adult rat myocyte culture; patch clamp; fura-2; edge detection; excitation-contraction coupling PHOSPHOLEMMAN (PLM), a 72-amino acid membrane phosphoprotein with a single transmembrane domain (13), belongs to the FXYD gene family of small ion transporter regulators (18). In the heart and skeletal muscle, PLM is a major sarcolemmal substrate for protein kinases A and C (9, 14). Recent studies suggest that PLM regulates both Na ϩ -K ϩ -ATPase (4, 25) and Na ϩ /Ca 2ϩ exchanger (NCX1) (24) activities in cardiac muscle. In rat hearts that have survived myocardial infarction (MI), expression of PLM mRNA was increased twofold as early as 3 days after MI and remained elevated for at least 2 wk after MI (15). Interestingly, overexpression of PLM in normal adult rat cardiac myocytes affected myocyte contractility and cytosolic Ca 2ϩ concentration ([Ca 2ϩ ] i ) transients (17) in a pattern similar to the changes observed in post-MI rat myocytes (2,22). It is noteworthy that in post-MI rat myocytes, Na ϩ -dependent Ca 2ϩ uptake in sarcolemmal (SL) vesicles (5), NCX1 currents (27), and Na (6) were depressed. On the basis of the above observations, an attractive hypothesis is that overexpression of PLM in post-MI rat myocytes, by inhibiting two major SL ion transporters, resulted in abnormal [Ca 2ϩ ] i homeostasis and altered contractility. Downregulating PLM would therefore offer a rational approach to ameliorating contractile abnormalities post-MI. There are no published studies on the effects of PLM downregulation in cardiac tissues. The present study was undertaken to test the hypothesis that in adult rat cardiac myocytes, PLM downregulation alters cardiac myocyte contraction, [Ca 2ϩ ] i transient dynamics, and Na ϩ /Ca 2ϩ exchanger function. METHODSMyocyte isolation and culture. The protocol for myocyte isolation was approved by the Institutional Animal Care and Use Committee. Cardiac myocytes were isolated from the septum and left ventricular (LV) free wall of male Sprague-Dawley rats (ϳ280 g) as previously described (3). Isolated myocytes were seeded on laminin-coated coverslips and cultured with serum-free medum 199 (Earle's salts without L-glutamine and NaHCO3) supplemented with creatine, carnitine, taurine, and NaHCO 3 (17, 26). After 2 h, media were changed to remove nonadherent myocytes. Six hours after isolation, cultured myocytes were electrically paced {1 Hz, extracellular Ca 2ϩ concentration ([Ca 2ϩ ]o) ϭ 1.8 mM} (17,26). Culture media were changed daily over the course of experiments. Under continuous pacing culture conditions, we have previously demonstrated that myocyte contractility did not decline for at least 72 h (17).Construction of recombinant replication-deficient adenovirus expressing antisense PLM. The basic protocol has been described by He et al. (7). Initially, the coding sequence of dog heart PLM together with 5Ј-untranslated and 3Ј-untranslated sequences (13, 17) was

Background Predictors of atrial fibrillation (AF) recurrence after catheter ablation (CA) are not fully defined. We hypothesized that 2D left atrial (LA) regional strain maps would help identify abnormal atrial substrate that increases susceptibility to AF recurrence post-CA. Methods and Results Sixty-three patients (63±10 years, 60% male) underwent CA for symptomatic paroxysmal (75%) or persistent (25%) AF. Baseline LA mechanical function determined using speckle tracking echocardiography was compared between those with AF recurrence (AFR) and no recurrence post-CA. Bi-dimensional global and regional maps of LA wall velocity, strain, and strain rate (SR) were obtained during end ejection and early diastole. After 18±12 months of follow-up, 34 patients were free of AFR post-CA. There were no differences in clinical characteristics, LA and LV volumes, and Doppler estimates of LV diastolic function and filling pressures at baseline between patients with recurrent AF and those that maintained sinus rhythm. However, the LA emptying fraction (55±17% vs. 64±14%, p=0.04), global and regional systolic and diastolic strains, SR, and velocities were reduced in patients with recurrent AF. There was marked attenuation of peak LA lateral wall longitudinal strain (LS; 11±7% vs. 20±14%, p=0.007) and SR (0.9±0.4 vs. 1.3±0.6 s−1, p=0.01). Multivariate analysis revealed lateral wall LS (odds ratio=1.15, 95% CI=1.02–1.28, p=0.01) as an independent predictor of AFR. Conclusions Regional LA lateral wall LS is a pre-procedural determinant of AFR in patients undergoing CA, independent of LA enlargement. Characterization of atrial myocardial tissue properties by speckle tracking echo may aid the appropriate selection of adjunctive strategies and prognostication of patients undergoing CA.

Synopsis Aging is associated with an increased prevalence of cardiac arrhythmias, which contribute to higher morbidity and mortality in the elderly. The frequency of cardiac arrhythmias, particularly atrial fibrillation and ventricular tachyarrhythmia, is projected to increase as the population ages, greatly impacting health care resource utilization. Several clinical factors associated with the risk of arrhythmias have been identified in the population, yet the molecular bases for the increased predisposition to arrhythmogenesis in the elderly are not fully understood. Therefore, only limited therapeutic strategies directed at pathophysiological processes that enhance cardiac vulnerability to arrhythmias are available. This is further compounded by the paucity of outcome studies providing evidence on which optimal management guidelines can be formulated for the very elderly. This review highlights the epidemiology of cardiac dysrhythmias, changes incardiac structure and function associated with aging, and the basis for arrhythmogenesis in the elderly, the understanding of which is critical to formulate preventive strategies.

Background Sleep disturbance caused by obstructive sleep apnea is recognized as a contributing factor to adverse cardiovascular outcomes. However, the effect of restless legs syndrome (RLS), another common cause of fragmented sleep, on cardiac structure, function and long-term outcomes is not known. We assessed the effect of frequent leg movement during sleep on cardiac structure and outcomes in patients with RLS. Methods In our retrospective study, RLS patients referred for polysomnography were divided into those with frequent (periodic movement index >35/hour) and infrequent (≤35/hour) leg movement during sleep. Long-term outcomes were determined using Kaplan-Meier and logistic regression models. Results Of 584 patients, 47% had periodic movement index >35/hour. Despite similarly preserved left ventricular ejection fraction, the group with periodic movement index >35/hour had significantly higher left ventricular mass and mass index reflective of left ventricular hypertrophy (LVH). There were no significant baseline differences in the proportion of patients with hypertension, diabetes, hyperlipidemia, prior myocardial infarction, stroke or heart failure or use of antihypertensive medications between the groups. Patients with frequent periodic movement index were older, predominantly male and had more prevalent coronary artery disease and atrial fibrillation. However, on multivariate analysis, periodic movement index >35/hour remained the strongest predictor for LVH (odds ratio 2.45, 95% confidence interval 1.67–3.59, P<0.001). Advanced age, female sex and apnea-hypopnea index were other predictors for LVH. Patients with periodic movement index >35/hour had significantly higher heart failure and mortality rates over 33-month median follow-up. Conclusions Frequent periodic leg movement during sleep is an independent predictor of severe LVH and associated with increased cardiovascular morbidity and mortality.

Postoperative atrial fibrillation (PoAF), a common complication of cardiac surgery, contributes significantly to morbidity, mortality, and increasing health care costs. Despite advances in surgical and medical management, the overall incidence of PoAF has not changed significantly, partly due to the limited understanding of mechanisms underlying acute surgery-related factors, such as myocardial injury, inflammation, sympathetic activation, and oxidative stress, which play an important role in the initiation of PoAF, while a preexisting atrial substrate appears to be more important in the maintenance of this dysrhythmia. Thus, in a majority of patients, PoAF becomes a manifestation of an underlying arrhythmogenic substrate that is unmasked following acute surgical stress. As such, the ability to identify which patients have this proarrhythmic substrate and are, therefore, at high risk for developing AF postoperatively, is important for the improved selection for prophylactic interventions, closer monitoring for complications, and establishing the probability of AF in the long term. This review highlights the role of the underlying substrate in promoting PoAF, proposed mechanisms, and the potential role of serum biomarkers to identify patients at risk for PoAF.

Background-Predictors of atrial fibrillation (AF) recurrence after catheter ablation (CA) are not fully defined. We hypothesized that 2D left atrial (LA) regional strain maps would help identify abnormal atrial substrate that increases susceptibility to AF recurrence post-CA. Methods and Results-Sixty-three patients (63±10 years, 60% male) underwent CA for symptomatic paroxysmal (75%) or persistent (25%) AF. Baseline LA mechanical function determined using speckle tracking echocardiography was compared between those with AF recurrence (AFR) and no recurrence post-CA. Bi-dimensional global and regional maps of LA wall velocity, strain, and strain rate (SR) were obtained during end ejection and early diastole. After 18±12 months of follow-up, 34 patients were free of AFR post-CA. There were no differences in clinical characteristics, LA and LV volumes, and Doppler estimates of LV diastolic function and filling pressures at baseline between patients with recurrent AF and those that maintained sinus rhythm. However, the LA emptying fraction (55±17% vs. 64±14%, p=0.04), global and regional systolic and diastolic strains, SR, and velocities were reduced in patients with recurrent AF. There was marked attenuation of peak LA lateral wall longitudinal strain (LS; 11±7% vs. 20±14%, p=0.007) and SR (0.9±0.4 vs. 1.3±0.6 s −1 , p=0.01). Multivariate analysis revealed lateral wall LS (odds ratio=1.15, 95% CI=1.02-1.28, p=0.01) as an independent predictor of AFR. Conclusions-Regional LA lateral wall LS is a pre-procedural determinant of AFR in patients undergoing CA, independent of LA enlargement. Characterization of atrial myocardial tissue properties by speckle tracking echo may aid the appropriate selection of adjunctive strategies and prognostication of patients undergoing CA.

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A paradoxical relationship between BMI and mortality risk is present in elderly patients with ICD at high risk of sudden death with a lower mortality in obese or overweight patients than in those with normal BMI.