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BackgroundAtrial fibrillation (AF) is associated with left ventricular (LV) systolic dysfunction which may improve after AF ablation. We hypothesised that increased ventricular irregularity, as measured by R-R dispersion on the baseline ECG, would predict improvement in the left ventricular ejection fraction (LVEF) after AF ablation.MethodsPatients with LVEF 7.5%. Multivariable logistic regression (restricted to echocardiographic/ECG variables) was performed to evaluate predictors of LVEF improvement.ResultsFifty-two patients were included in this study. LVEF improved in 30 patients (58%) and was unchanged/worsened in 22 patients (42%). Those with versus without LVEF improvement had an increased baseline R-R dispersion (645±155 ms vs 537±154 ms, p=0.02, respectively). The average baseline heart rate in all patients was 93 beats per minute. After multivariable logistic regression, increased R-R dispersion (OR 1.59, 95% CI 1.00 to 2.55, p=0.03) predicted LVEF improvement.ConclusionsIncreased R-R dispersion on ECG was independently associated with improved systolic function after AF ablation. This broadens the existing knowledge of arrhythmia-induced cardiomyopathy, demonstrating that irregular electrical activation (as measured by increased R-R dispersion on ECG) is associated with a cardiomyopathy capable of improving after AF ablation.

Abstract Background The value of Single Photon Emission Computed Tomography stress myocardial perfusion imaging (SPECT-MPI) for detecting graft disease after coronary artery bypass surgery (CABG) has not been studied prospectively in an unselected cohort. Methods Radial Artery Versus Saphenous Vein Graft Study is a Veterans Affairs Cooperative Study to determine graft patency rates after CABG surgery. Seventy-nine participants agreed to SPECT-MPI within 24 hours of their coronary angiogram, one-year after CABG. The choice of the stress protocol was made at the discretion of the nuclear radiologist and was either a symptom-limited exercise test (n = 68) or an adenosine infusion (n = 11). The SPECT-MPI results were interpreted independent of the angiographic results and estimates of sensitivity, specificity and accuracy were based on the prediction of a graft stenosis of ≥70% on coronary angiogram. Results A significant stenosis was present in 38 (48%) of 79 patients and 56 (22%) of 251 grafts. In those stress tests with an optimal exercise heart rate response (>80% maximum predicted heart rate) (n = 26) sensitivity, specificity and accuracy of SPECT-MPI for predicting the graft stenosis was 77%, 69% and 73% respectively. With adenosine (n = 11) it was 75%, 57% and 64%, respectively. Among participants with a suboptimal exercise heart rate response, the sensitivity of SPECT-MPI for predicting a graft stenosis was Conclusions Under optimal stress conditions, SPECT-MPI has a good sensitivity and accuracy for detecting graft disease in an unselected patient population 1 year post-CABG.

Objective: The antimalarial drug halofantrine has been associated with QT interval prolongation and with fatal and nonfatal arrhythmias in patients without known underlying cardiac abnormalities. A common target for QT interval-prolonging drugs is the human ether-a-go-go gene (HERG) which encodes the pore forming subunit of the rapidly activating delayed rectifier K+ current (IKr). Methods: We studied the effects of halofantrine (0.1–1000 nM) and its major metabolite N-desbutylhalofantrine (3–1000 nM) on wild type HERG K+ channels stably expressed in HEK 293 cells, using the whole cell patch-clamp recording technique. Results: Halofantrine and N-desbutylhalofantrine blocked HERG K+ channels in a concentration-dependent manner with a half-maximal inhibitory concentration of 21.6 nM (n = 31 cells) and 71.7 nM (n = 18 cells), respectively. The development of drug block for both halofantrine and N-desbutylhalofantrine required channel activation indicative of open and/or inactivated state block. Drug washout or cell hyperpolarization resulted in minimal current recovery consistent with virtually irreversible binding. Using a ventricular action potential voltage clamp protocol, halofantrine and N-desbutylhalofantrine block of HERG current was greatest during phases 2 and 3 of the action potential waveform. Conclusion: We conclude that both halofantrine and N-desbutylhalofantrine cause high affinity block of HERG K+ channels. Although N-desbutylhalofantrine has been suggested to be a safer antimalarial agent compared to halofantrine, our results suggest that the gain in the safety margin for QT interval prolongation-related cardiotoxicity is minimal. [ABSTRACT FROM AUTHOR]

Introduction: Coenzyme Q10 (CoQ10) is an essential component of Complex III of the electron transport chain of mitochondria. Daily supplementation has been shown to reduce oxidant stress in patients with ischemic heart tissue, and might reduce the incidence of postoperative troponin elevations among patients undergoing vascular surgery. Hypothesis: Among patients undergoing elective vascular surgery, administration of CoQ10 (400 mg Qd) for 3 days prior to surgery reduces the incidence of an elevated cardiac troponin I at 24 hours following surgery. Methods: This was a randomized, double-blind controlled study in a single center. The primary end-point was the incidence of elevated troponins at 24 hours following surgery. The study design assumed a 35% reduction in the primary end-point and called for a sample size of 150, to achieve 80% power. The patients were assigned to either CoQ10 or placebo and agents were dispensed in a blinded fashion, by a research pharmacist. Preoperative and postoperative blood samples were obtained for cardiac troponin I and hs C-reactive protein along with daily EKGs. Adjudication of perioperative MI was done independently and blinded to treatment strategies. Results: A total of 147 patients were enrolled in the study. Clinical variables including age, type of surgery and co-morbid conditions were evenly distributed among groups (Figure 1). The majority of patients were taking ASA and statins prior to surgery. In all patients, the primary outcome, defined by an elevated troponin above the URL at 24 hours following surgery occurred in 34 (23%) while 4 (3%) were diagnosed with a perioperative MI. Differences between groups are shown in Figure 1, and demonstrate that CoQ10 had a 21% reduction in the primary end-point and 40% reduction in median troponin levels. Conclusions: In the preliminary data from this randomized controlled trial, administration of CoQ10 prior to surgery reduced the incidence of elevated troponins and the absolute levels at 24 hours post-surgery. Although the study was not adequately powered to show significance, it provides preliminary proof-of-principle that reducing oxidant stress with CoQ10 may reduce myocardial injury. [ABSTRACT FROM AUTHOR]

Introduction: Among asymptomatic patients, the value of stress imaging at 1 year following successful CABG for predicting long-term adverse outcomes has not been shown. Hypothesis: Among patients enrolled in a VA cooperative study to detect graft patency at 1-year post-CABG, SPECT-MPI predicts long-term risk of adverse cardiovascular events. Methods: At a single center participating in a VA Cooperative Study on long-term graft patency, enrolled patients underwent both coronary angiography and stress imaging at 1-year following CABG. Stress imaging was performed on the same day as the coronary angiogram and interpretation was blinded to the coronary angiogram. SPECT results were categorized according to the size of the perfusion defect, and graded as none, small or moderate to large. Results of the graft studies were categorized as either none or 1 or more grafts with a significant stenosis. Long-term adverse end-points include the composite of death and new diagnosis of heart failure. Results: Eighty-four participants underwent SPECT-MPI and coronary angiogram at one-year post-CABG. Graft disease was identified in 39 patients involving 56 of 251 potential graft sites (22%) and compared to those individuals with no graft disease, did not predict long-term adverse outcomes (31% vs 38% p=0.51). Those individuals with a poor long-term outcome failed to increase their LVEF at 1-year compared with pre-CABG (Figure 1). In addition, a moderate or larger sized defect on SPECT (N=18) was associated with a significant increased risk of adverse outcomes compared with those individuals with either no defect (N=57) or a small defect (N=27) (56% Versus 30%; Odds Ratio = 1.8, P<0.05) (Figure 2). Conclusions: Among asymptomatic patients at 1-year following CABG, assessment of LVEF and defect size with SPECT-MPI was a predictor of long-term risk of death and heart failure. Use of stress imaging, as a means of risk-stratification following bypass surgery, even among those patients without clinical symptoms, may have value. [ABSTRACT FROM AUTHOR]