Cardiothoracic

An estimated 18% of the early lung cancers detected by low-dose CT screening in the National Lung Screening Trial were likely indolent and probably represent overdiagnosis, according to a report published online Dec. 9 in JAMA Internal Medicine.

The National Lung Screening Trial (NLST) found "an encouraging" 20% relative reduction in lung cancer–specific mortality among high-risk patients who were screened using low-dose CT, compared with chest radiography. "These findings were met with enthusiasm, but before a widespread public health screening program is implemented, risks of screening also need to be considered," said Dr. Edward F. Patz Jr. of the department of radiology, Duke University Medical Center, Durham, N.C., and his associates in the NLST.

The chief risk in this case is overdiagnosis: identifying an early-stage lesion in an asymptomatic patient that would not progress or affect that patient’s long-term health. It is likely that some of the tumors detected on low-dose CT were just such indolent cancers, and that those patients unnecessarily underwent invasive diagnostic procedures, surgical resection, and multiple follow-up studies.

To estimate how many of the detected cancers in the NLST were indolent – and thus overdiagnosed – Dr. Patz and his colleagues used statistical probability methods to analyze extended follow-up data from the study.

The NLST involved 53,452 men and women aged 55-74 years who were enrolled during 2002-2004 and who had at least a 30-pack-year history of cigarette smoking. The patients were randomly assigned to undergo lung cancer screening using either three annual low-dose CT exams or three annual single-view chest radiographs.

Mean follow-up was approximately 6 years. "At the end of the entire trial, there were 1,089 total lung cancer cases in the low-dose CT arm (649 detected by low-dose CT screening) and 969 cases in the [radiology] arm, for an excess of 120 cases. This gives [an] excess cancer rate of 18.5%," the investigators said (JAMA Intern. Med. 2013 Dec. 9 [doi:10.1001/jamainternmed.2013.12738]).

"The data from this study suggest that ... 18% of persons in the low-dose CT arm with screen-detected lung cancer and 22% of those in the low-dose CT arm with screen-detected NSCLC [non–small cell lung cancer] may be cases of overdiagnosis," Dr. Patz and his associates said. "In other words, if these individuals had not entered the NLST, they would not have received a lung cancer diagnosis or treatment, at least for the next 5 years."

In the future, the study authors noted, "once there are better biomarkers and imaging techniques to predict which individuals with a diagnosis of lung cancer will have more or less aggressive disease, treatment options can be optimized, and a mass screening program can become more valuable."

The National Institutes of Health supported the NSLT. No financial conflicts of interest were reported.

An estimated 18% of the early lung cancers detected by low-dose CT screening in the National Lung Screening Trial were likely indolent and probably represent overdiagnosis, according to a report published online Dec. 9 in JAMA Internal Medicine.

The National Lung Screening Trial (NLST) found "an encouraging" 20% relative reduction in lung cancer–specific mortality among high-risk patients who were screened using low-dose CT, compared with chest radiography. "These findings were met with enthusiasm, but before a widespread public health screening program is implemented, risks of screening also need to be considered," said Dr. Edward F. Patz Jr. of the department of radiology, Duke University Medical Center, Durham, N.C., and his associates in the NLST.

The chief risk in this case is overdiagnosis: identifying an early-stage lesion in an asymptomatic patient that would not progress or affect that patient’s long-term health. It is likely that some of the tumors detected on low-dose CT were just such indolent cancers, and that those patients unnecessarily underwent invasive diagnostic procedures, surgical resection, and multiple follow-up studies.

To estimate how many of the detected cancers in the NLST were indolent – and thus overdiagnosed – Dr. Patz and his colleagues used statistical probability methods to analyze extended follow-up data from the study.

The NLST involved 53,452 men and women aged 55-74 years who were enrolled during 2002-2004 and who had at least a 30-pack-year history of cigarette smoking. The patients were randomly assigned to undergo lung cancer screening using either three annual low-dose CT exams or three annual single-view chest radiographs.

Mean follow-up was approximately 6 years. "At the end of the entire trial, there were 1,089 total lung cancer cases in the low-dose CT arm (649 detected by low-dose CT screening) and 969 cases in the [radiology] arm, for an excess of 120 cases. This gives [an] excess cancer rate of 18.5%," the investigators said (JAMA Intern. Med. 2013 Dec. 9 [doi:10.1001/jamainternmed.2013.12738]).

"The data from this study suggest that ... 18% of persons in the low-dose CT arm with screen-detected lung cancer and 22% of those in the low-dose CT arm with screen-detected NSCLC [non–small cell lung cancer] may be cases of overdiagnosis," Dr. Patz and his associates said. "In other words, if these individuals had not entered the NLST, they would not have received a lung cancer diagnosis or treatment, at least for the next 5 years."

In the future, the study authors noted, "once there are better biomarkers and imaging techniques to predict which individuals with a diagnosis of lung cancer will have more or less aggressive disease, treatment options can be optimized, and a mass screening program can become more valuable."

The National Institutes of Health supported the NSLT. No financial conflicts of interest were reported.

An estimated 18% of the early lung cancers detected by low-dose CT screening in the National Lung Screening Trial were likely indolent and probably represent overdiagnosis, according to a report published online Dec. 9 in JAMA Internal Medicine.

The National Lung Screening Trial (NLST) found "an encouraging" 20% relative reduction in lung cancer–specific mortality among high-risk patients who were screened using low-dose CT, compared with chest radiography. "These findings were met with enthusiasm, but before a widespread public health screening program is implemented, risks of screening also need to be considered," said Dr. Edward F. Patz Jr. of the department of radiology, Duke University Medical Center, Durham, N.C., and his associates in the NLST.

The chief risk in this case is overdiagnosis: identifying an early-stage lesion in an asymptomatic patient that would not progress or affect that patient’s long-term health. It is likely that some of the tumors detected on low-dose CT were just such indolent cancers, and that those patients unnecessarily underwent invasive diagnostic procedures, surgical resection, and multiple follow-up studies.

To estimate how many of the detected cancers in the NLST were indolent – and thus overdiagnosed – Dr. Patz and his colleagues used statistical probability methods to analyze extended follow-up data from the study.

The NLST involved 53,452 men and women aged 55-74 years who were enrolled during 2002-2004 and who had at least a 30-pack-year history of cigarette smoking. The patients were randomly assigned to undergo lung cancer screening using either three annual low-dose CT exams or three annual single-view chest radiographs.

Mean follow-up was approximately 6 years. "At the end of the entire trial, there were 1,089 total lung cancer cases in the low-dose CT arm (649 detected by low-dose CT screening) and 969 cases in the [radiology] arm, for an excess of 120 cases. This gives [an] excess cancer rate of 18.5%," the investigators said (JAMA Intern. Med. 2013 Dec. 9 [doi:10.1001/jamainternmed.2013.12738]).

"The data from this study suggest that ... 18% of persons in the low-dose CT arm with screen-detected lung cancer and 22% of those in the low-dose CT arm with screen-detected NSCLC [non–small cell lung cancer] may be cases of overdiagnosis," Dr. Patz and his associates said. "In other words, if these individuals had not entered the NLST, they would not have received a lung cancer diagnosis or treatment, at least for the next 5 years."

In the future, the study authors noted, "once there are better biomarkers and imaging techniques to predict which individuals with a diagnosis of lung cancer will have more or less aggressive disease, treatment options can be optimized, and a mass screening program can become more valuable."

The National Institutes of Health supported the NSLT. No financial conflicts of interest were reported.

SAN FRANCISCO – Treating bare metal stent in-stent restenosis using a drug-eluting stent yielded a significantly larger minimal lumen diameter 1 year later, compared with treatment using a drug-eluting balloon in a study of 189 patients.

A second-generation everolimus-eluting stent bested a paclitaxel-eluting balloon in the primary outcome of the prospective, randomized trial after adjusting for age, smoking history, stenosis, and the presence of diabetes.

The in-segment minimal lumen diameter was 2.36 mm for the 94 patients in the stent group and 2.01 mm for the 95 patients in the balloon group. The in-lesion minimal lumen diameter was 2.44 mm in the stent group and 2.03 mm in the balloon group. Both differences were statistically significant, Dr. Fernando Alfonso and his associates reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

The rate of restenosis (greater than 50% lumen diameter narrowing) at the 1-year follow-up point was very low in both groups: 4.7% in the stent group and 9.5% in the balloon group. That difference was not statistically significant between groups.

Median in-segment late loss (the difference between minimal lumen diameter at completion of the procedure and at 1 year follow-up) was strikingly small and did not differ significantly between groups, reported Dr. Alfonso, an interventional cardiologist at Hospital Universitario Clinico San Carlos, Madrid.

Late loss in the stent group was 0.04 mm and in the balloon group was 0.14 mm, he added.

Rates of major adverse cardiac events were similar between groups: 94% in the stent group and 91% in the balloon group died of cardiac-related causes or had an MI or target vessel revascularization within a year of treatment. Rates of major adverse events also were statistically similar between groups in the RIBS V (Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs. Everolimus-Eluting Stent) trial.

A total of 6% of patients in the stent group and 12% in the balloon group developed a major adverse event; these rates were statistically similar. Four patients in the balloon group and none in the stent group died; three of the deaths were from noncardiac causes. Four patients in the stent group and three in the balloon group had an acute MI. Two patients in the stent group and six in the balloon group underwent target vessel revascularization. (Some patients had more than one adverse event.)

"In patients with bare metal stent in-stent restenosis, both drug-eluting balloons and everolimus-eluting stents provide excellent clinical outcomes" and excellent angiographic findings with very low late loss and low restenosis rates, Dr. Alfonso said at the meeting, cosponsored by the American College of Cardiology. "Further studies with larger numbers of patients and longer follow-up are required to elucidate if these superior late angiographic findings may eventually translate into a clinical benefit." In the meantime, drug-eluting balloons appear to offer "a very good alternative" for patients who may not be good candidates for drug-eluting stents, he said.

The study included patients aged 20-85 years at 25 Spanish centers who had more than 50% stenosis in a bare metal stent and angina or silent ischemia. In-segment quantitative coronary angiography measurements were similar between groups at baseline: the reference diameter was 2.63 mm in the stent group and 2.62 mm in the balloon group, and the lesion length was 13.8 mm in the stent group and 13.7 mm in the balloon group.

Patients who were randomized in 2010-2012 to receive Xience Prime everolimus-eluting stents (by Abbott Vascular) were significantly younger, compared with those who got SeQuent Please paclitaxel-eluting balloons (by B. Braun Surgical) – 64 vs. 67 years, respectively. Those in the stent group also were more likely to have ever smoked (75% vs. 59%, respectively). Eight patients in the balloon group eventually crossed over to stent implantation, and no patients in the stent group crossed over to balloons.

One-year follow-up was available for 170 patients (92%), and results were calculated in intent-to-treat analyses.

Dr. Alfonso reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Treating bare metal stent in-stent restenosis using a drug-eluting stent yielded a significantly larger minimal lumen diameter 1 year later, compared with treatment using a drug-eluting balloon in a study of 189 patients.

A second-generation everolimus-eluting stent bested a paclitaxel-eluting balloon in the primary outcome of the prospective, randomized trial after adjusting for age, smoking history, stenosis, and the presence of diabetes.

The in-segment minimal lumen diameter was 2.36 mm for the 94 patients in the stent group and 2.01 mm for the 95 patients in the balloon group. The in-lesion minimal lumen diameter was 2.44 mm in the stent group and 2.03 mm in the balloon group. Both differences were statistically significant, Dr. Fernando Alfonso and his associates reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

The rate of restenosis (greater than 50% lumen diameter narrowing) at the 1-year follow-up point was very low in both groups: 4.7% in the stent group and 9.5% in the balloon group. That difference was not statistically significant between groups.

Median in-segment late loss (the difference between minimal lumen diameter at completion of the procedure and at 1 year follow-up) was strikingly small and did not differ significantly between groups, reported Dr. Alfonso, an interventional cardiologist at Hospital Universitario Clinico San Carlos, Madrid.

Late loss in the stent group was 0.04 mm and in the balloon group was 0.14 mm, he added.

Rates of major adverse cardiac events were similar between groups: 94% in the stent group and 91% in the balloon group died of cardiac-related causes or had an MI or target vessel revascularization within a year of treatment. Rates of major adverse events also were statistically similar between groups in the RIBS V (Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs. Everolimus-Eluting Stent) trial.

A total of 6% of patients in the stent group and 12% in the balloon group developed a major adverse event; these rates were statistically similar. Four patients in the balloon group and none in the stent group died; three of the deaths were from noncardiac causes. Four patients in the stent group and three in the balloon group had an acute MI. Two patients in the stent group and six in the balloon group underwent target vessel revascularization. (Some patients had more than one adverse event.)

"In patients with bare metal stent in-stent restenosis, both drug-eluting balloons and everolimus-eluting stents provide excellent clinical outcomes" and excellent angiographic findings with very low late loss and low restenosis rates, Dr. Alfonso said at the meeting, cosponsored by the American College of Cardiology. "Further studies with larger numbers of patients and longer follow-up are required to elucidate if these superior late angiographic findings may eventually translate into a clinical benefit." In the meantime, drug-eluting balloons appear to offer "a very good alternative" for patients who may not be good candidates for drug-eluting stents, he said.

The study included patients aged 20-85 years at 25 Spanish centers who had more than 50% stenosis in a bare metal stent and angina or silent ischemia. In-segment quantitative coronary angiography measurements were similar between groups at baseline: the reference diameter was 2.63 mm in the stent group and 2.62 mm in the balloon group, and the lesion length was 13.8 mm in the stent group and 13.7 mm in the balloon group.

Patients who were randomized in 2010-2012 to receive Xience Prime everolimus-eluting stents (by Abbott Vascular) were significantly younger, compared with those who got SeQuent Please paclitaxel-eluting balloons (by B. Braun Surgical) – 64 vs. 67 years, respectively. Those in the stent group also were more likely to have ever smoked (75% vs. 59%, respectively). Eight patients in the balloon group eventually crossed over to stent implantation, and no patients in the stent group crossed over to balloons.

One-year follow-up was available for 170 patients (92%), and results were calculated in intent-to-treat analyses.

Dr. Alfonso reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Treating bare metal stent in-stent restenosis using a drug-eluting stent yielded a significantly larger minimal lumen diameter 1 year later, compared with treatment using a drug-eluting balloon in a study of 189 patients.

A second-generation everolimus-eluting stent bested a paclitaxel-eluting balloon in the primary outcome of the prospective, randomized trial after adjusting for age, smoking history, stenosis, and the presence of diabetes.

The in-segment minimal lumen diameter was 2.36 mm for the 94 patients in the stent group and 2.01 mm for the 95 patients in the balloon group. The in-lesion minimal lumen diameter was 2.44 mm in the stent group and 2.03 mm in the balloon group. Both differences were statistically significant, Dr. Fernando Alfonso and his associates reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

The rate of restenosis (greater than 50% lumen diameter narrowing) at the 1-year follow-up point was very low in both groups: 4.7% in the stent group and 9.5% in the balloon group. That difference was not statistically significant between groups.

Median in-segment late loss (the difference between minimal lumen diameter at completion of the procedure and at 1 year follow-up) was strikingly small and did not differ significantly between groups, reported Dr. Alfonso, an interventional cardiologist at Hospital Universitario Clinico San Carlos, Madrid.

Late loss in the stent group was 0.04 mm and in the balloon group was 0.14 mm, he added.

Rates of major adverse cardiac events were similar between groups: 94% in the stent group and 91% in the balloon group died of cardiac-related causes or had an MI or target vessel revascularization within a year of treatment. Rates of major adverse events also were statistically similar between groups in the RIBS V (Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs. Everolimus-Eluting Stent) trial.

A total of 6% of patients in the stent group and 12% in the balloon group developed a major adverse event; these rates were statistically similar. Four patients in the balloon group and none in the stent group died; three of the deaths were from noncardiac causes. Four patients in the stent group and three in the balloon group had an acute MI. Two patients in the stent group and six in the balloon group underwent target vessel revascularization. (Some patients had more than one adverse event.)

"In patients with bare metal stent in-stent restenosis, both drug-eluting balloons and everolimus-eluting stents provide excellent clinical outcomes" and excellent angiographic findings with very low late loss and low restenosis rates, Dr. Alfonso said at the meeting, cosponsored by the American College of Cardiology. "Further studies with larger numbers of patients and longer follow-up are required to elucidate if these superior late angiographic findings may eventually translate into a clinical benefit." In the meantime, drug-eluting balloons appear to offer "a very good alternative" for patients who may not be good candidates for drug-eluting stents, he said.

The study included patients aged 20-85 years at 25 Spanish centers who had more than 50% stenosis in a bare metal stent and angina or silent ischemia. In-segment quantitative coronary angiography measurements were similar between groups at baseline: the reference diameter was 2.63 mm in the stent group and 2.62 mm in the balloon group, and the lesion length was 13.8 mm in the stent group and 13.7 mm in the balloon group.

Patients who were randomized in 2010-2012 to receive Xience Prime everolimus-eluting stents (by Abbott Vascular) were significantly younger, compared with those who got SeQuent Please paclitaxel-eluting balloons (by B. Braun Surgical) – 64 vs. 67 years, respectively. Those in the stent group also were more likely to have ever smoked (75% vs. 59%, respectively). Eight patients in the balloon group eventually crossed over to stent implantation, and no patients in the stent group crossed over to balloons.

One-year follow-up was available for 170 patients (92%), and results were calculated in intent-to-treat analyses.

Dr. Alfonso reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

An abrupt and unexpected increase in pump thrombosis has occurred since March 2011 in patients with advanced heart failure who received the HeartMate II left ventricular assist device, according to a report published online Nov. 27 in the New England Journal of Medicine.

Those who develop LVAD thrombosis are at substantial risk of death and morbidity unless the device is replaced or cardiac transplantation is performed, said Dr. Randall C. Starling of the Cleveland Clinic and his associates.

The reason for the sudden rise in pump thrombosis is not yet known, but it may be related to excess "deposition of material (fibrin and denatured protein) in proximity to the inflow bearing" of the device, which has been observed by clinicians in at least three cardiac centers.

"Our data suggest that the HeartMate II may have a more narrow tolerance with respect to thrombus formation than originally understood, and may be vulnerable to the timing and intensity of anticoagulation," Dr. Starling and his colleagues noted.

The HeartMate II, made by Thoratec, is a small axial-flow LVAD that "rapidly became integral in the treatment of patients with advanced heart failure" after it was introduced. Early trials and postmarketing approval studies reported a 2%-4% incidence of thrombosis. But a quality review at the Cleveland Clinic showed a sudden, marked increase in that rate beginning in March 2011.

Researchers at the Cleveland Clinic then pooled their data on the HeartMate II (from October 2004 to February 2013) with data on the device from two other high-volume cardiology centers: Washington University Barnes-Jewish Hospital, St. Louis (January 2004 to April 2013) and Duke University Medical Center, Durham, N.C. (May 2005 to May 2013). They now report on their findings from 895 HeartMate II LVADs implanted in 837 patients during that time.

"The HeartMate II may have a more narrow tolerance with respect to thrombus formation than originally understood, and may be vulnerable to the timing and intensity of anticoagulation..."

The mean patient age was 55 years, and 21% of patients were women.

The primary endpoint of the study was confirmed LVAD thrombosis, defined as a finding at pump replacement, urgent transplantation, or autopsy of a thrombus on the blood-contacting surface of the device, its inflow cannula, or its outflow conduit. A total of 72 such thromboses were found in 66 patients; in addition, 36 cases of suspected thromboses occurred.

The rate of confirmed pump thrombosis was initially stable at roughly 2.2% for several years, then rose steeply after March 2011 to 8.4%. This pattern was seen at all three medical centers and across all the cardiac surgeons at those centers.

The median time interval from implantation to pump thrombosis had been 18.6 months before March 2011, but that rate plummeted to 2.7 months during and after March 2011, Dr. Starling and his associates reported (N. Engl. J. Med. 2013 Nov. 27 [doi: 10.1056/NEJMoa1313385]).

The investigators also reviewed serial measurements of lactate dehydrogenase (LDH) that had been taken in recipients of 568 of the devices. Elevated LDH indicates hemolysis that may herald impending thrombosis.

"The graph of the occurrence of LDH levels above 1000 IU per liter ... was nearly superimposable on the graph of the occurrence of confirmed pump thrombosis. The LDH data showed a parallel tendency for elevations to occur early after implantation beginning in approximately March 2011," they said.

The LDH level typically rose from an average of 540 IU/L to an average of 1,490 IU/L during the weeks leading up to LVAD thrombosis at all three medical centers. This confirms that LDH level is a useful clinical biomarker of hemolysis associated with LVAD thrombosis, the researchers said.

Of the 72 pump thromboses, 11 were managed by heart transplantation and 21 by pump replacement. Of the remaining 40 thromboses, 2 were managed by LVAD removal because left ventricular function had improved, and 38 were managed medically, with augmentation of anticoagulation therapy and thrombolytic agents. This stabilized the clinical course in some patients, but others elected withdrawal of care, citing "futility."

Mortality was 48% among the patients who could not be managed by heart transplantation or pump replacement, and this elevated rate was consistent across the three medical centers.

The reasons for this abrupt, dramatic rise in thromboses associated with the HeartMate II are not known. There were no changes in LVAD implantation techniques at any of the three medical centers during the course of this study, "and we could find no association between pump thrombosis and the surgeon performing the implantation." The design of the HeartMate II was changed during this interval – "modification of the outflow graft and bend relief, inflow conduit, and software" was introduced – but these changes have not been linked to pump thrombosis as yet.

Dr. Starling and his associates did note the deposition of fibrin and denatured protein around the inflow bearing, which could narrow the inflow pathway, "increasing shear stress on the red cells and, if the deposition is large enough, decreasing the ability of the pump to unload the left ventricle." But it remains to be seen whether this or other factors played a role.

"Further investigation of predisposing patient and device factors and preventive and therapeutic strategies are urgently needed to resolve this important safety issue," the investigators said.

They added that a fourth cardiology center, the University of Pennsylvania, Philadelphia, found a similar pattern in a preliminary analysis that was reported as the article went to press. In that report on 150 HeartMate II LVADs implanted in 148 patients between November 2005 and September 2013, there were 15 thrombotic events. "Similar to the findings in our study, the event rate has increased abruptly and unexpectedly, with a rate of confirmed thrombosis that continues to rise," Dr. Starling and his associates said.

Dr. Starling reported ties to Thoratec and HeartWare, and his associates reported ties to Thoratec, HeartWare, Abiomed, and Syncardia.

An abrupt and unexpected increase in pump thrombosis has occurred since March 2011 in patients with advanced heart failure who received the HeartMate II left ventricular assist device, according to a report published online Nov. 27 in the New England Journal of Medicine.

Those who develop LVAD thrombosis are at substantial risk of death and morbidity unless the device is replaced or cardiac transplantation is performed, said Dr. Randall C. Starling of the Cleveland Clinic and his associates.

The reason for the sudden rise in pump thrombosis is not yet known, but it may be related to excess "deposition of material (fibrin and denatured protein) in proximity to the inflow bearing" of the device, which has been observed by clinicians in at least three cardiac centers.

"Our data suggest that the HeartMate II may have a more narrow tolerance with respect to thrombus formation than originally understood, and may be vulnerable to the timing and intensity of anticoagulation," Dr. Starling and his colleagues noted.

The HeartMate II, made by Thoratec, is a small axial-flow LVAD that "rapidly became integral in the treatment of patients with advanced heart failure" after it was introduced. Early trials and postmarketing approval studies reported a 2%-4% incidence of thrombosis. But a quality review at the Cleveland Clinic showed a sudden, marked increase in that rate beginning in March 2011.

Researchers at the Cleveland Clinic then pooled their data on the HeartMate II (from October 2004 to February 2013) with data on the device from two other high-volume cardiology centers: Washington University Barnes-Jewish Hospital, St. Louis (January 2004 to April 2013) and Duke University Medical Center, Durham, N.C. (May 2005 to May 2013). They now report on their findings from 895 HeartMate II LVADs implanted in 837 patients during that time.

"The HeartMate II may have a more narrow tolerance with respect to thrombus formation than originally understood, and may be vulnerable to the timing and intensity of anticoagulation..."

The mean patient age was 55 years, and 21% of patients were women.

The primary endpoint of the study was confirmed LVAD thrombosis, defined as a finding at pump replacement, urgent transplantation, or autopsy of a thrombus on the blood-contacting surface of the device, its inflow cannula, or its outflow conduit. A total of 72 such thromboses were found in 66 patients; in addition, 36 cases of suspected thromboses occurred.

The rate of confirmed pump thrombosis was initially stable at roughly 2.2% for several years, then rose steeply after March 2011 to 8.4%. This pattern was seen at all three medical centers and across all the cardiac surgeons at those centers.

The median time interval from implantation to pump thrombosis had been 18.6 months before March 2011, but that rate plummeted to 2.7 months during and after March 2011, Dr. Starling and his associates reported (N. Engl. J. Med. 2013 Nov. 27 [doi: 10.1056/NEJMoa1313385]).

The investigators also reviewed serial measurements of lactate dehydrogenase (LDH) that had been taken in recipients of 568 of the devices. Elevated LDH indicates hemolysis that may herald impending thrombosis.

"The graph of the occurrence of LDH levels above 1000 IU per liter ... was nearly superimposable on the graph of the occurrence of confirmed pump thrombosis. The LDH data showed a parallel tendency for elevations to occur early after implantation beginning in approximately March 2011," they said.

The LDH level typically rose from an average of 540 IU/L to an average of 1,490 IU/L during the weeks leading up to LVAD thrombosis at all three medical centers. This confirms that LDH level is a useful clinical biomarker of hemolysis associated with LVAD thrombosis, the researchers said.

Of the 72 pump thromboses, 11 were managed by heart transplantation and 21 by pump replacement. Of the remaining 40 thromboses, 2 were managed by LVAD removal because left ventricular function had improved, and 38 were managed medically, with augmentation of anticoagulation therapy and thrombolytic agents. This stabilized the clinical course in some patients, but others elected withdrawal of care, citing "futility."

Mortality was 48% among the patients who could not be managed by heart transplantation or pump replacement, and this elevated rate was consistent across the three medical centers.

The reasons for this abrupt, dramatic rise in thromboses associated with the HeartMate II are not known. There were no changes in LVAD implantation techniques at any of the three medical centers during the course of this study, "and we could find no association between pump thrombosis and the surgeon performing the implantation." The design of the HeartMate II was changed during this interval – "modification of the outflow graft and bend relief, inflow conduit, and software" was introduced – but these changes have not been linked to pump thrombosis as yet.

Dr. Starling and his associates did note the deposition of fibrin and denatured protein around the inflow bearing, which could narrow the inflow pathway, "increasing shear stress on the red cells and, if the deposition is large enough, decreasing the ability of the pump to unload the left ventricle." But it remains to be seen whether this or other factors played a role.

"Further investigation of predisposing patient and device factors and preventive and therapeutic strategies are urgently needed to resolve this important safety issue," the investigators said.

They added that a fourth cardiology center, the University of Pennsylvania, Philadelphia, found a similar pattern in a preliminary analysis that was reported as the article went to press. In that report on 150 HeartMate II LVADs implanted in 148 patients between November 2005 and September 2013, there were 15 thrombotic events. "Similar to the findings in our study, the event rate has increased abruptly and unexpectedly, with a rate of confirmed thrombosis that continues to rise," Dr. Starling and his associates said.

Dr. Starling reported ties to Thoratec and HeartWare, and his associates reported ties to Thoratec, HeartWare, Abiomed, and Syncardia.

An abrupt and unexpected increase in pump thrombosis has occurred since March 2011 in patients with advanced heart failure who received the HeartMate II left ventricular assist device, according to a report published online Nov. 27 in the New England Journal of Medicine.

Those who develop LVAD thrombosis are at substantial risk of death and morbidity unless the device is replaced or cardiac transplantation is performed, said Dr. Randall C. Starling of the Cleveland Clinic and his associates.

The reason for the sudden rise in pump thrombosis is not yet known, but it may be related to excess "deposition of material (fibrin and denatured protein) in proximity to the inflow bearing" of the device, which has been observed by clinicians in at least three cardiac centers.

"Our data suggest that the HeartMate II may have a more narrow tolerance with respect to thrombus formation than originally understood, and may be vulnerable to the timing and intensity of anticoagulation," Dr. Starling and his colleagues noted.

The HeartMate II, made by Thoratec, is a small axial-flow LVAD that "rapidly became integral in the treatment of patients with advanced heart failure" after it was introduced. Early trials and postmarketing approval studies reported a 2%-4% incidence of thrombosis. But a quality review at the Cleveland Clinic showed a sudden, marked increase in that rate beginning in March 2011.

Researchers at the Cleveland Clinic then pooled their data on the HeartMate II (from October 2004 to February 2013) with data on the device from two other high-volume cardiology centers: Washington University Barnes-Jewish Hospital, St. Louis (January 2004 to April 2013) and Duke University Medical Center, Durham, N.C. (May 2005 to May 2013). They now report on their findings from 895 HeartMate II LVADs implanted in 837 patients during that time.

"The HeartMate II may have a more narrow tolerance with respect to thrombus formation than originally understood, and may be vulnerable to the timing and intensity of anticoagulation..."

The mean patient age was 55 years, and 21% of patients were women.

The primary endpoint of the study was confirmed LVAD thrombosis, defined as a finding at pump replacement, urgent transplantation, or autopsy of a thrombus on the blood-contacting surface of the device, its inflow cannula, or its outflow conduit. A total of 72 such thromboses were found in 66 patients; in addition, 36 cases of suspected thromboses occurred.

The rate of confirmed pump thrombosis was initially stable at roughly 2.2% for several years, then rose steeply after March 2011 to 8.4%. This pattern was seen at all three medical centers and across all the cardiac surgeons at those centers.

The median time interval from implantation to pump thrombosis had been 18.6 months before March 2011, but that rate plummeted to 2.7 months during and after March 2011, Dr. Starling and his associates reported (N. Engl. J. Med. 2013 Nov. 27 [doi: 10.1056/NEJMoa1313385]).

The investigators also reviewed serial measurements of lactate dehydrogenase (LDH) that had been taken in recipients of 568 of the devices. Elevated LDH indicates hemolysis that may herald impending thrombosis.

"The graph of the occurrence of LDH levels above 1000 IU per liter ... was nearly superimposable on the graph of the occurrence of confirmed pump thrombosis. The LDH data showed a parallel tendency for elevations to occur early after implantation beginning in approximately March 2011," they said.

The LDH level typically rose from an average of 540 IU/L to an average of 1,490 IU/L during the weeks leading up to LVAD thrombosis at all three medical centers. This confirms that LDH level is a useful clinical biomarker of hemolysis associated with LVAD thrombosis, the researchers said.

Of the 72 pump thromboses, 11 were managed by heart transplantation and 21 by pump replacement. Of the remaining 40 thromboses, 2 were managed by LVAD removal because left ventricular function had improved, and 38 were managed medically, with augmentation of anticoagulation therapy and thrombolytic agents. This stabilized the clinical course in some patients, but others elected withdrawal of care, citing "futility."

Mortality was 48% among the patients who could not be managed by heart transplantation or pump replacement, and this elevated rate was consistent across the three medical centers.

The reasons for this abrupt, dramatic rise in thromboses associated with the HeartMate II are not known. There were no changes in LVAD implantation techniques at any of the three medical centers during the course of this study, "and we could find no association between pump thrombosis and the surgeon performing the implantation." The design of the HeartMate II was changed during this interval – "modification of the outflow graft and bend relief, inflow conduit, and software" was introduced – but these changes have not been linked to pump thrombosis as yet.

Dr. Starling and his associates did note the deposition of fibrin and denatured protein around the inflow bearing, which could narrow the inflow pathway, "increasing shear stress on the red cells and, if the deposition is large enough, decreasing the ability of the pump to unload the left ventricle." But it remains to be seen whether this or other factors played a role.

"Further investigation of predisposing patient and device factors and preventive and therapeutic strategies are urgently needed to resolve this important safety issue," the investigators said.

They added that a fourth cardiology center, the University of Pennsylvania, Philadelphia, found a similar pattern in a preliminary analysis that was reported as the article went to press. In that report on 150 HeartMate II LVADs implanted in 148 patients between November 2005 and September 2013, there were 15 thrombotic events. "Similar to the findings in our study, the event rate has increased abruptly and unexpectedly, with a rate of confirmed thrombosis that continues to rise," Dr. Starling and his associates said.

Dr. Starling reported ties to Thoratec and HeartWare, and his associates reported ties to Thoratec, HeartWare, Abiomed, and Syncardia.

SYDNEY, AUSTRALIA – Video-assisted thoracoscopic partial pleurectomy significantly improved quality of life and control of pleural effusion compared with talc pleurodesis in patients with malignant mesothelioma in a randomized, controlled, multicenter trial.

However, pleurectomy did not increase overall survival in the study, based on data presented in a plenary session at a world conference on lung cancer.

"The problem we now have is, we’ve got a negative result and a positive result because of the primary endpoint, so detractors could say there’s a negative endpoint so there’s no role for surgery," lead researcher Dr. Robert Rintoul said in an interview at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

Courtesy Dr. Robert Rintoul

The MesoVATS trial is an open-label, parallel-group, multicenter trial that included 175 patients with malignant pleural mesothelioma and pleural effusion. Patients were randomized to either partial pleurectomy (n = 87) or talc pleurodesis with slurry or poudrage (n = 88).

At 1 year, survival rates were 57% in patients who received talc pleurodesis and 52% in those randomized to pleurectomy (hazard ratio, 1.03; 95% confidence interval, 0.76-1.42; P = .83).

In the secondary outcome measures, however, pleural effusion was controlled at 1 month in 37% of patients in the talc group and in 59% of patients in the pleurectomy group (P = .008). At 6 months, pleural effusion was controlled in 57% of talc and 76% of pleurectomy patients (P = .04). Control of pleural effusion did not significantly differ at 9 and 12 months.

The EQ-5D quality-of-life measure was significantly improved with pleurectomy versus talc at 6 months (mean difference, 0.08 [95% CI, 0.003-0.16; P = .042]). Quality of life at 12 months also was significantly better with pleurectomy, but this finding became nonsignificant after adjustment for bias due to missing data.

Median hospital stay was significantly longer in the pleurectomy group (8 vs. 6 days; P < .001), and complications such as prolonged air leak were seen in 26% of those in the surgery arm and 8% of the talc arm (P = .009). The groups did not differ significantly in the incidence of serious adverse events.

Previous, nonrandomized research had suggested that pleurectomy may be associated with increased survival and better control of pleural effusion.

While the study failed to find a significant effect of surgery on the primary endpoint of survival at 12 months, the improvements in quality of life were particularly relevant for patients with malignant mesothelioma, said Dr. Rintoul, consultant respiratory physician at Papworth Hospital, Cambridge, England. "Quality of life in those last 12-13 months of life is very important, and [surgery] is something that is fairly well tolerated and doesn’t require a lot longer hospital stay."

Although the surgical procedure was more expensive than talc pleurodesis, Dr. Rintoul said it was worth giving patients the choice.

No relevant conflicts of interest were declared.

SYDNEY, AUSTRALIA – Video-assisted thoracoscopic partial pleurectomy significantly improved quality of life and control of pleural effusion compared with talc pleurodesis in patients with malignant mesothelioma in a randomized, controlled, multicenter trial.

However, pleurectomy did not increase overall survival in the study, based on data presented in a plenary session at a world conference on lung cancer.

"The problem we now have is, we’ve got a negative result and a positive result because of the primary endpoint, so detractors could say there’s a negative endpoint so there’s no role for surgery," lead researcher Dr. Robert Rintoul said in an interview at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

Courtesy Dr. Robert Rintoul

The MesoVATS trial is an open-label, parallel-group, multicenter trial that included 175 patients with malignant pleural mesothelioma and pleural effusion. Patients were randomized to either partial pleurectomy (n = 87) or talc pleurodesis with slurry or poudrage (n = 88).

At 1 year, survival rates were 57% in patients who received talc pleurodesis and 52% in those randomized to pleurectomy (hazard ratio, 1.03; 95% confidence interval, 0.76-1.42; P = .83).

In the secondary outcome measures, however, pleural effusion was controlled at 1 month in 37% of patients in the talc group and in 59% of patients in the pleurectomy group (P = .008). At 6 months, pleural effusion was controlled in 57% of talc and 76% of pleurectomy patients (P = .04). Control of pleural effusion did not significantly differ at 9 and 12 months.

The EQ-5D quality-of-life measure was significantly improved with pleurectomy versus talc at 6 months (mean difference, 0.08 [95% CI, 0.003-0.16; P = .042]). Quality of life at 12 months also was significantly better with pleurectomy, but this finding became nonsignificant after adjustment for bias due to missing data.

Median hospital stay was significantly longer in the pleurectomy group (8 vs. 6 days; P < .001), and complications such as prolonged air leak were seen in 26% of those in the surgery arm and 8% of the talc arm (P = .009). The groups did not differ significantly in the incidence of serious adverse events.

Previous, nonrandomized research had suggested that pleurectomy may be associated with increased survival and better control of pleural effusion.

While the study failed to find a significant effect of surgery on the primary endpoint of survival at 12 months, the improvements in quality of life were particularly relevant for patients with malignant mesothelioma, said Dr. Rintoul, consultant respiratory physician at Papworth Hospital, Cambridge, England. "Quality of life in those last 12-13 months of life is very important, and [surgery] is something that is fairly well tolerated and doesn’t require a lot longer hospital stay."

Although the surgical procedure was more expensive than talc pleurodesis, Dr. Rintoul said it was worth giving patients the choice.

No relevant conflicts of interest were declared.

SYDNEY, AUSTRALIA – Video-assisted thoracoscopic partial pleurectomy significantly improved quality of life and control of pleural effusion compared with talc pleurodesis in patients with malignant mesothelioma in a randomized, controlled, multicenter trial.

However, pleurectomy did not increase overall survival in the study, based on data presented in a plenary session at a world conference on lung cancer.

"The problem we now have is, we’ve got a negative result and a positive result because of the primary endpoint, so detractors could say there’s a negative endpoint so there’s no role for surgery," lead researcher Dr. Robert Rintoul said in an interview at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

Courtesy Dr. Robert Rintoul

The MesoVATS trial is an open-label, parallel-group, multicenter trial that included 175 patients with malignant pleural mesothelioma and pleural effusion. Patients were randomized to either partial pleurectomy (n = 87) or talc pleurodesis with slurry or poudrage (n = 88).

At 1 year, survival rates were 57% in patients who received talc pleurodesis and 52% in those randomized to pleurectomy (hazard ratio, 1.03; 95% confidence interval, 0.76-1.42; P = .83).

In the secondary outcome measures, however, pleural effusion was controlled at 1 month in 37% of patients in the talc group and in 59% of patients in the pleurectomy group (P = .008). At 6 months, pleural effusion was controlled in 57% of talc and 76% of pleurectomy patients (P = .04). Control of pleural effusion did not significantly differ at 9 and 12 months.

The EQ-5D quality-of-life measure was significantly improved with pleurectomy versus talc at 6 months (mean difference, 0.08 [95% CI, 0.003-0.16; P = .042]). Quality of life at 12 months also was significantly better with pleurectomy, but this finding became nonsignificant after adjustment for bias due to missing data.

Median hospital stay was significantly longer in the pleurectomy group (8 vs. 6 days; P < .001), and complications such as prolonged air leak were seen in 26% of those in the surgery arm and 8% of the talc arm (P = .009). The groups did not differ significantly in the incidence of serious adverse events.

Previous, nonrandomized research had suggested that pleurectomy may be associated with increased survival and better control of pleural effusion.

While the study failed to find a significant effect of surgery on the primary endpoint of survival at 12 months, the improvements in quality of life were particularly relevant for patients with malignant mesothelioma, said Dr. Rintoul, consultant respiratory physician at Papworth Hospital, Cambridge, England. "Quality of life in those last 12-13 months of life is very important, and [surgery] is something that is fairly well tolerated and doesn’t require a lot longer hospital stay."

Although the surgical procedure was more expensive than talc pleurodesis, Dr. Rintoul said it was worth giving patients the choice.

No relevant conflicts of interest were declared.

Mitral valve repair was no better than chordal-sparing mitral valve replacement in the first randomized clinical trial attempting to settle the controversy over which procedure is superior for treating functional ischemic mitral regurgitation, which was simultaneously reported at the annual scientific sessions of the American Heart Association and online Nov. 18 in the New England Journal of Medicine.

In the past few years, the use of mitral valve repair has far exceeded that of mitral valve replacement for this indication, largely on the basis of reports that the repair procedure yields lower operative mortality, improved left ventricular function, and higher long-term survival rates. In particular, a 2011 meta-analysis found a 35% lower relative risk of death in the long term with mitral valve repair, compared with replacement, said Dr. Michael A. Acker and his associates in the Cardiothoracic Surgical Trials Network (CTSN).

But in their multicenter study directly comparing the two procedures in 251 patients with severe functional ischemic mitral regurgitation, there was no significant difference between the surgeries in left ventricular end-systolic volume index at 1 year, nor in mortality at either 1 month or 1 year.

Moreover, study participants who underwent mitral valve repair showed a disturbing excess in the rate of recurrence of mitral regurgitation at 1 year, with a rate that was 30 percentage points higher than that among patients who underwent mitral valve replacement. "This lack of durability in correction of mitral regurgitation is disconcerting, given its reported association with further progression and long-term negative outcomes," said Dr. Acker of the division of cardiovascular surgery, University of Pennsylvania, Philadelphia, and his associates.

Functional ischemic mitral regurgitation, a "high-prevalence" condition affecting an estimated 2-3 million Americans, differs from primary degenerative mitral regurgitation in that the valve leaflets themselves remain normal while the defect occurs in the myocardium. "Ischemic mitral regurgitation is a consequence of adverse left ventricular remodeling after myocardial injury, with enlargement of the left ventricular chamber and mitral annulus, apical and lateral migration of the papillary muscles, leaflet retethering, and reduced closing forces.

"These processes lead to malcoaptation of the leaflets and variable degrees of mitral regurgitation that can fluctuate dynamically as a function of volume status, afterload, heart rhythm, and residual ischemia," the researchers said.

Current practice guidelines recommend mitral valve repair or chordal-sparing mitral valve replacement for severe regurgitation unresponsive to medical therapy, but do not specify which procedure is preferred because there is no conclusive evidence demonstrating the superiority of one over the other. "Recently, the field has embraced mitral valve repair over replacement," even without such evidence, Dr. Acker and his colleagues said.

The CTSN performed this study at 22 medical centers to assess the relative benefits of the two surgeries, with 126 patients randomized to undergo mitral valve repair and 125 to undergo replacement that included complete preservation of the subvalvular apparatus.

The primary endpoint was the degree of LV reverse remodeling, as measured by the left ventricular end-systolic volume index (LVESVI) on transthoracic echocardiography, at 1 year. The mean LVESVI was not significantly different between the repair group (54.6 mL per square meter) and the replacement group (60.7 mL per square meter), reflecting decreases of 6.6 mL per square meter and 6.8 mL per square meter, respectively, the investigators said (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1312808]).

The median between group difference in the change in LVESVI score after surgery also was not clinically significant.

However, 32.6% of patients who underwent mitral valve repair had a recurrence of regurgitation within 1 year, compared with only 2.3% of those who had mitral valve replacement. Three patients in the repair group required reoperation, compared with none in the replacement group.

There were no significant differences in cumulative mortality, 30-day postoperative mortality, or 1-year mortality between the two study groups, and no significant difference in a composite endpoint of major adverse cardiac or cerebrovascular events.

Rates of serious adverse events were similar, and the durations of hospitalization were similar between the two study groups, as were rates of readmission. All measures of quality of life and functional status on two different assessment tools also were similar.

"Our findings contradict much of the published literature on this topic, which reports several advantages to mitral valve repair over replacement, including lower operative mortality, improved left ventricular function, and higher rates of long-term survival," Dr. Acker and his associates noted.

The evolution of the valve replacement procedure, which now includes chordal sparing, "may account for the improved results we observed, as compared with previous studies, since the retention of the internal architectural support of the left ventricle may preserve contractile efficiency and reduce left ventricular dilatation and dysfunction," they said.

This study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Diseases and Stroke, and the Canadian Institutes of Health Research. Dr. Acker and his associates reported no financial conflicts of interest.

Mitral valve repair was no better than chordal-sparing mitral valve replacement in the first randomized clinical trial attempting to settle the controversy over which procedure is superior for treating functional ischemic mitral regurgitation, which was simultaneously reported at the annual scientific sessions of the American Heart Association and online Nov. 18 in the New England Journal of Medicine.

In the past few years, the use of mitral valve repair has far exceeded that of mitral valve replacement for this indication, largely on the basis of reports that the repair procedure yields lower operative mortality, improved left ventricular function, and higher long-term survival rates. In particular, a 2011 meta-analysis found a 35% lower relative risk of death in the long term with mitral valve repair, compared with replacement, said Dr. Michael A. Acker and his associates in the Cardiothoracic Surgical Trials Network (CTSN).

But in their multicenter study directly comparing the two procedures in 251 patients with severe functional ischemic mitral regurgitation, there was no significant difference between the surgeries in left ventricular end-systolic volume index at 1 year, nor in mortality at either 1 month or 1 year.

Moreover, study participants who underwent mitral valve repair showed a disturbing excess in the rate of recurrence of mitral regurgitation at 1 year, with a rate that was 30 percentage points higher than that among patients who underwent mitral valve replacement. "This lack of durability in correction of mitral regurgitation is disconcerting, given its reported association with further progression and long-term negative outcomes," said Dr. Acker of the division of cardiovascular surgery, University of Pennsylvania, Philadelphia, and his associates.

Functional ischemic mitral regurgitation, a "high-prevalence" condition affecting an estimated 2-3 million Americans, differs from primary degenerative mitral regurgitation in that the valve leaflets themselves remain normal while the defect occurs in the myocardium. "Ischemic mitral regurgitation is a consequence of adverse left ventricular remodeling after myocardial injury, with enlargement of the left ventricular chamber and mitral annulus, apical and lateral migration of the papillary muscles, leaflet retethering, and reduced closing forces.

"These processes lead to malcoaptation of the leaflets and variable degrees of mitral regurgitation that can fluctuate dynamically as a function of volume status, afterload, heart rhythm, and residual ischemia," the researchers said.

Current practice guidelines recommend mitral valve repair or chordal-sparing mitral valve replacement for severe regurgitation unresponsive to medical therapy, but do not specify which procedure is preferred because there is no conclusive evidence demonstrating the superiority of one over the other. "Recently, the field has embraced mitral valve repair over replacement," even without such evidence, Dr. Acker and his colleagues said.

The CTSN performed this study at 22 medical centers to assess the relative benefits of the two surgeries, with 126 patients randomized to undergo mitral valve repair and 125 to undergo replacement that included complete preservation of the subvalvular apparatus.

The primary endpoint was the degree of LV reverse remodeling, as measured by the left ventricular end-systolic volume index (LVESVI) on transthoracic echocardiography, at 1 year. The mean LVESVI was not significantly different between the repair group (54.6 mL per square meter) and the replacement group (60.7 mL per square meter), reflecting decreases of 6.6 mL per square meter and 6.8 mL per square meter, respectively, the investigators said (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1312808]).

The median between group difference in the change in LVESVI score after surgery also was not clinically significant.

However, 32.6% of patients who underwent mitral valve repair had a recurrence of regurgitation within 1 year, compared with only 2.3% of those who had mitral valve replacement. Three patients in the repair group required reoperation, compared with none in the replacement group.

There were no significant differences in cumulative mortality, 30-day postoperative mortality, or 1-year mortality between the two study groups, and no significant difference in a composite endpoint of major adverse cardiac or cerebrovascular events.

Rates of serious adverse events were similar, and the durations of hospitalization were similar between the two study groups, as were rates of readmission. All measures of quality of life and functional status on two different assessment tools also were similar.

"Our findings contradict much of the published literature on this topic, which reports several advantages to mitral valve repair over replacement, including lower operative mortality, improved left ventricular function, and higher rates of long-term survival," Dr. Acker and his associates noted.

The evolution of the valve replacement procedure, which now includes chordal sparing, "may account for the improved results we observed, as compared with previous studies, since the retention of the internal architectural support of the left ventricle may preserve contractile efficiency and reduce left ventricular dilatation and dysfunction," they said.

This study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Diseases and Stroke, and the Canadian Institutes of Health Research. Dr. Acker and his associates reported no financial conflicts of interest.

Mitral valve repair was no better than chordal-sparing mitral valve replacement in the first randomized clinical trial attempting to settle the controversy over which procedure is superior for treating functional ischemic mitral regurgitation, which was simultaneously reported at the annual scientific sessions of the American Heart Association and online Nov. 18 in the New England Journal of Medicine.

In the past few years, the use of mitral valve repair has far exceeded that of mitral valve replacement for this indication, largely on the basis of reports that the repair procedure yields lower operative mortality, improved left ventricular function, and higher long-term survival rates. In particular, a 2011 meta-analysis found a 35% lower relative risk of death in the long term with mitral valve repair, compared with replacement, said Dr. Michael A. Acker and his associates in the Cardiothoracic Surgical Trials Network (CTSN).

But in their multicenter study directly comparing the two procedures in 251 patients with severe functional ischemic mitral regurgitation, there was no significant difference between the surgeries in left ventricular end-systolic volume index at 1 year, nor in mortality at either 1 month or 1 year.

Moreover, study participants who underwent mitral valve repair showed a disturbing excess in the rate of recurrence of mitral regurgitation at 1 year, with a rate that was 30 percentage points higher than that among patients who underwent mitral valve replacement. "This lack of durability in correction of mitral regurgitation is disconcerting, given its reported association with further progression and long-term negative outcomes," said Dr. Acker of the division of cardiovascular surgery, University of Pennsylvania, Philadelphia, and his associates.

Functional ischemic mitral regurgitation, a "high-prevalence" condition affecting an estimated 2-3 million Americans, differs from primary degenerative mitral regurgitation in that the valve leaflets themselves remain normal while the defect occurs in the myocardium. "Ischemic mitral regurgitation is a consequence of adverse left ventricular remodeling after myocardial injury, with enlargement of the left ventricular chamber and mitral annulus, apical and lateral migration of the papillary muscles, leaflet retethering, and reduced closing forces.

"These processes lead to malcoaptation of the leaflets and variable degrees of mitral regurgitation that can fluctuate dynamically as a function of volume status, afterload, heart rhythm, and residual ischemia," the researchers said.

Current practice guidelines recommend mitral valve repair or chordal-sparing mitral valve replacement for severe regurgitation unresponsive to medical therapy, but do not specify which procedure is preferred because there is no conclusive evidence demonstrating the superiority of one over the other. "Recently, the field has embraced mitral valve repair over replacement," even without such evidence, Dr. Acker and his colleagues said.

The CTSN performed this study at 22 medical centers to assess the relative benefits of the two surgeries, with 126 patients randomized to undergo mitral valve repair and 125 to undergo replacement that included complete preservation of the subvalvular apparatus.

The primary endpoint was the degree of LV reverse remodeling, as measured by the left ventricular end-systolic volume index (LVESVI) on transthoracic echocardiography, at 1 year. The mean LVESVI was not significantly different between the repair group (54.6 mL per square meter) and the replacement group (60.7 mL per square meter), reflecting decreases of 6.6 mL per square meter and 6.8 mL per square meter, respectively, the investigators said (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1312808]).

The median between group difference in the change in LVESVI score after surgery also was not clinically significant.

However, 32.6% of patients who underwent mitral valve repair had a recurrence of regurgitation within 1 year, compared with only 2.3% of those who had mitral valve replacement. Three patients in the repair group required reoperation, compared with none in the replacement group.

There were no significant differences in cumulative mortality, 30-day postoperative mortality, or 1-year mortality between the two study groups, and no significant difference in a composite endpoint of major adverse cardiac or cerebrovascular events.

Rates of serious adverse events were similar, and the durations of hospitalization were similar between the two study groups, as were rates of readmission. All measures of quality of life and functional status on two different assessment tools also were similar.

"Our findings contradict much of the published literature on this topic, which reports several advantages to mitral valve repair over replacement, including lower operative mortality, improved left ventricular function, and higher rates of long-term survival," Dr. Acker and his associates noted.

The evolution of the valve replacement procedure, which now includes chordal sparing, "may account for the improved results we observed, as compared with previous studies, since the retention of the internal architectural support of the left ventricle may preserve contractile efficiency and reduce left ventricular dilatation and dysfunction," they said.

This study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Diseases and Stroke, and the Canadian Institutes of Health Research. Dr. Acker and his associates reported no financial conflicts of interest.

Postmarket outcomes with the first commercially available U.S. transcatheter aortic valve replacement device are comparable with randomized trial and international registry experience, national registry results suggest.

The Edwards LifeSciences Sapien XT valve was successfully implanted in 92% of 7,710 TAVR patients, two-thirds with a transfemoral approach.

The primary outcomes of in-hospital all-cause mortality and stroke were 5.5% and 2%, respectively, Dr. Michael J. Mack reported at the American Heart Association scientific sessions.

Conversion to open-heart surgery was needed in only 1% of patients, but associated with a 49% incidence of in-hospital mortality.

Major bleeding and vascular complications were relatively low, at 3.5% and 6.4%, respectively, despite the overall lack of experience and use of larger sheath delivery systems. Acute renal insufficiency occurred in 5.5% of patients.

The 30-day death and stroke rates were 7.6% and 2.8% among 3,113 patients with sufficient follow-up. Most deaths were due to noncardiovascular causes, he noted.

This is the first public report from the national Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry, and comes amid calls for increased postmarket surveillance of high-risk medical devices.

The results also help address whether outcomes after a controlled commercial rollout of the first-generation valve hold up to those from clinical trials and the global TAVR experience, now based on second- and third-generation devices, according to Dr. Mack, past STS president and director of cardiovascular research and medicine at the Heart Hospital Baylor Plano in Plano, Texas.

The Food and Drug Administration initially approved the Edwards valve for severe, symptomatic aortic stenosis in inoperable patients in 2011 and expanded its label in September 2012 to include operable, high-risk patients using either a transfemoral or transapical approach.

The TVT analysis comprised 1,559 inoperable and 6,151 high-risk, operable patients who underwent TAVR at 224 participating registry hospitals from November 2011 to May 2013. Their median STS predicted risk of operative mortality (PROM) was 7%, but varied widely from 1.2% to 17.4%. Their median age was 84 years.

The risk profile of patients was generally lower in the registry than in randomized trials and European reports, and may have contributed to the good outcomes, Dr. Mack acknowledged. The mean PROM was 11.2% among inoperable patients and 11.8% among high-risk, operable patients in the pivotal PARTNER trial, which was used for the device’s approval.

Although incomplete data may have been entered into the risk calculator, the other plausible explanation is "risk creep," or that patients with lower surgical risk are being treated with the less-invasive procedure, leading to better outcomes, he noted.

Other possible contributors to the registry outcomes include a shorter U.S. learning curve due to international collaboration, inclusion of at least 35 highly experienced PARTNER study centers in the registry, and mandated training by the manufacturer including a company employed clinical specialist during all procedures.

Still, the results stack up well. Germany, which has led the TAVR revolution, had an in-hospital mortality of 5.1% with a transfemoral approach and 7.7% with a transapical approach in 2011 in the German Aortic Valve Registry.

In the PARTNER trial, 30-day mortality was 5% among inoperable patients, 3.7% among high-risk, operable patients by a transfemoral approach, and 8.7% among high-risk, operable patients by a transapical approach.

This compares with 30-day mortality rates of 6.1%, 4.6%, and 9.8%, respectively, in the TVT registry, Dr. Mack reported.

The TVT registry captured an estimated 88% of TAVR procedures performed between May 2012, when the Centers for Medicare and Medicaid Services issued its national coverage determination, and the end of the study. Notably, 30-day outcomes were reported from only 114 hospitals or 51% of the 244 hospitals in the registry. The results were published simultaneously with Dr. Mack’s presentation (JAMA 2013;310:2069-77. doi:10.1001/jama/2013.282043).

More complete long-term outcomes at 30 days and 1 year are needed to have a more comprehensive assessment of TAVR outcomes in the United States, Dr. Mack cautioned. Patient health status and quality of life outcomes will also be addressed in subsequent reports.

So far, it’s known that most (63%) patients were discharged home, 6% experienced new-onset atrial fibrillation, and 6.6% needed a new permanent pacemaker or implantable cardioverter-defibrillator.

The study was funded by the American College of Cardiology Foundation and the Society of Thoracic Surgeons. Dr. Mack reported no other disclosures; a co-author reported travel support from the STS and a second reported consulting for Janssen, Boehringer Ingelheim, and Sanofi.

[email protected]

Postmarket outcomes with the first commercially available U.S. transcatheter aortic valve replacement device are comparable with randomized trial and international registry experience, national registry results suggest.

The Edwards LifeSciences Sapien XT valve was successfully implanted in 92% of 7,710 TAVR patients, two-thirds with a transfemoral approach.

The primary outcomes of in-hospital all-cause mortality and stroke were 5.5% and 2%, respectively, Dr. Michael J. Mack reported at the American Heart Association scientific sessions.

Conversion to open-heart surgery was needed in only 1% of patients, but associated with a 49% incidence of in-hospital mortality.

Major bleeding and vascular complications were relatively low, at 3.5% and 6.4%, respectively, despite the overall lack of experience and use of larger sheath delivery systems. Acute renal insufficiency occurred in 5.5% of patients.

The 30-day death and stroke rates were 7.6% and 2.8% among 3,113 patients with sufficient follow-up. Most deaths were due to noncardiovascular causes, he noted.

This is the first public report from the national Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry, and comes amid calls for increased postmarket surveillance of high-risk medical devices.

The results also help address whether outcomes after a controlled commercial rollout of the first-generation valve hold up to those from clinical trials and the global TAVR experience, now based on second- and third-generation devices, according to Dr. Mack, past STS president and director of cardiovascular research and medicine at the Heart Hospital Baylor Plano in Plano, Texas.

The Food and Drug Administration initially approved the Edwards valve for severe, symptomatic aortic stenosis in inoperable patients in 2011 and expanded its label in September 2012 to include operable, high-risk patients using either a transfemoral or transapical approach.

The TVT analysis comprised 1,559 inoperable and 6,151 high-risk, operable patients who underwent TAVR at 224 participating registry hospitals from November 2011 to May 2013. Their median STS predicted risk of operative mortality (PROM) was 7%, but varied widely from 1.2% to 17.4%. Their median age was 84 years.

The risk profile of patients was generally lower in the registry than in randomized trials and European reports, and may have contributed to the good outcomes, Dr. Mack acknowledged. The mean PROM was 11.2% among inoperable patients and 11.8% among high-risk, operable patients in the pivotal PARTNER trial, which was used for the device’s approval.

Although incomplete data may have been entered into the risk calculator, the other plausible explanation is "risk creep," or that patients with lower surgical risk are being treated with the less-invasive procedure, leading to better outcomes, he noted.

Other possible contributors to the registry outcomes include a shorter U.S. learning curve due to international collaboration, inclusion of at least 35 highly experienced PARTNER study centers in the registry, and mandated training by the manufacturer including a company employed clinical specialist during all procedures.

Still, the results stack up well. Germany, which has led the TAVR revolution, had an in-hospital mortality of 5.1% with a transfemoral approach and 7.7% with a transapical approach in 2011 in the German Aortic Valve Registry.

In the PARTNER trial, 30-day mortality was 5% among inoperable patients, 3.7% among high-risk, operable patients by a transfemoral approach, and 8.7% among high-risk, operable patients by a transapical approach.

This compares with 30-day mortality rates of 6.1%, 4.6%, and 9.8%, respectively, in the TVT registry, Dr. Mack reported.

The TVT registry captured an estimated 88% of TAVR procedures performed between May 2012, when the Centers for Medicare and Medicaid Services issued its national coverage determination, and the end of the study. Notably, 30-day outcomes were reported from only 114 hospitals or 51% of the 244 hospitals in the registry. The results were published simultaneously with Dr. Mack’s presentation (JAMA 2013;310:2069-77. doi:10.1001/jama/2013.282043).

More complete long-term outcomes at 30 days and 1 year are needed to have a more comprehensive assessment of TAVR outcomes in the United States, Dr. Mack cautioned. Patient health status and quality of life outcomes will also be addressed in subsequent reports.

So far, it’s known that most (63%) patients were discharged home, 6% experienced new-onset atrial fibrillation, and 6.6% needed a new permanent pacemaker or implantable cardioverter-defibrillator.

The study was funded by the American College of Cardiology Foundation and the Society of Thoracic Surgeons. Dr. Mack reported no other disclosures; a co-author reported travel support from the STS and a second reported consulting for Janssen, Boehringer Ingelheim, and Sanofi.

[email protected]

Postmarket outcomes with the first commercially available U.S. transcatheter aortic valve replacement device are comparable with randomized trial and international registry experience, national registry results suggest.

The Edwards LifeSciences Sapien XT valve was successfully implanted in 92% of 7,710 TAVR patients, two-thirds with a transfemoral approach.

The primary outcomes of in-hospital all-cause mortality and stroke were 5.5% and 2%, respectively, Dr. Michael J. Mack reported at the American Heart Association scientific sessions.

Conversion to open-heart surgery was needed in only 1% of patients, but associated with a 49% incidence of in-hospital mortality.

Major bleeding and vascular complications were relatively low, at 3.5% and 6.4%, respectively, despite the overall lack of experience and use of larger sheath delivery systems. Acute renal insufficiency occurred in 5.5% of patients.

The 30-day death and stroke rates were 7.6% and 2.8% among 3,113 patients with sufficient follow-up. Most deaths were due to noncardiovascular causes, he noted.

This is the first public report from the national Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry, and comes amid calls for increased postmarket surveillance of high-risk medical devices.

The results also help address whether outcomes after a controlled commercial rollout of the first-generation valve hold up to those from clinical trials and the global TAVR experience, now based on second- and third-generation devices, according to Dr. Mack, past STS president and director of cardiovascular research and medicine at the Heart Hospital Baylor Plano in Plano, Texas.

The Food and Drug Administration initially approved the Edwards valve for severe, symptomatic aortic stenosis in inoperable patients in 2011 and expanded its label in September 2012 to include operable, high-risk patients using either a transfemoral or transapical approach.

The TVT analysis comprised 1,559 inoperable and 6,151 high-risk, operable patients who underwent TAVR at 224 participating registry hospitals from November 2011 to May 2013. Their median STS predicted risk of operative mortality (PROM) was 7%, but varied widely from 1.2% to 17.4%. Their median age was 84 years.

The risk profile of patients was generally lower in the registry than in randomized trials and European reports, and may have contributed to the good outcomes, Dr. Mack acknowledged. The mean PROM was 11.2% among inoperable patients and 11.8% among high-risk, operable patients in the pivotal PARTNER trial, which was used for the device’s approval.

Although incomplete data may have been entered into the risk calculator, the other plausible explanation is "risk creep," or that patients with lower surgical risk are being treated with the less-invasive procedure, leading to better outcomes, he noted.

Other possible contributors to the registry outcomes include a shorter U.S. learning curve due to international collaboration, inclusion of at least 35 highly experienced PARTNER study centers in the registry, and mandated training by the manufacturer including a company employed clinical specialist during all procedures.

Still, the results stack up well. Germany, which has led the TAVR revolution, had an in-hospital mortality of 5.1% with a transfemoral approach and 7.7% with a transapical approach in 2011 in the German Aortic Valve Registry.

In the PARTNER trial, 30-day mortality was 5% among inoperable patients, 3.7% among high-risk, operable patients by a transfemoral approach, and 8.7% among high-risk, operable patients by a transapical approach.

This compares with 30-day mortality rates of 6.1%, 4.6%, and 9.8%, respectively, in the TVT registry, Dr. Mack reported.

The TVT registry captured an estimated 88% of TAVR procedures performed between May 2012, when the Centers for Medicare and Medicaid Services issued its national coverage determination, and the end of the study. Notably, 30-day outcomes were reported from only 114 hospitals or 51% of the 244 hospitals in the registry. The results were published simultaneously with Dr. Mack’s presentation (JAMA 2013;310:2069-77. doi:10.1001/jama/2013.282043).

More complete long-term outcomes at 30 days and 1 year are needed to have a more comprehensive assessment of TAVR outcomes in the United States, Dr. Mack cautioned. Patient health status and quality of life outcomes will also be addressed in subsequent reports.

So far, it’s known that most (63%) patients were discharged home, 6% experienced new-onset atrial fibrillation, and 6.6% needed a new permanent pacemaker or implantable cardioverter-defibrillator.

The study was funded by the American College of Cardiology Foundation and the Society of Thoracic Surgeons. Dr. Mack reported no other disclosures; a co-author reported travel support from the STS and a second reported consulting for Janssen, Boehringer Ingelheim, and Sanofi.

[email protected]

CHICAGO – One in three patients sent to surgery for a suspicious lung nodule by their community pulmonologist did not have cancer in a retrospective analysis of 385 patients.

In addition, half of patients with benign disease underwent an invasive procedure, Dr. Nichole Tanner said at the annual meeting of the American College of Chest Physicians (ACCP).

Physician judgment plays a key role in the newly updated ACCP lung cancer guidelines (Chest 2013;143:e93S-e120S). They recommend that clinicians estimate the pretest probability of malignancy for indeterminate nodules larger than 8 mm either qualitatively by using their clinical judgment and/or quantitatively with a validated risk model.

Patients in the study, conducted at 16 sites across the country, had 8- to 20-mm nodules, and were mostly former (45%) or current smokers (27.5%), white (86%), and covered by private insurance (55.3%) or Medicare (38.2%). Their average age was 64.5 years.

Invasive procedures included anything outside of simple imaging for monitoring. Computed tomography (CT)- and bronchoscopic-guided biopsy were considered minor invasive procedures, while major invasive procedures included any surgical procedure such as mediastinoscopy, thoracotomy, and video-assisted thorascopic surgery (VATS).

Monitoring only was used for 184 patients, and ran the gamut from one to a "shocking seven" CT or positron-emission tomography (PET) scans in 2 years, said Dr. Tanner, with the Medical University of South Carolina, Charleston. None of these nodules were malignant.

Of the 124 nodules biopsied, 35% were malignant, 56% were diagnosed as benign, and 8% were benign based on stability.

Of the 77 nodules surgically removed, 64% were malignant and 36% were benign, she said.

While a reassuring 76% of nodules seen by community pulmonologists were benign, the results highlight the complexity involved in managing a patient population that is surely on the rise as lung cancer screening spreads nationally.

During a rousing debate that followed the presentation, audience members expressed concern over the 36% of patients taken to surgery for benign disease, highlighting a 3% death rate associated with thoracotomy and the potential for reduced lung function after surgery.

Others, including a thoracic surgeon, countered that removal of a suspicious nodule can catch lung disease at an earlier stage, eliminates the need for repeat CT/PET imaging exposure, and is requested by some patients for their peace of mind or even to pass a pre-employment physical.

Session comoderator and interventional respirologist Dr. Anne Gonzalez, with McGill University Health Center, Montreal, said in an interview, "I was perhaps shocked there were so many [patients] that went directly to surgery, but on the other hand, the guidelines do recommend that if the suspicion of lung cancer is high enough – 65% – patients should go to surgery."

Dr. Gonzalez also echoed comments from the floor that, importantly, the study failed to detail whether patients’ nodules were identified as incidental findings or were the result of symptom-driven screening.

In a multivariate analysis, current smoking (odds ratio, 3.28) and larger nodule size (12-15 mm: OR, 3.30; 16-20 mm: OR, 4.97) influenced who underwent invasive procedures, Dr. Tanner said. Geographic region of the country did not pan out as a predictor.

Cancer was present in 39% of 16- to 20-mm nodules and 31% of 12- to 15-mm nodules, compared with 12% of 8- to 11-mm nodules.

One attendee commented that the number of patients undergoing surgery for benign disease at his institution has dramatically declined with the establishment of a 45-member multidisciplinary tumor board to review and manage patients with lung nodules.

This approach is helpful in that patients won’t be lost to follow-up and can be presented with a plan that has the support of multiple physicians, but "I don’t see this as a feasible way with which to manage every pulmonary nodule," Dr. Tanner said in an interview. "In the lung cancer screening program we’re implementing at our Veterans Affairs hospital in the very near future, we will have a nodule tracking system to ensure that no patients are lost to follow-up and will make treatment and diagnostic decisions based on the Fleischner criteria for radiographic follow-up of lung nodules, as well as the ACCP guidelines."

Dr. Tanner reported consulting for the study sponsor, Integrated Diagnostics.

[email protected]

CHICAGO – One in three patients sent to surgery for a suspicious lung nodule by their community pulmonologist did not have cancer in a retrospective analysis of 385 patients.

In addition, half of patients with benign disease underwent an invasive procedure, Dr. Nichole Tanner said at the annual meeting of the American College of Chest Physicians (ACCP).

Physician judgment plays a key role in the newly updated ACCP lung cancer guidelines (Chest 2013;143:e93S-e120S). They recommend that clinicians estimate the pretest probability of malignancy for indeterminate nodules larger than 8 mm either qualitatively by using their clinical judgment and/or quantitatively with a validated risk model.

Patients in the study, conducted at 16 sites across the country, had 8- to 20-mm nodules, and were mostly former (45%) or current smokers (27.5%), white (86%), and covered by private insurance (55.3%) or Medicare (38.2%). Their average age was 64.5 years.

Invasive procedures included anything outside of simple imaging for monitoring. Computed tomography (CT)- and bronchoscopic-guided biopsy were considered minor invasive procedures, while major invasive procedures included any surgical procedure such as mediastinoscopy, thoracotomy, and video-assisted thorascopic surgery (VATS).

Monitoring only was used for 184 patients, and ran the gamut from one to a "shocking seven" CT or positron-emission tomography (PET) scans in 2 years, said Dr. Tanner, with the Medical University of South Carolina, Charleston. None of these nodules were malignant.

Of the 124 nodules biopsied, 35% were malignant, 56% were diagnosed as benign, and 8% were benign based on stability.

Of the 77 nodules surgically removed, 64% were malignant and 36% were benign, she said.

While a reassuring 76% of nodules seen by community pulmonologists were benign, the results highlight the complexity involved in managing a patient population that is surely on the rise as lung cancer screening spreads nationally.

During a rousing debate that followed the presentation, audience members expressed concern over the 36% of patients taken to surgery for benign disease, highlighting a 3% death rate associated with thoracotomy and the potential for reduced lung function after surgery.

Others, including a thoracic surgeon, countered that removal of a suspicious nodule can catch lung disease at an earlier stage, eliminates the need for repeat CT/PET imaging exposure, and is requested by some patients for their peace of mind or even to pass a pre-employment physical.

Session comoderator and interventional respirologist Dr. Anne Gonzalez, with McGill University Health Center, Montreal, said in an interview, "I was perhaps shocked there were so many [patients] that went directly to surgery, but on the other hand, the guidelines do recommend that if the suspicion of lung cancer is high enough – 65% – patients should go to surgery."

Dr. Gonzalez also echoed comments from the floor that, importantly, the study failed to detail whether patients’ nodules were identified as incidental findings or were the result of symptom-driven screening.

In a multivariate analysis, current smoking (odds ratio, 3.28) and larger nodule size (12-15 mm: OR, 3.30; 16-20 mm: OR, 4.97) influenced who underwent invasive procedures, Dr. Tanner said. Geographic region of the country did not pan out as a predictor.

Cancer was present in 39% of 16- to 20-mm nodules and 31% of 12- to 15-mm nodules, compared with 12% of 8- to 11-mm nodules.

One attendee commented that the number of patients undergoing surgery for benign disease at his institution has dramatically declined with the establishment of a 45-member multidisciplinary tumor board to review and manage patients with lung nodules.

This approach is helpful in that patients won’t be lost to follow-up and can be presented with a plan that has the support of multiple physicians, but "I don’t see this as a feasible way with which to manage every pulmonary nodule," Dr. Tanner said in an interview. "In the lung cancer screening program we’re implementing at our Veterans Affairs hospital in the very near future, we will have a nodule tracking system to ensure that no patients are lost to follow-up and will make treatment and diagnostic decisions based on the Fleischner criteria for radiographic follow-up of lung nodules, as well as the ACCP guidelines."

Dr. Tanner reported consulting for the study sponsor, Integrated Diagnostics.

[email protected]

CHICAGO – One in three patients sent to surgery for a suspicious lung nodule by their community pulmonologist did not have cancer in a retrospective analysis of 385 patients.

In addition, half of patients with benign disease underwent an invasive procedure, Dr. Nichole Tanner said at the annual meeting of the American College of Chest Physicians (ACCP).

Physician judgment plays a key role in the newly updated ACCP lung cancer guidelines (Chest 2013;143:e93S-e120S). They recommend that clinicians estimate the pretest probability of malignancy for indeterminate nodules larger than 8 mm either qualitatively by using their clinical judgment and/or quantitatively with a validated risk model.

Patients in the study, conducted at 16 sites across the country, had 8- to 20-mm nodules, and were mostly former (45%) or current smokers (27.5%), white (86%), and covered by private insurance (55.3%) or Medicare (38.2%). Their average age was 64.5 years.

Invasive procedures included anything outside of simple imaging for monitoring. Computed tomography (CT)- and bronchoscopic-guided biopsy were considered minor invasive procedures, while major invasive procedures included any surgical procedure such as mediastinoscopy, thoracotomy, and video-assisted thorascopic surgery (VATS).

Monitoring only was used for 184 patients, and ran the gamut from one to a "shocking seven" CT or positron-emission tomography (PET) scans in 2 years, said Dr. Tanner, with the Medical University of South Carolina, Charleston. None of these nodules were malignant.

Of the 124 nodules biopsied, 35% were malignant, 56% were diagnosed as benign, and 8% were benign based on stability.

Of the 77 nodules surgically removed, 64% were malignant and 36% were benign, she said.

While a reassuring 76% of nodules seen by community pulmonologists were benign, the results highlight the complexity involved in managing a patient population that is surely on the rise as lung cancer screening spreads nationally.

During a rousing debate that followed the presentation, audience members expressed concern over the 36% of patients taken to surgery for benign disease, highlighting a 3% death rate associated with thoracotomy and the potential for reduced lung function after surgery.

Others, including a thoracic surgeon, countered that removal of a suspicious nodule can catch lung disease at an earlier stage, eliminates the need for repeat CT/PET imaging exposure, and is requested by some patients for their peace of mind or even to pass a pre-employment physical.

Session comoderator and interventional respirologist Dr. Anne Gonzalez, with McGill University Health Center, Montreal, said in an interview, "I was perhaps shocked there were so many [patients] that went directly to surgery, but on the other hand, the guidelines do recommend that if the suspicion of lung cancer is high enough – 65% – patients should go to surgery."

Dr. Gonzalez also echoed comments from the floor that, importantly, the study failed to detail whether patients’ nodules were identified as incidental findings or were the result of symptom-driven screening.

In a multivariate analysis, current smoking (odds ratio, 3.28) and larger nodule size (12-15 mm: OR, 3.30; 16-20 mm: OR, 4.97) influenced who underwent invasive procedures, Dr. Tanner said. Geographic region of the country did not pan out as a predictor.

Cancer was present in 39% of 16- to 20-mm nodules and 31% of 12- to 15-mm nodules, compared with 12% of 8- to 11-mm nodules.

One attendee commented that the number of patients undergoing surgery for benign disease at his institution has dramatically declined with the establishment of a 45-member multidisciplinary tumor board to review and manage patients with lung nodules.

This approach is helpful in that patients won’t be lost to follow-up and can be presented with a plan that has the support of multiple physicians, but "I don’t see this as a feasible way with which to manage every pulmonary nodule," Dr. Tanner said in an interview. "In the lung cancer screening program we’re implementing at our Veterans Affairs hospital in the very near future, we will have a nodule tracking system to ensure that no patients are lost to follow-up and will make treatment and diagnostic decisions based on the Fleischner criteria for radiographic follow-up of lung nodules, as well as the ACCP guidelines."

Dr. Tanner reported consulting for the study sponsor, Integrated Diagnostics.

[email protected]

CHICAGO – Taking a personalized approach to treating dyspnea will result in better outcomes, and will make choosing between surgical and the increasing number of nonsurgical techniques an easier process, according to Dr. Frank Sciurba, a presenter at the annual meeting of the American College of Chest Physicians.

In a talk that reviewed current and trial surgical and bronchoscopic treatments of dyspnea in chronic obstructive pulmonary disease, Dr. Sciurba said, "Just treating diseases that are now naively classified as COPD or [interstitial lung disease] is not enough. We can instead look at variations within those diseases that may or may not be responsive to different therapies."

For example, because the Impact of Heterogeneity on Outcome Following Endobronchial Valves (VENT) trial data showed that fissure integrity (collateral tracts) significantly influenced target and adjacent lobe volume changes, Dr. Sciurba said that medical device manufacturers have begun to develop technologies that are more specific to the patient.

Straight nitinol coils (PneumRx), which are placed bronchoscopically, are implanted in stages, and according to collateral tracts. "The concept is to target the most affected areas of the lung, allowing regional expansion of the least affected lung. It’s not dependent on just lobar re-expansion," said Dr. Sciurba, director of the emphysema research center at the University of Pittsburgh Medical Center. 

Pilot trial data for this technique published in CHEST earlier this year showed that patients (n = 56) had a 17.5% improvement in forced expiratory volume in 1 second (FEV₁) and a greater than 10% drop in residual volume, and clinical meaningful improvements in 6-minute walk distances at more than a 28% improvement from baseline: 73% had a greater than 25 meter improvement at 6 months post treatment.

The hydro-gel foam, AeriSeal (Aeris) is another bronchoscopic technique currently undergoing a small (n = 20) pilot trial. After fibrinogen was eliminated from the sealant, this polymeric lung volume reduction technology was cleared by the Food and Drug Administration for testing in humans.

The sealant is administered into specific subsegments of the lungs, where the foam adheres to surrounding tissues; air and water in the foam are reabsorbed when collapse occurs, with durable absorption in atelectasis.

The results will soon be published, although Dr. Sciurba said that at this point, "the mechanical benefits seem to exceed the symptomatic benefits," but that a trial in a larger population would produce more definitive results.

Other factors to consider include "understanding the pulmonary physiologic interaction in lung volume reduction, and how that translates downstream, and the importance of linking the mechanical intervention with pulmonary rehab."

Expanding the ‘tool chest’

In determining whether bronchoscopic solutions can achieve the same benefits of surgical ones, while also minimizing adverse effects, Dr. Sciurba said, the FDA is beginning to take a more personalized view when approving trials, which he hopes will increase the "tool chest" available to physicians.

Clinical trials going forward may need to consider selection criteria such as interlobar collaterals, regional emphysema heterogeneity, and the degree of hyperinflation, as well as the most relevant outcomes when determining adverse events, Dr. Sciurba said.

Whether therapies are reversible also will be relevant, and will have an impact on future criteria for lung volume reduction surgery and transplant candidacy.

"If we actually look in a little more detail and start to classify these patients both on physiologic and clinical patterns, and as we evolve, on genetic patterns and molecular patterns, we will isolate groups of patients who are home run responders from those in whom certain therapies may not be cost effective."

Dr. Sciurba disclosed that he has received support from AstraZeneca, GlaxoSmithKline, Pfizer, and other companies, as well as grant monies from the National Institutes of Health and the University of Pittsburgh.

[email protected]

CHICAGO – Taking a personalized approach to treating dyspnea will result in better outcomes, and will make choosing between surgical and the increasing number of nonsurgical techniques an easier process, according to Dr. Frank Sciurba, a presenter at the annual meeting of the American College of Chest Physicians.

In a talk that reviewed current and trial surgical and bronchoscopic treatments of dyspnea in chronic obstructive pulmonary disease, Dr. Sciurba said, "Just treating diseases that are now naively classified as COPD or [interstitial lung disease] is not enough. We can instead look at variations within those diseases that may or may not be responsive to different therapies."

For example, because the Impact of Heterogeneity on Outcome Following Endobronchial Valves (VENT) trial data showed that fissure integrity (collateral tracts) significantly influenced target and adjacent lobe volume changes, Dr. Sciurba said that medical device manufacturers have begun to develop technologies that are more specific to the patient.

Straight nitinol coils (PneumRx), which are placed bronchoscopically, are implanted in stages, and according to collateral tracts. "The concept is to target the most affected areas of the lung, allowing regional expansion of the least affected lung. It’s not dependent on just lobar re-expansion," said Dr. Sciurba, director of the emphysema research center at the University of Pittsburgh Medical Center. 

Pilot trial data for this technique published in CHEST earlier this year showed that patients (n = 56) had a 17.5% improvement in forced expiratory volume in 1 second (FEV₁) and a greater than 10% drop in residual volume, and clinical meaningful improvements in 6-minute walk distances at more than a 28% improvement from baseline: 73% had a greater than 25 meter improvement at 6 months post treatment.

The hydro-gel foam, AeriSeal (Aeris) is another bronchoscopic technique currently undergoing a small (n = 20) pilot trial. After fibrinogen was eliminated from the sealant, this polymeric lung volume reduction technology was cleared by the Food and Drug Administration for testing in humans.

The sealant is administered into specific subsegments of the lungs, where the foam adheres to surrounding tissues; air and water in the foam are reabsorbed when collapse occurs, with durable absorption in atelectasis.

The results will soon be published, although Dr. Sciurba said that at this point, "the mechanical benefits seem to exceed the symptomatic benefits," but that a trial in a larger population would produce more definitive results.

Other factors to consider include "understanding the pulmonary physiologic interaction in lung volume reduction, and how that translates downstream, and the importance of linking the mechanical intervention with pulmonary rehab."

Expanding the ‘tool chest’

In determining whether bronchoscopic solutions can achieve the same benefits of surgical ones, while also minimizing adverse effects, Dr. Sciurba said, the FDA is beginning to take a more personalized view when approving trials, which he hopes will increase the "tool chest" available to physicians.

Clinical trials going forward may need to consider selection criteria such as interlobar collaterals, regional emphysema heterogeneity, and the degree of hyperinflation, as well as the most relevant outcomes when determining adverse events, Dr. Sciurba said.

Whether therapies are reversible also will be relevant, and will have an impact on future criteria for lung volume reduction surgery and transplant candidacy.

"If we actually look in a little more detail and start to classify these patients both on physiologic and clinical patterns, and as we evolve, on genetic patterns and molecular patterns, we will isolate groups of patients who are home run responders from those in whom certain therapies may not be cost effective."

Dr. Sciurba disclosed that he has received support from AstraZeneca, GlaxoSmithKline, Pfizer, and other companies, as well as grant monies from the National Institutes of Health and the University of Pittsburgh.

[email protected]

CHICAGO – Taking a personalized approach to treating dyspnea will result in better outcomes, and will make choosing between surgical and the increasing number of nonsurgical techniques an easier process, according to Dr. Frank Sciurba, a presenter at the annual meeting of the American College of Chest Physicians.

In a talk that reviewed current and trial surgical and bronchoscopic treatments of dyspnea in chronic obstructive pulmonary disease, Dr. Sciurba said, "Just treating diseases that are now naively classified as COPD or [interstitial lung disease] is not enough. We can instead look at variations within those diseases that may or may not be responsive to different therapies."

For example, because the Impact of Heterogeneity on Outcome Following Endobronchial Valves (VENT) trial data showed that fissure integrity (collateral tracts) significantly influenced target and adjacent lobe volume changes, Dr. Sciurba said that medical device manufacturers have begun to develop technologies that are more specific to the patient.

Straight nitinol coils (PneumRx), which are placed bronchoscopically, are implanted in stages, and according to collateral tracts. "The concept is to target the most affected areas of the lung, allowing regional expansion of the least affected lung. It’s not dependent on just lobar re-expansion," said Dr. Sciurba, director of the emphysema research center at the University of Pittsburgh Medical Center. 

Pilot trial data for this technique published in CHEST earlier this year showed that patients (n = 56) had a 17.5% improvement in forced expiratory volume in 1 second (FEV₁) and a greater than 10% drop in residual volume, and clinical meaningful improvements in 6-minute walk distances at more than a 28% improvement from baseline: 73% had a greater than 25 meter improvement at 6 months post treatment.

The hydro-gel foam, AeriSeal (Aeris) is another bronchoscopic technique currently undergoing a small (n = 20) pilot trial. After fibrinogen was eliminated from the sealant, this polymeric lung volume reduction technology was cleared by the Food and Drug Administration for testing in humans.

The sealant is administered into specific subsegments of the lungs, where the foam adheres to surrounding tissues; air and water in the foam are reabsorbed when collapse occurs, with durable absorption in atelectasis.

The results will soon be published, although Dr. Sciurba said that at this point, "the mechanical benefits seem to exceed the symptomatic benefits," but that a trial in a larger population would produce more definitive results.

Other factors to consider include "understanding the pulmonary physiologic interaction in lung volume reduction, and how that translates downstream, and the importance of linking the mechanical intervention with pulmonary rehab."

Expanding the ‘tool chest’

In determining whether bronchoscopic solutions can achieve the same benefits of surgical ones, while also minimizing adverse effects, Dr. Sciurba said, the FDA is beginning to take a more personalized view when approving trials, which he hopes will increase the "tool chest" available to physicians.

Clinical trials going forward may need to consider selection criteria such as interlobar collaterals, regional emphysema heterogeneity, and the degree of hyperinflation, as well as the most relevant outcomes when determining adverse events, Dr. Sciurba said.

Whether therapies are reversible also will be relevant, and will have an impact on future criteria for lung volume reduction surgery and transplant candidacy.

"If we actually look in a little more detail and start to classify these patients both on physiologic and clinical patterns, and as we evolve, on genetic patterns and molecular patterns, we will isolate groups of patients who are home run responders from those in whom certain therapies may not be cost effective."

Dr. Sciurba disclosed that he has received support from AstraZeneca, GlaxoSmithKline, Pfizer, and other companies, as well as grant monies from the National Institutes of Health and the University of Pittsburgh.

[email protected]

CHICAGO – Penetration of the inferior vena cava and adjacent organs occurred with 46% of IVC filters placed among 262 patients, an award-winning analysis shows.

Grade 2 or 3 penetration was significantly associated with filter type (49% temporary vs. 5.3% permanent; P = .0001) and length of time in place (18.2% less than 30 days vs. 57.3% 30 days or more; P less than .0001).

"The majority of filters were placed for prophylaxis or relative indications and were temporary," Dr. Michael Go said at the annual meeting of the Midwestern Vascular Surgical Society.

The filter penetrated the aorta in 12 cases; duodenum in 26; and spine, colon, or kidney in 6; and simultaneously penetrated two organs in 7. Another 100 filters had struts immediately adjacent to the external aspect of the IVC, possibly indicating tenting of the cava.

Patrice Wendling/IMNG Medical Media

Only 1.6% of temporary filters, however, were retrieved during the 3-year study period, he said.

A filter retrieval rate between 1.2% and 5.1% was cited in a recent Medicare data analysis, which reported an alarming 111% increase in the rate of IVC filter placement from 1999 through 2008 (J. Am. Coll. Radio. 2011;8:483-9).

"IVC filter placement is an epidemic because of the ever-increasing number of risk factors being identified for VTE [venous thromboembolism]," said Dr. Go, with the division of vascular diseases and surgery, Ohio State University Medical Center, Columbus.

Other culprits behind the explosive growth of IVC filters are that angiography suites and catheter labs are now commonplace, the skill needed to insert a filter is easily disseminated, and temporary filters have decreased the threshold for placement.

"Concern over filter complications is increasing, as are referrals for removal, but little long-term data exist," he remarked.

A total of 591 patients had an IVC filter placed at Ohio State University between January 2006 and December 2009, with an adequate postfilter computed tomography (CT) scan available in 262. CT findings were graded, based on a modified, previously published scale (J. Vasc. Interv. Radiol. 2011;22:70-4), ranging from 0 (struts confined entirely within the IVC) to 3 (strut interacts with aorta, duodenum, or other organs).

Indications for filter placement were prophylaxis in 16.4% and VTE in 83.6%. Among the filters placed for VTE, 44.7% were for absolute indications (inability/failure of anticoagulation) and 55.3% for relative indications.

Grade 0 penetration occurred in 42 filters, grade 1 in 100, grade 2 in 83, and grade 3 in 37, Dr. Go said.

Grade 2 or 3 penetration was present in 44.6% of Tulip filters, 74.4% of Celect, 5.3% of Greenfield, and 0% of Optease (P = .0000), according to the analysis, which won this year’s Pfeifer Venous Award from the society.

There was a trend toward increased grade 2 or 3 penetration with uniconical filters vs. biconical filters (46.7% vs. 0%; P = .0645).

In all, 32 patients sought clinical follow-up for abdominal or back pain, but none were conclusively tied to filter problems or penetration.

"It remains unclear if most penetrations caused clinically significant problems," he said. "Monitoring of penetrations with CT, or some other follow-up, may be important to understand the natural history of this condition."

Audience members remarked that the retrieval rate in the series was extremely low and asked whether efforts, such as percutaneous retrieval, were being undertaken.

"We have attempted to remove some of these filters, sometimes successfully, sometimes not," Dr. Go responded. "As far as our retrieval rate, I agree 1.6% is dismal. Vascular surgery put in 19% of the filters. We don’t have a specific protocol in place, other than hyperawareness amongst all of us partners about who has a filter in place and to bring them back when appropriate."

He also observed that even when retrieval is undertaken, technical failure rates are high at about 8.5% in the recent literature (Eur. J. Vasc. Endovasc. Surg. 2013;46:353-9).

Dr. Go and his coauthors reported no financial disclosures.

[email protected]

CHICAGO – Penetration of the inferior vena cava and adjacent organs occurred with 46% of IVC filters placed among 262 patients, an award-winning analysis shows.

Grade 2 or 3 penetration was significantly associated with filter type (49% temporary vs. 5.3% permanent; P = .0001) and length of time in place (18.2% less than 30 days vs. 57.3% 30 days or more; P less than .0001).

"The majority of filters were placed for prophylaxis or relative indications and were temporary," Dr. Michael Go said at the annual meeting of the Midwestern Vascular Surgical Society.

The filter penetrated the aorta in 12 cases; duodenum in 26; and spine, colon, or kidney in 6; and simultaneously penetrated two organs in 7. Another 100 filters had struts immediately adjacent to the external aspect of the IVC, possibly indicating tenting of the cava.

Patrice Wendling/IMNG Medical Media

Only 1.6% of temporary filters, however, were retrieved during the 3-year study period, he said.

A filter retrieval rate between 1.2% and 5.1% was cited in a recent Medicare data analysis, which reported an alarming 111% increase in the rate of IVC filter placement from 1999 through 2008 (J. Am. Coll. Radio. 2011;8:483-9).

"IVC filter placement is an epidemic because of the ever-increasing number of risk factors being identified for VTE [venous thromboembolism]," said Dr. Go, with the division of vascular diseases and surgery, Ohio State University Medical Center, Columbus.

Other culprits behind the explosive growth of IVC filters are that angiography suites and catheter labs are now commonplace, the skill needed to insert a filter is easily disseminated, and temporary filters have decreased the threshold for placement.

"Concern over filter complications is increasing, as are referrals for removal, but little long-term data exist," he remarked.

A total of 591 patients had an IVC filter placed at Ohio State University between January 2006 and December 2009, with an adequate postfilter computed tomography (CT) scan available in 262. CT findings were graded, based on a modified, previously published scale (J. Vasc. Interv. Radiol. 2011;22:70-4), ranging from 0 (struts confined entirely within the IVC) to 3 (strut interacts with aorta, duodenum, or other organs).

Indications for filter placement were prophylaxis in 16.4% and VTE in 83.6%. Among the filters placed for VTE, 44.7% were for absolute indications (inability/failure of anticoagulation) and 55.3% for relative indications.

Grade 0 penetration occurred in 42 filters, grade 1 in 100, grade 2 in 83, and grade 3 in 37, Dr. Go said.

Grade 2 or 3 penetration was present in 44.6% of Tulip filters, 74.4% of Celect, 5.3% of Greenfield, and 0% of Optease (P = .0000), according to the analysis, which won this year’s Pfeifer Venous Award from the society.

There was a trend toward increased grade 2 or 3 penetration with uniconical filters vs. biconical filters (46.7% vs. 0%; P = .0645).

In all, 32 patients sought clinical follow-up for abdominal or back pain, but none were conclusively tied to filter problems or penetration.

"It remains unclear if most penetrations caused clinically significant problems," he said. "Monitoring of penetrations with CT, or some other follow-up, may be important to understand the natural history of this condition."

Audience members remarked that the retrieval rate in the series was extremely low and asked whether efforts, such as percutaneous retrieval, were being undertaken.

"We have attempted to remove some of these filters, sometimes successfully, sometimes not," Dr. Go responded. "As far as our retrieval rate, I agree 1.6% is dismal. Vascular surgery put in 19% of the filters. We don’t have a specific protocol in place, other than hyperawareness amongst all of us partners about who has a filter in place and to bring them back when appropriate."

He also observed that even when retrieval is undertaken, technical failure rates are high at about 8.5% in the recent literature (Eur. J. Vasc. Endovasc. Surg. 2013;46:353-9).

Dr. Go and his coauthors reported no financial disclosures.

[email protected]

CHICAGO – Penetration of the inferior vena cava and adjacent organs occurred with 46% of IVC filters placed among 262 patients, an award-winning analysis shows.

Grade 2 or 3 penetration was significantly associated with filter type (49% temporary vs. 5.3% permanent; P = .0001) and length of time in place (18.2% less than 30 days vs. 57.3% 30 days or more; P less than .0001).

"The majority of filters were placed for prophylaxis or relative indications and were temporary," Dr. Michael Go said at the annual meeting of the Midwestern Vascular Surgical Society.

The filter penetrated the aorta in 12 cases; duodenum in 26; and spine, colon, or kidney in 6; and simultaneously penetrated two organs in 7. Another 100 filters had struts immediately adjacent to the external aspect of the IVC, possibly indicating tenting of the cava.

Patrice Wendling/IMNG Medical Media

Only 1.6% of temporary filters, however, were retrieved during the 3-year study period, he said.

A filter retrieval rate between 1.2% and 5.1% was cited in a recent Medicare data analysis, which reported an alarming 111% increase in the rate of IVC filter placement from 1999 through 2008 (J. Am. Coll. Radio. 2011;8:483-9).

"IVC filter placement is an epidemic because of the ever-increasing number of risk factors being identified for VTE [venous thromboembolism]," said Dr. Go, with the division of vascular diseases and surgery, Ohio State University Medical Center, Columbus.

Other culprits behind the explosive growth of IVC filters are that angiography suites and catheter labs are now commonplace, the skill needed to insert a filter is easily disseminated, and temporary filters have decreased the threshold for placement.

"Concern over filter complications is increasing, as are referrals for removal, but little long-term data exist," he remarked.

A total of 591 patients had an IVC filter placed at Ohio State University between January 2006 and December 2009, with an adequate postfilter computed tomography (CT) scan available in 262. CT findings were graded, based on a modified, previously published scale (J. Vasc. Interv. Radiol. 2011;22:70-4), ranging from 0 (struts confined entirely within the IVC) to 3 (strut interacts with aorta, duodenum, or other organs).

Indications for filter placement were prophylaxis in 16.4% and VTE in 83.6%. Among the filters placed for VTE, 44.7% were for absolute indications (inability/failure of anticoagulation) and 55.3% for relative indications.

Grade 0 penetration occurred in 42 filters, grade 1 in 100, grade 2 in 83, and grade 3 in 37, Dr. Go said.

Grade 2 or 3 penetration was present in 44.6% of Tulip filters, 74.4% of Celect, 5.3% of Greenfield, and 0% of Optease (P = .0000), according to the analysis, which won this year’s Pfeifer Venous Award from the society.

There was a trend toward increased grade 2 or 3 penetration with uniconical filters vs. biconical filters (46.7% vs. 0%; P = .0645).

In all, 32 patients sought clinical follow-up for abdominal or back pain, but none were conclusively tied to filter problems or penetration.

"It remains unclear if most penetrations caused clinically significant problems," he said. "Monitoring of penetrations with CT, or some other follow-up, may be important to understand the natural history of this condition."

Audience members remarked that the retrieval rate in the series was extremely low and asked whether efforts, such as percutaneous retrieval, were being undertaken.

"We have attempted to remove some of these filters, sometimes successfully, sometimes not," Dr. Go responded. "As far as our retrieval rate, I agree 1.6% is dismal. Vascular surgery put in 19% of the filters. We don’t have a specific protocol in place, other than hyperawareness amongst all of us partners about who has a filter in place and to bring them back when appropriate."

He also observed that even when retrieval is undertaken, technical failure rates are high at about 8.5% in the recent literature (Eur. J. Vasc. Endovasc. Surg. 2013;46:353-9).

Dr. Go and his coauthors reported no financial disclosures.

[email protected]

For diabetic patients who have multivessel coronary artery disease, bypass surgery provides slightly better quality of life and cardiovascular-related health status than does stenting for roughly 2 years, according to a substudy of the FREEDOM trial reported online Oct. 15 in JAMA.

Beyond 2 years, there are no significant differences between the two approaches regarding health status and quality of life in this patient group, said Dr. Mouin S. Abdallah of St. Luke’s Mid America Heart Institute, Kansas City, Mo., and his associates.

Both revascularization strategies yield substantial and sustained improvements for patients who have concomitant multivessel coronary artery disease (CAD) and diabetes, but coronary artery bypass graft surgery generally is preferred because it has a small but significant edge in reducing morbidity and mortality, is less expensive, and produces markedly more durable results. However, the risk of stroke is higher with CABG, and it requires a longer recovery period because it is more invasive, "which may be particularly relevant to patients who are more concerned about quality rather than duration of life," the investigators noted.

"For such patients, our study provides reassurance that there are not major differences in long-term health status and quality of life between the two treatment strategies," they said.

Dr. Abdallah and his colleagues performed a prospective substudy of quality-of-life issues alongside the FREEDOM (Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease) clinical trial. In FREEDOM, 1,900 patients from 18 countries were randomly assigned to undergo either CABG or percutaneous coronary intervention with drug-eluting stents during 2005-2010.

For their substudy, Dr. Abdallah and his associates assessed 935 participants who were assigned to CABG and 945 assigned to PCI. The mean patient age was 63 years, and 72% were men. Median follow-up was 44-47 months.

Patients in both study groups reported substantial and long-lasting improvements in cardiovascular-specific health status, as measured by the Seattle Angina Questionnaire and the Rose Dyspnea Scale. Scores on these instruments improved markedly within 1 month of both procedures and remained high throughout follow-up.

Patients in the PCI group showed more rapid improvement following the procedure, "but these benefits were transient and largely restricted to the first month of follow-up," the researchers said.

"Between 6 months and 2 years, health status was slightly better with CABG across a range of cardiac-specific domains including angina relief, physical function, and overall quality of life. Beyond 2 years, there were no consistent differences in any health status or quality-of-life domains between the CABG and PCI strategies," they reported (JAMA 2013;310:1581-90).

For example, the proportion of angina-free patients was slightly but significantly greater with CABG than with PCI at 6 months (83.7% vs. 78.1%) and at 12 months (83.5% vs. 79.5%), but was not significantly different thereafter.

Similarly, measures of physical limitations imposed by CAD were "modestly" higher with CABG than with PCI for 3 years after the procedure, but there were no significant between-group differences after year 3.

And dyspnea improved faster after PCI than after CABG, but by 6 months this difference had disappeared. By 1 year, the proportion of patients who reported moderate dyspnea was only 9% in both groups, and that proportion stayed fairly steady at 10%-12% in both groups for the remainder of follow-up.

The findings were similar in a sensitivity analysis and in a further analysis restricted only to patients who had reported daily or weekly angina at baseline.

In the FREEDOM trial, CABG showed a clear benefit over PCI for the composite endpoint of death, myocardial infarction, or stroke in patients with concomitant multivessel CAD and diabetes. CABG also afforded slightly better angina relief, especially in patients who had the most severe angina at baseline.

Moreover, patients in the PCI group were more likely to require continuing antianginal medication and twice as likely to undergo repeat revascularization procedures than those in the CABG group.

However, the study findings demonstrate that PCI is clearly beneficial for patients who want to avoid the acute risks of CABG surgery, and is an excellent alternative for those who want a less invasive treatment, Dr. Abdallah and his associates said.

This study was supported by the National Heart, Lung, and Blood Institute. Cordis and Boston Scientific provided the drug-eluting stents, Eli Lilly provided abciximab and research funds, and Sanofi-Aventis and Bristol-Myers Squibb provided clopidogrel. Dr. Abdallah reported no relevant financial conflicts of interest; his associates reported numerous ties to industry sources.

For diabetic patients who have multivessel coronary artery disease, bypass surgery provides slightly better quality of life and cardiovascular-related health status than does stenting for roughly 2 years, according to a substudy of the FREEDOM trial reported online Oct. 15 in JAMA.

Beyond 2 years, there are no significant differences between the two approaches regarding health status and quality of life in this patient group, said Dr. Mouin S. Abdallah of St. Luke’s Mid America Heart Institute, Kansas City, Mo., and his associates.

Both revascularization strategies yield substantial and sustained improvements for patients who have concomitant multivessel coronary artery disease (CAD) and diabetes, but coronary artery bypass graft surgery generally is preferred because it has a small but significant edge in reducing morbidity and mortality, is less expensive, and produces markedly more durable results. However, the risk of stroke is higher with CABG, and it requires a longer recovery period because it is more invasive, "which may be particularly relevant to patients who are more concerned about quality rather than duration of life," the investigators noted.

"For such patients, our study provides reassurance that there are not major differences in long-term health status and quality of life between the two treatment strategies," they said.

Dr. Abdallah and his colleagues performed a prospective substudy of quality-of-life issues alongside the FREEDOM (Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease) clinical trial. In FREEDOM, 1,900 patients from 18 countries were randomly assigned to undergo either CABG or percutaneous coronary intervention with drug-eluting stents during 2005-2010.

For their substudy, Dr. Abdallah and his associates assessed 935 participants who were assigned to CABG and 945 assigned to PCI. The mean patient age was 63 years, and 72% were men. Median follow-up was 44-47 months.

Patients in both study groups reported substantial and long-lasting improvements in cardiovascular-specific health status, as measured by the Seattle Angina Questionnaire and the Rose Dyspnea Scale. Scores on these instruments improved markedly within 1 month of both procedures and remained high throughout follow-up.

Patients in the PCI group showed more rapid improvement following the procedure, "but these benefits were transient and largely restricted to the first month of follow-up," the researchers said.

"Between 6 months and 2 years, health status was slightly better with CABG across a range of cardiac-specific domains including angina relief, physical function, and overall quality of life. Beyond 2 years, there were no consistent differences in any health status or quality-of-life domains between the CABG and PCI strategies," they reported (JAMA 2013;310:1581-90).

For example, the proportion of angina-free patients was slightly but significantly greater with CABG than with PCI at 6 months (83.7% vs. 78.1%) and at 12 months (83.5% vs. 79.5%), but was not significantly different thereafter.

Similarly, measures of physical limitations imposed by CAD were "modestly" higher with CABG than with PCI for 3 years after the procedure, but there were no significant between-group differences after year 3.

And dyspnea improved faster after PCI than after CABG, but by 6 months this difference had disappeared. By 1 year, the proportion of patients who reported moderate dyspnea was only 9% in both groups, and that proportion stayed fairly steady at 10%-12% in both groups for the remainder of follow-up.

The findings were similar in a sensitivity analysis and in a further analysis restricted only to patients who had reported daily or weekly angina at baseline.

In the FREEDOM trial, CABG showed a clear benefit over PCI for the composite endpoint of death, myocardial infarction, or stroke in patients with concomitant multivessel CAD and diabetes. CABG also afforded slightly better angina relief, especially in patients who had the most severe angina at baseline.

Moreover, patients in the PCI group were more likely to require continuing antianginal medication and twice as likely to undergo repeat revascularization procedures than those in the CABG group.

However, the study findings demonstrate that PCI is clearly beneficial for patients who want to avoid the acute risks of CABG surgery, and is an excellent alternative for those who want a less invasive treatment, Dr. Abdallah and his associates said.

This study was supported by the National Heart, Lung, and Blood Institute. Cordis and Boston Scientific provided the drug-eluting stents, Eli Lilly provided abciximab and research funds, and Sanofi-Aventis and Bristol-Myers Squibb provided clopidogrel. Dr. Abdallah reported no relevant financial conflicts of interest; his associates reported numerous ties to industry sources.

For diabetic patients who have multivessel coronary artery disease, bypass surgery provides slightly better quality of life and cardiovascular-related health status than does stenting for roughly 2 years, according to a substudy of the FREEDOM trial reported online Oct. 15 in JAMA.

Beyond 2 years, there are no significant differences between the two approaches regarding health status and quality of life in this patient group, said Dr. Mouin S. Abdallah of St. Luke’s Mid America Heart Institute, Kansas City, Mo., and his associates.

Both revascularization strategies yield substantial and sustained improvements for patients who have concomitant multivessel coronary artery disease (CAD) and diabetes, but coronary artery bypass graft surgery generally is preferred because it has a small but significant edge in reducing morbidity and mortality, is less expensive, and produces markedly more durable results. However, the risk of stroke is higher with CABG, and it requires a longer recovery period because it is more invasive, "which may be particularly relevant to patients who are more concerned about quality rather than duration of life," the investigators noted.

"For such patients, our study provides reassurance that there are not major differences in long-term health status and quality of life between the two treatment strategies," they said.

Dr. Abdallah and his colleagues performed a prospective substudy of quality-of-life issues alongside the FREEDOM (Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease) clinical trial. In FREEDOM, 1,900 patients from 18 countries were randomly assigned to undergo either CABG or percutaneous coronary intervention with drug-eluting stents during 2005-2010.

For their substudy, Dr. Abdallah and his associates assessed 935 participants who were assigned to CABG and 945 assigned to PCI. The mean patient age was 63 years, and 72% were men. Median follow-up was 44-47 months.

Patients in both study groups reported substantial and long-lasting improvements in cardiovascular-specific health status, as measured by the Seattle Angina Questionnaire and the Rose Dyspnea Scale. Scores on these instruments improved markedly within 1 month of both procedures and remained high throughout follow-up.

Patients in the PCI group showed more rapid improvement following the procedure, "but these benefits were transient and largely restricted to the first month of follow-up," the researchers said.

"Between 6 months and 2 years, health status was slightly better with CABG across a range of cardiac-specific domains including angina relief, physical function, and overall quality of life. Beyond 2 years, there were no consistent differences in any health status or quality-of-life domains between the CABG and PCI strategies," they reported (JAMA 2013;310:1581-90).

For example, the proportion of angina-free patients was slightly but significantly greater with CABG than with PCI at 6 months (83.7% vs. 78.1%) and at 12 months (83.5% vs. 79.5%), but was not significantly different thereafter.

Similarly, measures of physical limitations imposed by CAD were "modestly" higher with CABG than with PCI for 3 years after the procedure, but there were no significant between-group differences after year 3.

And dyspnea improved faster after PCI than after CABG, but by 6 months this difference had disappeared. By 1 year, the proportion of patients who reported moderate dyspnea was only 9% in both groups, and that proportion stayed fairly steady at 10%-12% in both groups for the remainder of follow-up.

The findings were similar in a sensitivity analysis and in a further analysis restricted only to patients who had reported daily or weekly angina at baseline.

In the FREEDOM trial, CABG showed a clear benefit over PCI for the composite endpoint of death, myocardial infarction, or stroke in patients with concomitant multivessel CAD and diabetes. CABG also afforded slightly better angina relief, especially in patients who had the most severe angina at baseline.

Moreover, patients in the PCI group were more likely to require continuing antianginal medication and twice as likely to undergo repeat revascularization procedures than those in the CABG group.

However, the study findings demonstrate that PCI is clearly beneficial for patients who want to avoid the acute risks of CABG surgery, and is an excellent alternative for those who want a less invasive treatment, Dr. Abdallah and his associates said.

This study was supported by the National Heart, Lung, and Blood Institute. Cordis and Boston Scientific provided the drug-eluting stents, Eli Lilly provided abciximab and research funds, and Sanofi-Aventis and Bristol-Myers Squibb provided clopidogrel. Dr. Abdallah reported no relevant financial conflicts of interest; his associates reported numerous ties to industry sources.