The Role of Catheter Ablation Techniques in the Treatment of Classic (Type 1) Atrial Flutter

Several attempts at circuit interruption of type 1 atrial flutter by means of surgical or catheter techniques have been published. We recently reported the results of a series of patients who underwent catheter fulguration of the low septal right atrium, with a mean follow-up of almost 3 years. True electrophysiological success was observed in 7/14 patients (50%). Clinical success, defined as absence of symptoms, was observed in 8/14 (57%) in this patient population. No serious complications were encountered, but the potential risks of DC shock, and the experience that we gained in right atrial mapping using this approach, led us to reconsider the role of atrial DC ablation in these patients. Additional studies assessing the meaning of fragmented electrograms, and identification of one for of severall slow conduction areas of the reentrant circuit are ongoing.     

Retrospective,observational, multicentre study on an Italian population affected by chronic hepatitis C who failed to clear HCV‐RNA after the combined therapy (PEG‐IFN and ribavirin): NADIR study

Summary. There is a lack of information on the characteristics of patients with chronic hepatitis C virus infection (HCV) who fail to respond to antiviral treatment. We studied HCV‐positive subjects with chronic liver diseases treated with pegylated‐interferon (PEG‐IFN) and ribavirin (RBV) who failed to clear HCV in routine clinical practice. A total of 2150 consecutive adult patients treated with PEG‐IFN plus RBV therapy in 46 Italian centres between 1 July 2004, and 30 June 2005, were studied. Of the 2150 patients, 923 (42.9%) (M/F 585/335, mean age 54.8 years) failed to achieve a serum HCV‐RNA clearance. Of these 923 patients, 429 (46.5%) were nonresponders, 298 (32.3%) relapsers, 168 (18.2%) drop‐outs for noncompliance or adverse events and 28 (3.0%) were lost during follow‐up. Overall, 642 (70.6%) patients received adequate therapy (defined as more than 80% of the drug doses for >80% of the time). Genotypes 1–4 were observed in 76.9% of cases; genotypes 2–3 in 21.2% and mixed in 1.9%, respectively. Multiple logistic regression analysis identified genotypes 1 and 4 as the sole independent predictors of the likelihood of nonresponse to therapy compared with relapse (OR: 4.38; 95% CI = 2.28–8.4). Age older than 65 years was the sole independent factor associated with no adherence to therapy (OR: 2.22; 95% CI = 1.36–3.62). Patients who fail to respond to treatment are a nonhomogeneous population with different features, and the sole factor that discriminates nonresponse from relapse is the distribution of genotypes 1–4. Co‐morbidities are unable to determine the type of treatment failure and inadequate adherence to therapy mostly affects patients older than 65 years of age.     

The Effect of Intracoronary β-Radiation on Neointimal Formation and Vascular Remodeling in Balloon-Injured Porcine Coronary Arteries: Effect of Dose Rate

Background: Neointimal formation and vascular remodeling are major mechanisms contributing to coronary restenosis after percutaneous transluminal coronary angioplasty. Intracoronary γ- and β-radiation have been shown to inhibit neointimal formation in balloon-injured porcine coronary arteries. However, the effects of Intracoronary radiation (ICR) dose and dose rate on vascular remodeling versus inhibition of neointimal formation have not been evaluated. Methods and Results: Forty-one Hanford Miniature swine were subjected to oversized balloon injury in the left anterior descending and right coronary artery. A spiral centering catheter with perfusion capabilities was placed in the injured segment for circumferentially uniform radiation dose delivery to the vessel wall. Each artery was randomly afterloaded with a dummy wire or an active wire with the ³²P source encapsulated in either a short (3 mm) or long (27 mm) segment at the distal end of the wire. The 3-mm source wire was used to deliver 650, 1,300, and 1,900 cGy while the 27-mm source wire was used to deliver 1,200 and 3,500 cGy of β-radiation to the adventitia (～ 0.5 mm into the vessel wall). The dose rate for ICR varied from 2.5 to 140 cGylsec, depending on the mCi strength of the ³²P source at the time of endovascular radiation. One month later, repeat coronary angiography and intravascular ultrasound (IVUS) to measure the external elastic lamina (EEL) area were done. The animals were sacrificed and the coronary vasculature was perfusion fixed. Morphometric, quantitative coronary angiographic, and IVUS analyses were carried out in a blinded fashion. A significant reduction in percent area stenosis (PAS) and neointimal area (NA) was observed on morphometry in coronary arteries treated with 3,500 cGy of β-radiation. The PAS and NA was 44%± 13% and 0.96 ± 0.25 mm² in the control groups versus 19%± 14% and 0.30 ± 0.23 mm² in the 3,500-cGy group (P < 0.02). There was no significant difference on morphometry between the control and the other four β-radiationtreated groups. There was no significant improvement in the change in minimum lumen diameter (ΔMLD) between the control and the five radiation-treated groups. Further analysis of angiographic data revealed that the apparent lack of beneficial effect on angiography was due to significant reductions in lumen diameter in the subgroups of arteries subjected to ICR at a dose rate > 50 cGylsec with the 3-mm source wire only. The ΔMLD was -1.39 ± 0.49, –1.79 ± 0.64, and -1.79 ± 0.39 mm in the 650-, 1,300-, and 1,900-cGy groups treated with a dose rate > 50 cGylsec versus -0.56 ± 0.95 in control (P < 0.05). This reduction in lumen diameter on angiography was associated with a significant reduction in vessel (EEL) area especially in the groups treated with the 3 mm source at a dose rate > 50 cGylsec. The EEL area was 8.8 ± 1.7, 9.9 ± 1.7, and 8.9 ± 0.6 mm² in the 650, 1,300, and 1,900 cGy groups treated at a dose rate > 50 cGylsec compared to 11.7 ± 1.6 mm² in control arteries (P < 0.001). Conclusions: Endovascular β-radiation at high doses (3,500 cGy to adventitia) and dose rate < 50 cGylsec inhibits restenosis after balloon injury in the porcine model of coronary restenosis. This dose and dose rate is associated with a neutral effect on vascular remodeling. While lower doses of ICR did not worsen the PAS, a reduction in MLD and EEL area were observed. However, this adverse effect on angiographic restenosis and vascular remodeling appears to be largely limited to the subgroups treated at dose rates > 50 cGylsec.     

IDENTIFICATION OF SUBSETS OF PATIENTS WITH GRAVES''DISEASE BY CLUSTER ANALYSIS

We have applied cluster analysis methods to forty-nine laboratory and clinical characteristics (including 26 HLA-A, B antigens) observed in 196 Graves' disease patients. Three subgroups could be identified: group I (seventy-nine patients) had small goitres, low indices of autoimmunity and a tendency to remission with medical treatment; group IIa (twenty-nine patients) had clinical and laboratory features of 'Hashitoxicosis'; Group IIb (eighty-four patients) had a high incidence of ophthalmopathy, familial aggregation, marked evidence of autoaggression and a tendency to relapsing hyperthyroidism. The prevalence of HLA-B8 was 8.9% in group I, 20.7% in group IIa and 86.9% in group IIb. This study demonstrates that Graves' disease can be subdivided using cluster analysis into clinically relevant subgroups which are further distinguished by their correlation with HLA-B8. Possible immunological bases for these observed patterns are discussed.     

Catheter Ablation Induced Reversal of Chronic Left Ventricular Dysfunction in Permanent Junctional Tachycardia

Three patients with the permanent form of junctional tachycardia are reported. All had a normal cardiac function when the rhythm disorder was discovered. The basis for tachycardia in the three cases was atrioventricular junctional reentry whose retrograde limb was a concealed posteroseptal accessory pathway. Because of the development of heart failure over the years, one patient had His bundle ablation combined with pacemaker insertion, and the others underwent catheter ablation of the accessory pathway. Reversal of left ventricular involvement, as ossessed by chest X ray and echocardiography was noted in every patient. Ejection fraction in one patient, measured by radionuclide angiography, returned to normal 3 months later. Thus catheter ablation of permanent junctional tachycardia can effectively suppress rhythmic cardiomyopathy.