Relationship between catheter contact force and radiofrequency lesion size and incidence of steam pop in the beating canine heart: electrogram amplitude, impedance, and electrode temperature are poor predictors of electrode-tissue contact force and lesion size.

BACKGROUND: Electrode-tissue contact force (CF) is believed to be a major factor in radiofrequency lesion size. The purpose of this study was to determine, in the beating canine heart, the relationship between CF and radiofrequency lesion size and the accuracy of predicting CF and lesion size by measuring electrogram amplitude, impedance, and electrode temperature. METHODS AND RESULTS: Eight dogs were studied closed chest. Using a 7F catheter with a 3.5 mm irrigated electrode and CF sensor (TactiCath, St. Jude Medical), radiofrequency applications were delivered to 3 separate sites in the right ventricle (30 W, 60 seconds, 17 mL/min irrigation) and 3 sites in the left ventricle (40 W, 60 seconds, 30 mL/min irrigation) at (1) low CF (median 8 g); (2) moderate CF (median 21 g); and (3) high CF (median 60 g). Dogs were euthanized and lesion size was measured. At constant radiofrequency and time, lesion size increased significantly with increasing CF (P<0.01). The incidence of a steam pop increased with both increasing CF and higher power. Peak electrode temperature correlated poorly with lesion size. The decrease in impedance during the radiofrequency application correlated well with lesion size for lesions in the left ventricle but less well for lesions in the right ventricle. There was a poor relationship between CF and the amplitude of the bipolar or unipolar ventricular electrogram, unipolar injury current, and impedance. CONCLUSIONS: Radiofrequencylesion size and the incidence of steam pop increase strikingly with increasing CF. Electrogram parameters and initial impedance are poor predictors of CF for radiofrequency ablation.

The Propensity for Inducing Atrial Fibrillation: A Comparative Study on Old versus Young Rabbits.

It is well established that atrial fibrillation (AF) is far more common in elderly humans. Autonomic activation is thought to be an operative mechanism for AF propensity. The aim of the study was to investigate the impact of age on atrial tachyarrhythmia induction in a rabbit model. Six old (aged 4-6 years) and 9 young (aged 3-4 months) New Zealand white rabbits were subjected to a catheter-based electrophysiological study. Atrial tachyarrhythmia susceptibility was tested by burst pacing before and after infusion of increasing concentrations of acetylcholine. Both young and old rabbits were in normal sinus rhythm at the beginning of the infusion/burst pacing protocol. The old rabbits had faster heart rates and a marked increase in atrial tachyarrhythmias compared to the young rabbits. Nonsustained and sustained AF events were more frequent in the old rabbits. No significant fibrosis was observed in the atria of either young or old rabbits. In conclusion, the old rabbits have a greater propensity for induction of AF. The significantly faster heart rates in the old rabbits suggest that dominant sympathetic activity may play an important role in the propensity for AF in this group.

Atrial tachycardia provoked in the presence of activating autoantibodies to ß2-adrenergic receptor in the rabbit.

BACKGROUND: A recent clinical study of patients with inappropriate sinus tachycardia reported that autoantibodies to ß-adrenergic receptors (ß2ARs) could act as agonists to induce atrial arrhythmias. OBJECTIVE: To test the hypothesis that activating autoantibodies to the ß2AR in the rabbit atrium are arrhythmogenic. METHODS: Five New Zealand white rabbits were immunized with a ß2AR second extracellular loop peptide to raise ß2AR antibody titers. A catheter-based electrophysiologic study was performed on anesthetized rabbits before and after immunization. Arrhythmia occurrence was determined in response to burst pacing before and after the infusion of acetylcholine in incremental concentrations of 10 µM, 100 µM, and 1 mM at 1 mL/min. RESULTS: In the preimmune studies when ß2AR antibody titers were undetectable, of a total of 20 events, only 3 episodes of nonsustained (<10 seconds) atrial arrhythmias were induced. In the postimmune studies when ß2AR antibody titers ranged from 1:160,000 to 1:1.28 million, burst pacing induced 10 episodes of nonsustained or sustained (≥10 seconds) arrhythmias in 20 events (P = .04 vs preimmune; χ(2) and Fisher exact test). Taking into account only the sustained arrhythmias, there were 6 episodes in 20 events in the postimmune studies compared with 0 episodes in 20 events in the preimmune studies (P = .02). Immunized rabbits demonstrated immunoglobulin G deposition in the atria, and their sera induced significant activation of ß2AR in transfected cells in vitro compared to the preimmune sera. CONCLUSIONS: Enhanced autoantibody activation of ß2AR in the rabbit atrium leads to atrial arrhythmias mainly in the form of sustained atrial tachycardia.

Onycholemmal carcinoma: a morphologic comparison of 6 reported cases.

BACKGROUND: We report 6 new cases of onycholemmal carcinoma, a rare, often misdiagnosed, subcategory of squamous cell carcinoma. All reported cases to date have been treated with amputation of the affected digit. OBJECTIVE: The purpose of this study was to present the clinical and pathological features of each new case and to discuss treatment options that spare digit functionality. METHODS: Hematoxylin-eosin stains were performed on tumor sections and examined using light microscopy. In situ hybridization using probes against human papillomavirus were examined in 1 case. RESULTS: The female to male ratio was 1:1 with involvement of fingers in 3, thumb in 1, and toe in 1. Among the symptoms were onycholysis, periungual erythema, and pain; symptom duration ranged from 6 months to 2 years. Histologically, all cases showed a well-differentiated atypical infiltrative squamous proliferative lesion exhibiting a lobulated and cystic pattern of growth in the dermis. Abrupt keratinization reminiscent of trichilemmal keratinization was noted. Mohs micrographic surgery and radiation therapy were used as primary treatment modalities, maintaining digit functionality and achieving remission. LIMITATIONS: Limitations of this study included the small number of cases, the infrequency with which this tumor has been reported in the literature, and the inability to obtain follow-up on an older archival case. CONCLUSIONS: Onycholemmal carcinoma is a distinct type of squamous cell carcinoma arising from the nail isthmus; its natural clinical course is indolent. In this regard less aggressive digit-sparing treatment modalities such as radiation or Mohs micrographic surgery should be considered.

Cytogenetic and comparative genomic hybridization studies of an esophageal giant fibrovascular polyp: a case report.

Esophageal giant fibrovascular polyps are rare and are thought to represent redundant tumorlike or hamartomatous esophageal folds. Although most patients present with slowly evolving dysphagia, a minority present with acute respiratory distress or even death caused by asphyxia. We present the pathologic and cytogenetic findings of an 18-cm esophageal giant fibrovascular polyp in a 49-year-old woman who presented with odynophagia and dysphagia. The histologic findings are that of classic esophageal giant fibrovascular polyp as previously described in the literature. Cytogenetic study revealed an abnormal karyotype, and comparative genomic hybridization analysis showed regional amplifications of chromosomes 3 and 12 and a possible loss of 22q13.3-qter. The significance of these cytogenetic findings is unclear but may suggest a neoplastic process in the pathogenesis of esophageal giant fibrovascular polyps.

Tracheal and endobronchial involvement in disseminated histoplasmosis: a case report.

Histoplasmosis is an endemic fungal infection that can involve any organ when disseminated. Although oral, pharyngeal, laryngeal, and endobronchial involvement have been described, direct tracheal involvement has not been reported. We describe the first case of disseminated histoplasmosis with direct involvement of the trachea. The endobronchial manifestations of histoplasmosis are reviewed.

Canine model of esophageal injury and atrial-esophageal fistula after applications of forward-firing high-intensity focused ultrasound and side-firing unfocused ultrasound in the left atrium and inside the pulmonary vein.

BACKGROUND: Left atrial-esophageal fistula is a serious and poorly understood complication of catheter ablation of atrial fibrillation. The purpose of this study was to (1) develop a canine model of esophageal injury and left atrial-esophageal fistula after applications of forward-firing high-intensity focused ultrasound (HIFU) and side-firing unfocused ultrasound (SFU); (2) examine the relationship to esophageal temperature (Eso-temp); and (3) study the evolution of injury/healing. METHODS AND RESULTS: Twenty dogs were studied. After transeptal puncture, HIFU catheter (ProRhythm Inc; 13 dogs) was positioned close to the esophagus, either outside (n=6) or inside (n=7) the inferior pulmonary vein (PV). In 7 other dogs, an SFU catheter was placed deep inside the PV, close to the esophagus. A balloon (20- to 25-mm diameter) with 7 thermocouples (2-mm separation) was positioned in the esophagus (Eso-balloon). Variable air filling of the Eso-balloon controlled the distance from the esophagus to the sonication source, pressing the esophagus against left atrium/PV. One to 9 (median, 5) HIFU (35 W) and 5 to 7 (median, 5) SFU (40 W) sonications were delivered for 40 seconds. Maximum luminal Eso-temp was closely related to HIFU Eso-balloon distance. For HIFU outside PV, Eso-temp >or=50 degrees C occurred only for HIFU Eso-balloon distance or=50 degrees C, with HIFU Eso-balloon distance up to 6.8 mm. Endoscopy identified esophageal ulcer immediately after ablation in 11 of 13 HIFU dogs and 7 of 7 SFU dogs, all with Eso-temp >or=50 degrees C. Endoscopy at 2 weeks showed ulcer healing in 5 of 11 chronic dogs and ulcer size progression with relaxation of the lower esophageal sphincter and esophagitis in 6 dogs. Two dogs developed left atrial-esophageal fistula and died at 2 weeks. CONCLUSIONS: This model produces esophageal ulcer when Eso-temp is >or=50 degrees C. Eso-temp is higher with HIFU/SFU applications closer to the esophagus and with HIFU/SFU applications inside the PV. Ulcer progression and left atrial-esophageal fistula were associated with reflux esophagitis.

Atypical distinctive dermal clear cell mesenchymal neoplasm arising in the scalp.

Distinctive dermal clear cell mesenchymal neoplasm (DDCCMN) is a newly described entity characterized by a dermal proliferation of neoplastic cells with clear to reticulated cytoplasm and vesicular nuclei. Atypical features in the form of nuclear pleomorphism and mitoses may be found. The histogenesis of these neoplastic clear cells is not currently known but they are thought to be mesenchymal in origin. Immunohistochemically, they stain positively for NKI-C3 and negatively for melanocytic, epithelial and lymphoid markers. All five cases originally reported by Lazar and Fletcher occurred in the lower extremities. We report herein a case of DDCCMN with atypical features arising in the scalp.

Novel contact force sensor incorporated in irrigated radiofrequency ablation catheter predicts lesion size and incidence of steam pop and thrombus.

BACKGROUND: An open-irrigated radiofrequency (RF) ablation catheter was developed to measure contact force (CF). Three optical fibers measure microdeformation of the catheter tip. The purpose of this study was to (1) validate the accuracy of CF sensor (CFS) (bench test); and (2) determine the relationship between CF and tissue temperatures, lesion size, steam pop, and thrombus during RF ablation using a canine thigh muscle preparation. METHODS AND RESULTS: CFS measurements (total 1409) from 2 catheters in 3 angles (perpendicular, parallel, and 45 degrees ) were compared with a certified balance (range, 0 to 50 g). CFS measurements correlated highly (R(2) > or =0.988; mean error, < or =1.0 g). In 10 anesthetized dogs, a skin cradle over the thigh muscle was superfused with heparinized blood at 37 degrees C. A 7F catheter with 3.5-mm saline-irrigated electrode and CFS (Endosense) was held perpendicular to the muscle at CF of 2, 10, 20, 30, and 40 g. RF was delivered (n=100) for 60 seconds at 30 or 50 W (irrigation 17 or 30 mL/min). Tissue temperature (3 and 7 mm depths), lesion size, thrombus, and steam pop increased significantly with increasing CF at each RF power. Lesion size was greater with applications of lower power (30 W) and greater CF (30 to 40 g) than at high power (50 W) with lower CF (2 to 10 g). CONCLUSIONS: This novel ablation catheter, which accurately measures CF, confirmed CF is a major determinant of RF lesion size. Steam pop and thrombus incidence also increases with CF. CFS in an open-irrigated ablation catheter that may optimize the selection of RF power and application time to maximize lesion formation and reduce the risk of steam pop and thrombus.

End-stage renal disease due to polyomavirus in a cardiac transplant patient.

BACKGROUND: A 51-year-old male orthotopic cardiac transplant recipient experienced a prolonged rejection episode immediately after transplantation. Three years and 5 months after transplantation, he presented with lower extremity swelling; at this presentation, the patient's serum creatinine level was 345 micromol/l (3.9 mg/dl), his urinalysis was trace positive for both protein and blood, the urinary sediment had no casts and his 24-hour urine collection showed 750 mg protein. The patient's renal function deteriorated over the next month, with his serum creatinine level reaching a peak of 530 micromol/l (6 mg/dl). He died 4 years and 3 months after transplantation as a result of an arrhythmia. INVESTIGATIONS: Physical examination, urine and blood analyses, ultrasound-guided renal biopsy and autopsy. DIAGNOSIS: Polyomavirus-associated nephropathy with the development of end-stage renal disease. MANAGEMENT: Adjustment of immunosuppressive therapy and initiation of hemodialysis.

Comparison of electrode cooling between internal and open irrigation in radiofrequency ablation lesion depth and incidence of thrombus and steam pop.

BACKGROUND: Electrode cooling by circulating fluid within the electrode (closed loop) or open irrigation facilitates radiofrequency (RF) ablation. This study compared lesion parameters between closed loop and open irrigation with the use of a canine model. METHODS AND RESULTS: In 8 anesthetized dogs, the skin over the thigh muscle was incised and raised, forming a cradle superfused with heparinized blood (activated clotting time >350 seconds) at 37 degrees C. A 7F 4-mm closed loop electrode (irrigation 36 mL/min) and 7.5F 3.5-mm open irrigation electrode (irrigation 17 mL/min) were positioned perpendicular to the thigh muscle at 10 g contact weight. RF was applied (n=121) at 20 or 30 W for 60 seconds in low (0.1 m/s) or high (0.5 m/s) pulsatile blood flow. Temperatures were measured in the electrode, electrode-tissue interface, and within the tissue at 3- and 7-mm depths. After each RF, the cradle was emptied to examine the electrode and interface for thrombus. There was no difference between closed loop and open irrigation in impedance, lesion depth, or tissue temperature at 20 or 30 W. Interface temperature and electrode temperature were greater in the closed loop application. Thrombus occurred in 32 of 63 closed loop versus 0 of 58 open irrigation RF applications (P<0.05) with interface temperature > or =80 degrees C in all 32 (electrode temperature <40 degrees C in 1, 40 degrees C to 50 degrees C in 26, and >50 degrees C in 5). With closed loop, interface temperature and thrombus incidence were greater at 30 W and low blood flow. With open irrigation, interface temperature remained low (< or =71 degrees C) with no difference between 20 and 30 W or between low and high blood flow. Steam pop occurred at 20 W in 4 of 35 closed loop and 0 of 30 open irrigation and at 30 W in 15 of 28 closed loop and 4 of 28 open irrigation applications (P<0.05). CONCLUSIONS: Lower interface temperature, thrombus, and steam pop, especially in low blood flow, indicate greater interface cooling with open irrigation.

Comparison of cryothermia and radiofrequency current in safety and efficacy of catheter ablation within the canine coronary sinus close to the left circumflex coronary artery.

INTRODUCTION: A canine model was used to compare cryoablation and radiofrequency ablation (RFA) within the coronary sinus (CS) in the ability to create a transmural CS myocardial (Trans-CSM) lesion and risk of coronary artery stenosis. METHODS: After CS and left circumflex (LCx) coronary angiography, an intravascular ultrasound (IVUS) probe was placed in LCx in 29 dogs. An irrigated RFA catheter (8 dogs) or N(2)O cryoablation catheter (21 dogs) was inserted into the CS and positioned within 2 mm of LCx, confirmed by IVUS. RF (30-50W) was applied for 60 seconds at 10 CS sites. Cryoablation (-75 degrees C) was performed with one (n = 7) or two (n = 14) 4-minute applications. Dogs were sacrificed at 1 week (8 RFA and 13 cryoablation) or 3 months (8 cryoablation). RESULTS: During RFA, IVUS showed wall thickening and LCx narrowing in 9 of 10 sites. Angiography at 5-minute post-RFA identified LCx narrowing (25-90%) at 6 of 10 sites and 25-75% narrowing at 4 of 9 sites at 1-week post-RFA. During cryoablation, IVUS showed reversible ice ball compression of LCx, and no LCx narrowing by angiography at 5 minutes, 1 week, or 3 months. Histology showed Trans-CSM lesion at 10 of 10 RFA sites and 20 of 21 cryoablation sites. RFA produced LCx medial necrosis at 7 of 10 sites, involving 20-50%(median 32.5%) of LCx circumference with loss of intima at 5 of 7 sites. Single and twice 4-minute cryoablation produced LCx medial necrosis at 2 of 7 and 8 of 14 sites (5-40%, median 25% circumference). Intima was preserved at 1 week (13/13) with minor proliferation (without narrowing) at 2 of 8 sites at 3 months. CONCLUSIONS: Cryoablation in CS within 2 mm of LCx produces Trans-CSM lesions similar to RFA with lower risk of LCx stenosis than RFA.

High incidence of thrombus formation without impedance rise during radiofrequency ablation using electrode temperature control.

The authors hypothesized that during RF ablation, the electrode to tissue interface temperature may significantly exceed electrode temperature in the presence of cooling blood flow and produce thrombus. In 12 anesthetized dogs, the skin over the thigh muscle was incised and raised to form a cradle that was superfused with heparinized canine blood (ACT > 350 s) at 37 degrees C. A 7 Fr, 4-mm or 8-mm ablation electrode containing a thermocouple was held perpendicular to the thigh muscle at 10-g contact weight. Interface temperature was measured at opposite sides of the electrode using tiny optical probes. RF applications (n = 157) were delivered at an electrode temperature of 45 degrees C, 55 degrees C, 65 degrees C, and 75 degrees C for 60 seconds, with or without pulsatile blood flow (150 mL/min). Without blood flow, the interface temperature was similar to the electrode temperature. With blood flow, the interface temperature (side opposite blood flow) was up to 36 degrees C and 57 degrees C higher than the electrode temperature using the 4- and 8-mm electrodes, respectively. After each RF, the cradle was emptied and the electrode and interface were examined. Thrombus developed without impedance rise at an interface temperature as low as 73 degrees C without blood flow and 80 degrees C with blood flow (11/16 RFs at 65 degrees C electrode temperature using 4 mm and 13/13 RFs at an electrode temperature of 55 degrees C using an 8-mm electrode with blood flow). With blood flow, interface temperature markedly exceeded the electrode temperature and the difference was greater with an 8-mm electrode (due to greater electrode cooling). In the presence of blood flow, thrombus occurred without an impedance rise at an electrode temperature as low as 65 degrees C with a 4-mm electrode and 55 degrees C with an 8-mm electrode.

Pan-cadherin as a high level phenotypic biomarker for prostate cancer.

PURPOSE: High level phenotypic biomarkers such as cadherins are needed to identify individuals at risk for biologically active prostate cancer and determine which individuals with elevated prostate specific antigen or a prostate nodule are candidates for re-biopsy. Cadherins are a high level phenotypic biomarker associated with decreased cell adhesion, which is a cardinal event in carcinogenesis. Recently we reported that G-actin and tissue transglutaminase type II are potential biomarkers for prostate cancer. In this study we present cadherins as a potential third component of the biomarker profile. MATERIALS AND METHODS: Prostate tissues from 38 patients with cancer and 33 controls with a 10-year prostate cancer-free followup were labeled for pan-cadherin by immunohistochemical testing. Immunoreactivity was quantified using a Pathology Workstation (Autocyte Inc., Elon College, North Carolina). RESULTS: Visually benign glands from controls generally expressed cadherins, whereas regions of adenocarcinoma were generally negative. On quantitative immunohistochemistry 36 of 38 prostate cancer cases expressed a lower mean percent area positive for cadherin than the 19 benign prostatic hyperplasia and 14 prostatitis cases (odds ratio 978, 95% confidence interval 45 to 21,140, relative risk 18, 95% confidence interval 5 to 67, p <0.0001). Receiver operating characteristics analysis of immunohistochemical testing data showed that an optimal threshold of 7 produced 95% sensitivity and 100% specificity. CONCLUSIONS: Quantitative down-regulation of cadherin expression in prostate cancer tissue sections is a strong biomarker for prostate cancer. Analysis of cadherin and other high level phenotypic biomarker expression in the premalignant field may provide additional diagnostic information to decide which patients need re-biopsy, more intensive monitoring or chemoprevention.