Despite excellent diagnostic and therapeutic tools for myocardial infarction (MI), major adverse cardiac events (MACE) and progression of MI area is still a critical point. After MI, reperfusion by percutaneous coronary intervention is the most efficacious and utilized strategy. MACE limits the overall long-term survival. Post-MI remodeling of the left ventricle (LV) is one of the most common causes of heart failure (HF) with a poor prognosis5. Local expansion of the MI area, due to non-optimal healing, contribute to LV dilatation, anomalous remodeling, and HF. So, improving early phase treatments is crucial in preventing progression of cardiac dilatation and dysfunctions. Promoting myocardial healing and reducing infarct expansion could avoid altered LV geometry and progressive remodelling. Few therapies are available to improve local myocardial repair. Experimental evidence in mouse models suggests that coagulation factor XIII (FXIII) plays a key role in myocardial healing and its low values led to cardiac rupture and post-MI death Strategies improving local myocardial healing are addressed to limit MI expansion to prevent/attenuate LV dilation/remodelling and several approaches have been utilized. They include passive restraint of the LV and modification of MI scar constituents by means of cell transplantation or injection of biocompatible fibrin-alginate-FXIII material. This last had reduction on both LV wall thickness and infarct expansion. Intravenous FXIII injection, is undoubtedly the easier way to handle pro-healing strategies8, if FXIII will have significant effects on overall long-term survival. We recognized a mean FXIII decrease 3-4 days after MI, but not all cases had drastic diminishing and this was also genotype dependent. Our first objective is to find FXIII thresholds in the acute phase with positive/negative effects on survival to identify those cases potentially eligible for FXIII treatment and check a possible genotype dependence. The second aim is to express rFXIII containing selected single/combined variants to biochemically characterize also the rare combinations. We think that by analyzing hundreds of patients (200/year) during the acute phase we could recognize if FXIII depression and/or late recovery is a key parameter for poor prognosis. If a definite cut-off will be identified, below which prognosis is poor, we could select in advance cases really needing FXIII treatment. This should reduce the risk of potential undesirable thrombotic effects of FXIII infusion.
FXIII levels in myocardial infarction: a novel prognostic biomarker? From Pharmacogenetics to tailored therapeutic approaches. (Bando-ALT 2010; Associazione Lotta alla Trombosi e alle Malattie Cardiovascolari). Finanziato per il triennio 2011-2013 con 150.000 euro.
GEMMATI, Donato
2010
Abstract
Despite excellent diagnostic and therapeutic tools for myocardial infarction (MI), major adverse cardiac events (MACE) and progression of MI area is still a critical point. After MI, reperfusion by percutaneous coronary intervention is the most efficacious and utilized strategy. MACE limits the overall long-term survival. Post-MI remodeling of the left ventricle (LV) is one of the most common causes of heart failure (HF) with a poor prognosis5. Local expansion of the MI area, due to non-optimal healing, contribute to LV dilatation, anomalous remodeling, and HF. So, improving early phase treatments is crucial in preventing progression of cardiac dilatation and dysfunctions. Promoting myocardial healing and reducing infarct expansion could avoid altered LV geometry and progressive remodelling. Few therapies are available to improve local myocardial repair. Experimental evidence in mouse models suggests that coagulation factor XIII (FXIII) plays a key role in myocardial healing and its low values led to cardiac rupture and post-MI death Strategies improving local myocardial healing are addressed to limit MI expansion to prevent/attenuate LV dilation/remodelling and several approaches have been utilized. They include passive restraint of the LV and modification of MI scar constituents by means of cell transplantation or injection of biocompatible fibrin-alginate-FXIII material. This last had reduction on both LV wall thickness and infarct expansion. Intravenous FXIII injection, is undoubtedly the easier way to handle pro-healing strategies8, if FXIII will have significant effects on overall long-term survival. We recognized a mean FXIII decrease 3-4 days after MI, but not all cases had drastic diminishing and this was also genotype dependent. Our first objective is to find FXIII thresholds in the acute phase with positive/negative effects on survival to identify those cases potentially eligible for FXIII treatment and check a possible genotype dependence. The second aim is to express rFXIII containing selected single/combined variants to biochemically characterize also the rare combinations. We think that by analyzing hundreds of patients (200/year) during the acute phase we could recognize if FXIII depression and/or late recovery is a key parameter for poor prognosis. If a definite cut-off will be identified, below which prognosis is poor, we could select in advance cases really needing FXIII treatment. This should reduce the risk of potential undesirable thrombotic effects of FXIII infusion.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
