Combination of FLNC and JUP variants causing arrhythmogenic cardiomyopathy in an Iranian family with different clinical features.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) characterized by progressive myocardial loss and replacement with fibro-fatty tissue is a major cause of sudden cardiac death (SCD). In particular, ACM with predominantly left ventricular involvement, known as arrhythmogenic left ventricular cardiomyopathy (ALVC), has a poor prognosis. METHODS: The proband underwent whole-exome sequencing (WES) to determine the etiology of ALVC. Family members were then analyzed using PCR and Sanger sequencing. Clinical evaluations including 12-lead ECG, transthoracic echocardiography, and cardiac MRI were performed for all available first-degree relatives. RESULTS: WES identified two variants in the FLNC (c.G3694A) and JUP (c.G1372A) genes, the combination of which results in ALVC and SCD. CONCLUSION: The present study comprehensively investigates the involvement of two discovered variants of FLNC and JUP in the pathogenesis of ALVC. More study is necessary to elucidate the genetic factors involved in the etiology of ALVC.

Role of non-coding variants in cardiovascular disease.

Cardiovascular diseases (CVDs) constitute one of the significant causes of death worldwide. Different pathological states are linked to CVDs, which despite interventions and treatments, still have poor prognoses. The genetic component, as a beneficial tool in the risk stratification of CVD development, plays a role in the pathogenesis of this group of diseases. The emergence of genome-wide association studies (GWAS) have led to the identification of non-coding parts associated with cardiovascular traits and disorders. Variants located in functional non-coding regions, including promoters/enhancers, introns, miRNAs and 5'/3' UTRs, account for 90% of all identified single-nucleotide polymorphisms associated with CVDs. Here, for the first time, we conducted a comprehensive review on the reported non-coding variants for different CVDs, including hypercholesterolemia, cardiomyopathies, congenital heart diseases, thoracic aortic aneurysms/dissections and coronary artery diseases. Additionally, we present the most commonly reported genes involved in each CVD. In total, 1469 non-coding variants constitute most reports on familial hypercholesterolemia, hypertrophic cardiomyopathy and dilated cardiomyopathy. The application and identification of non-coding variants are beneficial for the genetic diagnosis and better therapeutic management of CVDs.

A survival analysis of bipolar steroid-eluting and unipolar nonsteroid-eluting epicardial leads.

INTRODUCTION: Epicardial pacemakers are known as an alternative for endocardial pacemakers in some cases such as heart block, and complex congenital heart diseases. Considering recent advances and improvement of epicardial lead subtypes, it is essential to investigate the long-term function of them. In this study, we aimed to assess the sensing and pacing characteristics, and survival of bipolar steroid-eluting and unipolar nonsteroid-eluting epicardial pacemakers. METHODS: We conducted an entirely concentrated search on the documents of all patients who had undergone epicardial lead implantation in the Shaheed Rajaie Cardiovascular, Medical & Research Center during 2015-2018. Implant, and follow-up data were extracted. Kaplan-Meier analysis and Weibull regression hazards model were applied for the survival analysis. RESULTS: Eighty-nine leads were implanted for 77 patients. Of the total leads, 52.81%, 53.93%, and 47.19% were implanted in children (under 18-year-old), females, and patients with congenital heart diseases, respectively. Bipolar steroid-eluting leads comprised 33.71% of 89 leads. The pacing threshold of unipolar nonsteroid-eluting leads that were implanted on the left ventricle and right atrium increased significantly during the follow-up to greater records than bipolar steroid-eluting leads. Survival analysis also revealed that bipolar steroid-eluting leads are significantly better in 48-month survival (Weibull hazard ratio [HR]: 0.13 (95% confidence interval [CI]: 0.02-0.99), p = .049). Age, ventricular location of the lead, and acute pacing characteristics were not associated with survival. CONCLUSIONS: Bipolar steroid-eluting epicardial leads have an acceptable survival compared with unipolar nonsteroid-eluting, without a significant difference regarding patients age. Therefore, they could be an excellent alternative for endocardial ones.

Electrocardiographic manifestations of pulmonary stenosis versus pulmonary hypertension.

BACKGROUND: Right ventricular hypertrophy can be caused by conditions such as pulmonary stenosis and pulmonary hypertension. ECG is a readily available and affordable test, the aim of this study was the evaluation of the electrocardiographic aspects of pulmonary stenosis, and pulmonary hypertension. METHODS: A list of patients diagnosed with isolated pulmonary stenosis and pulmonary hypertension patients hospitalized and treated between 2019 and 2021 were extracted from the hospital archives. Furthermore, the ECG of the patients was analyzed in terms of the prevalence of the variables in the study using FECG Caliper software. Finally, the data of 93 patients (in both groups) were analyzed. RESULTS: In this study, 46 patients were in the severe pulmonary stenosis group, and 49 were in the severe or moderate-to-severe pulmonary hypertension group. The heart rate in the pulmonary hypertension group was significantly higher. R/S > 1 in precordial leads differs between the two groups and higher amplitude R wave in V1(p-value = 0.05). in the pulmonary stenosis group. While in the pulmonary hypertension group, R wave growth occurs later, and this ratio is greater than one after V4. Bundle block in the form of RBBB(p-value <0.001) and maximum QRS duration is more in the pulmonary stenosis group(p-value = 0.001). CONCLUSION: Our findings show the different strains of the right ventricle in two groups. It can be concluded that the effects of severe pulmonary stenosis on the ECG are more on the QRS wave and in the form of a block, while severe pulmonary hypertension affects the ST segment and T wave.

Atrial fibrillation in ß-thalassemia patients with a focus on the role of iron-overload and oxidative stress: A review.

Cardiac complications including arrhythmia and especially atrial fibrillation (AF) are common causes of death in ß-thalassemia patients. The main factor in the etiopathogenesis of these complications is iron overload, which results in increased oxidative stress. Although there is a known association between cardiac complications and iron overload in ß-thalassemia patients, there is no comprehensive review on AF and excessive iron with a focus on oxidative stress in these patients. The aim of this article was to review the different aspects of AF in ß-thalassemia patients with a focus on the prevention and treatment of AF by using iron chelators and/or anti-oxidants. AF in ß-thalassemia patients is more common than in the general population. One of the most important causes of AF is cardiac iron overload and the harmful effects of increased oxidative stress. Iron-induced AF can be reversed by using an intensive iron chelation regimen. Based on a few experimental studies, the combination of iron chelators with some anti-oxidants, including NAC, vitamin C, and acetaminophen, can lead to improved cardiac protection. However, the effect of such combinations on cardiac arrhythmias should be further evaluated with animal and human studies.

Detection of a novel pathogenic variant in KCNH2 associated with long QT syndrome 2 using whole exome sequencing.

BACKGROUND: Long QT syndrome (LQTS) is a cardiac channelopathy characterized by impaired myocardial repolarization that predisposes to life-threatening arrhythmias. This study aimed to elucidate the genetic basis of LQTS in an affected Iranian family using whole exome sequencing (WES). METHODS: A 37-year-old woman with a personal and family history of sudden cardiac arrest and LQTS was referred for genetic study after losing her teenage daughter due to sudden cardiac death (SCD). WES was performed and variants were filtered and prioritized based on quality, allele frequency, pathogenicity predictions, and conservation scores. Sanger sequencing confirmed segregation in the family. RESULTS: WES identified a novel heterozygous frameshift variant (NM_000238.4:c.3257_3258insG; pGly1087Trpfs*32) in the KCNH2 encoding the α-subunit of the rapid delayed rectifier potassium channel responsible for cardiac repolarization. This variant, predicted to cause a truncated protein, is located in the C-terminal region of the channel and was classified as likely pathogenic based on ACMG guidelines. The variant was absent in population databases and unaffected family members. CONCLUSION: This study reports a novel KCNH2 frameshift variant in an Iranian family with LQTS, expanding the spectrum of disease-causing variants in this gene. Our findings highlight the importance of the C-terminal region in KCNH2 for proper channel function and the utility of WES in identifying rare variants in genetically heterogeneous disorders like LQTS. Functional characterization of this variant is warranted to fully elucidate its pathogenic mechanisms and inform personalized management strategies.

Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies.

The giant protein titin (TTN) is a sarcomeric protein that forms the myofibrillar backbone for the components of the contractile machinery which plays a crucial role in muscle disorders and cardiomyopathies. Diagnosing TTN pathogenic variants has important implications for patient management and genetic counseling. Genetic testing for TTN variants can help identify individuals at risk for developing cardiomyopathies, allowing for early intervention and personalized treatment strategies. Furthermore, identifying TTN variants can inform prognosis and guide therapeutic decisions. Deciphering the intricate genotype-phenotype correlations between TTN variants and their pathologic traits in cardiomyopathies is imperative for gene-based diagnosis, risk assessment, and personalized clinical management. With the increasing use of next-generation sequencing (NGS), a high number of variants in the TTN gene have been detected in patients with cardiomyopathies. However, not all TTN variants detected in cardiomyopathy cohorts can be assumed to be disease-causing. The interpretation of TTN variants remains challenging due to high background population variation. This narrative review aimed to comprehensively summarize current evidence on TTN variants identified in published cardiomyopathy studies and determine which specific variants are likely pathogenic contributors to cardiomyopathy development.

Identification of a novel pathogenic variant in KCNH2 in an Iranian family with long QT syndrome 2 by whole-exome sequencing.

Background: Long QT syndrome (LQTS) is a lethal cardiac condition. However, the clinical implementation of genetic testing has now made LQTS eminently treatable. Next-generation sequencing has remarkable potential for both clinical diagnostics and research of LQTS. Here, we investigated the genetic etiology in an LQTS-suspected Iranian pedigree by whole-exome sequencing and collected all KCNH2 variants with consensus based on publications. Methods: WES was performed on the proband of this pedigree to reveal the underlying cause of sudden cardiac death (SCD). The variant found was validated and segregated by polymerase chain reaction and Sanger sequencing. Based on the literature review, KCNH2 variants were retrospectively analyzed to identify pathogenic variants, likely pathogenic variants, and variants of uncertain significance by using different prediction tools. Results: WES identified an autosomal dominant nonsense variant, c.1425C>A: p.Tyr475Ter, in the KCNH2 gene, which appeared to be the most likely cause of LQTS in this pedigree. Moreover, our comprehensive literature review yielded 511 KCNH2 variants in association with the LQTS phenotype, with c.3002G>A (CADD Phred=49) being the most pathogenic variant. Conclusions: Variants in the KCNH2 gene are considered a major cause of LQTS worldwide. The detected c.1425C>A is a novel variant to be reported from Iran for the first time. This result indicates the importance of KCNH2 screening in a pedigree with SCD cases.

Comparison of de novo implantation vs. upgrade cardiac resynchronisation therapy: a multicentre experience.

BACKGROUND: The clinical safety and consequences of upgrade procedures compared with de novo cardiac resynchronisation therapy (CRT) implantation in heart failure remain unclear. The present study aimed to assess clinical and procedural consequences of patients undergoing CRT upgrade as compared to de novo CRT implantations. METHODS: In this prospective cohort study, two subgroups were considered as the study population as (1) de novo group that CRT was considered on optimised medical treatment with heart failure of NYHA functional class from II to IV, left ventricular ejection fraction (LVEF) of ≤35%, and QRS width of >130 ms and (2) upgrade group including the patients with previously implantable cardioverter defibrillator (ICD) with the indications for upgrading to CRT. The two groups were compared regarding the changes in clinical outcome and echocardiography parameters. RESULTS: The procedure was successful in 95.9% of patients who underwent CRT upgrade and 100% of those who underwent de novo CRT implantation. It showed a significant improvement in LVEF, severity of mitral regurgitation and NYHA functional classification, without any difference between the two study groups. Overall procedural related complications were reported in 10.8% and 3.8% (p = .093) and cardiac death in 5.4% and 2.5% (p = .360), respectively, with no overall difference in postoperative outcome between the two groups. CONCLUSIONS: Upgrading to CRT is a safe and effective procedure regarding improvement of functional class, left ventricular function status and post-procedural outcome.

Efficacy and safety of different antitachycardia pacing sites in the termination of ventricular tachycardia in patients with biventricular implantable cardioverter-defibrillator.

AIMS: We sought to evaluate the efficacy and safety of different antitachycardia pacing (ATP) sites in heart failure (HF) patients with a biventricular implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: Between January 2003 and December 2008, 89 consecutive patients with biventricular (BiV) ICDs (Medtronic Inc., St Paul, Minnesota, USA) were enrolled. In these patients, stored electrograms of the true spontaneous ventricular tachycardia (VT) episodes with at least one ATP therapy were analysed. Out of the 89 patients, 46 experienced 259 VT episodes. When we considered all VT forms, both left ventricular (LV)-ATP (91%) and BiV-ATP (89%) were significantly better than right ventricular (RV)-ATP (72%) in terminating VTs (P = 0.03 and 0.04, respectively). In the fastVT zone, there was a trend for higher efficacy of BiV-ATP compared with RV-ATP and LV-ATP (75 vs. 60 vs. 60%, P = 0.10). Fast VT acceleration occurred to a similar extent in all ATP groups (20% in RV-ATP vs. 20% in LV-ATP vs. 20% in BiV-ATP, P = NS). In the slow VT zone, RV-ATP was significantly less effective than LV-ATP (74 vs. 100%, P = 0.001) and BiV-ATP (74 vs. 100%, P = 0.014). Incidence of acceleration was lower with LV-ATP and BiV-ATP than RV-ATP (0 vs. 0 vs. 9%, P = 0.03) in the slow VT zone. CONCLUSIONS: In HF patients treated with BiV ICD, overall ATP efficacy is higher when delivered from LV or BiV than from RV. Biventricular-ATP and LV-ATP are also safer than RV-ATP in the slow VT zone.

Delayed cardiac perforation by one small body diameter defibrillator lead.

We report a 37-year-old man who presented with continuous chest pain 6 weeks after implantable cardioverter-defibrillator implantation. Implantable cardioverter-defibrillator interrogation indicated complete loss of capture even with maximum output. Chest radiography and echocardiography confirmed extracardiac location of lead tip. After lead repositioning in electrophysiology laboratory, acceptable pacing threshold was obtained with no complication. This report demonstrates a case of delayed cardiac perforation after implantation of the St Jude Medical Durata implantable cardioverter-defibrillator lead.

Absent left atrial appendage: case report and review of the literature.

Congenital absence of left atrial appendage (LAA) is an extremely rare condition and is usually diagnosed incidentally in imaging intended for other purposes. Herein, we report a rare case of absent left atrial appendage in an 80-year-old gentleman who was candidate for radiofrequency catheter ablation procedure for atrial flutter rhythm in whom we observed the absence of left atrial appendage in echocardiographic examination. Computed tomography angiographic examination performed in the evaluation course of the patient was also confirmative of this finding. As there is no data on anticoagulating of patients with absent left atrial appendage, after successful radiofrequency catheter ablation procedure, we continued rivaroxaban per guidelines. The results of a second imaging modality and a thorough medical history are critical for diagnosis of absent left atrial appendage. These steps are required to rule out imitating conditions such as prior surgical/percutaneous exclusion, unusual anatomical features or flush thrombotic exclusion of left atrial appendage. In this case report, we also provide a brief review of the characteristics of 17 cases that have been reported in the literature so far.

The Role of Heart Rate Variability and Fragmented QRS for Determination of Subclinical Cardiac Involvement in Beta-Thalassemia Major.

BACKGROUND: Iron accumulation leads to increased susceptibility to cardiovascular diseases in thalassemia major (TM) patients. Depressed heart rate variability (HRV) and development of arrhythmia are among the manifestations of subclinical cardiac involvement in TM cases. Determination of subclinical cardiac involvement is essential for preventive measures. Thus, we aimed to evaluate the best method for identification of subclinical cardiac dysfunction in TM cases. MATERIALS AND METHODS: In this prospective study, 45 TM and 45 non-TM cases, who were referred for cardiac evaluation, were enrolled. Exclusion criteria included non-sinus rhythm and overt cardiac disease. TM cases underwent cardiac MRI, electrocardiography (ECG), and Holter monitoring. TM cases were divided into two groups of normal versus iron overload with a cardiac T2* of more or less than 20 ms, respectively. The non-TM cases underwent only ECG and Holter monitoring. RESULTS: We observed no significant difference regarding HRV between normal versus iron overload TM and non-TM cases. Higher rates of premature atrial complex, low limb voltage, low atrial rhythm, as well as minimum and average HR with lower QRS duration and PR interval were detected in TM versus non-TM cases (p value <0.05). CONCLUSIONS: We observed a higher prevalence of low limb voltage and low atrial rhythm in TM cases versus non-TM cases. Indeed, the role of fragmented QRS (fQRS) for subclinical detection of cardiac disease in TM cases is still so controversial and needs more evaluation. Application of HRV and fQRS in this regard may need to be performed at the right time point after initiation of blood transfusion, but this needs to be determined.

Prediction of response to cardiac resynchronization therapy using simple electrocardiographic and echocardiographic tools.

AIMS: To predict response to cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and intraventricular conduction delay. METHODS AND RESULTS: The study population consisted of 82 consecutive HF patients with standard CRT indications. Patients were classified as responders, if they were alive without cardiac decompensation and experienced >or=15% decrease in left ventricular end-systolic volume. Sixty-eight percent of the enrolled patients responded to CRT. When compared with non-responders, responders had a wider baseline QRS width (P = 0.001), more marked QRS shortening (DeltaQRS) immediately after CRT (P = 0.001), and a better improvement in aortic velocity time integral (VTI) 24 h after CRT (P = 0.02). Moreover, there was a trend towards a greater baseline intraventricular dyssynchrony in the responder group (P = 0.07). By multivariable logistic regression, the baseline QRS width (OR: 0.95, 95% CI: 0.90-0.97, P = 0.001), DeltaQRS (OR: 1.038, 95% CI: 1.012-1.064, P = 0.003), and acute aortic VTI (OR: 0.81, 95% CI: 0.68-0.96, P = 0.017) emerged as independent predictors of response to CRT. Receiver operating characteristic curve analysis identified a QRS width >145 ms, DeltaQRS >20 ms, and aortic VTI >14 cm to predict responders. CONCLUSION: A positive response to CRT was observed in 68% of the patients. Cardiac resynchronization therapy response is predictable using simple electrocardiographic and echocardiographic data.

ST-segment depression as a risk factor in hypertrophic cardiomyopathy.

AIMS: From the spectrum of electrocardiogram (ECG) changes that may occur in hypertrophic cardiomyopathy (HCM), there is no criterion reported to be useful for risk stratification. We sought to determine whether there was a relationship between the resting ECG findings and prognosis in patients with HCM. METHODS AND RESULTS: We retrospectively analysed data on 173 consecutive patients admitted to our centre with a diagnosis of HCM. The 12-lead ECGs were assessed for underlying rhythm, PR interval, QRS voltages, QRS width, corrected QT interval, ST-segment deviation, T-wave inversion, and left atrial enlargement (LAE). During a mean follow-up of 50 months, 6.4% of patients had a combined endpoint [sudden death or appropriate implantable cardioverter-defibrillator (ICD) therapy]. The frequency of the combined endpoint was greater in patients with syncope, non-sustained ventricular tachycardia, maximal left ventricular (LV) wall thickness >or=30 mm, and ST-segment depression in the high lateral leads (all P < 0.05). Other ECG findings (LV hypertrophy, LAE, abnormal Q wave, abnormal ST-T changes, and underlying rhythm), family history of sudden death, and LV outflow obstruction were not related to the combined endpoint. The results of our multivariate analysis demonstrated that ST-segment depression in the high lateral leads (OR: 20.0, 95% CI: 12.7-27.5; P = 0.0001) and syncope (OR: 19.0, 95% CI: 11.7-26.9; P = 0.0001) were the predictors of sudden death or appropriate ICD therapy in patients with HCM. CONCLUSION: The results of this study indicated that, in addition to generally accepted risk factors, ST-segment depression in the high lateral leads could be of prognostic significance in HCM patients.

Effect of right ventricular lead location on response to cardiac resynchronization therapy in patients with end-stage heart failure.

AIMS: It is currently recommended to implant the left ventricular (LV) pacing lead at the lateral wall. However, the optimal right ventricular (RV) pacing lead location for cardiac resynchronization therapy (CRT) remains controversial. We sought to investigate whether optimizing the site for placement of the RV lead could further improve the long-term response to CRT in patients with advanced heart failure. METHODS AND RESULTS: Between October 2006 and December 2007, a total of 73 consecutive patients with standard indication for CRT were enrolled. The enrolled patients were divided into two groups based on the RV lead location. There were 50 patients in RV apex (RVA) group and 23 patients in RV high septum (RVHS). The primary study endpoint was a decrease in LV end-systolic volume (LVESV) by >15% at 6-month follow-up. The secondary endpoints were improvement in New York Heart Association (NYHA) class by >or=1 point and decrease in brain-type natriuretic peptide (BNP) levels by >50% after CRT. At 6-month follow-up, improvement in NYHA class by >or=1 point (RVA: 72% vs. RVHS: 74%, P = 0.76), decrease in LVESV by >or=15% (RVA: 65% vs. RVHS: 64%, P = 0.76), and decrease in BNP level by >50% (RVA: 70% vs. RVHS: 69%, P = 0.88) were observed in similar proportion of the two groups. When we separately assessed the significance of RV pacing site in three LV stimulation sites, there were no significant differences in terms of clinical improvement (62 vs. 64%, P = 0.74) and decrease in LVESV by >15% (63 vs. 62%, P = 0.78) between RVA and RVHS pacing when the LV stimulation site was lateral cardiac vein. In anterolateral vein pacing site, the RVA stimulation was associated with higher clinical (88 vs. 47%, P = 0.05), echocardiographic (75 vs. 32%, P = 0.02), and neurohormonal responses (80 vs. 50%, P = 0.04) compared with that in RVHS site. When LV was paced from posterolateral vein, RVHS pacing was superior to RVA in terms of the clinical improvement (85 vs. 35%, P = 0.01), echocardiographic response (72 vs. 30%, P = 0.01), and decrease in BNP levels (75 vs. 50%, P = 0.04). CONCLUSION: The present study did not show any difference between RVA and RVHS pacing sites in terms of overall improvement in clinical outcome and LV reverse remodelling following CRT. However, effect of RV lead location on CRT response varies depending on LV stimulation site.

Predictors of syncope in patients with hypertrophic cardiomyopathy.

BACKGROUND: Approximately 30% of patients with hypertrophic cardiomyopathy (HCM) suffer syncope and syncope was the only symptom associated with sudden death. However, no systematic studies in large cohorts looking at predictors of syncope are available in the literature. Therefore, we sought to determine predictors of syncope in patients with HCM. METHODS: One hundred and seventy-three consecutive patients with HCM and a mean age of 42 +/- 18 years (range 10-78) underwent extensive clinical, electrocardiographic, and echocardiographic testing to identify predictors of syncope. RESULTS: During the mean follow-up duration of 50 months, syncope occurred in 28% of the HCM patients. Univariate analysis showed male gender, age <40 years, family history of sudden death, PR interval, QRS width, >or=2 bursts of nonsustained ventricular tachycardia (NSVT), >or=3 bursts of nonsustained supraventricular tachycardia (NSSVT), maximum left ventricular wall thickness >or=30 mm, and abnormal blood pressure response, out of 24 demographic, clinical, hemodynamic, electrocardiographic, and echocardiographic features, to be significantly associated with syncope. Of these nine variables, the only independent predictors of syncope at multivariate analysis were age <40 years (odds ratio [OR]: 4.4, 95% confidence interval [CI]: 2.2-16, P = 0.003), >or=2 bursts of NSVT (OR: 9.9, 95% CI: 2.0-46, P = 0.0001), and >or=3 bursts of NSSVT (OR: 2.7, 95% CI: 0.38-8.25, P = 0.001). The concomitant occurrence of all three variables had a sensitivity of 87% and specificity of 73% in identifying the patients with syncopal events. CONCLUSIONS: The results of this study showed that age <40 years, bursts of NSVT, and NSSVT were independently associated with the risk of syncope in patients with HCM. Demographic data and ambulatory ECG findings could help in risk stratification of patients with HCM.

Can successful radiofrequency ablation of atrioventricular nodal reentrant tachycardia be predicted by pattern of junctional ectopy?

BACKGROUND: Emergence of junctional rhythm (JR) during radiofrequency (RF) current delivery directed at the periatrioventricular nodal region has been shown to be a marker of success in atrioventricular nodal reentrant tachycardia (AVNRT). Whereas the characteristics of JR during RF ablation of slow pathway have already been studied, the electrophysiologic features of different patterns of JR are yet to be evaluated. The aim of this study was to investigate in detail the characteristics of the JR that develops during the RF ablation of the slow pathway. MATERIALS AND RESULTS: The study population consisted of 95 patients: 56 women and 33 men (mean age, 47.2 +/- 16.3 years) who underwent slow pathway ablation because of AVNRT. A combined anatomical and electrogram mapping approach was used, and AVNRT was successfully eliminated in all patients. This study identified 7 patterns for JR during the RF ablation of slow pathway: junction-junction-junction, sinus-junction-sinus, intermittent burst, sparse, no junction, sinus-junction-junction, and sinus-junction-block . The characteristics of JR, such as mean cycle length and total number, were gathered. The incidence of JR was significantly higher during effective applications of RF energy than during ineffective applications (P = .001). The mean number of junctional ectopy was 19.6 +/- 19. The total number of junctional ectopy was significantly higher during effective applications of RF energy than during ineffective applications (24.6 +/- 18.8 vs 8.4 +/- 13.2; P < .001). We found a significant difference between the effective and ineffective applications of RF energy in the mean cycle length of the junctional ectopy (464.6 +/- 167.5 vs 263.4 +/- 250.2; P < .01). The patterns of JR were compared between effective and ineffective applications. We managed to show a significant correlation between patterns of JR and successful ablation (P = .01). Logistic regression analysis revealed that the presence of sinus-junction-sinus, sinus-junction-junction, and sinus-junction-block patterns of JR was a predictor of a successful RF ablation (confidence interval [CI], 1.67-15.92 [P < .004]; CI, 1.02-85.62 [P = .048]; and CI, 1.06-32.02 [P = .042], respectively). CONCLUSION: This study confirms that JR is often present during successful slow pathway ablation. The pattern of JR is useful as indicator of success.

Detection of a new KCNQ1 frameshift mutation associated with Jervell and Lange-Nielsen syndrome in 2 Iranian families.

Jervell-Lange Nielsen syndrome (JLNS) with autosomal recessive inheritance is a congenital cardiovascular disorder characterized by prolongation of QT interval on the ECG and deafness. We have performed molecular investigation by haplotype analysis and DNA Sanger sequencing in 2 unrelated Iranian families with a history of syncope. Mutational screening of KCNQ1 gene revealed the novel homozygous frameshift mutation c.733-734delGG (p.G245Rfs*39) in 2 obviously unrelated cases of JLNS which is probably a founder mutation in Iran. The novel mutation detected in this study is the first time reported among Iranian population and will be beneficial in the tribe and region-specific cascade screening of LQTS in Iran.

Novel frameshift mutation in the KCNQ1 gene responsible for Jervell and Lange-Nielsen syndrome.

OBJECTIVES: Jervell and Lange-Nielsen syndrome is an autosomal recessive disorder caused by mutations in KCNQ1 or KCNE1 genes. The disease is characterized by sensorineural hearing loss and long QT syndrome. MATERIALS AND METHODS: Here we present a 3.5-year-old female patient, an offspring of consanguineous marriage, who had a history of recurrent syncope and congenital sensorineural deafness. The patient and the family members were screened for mutations in KCNQ1 gene by linkage analysis and DNA sequencing. RESULTS: DNA sequencing showed a c.1532_1534delG (p. A512Pfs*81) mutation in the KCNQ1 gene in homozygous form. The results of short tandem repeat (STR) markers showed that the disease in the family is linked to the KCNQ1 gene. The mutation was confirmed in the parents in heterozygous form. CONCLUSION: This is the first report of this variant in KCNQ1 gene in an Iranian family. The data of this study could be used for early diagnosis of the condition in the family and genetic counseling.