Serial echocardiographic left ventricular ejection fraction measurements: A tool for detecting thalassemia major patients at risk of cardiac death

Cardiac damage remains a major cause of mortality among patients with thalassemia major. The detection of a lower cardiac magnetic resonance T2* (CMR-T2*) signal has been suggested as a powerful predictor of the subsequent development of heart failure. However, the lack of worldwide availability of CMR-T2* facilities prevents its widespread use for follow-up evaluations of cardiac function in thalassemia major patients, warranting the need to assess the utility of other possible procedures. In this setting, the determination of left ventricular ejection fraction (LVEF) offers an accurate and reproducible method for heart function evaluation. These findings suggest a reduction in LVEF ≥ 7%, over time, determined by 2-D echocardiography, may be considered a strong predictive tool for the detection of thalassemia major patients with increased risk of cardiac death. The reduction of LVEF ≥ 7% had higher (84.76%) predictive value. Finally, Kaplan–Meier survival curves of thalassemia major patients with LVEF ≥ 7% showed a statistically significant decreased probability of survival for heart disease (p = 0.0022).However, because of limitations related to the study design, such findings should be confirmed in a large long-term prospective clinical trial.     

DPP4‐inhibitor improves neuronal insulin receptor function,brain mitochondrial function and cognitive function in rats with insulin resistance induced by high‐fat diet consumption

High‐fat diet (HFD) consumption has been demonstrated to cause peripheral and neuronal insulin resistance, and brain mitochondrial dysfunction in rats. Although the dipeptidyl peptidase‐4 inhibitor, vildagliptin, is known to improve peripheral insulin sensitivity, its effects on neuronal insulin resistance and brain mitochondrial dysfunction caused by a HFD are unknown. We tested the hypothesis that vildagliptin prevents neuronal insulin resistance, brain mitochondrial dysfunction, learning and memory deficit caused by HFD. Male rats were divided into two groups to receive either a HFD or normal diet (ND) for 12 weeks, after which rats in each group were fed with either vildagliptin (3 mg/kg/day) or vehicle for 21 days. The cognitive function was tested by the Morris Water Maze prior to brain removal for studying neuronal insulin receptor (IR) and brain mitochondrial function. In HFD rats, neuronal insulin resistance and brain mitochondrial dysfunction were demonstrated, with impaired learning and memory. Vildagliptin prevented neuronal insulin resistance by restoring insulin‐induced long‐term depression and neuronal IR phosphorylation, IRS‐1 phosphorylation and Akt/PKB‐ser phosphorylation. It also improved brain mitochondrial dysfunction and cognitive function. Vildagliptin effectively restored neuronal IR function, increased glucagon‐like‐peptide 1 levels and prevented brain mitochondrial dysfunction, thus attenuating the impaired cognitive function caused by HFD.     

Heart rate variability and exercise capacity of patients with repaired tetralogy of Fallot

Heart rate variability (HRV) has been used as a reliable method to detect cardiac autonomic nervous system activity. Peak oxygen uptake (VO₂ peak) has been a predictor of death for adults with repaired tetralogy of Fallot (TOF). This study investigated the correlation between HRV and exercise capacity in 30 patients with TOF after surgery for total correction. The median age of the patients was 14 years (range, 9–25 years), and the median follow-up period was 11.6 months (range, 5.3–20.2 months). Low- and high-frequency-domain HRV significantly correlated with VO₂ peak (r = 0.56, P = 0.001 and r = 0.44, P = 0.02, respectively). After the 1-year follow-up evaluation, VO₂ peak and HRV analysis did not differ from those at entry to the study. However, low- and high-frequency-domain HRV still correlated significantly with VO₂ peak (r = 0.43, P = 0.03 and r = 0.52, P = 0.007, respectively). Left ventricular early diastolic myocardial velocity was most closely correlated with the VO₂ peak (r = 0.51, P = 0.005). Impaired cardiovascular autonomic control and left ventricular diastolic dysfunction may be responsible for exercise intolerance in patients with repaired TOF. Long-term follow-up evaluation with exercise testing and 24-h Holter monitoring are warranted.     

Effects of left ventricular function on the exercise capacity in patients with repaired tetralogy of Fallot

Background: Tissue Doppler imaging has been recently used to evaluate ventricular function. Peak oxygen uptake (V^?O₂peak) has been demonstrated as a predictor for death in adults with repaired tetralogy of Fallot (TOF). The aim of this study was to determine which Doppler parameters correlated with V^?O₂peak in patients with repaired TOF. Method and Results: Doppler echocardiography, tissue Doppler imaging, and exercise test were performed in 30 patients with TOF after surgical repair. In 30 patients with repaired TOF (median age 14 years, range 9–25 years), 11 patients (37%) were female. Seven patients (median age 12 years) had normal left ventricular diastolic function, whereas the rest of the patients were classified as diastolic dysfunction grade II (median age 15 years; n = 15) and III and IV (median age 18 years; n = 8). The oxygen uptake at anaerobic threshold (V^?O_2AT) and peak exercise in patients with left ventricular diastolic dysfunction was significantly lower than that in those with normal diastolic function. Also, V^?O_2AT and V^?O₂peak in patients with diastolic dysfunction grade III and IV were significantly lower than that in those with diastolic dysfunction grade II. Left ventricular early diastolic myocardial velocity was most closely correlated to V^?O₂peak (r = 0.51; P = 0.005). Peak early ventricular filling velocity to early diastolic myocardial velocity ratio was significantly correlated with V^?O₂peak (r =?0.50; P = 0.006). Conclusion: Left ventricular diastolic dysfunction is correlated with V^?O₂peak. Left ventricular diastolic function should be a routine echocardiographic assessment in patients with repaired TOF. (Echocardiography 2011;28:1019‐1024)     

Calcium channels and iron uptake into the heart

Iron overload can lead to iron deposits in many tissues,particularly in the heart.It has also been shown to be associated with elevated oxidative stress in tissues.Elevated cardiac iron deposits can lead to iron overload cardiomyopathy,a condition which provokes mortality due to heart failure in iron-overloaded patients.Currently,the mechanism of iron uptake into cardiomyocytes is still not clearly understood.Growing evidence suggests L-type Ca2+channels(LTCCs)as a possible pathway for ferrous iron(Fe2+)uptake into cardiomyocytes under iron overload conditions.Nevertheless,controversy still exists since some findings on pharmacological interventions and those using different cell types do not support LTCC’s role as a portal for iron uptake in cardiac cells.Recently,T-type Ca2+channels (TTCC)have been shown to play an important role in the diseased heart.Although TTCC and iron uptake in cardiomyocytes has not been investigated greatly,a recent finding indicated that TTCC could be an important portal in thalassemic hearts.In this review,comprehensive findings collected from previous studies as well as a discussion of the controversy regarding iron uptake mechanisms into cardiomyocytes via calcium channels are presented with the hope that understanding the cellular iron uptake mechanism in cardiomyocytes will lead to improved treatment and prevention strategies,particularly in iron-overloaded patients.     

Effect of rosiglitazone on cardiac electrophysiology, infarct size and mitochondrial function in ischaemia and reperfusion of swine and rat heart

Rosiglitazone, a peroxisome proliferator-activated receptor γ agonist, has been used to treat type 2 diabetes. Despite debates regarding its cardioprotection, the effects of rosiglitazone on cardiac electrophysiology are still unclear. This study determined the effect of rosiglitazone on ventricular fibrillation (VF) incidence, VF threshold (VFT), defibrillation threshold (DFT) and mitochondrial function during ischaemia and reperfusion. Twenty-six pigs were used. In each pig, either rosiglitazone (1 mg kg(-1)) or normal saline solution was administered intravenously for 60 min. Then, the left anterior descending coronary artery was ligated for 60 min and released to promote reperfusion for 120 min. The cardiac electrophysiological parameters were determined at the beginning of the study and during the ischaemia and reperfusion periods. The heart was removed, and the area at risk and infarct size in each heart were determined. Cardiac mitochondria were isolated for determination of mitochondrial function. Rosiglitazone did not improve the DFT and VFT during the ischaemia-reperfusion period. In the rosiglitazone group, the VF incidence was increased (58 versus 10%) and the time to the first occurrence of VF was decreased (3 ± 2 versus 19 ± 1 min) in comparison to the vehicle group (P < 0.05). However, the infarct size related to the area at risk in the rosiglitazone group was significantly decreased (P < 0.05). In the cardiac mitochondria, rosiglitazone did not alter the level of production of reactive oxygen species and could not prevent mitochondrial membrane potential changes. Rosiglitazone increased the propensity for VF, and could neither increase defibrillation efficacy nor improve cardiac mitochondrial function.