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David Keane

Publications and source records attributed to David Keane.

At least 19 recordsLinked to original sources

3-[6-(2-Dimethylamino-1-imidazol-1-yl-butyl)-naphthalen-2-yloxy]-2,2-dimethyl-propionic acid as a highly potent and selective retinoic acid metabolic blocking agent.

3-[6-(2-Dimethylamino-1-imidazol-1-yl-butyl)-naphthalen-2-yloxy]-2,2-dimethyl-propionic acid and analogs were designed and synthesized as highly potent and selective CYP26 inhibitors, serving as retinoic acid metabolic blocking agents (RAMBAs), with demonstrated in vivo efficacy to increase the half-life of exogenous atRA.

Chromatography, High Pressure Liquid↗

How specific is case specificity?

OBJECTIVES: Case specificity implies that success on any case is specific to that case. In examining the sources of error variance in performance on case-based examinations, how much error variance results from differences between cases compared with differences between items within cases? What is the optimal number of cases and questions within cases to maximise test reliability given some fixed period of examination time? METHODS: G and D generalisability studies were conducted to identify variance components and reliability for each examination analysed, and to optimise the reliability of the given test composition (1, 1.5, 2, 3, 4 and 5 questions per case), using data from 3 key features examinations of the Medical Council of Canada (n = 6342 graduating medical students), each of which consisted of about 35 written cases followed by 1- questions regarding specific key elements of data gathering, diagnosis and/or management. RESULTS: The smallest variance component was due to subjects; the variance due to subject-item interaction was over 5 times the interaction with cases (on average, 0.1106 compared with 0.0195). Relatively little variance was due to differences between cases; about 80% of the error variance was due to variability in performance among items within cases. The D study showed that reliability varied between 0.541 and 0.579, was least with 1 item per case and highest at 2 and 3 items per case. CONCLUSIONS: The main source of error variance was items within cases, not cases, and the optimal strategy in terms of enhancing reliability would use cases with 2-3 items per case.

Analysis of Variance↗

Atrial fibrillation originating from persistent left superior vena cava.

BACKGROUND: The left superior vena cava (LSVC) is the embryological precursor of the ligament of Marshall, which has been implicated in the initiation and maintenance of atrial fibrillation (AF). Rarely, the LSVC may persist and has been associated with some organized arrhythmias, though not with AF. We report 5 patients in whom the LSVC was a source of ectopy, initiating AF. METHODS AND RESULTS: In 5 patients (4 men; age, 46+/-11 years) with symptomatic drug-refractory AF, ectopy from the LSVC resulting in AF was observed after pulmonary vein isolation. The ectopics were spontaneous in 2 and induced by isoproterenol in the others and preceded P-wave onset by 67+/-13 ms. During multielectrode or electroanatomic mapping, venous potentials were recorded circumferentially at the proximal LSVC near its junction with the coronary sinus (CS), but at the mid-LSVC level, they were recorded only on part of the circumference. The LSVC was electrically connected to the lateral left atrium (LA) and through the CS to the right atrium, with 4.1+/-2.3 CS-LSVC and 1.6+/-0.5 LA-LSVC connections per patient. Catheter ablation in the LSVC targeting these connections resulted in electrical isolation in 4 of the 5 patients without complications. After 15+/-10 months, the 4 patients with successful isolation, including 1 who had successful reablation for LA flutter, remained in sinus rhythm without drugs. CONCLUSIONS: The LSVC can be the arrhythmogenic source of AF with connections to the CS and LA. Ablation of these connections resulted in electrical isolation.

Adrenergic beta-Agonists↗

Successful release of entrapped circumferential mapping catheters in patients undergoing pulmonary vein isolation for atrial fibrillation.

OBJECTIVES: The purpose of this study was to demonstrate a method for successful and safe release of an entrapped circular catheter. BACKGROUND: Segmental pulmonary vein (PV) isolation is widely practiced for patients with symptomatic drug-refractory atrial fibrillation. A circular mapping catheter is sometimes used with this technique to map the electrical connection between the left atrium (LA) and the PVs. This catheter reportedly can become entrapped in the mitral valve apparatus. Attempts to free the entrapped catheter can result in serious complications, including damage to the mitral valve chordae tendineae or fracture of the catheter itself. METHODS: Three patients were referred for PV isolation for atrial fibrillation. A circular mapping catheter was used to map the sites of LA-PV electrical connections. RESULTS: During the procedure, the circular mapping catheter became entrapped in the mitral valve apparatus in two patients and in the PV in one patient. A series of maneuvers, which included use of another catheter and guiding sheaths as well as pushing forward rather than pulling back on the entrapped catheter, allowed safe and successful release of the entrapped catheter in all patients. CONCLUSIONS: Entrapment of the circular mapping in the mitral valve apparatus or the PVs during PV isolation is a rare complication associated with use this catheter. We describe a series of maneuvers that may allow safe and successful release of the entrapped catheter.

Adult↗

In vitro and in vivo evaluation of the thermal patterns and lesions of catheter ablation with a microwave monopole antenna.

BACKGROUND: Radiofrequency (RF) catheter ablation is an effective treatment for supraventricular tachycardia. The effectiveness of the technique is at times limited by the small lesion size produced by RF energy delivery. Previous reports have indicated that microwave energy is capable of producing a larger volume of heated tissue than radiofrequency energy, raising the possibility that microwave energy may offer a potential alternative energy source to radiofrequency for the substrate ablation of certain arrhythmias such as ventricular tachycardia or atrial flutter. METHODS: The present study evaluated the thermal profiles of a monopole microwave antenna delivering energy at 2.45 GHz frequency in a phantom tissue-equivalent material with dielectric and thermal properties similar to myocardium. In addition, microwave catheter ablations were performed in vivo in the ventricles of goats prior to the examination of the lesions. RESULTS: The measured thermal profiles in the phantom revealed that the antenna is capable of producing heating to a temperature associated with myocardial necrosis to a controllable depth that can be more than 8 mm, while the endocardial temperature is maintained relatively low. The ablation volume is significantly reduced but is still effective when there is only a partial contact between the antenna and the tissue surface. In vivo studies on goat models confirmed that the monopole antenna can produce a deep transmural lesion in the left ventricle without causing coagulation or charring on the endocardial surface.

Animals↗

Efficacy and safety of segmental ostial versus circumferential extra-ostial pulmonary vein isolation for atrial fibrillation.

INTRODUCTION: Pulmonary vein (PV) isolation for atrial fibrillation (AF) can be performed using a segmental ostial or a circumferential extra-ostial approach. The relative merits and potential limitations of each approach are currently debated. Here we report our early experience with each of these approaches, including their relative efficacy and safety. METHODS AND RESULTS: Forty patients with drug-refractory AF underwent segmental ostial PV isolation and were compared to 40 consecutive patients who underwent PV isolation using a circumferential extra-ostial approach. The latter approach described here is novel in two aspects: (1) the endpoint for ablation was PV isolation and not only delay in left atrial to PV conduction time, and (2) isolation of the right and left PVs was achieved by a single encirclement of ipsilateral veins. At follow-up, 60% of the patients in the segmental group were free of AF compared to 75% of the patients in the circumferential group. There was one thromboembolic cerebrovascular complication during the ablation procedure in each group. CONCLUSION: PV isolation using a circumferential extra-ostial approach, where the ipsilateral PVs are isolated together by one encircling line of block using electroanatomic mapping, is a technically feasible procedure. This approach is at least as effective and safe as the more established segmental ostial approach for AF ablation.

Atrial Fibrillation↗

Assessment of pulmonary vein anatomic variability by magnetic resonance imaging: implications for catheter ablation techniques for atrial fibrillation.

INTRODUCTION: Pulmonary vein (PV) isolation for atrial fibrillation (AF) currently is performed using either an ostial or an extra-ostial approach. The objective of this study was to analyze by three-dimensional (3D) magnetic resonance angiography (MRA) the anatomy of the PVs in order to detect structural variability that would impact the choice of ablation approach. METHODS AND RESULTS: Three-dimensional MRA was performed in 105 patients undergoing PV isolation. The ostial diameter, branching pattern, and PV angulation were analyzed. Fifty-nine (56%) patients had the typical pattern of 4 PVs with 4 separate ostia, 30 (29%) patients had an additional PV, and 18 (17%) patients had a left common PV trunk. In two patients, there were three right-sided veins and a common left-sided trunk, giving rise to four ostia: three on the right and one on the left. Two different populations of right middle PVs were noted: one where the additional vein projected anteriorly to drain the right middle lobe and one posterior to drain the superior portion of the right lower lobe. The average intrapatient variability in PV diameter was 7.9 +/- 4.2 mm. The PV ostium was <10 mm in 26 (25%) patients and >25 mm in 15 (14%) patients. The first branch originated 6.7 +/- 2.3 mm from the ostium. The left superior, right superior, right inferior, and left inferior PVs were found to enter the left atrium at the following angles: 32 +/- 13 degrees, 131 +/- 11 degrees, 206 +/- 16 degrees, and 329 +/- 14 degrees, respectively. Forty-nine patients (47%) had at least one funnel shaped PV. CONCLUSION: This largest PV imaging study to date demonstrates that MRA is a valuable tool that allows detection of marked intrapatient and interpatient anatomic variability of the PVs. These findings suggest that, at least in some patients, circumferential extra-ostial left atrial encirclement of the PVs may be preferable to ostial PV isolation. These findings also may have significant implications on the future development of coil- and balloon-based catheter ablation designs for AF ablation.

Atrial Fibrillation↗

Catheter ablation of atrial flutter after orthotopic heart transplantation.

INTRODUCTION: Atrial arrhythmias, including atrial flutter, are common in orthotopic heart transplant recipients. However, only a small number of individual case reports describe the electrical circuit and catheter ablation of atrial flutter after heart transplantation. METHODS AND RESULTS: Detailed electrophysiologic evaluation and radiofrequency ablation of atrial flutter were performed in three patients after orthotopic heart transplantation. All cases involved a counterclockwise flutter circuit around the tricuspid annulus. All were successfully ablated at the isthmus between the tricuspid valve and the atrial anastomosis adjacent to the inferior vena cava. CONCLUSION: Atrial flutter involving a counterclockwise circuit around the tricuspid annulus is common in the heart transplant population. Based on the patients described in this study and other cases reported in the literature, this arrhythmia often is treated successfully by ablation of the isthmus between the tricuspid valve and the atrial anastomosis near the inferior vena cava.

Adult↗

Use of a diode laser balloon ablation catheter to generate circumferential pulmonary venous lesions in an open-thoracotomy caprine model.

Electrical isolation of the pulmonary veins (PVs) can be curative in certain patients with atrial fibrillation. The ability of a diode laser balloon ablation catheter to isolate PVs was assessed in an open-thoracotomy caprine model system. After a median sternotomy, the left atrial appendage was cannulated in 19 goats. A laser balloon catheter was placed at the PV ostia and used to deliver photonic energy to the periostial tissue. The applications were delivered at 3.7, 4.5, or 5.4 W/cm for 90-150 seconds. Electrical continuity of the PV with the left atrium was assessed using a multielectrode mapping catheter. After a single application of photonic energy, electrical isolation of the PVs was achieved in (70%) 19/27 PVs. However, the success of electrical PV isolation did not correlate with the dose or duration of the applications. When reflectance spectroscopy was utilized to ensure adequate orientation and contact of the laser balloon catheter with the left atrial myocardium, complete PV isolation was achieved in 5/5 veins at 3.5 W/cm for 120 seconds. Pathological examination revealed no PV stenosis, no pericardial damage, minor lung lesions without pleural perforation, minimal endothelial disruption, and, in the presence of adequate heparinization, no endocardial charring or overlying thrombus. Effective isolation of the PVs can be achieved by delivery of a continuous circular beam of photonic energy to ablate the left atrial - pulmonary venous junction. The use of reflectance spectroscopy to provide real-time monitoring of the blanching effect of balloon-tissue contact optimizes lesion delivery.

Animals↗

Persistence of septal defects after transeptal puncture for pulmonary vein isolation procedures.

Pulmonary vein isolation (PVI) is widely practiced as a means of potentially curing atrial fibrillation (AF). Transeptal puncture is performed for PVI procedures, often two such punctures are performed. We sought to examine the prevalence of medium- to long- term iatrogenic septal defects after such procedures. Thirty-one patients who were undergoing their second PVI procedure were studied with transesophageal echocardiography (TEE) with two-dimensional imaging and color Doppler, examining the fossa ovalis for defects. Mean time from the original PVI to the time of TEE was 35 weeks. Two patients were discovered to have iatrogenic septal defects. The interval between the first PVI procedure and the TEE showing a septal defect was 33.7 weeks in one patient and 14.3 weeks in the other. Iatrogenic septal defects may occur in the medium- to long-term in patients undergoing PVI procedures for AF. The clinical implications of such defects are unknown.

Adult↗

Morphology of atrial myocardium in human pulmonary veins: a postmortem analysis in patients with and without atrial fibrillation.

OBJECTIVES: We report an in-depth postmortem morphologic analysis of atrial myocardium in human pulmonary veins (PVs) from patients with and without atrial fibrillation (AF). BACKGROUND: Electrophysiologic studies established the critical role of PVs in the initiation of AF. To date, a paucity of data exists about PV morphology as an arrhythmogenic substrate. METHODS: Longitudinal tissue-strips of PVs were excised and histologically analyzed from the distal part to just beyond the atriovenous junction in the left atrium from 20 patients, obtained at autopsy. Anatomical measurements, including diameters, lengths, and wall-thicknesses of PVs, obtained at autopsy, were made. RESULTS: Histological analysis revealed extension of atrial myocardium into 89% of all PVs. Prevalence of myocardial extension was significantly higher in veins of 6 patients with compared with 14 patients without AF. Other significant differences in the histology of PVs between the two groups were a higher frequency of discontinuity and hypertrophy and a higher degree of fibrosis of the atrial myocardium in the PVs of patients with AF. A marked variation existed in anatomical dimensions of PVs, although no differences were observed between patients with or without AF. CONCLUSIONS: Atrial myocardium was more often present in the PVs of patients with compared with patients without AF. In the first group, the atrial myocardium in the PVs was characterized by more severe discontinuity, hypertrophy, and fibrosis. A marked variation in anatomical dimensions of the PVs existed.

Adolescent↗

Transcatheter left atrial appendage occlusion with Amplatzer devices to obviate anticoagulation in patients with atrial fibrillation.

It is assumed that over 90% of clinically apparent embolisms in atrial fibrillation originate from the left atrial appendage. Recently, a percutaneous method (PLAATO technique) to occlude the left atrial appendage to the end of preventing thromboembolic complications of atrial fibrillation has been introduced into clinical practice. This technique is quite intricate and requires general anesthesia. The Amplatzer atrial septal occluder lends itself for a more simple approach to this intervention. The first 16 patients treated at four centers are described. Their age varied from 58 to 83 years. All suffered from atrial fibrillation but eight of them were in sinus rhythm at the time of implantation. All but two procedures were done under local anesthesia of the groin only. There was one technical failure (device embolization) requiring surgery. All other patients left the hospital a day after the procedure without complications. There were no problems or embolic events during an overall follow-up of 5 patient-years and all left atrial appendages were completely occluded without evidence of thrombosis at the atrial side of the device at the latest follow-up echocardiography. With the Amplatzer technique, the left atrial appendage can be percutaneously occluded with a venous puncture under local anesthesia, without echocardiographic guidance, and at a reasonable risk. It remains to be evaluated in larger series or randomized trials how the simpler Amplatzer technique compares with the complex PLAATO technique, and whether left atrial appendage closure is competitive with oral anticoagulation with warfarin or the novel ximelagatran to prevent thromboembolism in atrial fibrillation.

Aged↗

Incessant nonreentrant tachycardia due to simultaneous conduction over dual atrioventricular nodal pathways mimicking atrial fibrillation in patients referred for pulmonary vein isolation.

It has been reported that conduction over the fast and slow pathways of the AV node can occur simultaneously, leading to a double ventricular response from each atrial beat. We report the cases of two patients referred to us for evaluation of symptomatic, incessant, and irregular narrow-complex tachycardia, misdiagnosed as atrial fibrillation, for consideration of pulmonary vein isolation. At presentation, careful evaluation of the electrograms revealed the presence of two ventricular activations for each atrial beat. At electrophysiologic study, both patients were found to have nonreentrant tachycardias arising from simultaneous conduction over the fast and slow pathways of the AV node. In one patient, the tachycardia had resulted in cardiomyopathy. Slow AV nodal pathway ablation performed in both patients resulted in cure of their tachycardias and recovery of ventricular function in the patient with cardiomyopathy.

Adult↗

Para-Hisian entrainment: a novel pacing maneuver to differentiate orthodromic atrioventricular reentrant tachycardia from atrioventricular nodal reentrant tachycardia.

INTRODUCTION: Para-Hisian pacing during sinus rhythm can help to identify the presence of an accessory pathway (AP). In this maneuver, the retrograde activation time and pattern are compared during capture and loss-of-capture of the His bundle while pacing from a para-Hisian position. However, identification of a retrograde AP does not necessitate that it is operative during the tachycardia of interest; conversely, slowly conducting or "distant" bypass tracts may not be identified. We evaluated the utility of entrainment or resetting of tachycardias from the para-Hisian position to help distinguish atrioventricular nodal reentrant tachycardia (AVNRT) from orthodromic atrioventricular tachycardia (AVRT). METHODS AND RESULTS: Para-Hisian entrainment/resetting was evaluated in 50 patients: 33 with AVNRT and 17 with AVRT. The maneuvers were performed using a standard quadripolar catheter placed at the His position: low output for right ventricular (RV) capture and high output for both RV and His capture. The retrograde atrial activation sequence, SA interval (interval from stimulus to earliest retrograde atrial activation), and "local" VA interval (interval between the ventricular and atrial electrograms at the site of earliest retrograde atrial activation) were compared between His and His/RV capture. The DeltaSA was > 40 ms in patients with AVNRT and was < 40 ms in all but one patient with AVRT. In concert with the DeltaSA interval, the DeltaVA interval was able to fully define the mechanism of the tachycardia in all patients studied. CONCLUSION: Para-Hisian entrainment/resetting can determine the course of retrograde conduction operative during narrow complex tachycardias. It is a useful diagnostic maneuver in differentiating AVNRT and orthodromic AVRT.

Adolescent↗