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Biomedical subjects

D E Ward

Publications and source records attributed to D E Ward.

At least 37 records · Page 2Linked to original sources
PubMed1998

Initiating sequences in exercise induced idiopathic ventricular tachycardia of left bundle branch-like morphology.

Initiating sequences for VT may infer the underlying arrhythmogenic mechanisms. This study examines the initiating sequences of exercise induced idiopathic VT of left bundle branch block-like (LBBB-like) morphology and makes an attempt to relate these to clinical aspects and the mechanisms of arrhythmia. Thirty-two patients (mean age 33.4 +/- 13.2 years; 18 men) with exercise induced VT in the absence of structural cardiac abnormality on history, clinical examination, and noninvasive and invasive investigations were divided into two groups on the basis of the initiating sequence of VT on exercise. Group I consisted of patients with long-short sequence of RR intervals prior to the onset of VT (initiating/preinitiating cycle length ratio < or = 0.78). Group II consisted of patients without changes in cycle length prior to VT. Group I mechanism would suggest delayed afterdepolarizations (DADs) or reentry whereas group II mechanism triggered activity due to early afterdepolarizations. Fourteen patients (group I) had long-short sequence and 18 patients (group II) were without cycle length changes prior to VT initiated during exercise. VT axis was inferior in all 18 patients in group II but only in 9 patients in group I (P = 0.02). In these predefined patient groups, sustained monomorphic VT could not be initiated by programmed stimulation in any patient in group I, whereas four patients in group II had inducible VT. Patients in group II also had higher incidence of sustained VT on ambulatory monitoring (P < 0.05). The two groups did not differ in other respects. This study demonstrates the existence of at least two possible mechanisms of initiation of exercise induced idiopathic VT of LBBB-like morphology. VT initiated without cycle length changes is more common, more likely to have an inferior axis suggesting an outflow tract origin, and is probably related to triggered activity secondary to DADs. VT initiated with a long-short sequence is more often nonsustained and may have a superior axis suggesting an origin from the body or septal region of the ventricle. The two groups, therefore, exhibit differences in electrophysiological characteristics that may aid classification and therapy of this arrhythmia.

Adult↗
PubMed1998

Myocardial injury induced by radiofrequency and low energy ablation: a quantitative study of CK isoforms, CK-MB, and troponin-T concentrations.

We conducted a prospective, controlled study to investigate the use of CK-MB concentration and newer methods such as troponin-T concentration and CK isoforms, in the assessment of myocardial damage caused by radiofrequency current or low energy DC catheter ablation. The study population consisted of 3 consecutive patients who underwent low energy catheter ablation, 28 consecutive patients subjected to radiofrequency ablation, and 4 patients who were subjected to radiofrequency energy ablation but also had external DC shocks for cardioversion of atrial fibrillation that occurred during the procedure. The control group comprised eight subjects undergoing electrophysiological study. Prior to ablation and at 30 minutes, 1, 2, 6, and 12 hours following the procedure, serial blood samples were taken for measurement of troponin-T and CK-MB concentrations, and calculation of the MM3/MM1 and MB2/MB1 ratios. Troponin-T concentration was raised above normal in all patients subjected to low energy ablation and in all but two patients subjected to radiofrequency ablation. Only 42% of all patients subjected to ablation had at least one raised CK-MB concentration postablation. The MB2/MB1 ratio was raised in all but had at least one raised CK-MB concentration postablation. The MB2/MB1 ratio was raised in all but two patients following radiofrequency or low energy ablation but it was also abnormal in the preablation samples in nine patients. The MM3/MM1 ratio failed to detect myocardial damage in 71% of all patients. There was a statistically significant difference between the control and patient groups regarding all four indices of myocardial damage. Low energy ablation caused a significantly higher degree of myocardial damage compared with radiofrequency (RF); this effect could not be attributed to different numbers of total energy discharges. Our results indicate that catheter ablation, regardless of the mode of energy used, inflicts detectable injury upon the myocardium. This injury can be quantitated by using newer analytical techniques, such as serial, postablation measurements of troponin-T concentration.

Adult↗
PubMed1997

Cytogenetic rearrangements involving the loss of the Sonic Hedgehog gene at 7q36 cause holoprosencephaly.

Holoprosencephaly (HPE) is a genetically heterogeneous disorder that affects the midline development of the forebrain and midface in humans. As a step toward identifying one of the HPE genes, we have set out to refine the HPE3 critical region on human chromosome 7q36 by analyzing 34 cell lines from families with cytogenetic abnormalities involving 7q, 24 of which are associated with HPE. Genomic clones surrounding the DNA marker D7S104, which has previously been shown to be in the HPE3 critical region, have been examined by fluorescent in situ hybridization and microsatellite analysis of our panel of patient cell lines. We report the analysis of a cluster of four translocation breakpoints within a 300-kb region of 7q36 that serves to define the minimal critical region for HPE3 and that has directed the search for candidate genes. The human Sonic Hedgehog (hSHH) gene maps to this region and has been shown to be HPE3 on the basis of mutations within the coding region of the gene. We present evidence that cytogenetic deletions and/or rearrangements of this region of chromosome 7q containing Sonic Hedgehog, and translocations that may suppress Sonic Hedgehog gene expression through a position effect are common mechanisms leading to HPE.

Body Patterning↗
PubMed1997

A novel phenotypic pattern in X-linked inheritance: craniofrontonasal syndrome maps to Xp22.

Craniofrontonasal syndrome (CFNS, OMIM 304110) is a distinctive genetic disorder whose main clinical manifestations include coronal synostosis, widely spaced eyes, clefting of the nasal tip and various skeletal anomalies. CFNS originally was thought to be transmitted as an autosomal dominant trait, but recent studies suggest that it is X-linked dominant, whereby all daughters of males are affected, whereas none of their sons are affected. Here we report data confirming that CFNS is X-linked, mapping to a 13 cM interval in Xp22 with a maximum two-point lod score of 3.9 (theta = 0) at DXS8022 and a multipoint lod score of 5.08 at DXS1224. Detailed phenotypic analysis shows that females are more severely affected than males, a highly unusual characteristic for an X-linked disorder. CFNS represents the first multiple congenital anomaly syndrome with this unusual phenotypic pattern of X-linked inheritance.

Chromosome Mapping↗
PubMed1997

Use of troponin-T concentration and kinase isoforms for quantitation of myocardial injury induced by radiofrequency catheter ablation.

BACKGROUND: Although there remains particular concern about late malignant ventricular arrhythmias arising from myocardial damage induced by catheter ablation, the extent of myocardial injury resulting from clinical ablation procedures has not been fully studied. We conducted a prospective, controlled study to investigate the use of two newer markers of myocardial integrity, troponin-T concentration and creatine kinase isoforms, and a traditional marker, creatine kinase-MB concentration, in the assessment of myocardial injury following radiofrequency catheter ablation. METHODS AND RESULTS: The study population consisted of 28 consecutive patients subjected to radiofrequency catheter ablation, and the control group comprised eight subjects undergoing diagnostic electrophysiology study. Prior to ablation and at 30 min, 1, 2, 6, and 12 h following the procedure, blood samples were taken to measure troponin-T and creatine kinase-MB concentrations, and the separation of creatine kinase isoforms (MM3/MM1 and MB2/MB1 ratios). The troponin-T concentration was above normal in all but two patients following radiofrequency ablation, and the MB2/MB1 ratio was raised in all but one patient following ablation, but was also abnormal in the pre-ablation samples in seven patients. The MM3/MM1 ratio failed to detect myocardial injury in 75% of patients. Of patients subjected to ablation, in only 36% was the creatine kinase-MB concentration raised at least once post-ablation. Thirty minutes post-ablation, there was a statistically significant difference between the control and patient groups only as regards troponin-T concentration. There was a significant association between troponin-T concentration immediately post-procedure, the number of discharges delivered (r = 0.52, P = 0.006) and maximum power used (r = 0.48, P = 0.009). CONCLUSION: Our results indicate that catheter ablation inflicts a cumulative, detectable injury upon the myocardium. This injury can be quantitated by using newer analytical techniques, such as serial, post-ablation measurements of troponin-T concentration.

Adult↗
PubMed1997

Performance of basic ventricular tachycardia detection algorithms in implantable cardioverter defibrillators: implications for device programming.

Around 20% of patients with third generation implantable cardioverter defibrillators receive inappropriate therapy, usually triggered by atrial fibrillation. This is because the criteria used for ventricular tachycardia detection by current implantable cardioverter defibrillators are based on the analysis of a sequence of RR intervals and may be inappropriately satisfied by supraventricular tachyarrhythmias. Algorithms for ventricular tachycardia detection were challenged against the full RR interval sequences from 482 spontaneous episodes of atrial fibrillation and 260 spontaneous episodes of ventricular tachycardia to determine their ability to discriminate between the arrhythmias. The sensitivities and specificities of the algorithms were calculated over a wide range of programmable parameters. For a given window length and detection interval, the most stringent algorithms, that required all beats to be classified as "fast", were more specific than those allowing a proportion of "normal" intervals, even after adjustment for differing sensitivity. These differences were less marked for faster tachycardias. Specificity increased with the detection window length to a limit of approximately 18 beats. We conclude that ventricular tachycardia is detected with the highest specificity if all beats in an analyzed sequence are required to be "fast," even after lengthening of the tachycardia detection interval to maintain sensitivity. Further improvement in algorithm performance may require the incorporation of criteria such as tachycardia onset and stability.

Algorithms↗
PubMed1997

Radiofrequency catheter ablation of accessory atrioventricular pathways: primary failure and recurrence of conduction.

OBJECTIVE: To identify possible factors associated with primary failure of radiofrequency ablation of accessory pathways or recurrence of accessory pathway conduction. PATIENTS AND METHODS: Radiofrequency ablation of accessory pathways failed in 25 of 243 patients, and recurrence of accessory pathway conduction occurred in an additional 13 patients. Factors possibly related to primary failure and recurrence were analysed. RESULTS: Primary failure and recurrence were less frequent in patients with left sided pathways (7% v 19%; 4% v 24%; P = 0.04). The factors that might relate to primary failure included an unstable catheter position (seven patients), a possible epicardial pathway (six patients), or misdiagnosis of accessory pathway location (two patients). The major factors for recurrence included the stability of the local atrial electrogram < or = 0.5 together with the stability of the local ventricular electrogram < or = 0.8, and prolonged time to pathway conduction block > or = 12 seconds). Thirty one patients underwent repeat ablation which was successful in 28. CONCLUSIONS: Primary failure and recurrence were more frequent in patients with right sided pathways. An unstable catheter position and a possible epicardial pathway location are the main contributing factors for primary failure, while unstable local electrograms and prolonged time to block are independent predictors for recurrence.

Adolescent↗
PubMed1996

Characteristics of bipolar electrograms during anterograde mapping: the importance of accessory atrioventricular pathway location.

Local endocardial electrograms recorded at successful radiofrequency ablation sites during anterograde mapping (QRS-V interval, atrioventricular [AV] interval, AV ratio, the presence of accessory pathway potential, and stability of atrial and ventricular electrogram) were analyzed and compared according to location of accessory pathways. The mitral and tricuspid annuli were divided into 10 regions. Endocardial electrograms differed with regard to location of accessory AV pathways. The QRS-V interval was more negative in right posteroseptal, right free wall and right anteroseptal locations than the interval in other locations. The AV interval was longer in posteroseptal than the interval in left and right free wall sites. The stability of atrial and ventricular electrograms was better in left free wall sites than in posteroseptal sites and worst in right free wall and right anteroseptal sites. The variation in local electrograms at successful ablation sites with respect to pathway location may partly explain the low predictive value and the marked variation in previously suggested criteria for selecting target sites for radiofrequency energy delivery. The results also imply that the influence of accessory pathway location must be considered when attempts are made to establish electrogram-based criteria for predicting successful ablation of accessory pathways.

Adolescent↗
PubMed1996

Molecular characterization of breakpoints in patients with holoprosencephaly and definition of the HPE2 critical region 2p21.

Holoprosencephaly (HPE) is a common developmental defect involving the brain and face in humans. Cytogenetic deletions in patients with HPE have localized one of the HPE genes (HPE2) to the chromosomal region 2p21. Here we report the molecular genetic characterization of nine HPE patients with cytogenetic deletions or translocations involving 2p21. We have determined the parental origin of the deleted chromosomes and defined the HPE2 critical region between D2S119 and D2S88/D2S391. As a first step towards cloning the HPE2 gene which is crucial for normal brain development we have constructed a YAC contig which spans the smallest region of deletion overlap. Several of these YACs could be identified which span three different 2p21 breakpoints in HPE patients. These YACs narrow the HPE2 critical region to less than 1 Mb and are now being further analyzed to identify the gene causing holoprosencephaly on chromosome 2.

Base Sequence↗
PubMed1996

Successful radiofrequency ablation of accessory pathways with the first energy delivery: the anatomic and electrical characteristics.

Successful ablation of accessory pathways has been achieved at the first energy delivery site in some patients, but factors permitting success at the first site are unclear. Accessory pathway location, surface and endocardial electrogram characteristics in each location were analysed and compared between the patients with first site block (group A, 34 patients) and those in whom multiple sites (median seven sites) were required (group B, 133 patients). No patients with right free-wall pathways had first site block. In group A surface electrocardiograms were more pre-excited (QRS duration: 132 +/- 20 vs 120 +/- 17 ms, P < 0.01). For left free-wall and septal pathways, the interval from the onset of the earliest delta wave on surface electrocardiogram to local ventricular activation (QRS-V) was more negative and the local atrioventricular interval (AV) was shorter in group A; the positive predictive value of a QRS-V < or = 0 ms, an AV < or = 30 ms and the presence of a possible accessory pathway potential was 67% for left free-wall and of a QRS-V < or = -10 ms with an AV < or = 30 ms was 100% for septal pathways. During retrograde mapping of concealed left free-wall and right anteroseptal pathways (first site block was not achieved in other locations) the positive predictive value of a local ventriculoatrial interval < or = 30 ms was 55%. Accessory pathway location correlated strongly with the chances of first site block, suggesting that anatomical features are important. Maximizing pre-excitation may be of benefit in achieving first site block. Delivery of energy to a site with special endocardial electrogram features was associated with an increased likelihood of first site block.

Accessory Nerve↗
PubMed1996

Catheter ablation for successful management of left posterior fascicular tachycardia: an approach guided by recording of fascicular potentials.

OBJECTIVE: To assess whether catheter ablation of fascicular tachycardia can be facilitated by the recording of sharp deflections arising from the mid-septum---inferior apical septum of the left ventricle. PATIENTS AND METHODS: Seven consecutive patients (mean age 29 (range 16-43) years) with ventricular tachycardia originating from the left posterior fascicle underwent electrophysiology study and detailed mapping of endocardial activation. Selection of ablation sites in the last five patients was based on the recording, during left posterior fascicular tachycardia and sinus rhythm, of a discrete potential preceding the earliest ventricular electrogram, which was thought to represent conduction through the posterior fascicle. RESULTS: Patients were treated with low energy direct current or radiofrequency current ablation. The median fluoroscopy and procedure times were 23 (range 6-42) min and 110 (range 50-176) min, respectively. In a follow up period of 4 to 16 months, six patients were asymptomatic and one had minor symptoms. No patient had any change in intraventricular conduction. Similar potentials were also recorded from the left posterobasal septum in three of eight patients who underwent catheter ablation of left free wall accessory pathways. CONCLUSION: Fascicular potentials can be reproducibly recorded in left posterior fascicular tachycardia and may serve as a reliable marker for successful ablation procedures. The relation of these potentials with the substrate of the tachycardia, however, remains obscure.

Adult↗
PubMed1996

Low energy internal cardioversion of atrial fibrillation resistant to transthoracic shocks.

OBJECTIVE: To investigate the efficacy of internal cardioversion using low energy shocks delivered with a biatrial electrode configuration in chronic atrial fibrillation resistant to transthoracic shocks. METHODS: Low energy internal cardioversion was attempted in 11 patients who had been in atrial fibrillation for 233 (SD 193) days and had failed to cardiovert with transthoracic shocks of 360 J in both apex-base and anterior-posterior positions. Synchronised biphasic shocks of up to 400 V (approximately 6 J) were delivered, usually with intravenous sedation only, between high surface area electrodes in the right atrium and the left atrium (coronary sinus in nine, left pulmonary artery in one, left atrium via patent foramen ovale in one). RESULTS: Sinus rhythm was restored in 8/11 patients. The mean leading edge voltage of successful shocks was 363 (46) V [4.9 (1.2) J]. Higher energy shocks induced transient bradycardia [time to first R wave 1955 (218) ms]. No proarrhythmia or other acute complications were observed. CONCLUSIONS: Low energy internal cardioversion of atrial fibrillation can restore sinus rhythm in patients in whom conventional transthoracic shocks have failed.

Adult↗
PubMed1995

Prediction of atrioventricular block during radiofrequency ablation of the slow pathway of the atrioventricular node.

BACKGROUND: Selective radiofrequency (RF) ablation of the slow pathway is an effective treatment for atrioventricular (AV) nodal reentry tachycardia. A previous report showed that rapid junctional tachycardia (JT) caused by RF associated with loss of ventriculoatrial (VA) conduction is related to increased risk for AV block. However, this can be difficult to detect during energy delivery, and more importantly, it cannot be measured before the onset of RF energy delivery. The aim of our study was to determine whether measurements made from electrograms could be used to predict the risk of AV block before RF energy is delivered. METHODS AND RESULTS: Fifty-eight patients underwent 63 selective slow pathway RF ablation procedures. In 46 (26.9%) of 172 JTs caused by RF, VA block was observed, and in 11 this was followed by AV block of various degrees. Electrograms before each application of RF were analyzed for the interval between the atrial signals in the His bundle catheter and in the distal mapping catheter [A(H)-A(Md)], the interval between the atrial signals in the His bundle catheter and in the proximal coronary sinus catheter [A(H)-A(CS)], the AV ratio, and the presence of a slow pathway potential or a fractionated atrial signal in the distal mapping catheter. Mean cycle length (CL) of JT was calculated if it consisted of at least 10 beats. These parameters were compared between patients with JT who developed VA block and subsequent AV block (group 1), patients with JT and VA block but without subsequent AV block (group 2), and patients with JT without VA block (group 3). The A(H)-A(Md) interval was significantly shorter in group 1 (17 +/- 8 ms) than in groups 2 (33 +/- 8 ms, P < .001) and 3 (32 +/- 10 ms, P < .001), whereas the A(H)-A(Md) intervals of groups 2 and 3 did not differ from each other. CL of JT, A(H)-A(CS) interval, AV ratio, presence of a slow pathway potential, or a fractionated atrial electrogram were not related to the occurrence of AV block. CONCLUSIONS: The A(H)-A(Md) interval provides an electrophysiological marker that can be used in addition to the radiological catheter position to assess the risk for AV block before onset of RF delivery. CL of JT and occurrence of VA block are not related to the risk of AV block.

Atrioventricular Node↗
PubMed1995

Primary ventricular fibrillation is associated with increased paced right ventricular electrogram fractionation.

BACKGROUND: The mechanisms of spontaneous ventricular fibrillation (primary VF) in patients without structural heart disease are obscure. A new technique has shown that in patients with hypertrophic cardiomyopathy conduction of fractionated ventricular paced beats, recorded at several right ventricular sites, is prolonged in individuals who have suffered a VF arrest, and this may reveal one component of a reentrant substrate. Patients with primary VF were studied with the same methods to determine whether similar abnormalities are present in this group. METHODS AND RESULTS: Nine patients with primary VF were studied by pacing one right ventricular (RV) site by use of a constant drive train with an extrastimulus inserted every third beat and reducing the extrastimulus coupling interval (S1S2 interval) by 1 ms on each occasion while recording at three other sites. The delay of each fractionated potential in the high-pass-filtered electrograms in response to the extrastimulus was determined and used to form conduction curves of delay versus the S1S2 interval. These curves were repeated by pacing each RV site in turn and recording from the other three sites. The curves were characterized by determining the S1S2 interval at which electrogram components increased in delay by 0.75 ms/20 ms reduction in S1S2 interval and the increase in electrogram duration between a coupling interval of 350 ms and 1 ms above refractoriness. Seven control patients were studied using the same method. The mean increase in electrogram duration in VF patients was 13 ms (range, 3 to 23 ms) compared with 4 ms (range, -2 to 14 ms) in unaffected control patients. The extrastimulus coupling interval at which delay increased was 318 ms (range, 293 to 334 ms) in VF patients and 274 ms (range, 265 to 284 ms) in control patients (P < .01). There was no difference between the number of fractionated potentials in VF patients and control patients. CONCLUSIONS: In primary VF patients, the individual potentials within fractionated electrograms have increased delays when compared with control patients. This may identify one component of a reentrant arrhythmic substrate.

Adolescent↗
PubMed1995

Comparison of aceclofenac with diclofenac in the treatment of osteoarthritis.

A multicentre randomised, double-blind, parallel group, general practice study was undertaken to investigate the efficacy and safety of aceclofenac (200 patients, 100 mg twice daily and placebo once daily) in comparison with diclofenac (197 patients, 50mg three times daily) in patients with osteoarthritis of the knee. The treatment period of twelve weeks was preceded by a washout period of two weeks duration. At end point, patients in both aceclofenac and diclofenac-treated groups exhibited significant improvement in pain intensity (p = 0.0001). Although both treatment groups showed significant improvement in all investigators' clinical assessments (joint tenderness, swelling, pain on movement, functional capacity, overall assessment), there were no significant differences between the groups. There was, however, a trend towards greater improvement in complete knee movement and reduced pain on movement with aceclofenac. In patients with initial flexion deformity, aceclofenac was significantly more effective than diclofenac in improving knee flexion after 2-4 weeks treatment. Patients' subjective assessment of pain relief demonstrated significantly greater efficacy with aceclofenac. At end point, 71% of patients in the aceclofenac group reported improvement in pain intensity as compared to 59% treated with diclofenac (p = 0.005). Tolerability of aceclofenac was better than with diclofenac as fewer patients experienced gastrointestinal adverse events. In particular, the incidence of treatment related diarrhoea was less with aceclofenac (1%) than the diclofenac (6.6%). In summary, this study supports a therapeutic role for aceclofenac in arthritis and suggests that it is an alternative NSAID to diclofenac in the treatment of osteoarthritis.

Adolescent↗
PubMed1995

Efficacy and tolerability of transvenous low energy cardioversion of paroxysmal atrial fibrillation in humans.

OBJECTIVES: This study investigated the efficacy and tolerability of low energy shocks for termination of atrial fibrillation in patients, using an endocardial electrode configuration that embraced both atria. BACKGROUND: In animals, low energy biphasic shocks delivered between electrodes in the coronary sinus and right atrium have effectively terminated atrial fibrillation. If human defibrillation thresholds are sufficiently low, atrial defibrillation could be achieved in conscious patients using an implanted device. METHODS: Twenty-two consecutive patients with stable atrial fibrillation were studied during electrophysiologic testing. Biphasic R wave synchronous shocks were delivered between large surface area electrodes in the coronary sinus and high right atrium, using a step-up voltage protocol starting at 10 or 20 V and increasing to a maximum of 400 V. Patients were conscious at the start of the study and were asked to report on symptoms but were sedated later if shocks were not tolerated. RESULTS: Cardioversion was achieved in all 19 patients who completed the study, with a mean (+/- SD) leading-edge voltage of 237 +/- 55 V (range 140 to 340) and mean energy of 2.16 +/- 1.02 J (range 0.7 to 4.4). The mean maximal shock delivered without sedation was 116 +/- 51 V (range 60 to 180). No proarrhythmia or mechanical complications occurred. CONCLUSIONS: The delivery of biphasic R wave synchronous shocks between the high right atrium and coronary sinus can terminate atrial fibrillation with very low energies. General anaesthesia is not required, and a minority of fully conscious patients are able to tolerate this method of cardioversion.

Adult↗