Background-Although dofetilide is widely used in the United States for rhythm control of atrial fibrillation, there is limited postapproval safety data in the atrial fibrillation population despite its known risk of Torsade de pointes (TdP). Methods and Results-We conducted a retrospective chart review of a cohort of 1404 patients initially loaded on dofetilide for atrial fibrillation suppression at the Cleveland Clinic from 2008 to 2012 to evaluate the incidence and risk factors for in-hospital adverse events and the long-term safety of continued use. Of the 17 patients with TdP during loading (1.2%), 10 had a cardiac arrest requiring resuscitation (1 death), 5 had syncope/presyncope, and 2 were asymptomatic. Dofetilide loading was stopped for 105 patients (7.5%) because of QTc prolongation or TdP. Variables correlated with TdP were (1) female sex, 2) 500-μg dose, (3) reduced ejection fraction, and (4) increase in QTc from baseline. One-year all-cause mortality was higher in patients who continued dofetilide compared with those who discontinued use (hazard ratio, 2.48; 95% confidence interval, 1.08-5.71; P=0.03). Those patients who had a TdP event had higher one-year all-cause mortality than those who did not (17.6% versus 3% at 1 year; P<0.001). Conclusions-Dofetilide loading has a low but finite risk of TdP and other adverse events that warrant the current Food and Drug Administration-mandated practice of inpatient monitoring during drug loading. In this cohort, all-cause mortality was higher at 1 year in those patients continued on dofetilide and in those patients who experienced TdP while loading. (Circ Arrhythm Electrophysiol. 2015;8:772-776.
Background Vascular complications are a known risk of catheter-based pulmonary vein antral isolation (PVAI). Procedure-related thromboembolic events necessitate full-dose anticoagulation, which worsens outcomes in the event of vascular access injury. Objective Real-time ultrasound allows direct visualization of vascular structures. We hypothesized that ultrasound use with venipuncture reduces vascular complications associated with PVAI. Methods Retrospective analysis of all adverse events occurring with PVAI was performed during two periods: 2005– 2006 when ultrasound was not used and 2008–2010 when ultrasound was routinely employed. All patients received full-dose IV heparin during PVAI. In the no ultrasound cohort, only 14 % underwent PVAI without stopping warfarin, while 91 % of patients in the ultrasound cohort were on continued warfarin. Only patients deemed at high risk for thromboembolism with a periprocedural international normalized ratio (INR) less than 2 were bridged with subcutaneous low-molecular-weight heparin. Results Ultrasound reduced total vascular complications (1.7 vs. 0.5 %, p<0.01) and decreased the incidence of major vascular complications by sevenfold. Warfarin with INR≥1.2 on the day of PVAI was associated with more vascular complications (4.3 vs. 1.2 %, p<0.01). Ultrasound guidance overcame the risk associated with warfarin therapy. Vascular complications in anticoagulated patients with INR≥1.2 using ultrasound guidance were two- and ninefold lower than those in patients not using ultrasound with an INR<1.2 (0.5 vs. 1.2 %, p<0.05) and INR≥1.2 (0.5 vs. 4.3 %, p<0.01), respectively. Conclusion Ultrasound-guided venipuncture improves the safety profile of PVAI, reducing vascular complications in patients on warfarin to levels below those with no ultra-sound and off warfarin.
Myocardial injury is increased in the aged heart following ischemia and reperfusion (I-R) in both humans and experimental models. Hearts from aged 24 mo. old Fischer 344 rats sustain greater cell death and decreased contractile recovery after I-R compared to 6 mo. adult controls. Cardiac mitochondria incur damage during I-R contributing to cell death. Aged rats have a defect in complex III of the mitochondrial electron transport chain (ETC) localized to the interfibrillar population of cardiac mitochondria (IFM), situated in the interior of the cardiomyocyte among the myofibrils. The defect involves the quinol oxidation site (Qo) and increases the production of reactive oxygen species (ROS) in the baseline state. Ischemia further decreases complex III activity via functional inactivation of the iron-sulfur subunit. We studied the contribution of ischemia-induced defects in complex III to the increased cardiac injury in the aged heart. The reversible blockade of the ETC proximal to complex III during ischemia using amobarbital protects mitochondria against ischemic damage, removing the ischemia component of mitochondrial dysfunction. Reperfusion of the aged heart in the absence of ischemic mitochondrial damage decreases net ROS production from mitochondria and reduces cell death. Thus, even despite the persistence of the age-related defects in electron transport, protection against ischemic damage to mitochondria can reduce injury in the aged heart. The direct therapeutic targeting of mitochondria protects against ischemic damage and decreases cardiac injury during reperfusion in the high risk elderly heart.
Catheter directed electrophysiology (EP) studies and ablations have emerged as common and widely accepted therapies for various types of arrhythmia. The femoral vasculatures serve as access sites, in the majority of instances. Despite the need for multiple venous sheath placement within a single vein, early reporting of vascular related bleeding complications was naught [1,2]. With increasing frequency of complex procedures such as pulmonary vein antral isolation (PVAI) performed with maintenance of peri-procedural anticoagulation and those necessitating arterial access, vascular complication rates rose to 1-2% [3,4]. In spite of advancements in catheterbased EP procedures in the past two decades leading to improved efficacy and overall safety, the incidence of vascular complication has remained unchanged [5,6].Vascular complications directly impact patient morbidity and increase health care costs. They are usually the consequence of inadvertent arterial puncture and cannulation, particularly when using large diameter sheaths and/or with aggressive anticoagulation. Baum et al. described overlap of the femoral artery (CFA) and common femoral vein (CFV) along some portion of their course in two-thirds of patients studied, predisposing to simultaneous puncture of the overlapping artery during intended venous cannulation and resulting in arteriovenous fistula formation. High bifurcation of the CFA at the level of the mid femoral head was also found to be not uncommon [7]. Such anatomic variation cannot be appreciated without real-time imaging, and increases risk for pseudoaneurysm formation due to accidental puncture of the superficial femoral artery [8].Real-time ultrasound guidance (US) allows direct visualization of vascular structures, and its use has been shown to significantly improve procedural success and/or reduce complications. US has been endorsed in Practice Guidelines put forth by various societies [9][10][11]. Yet in spite of wide acceptance in the medical and surgical communities, US guidance has not been routinely utilized in all EP labs. The first reported comparative study was from our institution and included 3510 patients undergoing PVAI, requiring multiple femoral venous accesses [12]. US guided femoral venous access reduced total and major vascular complications by 3-fold and 7-fold. This result was even more significant, given that 73% of patients undergoing US guided venipuncture had an INR ≥1.9 on the day of the procedure. This was in comparison with the non-US guidance group, in whom only 9% of patients had an INR ≥1.9 on the day of the procedure. This finding is a testament to the protective effect of US, apparent even in the cohort at greater risk for bleeding. Similar improved outcomes have been corroborated by publications from three other institutions, forming a robust experience that confirms the effectiveness of US in reducing vascular complications during EP procedures [13][14][15]. A summary of these four publications by Sobolev et al., including over 4000 subjects, showed a 60% re...
MR antagonism regresses rapid pacing-induced electrical delays, inflammatory cytokine gene activation, and fibrosis in heart failure. Ventricular arrhythmia vulnerability in heart failure is correlated with extent of fibrosis and electrical activation delays during premature excitation.
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