Antral pulmonary vein isolation (PVI) for treatment of atrial fibrillation may induce left atrial tachycardias (ATs).
To determine the prevalence, time course of occurrence, mechanisms, and ...correlation with the electrocardiogram as well as the outcome of ablation of these tachycardias.
Out of the 839 patients who underwent circumferential antral radiofrequency PVI guided by a circumferential pulmonary vein catheter at our institution between February 2005 and April 2011, 35 patients (4%) developed AT during follow-up. Six patients with left AT and a previous PVI at other institutions were also included. Of these 41 patients (26 men, 63%; age 59 ± 10 years), 26 (63%) had underlying paroxysmal atrial fibrillation and 15 (37%) had persistent atrial fibrillation. AT ablation was performed 47 ± 60 weeks after initial PVI, within the first 3 months in 16 patients (39%). The tachycardia mechanism was focal in 15 patients (37%), macroreentry in 25 patients (61%), and undetermined in 1 (2%). Focal tachycardias had an isoelectric line between distinct P waves in 13 of the 15 patients (87%), while only 4 (16%) with a macroreentrant mechanism had an isoelectric line (P <.001). Although difficult to measure, a P-wave width of >140 ms had the highest sensitivity and specificity to identify macroreentrant mechanism. Ablation was acutely successful in 32 patients (78%) and not successful in 4 (10%). In 5 patients, success could not be determined as the tachycardia terminated or degenerated during mapping. During a mean follow-up of 31 ± 17 months, 11 patients (27%; n = 9 82% with macroreentry) underwent repeat ablation procedure for AT. Eight patients had true recurrence, for example, the same AT, and 3 patients had a second mechanism of AT.
With the use of an identical ablation protocol, it was found that approximately 4% of the patients developed AT after mere circumferential antral PVI. The majority of ATs developed within a few months after ablation but occurred as late as several years after the initial PVI. Macroreentry was more frequent than a focal mechanism. Broad P waves and isoelectric lines between P waves help to distinguish a focal mechanism from a macroreentrant mechanism. Ablation has a high acute success rate, and AT recurrence occurs predominantly in macroreentrant AT.
Recent evidence suggests that cardiac sarcoidosis (CS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) can manifest very similarly.
To investigate whether there are significant demographic ...and electrophysiological differences between patients with CS and ARVC.
We prospectively compared patients with proven CS or ARVC who underwent radiofrequency catheter ablation of ventricular tachycardias by using 3-dimensional electroanatomical mapping. Furthermore, we evaluated whether the diagnostic criteria for ARVC would have excluded ARVC in patients with CS.
Eighteen patients (13 men; mean age 44.9 years) were included. All 18 patients had mild to moderately reduced right ventricular ejection fraction. Patients with cardiac sarcoidosis (n = 8) had a significantly lower mean left ventricular ejection fraction (35.6±19.3 vs 60.6±9.4; P = .002). Patients with CS had a significantly wider QRS (0.146 vs 0.110s; P = .004). Five of 8 (63%) patients with CS fulfilled the diagnostic ARVC criteria. Ventricular tachycardias (VTs) with a left bundle branch block pattern were documented in all but one patient (with CS). Programmed ventricular stimulation induced an average of 3.7 different monomorphic VTs in patients with CS vs 1.8 in patients with ARVC (P = .01). VT significantly more often originated in the apical region of the right ventricle in CS vs ARVC (P = .001), with no other predilection sites. Ablation success and other electrophysiological parameters were not different.
The current diagnostic ARVC guidelines do not reliably exclude patients with CS. Clinical and electrophysiological parameters that were characteristic of CS in our patients include reduced left ventricular ejection fraction, a significantly wider QRS, right-sided apical VT, and more inducible forms of monomorphic VT.
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.
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.
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.
Three months after CRT, LV ejection fraction increased an average of 14.5% (
< 0.001) in 13 patients (responders), while no change was observed in 15 patients (non-responders). End-systolic diameter decreased 16% (
< 0.001) in responders, with no change in non-responders. ROCK activation in PBMCs decreased 66% in responders (
< 0.05) but increased 10% in non-responders (NS). LV end-diastolic diameter was also 5.2 mm larger in non-responders vs. responders (
= 0.058). LV ejection fraction, systolic diameter, and ROCK activation levels were similar in both groups at baseline.
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.
Abstract 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.
Pulmonary vein (PV) electrical isolation is a therapeutic option in atrial fibrillation (AF). New technologies may reduce the complexity of the procedure.
The aim of the present study was to compare ...immediate results and short-term efficacy of a new circular ablation catheter (PVAC) with a conventional point-by-point ablation.
The prospective study enrolled 80 consecutive patients with paroxysmal AF or persistent AF, refractory to antiarrhythmic drugs, who were randomized to radiofrequency ablation using duty-cycled bipolar and unipolar radiofrequency by a decapolar circular catheter (PVAC group) or to point-by-point ablation supported by a 3-dimensional mapping system (3D group).
Forty patients per group were included. Mean age was 58 ± 10 years, 64% were male; 55% had paroxysmal AF, 45% had persistent AF. There were no significant differences between groups. Complete electrical isolation was reached in all but 1 PV, which was not isolated in the PVAC group because of phrenic nerve capture. Procedure and fluoroscopy times were lower in the PVAC group: 171 ± 40 minutes vs. 224 ± 27 minutes, P < .001; 26 ± 8 minutes vs. 35 ± 9 minutes, P < .001; respectively. There were no major complications. During a mean follow-up of 254 ± 99 days, 72% in the PVAC group and 68% in the 3D group were free of AF recurrences irrespective of the initial AF type (P = NS).
PVAC represents a safe alternative for PV isolation. It reduces both procedure and fluoroscopy time. The short- and middle-term efficacy is comparable to a conventional point-by-point antral ablation technique.
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).
To characterize the subgroup of ventricular arrhythmias arising from the MA.
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.
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.
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.
Abstract 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.
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.
•Excessive ROS production leads to oxidative damage to DNA, proteins and lipids.•Mitochondrial SOD2 protects cells against mitochondria-generated ROS toxicity.•SOD2-deficiency leads to excessive ROS production and oxidative stress.•Knockdown of SOD2 inhibits hormone-stimulated granulosa cell steroidogenesis.•SOD2 deficiency attenuates the expression of StAR and key steroidogenic genes.
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.
•ZDSD rat is a polygenic model of obesity, MetS and T2D with an intact leptin pathway.•ZDSD rats develop prediabetes, MetS and T2D that mimic development in humans.•ZDSD rats exhibit altered expression of key hepatic metabolic enzymes/proteins.•ZDSD rats exhibit elevated levels of ER stress/UPR markers.•Enhanced ER stress/UPR contributes to IR and associated metabolic abnormalities.
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