Chronic Kidney Disease and Mortality in Implantable Cardioverter-Defibrillator Recipients

Incidence of sudden cardiac death (SCD) in end-stage renal disease (ESRD) remains high. Limited data is available about whether implantable cardioverter-defibrillators (ICDs) can prevent arrhythmic death in patients with chronic kidney disease (CKD). The purpose of this retrospective study was to determine the impact of CKD on all-cause and sudden cardiac death in ICD recipients. We evaluated 441 consecutive patients who underwent ICD implantation at our center between 1994 and 2002. We found that mortality rate was higher in patients with eGFR <60 mL/min and those with ESRD on hemodialysis (43%, n = 69/162 and 54%, n = 12/22, resp.) than in patients with eGFR ≥60 mL/min (23%, n = 58/257; P < .0005). The SCD rate was also higher in the patients with ESRD (50%) than in CKD patients not on dialysis (10.2%; P < .0005). Mortality rate for single-chamber ICDs was 56.8% in comparison with dual-chamber ICDs (38.1%) and for biventricular ICDs (5.0%) (P < .0005)

Essentials of Herb-Drug Interactions in the Elderly With Cardiovascular Disease

As the number of individuals, particularly the elderly, using herbal products with prescription drugs continues to grow, the risk for adverse interactions increases but remains poorly recognized. The true incidence and nature of adverse herb reactions or herb-drug interactions remains unknown since no postmarketing surveillance mechanism exists. Adverse events are greatly underreported, and information regarding safety mainly comes from case reports and suboptimally conducted studies in a limited number of healthy young volunteers or patients with limited comorbidities. Therefore, convincing evidence for the safety of herbal products in the elderly is lacking, and the true magnitude of problems that herb-drug interactions pose to public health, particularly in elderly patients with cardiovascular diseases, is not known. Since cardiovascular diseases themselves are life threatening, necessitate use of multiple medications and occur in a population with extensive comorbidities, the risk of herb-drug and herb-disease interactions is not minor and cannot be ignored. This review addresses these concerns in an effort to raise awareness about the use of herbal medicine by the elderly and its potential adverse impact on the efficacy of prescription medications that can increase predisposition to catastrophic events such as major bleeding, inadequate anticoagulation leading to undesired clotting, transplant organ rejection and life-threatening cardiac arrhythmias

Essentials of Herb-Drug Interactions in the Elderly With Cardiovascular Disease

As the number of individuals, particularly the elderly, using herbal products with prescription drugs continues to grow, the risk for adverse interactions increases but remains poorly recognized. The true incidence and nature of adverse herb reactions or herb-drug interactions remains unknown since no postmarketing surveillance mechanism exists. Adverse events are greatly underreported, and information regarding safety mainly comes from case reports and suboptimally conducted studies in a limited number of healthy young volunteers or patients with limited comorbidities. Therefore, convincing evidence for the safety of herbal products in the elderly is lacking, and the true magnitude of problems that herb-drug interactions pose to public health, particularly in elderly patients with cardiovascular diseases, is not known. Since cardiovascular diseases themselves are life threatening, necessitate use of multiple medications and occur in a population with extensive comorbidities, the risk of herb-drug and herb-disease interactions is not minor and cannot be ignored. This review addresses these concerns in an effort to raise awareness about the use of herbal medicine by the elderly and its potential adverse impact on the efficacy of prescription medications that can increase predisposition to catastrophic events such as major bleeding, inadequate anticoagulation leading to undesired clotting, transplant organ rejection and life-threatening cardiac arrhythmias

Frequent periodic leg movement during sleep is an unrecognized risk factor for progression of atrial fibrillation.

Sleep apnea has been recognized as a factor predisposing to atrial fibrillation recurrence and progression. The effect of other sleep-disturbing conditions on atrial fibrillation progression is not known. We sought to determine whether frequent periodic leg movement during sleep is a risk factor for progression of atrial fibrillation. In this retrospective study, patients with atrial fibrillation and a clinical suspicion of restless legs syndrome who were referred for polysomnography were divided into two groups based on severity of periodic leg movement during sleep: frequent (periodic movement index >35/h) and infrequent (≤35/h). Progression of atrial fibrillation to persistent or permanent forms between the two groups was compared using Wilcoxon rank-sum test, chi-square tests and logistic regression analysis. Of 373 patients with atrial fibrillation (77% paroxysmal, 23% persistent), 108 (29%) progressed to persistent or permanent atrial fibrillation during follow-up (median, 33 months; interquartile range, 16-50). Compared to patients with infrequent periodic leg movement during sleep (n=168), patients with frequent periodic leg movement during sleep (n=205) had a higher rate of atrial fibrillation progression (23% vs. 34%; p=0.01). Patients with frequent periodic leg movement during sleep were older and predominantly male; however, there were no significant differences at baseline in clinical factors that promote atrial fibrillation progression between both groups. On multivariate analysis, independent predictors of atrial fibrillation progression were persistent atrial fibrillation at baseline, female gender, hypertension and frequent periodic leg movement during sleep. In patients with frequent periodic leg movement during sleep, dopaminergic therapy for control of leg movements in patients with restless legs syndrome reduced risk of atrial fibrillation progression. Frequent leg movement during sleep in patients with restless legs syndrome is associated with progression of atrial fibrillation to persistent and permanent forms

Effects of aging on cardiac oxidative stress and transcriptional changes in pathways of reactive oxygen species generation and clearance

Background: Age-related heart diseases are significant contributors to increased morbidity and mortality. Emerging evidence indicates that mitochondria within cardiomyocytes contribute to age-related increased reactive oxygen species (ROS) generation that plays an essential role in aging-associated cardiac diseases. Methods and Results: The present study investigated differences between ROS production in cardiomyocytes isolated from adult (6 months) and aged (24 months) Fischer 344 rats, and in cardiac tissue of adult (18-65 years) and elderly (\u3e65 years) patients with preserved cardiac function. Superoxide dismutase inhibitable ferricytochrome c reduction assay (1.32±0.63 versus 0.76±0.31 nMol/mg per minute; P=0.001) superoxide and H2O2 production, measured as dichlorofluorescein diacetate fluorescence (1646±428 versus 699±329, P=0.04), were significantly higher in the aged versus adult cardiomyocytes. Similarity in age-related alteration between rats and humans was identified in mitochondrial-electron transport chain-complex-I-associated increased oxidative-stress by MitoSOX fluorescence (53.66±18.58 versus 22.81±12.60; P=0.03) and in 4-HNE adduct levels (187.54±54.8 versus 47.83±16.7 ng/mg protein, P=0.0063), indicative of increased peroxidation in the elderly. These differences correlated with changes in functional enrichment of genes regulating ROS homeostasis pathways in aged human and rat hearts. Functional merged collective network and pathway enrichment analysis revealed common genes prioritized in human and rat aging-associated networks that underlay enriched functional terms of mitochondrial complex I and common pathways in the aging human and rat heart. Conclusions: Aging sensitizes mitochondrial and extramitochondrial mechanisms of ROS buildup within the heart. Network analysis of the transcriptome highlights the critical elements involved with aging-related ROS homeostasis pathways common in rat and human hearts as targets

Effect of aging on mitochondrial energetics in the human atria

Energy production in myocardial cells occurs mainly in the mitochondrion. Although alterations in mitochondrial functions in the senescent heart have been documented, the molecular bases for the aging-associated decline in energy metabolism in the human heart are not fully understood. In this study, we examined transcription profiles of genes coding for mitochondrial proteins in atrial tissue from aged (≥65 years old) and comorbidities-matched adult (old) patients with preserved left ventricular function. We also correlated changes in functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes with gene expression changes. There was significant alteration in the expression of 10% (101/1,008) of genes coding for mitochondrial proteins, with 86% downregulated (87/101). Forty-nine percent of the altered genes were confined to mitochondrial energetic pathways. These changes were associated with a significant decrease in respiratory capacity of mitochondria oxidizing glutamate and malate and functional activity of complex I activity that correlated with the downregulation of NDUFA6, NDUFA9, NDUFB5, NDUFB8, and NDUFS2 genes coding for NADH dehydrogenase subunits. Thus, aging is associated with a decline in activity of OXPHOS within the broader transcriptional downregulation of genes regulating mitochondrial energetics, providing a substrate for reduced energetic efficiency in the senescent human atria

Aging-associated changes in atrial G6P, G1P, and G3P ¹⁸O-metabolic–labeling indicating alterations in glycolytic, glycogenolytic, and substrate shuttle activities.

<p>A, Aging and stress (ISO) effects on atrial G6P turnover, indicators of glycolytic rate. B, Aging and stress effects on atrial G1P turnover, indicators of glycogenolytic rate. C, Aging and stress effects on atrial G3P turnover, indicators of substrate shuttle activity. D, Aging and stress (ISO) effects on atrial Pi/γ-ATP ¹⁸O-labeling ratio, indicators of energetic communication between ATP consumption and ATP production processes. E, Schematic representation of reaction sequences and metabolite¹⁸O-labeling allowing to track glycolytic, glycogenolytic, and α-glycerophosphate substrate shuttle dynamics. * <i>P</i><0.05 and ** <i>P</i><0.01. G1P indicates glucose-1-phosphate; G3P, glycerol-3-phosphate; G6P, glucose-6-phosphate; ISO, isoproterenol; Pi, inorganic phosphate.</p