Iron overload thalassemic cardiomyopathy: Iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity

Patients with thalassemia major have inevitably suffered from complications of the disease, due to iron overload. Among such complications, cardiomyopathy is the leading cause of morbidity and mortality (63.6% to 71%). The major causes of death in this group of patients are congestive heart failure and fatal cardiac tachyarrhythmias leading to sudden cardiac death. The free radical-mediated pathway is the principal mechanism of iron toxicity. The consequent series of events caused by iron overload lead to catastrophic cardiac effects. The authors review the electrophysiological and molecular mechanisms, pathophysiology and correlated clinical insight of heart failure and arrhythmias in iron overload thalassemic cardiomyopathy.     

Three-dimensional mapping of earliest activation after near-threshold ventricular defibrillation shocks

INTRODUCTION: Following shocks with a 50% defibrillation success (DFT50) delivered from electrodes at the right ventricular (RV) apex and superior vena cava (SVC), the earliest epicardial postshock activation always appears focally in the left ventricular (LV) apex for both successful and failed shocks. Because the heart is a three-dimensional (3D) structure, questions remain whether this activation truly arises from a focus or the focal pattern represents epicardial breakthrough resulting from intramural reentry. To answer these questions, 3D electrical mapping was performed. METHODS AND RESULTS: In six pigs, 60 to 84 epoxy fiberglass needles (0.7-mm-diameter), each containing six electrodes 2 mm apart, were inserted into the LV with 3- to 5-mm spacing around the apex and 5- to 10-mm spacing near the base. Ten DFT50 shocks (RV-->SVC, biphasic, 6/4 msec) were delivered after 10 seconds of fibrillation in each animal. The first five activations after each shock were mapped. Of 60 DFT50 shocks, 31 were successful, of which the first postshock cycle was a sinus beat in 13. In the other 18 successful shock episodes, the first postshock activation was detected 63 +/- 16 msec after the shock, which was not significantly different from the 58 +/- 23 msec postshock interval for the 29 failed shock episodes. In these 47 successful and failed shock episodes, the earliest postshock activation always arose focally from the LV apex. Its origin was in the subepicardium in 76% +/- 17%, midmyocardium in 16% +/- 12%, and subendocardium in 8% +/- 6% of cases. CONCLUSION: Following near-DFT50 shocks, the first postshock cycles did not arise by macroreentry. Instead, they originated from a true focus or microreentry, most commonly near the epicardium.     

Physical check-up and blood data analysis in the Thai elderly of Chaingmai Province, Thailand

Introduction:   Chiangmai is one of the provinces in Northern Thailand. The Aging population has increased rapidly since family planning commenced in 1972. For the surveillance of aging, we started a health investigation of the elderly over 60 years of age in the suburban area of Chiangmai since 1997 with the Nippon Medical School Team.
Materials and Method:   Medical examination was carried out for the elderly (male = 34, female = 73) at Department of Family Medicine, Chiangmai University, Chiangmai Thailand in August 2002. Chula Mental Test (CMT) was used for cognitive function and Geriatric Depression Scale was used for evaluation of depressive condition.
Results:   The major health problems of this group of elderly in Chiangmai Province were visual acuity abnormality (98.1%), anemia (66.4%), hypertension (37.4%), dental caries (29%), bone and joint disease (23.4%), cardiovascular disease (11.2%), gingivitis (11.2%), diabetes mellitus (9.3%), digestive system disease (8.4%), and presbycrusis (8.4%). The prevalence of cognitive impairment and depression were 0.9 and 2.8%, respectively. The prevalence of high cholesterol, triglyceride, and LDL cholesterol were 43.9, 29.0, and 15.9%, respectively. The prevalence of high BUN, creatinine, and uric acid were 17.8, 11.2, and 29.9%, respectively. The prevalence of high GOT, GPT, gamma GT, ZTT, and TTT were 4.7, 1.9, 53.3, 35.5, and 21.5%, respectively. The prevalence of low hemoglobin was 66.4%.
Conclusion:   There was a high prevalence of anemia and hyperlipidemia in this group of elderly in Chiangmai Province. The analysis of background factors and further investigation should be carried out continuously.     

Effects of Metformin on Hepatic Steatosis in Adults with Nonalcoholic Fatty Liver Disease and Diabetes: Insights from the Cellular to Patient Levels

Nonalcoholic fatty liver disease (NAFLD) patients with diabetes constitute a subgroup of patients with a high rate of liver-related complications. Currently, there are no specific drug recommendations for these patients. Metformin, a conventional insulin sensitizer agent, has been widely prescribed in patients with diabetes. Metformin treatment has been shown to be effective at alleviating hepatic lipogenesis in animal models of NAFLD, with a variety of mechanisms being deemed responsible. To date, most studies have enrolled diabetic patients who are treated with metformin, with the drug being taken continuously throughout the study. Although evidence exists regarding the benefits of metformin for NAFLD in preclinical studies, reports on the efficacy of metformin in adult NAFLD patients have had some discrepancies regarding changes in liver biochemistry and hepatic fat content. Evidence has also suggested possible effects of metformin as regards the prevention of hepatocellular carcinoma tumorigenesis. This review was performed to comprehensively summarize the available in vitro, in vivo and clinical studies regarding the effects of metformin on liver steatosis for the treatment of adult NAFLD patients with diabetes. Consistent reports as well as controversial findings are included in this review, and the mechanistic insights are also provided. In addition, this review focuses on the efficacy of metformin as a monotherapy and as a combined therapy with other antidiabetic medications.     

Endometrial adenocarcinoma in young thai women

Objective: To evaluate the clinicopathological characteristics and survival analysis in endometrial adenocarcinoma women younger than the age of 40 years compare to older women. Methods: Medical records of 423 endometrial adenocarcinoma patients who received primary surgical treatment at King Chulalongkorn Memorial Hospital during 1996-2005 were reviewed. The patients were divided into two groups; 40 years of age or younger (group A, 42 patients) and older than 40 years (group B, 381 patients). Results: Up to 10% (42/423) of endometrial adenocarcinoma patients were younger than the age of 40 years. The higher incidence of nulliparous and obesity (BMI > 30 kg/m2) was significantly demonstrated in group A (81%/34.1% and 52.4%/25.2%, respectively). However, obesity was an only independent factor in multivariate analysis. No significant difference in surgical stage distribution and the other pathologic characteristics was demonstrated between both groups. However, poor histologic grade (grade 3) and deep myometrial invasion (myometrial invasion more than 50%) tended to be found more frequent in the patients older than the age of 40 years, although there was no statistical significance (16% versus 4.7% and 31% versus 14.3%, respectively). Moreover, synchronous ovarian cancer seemed to be higher in young patients (7.1% and 2.9%, p> 0.05). Median time to follow was 63 months (range-145 months). Five years disease free survival and 5 years overall survival were 87.3% and 92.4% in group A versus 83.8% and 88.0% in group B without statistical significance between both groups. Conclusions: Obesity was the only independent factor associated with endometrial adenocarcinoma in young patients. Distribution of the surgical stage and the other pathologic characteristics were similar between both groups without survival benefit in young patients.     

Effect of Altering the Left Ventricular Pressure on Epicardial Activation Time in Dogs with and without Pacing-Induced Heart Failure

Background: The influence of an increased left ventricular end-diastolic pressure (LVEDP) on the development of lethal arrhythmias in chronic heart failure is unclear. We investigated the effect of chronic and acute LVEDP increase on the epicardial activation time of sinus (SB) and paced (PB) beats. Methods: Six dogs underwent rapid ventricular pacing at 220–280[emsp4 ]beats/min for 6–14 weeks for induction of heart failure. On the study day, baseline (ba) LVEDP was determined for the surviving heart failure animals (HF-ba), and for seven control animals (C-ba). The epicardial activation time (EAT, time between the earliest and latest epicardial activation) for five consecutive SB and five ventricular PB during the baseline hemodynamic state were recorded using a 504 electrode mapping-sock. In the control animals a 2-litre volume (vl) was infused over 10[emsp4 ]min to acutely increase the LVEDP (C-vl) to a level comparable to the chronic increased LVEDP of the HF-ba. The same volume challenge was performed in two HF animals (HF-vl) and the EAT for SB and PB was redetermined. Results: Three of six HF animals died during induction of heart failure. In the three remaining HF animals, chronic LVEDP increased from 6±1 to 17±10.8[emsp4 ]mmHg (P=0.07), EAT for SB increased by 68±% compared to control animals (HF-ba vs. C-ba, P<0.05). In contrast, in the control animals the acute rise in LVEDP from 6.8±4.5 to 14.7±6.2 mmHg P<0.05), shortened the EAT for SB (C-ba vs. C-vl, P<0.05). A similar decrease in EAT for SB caused by acute volume load was seen in the HF animals, but did not reach significance due to the small sample size (one of the three remaining HF animals died of spontaneous ventricular fibrillation before the volume load). Chronic LVEDP elevation significantly prolonged the EAT for PB from 72±11 to 120±31[emsp4 ]ms (C-ba vs. HF-ba) while acute LVEDP increase had no significant effect on EAT for PB. Conclusion: Chronic HF increases LVEDP and prolongs EAT, while an acute increase in LVEDP shortens the EAT for sinus beats. A prolongation of EAT in heart failure may make the heart more susceptible to ventricular arrhythmias and electromechanical dissociation.     

Effects of curcuminoid supplement on cardiac autonomic status in high-fat–induced obese rats

ObjectiveSudden cardiac death in obesity is frequently associated with sympathetic activation due to an elevated plasma free-fatty acid (FFA) level. Curcuminoids, the phenolic yellowish pigments of turmeric, display antioxidative and lipid-lowering activities. We hypothesized that curcuminoids ameliorate cardiac sympathovagal disturbance in high-fat–induced obese rats.MethodsMale Wistar rats were divided into five groups. A normal-diet control (NDC) group received a normal-fat diet (12% calories as fat) and a high-fat–diet control (HDC) group received a high-fat diet (60% calories as fat) for 12 wk. Three other groups received high-fat diets with curcuminoid supplement at concentrations of 30 mg (HD₃₀), 60 mg (HD₆₀), and 90 mg (HD₉₀) per kilogram of body weight every day for 12 wk. Heart rate variability was determined to assess cardiac autonomic status at weeks 0 and 12.ResultsBody weight, visceral fat mass, plasma FFA, and glucose levels increased significantly in the HDC group compared with the NDC group. Low frequency power in normalized units (LFnu) and the ratio of LF to high-frequency power (HF) in the HDC group were significantly higher, whereas HFnu in the HDC group was significantly lower than in the NDC group. Plasma FFA levels correlated significantly with LFnu and LF/HF ratio. Compared with the HDC group, plasma FFA, glucose levels, LFnu, and LF/HF ratio were significantly decreased in the HF₃₀, HF₆₀, and HF₉₀ groups.ConclusionElevated plasma FFA in high-fat–induced obese rats is associated with an increased LF/HF ratio, an expression of sympathovagal disturbance. Curcuminoid supplementation ameliorates cardiac autonomic imbalance in high-fat–fed rats, probably due to its lipid-lowering effect.     

Heart rate variability in myocardial infarction and heart failure

The need to refine the identification of patients who might benefit from implantation of an implantable cardioverter defibrillator has been risen by the results of many clinical trials on ICD therapy. Traditional parameters such as left ventricular ejection fraction and the presence of non-sustained ventricular tachycardia were not strong enough to achieve this goal with reasonable cost-effectiveness. Heart rate variability (HRV) is one of the most popular parameters used to assess the autonomic tone. HRV has been reported as a strong predictor of cardiovascular mortality. Currently, three different categories of methods in HRV analysis are being used; the time domain, frequency domain, and non-linear dynamic analysis. Both time domain and frequency domain analyses of HRV have been investigated extensively regarding their use as a prognostic marker for cardiovascular mortality. The non-linear dynamic analysis is the latest tool that has shown to have an even higher predictive value than any of the traditional parameters. However, standardized and supporting evidence on this new technique is still lacking. In this article, the current role of HRV in the prediction of cardiovascular mortality in myocardial infarction and heart failure patients has been reviewed.     

Matrix metalloproteinases and myocardial infarction

Acute myocardial infarction (AMI) is currently one of the most important health problems in many countries around the world. Following AMI, many cytokines and proteolytic enzymes are released. Among these, matrix metalloproteinases (MMPs) are important proteolytic enzymes that lead to degradation of the extracellular matrix and to changes in cardiomyocytes in both infarcted and noninfarcted myocardium. This process is known as cardiac remodelling. It has been demonstrated that more than one type of MMP is present in the circulation after cardiomyocyte injury. A number of studies have demonstrated the correlations between these MMP levels and the severity of a coronary lesion, the progression of left ventricular dimension and the survival rate following AMI in both animal and human studies. MMPs have also been proposed as a possible novel prognostic indicator for myocardial infarction patients. Although the use of MMP inhibitors to improve cardiac outcome in AMI patients has been investigated, discrepancies in the results from those studies indicate that further research is still needed to warrant their beneficial effects. In the present review article, the roles of MMPs as prognostic indicators, as well as the factors influencing MMP expression, are discussed. Current findings on the role of MMP inhibitors in cardiac remodelling and the prognosis after AMI in both animal models and clinical studies are also examined.     

Modulating mitochondrial dynamics attenuates cardiac ischemia-reperfusion injury in prediabetic rats

Mitochondria are extraordinarily dynamic organelles that have a variety of morphologies,the status of which are controlled by the opposing processes of fission ...