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Proteins may predict who benefits most from cardiac surgery

Researchers have identified two proteins that may indicate which patients suffering from acute coronary syndrome (ACS) would benefit from revascularization procedures such as angioplasty or coronary bypass surgery and which could be treated safely with less aggressive measures. The discovery is significant because it could allow physicians to tailor treatment plans more precisely for each patient, reducing the potential risks associated with revascularization and increasing survivorship.

Is revascularization always necessary?
Acute coronary syndrome is the term used to describe symptoms such as chest pain that represent a potential heart attack. It is standard practice to perform revascularization quickly on patients with cardiac-related chest pain because the pain signifies the heart muscle is dying from lack of oxygen-rich blood.

Until recently, it was not known which patients were most likely to benefit from revascularization and which could be treated safely with medications alone. Finding a reliable way to distinguish between the two courses of action meant that some patients would be spared the risks and possible lengthy hospital stay of revascularization when that choice would not improve outcomes.

Researchers studied the results of revascularization in a group of patients enrolled in the Global Utilization of Strategies to Open Occluded Arteries (GUSTO-IV) trial, a worldwide study that examined the effects of a blood clot-reducing agent (ReoPro/abciximab) administered intravenously. Patients were selected for the trial because of at least one recent episode of non-STsegment elevation ACS. This means that an electrocardiogram indicated coronary arteries were blocked but not completely closed. In all patients, ACS lasted five minutes or more and occurred within 24 hours of admission into the trial.

Within the first 30 days of the trial, at least 2,300 of the 7,800 subjects taking part in GUSTO-IV required revascularization by usual criteria. These patients were compared with trial participants who did not undergo surgical intervention during that time. For study purposes, the group was divided into smaller subgroups determined by factors such as age, gender, EKG changes, and whether they were undergoing treatment with beta-blockers, nitroglycerin or digitalis.

Levels of several biochemical markers were examined including C-reactive protein, an indicator of inflammation released from the liver; troponin-T (TnT), which is released as heart muscles die, and N-terminal pro-B-type natriuretic peptide (NT-proBNP), secreted from heart muscle cells in time of stress.

Impact on survivorship
Using one-year mortality as a measure, researchers found that patients with high levels of the blood proteins TnT and NT-proBNP benefited from revascularization after suffering non-ST segment elevation ACS. Patients with low levels of either protein fared worse with revascularization.

The protein TnT showed the best ability to predict outcome after revascularization. When patients with high levels of TnT underwent revascularization, their one-year mortality rate dropped significantly compared to patients who had not undergone revascularization (6.9 percent vs. 2.2 percent).

Similarly, one-year mortality also fell in patients with high levels of NT-proBNP who underwent revascularization compared to those who did not, (7.0 percent vs. 2.7 percent). In contrast, patients with low levels of the same protein had such a low long-term risk of death that cardiac surgery, particularly higher-risk coronary bypass surgery, was not justified.

Researchers concluded that in patients with non-ST-segment elevation ACS, high TnT or NT-proBNP levels were good predictors of high mortality, and revascularization should be performed as early as possible. In patients with low levels of both proteins, invasive procedures were more likely to increase the risk of death and aggressive medical management should be used instead.