[Metabolic therapy for heart failure]. / Terapia metabolica per l'insufficienza cardiaca.

Heart failure may promote metabolic changes such as insulin resistance, in part through neurohumoral activation, and determining an increased utilization of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation have been shown to be increased in patients with heart failure. The result is depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include several pharmacological agents that directly inhibit fatty acid oxidation. The results of current research are supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with heart failure. Trimetazidine is the most studied drug in this context. Several small studies have evidenced the usefulness of such additional therapeutic tools for heart failure. More specifically, recent meta-analyses and a multicenter retrospective study have shown that additional use of trimetazidine in patients with heart failure, along with symptoms and cardiac function improvement, also provides a significant protective effect on all-cause mortality, cardiovascular events and hospitalization due to cardiac causes. Nevertheless, the exact role of metabolic therapy in heart failure is yet to be established, and a large multicenter randomized trial is necessary.

Prognostic role of stress/rest myocardial perfusion scintigraphy in patients with cardiac syndrome x.

AIM: The prognostic utility of myocardial perfusion scintigraphy (MPS) in patients with angiographically normal coronary arteries has not been evaluated yet. Our aim was to determine the prognostic role of positive MPS in patients with angina, positive exercise test and smooth coronary arteries (syndrome X). METHODS: A total of 156 patients with angina, positive exercise test, positive MPS and normal coronary arteries and 172 patients with angina and positive exercise test who had negative MPS were selected for study. The primary endpoint was combined all-cause mortality and hospitalizations for cardiac causes. The secondary endpoint was hospitalization for cardiac causes. RESULTS: Kaplan-Meier analysis showed a greater (p=0.001) incidence of the primary endpoint in patients with positive MPS, compared to those with negative MPS. Additionally, Kaplan-Meier analysis for cardiovascular hospitalization showed a significant difference (p=0.003) between the two groups. Cox regression analysis, adjusted for age, sex, BMI and antianginal therapy confirmed a significant risk increase for patients with positive MPS, with a hazard ratio (HR)=3.20 (CI 95%: 1.14-9.02; p=0.028). Cox analysis for cardiovascular hospitalization also showed a significant risk increase for patients with positive MPS (HR=3.19; CI 95%: 1.13-9.00; p=0.03). Finally, Cox analysis showed that patients with positive MPS tend to have a higher risk to remain symptomatic in the follow-up period (HR=1.614; CI 95%: 0.999-2.607; p=0.51). CONCLUSIONS: This study shows that inducible myocardial hypoperfusion at MPS in patients with syndrome X could discriminate patients with a more severe prognosis, especially in terms of further hospitalization and symptomatic burden.

[Cardiovascular involvement in Erdheim-Chester syndrome: clinical and therapeutic implications]. / Coinvolgimento cardiovascolare nella sindrome di Erdheim-Chester: aspetti clinici e terapeutici.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans' cell histiocytosis of unknown etiology and its incidence is constantly increasing. ECD is characterized by a xantomatous or xanthogranulomatous infiltration of various tissues by foamy histiocytes surrounded by fibrosis. ECD is characterized by multi-organ involvement and is generally associated with a poor prognosis with a median survival of 32 months after diagnosis. Cardiovascular involvement concerns mainly the thoraco-abdominal aorta and pericardium. Less frequently, infiltration affects the myocardial tissue, especially the right atrium, and the valvular endocardium. Recently, the involvement of the vena cava has also been described. The diagnosis of ECD is made by the identification of foamy histiocytes CD68 positive and CD1a/S100 negative embedded in a polymorphic inflammatory tissue on biopsy. Despite the adoption of several therapeutic strategies until now prognosis has remained poor. Interferon-α can be considered the first line therapy, but its effects on central nervous system and cardiovascular localization have been shown to be often poor. In this context a combined treatment with the anti-TNFα monoclonal antibody infliximab and methotrexate seems to be effective and well tolerated.