ATP1A3 mutations in infants: a new rapid‐onset dystonia–Parkinsonism phenotype characterized by motor delay and ataxia

We report new clinical features of delayed motor development, hypotonia, and ataxia in two young children with mutations (R756H and D923N) in the ATP1A3 gene. In adults, mutations in ATP1A3 cause rapid‐onset dystonia–Parkinsonism (RDP, DYT12) with abrupt onset of fixed dystonia. The parents and children were examined and videotaped, and samples were collected for mutation analysis. Case 1 presented with fluctuating spells of hypotonia, dysphagia, mutism, dystonia, and ataxia at 9 months. After three episodes of hypotonia, she developed ataxia, inability to speak or swallow, and eventual seizures. Case 2 presented with hypotonia at 14 months and pre‐existing motor delay. At age 4 years, he had episodic slurred speech, followed by ataxia, drooling, and dysarthria. He remains mute. Both children had ATP1A3 gene mutations. To our knowledge, these are the earliest presentations of RDP, both with fluctuating features. Both children were initially misdiagnosed. RDP should be considered in children with discoordinated gait, and speech and swallowing difficulties.     

The Origin of Epicardial Ventricular Tachycardia Revealed by Entrainment From a Permanent Epicardial Left Ventricular Pacing Lead

Entrainment From Left Ventricular Pacing Lead. Recognizing ventricular tachycardias (VTs) that require epicardial ablation is desirable, but challenging when prior surgery prevents percutaneous epicardial mapping. This patient had cardiomyopathy, prior cardiac surgery, and VT that failed endocardial ablation. Observing that the Bi‐V implantable cardioverter defibrillator (ICD), left ventricular (LV) lead was epicardial to the area of infarct scar, it was used to pace during VT. Entrainment with concealed fusion with long stimulus to QRS interval, consistent with an epicardial VT circuit, was observed. Surgical cryoablation targeting the area around the LV lead eliminated VT. Thus pacing maneuvers from permanent epicardial leads can occasionally help identify an epicardial VT origin. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1293‐1295, November 2010)     

Cell-to-Cell Electrical Interactions During Early and Late Repolarization

Cardiac electrical activity is significantly affected by variations in the conductance of gap junctions that connect myocytes to one another. To better understand how intrinsic (single cell) electrical activity is modulated by junctional conductance, we used a two-myocyte coupling system in which physically separate cells were electrically coupled via a variable resistance set by the investigator. This brief review summarizes our findings regarding: (1) the effect of the early phase of action potential repolarization (phase 1) and transient outward current ( I _to) on action potential conduction, and (2) the effect of coupling on the action potential plateau (late repolarization). We found that inhibition of I _to markedly increased the ability of action potentials to propagate from cell-to-cell when junctional conductance was low. Electrically coupling two myocytes together also suppressed their beat-to-beat variability in action potential duration and contraction. Similarly, early afterdepolarizations (EADS) were readily suppressed by connecting a normal myocyte to one generating EADs. This high sensitivity of the plateau to variations in junctional interactions arises from the large increase in membrane resistance that occurs during this phase of the action potential.     

Pulmonary Vein Isolation Alone in Patients with Persistent Atrial Fibrillation: An Ablation Strategy Facilitated by Antiarrhythmic Drug Induced Reverse Remodeling

PVI Alone in Patients with Persistent AF . Introduction: Pulmonary vein isolation (PVI) alone has been thought to be insufficient in patients with persistent atrial fibrillation (PersAF). We hypothesized that preablation treatment of PersAF with a potent antiarrhythmic drug (AAD) would facilitate reverse atrial remodeling and result in high procedural efficacy after PVI alone. Methods and Results: Seventy‐one consecutive patients (59.4 ± 9.8 years) with PersAF and prior AAD failure were treated with oral dofetilide (768 ± 291 mcg/day) for a median of 85 days pre‐PVI. P‐wave duration (Pdur) on ECG was used to assess reverse atrial remodeling. Thirty‐five patients with paroxysmal (P) AF not treated with an AAD served as controls. All patients underwent PVI alone; dofetilide was discontinued 1–3 mos postablation. In the PersAF patients, the Pdur decreased from 136.3 ± 21.7 ms (assessed postcardioversion on dofetilide) to 118.6 ± 20.4 ms (assessed immediately prior to PVI) (P < 0.001). In contrast, no change in Pdur (122.6 ± 11.5 ms vs. 121.3 ± 13.7 ms, P = NS) was observed in PAF patients. The 6 and 12 mos AAD‐free response to ablation was 76% and 70%, respectively, in PersAF patients, similar to the 80% and 75%, response in PAF patients (P = NS). A decline in Pdur in response to dofetilide was the only predictor of long‐term clinical response to PVI in patients with PersAF. Conclusions: Pre‐treatment with AAD resulted in a decrease in Pdur suggesting reverse atrial electrical remodeling in PersAF patients. This may explain the excellent clinical outcomes using PVI alone, and may suggest an alternative ablation strategy for PersAF. (J Cardiovasc Electrophysiol, Vol. 22, pp. 142‐148, February 2011)     

The interaction of human T-lymphocytes and Entamoeba histolytica: killing of virulent amoebae by lectin-dependent lymphocytes

Clinical and experimental studies indicate that following invasive disease due to Entamoeba histolytica, development of human cell-mediated immune mechanisms may provide protective immunity. Activated, human monocyte-derived macrophages in vitro can kill virulent axaenic amoebic trophozoites. This study describes the interaction of lectin-stimulated T-lymphocytes and E. histolytica trophozoites (virulent strain HM1-IMSS). Amoebae progressively killed unstimulated nonimmune T-lymphocytes over 18 h incubation with no effect on amoebic viability. T-lymphocytes, stimulated with phytohaemagglutinin (PHA), were progressively cytotoxic for virulent HMI amoebae over 18 h incubation, but were also reduced in viability themselves. Lymphocyte cytotoxicity for amoebae was absent if PHA was removed before or added only during the assay. PHA-stimulated T-lymphocytes killed amoebae at cell ratios of lymphocytes to amoebae as low as 50:1 and cytotoxicity was antibody-independent. PHA-stimulated T-lymphocytes, depleted of T8-bearing cells by complement-mediated lysis, were unable to kill amoebae. Adherence of PHA-stimulated T-lymphocytes to amoebae was greater than with unstimulated T-lymphocytes. Inhibition of the amoebic adherence lectin with N-acetyl-D-galactosamine decreased lymphocyte-amoebic adherence and resulted in increased lymphocyte amoebicidal activity and lymphocyte survival. Suspension of amoebae with or without adherent PHA-stimulated T-lymphocytes in a 10% dextran solution indicated that cytotoxicity was contact dependent. In summary, PHA-stimulated T-lymphocytes of the T8-phenotype can kill virulent axaenic E. histolytica trophozoites through a contact-dependent, antibody-independent mechanism.     

Outcomes in Patients Requiring Cardioversion Following Catheter Ablation of Atrial Fibrillation

Outcomes of Cardioversion Post AF Ablation.   Introduction: Early recurrence of atrial tachyarrhythmias is commonly noted after catheter ablation of atrial fibrillation (AF). The long-term outcomes of patients who require cardioversion for persistent AF after AF ablation is not known. This study reports the outcomes of patients who underwent cardioversion for persistent AF or atrial flutter following an AF ablation procedure.
Methods: The patient population comprised 55 patients (mean age 58 ± 10 years, 35% paroxysmal) who underwent catheter ablation of AF and subsequently required electrical cardioversion for persistent AF (45 patients) or atrial flutter (10 patients). Cardioversion was defined as early (within 90 days of the ablation procedure) or late (between 90 and 180 days following ablation).
Results: The mean follow-up duration was 15 ± 8 months. Forty-six of the 55 patients (84%) patients experienced recurrence during follow-up. The average time to recurrence after cardioversion was 37 days. Of the 55 patients, 8 (15%) patients had a complete success, 11 (20%) patients had a partial success and 36 patients (65%) had a failed outcome. Seven of the 43 patients (16%) who underwent early cardioversion had a complete success as opposed to one of 12 patients (8%) who underwent late cardioversion (P = 0.49).
Conclusions: This study shows that >80% of patients who undergo cardioversion for persistent AF or atrial flutter after AF ablation have recurrence. The timing of cardioversion did not affect the outcome. These findings allow clinicians to provide realistic expectations to patients regarding the long-term outcome and/or requirement for a second ablation procedure. (J Cardiovasc Electrophysiol, Vol. 21, pp. 27–32, January 2010)     

Radiofrequency Catheter Ablation of AtypicalAtrioventricular Nodal Reentrant Tachycardia

Ablation of Atypical Atrioventricular Nodal Reentrant Tachycardia, Introduction: Published reports of radiofrequency ablation of atypical atrioventricular nodal reentranttacbycardia (AVNRT) have been limited. We present our experience in 10 consecutive patientswith atypical AVNRT wbo underwent radiofrequency ablation of the "slow" AV nodal pathway.
Methods and Resttlts: there were 9 females and 1 male; their mean age was 44 ± 19 years (± SD), the mean AVNRT cycle length and ventriculoatrial (VA) interval at the His positionduring AVNRT were 340 ± 50 msec and 200 ± 70 msec, respectively. the slow pathway wassuccessfully ablated in all patients with a mean of 10 ± 7 radiofrequency energy applications inthe posteroseptal right atritim near the coronary sinus os. The mean procedure duration was 100 ± 35 minutes. There were no complications. In 4 patients, target sites were identified during sinus rhythm by mapping for possible slow pathway potentials, In the other 6 patients, target sites were identified by mapping retrograde atrial activation during AVNRT or ventricularpacing, The VA times at successful target sites were a mean of 45 ± 30 msec less tban the VAtime at the His cathetcr during AVNRT, There were no differences in success rate, number ofradiofrequency energy applications, or procedure duration between patients in whom mappingwas guided by possible slow pathway potentials or by retrograde atrial activation, During 6 ± 3 months of followup, 1 patient bad a recurrence of atypical AVNRT and underwent a secondablation procedure, which was successful.
Conclusion: Radiofrequency ablation of atypical AVNRT can be safely and effectivelyaccomplisbed when target sites are identified based either on possible slow pathway potentialsduring sinus rbytbm or retrograde atrial activation times during tachycardia.     

Autonomic Modulation for the Treatment of Ventricular Arrhythmias: Therapeutic Use of Percutaneous Stellate Ganglion Blocks

Ventricular tachycardia (VT), ventricular fibrillation (VF), and electrical storm are commonly encountered emergency conditions in cardiac and surgical intensive care units. In most cases, recurrent ventricular arrhythmias or electrical storm are associated with a heightened sympathetic tone. These arrhythmias can be difficult to treat and may be refractory to beta‐blockade, antiarrhythmic therapy, sedation, and mechanical hemodynamic support. While monomorphic ventricular tachycardia and PVC‐triggered polymorphic ventricular tachycardia may sometimes be amenable to successful ablation, some patients may be too critically ill to make such an approach feasible. We present 2 cases of minimally invasive stellate ganglion blocks for the treatment of electrical storm in patients with advanced heart failure on mechanical life support. These cases are part of a collaborative initiative at our institution to use percutaneous stellate ganglion block as an adjunctive intervention to achieve control of life‐threatening ventricular arrhythmias.     

Rising Charges and Costs for Pediatric Catheter Ablation

Pediatric Ablation Charges and Costs Are Rising. Introduction: Catheter ablation has been shown to be effective for pediatric tachyarrhythmias, but the associated charges and costs have not been described in the recent era. Understanding such contemporary trends may identify ways to keep an effective therapy affordable while optimizing clinical outcomes. Methods: We used the 1997–2009 Kids’ Inpatient Databases to examine trends in charges and costs for pediatric catheter ablation and identify determinants of temporal changes. Results: There were 7,130 discharges for catheter ablation in the sample. Mean age at ablation was 12.1 ± 0.2 years. Patients with congenital heart disease (CHD) made up 10% of the sample. Complications occurred in 8% of discharges. Mean total charges rose 219% above inflation (from $23,798 ± 1,072 in 1997 to $75,831 ± 2,065 in 2009). From 2003 to 2009, costs rose 25% (from $20,459 ± 780 in 2003 to $25,628 ± 992 in 2009). Charges for ablation increased markedly relative to surgical procedures, but with a similar slope to other catheter‐based interventions. Multivariable analysis revealed that year (P < 0.0001), payer (P = 0.0002), CHD (P < 0.0001), valvular heart disease (P = 0.0004), cardiomyopathy (P = 0.0009), hospital region (P < 0.0001), length of stay (P < 0.0001), and complications (P < 0.0001) predicted increased charges. The same factors also predicted increased costs. Charges and costs varied considerably by region, particularly for high‐volume centers (P < 0.0001). Conclusions: Charges and costs for pediatric catheter ablation increased relative to other procedures and significantly outstripped inflation. Further study of complications, length of stay, and regional differences may help control rising costs while maintaining quality of care. (J Cardiovasc Electrophysiol, Vol. 24, pp. 162‐169, February 2013)