Cardiac effects of deferasirox in transfusion-dependent patients with myelodysplastic syndromes: TELESTO study.

Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion-dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo-controlled, randomised study to evaluate the iron chelator deferasirox in patients with low- or intermediate-1-risk MDS and iron overload. Echocardiographic parameters were collected at screening and during treatment. Patients receiving deferasirox experienced a significant decrease in the composite risk of hospitalisation for congestive heart failure (CHF) or worsening of cardiac function (HR = 0.23; 95% CI: 0.05, 0.99; nominal p = 0.0322) versus placebo. No significant differences between the arms were found in left ventricular ejection fraction, ventricular diameter and mass or pulmonary artery pressure. The absolute number of events was low, but the enrolled patients were younger than average for patients with MDS, with no serious cardiac comorbidities and a modest cardiovascular risk profile. These results support the effectiveness of deferasirox in preventing cardiac damage caused by iron overload in this patient population. Identification of patients developing CHF is challenging due to the lack of distinctive echocardiographic features. The treatment of iron overload may be important to prevent cardiac dysfunction in these patients, even those with moderate CHF risk.

Potential of creatine or phosphocreatine supplementation in cerebrovascular disease and in ischemic heart disease.

Creatine is of paramount importance for maintaining and managing cellular ATP stores in both physiological and pathological states. Besides these "ergogenic" actions, it has a number of additional "pleiotropic" effects, e.g., antioxidant activity, neurotransmitter-like behavior, prevention of opening of mitochondrial permeability pore and others. Creatine supplementation has been proposed for a number of conditions, including neurodegenerative diseases. However, it is likely that creatine's largest therapeutic potential is in those diseases caused by energy shortage or by increased energy demand; for example, ischemic stroke and other cerebrovascular diseases. Surprisingly, despite a large preclinical body of evidence, little or no clinical research has been carried out in these fields. However, recent work showed that high-dose creatine supplementation causes an 8-9 % increase in cerebral creatine content, and that this is capable of improving, in humans, neuropsychological performances that are hampered by hypoxia. In addition, animal work suggests that creatine supplementation may be protective in stroke by increasing not only the neuronal but also the endothelial creatine content. Creatine should be administered before brain ischemia occurs, and thus should be given for prevention purposes to patients at high risk of stroke. In myocardial ischemia, phosphocreatine has been used clinically with positive results, e.g., showing prevention of arrhythmia and improvement in cardiac parameters. Nevertheless, large clinical trials are needed to confirm these results in the context of modern reperfusion interventions. So far, the most compelling evidence for creatine and/or phosphocreatine use in cardiology is as an addition to cardioplegic solutions, where positive effects have been repeatedly reported.