antiarrhythmics 38%, anesthetics 29%, antibiotics 15%, antineoplastics 3%, other 2%. QTc prolongation was due to the combination of ≥2 responsible drugs in 46 (54%) patients, and to the use of a single drug in 39 (46%).

Twenty-one patients (25%) presented ventricular arrhythmias at the time of drug-induced QT prolongation: 10 (12%) ventricular fibrillation, 7 (8%) sustained ventricular tachycardia, 3 (3%) non-sustained ventricular tachycardia, 1 (1%) frequent ventricular extrasystole. Patients with ventricular arrhythmias were older (73±12 vs 62±15 years, p<0.05) and exhibited longer QTc prolongation (600±59 vs 528±42 ms, p<0.05).

Conclusion

The DI-LQTS is a rare clinical entity but may be cause of clinically-relevant ventricular arrhythmias. Older age and greater prolongation of the QTc interval are associated with an increased risk of ventricular arrhythmic events.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Health Institute Carlos III, Spain
Brugada syndrome in Portugal: a cohort characterization
Authors: Oliveira C , Silverio Antonio P , Couto Pereira S , Brito J , Valente Silva B , Alves Da Silva P , Garcia B , Martins M , Raposo M , Nunes Ferreira A , Lima Silva G , Carpinteiro L , Cortez-Dias N , J Pinto F , Sousa J
Published: October 2022

Introduction

Brugada syndrome (BrS) is an inherited cardiac arrhythmic disorder that can lead to sudden death. Although SCN5A was the first pathogenic associated gene, other potential genes have been described. The relationship between SCN5A, spontaneous type 1 pattern and the predisposition to ventricular arrhythmias is not totally understood.

Purpose

To characterize mutations in a Portuguese cohort with BrS and explore the genotype-phenotype association in terms of electrocardiographic pattern and arrhythmic risk.

Methods

Prospective single-center study of patients (pts) with BrS. Genetic test included SCN5A direct sequencing from 2003 a broad panel of 120 genes associated with cardiomyopathies and arrhythmic disorders from 2018. Genetic test results were classified according to pathogenicity: mutations of unknown significance (MUS), mutations potentially pathogenic (MPP) and known pathogenic mutations (KPM). Kaplan-Meyer survival analysis was used to explore the association between genetic test results and the risk of arrhythmic events.

Results

A total of 94 pts [46±12 years, 67% male,64.9% with type 1 spontaneous pattern] were submitted to genetic testing. No relevant mutations were identified in 68pts and suspicious or pathogenic mutations were recognized in 26pts. The most frequent mutations occurred in SCN5A (N=20,76.9%), and included 8 KPM: 4 in exon 23 (3 of them had the same mutation,c.4018G>A), 2 in exon 26 (c.4534C>T), 1 in exon 28 and 1 in exon 16. All MPP in SCN5A occurred either in exon 23 or 28. Considering MUS, different mutations were described in 6 different exons (8,15,18,23,25 and two in 28). Additionally, 6 pts presented MUS in other genes: SCN10A (N=2), ANK2 (N=2), SFM13A, CAV2 (associated with long QT), CACNA1D and PXDNL.

We found no differences in the prevalence of spontaneous type 1 pattern considering gene mutation or mutation pathogenicity. A non-significant trend to higher arrhythmic risk was observed in pts presenting genetic mutations (either KPM, MPP or MUS), Long-Rank: 1.743, p=0.187.

Conclusion

Gene mutations are identified in a minority of BrS pts, mostly at SCN5A gene. No association was noticed between genetic test results and the ECG pattern. However, pts with identified mutation presented a tendency to higher arrhythmic risk. At present time, genetic tests in BrS are only relevant for familial screening, but long-term collection of data is crucial to elucidate the genotype-phenotype relation and arrhythmic risk.

Funding Acknowledgement

Type of funding sources: None.
Characterization of sudden death etiologies in a Portuguese population younger than 40 years-old
Authors: Carrington M , Henriques De Gouveia R , Corte-Real F , Goncalves L , Providencia R
Published: October 2022

Background

The incidence and pathogenesis of sudden death (SD) in the young adult population in Portugal remains to be clarified. Some of the causes are known to be hereditary and a better understanding of these can have implications on the development of a national screening program for relatives of SD victims.

Purpose

To describe the leading causes of sudden cardiac and non-cardiac death in a young adult Portuguese population (≤40 years-old).

Methods

The authors retrospectively reviewed cases from a national database regarding individuals who underwent an autopsy, between 2012 and 2016, at 6 districts of mainland Portugal plus the islands. All young adults (1–40 years-old) who had a sudden unexpected death were included and violent deaths were excluded. This study was approved by the Institute Ethics Committee. We reviewed the autopsy files and collected demographic, clinical, necropsic, anatomopathological and toxicological data from each case. We performed statistical analysis using Stata 13.0 software.

Results

During a 5-year period, out of an estimated total of 2101 deaths in ages 1 to 40, 175 SD were identified. SD victims had a mean age of 32±9 years-old, the majority being of male gender (69%,n=120). There were 115 (66%) cases of SD of confirmed cardiac origin (see Table 1). The remaining causes were respiratory (18%), cerebral (7%), digestive (6%), endocrinologic (2%), urinary (1%), infectious (1%). The most frequent cardiac cause being coronary atherosclerosis (n=40,35%), which included lesions with estimated luminal narrowing >75% and/or documented type 1 acute myocardial infarction. These patients were older (31±8 vs 35±4, p<0.020), had a minimum age of 26 years, and more frequently male (85% vs 61%, p=0.011). There were 17 (15%) victims who had cardiopathy with histopathological hypertrophy (5 of them with associated fibrosis), and the diagnosis of hypertrophic cardiomyopathy (HCM) was possible in only 3 (3%) victims. In addition, there were 15 (13%) who died from pulmonary embolism who were predominantly women (23% vs 80%, p<0.001). There were 8 (7%) victims with a final diagnosis of cardiopathy with histopathological dilation, 2 possibly corresponding to post-partum cardiomyopathy (CMP), 1 to ethanolic CMP and 1 to ventricular dilation and fibrosis due to previous myocarditis, who had associated hepatitis with signs of activity. Six cases of acute myocarditis were identified, who were significantly younger, comparing to patients dying from other cardiac causes (23±13 vs 33±7, p=0,011). There were 2 cases of HCM with genetic data, one of which was complemented during molecular autopsy.

Conclusions

During a 5-year period, the cumulative incidence of SD in a region of Portugal is very low (n=175), cardiac causes being present in 66% of the cases. The most frequent cardiac cause is coronary atherosclerosis (35%).

Funding Acknowledgement

Type of funding sources: None.
Late gadolinium enhancement is a strong predictor of life threatening arrhythmias in patients with dilated cardiomyopathy undergoing ICD implantation for primary prevention of sudden cardiac death
Authors: Lopes Da Cunha G J , Lopes P , Freitas P , Rocha B , Gomes D , Paiva M , Amador R , Abecasis J , Guerreiro S , Matos D , Rodrigues G , Carvalho M S , Mendes M , Adragao P , Ferreira A
Published: October 2022

Background

The usefulness of implantable cardioverter defibrillators (ICD) for primary prevention of arrhythmic sudden cardiac death (SCD) in patients with non-ischemic dilated cardiomyopathy (DCM) has been questioned. Efforts to improve risk stratification have included scores such as the “MADIT-ICD benefit score”, and the use of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR).

The purpose of this study was to evaluate the potential usefulness of these two tools to assess the risk of life-threatening arrhythmias in patients with non-ischemic DCM undergoing ICD implantation for primary prevention of SCD.

Methods

We conducted a single-center retrospective study of consecutive patients who underwent contrast-enhanced CMR before ICD implantation for primary prevention of SCD. Patients with ischemic cardiomyopathy were used as reference. Patients with non-dilated cardiomyopathies were excluded.

The arrhythmic component of the MADIT-ICD benefit score (VT/VF score) was calculated for each patient, and considered high if ≥7, as recommended.

The primary endpoint was the occurrence of SCD or life-threatening arrhythmias (VF or VT >200 bpm). Follow-up was performed by device interrogation in all patients except those who suffered SCD.

Results

A total of 151 patients (93 ischemic, mean age 62±13 years, 75% male) with mean left ventricular ejection fraction (LVEF) of 27±8% were included. Overall, 72% (n=67) ischemic and 45% (n=26) non-ischemic patients had scores ≥7 and were considered high-risk. LGE was present in all patients with ischemic cardiomyopathy, and in 76% (n=44) of patients with non-ischemic DCM.

During a median follow-up of 21 (8–38) months, 21 patients (13.9%, 11 ischemic and 10 non-ischemic) met the primary endpoint.

Overall, the event-free survival of non-ischemic patients was similar to that of ischemic patients (log rank p=0.269). In patients with non-ischemic DCM, there were 7 arrhythmic events (26.9%) in those with MADIT-ICD VT/VF scores ≥7, and 3 events (9.4%) in those with scores <7 (log rank p=0.104).

In the same population, there were 10 arrhythmic events (23%) in patients with LGE, but no events in patients without LGE (log rank p=0.036).

LVEF was similar in patients with and without arrhythmic events (26±8% vs. 27±7%, p=0.717), and in those with and without LGE (26±7% vs. 28±9%, p=0.342).

Conclusion

The presence of LGE is a strong predictor of life threatening arrhythmias in patients in non-ischemic DCM undergoing ICD implantation for primary prevention, seemingly outperforming the clinical MADIT-ICD benefit score.

Funding Acknowledgement

Type of funding sources: None.
High prevalence of malignant ventricular arrhythmias in patients with early-stage left ventricular noncompaction
Authors: Sivilotti F , Villatore A , Berg J , Romano S C , Parciante A , Pili G , Fioravanti F , El Sawaf B , Sala S , Della Bella P , Peretto G
Published: October 2022

Background

Early-stage left ventricular non compaction (LVNC) is a nonischemic cardiomyopathy characterized with nondilated phenotype and unpredictable risk of malignant ventricular arrhythmias (MVA).

Purpose

To report the occurrence of MVA in patients with early-stage LVNC.

Methods

Consecutive patients (n=63) diagnosed with LVNC according to recognized criteria either on transthoracic echocardiogram or cardiac magnetic resonance were retrospectively enrolled. Patients with late-stage LVNC, defined by a coexistent dilated cardiomyopathy phenotype, were excluded (n=49). Patient-tailored medical treatment, as well as ICD implantation strategies, were based on the updated ESC guidelines integrated by the experience of a referral center for arrhythmia management. The study endpoint was the occurrence of MVA (defined as sustained VT, VF, or appropriate ICD therapy) by 5-year follow-up.

Results

The study cohort consisted of 14 patients (mean age 37±17 y, 64% males), presenting with palpitation (n=4), syncope (n=4), or dyspnea on effort (n=6). LVNC was diagnosed by echocardiogram and cardiac magnetic resonance in 13 and 1 patients, respectively. Because of nonmalignant VA, seven patients (50%) underwent ICD implant before discharge. By 5-year follow-up, 5 patients (36%) experienced MVA, including VF or appropriate ICD shocks for fast VT. Left ventricular ejection fraction (LVEF) ≥45% was the only factor associated with the occurrence of MVA (5/11 event in cases with LVEF ≥45% vs. 0/3 events in controls with LVEF <45%; p=0.145). Baseline features, including age, gender, NC/C ratio, and clinical presentation were comparable between cases with LVEF ≥45% and controls, all p>0.05. Drug treatment, including RAAS inhibitors, betablockers and antiarrhythmics was also comparable.

Conclusions

Our preliminary data show that in early-stage LVNC the occurrence of MVA is higher for patients with LVEF ≥45%. Efforts are needed to identify earlier predictors of arrhythmic risk, to improve patient selection for ICD implant.

Funding Acknowledgement

Type of funding sources: None.
Prediction of programmed ventricular stimulation inducibility using machine learning in post-myocardial infarction patients at risk for sudden cardiac arrest with preserved ejection fraction ≥40%
Authors: Xintarakou A , Arsenos P , Gatzoulis K , Manis G , Trachanas K , Soulaidopoulos S , Dilaveris P , Doundoulakis I , Kordalis A , Laina A , Xydis P , Tsimos K , Korantzopoulos P , Kolettis T , Tsioufis K
Published: October 2022

Introduction

Sudden cardiac death (SCD) in post myocardial infarction (post-MI) patients with a relatively preserved left ventricular ejection fraction (LVEF ≥40%) has 1% annual incidence. In the PRESERVE-EF study, we used a two-step SCD risk stratification approach to detect patients with a relatively preserved left ventricular ejection fraction ≥40% at risk for major arrhythmic events. Seven noninvasive risk factors (NIRFs) were extracted from ambulatory electrocardiography. Patients with at least one NIRF present were referred for invasive programmed ventricular stimulation (PVS). Inducible patients received an ICD.

Purpose

The present study examines the performance of machine learning technology for the prediction of the inducible patients in PRESERVE-EF study.

Methods

After first step screening with NIRFs, 152 out of 575 patients underwent PVS and 41 of them were inducible. For the present analysis, data from these 152 patients were analysed. We used machine learning of NIRFs to predict these inducible high risk patients. We selected as classification method the Nearest Neighbour (NN) algorithm, after experimentation with several classifiers. NN classifies each subject according to the class of the N nearest neighbours. For each subject, we created a vector with the following 7 features: SAECG Late Potentials, Ventricular Premature beats ≥30/hour, Non-sustained Ventricular Tachycardia ≥1 episode (s)/24 hours, Fredericia corrected QT interval ≥45 0ms, SDNN/HRV ≤75 ms, T Wave Alternans ≥65 μV, Combined Deceleration capacity (DC) ≤4.5 ms and Heart Rate Turbulence Onset (To) ≥0% and Heart Rate Turbulence Slope (Ts) ≤2.5 ms.

Results

The achieved accuracy reached up to 72.2% when N was set to 7. We had totally 144 samples, 41 of which were inducible high risk patients. Results were similar for other values of N. To ensure independence of train and test sets, we employed 10-fold cross validation.

Conclusions

Inducible on PVS patients in PRESERVE-EF study were predicted with machine learning classification of NIRFs.

Funding Acknowledgement

Type of funding sources: None.
Risk factors for the development of premature ventricular complex-induced cardiomyopathy: a systematic review and meta-analysis
Authors: Serban T , Du Fay De Lavallaz J , Mezier J , Mertz L , Mannhart D , Kuehne M , Sticherling C , Badertscher P
Published: October 2022

Background

Premature ventricular complexes (PVCs) can be a reversible cause of heart failure. To date, it is unclear which risk factors contribute to the development of impaired left ventricular function.

Objective

Systematically assessing risk factors for the development of PVC-induced cardiomyopathy (PVC-CM).

Methods

We performed a structured database search of the scientific literature for studies investigating risk factors for the development of PVC-induced Cardiomyopathy. We investigated the reporting of PVC-induced Cardiomyopathy risk factors (RF) and assessed the comparative association of the different RF using random-effect meta-analysis.

Results

A total of 26 studies (9 prospective and 17 retrospective studies) involving 16.764.641 patients were analyzed (mean age 55 y, 58% women, mean PVC burden 17%). Suitable for quantitative analysis were 25 studies examining 6738 (0.04%) patients and 11 RF (≥3 occurrences in multivariable model assessing a binary change in left ventricular - LV- function). Among these risk factors, age (OR 1.02 per increase in the year of age, 95%-CI [1.01, 1.02]), the presence of symptoms (OR 0.18, 95%-CI [0.05, 0.64]), non-sustained VTs (OR 3.01, 95%-CI [1.39, 6.50]), LV origin (OR 2.20, 95%-CI [1.14, 4.23]), epicardial origin (OR 4.72, 95%-CI [1.81, 12.34]), the presence of interpolation - PVCs that do not reset the RR interval (OR 4.93, 95%-CI [1.66, 14.69]) and overall PVC burden (OR 1.06, 95%-CI [1.04, 1.08]) were all significantly associated with PVC-induced Cardiomyopathy. (Figures 1,2)

Conclusion

In this meta-analysis, the most consistent risk factors for PVC-CM were age, non-sustained VTs, LV and epicardial origin, interpolation, and PVC burden, while the presence of symptoms significantly reduced the risk. These findings help tailor stringent follow-up to patients presenting with frequent PVCs and normal LV function.

Funding Acknowledgement

Type of funding sources: None.
Implantable defibrillator-detected heart failure status predicts ventricular tachyarrhythmias
Authors: Compagnucci P , Casella M , Bianchi V , Giano A , Calo' L , Bertini M , Santini L , Savarese G , Santobuono V E , Mattera A , Lavalle C , Amellone C , La Greca C , Dello Russo A
Published: October 2022

Background

The occurrence of ventricular tachyarrhythmias is associated with increased mortality and hospitalizations for heart failure in implantable cardioverter defibrillator (ICD) patients. Nonetheless, the temporal relationship between heart failure worsening and ventricular tachyarrhythmias has been scarcely explored so far.

Purpose

We hypothesized that in patients with heart failure and reduced ejection fraction with ICDs, physiological sensor-based heart failure status, as reflected in the HeartLogic index, would predict appropriate device therapies for ventricular tachyarrhythmias (shocks and antitachycardia pacing).

Methods and results

568 patients implanted with ICDs (n=410, 72%) or cardiac resynchronization therapy-defibrillators (CRT-D, n=158, 28%) endowed with the HeartLogic algorithm were included in this prospective observational multicenter analysis. Over a follow-up of 25 [25th-75th percentile: 15–35] months, 122 (21%) patients received an appropriate device therapy (shock, n=74, 13%), while the HeartLogic index crossed the threshold value 1200 times (0.71 alerts/patient-year) in 370 subjects (65%). The occurrence of at least one HeartLogic alert was significantly associated with both appropriate shocks (HR: 2.44, 95% CI: 1.49–3.97, p=0.003) and any ICD therapies (HR: 1.95, 95% CI: 1.37–2.85, p=0.003). Using a time-dependent Cox model, the weekly IN-alert state was the strongest predictor of ICD shocks (HR: 2.94, 95% CI: 1.73–5.01, p<0.001), after correction for age, secondary prevention, and use of CRT. As compared to clinically stable subjects with no therapies, patients experiencing shocks had significantly higher baseline values of the HeartLogic index, third heart sound amplitude, and respiratory rate. Beginning about one month prior to the arrhythmic event, we noticed further increase of the combined index and the third heart sound amplitude, a decrease of thoracic impedance, and higher resting heart rate (Figure 1).

Conclusions

The HeartLogic index is an independent predictor of appropriate defibrillator therapies. The combined index and its individual physiological components change well before the arrhythmic event, suggesting the existence of a window of opportunity to prevent shocks.

Funding Acknowledgement

Type of funding sources: None.
Safe electrophysiologic profile of the neprilysin-inhibitor sacubitril in combination with different antiarrhythmic drugs
Authors: Frommeyer G , Mengel C , Wolfes J , Eckardt L , Ellermann C
Published: October 2022

Background

Observational clinical data suggest a direct effect of sacubitril on cardiac electrophysiology. However, data concerning the impact of combination of sacubitril with antiarrhythmic drug therapy is sparse.

Purpose

We aimed at characterizing the electrophysiologic effects of a combination therapy of sacubitril with the class III-drug sotalol and the class IB-agent mexiletine in a sensitive, experimental whole-heart model.

Methods and results

25 isolated rabbit hearts were retrogradely perfused. Hearts were treated with mexiletine (25 μM, 13 hearts) or sotalol (100 μM, 12 hearts) after generating baseline data. Eight endo- and epicardial monophasic action potentials and ECG recordings demonstrated an abbreviation of action potential duration (APD90, −21 ms, p<0.01) and no significant changes of QT interval (+10ms, p=ns) after administration of mexiletine. Spatial dispersion of repolarization (SDR) remained stable after mexiletine treatment (+6 ms, p=ns) whereas effective refractory periods (ERP) were significantly prolonged (+80 ms, p<0.01). Sotalol prolonged cardiac repolarization (APD90: +1 ms, p=ns; QT: +24 ms, p<0.01) and amplified spatial dispersion (+19 ms, p<0.01) without changing ERP (+8 ms, p=ns). Additional treatment with sacubitril (5 μM) led to a significant reduction of APD90 (−12 ms, p<0.01), QT interval (−20 ms, p<0.01) and ERP (−23 ms, p<0.01) in the presence of a stable SDR (−4 ms, p=ns) in the mexiletine group. In the sotalol group, additional administration of sacubitril abbreviated APD90 (−9 ms, p<0.05) and QT interval (−13 ms, p<0.01) and reduced ERP (−18 ms, p<0.01) without affecting SDR (−3 ms, p=ns). Ventricular vulnerability was assessed by a predefined pacing protocol employing premature extra stimuli and burst stimulation. After lowering the potassium concentration, 30 episodes of torsade de pointes tachycardia were observed after sotalol treatment (vs. 0 episodes under baseline, p<0.05). Additional sacubitril treatment significantly suppressed torsade de pointes tachycardia (8 episodes, p<0.05) in the sotalol-group. No proarrhythmic effect was observed after mexiletine treatment (8 episodes vs. 3 episodes under baseline conditions, p=ns). Additional sacubitril treatment did not increase ventricular vulnerability (32 episods, p=ns).

Conclusion

Sacubitril in combination with antiarrhythmic drugs demonstrates a safe electrophysiologic profile. In class IB- and class III-pretreated hearts, sacubitril abbreviates cardiac repolarization duration and effective refractory periods without changing spatial dispersion of repolarization. Thereby, sacubitril reduces the occurrence of torsade de pointes-tachycardia in antiarrhythmic pretreated hearts.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Deutsche Stiftung für Herzforschung (to G.F.)