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Biomedical subjects

M O Tang

Publications and source records attributed to M O Tang.

13 recordsLinked to original sources

Evaluation of CYP2D6 oxidation of dextromethorphan and propafenone in a Chinese population with atrial fibrillation.

The objective of this study was to determine the percentage of patients with paroxysmal atrial fibrillation who were poor metabolizers of CYP2D6 in a Chinese population from Hong Kong and to assess the relationship between the dextromethorphan/dextrorphan ratio and the propafenone/5-hydroxypropafenone ratio or the steady-state propafenone concentration. Patients (n = 60) were recruited from the Arrhythmia Clinic at the University of Hong Kong and given dextromethorphan 30 mg. The dextromethorphan and dextrorphan concentrations in urine over the next 8 hours were used to determine metabolizer status. If the metabolic ratio was greater than 0.3, the patient was determined to be a poor metabolizer. In phase 2, patients (n = 38) were given propafenone 150 mg twice daily, and at steady state, the propafenone and 5-OH propafenone plasma concentrations were determined. It was found that 15% of the patients were poor metabolizers of dextromethorphan. There was a significant correlation between the metabolic ratios of dextromethorphan/dextrorphan and propafenone/5-OH propafenone (r = 0.49, p = 0.0019) and between the dextromethorphan/dextrorphan ratio and the concentration of propafenone (r = 0.32, p = 0.05). No correlations were found in the extensive or poor metabolizer subgroups. It was concluded that the percentage of poor metabolizers in atrial fibrillation patients from Hong Kong was much larger than in previous studies of Chinese patients who were not from Hong Kong. The ability to metabolize dextromethorphan to dextrorphan is related to the ability to metabolize propafenone to 5-hydroxypropafenone.

Anti-Arrhythmia Agents↗

Control of paroxysmal atrial fibrillation recurrence using combined administration of propafenone and quinidine.

The frequent recurrence of paroxysmal atrial fibrillation (PAF) despite the use of standard antiarrhythmic agents prompted the use of new therapeutic approaches. There are few data on systematic assessment of PAF control with stepwise dose escalation and the use of a drug combination. Low-dose quinidine may promote the efficacy of propafenone by inhibiting its degradation through the cytochrome P450 pathway (CYP2D6). We prescribed propafenone 300 to 450 mg/day to 60 patients with PAF for 8 weeks, and 62% were symptomatically controlled. The 19 refractory patients were randomized in a double-blinded fashion to receive either a higher dose of propafenone (450 to 675 mg/day) or the standard dose of propafenone with low-dose quinidine 150 mg/day, each for an 8-week study period, and subsequently crossed over to the alternative treatment. The resulting serum propafenone concentrations were 259 +/- 208 and 336 +/- 237 mg/day (p >0.5), respectively. Both treatment arms prolonged the time to the first symptomatic atrial fibrillation (AF) recurrence and the interval between attacks, and AF was controlled in 37% of patients. However, the higher dose of propafenone was associated with gastrointestinal side effects not present with the low-dose quinidine combination. Of the 10 refractory patients, 7 were further controlled with a standard dose of propafenone plus quinidine (600 mg/day). Overall, control of PAF was achieved in 85% of patients at the end of 8 months; adverse effects necessitating withdrawal were observed in 6%, and uncontrolled AF in 5% of patients. There was no difference in the mean AF rate during recurrences in all phases, and ventricular proarrhythmia was not seen. This study documents the role of stepwise antiarrhythmic treatment of PAF. The use of a standard dose of propafenone, followed by low-dose quinidine combination to reduce propafenone degradation, and the combined standard dose of propafenone and quinidine may be used to maximize efficacy and tolerability.

Adolescent↗

Efficacy and tolerability of continuous overdrive atrial pacing in atrial fibrillation.

Overdrive right atrial pacing has been used to prevent atrial fibrillation, but its efficacy in atrial fibrillation prevention and the patient tolerability and quality of life during high rate pacing remain uncertain. The objective of this study was to test the effects of a consistent atrial pacing algorithm that automatically paced the atrium at 30 ms shorter than the sinus P-P interval for atrial fibrillation prevention. Fifteen patients with sick sinus syndrome implanted with a Thera DR (model 7940 or 7960, Medtronic Inc.) were randomly programmed to rate adaptive dual chamber pacing (DDDR) or DDDR + consistent atrial pacing mode, each for an 8-week study period. The efficacy of consistent atrial pacing was assessed by the number of automatic mode switching and the number of premature atrial complexes. Symptoms and quality of life were assessed by the SF-36 quality of life questionnaire and an atrial fibrillation symptom checklist. The percentage of atrial pacing increased from 57 +/- 32% to 86 +/- 28%. Overall, there was no significant difference in the number of automatic mode switching episodes between DDDR and DDDR + consistent atrial pacing (47 +/- 90 vs 42 +/- 87, P > 0.05), but a significant reduction in premature atrial complexes by 74.7% (P < 0.001). There was no undue increase in atrial rate by the DDDR + consistent atrial pacing mode versus DDDR (63 +/- 13 vs 70 +/- 7 bpm). There was no significant difference in quality of life scores and symptom severity on frequency between the two modes of pacing, but a trend towards a lower frequency of symptoms in the DDDR + consistent atrial pacing mode compared with baseline (29.5 +/- 10.2 vs 25.1 +/- 9.7, P = 0.07). An algorithm that provides consistent atrial overdrive pacing can suppress atrial fibrillation triggering premature atrial complexes without the need to increase the overall atrial rate compared with conventional pacing. The algorithm appears to be well-tolerated, but further studies are needed to address the clinical impact of this atrial fibrillation prevention algorithm.

Aged↗

A comparative study on the behavior of three different automatic mode switching dual chamber pacemakers to intracardiac recordings of clinical atrial fibrillation.

Automatic mode switching (AMS) allows patients with dual chamber pacemakers who develop paroxysmal AF to have a controlled ventricular rate. The aim of this study was to (1) compare the rate-controlled behavior of three AMS algorithms in response to AF, in terms of speed and stability of response and resynchronization to sinus rhythm, and (2) compare the influence of pacemaker programming on optimal mode switching. We studied 17 patients (12 men, 5 women; mean age 59 +/- 15 years) who developed AF during electrophysiological study. Unfiltered bipolar atrial electrograms during sinus rhythm and AF were recorded onto high fidelity tapes and replayed into the atrial port of three dual chamber pacemakers with different mode switching algorithms (Thera, Marathon, Meta). The Thera pacemaker uses rate smoothing, and mode switches occur when mean sensed atrial rate exceeds the predefined AMS rate (MR). Marathon mode switches after a programmable number of consecutive rapid atrial events (NR). Meta DDDR monitors the atrial rate by a counter for atrial cycles faster than the programmed AMS rate. It increases or decreases the counter if the atrial cycle length is shorter or longer than the programmed AMS interval, respectively. Mode switch occurs when the AF detection criteria are met (CR). A total of 260 rhythms were studied. NR was significantly faster than MR and CR (latency 2.5 +/- 3 s vs 26 +/- 7 s vs 15 +/- 22 s, respectively, P < 0.0001). During sustained AF, MR resulted in the most stable and regular ventricular rhythm compared to NR or CR. In CR, ventricular rate oscillated between AMS and atrial tracking (cycle length variations: 44 +/- 2 s vs 346 +/- 109 s vs 672 +/- 84 s, P < 0.05). At resumption of sinus rhythm, MR resynchronized after 143 +/- 22 s versus 3.4 +/- 0.7 s for NR and 5.9 +/- 1.1 s for CR, resulting in long periods of AV dissociation when a VVI/VVIR mode is used after AMS. Programming of atrial refractory periods did not affect AMS response, although the speed of AMS onset can be adjusted by programming of onset criteria in the Meta DDDR. AMS algorithms differ in their ability to handle recorded clinical atrial arrhythmias. The rapid-responding algorithm exhibits rate instability, whereas slow responding algorithm shows a long delay in response and risk of AV dissociation. Thus different instrumentation of AMS may have clinical implications in patients with dual chamber pacemakers who develop AF.

Adult↗

Reversal of left ventricular remodeling by synchronous biventricular pacing in heart failure.

Synchronous biventricular pacing is a new nonpharmacological supplemental treatment of advanced heart failure associated with electromechanical conduction delay. However, the role of pacing on left ventricular remodeling is unknown. Eleven patients with New York Heart Association Class III to IV heart failure, a left ventricular ejection fraction < 35%, and a QRS duration > or = 140 ms received a biventricular dual chamber pacemaker. Serial echocardiography, 6-minute hall walk, and Minnesota Living with Heart Failure quality-of-life (QOL) questionnaire were performed before and after up to 3 months of pacing. At 3 months there was a significant increase in fractional shortening (P < 0.001), ejection fraction (P < 0.001), and cardiac output (P < 0.05). The left ventricular end-diastolic volume (245 +/- 70 vs 185 +/- 37 mL, P < 0.05), end-systolic volume (209 +/- 69 vs 140 +/- 44 mL P < 0.05), and mitral regurgitation were reduced (P < 0.05), and diastolic filling time was lengthened (P < 0.05). There were also improvements in heart failure symptoms, an increase in 6-minute walk distance, and a decrease in QOL scores. Synchronous biventricular pacing for 3 months was associated with hemodynamic improvements, reversal of left ventricular remodeling, and increase in left ventricular systolic function, and a decrease in secondary mitral regurgitation.

Cardiac Pacing, Artificial↗

Automatic optimization of resting and exercise atrioventricular interval using a peak endocardial acceleration sensor: validation with Doppler echocardiography and direct cardiac output measurements.

Peak endocardial acceleration (PEA) measured by an implantable acceleration sensor inside the tip of a pacing lead reflects ventricular filling and myocardial contractility. The contribution of the plateau phase of PEA as an indicator of optimal ventricular filling, hence of the appropriate atrioventricular interval (AVI) at rest and during exercise, was studied in 12 patients (age 69 +/- 6 years) with complete AV block and a PEA sensing DDDR pacemakers (Living 1 Plus, Sorin Biomedica). At a mean resting heart rate of 79 +/- 15 beats/min, the mean AVI optimized by PEA versus Doppler echocardiography (echo) were identical (142 +/- 37 vs 146 +/- 26 ms, P = 0.59). During submaximal exercise at a mean heart rate of 134 +/- 6 beats/min, AVI optimized by PEA was 135 +/- 37 ms. Cardiac output at rest, measured by the CO2 rebreathing method, was comparable with AVI determined by echo versus PEA (4.3 +/- 2.9 and 3.7 +/- 2.4 L/min, respectively), and increased to the same extent (8.0 +/- 3.9 vs 8.3 +/- 5.2 L/min) during submaximal exercise. In patients with AV block, AVI automatically set by PEA was comparable with AVI manually optimized by Doppler echocardiography and was associated with comparable exercise induced hemodynamic changes.

Aged↗

Efficacy of ventricular rate stabilization by right ventricular pacing during atrial fibrillation.

To assess the effect of right ventricular pacing on rate regularity during exercise and daily life activities, 16 patients with sinoatrial disease and chronic atrial fibrillation (AF) were studied. Incremental ventricular pacing was commenced at 40 beats/min until > 95% of ventricular pacing were achieved during supine, sitting, and standing. Thirteen patients also underwent randomized paired submaximal exercise tests in either a fixed rate mode. (VVI) or a ventricular rate stabilization (VRS) mode in which the pacing rate was set manually at 10 beats/min above the average AF rate during the last minute of each exercise stage. The pacing interval for rate regularization was shortest during standing (692 +/- 26 ms) compared with either supine or sitting (757 +/- 30 and 705 +/- 26 ms, respectively, P < 0.05). During exercise VRS pacing significantly increased the maximum rate (119 +/- 5.2 vs 106 +/- 4.2 ms, P < 0.05), percent of ventricular pacing (85% +/- 5% vs 23% +/- 7%, P < 0.05), rate regularity index (5.8% +/- 1.6% vs 13.4% +/- 1.9%, P < 0.05), and maximum level of oxygen consumption (12.4 +/- 0.5 vs 11.3 +/- 0.5 mL/kg, P < 0.05) compared with VVI pacing. There was no change in oxygen pulse or difference in symptom scores in this acute study between the two pacing modes. It is concluded that right ventricular pacing may significantly improve rate regularity and cardiopulmonary performance in patients with chronic AF. This may be incorporated in a pacing device for rate regularization of AF using an algorithm that is rate adaptive to postural and exercise stresses.

Adult↗

An integrated dual sensor system automatically optimized by target rate histogram.

The use of combined sensors and advanced algorithms using different principles can improve rate performance over a single sensor system. Combinations of sensors and more sophisticated algorithms, however, invariably increase the complexity of pacemaker programming. An automatically optimized combined minute ventilation and activity DDDR pacemaker was developed to minimize repeated sensor adjustment. The device used subthreshold (below cardiac stimulation threshold) lead impedance to detect lead configuration at implantation automatically, followed by "implant management," including setting of lead polarity and initiation of DDDR pacing. Automatic sensor adaptation was achieved by programming a "target rate histogram" based on the patient's activity level and frequency of exertion, and the rate profile optimization process matched the recorded integrated sensor response to the target rate histogram profile. In nine patients implanted with the DX2 pacemakers, the implant management gave 100% accuracy in the detection of lead polarity. Rate profile optimization automatically increased the pacing rate during exercise between discharge and 3-month follow-up (hall walk: 78 +/- 3 vs 98 +/- 3 beats/min, and maximal treadmill exercise: 89 +/- 6 vs 115 +/- 5 beats/min, P < 0.001) with a significant increase in exercise duration during maximal exercise (7.18 +/- 1 min vs 9.56 +/- 2 min, P = 0.05). The accuracy of rate profile optimization versus manual programming was assessed at 1 month, and there was no significant difference between pacing rate kinetics and maximal pacing rate between the two methods of programming. In conclusion, pacemaker automaticity can be initiated at implantation and the self-optimized rate adaptive response appeared to be comparable to that derived from a manual programming procedure, which may reduce the need to perform time consuming sensor programming.

Aged↗

Cardiac output is a sensitive indicator of difference in exercise performance between single and dual sensor pacemakers.

Although multisensor pacing may compensate the inadequacy of rate adaptation in a single sensor system, the clinical role of multisensor driven rate adaptive pacing remains unclear. We compared the performance between single sensor and dual sensor driven pacemakers using exercise cardiac output (CO) as a marker of cardiac performance. Eight patients with a mean age of 63 +/- 3 years implanted with a dual sensor pacemaker driven by combined activity (ACT) and QT interval sensors were studied in the ACT-, QT- only and the dual QT + ACT-VVIR modes. Patients performed submaximal and maximal exercise tests with CO assessed by carbon dioxide rebreathing method. Comparing the HR response based on the change in metabolic workload, the ACT-VVIR "overpaced," the QT-VVIR "underpaced," and the QT + ACT-VVIR achieved the best approximation to normal. The percentages of CO increase in ACT-VVIR and QT + ACT-VVIR modes over resting CO were higher at 1 minute of exercise (295 +/- 85% and 165 +/- 49%, respectively) compared to the QT-VVIR mode (81 +/- 40%, P < or = 0.05). During exercise, stroke volume changes from baseline were similar between ACT-VVIR and QT + ACT-VVIR modes, but a compensatory increase in stroke volume occurred in the QT-VVIR mode during submaximal exercise (50 +/- 11 mL vs 24 +/- 17 mL in the QT + ACT-VVIR and 14 +/- 4 in ACT-VVIR, P < or = 0.003). There was no difference in the maximal exercise workload, exercise duration and CO at the submaximal and maximal exercise between the 3 sensor modes. Thus, exercise capacity is a poor indicator of sensor performance while CO measurement is a sensitive indicator of sensor mode differences especially at low workload exercise. The ACT-VVIR gave the fastest increase in CO at start of exercise at the expanse of overpacing, whereas the "under-paced" QT-VVIR compensated for the slower rate increase by utilizing contractility reserve during submaximal exercise. Dual sensor pacing, by achieving the best heart rate to workload relationship, provided a CO response without overpacing or using contractility reserve during exercise.

Adaptation, Physiological↗

Programmed atrial sensitivity: a critical determinant in atrial fibrillation detection and optimal automatic mode switching.

Automatic mode switching (AMS) prevents tracking of paroxysmal atrial fibrillation (AF) in dual chamber pacing. The correct detection of AF can be affected by the programmed atrial sensitivity (AS). We prospectively studied the relationship between AS, AF undersensing, and AMS, using unfiltered bipolar intracardiac atrial electrograms recorded from 17 patients during sinus rhythm (SR) and in AF. Overall, 780 rhythms were recorded and replayed onto three dual chamber pacemaker models using different AMS algorithms (Thera DR 7940, Marathon DDDR 294-09, and Meta DDDR 1254), and the ventricular responses were measured. AS was randomly programmed in steps from the highest available AS to half of the mean atrial P wave amplitude (PWA), and the percentage of appropriate AMS responses (defined as a ventricular pacing rate at the expected AMS mode) were recorded. AMS efficacy was related to the programmed AS settings in an exponential manner. At low AS settings, a higher percentage of tests were associated with absence of, or with intermittent AMS and tracking of AF, whereas at higher AS, oversensing of noise during SR occurred. An optimal AS measured approximately 1.3 mV, representing about one-third of the PWA measured during SR, although oversensing of SR and undersensing of AF continued to occur in 14% of tests and time, respectively, due to the high variation in PWA during AF. Thus, a fixed AS cannot eliminate AF undersensing without inviting noise oversensing, suggesting the need for automatic adjustments of AS, or the use of a rate-limiting algorithm to prevent rate oscillation during intermittent AF sensing. In conclusion, AMS functions of existing pacemakers were significantly limited by the undersensing of AF and oversensing of noise. Proper adjustment of the AS is important to enable effective AMS during AF.

Algorithms↗

New integrated sensor pacemaker: comparison of rate responses between an integrated minute ventilation and activity sensor and single sensor modes during exercise and daily activities and nonphysiological interference.

A dual sensor DDDR pacemaker (DX2 Model 7970, Medtronic Inc.) has integrated the rate response of minute ventilation (MV) and activity (ACT) sensors. False rate acceleration by the ACT (constrained upper rate) and MV (cross-checked by ACT) is reduced. We examined the rate response profile and rate kinetics of the automatically optimized integrated sensor by comparing with the projected rate response of ACT and MV sensors alone in nine patients. After 1 month of sensor optimization using rate profile optimization (RPO), patients underwent maximal and submaximal treadmill exercises and performed activities of daily living (ADL). The integrated sensor mode gave a faster speed of rate response with a shorter delay time, time to 50% rate response and time to 90% of rate response compared to the MV sensor during hall walk (0.37 +/- 0.08, 0.7 +/- 0.09, 1.43 +/- 0.19 vs 1.11 +/- 0.1, 1.75 +/- 0.14, 2.91 +/- 0.17 min; P < 0.05). The average maximal sensor rates were significantly more proportional for the integrated sensor mode compared with either the ACT or MV mode. There was no significant difference in both the maximal pacing rate among the three sensor modes during maximal exercise and the rate decay during recovery. During interference studies by arm swinging (30-40 swings/min) and external tapping of the pacemakers (2 taps/s), there was only a moderate increase in pacing rate by 13 +/- 9, 16 +/- 5 beats/min. Hence, the new integrated sensor with the automatic rate profile optimization algorithm resulted in improved rate response profiles during submaximal exercise and ADL compared to the individual sensor response, and the sensor blending and cross-checking algorithm made the pacemaker relatively immune to false triggering of both the ACT and MV sensors.

Activities of Daily Living↗

Quality-of-life in DDDR pacing: atrioventricular synchrony or rate adaptation?

Although differences in exercise performance have been observed between different rate adaptive modes, the relative impact of atrioventricular (AV) synchrony and rate adaptation on quality of life (QOL) have not been determined. Thirty-three patients with either sinoatrial disease (18) or complete atrioventricular (AV) block (15) received DDDR pacemakers (16 minute ventilation sensing, 17 activity sensing). There were 11 males and 22 females, with a mean age of 66 +/- 1 (range 39-78) years. The study was a double-blind, triple cross-over study comparing DDDR, DDD, and VVIR modes. At the end of each 8-week study period in each mode, QOL was assessed by a questionnaire evaluating patients' functional class (Classes I-IV), physical malaise inventory (41 items), illness perception (43 items), and overall QOL rating based on a 48 items measure covering different aspects of the patients' daily life adjustment. Two patients required early crossover from VVIR mode during the study. Patients experienced significantly fewer physical malaise such as temperature intolerance, dyspnea, and palpitations in the DDDR mode, compared with either DDD or VVIR pacing. DDDR pacing reduced the perception of illness in 5 of 43 items compared to VVIR pacing, and improved stamina and appetite compared to DDD pacing. The overall QOL score was 102 +/- 2, 105 +/- 2, 113 +/- 2 in the DDDR, DDD, and VVIR modes, respectively, with a higher score indicating a poorer QOL (DDDR/DDD vs VVIR, P < 0.02). There was no change in functional classes between the three pacing modes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparative evaluation of bipolar atrial electrogram amplitude during everyday activities: atrial active fixation versus two types of single pass VDD/R leads.

Endocardial P wave amplitude (PWA) is an important determinant of the atrial sensing capabilities of an atrial-based pacing system. Although changes in PWA during physical activities are known to occur in DDD/R pacing, there is little information on the P wave stability in single pass lead VDD/R pacemakers using floating P wave sensing. We investigated the variation of PWA during daily life activities using telemetry recorded atrial electrograms in 21 patients with DDDR pacemakers (Relay or Elite) and 29 patients with single lead VDD/R pacemakers (Unity or Thera). Physical activities resulted in marked individual variability of PWA but, as a group, there was no significant difference between PWA during sitting, standing, lying down, and coughing in both DDDR and VDD/R pacing. In the Elite II pacemaker, walking at 2 miles per hour resulted in significant reduction of PWA (11.6% compared with sitting, P < 0.05). The most consistent reduction in PWA occurred in the relaxation phase of the Valsalva maneuver (VM), with all pacemakers showing a reduction in PWA (mean reduction in PWA compared with sitting in DDDR and VDD/R were 16.6% and 12.8%, respectively). Two patients with DDDR pacemakers (Relay) and three patients with VDD/R pacemakers (1 Unity and 2 Thera) had atrial sensing failure during VM or walking. In conclusion, large variation in PWA occurs during daily life activities. The extent of variation is dependent on the patients, types of atrial lead, and the maneuvers performed. A twice sensing threshold may be insufficient to ensure adequate atrial sensing during these activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗