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Elevated Biomarkers after CABG and Increased Risk of Death
Elevated Levels of Cardiac Biomarkers Following Coronary Artery Bypass Graft Surgery Associated With Increased Risk of Death
CHICAGO—Patients who underwent coronary artery bypass graft surgery and had elevated levels of the cardiac enzymes creatine kinase or troponin in the 24 hours following surgery had an associated intermediate and long-term increased risk of death, according to a study in the February 9 issue of JAMA.
"About 400,000 coronary artery bypass grafting (CABG) procedures are performed annually in the United States, giving public health significance to factors that affect the outcome of these procedures," the authors write. Increases in creatine kinase (CK-MB) or troponin levels following CABG is common, and are an indicator of myocardial necrosis (death of heart muscle cells). Small amounts of necrosis are often regarded as insignificant. However, several small studies have suggested that cardiac enzyme elevation in the 24 hours following CABG surgery is associated with worse prognosis, but a definitive study has not been available, according to background information in the article.
Michael J. Domanski, M.D., of the Mount Sinai Cardiovascular Institute, New York, and colleagues examined the relationship between post-CABG elevation of enzyme markers of myocardial damage and early, intermediate-, and long-term mortality. The researchers analyzed data from randomized clinical trials or registries in which patients underwent CABG surgery and postprocedure biomarker (CK-MB, troponin, or both) and mortality data were collected. For this analysis, the researchers identified 7 studies, which included a total of 18,908 patients. Follow-up varied from 3 months to 5 years.
For each patient, the CK-MB ratio was calculated as the ratio between the peak CK-MB and the upper limit of normal for the participating laboratory of each study. The researchers found that higher ratios were associated with greater risk of death. The 30-day mortality rates by categories of CK-MB ratio were 0.63 percent for 0 to less than 1, 0.86 percent for 1 to less than 2, 0.95 percent for 2 to less than 5, 2.09 percent for 5 to less than 10, 2.78 percent for 10 to less than 20, and 7.06 percent for 20 to 40 or greater. "The model suggests that a CK-MB ratio value of 4 to 5 results in an expected 30-day mortality that is more than double that for a CK-MB ratio of 1. Available troponin data yielded a similar relationship," the authors write.
The researchers also found that of the variables in the model, including CK-MB ratio, age, history of kidney dysfunction, and prior heart attack, the CK-MB ratio was the strongest predictor of death and remained significant even after adjusting for baseline risk factors. This result was strongest at 30 days, but the adjusted association persisted from 30 days to 1 year and a trend was present from 1 year to 5 years. The findings were similar when the troponin ratio, rather than CK-MB ratio, was examined.
"Although enzyme elevations are common following CABG surgery, our data make clear that the long-term prognosis is worse for patients who experience even a small elevation of CK-MB than those who do not experience such a increase," the researchers write.
"These findings may inform the design of future clinical trials with respect to using cardiac markers as an outcome measure following CABG surgery. Although these findings require confirmation in large prospective studies, they suggest that there are clinical implications in terms of long-term prognosis for cardiac enzyme elevations following CABG surgery, particularly among those with very high levels."
Abstract
Association of Myocardial Enzyme Elevation and Survival Following Coronary Artery Bypass Graft Surgery
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Michael J. Domanski, MD et al
Author Affiliations: The Mount Sinai Cardiovascular Institute, New York, New York (Drs Domanski and Farkouh); et al
Context Several small studies have suggested that cardiac enzyme elevation in the 24 hours following coronary artery bypass graft (CABG) surgery is associated with worse prognosis, but a definitive study is not available. Also, the long-term prognostic impact of small increases of perioperative enzyme has not been reported.
Objective To quantify the relationship between peak post-CABG elevation of biomarkers of myocardial damage and early, intermediate-, and long-term mortality, including determining whether there is a threshold below which elevations lack prognostic significance.
Data Sources Studies (randomized clinical trials or registries) of patients undergoing CABG surgery in which postprocedural biomarker and mortality data were collected and included. A search of the PubMed database was performed in July 2008 using the search terms coronary artery bypass, troponin, CK-MB, and mortality.
Study Selection Studies evaluating mortality and creatine kinase (CK-MB), troponin, or both were included. One study investigator declined to participate and 3 had insufficient data.
Data Extraction Two independent reviewers determined study eligibility. The principal investigator from each eligible study was contacted to request his/her participation. Once institutional review board approval for the use of these data for this purpose was obtained, we requested patient-level data from each source. Data were examined to ensure that cardiac markers had been measured within 24 hours after CABG surgery, key baseline covariates, and mortality were available.
Results A total of 18 908 patients from 7 studies were included. Follow-up varied from 3 months to 5 years. Mortality was found to be a monotonically increasing function of the CK-MB ratio.
The 30-day mortality rates by categories of CK-MB ratio were 0.63% (95% confidence interval [CI], 0.36%-1.02%) for 0 to <1, 0.86% (95% CI, 0.49%-1.40%) for 1 to <2, 0.95% (95% CI, 0.72%-1.22%) for 2 to <5, 2.09% (95% CI, 1.69%-2.57%) for 5 to <10, 2.78% (95% CI, 2.12%-3.58%) for 10 to <20, and 7.06% (95% CI, 5.46%-8.96%) for 20 to ≥40. Of the variables considered, the CK-MB ratio was the strongest independent predictor of death to 30 days and remained significant even after adjusting for a wide range of baseline risk factors (χ2 = 143, P < .001; hazard ratio [HR] for each 5 point-increment above the upper limits of normal [ULN] = 1.12; 95% CI, 1.10-1.14). This result was strongest at 30 days, but the adjusted association persisted from 30 days to 1 year (χ2 = 24; P < .001; HR for each 5-point increment above ULN = 1.17; 95% CI, 1.10-1.24) and a trend was present from 1 year to 5 years (χ2 = 2.8; P = .10; HR for each 5-point increment above ULN = 1.05; 95% CI, 0.99-1.11). Similar analyses using troponin as the marker of necrosis led to the same conclusions (χ2 = 142 for 0-30 days and χ2 = 40 for 30 days to 6 months, both P < .001; HR for each 50 points above the ULN = 1.28; 95% CI, 1.23-1.33 and 1.15; 95% CI, 1.10-1.21, respectively).
Conclusions Among patients who had undergone CABG surgery, elevation of CK-MB or troponin levels within the first 24 hours was independently associated with increased intermediate- and long-term risk of mortality.
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Highlights of Article by Dr. Erik Hess et of Mayo Clinic ;CIRCOUTCOMES 2012
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Chest pain is the 2nd most common reason patients come to EDs across the United States
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Initial testing – including information obtained from the history, physical exam, electrocardiogram, and cardiac troponin – identifies > 98% of heart attacks
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To avoid missing a diagnosis of heart attack or pre-heart attack symptoms, emergency physicians often admit patients to observation units or to the hospital for extensive diagnostic testing, including stress testing
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This results in false positive test results, unnecessary exposure to radiation, and unnecessary downstream procedures such as stent placement in arteries of the heart
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Decision aids are evidence-based tools designed to educate and engage patients in decisions regarding their care
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We hypothesized that patients who were educated regarding their future risk for a heart attack and engaged in the decision of whether to be admitted to the observation unit for stress testing or to follow-up with a Mayo Clinic heart doctor in the next 72 hours would have greater knowledge about their short-term risk for heart attack, be more aware of the management options, and choose less intensive approaches to evaluation
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We randomly assigned 204 patients who came to the ED with chest pain and were being considered for observation unit admission to the decision aid or to usual care
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Decision aid patients:
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Had greater knowledge regarding their short-term risk for a heart attack
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Less frequently decided to be admitted to the observation unit for stress testing
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Had 4 times greater engagement in the decision making process
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Had no adverse events within 30 days of the ED visit
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Take home points
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Patients want to be educated and engaged in decisions regarding their care
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Once properly informed and engaged in treatment decisions, patients often choose less intensive treatment options
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Integrated health systems like the Mayo Clinic in which physicians collaboratively work together to provide ER patients ready access to outpatient follow-up have potential to improve the value of Emergency care
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Glucose, Insulin and Potassium (“GIK”) TO MINIMIZE IMPACT OF HEART ATTACKS BEFORE PATIENTS GET TO THE HOSPITAL
Study puts life-saving drugs in the hands of paramedics, decreasing rate of cardiac arrest and death from heart attacks
CHICAGO (March 27, 2012) — Paramedics can potentially reduce someone’s chances of having a cardiac arrest or dying by 50 percent by immediately administering a mixture of glucose, insulin and potassium (“GIK”) to people having a heart attack, according to research presented today at the American College of Cardiology’s 61st Annual Scientific Session. The Scientific Session, the premier cardiovascular medical meeting, brings cardiovascular professionals together to further advances in the field.
The study showed that patients who received GIK immediately after being diagnosed with acute coronary syndrome — which indicates a possible heart attack is either in progress or on the way — were 50 percent less likely to have cardiac arrest (a condition in which the heart suddenly stops beating) or die than those who received a placebo, although the treatment did not prevent the heart attack from occurring. The reduction in in-hospital cardiac arrest or death was a “secondary endpoint”, so statistically was not definitive, but was consistent with how GIK seems to work in experimental models of heart attack.
The effect was also present for patients with ST-elevation heart attacks, which require immediate treatment. For those patients, immediate GIK was associated with a 60 percent reduction in in-hospital cardiac arrest or death.
“When started immediately in the home or on the way to the hospital — even before the diagnosis is completely established — GIK appears not completely prevent any heart attack from occurring, but appeared in this trial to reduce the size of heart attacks and to reduce by half the risk of having a cardiac arrest or dying,” said Harry P. Selker, MD, MSPH, executive director of the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center, who led the study with Joni Beshansky, RN, MPH, co-principal investigator and project director. “Acute coronary syndromes represent the largest cause of death in this country. GIK is a very inexpensive treatment that appears to have promise in reducing those deaths and morbidity.”
The cost of the treatment is about $50.
“Because the trial is the first to show GIK could be effective when used by paramedics in real-world community settings, it could have important implications for the treatment of heart attacks,” Dr. Selker said. Previous clinical trials have shown no consistent effect, likely because the GIK was given too late to help. This study, the “IMMEDIATE Trial,” was the first to test the effectiveness of administering GIK at the very first signs of a threatening heart attack, in the community, rather than waiting hours until the diagnosis was well-established at a hospital, as done in previous clinical trials.
“We wanted to do something that is effective and can be used anywhere,” said Dr. Selker. “We’ve done a lot of studies of acute cardiac care in emergency departments and hospitals, but more people die of heart attacks outside the hospital than inside the hospital. Hundreds of thousands of people per year are dying out in the community; we wanted to direct our attention to those patients.”
The researchers trained paramedics in 36 Emergency Medical Services systems in 13 cities across the country to administer GIK after determining that a patient was likely having a threatened or already established heart attack using electrocardiograph-based ACI-TIPI (acute cardiac ischemia time-insensitive predictive instrument) and thrombolytic predictive instrument decision support that prints patient-specific predictions on the top of an electrocardiogram. The paramedics used these predictions to decide if a patient would likely benefit from treatment. There were 911 patients randomized to receive either the GIK treatment or a placebo.
Administering GIK immediately also reduced the severity of the damage to the heart tissue from the heart attack. On average, 2 percent of the heart tissue was destroyed by the heart attack in people receiving GIK, compared with 10 percent in those who received the placebo. Although a significant proportion of suspected heart attacks are later determined to be false alarms (23 percent in this study), administering GIK does not appear to cause any harmful effects in such patients.
The research team will follow up with study participants at six and 12 months to evaluate the longer-term benefit of the GIK treatment.
This study was funded by the NIH’s National Heart, Lung and Blood Institute.
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Amazon.com 's Editorial Reviews
Angina: New Ways to Treat
Chronic Chest Pain
Part of the award winning public television series Healthy head
/Healthy Mind. It's one of the scariest medical symptoms for people who are generally healthy: a tightening, painful feeling in the chest known as Angina. In some cases this chest pain can be a serious warning that requires immediate treatment. But for the millions of people with chronic, stable angina the discomfort is something that can be readily managed with a variety of treatments. In this program we take a look at what generally causes angina, what can be done to prevent it and how it can be effectively treated with lifestyle changes, innovative drug therapies and medical procedures.
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Amazon.com Editorial Review:
Philips HeartStart Home Defibrillator (AED)
Be prepared for the unexpected.
When sudden cardiac arrest (SCA) strikes, the electrical system of the heart short circuits, causing the heart to quiver rather than pump in a normal rhythm. It typically results in the abnormal heart rhythm know as ventricular fibrillation (VF). It usually happens without warning and the majority of people have no previously recognized symptoms of heart disease. And it most often happens at home. For the best chance of survival from SCA caused by VF, a defibrillator should be used within 5 minutes. Yet, less than 1 in 20 people survive largely because a defibrillator does not arrive in time.
Just as seat belts or airbags do not save every life in a traffic accident, a defibrillator will not save every person who suffers a sudden cardiac arrest. Yet many lives could be saved if more people could be reached more quickly.
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