CONFIRM Enhances Position of CT Angiography

DENVER – A cascade of data generated recently by the CONFIRM registry is turning heads and winning converts to coronary CT angiography as a reasonable first-line test to diagnose or exclude coronary artery disease in many symptomatic patients with no history of the disease.

"The CONFIRM information about the need to rethink people’s pretest likelihood of CAD is enormously important. It shows that if we think a patient’s likelihood is intermediate, it’s actually low. So CT angiography might be the least expensive way to exclude CAD," Dr. James E. Udelson observed during a panel discussion at the annual meeting of the American Society of Nuclear Cardiology.

In addition to being less expensive than SPECT (single-photon emission CT) myocardial perfusion imaging for this purpose, CTA also confers less radiation exposure, which is a particularly important consideration given that that the majority of patients undergoing evaluation for symptoms suggestive of CAD turn out not to have it, added Dr. Udelson, chief of cardiology and director of the nuclear cardiology laboratory at Tufts Medical Center, Boston.

Dr. Udelson is not a CT angiographer and is not involved with CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry). Neither is fellow panelist Dr. John J. Mahmarian. But he too finds CONFIRM compelling.

"I’m really intrigued by the CONFIRM data on nonobstructive plaque. These individuals with nonobstructive atherosclerotic plaque have a good short-term risk but may not have a good long-term risk. With the armamentarium we have today, it’s important to know that so we can treat people more aggressively and impact the disease process," said Dr. Mahmarian, ASNC president-elect and director of nuclear cardiology and CT services at the Methodist DeBakey Heart and Vascular Institute, Houston.

Their comments came in reaction to a wide-ranging update on the registry by CONFIRM investigator Dr. James K. Min of Cedars-Sinai Medical Center in Los Angeles.

Dr. Min explained that CONFIRM is a prospective, multinational registry including more than 32,000 consecutive patients who have undergone CTA at 18 participating sites. The registry was created to answer three questions of fundamental importance regarding the noninvasive imaging procedure: Does it have the ability to diagnose or exclude CAD as well as does invasive coronary angiography? Does it reduce the need for percutaneous angiography? And does it improve health outcomes for patients with acute chest pain who present to emergency departments and other settings?

The answer on all three counts is ‘yes,’ although some of the data are preliminary, Dr. Min said. The registry is being expanded, with follow-up to be extended to a median of 5 years, along with the possible addition of another 12,000-15,000 patients in order to strengthen the findings.

The power of CTA as a risk stratification tool was highlighted in a recent CONFIRM publication (J. Am. Coll. Cardiol. 2011;58:849-60). Dr. Min and his coworkers reported on nearly 24,000 consecutive patients without known pretest CAD who were prospectively followed for a mean of 2.3 years after undergoing CTA for assessment of suspected CAD. These were mainly middle-aged patients with a high prevalence of cardiovascular risk factors. In all, 71% had an intermediate or high pretest likelihood of obstructive CAD.

In this study population, a normal CTA study (found in 43% of patients) was associated with a highly favorable prognosis – namely, an all-cause mortality rate of just 0.28% per year. Moreover, a normal CTA result carried a 4-year "warranty."

Another key finding was that nonobstructive CAD (that is, a 1%-49% stenosis) was associated with a 1.6-fold increased risk of mortality in a multivariate risk-adjusted analysis. Nonobstructive CAD was detected in 34% of subjects.

Mortality risk climbed stepwise with the number of coronary vessels showing obstructive CAD on CTA: a doubling of risk in patients with single-vessel obstructive disease relative to the risk in those with a normal study; a 2.92-fold increased risk in those with two-vessel obstructive CAD; and a 3.7-fold increased risk in patients with triple-vessel or left anterior descending obstructive disease.

The mortality risk associated with obstructive CAD varied by age and sex. Patients younger than age 65 had a significantly greater mortality risk for two-vessel disease than did those aged 65 years or older. The younger patients with two-vessel obstructive disease had a fourfold greater death rate than did young patients with a normal CTA study, whereas older patients with double-vessel disease had a 2.46-fold increased risk. Similarly, triple-vessel obstructive disease in patients younger than age 65 was associated with a 6.2-fold increased risk of death, compared with those who had a normal CTA, a risk twice that conferred by three-vessel obstructive disease in older patients.

The relative hazards for single- and double-vessel obstructive CAD were not significantly different for men vs. women. However, women with three-vessel disease had a 4.2-fold increased mortality risk, significantly greater than the 3.3-fold risk associated with triple-vessel disease in men.

In another CONFIRM analysis, this one involving roughly 8,100 patients with an average pretest likelihood of obstructive CAD of 50% by the widely used Diamond Forrester clinical risk score, investigators found that the actual prevalence of obstructive CAD on CTA was only 18%. The take-home lesson here is that cardiologists severely overestimate the likelihood of significant disease when they rely on clinical risk scores that were developed in an earlier era, Dr. Min emphasized.

Another CONFIRM analysis involved 15,223 patients, 7.2% of whom underwent coronary revascularization following CTA. Among the subgroup with high-risk CAD as defined by the Duke severity categorization criteria – for example, three vessels having moderate stenoses or two with severe stenoses – the mortality rate during an average 2.3 years of follow-up was 2.3% in those who were revascularized, significantly better than the 5.3% rate with medical management.

Thus, it appears that using CTA to identify patients with high-risk CAD results in a therapeutic benefit when such patients undergo revascularization, according to Dr. Min. In contrast, in patients with CTA findings indicative of non–high-risk CAD, mortality rates weren’t significantly different between those who had revascularization and those who had medical management only.

CONFIRM has also showed that CTA reduces the need for invasive coronary angiography. Patients with a normal CTA had a 3-year rate of invasive coronary angiography of 2.5%, and a 0.3% revascularization rate. These rates rose in graded fashion to a 44% invasive angiography rate and a 28% revascularization rate in patients with obstructive single-vessel disease on CTA; a 53% invasive coronary angiography rate and 44% revascularization for those identified as having obstructive two-vessel disease; and a 69% coronary angiography rate and 67% revascularization among patients found on CTA to have obstructive three-vessel or left anterior descending disease.

Dr. Min said that at present there is no evidence-based role for CTA in the evaluation of patients without chest pain or other symptoms suggestive of CAD. And there are better prognostic tests for those with known CAD, he added.

"I must say, looking at it from the outside, it’s really breathtaking how fast the data have grown over the last few years for CT angiography," Dr. Udelson commented. "You in the CT world have, in just a few short years, developed enormous databases it took those of us in nuclear imaging much longer to develop, and you can look at things nuclear can’t, like nonobstructive plaque, where the outcome is different than in people with normal coronary arteries."

Dr. Min has received research grants and is on the speakers bureau for GE Healthcare.

DENVER – A cascade of data generated recently by the CONFIRM registry is turning heads and winning converts to coronary CT angiography as a reasonable first-line test to diagnose or exclude coronary artery disease in many symptomatic patients with no history of the disease.

"The CONFIRM information about the need to rethink people’s pretest likelihood of CAD is enormously important. It shows that if we think a patient’s likelihood is intermediate, it’s actually low. So CT angiography might be the least expensive way to exclude CAD," Dr. James E. Udelson observed during a panel discussion at the annual meeting of the American Society of Nuclear Cardiology.

In addition to being less expensive than SPECT (single-photon emission CT) myocardial perfusion imaging for this purpose, CTA also confers less radiation exposure, which is a particularly important consideration given that that the majority of patients undergoing evaluation for symptoms suggestive of CAD turn out not to have it, added Dr. Udelson, chief of cardiology and director of the nuclear cardiology laboratory at Tufts Medical Center, Boston.

Dr. Udelson is not a CT angiographer and is not involved with CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry). Neither is fellow panelist Dr. John J. Mahmarian. But he too finds CONFIRM compelling.

"I’m really intrigued by the CONFIRM data on nonobstructive plaque. These individuals with nonobstructive atherosclerotic plaque have a good short-term risk but may not have a good long-term risk. With the armamentarium we have today, it’s important to know that so we can treat people more aggressively and impact the disease process," said Dr. Mahmarian, ASNC president-elect and director of nuclear cardiology and CT services at the Methodist DeBakey Heart and Vascular Institute, Houston.

Their comments came in reaction to a wide-ranging update on the registry by CONFIRM investigator Dr. James K. Min of Cedars-Sinai Medical Center in Los Angeles.

Dr. Min explained that CONFIRM is a prospective, multinational registry including more than 32,000 consecutive patients who have undergone CTA at 18 participating sites. The registry was created to answer three questions of fundamental importance regarding the noninvasive imaging procedure: Does it have the ability to diagnose or exclude CAD as well as does invasive coronary angiography? Does it reduce the need for percutaneous angiography? And does it improve health outcomes for patients with acute chest pain who present to emergency departments and other settings?

The answer on all three counts is ‘yes,’ although some of the data are preliminary, Dr. Min said. The registry is being expanded, with follow-up to be extended to a median of 5 years, along with the possible addition of another 12,000-15,000 patients in order to strengthen the findings.

The power of CTA as a risk stratification tool was highlighted in a recent CONFIRM publication (J. Am. Coll. Cardiol. 2011;58:849-60). Dr. Min and his coworkers reported on nearly 24,000 consecutive patients without known pretest CAD who were prospectively followed for a mean of 2.3 years after undergoing CTA for assessment of suspected CAD. These were mainly middle-aged patients with a high prevalence of cardiovascular risk factors. In all, 71% had an intermediate or high pretest likelihood of obstructive CAD.

In this study population, a normal CTA study (found in 43% of patients) was associated with a highly favorable prognosis – namely, an all-cause mortality rate of just 0.28% per year. Moreover, a normal CTA result carried a 4-year "warranty."

Another key finding was that nonobstructive CAD (that is, a 1%-49% stenosis) was associated with a 1.6-fold increased risk of mortality in a multivariate risk-adjusted analysis. Nonobstructive CAD was detected in 34% of subjects.

Mortality risk climbed stepwise with the number of coronary vessels showing obstructive CAD on CTA: a doubling of risk in patients with single-vessel obstructive disease relative to the risk in those with a normal study; a 2.92-fold increased risk in those with two-vessel obstructive CAD; and a 3.7-fold increased risk in patients with triple-vessel or left anterior descending obstructive disease.

The mortality risk associated with obstructive CAD varied by age and sex. Patients younger than age 65 had a significantly greater mortality risk for two-vessel disease than did those aged 65 years or older. The younger patients with two-vessel obstructive disease had a fourfold greater death rate than did young patients with a normal CTA study, whereas older patients with double-vessel disease had a 2.46-fold increased risk. Similarly, triple-vessel obstructive disease in patients younger than age 65 was associated with a 6.2-fold increased risk of death, compared with those who had a normal CTA, a risk twice that conferred by three-vessel obstructive disease in older patients.

The relative hazards for single- and double-vessel obstructive CAD were not significantly different for men vs. women. However, women with three-vessel disease had a 4.2-fold increased mortality risk, significantly greater than the 3.3-fold risk associated with triple-vessel disease in men.

In another CONFIRM analysis, this one involving roughly 8,100 patients with an average pretest likelihood of obstructive CAD of 50% by the widely used Diamond Forrester clinical risk score, investigators found that the actual prevalence of obstructive CAD on CTA was only 18%. The take-home lesson here is that cardiologists severely overestimate the likelihood of significant disease when they rely on clinical risk scores that were developed in an earlier era, Dr. Min emphasized.

Another CONFIRM analysis involved 15,223 patients, 7.2% of whom underwent coronary revascularization following CTA. Among the subgroup with high-risk CAD as defined by the Duke severity categorization criteria – for example, three vessels having moderate stenoses or two with severe stenoses – the mortality rate during an average 2.3 years of follow-up was 2.3% in those who were revascularized, significantly better than the 5.3% rate with medical management.

Thus, it appears that using CTA to identify patients with high-risk CAD results in a therapeutic benefit when such patients undergo revascularization, according to Dr. Min. In contrast, in patients with CTA findings indicative of non–high-risk CAD, mortality rates weren’t significantly different between those who had revascularization and those who had medical management only.

CONFIRM has also showed that CTA reduces the need for invasive coronary angiography. Patients with a normal CTA had a 3-year rate of invasive coronary angiography of 2.5%, and a 0.3% revascularization rate. These rates rose in graded fashion to a 44% invasive angiography rate and a 28% revascularization rate in patients with obstructive single-vessel disease on CTA; a 53% invasive coronary angiography rate and 44% revascularization for those identified as having obstructive two-vessel disease; and a 69% coronary angiography rate and 67% revascularization among patients found on CTA to have obstructive three-vessel or left anterior descending disease.

Dr. Min said that at present there is no evidence-based role for CTA in the evaluation of patients without chest pain or other symptoms suggestive of CAD. And there are better prognostic tests for those with known CAD, he added.

"I must say, looking at it from the outside, it’s really breathtaking how fast the data have grown over the last few years for CT angiography," Dr. Udelson commented. "You in the CT world have, in just a few short years, developed enormous databases it took those of us in nuclear imaging much longer to develop, and you can look at things nuclear can’t, like nonobstructive plaque, where the outcome is different than in people with normal coronary arteries."

Dr. Min has received research grants and is on the speakers bureau for GE Healthcare.

DENVER – A cascade of data generated recently by the CONFIRM registry is turning heads and winning converts to coronary CT angiography as a reasonable first-line test to diagnose or exclude coronary artery disease in many symptomatic patients with no history of the disease.

"The CONFIRM information about the need to rethink people’s pretest likelihood of CAD is enormously important. It shows that if we think a patient’s likelihood is intermediate, it’s actually low. So CT angiography might be the least expensive way to exclude CAD," Dr. James E. Udelson observed during a panel discussion at the annual meeting of the American Society of Nuclear Cardiology.

In addition to being less expensive than SPECT (single-photon emission CT) myocardial perfusion imaging for this purpose, CTA also confers less radiation exposure, which is a particularly important consideration given that that the majority of patients undergoing evaluation for symptoms suggestive of CAD turn out not to have it, added Dr. Udelson, chief of cardiology and director of the nuclear cardiology laboratory at Tufts Medical Center, Boston.

Dr. Udelson is not a CT angiographer and is not involved with CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry). Neither is fellow panelist Dr. John J. Mahmarian. But he too finds CONFIRM compelling.

"I’m really intrigued by the CONFIRM data on nonobstructive plaque. These individuals with nonobstructive atherosclerotic plaque have a good short-term risk but may not have a good long-term risk. With the armamentarium we have today, it’s important to know that so we can treat people more aggressively and impact the disease process," said Dr. Mahmarian, ASNC president-elect and director of nuclear cardiology and CT services at the Methodist DeBakey Heart and Vascular Institute, Houston.

Their comments came in reaction to a wide-ranging update on the registry by CONFIRM investigator Dr. James K. Min of Cedars-Sinai Medical Center in Los Angeles.

Dr. Min explained that CONFIRM is a prospective, multinational registry including more than 32,000 consecutive patients who have undergone CTA at 18 participating sites. The registry was created to answer three questions of fundamental importance regarding the noninvasive imaging procedure: Does it have the ability to diagnose or exclude CAD as well as does invasive coronary angiography? Does it reduce the need for percutaneous angiography? And does it improve health outcomes for patients with acute chest pain who present to emergency departments and other settings?

The answer on all three counts is ‘yes,’ although some of the data are preliminary, Dr. Min said. The registry is being expanded, with follow-up to be extended to a median of 5 years, along with the possible addition of another 12,000-15,000 patients in order to strengthen the findings.

The power of CTA as a risk stratification tool was highlighted in a recent CONFIRM publication (J. Am. Coll. Cardiol. 2011;58:849-60). Dr. Min and his coworkers reported on nearly 24,000 consecutive patients without known pretest CAD who were prospectively followed for a mean of 2.3 years after undergoing CTA for assessment of suspected CAD. These were mainly middle-aged patients with a high prevalence of cardiovascular risk factors. In all, 71% had an intermediate or high pretest likelihood of obstructive CAD.

In this study population, a normal CTA study (found in 43% of patients) was associated with a highly favorable prognosis – namely, an all-cause mortality rate of just 0.28% per year. Moreover, a normal CTA result carried a 4-year "warranty."

Another key finding was that nonobstructive CAD (that is, a 1%-49% stenosis) was associated with a 1.6-fold increased risk of mortality in a multivariate risk-adjusted analysis. Nonobstructive CAD was detected in 34% of subjects.

Mortality risk climbed stepwise with the number of coronary vessels showing obstructive CAD on CTA: a doubling of risk in patients with single-vessel obstructive disease relative to the risk in those with a normal study; a 2.92-fold increased risk in those with two-vessel obstructive CAD; and a 3.7-fold increased risk in patients with triple-vessel or left anterior descending obstructive disease.

The mortality risk associated with obstructive CAD varied by age and sex. Patients younger than age 65 had a significantly greater mortality risk for two-vessel disease than did those aged 65 years or older. The younger patients with two-vessel obstructive disease had a fourfold greater death rate than did young patients with a normal CTA study, whereas older patients with double-vessel disease had a 2.46-fold increased risk. Similarly, triple-vessel obstructive disease in patients younger than age 65 was associated with a 6.2-fold increased risk of death, compared with those who had a normal CTA, a risk twice that conferred by three-vessel obstructive disease in older patients.

The relative hazards for single- and double-vessel obstructive CAD were not significantly different for men vs. women. However, women with three-vessel disease had a 4.2-fold increased mortality risk, significantly greater than the 3.3-fold risk associated with triple-vessel disease in men.

In another CONFIRM analysis, this one involving roughly 8,100 patients with an average pretest likelihood of obstructive CAD of 50% by the widely used Diamond Forrester clinical risk score, investigators found that the actual prevalence of obstructive CAD on CTA was only 18%. The take-home lesson here is that cardiologists severely overestimate the likelihood of significant disease when they rely on clinical risk scores that were developed in an earlier era, Dr. Min emphasized.

Another CONFIRM analysis involved 15,223 patients, 7.2% of whom underwent coronary revascularization following CTA. Among the subgroup with high-risk CAD as defined by the Duke severity categorization criteria – for example, three vessels having moderate stenoses or two with severe stenoses – the mortality rate during an average 2.3 years of follow-up was 2.3% in those who were revascularized, significantly better than the 5.3% rate with medical management.

Thus, it appears that using CTA to identify patients with high-risk CAD results in a therapeutic benefit when such patients undergo revascularization, according to Dr. Min. In contrast, in patients with CTA findings indicative of non–high-risk CAD, mortality rates weren’t significantly different between those who had revascularization and those who had medical management only.

CONFIRM has also showed that CTA reduces the need for invasive coronary angiography. Patients with a normal CTA had a 3-year rate of invasive coronary angiography of 2.5%, and a 0.3% revascularization rate. These rates rose in graded fashion to a 44% invasive angiography rate and a 28% revascularization rate in patients with obstructive single-vessel disease on CTA; a 53% invasive coronary angiography rate and 44% revascularization for those identified as having obstructive two-vessel disease; and a 69% coronary angiography rate and 67% revascularization among patients found on CTA to have obstructive three-vessel or left anterior descending disease.

Dr. Min said that at present there is no evidence-based role for CTA in the evaluation of patients without chest pain or other symptoms suggestive of CAD. And there are better prognostic tests for those with known CAD, he added.

"I must say, looking at it from the outside, it’s really breathtaking how fast the data have grown over the last few years for CT angiography," Dr. Udelson commented. "You in the CT world have, in just a few short years, developed enormous databases it took those of us in nuclear imaging much longer to develop, and you can look at things nuclear can’t, like nonobstructive plaque, where the outcome is different than in people with normal coronary arteries."

Dr. Min has received research grants and is on the speakers bureau for GE Healthcare.