Pirfenidone Treat Myocardial Fibrosis After Acute Myocardial Infarction

Overview

Acute myocardial infarction (AMI) is myocardial necrosis caused by acute and continuous ischemia and hypoxia of coronary artery. It can be complicated with arrhythmia, shock or heart failure, which is often life-threatening. The disease is the most common in Europe and the United States, where about 1.5 million people suffer from myocardial infarction every year. China has shown an obvious upward trend in recent years, with at least 500000 new cases every year and at least 2 million current cases . At present, China has a high incidence rate of heart failure after myocardial infarction. The incidence of heart failure within 7 days after myocardial infarction is 19.3%, and the incidence of heart failure from 30 days to 6.7 years after myocardial infarction is 13.1%\~37.5%. The incidence of heart failure after myocardial infarction significantly increases the risk of short-term and long-term death, and the prognosis is poor. At present, there is a lack of unified guidance and norms for the diagnosis, treatment and prevention and control strategies of heart failure after myocardial infarction. Cardiac remodeling is the basic pathological process of heart failure after myocardial infarction, and it is also one of the main factors affecting the prognosis of patients. Studies have shown that 30% of AMI have ventricular remodeling 6 months after percutaneous coronary intervention (PCI), and the risk of ventricular remodeling in anterior wall myocardial infarction is the highest. According to foreign literature data, the probability of ventricular remodeling after anterior wall acute myocardial infarction is about 13%, which is 1.9 times higher than that in other parts.Opening the infarct related coronary artery early can save the dying myocardium, reduce the infarct myocardial area and reduce the loss of cardiomyocytes.

It plays an important role in preventing or delaying the occurrence of heart failure after myocardial infarction.However,even if the blood supply of infarct related vessels is restored, the immune injury, inflammatory response and RAAS activation caused by apoptotic and necrotic cardiomyocytes after myocardial infarction will still directly lead to a series of pathophysiological changes and aggravate cardiac remodeling. Based on the above targets β Receptor blockers, ACEI / ARB / Arni and aldosterone receptor antagonists have become the cornerstone of drug therapy for cardiac remodeling after myocardial infarction. However, myocardial fibrosis also plays an important role in the process of cardiac remodeling after myocardial infarction. Ischemic death of cardiomyocytes after myocardial infarction can induce repair response, and the damaged tissue is replaced by fibrotic scar produced by fibroblasts and myofibroblasts. Although the initial reparative fibrosis is very important to prevent ventricular wall rupture, excessive fibrosis and reactive fibrosis in non infarcted areas, including myocardial interstitial and perivascular fibrosis, will cause changes in cardiac morphology and biomechanics, further aggravate cardiac remodeling, damage cardiac function, and eventually lead to heart failure. Therefore, inhibition of reactive fibrosis in non infarcted areas is an important supplement to the current treatment of traditional anti cardiac remodeling drugs. In order to reduce the degree of reactive fibrosis in non infarct areas, a potentially feasible method is to inhibit the signal pathway promoting fibrosis. TGF- β Signal pathway plays an important role in promoting fibrosis signal pathway. It can promote the proliferation of fibroblasts, the differentiation and transfer of myofibroblasts, the deposition of collagen and the survival of myofibroblasts, so it can inhibit TGF- β Signal pathway is an effective method to inhibit myocardial fibrosis. Pirfenidone (PFD) is TGF- β The inhibitor can be used to delay the progression of idiopathic pulmonary fibrosis (IPF). Animal experiments also show that PFD can inhibit TGF- β Reduce myocardial fibrosis and improve the ability of myocardial contraction and relaxation. In the mouse model of dilated cardiomyopathy, it can effectively inhibit the pathological process of dilated cardiomyopathy, improve the degree of cardiac dilation and ventricular wall thickness. Preclinical studies have shown that PFD can inhibit myocardial fibrosis and protect the heart. A recently published phase II clinical study showed that compared with placebo, PFD significantly reduced EF value, preserved myocardial extracellular volume (ECV) and improved myocardial fibrosis in patients with heart failure (HFPEF). In view of the above background, we propose a research assumption: for patients after AMI, PFD drug intervention on the basis of standard treatment may achieve the effect of inhibiting myocardial fibrosis in non infarcted areas, so as to prevent or delay the occurrence of ventricular remodeling and heart failure after myocardial infarction, improve the quality of life and improve the prognosis of patients