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Background: Variants in KCNH2, encoding the human ether a-go-go (hERG) channel that is responsible for the rapid component of the cardiac delayed rectifier K+ current (IKr), are causal to long QT syndrome type 2 (LQTS2). We identified eight index patients with a new variant of unknown significance (VUS), KCNH2:c.2717C > T:p.(Ser906Leu). We aimed to elucidate the biophysiological effect of this variant, to enable reclassification and consequent clinical decision-making. Methods: A genotype–phenotype overview of the patients and relatives was created. The biophysiological effects were assessed independently by manual-, and automated calibrated patch clamp. HEK293a cells expressing (i) wild-type (WT) KCNH2, (ii) KCNH2-p.S906L alone (homozygous, Hm) or (iii) KCNH2-p.S906L in combination with WT (1:1) (heterozygous, Hz) were used for manual patching. Automated patch clamp measured the variants function against known benign and pathogenic variants, using Flp-In T-rex HEK293 KCNH2-variant cell lines. Results: Incomplete penetrance of LQTS2 in KCNH2:p.(Ser906Leu) carriers was observed. In addition, some patients were heterozygous for other VUSs in CACNA1C, PKP2, RYR2 or AKAP9. The phenotype of carriers of KCNH2:p.(Ser906Leu) ranged from asymptomatic to life-threatening arrhythmic events. Manual patch clamp showed a reduced current density by 69.8 and 60.4% in KCNH2-p.S906L-Hm and KCNH2-p.S906L-Hz, respectively. The time constant of activation was significantly increased with 80.1% in KCNH2-p.S906L-Hm compared with KCNH2-WT. Assessment of KCNH2-p.S906L-Hz by calibrated automatic patch clamp assay showed a reduction in current density by 35.6%. Conclusion: The reduced current density in the KCNH2-p.S906L-Hz indicates a moderate loss-of-function. Combined with the reduced penetrance and variable phenotype, we conclude that KCNH2:p.(Ser906Leu) is a low penetrant likely pathogenic variant for LQTS2.

Permanent pacemaker implantation (PPI) and left bundle branch block (LBBB) fre-quency after transcatheter aortic valve implantation (TAVI) and their effect on left ven-tricular ejection fraction (LVEF) remain controversial. We evaluated the incidence of PPI and new-onset LBBB after TAVI and their impact on LVEF at 6-month follow-up. More-over, the impact of right ventricular (RV) pacing burden on changes in LVEF after TAVI was analyzed. The electrocardiograms of 377 patients (age 80 +/- 7 years, 52% male) treated with TAVI were collected at baseline, after the procedure, at discharge, and at each outpatient follow-up. LVEF was measured at baseline before TAVI and 6 months after the procedure. Patients were divided into 3 groups according to the occurrence of LBBB, the need for PPI, or the absence of new conduction abnormalities. In patients with PPI, the influence of RV pacing burden on LVEF was analyzed. New-onset LBBB after TAVI occurred in 92 patients (24%), and PPI was required in 55 patients (15%). In patients without new conduction abnormalities, LVEF significantly increased during fol-low-up (56 +/- 14% to 61 +/- 12%, p < 0.001). Patients with a baseline LVEF

Funding Acknowledgements Type of funding sources: None. Background In patients with hypertrophic cardiomyopathy (HCM) accurate risk stratification for new onset atrial fibrillation (AF) has important prognostic implications. Left atrioventricular coupling index (LACI) has been recently associated with the occurrence of AF in patients without history of cardiovascular disease. Purpose The objective of this study was to investigate the association between LACI and new onset AF in HCM patients and its incremental value over conventional left atrial (LA) parameters. Methods A total of 373 HCM patients without history of AF (48 ± 17 years, 66% men) were evaluated by transthoracic echocardiography. LACI was defined by the ratio of the LA end-diastolic volume divided by the LV end-diastolic volume. The cut-off value for LACI (≥40%) to identify LA-left ventricular (LV) uncoupling was chosen based on the risk excess of new-onset AF described with a spline curve analysis. Cox proportional hazard models were used to evaluate the association between LACI and the occurrence of AF. Results The median LACI was 38% (interquartile range: 24-56) and LA-LV uncoupling (LACI ≥40%) was observed in 171 (45.8%) patients. During a mean follow-up of 11.0 ± 5.6 years, 118 subjects (31.6%) developed new-onset AF. The cumulative event-free survival at 10 years was 53% for patients with LA-LV uncoupling (LACI ≥40%) versus 94% for patients without LA-LV uncoupling (LACI Conclusion Greater LACI, indicative of LA-LV uncoupling, was independently associated with the occurrence of new-onset AF in patients with HCM and demonstrated a stronger risk discrimination power compared to conventional LA parameters. This simple ratio may be easily implemented in clinical practice to improve risk stratification for new-onset AF in HCM. Abstract Figure. Incident AF according to LACI Abstract Figure.

Aims We describe five patients with syncope caused by a complete atrioventricular block (AVB) while they were bending forward, not rising after bending, and aim to describe the occurrence and the association between bending forward and AVB. Methods and results In two patients, bending forward was the exclusive trigger for syncope, while in the remaining three, other postural changes (sitting down, standing up, and exertion) could also provoke syncope. Complete AVB as the cause of syncope was documented using ECG monitoring in two cases and an implantable loop recorder in the other three. Ectopic beats without preceding sinus slowing occurred before syncope in four cases. Two cases had a left bundle branch block. All patients responded favourably to cardiac pacing. Conclusion This is the first case series on complete AVB provoked by bending forward. Syncope during bending forward should suggest a search for an AVB. Arguments in favour of a vagal mechanism were syncope triggered by bending forward, and that other triggers could also evoke syncope. However, the absence of sinus slowing before syncope in some cases and the fact that bending forward did not seem to provoke reflex syncope without AVB, cast doubts on a reflex mechanism. There were also arguments favouring conduction disorder: i.e. ectopic beats before syncope and pre-existing conduction disturbances in two cases. The cases are reminiscent of paroxysmal AVB. Discrimination between paroxysmal AVB and vagal AVB is important because a pacemaker is warranted in arrhythmic complete AVB, while the benefit is limited or absent in reflex AVB.

Background: QT interval variability (QTV) and heart rate turbulence (HRT) are measures of cardiac autonomic function, which, when abnormal, are correlated with ventricular arrhythmias and worse clinical outcome. This study aims to evaluate QTV and HRT in patients with a systemic right ventricle (RV) and to assess correlations with clinical characteristics.Methods: In a retrospective cohort study, QTV and HRT were derived from 24-h Holter registrations of patients with a systemic RV and healthy controls. QTV and HRT were compared between groups. In patients, the association between QTV, HRT, and clinical characteristics was assessed.Results: Holter recordings from 40 patients (mean age 40 years, 16 females) and 37 healthy controls (mean age 42 years, 21 females) were analyzed. Groups were comparable in terms of age and sex. QTV was increased in patients compared with controls (p < 0.001), HRT did not differ significantly between the groups. Increased QTV and decreased HRT correlated with medication use, especially of diuretics, and with clinical events, particularly supraventricular arrhythmias. Increased QTV correlated with reduced systemic RV function. Decreased HRT was independently associated with a larger number of past clinical events (estimate -0.33, 95% CI -0.63 to -0.02, p = 0.037). QTV was higher in women in both patients and controls (p = 0.041 and p = 0.034, respectively).Conclusions: QTV and HRT are associated with clinical factors and events in patients with a systemic RV. Further studies are mandatory to confirm their prognostic value. (C) 2020 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.

Cardiac resynchronization therapy (CRT) is a well-established heart failure (HF) treatment and exerts its effects through restoration of synchronous ventricular contraction. Myocardial work (MW) is a novel semiautomatic echocardiographic method which characterizes the efficacy of the left

AimsIdiopathic ventricular fibrillation (IVF) is a rare cause of sudden cardiac arrest. Implantable cardioverter-defibrillator (ICD) implantation is currently the only treatment option. Limited data are available on the prevalence and complications of ICD therapy in these patients. We sought to investigate ICD therapy and its complications in patients with IVF.Methods and resultsPatients were selected from a national registry of IVF patients. Patients in whom no underlying diagnosis was found during follow-up were eligible for inclusion. Recurrence of ventricular arrhythmia (VA) was derived from medical and ICD records, electrogram records of ICD therapies were used to differentiate between appropriate or inappropriate interventions. Independent predictors for appropriate ICD shock were calculated using cox regression. In 217 IVF patients, recurrence of sustained VAs occurred in 66 patients (30%) during a median follow-up period of 6.1 years. Ten patients died (4.6%). Thirty-eight patients (17.5%) experienced inappropriate ICD therapy, and 32 patients (14.7%) had device-related complications. Symptoms before cardiac arrest [hazard ratio (HR): 2.51, 95% confidence interval (CI): 1.48–4.24], signs of conduction disease (HR: 2.27, 95% CI: 1.15–4.47), and carrier of the DPP6 risk haplotype (HR: 3.24, 1.70–6.17) were identified as independent predictors of appropriate shock occurrence.ConclusionImplantable cardioverter-defibrillator therapy is an effective treatment in IVF, treating recurrences of potentially lethal VAs in approximately one-third of patients during long-term follow-up. However, device-related complications and inappropriate shocks were also frequent. We found significant predictors for appropriate ICD therapy. This may imply that these patients require additional management to prevent recurrent events.

Right ventricular (RV) dysfunction is a well-known prognostic factor in several cardiac diseases. However, the prevalence of RV dysfunction in hypertrophic cardiomyopathy (HC) is unclear and its prognostic value is unknown. This study aims at addressing these issues assessing RV function with speckle tracking echocardiography. In 267 HC patients (52 +/- 15 years, 68% male), standard and advanced echocardiographic measurements of RV function were performed including RV 4-chamber longitudinal strain (RV4CLS) and RV free wall longitudinal strain (RVFWLS). The primary end point was all-cause mortality and heart failure development. RV dysfunction was observed in 9% of patients based on tricuspid annular plane systolic excursion (=-19%, 39% based on RVFWLS >=-23%, and 55% based on RV4CLS >=-20%. In total 59 (22%) patients reached the primary end point during a median follow-up of 6.7 (interquartile range 4.2 to 9.8) years. Kaplan-Meier survival curve showed a significant worse survival free of the end point for patients with impaired RV4CLS >=-20% versus patients with preserved RV4CLS =-19% versus patients with preserved RVFWLS

Aims Genetic, dilated cardiomyopathy (DCM) can be caused by a large variety of mutations. Mutation carriers are often asymptomatic until DCM is well established, presenting with heart failure, arrhythmias, or sudden cardiac death. Preventive strategies can only be applied if DCM can be detected early. Echocardiographic, left ventricular (LV) global longitudinal strain (GLS) is a promising tool for early diagnosis, i.e. before a decrease in LV ejection fraction (EF) has occurred. We, therefore, investigated the role of LV GLS as an early disease marker in genetic DCM.Methods and results Genetic DCM patients and genotyped family members were evaluated. The study population was grouped as (i) genotype-positive, phenotype-positive (GPFP) patients with a pathogenic mutation and LVEF = 55%, and (iii) genotype-negative, phenotype-negative (GNFN) individuals without a pathogenic mutation and LVEF >= 55%. One hundred and fifteen individuals (53 +/- 15 years, 51% male) were analysed: 28 (24%) were classified as GNFN, 50 (44%) as GPFN, and 37 (32%) as GPFP. Various mutations were represented: 39 (34%) titin, 14 (12%) lamin A/C, 13 (11%) sarcomeric, and 21 (18%) less frequent mutations (grouped together). The mean LVEF was 58 +/- 14% for all subjects. The mean LV GLS in the GNFN group was -21.7 +/- 1.5% vs. -19.7 +/- 3.5% for the GPFN group (P = 0.036). The mean LV GLS was -12.9 +/- 4.3% for the GPFP category (P < 0.001 vs. GPFN and GNFN).Conclusion Decreased LV GLS discriminates GPFN individuals from normal controls, which may permit early institution of therapy for genetic DCM.

The etiology of dilated cardiomyopathy (DCM) can be grouped as either genetic or nongenetic. More than 50 pathogenic genes have been described, with sarcomeric and lamin A/C mutations being the most common. Mutation carriers for genetic DCM are often asymptomatic until cardiac disease manifests with heart failure, arrhythmias, or sudden cardiac death. Preventive strategies are promising but can only be applied and tested adequately if genetic DCM can be diagnosed at an early stage. Early diagnosis of mutation carriers that may develop overt DCM requires advanced imaging techniques that can detect subtle structural and functional abnormalities. Advanced echocardiographic techniques such as tissue Doppler imaging and speckle tracking strain analysis permit early detection of functional abnormalities, whereas cardiovascular magnetic resonance techniques provide information on tissue characterization and myocardial energetics that may be altered at an early stage. Furthermore, nuclear imaging techniques provide information on cellular function (metabolism, perfusion). Once the diagnosis of overt DCM has been established, various imaging parameters such as echocardiography-based myocardial mechanics and cardiovascular magnetic resonance-based tissue characterization have shown incremental benefit to left ventricular ejection fraction in risk stratification. Further research is required to understand how imaging techniques may help to choose management strategies that could delay progression when instituted early in the course of the disease. The present article reviews the role of imaging in the risk stratification of genetic DCM in general, with specific emphasis on DCM associated with neuromuscular disorders.

ObjectivesThe purpose of this study was to investigate the relationship between the onset of asystole and transient loss of consciousness (TLOC) in tilt-induced reflex syncope and estimate how often asystole was the principal cause of TLOC.BackgroundThe presence of asystole in vasovagal syncope (VVS) may prompt physicians to consider pacemaker therapy for syncope prevention, but the benefit of pacing is limited in VVS.MethodsWe evaluated electrocardiography, electroencephalography, blood pressure, and clinical findings during tilt-table tests. Inclusion required TLOC (video), electroencephalographic slowing, accelerating blood pressure decrease, and an RR interval ≥3 s. We excluded cases with nitroglycerin provocation. Asystole after onset of TLOC (group A) or within 3 seconds before TLOC (group B) was unlikely to cause TLOC, but an earlier start of asystole (group C) could be the cause of TLOC.ResultsIn one-third of 35 cases (groups A [n = 9] and B [n = 3]), asystole was unlikely to be the primary cause of TLOC. The median of the mean arterial pressure at the onset of asystole was higher when asystole occurred early (45.5 mm Hg, group C) than when it occurred late (32.0 mm Hg, groups A and B), which suggests that vasodepression was not prominent at the start of asystole in early asystole, further suggesting that early asystole was the prime mechanism of syncope.ConclusionsIn one-third of cases of tilt-induced asystolic reflex syncope, asystole occurred too late to have been the primary cause of TLOC. Reliance on electrocardiography data only is likely to overestimate the importance of asystole.

Background— Interpretation of missense variants can be especially difficult when the variant is also found in control populations. This is what we encountered for the LMNA c.992G>A (p.(Arg331Gln)) variant. Therefore, to evaluate the effect of this variant, we combined an evaluation of clinical data with functional experiments and morphological studies. Methods and Results— Clinical data of 23 probands and 35 family members carrying this variant were retrospectively collected. A time-to-event analysis was performed to compare the course of the disease with carriers of other LMNA mutations. Myocardial biopsies were studied with electron microscopy and by measuring force development of the sarcomeres. Morphology of the nuclear envelope was assessed with immunofluorescence on cultured fibroblasts. The phenotype in probands and family members was characterized by atrioventricular conduction disturbances (61% and 44%, respectively), supraventricular arrhythmias (69% and 52%, respectively), and dilated cardiomyopathy (74% and 14%, respectively). LMNA p.(Arg331Gln) carriers had a significantly better outcome regarding the composite end point (malignant ventricular arrhythmias, end-stage heart failure, or death) compared with carriers of other pathogenic LMNA mutations. A shared haplotype of 1 Mb around LMNA suggested a common founder. The combined logarithm of the odds score was 3.46. Force development in membrane-permeabilized cardiomyocytes was reduced because of decreased myofibril density. Structural nuclear LMNA -associated envelope abnormalities, that is, blebs, were confirmed by electron microscopy and immunofluorescence microscopy. Conclusions— Clinical, morphological, functional, haplotype, and segregation data all indicate that LMNA p.(Arg331Gln) is a pathogenic founder mutation with a phenotype reminiscent of other LMNA mutations but with a more benign course.

Background— Current methods for predicting adverse events in patients with hypertrophic cardiomyopathy are still limited. Left ventricular global longitudinal strain (GLS) and left atrial volume index (LAVI) have been recently proposed as novel prognostic factors in several cardiovascular diseases. The objective of this study was to evaluate the prognostic value of GLS and LAVI in patients with hypertrophic cardiomyopathy. Methods and Results— Two-dimensional echocardiography was performed in 427 patients with hypertrophic cardiomyopathy (66% men, age 52±15 years), and LAVI and GLS were assessed. During follow-up, the primary end point of all-cause mortality, heart transplantation, sudden cardiac death, and appropriate implantable cardioverter defibrillator therapy was noted. A total of 103 patients reached the primary end point during a follow-up of 6.7 (interquartile range, 3.3–10.0) years. Multivariable Cox regression analysis revealed GLS and LAVI to be independently associated with the primary end point (hazard ratio GLS, 1.10 [1.03–1.19], P =0.007; hazard ratio LAVI, 4.27 [2.35–7.74], P 2 for LAVI and −15% for GLS, Kaplan–Meier survival curves showed significant better survival for patients with LAVI 2 ( P P P Conclusions— GLS and LAVI are independently associated with adverse outcome in patients with hypertrophic cardiomyopathy and may help to optimize risk stratification in these patients.

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. Electronic supplementary material The online version of this article (10.1007/s12471-017-1037-5) contains supplementary material, which is available to authorized users.

High sensitive troponin T (hs-cTnT) assays facilitate early detection of myocardial necrosis. However, their prognostic value is yet uncertain. The value of peak and serial 6 hour hs-cTnT for estimation of infarct size, reflected as 48 hour cumulative creatine kinase release (Q48CK), and

Aims The number of implanted cardiac rhythm devices has rapidly increased in the past decade. Subsequently, the need for lead extraction has also increased. Several techniques of lead removal have been documented from manual traction of the lead to lead extraction assisted with mechanical or laser sheaths. The goal of this study was to review our experience with lead removal using manual traction without the assistance of extraction sheaths. Methods and results In the Leiden University Medical Center all leads are removed using manual traction without the assistance of extraction sheaths. We have retrospectively reviewed all lead removal procedures performed between 2000 and 2009. Procedures were reviewed for indication, success, complication rates, and mortality. In total, 279 lead removal procedures were included. During these procedures 445 leads were removed. Time since lead implantation: 4.2 ± 4.7 years. During extraction 53(11.9%) leads fractured, of which >50% could still be completely removed using a femoral approach. A longer implantation duration [odds ratio (OR) 1.16 per year, 95% confidence interval (CI) 1.09-1.23] and passive fixation (OR 2.52, 95%CI 1.17-5.45) significantly associated with the chance of lead fracture during lead removal. Clinical success, using the primary approach of manual traction from the pectoral area, was obtained in 228 (84.8%) procedures. Major complications occurred in 2(0.7%) and minor in 13(4.7%) procedures. One patient died within 24 h after the procedure due to septic shock. There was no further mortality within the first month after the procedure. Conclusion Lead removal using manual traction, without the assistance of lead extraction sheaths, is clinically successful in ~85% of the lead extraction procedures. Concomitant morbidity and mortality are low. The highest clinical success (~95%) was observed in patients with leads implanted less than 2.6 years.

AIMS To evaluate the clinical outcomes of sirolimus-eluting stent (SES) versus bare metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) at long-term follow-up. METHODS AND RESULTS After five years, 310 STEMI patients randomly assigned to implantation of either SES or BMS, were compared. Survival rates were comparable between groups (SES 94.3% vs. BMS 92.8%, p=0.57), as were the rates of reinfarction (10.6% vs. 13.7%, p=0.40), freedom of death/re-MI (84.4% vs. 79.8%, p=0.29) and target vessel failure (14.9% vs. 21.7%, p=0.11). Likewise, rates of overall stent thrombosis (ST) (5.4% vs. 2.7%, p=0.28) and very late ST (4.1% vs. 0.7%, p=0.07) did not significantly differ between the SES- and BMS-group. In 184 patients with IVUS data, definite and definite/probable VLST was more common in those with late stent malapposition versus those without late stent malapposition (4.3% and 6.6% vs. no events [p=0.018 and p=0.004], respectively). The cumulative incidences of target vessel and target lesion revascularisation (TVR and TLR) were not significantly lower in the SES-group (11.2% vs. 17.9%, p=0.09 and 7.2% vs. 12.9%, p=0.08), as was the rate of clinically driven TLR (6.6% vs. 9.5%, p=0.30). CONCLUSIONS SES implantation was neither associated with increased rates of major adverse cardiac events, nor with a reduction in re-intervention, compared to implantation of a BMS in patients with STEMI after five years. However, a trend of more very late stent thrombosis was observed after SES implantation (ISRCTN62825862).

Background and purpose Left ventricular ejection fraction lacks specificity to predict sudden cardiac death in heart failure. T-wave alternans (TWA; beat-to-beat T-wave instability, often measured during exercise) is deemed a promising noninvasive predictor of major cardiac arrhythmic event. Recently, it was demonstrated that TWA during recovery from exercise has additional predictive value. Another mechanism that potentially contributes to arrhythmogeneity is exercise-recovery hysteresis in action potential morphology distribution, which becomes apparent in the spatial ventricular gradient (SVG). In the current study, we investigated the performance of TWA amplitude (TWAA) during a complete exercise test and of exercise-recovery SVG hysteresis (SVGH) as predictors for lethal arrhythmias in a population of heart failure patients with cardioverter-defibrillators (ICDs) implanted for primary prevention. Methods We performed a case-control study with 34 primary prevention ICD patients, wherein 17 patients (cases) and 17 patients (controls) had no ventricular arrhythmia during follow-up. We computed, in electrocardiograms recorded during exercise tests, TWAA (maximum over the complete test) and the exercise-recovery hysteresis in the SVG. Statistical analyses were done by using the Student t test, Spearman rank correlation analysis, receiver operating characteristics analysis, and Kaplan-Meier analysis. Significant level was set at 5%. Results Both SVGH and TWAA differed significantly ( P μ V) and controls (SVGH: 5% ± 26%, TWAA: 49 ± 20 μ V). Values of TWAA and SVGH showed no significant correlation in cases ( r = −0.16, P = .56) and in controls ( r = −0.28, P = .27). Receiver operating characteristics of SVGH (area under the curve=0.734, P = .020) revealed that SVGH less than 14.8% discriminated cases and controls with 94.1% sensitivity and 41.2% specificity; hazard ratio was 3.34 (1.17-9.55). Receiver operating characteristics of TWA (area under the curve=0.699, P = .048) revealed that TWAA greater than 32.5 μ V discriminated cases and controls with 93.8% sensitivity and 23.5% specificity; hazard ratio was 2.07 (0.54-7.91). Discussion and conclusion Spatial ventricular gradient hysteresis bears predictive potential for arrhythmias in heart failure patients with an ICD for primary prevention, whereas TWA analysis seems to have lesser predictive value in our pilot group. Spatial ventricular gradient hysteresis is relatively robust for noise, and, as it rests on different electrophysiologic properties than TWA, it may convey additional information. Hence, joint analysis of TWA and SVGH may, possibly, improve the noninvasive identification of high-risk patients. Further research, in a large group of patients, is required and currently carried out by our group.

Aims Myocardial excitability is known (amongst other reasons) to be related to the degree of ischaemia, contractile dysfunction and heart failure. It was hypothesized that the right ventricular (RV) stimulation threshold has prognostic value with respect to the occurrence of ventricular arrhythmias (VAs) and patient survival in recipients of an implantable cardioverter defibrillator (ICD). Methods and results Ischaemic heart disease patients receiving an ICD at Leiden University Medical Center as primary prevention for sudden cardiac death were included in this study. Right ventricular thresholds were determined at ICD implant. Data were collected on VAs triggering ICD therapy and on all-cause mortality. A total of 689 consecutive patients were included (87% male, age 63 ± 11 years, left ventricular ejection fraction (LVEF) 29 ± 11%) and followed for a median of 28 months. Post-implant RV-threshold was 0.7 ± 0.5 volt (V) at 0.5 ms pulse duration. Best dichotomous separation was reached at a cut-off of 1 V. During follow-up, 167 (24%) patients received appropriate ICD therapy, 88 (13%) had appropriate shocks and 134 (19%) died. Cumulative appropriate shock incidence for patients with RV threshold ≥1 V ( n = 166) was 16% at 1 year, 24% at 3 years and 34% at 5 years compared with 4, 11 and 17% for patients with an RV-threshold

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-AMT 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) mu g/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.)

Aims To assess the number of patients in daily clinical practice that meets criteria for implantation of an implantable cardioverter defibrillator (ICD) following acute myocardial infarction (AMI) when treated according to an aggressive treatment protocol. Methods and results Patients were treated according to the MISSION! protocol. The protocol encompasses pre-hospital, in-hospital, and outpatient clinical framework for the acute and chronic treatment of AMI patients and the decision making regarding primary prevention of sudden cardiac death (SCD). A total of 676 consecutive AMI patients (78% male, mean age 59 +/-\12 years) treated according to the MISSION! protocol were included in this analysis. Left ventricular ejection fraction at 3 months was 54 +/- 10%. Only 39 (6%) patients met criteria for implantation of an ICD

UNLABELLED Homografts and stentless xenografts are increasingly used in aortic valve surgery. Echocardiography technicians and cardiologists have to know what they will find when performing an echo-Doppler examination in patients who received a stentless valve. We therefore evaluated echocardiographic images of 74 patients who received a Freestyle stentless bioprosthesis with three techniques and a follow-up of 2 years in two high-volume hospitals. Of the patients studied, 81% were operated using the subcoronary technique, 12% using the root-inclusion technique, and 7% using the full-root technique. RESULTS Transvalvular gradients across the stentless valves were low: 8.0 mmHg when implanted with the subcoronary technique, 8.2 +/- 5.1 mmHg using the root-inclusion technique, and 6.5 mmHg using the full-root technique. Trivial aortic insufficiency (grade 1) was observed in 10.7% of the patients (8.9% for the subcoronary technique, 13% for the root-inclusion technique, and 0% for the full-root technique). When the bioprosthesis was implanted using the subcoronary technique or the root-inclusion technique, the prosthesis was placed inside the recipient aortic root. Using these techniques, a lumen between the double layer of the xenograft and the aortic wall could be observed. With the root-replacement technique, the porcine root became the most proximal part of the ascending aorta. As the native aortic wall was removed, in most cases, no double lumen could be observed with imaging of the ascending aorta.

The use of advanced imaging modalities for early determination of infarct size is limited in daily practice and therefore, it would be of particular use to estimate infarct size and prognosis by troponin (cTnT). The value of peak and serial 6h high-sensitive (hs) cTnT for estimation of infarct size