Large Animal Models of Heart Failure With Reduced Ejection Fraction (HFrEF)

Heart failure is a life-threatening disease and addressing it should be considered a global health priority. At present, approximately 26 million people worldwide are living with heart failure. The outlook for such patients is poor, with survival rates worse than those for bowel, breast or prostate cancer. Furthermore, heart failure places great stresses on patients, caregivers and healthcare systems. Demands on healthcare services, in particular, are predicted to increase dramatically over the next decade as patient numbers rise owing to ageing populations, detrimental lifestyle changes and improved survival of those who go on to develop heart failure as the final stage of another disease. It is time to ease the strain on healthcare systems through clear policy initiatives that prioritize heart failure prevention and champion equity of care for all. Despite the burdens that heart failure imposes on society, awareness of the disease is poor. As a result, many premature deaths occur. This is in spite of the fact that most types of heart failure are preventable and that a healthy lifestyle can reduce risk. Even after heart failure has developed, premature deaths could be prevented if people were taught to recognize the symptoms and seek immediate medical attention. Public awareness campaigns focusing on these messages have great potential to improve outcomes for patients with heart failure and ultimately to save lives. Compliance with clinical practice guidelines is also associated with improved outcomes for patients with heart failure. However, in many countries, there is considerable variation in how closely physicians follow guideline recommendations. To promote equity of care, improvements should be encouraged through the use of hospital performance measures and incentives appropriate to the locality. To this end, policies should promote the research required to establish an evidence base for performance measures that reflect improved outcomes for patients. Continuing research is essential if we are to address unmet needs in caring for patients with heart failure. New therapies are required for patients with types of heart failure for which current treatments relieve symptoms but do not address the disease. More affordable therapies are desperately needed in the economically developing world. International collaborative research focusing on the causes and treatment of heart failure worldwide has the potential to benefit tens of millions of people. Change at the policy level has the power to drive improvements in prevention and care that will save lives. It is time to make a difference across the globe by confronting the problem of heart failure.

The present study was done to quantitate the evolution of myocardial ischemic cell death within the framework of (1) the anatomical boundaries of the ischemic bed at risk and (2) the magnitude and transmural distribution of collateral blood flow. Myocardial ischemia was produced by proximal circumflex (LCC) occlusions in open chest dogs. Infarcts reperfused at 40 minutes, 3 hours, or 6 hours were compared with permanent infarcts. All dogs were sacrificed at 4 days. Regional myocardial blood flow was measured with 9-micrometer tracer microspheres before, and 20 minutes after, LCC occlusion. The location and size of the ischemic LCC bed at risk was determined by a dye injection technique. Infarct size was quantitated from multiple histologic sections. Necrosis involved 28 per cent, 70 per cent, and 72 per cent of the ischemic bed at risk in infarcts reperfused at 40 minutes, 3 hours, and 6 hours versus 79 per cent following permanent LCC ligation. Viable and potentially salvageable subepicardial muscle persisted for at least 3 hours after the onset of ischemia. Most of the salvageable myocardium was in the subepicardial region. In all groups, the lateral margins of necrosis were sharp in the subendocardial zone and were determined by the anatomical boundaries of the ischemic LCC bed at risk. LCC bed size ranged from 29 to 48 per cent of the left ventricle and thus contributed to variation in infarct size. However, infarct size, as a percentage of bed size, was determined by the transmural extent of necrosis within that bed (r = -0.97). This transmural extent of necrosis was related to subepicardial collateral flow after 3 hours (r = 0.92) and 6 or 96 hours (r = -0.85) but not after 40 minutes (r = -0.26) of ischemia. Thus, irreversible injury of ischemic myocardium developed as a transmural wavefront, occurring first in the subendocardial myocardium but ultimately becoming nearly transmural. Eventual transmural necrosis, and therefore over-all infarct size was determined by, and can be predicted from flow measurements obtained shortly after coronary occlusion.

The purpose of this study was to describe the temporal trends in prevalence of left ventricular systolic dysfunction (LVSD) in individuals without and with heart failure (HF) in the community over a 3-decade period of observation.