bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting cardiovascular risk traits from pet myocardial perfusion imaging with deep learning
Authors: Juarez-Orozco L , Yeung M.W , Knol R.J.J , Benjamins J.W , Ruijsink B , Martinez-Manzanera O , Knuuti J , Asselbergs F , Van Der Zant F.M , Van Der Harst P
Published: November 2020

Background and aim

Deep Learning has revolutionised image analysis and its implementation in cardiology is rapidly advancing. DL offers the possibility to abstract highly-complex patterns from any image in order to optimise classification and prediction tasks. At the same time, positron emission tomography (PET) represents the reference technique for quantitative evaluation of myocardial perfusion and is a powerful tool for the diagnosis of myocardial ischemia and infarction. Although pathological perfusion patterns in PET are easily recognised by expert clinicians, it is unclear whether PET images harbour complex patterns inherent to traditional cardiovascular risk traits (factors) recognisable in an individual-patient basis. Hence, we aimed to deploy Deep Learning in order to predict cardiovascular risk traits from individual quantitative PET myocardial perfusion images.

Methods

Data form 1180 patients evaluated through quantitative N13-ammonia PET-imaging for suspected myocardial ischemia was analysed. We implemented transfer learning with fine-tuning of individual concatenated instances of an ImageNet pre-trained convolutional neural network (ResNet-50). From each PET scan, the 3 standard quantitative polar maps (rest/stress/perfusion reserve) were used as network input. A 5-fold cross validation policy was applied to training and validation for hyperparameters optimisation. Deep Learning modelling was deployed to independently predict: sex, smoking, arterial hypertension, dyslipidemia and type 2 diabetes mellitus as cardiovascular risk traits. Final model performance was evaluated through AUC and accuracy (with associated standard deviations [SD]) on a hold-out test set of 104 scans. Deep Learning-based heat maps were generated to identify regions of interest in PET imaging related to each of the predicted risk trait

Results

Deep Learning was able to strongly predict sex (0.87±0.04, 78%±4) and diabetes mellitus (0.75±0.13,71%±8), while its performance was only discrete for smoking (0.63±0.11, 85%±2), hypertension (0.61±0.06,58%±3) and dyslipidemia (0.59±0.05,57%±3), albeit all statistically significant (p<0.01).

Conclusion

Deep Learning is able to significantly predict cardiovascular risk traits from individual quantitative PET myocardial perfusion images. This suggests the existence of complex high-dimensional and localised features within cardiac imaging that relate to cardiovascular risk factors at the individual level, which definitely warrants further research.

Funding Acknowledgement

Type of funding source: None
The effects of chemotherapy on arterial inflammation assessed by 18 FDG PET-CT in patients with Lymphoma
Authors: Solomou E , Koutagiar I , Ioakimidis N , Terentes-Printzios D , Georgakopoulos A , Pouli A , Sioni A , Karakitsios I , Kafouris P , Gaitanis A , Pianou N , Aggeli C , Tousoulis D , Vlachopoulos C , Anagnostopoulos C
Published: November 2020

Introduction

Anti-cancer treatment can lead to increased cardiovascular morbidity among lymphoma survivors. This may be the result of direct effect of treatment on heart function, or indirect acceleration of atherosclerosis. 18F-fluorodeoxyglucose (FDG) uptake is a sensitive and robust marker for assessment of atherosclerotic inflammation.

Purpose

To investigate the effects of chemotherapy on arterial inflammation using FDG-PET CT in patients with lymphoma.

Methods

Fifty nine (mean age 58±17 years) patients with Hodgkin (n=39) or non-Hodgkin lymphomas (n=20) underwent 18FDG PET-CT imaging at baseline, interim and after completion of chemotherapy as part of their routine protocol. Arterial inflammation was assessed by arterial target to background ratio (TBR) of the aortic wall along the entire aorta. The index vessel TBR (the vessel with the higher value at baseline) was used for assessment of arterial inflammation. Patients with Hodgkin Lymphomas (HL) underwent therapy with Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The interim of their treatment was set at 1 to 3 days prior to initiating the 3rd chemotherapy cycle. Patients with non Hodgkin Lymphomas (NHL) underwent therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone+rituximab (R-CHOP). The interim of their treatment was set at 2 weeks post the 4th chemotherapy cycle. All patients we reassessed 6 weeks after chemotherapy completion.

Results

There were no differences in age and atherosclerotic risk factors (hypertension, diabetes, dyslipidemia and smoking), between the two groups (all P>0.05). Similarly, there were no differences in mean (±SD) index vessel TBR between HL and NHL patients (2.4±0.7 vs 2.7±0.9, respectively, P=0.65). In the whole study population the index vessel TBR progressively decreased after the end of therapy (by 0.53±0.11, from baseline to 6 weeks following the end of therapies) (F=10.94, P<0.001, ANOVA). The index vessel TBR decreased in both HL and NHL patients at 6 weeks after therapy compared to baseline level (all P<0.01, ANOVA, figure). The decrease at the interim scan was more pronounced in NHL compared to HL patients, however at 6 weeks after chemotherapy completion the index vessel TBR decreased further in patients with HL, while it increased slightly compared to interim levels in NHL patients (figure 1).

Conclusion

Arterial inflammation is reduced during and post-chemotherapy in patients with lymphoma. The index vessel TBR changes at the interim phase and 6 weeks after therapy completion indicate a different effect of specific treatment regimes in arterial inflammation between HL and NHL patients.

Figure 1

Funding Acknowledgement

Type of funding source: None
Left atrial late gadolinium enhancement is associated with atrial fibrillation as detected by continuous monitoring
Authors: Bertelsen L , Diederichsen S.Z , Haugan K.J , Brandes A , Graff C , Krieger D , Kronborg C , Kober L , Peters D.C , Olesen M.S , Hojberg S , Vejlstrup N , Svendsen J.H
Published: November 2020

Background

Left atrial late gadolinium enhancement (LA LGE) measured with cardiac magnetic resonance (CMR) imaging is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures. However, the prognostic value of LA LGE for incident AF remains unknown.

Methods

CMR including measurement of left ventricular (LV) and LA volumes and function, as well as LV extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received and implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists.

Results

Patients were monitored for AF with implantable loop recorder during a median of 41 [36; 43] months. AF episodes lasting ≥6 minutes were detected in 32 patients (47%) and 16 patients (24%) experienced AF episodes lasting ≥5.5-hour. In Cox regression analyses adjusted for sex, age and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratio for time to AF episodes lasting ≥6 minutes and ≥5.5 hours were 1.40 (1.03, 1.89) per 10 cm2 increase (p=0.03) and 1.63 (1.11, 2.40) per 10 cm2 increase (p=0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value.

Conclusions

Extent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Innovation Fund Denmark, The Research Foundation for the Capital Region of Denmark [no grant number]
Predictors for rapid progression of coronary calcification: an optical coherence tomography (OCT) study
Authors: Nakajima A , Araki M , Kurihara O , Minami Y , Soeda T , Higuma T , Kakuta T , Lee H , Malhotra R , Nakamura S , Jang I.K
Published: November 2020

Background

The natural progression of coronary calcification has not been systematically studied. In vivo coronary calcium can be evaluated by OCT.

Purpose

To identify the incidence and predictors for rapid progression of coronary calcification.

Methods

Patients with serial OCT imaging at baseline and at 6 months were selected from our database. Changes in calcium index during 6-month follow-up and predictors for progression of calcification were studied. Calcium index was defined as the product of the mean calcium arc and calcium length. Rapid progression of calcification was defined as an increase in calcium index above the median value.

Results

Among 187 patients who had serial OCT imaging, 235 calcified plaques were identified in 108 patients (57.8%) at baseline with median calcium index of 132.0 (Interquartile range 58.5–281.2). After 6 months, the calcium index increased in 95.3% of calcified plaques from 132.0 to 178.2 (p<0.001). In multivariable analysis, diabetes mellitus (DM), chronic kidney disease (CKD), lipid-rich plaque, and macrophages were found to be independent predictors for rapid progression of coronary calcification (table). Interestingly, rapid progression of calcification was associated with a significant reduction of inflammatory features (thin-cap fibroatheroma [TCFA]; baseline 21.2% vs. follow-up 11.9%, p=0.003, macrophages; baseline 74.6% vs. follow-up 61.0%, p=0.001).

Conclusions

This study demonstrated that DM, CKD, lipid-rich plaque, and macrophages were independent predictors for rapid progression of coronary calcification. High level of vascular inflammation may stimulate rapid progression of calcification.

Funding Acknowledgement

Type of funding source: None
Beneficial electrophysiologic effects of sacubitril in different arrhythmia syndromes
Authors: Frommeyer G , Dimanski D , Ellermann C , Wolfes J , Eckardt L
Published: November 2020

Background

Previous studies report conflicting data regarding anti- or proarrhythmic effects of sacubitril. The aim of the presents study was to assess the impact of sacubitril in different arrhythmia models.

Methods and results

In 12 isolated rabbit hearts, sacubitril was infused in rising concentrations (3, 5, 10μM) after obtaining baseline data. In 12 further hearts, erythromycin was administered to simulate long QT syndrome-2 (LQT2). Other 12 hearts were perfused with veratridine to mimic long QT syndrome-3 (LQT3). Both LQT groups were treated with sacubitril (5μM). Ventricular vulnerability was assessed by a pacing protocol. AV-blocked bradycardic hearts were perfused with a hypokalemic solution to trigger torsade de pointes (TdP). In further 13 hearts, AF was induced by a combination of acetylcholine and isoproterenol (ACH/ISO) and sacubitril (5μM) was added afterwards. With sacubitril, action potential duration (APD) was abbreviated whereas spatial dispersion of repolarization (SDR) remained stable. In both LQT groups, APD and SDR were increased. Infusion of sacubitril reduced APD and SDR in the LQT2-group (APD: −21 ms, p<0.05; SDR: −8 ms, p=ns) and did not alter APD but reduced SDR in the LQT3-group (APD: +2 ms, p=ns; SDR: −9 ms, p<0.05). Ventricular vulnerability was not altered by sacubitril. No TdP were observed with sacubitril treatment or under baseline conditions in any group. Erythromycin provoked 43 episodes of TdP (p<0.05). Additional treatment with sacubitril significantly suppressed TdP (3 episodes, p<0.05). With veratridine, 16 episodes of TdP (p=0.07) occurred. Further treatment with sacubitril did not reduce TdP (10 episodes, p=ns) significantly. Infusion of ACH/ISO led to an increased inducibility of atrial fibrillation (31 vs. 7 episodes). Additional infusion of sacubitril increased atrial ERP (+21ms, p<0.05) and reduced inducibility of AF (9 episodes).

Conclusion

Sacubitril abbreviated APD and was not proarrhythmic. SDR is a major pathomechanism of TdP and was reduced by sacubitril in both LQT groups. Thereby, sacubitril exhibits antiarrhythmic effects in LQT2 and may be beneficial in LQT3. Furthermore, sacubitril suppressed AF by prolonging aERP. Our results indicate beneficial effects of sacubitril on cardiac electrophysiology.

Funding Acknowledgement

Type of funding source: None
Splice site mutation of LMNA causes severe dilated cardiomyopathy via strong dominant reduction of total lamin expression
Authors: Kato K , Ohno S , Sonoda K , Makiyama T , Ozawa T , Horie M
Published: November 2020

Objective

LMNA is a known causative gene of dilated cardiomyopathy (DCM) and familial cardiac conduction disturbance (CCD). Genetic variants affecting the pre-mRNA splicing process often lead to premature stop codons and result in nonsense-mediated mRNA decay (NMD), followed by degradation of mutated alleles. The misssense variant LMNA c. 936G>C was previously reported in a French family affected by muscular dystrophy, CCD, and DCM, but no detailed analysis has been performed. We so far identified the same variant in two Japanese families affected by CCD and DCM. In this study, we investigated the molecular consequences of the variant located at the last codon of LMNA exon5 to demonstrate its pathogenicity.

Methods

Genomic DNA and total RNA were isolated from patients' peripheral blood lymphocytes or cardiac tissue. LMNA-coding exons were screened by direct sequencing. Complementary DNAs (cDNAs) were generated by reverse transcription PCR from RNA. Quantitative PCR (qPCR) was performed to quantify the LMNA cDNA amount by using specific primers for lamins A and C. The protein expressions of both isoforms were analyzed by western blotting.

Results

We detected the heterozygous LMNA c.936 G>C (p. Q312H) variant at the end of exon 5 by genomic DNA sequencing in two unrelated Japanese families (figure. pedigree) affected by DCM and CCD. In a genomic database survey, we did not find the variant in either gnomAD, TogoVar, or the Human Genetic Variation Database. The two commonly used splice site predictor tools, NetGene2 and FSPLICE, estimated that this site was a splice donor site. Sequencing of cDNA demonstrated that the mutated allele was absent. By qPCR assay, we confirmed a 90% reduction in LMNA cDNA. Western blot analysis revealed that lamin A and C expression was reduced far more than 50% (figure. western blot).

Conclusions

We report a LMNA missense mutation found in two families, which disrupts a normal splicing site, leads to NMD, and resulted in severe cardiac laminopathy. The drastic reductions of lamin expression at the cDNA and protein levels suggested that other co-existing mechanisms may also have suppressed the expression of the healthy wild type allele.

Pedigree and western blot assay

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science KAKENHI
The repolarization pattern of ARVC patients, healthy gene carriers and controls as analyzed with a 252-leads Body Surface Mapping Vest
Authors: Kommata V , Elshafie M.I , Perez M , Augustine R , Blomstrom-Lundquist C
Published: November 2020

Background

Repolarization abnormalities have a central role on the diagnosis of ARVC according to recent HRS consensus document from 2019 stating that T wave inversion in the right precordial leads is a major criteria if it appears in V1-V3 or a minor criteria if it appears in only V1-V2.

Purpose

The aim of our study was to investigate whether repolarization patterns as recorded by a Body Surface Mapping (BSM) system consisting of a vest with 252 ECG leads, could differentiate ARVC patients and even gene carriers from normal individuals. Our hypothesis is that the method can potentially identify repolarization disturbances earlier or better than conventional 12-lead ECG.

Method

12 definite ARVC patients, 20 healthy gene carriers and 8 family members who tested negative for the family mutation (controls) were included. All patients underwent 12-lead ECG, including right precordial leads (V4R) and BSM recordings. Repolarization (T-wave polarity and concordance with QRS complex vector) was analyzed qualitatively in all BSM recordings, the results of which were displayed on a color code map (fig.1).

Results

The mean age was 49.6, 43.6 and 38.8 years in ARVC patients, healthy gene carriers and controls, respectively. The number of males in the three groups were 8/12, 8/20 and 5/8, respectively.

All 8 controls had similar repolarization patterns with negative and concordant T waves on the right back panel, and T waves that successively changed from negative concordant (green) to positive disconcordant (red) and finally positive concordant (blue) on the left front panel (pattern 1). All 12 ARVC patients had different repolarization patterns as compared to the controls. Two of these patients had no apparent repolarization changes on conventional 12 lead ECG. The pattern type 2 repolarization, as defined by same pattern as the controls at the right back panel but different pattern at the front left panel was seen in 3/12 ARVC patients. The remaining 9 ARVC patients had different repolarization patterns both on the front and on the back panel (pattern 3). Among gene carriers, 15 had a normal repolarization pattern (pattern 1) and 5 demonstrated an abnormal repolarization pattern (4 had pattern type 2 and one pattern 3) despite normal surface ECG.

Conclusions

Using BSM recordings, abnormal repolarization patterns can be detected in all ARVC patients, even in those without repolarization changes on conventional surface ECG. The observation that 25% of gene carriers had divergent repolarization patterns, may indicate an early stage of the disease, and be used as an early diagnostic marker of the disease. Further and larger studies are warranted to confirm these observations.

Repolarisation patterns recorded by BSM

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Selanders Stiftelse
Comparison of variant detection rate in genes between two cohorts of Czech living patients versus victims of sudden cardiac death with clinical / post mortem diagnosis of non-ischemic cardiomyopathy
Authors: Borisincova E , Votypka P , Rucklova K , Pilin A , Kulvajtova M , Pohlova Kucerova S , Tavacova T , Kubanek M , Petrkova J , Dobias M , Tomasek P , Macek Jr M , Janousek J , Krebsova A , Kautzner J
Published: November 2020

Introduction

Hereditary cardiomyopathy is associated with an increased risk of ventricular arrhythmia and sudden cardiac death (SCD). Genetic stratification substantiates risk assessment and enables the primary prevention of SCD in relatives at risk. We have analyzed the genetic aetiology of SCD in a representative Czech cohort with post mortem diagnosis of various forms of cardiomyopathy and compared it to living cases with these cardiac disorders.

Patients and methods

Between 2018 and 2019, altogether 47 victims of SCD with post mortem diagnosis of hypertrophic- (HCM; 18/47), arrhythmogenic- (ACM; 19/47) and dilated cardiomyopathy (DCM; 10/47) were identified. Concurrently, genetic testing was performed in 114 living patients (HCM 54/114, ACM 22/114, DCM 38/114). Genetic counselling and cardiologic examination had been carried out in first-degree relatives in all patients/SCD victims. Massively parallel sequencing (MiSeq platform; Illumina.com) was utilized for a custom-made panel comprising 100 candidate genes (Sophia Genetics, Switzerland). The presence of pathogenic variants was validated by Sanger DNA sequencing and through family segregation analyses.

Results

The causative detection rate (according to ACMG.net classes 4 or 5) in SCD victims with DCM was 60% (6/10) and in living patients with DCM 47.4% (18/38). Variants in TTN, RBM20, DES and FLNC (mainly truncating variants) prevailed in both groups. The detection rate in ACM was 5% (1/19 in SCN5A gene) in SCD victims and 31.8% (7/22) in living patients. Interestingly, the most prevalent mutated gene PKP2 in living patients was not detected in SCD victims. The detection rate in SCD victims with post mortem diagnosis of HCM was 16% (3/18) and in living patients 35% (19/54). The most prevalent gene was MYBPC3 in both groups, while PRKAG2 was detected in one SCD victim and in one living case who survived cardiac arrest.

Conclusion

Post-mortem genetic analysis in DCM yields a high detection rate and allows potentially effective primary prevention of SCD in relatives at risk. In contrast, the molecular autopsy of HCM and ACM renders a much lower yield which is below the mutation detection rate in living phenotype positive individuals. The results help to improve the genetic counselling in affected families in Czech Republic.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic
Altered auto-phosphorylation of novel TNNI3K variants associated with AV-nodal re-entry tachycardia and conduction disease
Authors: Pham C , Munoz-Martin N , Podliesna S , Milano A , Beekman L , Vermeer A , Frantzen C , Jansen S , Van De Laar I , Nieuwhof K , Christiaans I , Bezzina C.R , Lodder E.M
Published: November 2020

Background

In the past decade, we and others have reported three families with rare genetic variants in TNNI3K, encoding the cardiac-specific troponin-I interacting kinase (TNNI3K), co-segregating with a mixed, but highly penetrant, cardiac phenotype that features predominant atrial/junctional tachycardia occurring in combination with cardiac conduction disease and dilated cardiomyopathy. We demonstrated that while the p.Thr539Ala and p.Gly526Asp TNNI3K variants had decreased auto-phosphorylation activity the p.Glu768Lys variant, present in 3 independent families, leads to increased auto-phosphorylation levels, in line with the finding that increased levels of Tnni3k expression are associated with slower atrial-ventricular conduction in mice.

Objective

Identifying new genetic variants in the TNNI3K gene associated with cardiac disease and assessing their impact on TNNI3K auto-phosphorylation levels.

Methods

Through next generation sequencing of a panel of genes associated with cardiac disease we assessed TNNI3K in patients with cardiac arrhythmias and cardiomyopathies. All variants identified were assessed in vitro for effects on auto-phosphorylation. Briefly, wild-type and mutant TNNI3K constructs were transfected into HEK293 cells, protein was extracted after 48 hours and analyzed with anti-flag and anti-phospho-tyrosine antibodies on Western blot.

Results

We identified 7 novel and rare variants in TNNI3K in 11 additional probands, with predominantly cardiac conduction disease, with or without dilated cardiomyopathy, and atrial-ventricular-re-entry-tachycardia (AVNRT). Of these, multiple variants were found to have aberrant auto-phosphorylation including almost absent auto-phosphorylation capacity for one (TNNI3K-p.Val510Leu). All three-independent wild type TNNI3K transfected HEK293 cell lysates showed similar phosphorylated TNNI3K levels and the kinase-dead negative control demonstrated no phosphorylation activity.

Conclusion

We here present 7 novel genetic variants in TNNI3K in patients with a remarkable overlap in cardiac phenotype consisting mainly of AVNRT and cardiac conduction disease. We further show that some of these variants alter the auto-phosphorylation of TNNI3K. These results indicate a more prevalent role of variants in TNNI3K in human cardiac disease and a possible in vitro functional assay to assess the pathogenicity of such variants.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Dutch Research Council (NWO Talent Scheme VIDI-91718361)
Short and long-term outcomes of medical management of patients with a first episode of arrhythmic storm
Authors: Gonzalez De La Portilla-Concha C.M , Acosta Martinez J , Dominguez Cano J.L , Caballero Valderrama M.R , Abril Molina A , Campos Pareja A , Frutos Lopez M , Garcia Riesco L , Arana Rueda A , Pedrote Martinez A
Published: November 2020

Introduction

There is few data about long-term outcomes of conservative management (without catheter ablation) of patients with a first episode of arrhythmic storm (AS) in the current context. This study analyzes the short and long-term outcomes of implantable cardioverter defibrillator (ICD) patients with a first episode of AS receiving non-interventional management.

Methods

Consecutive patients admitted with a first episode of AS between January 2008 and June 2019 receiving medical management without catheter ablation were included. AS was defined as 3 or more appropriate ICD therapies occurring during a 24 h span. Medical management included: correction of triggers, sedation/mechanical ventilation, antiarrhythmic drugs, ICD reprogramming and neuraxial modulation. Baseline clinical characteristics and follow-up data were recorded. All patients were followed every 6 months at the ICD office. The primary end-point was all-cause mortality.

Results

60 patients (81% male, 62.8±16.2 years, 43% ischaemic, LVEF 35.4±14%) with a first episode of AS treated conservatively were included. Thirty-day survival was 96.5% and 1-year survival was 82%. During a median (interquartilic range) follow-up of 31 (6–69) months, 31 (51.7%) patients died (51.6% due to cardiovascular aetiology) and 35 (58.3%) patients were readmitted (48.5% due to recurrent arrhythmic events and 45.7% due to heart failure). Age [HR 1.05 (95% confidence interval: 1.01–1.08)] and end-diastolic diameter [HR 1.05 (95% confidence interval: 1–2)] were the strongest independent predictors of all-cause mortality.

Conclusion

Despite the severity of this entity, medical management (without catheter ablation) of a first episode of AS is reasonable given its good 30-day and 1-year survival. However, a high rate of AS recurrence and readmissions are observed during long-term follow-up. Efforts are needed in order to identify those patients with a first episode of AS that could benefit from an early catheter ablation strategy.

Funding Acknowledgement

Type of funding source: None
Diabetes mellitus is associated with higher risk of third degree atrioventricular block – a Danish nationwide registry study
Authors: Haxha S , Pedersen-Bjergaard U , Philbert B.T , Lindhardt T.B , Hoejberg S , Schjerning A.M , Ruwald M.H , Gislason G.H , Torp-Pedersen C , Bang C.N
Published: November 2020

Background

Diabetes mellitus (DM) is a risk factor for cardiovascular disease and sudden cardiac death. Increasing evidence shows that DM may be associated with electric disturbances including arrhythmias and atrioventricular block (AVB). However, the association of DM and AVB has never been confirmed in large studies.

Purpose

The present study aims to determine the association of DM and third-degree AVB.

Method

A nationwide nested case-control study of patients >40 years with third-degree AVB between 1995 and end of 2017, matched 1:2 on age and gender with controls from the Danish background population. DM was defined if patients were prescribed oral antidiabetics or insulin, or if they were diagnosed with an ICD10 code of DM type I or II. Data on medication, comorbidity, and outcomes were collected from Danish nationwide registries. Conditional logistic regression was used to estimate hazard ratio (HR) and 95% confidence intervals (95% CI) of third degree AVB.

Results

Out of a total population of 8,964,086, we located a total of 32,722 cases with third degree AVB, that were matched 1:2 with 65,422 controls, with a mean age of 75.3 years and 59.1% males. The case group had more DM 18,5% vs 13,3%, acute myocardial infarction 27,0% vs 16.0%, stroke 18.5% vs 16.2%, heart failure 20.0% vs 8.5% and chronic kidney disease 4.7% vs 2.5% compared to the control group. In multivariable analysis adjusted for comorbidities DM remained significantly associated with third degree AVB [HR 1.30 (95% CI: 1.25–1.35)] (Figure)

Conclusion

In this nationwide population study, DM was associated with a higher risk of third degree AVB compared to matched controls without DM. This suggests a low threshold for use of ECG evaluation in case of dizziness or syncope in DM patients, and further, that ECG should be a part of routine controls of DM patients.

Risk of third degree AV block

Funding Acknowledgement

Type of funding source: None
Risk factors for silent and symptomatic atrial fibrillation in an elderly population screening programme:a report from the noninvasive monitoring for early detection of atrial fibrillation (NOMED-AF)
Authors: Mitrega K , Sredniawa B , Stokwiszewski J , Sokal A , Boidol J , Wierucki L , Bleszynska E , Bandosz P , Rutkowski M , Zdrojewski T , Kazmierczak J , Opolski G , Grodzicki T , Lip G.Y.H , Kalarus Z
Published: November 2020

Background

It is important to determine the risk factors that predispose elderly subjects from the general population for symptomatic atrial fibrillation and atrial flutter (AF/AFl), but population-based data for silent AF (SAF) are limited.

Aim

To study risk factors for symptomatic AF and SAF in a general population screen for subjects age ≥65 where continuous monitoring was performed up to 30 days with a vest-based monitor.

Methods

The NOMED-AF study was a cross-sectional study based on a representative population sample (n=3014; mean age 77.5±7.9 years; F=1479). In 680 subjects AF/AFl (including 279 with SAF) was diagnosed. Independent risk factors for AF/AFl and SAF were determine on weighted data using multiple logistic regression.

Results

The independent risk factors for AF/AFl and SAF are summarised in the Table. There are nine independent risk factors for AF/AFl and eight for SAF. Revascularization and obesity were independently associated with patients with (symptomatic) AF/AFl, and CKD was associated with SAF. Other risk factors are common for AF/AFl and SAF.

Conclusions

AF/AFl and SAF have slightly different associated clinical risk factors in this representative population sample aged ≥65 years. This may facilitated targeted screening programmes for high risk subgroups, particularly for SAF.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): The research has received funding from the National Centre for Research and Development under grant agreement (STRATEGMED2/269343/18/NCBR/2016)
Association of QRS duration changes during ergonovine provocation test with arrhythmic complications
Authors: Im S.I
Published: November 2020

Background

Ergonovine is ergoline-derivatives that act at serotonin-receptors (5-HT2receptor). Influence of serotonin and 5-HT2 receptor agonist on cardiomyocytes has been known.

Purpose

However, there was limited data about the association between QRS duration changes during ergonovine provocation test (EPT) and arrhythmic complications.

Methods

A total of 182 patients who underwent coronary angiography (CAG) with EPT were consecutively enrolled (mean age; 53.9±10.4 years, 59.3% male) at our hospital from 2018 to 2019. ECGs recorded closest to the time of CAG were carefully reviewed and measured PR interval, QRS duration, QT and QTc intervals.

Results

41 (22.5%) patients had arrhythmic events including atrial, and ventricular tachycarrhythmia during follow-up. The patients with QRS prolongations had higher incidences of arrhythmic events compared with those without QRS changes (P=0.025). In univariate analysis, diabetes mellitus (P=0.05), coronary artery spasm (P=0.031) and QRS prolongations (P=0.036) were significantly associated with arrhythmic events. In multivariate analysis, QRS prolongations [OR 2.496 (1.077–5.784), P=0.033] was independent risk factors for arrhythmic events at the long-term follow-up. ROC curve analysis were performed to define cut-off point for arrhythmic events (QRS prolongation during EPT>10.6 msec [sensitivity = 0.972; specificity = 0.943]; AUC=0.632; P=0.015)

Conclusion

The patients with QRS duration prolongations during Ergonovine provocation test were associated with higher incidence of arrhythmic events, suggesting more intensive medical therapy with close clinical follow-up will be required.

Funding Acknowledgement

Type of funding source: None
Advanced interatrial block is associated with worst prognosis in patients with previous coronary acute syndrome
Authors: Garcia Talavera C.S , Acena Navarro A , Esteban-Chapel J.A , Camblor Blasco A , Franco Pelaez J.A , Pello Lazaro A.M , Lopez Castillo M , Martin Mariscal M , Hernandez Gonzalez I , Venegas Rodriguez A.M , Canovas Rodriguez E , Kallmeyer Mayor A , Tunon Fernandez J
Published: November 2020

Background

The interatrial block (IAB) has been directly related to the appearance of several atrial tachyarrhythmias. The objective of this study is to establish whether the duration of p wave could predict the appearance of atrial fibrillation (AF), death or stroke in patients with a previous acute coronary syndrome (ACS).

Methods

We have reviewed all ECG of patients with an ACS admitted to our hospital from July 2006 to June 2014 looking for advanced IAB defined as (P-wave duration was ≥120 ms and presented biphasic morphology), excluding those patients with previous AF and who received anticoagulant therapy. These patients were part of the population of the BACS & BAMI (Biomarkers in Acute Coronary Syndrome & Biomarkers in Acute Myocardial Infarction) studies. For all patients we have determined their cardiovascular risk factors. The primary outcome was a combined endpoint that included death, stroke and development of AF. Cox regression was used for the analysis.

Results

A total of 423 patients were included, the mean age was 67.8 years (± 14), and 72.3% were male. Only 12 patients (2.8%) presented advanced IAB. After a median follow-up of 54.7 months, there were 51 events (21 deaths (41.2%) were observed, 17 patients (33.3%) had experienced stroke, and 13 patients (25.5%) had developed AF). Patients with development of primary endpoint were older with higher rates of cardiovascular risk factors, advance IAB and diuretic treatment at discharge.

After a multivariate Cox regression analysis, advanced IAB [HR=2.65 (1.03–6.86); p=0.044], age [HR=1.06 (1.03–1.09) per year; p<0.001] and diuretic treatment at discharge of ACS [HR=1.87 (1.03–3.39); p=0.039] were independent predictors of worse prognosis.

Conclusion

Advanced IAB in ECG at admission with ACS could be a predictor of stroke, development of AF or death in follow up.

Funding Acknowledgement

Type of funding source: None
Electrocardiographic parameters among beta-thalassemia major patients
Authors: Patsourakos D , Aggeli C , Gatzoulis K , Delicou S , Dimitroglou Y , Androulakis A , Tousoulis D
Published: November 2020

Background/Introduction

The majority of beta thalassemia major (β-TM) patients suffer from cardiac disorders, while a significant proportion of them die suddenly. Twelve-lead and signal-averaged electrocardiography are simple, inexpensive, readily available tools for identifying an unfavorable arrhythmiological substrate by detecting the presence of arrhythmias, conduction abnormalities and late potentials (LPs) in these patients.

Methods

47 β-TM patients and 30 healthy controls were submitted to twelve-lead and signal-averaged electrocardiography. Basal rhythm, heart rate, PR interval duration, QRS complex duration and morphology, QTc interval duration and prevalence of LPs were recorded.

Results

β-TM patients demonstrated a more prolonged PR segment (167.74 msec vs. 147.07 msec) (p=0.043), a higher prevalence of PR prolongation (21.05% vs. 0%) (p=0.013) and a higher prevalence of LPs (18/47, 38.3% vs. 2/30, 6.7%) (p=0.002) compared with controls. In particular, every single SAECG parameter significantly differed among patients compared with controls. Among patients, left ventricular ejection fraction was marginally lower and QTc more prolonged among LPs positive subgroup compared with LPs negative subgroup. The prevalence of atrial fibrillation among b-TM patients was estimated at 10.64%.

Conclusions

β-TM patients have a higher prevalence of a prolonged PR segment, atrial fibrillation and LPs. Twelve-lead and SAECG performance was feasible in all subjects and constitutes a readily available tool for assessing myocardial electrophysiological alterations in this patient group, that could have significant impact on survival and quality of life with timely application of appropriate treatment.

Funding Acknowledgement

Type of funding source: None
Identifying at-risk subjects for sustained atrial high-rate episodes using the C2HEST score: the West Birmingham AF project
Authors: Li Y.G , Pastori D , Miyazawa K , Shahid F , Lip G.Y.H
Published: November 2020

Background

Sustained atrial high-rate episodes (SAHREs) (lasting >24h) was associated with unfavorable pragnosis.

Objectives

To evaluate the performance of the C2HEST score in assessing individuals' risk of SAHRE.

Methods

The West Birminghan Atrial Fibrillation (AF) Project included 500 consecutive non-AF patients with implantable cardiac electronic device. The role of the C2HEST score for SAHRE risk stratification was evaluated.

Results

SAHRE was detected in 8.8% of patients (2.09%/year, 95% CI 1.47–2.71) over a mean 4.4 years of follow-up. SAHRE was associated with increased all-cause mortality (P<0.001). The risk of SAHRE increased by C2HEST score (39% higher risk per point increase). The C2HEST score had moderate predictive capability (c-index 0.706 [0.615–0.798], log-rank P=0.003) for SAHRE, which was better than other clinical scores (CHA2DS2-VASc, CHADS2, HATCH).

Conclusions

The C2HEST score was predictive of SAHRE, which may help to identify at-risk subjects who may need intensive device review.

Central Illustration

Funding Acknowledgement

Type of funding source: None
Frequent premature atrial complexes and risk of concurrent atrial fibrillation
Authors: Johnson L.S.B , Napiorkowski N , Dziubinski M , Conen D , Healey J.S , Engstrom G
Published: November 2020

Background

Premature atrial complexes (PACs) predict incident atrial fibrillation (AF) in long-term follow-up studies. It is unclear whether frequent PACs on ambulatory ECG recordings indicate a higher likelihood of concurrent, undiagnosed AF. Furthermore, the reproducibility of a 24 h PAC count is unclear.

Objectives

To determine if frequent PACs on 24 h ambulatory ECG monitoring predicts concurrent AF during subsequent, prolonged ECG monitoring and to assess the diagnostic reliability of PAC counts on a 24 hour ECG recording.

Methods

AF was defined as ≥30 seconds of irregular rhythm without P waves, which was detected by a proprietary algorithm and manually verified. The proportion of AF occurrence during the remainder of the monitoring period was calculated for pre-specified levels of PACs during the first 24 h, and a function describing the association was fitted. The diagnostic reproducibility of a 24 h PAC count was assessed by calculating the likelihood of a PAC count ≥1000/day during the entire monitoring duration for prespecified PAC count levels during the first 24h.

Results

The study population comprised 20,973 patients (41% men, mean age 69.5 years) who had recorded an ambulatory ECG with a monitoring duration of 4–30 days in the United States during the year 2017 (median monitoring duration 16 days). AF was detected in 2,029 (9.7%) of patients and the median time to first occurrence of AF was 5 days. PAC frequency during the first 24 h was associated with AF during the monitoring period beyond the first 24 h, increasing steadily from 4.2% among those with 0–5 PACs, to a plateau around 17% among those with 250–1000 PACs per day and above. (Fig. 1A). The reproducibility of low PAC counts was good. Only 5.5% of patients with 0–5 PACs during the first 24 h of monitoring (31.8% of the population), had ≥1000 PACs on an alternate monitoring day. In contrast, among subjects with 100 PACs the probability of a day with ≥1000 PACs was close to 50% (Fig. 1B).

Conclusion

In patients undergoing ambulatory ECG monitoring, frequent PACs during the first 24 h indicate a higher likelihood of AF occurrence during subsequent days of monitoring. Less than 5 PACs during the first 24 h indicate a low probability of AF or frequent PACs on a subsequent day of ECG monitoring.

Figure 1

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): The Swedish Heart and Lung Foundation; The Swedish Heart and Lung Association
Relations between voltage mapping and diagnosis and genetics in patients with arrhythmogenic right ventricular cardiomyopathy
Authors: Delasnerie H , Mandel F , Domain G , Voglimacci Q , Mondoly P , Rollin A , Maury P
Published: November 2020

Introduction

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

Objective

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

Method

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

Results

44/70 fulfilled ARVC Task Force criteria and 25/70 had culprit mutations. Endocardial (38/44 vs 16/26, p=0.02) and especially infero-lateral scars (31/44 vs 9/26, p=0.003) were more often present in patients fulfilling Task force criteria vs suspected ARVC, with larger scars (area 23±27 vs 8±11 cm2, p=0.04, perimeter 17±10 vs 11±7 cm, p=0.03) (sensitivity 86%). Mutated patients had more infero-lateral (19/25 vs 21/45, p=0.01), multiple (12/20 vs 11/34, p=0.04) and larger scars (perimeter 21±10 vs 12±7 cm, p=0.01) vs non mutated patients. In patients with ARVC diagnosed according to the Task Force criteria, there was a trend toward more infero-lateral (p=0.09) and larger scars (p=0.08) in mutated cases. PKP2-mutated cases tended to have less ourflow tract (p=0.08) and less multiple scars (p=0.09) vs other mutations.

Conclusion

3D endocardial mapping could have an important role for ARVC diagnosis and may be able to detect minor forms with otherwise insufficiant criteria for diagnosis. More frequent and larger infero-lateral scars are present in mutated patients with bordeline differences according to the mutated genes.

Funding Acknowledgement

Type of funding source: None
Efficacy and safety of dronedarone vs placebo in patients with atrial fibrillation or atrial flutter across a spectrum of renal function: post hoc analyses of the EURIDIS-ADONIS trials
Authors: Thind M , Zareba W , Atar D , Crijns H , Zhu J , Pak H.-N , Reiffel J , Ludwigs U , Wieloch M , Stewart J , Kowey P
Published: November 2020

Background/Introduction

The use of antiarrhythmic drugs in patients with chronic kidney disease (CKD) is complex because impaired renal clearance can cause increased drug levels, and risk of intolerance or adverse events. Since CKD commonly co-occurs with atrial fibrillation/atrial flutter (AF/AFL), it is important to establish efficacy and safety for such drugs when used in AF/AFL patients with CKD.

Purpose

To evaluate the efficacy and safety of dronedarone in patients with AF or AFL across different levels of renal function.

Methods

This post hoc analysis evaluated pooled data from two multicentre, double-blind, randomised (2:1) trials of rhythm control with dronedarone 400 mg twice daily vs placebo. Primary endpoint was time to first recurrence of AF or AFL. Renal function (estimated glomerular filtration rate [eGFR]) was assessed with the CKD-Epidemiology Collaboration equation. Patients were grouped by eGFR strata. Log-rank testing and Cox regression were used to compare time to events between treatment groups.

Results

Most (85%) patients had mild or mild-to-moderate decrease in eGFR (Table 1). Median time to first AF recurrence was significantly longer in the dronedarone vs placebo group for all eGFR subgroups except the 30–44 mL/min group (Figure 1), where the trend was consistent; however, the small population size may have precluded meaningful analyses in this subgroup. Serious adverse events, deaths, and treatment discontinuations did not differ notably between each group irrespective of eGFR strata.

Conclusions

This analysis confirms the efficacy and safety of dronedarone in patients with AF across a wide spectrum of renal function.

Figure 1

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Sanofi
Ventricular premature contractions coupling interval behavior and efficacy of anti-arrhythmic drugs
Authors: Abdel-Wahed A , Abdel-Wahed A , Maekynen H , Raatikainen P
Published: November 2020

Introduction

The Idiopathic ventricular arrhythmias are special type of arrhythmia that occurs in the absence of clinically apparent structural heart. They have different pattern of recurrence sporadic, bigeminy, trigeminy, couplets and Ventricular tachycardia runs. They have special behavior of relatively constant coupling interval and recurrence depending on heart rate variability and autonomic nervous system dominance.Objectives: To assess the effect of Coupling interval on the efficacy of different anti-arrhythmic drug.

Methods

Each subject among 125 consecutive patients with high ventricular premature contractions burden, 24 h ambulatory electrocardiograms were recorded in the absence of anti-arrhythmic drug (control), and during treatment with various anti-arrhythmic drugs. The ratio of the coupling interval (CI) to the preceding R-R intervals was calculated.Patients were treated by different anti-arrhythmic therapy. Efficacy of anti-arrhythmic therapy was documented by ambulatory electrocardiogram for 24 hour by estimating the reduction of Ventricular arrhythmia burden.

Results

The burden of ventricular premature contractions was reduced effectively (>70% reduction of PVCs burden) in patients receiving BB with RR interval <680 ms, CI/RR <0.4, (P=0.002) (relative tachycardia), while in patients receiving CCB it was effective with RR 650- 830 ms, CI/RR 0.4–0.7, (P=0.04) (average heart rate). While in patients receiving Flecanide were found to have effective therapy with RR >900 ms, CI/RR>0.7, (relative bradycardia) (P=0.005).

Conclusion

The coupling interval of ventricular premature contractions can predict the efficacy of anti-arrhythmic drugs. The efficacy of anti-arrhythmic therapy may be dependent on the ventricular arrhythmia behavior of the coupling interval and RR interval of the preceding sinus rhythm.

Efficacy of different anti-arrhythmic

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Egyptian Ministry of Higher Education