Clinical Application of PET/CT Fusion Imaging for Three-Dimensional Myocardial Scar and Left Ventricular Anatomy during Ventricular Tachycardia Ablation

Background: Image integration has the potential to display three-dimensional (3D) scar anatomy and facilitate substrate characterization for ventricular tachycardia (VT) ablation. However, the current generation of clinical mapping systems cannot display 3D left ventricle (LV) anatomy with embedded 3D scar reconstructions or allow display of border zone and high-resolution anatomic scar features.
Objective: This study reports the first clinical experience with a mapping system allowing an integrated display of 3D LV anatomy with detailed 2D/3D scar and border zone reconstruction.
Methods: Ten patients scheduled for VT ablation underwent contrast-enhanced computed tomography (CT) and Rubidium-82 perfusion/F-18 Fluorodeoxyglucose metabolic Positron Emission Tomography (PET) imaging to reconstruct 3D LV and scar anatomy. LV and scar models were co-registered using a 3D mapping system and analyzed with a 17-segment model. Metabolic thresholding was used to reconstruct the 3D border zone. Real-time display of CT images was performed during ablation.
Results: Co-registration (error 4.3 ± 0.7 mm) allowed simultaneous visualization of 3D LV anatomy and embedded scar and guided additional voltage mapping. Segments containing homogenous or partial scar correlated in 94.4% and 85.7% between voltage maps and 3D PET scar reconstructions, respectively. Voltage-defined scar and normal myocardium had relative FDG uptakes of 40 ± 13% and 89 ± 30% (P < 0.05). The 3D border zone correlated best with a 46% metabolic threshold. Real-time display of registered high-resolution CT images allowed the simultaneous characterization of scar-related anatomic changes.
Conclusion: Integration of PET/CT reconstruction allows simultaneous 3D display of myocardial scar and border zone embedded into the LV anatomy as well as the display of detailed scar anatomy. Multimodality imaging may enable a new image-guided approach to substrate-guided VT ablation.     

Multislice Computed Tomographic Findings in Symptomatic Patients After Amplatzer Septal Occluder Device Implantation

Background: Complications of transcatheter closure of atrial septal defects (ASDs) include pericardial effusion, tamponade, and even death. Transthoracic echocardiography in the adult is often limited by poor acoustic windows that lead to incomplete device assessment. Advances in multislice computed tomography (MSCT) provide an alternative modality to assess the anatomy of the Amplatzer Septal Occluder (ASO) device.
Objective: The purpose of this study was to determine the feasibility of MSCT in providing anatomic information in patients with persistent or recurrent symptoms after transcatheter closure of ASDs with ASO devices.
Methods: A retrospective analysis of adult patients who underwent ASO device implantation with subsequent MSCT imaging as a result of symptoms from June 2006 to May 2007 was performed. Data analysis included age, gender, size of ASO device, relationship of the device to surrounding structures, symptoms, and the length of time between device implantation and onset of symptoms.
Results: Eleven patients were identified with a mean age of 41 years. Patients presented with symptoms 1 week to 2.4 years after implantation. ASO size ranged from 8 to 36 mm. MSCT provided detailed information in all 11 cases regarding anatomic location of the device with respect to surrounding structures. Nonobstructive coronary plaque disease was identified in one patient. Two patients had pericardial effusions.
Conclusions: Cardiac symptoms after ASO implant deserve thorough investigation. MSCT is feasible in the assessment of such patients and offers a unique assessment of the device to surrounding anatomic structures and should be considered as a useful adjunct to echocardiography in symptomatic patients.     

Evaluation of recombinant protein r140, a polypeptide segment of tegumental glycoprotein Sm25, as a defined antigen vaccine against Schistosoma mansoni

To investigate the role of tegumental glycoprotein Sm25 in protective immunity against schistosomiasis, codons 43-182 of its gene (GP22) were amplified by PCR and cloned in the pET 15b bacterial expression system. Recombinant protein r140 was inducibly expressed in the presence of rifampicin and purified by Ni-affinity chromatography. In different vaccination trials, Balb/c mice and Fischer rats repeatedly immunized with r140 in combination with one of several adjuvants (alum, cholera toxin or complexed into proteosomes) produced high titre anti-r140 responses. These antibodies detected an N-glycanase sensitive, 25 kDa antigen in a detergent solubilized worm fraction using Western immunoblotting. The choice of adjuvant affected the isotype distribution of the specific anti-r140 antibodies. Despite the presence of high antibody titres and isotypes which have been shown to correlate with protective immunity, protection against subsequent cercarial challenge was not observed. In addition, no appreciable effects on worm sex ratios or liver egg yields were detected in mice. Studies involving biotin labelling of membrane proteins in live worms showed that the majority of anti-r140 reactive molecules present in adult schistosomes are biotinylated after permeabilization of the parasite surface. Several possibilities to account for the lack of protective immunity are analysed .     

Follow-up of Gambian children recruited to a pilot safety and immunogenicity study of the malaria vaccine SPf66

A pilot safety and immunogenicity trial of the malaria vaccine SPf66 was undertaken in The Gambia in 1993. One hundred and fifty infants aged 6–11 months were immunized with either 0.5 mg or 1.0 mg of SPf66 produced either in Colombia or in the USA or with a control vaccine. Children who received SPf66 experienced more clinical attacks of malaria than did children in the control group during the first period of surveillance and the difference in incidence between children who had received high dose Colombian vaccine and the control children was statistically significant at the 5% level. During the 1995 malaria transmission season, 127 children from the original cohort of 150 were observed. During 18 weeks of intensive surveillance, the incidence of clinical malaria was again higher among children who had received SPf66 than among children who had received inactivated polio vaccine (6.23 vs 4.89 clinical attacks per 1000 days at risk), the effect being most marked among children who were in the high dose groups, but differences between groups were now no longer statistically significant .     

Malignancy: Granulocyte Colony Stimulating Factor Increases the Efficacy of Conventional Amphotericin in the Treatment of Presumed Deep-Seated Fungal Infection in Neutropenic Patients following Intensive Chemotherapy or Bone Marrow Transplantation for Haematological Malignancies

A prospective, comparative study of empiric amphotericin B with, or without, granulocyte colony stimulating factor was carried out to assess whether the addition of granulocyte colony stimulating factor to empiric amphotericin B improves the clinical response in neutropenic patients with suspected or proven fungal infection. Fifty nine neutropenic adults with haematological malignancy and antibiotic-refractory fever or clinical evidence of deep-seated fungal infection were studied. Patients received intravenous colloidal amphotericin B (1 milligram per kilogram body weight) with or without subcutaneous granulocyte colony stimulating factor (three to five micrograms per kilogram body weight). Thirty patients received amphotericin alone and 29 amphotericin plus granulocyte colony stimulating factor. Nearly twice as many patients responded to amphotericin B with concomitant administration of granulocyte colony stimulating factor (62%) as responded to amphotericin alone (33%; difference in proportions 0.29, 95%CI 0.03-0.54). Clinical response in patients receiving granulocyte colony stimulating factor coincided with neutrophil recovery in most cases. Addition of granulocyte colony stimulating factor to empiric amphotericin B significantly reduced the number of patients requiring salvage therapy with lipid-associated or liposomal formulations of amphotericin B addition of granulocyte colony stimulating factor to empiric intravenous amphotericin B improves the response rate and thereby reduces the number of patients requiring salvage therapy with liposomal or lipid-associated preparations of amphotericin B.     

A New Defibrillator Discrimination Algorithm Utilizing Electrogram Morphology Analysis

Inappropriate therapies delivered by implantable cardioverter defibrillators (ICDs) for supraventricular arrhythmias remain a common problem, particularly in the event of rapidly conducted atrial fibrillation or marked sinus tachycardia. The ability to differentiate between ventricular tachycardia and supraventricular arrhythmias is the major goal of discrimination algorithms. Therefore, we developed a new algorithm, SimDis, utilizing morphological features of the shocking electrograms. This algorithm was developed from electrogram data obtained from 36 patients undergoing ICD implantation. An independent test set was evaluated in 25 patients. Recordings were made in sinus rhythm, sinus tachycardia, and following the induction of ventricular tachycardia and atrial fibrillation. The arrhythmia complex is defined as wide if the duration is at least 30% greater than the template in sinus rhythm. For narrow complexes, four maximum and minimum values were measured to form a 4-element feature vector, which was compared with a representative feature vector during normal sinus rhythm. For each rhythm, any wide complex was classified as ventricular tachycardia. For narrow complexes, the second step of the algorithm compared the electrogram with the template, computing similarity and dissimilarity values. These values were then mapped to determine if they fell within a previously established discrimination boundary. On the independent test set, the SimDis algorithm correctly classified 100% of ventricular tachycardias (27/27), 98% of sinus tachycardias (54/55), and 100% of episodes of atrial fibrillation (37/37). We conclude that the SimDis algorithm yields high sensitivity (100%) and specificity (99%) for arrhythmia discrimination, using the computational capabilities of an ICD system.     

Anatomy of the Coronary Sinus and Epicardial Coronary Venous System in 620 Hearts: An Electrophysiology Perspective

Anatomy of the Coronary Venous System . Introduction: Cannulation of the coronary sinus (CS) is a prerequisite for left ventricular (LV) pacing and certain ablation procedures. The detailed regional anatomy for the coronary veins and potential anatomic causes for difficulty with these procedures has not been established. Methods and Results: Therefore, we performed macroscopic measurements in 620 autopsied hearts (mean age 60 ± 23 years, 44% female). The CS was preserved for analysis in 96%. Sixty‐three percent had a Thebesian valve that covered the posterior aspect of the CS ostium with extension to the superior (50%) and inferior aspects (18%) and was obstructive with fenestrations in 3 specimens. Partial or near occlusive valves were present occasionally at the ostium of the great cardiac vein (Vieussens; 8%) and middle cardiac vein (5%). Ninety‐three percent had left atrial branches, and 41% had at least one branch with lumen > 3 French. For CRT lead placement, the mid‐lateral LV was accessible from the middle cardiac vein (20%), the left posterior vein (92%) or the anterior interventricular vein (86%). Among specimens where the left phrenic nerve was preserved it crossed the LV mid‐lateral wall in 45%. Conclusions: Epicardial coronary vein anatomy is variable, and the mid‐lateral LV wall can potentially be accessed through various tributaries of the epicardial veins. The orientation of the Thebesian valve favors cannulation of the CS from an anterior (ventricular) and inferior approach. Anterobasal, mid‐lateral, and inferior apical LV coronary veins lie in proximity to the course of the phrenic nerve. (J Cardiovasc Electrophysiol, Vol. 24, pp. 1‐6, January 2013)     

Failure of Rate Responsive Ventricular Pacing to Improve Physiological Performance in the Univentricular Heart

The physiological efficacy of single chamber, rate responsive ventricular pacing (VVIR) is unknown for symptomatic patients following the Fontan procedure for univentricular hearts. A total of six postoperative children, ages 6–21 years (mean 13), with symptomatic bradycardia requiring pacing therapy, underwent comparative treadmill exercise testing in randomized fixed rate (VVI) and VVIR pacing modes. In all instances, implanted activity pulse generators (Medtronic Model 8403) were programmed to identical age-appropriate low paced rates during WI and VVIR modes with the upper rate response at 150 ppm. All studies were performed at least 2 weeks apart. Physiological values of heart rate, blood pressure, work rate (watts), oxygen comsumption (VO₂), carbon dioxide production (VCO₂), and respiratory exchange ratio (RER) were monitored continuously during each test using a 1 minute incremental treadmill protocol. Ventilatory anaerobic threshold (VAT) was calculated from VO₂, VCO₂, and minute ventilation. The results demonstrated that although there was a significant increase in paced heart rate per minute throughout exercise (P < 0.01) with VVIR pacing, maximum watts, VO₂, and VAT remained unchanged. These findings indicate that in spite of an improved chronotropic response to exercise, children with Univentricular hearts following the Fontan procedure continue to demonstrate altered hemodynamics which negate potential benefits of VVIR pacing.     

Crohn's Disease of the Colon

Using accepted diagnostic criteria we have selected, for study, 160 patients with Crohn's disease involving the colon. There is a remarkable discrepancy between the clinical diagnosis prior to or at the time of initial admission to this hospital and the diagnosis following definitive investigation and observation of the progression of disease.
The peak age incidence occurred in the second decode The colitis group showed a greater percentage of patients over 30 years of age. Although histopathology was not obtained in all patients, there appeared to be sparing of the ascending colon in a small percentage (9%) of patients with ileocolitis.
Comparison of the clinical features of granulomatous disease limited to the colon and granulomatous ileocolitis shows a significantly greater incidence of extraintestinal symptoms and overt bleeding in the former. Nausea, vomiting, subacute obstruction, abdominal mass and internal fistulas were substantially more common in ileocolitis but the difference was not statistically significant. In this series retroperitoneal abscess did not occur in patients with disease localized to the colon. In the 10 patients with ileocolitis who developed an abscess, however, the site of fistula was the colon in four patients. In one of these, the abscess was left-sided.     

The views of general practitioners on the reuse of patients' own drugs

□ The quality of patient care could potentially improve through patients' own drugs (POD) schemes □ POD schemes need to be promoted to primary care professionals