Is ablation of atrial flutter always safe?

BACKGROUND: Radiofrequency ablation of typical atrial flutter is largely used and is considered as safe. The purpose of the study was to evaluate the prevalence and the causes of severe adverse event (AE) following atrial flutter ablation. METHODS: Ablation of typical flutter was performed by conventional method with an 8-mm-tip electrode catheter, a maximum power of 70 W, and a maximum target temperature of 70° for 60 seconds in 883 patients, (685 males and 198 females aged from 18 to 93 years [64 ± 11.5]; 664 had heart disease [HD]). RESULTS: AE occurred in 44 patients (5%). AE was life threatening in 14 patients: poorly tolerated bradycardia (transient complete atrioventricular block [AVB] or sinus bradycardia [SB] <40 beats per minute) associated with cardiac shock and acute renal failure in five patients, tamponade (n = 1), bleeding leading to death (n = 1), various AE-related deaths (n = 2), ventricular tachycardia-related death (n = 1), definitive complete AVB (n = 3), and right coronary artery occlusion-related complete AVB (n = 1). Less serious AE occurred in 30 patients: transitory major SB or second- or third-degree AVB (n = 23), bleeding (n = 4), transient ischemic attack (n = 1), and various AE (n = 2). Most of the bradycardia was related to ß-blockers or other antiarrhythmic drugs used to slow atrial flutter. Factors of AE were female gender (36% vs 22%, P < 0.02) and the presence of ischemic (P < 0.03) or valvular HD (P < 0.01). CONCLUSIONS: AE following atrial flutter ablation occurred in 5% of patients. Most of them are avoidable by control of anticoagulants and arrest of rate-control drugs used to slow the rate of atrial flutter.

Global array-based transcriptomics from minimal input RNA utilising an optimal RNA isolation process combined with SPIA cDNA probes.

BACKGROUND: Technical advances in the collection of clinical material, such as laser capture microdissection and cell sorting, provide the advantage of yielding more refined and homogenous populations of cells. However, these attractive advantages are counter balanced by the significant difficulty in obtaining adequate nucleic acid yields to allow transcriptomic analyses. Established technologies are available to carry out global transcriptomics using nanograms of input RNA, however, many clinical samples of low cell content would be expected to yield RNA within the picogram range. To fully exploit these clinical samples the challenge of isolating adequate RNA yield directly and generating sufficient microarray probes for global transcriptional profiling from this low level RNA input has been addressed in the current report. We have established an optimised RNA isolation workflow specifically designed to yield maximal RNA from minimal cell numbers. This procedure obtained RNA yield sufficient for carrying out global transcriptional profiling from vascular endothelial cell biopsies, clinical material not previously amenable to global transcriptomic approaches. In addition, by assessing the performance of two linear isothermal probe generation methods at decreasing input levels of good quality RNA we demonstrated robust detection of a class of low abundance transcripts (GPCRs) at input levels within the picogram range, a lower level of RNA input (50 pg) than previously reported for global transcriptional profiling and report the ability to interrogate the transcriptome from only 10 pg of input RNA. By exploiting an optimal RNA isolation workflow specifically for samples of low cell content, and linear isothermal RNA amplification methods for low level RNA input we were able to perform global transcriptomics on valuable and potentially informative clinically derived vascular endothelial biopsies here for the first time. These workflows provide the ability to robustly exploit ever more common clinical samples yielding extremely low cell numbers and RNA yields for global transcriptomics.

The cumulative effect of acute rejection on development of cardiac allograft vasculopathy.

BACKGROUND: Acute rejection increases the inflammatory burden of the transplanted organ and predisposes to cardiac allograft vasculopathy (CAV). In this study we aim to determine the magnitude of the association, and to differentiate between the effects of mild vs severe rejection episodes. METHODS: Between 1988 and 2003, 489 1-year survivors of heart transplantation underwent 1,435 angiograms. These patients were classified as having no CAV (0% stenosis), mild/moderate CAV (<70%) or severe CAV (>70%). Acute rejection was considered either mild (Grades 1A, 1B and 2 untreated) or moderate/severe (Grade 2 treated on a clinical basis and Grades 3A, 3B and 4). We used multi-state Markov models to examine risk factors for the onset of CAV. RESULTS: Expressed as relative risk, the onset of CAV was significantly increased by donor age (1.26 per 10 years, 95% confidence interval [CI] 1.12 to 1.42), male recipient (1.72, 95% CI 1.01 to 2.94), pre-transplant recipient ischemic disease (1.53, 95% CI 1.14 to 2.06) and cumulative number of moderate/severe rejections (1.10 per episode, 95% CI 1.03 to 1.18). Human leukocyte antigen (HLA) and cytomegalovirus (CMV) matching, donor gender, recipient age, smoking, cumulative CMV infections and mild rejections were not significant risk factors. Estimated annual onset rate of CAV was 11.3% for patients with no moderate/severe rejection, rising to 13.6% for those with two and 18.0% for those with five such rejections. CONCLUSIONS: Acute moderate/severe cellular rejection has a cumulative impact on CAV onset, whereas mild, untreated rejection is not associated with CAV.