Acquired Cardiovascular Disease

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.