A Multicenter External Validation of a Score Model to Predict Risk of Events in Patients With Brugada Syndrome.

A multivariate risk score model was proposed by Sieira et al in 2017 for sudden death in Brugada syndrome; their validation in 150 patients was highly encouraging, with a C-index of 0.81; however, this score is yet to be validated by an independent group. A total of 192 records of patients with Brugada syndrome were collected from 2 centers in the United Kingdom and retrospectively scored according to a score model by Sieira et al. Data were compiled summatively over follow-up to mimic regular risk re-evaluation as per current guidelines. Sudden cardiac death survivor data were considered perievent to ascertain the utility of the score before cardiac arrest. Scores were compared with actual outcomes. Sensitivity in our cohort was 22.7%, specificity was 57.6%, and C-index was 0.58. In conclusion, up to 75% of cardiac arrest survivors in this cohort would not have been offered a defibrillator if evaluated before their event. This casts doubt on the utility of the score model for primary prevention of sudden death. Inherent issues with modern risk scoring strategies decrease the likelihood of success even in robustly designed tools such as the Sieira score model.

Yixin-Fumai granules improve sick sinus syndrome in aging mice through Nrf-2/HO-1 pathway: A new target for sick sinus syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Yixin-Fumai granules (YXFMs)-composed of Ginseng quinquefolium (L.) Alph. Wood, Ophiopogon japonicus (Thunb.) Ker Gawl, Schisandra arisanensis Hayata, Astragalus aaronsohnianus Eig, Salvia cryptantha Montbret & Aucher ex Benth, and Ligusticum striatum DC-are compound granules used in traditional Chinese medicine to increase heart rate and thus treat bradyarrhythmia. It may be effective in treating sick sinus syndrome (SSS). AIM: To observe the effect of YXFMs on aging-induced SSS in mice and explore whether this effect is related to the Nrf-2/HO-1 signaling pathway. MATERIALS AND METHODS: Mice with a significant decrease in the heart rate due to natural aging were selected to construct an SSS model. After the mice were administered YXFMs, the damage to their sinoartrial node (SAN) was assessed through electrocardiography, Masson's trichrome staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Dihydroethidium staining and immunofluorescence staining were used to assay reactive oxygen species (ROS) content and HCN4, respectively. Moreover, to observe the effects of YXFMs in vitro, the HL-1 cell line, derived from mouse atrial myocytes, was used to simulate SAN pacemaker cells, with H2O2 used as the cellular oxidative stress (OS) inducer. 2,7-Dichlorodihydrofluorescein diacetate staining was used to assay ROS content, whereas immunofluorescence staining and Western blotting were used to elucidate the related protein expression. Finally, mice were injected the Nrf-2 inhibitor ML385 to reversely verify the effects of YXFMs. RESULTS: In our in vivo experiments, YXFMs significantly inhibited aging-induced SSS, shortened the R-R interval, increased heart rate, alleviated fibrosis, reduced apoptosis rate and ROS content, and promote HCN4 expression in the SAN. In our in vitro experiments, YXFMs significantly inhibited H2O2-induced cell peroxidation damage, promoted Nrf-2 activation and nuclear metastasis, increased HO-1 expression- thereby inhibiting ROS accumulation-and finally, upregulated HCN4 expression through the inhibition of histone deacetylase 4 (HDAC4) expression and its nuclear metastasis. Finally, injection of the Nrf-2 inhibitor ML385 after YXFMs administration inhibited their protective effect in the mice. CONCLUSION: Here, we elaborated on the relationship between aging-induced SSS and the Nrf-2/HO-1 pathway for the first time and proposed that YXFMs improve SSS via the Nrf-2/HO-1 axis. Specifically, YXFMs promoted Nrf-2 activation and plasma-nuclear transfer to enhance HO-1 expression via the Nrf-2/HO-1 axis. This inhibited OS and reduced ROS accumulation in the SAN, and then, through the ROS/HDAC4 axis, reduced HDAC4 expression and plasma-nuclear transfer. Thereby, the OS-induced HCN4 loss in the SAN was inhibited-improving the function of If channel and thus producing SAN protection effect against SSS and improving the heart rate and R-R interval. In the future, we plan to use bioinformatics analysis technology to execute the next step of our research, namely to determine the effect of isolated, purified components of YXFMs in SSS, to increase its efficiency and reduce the toxicity of YXFMs.

Conceptos actuales sobre la clasificación clínica y alteraciones electrofisiológicas en la disfunción del nódulo sinusal / Current concepts about the clinical classification and electrophysiological alterations in the sinus node dysfunction

La disfunción del nódulo sinusal (DNS) es generalmente secundaria a la senescencia del nodo sinusal y del miocardio auricular circundante. Los pacientes con este trastorno son a menudo añosos y en general presentan otras comorbilidades. Los pacientes a menudo buscan atención médica con síntomas de aturdimiento, pre-síncope, síncope y, en pacientes con periodos alternantes de bradicardia y taquicardia, palpitaciones u otros síntomas asociados con una frecuencia cardíaca rápida. Debido a que los síntomas pueden ser de naturaleza variable, inespecíficos y frecuentemente transitorios, a veces puede ser difícil establecer esta relación síntoma-alteración electrocardiográfica. Los hallazgos electrocardiográficos típicos son uno o más episodios de bradicardia sinusal extrema (Rubenstein Tipo I), o pausas sinusales, paro y bloqueo de salida sinoatrial (Rubenstein Tipo II), o episodios de bradicardia y/o pausas alternantes con taquiarritmias auriculares (Rubenstein Tipo III). Las investigaciones basadas en el registro de electrogramas locales auriculares anormalmente prolongados y fraccionados durante el ritmo sinusal y su distribución característica en la aurícula derecha de pacientes con DNS han aportado un conocimiento importante sobre las propiedades electrofisiológicas de la aurícula patológica. El electrograma auricular anormal traduce una conducción auricular irregular, caracterizada por una actividad eléctrica local no homogénea, relacionada con una conducción anisotrópica, no uniforme y retardada a través de un miocardio auricular patológico, en el que se pueden originar arritmias por reentrada. La detección de electrogramas auriculares anormales en la DNS identifica a un grupo de pacientes con vulnerabilidad auricular aumentada y con una incidencia significativamente mayor de episodios espontáneos o inducidos de fibrilación auricular(AU)

Sinus node dysfunction (SND) is often secondary to senescence of the sinus node and surrounding atrial myocardium. Patients with this disorder are frequently elderly and generally have other comorbidities. Patients with SND often seek medical attention with symptoms of lightheadedness, presyncope, syncope, and, in patients with alternating periods of bradycardia and tachycardia, palpitations and/or other symptoms associated with a rapid heart rate. Because symptoms may be variable in nature, nonspecific, and frequently transient, it may be challenging at times to establish this symptom-rhythm relationship. Typical electrocardiographic findings are one or more episodes of extreme sinus bradycardia (Rubenstein type I), or sinus pauses, arrest, and sinoatrial exit block (Rubenstein type II), or alternating bradycardia and atrial tachyarrhythmias (Rubenstein type III). Investigations based on the recording of abnormally prolonged and fractionated local atrial electrograms during sinus rhythm and their characteristic distribution in the right atrium of patients with SND have provided important knowledge about the pathological atrium electrophysiological properties. Abnormal atrial electrogram results in an irregular atrial conduction, characterized by a non-homogeneous local electrical activity, related to an anisotropic, non-uniform and delayed conduction through a pathological atrial myocardium, in which reentry arrhythmias may arise. Abnormal atrial electrograms detection in SND identifies a group of patients with increased atrial vulnerability and a significantly higher incidence of spontaneous or induced episodes of atrial fibrillation(AU)

Inappropriate automatic mode switching episodes: What's the mechanism?

We present a case series of five patients reporting abnormal automatic mode switching (AMS) episodes during routinary cardiac defibrillator (ICD) and pacemaker (PM) follow-up. This non-previously described phenomenon was reported to St. Jude Medical (Abbott) Technical Support that confirmed the inappropriate automatic mode switching.

Comparative Assessment of the Heart's Functioning by Using the Akabane Test and Classical Methods of Instrumental Examination.

Acupuncture physicians have studied the application of reflexotherapy to cardiology. However, no one has investigated the connection of ancient Chinese diagnostic methods with modern tools. A total of 102 patients (54 men and 48 women) with heart pathology, namely, sick-sinus syndrome, Wolff-Parkinson-White syndrome, and atrioventricular blockade, were studied using the usual instrumental methods (transesophageal electrophysiological study of the heart, echocardiography), after which they underwent Akabane thermopuncture testing as in traditional Chinese medicine. The results of cardio examination from one side of the Akabane test with that from the other side were compared by means of a multiple stepwise regression analysis. We revealed the effects on the characteristic pattern of acupuncture channel lesions inherent in a definite heart pathology, i.e., the most vulnerable acupuncture channel (AC), of such factors as disturbances of the contractile, conductive, or automatic heart functions, and changes in the chambers' size or circulation volume. Сhanges in the indices of the left and the right branches of these channels usually reflect the opposing natures of the changes in these indicators, which should be considered in reflexotherapy. The main value of the Akabane test along with the use of mathematical analysis lies in early, quick, and inexpensive detection of the above-mentioned heart disturbances.

Rescuing cardiac automaticity in L-type Cav1.3 channelopathies and beyond.

Pacemaker activity of the sino-atrial node generates the heart rate. Disease of the sinus node and impairment of atrioventricular conduction induce an excessively low ventricular rate (bradycardia), which cannot meet the needs of the organism. Bradycardia accounts for about half of the total workload of clinical cardiologists. The 'sick sinus' syndrome (SSS) is characterized by sinus bradycardia and periods of intermittent atrial fibrillation. Several genetic or acquired risk factors or pathologies can lead to SSS. Implantation of an electronic pacemaker constitutes the only available therapy for SSS. The incidence of SSS is forecast to double over the next 50 years, with ageing of the general population thus urging the development of complementary or alternative therapeutic strategies. In recent years an increasing number of mutations affecting ion channels involved in sino-atrial automaticity have been reported to underlie inheritable SSS. L-type Cav 1.3 channels play a major role in the generation and regulation of sino-atrial pacemaker activity and atrioventricular conduction. Mutation in the CACNA1D gene encoding Cav 1.3 channels induces loss-of-function in channel activity and underlies the sino-atrial node dysfunction and deafness syndrome (SANDD). Mice lacking Cav 1.3 channels (Cav 1.3-/- ) fairly recapitulate SSS and constitute a precious model to test new therapeutic approaches to handle this disease. Work in our laboratory shows that targeting G protein-gated K+ (IKACh ) channels effectively rescues SSS of Cav 1.3-/- mice. This new concept of 'compensatory' ion channel targeting shines new light on the principles underlying the pacemaker mechanism and may open the way to new therapies for SSS.

Electrical Remodeling of the Atrioventricular Node Caused by Persistent Atrial Fibrillation in Humans.

BACKGROUND: An animal experiment showed that long-term atrial pacing or persistent atrial fibrillation (AF) caused electrical remodeling of the atrioventricular (AV) node. We aimed to test the hypothesis that persistent AF decreases the AV conductivity in human hearts. METHODS AND RESULTS: We retrospectively compared the cardiac electrophysiological properties between patients with paroxysmal AF who underwent catheter ablation (PXAF, N = 254) and those with persistent or longstanding persistent AF (PSAF, N = 213). The PSAF patients were more likely than PXAF patients to have longer atrial-His (AH) (96.3 ± 25.7 vs. 91.3 ± 20.4 milliseconds; P = 0.02) and His-ventricle (HV) (43.1 ± 9.4 vs. 41.2 ± 8.6 milliseconds; P = 0.02) intervals. The AV nodal effective refractory period (ERP) (299.1 ± 74.6 vs. 276.2 ± 58.9 milliseconds; P < 0.001) and Wenckebach cycle length (420.9 ± 80.3 vs. 386 ± 58.6 milliseconds; P < 0.001) were also more prolonged in the PSAF patients. We found a dual AV nodal physiology with a similar frequency in both groups. The AH interval, fast pathway ERP, and Wenckebach cycle length in the PSAF patients were more likely than in the PXAF patients to be prolonged among the patients without dual pathways, while those intergroup differences were never seen among the patients with dual pathways. In subgroup analyses including only PSAF patients, there was no difference in the AV conductivity between the patients with persistent AF and those with longstanding persistent AF. CONCLUSIONS: Persistent AF may cause a mild decrease in the AV nodal function in human hearts. Electrical remodeling may be uncommon if dual AV nodal pathways are present, and its extent may not depend on the duration of persistent AF.

Device malfunction caused by "auto-oversensing" of transthoracic impedance measurement test pulses in a modern minute ventilation dual-chamber pacemaker.

Oversensing of physiologic and non-physiologic electrical signals is a relevant cause of malfunctions in subjects with CIED. Physicians taking care of CIED patients must be aware of the potential causes of oversensing and their pattern in EGMs. The present case describes an uncommon source and unique underlying root cause for oversensing in a modern dual-chamber MV rate-adaptive pacemaker.

INFLUENCE OF PERMANENT PACING OF THE ATRIA FROM UPPER ANTERIOR AREA OF INTERCARDIAC SEPTA (AREA OF BAKHMAN'S FASCICLES) ON THE PART OF AMOTIVATIONAL VENTRICLE STIMULATION.

This research includes 74 patients with syndrome of the sinus node asthenia. The application of permanent bilocular pacing was indicated for these patients. An atrial electrode was located in the right atrial auricle in 37 patients and it was in the area of Bakhman's fascicles in other 37 patients. All the patients had a stimulated atrio-ventricular delay on 250 ms, but sensing delay was shorter on 20 ms. Given data were analyzed after operation in the periods of 6 and 12 months. Cumulative percent of ventricular stimulation was significantly less in the group with electrode in the area of Bakhman's fascicles (6%) as compared with the group where electrode installed in the right atrial auricle (41%) after 6 months. There were 4% in comparison with 43% after 12 months. The localization of atrial electrode in the area of Bakhman's fascicles led to reduction of cumulative percent of ventricular stimulation on 35% after 6 months and on 39% after 12 months. Permanent pacing in the area of Bakhman's fascicles could be an effective mode to decrease the part of amotivational stimulation of the right ventricle.

Atrial standstill in sinus node disease due to extensive atrial fibrosis: impact on dual chamber pacemaker implantation.

AIMS: Atrial standstill is characterized by the absence of atrial activity. We report about a series of cases, in which conventional atrial pacemaker lead implantation in patients with symptomatic sinus node disease failed due to lack of excitable right atrial tissue, thus, prompting the diagnosis of atrial standstill. We hypothesized that mapping of the atria with subsequent identification of myocardium still amenable to atrial pacing would allow dual chamber pacemaker implantation. METHODS AND RESULTS: In four patients, atrial lead implantation failed. In these patients, spontaneous or fibrillatory electrical activity was absent but the atria could not be captured despite high stimulation voltages at conventional atrial sites. We suspected partial or complete atrial standstill and subsequently confirmed this hypothesis by conventional (n = 1) or electroanatomical mapping (n = 3). Areas of fibrotic tissue were present in all patients as identified by lack of spontaneous electrical activity and inability of local electrical capture via the mapping catheter. Surviving atrial tissue, which could be electrically captured with subsequent conduction of activity to the atrioventricular (AV) node, was present in three patients. Successful targeted atrial lead implantation at these sites was achieved in all these patients. Isolated sinus node activity without conduction to the atria was found in one patient. CONCLUSION: Partial atrial standstill may be present and prevent atrial lead implantation in patients with sinus node disease. In these patients, recognition of partial atrial standstill and identification of surviving muscular islets with connection to the AV node by mapping studies may still allow synchronous AV sequential pacing.

Sodium Hydroxide Pinpoint Pressing Permeation Method for the Animal Modeling of Sick Sinus Syndrome.

Sodium hydroxide pinpoint pressing permeation (SHPPP) was investigated in order to build a rat model of sick sinus syndrome (SSS), which is easy to operate and control the degree of damage, with fewer complications and applicable for large and small animals.Thirty healthy Wistar rats (15 males and 15 females, weighing 250-350 g) were randomly divided into 3 groups, namely a formaldehyde thoracotomy wet compressing group (FTWC), formaldehyde pinpoint pressing permeation group (FPPP) group, and SHPPP group. The number of surviving rats, heart rate (HR), sinoatrial node recovery time (SNRT), corrected SNRT (CSNRT), and sinoatrial conduction time (SACT) were recorded 3 days, one week, and two weeks after modeling.The achievement ratio of modeling was 10% in the FTWC group, 40% in the FPPP group, and 70% in the SHPPP group, and the differences were statistically significant (χ(2) = 7.250, P = 0.007). Meanwhile, the HR was reduced by about 37% in these 3 groups 3 days after modeling, while the reduction was maintained only in SHPPP (P > 0.05) and the HR was re-elevated in the FTWC and FPPP groups 2 weeks after modeling (P < 0.05). Additionally, the SNRT, cS-NRT, and SACT were significantly prolonged compared with pre-modeling in all 3 groups (P < 0.01).SHPPP was the best method with which to build an SSS model with stable and lasting low HR and high success rate of modeling, which might be helpful for further studies on the SSS mechanisms and drugs.

Acute His-Bundle Injury Current during Permanent His-Bundle Pacing Predicts Excellent Pacing Outcomes.

INTRODUCTION: His-bundle (HB) pacing (P) is a physiological alternative to right ventricular pacing (RVP), but is technically challenging and limited by higher pacing thresholds. Myocardial injury current (IC) recorded during right ventricular lead placement implies good tissue contact and is associated with low-pacing thresholds. IC at the HB has not been previously described. We hypothesized that HBIC during permanent HBP may be associated with lower pacing thresholds. METHODS: Permanent HBP was performed using Medtronic Select Secure(tm) (Medtronic Inc., Minneapolis, MN, USA) delivered via a fixed-curve (C315 His) sheath. HB electrogram (EGM) was recorded in a unipolar fashion from the lead tip. Presence or absence of HBIC was documented. HBP threshold, sensing, and impedances were recorded at implant, 2 weeks, 2 months, and 1 year. RESULTS: Sixty patients (age 72 ± 15 years; male 55%, sick sinus syndrome 40%, atrioventricular block 60%, fluoroscopy duration 9.2 ± 3.7 minutes) underwent successful permanent HBP. HBIC was recorded in 22 (37%) patients (group I). HBEGM without IC was recorded in the remaining 38 (63%) patients (group II). Pacing threshold at implant, 2 weeks, 2 months, and 1 year were significantly lower in group I (1.16 ± 0.4 V; 1.18 ± 0.5 V; 1.23 ± 0.6 V; 1.3 ± 0.6 V @ 0.5 ms) compared to group II (1.75 ± 0.7 V; 1.82 ± 0.8 V; 1.93 ± 0.8 V; 1.98 ± 0.9 V @ 0.5 ms, P < 0.05), respectively. CONCLUSIONS: IC can be recorded at the HB during permanent HBP in 37% of patients. HBIC is associated with significantly lower pacing thresholds compared to patients in whom HBIC was not recorded. HBIC may be a marker for superior short-term HBP thresholds.

[Atrial mechanical and electrical dysfunction in patient with Emery-Dreifuss muscular dystrophy reason of change in electrotherapeutical approach: frequent result of rare disease]. / Elektryczna i mechaniczna dysfunkcja przedsionków u pacjenta z dystrofia miesniowa Emery-Dreifussa przyczyna zmiany wyboru optymalnej formy elektroterapii: czeste powiklanie rzadkiej choroby.

We present a case of a 35 year-old male patient with Emery-Dreifuss muscular dystrophy diagnosed in the age of 12 who was assigned to dual chamber pacing system due to bradycardia primarily recognised as sinus node insufficiency with the atrio-ventricular nodal rhythm. During the procedure permanent electrical atrial stand-still without atrial capture were detected and the mode of stimulation was change to VVIR.

Sinus node dysfunction in atrial fibrillation patients: the evidence of regional atrial substrate remodelling.

AIMS: It remains unclear as to whether regional atrial substrates of certain areas of the atrium in patients with atrial fibrillation (AF) can be related to sinoatrial node dysfunction. We investigated the relationship between the biatrial substrate characteristics and sinus node function in these patients. METHODS AND RESULTS: The study enrolled 34 patients (aged 57 ± 11 years old; 20 males) who underwent catheter ablation for symptomatic paroxysmal AF. Sinus node dysfunction was defined as having corrected sinus node recovery time longer than 550 ms. Atrial substrate analyses of both atria and atrial conductive properties were investigated in patients with (Group 1) and without sinus node dysfunction (Group 2). The mean global bipolar voltage of both atria and the atrial refractory period were similar between the two groups. Regional analysis showed that the mean bipolar voltage for patients in Group 1 was lower than in Group 2 (1.0 ± 0.3 vs. 2.1 ± 0.7 mV, P < 0.001) only in the sinus node region, while the electrophysiological properties were similar for both groups in other anatomic regions of both atria. The right atrial total activation time was significantly longer (97 ± 9 vs. 89 ± 10 ms, P = 0.023) and the conduction velocity along the crista terminalis was significantly slower (1.0 ± 0.2 vs. 1.2 ± 0.3 m/s, P = 0.019) in Group 1 patients than in Group 2 patients. CONCLUSION: In patients with AF, regional atrial remodelling near the sinus node area was associated with sinus node dysfunction.

[Antiarrhythmic therapy of paroxysmal tachycardias and extrasystoles in patients with sinus node dysfunction].

Antiarrhythmic therapy of patients with disturbed automatism of the sinus node and impaired atrioventricular conductance may be complicated by hemodynamically significant bradycardias and contraindications for implantation of a cardiac electrical stimulator This study aimed at estimating effect of antiarrhythmic therapy with allapinin on the function of sinus and atrioventricular nodes. It included 20 patients (mean age 37.5+-2.3 years) with disturbed cardiac rhythm and sinus node dysfunction treated with allapinin (37.5 - 50 mg/d per os). This therapy had well apparent antiarrhythmic effect manifest as improvement of supraventricular and ventricular ectopic activities in the absence of negative influence on the function of sinus and atrioventricular nodes.

Comparative study between original and traditional method in establishing a chronic sinus node damage model in rabbit.

Sick Sinus Syndrome is a common and refractory arrhythmia, needing further study in which setting up a credible sinus node damage model is important. To explore the feasibility and superiority of an original formaldehyde pinpoint pressing permeation (FPPP) method for building a chronic sinus node damage (CSND) model, 5 rabbits were chosen from 35 as a sham-operation group, and the remaining were randomly divided into two groups: the formaldehyde wet compressing (FWC) group, in which models were established by applying a cotton bud dipped in 20% formaldehyde onto the sinus node (SN) area, and the FPPP group, in which models were established by injecting formaldehyde into the SN area through a self-made pinpointing and injecting electrode. We found that in both groups, the HR at 2 h, 24 h, 1 wk, and 2 wk after modeling decreased compared with premodeling; sinoatrial conduction time, sinus node recovery time, and corrected sinus node recovery time were prolonged compared with premodeling. The indexes mentioned shortened by 2 wk after modeling compared with 2 h in the FWC group, whereas they were stable after modeling in the FPPP group. The modeling achievement ratio in the FPPP group was higher and the death rate was lower. Under light microscope, paraffin sections of the SN tissue and cells showed severe injury in both groups. The results indicate that the CSND models in rabbits can be successfully established by the FPPP method, with higher achievement ratio, lower death rate, better stabilization effect, and less damaging comparing with the traditional method.