Atrioventricular Node Dysfunction and Ion Channel Transcriptome in Pulmonary Hypertension.

BACKGROUND: Heart block is associated with pulmonary hypertension, and the aim of the study was to test the hypothesis that the heart block is the result of a change in the ion channel transcriptome of the atrioventricular (AV) node. METHODS AND RESULTS: The most commonly used animal model of pulmonary hypertension, the monocrotaline-injected rat, was used. The functional consequences of monocrotaline injection were determined by echocardiography, ECG recording, and electrophysiological experiments on the Langendorff-perfused heart and isolated AV node. The ion channel transcriptome was measured by quantitative PCR, and biophysically detailed computer modeling was used to explore the changes observed. After monocrotaline injection, echocardiography revealed the pattern of pulmonary artery blood flow characteristic of pulmonary hypertension and right-sided hypertrophy and failure; the Langendorff-perfused heart and isolated AV node revealed dysfunction of the AV node (eg, 50% incidence of heart block in isolated AV node); and quantitative PCR revealed a widespread downregulation of ion channel and related genes in the AV node (eg, >50% downregulation of Cav1.2/3 and HCN1/2/4 channels). Computer modeling predicted that the changes in the transcriptome if translated into protein and function would result in heart block. CONCLUSIONS: Pulmonary hypertension results in a derangement of the ion channel transcriptome in the AV node, and this is the likely cause of AV node dysfunction in this disease.

Cryptostegia grandiflora Toxicity Manifesting as Hyperkalemia, Complete Heart Block and Thrombocytopenia.

Cardiac glycosides are widely available in botanic products and other naturally occurring substances worldwide. Accidental consumption of it leads to digitalis toxicity with varied systemic manifestations. We describe a case of consumption of extract of leaves of the Indian rubber vine plant (Crytostegia grandiflora) which led to gastrointestinal, cardiac, electrolyte, and hematological disturbances.

ECG in neonate mice with spinal muscular atrophy allows assessment of drug efficacy.

Molecular technologies have produced diverse arrays of animal models for studying genetic diseases and potential therapeutics. Many have neonatal phenotypes. Spinal muscular atrophy (SMA) is a neuromuscular disorder primarily affecting children, and is of great interest in translational medicine. The most widely used SMA mouse models require all phenotyping to be performed in neonates since they do not survive much past weaning. Pre-clinical studies in neonate mice can be hindered by toxicity and a lack of quality phenotyping assays, since many assays are invalid in pups or require subjective scoring with poor inter-rater variability. We find, however, that passive electrocardiography (ECG) recording in conscious 11-day old SMA mice provides sensitive outcome measures, detecting large differences in heart rate, cardiac conduction, and autonomic control resulting from disease. We find significant drug benefits upon treatment with G418, an aminoglycoside targeting the underlying protein deficiency, even in the absence of overt effects on growth and survival. These findings provide several quantitative physiological biomarkers for SMA preclinical studies, and will be of utility to diverse disease models featuring neonatal cardiac arrhythmias.

Model of bipolar electrogram fractionation and conduction block associated with activation wavefront direction at infarct border zone lateral isthmus boundaries.

BACKGROUND: Improved understanding of the mechanisms underlying infarct border zone electrogram fractionation may be helpful to identify arrhythmogenic regions in the postinfarction heart. We describe the generation of electrogram fractionation from changes in activation wavefront curvature in experimental canine infarction. METHODS AND RESULTS: A model was developed to estimate the extracellular signal shape that would be generated by wavefront propagation parallel to versus perpendicular to the lateral boundary (LB) of the reentrant ventricular tachycardia (VT) isthmus or diastolic pathway. LBs are defined as locations where functional block forms during VT, and elsewhere they have been shown to coincide with sharp thin-to-thick transitions in infarct border zone thickness. To test the model, bipolar electrograms were acquired from infarct border zone sites in 10 canine heart experiments 3 to 5 days after experimental infarction. Activation maps were constructed during sinus rhythm and during VT. The characteristics of model-generated versus actual electrograms were compared. Quantitatively expressed VT fractionation (7.6±1.2 deflections; 16.3±8.9-ms intervals) was similar to model-generated values with wavefront propagation perpendicular to the LB (9.4±2.4 deflections; 14.4±5.2-ms intervals). Fractionation during sinus rhythm (5.9±1.8 deflections; 9.2±4.4-ms intervals) was similar to model-generated fractionation with wavefront propagation parallel to the LB (6.7±3.1 deflections; 7.1±3.8-ms intervals). VT and sinus rhythm fractionation sites were adjacent to LBs ≈80% of the time. CONCLUSIONS: The results suggest that in a subacute canine infarct model, the LBs are a source of activation wavefront discontinuity and electrogram fractionation, with the degree of fractionation being dependent on activation rate and wavefront orientation with respect to the LB.

[Twiddler's syndrome: a new face of the old problem]. / Zespól Twiddlera: nowe oblicze starego powiklania.

Twiddler's syndrome (TS) is the well known late electrotherapy complication. The typical TS develops as a result of the pulse generator rotation with retraction of the leads and consequent interruption of pacing. We reported 2 cases illustrating late TS without spontaneous old, ingrown lead extraction and very different leads damage.

Complete heart block during potassium therapy in thyrotoxic periodic paralysis.

BACKGROUND: Although cardiac dysrhythmia is common in patients with thyrotoxic periodic paralysis (TPP), high-degree atrioventricular (AV) block complicated by cardiogenic shock, even under KCl supplementation, is rarely described. OBJECTIVES: To present a case of TPP in a patient who developed complete AV block with severe consequences due to paradoxical hypokalemia during KCl therapy. In addition, the management of acute hypokalemia in TPP is reviewed. CASE REPORT: A 41-year-old Chinese man with TPP presented to the Emergency Department with a 2-day history of paralysis in the extremities. He developed complete AV block with cardiogenic shock and respiratory failure, necessitating ventilatory support when plasma K(+) level decreased from 1.7 mmol/L to 1.3 mmol/L during KCl replacement of 30 mmol in 2 h. The administration of another 60 mmol KCl over 3 h achieved a plasma K(+) level of 2.1 mmol/L, resulting in the resolution of AV block and successful weaning. However, rebound hyperkalemia (K(+) 5.6 mmol/L) upon recovery was evident and uneventfully corrected. CONCLUSION: A paradoxical fall in serum K(+) concentration with potentially life-threatening complication is still underappreciated in patients with TPP on KCl supplementation. Early recognition and prompt therapy prevent untoward consequences.

A novel criterion for conduction block after catheter ablation of right atrial tachycardia after mitral valve surgery.

BACKGROUND: One operative approach to the mitral valve, the superior transseptal incision, is proarrhythmic because of extensive atriotomies. The objective of this study is to describe complex atrial tachycardias (ATs) that occur after this approach and propose methods to verify lines of block as an end point for catheter ablation. METHODS AND RESULTS: Of the 69 patients who had electrophysiological studies for AT after mitral valve surgery, 20 patients had prior superior transseptal incisions. Of these, 14 had complex ATs involving the lateral right atrium (RA). There were 9 dual-loop, 4 single-loop, and 1 focal tachycardias. Lateral wall ablation was performed either by creating a linear lesion from the lateral atriotomy to the inferior vena cava, superior vena cava, or tricuspid annulus or by ablating focally in the lateral RA. After a single ablation procedure, conduction block in the lateral wall was verified in 10 of 14 patients using 1 of 2 distinct patterns of block. One pattern consisted of late activation in an anterolateral corridor of the RA, and a second pattern consisted of wide-spaced double potentials. Recurrent conduction through the lateral wall lesions was associated with intraprocedural and late recurrences of ATs. CONCLUSIONS: The optimal end point for ablating ATs after mitral valve surgery with the superior transseptal approach is to establish lines of block that can be recognized by characteristic patterns of activation in the lateral RA. A novel criterion for lateral conduction block after catheter ablation is identification of a late-activated corridor in the anterolateral RA.

Intra-atrial conduction block mimicking atrioventricular nodal block after multiple catheter ablation procedures for atrial tachycardia in a patient with cardiomyopathy.

A 42-year-old woman with a history of cardiomyopathy and multiple ablation procedures for atrial tachycardia developed intra-atrial conduction block that mimicked atrioventricular (AV) nodal block during radiofrequency ablation at the cavotricuspid isthmus. She was treated with atrial pacing (from the coronary sinus), which overcame intra-atrial conduction block and resulted in AV nodal conduction.

Transcoronary ethanol ablation for recurrent ventricular tachycardia after failed catheter ablation: an update.

BACKGROUND: Despite substantial progress, radiofrequency catheter ablation (RFCA) fails in some patients. After encouraging results with transcoronary ethanol ablation (TCEA), we began offering TCEA routinely when endocardial and epicardial RFCA failed or a deep intramural substrate was likely. METHODS AND RESULTS: Among 274 consecutive patients who underwent 408 ventricular tachycardia (VT) ablation procedures, 27 patients (21 men; age, 63 ± 13 years; left ventricular ejection fraction, 30 ± 11%; ischemic cardiomyopathy, 14) had 29 TCEA procedures attempted. In 5 patients, TCEA was abandoned because of unfavorable anatomy. In 22 patients, a mean of 1.3 ± 0.6 arteries (range, 1-3 arteries) were targeted for TCEA. After ablation, the targeted VT was no longer inducible in 18 of 22 (82%) patients. Complete heart block occurred in 5 patients, and 3 patients with advanced heart failure died within 30 days of the procedure. After the last TCEA procedure, a VT recurred in 64% of patients, and overall, 32% of patients died. Of 11 patients with prior VT storm, 9 were free of VT storm. At repeat study in 8 patients who had a recurrence, 7 had a new QRS morphology of VT originating from the same general substrate region as the prior VT. CONCLUSIONS: In patients with difficult-to-control VT in whom RFCA fails, TCEA prevents all VT recurrences in 36% and improves arrhythmia control in an additional 27%. Inadequate target vessels, collaterals, and recurrence of modified VTs limit efficacy, but TCEA continues to play an important role for difficult VTs in these high-risk patients.

A simple pacing method to diagnose postero-anterior (clockwise) cavo-tricuspid isthmus block after radiofrequency ablation.

AIMS: Bidirectional block of the cavo-tricuspid isthmus (CTI) is a widely accepted endpoint for typical atrial flutter ablation, but its evaluation may be difficult, especially in the postero-anterior (clockwise) direction. The main goal was to evaluate pacing at the septal edge of the ablation line as an indicator of clockwise CTI block and as a predictor for flutter recurrence. METHODS AND RESULTS: In 94 patients undergoing flutter ablation, CTI block in the antero-posterior (counterclockwise) direction was determined by differential pacing from several levels of the anterior right atrial (RA). CTI block in the clockwise direction was evaluated by analysing electrograms (EGM) at the ablation line during differential pacing of the septal RA (differential septal pacing) or by anterior sequence of RA during pacing septal isthmus, next to the ablation line (septal CTI pacing). Ablation produced bidirectional block in 78% of the patients, unidirectional counterclockwise block in 9% and bidirectional conduction persisted in 13%. After follow-up (37 +/- 23 months), flutter recurrence occurred in 13% (48% if persistent conduction vs. 3% if bidirectional block, P < 0.001). During differential septal pacing, EGMs were difficult to interpret in 36% of the patients; in these cases, the diagnosis of CTI block or conduction in the clockwise direction was clearly established by using septal CTI pacing. CONCLUSION: Activation sequence of anterior RA during septal CTI pacing, next to the ablation line, is a reliable and simple method to diagnose clockwise CTI block and is associated with a low flutter recurrence.

The surface electrocardiogram predicts risk of heart block during right heart catheterization in patients with preexisting left bundle branch block: implications for the definition of complete left bundle branch block.

BACKGROUND: Patients with left bundle branch block (LBBB) undergoing right heart catheterization can develop complete heart block (CHB) or right bundle branch block (RBBB) in response to right bundle branch (RBB) trauma. We hypothesized that LBBB patients with an initial r wave (>or=1 mm) in lead V1 have intact left to right ventricular septal (VS) activation suggesting persistent conduction over the left bundle branch. Trauma to the RBB should result in RBBB pattern rather than CHB in such patients. METHODS: Between January 2002 and February 2007, we prospectively evaluated 27 consecutive patients with LBBB developing either CHB or RBBB during right heart catheterization. The prevalence of an r wave >or=1 mm in lead V1 was determined using 118 serial LBBB electrocardiographs (ECGs) from our hospital database. RESULTS: Catheter trauma to the RBB resulted in CHB in 18 patients and RBBB in 9 patients. All 6 patients with >or=1 mm r wave in V1 developed RBBB. Among these 6 patients q wave in lead I, V5, or V6 were present in 3. Four patients (3 in CHB group and 1 in RBBB group) developed spontaneous CHB during a median follow-up of 61 months. V1 q wave >or=1 mm was present in 28% of hospitalized complete LBBB patients. CONCLUSIONS: An initial r wave of >or=1 mm in lead V1 suggests intact left to right VS activation and identifies LBBB patients at low risk of CHB during right heart catheterization. These preliminary findings indicate that an initial r wave of >or=1 mm in lead V1, present in approximately 28% of ECGs with classically defined LBBB, may constitute a new exclusion criterion when defining complete LBBB.

High-resolution optical mapping of ventricular tachycardia in rats with chronic myocardial infarction.

BACKGROUND: Ventricular tachycardia (VT) is a common cause of mortality in post-myocardial infarction (MI) patients, even in the current era of coronary revascularization treatment. We report a reproducible VT model in rats with chronic MI induced by ischemia-reperfusion and describe its electrophysiological characteristics using high-resolution optical mapping. METHODS: An MI was generated by left anterior descending coronary ligation (25 minutes) followed by reperfusion in 20 rats. Electrophysiology study and optical mapping were performed 5 weeks later using a Langendorff-perfused preparation and compared to normal rats. RESULTS: The conduction velocity of the MI border zone was decreased to 53% of the normal areas remote from the infarct (0.37 +/- 0.16 m/sec vs 0.70 +/- 0.09 m/sec, P < 0.0001). The rate of VT inducibility in MI rats was significantly greater than in normal control rats (70% vs 0%, P = 0.00002). VT circuits involving the infarct area were identified with optical mapping in 83% MI rats. In addition, fixed and functional conduction block were observed in the infarct border zone. CONCLUSION: This ischemia-reperfusion MI rat model is a reliable VT model, which simulates clinical revascularization treatment. High-resolution optical mapping in this model is useful to study the mechanism of VT and evaluate the effects of therapies.

Cardiac rhythm disturbance in a depressed patient after implantation with a vagus nerve stimulator.

A 52-year-old woman with a long-standing history of treatment-resistant depression failed multiple courses of electroconvulsive therapy and various trials of antidepressant medications. As a result, the patient was deemed a good candidate for vagus nerve stimulation (VNS) therapy and underwent VNS insertion in May 2006. However, in December 2007, she began to experience recurrent falls and was referred to a cardiologist for a syncope evaluation. During a portable 30-day cardiac event recording, she was noted to have intermittent second- and third-degree heart block with ventricular standstill, which was felt by her cardiologist to be associated with VNS stimulation. We believe this to be the first reported case of heart block related to VNS in a depressed patient.

[Chronic progressive external ophthalmoplegia: clinical and electromyographic manifestations in a series of cases]. / Oftalmoplejía externa progresiva crónica: manifestaciones clínicas y electromiográficas en una serie de casos.

INTRODUCTION: Chronic progressive external ophthalmoplegia (CPEO) is a common mitochondrial disease. The different conditions in this group of diseases overlap clinically, enzymatically and genetically. There is no effective treatment. Ptosis improves with corrective surgery involving tarsorrhaphy as a palliative measure. CASE REPORTS: Code numbers were examined in a retrospective study conducted in order to search for patients with ptosis or ophthalmoplegia who had either visited or been admitted to the neurology department over the last 10 years. Data concerning these patients' clinical features and results of complementary tests were collected. Six patients with CPEO were identified, five of whom were females. Ages ranged from 44 to 72 years. All the patients had ptosis, although 50% were asymmetric. Half of them reported mild dysphagia while swallowing liquids. Levels of creatine phosphokinase and acetylcholine antireceptor antibodies were normal. Half the patients showed increased jitter and a muscle biopsy revealed that five of them had ragged red fibres. The most frequent enzyme deficit was complex I and IV deficiency. There were no familial forms; the most common genetic anomaly was single deletion in the mitochondrial deoxyribonucleic acid. CONCLUSIONS: In cases of ptosis and ophthalmoplegia that do not respond to anticholinesterases, knowledge of this condition makes it possible to avoid the use of immunosuppressant drugs, which have important side effects.