Stem cell-derived nodal-like cardiomyocytes as a novel pharmacologic tool: insights from sinoatrial node development and function.

Since the first reports on the isolation and differentiation of stem cells, and in particular since the early success in driving these cells down a cardiac lineage, there has been interest in the potential of such preparations in cardiac regenerative therapy. Much of the focus of such research has been on improving mechanical function after myocardial infarction; however, electrophysiologic studies of these preparations have revealed a heterogeneous mix of action potential characteristics, including some described as "pacemaker" or "nodal-like," which in turn led to interest in the therapeutic potential of these preparations in the treatment of rhythm disorders; several proof-of-concept studies have used these cells to create a biologic alternative to electronic pacemakers. Further, there are additional potential applications of a preparation of pacemaker cells derived from stem cells, for example, in high-throughput screens of new chronotropic agents. All such applications require reasonably efficient methods for selecting or enriching the "nodal-like" cells, however, which in turn depends on first defining what constitutes a nodal-like cell since not all pacemaking cells are necessarily of nodal lineage. This review discusses the current state of the field in terms of characterizing sinoatrial-like cardiomyocytes derived from embryonic and induced pluripotent stem cells, markers that might be appropriate based on the current knowledge of the gene program leading to sinoatrial node development, what functional characteristics might be expected and desired based on studies of the sinoatrial node, and recent efforts at enrichment and selection of nodal-like cells.

Early plasma exchange for treating ricin toxicity in children after castor bean ingestion.

Plasma exchange (PE) for the treatment of ricin toxicity has not been previously reported. Here we describe the use of PE to treat children who experienced ricin toxicity after ingesting castor beans. Seven children (median age: 8.1 years) who consumed castor beans (median: 5 beans) were treated with PE. All had bradycardia and sinus arrhythmia, and most had experienced episodes of vomiting and/or diarrhea. PE settings were blood flow, 50-80 mL/min; PE rate, 600-800 mL/h; volume of exchange, 1440-1950 mL. Median time from ingestion to PE was 73 h. All clinical symptoms disappeared and vital signs rapidly returned to normal after PE; no severe organ dysfunction occurred. All children were discharged and recovered uneventfully. Concentrations of all serum biochemical parameters significantly decreased immediately after PE. Some, but not all, of these parameters were also significantly decreased at 48 and 72 h after PE compared with before PE. Our findings suggest that PE can be an effective early intervention in the treatment of ricin toxicity due to castor bean ingestion.

Permanent sinus dysfunction after pulmonary vein isolation ablation: observations and potential mechanisms.

Although transient sinus arrest has been reported during pulmonary vein isolation (PVI), the long-term impairment of sinus node after PVI has not been described. In this report, we present a case of sinus node dysfunction necessitating a permanent pacemaker, caused during PVI. Clinical data, intracardiac electrograms, and cardiac imaging were incompatible with previous sinus node dysfunction, sinus node artery occlusion, or an ectopic atrial rhythm from the pulmonary veins. Impairment of the neural pathways connecting the ganglionated plexi of the right superior pulmonary veins with the sinus node is a possible underlying mechanism.

Permanent epicardial pacing lead implantation for scheduled multistage operations in Fontan candidate.

The use of an epicardial pacing lead may be essential in pediatric patients with rhythm disturbances. In patients with single-ventricle physiology who need scheduled multistage operations, the lead could be an obstacle because of the induction of tight adhesions and the need for dissection in the next operation. We propose a novel reproducible technique for the placement of an epicardial pacing lead followed by easy dissection of the entire length of the lead in the next operation in neonates or young infants who need multistage operations.

Impact of right-ventricular apical pacing on the optimal left-ventricular lead positions measured by phase analysis of SPECT myocardial perfusion imaging.

PURPOSE: The use of SPECT phase analysis to optimize left-ventricular (LV) lead positions for cardiac resynchronization therapy (CRT) was performed at baseline, but CRT works as simultaneous right ventricular (RV) and LV pacing. The aim of this study was to assess the impact of RV apical (RVA) pacing on optimal LV lead positions measured by SPECT phase analysis. METHODS: This study prospectively enrolled 46 patients. Two SPECT myocardial perfusion scans were acquired under sinus rhythm with complete left bundle branch block and RVA pacing, respectively, following a single injection of (99m)Tc-sestamibi. LV dyssynchrony parameters and optimal LV lead positions were measured by the phase analysis technique and then compared between the two scans. RESULTS: The LV dyssynchrony parameters were significantly larger with RVA pacing than with sinus rhythm (p ~0.01). In 39 of the 46 patients, the optimal LV lead positions were the same between RVA pacing and sinus rhythm (kappa = 0.861). In 6 of the remaining 7 patients, the optimal LV lead positions were along the same radial direction, but RVA pacing shifted the optimal LV lead positions toward the base. CONCLUSION: The optimal LV lead positions measured by SPECT phase analysis were consistent, no matter whether the SPECT images were acquired under sinus rhythm or RVA pacing. In some patients, RVA pacing shifted the optimal LV lead positions toward the base. This study supports the use of baseline SPECT myocardial perfusion imaging to optimize LV lead positions to increase CRT efficacy.

Taquicardia sinusal inapropriada: o papel da ecocardiografia fetal transvaginal: relato de caso / Inappropriate sinus tachycardia: the role of trasvaginal fetal echocardiography: case report / Taquicardia Sinusal Inapropiada: El papel de la Ecocardiografía Fetal Transvaginal ­ Relato del Caso

Introdução: A taquicardia sinusal inapropriada é rara na população em geral, tem maior prevalência em mulheres jovens e sua etiologia é desconhecida. Caracteriza-se por uma frequência cardíaca, persistentemente, elevada com uma resposta exagerada à atividade física. Objetivo: Relatar um caso raro de taquicardia sinusal inapropriada em fase precoce da gestação, enfatizando a importância da ecocardiografia fetal transvaginal. Relato de caso: Gestante encaminhada para realização de ecocardiografia transvaginal por taquicardia fetal persistente. Ao exame de nove semanas, o feto apresentava uma FC de 240 batimentos por minuto (bpm), com condução atrioventricular de um para um e sem sinais de hidropisia. Utilizados a digoxina e, posteriormente, o flecainide, ambos sem sucesso terapêutico. Iniciado sotatol com redução gradual e posterior normalização da FC fetal. O parto ocorreu a termo, concepto nasceu bem e evoluiu com taquicardia persistente. O eletrocardiograma realizado demonstrou onda P com morfologia de ritmo sinusal. As possíveis causas de taquicardia sinusal foram afastadas, confirmando assim o diagnóstico acima. Comentários: O autor reforça a importância da ecocardiografia fetal transvaginal para o diagnóstico e tratamento precoce de arritmias fetais, evitando complicações.

Introduction: The inappropriate sinus tachycardia is rare in the general population, more frequently affects young women, and its etiology is unknow. It is characterized by a persistently elevated cardiac frequency with na exaggerated response to physical activity. Objective: Report a rare case of inappropriate sinus tachycardia in the early phase of pregnancy and emphasize the importance of transvaginal fetal echocardiography. Case report: Pregnant referred due to persistente fetal tachycardia after obstretic ultrasonography. The transvaginal echocardiogram performed at 9 weeks' gestation showed a fetal heart rate of 240 beats min (bpm) with normal conduction from atria to ventricle (1:1)and no signal hydropsy. Digoxin therapy and Flecainide were used with no sucess. Sotatol use was chose when the fetal heart rate (HR) reduced to tolerable levels and then the number of heartbeats normalized at thirty six weeks gestation. The baby was born well at term and developed persistente tachycardia. The electrocardiogram performed showed P-ware morphology of sinus rhythm. Possible causes of sinus tachycardia were excluded, thus confirming the diagnosis above. Comments: The author describes the imortance of transvaginal fetal echocardiography for the diagnosis and early treatment of fetal arrhythmias avoiding complications.

Introducción: La taquicardia sinusal inapropiada es rara en la población en general, predomina mayormente en mujeres jóvenes y su etiología es desconocida. Se caracteriza por una frecuencia cardíaca, persistentemente, elevada con una respuesta exagerada a la actividad física. Objetivo: Relatar un caso raro de taquicardia sinusal inapropiada en fase precoz de la gestación, enfatizando la importancia de la ecocardiografía fetal transvaginal. Relato del caso: Gestante derivada para la realización del ecocardiograma transvaginal por taquicardia fetal persistente. En el examen de nueve semanas, el feto presentaba una FC de 240 latidos por minuto (lpm), con conducción aurículoventricular de uno para uno y sin señales de hidropesía. Se utilizó la digoxina y, posteriormente, el flecainide, ambos sin éxito terapéutico. Iniciado sotatol con reducción gradual y posterior normalización de FC fetal. El parto ocurrió a término, nació bien y evolucionó con taquicardia persistente. El electrocardiograma realizado demostró onda P con morfología de ritmo sinusal. Las posibles causas de taquicardia sinusal se eliminaron, confirmando así el diagnóstico señalado. Comentarios: El autor refuerza la importancia de la ecocardiografía fetal transvaginal para el diagnóstico y tratamiento precoz de arritmias fetales, evitando complicaciones

The ventriculophasic response: relationship to sinus arrhythmia and the duration of interposed QRS complexes.

BACKGROUND: The ventriculophasic response (VR) refers to shortening of sinus cycle length during heart block when a QRS complex is interposed between 2 P waves. Our purpose was to analyze its relationship to respiratory sinus arrhythmia (SA) and to compare VR in relation to paced versus intrinsic QRS complexes. METHODS: Patients with advanced heart block had their pacer devices temporarily programmed to ventricular inhibited mode at 30 ppm. In 35 subjects, we analyzed VR and SA before, during and after 3 cycles of deep breathing. In 16 other patients we compared VR in the presence of paced versus narrower intrinsic QRS complexes. RESULTS: The magnitude of P-P interval shortening surrounding QRS complexes during inspiration correlated with SA (r = 0.36, P = 0.03). The prevalence of VR increased from 37% at baseline to 77% of subjects during deep breathing (P = 0.02). The mean P-P interval shortening was greater surrounding intrinsic QRS complexes than paced QRS complexes (3.6 ± 3.6% vs. 1.4 ± 1.1%, P = 0.02). The prevalence of VR increased from 25% during paced rhythm to 56% when intrinsic complexes were present. CONCLUSION: VR, like SA, increases with deep breathing and likely reflects intact parasympathetic nervous system function. Its increase in the presence of narrower beats suggests it may reflect ventricular synchrony.

Does respiratory sinus arrhythmia (RSA) predict anxiety reduction during cognitive behavioral therapy (CBT) for social anxiety disorder (SAD)?

Modifying dysfunctional emotion regulation is an important goal in psychological treatments for social anxiety disorder (SAD). Antecedent-focused strategies learned in cognitive behavioral therapy (CBT), such as cognitive reappraisal, have proven more effective in reducing social anxiety than response-focused strategies, such as expressive suppression. Still, not all patients with SAD respond well to CBT. Medications and physiological factors may also influence the clinical response. The purpose of the present study was to examine the role that these factors play in determining treatment response following CBT for SAD. Using multilevel modeling, we examined associations across four separate laboratory visits between change in self-reported anxiety and indices of reappraisal, suppression, medication status, and resting respiratory sinus arrhythmia (RSA), a proxy measure of self-regulatory capacity, in 23 socially anxious adults during a 12-week program of CBT. Most participants were ultimately classified as responders to CBT (n=15), but in some, anxiety levels remained unchanged (n=8). Medication use explained substantial variance related to individual differences in anxiety among participants. When modeled separately, reappraisal, suppression, and RSA each accounted for significant variance related to anxiety. However, the best-fitting model included reappraisal and RSA. Moreover, RSA reactivity (change in RSA levels over time) was more important for predicting anxiety reduction than were baseline levels of RSA. These findings suggest that reappraisal and parasympathetic responsiveness may be important in reducing anxiety in adults with SAD who respond well to CBT.

Performance of atrial tachyarrhythmia-sensing algorithms in dual-chamber pacing using a fixed long AV delay in patients with sinus node dysfunction.

AIMS: The aim of the study was to evaluate the performance of pacemakers (PM) atrial tachyarrhythmia (AT)-sensing algorithms in sinus node dysfunction (SND) patients with DDDR pacing programmed with a fixed long atrioventricular (AV) delay. METHODS: In a prospective study, a total of 60 patients with SND were implanted with a dual-chamber PM with two different algorithms for detection of ATs. The study was done with a 3 month data collection period retrieved from the memory of PM and with a 7 day external Holter recording period. RESULTS: In 13 of 16 (81 %) patients whose Holter recording revealed the presence of ATs, episodes of AT sensing were retrieved from the PM memory with electrograms verifications, confirming that the devices had detected the ATs. Very short ATs seen in Holter recordings were missed by the PM with three patients. However, with all these patients after 3 months of follow up period, there were recognized periods of ATs by the PM. With ten (17 %) patients, there were intermittent periods of undersensing by the PM although continuous atrial fibrillation (AF) was seen in the Holter recording. Retrograde conduction caused false AT detection due to repetitive non-reentrant ventriculoatrial synchronous rhythm (RNRVAS) in six (25 %) of the 24 patients with retrograde conduction. CONCLUSIONS: Even with long AV delay, ATs can be accurately identified. However, transient undersensing of continuous AF and non-detection of very short AT episodes can still occur. Programming a long AV delay predisposes to RNRVAS which can cause false AT detection and symptoms in SND patients who have retrograde conduction.

A decrease in serum aldosterone level is associated with maintenance of sinus rhythm after successful cardioversion of atrial fibrillation.

BACKGROUND: The activation of the renin-angiotensin-aldosterone system has been implicated in the progression of atrial structural remodeling during atrial fibrillation (AF). However, consequences of the changes of aldosterone in AF have not been evaluated. OBJECTIVES: This study's aim was to evaluate changes of serum aldosterone concentration after successful cardioversion of persistent AF and to determine the prognostic value of these changes. METHODS: The prospective, single center study included 45 consecutive patients with nonvalvular persistent AF and preserved left ventricular systolic function, referred for cardioversion. None of the patients were taking aldosterone antagonists. Blood samples for aldosterone measurement were collected twice: 24 hours before and 24 hours after cardioversion. RESULTS: Forty-three patients were successfully converted to sinus rhythm. On the 30th day following cardioversion, 24 patients maintained sinus rhythm (group A), 19 patients relapsed to AF (group B). Serum aldosterone concentration before cardioversion did not differ significantly between both groups (175.6 +/- 112.82 pg/mL vs 125.8 +/- 51.2 pg/mL; P = 0.25). However, in group A serum aldosterone level decreased significantly within 24 hours after cardioversion, from 175.6 +/- 112.8 pg/mL to 101.4 +/- 44.2 pg/mL (P = 0.0034). In group B, the aldosterone level before and after cardioversion did not differ significantly (125.8 +/- 51.2 pg/mL vs 118.2 +/- 59.6 pg/mL; P = 0.68). Logistic regression analysis revealed that a decrease in plasma aldosterone concentration after direct current cardioversion more than 13.2 pg/mL predicted sinus rhythm maintenance in a 30-day follow-up, with 87% sensitivity and 64% specificity. CONCLUSIONS: There is a positive correlation between the fall in aldosterone concentration 24 hours after cardioversion and maintenance of sinus rhythm during 30 days of observation.

[Determination of the cause of repetitive syncopal States with the help of registration of electrocardiogram at the background of provocative test].

A clinical case of repetitive syncopal states in an adolescent with episodes of significant asystoles lasting up to 32 s is presented. These episodes were detected only with the help of electrocardiogram registered during provocative test. Beyond provoking factors the child had signs of insignificant sinus node dysfunction which did not allow to designate the state of the patient as severe and prescribe adequate treatment. We consider this case as demonstration of necessity of provocative tests in conjunction with ECG monitoring in children with episodes of fainting (syncopal states).

Comparison of objective methods to classify the pattern of respiratory sinus arrhythmia during mechanical ventilation and paced spontaneous breathing.

Respiratory sinus arrhythmia (RSA) is a fluctuation of heart period that occurs during a respiratory cycle. It has been suggested that inspiratory heart period acceleration and expiratory deceleration during spontaneous ventilation (henceforth named positive RSA) improve the efficiency of gas exchange compared to the absence or the inversion of such a pattern (negative RSA). During mechanical ventilation (MV), for which maximizing the efficiency of gas exchange is of critical importance, the pattern of RSA is still the object of debate. In order to gain a better insight into this matter, we compared five different methods of RSA classification using the data of five mechanically ventilated piglets. The comparison was repeated using the data of 15 volunteers undergoing a protocol of paced spontaneous breathing, which is expected to result in a positive RSA pattern. The results showed that the agreement between the employed methods is limited, suggesting that the lack of a consensus about the RSA pattern during MV is, at least in part, of methodological origin. However, independently of the method used, the pattern of RSA within the respiratory cycle was not consistent among the subjects and conditions of MV considered. Also, the outcomes showed that even during paced spontaneous breathing a negative RSA pattern might be present, when a low respiratory frequency is imposed.

First case study of periodic hypokalemic thyreotoxic paresis with partial respiratory insufficiency and concomitant sinus bradycardia.

This report describes the case of a 29-year-old Chechen refugee with periodic hypokalemic thyreotoxic tetraparesis (PHTP). Besides a partial respiratory insufficiency, the patient was also presented with sinus bradycardia. Medical literature describes several cases of thyreotoxicosis in combination with bradycardia. For the first time, we were able to observe a case of PHTP in combination with sinus bradycardia. PHTP is rarely seen in central Europe. In this case establishing a final diagnosis was difficult because of the concomitant presence of bradycardia and Graves' disease.

Reduction of right ventricular pacing in patients with sinus node dysfunction through programming a long atrioventricular delay along with the DDIR mode.

BACKGROUND: Right ventricular (RV) pacing increases the incidence of atrial fibrillation (AF) and hospitalization rate for heart failure. Many patients with sinus node dysfunction (SND) are implanted with a DDDR pacemaker to ensure the treatment of slowly conducted atrial fibrillation and atrioventricular (AV) block. Many pacemakers are never reprogrammed after implantation. This study aims to evaluate the effectiveness of programming DDIR with a long AV delay in patients with SND and preserved AV conduction as a possible strategy to reduce RV pacing in comparison with a nominal DDDR setting including an AV search hysteresis. METHODS: In 61 patients (70 +/- 10 years, 34 male, PR < 200 ms, AV-Wenckebach rate at > or =130 bpm) with symptomatic SND a DDDR pacemaker was implanted. The cumulative prevalence of right ventricular pacing was assessed according to the pacemaker counter in the nominal DDDR-Mode (AV delay 150/120 ms after atrial pacing/sensing, AV search hysteresis active) during the first postoperative days and in DDIR with an individually programmed long fixed AV delay after 100 days (median). RESULTS: With the nominal DDDR mode the median incidence of right ventricular pacing amounted to 25.2%, whereas with DDIR and long AV delay the median prevalence of RV pacing was significantly reduced to 1.1% (P < 0.001). In 30 patients (49%) right ventricular pacing was almost completely (<1%) eliminated, n = 22 (36%) had >1% <20% and n = 4 (7%) had >40% right ventricular pacing. The median PR interval was 161 ms. The median AV interval with DDIR was 280 ms. CONCLUSIONS: The incidence of right ventricular pacing in patients with SND and preserved AV conduction, who are treated with a dual chamber pacemaker, can significantly be reduced by programming DDIR with a long, individually adapted AV delay when compared with a nominal DDDR setting, but nonetheless in some patients this strategy produces a high proportion of disadvantageous RV pacing. The DDIR mode with long AV delay provides an effective strategy to reduce unnecessary right ventricular pacing but the effect has to be verified in every single patient.

Change in blood pressure just after initiation of cardiac resynchronization therapy predicts long-term clinical outcome in patients with advanced heart failure.

BACKGROUND: The aim of this study was to retrospectively investigate the long-term effect of cardiac resynchronization therapy (CRT) and to clarify the useful predictors of clinical outcome. Methods and Results The study group comprised 43 patients with advanced heart failure who underwent CRT (10 females; 66+/-10 years): 23 were in sinus rhythm (SR group) and 20 had chronic atrial fibrillation (AF group). The clinical parameters and echocardiographic data were evaluated before and after CRT. There were no significant differences in the clinical parameters, echocardiographic data at baseline or frequency of responders between the 2 groups. In both groups, the clinical characteristics at baseline did not differ between the responders and non-responders. A prompt rise in systolic blood pressure (SBP) just after CRT was observed more often in responders than in non-responders, and SBP rise > or =5 mmHg was the only significant independent predictor of a CRT responder (P=0.0033). Furthermore, there was a significant difference in the event-free survival between patients with and without SBP rise > or =5 mmHg, demonstrated by Kaplan-Meier method, at 2 years of follow-up (P=0.045). Conclusion A prompt BP rise just after CRT may predict short- and long-term clinical improvement in CRT recipients.

Sinus node dysfunction after repair of partial anomalous pulmonary venous connection.

OBJECTIVES: Sinus node dysfunction is known as a major complication after repair of partial anomalous pulmonary venous connection. We retrospectively analyzed the results of the atrial wall flap technique compared with the results of patch repair or direct suturing in the intra-atrial tunnel technique. METHODS: Between 1991 and 2007, 23 patients (mean age, 6 years; range, 5 months-17 years) with partial anomalous pulmonary venous connection underwent surgical intervention. The right anomalous pulmonary veins drained to either the right atrium or superior vena cava in 8 and 15 patients, respectively. Patients were divided into 2 groups: group F (n = 14), who had repair with an atrial flap, and group N (n = 9), who had repair without an atrial flap. All patients had normal sinus rhythm preoperatively. RESULTS: No patients had signs of superior vena cava or pulmonary venous obstruction within a mean follow-up of 4.8 years. One patient in group F required pacemaker implantation. In the early postoperative period, sinus node dysfunction developed in 93% of group F and 44% of group N patients (P < .01) and was prolonged until discharge in 57% of group F and 0% of group N patients (P < .01). At the most recent clinical visit, sinus node dysfunction was identified in 50% of group F patients, whereas all patients in group N had normal sinus rhythm (P < .02). CONCLUSIONS: The atrial flap technique, which requires incision or suture crossing the crista terminalis, could cause sinus node dysfunction, whereas the intra-atrial rerouting method with a patch or direct suture maintains normal sinus node function postoperatively.