Sex-specific efficacy and safety of cryoballoon versus radiofrequency ablation for atrial fibrillation: An individual patient data meta-analysis

BACKGROUND: Atrial fibrillation (AF) is a growing health burden, and pulmonary vein isolation (PVI) using cryoballoon (CB) or radiofrequency (RF) represents an attractive therapeutic option. Sex-specific differences in the epidemiology, pathophysiology, and clinical presentation of AF and PVI are recognized. OBJECTIVE: We aimed at comparing the efficacy, safety, and procedural characteristics of CB and RF in women and men undergoing a first PVI procedure. METHODS: We searched for randomized controlled trials and prospective observational studies comparing CB and RF ablation with at least 1 year of follow-up. After merging individual patient data from 18 data sets, we investigated the sex-specific (procedure failure defined as recurrence of atrial arrhythmia, reablation, and reinitiation of antiarrhythmic medication), safety (periprocedural complications), and procedural characteristics of CB vs RF using Kaplan-Meier and multilevel models. RESULTS: From the 18 studies, 4840 men and 1979 women were analyzed. An analysis stratified by sex correcting for several covariates showed a better efficacy of CB in men (hazard ratio for recurrence 0.88; 95% confidence interval 0.78-0.98, P = .02) but not in women (hazard ratio 0.98; 95% confidence interval 0.83-1.16; P = .82). For women and men, the energy source had no influence on the occurrence of at least 1 complication. For both sexes, the procedure time was significantly shorter with CB (-22.5 minutes for women and -27.1 minutes for men). CONCLUSION: CB is associated with less long-term failures in men. A better understanding of AF-causal sex-specific mechanisms and refinements in CB technologies could lead to higher success rates in women

withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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Hypertrophy decreases cardiac KATP channel responsiveness to exogenous and locally generated (glycolytic) ATP

This study tests the hypothesis that glycolytic regulation of KATP channel activity is altered in myocardial hypertrophy. Left ventricular (LV) subendocardial myocytes were isolated from cats with normal or left ventricular hypertrophied hearts (LVH). Saponin-permeabilized open cell-attached patch configurations of normal and LVH cells were exposed to an exogenous ATP consuming system containing hexokinase and 2-deoxyglucose. Phosphoenol pyruvate (PEP, substrate for the last ATP producing step in glycolysis) was applied extracellularly; ADP was present. In both cell types, KATP channels were activated in the absence of PEP, inhibited when PEP was added and activated again when PEP was removed, indicating the cells retained metabolic integrity and generated ATP in the proximity of their KATP channels. Single channel conductance in the absence of PEP was similar (70 pS, normal; 66 pS, LVH). However, LVH KATP channels showed enhanced activity (P0=0.50+/-0.03); normal (0.41+/-0.03) in PEP absence (P<0. 05). PEP responsiveness was reduced in LVH, with IC50, PEP increased to 23 microM; (11 microM normal). Lactate failed to activate KATP channels in both cell types. The concentration-P0 response curves obtained during exposure of open cells to exogenous ATP also revealed reduced responsiveness to ATP of LVH KATP channels (IC50, ATP=283 microM LVH; 93 microM normal). Our data indicate myocardial hypertrophy increases the maximal activity of KATP channels in the absence of ATP and reduces their responsiveness to ATP, including locally generated glycolytic ATP. These alterations in metabolic regulation of myocardial electrophysiology may contribute to diversity of action potential shortening in hypertrophied hearts during acute ischemia

Angiographic Quantification of Angiogenesis

Therapeutic angiogenesis is the attempt to increase vascular density by means of an exogenously administered proangiogenic agent and offers a potential treatment for diseases associated with tissue ischemia. Vascular endothelial growth factor (VEGF) expressed by gene therapy has been shown to be a potent stimulator of angiogenesis and to improve the function of ischemic tissues in patients [Isner, 1998]. Unregulated gene therapy is disconcerting since there is no assurance that the treatment will target the ischemic territory. A new regulated adeno-associated viral vector expressing VEGF165 that is conditionally silenced has been developed by one of the authors (KAW). The transgene expression is regulated by silencing the genes in the absence of the disease and at the same time having strong and local activation in the presence of the disease. The purpose of this work is to establish protocols and techniques to quantify the efficacy of therapeutic angiogenesis. The initial phase of this research involves assessment of angiogenesis using an unregulated, adenoviral vector that is encoded to express VEGF165. Using the rabbit hind limb ischemia model, angiography was performed on animals that were given the proangiogenic treatment and on a sham group, in which phosphate buffered saline (PBS) was injected. Angiographic contrast intensity curves were obtained, modeled, and the optimized model parameters provided insight into flow characteristics within the targeted vascular bed. In the second phase of the project the conditionally silent vector will be employed using the developed protocols and methods of the first phase to afford comparisons with the previous groups

Characteristics of I(K) and its response to quinidine in experimental healed myocardial infarction

Mechanisms and drug treatment of serious ventricular arrhythmias in patients with healed myocardial infarction (HMI) are incompletely understood, in part because the electrophysiology and pharmacology of myocytes from noninfarcted regions of HMI hearts are not well characterized. We studied the delayed rectifier potassium current (I(K)) and quinidine responsiveness of single left ventricular subendocardial myocytes isolated from the region remote to the border zone of healed infarct myocardium (4 to 6 mm from scar edge) in cat hearts 2 months after coronary artery occlusion. Subendocardial cells isolated from corresponding regions of normal cat hearts provided controls. I(K) activation and tail currents were recorded using whole cell, voltage clamp techniques. Membrane capacitance of cells remote to HMI (187 +/- 7 pF) was significantly greater than normal (155 +/- 6 pF; P < 0.001). Action potential durations (APDs) recorded from myocytes in remote regions were prolonged (APD90 = 247 +/- 10 msec) compared to normal (214 +/- 11 msec; P < 0.05). Quinidine (1 microM) significantly prolonged APD90 in normal cells but not in remote cells. Density of I(K) (tail current) was significantly decreased in remote cells (3.1 +/- 0.3 pA/pF) compared to normal (3.9 +/- 0.3 pA/pF; P < 0.05), and voltage-dependent activation of I(K) was shifted in the positive direction. Quinidine had significantly less incremental blocking effect on I(K) already blunted by regional hypertrophy compared to its effect on normal cells in remote cells. IC50 shifted to 0.95 microM in remote cells compared with 0.50 microM in normal cells. Cells in noninfarct region remote from the scar are hypertrophied and display altered electrophysiology. Their reduced I(K) responsiveness to quinidine may explain, in part, failure of quinidine to prolong APD in such cells. Moreover, dispersion of repolarization may be decreased by the effect of quinidine on normal cells