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1.
BMC Cardiovasc Disord ; 19(1): 120, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113362

RESUMO

BACKGROUND: Atrial fibrillation (AF) is caused by different mechanisms but current treatment strategies do not target these mechanisms. Stratified therapy based on mechanistic drivers and biomarkers of AF have the potential to improve AF prevention and management outcomes. We will integrate mechanistic insights with known pathophysiological drivers of AF in models predicting recurrent AF and prevalent AF to test hypotheses related to AF mechanisms and response to rhythm control therapy. METHODS: We will harmonise and combine baseline and outcome data from 12 studies collected by six centres from the United Kingdom, Germany, France, Spain, and the Netherlands which assess prevalent AF or recurrent AF. A Delphi process and statistical selection will be used to identify candidate clinical predictors. Prediction models will be developed in patients with AF for AF recurrence and AF-related outcomes, and in patients with or without AF at baseline for prevalent AF. Models will be used to test mechanistic hypotheses and investigate the predictive value of plasma biomarkers. DISCUSSION: This retrospective, harmonised, individual patient data analysis will use information from 12 datasets collected in five European countries. It is envisioned that the outcome of this analysis would provide a greater understanding of the factors associated with recurrent and prevalent AF, potentially allowing development of stratified approaches to prevention and therapy management.

2.
Circulation ; 138(21): 2345-2358, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30571576

RESUMO

BACKGROUND: Long QT syndrome (LQTS) is associated with potentially fatal arrhythmias. Treatment is very effective, but its diagnosis may be challenging. Importantly, different methods are used to assess the QT interval, which makes its recognition difficult. QT experts advocate manual measurements with the tangent or threshold method. However, differences between these methods and their performance in LQTS diagnosis have not been established. We aimed to assess similarities and differences between these 2 methods for QT interval analysis to aid in accurate QT assessment for LQTS. METHODS: Patients with a confirmed pathogenic variant in KCNQ1(LQT1), KCNH2(LQT2), or SCN5A(LQT3) genes and their family members were included. Genotype-positive patients were identified as LQTS cases and genotype-negative family members as controls. ECGs were analyzed with both methods, providing inter- and intrareader validity and diagnostic accuracy. Cutoff values based on control population's 95th and 99th percentiles, and LQTS-patients' 1st and 5th percentiles were established based on the method to correct for heart rate, age, and sex. RESULTS: We included 1484 individuals from 265 families, aged 33±21 years and 55% females. In the total cohort, QTTangent was 10.4 ms shorter compared with QTThreshold (95% limits of agreement±20.5 ms, P<0.0001). For all genotypes, QTTangent was shorter than QTThreshold ( P<0.0001), but this was less pronounced in LQT2. Both methods yielded a high inter- and intrareader validity (intraclass correlation coefficient >0.96), and a high diagnostic accuracy (area under the curve >0.84). Using the current guideline cutoff (QTc interval 480 ms), both methods had similar specificity but yielded a different sensitivity. QTc interval cutoff values of QTTangent were lower compared with QTThreshold and different depending on the correction for heart rate, age, and sex. CONCLUSION: The QT interval varies depending on the method used for its assessment, yet both methods have a high validity and can both be used in diagnosing LQTS. However, for diagnostic purposes current guideline cutoff values yield different results for these 2 methods and could result in inappropriate reassurance or treatment. Adjusted cutoff values are therefore specified for method, correction formula, age, and sex. In addition, a freely accessible online probability calculator for LQTS ( www.QTcalculator.org ) has been made available as an aid in the interpretation of the QT interval.


Assuntos
Eletrocardiografia , Síndrome do QT Longo/diagnóstico , Adolescente , Adulto , Fatores Etários , Estudos de Casos e Controles , Criança , Bases de Dados Factuais , Canal de Potássio ERG1/genética , Feminino , Genótipo , Humanos , Canal de Potássio KCNQ1/genética , Síndrome do QT Longo/patologia , Masculino , Pessoa de Meia-Idade , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Estudos Retrospectivos , Fatores Sexuais , Adulto Jovem
3.
Biomed Res Int ; 2018: 9784259, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30320138

RESUMO

Introduction: The value of contact force information for ablation of LA anterior line is unknown. In a prospective randomized clinical trial, we investigated if information on contact force during left atrial (LA) anterior line ablation reduces total radiofrequency time and results in higher rates of bidirectional line block in patients undergoing pulmonary vein isolation (PVI) plus substrate modification. Methods: We included patients with indication for pulmonary vein isolation (PVI) and additional substrate modification. For LA anterior line ablation, patients were randomized to contact force information visible (n=35) or blinded (n=37). Patients received contrast enhanced cardiac magnetic resonance imaging (cMRI) before and 3-6 months after ablation to visualize the LA anterior line. Primary endpoint was radiofrequency time to achieve bidirectional line block. Secondary endpoints were completeness of the LA anterior line on cMRI, distribution of contact force, procedural data, adverse events, and 12 months success rate. Results: In 72 patients (64±9 years, 68% male), bidirectional LA anterior line block was achieved in 70 (97%) patients. Radiofrequency time to bidirectional block did not differ significantly across groups (contact force information visible 23±18min versus contact force information blinded 21±15min, p=0.50). The LA anterior line was discernable on cMRI in 40 patients (82%) without significant differences across randomization groups (p=0.46). No difference in applied contact force was found depending on cMRI line visibility. Twelve-month success and adverse event rates were comparable across groups. Conclusion: Information on contact force does not significantly improve the ablation of LA anterior lines. Clinical Trial Registration: The trial was registered at http://www.clinicaltrials.gov by identifier: NCT02217657.

4.
Eur Heart J ; 39(45): 4020-4029, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085086

RESUMO

Aims: Risks of catheter ablation for atrial fibrillation and flutter assessed in retrospective studies, registries, and controlled trials may underestimate 'real world' conditions. Methods and results: To assess complications in a nationwide approach, we included all cases undergoing catheter ablation for atrial fibrillation and atrial flutter in Germany in 2014, using ICD-10-GM-based German Diagnosis Related Group (G-DRG) codes and the well differentiated German Operation and Procedure Classification (OPS) analysing 33 353 in-hospital cases. For left atrial ablations (19 514 cases), the overall complication rate ranged from a mean of 11.7% to 13.8% depending on type and site of applied energy, including major complications ranging from 3.8% to 7.2%. Whereas overall complication rates were lower for atrial flutter ablations (13 871 cases, 10.5%; P < 0.001), interestingly, major complications occurred more frequently (7.4%; P < 0.001). Particularly, in-hospital death was four-times more common following right than following left atrial ablations (47 vs. 18 cases, 0.34% vs. 0.09%; P < 0.001). Stratified by centre ablation volume, significantly fewer overall complications occurred in centres performing >100 vs. ≤100 left atrial ablations annually (12.7% vs. 16.4%; P < 0.002). Conclusion: Administrative data of all atrial fibrillation ablations in Germany in 2014 revealed higher overall and major complication rates than previously reported. Few patients were treated in low volume centres, but were exposed to a higher overall complication risk. Atrial flutter ablations were associated with surprisingly high rates of life-threatening complications. Advanced age combined with highly prevalent cardiac, pulmonary and, vascular comorbidities likely play a major role. In addition, individual-level clinical studies need to address the safety and benefits of catheter ablation in an elderly, diseased population.

5.
Int J Cardiol ; 272: 168-174, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30126655

RESUMO

BACKGROUND: A novel, automatically annotating ultra-high density mapping system (Rhythmia©, Boston Scientific) collects a high number and quality of electrograms (EGMs). So far, data on general use in the electrophysiological laboratory are sparse. METHODS: We retrospectively analyzed all our ablations using Rhythmia and recorded patient clinical data, procedural parameters, and mapping parameters including the count of EGMs, mapping time, and mapping volume. Where appropriate, procedural parameters were compared over time to assess a learning curve. RESULTS: 400 patients underwent ablation of atrial fibrillation (n = 202), typical (n = 16) or atypical atrial flutter (n = 49), VT (n = 48), PVC (n = 35), accessory pathways (n = 14), AVNRT (n = 4), and focal atrial tachycardia (n = 32). System use was feasible, as no procedure had to be stopped for technical reasons and no ablation had to be withheld because of mapping failure, and safe, with an overall complication rate of 2.25%. Initial restrictions in manoeuvrability of the mapping catheter were overcome rapidly, as indicated by a significant decrease of fluoroscopy time (20 vs. 14 min, p = 0.02), use of contrast agent (50 vs. 40 ml; p < 0.01), and (not significant) lower procedure times (194 vs. 170 min; p = 0.12; comparing the first with the last third of patients undergoing pulmonary vein isolation only procedure). Ablation of complex left atrial, focal and ventricular tachycardias benefited from the reliable automatic annotation of a high number of EGMs. CONCLUSION: The use of the Rhythmia is feasible and safe. Initial restrictions in manoeuvrability of the Orion mapping catheter were overcome rapidly. The procedures that benefit the most from ultra-high density mapping are complex left atrial tachycardias, focal tachycardias, and ventricular tachycardias.

6.
Circ Genom Precis Med ; 11(1): e001758, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29874175

RESUMO

BACKGROUND: QT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest. METHODS AND RESULTS: We performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci. CONCLUSIONS: Our analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.

7.
Circ Genom Precis Med ; 11(5): e001663, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29752399

RESUMO

BACKGROUND: Genetic variants at the SCN5A/SCN10A locus are strongly associated with electrocardiographic PR and QRS intervals. While SCN5A is the canonical cardiac sodium channel gene, the role of SCN10A in cardiac conduction is less well characterized. METHODS: We sequenced the SCN10A locus in 3699 European-ancestry individuals to identify variants associated with cardiac conduction, and replicated our findings in 21,000 individuals of European ancestry. We examined association with expression in human atrial tissue. We explored the biophysical effect of variation on channel function using cellular electrophysiology. RESULTS: We identified 2 intronic single nucleotide polymorphisms in high linkage disequilibrium (r 2=0.86) with each other to be the strongest signals for PR (rs10428132, ß=-4.74, P=1.52×10-14) and QRS intervals (rs6599251, QRS ß=-0.73; P=1.2×10-4), respectively. Although these variants were not associated with SCN5A or SCN10A expression in human atrial tissue (n=490), they were in high linkage disequilibrium (r 2≥0.72) with a common SCN10A missense variant, rs6795970 (V1073A). In total, we identified 7 missense variants, 4 of which (I962V, P1045T, V1073A, and L1092P) were associated with cardiac conduction. These 4 missense variants cluster in the cytoplasmic linker of the second and third domains of the SCN10A protein and together form 6 common haplotypes. Using cellular electrophysiology, we found that haplotypes associated with shorter PR intervals had a significantly larger percentage of late current compared with wild-type (I962V+V1073A+L1092P, 20.2±3.3%, P=0.03, and I962V+V1073A, 22.4±0.8%, P=0.0004 versus wild-type 11.7±1.6%), and the haplotype associated with the longest PR interval had a significantly smaller late current percentage (P1045T, 6.4±1.2%, P=0.03). CONCLUSIONS: Our findings suggest an association between genetic variation in SCN10A, the late sodium current, and alterations in cardiac conduction.

8.
Circ Genom Precis Med ; 11(5): e002037, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29748316

RESUMO

BACKGROUND: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability. METHODS: We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval. RESULTS: We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction (P<1.2×10-6), including 11 novel loci that have not been reported previously. Many of these loci are involved in heart morphogenesis. In gene-based analysis, we found that multiple rare variants at MYH6 (P=5.9×10-11) and SCN5A (P=1.1×10-7) were associated with PR interval. SCN5A locus also was implicated in the common variant analysis, whereas MYH6 was a novel locus. CONCLUSIONS: We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health.

9.
Circ Arrhythm Electrophysiol ; 11(2): e005762, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29440187

RESUMO

BACKGROUND: We developed a novel electrocardiographic marker, T-wave area dispersion (TW-Ad), which measures repolarization heterogeneity by assessing interlead T-wave areas during a single cardiac cycle and tested whether it can identify patients at risk for sudden cardiac death (SCD) in the general population. METHODS AND RESULTS: TW-Ad was measured from standard digital 12-lead ECG in 5618 adults (46% men; age, 50.9±12.5 years) participating in the Health 2000 Study-an epidemiological survey representative of the Finnish adult population. Independent replication was performed in 3831 participants of the KORA S4 Study (Cooperative Health Research in the Region of Augsburg; 49% men; age, 48.7±13.7 years; mean follow-up, 8.8±1.1 years). During follow-up (7.7±1.4 years), 72 SCDs occurred in the Health 2000 Survey. Lower TW-Ad was univariately associated with SCD (0.32±0.36 versus 0.60±0.19; P<0.001); it had an area under the receiver operating characteristic curve of 0.809. TW-Ad (≤0.46) conferred a hazard ratio of 10.8 (95% confidence interval, 6.8-17.4; P<0.001) for SCD; it remained independently predictive of SCD after multivariable adjustment for clinical risk markers (hazard ratio, 4.6; 95% confidence interval, 2.7-7.4; P<0.001). Replication analyses performed in the KORA S4 Study confirmed an increased risk for cardiac death (unadjusted hazard ratio, 5.5; 95% confidence interval, 3.2-9.5; P<0.001; multivariable adjusted hazard ratio, 1.9; 95% confidence interval, 1.1-3.5; P<0.05). CONCLUSION: Low TW-Ad, reflecting increased heterogeneity of repolarization, in standard 12-lead resting ECGs is a powerful and independent predictor of SCD in the adult general population.

11.
Circ Cardiovasc Genet ; 10(5)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28974514

RESUMO

BACKGROUND: Atrial fibrillation (AF) affects over 33 million individuals worldwide. Genome-wide association studies have identified at least 30 AF loci, but the mechanisms through which individual variants lead to altered disease risk have remained unclear for the majority of these loci. At the 1q24 locus, we hypothesized that the transcription factor PRRX1 could be a strong candidate gene as it is expressed in the pulmonary veins, a source of AF in many individuals. We sought to identify the molecular mechanism, whereby variation at 1q24 may lead to AF susceptibility. METHODS AND RESULTS: We sequenced a ≈158 kb region encompassing PRRX1 in 962 individuals with and without AF. We identified a broad region of association with AF at the 1q24 locus. Using in silico prediction and functional validation, we identified an enhancer that interacts with the promoter of PRRX1 in cells of cardiac lineage. Within this enhancer, we identified a single-nucleotide polymorphism, rs577676, which alters enhancer activity in a mouse atrial cell line and in embryonic zebrafish and differentially regulates PRRX1 expression in human left atria. We found that suppression of PRRX1 in human embryonic stem cell-derived cardiomyocytes and embryonic zebrafish resulted in shortening of the atrial action potential duration, a hallmark of AF. CONCLUSIONS: We have identified a functional genetic variant that alters PRRX1 expression, ultimately resulting in electrophysiological alterations in atrial myocytes that may promote AF.


Assuntos
Potenciais de Ação/genética , Fibrilação Atrial , Proteínas de Homeodomínio , Células-Tronco Embrionárias Humanas/metabolismo , Miócitos Cardíacos/metabolismo , Polimorfismo de Nucleotídeo Único , Animais , Animais Geneticamente Modificados , Fibrilação Atrial/genética , Fibrilação Atrial/metabolismo , Fibrilação Atrial/fisiopatologia , Linhagem Celular , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Células-Tronco Embrionárias Humanas/patologia , Humanos , Camundongos , Miócitos Cardíacos/patologia , Peixe-Zebra
12.
Sci Rep ; 7(1): 11303, 2017 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-28900195

RESUMO

It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10-5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10-8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.

13.
Eur Heart J ; 38(35): 2641-2643, 2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-28934840
14.
Circ Cardiovasc Genet ; 10(4)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28794112

RESUMO

BACKGROUND: The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies. METHODS AND RESULTS: We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (P<5×10-8) novel loci and replicated a prior association with SCN10A. We identified 3 loci at SCN5A, TBX5, and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction. CONCLUSIONS: We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.


Assuntos
Eletrocardiografia , Loci Gênicos , Estudo de Associação Genômica Ampla , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatologia , Caveolina 1/genética , Caveolina 2/genética , Genótipo , Átrios do Coração/metabolismo , Humanos , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Proteínas com Domínio T/genética
15.
Value Health ; 20(6): 769-776, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28577694

RESUMO

OBJECTIVES: To compare complication rates, length of hospital stay, and resulting costs between the use of manual compression and a vascular closing device (VCD) in both diagnostic and interventional catheterization in a German university hospital setting. METHODS: A stratified analysis according to risk profiles was used to compare the risk of complications in a retrospective cross-sectional single-center study. Differences in costs and length of hospital stay were calculated using the recycled predictions method, based on regression coefficients from generalized linear models with gamma distribution. All models were adjusted for propensity score and possible confounders, such as age, sex, and comorbidities. The analysis was performed separately for diagnostic and interventional catheterization. RESULTS: The unadjusted relative risk (RR) of complications was not significantly different in diagnostic catheterization when a VCD was used (RR = 0.70; 95% confidence interval [CI] 0.22-2.16) but significantly lower in interventional catheterization (RR = 0.44; 95% CI 0.21-0.93). Costs were on average €275 lower in the diagnostic group (95% CI -€478.0 to -€64.9; P = 0.006) and around €373 lower in the interventional group (95% CI -€630.0 to -€104.2; P = 0.014) when a VCD was used. The adjusted estimated average length of stay did not differ significantly between the use of a VCD and manual compression in both types of catheterization. CONCLUSIONS: In interventional catheterization, VCDs significantly reduced unadjusted complication rates, as well as costs. A significant reduction in costs also supports their usage in diagnostic catheterization on a larger scale.


Assuntos
Cateterismo Cardíaco/métodos , Tempo de Internação/estatística & dados numéricos , Intervenção Coronária Percutânea/métodos , Dispositivos de Oclusão Vascular , Idoso , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/economia , Estudos Transversais , Feminino , Artéria Femoral , Alemanha , Custos Hospitalares , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Hospitais Universitários , Humanos , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/economia , Estudos Retrospectivos
16.
Eur Heart J ; 38(27): 2100-2106, 2017 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-28449090

RESUMO

Aims: Alcohol is a risk factor for cardiac arrhythmias. Retrospective analyses suggest supraventricular arrhythmias consecutive to acute alcohol consumption, but prospective data are limited. We intended to prospectively associate acute alcohol consumption with cardiac arrhythmias. Methods and results: At the 2015 Munich Octoberfest, we enrolled 3028 voluntary participants who received a smartphone-based ECG and breath alcohol concentration (BAC) measurements. ECGs were analysed for cardiac arrhythmias (sinus tachycardia, sinus arrhythmia, premature atrial/ventricular complexes, atrial fibrillation/flutter) and respiratory sinus arrhythmia. By multivariable adjusted logistic regression we associated BACs with cardiac arrhythmias. Similarly, we analysed 4131 participants of the community-based KORA S4 Study (Co-operative Health Research in the Region of Augsburg) and associated cardiac arrhythmias with chronic alcohol consumption. In our acute alcohol cohort (mean age 34.4 ± 13.3 years, 29% women), mean BAC was 0.85 ± 0.54 g/kg. Cardiac arrhythmias occurred in 30.5% (sinus tachycardia 25.9%; other arrhythmia subtypes 5.4%). Breath alcohol concentration was significantly associated with cardiac arrhythmias overall (odds ratio (OR) per 1-unit change 1.75, 95% confidence interval (CI) 1.50-2.05; P < 0.001) and sinus tachycardia in particular (OR 1.96, 95%CI 1.66-2.31; P < 0.001). Respiratory sinus arrhythmia measuring autonomic tone was significantly reduced under the influence of alcohol. In KORA S4, chronic alcohol consumption was associated with sinus tachycardia (OR 1.03, 95%CI 1.01-1.06; P = 0.006). Conclusions: Acute alcohol consumption is associated with cardiac arrhythmias and sinus tachycardia in particular. This partly reflects autonomic imbalance as assessed by significantly reduced respiratory sinus arrhythmia. Such imbalance might lead to sympathetically triggered atrial fibrillation resembling the holiday heart syndrome. ClinicalTrials.org accession number: NCT02550340.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Arritmias Cardíacas/etiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Arritmias Cardíacas/epidemiologia , Testes Respiratórios , Eletrocardiografia/instrumentação , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Prevalência , Estudos Prospectivos , Smartphone , Taquicardia Sinusal/epidemiologia , Taquicardia Sinusal/etiologia
17.
Sci Rep ; 6: 35371, 2016 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-27824142

RESUMO

Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in an independent cohort for replication, which included more than 2,363 AF cases and 114,746 AF-free referents. One interaction, between rs7164883 at the HCN4 locus and rs4980345 at the SLC28A1 locus, was found to be significantly associated with AF in the discovery cohorts (interaction OR = 1.44, 95% CI: 1.27-1.65, P = 4.3 × 10-8). Eight additional gene-gene interactions were also marginally significant (P < 5 × 10-7). However, none of the top interactions were replicated. In summary, we did not find significant interactions that were associated with AF susceptibility. Future increases in sample size and denser genotyping might facilitate the identification of gene-gene interactions associated with AF.


Assuntos
Fibrilação Atrial/genética , Estudos de Associação Genética , Idoso , Estudos de Coortes , Epistasia Genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Masculino , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Musculares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Canais de Potássio/genética
18.
Europace ; 18(8): 1170-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26759125

RESUMO

AIMS: Pulmonary vein isolation (PVI) is an established therapy for atrial fibrillation (AF). However, PVI remains a time-consuming procedure. A novel multipolar irrigated radiofrequency (RF) ablation catheter (nMARQ™) is aiming to improve PVI. We investigated the influence on procedural parameters and assessed clinical outcomes after PVI using this novel catheter. METHODS AND RESULTS: Fifty-eight consecutive patients with paroxysmal AF were equally allocated (n = 29/group) to PVI treatment with (i) the novel multipolar ablation catheter (nMARQ™) and (ii) a standard single-tip ablation catheter (SAC). Study endpoints included procedure time, fluoroscopy time, radiation dose, RF time, number of energy applications, and clinical outcome defined as freedom from AF after a single procedure. Successful PVI was confirmed by a separate circular, multipolar mapping catheter in all patients treated with the nMARQ™. Pulmonary vein isolation was achieved in 100% in the SAC group. In the nMARQ™ group, PVI was suggested in all patients. However, confirmatory mapping revealed persistent pulmonary vein (PV) conduction in 19 out of 29 nMARQ™ patients. These patients underwent further ablation, which still failed to achieve PVI in 5 of the 29 nMARQ™ patients, mainly due to significant temperature rise in the oesophagus and device-related limitations reaching the right inferior PV. Mean fluoroscopy time (31 ± 12 vs. 23 ± 10 min, P < 0.05) and (132 ± 37 vs. 109 ± 30 min, P < 0.05) were longer in nMARQ™ vs. SAC patients. Radiofrequency time was shorter in nMARQ™ vs. SAC group (21 ± 9 vs. 35 ± 12 min, P < 0.001). Radiation dose and the number of energy applications did not differ between both groups. Clinical outcome analysis revealed no significant differences (nMARQ™: 72 vs. SAC: 72%) after a mean follow-up of 373 ± 278 days. CONCLUSION: The use of the nMARQ™ catheter is associated with important device-related limitations to achieve successful PVI. However, clinical outcomes were equivalent in nMARQ™- and SAC-treated patients.


Assuntos
Fibrilação Atrial/terapia , Ablação por Cateter/instrumentação , Adenosina/sangue , Idoso , Anticoagulantes/uso terapêutico , Ablação por Cateter/efeitos adversos , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Fluoroscopia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Prospectivos , Veias Pulmonares/cirurgia , Resultado do Tratamento
19.
Europace ; 18(5): 718-25, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26759124

RESUMO

AIMS: Idiopathic ventricular fibrillation (iVF) accounts for up to 14% of VF incidence. Data regarding long-term outcome and clinical risk markers of arrhythmia recurrence are scarce. The objective of our study was to describe a long-term follow-up (FU) of a cohort of iVF survivors in our centre during the past 20 years, and to investigate the influence of clinical parameters, e.g. presence of an early repolarization pattern (ERP), on recurrence rate of arrhythmias. METHODS AND RESULTS: Thirty-five iVF survivors were identified and retrospectively analysed regarding recurrent implantable cardioverter-defibrillator (ICD) interventions and covariates potentially influencing arrhythmia recurrence. Appropriate ICD interventions occurred in 15 patients (43%) after a median of 6.6 years during a median FU period of 8.8 years. Two patients (13%) received the first appropriate therapy after an assumed average ICD battery longevity of 7 years, while in all other patients, the first therapy occurred within the first ICD period. Appropriate interventions were observed more often and earlier in patients with ERP (HR 3.9; 1.4-11.0; P = 0.01), whereas all other covariates failed to predict subsequent events. A high incidence of inappropriate ICD therapies (67 interventions in 14 patients) could be attributed to the occurrence of atrial fibrillation (66% of all inappropriate therapies). CONCLUSION: The recurrence rate of ventricular arrhythmias in iVF survivors is high and recurrence might occur delayed (>7 years after the initial event). ERP seems to be highly predictive with respect to early arrhythmia recurrence. Our results highlight that better pathophysiologic understanding of ERP might facilitate a better risk stratification before and an optimal treatment after an iVF event. The high rate of AF and ERP in iVF survivors might indicate an underlying heart disease or myocardial electrical disorder not apparent at the index event.


Assuntos
Morte Súbita Cardíaca/epidemiologia , Desfibriladores Implantáveis/efeitos adversos , Fibrilação Ventricular/diagnóstico por imagem , Fibrilação Ventricular/terapia , Adulto , Idoso , Morte Súbita Cardíaca/etiologia , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Alemanha , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco
20.
Nat Rev Cardiol ; 13(4): 230-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26701216

RESUMO

Despite remarkable advances in antiarrhythmic drugs, ablation procedures, and stroke-prevention strategies, atrial fibrillation (AF) remains an important cause of death and disability in middle-aged and elderly individuals. Unstructured management of patients with AF sharply contrasts with our detailed, although incomplete, knowledge of the mechanisms that cause AF and its complications. Altered calcium homeostasis, atrial fibrosis and ageing, ion-channel dysfunction, autonomic imbalance, fat-cell infiltration, and oxidative stress, in addition to a susceptible genetic background, contribute to the promotion, maintenance, and progression of AF. However, clinical management of patients with AF is currently guided by stroke risk parameters, AF pattern, and symptoms. In response to this apparent disconnect between the known pathophysiology of AF and clinical management, we propose a roadmap to develop a set of clinical markers that reflect the major causes of AF in patients. Thereby, the insights into the mechanisms causing AF will be transformed into a format that can underpin future personalized strategies to prevent and treat AF, ultimately informing better patient care.


Assuntos
Fibrilação Atrial/prevenção & controle , Cardiologia/normas , Medicina de Precisão/normas , Serviços Preventivos de Saúde/normas , Animais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Consenso , Humanos , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Resultado do Tratamento
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