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R Mehra

Publications and source records attributed to R Mehra.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of angiogenesis by a Semliki Forest virus vector expressing VEGFR-2 reduces tumour growth and metastasis in mice.

Inhibition of tumour angiogenesis has been shown to restrict primary tumour growth and metastatic spread. This study examines the active induction of immune responses against tumour endothelial cells following immunization with recombinant Semliki Forest virus (rSFV) particles encoding murine vascular endothelial growth factor receptor-2 (VEGFR-2). This approach was tested in two murine tumour models, CT26 colon carcinoma and 4T1 metastasizing mammary carcinoma. Tumour growth and metastatic spread were shown to be significantly inhibited in mice that were prophylactically vaccinated or therapeutically treated with rSFV particles coding for VEGFR-2. Microvessel density analysis showed that immunization with rSFV led to significant inhibition of tumour angiogenesis. Therapeutic efficacy was found to be associated with the induction of an antibody response against VEGFR-2. Co-immunization of mice with rSFV particles encoding VEGFR-2 and interleukin (IL)-12 completely abrogated both the antibody response and the antitumour effect. However, co-immunization of mice with VEGFR-2 and IL-4 encoding particles was shown both to induce higher titres of anti-VEGFR-2 antibodies and lead to enhanced survival following tumour challenge when compared to mice vaccinated with VEGFR-2 particles alone. These findings indicate that active immunization with rSFV particles coding for VEGFR-2 can break immunological tolerance and could potentially be used as part of a novel treatment for cancer.

Animals↗
PubMed2003

Chronic excess of corticosterone increases serotonergic fibre degeneration in aged rats.

Evidence is presented for the potentiating role of corticosterone on axonal degeneration of serotonergic neurones during ageing. Aged rats, 24 months old, were implanted subcutaneously with 2 x 100 mg pellets of corticosterone. Serotonergic and cholinergic (ChAT- and NADPHd-positive) fibre degenerations in the anteroventral thalamic nucleus (AVT) were measured 2 months after corticosterone implantation. Numbers of immunoreactive serotonergic raphe and mesolimbic cholinergic neurones were also quantified. Basal plasma corticosterone and adrenocorticotropin (ACTH) concentrations were assayed at 2, 4, 6, and 8 weeks after implantation in the plasma and at 1, 2, 4 and 6 weeks in urine. The degree of serotonergic fibre aberrations in the AVT increased significantly after corticosterone exposure, while that of ChAT-positive and NADPHd-stained axon aberrations showed a modest but nonsignificant increase. A positive correlation between the magnitudes of serotonergic and cholinergic fibre aberrations appeared in the AVT, but only in the corticosterone-treated rats. The number of serotonin immunopositive neurones in the raphe nuclei after corticosterone decreased marginally, while that of mesopontine ChAT-positive neurones was not influenced. Measurements of basal plasma corticosterone and ACTH, as well as urine corticosterone, revealed that the steroid implantation increased the plasma corticosterone level for at least 4 weeks and decreased ACTH level for at least 6 weeks. By the week 8, the pituitary-adrenal function was apparently restored. However, at sacrifice, both the weight of adrenal glands and that of thymus remained reduced, indicating the long-lasting effects of corticosterone on target tissues. It is concluded that the raphe serotonergic neurones and their projecting fibres are sensitive to corticosterone excess in aged rats and become more vulnerable to degeneration processes than under normal ageing conditions. Cholinergic neurones of brainstem origin, which also express massive NADPHd activity, are more resistant against corticosterone, but their axon degeneration correlates to serotonergic fibre degeneration.

Adrenal Glands↗
PubMed2001

Chronic graft-versus-host disease after allogeneic blood stem cell transplantation.

The incidence, characteristics, risk factors for, and impact of chronic graft-vs-host disease (GVHD) were evaluated in a consecutive series of 116 evaluable HLA-identical blood stem cell transplant recipients. Minimum follow-up was 18 months. Limited chronic GVHD occurred in 6% (95% confidence interval [CI], 0%-13%), and clinical extensive chronic GVHD in 71% (95% CI, 61%-80%). The cumulative incidence was 57% (95% CI, 48%-66%). In univariate analyses, GVHD prophylaxis other than tacrolimus and methotrexate, prior grades 2 to 4 acute GVHD, use of corticosteroids on day 100, and total nucleated cell dose were significant risk factors for clinical extensive chronic GVHD. On multivariate analysis, GVHD prophylaxis with tacrolimus and methotrexate was associated with a reduced risk of chronic GVHD (hazard ratio [HR], 0.35; P =.001), whereas the risk was increased with prior acute GVHD (HR, 1.67; P =.046). When adjusted for disease status at the time of transplantation, high-risk chronic GVHD had an adverse impact on overall mortality (HR, 6.6; P <.001) and treatment failure (HR, 5.2; P <.001) at 18 months. It was concluded that there is a substantial rate of chronic GVHD after HLA-identical allogeneic blood stem cell transplantation, that clinical factors may alter the risk of chronic GVHD, and that high-risk chronic GVHD adversely affects outcome.

Adolescent↗
PubMed2001

Atrial therapies reduce atrial arrhythmia burden in defibrillator patients.

BACKGROUND: Approximately 25% of patients who receive an implantable cardioverter-defibrillator (ICD) to treat ventricular tachyarrhythmias have documented atrial tachyarrhythmias before implantation. This study assessed the ability of device-based prevention and termination therapies to reduce the burden of spontaneous atrial tachyarrhythmias. METHODS AND RESULTS: Patients with a standard indication for the implantation of an ICD and 2 episodes of atrial tachyarrhythmias in the preceding year received a dual-chamber ICD (Medtronic 7250 Jewel AF) that uses pacing and shock therapies for prevention and/or termination of atrial tachyarrhythmias. In a multicenter trial, patients were randomized to 3-month periods with atrial therapies "on" or "off" and subsequently crossed over. Analysis was performed on the 52 of 269 patients who had episodes of atrial tachyarrhythmia and had >/=30 days of follow-up with atrial therapies on and off. The atrial therapies resulted in a reduction of atrial tachyarrhythmia burden from a mean of 58.5 to 7.8 h/mo. A paired analysis (Wilcoxon signed-rank test) showed that the median difference in burden (1.1 h/mo) was highly significant (P=0.007). When the subgroup of 41 patients treated only with atrial pacing therapies was analyzed, the reduction in burden persisted (P=0.01). CONCLUSIONS: In this study, patients with a standard ICD indication and atrial tachyarrhythmias had a significant reduction in atrial tachyarrhythmia burden with use of atrial pacing and shock therapies.

Aged↗
PubMed2001

Open-heart endocardial radiofrequency ablation: an alternative to incisions in Maze surgery.

BACKGROUND: Radiofrequency (RF) ablation produces transmural atrial lesions in vitro, and may provide advantages over incisions currently used in maze surgery. This study examines the feasibility, safety, and efficacy of open-heart endocardial RF ablation. METHODS: Eighteen sheep (42.8 +/- 4.4 kg, age < 2 years) underwent left thoracotomy with placement of pacing leads on a pulmonary vein and the left atrial dome. On cardiopulmonary bypass, lesions were made using incision and suture or a novel RF ablation device in three sites: PVC = circle excluding pulmonary veins, IAB = line across the interatrial bundle, SVC = line from the superior to the inferior vena cava. Pacing across the PVC lesion was attempted to assess the completeness of each lesion. Preselected animals (incision n = 4, RF n = 5) were recovered and pacing attempts were repeated at 1 month. After sacrifice, hearts were sectioned and measured for lesion size and completeness. RESULTS: RF ablation lesions took less time to create (total bypass time: RF 51.8 min vs incision 106 min, P < 0.001). No evidence of thromboembolism, atrial rupture, or coronary sinus thrombosis was seen. All PVC lesions were complete as demonstrated by the inability to pace across them. Stained sections demonstrated that acutely studied incision lesions were thinner than RF lesions; however, all lesions were transmural and similar in width at 1 month. CONCLUSIONS: RF ablation consistently created transmural lesions more quickly than the incision and suture method and without additional complications. Endocardial RF ablation appears to be a simple and effective alternative to surgical incisions during open-heart atrial Maze procedures.

Animals↗
PubMed2001

Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia.

Sixty-two adults underwent marrow or blood stem cell transplantation from an HLA-matched related donor using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen for treatment of advanced myelodysplastic syndrome (MDS) (refractory anemia with excess blasts with or without transformation) or acute myelogenous leukemia (AML) past first remission. All evaluable patients engrafted and had complete donor chimerism. A grade 3-4 regimen-related toxicity occurred in eight (13%) patients, and a diagnosis of MDS was the only independent risk factor for grade 3-4 regimen-related toxicity (hazard ratio 9.25, P = 0.01). Day-100 treatment-related mortality (TRM) was 19%. Poor-prognosis cytogenetics increased the risk of day-100 TRM (hazard ratio 11.4, P = 0.003), and use of tacrolimus for graft-versus-host disease prophylaxis reduced the risk of day-100 TRM (hazard ratio 0.13, P = 0.027). For all patients, the three-year relapse rate was 43% (95% CI, 28%-58%). Refractoriness to conventional induction chemotherapy prior to transplantation was an independent risk factor for relapse (hazard ratio 10.8, P = 0.02). Three-year survival was 26% (95% CI, 14%-37%); survival rates were 29% for those transplanted for AML in second remission, 31% transplanted for AML in relapse, and 17% with MDS, and there were no independent risk factors for survival. TBC is an active preparative regimen for advanced AML. Patients with advanced MDS appeared to have a higher risk of toxicity and early mortality, and alternative preparative regimens should be considered for these patients.

Adolescent↗
PubMed2001

Attenuation of interatrial conduction using right atrial septal catheter ablation.

OBJECTIVES: We sought to characterize a method of attenuating interatrial conduction using radiofrequency ablated lesions applied to the right atrial septum. BACKGROUND: Interatrial conduction occurs in specific zones. Recent data suggest that interatrial conduction can be important in triggering and sustaining atrial fibrillation. Therefore, a method for attenuating interatrial conduction may have therapeutic value. METHODS: In 13 healthy pigs, interatrial conduction was evaluated before and after sequential ablation of the right atrial septum, targeting interatrial conduction zones. In six animals, zone 1 (crista terminalis and limbus) was ablated first, followed by ablation of zone 2 (fossa ovalis and coronary sinus ostium). In the other seven animals, the order of ablation was reversed. Electrophysiologic and pathologic findings were correlated. RESULTS: After ablation of zone 1, interatrial conduction was slowed, but there was no block. After ablation of zone 2, conduction was unchanged. After ablation of both zones, complete block was observed in four animals, and there was left atrial quiescence. In the remaining nine animals, incomplete block was observed, with marked conduction slowing or block during sinus rhythm and pacing. Ablation did not adversely affect atrioventricular node conduction, nor did it facilitate sustenance of an atrial arrhythmia. Pathologic analysis revealed that complete interatrial conduction block was associated with confluent ablation of both targeted zones. CONCLUSIONS: Catheter ablation of the right atrial septum attenuated interatrial conduction without disturbing atrioventricular conduction.

Animals↗
PubMed2001

Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival.

The purpose of the study was to evaluate in patients with recurrent intermediate-grade NHL, the tolerance to and efficacy of an intensive salvage regimen consisting of high doses of ifosfamide, etoposide and mitoxantrone with G-CSF support, followed by autologous stem cell transplantation and to identify prognostic factors for survival in patients with recurrent aggressive lymphoma. Patients with recurrent intermediate-grade NHL under the age of 60 years were eligible. Induction consisted of ifosfamide 10 g/m(2) and etoposide 900 mg/m(2) with G-CSF 5 microg/kg twice a day. Upon recovery, patients underwent stem cell apheresis. Patients achieving complete remission (CR) underwent autologous stem cell transplantation using BEAM conditioning. Those with partial remission (PR) received treatment with ifosfamide 10 g/m(2), mitoxantrone 20 mg/m(2) and G-CSF 5 microg/kg. Those with CR received BEAM, those with PR received cyclophosphamide 4.5 g/m(2), etoposide 1200 mg/m(2) and cisplatin 135 mg/m(2) with stem cell rescue followed by BEAM. Antibiotic prophylaxis was given with all treatment cycles. The results were compared with those obtained in a prior study that used MINE-ESHAP salvage. Forty-four patients with recurrent intermediate-grade NHL were enrolled between March 1994 and September 1996. Median age was 50 years (24-61). Eleven patients had transformed lymphoma and seven had a T cell phenotype. Response rate to the high-dose ifosfamide regimen was 77% +/- 12% after two cycles and the complete response rate was 41% +/- 14%. Myelosuppression was profound but short. Median nadir ANC was 0 and the median duration of ANC <0.5 x 10(9)/l was 6 days (range 3-12). No severe infections occurred; 55% of the patients required blood transfusion and 42% required platelet transfusions. Myelosuppression and transfusion requirements were similar after the first and second cycles. Thirty-five of the 44 patients proceeded to autologous stem cell transplantation and one transplant-related death occurred. With a median follow-up of 52 months, progression-free survival at 2 years is 38% +/- 14% and survival is 52% +/- 15%. Data from these 44 patients were pooled with data on 53 patients who had received salvage treatment with MINE-ESHAP, for a multivariate analysis of prognostic factors. In multivariate analysis, serum LDH was strongly associated with survival. The use of a more intensive salvage regimen, did not result in a significant increase in long-term outcome, despite a high response rate. In conclusion, duration of treatment, response rates, treatment-related mortality and survival compare favorably with previous salvage regimens, but recurrence remains a major problem. Long-term survival in recurrent large cell lymphoma is influenced more by disease characteristics than by the type of salvage regimen used.

Adolescent↗
PubMed2001

Distribution of patients' paroxysmal atrial tachyarrhythmia episodes: implications for detection of treatment efficacy.

INTRODUCTION: Clinical trials of treatments for paroxysmal atrial tachyarrhythmia (pAT) often compare different treatment groups using the time to first episode recurrence. This approach assumes that the time to the first recurrence is representative of all times between successive episodes in a given patient. We subjected this assumption to an empiric test. METHODS AND RESULTS: Records of pAT onsets from a chronologic series of 134 patients with dual chamber implantable defibrillators were analyzed; 14 had experienced >10 pAT episodes, which is sufficient for meaningful statistical modeling of the time intervals between episodes. Episodes were independent and randomly distributed in 9 of 14 patients, but a fit of the data to an exponential distribution, required by the stated assumption, was rejected in 13 of 14. In contrast, a Weibull distribution yielded an adequate goodness of fit in 5 of the 9 cases with independent and randomly distributed data. Monte Carlo methods were used to determine the impact of violations of the exponential distribution assumption on clinical trials using time from cardioversion to first episode recurrence as the dependent measure. In a parallel groups design, substantial loss of power occurs with sample sizes <500 patients per group. In a cross-over design, there is insufficient power to detect a 30% reduction in episode frequency even with 300 patients. CONCLUSION: Clinical trials that rely on time to first episode recurrence may be considerably less able to detect efficacious treatments than may have been supposed. Analysis of multiple episode onsets recorded over time should be used to avoid this pitfall.

Aged↗
PubMed2001

Comparison of the effects on drug concentrations, electrophysiologic parameters, and termination of atrial fibrillation in dogs when procainamide and ibutilide are delivered into the right atrium versus intravenously.

INTRODUCTION: We tested the hypothesis that right intra-atrial (i.a.) administration of antiarrhythmic drugs resulted in higher peak serum drug concentrations, greater electrophysiologic effects, and greater efficacy for termination of atrial fibrillation (AF) than intravenous (i.v.) drug delivery. METHODS AND RESULTS: Eight dogs were treated with 9.7 mg/kg procainamide infusion and eight dogs with 0.02 mg/kg ibutilide infusion, injected over 5 minutes. Each dog had both an electrophysiologic (EP) and an AF termination study during i.a. and i.v. drug administration at > or = 2-day intervals (total four studies each). Right atrial pacing capture threshold, right atrial effective refractory period (ERP), right atrial and right ventricular monophasic action potential (MAP) durations at 70% and 90% of repolarization (MAPD70, MAPD90), AH, HV, and QT intervals, QRS width, intra-arterial systolic and diastolic blood pressures, and cardiac output were measured at different time-points. Blood samples were drawn from the coronary sinus and femoral vein for drug level determination. The right atrium was paced at 400-msec cycle length throughout the study. AF was induced by rapid right atrial pacing and maintained by methacholine infusion at 1.5 to 3 microg/kg/min. The sustained AF was allowed to persist for 10 minutes before starting the antiarrhythmic drug infusion. We found no significant difference between the procainamide concentrations in the coronary sinus and femoral vein during i.a. and i.v. drug delivery. The time course and extent of increase in right atrial ERP, MAPD70, MAPD90, and all the other measured EP parameters did not differ between the two routes of drug administration. No significant difference was found in termination of AF between i.v. (5/7 procainamide; 4/8 ibutilide) or i.a. (3/8 procainamide; 3/8 ibutilide) drug delivery or between drugs (8/15 procainamide; 7/16 ibutilide). CONCLUSION: Our data do not support any beneficial effect of i.a. versus i.v. procainamide or ibutilide delivery.

Animals↗
PubMed2001

Clinical experience with a dual-chamber implantable cardioverter defibrillator to treat atrial tachyarrhythmias.

INTRODUCTION: This study evaluated the safety and efficacy of a new dual-chamber implantable cardioverter defibrillator (ICD) to detect and treat atrial tachyarrhythmias in patients with drug-refractory atrial fibrillation (AF) and no indication for a ventricular ICD. METHODS AND RESULTS: A dual-chamber ICD (Medtronic 7250 Jewel AF) was implanted in 144 of 146 patients. The device discriminates atrial tachycardia from AF based on cycle length and regularity, and uses atrial overdrive pacing as well as shocks to terminate tachyarrhythmia episodes. Patients were followed for an average of 12.6+/-6.2 months. Use of antiarrhythmic drugs was 63% at baseline and did not change over time. Kaplan-Meier estimates of 12-month complication-free survival, device therapy survival, and patient survival were 85%, 91%, and 98%, respectively. Positive predictive accuracy of spontaneous atrial tachyarrhythmia detection was 99%, while atrial overdrive pacing and shocks terminated 40% and 87% of treated episodes, respectively. Median duration of successfully treated episodes was 8.9 minutes versus 144 minutes for the therapy failures. There was no reduction in the use of patient-activated shock therapy over time; at the 12-month follow-up evaluation, 94% of patients were in sinus rhythm. Ventricular tachyarrhythmias (67 episodes) were detected and appropriately treated in 7.6% of patients. CONCLUSION: This dual-chamber ICD appears to be safe and well tolerated in patients with drug-refractory symptomatic atrial tachyarrhythmias. The device, used in combination with drugs, effectively treats atrial tachyarrhythmias with pacing and/or shock therapies and decreases the median episode duration. In addition, the device protects from ventricular tachyarrhythmias in patients with AF and structural heart disease.

Aged↗
PubMed2000

Tacrolimus does not abrogate the increased risk of acute graft-versus-host disease after unrelated-donor marrow transplantation with allelic mismatching at HLA-DRB1 and HLA-DQB1.

One hundred patients of median age 34 years (range, 14-53) received bone marrow transplants from unrelated donors serologically matched for human leukocyte antigen HLA-A, HLA-B, and HLA-DR using tacrolimus and minimethotrexate for prevention of acute graft-versus-host disease (GVHD). Sixty-eight patient-donor pairs had allelic matches at HLA-DRB1 and HLA-DQB1, 20 pairs had a single mismatch at HLA-DRB1 or HLA-DQB1, and 12 were mismatched at both HLA-DRB1 and HLA-DQB1. Minimum follow-up time was 6 months. Grades 2 to 4 GVHD occurred in 43% of patients with matched donors, 69% with single allele-mismatched donors, and 71% with double allele-mismatched donors; grades 3 to 4 GVHD occurred in 22%, 43%, and 64%, respectively. On multivariate analysis, the relative risk of grades 2 to 4 GVHD was 2.2 (95% CI, 1.1-4.5; P = .03) with a single allele mismatch and 2.7 (95% CI, 1.2-6.0; P = .02) with a double allele mismatch. The relative risks of grades 3 to 4 GVHD were 3.0 (95% CI, 1.2-7.6; P = .02) and 5.0 (95% CI, 1.9-12.6; P = .001), respectively. Day 100 treatment-related mortality was also adversely affected by allelic mismatching, occurring in 21% of those with matched donors, 50% with single allele-mismatched donors, and 42% with double allele-mismatched donors (P = .02), but overall survival at day 180 did not differ significantly among the 3 groups. Tacrolimus does not abrogate the adverse impact of allele mismatching at HLA-DRB1 and HLA-DQB1 on the risk of moderate-to-severe acute GVHD.

Acute Disease↗
PubMed2000

Safety and efficacy of transurethral resection of the prostate under sedoanalgesia.

OBJECTIVE: To assess the safety and efficacy of sedoanalgesia (local anaesthesia with sedation) in patients with benign prostatic hyperplasia (BPH) undergoing transurethral resection of the prostate (TURP). PATIENTS AND METHODS: The study comprised 50 patients with BPH, two-thirds of whom were graded III-IV using the American Society of Anesthesiologists system. All patients had a topical instillation of lignocaine jelly 2% into their urethra, combined with 1% lignocaine (100-200 mg) with 1 : 400 000 adrenaline infiltration of the prostate via the perineal route. Sedation and anxiolysis were obtained with the intramuscular pethidine (0.5 mg/kg) and promethazine (1 mg/kg). Standard TURP was then carried out, with pain monitored during surgery using a visual analogue scale (VAS, maximum 10 points) and the amount of analgesic required after TURP recorded. The amount of prostatic tissue excised, duration of surgery, blood requirement, catheter interval, complications and hospital stay were recorded. The effectiveness of TURP was assessed by comparing symptom scores, uroflowmetry and postvoid residual volume before and after surgery. RESULTS: The mean intraoperative VAS was < or = 1 at any time during or after surgery; no patient required any postoperative analgesics. Only two patients complained of discomfort during the procedure and even they were comfortable after a supplemental dose of pethidine (12.5 mg). There were no conversions to general or regional anaesthesia. No blood transfusion was required in any patient. All patients began a normal diet 30 min after surgery and all were discharged within 48 h of surgery. There were no deaths; one patient had transient urinary incontinence and three had mild urinary tract infection. CONCLUSION: Sedoanalgesia was an effective, safe and simple alternative to general or regional anaesthesia for TURP in patients with BPH.

Adult↗
PubMed2000

High CD34 cell doses do not worsen regimen-related toxicity or early mortality after autologous blood stem cell transplantation for breast cancer.

BACKGROUND: Some transplant-related complications, such as the engraftment syndrome, are thought to be mediated by cytokines released during expansion of hematopoietic progenitors at the time of neutrophil recovery. Since there is an inverse correlation between CD34(+) cell dose and time to neutrophil recovery, we sought to determine if peritransplant toxicity and early mortality were adversely affected by high CD34(+) cell doses. METHODS: The study group included 186 women with breast cancer who received high-dose cyclophosphamide, carmustine, thiotepa and an autologous PBSC transplant. The median CD34(+) cell dose was 5.9 x 10(6)/kg (1.0-154.7 x 10(6)/kg). Patients were categorized by CD34(+) cell dose (1.0-3.5, 3.6-5.9, 6.0-19.9, and 20.0-154.7 x 10(6)/kg) for assessment of outcomes. RESULTS: Grades 2-4 mucositis occurred in 49%, cardiac toxicity in 7%, pulmonary toxicity in 5%, cystitis in 4%, diarrhea in 3%, renal toxicity in 1%, and central nervous system toxicity in 1%. A Grade 2-4 regimen-related toxicity occurred in 109 patients (59%) and Grade 3-4 in eight patients (4%). Overall survival was 100% at Day 30, 96% at Day 90, and 89% at 1 year. Treatment-related mortality was 3.8%. In multivariate analyses that included prior chemotherapy, disease status, visceral metastases, prior chest radiation and age, CD34(+) cell dose group was not an independent risk factor for Grade 2-4 mucositis, Grade 2-4 maximum toxicity, Grade > or =3 cumulative toxicity, 90 day survival or 1 year survival. DISCUSSION: We conclude that CD34(+) cell doses >20 x 10(6)/kg do not affect transplant outcome in a negative or positive fashion.

Adult↗
PubMed2000

High rate atrial tachyarrhythmia detections in implantable pulse generators: low incidence of false-positive detections. The PA Clinical Trial Investigators.

Some newer pulse generators have enhanced diagnostic features that provide information on the frequency, date, time of onset, and duration of atrial and/or ventricular tachyarrhythmias. However, the sensitivity and specificity of device-based atrial tachyarrhythmia detections may vary and depend, in part, on lead position and selected programming parameters. The prevalence of inappropriate detections of paroxysmal atrial fibrillation (PAF) was investigated in 97 patients who received a Thera DR pacemaker 3 months prior to a planned AV node ablation. Patients were randomized to no atrial or to rate adaptive atrial pacing therapy and followed for 3 months. Following a total AV node ablation, patients were randomized to DDDR versus VDD pacing and followed for 1 year. The high rate atrial episode diagnostic feature was used for detection of PAF and the diagnostic data were retrieved during follow-up visits. Criteria were developed to identify oversensing due to near-field P wave detections, far-field R wave detections, or competitive atrial pacing as causes of false-positive atrial tachyarrhythmia detections. A total of 1,636 detections of PAF were recorded in patients preablation. Only 48 episodes (2.9%) were characterized as false-positive detections; 25 episodes (1.5%) were classified as oversensing, and 23 episodes (1.4%) were classified as competitive atrial pacing. A total of 3,061 detections of PAF were recorded postablation. Only four episodes (0.1%) were classified as oversensing. Thus, the diagnostic atrial tachyarrhythmia detection feature in newer pacemakers is an effective method for evaluating the time course of PAF in patients with implantable pulse generators.

Atrial Fibrillation↗
PubMed2000

Effects of different atrioventricular intervals during dual-site right atrial pacing on left atrial mechanical function.

Recent studies have suggested that dual-site right atrial (RA) pacing via the high RA and coronary sinus ostium (CSos) prevents atrial fibrillation (AF). However, the programming of the atrioventricular (AV) interval associated with optimal left atrial (LA) mechanical function during high RA and dual-site RA pacing has not been defined. LA mechanical function was studied by measuring transmitral pulsed Doppler echocardiographic peak A wave velocity and percent A wave filling, in six women and three men, 67 +/- 8 years of age, who had received dual-site RA pacemakers in a randomized study. Serial echocardiographic measurements were performed during high RA or dual-site RA pacing at 80 beats/min with AV intervals of 50, 100, 150, or 200 ms tested in random order. High RA and dual-site RA pacing at an AV interval of 50 ms were associated with significantly lower peak A wave velocity and percent A wave filling, compared to the other AV intervals (all P < 0.05). Compared with high RA pacing, dual-site RA pacing was associated with significantly higher peak A wave velocity (85 +/- 12 vs 72 +/- 17 cm/s, P = 0.04) and percent A wave filling (24 +/- 3 vs 20 +/- 4%, P = 0.02) at an AV interval of 100 ms, but a lower peak A wave velocity at an AV interval of 200 ms (77 +/- 10 vs 84 +/- 8 cm/s, P = 0.004). In conclusion, variations in the AV interval during atrial pacing have significant effects on LA function. As a consequence of altered atrial activation, the AV interval associated with optimal LA mechanical function during dual-site RA pacing was significantly shorter than that during RA pacing. This observation has important implications with respect to the programming of dual-site RA pacemakers implanted to prevent AF for hemodynamic purpose.

Aged↗