Vinit Sawhney

A Randomized Controlled Trial of Catheter Ablation Versus Medical Treatment of Atrial Fibrillation in Heart Failure (The CAMTAF Trial)

Background—Restoring sinus rhythm in patients with heart failure (HF) and atrial fibrillation (AF) may improve left ventricular (LV) function and HF symptoms. We sought to compare the effect of a catheter ablation strategy with that of a medical rate control strategy in patients with persistent AF and HF. Methods and Results—Patients with persistent AF, symptomatic HF, and LV ejection fraction <50% were randomized to catheter ablation or medical rate control. The primary end-point was the difference between groups in LV ejection fraction at 6 months. Baseline LV ejection fraction was 32±8% in the ablation group and 34±12% in the medical group. Twenty-six patients underwent catheter ablation, and 24 patients were rate controlled. Freedom from AF was achieved in 21/26 (81%) at 6 months off antiarrhythmic drugs. LV ejection fraction at 6 months in the ablation group was 40±12% compared with 31±13% in the rate control group (P=0.015). Ablation was associated with better peak oxygen consumption (22±6 versus 18±6 mL/kg per minute; P=0.014) and Minnesota living with HF questionnaire score (24±22 versus 47±22; P=0.001) compared with rate control. Conclusions—Catheter ablation is effective in restoring sinus rhythm in selected patients with persistent AF and HF, and can improve LV function, functional capacity, and HF symptoms compared with rate control. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01411371

Mild chronic kidney disease is an independent predictor of long-term mortality after emergency angiography and primary percutaneous intervention in patients with ST-elevation myocardial infarction

Objective Moderate renal impairment (RI) with a glomerular filtration rate (GFR) <60 ml/min/1.73 m2 is known to predict survival. The authors investigated whether mild RI with an estimated GFR of 60–89 ml/min/1.73 m2 independently predicts survival in a contemporary population with ST segment elevation myocardial infarction (STEMI). Design This is a single-centre, observational, retrospective cohort study. Patients 601 patients with STEMI who underwent emergency catheter laboratory admission met the inclusion criteria for this study. Methods Estimated glomerular filtration rate (eGFR) was obtained by the Modified Diet in Renal Disease equation, and preprocedure renal function was subdivided into chronic kidney disease stages. Univariate and multivariate Cox regression analyses were performed to assess which of 17 patient or procedural variables were independent risk factors for death. Results Longitudinal data were collated for 576 patients (96.3%). Median follow-up time was 2.6 years. 30-day and long-term death rates were 5.7% and 12.5%, respectively. Following multivariable analysis, mild RI with an eGFR of 60–89 ml/min/1.73 m2 was a strong independent predictor of death, compared with an eGFR ≥90 ml/min/1.73 m2 (HR 2.79, 95% CI 1.98 to 3.92, p<0.001), and increasing chronic kidney disease stage was a strong predictor of death after both 30 days and long-term follow-up. An eGFR of 60–89 ml/min/1.73 m2 had a greater independent effect on short- and long-term mortality than the presence of diabetes mellitus (HR 2.0, 95% CI 1.2 to 3.33). Conclusion Mild RI (eGFR=60–89 ml/min/1.73 m2) on admission is strongly predictive of short- and long-term mortality in patients with STEMI admitted to the catheter laboratory. A redefined threshold of clinically significant impairment is now required (GFR<90 ml/min/1.73 m2).

A simple and novel method for RNA-seq library preparation of single cell cDNA analysis by hyperactive Tn5 transposase.

Background: Deep sequencing of single cell‐derived cDNAs offers novel insights into oncogenesis and embryogenesis. However, traditional library preparation for RNA‐seq analysis requires multiple steps with consequent sample loss and stochastic variation at each step significantly affecting output. Thus, a simpler and better protocol is desirable. The recently developed hyperactive Tn5‐mediated library preparation, which brings high quality libraries, is likely one of the solutions. Results and Conclusions: Here, we tested the applicability of hyperactive Tn5‐mediated library preparation to deep sequencing of single cell cDNA, optimized the protocol, and compared it with the conventional method based on sonication. This new technique does not require any expensive or special equipment, which secures wider availability. A library was constructed from only 100 ng of cDNA, which enables the saving of precious specimens. Only a few steps of robust enzymatic reaction resulted in saved time, enabling more specimens to be prepared at once, and with a more reproducible size distribution among the different specimens. The obtained RNA‐seq results were comparable to the conventional method. Thus, this Tn5‐mediated preparation is applicable for anyone who aims to carry out deep sequencing for single cell cDNAs. Developmental Dynamics 241:1584–1590, 2012.

Uninterrupted Warfarin for Periprocedural Anticoagulation in Catheter Ablation of Typical Atrial Flutter: A Safe and Cost‐Effective Strategy

Uninterrupted Warfarin for Periprocedural Anticoagulation in Catheter Ablation of Typical Atrial Flutter. Introduction: Many patients undergoing catheter ablation of atrial flutter (AFL) require periprocedural anticoagulation. We compared a strategy of conversion to low molecular weight heparin (LMWH) periprocedure to uninterrupted warfarinization in a nonrandomized, case‐controlled study.

Predictors of new onset atrial fibrillation in patients with heart failure

INTRODUCTION Stroke associated with atrial fibrillation (AF) is more frequent in heart failure. It is unknown what variables predict future AF in these patients and how AF might evolve over time. We investigated this in patients with implantable cardiac defibrillators (ICD) where AF detection is optimal. METHODS Single centre, retrospective, observational cohort study. All ischaemic cardiomyopathy patients with dual chamber, primary prevention ICD implants between Aug 2003 and Dec 2009 were screened and included if at implant, they had no known AF history. Nine variables were analysed. AF was defined as any atrial tachyarrhythmia ≥180 bpm and ≥30 s. Multivariable, binary logistic regression models were built by adding variables significant in the univariate models. Variables were retained in the final multivariate models if p<0.05. RESULTS n=197 met the inclusion criteria (85.8% male, median age: 66.8 years). After median follow-up for 2.8 years, 44.2% developed AF. After univariate analysis, the baseline variables associated with AF after implant were age, NYHA class and renal impairment (RI, defined eGFR<60 ml/min/1.73 m2) (p<0.05). After multivariable analysis, the only variable which was associated with AF was RI (HR: 2.04 (CI: 1.10-3.79)). Two baseline variables were independently associated with all-cause mortality: RI (HR: 2.42 (1.14-5.12)) and non-white ethnicity. CONCLUSION RI at time of implant was independently associated with both future AF and all-cause mortality during long-term follow-up. RI was a stronger predictor of AF than age. Those patients with heart failure and RI should be regularly screened for asymptomatic AF, regardless of age, to ensure that stroke prophylaxis may be initiated.

Panoramic atrial mapping with basket catheters: A quantitative analysis to optimize practice, patient selection, and catheter choice

Panoramic mapping with basket catheters has been used to map atrial fibrillation (AF). However, the limited tissue contact and coverage achieved has raised concerns.

Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients – Potential markers of ventricular arrhythmia

BACKGROUND Implantable cardioverter defibrillators (ICDs) reduce mortality in patients with ischaemic cardiomyopathy at high risk of ventricular arrhythmias (VA). However, the current indication for ICD prescription needs improvement. Telomere and telomerase in leucocytes have been shown to associate with biological ageing and pathogenesis of cardiovascular diseases. We hypothesised that leucocyte telomere length, load-of-short telomeres and/or telomerase activity are associated with VA occurrence in ischaemic cardiomyopathy patients. METHODS AND RESULTS 90 ischaemic cardiomyopathy patients with primary prevention ICDs were recruited. 35 had received appropriate therapy from the ICD for potentially-fatal VA while the remaining 55 patients had not. No significant differences in baseline demographic data relevant to telomere biology were seen between the two groups. There was no significant difference in the age and sex adjusted mean telomere length analysed by qPCR between the groups (p=0.88). In contrast, the load-of-short telomeres assessed by Universal-STELA method and telomerase activity by TRAP assay were both higher in patients who had appropriate ICD therapy and were significantly associated with incidence of ICD therapy (p=0.02, p=0.02). ROC analyses demonstrated that the sensitivity and specificity of these telomere dynamics in predicting potentially-fatal VA was higher than the current gold-standard - left ventricular ejection fraction (AUC 0.82 versus 0.47). CONCLUSION The load-of-short telomeres and telomerase activity had a significant association with ICD therapy (for VA) in ischaemic cardiomyopathy patients. These biomarkers should be tested in prospective studies to assess their clinical utility in predicting VA after myocardial infarction and guiding primary prevention ICD prescription.

Resolution of Brugada-pattern ECG after withdrawal of the selective serotonin reuptake inhibitor paroxetine

A 48-year-old school teacher was transferred to our institution after a syncopal episode, with unconsciousness lasting for approximately 1 min. A similar episode had occurred several years previously but had not been investigated. She had a diagnosis of obsessive-compulsive disorder and depression, for which she was taking paroxetine 10 mg daily. There was …

Moderate sedation in cardiac electrophysiology laboratory: a retrospective safety analysis

Objective Cardiac electrophysiology (EP) procedures can be performed under moderate sedation without the direct involvement of an anaesthetist. However, concerns have been raised over the safety of this approach. This study examines the use of a standardised nurse-led physician-directed sedation protocol for EP procedures to determine the safety of moderate sedation administered by non-anaesthesia personnel who have been trained in sedation techniques. Methods and results Consecutive EP procedures done under moderate sedation over 12 years at our institution were evaluated. Serious adverse events were defined as (i) procedural death related to sedation; (ii) intubation and ventilation; and (iii) hypotension requiring inotropic support. Reversal of sedation constituted a minor adverse event. Up to 7117 procedures were included. These comprised ablations (55%), devices (43%) and other procedures (2%). A majority of patients were men with a mean age of 61±10 years. 99.98% of procedures were completed successfully without sedation-related serious adverse events. Two patients (0.02%) required anaesthetic support for intubation. Sedation was reversed in 1.2% of procedures with less than 1% requiring reversal because of persistent drop in oxygen saturation, hypoventilation or markedly reduced level of consciousness. There was no significant difference in the patient characteristics, mean doses of sedative agents and procedure types in the group requiring reversal of sedation when compared with the whole cohort. Conclusions Our study demonstrates that nurse-led, physician-directed moderate sedation is safe. Anaesthesia services are not required routinely for invasive cardiac EP procedures and should be available on a need basis.

Association of genetic variation in telomere-related SNP and telomerase with ventricular arrhythmias in ischemic cardiomyopathy.

Telomeres are known to provide genomic stability and telomere length has been associated with cardiovascular diseases. Moreover, a higher telomerase activity has been shown to be associated with ventricular arrhythmias (VA) in ischemic cardiomyopathy. Increasing evidence suggests that genetic variation in key telomere genes has an impact on telomerase activity. Each copy of the minor allele of SNP rs12696304, at a locus including TERC (telomerase), has been associated with ∼75 base pairs reduction in mean telomere length likely mediated by an effect on TERC expression. We investigated the impact of genetic variation of this SNP on telomerase and its association with VA in ischemic cardiomyopathy patients.