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Biomedical subjects

Bruce B Lerman

Publications and source records attributed to Bruce B Lerman.

At least 37 records · Page 2Linked to original sources

Single-stage adenosine tilt testing in patients with unexplained syncope.

INTRODUCTION: We previously have shown that a 3-minute single-stage adenosine tilt test has a diagnostic yield comparable to a two-stage protocol consisting of a 30-minute drug-free tilt followed by a 15-minute isoproterenol tilt. In this study, we sought to further define the clinical utility of adenosine tilt testing in patients with unexplained syncope by prospectively evaluating test specificity and determining predictors of a positive test response. METHODS AND RESULTS: The specificity of single-stage adenosine tilt testing was determined using 30 control subjects. To determine the diagnostic yield of this protocol, adenosine tilts were performed in 129 patients with unexplained syncope. The adenosine tilt test protocol had high specificity (100%) but a low overall diagnostic yield (18%). However, the yield was affected significantly by age. In patients </=40 years of age, the tilt test was positive in 15 (41%) of 37 patients, which was significantly greater than the yield in patients between the ages of 41 and 64 years (6/41 patients [15%], P = 0.012) and those >/=65 years of age (2/41 patients [5%], P < 0.0001). CONCLUSION: These data support single-stage adenosine tilt testing in patients </=40 years of age because the diagnostic yield of the test is maximal in this group and the test can be completed in </=3 minutes. Conversely, the diagnostic yield of adenosine tilt testing in patients >40 years of age is low, suggesting that the clinical utility of this protocol is limited in these patients.

Adenosine↗

Time course and predictors of autonomic dysfunction after ablation of the slow atrioventricular nodal pathway.

Withdrawal of parasympathetic tone has been reported after ablation in the posteroseptal right atrium and has been attributed to injury of vagal efferent fibers. The purpose of this study was to assess the time course and predictors of autonomic dysfunction after slow pathway ablation. In 30 patients with AV nodal reentrant tachycardia, time- and frequency-domain measures of heart rate variability (HRV) were measured before, 30 minutes after, and 1 day after slow pathway ablation. There were significant reductions in mean RR interval (724 +/- 163 vs 836 +/- 164 ms, P < 0.05), SD of RR intervals (29 +/- 17 vs 40 +/- 18 ms, P < 0.05), root mean squared difference (15 +/- 8 vs 29 +/- 17 ms, P < 0.05), and high frequency power (4.1 +/- 0.4 vs 4.5 +/- 0.6 log10ms2, P < 0.05) 30 minutes after ablation. However, these parameters returned to baseline 1 day after ablation. Multivariate regression identified isoproterenol dose during the diagnostic study (P = 0.02) and radiofrequency duration (P = 0.02) as statistically significant predictors of heart rate change (R2= 0.45). These findings suggest that changes in autonomic tone after ablation in the posteroseptal right atrium are transitory and resolve within 1 day of the procedure. These short-term changes may be related to procedural variables rather than direct injury to vagal efferent fibers.

Adult↗

An update on electrical cardioversion of atrial fibrillation.

Atrial fibrillation is the most frequently encountered sustained arrhythmia in clinical practice. Electrical cardioversion of atrial fibrillation using damped sine wave shocks has been a mainstay of therapy for nearly 4 decades; its limitation remains a failure rate that approaches 20%. Although several alternatives have been proposed, including delivering 720 J shocks using dual monophasic defibrillators, ibutilide pretreatment and internal cardioversion, each of these approaches has significant limitations, which preclude its routine use. Recent data demonstrate that routine use of biphasic shocks for cardioversion of atrial fibrillation is associated with a marked improvement in cardioversion efficacy and suggest that biphasic shocks may be the preferred method for the transthoracic electrical cardioversion of atrial fibrillation.

Anti-Arrhythmia Agents↗

Molecular genetic analysis of PRKAG2 in sporadic Wolff-Parkinson-White syndrome.

INTRODUCTION: Mutations in the PRKAG2 gene that encodes the gamma2 regulatory subunit of AMP-activated protein kinase have been shown to cause autosomal dominant Wolff-Parkinson-White (WPW) syndrome associated with hypertrophic cardiomyopathy. Prior studies focused on familial WPW syndrome associated with other heart disease such as hypertrophic cardiomyopathy. However, such disease accounts for only a small fraction of WPW cases, and the contribution of PRKAG2 mutations to sporadic isolated WPW syndrome is unknown. METHODS AND RESULTS: Subjects presented for clinical electrophysiologic evaluation of suspected WPW syndrome. WPW syndrome was diagnosed by ECG findings and/or by clinically indicated electrophysiologic study prior to enrollment. Echocardiography excluded hypertrophic cardiomyopathy. Denaturing high-performance liquid chromatography and automated sequencing were used to search for PRKAG2 mutations. Twenty-six patients without a family history of WPW syndrome were studied. No subject had cardiac hypertrophy, and only one patient had associated congenital heart disease. Accessory pathways were detected at diverse locations within the heart. Two polymorphisms in PRKAG2 were detected. [inv6+36insA] occurred in intron 6 in 4 WPW patients and [inv10+10delT] in intron 10 in 1 WPW patient. Both occurred in normal unrelated chromosomes. No PRKAG2 mutations were detected. CONCLUSION: This study shows that, unlike familial WPW syndrome, constitutional mutation of PRKAG2 is not commonly associated with sporadic WPW syndrome. Although polymorphisms within the PRKAG2 introns were identified, there is no evidence that these polymorphisms predispose to accessory pathway formation because their frequency is similarly high in both WPW patients and normal individuals. Further studies are warranted to identify the molecular basis of common sporadic WPW syndrome.

AMP-Activated Protein Kinases↗

Endocardial detection of repolarization alternans.

Repolarization alternans (RPA) is prognostic of sudden cardiac death and is thought to be mechanistically linked to the initiation of ventricular tachyarrhythmias. Thus, implantable cardiac device detection of RPA may be therapeutically valuable. Because alternans detection is currently limited to surface electrocardiograms, we investigated whether RPA could be measured using a single right-ventricular endocardial lead in humans. Such a location was chosen because it is consistent with the requirements for long-term implantable-device implementation. During diagnostic electrophysiological testing, 28 patients (23 male, 5 female; 61 +/- 15 years) were evaluated for surface T-wave alternans (TWA; the current "gold standard" for RPA detection) and endocardial RPA during 5 min of 550-ms right-atrial pacing. Power spectral analysis indicated that 11/28 patients had both surface TWA and endocardial RPA, 9/28 patients had neither, and 8/28 patients had discordant results (71% concordance; p = 0.02). Importantly, unlike surface TWA, endocardial RPA was detectable on a beat-to-beat basis. Given the putative mechanistic link between RPA and ventricular arrhythmias, beat-to-beat endocardial RPA detection might be of diagnostic or therapeutic utility.

Algorithms↗

CVT-510: a selective A1 adenosine receptor agonist.

Adenosine is an endogenous nucleoside that has potent antiarrhythmic effects on paroxysmal supraventricular tachycardia (PSVT) due to its negative dromotropic effects on the atrioventricular node. In addition to its electrophysiologic effects, adenosine has important effects on vascular smooth muscle cells, inflammatory cells, the central nervous system, and the kidney. Four known adenosine receptor subtypes (A1, A2A, A2B, and A3) mediate the pleiotropic effects of adenosine in humans. These receptors are coupled to a wide range of second messenger cascades. Activation of the A1 adenosine receptor accounts for the negative chronotropic and dromotropic effects of adenosine, whereas A2A, A2B and A3 adenosine receptor activation are responsible for such effects as coronary vasodilation, bronchospasm, inhibition of platelet aggregation, and neuronal stimulation. Elucidation of the specific properties of each of the adenosine receptor subtypes has led to the development of selective ligands as potential therapeutic agents. CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside, was developed as a selective A1 adenosine receptor agonist that specifically targets the atrioventricular node for termination of PSVT. Preliminary clinical trials have shown that CVT-510 is effective in terminating PSVT and eliminating many of the undesirable adverse effects of adenosine. CVT-510 is also being explored as a potential agent for controlling the ventricular rate of atrial fibrillation and flutter.

Adenosine↗

Response to adenosine differentiates focal from macroreentrant atrial tachycardia: validation using three-dimensional electroanatomic mapping.

BACKGROUND: We previously proposed that adenosine has mechanism-specific effects on atrial tachycardia (AT), such that adenosine terminates AT attributable to triggered activity, transiently suppresses automatic rhythms, and has no effect on macroreentrant AT. This, however, remains controversial, because other studies have reported that adenosine terminates reentrant AT. To clarify this issue, we used 3D electroanatomic mapping to delineate the tachycardia circuit and thereby determine whether the response to adenosine differentiates focal from macroreentrant AT. METHODS AND RESULTS: We examined the effect of adenosine on 43 ATs in 42 consecutive patients (59+/-15 years of age; 26 female) who received adenosine during tachycardia and whose mechanism of AT was characterized by pharmacological perturbation, entrainment, 3D electroanatomic mapping, and results of radiofrequency ablation. Eight tachycardias were macroreentrant (noncavotricuspid isthmus-dependent), and 35 ATs were focal (either triggered or automatic). Adenosine administered during AT (at doses sufficient to result in AV block) terminated or transiently suppressed focal AT in 33 of 35 cases, whereas 8 of 8 macroreentrant ATs were adenosine insensitive (P<0.001). Twenty-eight of 35 focal ATs were located along the crista terminalis or tricuspid annulus. CONCLUSIONS: The response of AT to adenosine can immediately differentiate atrial tachycardia arising from a focal source from that attributable to macroreentry. This finding can be exploited to facilitate developing a focused, strategic ablative approach at the onset of a procedure.

Adenosine↗

Do atrial tachyarrhythmias beget ventricular tachyarrhythmias in defibrillator recipients?

OBJECTIVES: This study was designed to analyze the incidence of "dual tachycardia"-ventricular tachycardia (VT) or ventricular fibrillation (VF) preceded by paroxysmal atrial tachycardia (AT) or atrial fibrillation (AF)-in patients receiving dual-chamber implantable cardioverter defibrillators (ICDs). BACKGROUND: Paroxysmal AT/AF occurs commonly in patients who receive ICDs for the treatment of life-threatening VT/VF. Although AF is associated with an adverse prognosis in the setting of structural heart disease, the relationship between AT/AF and VT/VF is unclear. METHODS: We followed 537 patients undergoing implantation of the Jewel AF ICD (Model 7250, Medtronic, Minneapolis, Minnesota) for 11.4 +/- 8.2 months. These included 398 patients with a history of at least two episodes of AT or AF during the preceding year as well as 139 patients enrolled because of VT/VF alone. RESULTS: There were 233 dual tachycardia episodes in 45 patients during follow-up. Overall, 8.9% of episodes detected as VT/VF were dual tachycardias, and 20.3% of patients with VT/VF had at least one dual tachycardia episode. The median duration of AT/AF preceding the first VT/VF detection was 1.09 h (25% to 75% quartile 0.24 to 33.4 h). When AT/AF continued between two consecutive VT/VF detections, the median interdetection interval was 11 min. When AT/AF terminated either because of a ventricular therapy or spontaneously, the median interdetection interval was prolonged to 71 h (p < 0.001). CONCLUSIONS: Dual tachycardia is common in ICD recipients with a history of AT/AF. The duration of AT/AF preceding the first VT/VF detection is < or =1 h about 50% of the time. Termination of the AT/AF significantly delays the time to the next VT/VF detection.

Aged↗

Lesional tachycardias related to mitral valve surgery.

OBJECTIVES: The purpose of this study was to define the anatomic distribution of electrically abnormal atrial tissue and mechanisms of atrial tachycardia (AT) after mitral valve (MV) surgery. BACKGROUND: Atrial tachycardia is a well-recognized long-term complication of MV surgery. Because atrial incisions from repair of congenital heart defects provide a substrate for re-entrant arrhythmias in the late postoperative setting, we hypothesized that atriotomies or cannulation sites during MV surgery also contributed to postoperative arrhythmias. METHODS: In 10 patients with prior MV surgery, electroanatomic maps were constructed of 11 tachycardias (6 right atrium [RA], 4 left atrium [LA] and 1 biatrial). Activation and voltage maps were used to identify areas of low voltage, double potentials and conduction block. RESULTS: Lesions were present in the lateral wall of the RA (six of seven maps) and in the LA along the septum adjacent to the right pulmonary veins (four of five maps). In 8 of 10 patients, these findings corresponded to atrial incisions or cannulation sites. Arrhythmia mechanisms were identified for 9 of 11 tachycardias. A macro-re-entrant circuit was mapped in six cases, three involving lesions in the lateral wall of the RA and three involving the LA septum and right pulmonary veins. In three of these cases figure-of-eight re-entry was demonstrated, and in the other three a single macro-re-entrant circuit was observed. In three other cases, a focal origin was identified adjacent to abnormal tissue in the RA (two cases) or within a pulmonary vein (one case). CONCLUSIONS: Surgical incisions for MV surgery provide a substrate for atrial arrhythmias. Both macro-re-entrant and focal mechanisms contribute to AT after MV surgery.

Aged↗