Nordihydroguaiaretic Acid, a Lignan from Larrea tridentata (Creosote Bush), Protects Against American Lifestyle-Induced Obesity Syndrome Diet-Induced Metabolic Dysfunction in Mice.

To determine the effects of nordihydroguaiaretic acid (NDGA) on metabolic and molecular changes in response to feeding a typical American fast food or Western diet, mice were fed an American lifestyle-induced obesity syndrome (ALIOS) diet and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to the ALIOS diet, the ALIOS diet supplemented with NDGA (NDGA+ALIOS), or a control diet and were maintained on the specific diet for 8 weeks. Mice fed the ALIOS diet showed increased body, liver, and epididymal fat pad weight as well as increased plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels (a measure of liver injury) and liver triglyceride content. Coadministration of NDGA normalized body and epididymal fat pad weight, ALT and AST levels, and liver triglycerides. NDGA treatment also improved insulin sensitivity but not glucose intolerance in mice fed the ALIOS diet. In mice fed the NDGA+ALIOS diet, NDGA supplementation induced peroxisome proliferator-activated receptor α (PPARα; the master regulator of fatty acid oxidation) and mRNA levels of carnitine palmitoyltransferases Cpt1c and Cpt2, key genes involved in fatty acid oxidation, compared with the ALIOS diet. NDGA significantly reduced liver endoplasmic reticulum (ER) stress response C/EBP homologous protein, compared with chow or the ALIOS diet, and also ameliorated ALIOS diet-induced elevation of apoptosis signaling protein, caspase 3. Likewise, NDGA downregulated the ALIOS diet-induced mRNA levels of Pparg, fatty acid synthase Fasn, and diacylglycerol acyltransferase Dgat2 NDGA treatment of ALIOS-fed mice upregulated the hepatic expression of antioxidant enzymes, glutathione peroxidase 4, and peroxiredoxin 3 proteins. In conclusion, we provide evidence that NDGA improves metabolic dysregulation by simultaneously modulating the PPARα transcription factor and key genes involved in fatty acid oxidation, key antioxidant and lipogenic enzymes, and apoptosis and ER stress signaling pathways.

Esophageal and Mediastinal Lesions Following Multielectrode Duty-Cycled Radiofrequency Pulmonary Vein Isolation: Simple Equals Safe?

BACKGROUND: The development of esophageal lesions following atrial fibrillation (AF) ablation has frequently been reported. Mediastinal tissue layers and the posterior wall of the left atrium are in close proximity to the site of ablation. Hence, mucosal lesions might solely represent the "tip of the iceberg." We therefore investigated patients undergoing multielectrode phased radiofrequency (RF) ablation (PVAC®, Medtronic Inc., Minneapolis, MN, USA) for symptomatic AF by radial endosonography (EUS) in conjunction with conventional endoscopy esophago-gastro-duodenoscopy (EGD) to visualize potential mediastinal injuries following pulmonary vein isolation (PVI). METHODS AND RESULTS: Eighteen patients (six women, mean age 52.8 ± 12.8 years, range 32-72 years) underwent PVI using multielectrode phased RF ablation and EGD and EUS following PVI within 48 hours. Postablation periesophageal lesions were detected by EUS in 10 out of 18 patients (56%). Four out of 10 lesions consisted of mild changes like small pericardial effusions, whereas six out of 10 patients had more severe lesions of the mediastinum, including one patient with changes of the esophageal mucosa. No atrio-esophageal fistula developed during follow-up (FU; mean FU 215 ± 105 days). CONCLUSIONS: Mediastinal and esophageal structural changes occurred in a substantial number of patients. These findings highlight the necessity of close FU and the awareness of the potential development of an atrio-esophageal fistula also after multielectrode catheter ablation.

Electrophysiology study without intracardiac catheters. The value of proper Holter interpretation: a case report.

This case report presents the case of a 55-year-old male patient with a long-standing history of palpitations. A 24-h Holter monitor revealed an incessant form of long-RP supraventricular tachycardia. The differential diagnosis is presented and discussed. In a stepwise approach, it is explained how the exact mechanism of the tachycardia can be inferred through careful examination of the multiple onsets, terminations and response to spontaneous monomorphic premature ventricular contractions.

[Cardiac resynchronization therapy in patients with heart failure: a 10-year experience]. / Terapia de resincronización en pacientes con insuficiencia cardiaca: experiencia acumulada de 10 años.

BACKGROUND: Multiple randomized trials support the clinical benefits of cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and ventricular dyssynchrony. Since the year 2000 this therapy has been increasingly used in Chile. AIM: To describe the clinical characteristics and follow-up of HF patients undergoing CRT in a single Chilean university hospital during the last 10 years. PATIENTS AND METHODS: All patients undergoing CRT between 2000 and 2010 in our university hospital were included. Clinical and echocardiographic data were extracted from medical records and mortality causes were obtained from the National Identification Service. RESULTS: A total of 252 patients underwent CRT during the study period. Seventy five percent were in New York Heart Associatin (NYHA) functional class III and mean ejection fraction was 29 ± 10%. Complete left bundle branch block was present in 55% and 20% had permanent atrial fibrillation (AF). Mean survival was 86% at 1 year and 82% of patients in NYHA class III-IV improved at least one functional class. Survival was poorer in patients with ischemic etiology (hazard ratio (HR) 1.48), functional class IV (HR 2.2), right bundle branch block (RBBB) (HR 3.1) and AF (HR 3.4). No survival differences were observed between patients with and without an implanted cardiodefibrillator. CONCLUSIONS: This series show good clinical outcomes, comparable to those reported in randomized trials. Predictors of worse survival included an ischemic etiology, functional class IV, RBBB and AF. Patients with a defibrillator had no better survival, which could be relevant in countries with limited health care resources.

Successful treatment of catecholaminergic polymorphic ventricular tachycardia with flecainide: a case report and review of the current literature.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease that can cause sudden cardiac death due to ventricular fibrillation (VF). While pharmacological therapy with beta-blockers and/or Ca(2)(+) antagonists is often unreliable, a recent study has demonstrated that flecainide can effectively suppress arrhythmia in a murine model of CPVT as well as clinically in two human subjects suffering from CPVT. We here present the case of an 11-year-old boy suffering from CPVT-1 as well as a review of the current relevant literature. After resuscitation due to VF at age 9, an automated implantable cardioverter-defibrillator (ICD) was implanted in 2007. Under beta-blocker therapy, repeated shocks were delivered due to either fast ventricular tachycardia (VT) or VF. This persisted under additional therapy with verapamil. Implantable cardioverter-defibrillator routine interrogations showed frequent non-sustained VT with an average of 8.8 per day. Additionally, the patient suffered from impaired physical performance due to decreased chronotropic competence. In July 2009, flecainide was added to the beta-blocker/verapamil regimen, resulting in a plasma level of 0.20 mg/L. No ICD shock or sustained VT occurred until December 2010. Genetic testing revealed an RyR2 receptor mutation. The case demonstrates the challenge of diagnosis and management of CPVT. It furthermore supports recent experimental evidence that the class 1 antiarrhythmic drug flecainide can suppress CPVT. The presented case supports a novel strategy in treating CPVT with the class I antiarrhythmic agent flecainide.

Pulmonary vein variants predispose to atrial fibrillation: a case-control study using multislice contrast-enhanced computed tomography.

AIMS: Pulmonary veins (PV) play a pivotal role in atrial fibrillation (AF). Anatomical variants of PV have been described and related to a higher arrhythmogenic potential. The aim of this study was to compare the prevalence of PV variants and diameters of PV ostia in AF patients and controls. METHODS AND RESULTS: Variants of PV were defined as right or left common ostia (RCO, LCO), a right middle or right top PV . A long common trunk (LCT) was defined as an LCO with a distance to the first branching ≥ 10 mm. Multislice contrast-enhanced thoracic computed tomography was performed prior to AF ablation in 166 consecutive patients, 47.6% with paroxysmal, 52.4% with persistent AF, as well as in a sex- and age-matched control group without AF, for non-cardiological indications. Images were evaluated by two independent observers. The mean age was 59 ± 10 years, 108 were men (65.1%). A higher prevalence of LCO was found in the AF group: 33.7 vs. 19.9% (P= 0.004), odds ratio (OR) 2.1; 15.4% in patients vs. 10.2% in controls had an LCT (P= 0.14). No differences in other PV variants were found. The ostial diameters were greater in AF-patients (P< 0.001). CONCLUSIONS: To the best of our knowledge, the present study shows for the first time a higher prevalence of an LCO in patients with AF as compared with controls, with an OR of 2.1. This suggests a pre-disposing role of LCO in the development of AF.

Patient With Presyncope and Variable PR Interval and QRS Morphology.

We describe the case of a 72-year-old female patient, presenting with presyncope and variable PR Interval and changing QRS morphology on the electrocardiogram. Differential diagnosis is discussed. (Level of Difficulty: Beginner.).

SOD2 deficiency-induced oxidative stress attenuates steroidogenesis in mouse ovarian granulosa cells.

This study investigated the effects of SOD2 (MnSOD)-deficiency-induced excessive oxidative stress on ovarian steroidogenesis in vivo and isolated and cultured granulosa cells using WT and Sod2+/- mice. Basal and 48 h eCG-stimulated plasma progesterone levels were decreased ~50% in female Sod2+/- mice, whereas plasma progesterone levels were decreased ~70% in Sod2+/- mice after sequential stimulation with eCG followed by hCG. Sod2+/- deficiency caused about 50% reduction in SOD2 activity in granulosa cells. SOD2-deficiency also caused a marked reduction in progestins and estradiol in isolated granulosa cells. qRT-PCR measurements indicated that the mRNA expression levels of StAR protein and steroidogenic enzymes are decreased in the ovaries of Sod2+/- mice. Further studies showed a defect in the movement of mobilized cytosolic cholesterol to mitochondria. The ovarian membrane from Sod2+/- mice showed higher susceptibility to lipid peroxidation. These data indicates that SOD2-deficiency induced oxidative stress inhibits ovarian granulosa cell steroidogenesis primarily by interfering with cholesterol transport to mitochondria and attenuating the expression of Star protein gene and key steroidogenic enzyme genes.

Reverse Remodeling in Human Heart Failure after Cardiac Resynchronization Therapy Is Associated With Reduced RHO-Kinase Activation.

Background: Reverse remodeling is a clinically relevant endpoint in heart failure with reduced ejection fraction (HFrEF). Rho-kinase (ROCK) signaling cascade activation correlates with cardiac remodeling and left ventricular (LV) systolic dysfunction in HFrEF patients. Cardiac resynchronization therapy (CRT) is effective in HFrEF, especially when there is a left bundle block, as this treatment may stimulate reverse remodeling, thereby improving quality of life and prolonging survival for patients with this severe condition. Here, we evaluate the hypothesis that ROCK activation is reduced after effective CRT in HFrEF. Methods: ROCK activation in circulating leukocytes was evaluated in 28 HFrHF patients, using Western blot (myosin light chain phosphatase subunit 1 phosphorylation, MYPT1p/t), before and three months after initiation of CRT. LV systolic function and remodeling were assessed by echocardiography. Results: Three months after CRT, LV ejection fraction increased an average of 14.5% (p < 0.001) in 13 patients (responders), while no change was observed in 15 patients (non-responders). End-systolic diameter decreased 16% (p < 0.001) in responders, with no change in non-responders. ROCK activation in PBMCs decreased 66% in responders (p < 0.05) but increased 10% in non-responders (NS). LV end-diastolic diameter was also 5.2 mm larger in non-responders vs. responders (p = 0.058). LV ejection fraction, systolic diameter, and ROCK activation levels were similar in both groups at baseline. Conclusion: In HFrEF patients, 3 months of effective CRT induced reverse myocardial remodeling, and ROCK activation was significantly decreased in circulating leukocytes. Thus, decreased ROCK activation in circulating leukocytes may reflect reverse cardiac remodeling in patients with heart failure.

Molecular changes in hepatic metabolism in ZDSD rats-A new polygenic rodent model of obesity, metabolic syndrome, and diabetes.

In recent years, the prevalence of obesity, metabolic syndrome and type 2 diabetes is increasing dramatically. They share pathophysiological mechanisms and often lead to cardiovascular diseases. The ZDSD rat was suggested as a new animal model to study diabetes and the metabolic syndrome. In the current study, we have further characterized metabolic and hepatic gene expression changes in ZDSD rats. Immuno-histochemical staining of insulin and glucagon on pancreas sections of ZDSD and control SD rats revealed that ZDSD rats have severe damage to their islet structures as early as 15 weeks of age. Animals were followed till they were 26 weeks old, where they exhibited obesity, hypertension, hyperglycemia, dyslipidemia, insulin resistance and diabetes. We found that gene expressions involved in glucose metabolism, lipid metabolism and amino acid metabolism were changed significantly in ZDSD rats. Elevated levels of ER stress markers correlated with the dysregulation of hepatic lipid metabolism in ZDSD rats. Key proteins participating in unfolded protein response pathways were also upregulated and likely contribute to the pathogenesis of dyslipidemia and insulin resistance. Based on its intact leptin system, its insulin deficiency, as well as its timeline of disease development without diet manipulation, this insulin resistant, dyslipidemic, hypertensive, and diabetic rat represents an additional, unique polygenic animal model that could be very useful to study human diabetes.

Anti-hyperlipidaemic effects of synthetic analogues of nordihydroguaiaretic acid in dyslipidaemic rats.

BACKGROUND AND PURPOSE: Previous studies have shown that Creosote bush-derived nordihydroguaiaretic acid (NDGA) exerts beneficial actions on the key components of metabolic syndrome including dyslipidaemia, insulin resistance and hypertension in several relevant rodent models. Here, we synthesized and screened a total of 6 anti-hyperlipidaemic analogues of NDGA and tested their efficacy against hepatic lipid metabolism in a high-fructose diet (HFrD) fed dyslipidaemic rat model. EXPERIMENTAL APPROACH: HFrD fed Sprague-Dawley rats treated with NDGA or one of the six analogues were used. Serum samples were analysed for blood metabolites, whereas liver samples were quantified for changes in various mRNA levels by real-time RT-PCR. KEY RESULTS: Oral gavage of HFrD-fed rats for 4 days with NDGA analogues 1 and 2 (100 mg·kg-1 ·day-1 ) suppressed the hepatic triglyceride content, whereas the NDGA analogues 2, 3 and 4, like NDGA, decreased the plasma triglyceride levels by 70-75%. qRT-PCR measurements demonstrated that among NDGA analogues 1, 2, 4 and 5, analogue 4 was the most effective at inhibiting the mRNA levels of some key enzymes and transcription factors involved in lipogenesis. All four analogues almost equally inhibited the key genes involved in triglyceride synthesis and fatty acid elongation. Unlike NDGA, none of the analogues affected the genes of hepatic fatty acid oxidation or transport. CONCLUSIONS AND IMPLICATIONS: Our data suggest that NDGA analogues 1, 2, 4 and 5, particularly analogue 4, exert their anti-hyperlipidaemic actions by negatively targeting genes of key enzymes and transcription factors involved in lipogenesis, triglyceride synthesis and fatty acid elongation. These analogues have therapeutic potential.

Cuantificación de la extrasistolía supraventricular y ventricular en el holter de 24 horas: significación pronóstica en estudios actuales / Quantification and clinical significance of supraventricular and ventricular extrasystoles in holter recordings: a review

En la actualidad existen diferencias en la interpretación y cuantificación de los extrasístoles supraventriculares y ventriculares en el Holter de ritmo cardíaco y no existe siempre una misma definición e interpretación de lo que se denomina como "escaso", "ocasional", "frecuente" o "muy frecuente". El objetivo del presente trabajo ha sido revisar las evidencias actuales y sus fundamentos en relación a la cuantificación o carga de la extrasistolía supraventricular y ventricular en un Holter de ritmo cardíaco, lo que debiera contribuir a una mayor precisión y mejor interpretación de la información cuantitativa en la práctica clínica diaria con este examen. Se revisa en la literatura el concepto de carga de extrasístoles supraventriculares y ventriculares y su relación con eventos clínicos: fibrilación auricular y accidente cerebrovascular en el caso de la extrasistolía supraventricular y mortalidad post infarto y deterioro de la función ventricular en el caso de la extrasistolía ventricular. De esta manera se cuantifica en base a la evidencia la extrasistolía supraventricular y ventricular.

Considerable differences exist in the quantification and clinical significance of both supraventricular and ventricular extrasystoles found in Holter recordings. Usually extrasystoles were classified as rare, occasional, frequent and very frequent. Current publications were analyzed regarding the frequency and clinical significance or these arrhythmias, especially in in relation to prior myocardial infarction, ventricular dysfunction, atrial fibrillation and cerebro vascular events. Tables showing limits to define the severity of supraventricular and ventricular extrasystoles are included.

Microarray analysis of gene expression in liver, adipose tissue and skeletal muscle in response to chronic dietary administration of NDGA to high-fructose fed dyslipidemic rats.

Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote Bush, has been shown to have profound effects on the core components of metabolic syndrome, including lowering of blood glucose, free fatty acids and triglyceride levels, attenuating elevated blood pressure in several rodent models of dyslipidemia, and improving body weight, insulin resistance, diabetes and hypertension. In the present study, a high-fructose diet fed rat model of hypertriglyceridemia, dyslipidemia, insulin resistance and hepatic steatosis was employed to investigate the global transcriptional changes in the lipid metabolizing pathways in three insulin sensitive tissues: liver, skeletal muscle and adipose tissue in response to chronic dietary administration of NDGA. Sprague-Dawley male rats (SD) were fed a chow (control) diet, high-fructose diet (HFrD) or HFrD supplemented with NDGA (2.5 g/kg diet) for eight weeks. Dietary administration of NDGA decreased plasma levels of TG, glucose, and insulin, and attenuated hepatic TG accumulation. DNA microarray expression profiling indicated that dietary administration of NDGA upregulated the expression of certain genes involved in fatty acid oxidation and their transcription regulator, PPARα, decreased the expression of a number of lipogenic genes and relevant transcription factors, and differentially impacted the genes of fatty acid transporters, acetyl CoA synthetases, elongases, fatty acid desaturases and lipid clearance proteins in liver, skeletal muscle and adipose tissues. These findings suggest that NDGA ameliorates hypertriglyceridemia and steatosis primarily by inhibiting lipogenesis and enhancing fatty acid catabolism in three major insulin responsive tissues by altering the expression of key enzyme genes and transcription factors involved in de novo lipogenesis and fatty acid oxidation.

Effects of carvedilol upon intra- and interventricular synchrony in patients with chronic heart failure.

Radionuclide isotopic ventriculography with phase analysis was performed in 30 patients with stable heart failure (HF), determining left ventricular (LV) and interventricular contraction synchrony at baseline and after 6 months of treatment with maximal tolerated doses of carvedilol. Patients with HF had significant ventricular dyssynchrony compared with a normal population. The 50th percentile of patients with the greatest dyssynchrony at baseline showed significant improvement in ventricular synchrony after receiving carvedilol, and this was correlated positively with a reduction in end-diastolic LV volumes.

Effect of Creosote Bush-Derived NDGA on Expression of Genes Involved in Lipid Metabolism in Liver of High-Fructose Fed Rats: Relevance to NDGA Amelioration of Hypertriglyceridemia and Hepatic Steatosis.

Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote bush, has been shown to have profound effects on the core components of the metabolic syndrome (MetS), lowering blood glucose, free fatty acids (FFA) and triglyceride (TG) levels in several models of dyslipidemia, as well as improving body weight (obesity), insulin resistance, diabetes and hypertension, and ameliorating hepatic steatosis. In the present study, a high-fructose diet (HFrD) fed rat model of hypertriglyceridemia was employed to further delineate the underlying mechanism by which NDGA exerts its anti-hypertriglyceridemic action. In the HFrD treatment group, NDGA administration by oral gavage decreased plasma levels of TG, glucose, FFA, and insulin, increased hepatic mitochondrial fatty acid oxidation and attenuated hepatic TG accumulation. qRT-PCR measurements indicated that NDGA treatment increased the mRNA expression of key fatty acid transport (L-FABP, CD36), and fatty acid oxidation (ACOX1, CPT-2, and PPARα transcription factor) genes and decreased the gene expression of enzymes involved in lipogenesis (FASN, ACC1, SCD1, L-PK and ChREBP and SREBP-1c transcription factors). Western blot analysis indicated that NDGA administration upregulated hepatic insulin signaling (P-Akt), AMPK activity (P-AMPK), MLYCD, and PPARα protein levels, but decreased SCD1, ACC1 and ACC2 protein content and also inactivated ACC1 activity (increased P-ACC1). These findings suggest that NDGA ameliorates hypertriglyceridemia and hepatic steatosis primarily by interfering with lipogenesis and promoting increased channeling of fatty acids towards their oxidation.

p38 MAPK regulates steroidogenesis through transcriptional repression of STAR gene.

STAR/StarD1, part of a protein complex, mediates the transport of cholesterol from the outer to inner mitochondrial membrane, which is the rate-limiting step for steroidogenesis, and where steroid hormone synthesis begins. Herein, we examined the role of oxidant-sensitive p38 MAPKs in the regulation of STAR gene transcription, using model steroidogenic cell lines. Our data indicate that oxidant activation of p38 MAPK exhibits a negative regulatory role in the induction of functional expression of STAR, as evidenced by enhanced induction of STAR (mRNA/protein) expression and increased steroidogenesis during pharmacological inhibition of p38 MAPK or in cells with increased transient overexpression of a dominant-negative (dn) form of p38 MAPKα or p38 MAPKß. Studies with rat Star-promoter demonstrated that overexpression of p38 MAPKα-wt, -ß, or -γ significantly reduced both basal and cAMP-sensitive promoter activity. In contrast, overexpression of p38 MAPKα-dn, -ß, or -γ enhanced the Star promoter activity under basal conditions and in response to cAMP stimulation. Use of various constitutively active and dn constructs and designer knock-out cell lines demonstrated that MKK3 and MKK6, the upstream activators of p38 MAPKs, play a role in p38 MAPKα-mediated inhibition of Star promoter activity. In addition, our studies raised the possibility of CREB being a potential target of the p38 MAPK inhibitory effect on Star promoter activity. Collectively, these data provide novel mechanistic information about how oxidant-sensitive p38 MAPKs, particularly p38 MAPKα, contribute to the negative regulation of Star gene expression and inhibit steroidogenesis.

Compromiso de conciencia y bradicardia / Unconciousness and bradycardia

Resumen: Mujer de 71 años, institucionalizada con antecedentes de esquizofrenia y tabaquismo. Consulta en el servicio de urgencias tras ser encontrada a la intemperie comprometida de conciencia. Al llegar la ambulancia se constata mal perfundida, bradipsíquica y bradicárdica, siendo trasladada al servicio de Urgencia. A su ingreso el ECG mostró bradicardia sinusal con trastorno de la conducción intraventricular y prolongación del intervalo QT. Los exámenes de laboratorio al ingreso resultaron dentro de límites normales. La historia clínica y los trazados electrocardiográficos son presentados, siendo discutidos junto al manejo médico.

Abstracts: A 71year old woman, institutionalized with a history of schizophrenia and smoking. She was transported to a local emergency room after being found laying outside unconscious. She was hypoperfused, bradypsychic and bradycardic, being transferred to the emergency service. On admission, the ECG showed sinus bradycardia with intraventricular conduction delay and QT prolongation. Laboratory tests were normal. Clinical history, physical examination and ECG tracings are presented and management is discussed.

Ventricular arrhythmias from the mitral annulus: patient characteristics, electrophysiological findings, ablation, and prognosis.

BACKGROUND: Symptomatic, premature ventricular contractions (PVCs) frequently originate in the right ventricular outflow tract, less frequently in the left ventricular outflow tract, aortic root, or mitral annulus (MA). Little is known about the patient population presenting with MA PVC and/or ventricular tachycardia (VT). OBJECTIVE: To characterize the subgroup of ventricular arrhythmias arising from the MA. METHODS: Among 404 consecutive patients who presented for catheter ablation of idiopathic PVC/VT over a period of 9 years, patients who were found to have an ablation site at the MA were analyzed for clinical and electrophysiological parameters. RESULTS: Twenty-two (5%) patients (mean age 45 ± 18 years; range 16-76 years; 14 [64%] men) had PVC/VT arising from the MA. History of PVC ranged from 2 days in a case with suspected focal myocarditis to 19 years. No patient had severely depressed left ventricular function or significant heart disease, which was determined by echocardiogram, magnetic resonance imaging, and/or coronary angiogram. Sites of origin were distributed around the MA with no preferential area. Ablation was successful in 13 of 16 (81%) patients. One 28-year-old female patient with normal magnetic resonance imaging and no structural heart disease died suddenly 3 months after ablation. CONCLUSIONS: Ventricular arrhythmias from the MA represent a rare subgroup of idiopathic PVC/VT. They appear to occur at any age and do not indicate underlying structural heart disease. Catheter ablation has a success rate comparable to that of outflow tract tachycardia. Prognosis remains unclear.

Isthmus-dependent right atrial flutter as the leading cause of atrial tachycardias after surgical atrial septal defect repair.

OBJECTIVES: The purpose of this study was to evaluate clinical and electrophysiologic characteristics of AT in patients after surgical ASD repair as well as outcome after ablation. BACKGROUND: Atrial tachycardias (AT) are a common complication after surgical closure of an atrial septal defect (ASD). METHODS: From a prospective ablation database we analyzed data of patients with a history of ASD repair who presented to our institution for AT ablation. We investigated ECG characteristics and the electrophysiologic mechanism of AT in this collective and analyzed follow-up data. RESULTS: Data of 54 patients (47.3 ± 14.5 years, 35 females) were included. In 30 patients (55.6%) ASD had been closed by direct suture, 24 patients (44.4%) had a patch for ASD repair without significant difference in terms of gender and age at the time of the procedure (p=0.234, p=0.231). In 42 patients (77.8%), electrophysiological studies were performed in AT. All patients had right atrial macro-reentrant AT. The leading mechanism was isthmus-dependent right atrial flutter in 29 patients (69.0%) with clockwise atrial activation in 41%. The mechanism of AT (typical atrial flutter (n=29), atriotomy-dependent flutter (n=7), and double loop flutter (n=5)) did not differ with regard to type of surgery. Only 70.6% of patients with proven isthmus dependent counter-clockwise atrial flutter presented with an ECG morphology typical for this mechanism. However, all clockwise typical atrial flutter patients showed the characteristic positive P-waves in the inferior leads. Of note, 83.3% of clockwise typical flutter ECGs had long isoelectric lines (mean 74.5 ms). Follow-up was complete in 45 of 54 patients. During a mean follow-up of 7.7 ± 3.7 years, 27 patients (60%) remained free of any arrhythmia, two patients had AT recurrence with different mechanisms compared to the first procedure and underwent successful ablation. Five patients (11%) developed atrial fibrillation. CONCLUSION: Isthmus dependent right atrial flutter is the leading AT mechanism in patients with a history of ASD repair. The mechanism of atrial flutter did not differ in relation to the mode of ASD closure (direct suture versus patch closure). ECG characteristics of the tachycardia may be misleading as they are more often atypical in patients after ASD repair.