Richard Mark Kirkner

An acute aortic tear can be lethal, and more cardiac surgeons are favoring extended aortic arch replacement in these cases. Cardiac surgeons have tried many different arch replacement techniques, but en bloc repair and double- or triple-branch stent grafting carry significant risks, so a team of cardiac surgeons in Beijing has reported good 2-year results with a novel technique that combines stented elephant-trunk implantation with preservation of key vessels.

The technique accomplishes total arch replacement with the stent while preserving the autologous brachiocephalic vessels.

“This technique simplified hemostasis and anastomosis, reduced the size of the residual aortic patch wall, and preserved the autologous brachiocephalic vessels, yielding satisfactory surgical results,” wrote Dr. Li-Zhong Sun and colleagues at Beijing’s Capital Medical University (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.03.002]).

There are four keys to the procedure:

• The use of forceps to grasp the stent-free sewing edge of the stented elephant trunk and straightening of the spiral shaped Dacron graft to approximately 3 cm.

• Preservation of the native brachiocephalic vessels.

• Creating a residual aortic wall containing the innominate artery and LCCA that’s as small as possible.

• An end-to-side anastomosis between the left subclavian artery (LSCA) and the left common carotid artery (LCCA), a key junction in their technique.

The 20 study subjects had surgery within 2 weeks of the onset of pain. All 20 were discharged after the procedure, and in a mean follow-up period of 26 months, 18 had good outcomes while 1 patient had thoracoabdominal aortic replacement 9 months after the initial surgery (1 patient was lost to follow-up).

The researchers used computed tomography to confirm patency of the anastomosis between the LSCA and LCCA.

In 2 of the 20 patients, the aorta was normal with aortic dissection limited to the descending aorta. In the remaining patients, the investigators observed thrombus obliteration of the false lumen around the surgical graft in 16, partial thrombosis in 1 and patency in 1.

The surgical technique exposes the right axillary artery through a right subclavicular incision and a median sternotomy, then dissects and exposes the brachiocephalic vessels and the transverse arch. Dissection of the LSCA and LCCA is the key step in making the end-to-end anastomosis between the two vessels. The researchers accomplished this by partially transecting the sternocleidomastoid muscle and other cervical muscles.

Dr. Sun and coauthors said that a separated graft technique offers a number of advantages over other techniques for aortic arch reconstruction. While en bloc repair preserves the native brachiocephalic vessels and, thus, results in long-term patency, the technique carries risk for postoperative rupture of the aortic patch containing the brachiocephalic vessels. Double- or triple-branched stent grafting has resulted in shifting or kinking of the graft and eventually graft occlusion or aortic disruption.

The authors acknowledged the study’s small sample size, and that the outcomes are “preliminary.” They said long-term follow-up would be required to confirm the outcomes.

They had no disclosures to report.

An acute aortic tear can be lethal, and more cardiac surgeons are favoring extended aortic arch replacement in these cases. Cardiac surgeons have tried many different arch replacement techniques, but en bloc repair and double- or triple-branch stent grafting carry significant risks, so a team of cardiac surgeons in Beijing has reported good 2-year results with a novel technique that combines stented elephant-trunk implantation with preservation of key vessels.

The technique accomplishes total arch replacement with the stent while preserving the autologous brachiocephalic vessels.

“This technique simplified hemostasis and anastomosis, reduced the size of the residual aortic patch wall, and preserved the autologous brachiocephalic vessels, yielding satisfactory surgical results,” wrote Dr. Li-Zhong Sun and colleagues at Beijing’s Capital Medical University (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.03.002]).

There are four keys to the procedure:

• The use of forceps to grasp the stent-free sewing edge of the stented elephant trunk and straightening of the spiral shaped Dacron graft to approximately 3 cm.

• Preservation of the native brachiocephalic vessels.

• Creating a residual aortic wall containing the innominate artery and LCCA that’s as small as possible.

• An end-to-side anastomosis between the left subclavian artery (LSCA) and the left common carotid artery (LCCA), a key junction in their technique.

The 20 study subjects had surgery within 2 weeks of the onset of pain. All 20 were discharged after the procedure, and in a mean follow-up period of 26 months, 18 had good outcomes while 1 patient had thoracoabdominal aortic replacement 9 months after the initial surgery (1 patient was lost to follow-up).

The researchers used computed tomography to confirm patency of the anastomosis between the LSCA and LCCA.

In 2 of the 20 patients, the aorta was normal with aortic dissection limited to the descending aorta. In the remaining patients, the investigators observed thrombus obliteration of the false lumen around the surgical graft in 16, partial thrombosis in 1 and patency in 1.

The surgical technique exposes the right axillary artery through a right subclavicular incision and a median sternotomy, then dissects and exposes the brachiocephalic vessels and the transverse arch. Dissection of the LSCA and LCCA is the key step in making the end-to-end anastomosis between the two vessels. The researchers accomplished this by partially transecting the sternocleidomastoid muscle and other cervical muscles.

Dr. Sun and coauthors said that a separated graft technique offers a number of advantages over other techniques for aortic arch reconstruction. While en bloc repair preserves the native brachiocephalic vessels and, thus, results in long-term patency, the technique carries risk for postoperative rupture of the aortic patch containing the brachiocephalic vessels. Double- or triple-branched stent grafting has resulted in shifting or kinking of the graft and eventually graft occlusion or aortic disruption.

The authors acknowledged the study’s small sample size, and that the outcomes are “preliminary.” They said long-term follow-up would be required to confirm the outcomes.

They had no disclosures to report.

An acute aortic tear can be lethal, and more cardiac surgeons are favoring extended aortic arch replacement in these cases. Cardiac surgeons have tried many different arch replacement techniques, but en bloc repair and double- or triple-branch stent grafting carry significant risks, so a team of cardiac surgeons in Beijing has reported good 2-year results with a novel technique that combines stented elephant-trunk implantation with preservation of key vessels.

The technique accomplishes total arch replacement with the stent while preserving the autologous brachiocephalic vessels.

“This technique simplified hemostasis and anastomosis, reduced the size of the residual aortic patch wall, and preserved the autologous brachiocephalic vessels, yielding satisfactory surgical results,” wrote Dr. Li-Zhong Sun and colleagues at Beijing’s Capital Medical University (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.03.002]).

There are four keys to the procedure:

• The use of forceps to grasp the stent-free sewing edge of the stented elephant trunk and straightening of the spiral shaped Dacron graft to approximately 3 cm.

• Preservation of the native brachiocephalic vessels.

• Creating a residual aortic wall containing the innominate artery and LCCA that’s as small as possible.

• An end-to-side anastomosis between the left subclavian artery (LSCA) and the left common carotid artery (LCCA), a key junction in their technique.

The 20 study subjects had surgery within 2 weeks of the onset of pain. All 20 were discharged after the procedure, and in a mean follow-up period of 26 months, 18 had good outcomes while 1 patient had thoracoabdominal aortic replacement 9 months after the initial surgery (1 patient was lost to follow-up).

The researchers used computed tomography to confirm patency of the anastomosis between the LSCA and LCCA.

In 2 of the 20 patients, the aorta was normal with aortic dissection limited to the descending aorta. In the remaining patients, the investigators observed thrombus obliteration of the false lumen around the surgical graft in 16, partial thrombosis in 1 and patency in 1.

The surgical technique exposes the right axillary artery through a right subclavicular incision and a median sternotomy, then dissects and exposes the brachiocephalic vessels and the transverse arch. Dissection of the LSCA and LCCA is the key step in making the end-to-end anastomosis between the two vessels. The researchers accomplished this by partially transecting the sternocleidomastoid muscle and other cervical muscles.

Dr. Sun and coauthors said that a separated graft technique offers a number of advantages over other techniques for aortic arch reconstruction. While en bloc repair preserves the native brachiocephalic vessels and, thus, results in long-term patency, the technique carries risk for postoperative rupture of the aortic patch containing the brachiocephalic vessels. Double- or triple-branched stent grafting has resulted in shifting or kinking of the graft and eventually graft occlusion or aortic disruption.

The authors acknowledged the study’s small sample size, and that the outcomes are “preliminary.” They said long-term follow-up would be required to confirm the outcomes.

They had no disclosures to report.

While stent placement has proved to be safe and effective for acute esophageal perforation, a head-to-head comparison with surgical repair has never been reported, so a team of investigators performed a small, single-system analysis that compared stenting and surgery and found that while both are equally effective, esophageal stent placement resulted in lower costs and lower morbidity rates.

Investigators led by Dr. Richard Freeman of St. Vincent Hospital in Indianapolis published their results in the June issue of the Journal of Thoracic and Cardiovascular Surgery (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.01.066]). Their study evaluated only 60 patients who had either stent placement or an operation for acute intrathoracic esophageal perforation between 2009 and 2012 within Ascension Health, a national Catholic-based network of 36 regional health systems; but the authors noted that they had extracted their data from the national Premier Inc. database, which covers 20% of U.S. hospital discharges, and used propensity matching to generate similar stent and surgical groups. Dr. Freeman presented the results at the annual meeting of the American Association of Thoracic Surgery in Toronto, April 28-30.

Courtesy of AATS

Patients who received stents had intensive care unit stays about half that of the surgery group – an average of 2 vs. 4 days. Likewise, their total hospital stays were about half: 6 days vs. 11 days for the surgery group. Complication rates were comparable: postrepair leaks were reported in 17% of the stent group and 20% who had surgery. While reoperation rates were significantly lower in the stent group (3% vs. 13%), four patients (13%) of the stent group did have stent migration. Morbidity was significantly higher in the surgery group (43% vs. 17%). While postprocedure leak rates were similar, those who had surgery were more likely to have reoperation for persistent leaks, the authors said.

Further, stent recipients were able to take nutrition by mouth earlier after surgery and had lower rates of needing enteral feeding at discharge – 17% vs. 60% for the surgery group. Dr. Freeman and his team also analyzed costs between the two procedures and found that total costs, including inpatient and outpatient costs, averaged $142,000 for surgery vs. $91,000 for stenting.

Because the incidence of esophageal perforation is so low, Dr. Freeman and his coauthors reported that performing a randomized trial comparing esophageal stenting and surgery has been difficult. The off-label nature of stenting for esophageal perforation has also complicated funding of a prospective trial. The study authors said a prospective, randomized design would have been preferable to the propensity-matched approach.

Surgery for esophageal tear has been around for almost 70 years with many improvements in technique, anesthesia, and antimicrobial therapy, but with a need for prolonged inpatient and outpatient care along with a postoperative leak rate as high as 39% (Ann. Thorac. Surg. 2010;90:1669-73). “A persistent leak following operative repair may also result in the need for esophageal diversion and subsequent reconstruction with its associated significant morbidity and patient dissatisfaction,” Dr. Freeman and his coauthors said.

The authors acknowledged shortcomings of their study included not accounting for how different stents used in the stenting group and individual surgeons and facilities may have influenced outcomes. Other shortcomings were that cost calculations may not have accounted for inflation or costs outside the Ascension Health system and the uniqueness of the procedure itself. “Lastly, the fact that both treatment strategies employed for iatrogenic esophageal perforation are likely uncommon procedures at most treatment facilities implies that standardization, even at the local level, may be lacking,” the authors stated.

The authors reported having no financial disclosures.

While stent placement has proved to be safe and effective for acute esophageal perforation, a head-to-head comparison with surgical repair has never been reported, so a team of investigators performed a small, single-system analysis that compared stenting and surgery and found that while both are equally effective, esophageal stent placement resulted in lower costs and lower morbidity rates.

Investigators led by Dr. Richard Freeman of St. Vincent Hospital in Indianapolis published their results in the June issue of the Journal of Thoracic and Cardiovascular Surgery (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.01.066]). Their study evaluated only 60 patients who had either stent placement or an operation for acute intrathoracic esophageal perforation between 2009 and 2012 within Ascension Health, a national Catholic-based network of 36 regional health systems; but the authors noted that they had extracted their data from the national Premier Inc. database, which covers 20% of U.S. hospital discharges, and used propensity matching to generate similar stent and surgical groups. Dr. Freeman presented the results at the annual meeting of the American Association of Thoracic Surgery in Toronto, April 28-30.

Courtesy of AATS

Patients who received stents had intensive care unit stays about half that of the surgery group – an average of 2 vs. 4 days. Likewise, their total hospital stays were about half: 6 days vs. 11 days for the surgery group. Complication rates were comparable: postrepair leaks were reported in 17% of the stent group and 20% who had surgery. While reoperation rates were significantly lower in the stent group (3% vs. 13%), four patients (13%) of the stent group did have stent migration. Morbidity was significantly higher in the surgery group (43% vs. 17%). While postprocedure leak rates were similar, those who had surgery were more likely to have reoperation for persistent leaks, the authors said.

Further, stent recipients were able to take nutrition by mouth earlier after surgery and had lower rates of needing enteral feeding at discharge – 17% vs. 60% for the surgery group. Dr. Freeman and his team also analyzed costs between the two procedures and found that total costs, including inpatient and outpatient costs, averaged $142,000 for surgery vs. $91,000 for stenting.

Because the incidence of esophageal perforation is so low, Dr. Freeman and his coauthors reported that performing a randomized trial comparing esophageal stenting and surgery has been difficult. The off-label nature of stenting for esophageal perforation has also complicated funding of a prospective trial. The study authors said a prospective, randomized design would have been preferable to the propensity-matched approach.

Surgery for esophageal tear has been around for almost 70 years with many improvements in technique, anesthesia, and antimicrobial therapy, but with a need for prolonged inpatient and outpatient care along with a postoperative leak rate as high as 39% (Ann. Thorac. Surg. 2010;90:1669-73). “A persistent leak following operative repair may also result in the need for esophageal diversion and subsequent reconstruction with its associated significant morbidity and patient dissatisfaction,” Dr. Freeman and his coauthors said.

The authors acknowledged shortcomings of their study included not accounting for how different stents used in the stenting group and individual surgeons and facilities may have influenced outcomes. Other shortcomings were that cost calculations may not have accounted for inflation or costs outside the Ascension Health system and the uniqueness of the procedure itself. “Lastly, the fact that both treatment strategies employed for iatrogenic esophageal perforation are likely uncommon procedures at most treatment facilities implies that standardization, even at the local level, may be lacking,” the authors stated.

The authors reported having no financial disclosures.

While stent placement has proved to be safe and effective for acute esophageal perforation, a head-to-head comparison with surgical repair has never been reported, so a team of investigators performed a small, single-system analysis that compared stenting and surgery and found that while both are equally effective, esophageal stent placement resulted in lower costs and lower morbidity rates.

Investigators led by Dr. Richard Freeman of St. Vincent Hospital in Indianapolis published their results in the June issue of the Journal of Thoracic and Cardiovascular Surgery (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.01.066]). Their study evaluated only 60 patients who had either stent placement or an operation for acute intrathoracic esophageal perforation between 2009 and 2012 within Ascension Health, a national Catholic-based network of 36 regional health systems; but the authors noted that they had extracted their data from the national Premier Inc. database, which covers 20% of U.S. hospital discharges, and used propensity matching to generate similar stent and surgical groups. Dr. Freeman presented the results at the annual meeting of the American Association of Thoracic Surgery in Toronto, April 28-30.

Courtesy of AATS

Patients who received stents had intensive care unit stays about half that of the surgery group – an average of 2 vs. 4 days. Likewise, their total hospital stays were about half: 6 days vs. 11 days for the surgery group. Complication rates were comparable: postrepair leaks were reported in 17% of the stent group and 20% who had surgery. While reoperation rates were significantly lower in the stent group (3% vs. 13%), four patients (13%) of the stent group did have stent migration. Morbidity was significantly higher in the surgery group (43% vs. 17%). While postprocedure leak rates were similar, those who had surgery were more likely to have reoperation for persistent leaks, the authors said.

Further, stent recipients were able to take nutrition by mouth earlier after surgery and had lower rates of needing enteral feeding at discharge – 17% vs. 60% for the surgery group. Dr. Freeman and his team also analyzed costs between the two procedures and found that total costs, including inpatient and outpatient costs, averaged $142,000 for surgery vs. $91,000 for stenting.

Because the incidence of esophageal perforation is so low, Dr. Freeman and his coauthors reported that performing a randomized trial comparing esophageal stenting and surgery has been difficult. The off-label nature of stenting for esophageal perforation has also complicated funding of a prospective trial. The study authors said a prospective, randomized design would have been preferable to the propensity-matched approach.

Surgery for esophageal tear has been around for almost 70 years with many improvements in technique, anesthesia, and antimicrobial therapy, but with a need for prolonged inpatient and outpatient care along with a postoperative leak rate as high as 39% (Ann. Thorac. Surg. 2010;90:1669-73). “A persistent leak following operative repair may also result in the need for esophageal diversion and subsequent reconstruction with its associated significant morbidity and patient dissatisfaction,” Dr. Freeman and his coauthors said.

The authors acknowledged shortcomings of their study included not accounting for how different stents used in the stenting group and individual surgeons and facilities may have influenced outcomes. Other shortcomings were that cost calculations may not have accounted for inflation or costs outside the Ascension Health system and the uniqueness of the procedure itself. “Lastly, the fact that both treatment strategies employed for iatrogenic esophageal perforation are likely uncommon procedures at most treatment facilities implies that standardization, even at the local level, may be lacking,” the authors stated.

The authors reported having no financial disclosures.

How patients with hypertrophic obstructive cardiomyopathy who have already undergone alcohol septal ablation fare after going on to have surgical septal myectomy has been a matter of speculation and conjecture among cardiac surgeons for years, so a team of investigators set out to evaluate the outcomes among those patients.

What they found was that patients with a history of alcohol septal ablation may have an increased risk of cardiac death and complications after they have transaortic septal myectomy later on instead of just having septal myectomy as the primary procedure. In the Journal of Thoracic and Cardiovascular Surgery, Dr. Eduard Quintana of the University of Barcelona and the Mayo Clinic in Rochester, Minn., and coauthors reported that their findings support the use of surgical septal myectomy as the preferred treatment for septal reduction therapy for hypertrophic obstructive cardiomyopathy (HOCM) (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2015.03.044]).

This small study evaluated 31 patients who had a failed alcohol septal ablation and then underwent septal myectomy and compared them to a group of 62 patients who had a septal myectomy only for HOCM. A total of 28 of the failed septal ablation patients had one such previous procedure and three had two or more percutaneous procedures before undergoing surgical septal myectomy. Study outcomes were cardiac death, advanced heart failure, and placement of an implantable cardioverter defibrillator (ICD). The study was conducted at the Mayo Clinic.

Percutaneous alcohol septal ablation utilizes injection of ethanol to correct left ventricular outflow tract obstruction (LVOT) in hypertrophic cardiomyopathy. Dr. Quintana and his coauthors reported that despite the percutaneous nature of alcohol septal ablation, its incidence of death and morbidity are not lower than surgical myectomy. They also reported that some countries are using alcohol ablation exclusively for septal reduction in HOCM. The rate of recurrence of severe symptoms after septal ablation is 20%, Dr. Quintana and his colleagues pointed out. “Thus, a sizeable proportion of patients having alcohol septal ablation may require transaortic septal myectomy for relief of LVOT, and outcome of such patients may be impaired,” they reported.

The 31 prior-ablation patients had a three times higher rate of implanted ICDs (32% vs. 11%), more arrhythmias (43% vs. 13% based on preoperative Holter monitoring), and a 12 times higher rate of postoperative complete heart block (19.4% vs. 1.6%). The prior–septal ablation group progressed to advanced heart failure at twice the rate, 22.5% at an average follow-up of 3.2 years, compared with about 10% in the primary septal myectomy group.

The authors also reported the 31 prior-ablation patients had significantly higher rates of interstitial and endocardial fibrosis – 70% vs. 26% and 87% vs. 67%, respectively.

“Our data contributes to accumulating evidence that the infarction induced by alcohol septal ablation may have adverse and unexpected consequences,” Dr. Quintana and his colleagues said.

However, the authors also acknowledged that one limit of their study was that it could not identify the overall failure rate of alcohol septal ablation among the larger patient population that underwent the procedure – “the inability to clearly define the denominator.” Nineteen of the 31 prior-ablation subjects had been referred from other institutions.

Coauthor Dr. Anna Sabata-Rotes received funding from Fundacia La Caxia, Barcelona. The other authors had no relationships to disclose.

How patients with hypertrophic obstructive cardiomyopathy who have already undergone alcohol septal ablation fare after going on to have surgical septal myectomy has been a matter of speculation and conjecture among cardiac surgeons for years, so a team of investigators set out to evaluate the outcomes among those patients.

What they found was that patients with a history of alcohol septal ablation may have an increased risk of cardiac death and complications after they have transaortic septal myectomy later on instead of just having septal myectomy as the primary procedure. In the Journal of Thoracic and Cardiovascular Surgery, Dr. Eduard Quintana of the University of Barcelona and the Mayo Clinic in Rochester, Minn., and coauthors reported that their findings support the use of surgical septal myectomy as the preferred treatment for septal reduction therapy for hypertrophic obstructive cardiomyopathy (HOCM) (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2015.03.044]).

This small study evaluated 31 patients who had a failed alcohol septal ablation and then underwent septal myectomy and compared them to a group of 62 patients who had a septal myectomy only for HOCM. A total of 28 of the failed septal ablation patients had one such previous procedure and three had two or more percutaneous procedures before undergoing surgical septal myectomy. Study outcomes were cardiac death, advanced heart failure, and placement of an implantable cardioverter defibrillator (ICD). The study was conducted at the Mayo Clinic.

Percutaneous alcohol septal ablation utilizes injection of ethanol to correct left ventricular outflow tract obstruction (LVOT) in hypertrophic cardiomyopathy. Dr. Quintana and his coauthors reported that despite the percutaneous nature of alcohol septal ablation, its incidence of death and morbidity are not lower than surgical myectomy. They also reported that some countries are using alcohol ablation exclusively for septal reduction in HOCM. The rate of recurrence of severe symptoms after septal ablation is 20%, Dr. Quintana and his colleagues pointed out. “Thus, a sizeable proportion of patients having alcohol septal ablation may require transaortic septal myectomy for relief of LVOT, and outcome of such patients may be impaired,” they reported.

The 31 prior-ablation patients had a three times higher rate of implanted ICDs (32% vs. 11%), more arrhythmias (43% vs. 13% based on preoperative Holter monitoring), and a 12 times higher rate of postoperative complete heart block (19.4% vs. 1.6%). The prior–septal ablation group progressed to advanced heart failure at twice the rate, 22.5% at an average follow-up of 3.2 years, compared with about 10% in the primary septal myectomy group.

The authors also reported the 31 prior-ablation patients had significantly higher rates of interstitial and endocardial fibrosis – 70% vs. 26% and 87% vs. 67%, respectively.

“Our data contributes to accumulating evidence that the infarction induced by alcohol septal ablation may have adverse and unexpected consequences,” Dr. Quintana and his colleagues said.

However, the authors also acknowledged that one limit of their study was that it could not identify the overall failure rate of alcohol septal ablation among the larger patient population that underwent the procedure – “the inability to clearly define the denominator.” Nineteen of the 31 prior-ablation subjects had been referred from other institutions.

Coauthor Dr. Anna Sabata-Rotes received funding from Fundacia La Caxia, Barcelona. The other authors had no relationships to disclose.

How patients with hypertrophic obstructive cardiomyopathy who have already undergone alcohol septal ablation fare after going on to have surgical septal myectomy has been a matter of speculation and conjecture among cardiac surgeons for years, so a team of investigators set out to evaluate the outcomes among those patients.

What they found was that patients with a history of alcohol septal ablation may have an increased risk of cardiac death and complications after they have transaortic septal myectomy later on instead of just having septal myectomy as the primary procedure. In the Journal of Thoracic and Cardiovascular Surgery, Dr. Eduard Quintana of the University of Barcelona and the Mayo Clinic in Rochester, Minn., and coauthors reported that their findings support the use of surgical septal myectomy as the preferred treatment for septal reduction therapy for hypertrophic obstructive cardiomyopathy (HOCM) (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2015.03.044]).

This small study evaluated 31 patients who had a failed alcohol septal ablation and then underwent septal myectomy and compared them to a group of 62 patients who had a septal myectomy only for HOCM. A total of 28 of the failed septal ablation patients had one such previous procedure and three had two or more percutaneous procedures before undergoing surgical septal myectomy. Study outcomes were cardiac death, advanced heart failure, and placement of an implantable cardioverter defibrillator (ICD). The study was conducted at the Mayo Clinic.

Percutaneous alcohol septal ablation utilizes injection of ethanol to correct left ventricular outflow tract obstruction (LVOT) in hypertrophic cardiomyopathy. Dr. Quintana and his coauthors reported that despite the percutaneous nature of alcohol septal ablation, its incidence of death and morbidity are not lower than surgical myectomy. They also reported that some countries are using alcohol ablation exclusively for septal reduction in HOCM. The rate of recurrence of severe symptoms after septal ablation is 20%, Dr. Quintana and his colleagues pointed out. “Thus, a sizeable proportion of patients having alcohol septal ablation may require transaortic septal myectomy for relief of LVOT, and outcome of such patients may be impaired,” they reported.

The 31 prior-ablation patients had a three times higher rate of implanted ICDs (32% vs. 11%), more arrhythmias (43% vs. 13% based on preoperative Holter monitoring), and a 12 times higher rate of postoperative complete heart block (19.4% vs. 1.6%). The prior–septal ablation group progressed to advanced heart failure at twice the rate, 22.5% at an average follow-up of 3.2 years, compared with about 10% in the primary septal myectomy group.

The authors also reported the 31 prior-ablation patients had significantly higher rates of interstitial and endocardial fibrosis – 70% vs. 26% and 87% vs. 67%, respectively.

“Our data contributes to accumulating evidence that the infarction induced by alcohol septal ablation may have adverse and unexpected consequences,” Dr. Quintana and his colleagues said.

However, the authors also acknowledged that one limit of their study was that it could not identify the overall failure rate of alcohol septal ablation among the larger patient population that underwent the procedure – “the inability to clearly define the denominator.” Nineteen of the 31 prior-ablation subjects had been referred from other institutions.

Coauthor Dr. Anna Sabata-Rotes received funding from Fundacia La Caxia, Barcelona. The other authors had no relationships to disclose.

Individuals with chronic ischemic mitral regurgitation who undergo mitral valve replacement show significantly superior exercise performance up to almost 3½ years after the operation when compared with those who have restrictive mitral valve annuloplasty, according to a study in the June issue of the Journal of Cardiovascular Surgery. (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.03.003]).

Doctors at three institutions in France, Italy, and the United Kingdom set out to predict what factors determined long-term functional capacity in patients with chronic ischemic mitral regurgitation (CIMR) who had either mitral valve replacement (MVR) or annuloplasty. They performed a retrospective analysis of 121 patients with significant chronic mitral regurgitation, 62 of whom had restrictive mitral valve annuloplasty and 59 of whom underwent MVR between 2005 and 2011. All the subjects had a resting echocardiography and a 6-minute treadmill test before their procedures and again at an average of 41 months afterwards. The MVR group walked an average of 37 meters farther at the postoperative stress test, whereas the annuloplasty patients walked on average 24 meters less than their preoperative test.

“The most important finding of this study is that, in patients with CIMR who underwent mitral valve surgery, the improvement in functional capacity at long-term follow-up is mainly related to the type of treatment and to the mitral valve hemodynamic performance, as expressed by changes in IEOA [indexed effective orifice area] during exercise,” reported lead author Dr. Carlo Fino of the Bristol (England) Heart Institute and Pope John XXIII Hospital in Bergamo, Italy, and his colleagues. Investigators from Hospital Dupuytren in Limoges, France, also participated.

The study noted inconclusive results of previous reports of patients treated for mitral regurgitation: the Cardiothoracic Surgical Trials Network study that showed similar 1-year outcomes among patients who had either MVR or annuloplasty (N. Engl. J. Med. 2014;370:23-32) ; an earlier study that showed annuloplasty patients may develop functional mitral stenosis with decreasing functional capacity (J. Am. Coll. Cardiol. 2008;51:1692-1701); and Dr. Fino and colleagues’ previous work that showed worse hemodynamics in annuloplasty patients, compared with MVR counterparts (J. Thorac. Cardiovasc. Surg. 2014;148:447-53).

Other comparative measures the latest study evaluated were: change in exercise indexed effective orifice area, increasing from 1.3 to 1.5 cm²/m² in the MVR group vs. 1.1 to 1.2 cm²/m² in the annuloplasty group; change in mean mitral gradients from rest to exercise, which increased significantly in both groups – from 4.3 to 9 mm Hg in the replacement group and 4.4 to 11 mm Hg in the annuloplasty group; postoperative cardiovascular events – 8% in the MVR group and 21% in the annuloplasty population; and follow-up survival – 88% for MVR vs. 83% for annuloplasty.

The annuloplasty patients received either a Carpentier-Edwards Physio ring (71%) or Carpentier-Edwards Classic ring (29%); Edwards Lifesciences. The MVR group received either a biological or mechanical prosthesis, although the study did not report how many of each. All patients had associated coronary bypass grafting surgery and all achieved complete revascularization. The MVR and annuloplasty groups were similar in terms of demographics and cardiac function, although a higher percentage of patients in the annuloplasty group had severe mitral regurgitation preoperatively – 41% vs. 32% in the MVR group.

Procedures like annuloplasty that aim to restore ventricular geometry or target the subvalvular mechanism “seem to be promising but they require further scientific evidence,” Dr. Fino and his coauthors said. They suggested that until 24-month results from the Cardiothoracic Surgical Trials Network are available, MVR with chordal sparing might be a “reliable option” for patients with chronic ischemic mitral regurgitation.

The authors had no disclosures.

Individuals with chronic ischemic mitral regurgitation who undergo mitral valve replacement show significantly superior exercise performance up to almost 3½ years after the operation when compared with those who have restrictive mitral valve annuloplasty, according to a study in the June issue of the Journal of Cardiovascular Surgery. (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.03.003]).

Doctors at three institutions in France, Italy, and the United Kingdom set out to predict what factors determined long-term functional capacity in patients with chronic ischemic mitral regurgitation (CIMR) who had either mitral valve replacement (MVR) or annuloplasty. They performed a retrospective analysis of 121 patients with significant chronic mitral regurgitation, 62 of whom had restrictive mitral valve annuloplasty and 59 of whom underwent MVR between 2005 and 2011. All the subjects had a resting echocardiography and a 6-minute treadmill test before their procedures and again at an average of 41 months afterwards. The MVR group walked an average of 37 meters farther at the postoperative stress test, whereas the annuloplasty patients walked on average 24 meters less than their preoperative test.

“The most important finding of this study is that, in patients with CIMR who underwent mitral valve surgery, the improvement in functional capacity at long-term follow-up is mainly related to the type of treatment and to the mitral valve hemodynamic performance, as expressed by changes in IEOA [indexed effective orifice area] during exercise,” reported lead author Dr. Carlo Fino of the Bristol (England) Heart Institute and Pope John XXIII Hospital in Bergamo, Italy, and his colleagues. Investigators from Hospital Dupuytren in Limoges, France, also participated.

The study noted inconclusive results of previous reports of patients treated for mitral regurgitation: the Cardiothoracic Surgical Trials Network study that showed similar 1-year outcomes among patients who had either MVR or annuloplasty (N. Engl. J. Med. 2014;370:23-32) ; an earlier study that showed annuloplasty patients may develop functional mitral stenosis with decreasing functional capacity (J. Am. Coll. Cardiol. 2008;51:1692-1701); and Dr. Fino and colleagues’ previous work that showed worse hemodynamics in annuloplasty patients, compared with MVR counterparts (J. Thorac. Cardiovasc. Surg. 2014;148:447-53).

Other comparative measures the latest study evaluated were: change in exercise indexed effective orifice area, increasing from 1.3 to 1.5 cm²/m² in the MVR group vs. 1.1 to 1.2 cm²/m² in the annuloplasty group; change in mean mitral gradients from rest to exercise, which increased significantly in both groups – from 4.3 to 9 mm Hg in the replacement group and 4.4 to 11 mm Hg in the annuloplasty group; postoperative cardiovascular events – 8% in the MVR group and 21% in the annuloplasty population; and follow-up survival – 88% for MVR vs. 83% for annuloplasty.

The annuloplasty patients received either a Carpentier-Edwards Physio ring (71%) or Carpentier-Edwards Classic ring (29%); Edwards Lifesciences. The MVR group received either a biological or mechanical prosthesis, although the study did not report how many of each. All patients had associated coronary bypass grafting surgery and all achieved complete revascularization. The MVR and annuloplasty groups were similar in terms of demographics and cardiac function, although a higher percentage of patients in the annuloplasty group had severe mitral regurgitation preoperatively – 41% vs. 32% in the MVR group.

Procedures like annuloplasty that aim to restore ventricular geometry or target the subvalvular mechanism “seem to be promising but they require further scientific evidence,” Dr. Fino and his coauthors said. They suggested that until 24-month results from the Cardiothoracic Surgical Trials Network are available, MVR with chordal sparing might be a “reliable option” for patients with chronic ischemic mitral regurgitation.

The authors had no disclosures.

Individuals with chronic ischemic mitral regurgitation who undergo mitral valve replacement show significantly superior exercise performance up to almost 3½ years after the operation when compared with those who have restrictive mitral valve annuloplasty, according to a study in the June issue of the Journal of Cardiovascular Surgery. (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.03.003]).

Doctors at three institutions in France, Italy, and the United Kingdom set out to predict what factors determined long-term functional capacity in patients with chronic ischemic mitral regurgitation (CIMR) who had either mitral valve replacement (MVR) or annuloplasty. They performed a retrospective analysis of 121 patients with significant chronic mitral regurgitation, 62 of whom had restrictive mitral valve annuloplasty and 59 of whom underwent MVR between 2005 and 2011. All the subjects had a resting echocardiography and a 6-minute treadmill test before their procedures and again at an average of 41 months afterwards. The MVR group walked an average of 37 meters farther at the postoperative stress test, whereas the annuloplasty patients walked on average 24 meters less than their preoperative test.

“The most important finding of this study is that, in patients with CIMR who underwent mitral valve surgery, the improvement in functional capacity at long-term follow-up is mainly related to the type of treatment and to the mitral valve hemodynamic performance, as expressed by changes in IEOA [indexed effective orifice area] during exercise,” reported lead author Dr. Carlo Fino of the Bristol (England) Heart Institute and Pope John XXIII Hospital in Bergamo, Italy, and his colleagues. Investigators from Hospital Dupuytren in Limoges, France, also participated.

The study noted inconclusive results of previous reports of patients treated for mitral regurgitation: the Cardiothoracic Surgical Trials Network study that showed similar 1-year outcomes among patients who had either MVR or annuloplasty (N. Engl. J. Med. 2014;370:23-32) ; an earlier study that showed annuloplasty patients may develop functional mitral stenosis with decreasing functional capacity (J. Am. Coll. Cardiol. 2008;51:1692-1701); and Dr. Fino and colleagues’ previous work that showed worse hemodynamics in annuloplasty patients, compared with MVR counterparts (J. Thorac. Cardiovasc. Surg. 2014;148:447-53).

Other comparative measures the latest study evaluated were: change in exercise indexed effective orifice area, increasing from 1.3 to 1.5 cm²/m² in the MVR group vs. 1.1 to 1.2 cm²/m² in the annuloplasty group; change in mean mitral gradients from rest to exercise, which increased significantly in both groups – from 4.3 to 9 mm Hg in the replacement group and 4.4 to 11 mm Hg in the annuloplasty group; postoperative cardiovascular events – 8% in the MVR group and 21% in the annuloplasty population; and follow-up survival – 88% for MVR vs. 83% for annuloplasty.

The annuloplasty patients received either a Carpentier-Edwards Physio ring (71%) or Carpentier-Edwards Classic ring (29%); Edwards Lifesciences. The MVR group received either a biological or mechanical prosthesis, although the study did not report how many of each. All patients had associated coronary bypass grafting surgery and all achieved complete revascularization. The MVR and annuloplasty groups were similar in terms of demographics and cardiac function, although a higher percentage of patients in the annuloplasty group had severe mitral regurgitation preoperatively – 41% vs. 32% in the MVR group.

Procedures like annuloplasty that aim to restore ventricular geometry or target the subvalvular mechanism “seem to be promising but they require further scientific evidence,” Dr. Fino and his coauthors said. They suggested that until 24-month results from the Cardiothoracic Surgical Trials Network are available, MVR with chordal sparing might be a “reliable option” for patients with chronic ischemic mitral regurgitation.

The authors had no disclosures.

NEW YORK – What if correcting secondary mitral regurgitation doesn’t improve patients’ lives or helps them live longer? What if results of the COAPT trial of the MitraClip (Abbott Vascular) repair for mitral regurgitation are negative or inconclusive? What if transcatheter mitral valve repair works too well?

The answers to these questions could determine the future landscape of transcatheter mitral valve replacement (TMVR) for mitral regurgitation (MR) and the prosthetics in various stages of clinical and preclinical investigation, Dr. Michael Mack of Baylor University said at the 2015 Mitral Valve Conclave, which was sponsored by the American Association for Thoracic Surgery.

Dr. Mack reviewed the first four transcatheter mitral valve replacement devices approved for early feasibility studies in the United States, noting that “it has become a very crowded field very quickly,” especially when one considers that only between 20 and 50 TMVR procedures have been done worldwide up until now.

For the makers of the devices, it is becoming a potentially perilous field as well. Replacement, Dr. Mack said, does meet a “large clinical unmet need” in that it can completely correct mitral regurgitation better than valve repair.

“But what are the challenges for transcatheter mitral valve replacement and why isn’t this going to be the same as TAVR (transcatheter aortic valve replacement) all over again?” he said. “Unlike aortic stenosis, there is not a single cause of mitral regurgitation. In addition, it has never even been definitively proven that correcting MR helps prolong survival and improve quality of life.”

Another obstacle for TMVR is that delivery of the device into the mitral valve is more complex than doing so in the aortic valve. “The seating and the anchoring of the valve is more complex,” Dr. Mack said. “Based on the profile of the device, left ventricular outflow tract obstruction can be an issue, and perivalvular leak may carry more import here because mitral perivalvular leaks have the potential to cause hemololysis.”

He reviewed the four systems cleared for early feasibility studies.

CardiAQ (CardiAQ Valve Technologies), a porcine pericardial valve, has been implanted in eight patients worldwide and last month received Food and Drug Administration (FDA) approval for early feasibility study in 20 U.S. patients: 10 by a transfemoral approach and 10 by a transapical approach.

Tendyne Bioprosthetic Mitral Valve (Tendyne Holdings), a trileaflet porcine pericardium, also has been implanted in eight patients worldwide and was used for the first time in the United States last month by Dr. Wes Pederson and colleagues at the Minneapolis Heart Institute.

FORTIS (Edwards Lifesciences), a bovine pericardium valve, has been implanted in early feasibility trials in Europe and has been approved for an early feasibility trial of 15 patients in the United States.

Tiara (Neovasc), a D-shaped bovine pericardium valve, received FDA approval last year for the TIARA-I early feasibility trial in the United States (NCT02276547). The trial will enroll up to 30 patients worldwide.

At least five other TMVR devices are in preclinical studies, Dr. Mack said. These emerging devices face “threats and obstacles” as they move through the pipeline – a number of “what ifs,” Dr. Mack said.

“What if you can’t prove that correcting secondary mitral regurgitation makes a difference? What are the repercussions of the COAPT Trial (NCT01626079) of the MitraClip if it is positive and shows that correcting mitral regurgitation does make a difference? Does completely correcting mitral regurgitation then really make a difference? What if transcatheter mitral valve repair works too well?” (COAPT stands for Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation). “With the excellent safety profile of MitraClip, it may be hard to justify TMVR,” he said.

Dr. Mack noted that MitraClip for mitral valve repair has “a superb safety profile.” He added, “How do you choose what patients should be treated by a mitral valve replacement vs. a MitraClip by a transfemoral venous approach that enables them to go home the next day?”

The early feasibility trials of TMVR devices may point a way to answers.

Dr. Mack has received research grants from Edwards Lifesciences. He is a principal investigator in the ongoing COAPT Trial, which is sponsored by EVALVE with the collaboration of Abbott Vascular.

NEW YORK – What if correcting secondary mitral regurgitation doesn’t improve patients’ lives or helps them live longer? What if results of the COAPT trial of the MitraClip (Abbott Vascular) repair for mitral regurgitation are negative or inconclusive? What if transcatheter mitral valve repair works too well?

The answers to these questions could determine the future landscape of transcatheter mitral valve replacement (TMVR) for mitral regurgitation (MR) and the prosthetics in various stages of clinical and preclinical investigation, Dr. Michael Mack of Baylor University said at the 2015 Mitral Valve Conclave, which was sponsored by the American Association for Thoracic Surgery.

Dr. Mack reviewed the first four transcatheter mitral valve replacement devices approved for early feasibility studies in the United States, noting that “it has become a very crowded field very quickly,” especially when one considers that only between 20 and 50 TMVR procedures have been done worldwide up until now.

For the makers of the devices, it is becoming a potentially perilous field as well. Replacement, Dr. Mack said, does meet a “large clinical unmet need” in that it can completely correct mitral regurgitation better than valve repair.

“But what are the challenges for transcatheter mitral valve replacement and why isn’t this going to be the same as TAVR (transcatheter aortic valve replacement) all over again?” he said. “Unlike aortic stenosis, there is not a single cause of mitral regurgitation. In addition, it has never even been definitively proven that correcting MR helps prolong survival and improve quality of life.”

Another obstacle for TMVR is that delivery of the device into the mitral valve is more complex than doing so in the aortic valve. “The seating and the anchoring of the valve is more complex,” Dr. Mack said. “Based on the profile of the device, left ventricular outflow tract obstruction can be an issue, and perivalvular leak may carry more import here because mitral perivalvular leaks have the potential to cause hemololysis.”

He reviewed the four systems cleared for early feasibility studies.

CardiAQ (CardiAQ Valve Technologies), a porcine pericardial valve, has been implanted in eight patients worldwide and last month received Food and Drug Administration (FDA) approval for early feasibility study in 20 U.S. patients: 10 by a transfemoral approach and 10 by a transapical approach.

Tendyne Bioprosthetic Mitral Valve (Tendyne Holdings), a trileaflet porcine pericardium, also has been implanted in eight patients worldwide and was used for the first time in the United States last month by Dr. Wes Pederson and colleagues at the Minneapolis Heart Institute.

FORTIS (Edwards Lifesciences), a bovine pericardium valve, has been implanted in early feasibility trials in Europe and has been approved for an early feasibility trial of 15 patients in the United States.

Tiara (Neovasc), a D-shaped bovine pericardium valve, received FDA approval last year for the TIARA-I early feasibility trial in the United States (NCT02276547). The trial will enroll up to 30 patients worldwide.

At least five other TMVR devices are in preclinical studies, Dr. Mack said. These emerging devices face “threats and obstacles” as they move through the pipeline – a number of “what ifs,” Dr. Mack said.

“What if you can’t prove that correcting secondary mitral regurgitation makes a difference? What are the repercussions of the COAPT Trial (NCT01626079) of the MitraClip if it is positive and shows that correcting mitral regurgitation does make a difference? Does completely correcting mitral regurgitation then really make a difference? What if transcatheter mitral valve repair works too well?” (COAPT stands for Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation). “With the excellent safety profile of MitraClip, it may be hard to justify TMVR,” he said.

Dr. Mack noted that MitraClip for mitral valve repair has “a superb safety profile.” He added, “How do you choose what patients should be treated by a mitral valve replacement vs. a MitraClip by a transfemoral venous approach that enables them to go home the next day?”

The early feasibility trials of TMVR devices may point a way to answers.

Dr. Mack has received research grants from Edwards Lifesciences. He is a principal investigator in the ongoing COAPT Trial, which is sponsored by EVALVE with the collaboration of Abbott Vascular.

NEW YORK – What if correcting secondary mitral regurgitation doesn’t improve patients’ lives or helps them live longer? What if results of the COAPT trial of the MitraClip (Abbott Vascular) repair for mitral regurgitation are negative or inconclusive? What if transcatheter mitral valve repair works too well?

The answers to these questions could determine the future landscape of transcatheter mitral valve replacement (TMVR) for mitral regurgitation (MR) and the prosthetics in various stages of clinical and preclinical investigation, Dr. Michael Mack of Baylor University said at the 2015 Mitral Valve Conclave, which was sponsored by the American Association for Thoracic Surgery.

Dr. Mack reviewed the first four transcatheter mitral valve replacement devices approved for early feasibility studies in the United States, noting that “it has become a very crowded field very quickly,” especially when one considers that only between 20 and 50 TMVR procedures have been done worldwide up until now.

For the makers of the devices, it is becoming a potentially perilous field as well. Replacement, Dr. Mack said, does meet a “large clinical unmet need” in that it can completely correct mitral regurgitation better than valve repair.

“But what are the challenges for transcatheter mitral valve replacement and why isn’t this going to be the same as TAVR (transcatheter aortic valve replacement) all over again?” he said. “Unlike aortic stenosis, there is not a single cause of mitral regurgitation. In addition, it has never even been definitively proven that correcting MR helps prolong survival and improve quality of life.”

Another obstacle for TMVR is that delivery of the device into the mitral valve is more complex than doing so in the aortic valve. “The seating and the anchoring of the valve is more complex,” Dr. Mack said. “Based on the profile of the device, left ventricular outflow tract obstruction can be an issue, and perivalvular leak may carry more import here because mitral perivalvular leaks have the potential to cause hemololysis.”

He reviewed the four systems cleared for early feasibility studies.

CardiAQ (CardiAQ Valve Technologies), a porcine pericardial valve, has been implanted in eight patients worldwide and last month received Food and Drug Administration (FDA) approval for early feasibility study in 20 U.S. patients: 10 by a transfemoral approach and 10 by a transapical approach.

Tendyne Bioprosthetic Mitral Valve (Tendyne Holdings), a trileaflet porcine pericardium, also has been implanted in eight patients worldwide and was used for the first time in the United States last month by Dr. Wes Pederson and colleagues at the Minneapolis Heart Institute.

FORTIS (Edwards Lifesciences), a bovine pericardium valve, has been implanted in early feasibility trials in Europe and has been approved for an early feasibility trial of 15 patients in the United States.

Tiara (Neovasc), a D-shaped bovine pericardium valve, received FDA approval last year for the TIARA-I early feasibility trial in the United States (NCT02276547). The trial will enroll up to 30 patients worldwide.

At least five other TMVR devices are in preclinical studies, Dr. Mack said. These emerging devices face “threats and obstacles” as they move through the pipeline – a number of “what ifs,” Dr. Mack said.

“What if you can’t prove that correcting secondary mitral regurgitation makes a difference? What are the repercussions of the COAPT Trial (NCT01626079) of the MitraClip if it is positive and shows that correcting mitral regurgitation does make a difference? Does completely correcting mitral regurgitation then really make a difference? What if transcatheter mitral valve repair works too well?” (COAPT stands for Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation). “With the excellent safety profile of MitraClip, it may be hard to justify TMVR,” he said.

Dr. Mack noted that MitraClip for mitral valve repair has “a superb safety profile.” He added, “How do you choose what patients should be treated by a mitral valve replacement vs. a MitraClip by a transfemoral venous approach that enables them to go home the next day?”

The early feasibility trials of TMVR devices may point a way to answers.

Dr. Mack has received research grants from Edwards Lifesciences. He is a principal investigator in the ongoing COAPT Trial, which is sponsored by EVALVE with the collaboration of Abbott Vascular.

Although expert committees spend hours developing guidelines for best practices, clinicians on the front line of care can be somewhat hesitant to adopt them, as a recent study evaluating the use of guidelines for treatment of heart attack patients at three major cardiothoracic centers in London revealed.

The study, published in the Journal of Thoracic and Cardiovascular Surgery (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2014.10.110]) , found that surgeons more often than not flaunted the Joint European Society of Cardiology and European Association for Cardiothoracic Surgery (ESC/EACTS) guidelines that call for a multidisciplinary “Heart Team” to discuss each case of severe coronary artery disease before treatment.

The investigators looked at January-to-June periods in 2010 (before the guidelines) and 2012 (after the guidelines had been in place for 18 months) and found identical 17% rates of multidisciplinary team discussions before treatment. Both samples involved patients who had percutaneous coronary interventions (PCI). The 621 cases in the 2010 sample and 686 cases in the 2012 group comprise “a significant proportion of the coronary revascularization workload” of the National Health Service (NHS) hospitals in London, Dr. Martin T. Yates of St. George’s Hospital, University of London, and coauthors reported. The other participating centers were Barts Health NHS Trust and King College Hospital.

The ESC/EACTS guidelines (Eur. Heart J. 2010;31:2501-55) determined that PCI at the same catheterization session as the diagnostic angiogram and elective PCI are inappropriate for patients with severe coronary artery disease, defined as proximal left-anterior descending, left-main stem or three-vessel disease. The guidelines state that these patients should be considered for surgery first.

In a previous single-center study a year after the guidelines were adopted, Dr. Yates and his colleagues reported that almost a third of all elective PCI (29%) were carried out on patients who may have benefited more from coronary artery bypass grafting (CABG) (J. Thorac. Cardiovasc. Surg. 2014;147:606-10). Of those cases, the multidisciplinary team again discussed only 17% of cases before PCI.

Dr. Yates and his colleagues intimated that the rush to PCI might be circumventing in-depth discussions about more appropriate CABG for patients with severe coronary artery disease. “Furthermore, despite the guidelines suggesting that ad hoc PCI is inappropriate in the elective setting, this practice continues,” they said. “Although this is convenient for the patient and more cost effective, it does not allow time for Heart Team discussions prior to intervention.”

In the current study, the 2010 group included 187 patients with severe coronary artery disease who had treatment without a multidisciplinary team consultation, and less than half (44%) achieved complete revascularization. The 2012 group included 225 patients with severe heart disease, and precisely half achieved complete revascularization.

In both groups, a considerable majority of patients with three-vessel disease had PCI without the multidisciplinary team discussion: 76% in 2010 and 64% in 2012.

Dr. Yates and his associates noted that this is not a problem specific to London cardiac centers. They cited variations in the use of PCI and CABG in a large study of the New York State Registry, which showed that only 53% of patients suitable for CABG, according to the American College of Cardiology/American Heart Association guidelines, actually had the procedure (Circulation 2010;121:267-75). They cited similar results in a Canadian study (CMAJ 2012;184;179-86).

One way to get cardiac surgeons to adhere to guidelines is to tie payment to treatment – an approach that may work better in the United States than in Canada or the United Kingdom. “This may be easier to implement in countries with payment linked to insurance systems as opposed to those with a nationalized service,” Dr. Yates and his associates wrote.

The authors reported no financial disclosures.

Although expert committees spend hours developing guidelines for best practices, clinicians on the front line of care can be somewhat hesitant to adopt them, as a recent study evaluating the use of guidelines for treatment of heart attack patients at three major cardiothoracic centers in London revealed.

The study, published in the Journal of Thoracic and Cardiovascular Surgery (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2014.10.110]) , found that surgeons more often than not flaunted the Joint European Society of Cardiology and European Association for Cardiothoracic Surgery (ESC/EACTS) guidelines that call for a multidisciplinary “Heart Team” to discuss each case of severe coronary artery disease before treatment.

The investigators looked at January-to-June periods in 2010 (before the guidelines) and 2012 (after the guidelines had been in place for 18 months) and found identical 17% rates of multidisciplinary team discussions before treatment. Both samples involved patients who had percutaneous coronary interventions (PCI). The 621 cases in the 2010 sample and 686 cases in the 2012 group comprise “a significant proportion of the coronary revascularization workload” of the National Health Service (NHS) hospitals in London, Dr. Martin T. Yates of St. George’s Hospital, University of London, and coauthors reported. The other participating centers were Barts Health NHS Trust and King College Hospital.

The ESC/EACTS guidelines (Eur. Heart J. 2010;31:2501-55) determined that PCI at the same catheterization session as the diagnostic angiogram and elective PCI are inappropriate for patients with severe coronary artery disease, defined as proximal left-anterior descending, left-main stem or three-vessel disease. The guidelines state that these patients should be considered for surgery first.

In a previous single-center study a year after the guidelines were adopted, Dr. Yates and his colleagues reported that almost a third of all elective PCI (29%) were carried out on patients who may have benefited more from coronary artery bypass grafting (CABG) (J. Thorac. Cardiovasc. Surg. 2014;147:606-10). Of those cases, the multidisciplinary team again discussed only 17% of cases before PCI.

Dr. Yates and his colleagues intimated that the rush to PCI might be circumventing in-depth discussions about more appropriate CABG for patients with severe coronary artery disease. “Furthermore, despite the guidelines suggesting that ad hoc PCI is inappropriate in the elective setting, this practice continues,” they said. “Although this is convenient for the patient and more cost effective, it does not allow time for Heart Team discussions prior to intervention.”

In the current study, the 2010 group included 187 patients with severe coronary artery disease who had treatment without a multidisciplinary team consultation, and less than half (44%) achieved complete revascularization. The 2012 group included 225 patients with severe heart disease, and precisely half achieved complete revascularization.

In both groups, a considerable majority of patients with three-vessel disease had PCI without the multidisciplinary team discussion: 76% in 2010 and 64% in 2012.

Dr. Yates and his associates noted that this is not a problem specific to London cardiac centers. They cited variations in the use of PCI and CABG in a large study of the New York State Registry, which showed that only 53% of patients suitable for CABG, according to the American College of Cardiology/American Heart Association guidelines, actually had the procedure (Circulation 2010;121:267-75). They cited similar results in a Canadian study (CMAJ 2012;184;179-86).

One way to get cardiac surgeons to adhere to guidelines is to tie payment to treatment – an approach that may work better in the United States than in Canada or the United Kingdom. “This may be easier to implement in countries with payment linked to insurance systems as opposed to those with a nationalized service,” Dr. Yates and his associates wrote.

The authors reported no financial disclosures.

Although expert committees spend hours developing guidelines for best practices, clinicians on the front line of care can be somewhat hesitant to adopt them, as a recent study evaluating the use of guidelines for treatment of heart attack patients at three major cardiothoracic centers in London revealed.

The study, published in the Journal of Thoracic and Cardiovascular Surgery (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2014.10.110]) , found that surgeons more often than not flaunted the Joint European Society of Cardiology and European Association for Cardiothoracic Surgery (ESC/EACTS) guidelines that call for a multidisciplinary “Heart Team” to discuss each case of severe coronary artery disease before treatment.

The investigators looked at January-to-June periods in 2010 (before the guidelines) and 2012 (after the guidelines had been in place for 18 months) and found identical 17% rates of multidisciplinary team discussions before treatment. Both samples involved patients who had percutaneous coronary interventions (PCI). The 621 cases in the 2010 sample and 686 cases in the 2012 group comprise “a significant proportion of the coronary revascularization workload” of the National Health Service (NHS) hospitals in London, Dr. Martin T. Yates of St. George’s Hospital, University of London, and coauthors reported. The other participating centers were Barts Health NHS Trust and King College Hospital.

The ESC/EACTS guidelines (Eur. Heart J. 2010;31:2501-55) determined that PCI at the same catheterization session as the diagnostic angiogram and elective PCI are inappropriate for patients with severe coronary artery disease, defined as proximal left-anterior descending, left-main stem or three-vessel disease. The guidelines state that these patients should be considered for surgery first.

In a previous single-center study a year after the guidelines were adopted, Dr. Yates and his colleagues reported that almost a third of all elective PCI (29%) were carried out on patients who may have benefited more from coronary artery bypass grafting (CABG) (J. Thorac. Cardiovasc. Surg. 2014;147:606-10). Of those cases, the multidisciplinary team again discussed only 17% of cases before PCI.

Dr. Yates and his colleagues intimated that the rush to PCI might be circumventing in-depth discussions about more appropriate CABG for patients with severe coronary artery disease. “Furthermore, despite the guidelines suggesting that ad hoc PCI is inappropriate in the elective setting, this practice continues,” they said. “Although this is convenient for the patient and more cost effective, it does not allow time for Heart Team discussions prior to intervention.”

In the current study, the 2010 group included 187 patients with severe coronary artery disease who had treatment without a multidisciplinary team consultation, and less than half (44%) achieved complete revascularization. The 2012 group included 225 patients with severe heart disease, and precisely half achieved complete revascularization.

In both groups, a considerable majority of patients with three-vessel disease had PCI without the multidisciplinary team discussion: 76% in 2010 and 64% in 2012.

Dr. Yates and his associates noted that this is not a problem specific to London cardiac centers. They cited variations in the use of PCI and CABG in a large study of the New York State Registry, which showed that only 53% of patients suitable for CABG, according to the American College of Cardiology/American Heart Association guidelines, actually had the procedure (Circulation 2010;121:267-75). They cited similar results in a Canadian study (CMAJ 2012;184;179-86).

One way to get cardiac surgeons to adhere to guidelines is to tie payment to treatment – an approach that may work better in the United States than in Canada or the United Kingdom. “This may be easier to implement in countries with payment linked to insurance systems as opposed to those with a nationalized service,” Dr. Yates and his associates wrote.

The authors reported no financial disclosures.

NEW YORK – A simplified surgical approach that uses an adult-sized, basic ring annuloplasty with a complete edge-to-edge leaflet repair has been found to yield good outcomes in a group of children with connective tissue disorders like Marfan syndrome and Loeys-Dietz syndrome and mitral regurgitation, based on an evaluation of the technique at four centers.

Cardiac surgeons employed the simplified operation in 18 patients under age 18 (median age 8.2 years) and found that after 2.4 years of follow-up, no patients required another operation for mitral regurgitation, reported Dr. Luca Vricella, pediatrics director, pediatric cardiac surgery and heart transplantation, John Hopkins University, Baltimore.

The patients underwent the simplified mitral valve repair at Johns Hopkins Pediatric Cardiac Surgery in Baltimore and Orlando; Duke University School of Medicine in Durham, N.C.; and University of Pavia Medical School in Italy.

These young patients can be challenging to operate on because of skeletal abnormalities and marginal pulmonary reserve, Dr. Vricella said at the meeting sponsored by the American Association for Thoracic Surgery. Of the 18 children in the study, 15 had Marfan syndrome, a genetic disorder that commonly affects the heart valves and aorta. “The most common mode of early presentation of mitral valve pathology, from a morphological standpoint, is that mitral regurgitation is often characterized as severe bileaflet prolapse and annular and left ventricular dilation,” Dr. Vricella said.

The simplified technique involves an approach through an atriotomy and placing an adult-sized annuloplasty ring in the valve. The next step is to place an Alfieri stitch, named for the Italian cardiac surgeon Dr. Ottavio Alfieri, with a braided suture in the middle of the valve, which opposes the leaflet “very effectively,” Dr. Vricella said.

In the study group, all 18 patients had severe bileaflet prolapse and severe mitral regurgitation of grade 4 or higher, but all patients also had normal ejection fraction, Dr. Vricella said. One infant was being considered for a heart transplant.

The operation was achieved in isolation in less than an hour. Five patients underwent simultaneous valve-sparing aortic root replacement, one of whom died (one of two deaths in a larger 300-plus group of both adults and children who had valve-sparing aortic root repair). No other complications were reported among the 18-patient group. Median length of stay in the hospital was 9 days.

After the operation, all patients had significant reductions in mitral regurgitation. After 2.4 years, 94% of survivors maintained mild regurgitation or better without stenosis. Entering the study, the median left ventricular end-diastolic diameter (LVEDD) score of all patients was 4.9 (range 2.1-11.9), but at 2.4 years after the operation the median LVEDD score had regressed to 1.3 (range –0.51-4.3).

“In pediatric patients with severe mitral regurgitation and connective tissue disorders, a simplified repair can result in intermediate-term competency without systolic anterior motion and with no mitral stenosis,” Dr. Vricella said. “We’ve been pleasantly surprised in seeing this reduction in left ventricular enlargement, and particularly in this group of patients in which you may need to have a longer plant time, simplifying things so you don’t have to intervene on the subvalvular annuloplasty.”

NEW YORK – A simplified surgical approach that uses an adult-sized, basic ring annuloplasty with a complete edge-to-edge leaflet repair has been found to yield good outcomes in a group of children with connective tissue disorders like Marfan syndrome and Loeys-Dietz syndrome and mitral regurgitation, based on an evaluation of the technique at four centers.

Cardiac surgeons employed the simplified operation in 18 patients under age 18 (median age 8.2 years) and found that after 2.4 years of follow-up, no patients required another operation for mitral regurgitation, reported Dr. Luca Vricella, pediatrics director, pediatric cardiac surgery and heart transplantation, John Hopkins University, Baltimore.

The patients underwent the simplified mitral valve repair at Johns Hopkins Pediatric Cardiac Surgery in Baltimore and Orlando; Duke University School of Medicine in Durham, N.C.; and University of Pavia Medical School in Italy.

These young patients can be challenging to operate on because of skeletal abnormalities and marginal pulmonary reserve, Dr. Vricella said at the meeting sponsored by the American Association for Thoracic Surgery. Of the 18 children in the study, 15 had Marfan syndrome, a genetic disorder that commonly affects the heart valves and aorta. “The most common mode of early presentation of mitral valve pathology, from a morphological standpoint, is that mitral regurgitation is often characterized as severe bileaflet prolapse and annular and left ventricular dilation,” Dr. Vricella said.

The simplified technique involves an approach through an atriotomy and placing an adult-sized annuloplasty ring in the valve. The next step is to place an Alfieri stitch, named for the Italian cardiac surgeon Dr. Ottavio Alfieri, with a braided suture in the middle of the valve, which opposes the leaflet “very effectively,” Dr. Vricella said.

In the study group, all 18 patients had severe bileaflet prolapse and severe mitral regurgitation of grade 4 or higher, but all patients also had normal ejection fraction, Dr. Vricella said. One infant was being considered for a heart transplant.

The operation was achieved in isolation in less than an hour. Five patients underwent simultaneous valve-sparing aortic root replacement, one of whom died (one of two deaths in a larger 300-plus group of both adults and children who had valve-sparing aortic root repair). No other complications were reported among the 18-patient group. Median length of stay in the hospital was 9 days.

After the operation, all patients had significant reductions in mitral regurgitation. After 2.4 years, 94% of survivors maintained mild regurgitation or better without stenosis. Entering the study, the median left ventricular end-diastolic diameter (LVEDD) score of all patients was 4.9 (range 2.1-11.9), but at 2.4 years after the operation the median LVEDD score had regressed to 1.3 (range –0.51-4.3).

“In pediatric patients with severe mitral regurgitation and connective tissue disorders, a simplified repair can result in intermediate-term competency without systolic anterior motion and with no mitral stenosis,” Dr. Vricella said. “We’ve been pleasantly surprised in seeing this reduction in left ventricular enlargement, and particularly in this group of patients in which you may need to have a longer plant time, simplifying things so you don’t have to intervene on the subvalvular annuloplasty.”

NEW YORK – A simplified surgical approach that uses an adult-sized, basic ring annuloplasty with a complete edge-to-edge leaflet repair has been found to yield good outcomes in a group of children with connective tissue disorders like Marfan syndrome and Loeys-Dietz syndrome and mitral regurgitation, based on an evaluation of the technique at four centers.

Cardiac surgeons employed the simplified operation in 18 patients under age 18 (median age 8.2 years) and found that after 2.4 years of follow-up, no patients required another operation for mitral regurgitation, reported Dr. Luca Vricella, pediatrics director, pediatric cardiac surgery and heart transplantation, John Hopkins University, Baltimore.

The patients underwent the simplified mitral valve repair at Johns Hopkins Pediatric Cardiac Surgery in Baltimore and Orlando; Duke University School of Medicine in Durham, N.C.; and University of Pavia Medical School in Italy.

These young patients can be challenging to operate on because of skeletal abnormalities and marginal pulmonary reserve, Dr. Vricella said at the meeting sponsored by the American Association for Thoracic Surgery. Of the 18 children in the study, 15 had Marfan syndrome, a genetic disorder that commonly affects the heart valves and aorta. “The most common mode of early presentation of mitral valve pathology, from a morphological standpoint, is that mitral regurgitation is often characterized as severe bileaflet prolapse and annular and left ventricular dilation,” Dr. Vricella said.

The simplified technique involves an approach through an atriotomy and placing an adult-sized annuloplasty ring in the valve. The next step is to place an Alfieri stitch, named for the Italian cardiac surgeon Dr. Ottavio Alfieri, with a braided suture in the middle of the valve, which opposes the leaflet “very effectively,” Dr. Vricella said.

In the study group, all 18 patients had severe bileaflet prolapse and severe mitral regurgitation of grade 4 or higher, but all patients also had normal ejection fraction, Dr. Vricella said. One infant was being considered for a heart transplant.

The operation was achieved in isolation in less than an hour. Five patients underwent simultaneous valve-sparing aortic root replacement, one of whom died (one of two deaths in a larger 300-plus group of both adults and children who had valve-sparing aortic root repair). No other complications were reported among the 18-patient group. Median length of stay in the hospital was 9 days.

After the operation, all patients had significant reductions in mitral regurgitation. After 2.4 years, 94% of survivors maintained mild regurgitation or better without stenosis. Entering the study, the median left ventricular end-diastolic diameter (LVEDD) score of all patients was 4.9 (range 2.1-11.9), but at 2.4 years after the operation the median LVEDD score had regressed to 1.3 (range –0.51-4.3).

“In pediatric patients with severe mitral regurgitation and connective tissue disorders, a simplified repair can result in intermediate-term competency without systolic anterior motion and with no mitral stenosis,” Dr. Vricella said. “We’ve been pleasantly surprised in seeing this reduction in left ventricular enlargement, and particularly in this group of patients in which you may need to have a longer plant time, simplifying things so you don’t have to intervene on the subvalvular annuloplasty.”

Malignant mesothelioma poses a significant challenge for clinicians because of its ability to resist chemotherapy, but the use of three-dimensional tumor spheroid models has shown that local administration of paclitaxel in a nanoparticle platform achieved better tumor penetration than conventional paclitaxel therapy, investigators reported. The study is in the May issue of the Journal of Thoracic and Cardiovascular Surgery.

Dr. Hongyi Lei of Brigham and Women’s Hospital, Boston, and his colleagues used the in vitro mesothelioma spheroid model because two-dimensional in vitro monolayer cell culture experiments do not replicate the superior efficacy of paclitaxel-loaded expansile nanoparticles (Pax-eNPs), suggesting that Pax-eNPs utilize a unique drug delivery mechanism.

Courtesy of AATS

The study observed that spheroids treated with Pax-eNP showed increased drug penetration and a 38-fold higher intraspheroidal drug concentration at 24 hours than that of paclitaxel dissolved in Cremophor EL/ethanol (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2015.02.020]).

The researchers said their findings showed that three-dimensional spheroid models “are valuable tools for investigating cytotoxic mechanisms and nanoparticle-tumor interactions, particularly given the costs and limitations of in vivo animal studies.” Their findings were first presented at the 94th Annual Meeting of the American Association of Thoracic Surgery last year in Toronto.

Despite advances of nanoparticle-based drug delivery systems, difficulties in evaluating the effectiveness of these drugs in local chemotherapy have hindered their adoption in the clinic. Studies of the same agent utilizing in vitro vs. in vivo methods have shown conflicting results.

The observation that Pax-eNP treatment of intraperitoneal mesothelioma significantly improved survival in lab animals in vivo compared to conventional paclitaxel led to the use of the three-dimensional spheroid model. Dr. Lei and colleagues called this revelation “striking” because Pax-eNP exposure of the identical mesothelioma tumor cells plated as a two-dimensional monolayer in vitro demonstrated equal or worse results. “This suggested that eNP may be more effective at penetration and/or persistence within multicellular tumors and led to the use of a 3-D tumor spheroid mode,” they said.

“Given the high cost and limitations of in vivo animal studies, spheroid models may present a clinically relevant platform for screening novel pharmaceuticals and unique drug-delivery systems during the preclinical phase,” the researchers indicated.

They also investigated spheroid cytotoxicity in a clinic-like setting following a 4-hour, high-dose (1,000 ng/mL) paclitaxel exposure via conventional and eNP vehicles. They found that Pax-eNP exposure led to greater tumor cytotoxicity at 72 hours, and that cytotoxicity continued seven days later because Pax-eNPs rapidly enter the tumor spheroid and remain intracellular, slowly releasing the drug.

“The prolonged drug release mechanism that pH-triggered Pax-eNP uses appears to be unique, leading to markedly higher intraspheroidal drug delivery, prolonged intratumoral drug release and superior antitumor efficacy,” the investigators concluded. The authors had no disclosures.

Malignant mesothelioma poses a significant challenge for clinicians because of its ability to resist chemotherapy, but the use of three-dimensional tumor spheroid models has shown that local administration of paclitaxel in a nanoparticle platform achieved better tumor penetration than conventional paclitaxel therapy, investigators reported. The study is in the May issue of the Journal of Thoracic and Cardiovascular Surgery.

Dr. Hongyi Lei of Brigham and Women’s Hospital, Boston, and his colleagues used the in vitro mesothelioma spheroid model because two-dimensional in vitro monolayer cell culture experiments do not replicate the superior efficacy of paclitaxel-loaded expansile nanoparticles (Pax-eNPs), suggesting that Pax-eNPs utilize a unique drug delivery mechanism.

Courtesy of AATS

The study observed that spheroids treated with Pax-eNP showed increased drug penetration and a 38-fold higher intraspheroidal drug concentration at 24 hours than that of paclitaxel dissolved in Cremophor EL/ethanol (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2015.02.020]).

The researchers said their findings showed that three-dimensional spheroid models “are valuable tools for investigating cytotoxic mechanisms and nanoparticle-tumor interactions, particularly given the costs and limitations of in vivo animal studies.” Their findings were first presented at the 94th Annual Meeting of the American Association of Thoracic Surgery last year in Toronto.

Despite advances of nanoparticle-based drug delivery systems, difficulties in evaluating the effectiveness of these drugs in local chemotherapy have hindered their adoption in the clinic. Studies of the same agent utilizing in vitro vs. in vivo methods have shown conflicting results.

The observation that Pax-eNP treatment of intraperitoneal mesothelioma significantly improved survival in lab animals in vivo compared to conventional paclitaxel led to the use of the three-dimensional spheroid model. Dr. Lei and colleagues called this revelation “striking” because Pax-eNP exposure of the identical mesothelioma tumor cells plated as a two-dimensional monolayer in vitro demonstrated equal or worse results. “This suggested that eNP may be more effective at penetration and/or persistence within multicellular tumors and led to the use of a 3-D tumor spheroid mode,” they said.

“Given the high cost and limitations of in vivo animal studies, spheroid models may present a clinically relevant platform for screening novel pharmaceuticals and unique drug-delivery systems during the preclinical phase,” the researchers indicated.

They also investigated spheroid cytotoxicity in a clinic-like setting following a 4-hour, high-dose (1,000 ng/mL) paclitaxel exposure via conventional and eNP vehicles. They found that Pax-eNP exposure led to greater tumor cytotoxicity at 72 hours, and that cytotoxicity continued seven days later because Pax-eNPs rapidly enter the tumor spheroid and remain intracellular, slowly releasing the drug.

“The prolonged drug release mechanism that pH-triggered Pax-eNP uses appears to be unique, leading to markedly higher intraspheroidal drug delivery, prolonged intratumoral drug release and superior antitumor efficacy,” the investigators concluded. The authors had no disclosures.

Malignant mesothelioma poses a significant challenge for clinicians because of its ability to resist chemotherapy, but the use of three-dimensional tumor spheroid models has shown that local administration of paclitaxel in a nanoparticle platform achieved better tumor penetration than conventional paclitaxel therapy, investigators reported. The study is in the May issue of the Journal of Thoracic and Cardiovascular Surgery.

Dr. Hongyi Lei of Brigham and Women’s Hospital, Boston, and his colleagues used the in vitro mesothelioma spheroid model because two-dimensional in vitro monolayer cell culture experiments do not replicate the superior efficacy of paclitaxel-loaded expansile nanoparticles (Pax-eNPs), suggesting that Pax-eNPs utilize a unique drug delivery mechanism.

Courtesy of AATS

The study observed that spheroids treated with Pax-eNP showed increased drug penetration and a 38-fold higher intraspheroidal drug concentration at 24 hours than that of paclitaxel dissolved in Cremophor EL/ethanol (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2015.02.020]).

The researchers said their findings showed that three-dimensional spheroid models “are valuable tools for investigating cytotoxic mechanisms and nanoparticle-tumor interactions, particularly given the costs and limitations of in vivo animal studies.” Their findings were first presented at the 94th Annual Meeting of the American Association of Thoracic Surgery last year in Toronto.

Despite advances of nanoparticle-based drug delivery systems, difficulties in evaluating the effectiveness of these drugs in local chemotherapy have hindered their adoption in the clinic. Studies of the same agent utilizing in vitro vs. in vivo methods have shown conflicting results.

The observation that Pax-eNP treatment of intraperitoneal mesothelioma significantly improved survival in lab animals in vivo compared to conventional paclitaxel led to the use of the three-dimensional spheroid model. Dr. Lei and colleagues called this revelation “striking” because Pax-eNP exposure of the identical mesothelioma tumor cells plated as a two-dimensional monolayer in vitro demonstrated equal or worse results. “This suggested that eNP may be more effective at penetration and/or persistence within multicellular tumors and led to the use of a 3-D tumor spheroid mode,” they said.

“Given the high cost and limitations of in vivo animal studies, spheroid models may present a clinically relevant platform for screening novel pharmaceuticals and unique drug-delivery systems during the preclinical phase,” the researchers indicated.

They also investigated spheroid cytotoxicity in a clinic-like setting following a 4-hour, high-dose (1,000 ng/mL) paclitaxel exposure via conventional and eNP vehicles. They found that Pax-eNP exposure led to greater tumor cytotoxicity at 72 hours, and that cytotoxicity continued seven days later because Pax-eNPs rapidly enter the tumor spheroid and remain intracellular, slowly releasing the drug.

“The prolonged drug release mechanism that pH-triggered Pax-eNP uses appears to be unique, leading to markedly higher intraspheroidal drug delivery, prolonged intratumoral drug release and superior antitumor efficacy,” the investigators concluded. The authors had no disclosures.