Almost 3 decades ago, myocardial infarction (MI) was associated with very high morbidity and mortality. If a patient survived an acute infarct their prognosis was very poor and highly dependent on post-injury complications (1
). Acute complications such as rupture of the myocardium, contractile dysfunction, valvular disease, and heart block or long-term complications such as heart failure, and arrhythmias severely limited survival. Marked improvements were not seen until the mid-80s with the development of interventional and pharmacological therapies and the focus on early coronary reperfusion (1
). With clot-busting agents, coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and long-term treatment with ACE inhibitors and β-blockers, survival has increased to > 80% for the 30 day period post-MI; although, outcome is highly dependent on patient risk level and hospital performance (2
Of course, not all patients exert the same level of response or have the same infarct size. In addition, high risk patients are more prone to infarct expansion and border zone extension due, in part, to increased mechanical wall stress placed on the injured myocardium, which inevitably progresses into heart failure (4
). The border zone is characterized by a hypocontractile myocardium that is nonetheless perfused. With time adverse cellular and tissue remodeling events contribute, along with mechanical forces, to infarct expansion and border zone extension. This progressive maladaptive response is associated with increased myocyte apoptosis/necrosis and slippage, extracellular matrix (ECM) disturbances marked by fibrosis and changes in collagen makeup, and a complex wound healing process (6
). In time, the heart loses most of its function and pumping capacity due to chamber dilation and thinning of the ventricular wall (8
). Despite extensive research and discovery of large number of biomarkers that represent possible therapeutic targets, how the heart reaches this irreversible stage is still unclear.
Intense research has been focused recently on late stages of heart failure and novel strategies such as regenerative stem cell therapy and tissue engineering have emerged (9
). Some modest improvements in cardiac function have been documented in clinical trials of stem cell treatment (12
); however, reversing adverse remodeling and regenerating a fully functional and integrated myocardium is still a dream. Alternative strategies aimed at preventing adverse remodeling may represent a much more attainable goal. With that in mind, some groups have focused efforts on devising ways of preventing the initial injury, especially in patients with high risk factors, while others have focused on preventing adverse remodeling after the injury has occurred ().
Figure 1 ACC/AHA heart failure stages. Stage A: Patients at high risk but with normal cardiac function and no symptoms of heart failure. Patients in this category are treated with drugs that treat the underlying condition such as hypertension, obesity, CVD, or (more ...)
In this review we focus on therapeutic strategies that prevent adverse remodeling through the use of acellular biomaterials injected directly into the infarcted area of the heart in the early stages post-MI. The basis for this strategy is to decrease compliance of the infarcted myocardium, i.e., increase infarct stiffness, and thereby lessen wall stress on the surrounding myocardium. A dramatic proof of concept supporting the utility of this approach was recently reported (4
). A dermal filler agent sold to treat facial wrinkles was injected into a sheep anteroapical infarct 3 h post-MI (). In addition to increased infarct thickness and stiffness, they reported attenuated left ventricular remodeling and improved global LV function assessed 8 weeks later ().
Figure 2 Dermal filler injection limits limit infarct expansion. (A) Sheep heart after anteroapical infarction. (B) Same heart after administering dermal filler in 20 equal injections 3 h after coronary artery occlusion. Light blue line demarcates infarct and (more ...)
Figure 3 Dobutamine stress echocardiography for untreated sheep 8 weeks after anteroapical infarct, infarcted sheep treated with dermal filler 8 weeks after MI, and normal (uninfarcted) sheep. (A) LV systolic volume was significantly reduced in dermal filler treated (more ...)