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Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus. In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%. Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC. P.J. is supported by the Daniel Bravo Foundation grant and Spanish Society of Cardiology Magda Heras mobility grant, A.G. by the Wilton W. Webster Fellow of Heart Rhythm Society, The Johns Hopkins ARVD/C Programme by the Leonie-Wild Foundation, Leyla Erkan Family Fund for ARVD Research, The Hugh Calkins, Marvin H. Weiner, and Jacqueline J. Bernstein Cardiac Arrhythmia Center, Dr Francis P. Chiramonte Private Foundation, Dr Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins, Bogle Foundation, Campanella Family, Patrick J. Harrison Family, Peter French Memorial Foundation, and Wilmerding Endowments, H.K.J. by grants from Novo Nordisk Foundation, Denmark (NNF18OC0031258 and NNF20OC0065151), S.A.L. by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007, R.T. by the Canada Research Chairs programme, J.C.T. by the Philippa and Marvin Carsley Cardiology Research Chair. S.G.P. receives support from Ricerca Corrente funding scheme of the Italian Ministry of Health and Italian Ministry of Research and University Dipartimenti di Eccellenza 2018 to 2022 grant to the Molecular Medicine Department (University of Pavia). Sí

BACKGROUND: A variant in the SLC4A3 anion exchanger has been identified as a novel cause of short QT syndrome (SQTS), but the clinical importance of SLC4A3as a cause of SQTS or sudden cardiac death remains unknown.OBJECTIVE: The purpose of this study was to investigate the prevalence of potential disease-causing variants using gene panels including SLC4A3.METHODS: In this multicenter study, genetic testing was performed in 34 index patients with SQTS. The pathogenicity of novel SLC4A3variants was validated in a zebrafish embryo heart model.RESULTS: Potentially disease-causing variants were identified in 26% of patients and were mainly (15%) located in SLC4A3: 4 patients heterozygous for novel nonsynonymous SLC4A3 variants-p.Arg600Cys, p.Arg621Trp, p.Glu852Asp, and p.Arg952His-and 1 patient with the known p.Arg370His variant. In other SQTS genes, potentially disease-causing variants were less frequent (2× in KCNQ1, 1× in KCNJ2, and CACNA1C each). SLC4A3 variant carriers (n = 5) had a similar heart rate but shorter QT and J point to T wave peak intervals than did noncarriers (n = 29). Knockdown of slc4a3 in zebrafish resulted in shortened heart rate-corrected QT intervals (calculated using the Bazett interval) that could be rescued by overexpression of the native human SLC4A3-encoded protein (AE3), but neither by the mutant AE3 variants p.Arg600Cys, p.Arg621Trp, p.Glu852Asp nor by p.Arg952His, suggesting the pathogenicity of these variants. Dysfunction in slc4a3/AE3 was associated with alkaline cytosol and shortened action potential of cardiomyocytes.CONCLUSION: In about a quarter of patients with SQTS, a potentially disease-causing variant can be identified. Nonsynonymous variants in SLC4A3 represent the most common cause of SQTS, underscoring the importance of including SLC4A3in the genetic screening of patients with SQTS or sudden cardiac death.

PURPOSE: To evaluate the association between different right ventricular (RV) lead positions as assessed by cardiac computed tomography (CT) and echocardiographic and clinical outcomes in patients receiving cardiac resynchronization therapy (CRT).METHODS: We reviewed patient records of all 278 patients included in two randomized controlled trials (ImagingCRT and ElectroCRT) for occurrence of heart failure (HF) hospitalization or all-cause death (primary endpoint) during long-term follow-up. Outcomes were compared between RV lead positions using adjusted Cox regression analysis. Six months after CRT implantation, we estimated left ventricular (LV) reverse remodeling by measuring LV end-systolic and end-diastolic volumes by echocardiography. Changes from baseline to 6 months follow-up were compared between RV lead positions. Device-related complications were recorded at 6-month follow-up.RESULTS: During median (interquartile range) follow-up of 4.7 (2.9-7.1) years, the risk of meeting the primary endpoint was similar for patients with non-apical vs. apical RV lead position (adjusted hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.54-1.12, p = 0.17) and free wall vs. septal RV lead position (adjusted HR 1.03, 95% CI 0.72-1.47, p = 0.86). Changes in LV ejection fraction and dimensions were similar with the different RV lead positions. We observed no differences in device-related complications relative to the RV lead position.CONCLUSIONS: In patients receiving CRT, the risk of HF hospitalization or all-cause death during long-term follow-up, and LV remodeling and incidence of device-related complications after 6 months are not associated with different anatomical RV lead position as assessed by cardiac CT.

ObjectiveTo examine workforce attachment among patients with congenital long QT syndrome (cLQTS) following diagnosis and identify factors associated with workforce attachment.Methods and resultsIn this nationwide cohort study, all patients diagnosed with cLQTS in Denmark between 1996 and 2016 aged 18–60 years at diagnosis were identified using nationwide registries. Patients attached to the workforce at diagnosis were included. Attachment to the workforce 1 year after cLQTS diagnosis was examined and compared with a background population matched 1:4 on age, sex and employment status. Multiple logistic regression was performed to identify factors associated with 1-year workforce detachment among patients with cLQTS. 298 patients fulfilled the inclusion criteria. Six months after cLQTS diagnosis, 90.9% of patients with cLQTS were attached to the workforce compared with 95.0% in the background population (p=0.006 for difference). One year after diagnosis, 93.3% of patients with cLQTS were attached to the workforce compared with 93.8% in the background population (p=0.26). Among patients with cLQTS, a severe cLQTS disease manifestation was associated with workforce detachment 1 year after diagnosis (compared with asymptomatic patients; aborted cardiac arrest OR 20.4 (95% CI, 1.7 to 249.9); ventricular tachycardia/syncope OR 10.9 (95% CI, 1.1 to 110.5)). No other associated factors were identified.ConclusionsMore than 90% of patients with cLQTS remained attached to the workforce 1 year after diagnosis, which was similar to a matched background population. Patients with a severe cLQTS disease manifestation were less likely to be attached to the workforce 1 year after diagnosis.

Aims This study aims to investigate the long-term occurrence of the composite endpoint of heart failure (HF) hospitalization or all-cause death (primary endpoint) in patients randomized to cardiac resynchronization therapy (CRT) using individualized multimodality imaging-guided left ventricular (LV) lead placement compared with a routine fluoroscopic approach. Furthermore, this study aims to evaluate whether inter-lead electrical delay (IED) is associated with improved response rate of this endpoint. Methods and results We reviewed follow-up data until November 2020 for all 182 patients included in the ImagingCRT trial for the occurrence of HF hospitalization and all-cause death. During median (inter-quartile range) time to primary endpoint/censuring of 6.7 (3.3–7.9) years, the rate of the primary endpoint was 60% (n = 53) in the imaging group compared with 52% (n = 48) in the control group [hazard ratio (HR) 1.22, 95% confidence interval (CI) 0.83–1.81, P = 0.31]. Neither the risk of HF hospitalization (HR 1.11, 95% CI 0.62–1.99, P = 0.72) nor of all-cause death differed between treatment groups (HR 1.23, 95% CI 0.82–1.85, P = 0.32). The risk of the primary endpoint was significantly reduced among those with IED ≥100 ms when compared with those with IED Conclusions In this study, an individualized multimodality imaging-guided strategy targeting LV lead placement towards the latest mechanically activated non-scarred myocardial segment during CRT implantation did not reduce HF hospitalization or all-cause death when compared with routine LV lead placement during long-term follow-up. Targeting the latest electrical activation should be studied as an alternative individualized strategy for optimizing LV lead placement in CRT recipients.

BACKGROUND: Contact force (CF)-guided catheter ablation (CA) is a novel technology developed to improve efficacy and reduce complications. In a randomised controlled trial (RCT), we previously documented that after 3 months, rate of persistent conduction block was similar with and without using CF while performing CA for typical atrial flutter (AFL). Clinical effect of CF on recurrent arrhythmia is unknown. Our objective is to study recurrent atrial arrhythmia during 12-month follow-up in a RCT investigating whether CF-guided CA for typical AFL is superior to CF-blinded CA.METHODS: Patients were randomised 1:1 to CA guided by CF (intervention group) or blinded to CF (control group). After 12 months, patients attended clinical check-up preceded by a 5-day ambulatory Holter monitor recording. Primary outcome was any recurrent atrial arrhythmia ≥ 30 s within 12 months and documented in 12-lead ECG or Holter monitor recording.RESULTS: We included 156 patients, four patients withdrew consent and two died during follow-up. Thus, 150 patients were included in final analysis. Recurrent arrhythmia was detected in 36 of 77 (47%) patients in the intervention group, and 32 of 73 patients (44%) in the control group (p = 0.51). Atrial fibrillation was detected in 23 (30%) and 29 (40%) patients in the intervention and control groups respectively. AFL was detected in 11 (14%) and 5 (7%) patients in the intervention and control groups respectively.CONCLUSIONS: Contact force-guided ablation for typical atrial flutter does not reduce recurrent atrial arrhythmia after 12-month follow-up as compared with ablation blinded for contact force.

Background: Familial ST-depression syndrome is an inherited disease characterized by persistent, nonischemic ST-deviations, and risk of arrhythmias and heart failure. We aimed at further characterizing the ECG, arrhythmias, and structural characteristics associated with this novel syndrome. Methods: Retrospective analysis of data from consecutive families with familial ST-depression Syndrome in Denmark. ECG features, prevalence and type of arrhythmias, occurrence of systolic dysfunction, and medium-term outcome were analyzed. Results: Forty affected individuals (43% men; mean age at diagnosis 49.1 years) from 14 apparently unrelated families with ≥2 affected members were included. Autosomal dominant inheritance was observed in all families. The ECG phenotype seemed to develop in prepuberty and the ST-deviations were persistent and most pronounced in leads V4/V5/II, respectively. Serial ECG analyses showed stable to slow progression of the ECG phenotype. Exercise accentuated the ST-deviations with a maximum difference between rest/stress (mean) of −117 μV in lead V5. During a mean follow-up of 9.3±7.1 years 5 (13%) patients developed sustained ventricular arrhythmias or (aborted) sudden cardiac death, 10 (25%) developed atrial fibrillation, 2 (5%) other supraventricular arrhythmias, and 10 (25%) were diagnosed with left ventricular ejection fraction ≤50%. The ventricular arrhythmias were polymorphic with relatively short-coupled premature ventricular contractions at onset (300–360 ms); no QT prolongation was observed. Seven patients had at least one catheter ablation; 5 for supraventricular arrhythmias and 2 for ventricular arrhythmias. Males experienced more arrhythmic end points than females ( P Conclusions: The familial ST-depression ECG phenotype is stable to slowly progressive after medium-term follow-up. Clinically, both supra- and ventricular arrhythmias are common; as are some degree of left ventricular systolic dysfunction. Familial ST-depression represent a novel inherited cause of polymorphic ventricular tachycardia.

Contact force (CF)-guided catheter ablation (CA) is a novel technology developed to improve efficacy and reduce complications. In a randomised controlled trial (RCT), we previously documented that after 3 months, rate of persistent conduction block was similar with and without using CF while performing CA for typical atrial flutter (AFL). Clinical effect of CF on recurrent arrhythmia is unknown. Our objective is to study recurrent atrial arrhythmia during 12-month follow-up in a RCT investigating whether CF-guided CA for typical AFL is superior to CF-blinded CA.Patients were randomised 1:1 to CA guided by CF (intervention group) or blinded to CF (control group). After 12 months, patients attended clinical check-up preceded by a 5-day ambulatory Holter monitor recording. Primary outcome was any recurrent atrial arrhythmia ≥ 30 s within 12 months and documented in 12-lead ECG or Holter monitor recording.We included 156 patients, four patients withdrew consent and two died during follow-up. Thus, 150 patients were included in final analysis. Recurrent arrhythmia was detected in 36 of 77 (47%) patients in the intervention group, and 32 of 73 patients (44%) in the control group (p = 0.51). Atrial fibrillation was detected in 23 (30%) and 29 (40%) patients in the intervention and control groups respectively. AFL was detected in 11 (14%) and 5 (7%) patients in the intervention and control groups respectively.Contact force-guided ablation for typical atrial flutter does not reduce recurrent atrial arrhythmia after 12-month follow-up as compared with ablation blinded for contact force.

Background: Contact force (CF) guided catheter ablation (CA) is a novel technology developed to improve efficacy and reduce complications. In a randomised controlled trial (RCT), we previously documented that after three months, rate of persistent conduction block was similar with and without using CF while performing CA for typical atrial flutter (AFL). Clinical effect of CF on recurrent arrhythmia is unknown. Objective: To study recurrent atrial arrhythmia during 12-months follow-up in a RCT investigating whether CF-guided CA for typical AFL is superior to CF-blinded CA. Method: Patients were randomized 1:1 to CA guided by CF (intervention group) or blinded to CF (control group). After 12 months, patients attended clinical check-up preceded by a 5-day ambulatory Holter monitor recording. Primary outcome was any recurrent atrial arrhythmia ≥30 seconds within 12 months, symptomatic or asymptomatic and documented in 12-lead ECG or Holter monitor recording. We did intention-to-treat (ITT) analysis. Results: We included and randomized 156 patients, four patients withdrew consent and two died during follow-up. Thus, 150 patients were included in ITT-analysis, in which recurrent arrhythmia was detected in 47 (31%) patients, 25 in the intervention group and 22 in the control group (p = 0.25). Atrial fibrillation was detected in 38 patients (18 versus 20 patients), and AFL in the remaining 9 patients (7 versus 2 patients). Conclusion: Contact force guided ablation for typical atrial flutter does not reduce recurrent atrial arrhythmia after 12-months follow-up as compared with ablation blinded for contact force.

Background: A novel QDOT MICRO (Biosense Webster, Inc., Irvine, CA) catheter with optimized temperature control and microelectrodes was designed to incorporate real-time temperature sensing with contact force detection and microelectrodes to streamline ablation workflow. The QDOT-MICRO feasibility study evaluated the workflow, performance, and safety of temperature-controlled catheter ablation in patients with symptomatic paroxysmal atrial fibrillation with conventional ablation setting.Methods: This was a non-randomized, single-arm, first-in-human study. The primary outcome was pulmonary vein isolation (PVI), confirmed by entrance block after adenosine and/or isoproterenol challenge. Safety outcomes included incidences of early-onset primary adverse events (AEs) and serious adverse device effects (SADEs). Device performance was evaluated via physician survey.Results: All evaluated patients (n = 42) displayed 100% PVI. Two primary AEs (4.8%) were reported: 1 pericarditis and 1 vascular pseudoaneurysm. An additional SADE of localized infection was reported in 1 patient. No stroke, patient deaths, or other unanticipated AEs were reported. Average power delivered was 32.1±4.1 W, with a mean temperature of 40.8°C±1.6°C. Mean procedure (including 20-minute wait), fluoroscopy, and radiofrequency application times were 129.8, 6.7, and 34.0 minutes, respectively. On device performance, physicians reported overall satisfactory performance with the new catheter, with highest scores for satisfaction and usefulness of the temperature indicator.Conclusions: Initial clinical experience with the novel catheter showed 100% acute PVI success and acceptable safety and device performance in temperature-controlled ablation mode. There were no deaths, stroke, or unanticipated AEs. Fluoroscopy and procedural times were short and similar or better than reported for prior generation catheters.

Despite recent advances in treatment of severe aortic valve stenosis (AS), AS remains a common, life-threatening condition with no proven preventive therapy. Low-density lipoprotein cholesterol (LDL-C) and, particularly, lipoprotein(a) (Lp[a]) have been implicated in the pathobiology of AS. The

Cardiostim Vienna 2017 (18th June – 21th June) Title: A novel Triadin variant causes a severe clinical CPVT phenotype in two young brothers Authors: AK Broendberg1, C Dait2, J Bjerre3, LN Pedersen4, JC Nielsen1 , TJ Corydon2, & HK Jensen1 1Department of Cardiology, Aarhus University Hospital, Denmark 2Department of Biomedicine, Aarhus University, Denmark 3Department of Pediatrics, Aarhus University Hospital, Denmark 4Department of Molecular Medicine (MOMA), Aarhus University Hospital, Denmark Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited cardiac disorder, which enhances susceptibility to ventricular fibrillation (VF) due to altered intracellular calcium handling. The predominant gene in this disease is Ryanodine receptor-2 (RYR2), which is inherited in a dominant fashion. Mutations in Triadin (TRDN) is an extremely rare cause of CPVT and is inherited in a recessive manner. Purpose: To clinically characterize a family with a novel TRDN variant (NM_001251987)c.179T>C (p.Trp60Leu) and to establish functional properties of this variant. Methods: Genomic DNA purified from blood was used for genetic screening in our targeted next generation sequencing gene panel. TRDN wildtype and variant cDNA has been cloned in a pcDNA3.1 expression vector. Following transient transfection of human cells functional properties of Triadin wildtype and variant proteins have been obtained by means of Western blot analysis and immunostaining. Results: Two brothers both collapsed with exercise induced cardiac arrest and VF at the ages of three and two years, respectively. Both were treated with implantable cardioverter-defibrillator (ICD). The oldest brother has received appropriate shock therapy 6 times during exercise or emotional stress within 44 months of observation. He is currently stable on the combination of beta-blocker and flecainide. The youngest brother has not received any ICD therapy within 15 months on beta-blocker therapy. Genetic screening has revealed that both children are homozygote for the TRDN variant (p.Trp60Leu), which was found in heterozygous form in both parents, who are clinically unaffected. Preliminary functional studies have revealed reduced cellular expression of the variant form compared to wildtype. We still need to establish whether the observed findings are due to reduced expression of the TRDN gene and/or enhanced degradation of the corresponding variant protein. Conclusion: We found a novel TRDN variant, causing a severe clinical CPVT phenotype in two very young children. Preliminary functional studies have revealed reduced cellular expression of the variant form compared to wild type.

Andersen-Tawil syndrome (ATS) is a rare hereditary multi--system disorder consisting of a triad of symptoms, ventricular arrhythmias, periodic paralysis and dysmorphic features. The syndrome is associated with a loss of function mutation in the gene KCNJ2, which encodes the Kir2.1 inward rectifier potassium channel. We represent a case story of a 15-year-old girl who had unexplained arrhythmias for six years. Molecular genetic screening with a 75-heart-panel revealed a pathogenic KCNJ2 missense mutation. The patient was diagnosed with ATS.

Recent research in genetics has revealed that PCSK9 - which codes for proprotein convertase subtilisin/kexin type 9 (PCSK9) - plays a major role in cholesterol regulatory pathways. Normal genetic variations in PCSK9 have a great impact on low-density lipoprotein cholesterol levels and hence the risk of cardio-vascular disease. This has led to huge efforts in inhibiting PCSK9. Recent clinical phase II trials with monoclonal antibodies against PCSK9 have shown great results for lowering low-density lipoprotein cholesterol levels making the inhibition of PCSK9 a promising target in the prevention of cardiovascular disease.

Ventricular tachycardia (VT) occurs in up to 59% of patients with left ventricular assist devices (LVAD). In some of these patients, the VT cannot be managed medically or by implantable cardioverter-defibrillator. In this case, a 66-year-old male was successfully treated with radiofrequency ablation of intractable VT that developed months after implantation of an LVAD (Heartware). The LVAD provided haemodynamical support during mapping and did not interfere with the ablation.

We present a case regarding a 25-year-old woman who had been taking unauthorized weight loss pills prior to a sudden cardiac arrest from which she was resuscitated by paramedics. Her initial electrocardiogram revealed a prolonged corrected QT-interval (QTc). During admission she developed torsades de pointes and was treated with magnesium sulphate and temporary pacing. An electrophysiological study, a coronary angiogram and genetic testing for long QT syndrome all revealed normal results. After cessation of the pills the QTc normalized, and two weeks later she was discharged.

Verapamil administered intravenously is recommended as a first-line therapy in patients with supraventricular tachycardia. However, these patients may suffer from tachycardia-induced heart failure and particular caution is needed before prescription of verapamil in these cases. We present a case of fulminant acute heart failure following intravenous bolus administration of verapamil in a previously healthy young man. This case stresses the potential deleterious effects of this commonly prescribed drug.

The Atrial Fibrillation Ablation Pilot Study is a prospective, multinational registry conducted by the European Heart Rhythm Association of the European Society of Cardiology that has been designed to describe the clinical epidemiology of patients undergoing an atrial fibrillation (AFib) ablation procedure, and the diagnostic/therapeutic processes applied in these patients across Europe. We present the results of the short-term (in-hospital) analysis.A total of 72 centres in 10 European countries were asked to enrol 20 consecutive patients scheduled for a first AFib ablation procedure. Between October 2010 and May 2011, 1410 patients were included, of which 1391 underwent an AFib ablation (98.7%). The median age was 60 years [inter-quartile range (IQR) 52-66], and 28% were females. Two-thirds presented paroxysmal AFib and 38% lone AFib. Symptoms were present in 86%. The indications for ablation were mostly symptomatic AFib, but in over a third of patients there was also a desire for a drug-free lifestyle and the maintenance of sinus rhythm. Pulmonary vein isolation was attempted in 98.4% of patients, the roof line in 21.3% and the mitral isthmus line in 12.8%. Complex-fractionated atrial electrograms were targeted in 17.9% and the ganglionated plexi in 3.3%. Complications occurred in 7.7%, of which 1.7% was major (i.e. cardiac perforation, myocardial infraction, endocarditis, cardiac arrest, stroke, hemothorax, pneumothorax, and sepsis). The median duration of hospitalization was 3 days (IQR 2-4). At discharge, 91.4% of patients were in sinus rhythm, 88.3% of patients were given vitamin K antagonists, and 67% antiarrhythmic medication. There was one death after the ablation procedure.The AFib Ablation Pilot Study provides crucial information on AF ablation in clinical practice across Europe. These data are relevant for further improvement of the management strategies of patients suffering from atrial fibrillation.

An autopsy in a 28-year-old man did not explain the cause of sudden unexpected death. However, a history of episodes with tachycardia and dizziness and a reassessed previous electrocardiogram exhibiting ventricular pre-excitation was consistent with Wolff-Parkinson-White (WPW) syndrome. In this patient we believe that the occurrence of atrial fibrillation caused sudden cardiac death from ventricular fibrillation due to a short refractory period of an accessory atrioventricular pathway and a very rapid ventricular rate in atrial fibrillation.

Hypertrophic cardiomyopathy (HCM) may have sudden death as its first presentation. This case presentation describes a 25-year-old man with post-mortem finding of previously unknown left ventricular hypertrophy. Genetic analysis revealed a mutation in the myosin-binding protein C (MYBPC3). Autopsy combined with molecular genetic screening for mutations may give the relatives certainty of cause of death and the opportunity for genetic screening for diagnosis and treatment as well as prevention of sudden cardiac death.

Udgivelsesdato: 2009-null BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal repolarization is therefore warranted. Most drugs associated with risk are inhibitors of the rapidly activating delayed rectifier potassium current (I(Kr)). This current is also inhibited in the congenital type 2 form of the long QT syndrome (LQT2). It is therefore possible that electrocardiographic LQT2 patterns might be used to identify abnormal repolarization patterns induced by drugs. OBJECTIVE: To develop distinct T-wave morphology parameters typical of LQT2 and investigate their use as a composite measure for identification of d,l-sotalol (sotalol)-induced changes in T-wave morphology. METHODS: Three independent study groups were included: a group of 917 healthy subjects and a group of 30 LQT2 carriers were used for the development of T-wave morphology measures. The computerized measure for T-wave morphology (morphology combination score, MCS) was based on asymmetry, flatness and notching, which are typical ECG patterns in LQT2. Blinded to labels, the new morphology measures were tested in a third group of 39 healthy subjects receiving sotalol. Over 3 days the sotalol group received 0, 160 and 320 mg doses, respectively, and a 12-lead Holter ECG was recorded for 22.5 hours each day. Drug-induced prolongation of the heart rate corrected QT interval (QTcF) was compared with changes in the computerized measure for T-wave morphology. Effect sizes for QTcF and MCS were calculated at the time of maximum plasma concentrations and for maximum change from baseline. Accuracy for separating baseline from sotalol recordings was evaluated by area under the receiver operating characteristic curves (AUCs) using all recordings from the time immediately post-dose to maximum change. RESULTS: MCS separated baseline recordings from sotalol treatment with higher accuracy than QTcF for the 160 mg dose: (AUC) 84% versus 72% and for the 320 mg dose: (AUC) 94% versus 87%, p < 0.001. At maximum serum-plasma concentrations and at maximum individual change from baseline, the effect sizes for QTcF were less than half the effect sizes for MCS, p < 0.001. Effect sizes at peak changes of the mean were up to 3-fold higher for MCS compared with QTcF, p < 0.001. In subjects receiving sotalol, T-wave morphology reached similarity to LQT2, whereas QTcF did not. CONCLUSION: Distinct ECG patterns in LQT2 carriers effectively quantified repolarization changes induced by sotalol. Further studies are needed to validate whether this measure has general validity for the identification of drug-induced disturbed repolarization.

Segmental pulmonary vein isolation (SPVI) and circumferential pulmonary vein isolation (CPVI) are the two main approaches to radiofrequency ablation in patients with atrial fibrillation (AF). The aim of this retrospective study was to investigate the safety level and patient outcome of both approaches. The overall freedom from symptoms was 73% and 25% after CPVI and SPVI, respectively. Our study concludes that CPVI is an effective treatment of highly symptomatic and drug-resistant AF and when used in laboratories by experienced electrophysiologists has a promising and reproducible outcome ratio and safety level.

Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism characterized by very high plasma concentrations of low density lipoprotein cholesterol (LDLc), tendon xanthomas and increased risk of premature coronary heart disease (CHD). FH is a public health problem throughout the world. There are 10,000,000 people with FH worldwide, mainly heterozygotes, and approximately 85% of males and 50% of females with FH will suffer a coronary event before 65 years old if appropriate preventive efforts are not implemented. Early identification of persons with FH and their relatives, and the early start of treatment are essential issues in the prevention of premature cardiovascular disease (CVD) and death in this population. However, guidelines for the general population formally exclude FH from their diagnostic and treatment recommendations. These guidelines have been elaborated by a group of international experts with the intention to answer the main questions about heterozygous FH (heFH) subjects that physicians worldwide face in the diagnosis and management of these patients.

Patients with homozygous familial hypercholesterolaemia (FH) caused by receptor-negative, low-density lipoprotein (LDL) receptor gene mutations have higher concentrations of LDL-cholesterol in plasma and earlier onset of cardiovascular disease (CVD) than patients homozygous for receptor-defective, LDL receptor mutations. In contrast, it is uncertain whether the severity of atherosclerotic disease differs in heterozygous FH caused by receptor-negative and receptor-defective mutations. The present authors investigated the influence of LDL receptor mutation type on the clinical phenotype in 31 patients with heterozygous FH caused by the receptor-negative, Trp23-stop mutation and in 31 patients heterozygous for the receptor defective Trp66-Gly mutation. Untreated levels of plasma LDL-cholesterol and calculated cholesterol-years score did not differ significantly between the two groups of patients. Detection of vascular disease was based on two approaches: (1) measurement of coronary calcification by spiral computed tomography (CT) scanning; and (2) ultrasonic measurement of carotid intima-media thickness (IMT). Age was significantly correlated to the presence of coronary calcification, but controlling for relevant cofactors, there was no evidence that the receptor-negative mutation caused more calcification than the receptor-defective mutation. Furthermore, carotid IMT was significantly influenced by plasma concentrations of Lp(a) and triglycerides, as well as by age, sex and smoking status, but again, there was no statistically significant effect of LDL receptor gene mutational type. The similarity in vascular phenotypes was probably caused by a similar life-long burden of LDL-cholesterol in the two groups of patients.