Annual Meeting Of the Society Of Thoracic Surgeons

LOS ANGELES – A modified frailty index strongly predicts morbidity and mortality after esophagectomy, based on a study of more than 2,000 patients in a national database.

Both the rate of serious complications and the rate of death rose steadily and significantly with the index, which is derived from 11 common clinical variables.

Compared with their counterparts having the lowest index, patients having the highest index were 31 times more likely to die in the first postoperative month even after confounders were taken into account, according to data reported at the annual meeting of the Society of Thoracic Surgeons (STS).

"The modified frailty index appears to be an important predictor of morbidity and mortality. It can be used to guide surgeons in making more accurate predictions of complications. It also provides an objective guide for patients in decision making," commented lead investigator Dr. Arielle Hodari, a thoracic surgery resident at the Henry Ford Hospital in Detroit.

In the study, the investigators calculated a preoperative modified frailty index for 2,095 patients who underwent esophagectomy between 2005 and 2010. The index contains 11 variables chosen by mapping those used in the Canadian Study of Health and Aging Frailty Index (CMAJ 2005;173:489-95) onto those available in the National Surgical Quality Improvement Program (NSQIP) database.

The 11 variables in the index were (1) nonindependent functional status, (2) diabetes, (3) chronic obstructive pulmonary disease or pneumonia, (4) congestive heart failure, (5) myocardial infarction, (6) percutaneous coronary intervention, cardiac surgery, or angina, (7) hypertension, (8) peripheral vascular disease, (9) impaired sensorium, (10) transient ischemic attack or stroke without residual deficit, and (11) stroke with deficit.

The study patients had indexes ranging from a low of 0 (meaning 0 of 11 variables) to a high of 0.45 (5 of 11 variables). The large majority clustered at the lower end of the spectrum; only about 1% had an index of 0.45.

The main results showed that as the index increased from 0 to 0.45, there was also an increase in the rate of Clavien 4 complications from 18% to 62% (P less than .001), which are life-threatening complications leading to ICU admission, as well as an increase in the rate of 30-day mortality from 2% to 23% (P less than .001).

The findings were similar for respiratory complications and for cardiovascular complications individually, according to Dr. Hodari.

In a multivariate analysis, patients with the highest index had sharply elevated odds of death relative to their counterparts with the lowest index (odds ratio, 31.8; P = .015).

"The NSQIP data does not differentiate between pathology (squamous cell carcinoma vs. adenocarcinoma) or surgical modality," Dr. Hodari commented, discussing the study’s limitations. "We also need validation in a prospective study."

During the discussion following the presentation of the data, Dr. Hodari was asked about the number of patients who had received neoadjuvant/induction therapy before coming to surgery.

"What I find in my own personal practice is that it’s hard sometimes to say no [to surgery] altogether. So if somebody is T3 or N1, I’ll let them get some induction therapy and then get them back to reevaluate them," he said. "I’d be particularly interested in this type of analysis being applied then, because a lot of times [the patients] haven’t really been improved by that process, and maybe it just shows that I’ve procrastinated in making a difficult decision and probably made it even harder by putting it off until after their induction therapy. Do you know anything about the status of induction therapy in these patients, whether the frailness that was measured was in part due to the induction therapy and how that might affect your results?"

"Unfortunately, that is not available in NSQIP, so we don’t know which patients had neoadjuvant treatment," Dr. Hodari replied.

Regarding questions about the use of 30-day mortality as an endpoint, he responded, "I think it’s worthwhile – maybe it’s not in the database – to look at these figures at 90 days, because, of course, the high-risk patients die within 30 days. But there is a big increase in mortality, almost doubling, at 90 days."

An attendee noted that the original frailty index includes unintentional weight loss, but the modified one does not. "Why was that done for this particular patient population, because with esophageal cancer and dysphagia and unintentional weight loss being a big component of the comorbidity these patients have, wouldn’t you think that would be important to include that?"

That choice was made on the basis of data constraints, Dr. Hodari replied. "We chose variables by going through NSQIP and finding something that corresponds with the Canadian system," she explained.

Dr. Mark Krasna, a thoracic surgeon with Meridian Surgical Associates in Neptune, N.J., expressed reservations about using the NSQIP database to assess the outcomes of thoracic surgery.

"How many thoracic surgeons participate in the NSQIP data?" he asked. In the STS database, "I think we have a robust series of esophagectomists who are thoracic surgeons, and we know what those data are. But, for example, data that were presented from NSQIP [at another conference] were primarily from nonthoracic esophageal surgeons [and were associated] with a much higher mortality and morbidity. Personally, I’m not a NSQIP participant, and I don’t know if many people in this room are. Do you know how many of these were thoracic surgeons?"

"I know the majority of NSQIP esophagectomies are done by general surgeons. I don’t know the exact number," Dr. Hodari replied.

Dr. Krasna asked the audience to raise their hands if they participated in NSQIP, and only about half did so. "I would just say perhaps it’s worthwhile to reassess this [index] based on the STS database because I think you may actually find some change" in the results, he commented.

Dr. Hodari disclosed no relevant conflicts of interest.

LOS ANGELES – A modified frailty index strongly predicts morbidity and mortality after esophagectomy, based on a study of more than 2,000 patients in a national database.

Both the rate of serious complications and the rate of death rose steadily and significantly with the index, which is derived from 11 common clinical variables.

Compared with their counterparts having the lowest index, patients having the highest index were 31 times more likely to die in the first postoperative month even after confounders were taken into account, according to data reported at the annual meeting of the Society of Thoracic Surgeons (STS).

"The modified frailty index appears to be an important predictor of morbidity and mortality. It can be used to guide surgeons in making more accurate predictions of complications. It also provides an objective guide for patients in decision making," commented lead investigator Dr. Arielle Hodari, a thoracic surgery resident at the Henry Ford Hospital in Detroit.

In the study, the investigators calculated a preoperative modified frailty index for 2,095 patients who underwent esophagectomy between 2005 and 2010. The index contains 11 variables chosen by mapping those used in the Canadian Study of Health and Aging Frailty Index (CMAJ 2005;173:489-95) onto those available in the National Surgical Quality Improvement Program (NSQIP) database.

The 11 variables in the index were (1) nonindependent functional status, (2) diabetes, (3) chronic obstructive pulmonary disease or pneumonia, (4) congestive heart failure, (5) myocardial infarction, (6) percutaneous coronary intervention, cardiac surgery, or angina, (7) hypertension, (8) peripheral vascular disease, (9) impaired sensorium, (10) transient ischemic attack or stroke without residual deficit, and (11) stroke with deficit.

The study patients had indexes ranging from a low of 0 (meaning 0 of 11 variables) to a high of 0.45 (5 of 11 variables). The large majority clustered at the lower end of the spectrum; only about 1% had an index of 0.45.

The main results showed that as the index increased from 0 to 0.45, there was also an increase in the rate of Clavien 4 complications from 18% to 62% (P less than .001), which are life-threatening complications leading to ICU admission, as well as an increase in the rate of 30-day mortality from 2% to 23% (P less than .001).

The findings were similar for respiratory complications and for cardiovascular complications individually, according to Dr. Hodari.

In a multivariate analysis, patients with the highest index had sharply elevated odds of death relative to their counterparts with the lowest index (odds ratio, 31.8; P = .015).

"The NSQIP data does not differentiate between pathology (squamous cell carcinoma vs. adenocarcinoma) or surgical modality," Dr. Hodari commented, discussing the study’s limitations. "We also need validation in a prospective study."

During the discussion following the presentation of the data, Dr. Hodari was asked about the number of patients who had received neoadjuvant/induction therapy before coming to surgery.

"What I find in my own personal practice is that it’s hard sometimes to say no [to surgery] altogether. So if somebody is T3 or N1, I’ll let them get some induction therapy and then get them back to reevaluate them," he said. "I’d be particularly interested in this type of analysis being applied then, because a lot of times [the patients] haven’t really been improved by that process, and maybe it just shows that I’ve procrastinated in making a difficult decision and probably made it even harder by putting it off until after their induction therapy. Do you know anything about the status of induction therapy in these patients, whether the frailness that was measured was in part due to the induction therapy and how that might affect your results?"

"Unfortunately, that is not available in NSQIP, so we don’t know which patients had neoadjuvant treatment," Dr. Hodari replied.

Regarding questions about the use of 30-day mortality as an endpoint, he responded, "I think it’s worthwhile – maybe it’s not in the database – to look at these figures at 90 days, because, of course, the high-risk patients die within 30 days. But there is a big increase in mortality, almost doubling, at 90 days."

An attendee noted that the original frailty index includes unintentional weight loss, but the modified one does not. "Why was that done for this particular patient population, because with esophageal cancer and dysphagia and unintentional weight loss being a big component of the comorbidity these patients have, wouldn’t you think that would be important to include that?"

That choice was made on the basis of data constraints, Dr. Hodari replied. "We chose variables by going through NSQIP and finding something that corresponds with the Canadian system," she explained.

Dr. Mark Krasna, a thoracic surgeon with Meridian Surgical Associates in Neptune, N.J., expressed reservations about using the NSQIP database to assess the outcomes of thoracic surgery.

"How many thoracic surgeons participate in the NSQIP data?" he asked. In the STS database, "I think we have a robust series of esophagectomists who are thoracic surgeons, and we know what those data are. But, for example, data that were presented from NSQIP [at another conference] were primarily from nonthoracic esophageal surgeons [and were associated] with a much higher mortality and morbidity. Personally, I’m not a NSQIP participant, and I don’t know if many people in this room are. Do you know how many of these were thoracic surgeons?"

"I know the majority of NSQIP esophagectomies are done by general surgeons. I don’t know the exact number," Dr. Hodari replied.

Dr. Krasna asked the audience to raise their hands if they participated in NSQIP, and only about half did so. "I would just say perhaps it’s worthwhile to reassess this [index] based on the STS database because I think you may actually find some change" in the results, he commented.

Dr. Hodari disclosed no relevant conflicts of interest.

LOS ANGELES – A modified frailty index strongly predicts morbidity and mortality after esophagectomy, based on a study of more than 2,000 patients in a national database.

Both the rate of serious complications and the rate of death rose steadily and significantly with the index, which is derived from 11 common clinical variables.

Compared with their counterparts having the lowest index, patients having the highest index were 31 times more likely to die in the first postoperative month even after confounders were taken into account, according to data reported at the annual meeting of the Society of Thoracic Surgeons (STS).

"The modified frailty index appears to be an important predictor of morbidity and mortality. It can be used to guide surgeons in making more accurate predictions of complications. It also provides an objective guide for patients in decision making," commented lead investigator Dr. Arielle Hodari, a thoracic surgery resident at the Henry Ford Hospital in Detroit.

In the study, the investigators calculated a preoperative modified frailty index for 2,095 patients who underwent esophagectomy between 2005 and 2010. The index contains 11 variables chosen by mapping those used in the Canadian Study of Health and Aging Frailty Index (CMAJ 2005;173:489-95) onto those available in the National Surgical Quality Improvement Program (NSQIP) database.

The 11 variables in the index were (1) nonindependent functional status, (2) diabetes, (3) chronic obstructive pulmonary disease or pneumonia, (4) congestive heart failure, (5) myocardial infarction, (6) percutaneous coronary intervention, cardiac surgery, or angina, (7) hypertension, (8) peripheral vascular disease, (9) impaired sensorium, (10) transient ischemic attack or stroke without residual deficit, and (11) stroke with deficit.

The study patients had indexes ranging from a low of 0 (meaning 0 of 11 variables) to a high of 0.45 (5 of 11 variables). The large majority clustered at the lower end of the spectrum; only about 1% had an index of 0.45.

The main results showed that as the index increased from 0 to 0.45, there was also an increase in the rate of Clavien 4 complications from 18% to 62% (P less than .001), which are life-threatening complications leading to ICU admission, as well as an increase in the rate of 30-day mortality from 2% to 23% (P less than .001).

The findings were similar for respiratory complications and for cardiovascular complications individually, according to Dr. Hodari.

In a multivariate analysis, patients with the highest index had sharply elevated odds of death relative to their counterparts with the lowest index (odds ratio, 31.8; P = .015).

"The NSQIP data does not differentiate between pathology (squamous cell carcinoma vs. adenocarcinoma) or surgical modality," Dr. Hodari commented, discussing the study’s limitations. "We also need validation in a prospective study."

During the discussion following the presentation of the data, Dr. Hodari was asked about the number of patients who had received neoadjuvant/induction therapy before coming to surgery.

"What I find in my own personal practice is that it’s hard sometimes to say no [to surgery] altogether. So if somebody is T3 or N1, I’ll let them get some induction therapy and then get them back to reevaluate them," he said. "I’d be particularly interested in this type of analysis being applied then, because a lot of times [the patients] haven’t really been improved by that process, and maybe it just shows that I’ve procrastinated in making a difficult decision and probably made it even harder by putting it off until after their induction therapy. Do you know anything about the status of induction therapy in these patients, whether the frailness that was measured was in part due to the induction therapy and how that might affect your results?"

"Unfortunately, that is not available in NSQIP, so we don’t know which patients had neoadjuvant treatment," Dr. Hodari replied.

Regarding questions about the use of 30-day mortality as an endpoint, he responded, "I think it’s worthwhile – maybe it’s not in the database – to look at these figures at 90 days, because, of course, the high-risk patients die within 30 days. But there is a big increase in mortality, almost doubling, at 90 days."

An attendee noted that the original frailty index includes unintentional weight loss, but the modified one does not. "Why was that done for this particular patient population, because with esophageal cancer and dysphagia and unintentional weight loss being a big component of the comorbidity these patients have, wouldn’t you think that would be important to include that?"

That choice was made on the basis of data constraints, Dr. Hodari replied. "We chose variables by going through NSQIP and finding something that corresponds with the Canadian system," she explained.

Dr. Mark Krasna, a thoracic surgeon with Meridian Surgical Associates in Neptune, N.J., expressed reservations about using the NSQIP database to assess the outcomes of thoracic surgery.

"How many thoracic surgeons participate in the NSQIP data?" he asked. In the STS database, "I think we have a robust series of esophagectomists who are thoracic surgeons, and we know what those data are. But, for example, data that were presented from NSQIP [at another conference] were primarily from nonthoracic esophageal surgeons [and were associated] with a much higher mortality and morbidity. Personally, I’m not a NSQIP participant, and I don’t know if many people in this room are. Do you know how many of these were thoracic surgeons?"

"I know the majority of NSQIP esophagectomies are done by general surgeons. I don’t know the exact number," Dr. Hodari replied.

Dr. Krasna asked the audience to raise their hands if they participated in NSQIP, and only about half did so. "I would just say perhaps it’s worthwhile to reassess this [index] based on the STS database because I think you may actually find some change" in the results, he commented.

Dr. Hodari disclosed no relevant conflicts of interest.

LOS ANGELES – Aortic valve interventions rose sharply in the United Kingdom during a recent 5-year period, largely due to a spike in procedures among elderly patients, researchers reported at the annual meeting of the Society of Thoracic Surgeons.

In the study, the combined U.K. Cardiac Surgical and Transcatheter Aortic Valve Implantation (TAVI) Registries – known as SATIRE for short – the team analyzed data from 37,020 patients nationwide who underwent aortic valve interventions (excluding balloon valvuloplasty) between 2006 and 2010.

Results showed that the annual number of these procedures increased by 32% over the course of the study, with about half of the increase due to procedures among patients aged 80 years and older, reported lead investigator Dr. Neil E. Moat, a cardiac surgeon and codirector of the Transcatheter Valve Programme at the Royal Brompton Hospital in London.

Overall, the annual number of aortic valve interventions increased during the study period, from 6,217 in 2006 to 8,201 in 2010. This was driven largely by a near doubling in interventions among patients aged 80 years or older, from 1,055 to 2,035.

"In 2010, 25% of all aortic valve interventions in the U.K. were performed in patients aged 80 or over," Dr. Moat noted.

By type of intervention, there was an increase in the annual number of TAVIs (from none to 749) and conventional surgeries (from 6,217 to 7,252), although the latter stabilized toward the end of the period.

"This is the first time in the whole history – 35 years of collecting U.K. cardiac surgical data – that these numbers have plateaued," he commented.

As of 2010, TAVIs accounted for 9% of all aortic valve interventions studied.

Not surprisingly, patients undergoing TAVI surgery were older than their counterparts undergoing conventional surgery, had a higher risk profile, and had poorer postoperative survival, but their lengths of hospital stay were statistically indistinguishable.

Importantly, two scores used in Europe to predict mortality after such interventions showed differential performance.

"The logistic EuroSCORE does not predict operative outcomes of surgery or TAVI" and should not be used, Dr. Moat advised. "The EuroSCORE II is probably quite good for conventional surgery but again is rather poor for predicting mortality outcomes from TAVI. And I suppose on this side of the pond, you will be pleased to hear that the STS [U.S. Society of Thoracic Surgeons] score is far better than either of these European scores in our population."

In the discussion after the presentation of the study, Dr. Paul A. Kurlansky, a cardiothoracic surgeon from Miami, remarked, "Maybe our risk score is better on this side of the pond, but we do not have the merging of databases that you guys have over there [in the U.K.], or the completion of them. One opportunity that I was wondering if you had taken or are planning to take advantage of is the ability to do propensity score matching or use other statistical tools in order to really match patients so that you can compare outcomes."

"That’s a very interesting question and something that we have debated long and hard," Dr. Moat replied, citing reservations given by the study’s statisticians. "They are very firm in their belief that whilst you can apply those statistical techniques, they are actually not valid because you have so much confounding by indication that [you are unable] to propensity-match populations. So it’s a deliberate decision not to pursue that."

Main analyses in the study used prospectively collected registry data for 35,392 patients undergoing conventional surgery – either aortic valve replacement (AVR) alone or combined with coronary artery bypass grafting (CABG) – and 1,628 TAVIs.

"Because [the registries] are national and publicly funded, they are free from any commercial bias. These are mandatory registries and therefore free of any selection bias," Dr. Moat pointed out. Furthermore, there is good standardization of definitions and long-term follow-up of mortality.

"All cardiac surgical procedures and all TAVIs in the U.K. are entered into national registries hosted by the National Institute for Cardiovascular Outcomes Research. The data set and databases of all of these registries are designed to be compatible and comparable," he added.

Overall, compared with patients undergoing surgery, patients undergoing TAVI were on average older and had a higher risk profile in terms of cardiovascular measures and comorbidities, although there was substantial overlap.

The median postoperative length of stay was 8 days after conventional surgery and 7 days after TAVI. "Despite the TAVI patients being older and at increased risk, there was no difference in postoperative length of stay. If anything, it was marginally lower in the TAVI group," Dr. Moat commented. The distribution of length of stay was also much the same. "You see a substantial numbers of these elderly, frail, and high-risk patients [in the TAVI group] being discharged before day 6," he added.

Actuarial analyses in the study population overall showed poorer survival after TAVI than after conventional surgery (whether AVR alone or combined with CABG), both in the first year and longer term. However, the gaps between curves were smaller among patients aged 80 years or older.

Among the patients undergoing TAVI, longer-term survival after aortic valve intervention did not differ according to the number of diseased vessels treated.

"An interesting observation worthy of further study is that we are well aware that patients having combined AVR and CABG have worse earlier and late survival than patients having isolated AVR. But it would seem that the presence of concomitant coronary artery disease – despite much of it being left untreated – did not affect early or late survival following TAVI," Dr. Moat commented.

The EuroSCORE was a poor predictor of mortality after both conventional surgery and TAVI, but the EuroSCORE II performed fairly well after conventional surgery, whether isolated AVR (observed:expected ratio, 0.87; area under the curve, 0.78) or AVR plus CABG (observed:expected ratio, 1.0; area under the curve, 0.73).

Dr. Moat disclosed that he is on the speakers bureau for, and receives honoraria from, Abbott Laboratories, and sits on the consultant/advisory board of Medtronic.

LOS ANGELES – Aortic valve interventions rose sharply in the United Kingdom during a recent 5-year period, largely due to a spike in procedures among elderly patients, researchers reported at the annual meeting of the Society of Thoracic Surgeons.

In the study, the combined U.K. Cardiac Surgical and Transcatheter Aortic Valve Implantation (TAVI) Registries – known as SATIRE for short – the team analyzed data from 37,020 patients nationwide who underwent aortic valve interventions (excluding balloon valvuloplasty) between 2006 and 2010.

Results showed that the annual number of these procedures increased by 32% over the course of the study, with about half of the increase due to procedures among patients aged 80 years and older, reported lead investigator Dr. Neil E. Moat, a cardiac surgeon and codirector of the Transcatheter Valve Programme at the Royal Brompton Hospital in London.

Overall, the annual number of aortic valve interventions increased during the study period, from 6,217 in 2006 to 8,201 in 2010. This was driven largely by a near doubling in interventions among patients aged 80 years or older, from 1,055 to 2,035.

"In 2010, 25% of all aortic valve interventions in the U.K. were performed in patients aged 80 or over," Dr. Moat noted.

By type of intervention, there was an increase in the annual number of TAVIs (from none to 749) and conventional surgeries (from 6,217 to 7,252), although the latter stabilized toward the end of the period.

"This is the first time in the whole history – 35 years of collecting U.K. cardiac surgical data – that these numbers have plateaued," he commented.

As of 2010, TAVIs accounted for 9% of all aortic valve interventions studied.

Not surprisingly, patients undergoing TAVI surgery were older than their counterparts undergoing conventional surgery, had a higher risk profile, and had poorer postoperative survival, but their lengths of hospital stay were statistically indistinguishable.

Importantly, two scores used in Europe to predict mortality after such interventions showed differential performance.

"The logistic EuroSCORE does not predict operative outcomes of surgery or TAVI" and should not be used, Dr. Moat advised. "The EuroSCORE II is probably quite good for conventional surgery but again is rather poor for predicting mortality outcomes from TAVI. And I suppose on this side of the pond, you will be pleased to hear that the STS [U.S. Society of Thoracic Surgeons] score is far better than either of these European scores in our population."

In the discussion after the presentation of the study, Dr. Paul A. Kurlansky, a cardiothoracic surgeon from Miami, remarked, "Maybe our risk score is better on this side of the pond, but we do not have the merging of databases that you guys have over there [in the U.K.], or the completion of them. One opportunity that I was wondering if you had taken or are planning to take advantage of is the ability to do propensity score matching or use other statistical tools in order to really match patients so that you can compare outcomes."

"That’s a very interesting question and something that we have debated long and hard," Dr. Moat replied, citing reservations given by the study’s statisticians. "They are very firm in their belief that whilst you can apply those statistical techniques, they are actually not valid because you have so much confounding by indication that [you are unable] to propensity-match populations. So it’s a deliberate decision not to pursue that."

Main analyses in the study used prospectively collected registry data for 35,392 patients undergoing conventional surgery – either aortic valve replacement (AVR) alone or combined with coronary artery bypass grafting (CABG) – and 1,628 TAVIs.

"Because [the registries] are national and publicly funded, they are free from any commercial bias. These are mandatory registries and therefore free of any selection bias," Dr. Moat pointed out. Furthermore, there is good standardization of definitions and long-term follow-up of mortality.

"All cardiac surgical procedures and all TAVIs in the U.K. are entered into national registries hosted by the National Institute for Cardiovascular Outcomes Research. The data set and databases of all of these registries are designed to be compatible and comparable," he added.

Overall, compared with patients undergoing surgery, patients undergoing TAVI were on average older and had a higher risk profile in terms of cardiovascular measures and comorbidities, although there was substantial overlap.

The median postoperative length of stay was 8 days after conventional surgery and 7 days after TAVI. "Despite the TAVI patients being older and at increased risk, there was no difference in postoperative length of stay. If anything, it was marginally lower in the TAVI group," Dr. Moat commented. The distribution of length of stay was also much the same. "You see a substantial numbers of these elderly, frail, and high-risk patients [in the TAVI group] being discharged before day 6," he added.

Actuarial analyses in the study population overall showed poorer survival after TAVI than after conventional surgery (whether AVR alone or combined with CABG), both in the first year and longer term. However, the gaps between curves were smaller among patients aged 80 years or older.

Among the patients undergoing TAVI, longer-term survival after aortic valve intervention did not differ according to the number of diseased vessels treated.

"An interesting observation worthy of further study is that we are well aware that patients having combined AVR and CABG have worse earlier and late survival than patients having isolated AVR. But it would seem that the presence of concomitant coronary artery disease – despite much of it being left untreated – did not affect early or late survival following TAVI," Dr. Moat commented.

The EuroSCORE was a poor predictor of mortality after both conventional surgery and TAVI, but the EuroSCORE II performed fairly well after conventional surgery, whether isolated AVR (observed:expected ratio, 0.87; area under the curve, 0.78) or AVR plus CABG (observed:expected ratio, 1.0; area under the curve, 0.73).

Dr. Moat disclosed that he is on the speakers bureau for, and receives honoraria from, Abbott Laboratories, and sits on the consultant/advisory board of Medtronic.

LOS ANGELES – Aortic valve interventions rose sharply in the United Kingdom during a recent 5-year period, largely due to a spike in procedures among elderly patients, researchers reported at the annual meeting of the Society of Thoracic Surgeons.

In the study, the combined U.K. Cardiac Surgical and Transcatheter Aortic Valve Implantation (TAVI) Registries – known as SATIRE for short – the team analyzed data from 37,020 patients nationwide who underwent aortic valve interventions (excluding balloon valvuloplasty) between 2006 and 2010.

Results showed that the annual number of these procedures increased by 32% over the course of the study, with about half of the increase due to procedures among patients aged 80 years and older, reported lead investigator Dr. Neil E. Moat, a cardiac surgeon and codirector of the Transcatheter Valve Programme at the Royal Brompton Hospital in London.

Overall, the annual number of aortic valve interventions increased during the study period, from 6,217 in 2006 to 8,201 in 2010. This was driven largely by a near doubling in interventions among patients aged 80 years or older, from 1,055 to 2,035.

"In 2010, 25% of all aortic valve interventions in the U.K. were performed in patients aged 80 or over," Dr. Moat noted.

By type of intervention, there was an increase in the annual number of TAVIs (from none to 749) and conventional surgeries (from 6,217 to 7,252), although the latter stabilized toward the end of the period.

"This is the first time in the whole history – 35 years of collecting U.K. cardiac surgical data – that these numbers have plateaued," he commented.

As of 2010, TAVIs accounted for 9% of all aortic valve interventions studied.

Not surprisingly, patients undergoing TAVI surgery were older than their counterparts undergoing conventional surgery, had a higher risk profile, and had poorer postoperative survival, but their lengths of hospital stay were statistically indistinguishable.

Importantly, two scores used in Europe to predict mortality after such interventions showed differential performance.

"The logistic EuroSCORE does not predict operative outcomes of surgery or TAVI" and should not be used, Dr. Moat advised. "The EuroSCORE II is probably quite good for conventional surgery but again is rather poor for predicting mortality outcomes from TAVI. And I suppose on this side of the pond, you will be pleased to hear that the STS [U.S. Society of Thoracic Surgeons] score is far better than either of these European scores in our population."

In the discussion after the presentation of the study, Dr. Paul A. Kurlansky, a cardiothoracic surgeon from Miami, remarked, "Maybe our risk score is better on this side of the pond, but we do not have the merging of databases that you guys have over there [in the U.K.], or the completion of them. One opportunity that I was wondering if you had taken or are planning to take advantage of is the ability to do propensity score matching or use other statistical tools in order to really match patients so that you can compare outcomes."

"That’s a very interesting question and something that we have debated long and hard," Dr. Moat replied, citing reservations given by the study’s statisticians. "They are very firm in their belief that whilst you can apply those statistical techniques, they are actually not valid because you have so much confounding by indication that [you are unable] to propensity-match populations. So it’s a deliberate decision not to pursue that."

Main analyses in the study used prospectively collected registry data for 35,392 patients undergoing conventional surgery – either aortic valve replacement (AVR) alone or combined with coronary artery bypass grafting (CABG) – and 1,628 TAVIs.

"Because [the registries] are national and publicly funded, they are free from any commercial bias. These are mandatory registries and therefore free of any selection bias," Dr. Moat pointed out. Furthermore, there is good standardization of definitions and long-term follow-up of mortality.

"All cardiac surgical procedures and all TAVIs in the U.K. are entered into national registries hosted by the National Institute for Cardiovascular Outcomes Research. The data set and databases of all of these registries are designed to be compatible and comparable," he added.

Overall, compared with patients undergoing surgery, patients undergoing TAVI were on average older and had a higher risk profile in terms of cardiovascular measures and comorbidities, although there was substantial overlap.

The median postoperative length of stay was 8 days after conventional surgery and 7 days after TAVI. "Despite the TAVI patients being older and at increased risk, there was no difference in postoperative length of stay. If anything, it was marginally lower in the TAVI group," Dr. Moat commented. The distribution of length of stay was also much the same. "You see a substantial numbers of these elderly, frail, and high-risk patients [in the TAVI group] being discharged before day 6," he added.

Actuarial analyses in the study population overall showed poorer survival after TAVI than after conventional surgery (whether AVR alone or combined with CABG), both in the first year and longer term. However, the gaps between curves were smaller among patients aged 80 years or older.

Among the patients undergoing TAVI, longer-term survival after aortic valve intervention did not differ according to the number of diseased vessels treated.

"An interesting observation worthy of further study is that we are well aware that patients having combined AVR and CABG have worse earlier and late survival than patients having isolated AVR. But it would seem that the presence of concomitant coronary artery disease – despite much of it being left untreated – did not affect early or late survival following TAVI," Dr. Moat commented.

The EuroSCORE was a poor predictor of mortality after both conventional surgery and TAVI, but the EuroSCORE II performed fairly well after conventional surgery, whether isolated AVR (observed:expected ratio, 0.87; area under the curve, 0.78) or AVR plus CABG (observed:expected ratio, 1.0; area under the curve, 0.73).

Dr. Moat disclosed that he is on the speakers bureau for, and receives honoraria from, Abbott Laboratories, and sits on the consultant/advisory board of Medtronic.

LOS ANGELES – Some patients with a total artificial heart can safely go home with the use of a small portable driver while awaiting heart transplantation, according to data from the first U.S. patient cohort in whom this was attempted.

Investigators assessed outcomes in 13 total artificial heart recipients who were stable enough clinically to be transitioned from the usual driver to SynCardia Systems’ investigational portable driver, the Freedom Driver System. The driver weighs 14 pounds and allows several hours of untethered activity.

Eight of the patients were able to go home for an average of 5.5 months, lead investigator Dr. Vigneshwar Kasirajan reported at the annual meeting of the Society of Thoracic Surgeons.

They had a low rate of major bleeding and no major infections. There were roughly five device malfunctions per patient-year, but in all cases, patients were able to switch to a backup driver uneventfully.

 Twelve of the 13 total patients ultimately underwent transplantation, for a transplantation rate of 92%.

"The Freedom driver is effective in supporting circulation with a total artificial heart. Discharge home is safe and feasible," commented Dr. Kasirajan, who is director of heart transplantation, heart-lung transplantation, and mechanical circulatory support at Virginia Commonwealth University in Richmond.

"Further data on the completion of this study will help to demonstrate the efficacy and safety of the driver. In addition, important data on exercise capacity and quality of life will be valuable in finally moving the artificial heart technology to more widespread use," he said.

Session comoderator Dr. Todd M. Dewey, a cardiothoracic surgeon with Medical City Specialists in Dallas, noted, "The majority of patients on axial-flow left ventricular assist devices are discharged home. What percentage of total artificial heart patients do you think will ultimately leave the hospital?"

"We are close to 80% of our patients going home right now, at least in high-volume institutions," Dr. Kasirajan replied. Two patients have been at home for more than 2 years without readmissions related to the device, he added.

A pivotal study previously showed that the total artificial heart can be used as a bridge to transplantation in patients with irreversible biventricular failure (N. Engl. J. Med. 2004;351:859-67).

"Unfortunately, ... the widespread use of this technology is limited because of the inability to discharge these patients home, and that relates to the fact that the circulatory support system console has to be powered by compressed air either from the hospital or via a cylinder," Dr. Kasirajan explained.

However, once patients are stable, the driver settings need little adjustment, which spurred development of the portable driver. "The driver has two batteries that allow up to 3 hours of untethered activity. These can be charged in place using an alternating current output or car charger," he said.

The ongoing study of the driver will enroll up to 60 patients from 30 international sites. Patients are required to be wait-listed for heart transplantation and receive a total artificial heart, and to be clinically stable on the circulatory support system, with a cardiac index of at least 2.2 L/min/m². They are then switched to the portable driver with the intent of discharge from the hospital.

Dr. Kasirajan reported results for the first 13 patients enrolled from four U.S. sites. Overall, 5 of the patients remained in the hospital (because of medical reasons, discharge logistics, or personal preference), whereas 8 went home with the driver. The median duration out of the hospital in the latter group was 162 days (range, 39-437 days).

The 13 patients had maintenance of cardiac function, with a cardiac index averaging 3.3 L/min/m², and their laboratory values remained stable between baseline and 90 days. "Particularly, there was no evidence of hemolysis that was worse than at the beginning," he noted. "Increasing albumin levels reflect the increasing nutritional status in these patients."

The in-hospital group had a very similar rate of adverse events relative to an earlier comparison cohort of stable patients with a total artificial heart followed as part of postmarket surveillance, according to Dr. Kasirajan.

Within the study population, the out-of-hospital and in-hospital groups had similar rates of major bleeding (1.1 vs. 1.4 events per patient-year). The former had a lower rate of major infection (0 vs. 2.8 events per patient-year) but higher rates of device malfunction (4.6 vs. 0 events per patient-year) and hemolysis (2.3 vs. 0 events per patient-year).

The five device malfunctions in the out-of-hospital group were due to a Valsalva maneuver, a faulty sensor, hypertension, a kink in the driveline while a patient was getting into a car, and dropping of the driver while showering.

"All these patients remained stable and had no changes in cardiac output," Dr. Kasirajan pointed out. "They were able to switch to the backup driver as educated, and returned to the hospital."

Valsalva maneuvers can cause a sudden transient rise in intrathoracic pressure that a device sensor interprets as outside the set parameters, he explained; the software has since been modified to allow for these changes.

"The importance of hypertension management is critical," he commented. "The pump tolerates blood pressures at high levels for brief periods of time; however, prolonged hypertension leads to a decrease in left heart cardiac output and pulmonary edema."

The cases of hemolysis were due to transient rises in plasma free hemoglobin as a result of hemothorax and hydralazine-induced hemolytic anemia.

Only a single patient, in the out-of-hospital group, died before transplantation. This patient was stable on the driver for 437 days, but experienced a fall with a spinal cord hematoma, and developed fatal complications.

Dr. Kasirajan disclosed that he is a consultant to SynCardia Systems.

LOS ANGELES – Some patients with a total artificial heart can safely go home with the use of a small portable driver while awaiting heart transplantation, according to data from the first U.S. patient cohort in whom this was attempted.

Investigators assessed outcomes in 13 total artificial heart recipients who were stable enough clinically to be transitioned from the usual driver to SynCardia Systems’ investigational portable driver, the Freedom Driver System. The driver weighs 14 pounds and allows several hours of untethered activity.

Eight of the patients were able to go home for an average of 5.5 months, lead investigator Dr. Vigneshwar Kasirajan reported at the annual meeting of the Society of Thoracic Surgeons.

They had a low rate of major bleeding and no major infections. There were roughly five device malfunctions per patient-year, but in all cases, patients were able to switch to a backup driver uneventfully.

 Twelve of the 13 total patients ultimately underwent transplantation, for a transplantation rate of 92%.

"The Freedom driver is effective in supporting circulation with a total artificial heart. Discharge home is safe and feasible," commented Dr. Kasirajan, who is director of heart transplantation, heart-lung transplantation, and mechanical circulatory support at Virginia Commonwealth University in Richmond.

"Further data on the completion of this study will help to demonstrate the efficacy and safety of the driver. In addition, important data on exercise capacity and quality of life will be valuable in finally moving the artificial heart technology to more widespread use," he said.

Session comoderator Dr. Todd M. Dewey, a cardiothoracic surgeon with Medical City Specialists in Dallas, noted, "The majority of patients on axial-flow left ventricular assist devices are discharged home. What percentage of total artificial heart patients do you think will ultimately leave the hospital?"

"We are close to 80% of our patients going home right now, at least in high-volume institutions," Dr. Kasirajan replied. Two patients have been at home for more than 2 years without readmissions related to the device, he added.

A pivotal study previously showed that the total artificial heart can be used as a bridge to transplantation in patients with irreversible biventricular failure (N. Engl. J. Med. 2004;351:859-67).

"Unfortunately, ... the widespread use of this technology is limited because of the inability to discharge these patients home, and that relates to the fact that the circulatory support system console has to be powered by compressed air either from the hospital or via a cylinder," Dr. Kasirajan explained.

However, once patients are stable, the driver settings need little adjustment, which spurred development of the portable driver. "The driver has two batteries that allow up to 3 hours of untethered activity. These can be charged in place using an alternating current output or car charger," he said.

The ongoing study of the driver will enroll up to 60 patients from 30 international sites. Patients are required to be wait-listed for heart transplantation and receive a total artificial heart, and to be clinically stable on the circulatory support system, with a cardiac index of at least 2.2 L/min/m². They are then switched to the portable driver with the intent of discharge from the hospital.

Dr. Kasirajan reported results for the first 13 patients enrolled from four U.S. sites. Overall, 5 of the patients remained in the hospital (because of medical reasons, discharge logistics, or personal preference), whereas 8 went home with the driver. The median duration out of the hospital in the latter group was 162 days (range, 39-437 days).

The 13 patients had maintenance of cardiac function, with a cardiac index averaging 3.3 L/min/m², and their laboratory values remained stable between baseline and 90 days. "Particularly, there was no evidence of hemolysis that was worse than at the beginning," he noted. "Increasing albumin levels reflect the increasing nutritional status in these patients."

The in-hospital group had a very similar rate of adverse events relative to an earlier comparison cohort of stable patients with a total artificial heart followed as part of postmarket surveillance, according to Dr. Kasirajan.

Within the study population, the out-of-hospital and in-hospital groups had similar rates of major bleeding (1.1 vs. 1.4 events per patient-year). The former had a lower rate of major infection (0 vs. 2.8 events per patient-year) but higher rates of device malfunction (4.6 vs. 0 events per patient-year) and hemolysis (2.3 vs. 0 events per patient-year).

The five device malfunctions in the out-of-hospital group were due to a Valsalva maneuver, a faulty sensor, hypertension, a kink in the driveline while a patient was getting into a car, and dropping of the driver while showering.

"All these patients remained stable and had no changes in cardiac output," Dr. Kasirajan pointed out. "They were able to switch to the backup driver as educated, and returned to the hospital."

Valsalva maneuvers can cause a sudden transient rise in intrathoracic pressure that a device sensor interprets as outside the set parameters, he explained; the software has since been modified to allow for these changes.

"The importance of hypertension management is critical," he commented. "The pump tolerates blood pressures at high levels for brief periods of time; however, prolonged hypertension leads to a decrease in left heart cardiac output and pulmonary edema."

The cases of hemolysis were due to transient rises in plasma free hemoglobin as a result of hemothorax and hydralazine-induced hemolytic anemia.

Only a single patient, in the out-of-hospital group, died before transplantation. This patient was stable on the driver for 437 days, but experienced a fall with a spinal cord hematoma, and developed fatal complications.

Dr. Kasirajan disclosed that he is a consultant to SynCardia Systems.

LOS ANGELES – Some patients with a total artificial heart can safely go home with the use of a small portable driver while awaiting heart transplantation, according to data from the first U.S. patient cohort in whom this was attempted.

Investigators assessed outcomes in 13 total artificial heart recipients who were stable enough clinically to be transitioned from the usual driver to SynCardia Systems’ investigational portable driver, the Freedom Driver System. The driver weighs 14 pounds and allows several hours of untethered activity.

Eight of the patients were able to go home for an average of 5.5 months, lead investigator Dr. Vigneshwar Kasirajan reported at the annual meeting of the Society of Thoracic Surgeons.

They had a low rate of major bleeding and no major infections. There were roughly five device malfunctions per patient-year, but in all cases, patients were able to switch to a backup driver uneventfully.

 Twelve of the 13 total patients ultimately underwent transplantation, for a transplantation rate of 92%.

"The Freedom driver is effective in supporting circulation with a total artificial heart. Discharge home is safe and feasible," commented Dr. Kasirajan, who is director of heart transplantation, heart-lung transplantation, and mechanical circulatory support at Virginia Commonwealth University in Richmond.

"Further data on the completion of this study will help to demonstrate the efficacy and safety of the driver. In addition, important data on exercise capacity and quality of life will be valuable in finally moving the artificial heart technology to more widespread use," he said.

Session comoderator Dr. Todd M. Dewey, a cardiothoracic surgeon with Medical City Specialists in Dallas, noted, "The majority of patients on axial-flow left ventricular assist devices are discharged home. What percentage of total artificial heart patients do you think will ultimately leave the hospital?"

"We are close to 80% of our patients going home right now, at least in high-volume institutions," Dr. Kasirajan replied. Two patients have been at home for more than 2 years without readmissions related to the device, he added.

A pivotal study previously showed that the total artificial heart can be used as a bridge to transplantation in patients with irreversible biventricular failure (N. Engl. J. Med. 2004;351:859-67).

"Unfortunately, ... the widespread use of this technology is limited because of the inability to discharge these patients home, and that relates to the fact that the circulatory support system console has to be powered by compressed air either from the hospital or via a cylinder," Dr. Kasirajan explained.

However, once patients are stable, the driver settings need little adjustment, which spurred development of the portable driver. "The driver has two batteries that allow up to 3 hours of untethered activity. These can be charged in place using an alternating current output or car charger," he said.

The ongoing study of the driver will enroll up to 60 patients from 30 international sites. Patients are required to be wait-listed for heart transplantation and receive a total artificial heart, and to be clinically stable on the circulatory support system, with a cardiac index of at least 2.2 L/min/m². They are then switched to the portable driver with the intent of discharge from the hospital.

Dr. Kasirajan reported results for the first 13 patients enrolled from four U.S. sites. Overall, 5 of the patients remained in the hospital (because of medical reasons, discharge logistics, or personal preference), whereas 8 went home with the driver. The median duration out of the hospital in the latter group was 162 days (range, 39-437 days).

The 13 patients had maintenance of cardiac function, with a cardiac index averaging 3.3 L/min/m², and their laboratory values remained stable between baseline and 90 days. "Particularly, there was no evidence of hemolysis that was worse than at the beginning," he noted. "Increasing albumin levels reflect the increasing nutritional status in these patients."

The in-hospital group had a very similar rate of adverse events relative to an earlier comparison cohort of stable patients with a total artificial heart followed as part of postmarket surveillance, according to Dr. Kasirajan.

Within the study population, the out-of-hospital and in-hospital groups had similar rates of major bleeding (1.1 vs. 1.4 events per patient-year). The former had a lower rate of major infection (0 vs. 2.8 events per patient-year) but higher rates of device malfunction (4.6 vs. 0 events per patient-year) and hemolysis (2.3 vs. 0 events per patient-year).

The five device malfunctions in the out-of-hospital group were due to a Valsalva maneuver, a faulty sensor, hypertension, a kink in the driveline while a patient was getting into a car, and dropping of the driver while showering.

"All these patients remained stable and had no changes in cardiac output," Dr. Kasirajan pointed out. "They were able to switch to the backup driver as educated, and returned to the hospital."

Valsalva maneuvers can cause a sudden transient rise in intrathoracic pressure that a device sensor interprets as outside the set parameters, he explained; the software has since been modified to allow for these changes.

"The importance of hypertension management is critical," he commented. "The pump tolerates blood pressures at high levels for brief periods of time; however, prolonged hypertension leads to a decrease in left heart cardiac output and pulmonary edema."

The cases of hemolysis were due to transient rises in plasma free hemoglobin as a result of hemothorax and hydralazine-induced hemolytic anemia.

Only a single patient, in the out-of-hospital group, died before transplantation. This patient was stable on the driver for 437 days, but experienced a fall with a spinal cord hematoma, and developed fatal complications.

Dr. Kasirajan disclosed that he is a consultant to SynCardia Systems.

LOS ANGELES – A new investigational transcatheter aortic valve implantation system, the Engager system, yields generally good early results when used to treat severe aortic valve stenosis, according to an interim analysis of a pivotal European regulatory trial.

Among the first 61 patients who underwent implantation of the valve, which is performed transapically, the 30-day rate of all-cause mortality according to intention to treat (the trial’s primary end point) was about 10%, lead investigator Dr. David M. Holzhey reported at the annual meeting of the Society of Thoracic Surgeons.

Valve implantation reduced the mean aortic gradient, which translated to an improvement in New York Heart Association functional class in nearly all cases.

Most complications were uncommon, but one-third of patients needed new pacemakers after their procedure.

"The system works as expected. It reduces the gradient and it improved the clinical outcome in these patients with severe symptomatic aortic stenosis who were at high risk for surgical aortic valve replacement," commented Dr. Holzhey, a cardiac surgeon with Heart Center Leipzig (Germany).

"We had no positioning-related complications as we have seen with other valves before. The low incidence of paravalvular leak seems to prove the concept and the design of the Engager valve," he added.

Part of the reason for the reduced leakage with the Engager is its size, Dr. Holzhey said. "The current systems are 24-French or 26-French. The 29-French [with Engager] means it is 1 mm more. In the transapical setting, this has no impact at all because the tissue spreads easily, and it’s easy to close it again. So this is one of the advantages actually of the transapical access as compared to transfemoral, for instance, that you can have larger delivery systems without any more problems," Dr. Holzhey replied.

The unusually high pacemaker rate may be attributable to other design features. "The valve ... was meant to overcome some of the drawbacks of former devices and was designed for easy, intuitive implantation, also for sealing of the leaks. This is why the valve is maybe protruding a little more into the outflow track than other systems. This might be a cause for the higher pacemaker rate," Dr. Holzhey proposed. "So the major concern with the development and design of the valve was sealing off paravalvular leakages, which seems to work, maybe at the cost of a higher pacemaker rate."

In addition, the study centers were liberal in implanting pacemakers as soon as the first postoperative day because the patients were predominantly elderly and early postoperative mobilization was the first priority, he continued.

Session attendee Dr. Craig Miller of Stanford (Calif.) University also remarked on this complication, saying, "I am alarmed by that 32% pacemaker rate at 6 months. ... We have got to figure out what is causing that and fix that. ... What do you know ... about the patients that may have predisposed them to have this extraordinarily high need for pacemakers or perceived need?"

About half of the patients had true third-degree AV block, according to Dr. Holzhey. The other half had mixed indications, such as sinus bradycardia or sick sinus syndrome. "I cannot tell you at present what the exact indications were for each single patient, but this is being investigated."

Session attendee Dr. Lars Svensson of the Cleveland Clinic noted that the original Engager system was associated with vascular injury in some cases. "Any thoughts why they made the cuff so big and so far down into the ventricle?" he asked.

"The intention was to produce a valve that facilitates implantation, makes it easy, and maybe implanter-independent, with those arms that you just sort of pull back" to deploy the valve, Dr. Holzhey replied. "The first concern was that these arms might cause hematoma or even dissection. We haven’t seen that at all." The valve’s size and height again relate to better leak prevention, he said.

A total of 125 patients from Germany, Switzerland, Belgium, and Israel were enrolled in the trial, which is the pivotal trial for device CE marking in Europe. The interim analysis was based on the first 61 patients.

They were 82 years old, on average, and 62% were women. Most had a NYHA functional class of III or IV. One-third had atrial fibrillation or flutter.

The overall rate of device success, according to Valve Academic Research Consortium (VARC) criteria, was 94%, Dr. Holzhey reported.

None of the patients experienced annulus rupture, valve embolization, conversion to open aortic valve replacement, or coronary compromise or needed to undergo a second valve implantation.

In terms of valve performance, all patients had a reduction from baseline in mean aortic gradient at 30 days, which was sustained at 6 months. The proportion of patients having a NYHA class of I or II was just 12% at baseline, but it rose to 78% at 30 days and 82% at 6 months.

Actuarial analyses showed that the 30-day rate of all-cause mortality was 9.9% and the 6-month rate was 16.9%. "This is well in the range of other transapical devices that we have seen before in studies," Dr. Holzhey commented. The respective rates of stroke were 1.8% and 5.5%.

The 30-day rate of new pacemaker receipt was 30.2% and the 6-month rate was 32.4%. Corresponding rates of paravalvular leak were 24% and 13%; all cases were trace or mild.

Dr. Holzhey disclosed no relevant conflicts. Medtronic sponsored the trial and performed data analysis.

cardiologynews@elsevier.com

LOS ANGELES – A new investigational transcatheter aortic valve implantation system, the Engager system, yields generally good early results when used to treat severe aortic valve stenosis, according to an interim analysis of a pivotal European regulatory trial.

Among the first 61 patients who underwent implantation of the valve, which is performed transapically, the 30-day rate of all-cause mortality according to intention to treat (the trial’s primary end point) was about 10%, lead investigator Dr. David M. Holzhey reported at the annual meeting of the Society of Thoracic Surgeons.

Valve implantation reduced the mean aortic gradient, which translated to an improvement in New York Heart Association functional class in nearly all cases.

Most complications were uncommon, but one-third of patients needed new pacemakers after their procedure.

"The system works as expected. It reduces the gradient and it improved the clinical outcome in these patients with severe symptomatic aortic stenosis who were at high risk for surgical aortic valve replacement," commented Dr. Holzhey, a cardiac surgeon with Heart Center Leipzig (Germany).

"We had no positioning-related complications as we have seen with other valves before. The low incidence of paravalvular leak seems to prove the concept and the design of the Engager valve," he added.

Part of the reason for the reduced leakage with the Engager is its size, Dr. Holzhey said. "The current systems are 24-French or 26-French. The 29-French [with Engager] means it is 1 mm more. In the transapical setting, this has no impact at all because the tissue spreads easily, and it’s easy to close it again. So this is one of the advantages actually of the transapical access as compared to transfemoral, for instance, that you can have larger delivery systems without any more problems," Dr. Holzhey replied.

The unusually high pacemaker rate may be attributable to other design features. "The valve ... was meant to overcome some of the drawbacks of former devices and was designed for easy, intuitive implantation, also for sealing of the leaks. This is why the valve is maybe protruding a little more into the outflow track than other systems. This might be a cause for the higher pacemaker rate," Dr. Holzhey proposed. "So the major concern with the development and design of the valve was sealing off paravalvular leakages, which seems to work, maybe at the cost of a higher pacemaker rate."

In addition, the study centers were liberal in implanting pacemakers as soon as the first postoperative day because the patients were predominantly elderly and early postoperative mobilization was the first priority, he continued.

Session attendee Dr. Craig Miller of Stanford (Calif.) University also remarked on this complication, saying, "I am alarmed by that 32% pacemaker rate at 6 months. ... We have got to figure out what is causing that and fix that. ... What do you know ... about the patients that may have predisposed them to have this extraordinarily high need for pacemakers or perceived need?"

About half of the patients had true third-degree AV block, according to Dr. Holzhey. The other half had mixed indications, such as sinus bradycardia or sick sinus syndrome. "I cannot tell you at present what the exact indications were for each single patient, but this is being investigated."

Session attendee Dr. Lars Svensson of the Cleveland Clinic noted that the original Engager system was associated with vascular injury in some cases. "Any thoughts why they made the cuff so big and so far down into the ventricle?" he asked.

"The intention was to produce a valve that facilitates implantation, makes it easy, and maybe implanter-independent, with those arms that you just sort of pull back" to deploy the valve, Dr. Holzhey replied. "The first concern was that these arms might cause hematoma or even dissection. We haven’t seen that at all." The valve’s size and height again relate to better leak prevention, he said.

A total of 125 patients from Germany, Switzerland, Belgium, and Israel were enrolled in the trial, which is the pivotal trial for device CE marking in Europe. The interim analysis was based on the first 61 patients.

They were 82 years old, on average, and 62% were women. Most had a NYHA functional class of III or IV. One-third had atrial fibrillation or flutter.

The overall rate of device success, according to Valve Academic Research Consortium (VARC) criteria, was 94%, Dr. Holzhey reported.

None of the patients experienced annulus rupture, valve embolization, conversion to open aortic valve replacement, or coronary compromise or needed to undergo a second valve implantation.

In terms of valve performance, all patients had a reduction from baseline in mean aortic gradient at 30 days, which was sustained at 6 months. The proportion of patients having a NYHA class of I or II was just 12% at baseline, but it rose to 78% at 30 days and 82% at 6 months.

Actuarial analyses showed that the 30-day rate of all-cause mortality was 9.9% and the 6-month rate was 16.9%. "This is well in the range of other transapical devices that we have seen before in studies," Dr. Holzhey commented. The respective rates of stroke were 1.8% and 5.5%.

The 30-day rate of new pacemaker receipt was 30.2% and the 6-month rate was 32.4%. Corresponding rates of paravalvular leak were 24% and 13%; all cases were trace or mild.

Dr. Holzhey disclosed no relevant conflicts. Medtronic sponsored the trial and performed data analysis.

cardiologynews@elsevier.com

LOS ANGELES – A new investigational transcatheter aortic valve implantation system, the Engager system, yields generally good early results when used to treat severe aortic valve stenosis, according to an interim analysis of a pivotal European regulatory trial.

Among the first 61 patients who underwent implantation of the valve, which is performed transapically, the 30-day rate of all-cause mortality according to intention to treat (the trial’s primary end point) was about 10%, lead investigator Dr. David M. Holzhey reported at the annual meeting of the Society of Thoracic Surgeons.

Valve implantation reduced the mean aortic gradient, which translated to an improvement in New York Heart Association functional class in nearly all cases.

Most complications were uncommon, but one-third of patients needed new pacemakers after their procedure.

"The system works as expected. It reduces the gradient and it improved the clinical outcome in these patients with severe symptomatic aortic stenosis who were at high risk for surgical aortic valve replacement," commented Dr. Holzhey, a cardiac surgeon with Heart Center Leipzig (Germany).

"We had no positioning-related complications as we have seen with other valves before. The low incidence of paravalvular leak seems to prove the concept and the design of the Engager valve," he added.

Part of the reason for the reduced leakage with the Engager is its size, Dr. Holzhey said. "The current systems are 24-French or 26-French. The 29-French [with Engager] means it is 1 mm more. In the transapical setting, this has no impact at all because the tissue spreads easily, and it’s easy to close it again. So this is one of the advantages actually of the transapical access as compared to transfemoral, for instance, that you can have larger delivery systems without any more problems," Dr. Holzhey replied.

The unusually high pacemaker rate may be attributable to other design features. "The valve ... was meant to overcome some of the drawbacks of former devices and was designed for easy, intuitive implantation, also for sealing of the leaks. This is why the valve is maybe protruding a little more into the outflow track than other systems. This might be a cause for the higher pacemaker rate," Dr. Holzhey proposed. "So the major concern with the development and design of the valve was sealing off paravalvular leakages, which seems to work, maybe at the cost of a higher pacemaker rate."

In addition, the study centers were liberal in implanting pacemakers as soon as the first postoperative day because the patients were predominantly elderly and early postoperative mobilization was the first priority, he continued.

Session attendee Dr. Craig Miller of Stanford (Calif.) University also remarked on this complication, saying, "I am alarmed by that 32% pacemaker rate at 6 months. ... We have got to figure out what is causing that and fix that. ... What do you know ... about the patients that may have predisposed them to have this extraordinarily high need for pacemakers or perceived need?"

About half of the patients had true third-degree AV block, according to Dr. Holzhey. The other half had mixed indications, such as sinus bradycardia or sick sinus syndrome. "I cannot tell you at present what the exact indications were for each single patient, but this is being investigated."

Session attendee Dr. Lars Svensson of the Cleveland Clinic noted that the original Engager system was associated with vascular injury in some cases. "Any thoughts why they made the cuff so big and so far down into the ventricle?" he asked.

"The intention was to produce a valve that facilitates implantation, makes it easy, and maybe implanter-independent, with those arms that you just sort of pull back" to deploy the valve, Dr. Holzhey replied. "The first concern was that these arms might cause hematoma or even dissection. We haven’t seen that at all." The valve’s size and height again relate to better leak prevention, he said.

A total of 125 patients from Germany, Switzerland, Belgium, and Israel were enrolled in the trial, which is the pivotal trial for device CE marking in Europe. The interim analysis was based on the first 61 patients.

They were 82 years old, on average, and 62% were women. Most had a NYHA functional class of III or IV. One-third had atrial fibrillation or flutter.

The overall rate of device success, according to Valve Academic Research Consortium (VARC) criteria, was 94%, Dr. Holzhey reported.

None of the patients experienced annulus rupture, valve embolization, conversion to open aortic valve replacement, or coronary compromise or needed to undergo a second valve implantation.

In terms of valve performance, all patients had a reduction from baseline in mean aortic gradient at 30 days, which was sustained at 6 months. The proportion of patients having a NYHA class of I or II was just 12% at baseline, but it rose to 78% at 30 days and 82% at 6 months.

Actuarial analyses showed that the 30-day rate of all-cause mortality was 9.9% and the 6-month rate was 16.9%. "This is well in the range of other transapical devices that we have seen before in studies," Dr. Holzhey commented. The respective rates of stroke were 1.8% and 5.5%.

The 30-day rate of new pacemaker receipt was 30.2% and the 6-month rate was 32.4%. Corresponding rates of paravalvular leak were 24% and 13%; all cases were trace or mild.

Dr. Holzhey disclosed no relevant conflicts. Medtronic sponsored the trial and performed data analysis.

cardiologynews@elsevier.com

LOS ANGELES – Clinical staging of T2N0 esophageal cancer remains unreliable, despite advances in staging techniques, a study has shown.

The addition of endoscopic ultrasound and PET/CT has improved the ability to clinically stage esophageal cancer overall, but clinical staging of T2N0 disease has generally been less reliable than staging of more advanced disease. The subset of patients with T2N0 disease, which accounts for only a small portion of esophageal resections, has been a difficult group to study because single-center investigations involve a limited number of patients, Dr. Traves D. Crabtree said at the annual meeting of the Society of Thoracic Surgeons (STS), in the prestigious Richard E. Clark Paper for General Thoracic Surgery.

Courtesy Martin Allred

Dr. Crabtree of Washington University, St. Louis, and his colleagues examined the adequacy of clinical staging of T2N0 disease using the STS General Thoracic Surgery Database.

The researchers identified 810 patients clinically staged as T2N0 from 2002 to 2011 and excluded 58 because of inadequate pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded for each patient and multivariable analysis was used to identify factors associated with upstaging at the time of surgery.

Among 752 patients with clinically staged T2N0, the investigators found that 482 went directly to surgery. Of these, 27.4% (132) were confirmed as pathologic T2N0. A total of 25.9% (125) were downstaged (T1N0), while 46.7% (225) were upstaged (T3-4N0 or TanyN1-3). Tumor depth (pT3-4) accounted for 18.2% of upstaging while nodal upstaging occurred in approximately 82%. When logistic regression was used, male sex was associated with upstaging (odds ratio = 1.85, P = .024). By analyzing the part of the database that included tumor grade (between the years 2009 and 2011), the investigators found that a higher histologic grade was significantly associated with upstaging (P = .004).

"Over one-third of surgeons have opted to treat T2N0 disease with induction therapy, despite the fact that one-quarter of these patients will be pT1N0," he said.

"This is the first large-scale multi-institutional study of clinical T2N0 patients using the STS General Thoracic Surgery Database. These data highlight the inaccuracy associated with clinical staging of T2N0 esophageal cancer and may influence the surgeon’s decision-making process in choosing a treatment regimen for these patients," Dr. Crabtree added in an interview.

"Given the current limitations of clinical staging of T2N0 patients, the incidence of occult nodal disease, and the similar perioperative outcomes among patients treated with and without induction therapy, these patients may more likely be treated with induction therapy in the future. Additional studies are needed to compare long-term outcomes between patients receiving induction therapy, vs. those clinical T2N0 patients going directly to surgery, before a definitive recommendation can be made," he concluded.

Dr. Crabtree reported that he had no relevant financial disclosures.

m.lesney@elsevier.com

LOS ANGELES – Clinical staging of T2N0 esophageal cancer remains unreliable, despite advances in staging techniques, a study has shown.

The addition of endoscopic ultrasound and PET/CT has improved the ability to clinically stage esophageal cancer overall, but clinical staging of T2N0 disease has generally been less reliable than staging of more advanced disease. The subset of patients with T2N0 disease, which accounts for only a small portion of esophageal resections, has been a difficult group to study because single-center investigations involve a limited number of patients, Dr. Traves D. Crabtree said at the annual meeting of the Society of Thoracic Surgeons (STS), in the prestigious Richard E. Clark Paper for General Thoracic Surgery.

Courtesy Martin Allred

Dr. Crabtree of Washington University, St. Louis, and his colleagues examined the adequacy of clinical staging of T2N0 disease using the STS General Thoracic Surgery Database.

The researchers identified 810 patients clinically staged as T2N0 from 2002 to 2011 and excluded 58 because of inadequate pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded for each patient and multivariable analysis was used to identify factors associated with upstaging at the time of surgery.

Among 752 patients with clinically staged T2N0, the investigators found that 482 went directly to surgery. Of these, 27.4% (132) were confirmed as pathologic T2N0. A total of 25.9% (125) were downstaged (T1N0), while 46.7% (225) were upstaged (T3-4N0 or TanyN1-3). Tumor depth (pT3-4) accounted for 18.2% of upstaging while nodal upstaging occurred in approximately 82%. When logistic regression was used, male sex was associated with upstaging (odds ratio = 1.85, P = .024). By analyzing the part of the database that included tumor grade (between the years 2009 and 2011), the investigators found that a higher histologic grade was significantly associated with upstaging (P = .004).

"Over one-third of surgeons have opted to treat T2N0 disease with induction therapy, despite the fact that one-quarter of these patients will be pT1N0," he said.

"This is the first large-scale multi-institutional study of clinical T2N0 patients using the STS General Thoracic Surgery Database. These data highlight the inaccuracy associated with clinical staging of T2N0 esophageal cancer and may influence the surgeon’s decision-making process in choosing a treatment regimen for these patients," Dr. Crabtree added in an interview.

"Given the current limitations of clinical staging of T2N0 patients, the incidence of occult nodal disease, and the similar perioperative outcomes among patients treated with and without induction therapy, these patients may more likely be treated with induction therapy in the future. Additional studies are needed to compare long-term outcomes between patients receiving induction therapy, vs. those clinical T2N0 patients going directly to surgery, before a definitive recommendation can be made," he concluded.

Dr. Crabtree reported that he had no relevant financial disclosures.

m.lesney@elsevier.com

LOS ANGELES – Clinical staging of T2N0 esophageal cancer remains unreliable, despite advances in staging techniques, a study has shown.

The addition of endoscopic ultrasound and PET/CT has improved the ability to clinically stage esophageal cancer overall, but clinical staging of T2N0 disease has generally been less reliable than staging of more advanced disease. The subset of patients with T2N0 disease, which accounts for only a small portion of esophageal resections, has been a difficult group to study because single-center investigations involve a limited number of patients, Dr. Traves D. Crabtree said at the annual meeting of the Society of Thoracic Surgeons (STS), in the prestigious Richard E. Clark Paper for General Thoracic Surgery.

Courtesy Martin Allred

Dr. Crabtree of Washington University, St. Louis, and his colleagues examined the adequacy of clinical staging of T2N0 disease using the STS General Thoracic Surgery Database.

The researchers identified 810 patients clinically staged as T2N0 from 2002 to 2011 and excluded 58 because of inadequate pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded for each patient and multivariable analysis was used to identify factors associated with upstaging at the time of surgery.

Among 752 patients with clinically staged T2N0, the investigators found that 482 went directly to surgery. Of these, 27.4% (132) were confirmed as pathologic T2N0. A total of 25.9% (125) were downstaged (T1N0), while 46.7% (225) were upstaged (T3-4N0 or TanyN1-3). Tumor depth (pT3-4) accounted for 18.2% of upstaging while nodal upstaging occurred in approximately 82%. When logistic regression was used, male sex was associated with upstaging (odds ratio = 1.85, P = .024). By analyzing the part of the database that included tumor grade (between the years 2009 and 2011), the investigators found that a higher histologic grade was significantly associated with upstaging (P = .004).

"Over one-third of surgeons have opted to treat T2N0 disease with induction therapy, despite the fact that one-quarter of these patients will be pT1N0," he said.

"This is the first large-scale multi-institutional study of clinical T2N0 patients using the STS General Thoracic Surgery Database. These data highlight the inaccuracy associated with clinical staging of T2N0 esophageal cancer and may influence the surgeon’s decision-making process in choosing a treatment regimen for these patients," Dr. Crabtree added in an interview.

"Given the current limitations of clinical staging of T2N0 patients, the incidence of occult nodal disease, and the similar perioperative outcomes among patients treated with and without induction therapy, these patients may more likely be treated with induction therapy in the future. Additional studies are needed to compare long-term outcomes between patients receiving induction therapy, vs. those clinical T2N0 patients going directly to surgery, before a definitive recommendation can be made," he concluded.

Dr. Crabtree reported that he had no relevant financial disclosures.

m.lesney@elsevier.com

LOS ANGELES – Single-institution reports regarding the benefits of beta-blocker use are conflicting, despite the fact that preoperative beta-blockade for coronary artery bypass grafting has become an accepted hospital quality metric, according to Dr. Damien J. LaPar and his colleagues.

Dr. LaPar of the University of Virginia, Charlottesville reported the results of research undertaken to assess this issue based on a study of patient records from a statewide, multi-institutional Society of Thoracic Surgeons (STS)–certified database for isolated coronary artery bypass grafting (CABG) operations (2001-2011). He and his colleagues found that there was no difference seen in mortality, length of stay, or readmission comparing patients with or without preoperative beta-blocker use.

Courtesy Martin Allred

Their prestigious Richard E. Clark Paper for Adult Cardiac Surgery, presented at the annual meeting of the Society of Thoracic Surgeons, utilized the STS Adult Cardiac Surgery Database to demonstrate that the perceived benefits of using beta-blockers before CABG do not stand up as statistically significant improvements in outcomes.

"Preoperative beta-blocker use is not associated with improved patient outcomes or hospital resource utilization following" CABG, said Dr. LaPar.

Patients were stratified by preoperative beta-blocker use and the influence of preoperative beta-blockers on risk-adjusted outcomes was assessed by hierarchical regression modeling with adjustment for preoperative risk using calculated STS predictive risk indices.

A total of 43,747 patients with a mean age of around 64 years were included in the study; 80.2% of these patients were treated with beta-blockers. The median STS-predicted risk of mortality scores for beta-blocker patients were incrementally lower, compared with non–beta blocker patients (1.2% vs. 1.4%, P less than .001). Non–beta blocker patients more frequently developed pneumonia (3.5% vs. 2.8%, P = .001), while beta-blocker patients had surprisingly greater intraoperative blood usage (16.0% vs. 11.2%, P less than .001).

There was, however, no difference in unadjusted mortality (beta-blocker, 1.9%, vs. non beta-blocker, 2.2%; P = 0.15). After risk adjustment, preoperative beta-blocker use was not associated with mortality (P = .63), morbidity, length of stay (P = .79), or hospital readmission (P = .97).

"These data suggest that the use of preoperative beta-blockers for [CABG] operations should not be used as a measure of surgical quality," Dr. LaPar said.

"In an era of increasing pressure on individual hospital and surgical outcomes, the identification of appropriate measures of surgical quality remains critical," Dr. LaPar added in an interview.

"More importantly, as public reporting of surgeon outcomes becomes more common, the cardiothoracic surgical community must play a central role in providing updated data from which to base health care policy, hospital and surgeon reimbursement strategies, and referral patterns for cardiac surgical patients," he stated.

"The results of our study provide an updated reexamination of an issue of increasing debate and provide current clinical estimates on the adjusted impact of preoperative beta-blocker use on outcomes following isolated CABG operations. Future randomized controlled trials are needed to more clearly define a cause-effect relationship between preoperative beta-blocker therapy and coronary artery bypass grafting outcomes before the routine use of beta-blockade should be adopted as a quality performance measure by the cardiothoracic surgical community," Dr. LaPar concluded.

Dr. LaPar reported having no relevant conflicts of interest with regard to this paper; two of his colleagues reported serving as speakers or receiving funding from a variety of drug and device companies.

m.lesney@elsevier.com

LOS ANGELES – Single-institution reports regarding the benefits of beta-blocker use are conflicting, despite the fact that preoperative beta-blockade for coronary artery bypass grafting has become an accepted hospital quality metric, according to Dr. Damien J. LaPar and his colleagues.

Dr. LaPar of the University of Virginia, Charlottesville reported the results of research undertaken to assess this issue based on a study of patient records from a statewide, multi-institutional Society of Thoracic Surgeons (STS)–certified database for isolated coronary artery bypass grafting (CABG) operations (2001-2011). He and his colleagues found that there was no difference seen in mortality, length of stay, or readmission comparing patients with or without preoperative beta-blocker use.

Courtesy Martin Allred

Their prestigious Richard E. Clark Paper for Adult Cardiac Surgery, presented at the annual meeting of the Society of Thoracic Surgeons, utilized the STS Adult Cardiac Surgery Database to demonstrate that the perceived benefits of using beta-blockers before CABG do not stand up as statistically significant improvements in outcomes.

"Preoperative beta-blocker use is not associated with improved patient outcomes or hospital resource utilization following" CABG, said Dr. LaPar.

Patients were stratified by preoperative beta-blocker use and the influence of preoperative beta-blockers on risk-adjusted outcomes was assessed by hierarchical regression modeling with adjustment for preoperative risk using calculated STS predictive risk indices.

A total of 43,747 patients with a mean age of around 64 years were included in the study; 80.2% of these patients were treated with beta-blockers. The median STS-predicted risk of mortality scores for beta-blocker patients were incrementally lower, compared with non–beta blocker patients (1.2% vs. 1.4%, P less than .001). Non–beta blocker patients more frequently developed pneumonia (3.5% vs. 2.8%, P = .001), while beta-blocker patients had surprisingly greater intraoperative blood usage (16.0% vs. 11.2%, P less than .001).

There was, however, no difference in unadjusted mortality (beta-blocker, 1.9%, vs. non beta-blocker, 2.2%; P = 0.15). After risk adjustment, preoperative beta-blocker use was not associated with mortality (P = .63), morbidity, length of stay (P = .79), or hospital readmission (P = .97).

"These data suggest that the use of preoperative beta-blockers for [CABG] operations should not be used as a measure of surgical quality," Dr. LaPar said.

"In an era of increasing pressure on individual hospital and surgical outcomes, the identification of appropriate measures of surgical quality remains critical," Dr. LaPar added in an interview.

"More importantly, as public reporting of surgeon outcomes becomes more common, the cardiothoracic surgical community must play a central role in providing updated data from which to base health care policy, hospital and surgeon reimbursement strategies, and referral patterns for cardiac surgical patients," he stated.

"The results of our study provide an updated reexamination of an issue of increasing debate and provide current clinical estimates on the adjusted impact of preoperative beta-blocker use on outcomes following isolated CABG operations. Future randomized controlled trials are needed to more clearly define a cause-effect relationship between preoperative beta-blocker therapy and coronary artery bypass grafting outcomes before the routine use of beta-blockade should be adopted as a quality performance measure by the cardiothoracic surgical community," Dr. LaPar concluded.

Dr. LaPar reported having no relevant conflicts of interest with regard to this paper; two of his colleagues reported serving as speakers or receiving funding from a variety of drug and device companies.

m.lesney@elsevier.com

LOS ANGELES – Single-institution reports regarding the benefits of beta-blocker use are conflicting, despite the fact that preoperative beta-blockade for coronary artery bypass grafting has become an accepted hospital quality metric, according to Dr. Damien J. LaPar and his colleagues.

Dr. LaPar of the University of Virginia, Charlottesville reported the results of research undertaken to assess this issue based on a study of patient records from a statewide, multi-institutional Society of Thoracic Surgeons (STS)–certified database for isolated coronary artery bypass grafting (CABG) operations (2001-2011). He and his colleagues found that there was no difference seen in mortality, length of stay, or readmission comparing patients with or without preoperative beta-blocker use.

Courtesy Martin Allred

Their prestigious Richard E. Clark Paper for Adult Cardiac Surgery, presented at the annual meeting of the Society of Thoracic Surgeons, utilized the STS Adult Cardiac Surgery Database to demonstrate that the perceived benefits of using beta-blockers before CABG do not stand up as statistically significant improvements in outcomes.

"Preoperative beta-blocker use is not associated with improved patient outcomes or hospital resource utilization following" CABG, said Dr. LaPar.

Patients were stratified by preoperative beta-blocker use and the influence of preoperative beta-blockers on risk-adjusted outcomes was assessed by hierarchical regression modeling with adjustment for preoperative risk using calculated STS predictive risk indices.

A total of 43,747 patients with a mean age of around 64 years were included in the study; 80.2% of these patients were treated with beta-blockers. The median STS-predicted risk of mortality scores for beta-blocker patients were incrementally lower, compared with non–beta blocker patients (1.2% vs. 1.4%, P less than .001). Non–beta blocker patients more frequently developed pneumonia (3.5% vs. 2.8%, P = .001), while beta-blocker patients had surprisingly greater intraoperative blood usage (16.0% vs. 11.2%, P less than .001).

There was, however, no difference in unadjusted mortality (beta-blocker, 1.9%, vs. non beta-blocker, 2.2%; P = 0.15). After risk adjustment, preoperative beta-blocker use was not associated with mortality (P = .63), morbidity, length of stay (P = .79), or hospital readmission (P = .97).

"These data suggest that the use of preoperative beta-blockers for [CABG] operations should not be used as a measure of surgical quality," Dr. LaPar said.

"In an era of increasing pressure on individual hospital and surgical outcomes, the identification of appropriate measures of surgical quality remains critical," Dr. LaPar added in an interview.

"More importantly, as public reporting of surgeon outcomes becomes more common, the cardiothoracic surgical community must play a central role in providing updated data from which to base health care policy, hospital and surgeon reimbursement strategies, and referral patterns for cardiac surgical patients," he stated.

"The results of our study provide an updated reexamination of an issue of increasing debate and provide current clinical estimates on the adjusted impact of preoperative beta-blocker use on outcomes following isolated CABG operations. Future randomized controlled trials are needed to more clearly define a cause-effect relationship between preoperative beta-blocker therapy and coronary artery bypass grafting outcomes before the routine use of beta-blockade should be adopted as a quality performance measure by the cardiothoracic surgical community," Dr. LaPar concluded.

Dr. LaPar reported having no relevant conflicts of interest with regard to this paper; two of his colleagues reported serving as speakers or receiving funding from a variety of drug and device companies.

m.lesney@elsevier.com

LOS ANGELES – Ebstein’s malformation is a rare congenital cardiac anomaly. Surgery for Ebstein’s involves a range of procedures, and with low institutional volumes, the only available data on treatment are limited to individual reports demonstrating highly variable approaches. Neonates in particular are at risk for poor outcomes, showing significantly higher mortality than infants, children, and adults, according to a database study presented by Dr. Ryan R. Davies at the annual meeting of the Society of Thoracic Surgeons.

Dr. Davies of the Nemours/A.I. duPont Hospital for Children, Wilmington, Del., and his colleagues performed a retrospective study of procedures performed on patients with a primary diagnosis of Ebstein’s malformation (2002-2009) in the STS Congenital Heart Surgery Database.

A total of 595 operations on patients with Ebstein’s were included: 116 on neonates (19%), 122 on infants (21%), 264 on children (44%), and 93 on adults (16%). The authors found that average annual institutional case volumes were low (median, 1 case/year), and procedures varied according to age. Neonates had a high rate of palliative procedures: tricuspid valve (TV) closure (16%) and systemic-to-pulmonary shunts with or without TV closure (37%) and isolated TV closure (8.6%), with Ebstein’s repair or TV valvuloplasty performed in 32%.

Infants usually underwent superior cavopulmonary connections (52%).

Among older patients, procedures were mostly in three categories: TV surgery (children, 55%; adults, 69%), arrhythmia procedures (children, 9%; adults, 17%), and Fontan (children, 16%). In-hospital mortality was higher among neonatal patients (23%) than in infants (4%), children (0.8%), and adults (1.1%).

Among neonates, 36 subsequent procedures were performed during the same hospitalization in 27 patients (23%); including TV closure (11%); shunt (15%); Ebstein’s repair (17%) or TV replacement (15%); and heart transplantation (7.4%). Mortality was similar among neonates who had a second procedure and those who did not (27% vs. 23%, respectively). ECMO (extracorporeal membrane oxygenation) was used in 9% of neonates but in less than 2% of patients in other age groups.

"This study represents a broad overview of the diverse options for surgical treatment of Ebstein’s anomaly. It shows the challenges faced in caring for extremely ill neonatal patients. We have also shown that repair of Ebstein’s anomaly is performed infrequently at most centers, limiting the ability of individual series to define optimal management strategies," Dr. Davies said in an interview.

"Unfortunately, currently available databases do not contain information that may be important in defining such strategies (both surgical and nonsurgical), including anatomic and physiologic variables – whether they are neonates presenting in severe heart failure or older patients presenting for tricuspid valve repair or replacement," he added.

"We feel that in this setting, a prospective multi-institutional study would be of significant value. It should include operative and nonoperative patients, as well as precise diagnostic information and procedural details, to evaluate long-term outcomes including survival, reoperation and other reinterventions, as well as neurodevelopmental outcomes, functional health status, and quality of life," Dr. Davies concluded.

Dr. Davies and his colleagues reported having no relevant disclosures.

m.lesney@elsevier.com

LOS ANGELES – Ebstein’s malformation is a rare congenital cardiac anomaly. Surgery for Ebstein’s involves a range of procedures, and with low institutional volumes, the only available data on treatment are limited to individual reports demonstrating highly variable approaches. Neonates in particular are at risk for poor outcomes, showing significantly higher mortality than infants, children, and adults, according to a database study presented by Dr. Ryan R. Davies at the annual meeting of the Society of Thoracic Surgeons.

Dr. Davies of the Nemours/A.I. duPont Hospital for Children, Wilmington, Del., and his colleagues performed a retrospective study of procedures performed on patients with a primary diagnosis of Ebstein’s malformation (2002-2009) in the STS Congenital Heart Surgery Database.

A total of 595 operations on patients with Ebstein’s were included: 116 on neonates (19%), 122 on infants (21%), 264 on children (44%), and 93 on adults (16%). The authors found that average annual institutional case volumes were low (median, 1 case/year), and procedures varied according to age. Neonates had a high rate of palliative procedures: tricuspid valve (TV) closure (16%) and systemic-to-pulmonary shunts with or without TV closure (37%) and isolated TV closure (8.6%), with Ebstein’s repair or TV valvuloplasty performed in 32%.

Infants usually underwent superior cavopulmonary connections (52%).

Among older patients, procedures were mostly in three categories: TV surgery (children, 55%; adults, 69%), arrhythmia procedures (children, 9%; adults, 17%), and Fontan (children, 16%). In-hospital mortality was higher among neonatal patients (23%) than in infants (4%), children (0.8%), and adults (1.1%).

Among neonates, 36 subsequent procedures were performed during the same hospitalization in 27 patients (23%); including TV closure (11%); shunt (15%); Ebstein’s repair (17%) or TV replacement (15%); and heart transplantation (7.4%). Mortality was similar among neonates who had a second procedure and those who did not (27% vs. 23%, respectively). ECMO (extracorporeal membrane oxygenation) was used in 9% of neonates but in less than 2% of patients in other age groups.

"This study represents a broad overview of the diverse options for surgical treatment of Ebstein’s anomaly. It shows the challenges faced in caring for extremely ill neonatal patients. We have also shown that repair of Ebstein’s anomaly is performed infrequently at most centers, limiting the ability of individual series to define optimal management strategies," Dr. Davies said in an interview.

"Unfortunately, currently available databases do not contain information that may be important in defining such strategies (both surgical and nonsurgical), including anatomic and physiologic variables – whether they are neonates presenting in severe heart failure or older patients presenting for tricuspid valve repair or replacement," he added.

"We feel that in this setting, a prospective multi-institutional study would be of significant value. It should include operative and nonoperative patients, as well as precise diagnostic information and procedural details, to evaluate long-term outcomes including survival, reoperation and other reinterventions, as well as neurodevelopmental outcomes, functional health status, and quality of life," Dr. Davies concluded.

Dr. Davies and his colleagues reported having no relevant disclosures.

m.lesney@elsevier.com

LOS ANGELES – Ebstein’s malformation is a rare congenital cardiac anomaly. Surgery for Ebstein’s involves a range of procedures, and with low institutional volumes, the only available data on treatment are limited to individual reports demonstrating highly variable approaches. Neonates in particular are at risk for poor outcomes, showing significantly higher mortality than infants, children, and adults, according to a database study presented by Dr. Ryan R. Davies at the annual meeting of the Society of Thoracic Surgeons.

Dr. Davies of the Nemours/A.I. duPont Hospital for Children, Wilmington, Del., and his colleagues performed a retrospective study of procedures performed on patients with a primary diagnosis of Ebstein’s malformation (2002-2009) in the STS Congenital Heart Surgery Database.

A total of 595 operations on patients with Ebstein’s were included: 116 on neonates (19%), 122 on infants (21%), 264 on children (44%), and 93 on adults (16%). The authors found that average annual institutional case volumes were low (median, 1 case/year), and procedures varied according to age. Neonates had a high rate of palliative procedures: tricuspid valve (TV) closure (16%) and systemic-to-pulmonary shunts with or without TV closure (37%) and isolated TV closure (8.6%), with Ebstein’s repair or TV valvuloplasty performed in 32%.

Infants usually underwent superior cavopulmonary connections (52%).

Among older patients, procedures were mostly in three categories: TV surgery (children, 55%; adults, 69%), arrhythmia procedures (children, 9%; adults, 17%), and Fontan (children, 16%). In-hospital mortality was higher among neonatal patients (23%) than in infants (4%), children (0.8%), and adults (1.1%).

Among neonates, 36 subsequent procedures were performed during the same hospitalization in 27 patients (23%); including TV closure (11%); shunt (15%); Ebstein’s repair (17%) or TV replacement (15%); and heart transplantation (7.4%). Mortality was similar among neonates who had a second procedure and those who did not (27% vs. 23%, respectively). ECMO (extracorporeal membrane oxygenation) was used in 9% of neonates but in less than 2% of patients in other age groups.

"This study represents a broad overview of the diverse options for surgical treatment of Ebstein’s anomaly. It shows the challenges faced in caring for extremely ill neonatal patients. We have also shown that repair of Ebstein’s anomaly is performed infrequently at most centers, limiting the ability of individual series to define optimal management strategies," Dr. Davies said in an interview.

"Unfortunately, currently available databases do not contain information that may be important in defining such strategies (both surgical and nonsurgical), including anatomic and physiologic variables – whether they are neonates presenting in severe heart failure or older patients presenting for tricuspid valve repair or replacement," he added.

"We feel that in this setting, a prospective multi-institutional study would be of significant value. It should include operative and nonoperative patients, as well as precise diagnostic information and procedural details, to evaluate long-term outcomes including survival, reoperation and other reinterventions, as well as neurodevelopmental outcomes, functional health status, and quality of life," Dr. Davies concluded.

Dr. Davies and his colleagues reported having no relevant disclosures.

m.lesney@elsevier.com

LOS ANGELES – Use of lungs from donors who smoked heavily does not worsen lung transplantation outcomes including risk for lung cancer death, at least in the medium term.

At a median follow-up of 2 years for 5,900 adults who had double-lung transplants, those who received lungs from heavy smokers had an actuarial median overall survival of roughly 5.5 years, and their lung function was essentially the same as that of patients who received lungs from other donors, Dr. Sharven Taghavi reported at the annual meeting of the Society of Thoracic Surgeons.

The study data came from the United Network for Organ Sharing (UNOS) database. A team led by Dr. Taghavi, of Temple University Hospital in Philadelphia, compared data for double-lung transplants from 2005-2011, comparing donors with a history of smoking exceeding 20 pack-years with other donors.

About 13% of the study patients received lungs from donors who had smoked heavily. Compared with other recipients, these recipients were more likely to have a primary diagnosis of chronic obstructive pulmonary disease and less likely to have a diagnosis of idiopathic pulmonary fibrosis. Otherwise, they were similar.

The rate of deaths due to cancer was based on case reports, as UNOS does not capture this outcome. Cancer deaths were 5.8% among recipients of lungs from heavy smokers and 3.6% among other recipients.

"There is a fairly low capture rate for this field, so it’s difficult to draw significant conclusions from it," cautioned Dr. Taghavi.

Patients who received lungs from heavy smokers had a 1-day longer length of stay in the hospital (18 days vs. 17 days), which "may not really be clinically relevant." Rates of acute rejection during hospitalization were comparable (10.7% vs. 8.8%), as was post-transplant airway dehiscence (1.8% vs. 1.8%).

Post-transplant peak forced expiratory volume in 1 second (FEV₁) was the same (80% vs. 79%), as was decline in this measure over time. Median duration of freedom from bronchiolitis obliterans syndrome was 1,583 days vs. 1,827 days.

Risk-adjusted median all-cause survival – the study’s primary endpoint – did not differ significantly between the recipients given lungs from donors who smoked heavily and the other recipients (2,043 vs. 1,928 days).

The rate of cancer deaths did not differ significantly; however, the follow-up time is too short to address this concern in a meaningful way, Dr. Taghavi said.

"Currently, we recommend when evaluating a donor who has a heavy smoking history, that they undergo a thorough examination for lung tumors or evidence of cancer. This includes obtaining a chest x-ray, CT scans, and bronchoscopies. In addition, when the lungs are procured, they should undergo a very thorough visual inspection," he advised.

"Informed consent is very important. You have to discuss the donor’s smoking status with the recipient and explain the risks and the benefits," Dr. Taghavi said. Lung cancer risk, given the donor’s history, is about 1% to 2% annually, and that needs to be considered against the high likelihood of dying within 1 or 2 years without a transplant.

"One thing that is unquestionable is that survival will be better accepting these lungs than it will be sitting on a waiting list," he added. Only about half of the people listed for lung transplant in the United States each year actually undergo the surgery.

Recipients of lungs from heavy smokers do not need any extra follow-up or surveillance, as they are already diligently tested and monitored, according to Dr. Taghavi. The recipient’s immunosuppression does theoretically put one at additional risk for lung cancer.

Current guidelines of the International Society of Heart and Lung Transplantation advise against considering use of lungs from donors who have a smoking history of more than 20 pack-years, Dr. Taghavi noted. But he stopped short of saying that the study should prompt a formal revision of those guidelines.

"I think the findings start the conversation," he commented. "We should consider looking at these potential donors," especially when a recipient’s situation is dire.

Dr. Taghavi disclosed no conflicts of interest.

TOR@elsevier.com

LOS ANGELES – Use of lungs from donors who smoked heavily does not worsen lung transplantation outcomes including risk for lung cancer death, at least in the medium term.

At a median follow-up of 2 years for 5,900 adults who had double-lung transplants, those who received lungs from heavy smokers had an actuarial median overall survival of roughly 5.5 years, and their lung function was essentially the same as that of patients who received lungs from other donors, Dr. Sharven Taghavi reported at the annual meeting of the Society of Thoracic Surgeons.

The study data came from the United Network for Organ Sharing (UNOS) database. A team led by Dr. Taghavi, of Temple University Hospital in Philadelphia, compared data for double-lung transplants from 2005-2011, comparing donors with a history of smoking exceeding 20 pack-years with other donors.

About 13% of the study patients received lungs from donors who had smoked heavily. Compared with other recipients, these recipients were more likely to have a primary diagnosis of chronic obstructive pulmonary disease and less likely to have a diagnosis of idiopathic pulmonary fibrosis. Otherwise, they were similar.

The rate of deaths due to cancer was based on case reports, as UNOS does not capture this outcome. Cancer deaths were 5.8% among recipients of lungs from heavy smokers and 3.6% among other recipients.

"There is a fairly low capture rate for this field, so it’s difficult to draw significant conclusions from it," cautioned Dr. Taghavi.

Patients who received lungs from heavy smokers had a 1-day longer length of stay in the hospital (18 days vs. 17 days), which "may not really be clinically relevant." Rates of acute rejection during hospitalization were comparable (10.7% vs. 8.8%), as was post-transplant airway dehiscence (1.8% vs. 1.8%).

Post-transplant peak forced expiratory volume in 1 second (FEV₁) was the same (80% vs. 79%), as was decline in this measure over time. Median duration of freedom from bronchiolitis obliterans syndrome was 1,583 days vs. 1,827 days.

Risk-adjusted median all-cause survival – the study’s primary endpoint – did not differ significantly between the recipients given lungs from donors who smoked heavily and the other recipients (2,043 vs. 1,928 days).

The rate of cancer deaths did not differ significantly; however, the follow-up time is too short to address this concern in a meaningful way, Dr. Taghavi said.

"Currently, we recommend when evaluating a donor who has a heavy smoking history, that they undergo a thorough examination for lung tumors or evidence of cancer. This includes obtaining a chest x-ray, CT scans, and bronchoscopies. In addition, when the lungs are procured, they should undergo a very thorough visual inspection," he advised.

"Informed consent is very important. You have to discuss the donor’s smoking status with the recipient and explain the risks and the benefits," Dr. Taghavi said. Lung cancer risk, given the donor’s history, is about 1% to 2% annually, and that needs to be considered against the high likelihood of dying within 1 or 2 years without a transplant.

"One thing that is unquestionable is that survival will be better accepting these lungs than it will be sitting on a waiting list," he added. Only about half of the people listed for lung transplant in the United States each year actually undergo the surgery.

Recipients of lungs from heavy smokers do not need any extra follow-up or surveillance, as they are already diligently tested and monitored, according to Dr. Taghavi. The recipient’s immunosuppression does theoretically put one at additional risk for lung cancer.

Current guidelines of the International Society of Heart and Lung Transplantation advise against considering use of lungs from donors who have a smoking history of more than 20 pack-years, Dr. Taghavi noted. But he stopped short of saying that the study should prompt a formal revision of those guidelines.

"I think the findings start the conversation," he commented. "We should consider looking at these potential donors," especially when a recipient’s situation is dire.

Dr. Taghavi disclosed no conflicts of interest.

TOR@elsevier.com

LOS ANGELES – Use of lungs from donors who smoked heavily does not worsen lung transplantation outcomes including risk for lung cancer death, at least in the medium term.

At a median follow-up of 2 years for 5,900 adults who had double-lung transplants, those who received lungs from heavy smokers had an actuarial median overall survival of roughly 5.5 years, and their lung function was essentially the same as that of patients who received lungs from other donors, Dr. Sharven Taghavi reported at the annual meeting of the Society of Thoracic Surgeons.

The study data came from the United Network for Organ Sharing (UNOS) database. A team led by Dr. Taghavi, of Temple University Hospital in Philadelphia, compared data for double-lung transplants from 2005-2011, comparing donors with a history of smoking exceeding 20 pack-years with other donors.

About 13% of the study patients received lungs from donors who had smoked heavily. Compared with other recipients, these recipients were more likely to have a primary diagnosis of chronic obstructive pulmonary disease and less likely to have a diagnosis of idiopathic pulmonary fibrosis. Otherwise, they were similar.

The rate of deaths due to cancer was based on case reports, as UNOS does not capture this outcome. Cancer deaths were 5.8% among recipients of lungs from heavy smokers and 3.6% among other recipients.

"There is a fairly low capture rate for this field, so it’s difficult to draw significant conclusions from it," cautioned Dr. Taghavi.

Patients who received lungs from heavy smokers had a 1-day longer length of stay in the hospital (18 days vs. 17 days), which "may not really be clinically relevant." Rates of acute rejection during hospitalization were comparable (10.7% vs. 8.8%), as was post-transplant airway dehiscence (1.8% vs. 1.8%).

Post-transplant peak forced expiratory volume in 1 second (FEV₁) was the same (80% vs. 79%), as was decline in this measure over time. Median duration of freedom from bronchiolitis obliterans syndrome was 1,583 days vs. 1,827 days.

Risk-adjusted median all-cause survival – the study’s primary endpoint – did not differ significantly between the recipients given lungs from donors who smoked heavily and the other recipients (2,043 vs. 1,928 days).

The rate of cancer deaths did not differ significantly; however, the follow-up time is too short to address this concern in a meaningful way, Dr. Taghavi said.

"Currently, we recommend when evaluating a donor who has a heavy smoking history, that they undergo a thorough examination for lung tumors or evidence of cancer. This includes obtaining a chest x-ray, CT scans, and bronchoscopies. In addition, when the lungs are procured, they should undergo a very thorough visual inspection," he advised.

"Informed consent is very important. You have to discuss the donor’s smoking status with the recipient and explain the risks and the benefits," Dr. Taghavi said. Lung cancer risk, given the donor’s history, is about 1% to 2% annually, and that needs to be considered against the high likelihood of dying within 1 or 2 years without a transplant.

"One thing that is unquestionable is that survival will be better accepting these lungs than it will be sitting on a waiting list," he added. Only about half of the people listed for lung transplant in the United States each year actually undergo the surgery.

Recipients of lungs from heavy smokers do not need any extra follow-up or surveillance, as they are already diligently tested and monitored, according to Dr. Taghavi. The recipient’s immunosuppression does theoretically put one at additional risk for lung cancer.

Current guidelines of the International Society of Heart and Lung Transplantation advise against considering use of lungs from donors who have a smoking history of more than 20 pack-years, Dr. Taghavi noted. But he stopped short of saying that the study should prompt a formal revision of those guidelines.

"I think the findings start the conversation," he commented. "We should consider looking at these potential donors," especially when a recipient’s situation is dire.

Dr. Taghavi disclosed no conflicts of interest.

TOR@elsevier.com

LOS ANGELES – A novel genetic assay helps identify patients with early, aggressive lung cancer who might benefit from adjuvant therapy.

The assay, marketed as Pervino Lung RS by Life Technologies, is the only lung cancer signature to undergo blinded validation in two large cohorts from different countries, one in the United States and one in China (Lancet 2012;379:823-32).

It assesses expression of 14 genes involved in lung cancer tumorigenesis, including ones on the EGFR and KRAS signaling pathways. The assay provides considerably more prognostic information than do conventional criteria proposed by the National Comprehensive Cancer Network (NCCN) as defining high-risk tumors warranting treatment, according to Dr. Johannes R. Kratz, who reported the data at the annual meeting of the Society of Thoracic Surgeons.

The assay results were used to stratify the 269 study patients who had undergone resection of T1a node-negative and nonmetastatic, nonsquamous, non–small cell lung cancer (NSCLC) into groups with distinctly different 5-year survival rates.

Compared with their counterparts in the low-risk group, those in the intermediate- and high-risk groups had a respective doubling and more than tripling of the risk of death, said Dr. Kratz, who was the study’s lead investigator.

As a result of recommendations for CT screening in patients at high risk for lung cancer, resections of small node-negative tumors that are in fact deadly are likely to increase, he observed. Nearly 30% of all patients with stage IA tumors – the lowest level in the current classification system – will nonetheless die in the subsequent 5 years.

"These tumors with highly aggressive tumor biology can now be identified reliably with a prognostic gene signature. The identification of these small but deadly tumors may allow for personalized patient prognosis and could allow us to maximize the benefit of the early detection of these small but deadly tumors via low-dose CT screening," he added.

The current postoperative standard of care for stage IA disease is simply observation, according to Dr. Kratz, a former surgical resident at the Massachusetts General Hospital in Boston, and now a postdoctoral fellow at the University of California, San Francisco.

However, "we should strongly consider changing the way we think about patients with high-risk T1a tumors," he recommended. To that end, a randomized controlled trial of assay-guided adjuvant chemotherapy for early lung cancer is underway in China among roughly 1,000 patients.

Dr. Kratz said that studies to date have not examined a potential prognostic role of the assay in EGFR (epidermal growth factor receptor) mutations. "We haven’t performed an additional mutation analysis on these patients’ EGFR. The original assay was designed to work on patients with resected paraffin-embedded specimens and not fresh-frozen tissue specimens. As a result, it is difficult for us to do extensive EGFR mutation analysis. But that’s definitely something to consider, and it would be nice to explore that association."

It remains to be seen whether the assay, in fact, predicts chemotherapy benefit, he acknowledged in a related press conference. But research has suggested that such prognostic signatures in lung cancer are also predictive (J. Clin. Oncol. 2010;28:4417-24). "That is what we hope to show in the China trial as well," he said.

In the reported study, patients with T1a tumors were drawn from the initial validation cohorts. Fully 40% were under age 60. "This is important, because ... we’d like to be more aggressive in younger patients, both because they can tolerate it and we are more likely to treat them more aggressively," he noted.

The patients’ actual 5-year mortality rate was 32% overall, showing that "these tumors are as deadly as advertised."

The main study results, reported at the meeting and also published (JAMA 2012;308:1629-31), showed that the 5-year actuarial overall survival was 83%, 69%, and 52% among patients in assay-defined low-, medium-, and high-risk groups, respectively (P less than .0001).

In multivariate analyses, relative to their counterparts in the low-risk group, patients in the intermediate-risk group had a 2.0-fold higher risk of death (P = .04) and patients in the high-risk group had a 3.3-fold higher risk (P = .00).

The assay also showed good risk discrimination in analyses restricted to the smallest of tumors, those measuring 1.5 cm or less (P = .001 for difference across groups) and even those measuring 1.0 cm or less (P = .008).

And when compared with tumor size alone, the combination of the assay and tumor size significantly improved on the identification of patients who died (c-statistic, 0.68 vs. 0.57; P less than .0001).

Although these T1a tumors can be ablated nonoperatively, their genetic makeup offers a rich source of information about their subsequent behavior, Dr. Kratz said.

"Despite the popularity and endorsement of our radiology colleagues for techniques such as stereotactic radiation for small T1aN0M0 tumors, we should remember that these techniques don’t provide us with potentially important lung tissue that can provide prognostic and predictive information," he commented.

Dr. Kratz disclosed that he has been a consultant for Pinpoint Genomics, the company that developed the assay, and is a consultant for Life Technologies, which has acquired Pinpoint Genomics.

TOR@elsevier.com

LOS ANGELES – A novel genetic assay helps identify patients with early, aggressive lung cancer who might benefit from adjuvant therapy.

The assay, marketed as Pervino Lung RS by Life Technologies, is the only lung cancer signature to undergo blinded validation in two large cohorts from different countries, one in the United States and one in China (Lancet 2012;379:823-32).

It assesses expression of 14 genes involved in lung cancer tumorigenesis, including ones on the EGFR and KRAS signaling pathways. The assay provides considerably more prognostic information than do conventional criteria proposed by the National Comprehensive Cancer Network (NCCN) as defining high-risk tumors warranting treatment, according to Dr. Johannes R. Kratz, who reported the data at the annual meeting of the Society of Thoracic Surgeons.

The assay results were used to stratify the 269 study patients who had undergone resection of T1a node-negative and nonmetastatic, nonsquamous, non–small cell lung cancer (NSCLC) into groups with distinctly different 5-year survival rates.

Compared with their counterparts in the low-risk group, those in the intermediate- and high-risk groups had a respective doubling and more than tripling of the risk of death, said Dr. Kratz, who was the study’s lead investigator.

As a result of recommendations for CT screening in patients at high risk for lung cancer, resections of small node-negative tumors that are in fact deadly are likely to increase, he observed. Nearly 30% of all patients with stage IA tumors – the lowest level in the current classification system – will nonetheless die in the subsequent 5 years.

"These tumors with highly aggressive tumor biology can now be identified reliably with a prognostic gene signature. The identification of these small but deadly tumors may allow for personalized patient prognosis and could allow us to maximize the benefit of the early detection of these small but deadly tumors via low-dose CT screening," he added.

The current postoperative standard of care for stage IA disease is simply observation, according to Dr. Kratz, a former surgical resident at the Massachusetts General Hospital in Boston, and now a postdoctoral fellow at the University of California, San Francisco.

However, "we should strongly consider changing the way we think about patients with high-risk T1a tumors," he recommended. To that end, a randomized controlled trial of assay-guided adjuvant chemotherapy for early lung cancer is underway in China among roughly 1,000 patients.

Dr. Kratz said that studies to date have not examined a potential prognostic role of the assay in EGFR (epidermal growth factor receptor) mutations. "We haven’t performed an additional mutation analysis on these patients’ EGFR. The original assay was designed to work on patients with resected paraffin-embedded specimens and not fresh-frozen tissue specimens. As a result, it is difficult for us to do extensive EGFR mutation analysis. But that’s definitely something to consider, and it would be nice to explore that association."

It remains to be seen whether the assay, in fact, predicts chemotherapy benefit, he acknowledged in a related press conference. But research has suggested that such prognostic signatures in lung cancer are also predictive (J. Clin. Oncol. 2010;28:4417-24). "That is what we hope to show in the China trial as well," he said.

In the reported study, patients with T1a tumors were drawn from the initial validation cohorts. Fully 40% were under age 60. "This is important, because ... we’d like to be more aggressive in younger patients, both because they can tolerate it and we are more likely to treat them more aggressively," he noted.

The patients’ actual 5-year mortality rate was 32% overall, showing that "these tumors are as deadly as advertised."

The main study results, reported at the meeting and also published (JAMA 2012;308:1629-31), showed that the 5-year actuarial overall survival was 83%, 69%, and 52% among patients in assay-defined low-, medium-, and high-risk groups, respectively (P less than .0001).

In multivariate analyses, relative to their counterparts in the low-risk group, patients in the intermediate-risk group had a 2.0-fold higher risk of death (P = .04) and patients in the high-risk group had a 3.3-fold higher risk (P = .00).

The assay also showed good risk discrimination in analyses restricted to the smallest of tumors, those measuring 1.5 cm or less (P = .001 for difference across groups) and even those measuring 1.0 cm or less (P = .008).

And when compared with tumor size alone, the combination of the assay and tumor size significantly improved on the identification of patients who died (c-statistic, 0.68 vs. 0.57; P less than .0001).

Although these T1a tumors can be ablated nonoperatively, their genetic makeup offers a rich source of information about their subsequent behavior, Dr. Kratz said.

"Despite the popularity and endorsement of our radiology colleagues for techniques such as stereotactic radiation for small T1aN0M0 tumors, we should remember that these techniques don’t provide us with potentially important lung tissue that can provide prognostic and predictive information," he commented.

Dr. Kratz disclosed that he has been a consultant for Pinpoint Genomics, the company that developed the assay, and is a consultant for Life Technologies, which has acquired Pinpoint Genomics.

TOR@elsevier.com

LOS ANGELES – A novel genetic assay helps identify patients with early, aggressive lung cancer who might benefit from adjuvant therapy.

The assay, marketed as Pervino Lung RS by Life Technologies, is the only lung cancer signature to undergo blinded validation in two large cohorts from different countries, one in the United States and one in China (Lancet 2012;379:823-32).

It assesses expression of 14 genes involved in lung cancer tumorigenesis, including ones on the EGFR and KRAS signaling pathways. The assay provides considerably more prognostic information than do conventional criteria proposed by the National Comprehensive Cancer Network (NCCN) as defining high-risk tumors warranting treatment, according to Dr. Johannes R. Kratz, who reported the data at the annual meeting of the Society of Thoracic Surgeons.

The assay results were used to stratify the 269 study patients who had undergone resection of T1a node-negative and nonmetastatic, nonsquamous, non–small cell lung cancer (NSCLC) into groups with distinctly different 5-year survival rates.

Compared with their counterparts in the low-risk group, those in the intermediate- and high-risk groups had a respective doubling and more than tripling of the risk of death, said Dr. Kratz, who was the study’s lead investigator.

As a result of recommendations for CT screening in patients at high risk for lung cancer, resections of small node-negative tumors that are in fact deadly are likely to increase, he observed. Nearly 30% of all patients with stage IA tumors – the lowest level in the current classification system – will nonetheless die in the subsequent 5 years.

"These tumors with highly aggressive tumor biology can now be identified reliably with a prognostic gene signature. The identification of these small but deadly tumors may allow for personalized patient prognosis and could allow us to maximize the benefit of the early detection of these small but deadly tumors via low-dose CT screening," he added.

The current postoperative standard of care for stage IA disease is simply observation, according to Dr. Kratz, a former surgical resident at the Massachusetts General Hospital in Boston, and now a postdoctoral fellow at the University of California, San Francisco.

However, "we should strongly consider changing the way we think about patients with high-risk T1a tumors," he recommended. To that end, a randomized controlled trial of assay-guided adjuvant chemotherapy for early lung cancer is underway in China among roughly 1,000 patients.

Dr. Kratz said that studies to date have not examined a potential prognostic role of the assay in EGFR (epidermal growth factor receptor) mutations. "We haven’t performed an additional mutation analysis on these patients’ EGFR. The original assay was designed to work on patients with resected paraffin-embedded specimens and not fresh-frozen tissue specimens. As a result, it is difficult for us to do extensive EGFR mutation analysis. But that’s definitely something to consider, and it would be nice to explore that association."

It remains to be seen whether the assay, in fact, predicts chemotherapy benefit, he acknowledged in a related press conference. But research has suggested that such prognostic signatures in lung cancer are also predictive (J. Clin. Oncol. 2010;28:4417-24). "That is what we hope to show in the China trial as well," he said.

In the reported study, patients with T1a tumors were drawn from the initial validation cohorts. Fully 40% were under age 60. "This is important, because ... we’d like to be more aggressive in younger patients, both because they can tolerate it and we are more likely to treat them more aggressively," he noted.

The patients’ actual 5-year mortality rate was 32% overall, showing that "these tumors are as deadly as advertised."

The main study results, reported at the meeting and also published (JAMA 2012;308:1629-31), showed that the 5-year actuarial overall survival was 83%, 69%, and 52% among patients in assay-defined low-, medium-, and high-risk groups, respectively (P less than .0001).

In multivariate analyses, relative to their counterparts in the low-risk group, patients in the intermediate-risk group had a 2.0-fold higher risk of death (P = .04) and patients in the high-risk group had a 3.3-fold higher risk (P = .00).

The assay also showed good risk discrimination in analyses restricted to the smallest of tumors, those measuring 1.5 cm or less (P = .001 for difference across groups) and even those measuring 1.0 cm or less (P = .008).

And when compared with tumor size alone, the combination of the assay and tumor size significantly improved on the identification of patients who died (c-statistic, 0.68 vs. 0.57; P less than .0001).

Although these T1a tumors can be ablated nonoperatively, their genetic makeup offers a rich source of information about their subsequent behavior, Dr. Kratz said.

"Despite the popularity and endorsement of our radiology colleagues for techniques such as stereotactic radiation for small T1aN0M0 tumors, we should remember that these techniques don’t provide us with potentially important lung tissue that can provide prognostic and predictive information," he commented.

Dr. Kratz disclosed that he has been a consultant for Pinpoint Genomics, the company that developed the assay, and is a consultant for Life Technologies, which has acquired Pinpoint Genomics.

TOR@elsevier.com