Mitral annular disjunction in idiopathic ventricular fibrillation patients: just a bystander or a potential cause?

AIMS: Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort. METHODS AND RESULTS: This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female]. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579). CONCLUSION: A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay.

Separable mixing: The general formulation and a particular example focusing on mask efficiency.

The aim of this short note is twofold. First, we formulate the general Kermack-McKendrick epidemic model incorporating static heterogeneity and show how it simplifies to a scalar Renewal Equation (RE) when separable mixing is assumed. A key general feature is that all information about the heterogeneity is encoded in one nonlinear real valued function of a real variable. Next, we specialize the model ingredients so that we can study the efficiency of mask wearing as a non-pharmaceutical intervention to reduce the spread of an infectious disease. Our main result affirms that the best way to protect the population as a whole is to protect yourself. This qualitative insight was recently derived in the context of an SIR network model. Here, we extend the conclusion to proportionate mixing models incorporating a general function describing expected infectiousness as a function of time since infection.

Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study).

BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherlands Trial Register, NTR6268.

Fragmentomic analysis of circulating tumor DNA-targeted cancer panels.

BACKGROUND: The isolation of cell-free DNA (cfDNA) from the bloodstream can be used to detect and analyze somatic alterations in circulating tumor DNA (ctDNA), and multiple cfDNA-targeted sequencing panels are now commercially available for Food and Drug Administration (FDA)-approved biomarker indications to guide treatment. More recently, cfDNA fragmentation patterns have emerged as a tool to infer epigenomic and transcriptomic information. However, most of these analyses used whole-genome sequencing, which is insufficient to identify FDA-approved biomarker indications in a cost-effective manner. PATIENTS AND METHODS: We used machine learning models of fragmentation patterns at the first coding exon in standard targeted cancer gene cfDNA sequencing panels to distinguish between cancer and non-cancer patients, as well as the specific tumor type and subtype. We assessed this approach in two independent cohorts: a published cohort from GRAIL (breast, lung, and prostate cancers, non-cancer, n = 198) and an institutional cohort from the University of Wisconsin (UW; breast, lung, prostate, bladder cancers, n = 320). Each cohort was split 70%/30% into training and validation sets. RESULTS: In the UW cohort, training cross-validated accuracy was 82.1%, and accuracy in the independent validation cohort was 86.6% despite a median ctDNA fraction of only 0.06. In the GRAIL cohort, to assess how this approach performs in very low ctDNA fractions, training and independent validation were split based on ctDNA fraction. Training cross-validated accuracy was 80.6%, and accuracy in the independent validation cohort was 76.3%. In the validation cohort where the ctDNA fractions were all <0.05 and as low as 0.0003, the cancer versus non-cancer area under the curve was 0.99. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that sequencing from targeted cfDNA panels can be utilized to analyze fragmentation patterns to classify cancer types, dramatically expanding the potential capabilities of existing clinically used panels at minimal additional cost.

A Dutch MYH7 founder mutation, p.(Asn1918Lys), is associated with early onset cardiomyopathy and congenital heart defects.

BACKGROUND: Mutations in the myosin heavy chain 7 (MYH7) gene commonly cause cardiomyopathy but are less frequently associated with congenital heart defects. METHODS: In this study, we describe a mutation in the MYH7 gene, c. 5754C > G; p. (Asn1918Lys), present in 15 probands and 65 family members. RESULTS: Of the 80 carriers (age range 0-88 years), 46 (57.5%) had cardiomyopathy (mainly dilated cardiomyopathy (DCM)) and seven (8.8%) had a congenital heart defect. Childhood onset of cardiomyopathy was present in almost 10% of carriers. However, in only a slight majority (53.7%) was the left ventricular ejection fraction reduced and almost no arrhythmias or conduction disorders were noted. Moreover, only one carrier required heart transplantation and nine (11.3%) an implantable cardioverter defibrillator. In addition, the standardised mortality ratio for MYH7 carriers was not significantly increased. Whole exome sequencing in several cases with paediatric onset of DCM and one with isolated congenital heart defects did not reveal additional known disease-causing variants. Haplotype analysis suggests that the MYH7 variant is a founder mutation, and is therefore the first Dutch founder mutation identified in the MYH7 gene. The mutation appears to have originated in the western region of the province of South Holland between 500 and 900 years ago. CONCLUSION: Clinically, the p. (Asn1918Lys) mutation is associated with congenital heart defects and/or cardiomyopathy at young age but with a relatively benign course.

Quantifying within-household transmission of extended-spectrum ß-lactamase-producing bacteria.

OBJECTIVES: Patients can acquire extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae during hospitalization, and colonized patients may transmit these bacteria after discharge, most likely to household contacts. In this study, ESBL transmission was quantified in households. METHODS: Faecal samples were longitudinally collected from hospitalized patients colonized with ESBL-producing bacteria and from their household members during hospitalization of the index patient and at 3, 6, 12 and 18 months. A mathematical household model was developed, which allowed for person-to-person transmission, acquisition from other sources (background transmission), and losing carriage. Next, a deterministic population model with a household structure was created, informed by parameter values found in the household model. RESULTS: In all, 74 index patients and 84 household members were included. In more than half of the household members ESBL-producing bacteria were demonstrated at some time during follow up. Person-to-person transmission occurred at a rate of 0.0053/colonized person/day (0.0025-0.011), background transmission at 0.00015/day (95% CI 0.00002-0.00039), and decolonization at 0.0026/day (0.0016-0.0040) for index patients and 0.0090/day (0.0046-0.018) for household members. The estimated probability of transmission from an index patient to a household contact was 67% and 37% vice versa. CONCLUSION: There is frequent transmission of ESBL-producing bacteria in households, which may contribute to the observed endemicity of ESBL carriage in the Netherlands. However, the population model suggests that there is not a single dominant acquisition route in the community.

Epidemic potential of Escherichia coli ST131 and Klebsiella pneumoniae ST258: a systematic review and meta-analysis.

OBJECTIVES: Observational studies have suggested that Escherichia coli sequence type (ST) 131 and Klebsiella pneumoniae ST258 have hyperendemic properties. This would be obvious from continuously high incidence and/or prevalence of carriage or infection with these bacteria in specific patient populations. Hyperendemicity could result from increased transmissibility, longer duration of infectiousness, and/or higher pathogenic potential as compared with other lineages of the same species. The aim of our research is to quantitatively estimate these critical parameters for E. coli ST131 and K. pneumoniae ST258, in order to investigate whether E. coli ST131 and K. pneumoniae ST258 are truly hyperendemic clones. PRIMARY OUTCOME MEASURES: A systematic literature search was performed to assess the evidence of transmissibility, duration of infectiousness, and pathogenicity for E. coli ST131 and K. pneumoniae ST258. Meta-regression was performed to quantify these characteristics. RESULTS: The systematic literature search yielded 639 articles, of which 19 data sources provided information on transmissibility (E. coli ST131 n=9; K. pneumoniae ST258 n=10)), 2 on duration of infectiousness (E. coli ST131 n=2), and 324 on pathogenicity (E. coli ST131 n=285; K. pneumoniae ST258 n=39). Available data on duration of carriage and on transmissibility were insufficient for quantitative assessment. In multivariable meta-regression E. coli isolates causing infection were associated with ST131, compared to isolates only causing colonisation, suggesting that E. coli ST131 can be considered more pathogenic than non-ST131 isolates. Date of isolation, location and resistance mechanism also influenced the prevalence of ST131. E. coli ST131 was 3.2 (95% CI 2.0 to 5.0) times more pathogenic than non-ST131. For K. pneumoniae ST258 there were not enough data for meta-regression assessing the influence of colonisation versus infection on ST258 prevalence. CONCLUSIONS: With the currently available data, it cannot be confirmed nor rejected, that E. coli ST131 or K. pneumoniae ST258 are hyperendemic clones.

The effects of clinical and statistical heterogeneity on the predictive values of results from meta-analyses.

Variance between studies in a meta-analysis will exist. This heterogeneity may be of clinical, methodological or statistical origin. The last of these is quantified by the I(2) -statistic. We investigated, using simulated studies, the accuracy of I(2) in the assessment of heterogeneity and the effects of heterogeneity on the predictive value of meta-analyses. The relevance of quantifying I(2) was determined according to the likely presence of heterogeneity between studies (low, high, or unknown) and the calculated I(2) (low or high). The findings were illustrated by published meta-analyses of selective digestive decontamination and weaning protocols. As expected, I(2) increases and the likelihood of drawing correct inferences from a meta-analysis decreases with increasing heterogeneity. With low levels of heterogeneity, I(2) does not appear to be predictive of the accuracy of the meta-analysis result. With high levels of heterogeneity, even meta-analyses with low I(2) -values have low predictive values. Most commonly, the level of heterogeneity in a meta-analysis will be unknown. In these scenarios, I(2) determination may help to identify estimates with low predictive values (high I(2) ). In this situation, the results of a meta-analysis will be unreliable. With low I(2) -values and unknown levels of heterogeneity, predictive values of pooled estimates may range extensively, and findings should be interpreted with caution. In conclusion, quantifying statistical heterogeneity through I(2) -statistics is only helpful when the amount of clinical heterogeneity is unknown and I(2) is high. Objective methods to quantify the levels of clinical and methodological heterogeneity are urgently needed to allow reliable determination of the accuracy of meta-analyses.

Modeling non-inherited antibiotic resistance.

A mathematical model is presented for the increase and decrease of non-inherited antibiotic resistance levels in bacteria. The model is applied to experimental data on E. coli exposed to amoxicillin or tetracyclin in different concentrations. The parameters of the model are estimated using a Monte Carlo Markov Chain method. The model accurately describes build-up and decline of antibiotic resistance caused by physiological adaptations as long as no genetic changes have occurred. The main conclusion of the analysis is that short time periods are sufficient to re-obtain low MIC-values after long-lasting exposure to these antibiotics.

Transmissibility of livestock-associated methicillin-resistant Staphylococcus aureus (ST398) in Dutch hospitals.

We quantified nosocomial transmission rates of sequence type (ST) 398 methicillin-resistant Staphylococcus aureus (MRSA) (an emerging livestock-associated MRSA clone) and non-ST398 MRSA isolates in patients hospitalized without infection control measures in 51 Dutch hospitals. Identification of 174 index patients initiated 139 post-exposure screenings of 9925 persons. There were 65 genotype-confirmed secondary cases (three and 62 for ST398 and non-ST398 MRSA, respectively), yielding a relative transmission risk for ST398 MRSA of 0.28 (95% CI 0.09-0.90), which was not sensitive to adjustment for duration of hospitalization at time of detection. Nosocomial transmission of ST398 MRSA is 72% less likely than that of non-ST398 MRSA strains.

Standardised pre-hospital care of acute myocardial infarction patients: MISSION! guidelines applied in practice.

Background. To improve acute myocardial infarction (AMI) care in the region 'Hollands-Midden' (the Netherlands), a standardised guideline-based care program was developed (MISSION!). This study aimed to evaluate the outcome of the pre-hospital part of the MISSION! program and to study potential differences in pre-hospital care between four areas of residency.Methods. Time-to-treatment delays, AMI risk profile, cardiac enzymes, hospital stay, in-hospital mortality, and pre-AMI medication was evaluated in consecutive AMI patients (n=863, 61±13years, 75% male) transferred to the Leiden University Medical Center for primary percutaneous coronary intervention (PCI).Results. Median time interval between onset of symptoms and arrival at the catheterisation laboratory was 150 (interquartile range [IQR] 101-280) minutes. The alert of emergency services to arrival at the hospital time was 48 (IQR 40-60) minutes and the door-to-catheterisation laboratory time was 23 (IQR 13-42) minutes. Despite significant regional differences in ambulance transportation times no difference in total time from onset of symptoms to arrival at the catheterisation room was found. Peak troponin T was 3.33 (IQR 1.23-7.04) µg/l, hospital stay was 2 (IQR 2-3) days and in-hospital mortality was 2.3%. Twelve percent had 0 known risk factors, 30% had one risk factor, 45% two to three risk factors and 13% had four or more risk factors. No significant differences were observed for AMI risk profiles and medication pre-AMI. Conclusions. This study shows that a standardised regional AMI treatment protocol achieved optimal and uniformly distributed pre-hospital performance in the region 'Hollands-Midden', resulting in minimal time delays regardless of area of residence. Hospital stay was short and in-hospital mortality low. Of the patients, 88% had ≥1 modifiable risk factor. (Neth Heart J 2010;18:408-15.).

Risk factors and time delay associated with cardiac device infections: Leiden device registry.

AIMS: A nested case-control study of 75 patients with cardiac device infections (CDI) and 75 matched controls was conducted to evaluate time course, risk factors, culture results and frequency of CDI. METHODS AND RESULTS: CDI occurred in 75/3410 (2.2%) device implantation and revision procedures, performed between 2000 and 2007. The time delay between device procedure and infection ranged from 0 to 64 months (mean 14 (SD 16)), 21 patients (28%) had an early infection (<1 month), 26 (35%) a late infection (1-12 months) and 28 (37%) a delayed infection (>12 months). Of interest, 18 (24%) patients presented with an infection >24 months after the device-related procedure. Time delay until infection was significantly shorter when cultures were positive for micro-organisms compared to negative cultures (8 (12) vs 18 (18) months, p = 0.03). Pocket cultures in delayed infections remained more often negative (61% vs 23%, p = 0.01). Independent CDI risk factors were: device revision (odds ratio (OR) 3.67; 95% confidence interval (CI), 1.51 to 8.96), renal dysfunction defined as glomerular filtration rate <60 ml/min (OR 4.64; CI, 1.48 to 14.62) and oral anticoagulation use (OR 2.83; CI 1.20 to 6.68). CONCLUSION: CDI occurred in 2.2% of device procedures, with 24% occurring more than two years after the device-related procedure. Renal dysfunction, device revisions and oral anticoagulation are potent risk factors for CDI.

An algorithm to estimate the importance of bacterial acquisition routes in hospital settings.

An algorithm is presented to calculate likelihoods of acquisition routes using only individual patient data concerning period of stay and microbiologic surveillance (without genotyping). The algorithm also produces estimates for the prevalence and the number of acquisitions by each route. The algorithm is applied to colonization data of third-generation cephalosporin-resistant Enterobacteriaceae (CRE) from September 2001 to May 2002 in two intensive care units (ICUs) (n = 277 and n = 180, respectively) of Utrecht, Kingdom of the Netherlands. Genotyping and epidemiologic linkage are used as the reference standard. Surveillance cultures were obtained on admission and twice weekly thereafter. All CREs were genotyped. According to the reference standard, the daily prevalence of CRE in ICU-1 and ICU-2 was 26.1% (standard deviation: 15.4) and 15.1% (standard deviation: 13.4), respectively, with five of 23 (21.7%) and six of 21 (28.6%) cases of acquired colonization being of exogenous origin, respectively. On the basis of the algorithm, the endogenous route was responsible for more acquisitions than the exogenous route (p = 0.003 and p < 0.001 for ICU-1 and ICU-2, respectively). The estimated number of acquisitions is 30 and 27, and the estimated prevalence is 27.6% and 17.6% for ICU-1 and ICU-2, respectively. By use of longitudinal colonization data only, the algorithm determines the relative importance of acquisition routes taking patient dependency into account.

Potential confounding in evaluating infection-control interventions in hospital settings: changing antibiotic prescription.

The colonization dynamics of antibiotic-resistant pathogens in hospital settings are complex, with multiple and continuously interacting variables (e.g., introduction of resistance, infection-control practices, antibiotic use). Quantification of these variables is indispensable in the evaluation of intervention studies, because these variables represent potential confounders. In this article, the complexity of colonization dynamics is described. Through a systematic review, we identified studies that evaluated the modification of antibiotic prescription to reduce antibiotic resistance in intensive care units (n=19), and the extent of confounding-control was determined. Most studies evaluated antimicrobial restriction/substitution (n=12) or antibiotic rotation (n=4). Sixteen studies had a prospective cohort design (before-after), of which 12 were without a control group. Introduction of antibiotic resistance was determined in 10 studies. The relative importance of colonization routes and adherence to infection-control measures were not determined in any study. Therefore, it remains uncertain whether observed changes in the prevalence of antibiotic resistance after intervention were causally related to the intervention. Appropriate choices of study design, primary end point (colonization rates rather than infection rates) and statistical tests, determination of colonization routes, and control of potential confounders are needed to increase validity of intervention studies.

Controlling methicillin-resistant Staphylococcus aureus: quantifying the effects of interventions and rapid diagnostic testing.

Control of nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) has been unsuccessful in most countries. Yet, some countries have maintained low endemic levels by implementing nationwide MRSA-specific infection control measures, such as "search & destroy" (S&D). These strategies, however, are not based on well designed studies, and their use in countries with high levels of endemicity is controversial. We present a stochastic three-hospital model and an analytical one-hospital model to quantify the effectiveness of different infection control measures and to predict the effects of rapid diagnostic testing (RDT) on isolation needs. Isolation of MRSA carriers identified by clinical cultures is insufficient to control MRSA. However, combined with proactive search (of high-risk patients on admission and/or contacts of index patients), it will maintain prevalence levels <1%. Concerted implementation of S&D in countries with high nosocomial endemicity reduces nosocomial prevalence to <1% within 6 years. Stepwise implementation of control measures can reduce isolation capacities needed. RDT can reduce isolation needs by >90% in low-endemic settings and by 20% in high-endemic settings. Surveillance of colonization and improved hand hygiene can markedly increase control efficacy. These findings strongly suggest that: (i) causality exists between S&D and low MRSA prevalence; (ii) isolating MRSA carriers identified by clinical cultures as a single measure is insufficient for control; (iii) a combined approach of isolation and screening confers efficacy; and (iv) MRSA-prevalence levels can be reduced to <1% in high-endemic settings by S&D or a stepwise approach to interventions. RDT can markedly enhance feasibility.

Cardiac resynchronisation therapy in chronic atrial fibrillation: impact on left atrial size and reversal to sinus rhythm.

OBJECTIVE: To evaluate the impact of long term cardiac resynchronisation therapy (CRT) on left atrial and left ventricular (LV) reverse remodelling and reversal to sinus rhythm (SR) in patients with heart failure with atrial fibrillation (AF). PATIENTS: 74 consecutive patients (age 68 (8) years; 67 men) with advanced heart failure and AF (20 persistent and 54 permanent) were implanted with a CRT device. MAIN OUTCOME MEASURES: Patients were evaluated clinically (New York Heart Association (NYHA) class, quality of life, six minute walk test) and echocardiographically (LV ejection fraction, LV diameters, and left atrial diameters) before and after six months of CRT. Additionally, restoration of SR was evaluated after six months of CRT. RESULTS: NYHA class, quality of life score, six minute walk test, and LV ejection fraction had improved significantly after six months of CRT. In addition, left atrial and LV end diastolic and end systolic diameters had decreased from 59 (9) to 55 (9) mm, from 72 (10) to 67 (10) mm, and from 61 (11) to 56 (11) mm, respectively (all p < 0.01). During implantation 18 of 20 (90%) patients with persistent AF were cardioverted to SR. At follow up 13 of 18 (72%) patients had returned to AF and none had spontaneously reverted to SR; thus, only 5 of 74 (7%) were in SR. CONCLUSION: Six months of CRT resulted in significant clinical benefit with significant left atrial and LV reverse remodelling. Despite these beneficial effects, 93% of patients had not reverted to SR.

[Radiofrequency catheter ablation for treating children with cardiac arrhythmias: favourable results after a mean of 4 years]. / Katheterablatie met radiofrequente energie ter behandeling van kinderen met hartritmestoornissen: gunstige resultaten na gemiddeld 4 jaar.

OBJECTIVE: Analysis of long-term results with radiofrequency catheter ablation (RF ablation) in children. DESIGN: Retrospective. METHOD: Data were analysed from all 118 paediatric patients < or =18 years old who underwent RF ablation at the Leiden University Medical Centre (LUMC), the Netherlands, during the period 1 December 1992-31 May 2004. RESULTS: The group consisted of 6o boys and 58 girls with a mean age of 12.7 years (SD: 4.6). They underwent 140 RF ablation procedures for 122 disorders. Indications for RF ablation were: failure or side-effects of antiarrhythmic medication (45%), patient/parent choice (45%), cardiomyopathy or life-threatening arrhythmia (8%), and impending surgery for a congenital heart defect (2%). The mean follow-up interval was 4 years (SD: 3.2; range: 1.2 months-11.3 years). The final total success rate for RF was 93% (n = 110). 19 patients (16%) underwent a total of 22 repeat procedures. Recurrences occurred after a mean period of 2.3 months (SD: 2.5) following successful RF ablation. Major complications (2nd degree AV block) occurred in 2 patients. During follow-up, no evidence was found of new arrhythmias or of coronary artery lesion development as the result ofRF ablation. There was no difference between the < 10 years of age group and the > or = 10 years of age group in terms of final success rate (93% vs. 93%; p = 0.914) and complication rate (3% vs. 7%, p = 0.680). CONCLUSION: The long-term outcome of paediatric patients who underwent RF ablation was good. RF ablation in young children (< 10 years) was found to be safe and effective. These results demonstrate that it is also possible to curatively treat this group of patients with RF ablation in specialized centres.

[Risk of ventricular fibrillation in patients with Wolff-Parkinson White syndrome]. / Risico van het ontstaan van ventrikelfibrilleren bij patiënten met Wolff-Parkinson-White-syndroom.

A 16-year-old boy suddenly fell off his stool, a 26-year-old man had persistent palpitations and a 29-year-old man was reanimated without an incriminating anamnesis. The diagnosis 'Wolff-Parkinson-White(WPW)-syndrome' was made in all three cases. The boy died as a result of postanoxic neurological injury; in the two men, further cardiac rhythm disturbances were prevented by interrupting the accessory atrioventricular connection via radiofrequency catheter ablation. In ECG databases, a WPW-pattern is encountered in 1-3 of 1000 electrocardiograms. Atrial fibrillation with 1:1 conduction via the accessory pathway, leading to ventricular fibrillation, is the most common cause of sudden death in WPW-patients. In some cases, atrial fibrillation with a rapid ventricular response is the first sign of the syndrome. The risk of sudden death in these patients is estimated to be 0.0-0.6% per patient per year and cannot be predicted easily. Curative treatment is possible in the form of radiofrequency catheter ablation.