Idiopathic Arrhythmias Research Articles

Electrocardiographic differentiation of idiopathic right ventricular outflow tract ectopy from early arrhythmogenic right ventricular cardiomyopathy.

AimsThe differentiation between idiopathic right ventricular outflow tract (RVOT) arrhythmias and early arrhythmogenic right ventricular cardiomyopathy (ARVC) can be challenging. We aimed to assess whether QRS morphological features and coupling interval of ventricular ectopic beats (VEBs) can improve differentiation between the two conditions.Methods and ResultsTwenty desmosomal-gene mutation carriers (13 females, mean age 43 years) with no or mild ARVC phenotypic expression and 33 age- and sex-matched subjects with idiopathic RVOT arrhythmias were studied. All patients exhibited isolated monomorphic VEBs with left bundle branch block/inferior axis morphology. The predictive value of ectopic QRS morphology and coupling interval was evaluated. Five ectopic QRS features were significantly more common in desmosomal-gene mutation carriers than in idiopathic RVOT-ventricular arrhythmia patients: maximal QRS duration >160 ms (60 vs. 27%, P = 0.02), intrinsicoid deflection time >80 ms (65 vs. 24%, P = 0.01), initial QRS slurring (40 vs. 12%, P = 0.04), QS pattern in lead V1 (90 vs. 36%, P < 0.001), and QRS axis >90° in limb leads (60 vs. 24%, P = 0.01). In the multivariate analysis, intrinsicoid deflection time >80 ms [odds ratio (OR) = 9.9], QS pattern in lead V1 (OR = 28), and QRS axis >90° (OR = 5.7) remained independent predictors of early ARVC. The coupling interval did not differ between the two groups.ConclusionsIn patients with RVOT VEBs and no major electrocardiographic or echocardiographic abnormalities, the ectopic QRS morphology aids in the differential diagnosis between idiopathic RVOT arrhythmias and early ARVC.

Role of Inflammation, Viruses and Tissue Macrophages in the Development of Idiopathic Arrhythmia and Heart Failure

Endomyocardial biopsy is the gold standard in the diagnosis of myocardial pathology. Intravital study of endomyocardial samples offers the possibility to determine the morphological substrate and etiology of disease, to monitor the effectiveness of treatment. We studied morphological features, viral antigens, macrophages and specifically alternatively activated macrophages in endomyocardial biopsies of 25 patients with idiopathic arrhythmias and heart failure. Immunohistological study was performed to identify type of lymphocytes, macrophages and antigens of cardiotropic viruses. We observed the presence of alternatively activated macrophages in myocardium of patients with myocarditis and without it. We detected the presence of viral antigens in the myocardium of patients with myocardial fibrosis without of histological criteria myocarditis. Small focal infiltration of the myocardial CD68+ macrophages associated with heart failure and ventricular arrhythmias. The presence of virus antigens in myocardium associated with fewer myocardial stabilin-1+ macrophages [negative correlation]. On the other side small focal infiltration of stabilin-1+ macrophages correlated with severity of myocardial interstitial fibrosis [positive correlation]

Discrete potentials guided ablation for idiopathic outflow tract ventricular arrhythmias

Discrete potentials (DPs) have been recorded and targeted as the site of ablation of the outflow tract arrhythmias. The aim of the present study was to investigate the significance of DPs with respect to mapping and ablation for idiopathic outflow tract premature ventricular contractions (PVCs) or ventricular tachycardias (VTs). Seventeen out of 24 consecutive patients with idiopathic right or left ventricular outflow tract PVCs/VTs who underwent radiofrequency catheter ablation between September 2012 and December 2013 in our department were included. Intracardiac electrograms during the mapping and ablation were analyzed. During sinus rhythm, sharp high-frequency DPs that displayed double or multiple components were recorded following or buried in the local ventricular electrograms in all of the 17 patients, peak amplitude was (0.51 ± 0.21) mV. The same potential was recorded prior to the local ventricular potential of the PVCs/VTs. Spontaneous reversal of the relationship of the DPs to the local ventricular electrogram was noted during the arrhythmias. The DPs were related to a region of low voltage showed by intracardiac high-density contact mapping. At the sites with DPs, unipolar and bipolar ventricular voltage of sinus beats were lower compared with the adjacent regions without DPs (unipolar: (6.1 ± 1.8) mV vs. (8.3 ± 2.3) mV, P < 0.05; bipolar: (0.62 ± 0.45) mV vs. (1.03 ± 0.60) mV, P < 0.05). The targeted DPs were still present in 12 patients after successful elimination of the ectopies. Discrete potentials were not present in seven controls. Discrete potentials and related low-voltage regions were common in idiopathic outflow tract ventricular arrhythmias. Discrete potential- and substrate-guided ablation strategy could help to reduce the recurrence of idiopathic outflow tract arrhythmias.

0298 : Action potential shortening in the pig right ventricular outflow tract epicardium

The right ventricular outflow tract (RVOT) has a distinct embryological origin from the rest of the right ventricle (RV) and is a frequent origin for idiopathic and disease-related arrhythmias. We hypothesised that heterogeneous action potential duration (APD) across the right ventricle (RV) may contribute to RVOT arrhythmia generation. Pigs were anesthetized and monophasic action potentials (MAPs) recorded in sinus rhythm from the epicardium of the RV free wall and RVOT. The RV was isolated and perfused via both right and left anterior coronary arteries. The preparation was paced (1-5Hz) and the electrical activity optically mapped (di-4-ANEPPS, 10μM) on both epicardial (EPI) and endocardial (ENDO) surfaces. The expression of potassium channels was assessed by RT-PCR. In vivo, MAP durations measured at 20% and 80% repolarization were both significantly shorter in the RVOT than in the RV free wall EPI (P<0.05). Similar APD variations were observed ex vivo as RVOT APD20 and APD80 were decreased by 29% and 15% respectively compared to free wall (P<0.01). Interestingly, no APD difference was observed on the ENDO resulting in a larger transmural APD difference in the RVOT than in the RV free wall. The RVOT EPI APD80 shortening was preserved over a range of stimulation frequencies leading to a downward shift of the restitution curve and a significant decrease of its slope (P<0.05). In accordance with these results, expression level of mRNA coding for Kv4.3 (Ito) and Kv11.1 (IKr) were upregulated in the RVOT compared to the RV free wall epicardium (P<0.01) while no difference was found for Kv7.1 (IKs) or Kv4.2 (Ito). Moreover, no variation in K+ channel expression was observed across the RV endocardium. Action potentials are shorter in the RVOT than elsewhere in the RV EPI. This electrophysiological signature was mirrored by regional variations in specific K+ channels. The resulting APD dispersion may facilitate RV re-entrant arrhythmias in the context of a RVOT ectopy.

Reappraisal of cardiac magnetic resonance imaging in idiopathic outflow tract arrhythmias.

Because of prognostic and therapeutic implications, the distinction between idiopathic right ventricular (RV) outflow tract (iRVOT) and arrhythmogenic RV cardiomyopathy (ARVC) is clinically important. Over the last 2 decades multiple reports have identified RV abnormalities using CMR in patients with idiopathic VT, suggesting a link between these arrhythmias and ARVC. The purpose of this study was to assess for structural abnormalities in patients with iRVOT tachycardia using contemporary cardiac magnetic resonance (CMR) imaging. CMR was performed in 46 patients with iRVOT tachycardia and 16 normal controls, with quantitative evaluation of RV and left ventricular volumes and function, as well as assessment of myocardial fat and scar. iRVOT patients were similar to controls with respect to RV end-diastolic volumes (81 ± 19 mL/m(2) vs. 79 ± 18 mL/m(2) , P = 0.77) and RV ejection fraction (57 ± 8% vs. 59 ± 7%, P = 0.31). The prevalence of RV chamber dilation, defined using ARVC major task force criteria, was uncommon among iRVOT patients (9%) and controls (7%; P = 1.0). Regional RV wall motion abnormalities were present in 2 iRVOT patients who had concomitant RV dilation or dysfunction. CMR tissue characterization demonstrated absence of both myocardial scar and fat infiltration in all patients and controls. In patients with the clinical diagnosis of iRVOT tachycardia, CMR reveals RV structure, function, and myocardial tissue characteristics similar to normal controls. These findings suggest that the vast majority of patients with RVOT arrhythmias have a primary electrical disorder that is not a forme-fruste of ARVC.

Discrete potentials guided radiofrequency ablation for idiopathic outflow tract ventricular arrhythmias.

Discrete potentials (DPs) have been recorded and targeted as the site of ablation of the outflow tract arrhythmias. The aim of the present study was to investigate the significance of DPs with respect to mapping and ablation for idiopathic outflow tract premature ventricular contractions (PVCs) or ventricular tachycardias (VTs). Seventeen consecutive patients with idiopathic right or left ventricular outflow tract PVCs/VTs who underwent radiofrequency catheter ablation were included. Intracardiac electrograms during the mapping and ablation were analysed. During sinus rhythm, sharp high-frequency DPs that displayed double or multiple components were recorded following or buried in the local ventricular electrograms in all of the 17 patients, peak amplitude 0.51 ± 0.21 mV. The same potential was recorded prior to the local ventricular potential of the PVCs/VTs. Spontaneous reversal of the relationship of the DPs to the local ventricular electrogram during the arrhythmias was noted. The DPs were related to a region of low voltage showed by intracardiac high-density contact mapping. At the sites with DPs, lower unipolar and bipolar ventricular voltage of sinus beats were noted compared with the adjacent regions without DPs (unipolar: 6.1 ± 1.8 vs. 8.3 ± 2.3 mV, P < 0.05; bipolar: 0.62 ± 0.45 vs. 1.03 ± 0.60 mV, P < 0.05). The targeted DPs were still present in 12 patients after successful elimination of the ectopies. Discrete potentials were not present in seven controls. Discrete potentials and related low-voltage regions were common in idiopathic outflow tract ventricular arrhythmias. Discrete potential- and substrate-guided ablation strategy will help to reduce the recurrence of idiopathic outflow tract arrhythmias.

Quantifying late gadolinium enhancement on CMR provides additional prognostic information in early risk-stratification of nonischemic cardiomyopathy: a cohort study.

BackgroundSuspected nonischemic cardiomyopathy (NICM) is a common clinical setting with highly variable prognosis. Early noninvasive risk-stratification is important for justification of invasive examinations, specific treatment and patient surveillance. We studied the additional prognostic value of late gadolinium enhancement (LGE) and segmental wall motion abnormality (SWMA) extent on cardiovascular magnetic resonance (CMR) compared to traditional risk factors in suspected NICM.MethodsIn this observational cohort study, we enrolled 86 consecutive patients referred for CMR due to suspected NICM. Patients with ischemic cardiomyopathy were excluded. CMR images were analysed for left ventricular LGE and SWMA extents and patients were followed-up for major adverse cardiac events (MACE), including cardiovascular death, aborted sudden death and cardiac transplantation.ResultsOf 86 patients (median age: 53 years, 45% female), mainly presenting with ventricular arrhythmias (40%) and congestive heart failure (44%), 76% were finally diagnosed with NICM, 17% with left ventricle hypertrophy and 7% with idiopathic arrhythmia. On CMR, 61 patients (71%) had LGE and 56 (65%) SWMA. During median follow-up of 835 days, 15 patients (17%) reached MACE. In univariant analysis, LGE volume (hazard ratio [HR] 1.028 per 1% increase in LGE, p < 0.001), left ventricular ejection fraction (LVEF) (HR 0.959, p = 0.009) and SWMA score (HR 1.067, p = 0.012) had strongest associations with MACE. In multivariate analysis, the best overall model for event prediction included LGE volume (HR 1.027, p = 0.003), sustained ventricular tachycardia (HR 4.7, p = 0.011) and LVEF (HR 0.962, p = 0.034). Among patients with LGE, there was an event rate of 26% (14 of 61) versus 4% (1 of 25) in patients without LGE (p = 0.041, Log-rank). The highest event rate was observed in patients with LGE volume of ≥17%. Patients without SWMA did not experience MACE (p = 0.002, Log-rank), giving additional information in the subgroup of patients with preserved LVEF (≥50%).ConclusionsIn suspected NICM, presenting with ventricular arrhythmias or heart failure, LGE extent gives additional prognostic information compared to traditional risk factors, while the absence of SWMA may give prognostic information beyond normal LVEF. Even though the final diagnosis is uncertain in NICM, extensive amount of LGE should be considered as a sign of poor prognosis.

Idiopathic arrhythmias: possibilities of complex nosological diagnosis, and differentiated treatment

of the study was to elucidate nosological nature of "idiopathic" arrhythmias by means of complex clinical-morphological examination and to assess efficacy of differentiated (including etiotropic and pathogenetic) treatment. We examined 190 patients (117 women, mean age 45.33 ± 14.84 years) with "idiopathic" arrhythmias: atrial fibrillation (38.9%) (AF,) and flutter (11.1%), supraventricular (44.7%) and ventricular (55.3%) extrasystoles (SVE and VE), bouts of ventricular tachycardia (15.8%), atrioventricular block (22,6%) et al. Mean number of antiarrhythmic drugs per patient was 3 (from 1 to 8). Examination included Holter ECG monitoring, echocardiography, determination of anticardiac antibodies (97.4%) and markers of cardiotropic viruses (87.4%), treadmill test (26.3%), transesophageal cardiac pacing (12.1%), electrophysiological investigation (10%), multispiral computed tomography (22.1%), magnetic resonance tomography (21.6%), scintigraphy (27.4%), coronary angiography (10.0%), endomyocardial biopsy (EMB) (10.0%), DNA diagnostics (8.9%). EMB revealed immune-inflammatory (myo/endocarditis, systemic/myocardial vasculitis) or genetic pathology in 78.9 and 21.1% of cases, respectively. Level of anticardiac antibodies (including specific antinuclear factor) most closely correlated with EMB findings. On the basis of comparison of EMB data with data of complex examination we created algorithm of nosological diagnostics in "idiopathic" arrhythmias. According to nosology all patients were distributed in the following way: 1) chronic infectious-immune myocarditis (n=144, 75.7%), morphologically verified in 14, viral in 27 patients; 2) genetic cardiomyopathy (n=15, 7.9%), morphologically verified in 4, virus positive in 1 (arrhythmogenic right ventricular dysplasia, non-compaction myocardium, Fabri disease, Brugada syndrome, undetermined); in 4 patients mutations in plakophilin 2, desmoglein, desmin, -galactosidase A genes were found; 3) combination of genetic diseases with myocarditis (n=18; 9.5%) including viral (n=3); 4) isolated myocardiodystrophy (tonsillogenic< dyshormonal, n=3, 1.6%); 5) proper idiopathic arrhythmias (n=10, 5.3%). Therapy of myocarditis included antiviral (43.2%) and immunosuppressive (76.3%) drugs. Cardiotropic and antiarrhythmic therapy was also administered. Only in patients with myocarditis it was possible to withdraw effective antiarrhythmic (16.7%) and to improve effect of previously ineffective drugs. Surgical treatment (implantation of pacemaker or cardioverter-defibrillator, radiofrequency ablation) was more frequently used in patients with genetic (39.4%) and idiopathic arrhythmias (53.8%) than in patients with myocarditis (16.0%). Etiology of idiopathic arrhythmias can be established in most cases. Their main causes are immune-inflammatory diseases, genetic cardiomyopathies and their combination. Therapy of myocarditis improves antiarrhythmic activity of treatment, in some patients allows to withdraw antiarrhythmic drugs, decrease requirements in surgical treatment and to optimally prepare patients to radiofrequency ablation.

CLINICAL AND MORPHOLOGICAL APPROACH TO DIAGNOSIS OF "IDIOPATHIC" ARRHYTHMIAS AND DILATED CARDIOMYOPATHY SYNDROME AS A BASIS FOR DIFFERENTIATED THERAPY. Part II (Treatment)

Part I (Diagnostics), was published in the journal “Rational Pharmacotherapy in Cardiology” 2014;10(1):62-72 Aim. To develop a comprehensive clinical and morphological approach to the nosological diagnosis and treatment of idiopathic arrhythmias (IA) and the syndrome of dilated cardiomyopathy (DCM). Material and methods. Patients (n=320) with IA (n=190; 117 women, age 45.3±14.8 years) and DCM (n=130, 41 women, age 46.9±12.5 years) were included in the main group. 51 people (patients with ischemic heart disease; heart valve disease, hypertrophic cardiomyopathy, who underwent open-heart surgery; healthy volunteers) were included in the control group. Along with the standard tests evaluation of the level of anti-heart antibodies (185 patients with IA and 122 with DCM), viral serology (166 and 122), multispiral computed tomography (42 and 88), cardiac magnetic resonance imaging (41 and 22), coronary angiography (19 and 54), myocardial biopsy/autopsy (19/0 and 33/9) were performed. Results. According to morphological study infectious-immune myocarditis was found in 78.9% patients with IA and 66.7% patients with DCM, arrhythmogenic right ventricular dysplasia in 5.3% and 4.8% of patients, respectively. Other genetic cardiomyopathies, including combination with myocarditis were revealed in other patients. The frequency of the viral genome detection in the myocardium in IA, DCM and the control group was 17.6%, 66.7% and 77.1%, respectively. However in the control group the incidence of myocarditis and anti-heart antibodies titers were significantly lower than in the main group, where a strong correlation between myocarditis and anti-heart antibodies titers was found. The algorithm of noninvasive nosological diagnostics was developed; it allowed to verify diagnosis in 95% of IA patients and 89% DCM patients The basic therapy (antiviral drugs, corticosteroids, hydroxychloroquine, azathioprine) was performed in some patients with myocarditis. Improving of the antiarrhythmic effect of treatment in patients with IA, a significant increase in ejection fraction, a reducing of the size of the heart chambers and of pulmonary artery pressure in patients with DCM, a reducing of the need in surgical treatment (including in the virus-positive patients) occurred as results of treatment. Conclusion. Nosological cause of IA and DCM syndrome can be diagnosed in most patients by using an integrated clinical and morphological approach. This allows managing effective etiotropic and pathogenetic treatment.

CLINICAL AND MORPHOLOGICAL APPROACH TO DIAGNOSIS OF "IDIOPATHIC" ARRHYTHMIAS AND DILATED CARDIOMYOPATHY SYNDROME AS A BASIS FOR DIFFERENTIATED THERAPY. Part I (Diagnostics)

P Aim. To develop a comprehensive clinical and morphological approach to the nosological diagnosis and treatment of "idiopathic" arrhythmias (IA) and the syndrome of dilated cardiomyopathy (DCM). Material and methods. Patients (n=320) with IA (n=190; 117 women, age 45.3±14.8 years) and DCM (n=130, 41 women, age 46.9±12.5 years) were included in the main group. 51 people (patients with ischemic heart disease; heart valve disease, hypertrophic cardiomyopathy, who underwent open-heart surgery; healthy volunteers) were included in the control group. Along with the standard tests evaluation of the level of anti-heart antibodies (185 patients with IA and 122 with DCM), viral serology (166 and 122), multispiral computed tomography (42 and 88), cardiac magnetic resonance imaging (41 and 22), coronary angiography (19 and 54), myocardial biopsy/autopsy (19/0 and 33/9) were performed. Results. According to morphological study infectious-immune myocarditis was found in 78.9% of IA and 66.7% of DCM-patients, arrhythmogenic right ventricular dysplasia in 5.3% and 4.8% of patients, respectively. Other genetic cardiomyopathies, including combination with myocarditis were revealed in other patients. The frequency of the viral genome detection in the myocardium in IA, DCM and the control group was 17.6%, 66.7% and 77.1%, respectively. However in the control group the incidence of myocarditis and anti-heart antibodies titers were significantly lower, while in the main group a strong correlation between myocarditis and anti-heart antibodies titers was found. The algorithm of noninvasive nosological diagnostics was developed; it allowed to verify diagnosis in 95% of IA patients and 89% DCM patients. Conclusion. Nosological cause of IA and DCM syndrome can be diagnosed in most patients by using an integrated clinical and morphological approach.

CLINICAL AND HEMODYNAMIC INTERRELATIONS OF ARRHYTHMIA COURSE IN CHILDREN OF 0 TO 7 YEARS OLD

Aim. To study clinical and hemodynamic parallels in preschool children with arrhythmias in different age groups. Material and methods. Totally 195 children studied with idiopathic arrhythmias at the age of 0 to 7 y. o. — 82 with WPW syndrome, 55 with atrial tachiarrhythmias, 7 with AVNRT, 13 — with ventricular tachis (VT), 38 with ventricular and supraventricular onsets (isolated, group and their combination). Age groups: 1 — children 1 y. o. (n=72; 37%); 2 — 1-3 y. o. (n=37; 19%); 3 — 3-7 y. o. (n=87; 44%). All patients underwent standart laboratory assessment, electrocardiography in 12 standard leads, Holter monitoring, echocardiography. Results. In analysis of tachicardias course variants there was prevalence of of paroxysmal tachicardia in children of 3 to 7 y. o. (p=0,001) and permanent tachicardia in children less than 1 y. o. (p<0,001). Frequency of episodes in paroxysmal tachicardias in 1 y. o. children was higher than in those from 1 to 3 y. o. (p=0,028) and 3-7 y. o. children (p<0,001). In assessment of echocardiography of arrhythmic children depended on age there was significant prevalence of ACMP in older children comparing to the younger (p=0,002). Signs of heart failure were more common in children of 1 y. o. comparing to those of 1-3 and 3-7 y. o. (F=44,117; p=<0,001). Conclusion. So the arrhythmogenic heart remodeling mostly common for the children of 3 to 7 y. o. In less 1 year infants with arrhythmias clinical signs of HF are followed by diastolic disorders that develop before ACMP development, that is traditionally regarded as systolic dysfunction. Into the factors that influence these hemodynamic relations we include high mean heartrate, tendency of tachicardias to recurrent and permanent course, high frequency of attacks in paroxysmal tachicardias in infants before 1 year old.

Cellular quality control: A two-edged sword in Brugada syndrome

Two decades ago, sudden cardiac death without overt structural heart disease was often called an idiopathic ventricular fibrillation (VF). Focusing more interest on this entity, Pedro and Josep Brugada pointed out the link between conspicuous ECG features and lethal arrhythmias. Over the years, the stopgap diagnosis of idiopathic VF has become more doubtful because of the fast evolving field of cardiac genetic and molecular biology science. Today, we have to consider a large spectrum of channelopathies responsible for apparently idiopathic but fatal arrhythmias. How can those patients be stratified and protected? Because of various but well-defined phenotypes, the recent Expert Consensus Recommendations on long QT syndrome enable a cookbook-like risk stratification that leaves therapeutic space for at least some patients. In contrast, the management of patients revealing a Brugada syndrome (BS) appears more uncertain, and therapeutic consequences mostly result in defibrillator implantation. The first BS-responsible defect was detected in the SCN5A gene; it causes a dysfunction of the pore-forming α-subunit in the cardiac sodium channel. Meanwhile, approximately 300 SCN5A mutations have been linked with BS. Other related gene mutations, not exclusively sodium channel allocated, were found in GPD1L, CACNA1C, CACNB2b, SCN1B, SCN3B, KCNE3, KCNJ8, and HCN4. A recently published study screening 30 asymptomatic but BS-affected persons underlined the likely influence of further arrhythmogenic factors or modifier genes other than Na channel dysfunctions. The new detection of numerous mutations and conditions already was lamented years ago, and we keep on searching for clues to solve a clinical problem based on a multifactorial genetic disorder. In this issue of HeartRhythm, Fukuyama et al present a BS-related distinct mechanism for a CACNA1C L-type calcium channel (LTCC) disorder that differs from prior reports. The authors extracted data from 312 patients who had experienced fatal arrhythmias. In 68%, a BS was diagnosed; this indicates a high prevalence but is not unusual for Japan. Interestingly, the next most frequent diagnosis

HEART RHYTHM DISORDERS IN NEW-BORNS AND INFANTS: CLINICAL COURSE AND PERINATAL RISK FACTORS OF ARRHYTHMIAS APPEARANCE

Clinical course, prognosis and mechanisms of separate forms of heart rhythm disorders in children differ from those in adults. Especially, it refers to new-borns and infants whose conduction system differs by functional and morphologic immaturity. In connection with it, the assessment of natural history of heart rhythm disorders, occurred in a perinatal period, and determination of risk factors of arrhythmia appearance in infants are of some interest. 88 newborns took part in the study. The patients were involved by continuous sampling technique. Risk factors, occurred in a perinatal period and potentially influenced on development of heart rhythm disorders, were assessed. In our study we took biological, gynecologic and obstetric history, data of gestation and delivery course, early and late neonatal period, early infancy, Echo, neurosonography, Holter monitoring with determination of heart rhythm variability, and determined thyroid hormonal status. Maximum specific gravity had extrasystoles – 32.4% – in the structure of idiopathic arrhythmias in infants. Heart rhythm disorders with natural history were kept at six months of life only in 5,4% of children. Persistence of arrhythmias was marked during one year only for WPW syndrome. Heart rhythm disorders are often marked significantly in children whose mothers had acute respiratory disease during the pregnancy, or if the children were born from the first pregnancy, had the signs of central nervous system damage syndromes in an early perinatal period (arrest, intracranial hypertension, convulsive disorder). Disorders of autonomic imbalance of cardiac function and peculiarities of hemodynamics of pulmonary circulation contribute significantly into appearance and persistence of all types of arrhythmias. On the whole, the prognosis of heart rhythm disorders, occurred in the perinatal period, without organic and structural changes of myocardium is favorable. The exclusion can be made for congenital atrioventricular block and some types of supraventricular tachycardia which are not responded to treatment.

The role of Interleukin-6, its −174 G>C polymorphism and C-reactive protein in idiopathic cardiac arrhythmias in children

ABSTRACT Purpose: Knowledge about the role of inflammation in the pathogenesis of arrhythmias in children is limited. Several studies have suggested a relationship between plasma IL-6 levels and/or the -174G>C IL-6 gene polymorphism and atrial fibrillation in adults. Our present study was performed to investigate whether serum IL-6, -174G>C IL-6 polymorphism and C-reactive protein (CRP) are associated with arrhythmias of unknown origin in children. The study included 126 children diagnosed with supraventricular or ventricular arrhythmia. Patients with congenital heart defects as well as arrhythmias of known origin were excluded from the study. The control group comprised 37 healthy children. The 24 hour Holter electrocardiography monitoring was performed. Serum IL-6, -174 GC IL-6 polymorphism and CRP concentrations were measured on admission. There were no differences in IL-6, CRP and -174 G>C IL-6 genotype distribution between the control and patient groups. No significant differences in IL-6, CRP and -174 G>C IL-6 genotypes were observed between children with supraventricular or ventricular arrhythmias. The severity of arrhythmias showed also no associations with IL-6, CRP or -174 G>C IL-6 genotypes. The results suggest that idiopathic cardiac arrhythmias of unknown origin in children are not associated with selected pro-inflammatory markers of infections i.e. elevated IL-6, CRP or -174 G>C IL-6 polymorphism. This new information can effectively reduce the total financial cost of unnecessary diagnosis and treatment of children affected by cardiac arrhythmias.

New Diagnostic and Therapeutic Approaches to Treat Ventricular Tachycardias Originating at the Summit of the Left Ventricle

> In Latin “Similia similibus curantur” or, in English, “Like is cured by like.” > > Hippocrates of Kos (460 BC – 370 BC), Greece. The left ventricular (LV) summit is the most common site of idiopathic epicardial LV arrhythmias and frequently represents a diagnostic and a therapeutic challenge.1 We present a case of sustained monomorphic ventricular tachycardia (SMVT) originating at the LV summit that underwent failed cryosurgical epicardial ablation and was successfully treated with the aid of merged hemodynamic and contrast-enhanced MRI (CE-MRI). Editor’s Perspective see p e85 A 67-year-old man was admitted in 2010 for heart failure with severe LV dysfunction (ejection fraction 20%) initially attributed to alcohol consumption, and during the diagnostic work-up, a severe lesion at the bifurcation of the proximal left anterior descending artery with the first diagonal was percutaneously revascularized using a bifurcated drug-eluting stent, and he was discharged with the diagnosis of dilated cardiomyopathy of mixed pathogenesis (alcoholic and ischemic). In April 2011, he presented with SMVT with left-bundle branch block morphology. He underwent CE-MRI followed by an electrophysiologic study using an endocardial LV retrograde access, where frequent premature ventricular contractions (PVCs) with similar morphology to the clinical VT were ablated at the mitroaortic continuity, with partial success (ie, reduction in PVC density). The patient underwent implantable cardioverter-defibrillator (ICD) insertion and was discharged on amiodarone treatment. He remained free of arrhythmias until September 2012, when he was readmitted for a SMVT with left-bundle branch block morphology, right inferior axis at 140 beats per minute (below ICD detection rate), and early precordial transition (Figure 1). At the time of the EP study, SMVT was not inducible with programmed stimulation during isoproterenol infusion, but the patient presented frequent PVCs with identical morphology to the clinical VT (Figure 2C). A combined endoepicardial electroanatomical mapping (NaviStar ThermoCool, 3.5-mm tip, …

Concealed structural abnormalities in patients with apparently idiopathic arrhythmias of left ventricular origin: a magnetic resonance imaging study

Purpose: Monomorphic Ventricular Arrhythmias of LV origin (VAs-LV) are usually associated with structural heart disease. However, routine diagnostic work-up occasionally does not identify any abnormality; in these patients, VAs-LV are referred as idiopathic. Aim of the present study was to investigate the value of cardiac MRI for the detection of concealed myocardial structural changes in pts with apparently idiopathic monomorphic VAs-LV. Methods: 39 consecutive pts (64% males, mean age 44±14 years) with monomorphic VAs-LV (i.e. frequent ventricular premature beats, recurrent non-sustained or sustained ventricular tachycardia with right bundle branch block morphology) and negative routine diagnostic work-up were included in the study. For comparison purposes, 61 consecutive pts (62% males, mean age 40±16 years) with monomorphic VAs of Right Ventricular Outflow Tract (RVOT) origin (i.e. with left bundle branch block morphology and inferior axis) and negative routine diagnostic work-up were also included. Routine diagnostic work-up included physical examination, blood tests, 12-lead ECG, transthoracic echocardiography and exercise stress testing; multi-slice computed tomography or invasive coronary angiography were also performed in selected pts. Both groups of pts underwent comprehensive cardiac MRI study, to assess LV and RV function, myocardial fatty infiltration, edema, and necrosis/fibrosis. Results: The 2 groups of pts did not differ significantly in age (p=0.22) and gender (p=0.86). No significant difference was observed between patients with VAs-LV and VAs-RVOT regarding LVEDV (78±18ml/m2 vs. 76±14ml/m2; p=0.56), RVEDV (71±15ml/m2 vs. 72±13ml/m2; p=0.72), LVEF (66±9% vs. 66±8%; p=0.93) and RVEF (69±7% vs. 69±7%; p=0.71). Cardiac MRI demonstrated myocardial structural abnormalities in 16 (41%) pts with VAs-LV vs. 5 (8%) pts with VAs-RVOT (p<0.001). At multivariate analysis, male gender (OR=11.6, 95% CI 2.1-65.0; p=0.005), family history of sudden cardiac death and/or cardiomyopathy (OR=5.2, 95% CI 1.3-20.4; p=0.019) and VAs-LV (OR 11.5, 99%CI 3.0-43.7; p<0.001) were independently related to the presence of myocardial structural abnormalities. Conclusions: Cardiac MRI detects myocardial structural changes in a non-negligible proportion of pts with apparently idiopathic monomorphic VAs-LV. Accordingly, cardiac MRI should be implemented in the routine diagnostic work-up of these pts, in order to better characterize the pathogenic substrate of VAs and to better tailor specific therapy.

Radiofrequency ablation of idiopathic ventricular arrhythmia originating from the tricuspid annulus

A 20-year-old female patient was referred to our division for drug-resistant symptomatic ventricular extra-stimuli and short salvos of ventricular tachycardia. No underlying structural heart disease or detectable channelopathy was found during diagnostic tests. Her preprocedural electrocardiogram (Fig. 1, left panel) showed ‘notch’ in the limb leads, the precordial R-wave transition in leads V4 to V5, and increased Q-wave amplitude in each of leads V1 to V3, all suggesting the arrhythmia focus from the free wall of the tricuspid annulus (TA). During electrophysiologic study under the guidance of 3-dimensional electroanatomic mapping using the Carto 3 system (The Carto 3 System, Biosense Webster, Belgium) earliest local activation times during the arrhythmia were obtained from the anterolateral free wall of the TA (Fig. 2). Activation mapping also demonstrated the arrhythmia focus and its propagation to the other sites of the right ventricle (Movie). Initial radiofrequency ablation attempts using irrigated tip ablation catheter (Navistar® Thermocool®, Biosense Webster, Belgium) to this region stopped the arrhythmia abruptly. Then applying multiple lesions in close proximity to the initial site diminished the idiopathic arrhythmia completely (Fig. 2). Postprocedural electrocardiogram showed no residual arrhythmia with a regular sinus rhythm (Fig. 1, right panel).

Synthetic conformational antigen which simulates the extracellular part of the M2-muscarinic receptor: interaction with blood sera of patients suffering from idiopathic arrhythmias

Fragments corresponding to the 83–98 sequence of the first extracellular loop and to the 168–192 and 171–182 sequences of the second extracellular loop of the M2-muscarinic receptor (antibodies to this receptor could be markers of early symptoms of heart disorders) were synthesized by solid phase method using the Fmoc-SPPS strategy. A new conformational antigen with the natural location of the disulfide bridge was prepared by selective formation of disulfide bond between the corresponding cysteine residues in the synthe-sized peptides and characterized. The comparative analysis of reactivity of the synthesized peptides towards sera from patients which had no organic heart disease was performed. A new conformational antigen was effectively bound to the sera from patients with idiopathic arrhythmias, but without symptoms of organic heart disease.

Catheter ablation of arrhythmia from the aortic sinus cusp: the presence of a dead-end tract of the conduction system

We described a case of idiopathic arrhythmia originating from the coronary cusp. Intracardiac recordings showed a shorter HV interval (36–49 ms) during ectopic beats compared with the HV interval (55–62ms) during sinus. A potential was recorded at the right coronary cusp (RCC) …

Синтетический конформационный антиген, моделирующий внеклеточную часть мускаринового М2-рецептора, и его взаимодействие с сыворотками крови пациентов с идиопатическими аритмиями

Linear peptides corresponding to fragment 83-98 of the first loop and fragments 168-192 and 171-182 of the second extracellular loops of M2-muscarinic receptor (marker of early cardiac disorders and arrhythmias) were synthesized by Fmoc-SPPS method. A new conformational antigen was synthesized by method of selective ligation of linear peptides by disulfide bond with native localization. Peptides were studied in reaction with sera from patients with idiopathic arrhythmias. A new conformational antigen was recognized by sera from patients with idiopathic arrhythmias with high reactivity.