High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein-2 (DSG2) mutation carriers to those who carry the plakophilin-2 (PKP2) mutation, the most common ARVC/D-associated gene. METHODS AND RESULTS: Consecutive ARVC/D patients carrying a pathogenic mutation in PKP2 or DSG2 were selected from a national ARVC/D registry. The cumulative freedom from sustained ventricular arrhythmia and cardiac transplantation/death from heart failure (HF) during follow-up was assessed, compared between PKP2 and DSG2, and predictors for ventricular arrhythmia and HF events determined. Overall, 118 patients from 78 families were included: 27 (23%) carried a DSG2 mutation and 91 (77%) a PKP2 mutation. There were no significant differences between DSG2 and PKP2 mutation carriers concerning gender, proband status, age at diagnosis, T-wave inversion, or right ventricular dysfunction at baseline. DSG2 patients displayed more frequent epsilon wave (37% vs. 17%, P = 0.048) and left ventricular dysfunction at diagnosis (54% vs. 10%, P < 0.001). During a median follow-up of 5.6 years (2.5-16), DSG2 and PKP2 mutation carriers displayed a similar risk of sustained ventricular arrhythmia (log-rank P = 0.20), but DSG2 mutation carriers were at higher risk of transplantation/HF-related death (log-rank P < 0.001). The presence of a DSG2 mutation vs. PKP2 mutation was a predictor of transplantation/HF-related death in univariate Cox analysis (P = 0.0005). CONCLUSIONS: In this multicentre cohort, DSG2 mutation carriers were found to be at high risk of end-stage HF compared to PKP2 mutation carriers, supporting careful haemodynamic monitoring of these patients. The benefit of early HF treatment needs to be assessed in DSG2 carriers.

Electrocardiographic characteristics of patients with funnel chest before and after surgical correction using pectus bar: A new association with precordial J wave pattern.

OBJECTIVE: Abnormal ECG findings suggestive of cardiac disease are frequent in patients with funnel chest, although structural heart disease is rare. Electrocardiographic characteristics and changes following new surgical treatments in young adults are not described so far. The aim of the study was to analyze electrocardiographic characteristics of patients with funnel chest before and after minimally invasive funnel chest correction by the Nuss procedure. METHODS: Twenty-six patients with surgical correction of funnel chest using pectus bar were included. Twelve-lead ECGs before and later than one year after surgery were analyzed. RESULTS: In postoperative ECGs, amplitude of P wave in lead II and negative terminal amplitude of P wave in lead V1 decreased from 0.13 to 0.10mV (p=0.03), and from 0.10 to 0.04mV (p<0.001), respectively. Mean QRS duration decreased from 108ms to 98ms (p=0.003) after correction. A pathological left and right Sokolow-Lyon index was observed in 35% and 23% of patients before, versus 8% (p=0.04) and 0% (p=0.01) after correction, respectively. In contrast, the rate of patients with J wave pattern in precordial leads V4-V6 increased from 8% before to 42% after surgery (p=0.004). CONCLUSIONS: ECG abnormalities in patients with funnel chest are frequent, and can normalize after surgical correction by the Nuss procedure. De novo J wave pattern in precordial leads V4-V6 is a frequent finding after surgical funnel chest correction using pectus bar.

Time Course of Atrial Fibrillation in Patients With Congenital Heart Defects.

BACKGROUND: The incidence of atrial fibrillation (AF) is rising in the aging patients with congenital heart defects (CHD). However, studies reporting on AF in patients with CHD are scarce. The aim of this multicenter study was to examine in a large cohort of patients with a variety of CHD: (1) the age of onset and initial treatment of AF, coexistence of atrial tachyarrhythmia and (2) progression of paroxysmal to (long-standing) persistent/permanent AF during long-term follow-up. METHODS AND RESULTS: Patients (n=199) with 15 different CHD and documented AF episodes were studied. AF developed at 49±17 years. Regular atrial tachycardia (AT) coexisting with AF occurred in 65 (33%) patients; 65% initially presented with regular AT. At the end of a follow-up period of 5 (0-24) years, the ECG showed AF in 81 patients (41%). In a subgroup of 114 patients, deterioration from paroxysm of AF to (long-standing) persistent/permanent AF was observed in 29 patients (26%) after only 3 (0-18) years of the first AF episode. Cerebrovascular accidents/transient ischemic attacks occurred in 26 patients (13%), although a substantial number (n=16) occurred before the first documented AF episode. CONCLUSIONS: Age at development of AF in patients with CHD is relatively young compared with the patients without CHD. Coexistence of episodes of AF and regular AT occurred in a considerable number of patients; most of them initially presented with regular AT. The fast and frequent progression from paroxysmal to (long-standing) persistent or permanent AF episodes justifies close follow-up and early, aggressive therapy of both AT and AF.

Prevalence and significance of rare RYR2 variants in arrhythmogenic right ventricular cardiomyopathy/dysplasia: results of a systematic screening.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic disease predominantly caused by desmosomal gene mutations that account for only ~50% of cases. Ryanodine receptor 2 (RYR2) gene mutations usually cause catecholaminergic polymorphic ventricular tachycardia but have been associated with a peculiar phenotype named ARVC2. OBJECTIVE: We aimed to determine the prevalence and phenotype associated with RYR2 mutations in a large ARVC/D population. METHODS: We analyzed the whole RYR2 coding sequence by Sanger sequencing in 64 ARVC/D probands without desmosomal gene mutations. RESULTS: We have identified 6 rare missense variants: p.P1583S, p.A2213S, p.G2367R, p.Y2932H, p.V3219M, and p.L4670V. It corresponds to a 9% prevalence of rare RYR2 variants in the ARVC/D population (6 of 64 probands), which is significantly higher than the estimated frequency of rare RYR2 variants in controls (Fisher exact test, P = .03). Phenotypes associated with RYR2 variants were similar to desmosome-related ARVC/D, associating typical electrocardiographic abnormalities at rest, frequent monomorphic ventricular tachycardia, right ventricular dilatation, wall motion abnormalities, and fibrofatty replacement when histopathological examination was available. CONCLUSION: In this first systematic screening of the whole coding region of the RYR2 gene in a large ARVC/D cohort without mutation in desmosomal genes, we show that putative RYR2 mutations are frequent (9% of ARVC/D probands) and are associated with a conventional phenotype of ARVC/D, which is in contrast with previous findings. The results support the role of the RYR2 gene in conventional ARVC/D.

Usefulness of electrocardiographic parameters for risk prediction in arrhythmogenic right ventricular dysplasia.

The value of electrocardiographic findings predicting adverse outcome in patients with arrhythmogenic right ventricular dysplasia (ARVD) is not well known. We hypothesized that ventricular depolarization and repolarization abnormalities on the 12-lead surface electrocardiogram (ECG) predict adverse outcome in patients with ARVD. ECGs of 111 patients screened for the 2010 ARVD Task Force Criteria from 3 Swiss tertiary care centers were digitized and analyzed with a digital caliper by 2 independent observers blinded to the outcome. ECGs were compared in 2 patient groups: (1) patients with major adverse cardiovascular events (MACE: a composite of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or arrhythmic syncope) and (2) all remaining patients. A total of 51 patients (46%) experienced MACE during a follow-up period with median of 4.6 years (interquartile range 1.8 to 10.0). Kaplan-Meier analysis revealed reduced times to MACE for patients with repolarization abnormalities according to Task Force Criteria (p = 0.009), a precordial QRS amplitude ratio (∑QRS mV V1 to V3/∑QRS mV V1 to V6) of ≤ 0.48 (p = 0.019), and QRS fragmentation (p = 0.045). In multivariable Cox regression, a precordial QRS amplitude ratio of ≤ 0.48 (hazard ratio [HR] 2.92, 95% confidence interval [CI] 1.39 to 6.15, p = 0.005), inferior leads T-wave inversions (HR 2.44, 95% CI 1.15 to 5.18, p = 0.020), and QRS fragmentation (HR 2.65, 95% CI 1.1 to 6.34, p = 0.029) remained as independent predictors of MACE. In conclusion, in this multicenter, observational, long-term study, electrocardiographic findings were useful for risk stratification in patients with ARVD, with repolarization criteria, inferior leads TWI, a precordial QRS amplitude ratio of ≤ 0.48, and QRS fragmentation constituting valuable variables to predict adverse outcome.

Different prognostic value of functional right ventricular parameters in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: The value of standard 2-dimensional transthoracic echocardiographic parameters for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is controversial. METHODS AND RESULTS: We investigated the impact of RV fractional area change (FAC) and tricuspid annulus plane systolic excursion (TAPSE) for the prediction of major adverse cardiovascular events (MACE) defined as the occurrence of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or arrhythmogenic syncope. Among 70 patients who fulfilled the 2010 ARVC/D Revised Task Force Criteria and underwent baseline transthoracic echocardiography, 37 (53%) patients experienced MACE during a median follow-up period of 5.3 (interquartile range, 1.8-9.8) years. Average values for FAC, TAPSE, and TAPSE indexed to body surface area (BSA) decreased over time (P=0.03 for FAC, P=0.03 for TAPSE, and P=0.01 for TAPSE/BSA, each versus baseline). In contrast, median RV end-diastolic area increased (P=0.001 versus baseline). Based on the results of Kaplan-Meier estimates, the time between baseline transthoracic echocardiography and experiencing MACE was significantly shorter for patients with FAC <23% (P<0.001), TAPSE <17 mm (P=0.02), or right atrial short axis/BSA ≥25 mm/m(2) (P=0.04) at baseline. A reduced FAC constituted the strongest predictor of MACE (hazard ratio, 1.08 per 1% decrease; 95% confidence interval, 1.04-1.12; P<0.001) on bivariable analysis. CONCLUSIONS: This long-term observational study indicates that TAPSE and dilation of right-sided cardiac chambers are associated with an increased risk for MACE in patients with ARVC/D with advanced disease and a high risk for adverse events. However, FAC is the strongest echocardiographic predictor of adverse outcome in these patients. Our data advocate a role for transthoracic echocardiography in risk stratification in patients with ARVC/D, although our results may not be generalizable to lower-risk ARVC/D cohorts.

Radio-frequency ablation as primary management of well-tolerated sustained monomorphic ventricular tachycardia in patients with structural heart disease and left ventricular ejection fraction over 30%.

AIMS: Patients with well-tolerated sustained monomorphic ventricular tachycardia (SMVT) and left ventricular ejection fraction (LVEF) over 30% may benefit from a primary strategy of VT ablation without immediate need for a 'back-up' implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: One hundred and sixty-six patients with structural heart disease (SHD), LVEF over 30%, and well-tolerated SMVT (no syncope) underwent primary radiofrequency ablation without ICD implantation at eight European centres. There were 139 men (84%) with mean age 62 ± 15 years and mean LVEF of 50 ± 10%. Fifty-five percent had ischaemic heart disease, 19% non-ischaemic cardiomyopathy, and 12% arrhythmogenic right ventricular cardiomyopathy. Three hundred seventy-eight similar patients were implanted with an ICD during the same period and serve as a control group. All-cause mortality was 12% (20 patients) over a mean follow-up of 32 ± 27 months. Eight patients (40%) died from non-cardiovascular causes, 8 (40%) died from non-arrhythmic cardiovascular causes, and 4 (20%) died suddenly (SD) (2.4% of the population). All-cause mortality in the control group was 12%. Twenty-seven patients (16%) had a non-fatal recurrence at a median time of 5 months, while 20 patients (12%) required an ICD, of whom 4 died (20%). CONCLUSION: Patients with well-tolerated SMVT, SHD, and LVEF > 30% undergoing primary VT ablation without a back-up ICD had a very low rate of arrhythmic death and recurrences were generally non-fatal. These data would support a randomized clinical trial comparing this approach with others incorporating implantation of an ICD as a primary strategy.

Is 7-day event triggered ECG recording equivalent to 7-day Holter ECG recording for atrial fibrillation screening?

OBJECTIVE: Prolonged ECG monitoring is standard for atrial fibrillation (AF) screening. This study investigated whether 7-day event triggered (tECG) ECG recording is equivalent to 7-day continuous Holter (cECG) ECG recording for AF screening. DESIGN: Both a cECG (Lifecard CF) and a tECG (R.Test Evolution 3) were simultaneously worn for 7 days by patients with known or suspected paroxysmal AF. RESULTS: In 100 corresponding recordings, median effective duration of monitoring was 165 h (range 10-170 h) for cECG and 137 h (0-169 h) for tECG (p<0.001). Median number and total duration of arrhythmias (AF, atrial flutter or atrial tachycardia) of ≥30 s duration recorded by cECG were 10 (1-428) and 1030 min (≤1-10,020), respectively. An arrhythmia was recorded in 42 cECGs (42%) versus 37 tECGs (37%, p=0.56). Triggered ECG failed to record an arrhythmia in cECG positive cases because of interrupted monitoring in four cases and because of recording failure in one case. Sensitivity, specificity, and positive and negative predictive values of tECG therefore were 88%, 100%, 100%, and 92%, respectively. Quantitative cECG analysis required a median of 20 min (3-205 min) and qualitative tECG analysis 4 min (1-20 min; p<0.001). Skin irritation was a frequent side effect (42%) resulting in premature removal of devices in 16% of patients. CONCLUSION: Sensitivity of tECG for AF screening as compared to cECG is lower, mainly because of shorter effective monitoring duration. Qualitative tECG analysis is less time consuming than quantitative cECG analysis. Skin irritation is a frequent side effect and reason for premature device removal.

Long-term outcome of ablative therapy of post-operative atrial tachyarrhythmias in patients with tetralogy of Fallot: a European multi-centre study.

AIM: Post-operative atrial tachyarrhythmias (AT) in patients with tetralogy of Fallot (ToF) are associated with congestive heart failure, stroke, and cardiac death. Effective treatment is therefore essential. The aim of the study is to evaluate long-term outcome of ablative therapy of AT in ToF patients and to study characteristics of AT recurrences. METHODS AND RESULTS: Tetralogy of Fallot patients (N = 38, age 43 ± 12 years) referred for ablation of post-operative AT, appearing 26 ± 10 years after complete repair, were studied. Electro-anatomical/entrainment mapping was performed prior to ablation. Successful ablation was defined as (i) achievement of bi-directional conduction block for isthmus-dependent atrial flutter (IDAF), (ii) termination during ablation for intra-atrial reentrant tachycardia (IART) and focal atrial tachycardia (FAT). Fifty-two AT were ablated, including 37 IDAF [cycle length (CL) 294 ± 70 ms], 11 IART (CL 295 ± 46 ms), and 4 FAT (CL 371 ± 93 ms). Ablation was successful in 98%. Fifty-one of 52 AT involved the cavo-tricuspid isthmus and/or the area between scar tissue related to prior atriotomy incisions and the inferior caval vein. Multiple AT developed in 11 patients, with different mechanisms in 9. After 45 ± 24 months, 32 patients were in sinus rhythm; 5 used anti-arrhythmic drugs. CONCLUSION: Ablative therapy of AT in ToF patients is an effective curative treatment modality with a high procedural success rate. Sinus rhythm during long-term follow-up was obtained in the majority of patients. Fifty-one of 52 AT originated from sites related to surgical incisions created at complete repair, suggesting that extending the atriotomy incision towards the inferior caval vein during cardiac surgery combined with surgical ablation of the cavo-tricuspid isthmus will be effective in preventing development of AT.

Catheter ablation of arrhythmias in ebstein's anomaly: a multicenter study.

INTRODUCTION: In patients with Ebstein's anomaly (EA) arrhythmias are frequently encountered. Although most arrhythmias can be targeted with catheter ablation, specific issues render the procedure more challenging in EA. This study examines the mechanisms of the different arrhythmias related to EA and the outcome after catheter ablation. METHODS AND RESULTS: Clinical and procedural data of catheter ablation in patients with EA in 4 European centers were analyzed. In 32 patients (mean age 24 ± 15 years), 34 accessory pathways (APs), 8 intra-atrial reentry tachycardias (IART), 5 cavotricuspid isthmus-dependent atrial flutter (CTI-AFL), 2 focal atrial tachycardias, and 1 atrioventricular nodal reentry tachycardia were ablated. In 11 patients (34%), multiple ablation targets were present. Eighteen patients (56%) required multiple procedures either for repeat ablation of the same arrhythmia (n = 12), ablation of a different arrhythmia (n = 4), or both re-ablation of the same and of a different arrhythmia (n = 2). Procedural success rate after first ablation was 80% for APs and CTI-AFL ablation, and 100% for IART ablation. Redo procedures were necessary in 40% of the patients after ablation of an APs, and in 60% after CTI-AFL ablation, but in none of the patient with IART ablation. CONCLUSION: Most arrhythmias related to EA are amenable to catheter ablation. However, ablation procedures are challenging and the need for repeat procedure is particularly high, because some patients have multiple ablation targets and because of technical issues in relation with the dysplastic tricuspid annulus. In addition, several patients develop other arrhythmia mechanisms following ablation.

Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice.

AIMS: Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. METHODS AND RESULTS: Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C. We identified 41 different disease-causing mutations, including 28 novel ones, in 62 patients (46%). In addition, a genetic variant of unknown significance was identified in nine additional patients (7%). Distribution of genes was 31% (PKP2), 10% (DSG2), 4.5% (DSP), 1.5% (DSC2), and 0% (JUP). The presence of desmosomal mutations was not associated with familial context but was associated with young age, symptoms, electrical substrate, and extensive structural damage. When compared with other genes, DSG2 mutations were associated with more frequent left ventricular involvement (P = 0.006). Finally, complex genetic status with multiple mutations was identified in 4% of patients and was associated with more frequent sudden death (P = 0.047). CONCLUSION: This study supports the use of genetic testing as a new diagnostic tool in ARVC/D and also suggests a prognostic impact, as the severity of the disease appears different according to the underlying gene or the presence of multiple mutations.

Palliative care in heart failure: a position statement from the palliative care workshop of the Heart Failure Association of the European Society of Cardiology.

Heart failure is a serious condition and equivalent to malignant disease in terms of symptom burden and mortality. At this moment only a comparatively small number of heart failure patients receive specialist palliative care. Heart failure patients may have generic palliative care needs, such as refractory multifaceted symptoms, communication and decision making issues and the requirement for family support. The Advanced Heart Failure Study Group of the Heart Failure Association of the European Society of Cardiology organized a workshop to address the issue of palliative care in heart failure to increase awareness of the need for palliative care. Additional objectives included improving the accessibility and quality of palliative care for heart failure patients and promoting the development of heart failure-orientated palliative care services across Europe. This document represents a synthesis of the presentations and discussion during the workshop and describes recommendations in the area of delivery of quality care to patients and families, education, treatment coordination, research and policy.

His-Purkinje system re-entry in patients with clustering ventricular tachycardia episodes.

AIMS: Multiple arrhythmia re-inductions were recently shown in His-Purkinje system (HPS) ventricular tachycardia (VT). We hypothesized that HPS VT was a frequent mechanism of repetitive or incessant VT and assessed diagnostic criteria to select patients likely to have HPS VT. METHODS AND RESULTS: Consecutive patients with clustering VT episodes (>3 sustained monomorphic VT within 2 weeks) were included in the analysis. HPS VT was considered plausible in patients with (i) impaired left ventricular function associated with dilated cardiomyopathy or valvular heart disease; or (ii) ECG during VT similar to sinus rhythm QRS or to bundle-branch block QRS. HPS VT was plausible in 12 of 48 patients and HPS VT was demonstrated in 6 of 12 patients (50%, or 13% of the whole study group). Median VT cycle length was 318 ms (250-550). Catheter ablation was successful in all six patients. CONCLUSION: His-Purkinje system VT is found in a significant number of patients with repetitive or incessant VT episodes, and in a large proportion of patients with predefined clinical or electrocardiographic characteristics. Since it is easily amenable to catheter ablation, our data support the screening of all patients with repetitive VT in this regard and an invasive approach in a selected group of patients.

Inappropriate interventions during the long-term follow-up of patients with an implantable defibrillator.

QUESTIONS UNDER STUDY: In patients with an implantable defibrillator (ICD), inappropriate ICD interventions alter the quality of life, may cause hospitalisations and limit cost-effectiveness. The aim of the study was to determine the incidence and causes of inappropriate ICD interventions, and to identify patients at risk. METHODS: For this observational longitudinal study, consecutive patients undergoing ICD implantation at the University Hospital of Berne were included in a registry. All stored electrograms of episodes triggering ICD interventions were systematically reviewed and analysed to determine whether ICD interventions were appropriate or inappropriate. Inappropriate ICD interventions were classified according to their cause, and risk factors were sought. RESULTS: 214 consecutive patients were followed during a median time of 2.7 years (3.7 years IQR, 698 patient years). 81 inappropriate ICD interventions occurred in 58 patients (27%). Factors triggering inappropriate ICD interventions included atrial fibrillation and flutter (n = 35, 44%), sinus tachycardia (n = 26, 32%), lead fracture (n = 12), recurrent self-terminating ventricular tachycardia (n = 5), double-counting due to T-wave oversensing (n = 3). The only identifiable risk factor for inappropriate ICD interventions was sustained ventricular tachycardia as index arrhythmia. CONCLUSIONS: An important proportion of ICD patients suffer inappropriate ICD interventions that are most commonly due to supraventricular arrhythmias. Patients with ventricular tachycardia prior to ICD implantation are at higher risk of inappropriate ICD interventions. Interventions aiming at decreasing the risk of inappropriate ICD interventions should be considered in these patients.

Dual-loop circuits in postoperative atrial macro re-entrant tachycardias.

BACKGROUND: Patients may develop dual-loop re-entrant atrial arrhythmias late after open-heart surgery, and mapping and catheter ablation remain challenging despite computer-assisted mapping techniques. OBJECTIVES: The purpose of the study was to demonstrate the prevalence and characteristics of dual-loop re-entrant arrhythmias, and to define the optimal mapping and ablation strategy. METHODS: 40 consecutive patients (mean (SD) age 52 (12) years) with intra-atrial re-entrant tachycardia (IART) after open-heart surgery (with an incision of the right atrial free wall) were studied. Dual-loop IART was defined as the presence of two simultaneous atrial circuits. After an abrupt tachycardia change during radiofrequency ablation, electrical disconnection of the targeted re-entry isthmus from the remaining circuit was demonstrated by entrainment mapping. Furthermore, the second circuit loop was localised using electroanatomical mapping and/or entrainment mapping. RESULTS: Dual-loop IART was demonstrated in eight (20%, 5 patients with congenital heart disease, 3 with acquired heart disease) patients. Dual-loop IART included an isthmus-dependant atrial flutter combined with a re-entry related to the atriotomy scar. The diagnosis of dual-loop IART required the comparison of entrainment mapping before and after tachycardia modification. Overall, 35 patients had successful radiofrequency ablation (88%). Success rates were lower in patients with dual-loop IART than in patients without dual-loop IART. Ablation failures in three patients with dual-loop IART were related to the inability to properly transect the second tachycardia isthmus in the right atrial free wall. CONCLUSIONS: Dual-loop IART is relatively common after heart surgery involving a right atriotomy. Abrupt tachycardia change and specific entrainment mapping manoeuvres demonstrate these circuits. Electroanatomical mapping appears to be important to assist catheter ablation of periatriotomy circuits.

A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation.

OBJECTIVE: Brugada syndrome (BS) is an inherited electrical cardiac disorder characterized by right bundle branch block pattern and ST segment elevation in leads V1 to V3 on surface electrocardiogram that can potentially lead to malignant ventricular tachycardia and sudden cardiac death. About 20% of patients have mutations in the only so far identified gene, SCN5A, which encodes the alpha-subunit of the human cardiac voltage-dependent sodium channel (hNa(v)1.5). Fever has been shown to unmask or trigger the BS phenotype, but the associated molecular and the biophysical mechanisms are still poorly understood. We report on the identification and biophysical characterization of a novel heterozygous missense mutation in SCN5A, F1344S, in a 42-year-old male patient showing the BS phenotype leading to ventricular fibrillation during fever. METHODS: The mutation was reproduced in vitro using site-directed mutagenesis and characterized using the patch clamp technique in the whole-cell configuration. RESULTS: The biophysical characterization of the channels carrying the F1344S mutation revealed a 10 mV mid-point shift of the G/V curve toward more positive voltages during activation. Raising the temperature to 40.5 degrees C further shifted the mid-point activation by 18 mV and significantly changed the slope factor in Na(v)1.5/F1344S mutant channels from -6.49 to -10.27 mV. CONCLUSIONS: Our findings indicate for the first time that the shift in activation and change in the slope factor at a higher temperature mimicking fever could reduce sodium currents' amplitude and trigger the manifestation of the BS phenotype.

Irrigated-tip catheter ablation of intraatrial reentrant tachycardia in patients late after surgery of congenital heart disease.

OBJECTIVES: The aim of this study was to evaluate irrigated-tip catheter for ablation of intraatrial reentrant tachycardias late after surgical repair of congenital heart disease. BACKGROUND: In congenital heart disease patients, the right atrium can be markedly enlarged with areas of low blood flow. Radiofrequency (RF) lesion creation may be hampered by insufficient electrode cooling at sites with low blood flow. METHODS: Thirty-six consecutive patients with intraatrial reentrant tachycardia refractory to antiarrhythmic therapy from two centers were included in the study. Entrainment pacing and electroanatomic mapping (CARTO) were used to delineate reentrant circuits and critical isthmus sites. RF ablation was performed using an irrigated-tip catheter (Navistar Thermocool). RESULTS: Fifty-two intraatrial reentrant tachycardia circuits were identified, and 48 were targeted with RF ablation. RF ablation was performed using a mean of 13 +/- 11 irrigated RF applications per tachycardia isthmus with a mean power of 36 +/- 8 W. In a historical control group of congenital heart disease patients managed with conventional catheter ablation, the number of lesions per isthmus was higher (23 +/- 11) and mean power was lower (27 +/- 14 W). Acute success was achieved in 45 intraatrial reentrant tachycardias (94% of targeted tachycardias and 87% of all tachycardias). After a mean follow-up of 17 +/- 7 months, 33 (92%) of 36 patients were free of recurrence. Five patients (14%) developed paroxysmal atrial fibrillation. CONCLUSIONS: The combination of modern techniques including electroanatomic mapping and catheter irrigation allows safe and highly effective ablation of intraatrial reentrant tachycardia in patients with surgically repaired congenital heart disease.