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Biomedical subjects

John M Morgan

Publications and source records attributed to John M Morgan.

At least 19 recordsLinked to original sources
PubMed2006

External quality assurance of HER2 fluorescence in situ hybridisation testing: results of a UK NEQAS pilot scheme.

BACKGROUND AND AIMS: Trastuzumab provides clinical benefit for advanced and early breast cancer patients whose tumours over-express or have gene amplification of the HER2 oncogene. The UK National External Quality Assessment Scheme (NEQAS) for immunohistochemical testing was established to assess and improve the quality of HER2 immunohistochemical testing. However, until recently, no provision was available for HER2 fluorescence in situ hybridisation (FISH) testing. A pilot scheme was set up to review the performance of FISH testing in clinical diagnostic laboratories. METHODS: FISH was performed in 6 reference and 31 participating laboratories using a cell line panel with known HER2 status. RESULTS: Using results from reference laboratories as a criterion for acceptable performance, 60% of all results returned by participants were appropriate and 78% either appropriate or acceptable. However, 22.4% of results returned were deemed inappropriate, including 13 cases (4.2%) where a misdiagnosis would have been made had these been clinical specimens. CONCLUSIONS: The results of three consecutive runs show that both reference laboratories and a proportion of routine clinical diagnostic (about 25%) centres can consistently achieve acceptable quality control of HER2 testing. Data from a significant proportion of participating laboratories show that further steps are required, including those taken via review of performance under schemes such as NEQAS, to improve quality of HER2 testing by FISH in the "real world".

Biomarkers, Tumor↗
PubMed2006

A comparison of empiric to physician-tailored programming of implantable cardioverter-defibrillators: results from the prospective randomized multicenter EMPIRIC trial.

OBJECTIVES: The purpose of this randomized study was to determine whether a strategically chosen standardized set of programmable settings is at least as effective as physician-tailored choices, as measured by the shock-related morbidity of implantable cardioverter-defibrillator (ICD) therapy. BACKGROUND: Programming of ventricular tachyarrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF]) detection and therapy for ICDs is complex, requires many choices by highly trained physicians, and directly influences the frequency of shocks and patient morbidity. METHODS: A total of 900 ICD patients were randomly assigned to standardized (EMPIRIC, n = 445) or physician-tailored (TAILORED, n = 455) VT/VF programming and followed for 1 year. RESULTS: The primary end point was met: the adjusted percentages of both VT/VF (22.3% vs. 28.7%) and supraventricular tachycardia or other non-VT/VF event episodes (11.9% vs. 26.1%) that resulted in a shock were non-inferior and lower in the EMPIRIC arm compared to the TAILORED arm. The time to first all-cause shock was non-inferior in the EMPIRIC arm (hazard ratio = 0.95, 90% confidence interval 0.74 to 1.23, non-inferiority p = 0.0016). The EMPIRIC trial had a significant reduction of patients with 5 or more shocks for all-cause (3.8% vs. 7.0%, p = 0.039) and true VT/VF (0.9% vs. 3.3%, p = 0.018). There were no significant differences in total mortality, syncope, emergency room visits, or unscheduled outpatient visits. Unscheduled hospitalizations occurred significantly less often (p = 0.001) in the EMPIRIC arm. CONCLUSIONS: Standardized empiric ICD programming for VT/VF settings is at least as effective as patient-specific, physician-tailored programming, as measured by many clinical outcomes. Simplified and pre-specified ICD programming is possible without an increase in shock-related morbidity.

Aged↗
PubMed2006

Passive electrode effect reduces defibrillation threshold in bi-filament middle cardiac vein defibrillation.

AIMS: To investigate whether a passive electrode effect decreases defibrillation threshold (DFT) in multi-filament middle cardiac vein (MCV) defibrillation. METHODS AND RESULTS: Twelve pigs underwent active housing (AH) insertion, with defibrillation coils placed transvenously in right ventricular apex and superior vena cava. The MCV was cannulated, and 1.12F, 50 mm coil electrodes (Ela Medical SA, France) were deployed in its right and left branches. Lead placement was possible in 11 of 12 animals. DFT (J, mean +/- SD) was determined by three-reversal binary search and compared between the MCV monofilament (single filament deployed) and the AH (25.9 +/- 10.9) and the MCV mono + passive filaments (both filaments deployed, one connected) and the AH (19.9 +/- 11.4); 24% DFT reduction P = 0.008. CONCLUSION: A bystander electrode adjacent to a monofilament electrode in the MCV reduces DFT by 24% when compared with monofilament MCV alone. Microfilament electrodes decrease DFT as auxiliary anode but not as sole anode.

Animals↗
PubMed2005

Global dynamic coupling of activation and repolarization in the human ventricle.

BACKGROUND: The ability to determine spatial and dynamic changes in ventricular repolarization may help to understand arrhythmogenic mechanisms in humans. We hypothesized that noncontact mapping could be used to investigate global activation-repolarization coupling in the human ventricle during steady state and premature extrastimulation. METHODS AND RESULTS: Activation-recovery intervals (ARIs) determined from reconstructed unipolar electrograms by the Ensite system were analyzed during sinus rhythm, constant pacing, spontaneous ventricular ectopic beats, and premature stimulation at intermediate and short coupling intervals in the left or right ventricle of 13 patients (6 female; mean age, 48 years) without structural myocardial disease. ARIs were measured from 32 sites in each ventricle with the use of a method validated with monophasic action potential recordings and unipolar contact electrograms. Global T-wave distribution was displayed on a 3-dimensional geometry of the ventricle, with polarities opposite to the direction of activation during steady state and premature stimulation. There was a significant inverse correlation between activation times and ARIs during sinus rhythm, ventricular ectopy, and premature stimulation (r=0.72, slope=-0.76, P<0.001). Premature stimuli at short coupling intervals flattened the regression slope compared with sinus rhythm (-0.61 versus -0.81; P=0.05), but the global pattern of repolarization was preserved. In comparison to our method, the Wyatt method of ARI measurement failed to demonstrate significant coupling between activation and repolarization (r=0.34, slope=0.19). CONCLUSIONS: Global, dynamic repolarization mapping of the human ventricle is feasible. An inverse coupling of activation and repolarization during steady state and premature stimulation may preserve electric stability in the normal ventricle.

Atrial Fibrillation↗
PubMed2005

Global endocardial electrical restitution in human right and left ventricles determined by noncontact mapping.

OBJECTIVES: This study was aimed at evaluating global characteristics of electrical restitution in the human ventricle using noncontact mapping. BACKGROUND: Steep action potential restitution (slope >1) and conduction velocity (CV) restitution have been linked with propensity to ventricular fibrillation, but clinical measurement of global electrical restitution had not been feasible. METHODS: Activation-recovery interval (ARI) and CV restitution curves were simultaneously constructed from 16 regional segments of the left and right ventricles in 8 patients (6 male, 2 female, age 42 +/- 17 years) following successful ablation of idiopathic ventricular tachycardia in the absence of structural disease guided by the Ensite 3000 system (Endocardial Solutions Inc., St. Paul, Minnesota). The ARIs were determined from reconstructed unipolar electrograms as validated with monophasic action potential recordings. The ARI restitution slopes were determined using the overlapping least-squares linear segments. RESULTS: Global electrical restitution curves were heterogeneous in shape and distribution. ARI restitution slope was >1 at 25% of 128 sites. The overall mean slope was 0.79 and was greater in the left than the right ventricle (0.93 +/- 0.49 vs. 0.65 +/- 0.26, p < 0.001). Dispersion of ARI restitution slopes increased with decreasing diastolic intervals. The CV restitution operated over a narrower range of diastolic intervals compared with ARI restitution, reaching a plateau (10 +/- 6 ms vs. 38 +/- 13 ms, p < 0.001) after refractoriness. The magnitude of CV restitution was also greater (steeper) than ARI restitution (25 +/- 10% vs. 18 +/- 9%, p < 0.001). CONCLUSIONS: Noncontact mapping can be used to examine global electrical restitution in the human ventricle. The ARI restitution is heterogeneous, with a slope >1 at 25% of all sites. The heterogeneity of ARI and CV restitution may be important in determining myocardial electrical stability.

Adult↗
PubMed2005

Implantable loop recorders detect tachyarrhythmias in symptomatic patients with negative electrophysiological studies.

BACKGROUND: Implantable loop recorders (ILR) are a valuable tool in the investigation of syncope and compare favourably with non-invasive and intracardiac electrophysiological assessment of bradycardia. They are known to detect tachyarrhythmias but have not been shown to add to the diagnostic yield of electrophysiological testing in symptomatic patients. METHODS: We prospectively studied the first 41 patients (aged 48+/-19 years) in whom ILR were used at our institution after negative electrophysiological studies (EPS). All patients were symptomatic with palpitations (11), syncope (22) or both (8). Nine patients had known structural heart disease (two ischaemic, four cardiomyopathy, two valvular and one congenital). Patients were assessed according to demographic factors, symptoms and investigations. Loop recordings were analysed and assessed according to conventional criteria. RESULTS: Among 41 patients in whom electrophysiological studies had failed to demonstrate arrhythmias, six were found to have clinically significant tachyarrhythmias (four ventricular and two supraventricular). CONCLUSION: ILR diagnose prognostically significant tachyarrhythmias in symptomatic patients with negative electrophysiological studies.

Adult↗
PubMed2004

A trial design for evaluation of empiric programming of implantable cardioverter defibrillators to improve patient management.

The delivery of implantable cardioverter defibrillator (ICD) therapy is sophisticated and requires the programming of over 100 settings. Physicians tailor these settings with the intention of optimizing ICD therapeutic efficacy, but the usefulness of this approach has not been studied and is unknown. Empiric programming of settings such as anti-tachycardia pacing (ATP) has been demonstrated to be effective, but an empiric approach to programming all VT/VF detection and therapy settings has not been studied. A single standardized empiric programming regimen was developed based on key strategies with the intention of restricting shock delivery to circumstances when it is the only effective and appropriate therapy. The EMPIRIC trial is a worldwide, multi-center, prospective, one-to-one randomized comparison of empiric to physician tailored programming for VT/VF detection and therapy in a broad group of about 900 dual chamber ICD patients. The trial will provide a better understanding of how particular programming strategies impact the quantity of shocks delivered and facilitate optimization of complex ICD programming.

Journal Article↗
PubMed2004

Determination of human ventricular repolarization by noncontact mapping: validation with monophasic action potential recordings.

BACKGROUND: Noncontact mapping (NCM) has not been validated as a clinical technique to measure ventricular repolarization. We used NCM to determine repolarization characteristics by analysis of reconstructed unipolar electrograms (UEs) at the same sites as monophasic action potential (MAP) recordings in the human ventricle. METHODS AND RESULTS: MAPs were recorded from a total of 355 beats at 46 sites in the left or right ventricle of 9 patients undergoing ablation of ventricular tachycardia guided by NCM (EnSite system). Measurements were made during sinus rhythm, constant right ventricular pacing, and ventricular extrastimuli during restitution-curve construction. The EnGuide locator signal was used to document MAP catheter locations on the endocardial geometry. UE-determined activation-recovery interval (ARI) measured at the maximum derivative of the T wave (Wyatt method) and the minimum derivative of the positive T wave (alternative method) was correlated with MAP measured at 90% repolarization (MAP90%) at the same sites. ARI correlated with MAP90% during steady state by the Wyatt method (r=0.83, P<0.001) and the alternative method (r=0.94, P<0.001). Restitution curves constructed from MAP and UE data exhibited the same characteristics, with a mean correlation coefficient of 0.95 (range, 0.90 to 0.99, P<0.001). The error between ARI and MAP90% was greater over a shorter diastolic coupling interval but was not influenced by distance of the sampling site from the multielectrode array. CONCLUSIONS: NCM accurately determines steady-state and dynamic endocardial repolarization in humans. Global, high-density, NCM data could be used to characterize abnormalities of human ventricular repolarization.

Action Potentials↗
PubMed2004

Successful percutaneous ablation of ventricular tachycardia in congenitally corrected transposition of the great arteries, a case report.

Ventricular tachycardia (VT) is rarely recognized in patients with congenitally corrected transposition of the great arteries (CCTGA). We describe a 48-year-old woman with CCTGA, systemic atrioventricular valve replacement for Ebsteinoid malformation of the valve, ventricular dysfunction and ventricular tachycardia related to the previous surgical scar. The patient had successful non-contact mapping and radiofrequency ablation of the offending tachycardia substrate.

Cardiac Pacing, Artificial↗
PubMed2004

Radiofrequency ablation of idiopathic ventricular fibrillation guided by noncontact mapping.

A 32-year-old man with idiopathic ventricular fibrillation and an implantable cardioverter defibrillator presented during a ventricular fibrillation storm. Frequent monomorphic ventricular ectopics with left bundle branch block morphology were documented, some of which initiated fibrillation. He underwent noncontact mapping of the right ventricle, during which the ventricular ectopics were mapped to a site in the free wall displaying a diastolic potential 80 ms before ectopic QRS onset. Following three radiofrequency energy applications, the ectopics were abolished. After 11-month follow-up, he has experienced no further arrhythmias. Noncontact mapping may identify ablatable triggers of ventricular fibrillation and lead to successful outcomes even when only single ectopics are present.

Adult↗
PubMed2004

High-density mapping of left atrial endocardial activation during sinus rhythm and coronary sinus pacing in patients with paroxysmal atrial fibrillation.

INTRODUCTION: This study was designed to record global high-density maps of left atrial endocardial activation during sinus rhythm and coronary sinus pacing. METHOD AND RESULTS: Noncontact mapping of the left atrium was performed in nine patients with paroxysmal atrial fibrillation undergoing pulmonary vein ablation procedures. High-density isopotential and isochronal activation maps were superimposed on three-dimensional reconstructions of left atrial geometry. Mapping was repeated during pacing from sites within the coronary sinus. Earliest left atrial endocardial activation occurred anterior to the right pulmonary veins in seven patients and on the anterosuperior septum in two patients. A line of conduction block was seen in the posterior wall and inferior septum in all patients. The direction of activation in the left atrial myocardium overlying the coronary sinus was different from the electrogram sequence in the coronary sinus catheter in 6 of 9 patients. During coronary sinus pacing, activation entered the left atrium a mean (SD) of 41 (13) ms after the pacing stimulus at a site 12 (10) mm from the endocardium overlying the pacing electrode. Lines of conduction block were present in the posterior wall and inferior septum. CONCLUSION: In patients with paroxysmal atrial fibrillation, lines of conduction block are present in the left atrium during sinus rhythm and coronary sinus pacing. Electrograms recorded in the coronary sinus infrequently correspond to the direction of activation in the overlying left atrial myocardium.

Adult↗
PubMed2004

The effects of niacin on lipoprotein subclass distribution.

Dyslipidemia is a heterogeneous metabolic condition; high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein represent families of lipoprotein particles that differ in size and composition and vary in atherogenicity. Lipoprotein subclasses containing apolipoprotein B promote atherosclerosis, of which the most atherogenic appear to be the small, dense LDL and large very-low-density lipoprotein subclasses, while the large HDL2 subclass, which transports esterified cholesterol from the periphery to the liver, is considered the more cardioprotective. Niacin has long been known to improve concentrations of all major lipids and lipoproteins, but it also has consistently favorable effects on subclass distribution. A MEDLINE search was conducted for clinical studies reporting the effects of niacin on lipoprotein subclasses. The niacin-associated elevations in HDL cholesterol likely stem from differential drug effects on subclasses, producing favorable changes in levels of HDL2 and apolipoprotein A-I. Niacin has more moderate LDL cholesterol-lowering efficacy, but this change is associated with an increase in LDL particle size and a shift from small LDL to the less atherogenic, large LDL subclasses. In addition, it also tends to decrease concentrations of the larger very-low-density lipoprotein subclasses. Niacin confers diverse benefits with respect to both the quantity and quality of lipid and lipoprotein particles.

Anticholesteremic Agents↗
PubMed2004

Rosuvastatin alone or with extended-release niacin: a new therapeutic option for patients with combined hyperlipidemia.

Combination therapy with a statin and niacin may provide optimal therapy for patients with combined hyperlipidemia and low levels of high-density lipoprotein (HDL) cholesterol. The authors assessed the efficacy and safety of rosuvastatin monotherapy, extended-release (ER) niacin monotherapy, or rosuvastatin and ER niacin combined therapy in patients with atherogenic dyslipidemia. In a 24-week, open-label, multicenter trial, men and women aged > or =18 years with fasting levels of total cholesterol > or =200 mg/dL, HDL cholesterol > or =45 mg/dL, triglycerides 200-800 mg/dL, and apolipoprotein B > or =110 mg/dL were randomly assigned to one of four treatment groups: rosuvastatin 10-40 mg, ER niacin 0.5-2 g, rosuvastatin 40 mg plus ER niacin 0.5-1 g, or rosuvastatin 10 mg plus ER niacin 0.5-2 g. Daily doses of rosuvastatin 40 mg monotherapy reduced low-density lipoprotein (LDL) cholesterol and non-HDL cholesterol levels significantly more than did either ER niacin 2 g monotherapy or rosuvastatin 10 mg combined with ER niacin 2 g. Addition of ER niacin 1 g to rosuvastatin 40 mg did not further reduce total or non-HDL cholesterol. Triglyceride reductions were similar among the four treatment groups. ER niacin mono- and combined therapy produced significantly greater rises in HDL cholesterol and apolipoprotein A-1 than did rosuvastatin monotherapy. Rosuvastatin monotherapy was better tolerated than ER niacin taken either alone or with rosuvastatin. In this study, rosuvastatin very effectively improved the three major lipoprotein-lipid abnormalities of combined hyperlipidemia.

Adult↗
PubMed2004

Examination of a middle cardiac vein defibrillation coil as stand-alone anode, auxiliary anode, and bystander electrode in a transvenous defibrillation circuit.

In porcine studies anodes in the middle cardiac vein compare favorably with those in the RV. It has not been demonstrated whether the RV and middle cardiac vein or the middle cardiac vein alone anodes are superior when shocking to a conventional SVC and active housing cathode nor whether a bystander middle cardiac vein electrode exerts a passive electrode affect. Twelve pigs were anesthetized and had an active housing implanted in the left pectoral region and defibrillation coils placed at the RV apex and in the SVC. A custom-made defibrillation coil (Ela Medical) was advanced into the middle cardiac vein through a 9 Fr transvenous catheter. The DFT for three anodes (RV; RV and middle cardiac vein; middle cardiac vein) to the SVC and active housing was then assessed by a three reversal binary search, the order of testing was randomized. In seven animals DFT was assessed in the same way for the configuration of RV to SVC and active housing twice more, with and without a bystander middle cardiac vein coil electrode in place. The results were middle cardiac vein 7.5 +/- 1.7 J, RV and middle cardiac vein 7.3 +/- 1.7 J reduced DFT significantly compared to RV 13.8 +/- 4.2 J (both P < 0.000). There was no significant difference between the middle cardiac vein and the middle cardiac vein and RV (P = 0.67, 95% CI for difference -0.64-0.96). The DFT of RV to SVC and the active housing was the same with (13.2 +/- 4.0) and without (13.7 +/- 4.2) the middle cardiac vein bystander coil in place (P = 0.177, 95% CI for difference -0.33-1.33 J). Shocking to a SVC and active housing cathode, middle cardiac vein, and RV and middle cardiac vein anodes are equally effective in lowering DFT compared to the RV. The middle cardiac vein coil electrode does not exert a passive electrode affect on the RV to the SVC and active housing defibrillation.

Animals↗
PubMed2003

Effects of extended-release niacin on lipoprotein subclass distribution.

The efficacy of extended-release niacin (niacin ER) on lipoprotein subclasses was evaluated in patients with primary hypercholesterolemia using a proton nuclear magnetic resonance method. Paired plasma samples collected at baseline and after 12 weeks' treatment with niacin ER 1,000 (n = 21) or 2,000 (n = 20) mg/day or placebo (n = 19) were available for 60 eligible patients from a previous multicenter, randomized, controlled trial. Niacin ER increased high-density lipoprotein (HDL) cholesterol and decreased low-density lipoprotein (LDL) cholesterol and very low-density lipoprotein triglycerides in a dose-dependent manner relative to placebo. Niacin ER increased large HDL particles (H5 and H4, corresponding to the HDL(2ab) fraction) without having a net effect on small HDL particles (H3, H2, and H1, corresponding to the HDL(3abc) fraction). It also decreased smaller, denser LDL particles (L1 and L2) and increased the larger, more buoyant L3 subclass. The inhibitory effect of niacin ER on very low-density lipoprotein was evident on the larger particles (V6, V5, V4, and V3 subclasses) rather than the smaller ones (V2 and V1). The results show that niacin ER produces a beneficial effect on lipoprotein subclasses, specifically decreasing the more atherogenic small, dense LDL particles and enhancing the cardioprotective large HDL particles.

Adult↗