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‘Forever chemicals’ linked to hypertension in middle-aged women
In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk of hypertension in middle-aged women. Women in the highest tertile of overall PFAS concentrations had a 71% increased risk of developing hypertension.
“Our findings suggest that long-term cumulative exposure, even before midlife, may increase the risk of high blood pressure, and therefore, the benefit of reducing the population exposure to PFAS and potential prevention of high blood pressure and other health conditions would be enormous,” Sung Kyun Park, ScD, MPH, University of Michigan School of Public Health, Ann Arbor, said in an interview.
The study was published online in Hypertension.
Everywhere and forever
“PFAS are forever chemicals as well as everywhere chemicals,” Dr. Park noted.
Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and drinking water. They have been detected in the blood of most people and have been linked to a variety of health concerns.
“A few studies showed an association between PFAS and hypertension, but those were cross-sectional and examined prevalence of hypertension. It was unclear whether PFAS are associated with the development (incidence) of hypertension,” Dr. Park explained.
For their study, the researchers examined the association between serum concentrations of PFAS and risks of incident hypertension in 1,058 initially normotensive women participating in the Study of Women’s Health Across the Nation-Multi-Pollutant Study (SWAN-MPS). They were followed annually between 1999 and 2017.
During 11,722 person-years of follow-up, 470 of the women developed hypertension, at a rate of 40.1 cases per 1,000 person-years. Hypertension was defined as blood pressure of at least 140 mm Hg systolic or at least 90 mm Hg diastolic or receiving antihypertensive treatment.
Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension, compared with peers in the lowest tertile (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-1.68; P trend = .01).
Similar results were found for perfluorooctanoate (PFOA) and 2-N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), with 47% (aHR, 1.47; 95% CI, 1.24-1.75; P trend = .01) and 42% (aHR, 1.42; 95% CI, 1.19-1.70; P trend = .01) higher risks of incident hypertension, comparing the highest to the lowest tertiles.
The risks persisted after adjusting for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.
In the PFAS “mixture” analysis, women in the highest tertile of overall PFAS concentrations were 71% more likely to develop hypertension during follow-up, compared with women in the lowest tertile (aHR, 1.71; 95% CI, 1.15-2.54; P trend = .008).
“These findings suggest that PFAS might be an underappreciated contributing factor to women’s cardiovascular disease risk,” the researchers write.
They caution that the study only included middle-aged women and that it is unclear whether the findings hold for middle-aged men.
“This is an important question, but the answer is that we do not know,” Dr. Park told this news organization.
“Women become more susceptible to metabolic changes and hypertension risk during the menopausal transition. Our findings suggest that PFAS may play a role in the development of hypertension in women during this critical life stage,” Dr. Park said.
The researchers say more research is needed to confirm and expand the findings and to find ways to reduce PFAS exposure.
“If confirmed in future studies, these findings suggest that understanding human exposure to PFAS and developing effective strategies to reduce PFAS exposure may help prevent the development of hypertension and thereby reduce the global burden of CVD,” the researchers write.
‘The more we learn, the worse it gets’
This is an “interesting” study and shows that “the more we learn about PFAS, the worse it seems to get,” Ankur Shah, MD, division of kidney disease and hypertension, Warren Alpert Medical School of Brown University, Providence, R.I., said in an interview.
“This multisite, multiracial and multiethnic, community-based longitudinal study establishes an association between PFAS and hypertension,” said Dr. Shah, who wasn’t involved in the study.
“This adds to a growing literature base of associations of PFAS with illnesses, including malignancy, thyroid disorders, diabetes, ulcerative colitis, hyperlipidemia, and pregnancy-induced hypertension,” he noted.
Dr. Shah also noted that the authors adjusted for race and ethnicity, study site, education, financial strain, smoking status, environmental tobacco smoke, alcohol consumption, total calorie intake, and menopausal status “and still found a strong association.”
“Still to be determined are both whether PFAS are the causative agent or if there is an unmeasured/unadjusted for entity which has resulted in both increased PFAS exposure and hypertension, as well as if PFAS are causative, if reduction in PFAS exposure would be result in blood pressure reduction,” Dr. Shah added.
The study had no sources of funding. Dr. Park and Dr. Shah have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk of hypertension in middle-aged women. Women in the highest tertile of overall PFAS concentrations had a 71% increased risk of developing hypertension.
“Our findings suggest that long-term cumulative exposure, even before midlife, may increase the risk of high blood pressure, and therefore, the benefit of reducing the population exposure to PFAS and potential prevention of high blood pressure and other health conditions would be enormous,” Sung Kyun Park, ScD, MPH, University of Michigan School of Public Health, Ann Arbor, said in an interview.
The study was published online in Hypertension.
Everywhere and forever
“PFAS are forever chemicals as well as everywhere chemicals,” Dr. Park noted.
Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and drinking water. They have been detected in the blood of most people and have been linked to a variety of health concerns.
“A few studies showed an association between PFAS and hypertension, but those were cross-sectional and examined prevalence of hypertension. It was unclear whether PFAS are associated with the development (incidence) of hypertension,” Dr. Park explained.
For their study, the researchers examined the association between serum concentrations of PFAS and risks of incident hypertension in 1,058 initially normotensive women participating in the Study of Women’s Health Across the Nation-Multi-Pollutant Study (SWAN-MPS). They were followed annually between 1999 and 2017.
During 11,722 person-years of follow-up, 470 of the women developed hypertension, at a rate of 40.1 cases per 1,000 person-years. Hypertension was defined as blood pressure of at least 140 mm Hg systolic or at least 90 mm Hg diastolic or receiving antihypertensive treatment.
Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension, compared with peers in the lowest tertile (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-1.68; P trend = .01).
Similar results were found for perfluorooctanoate (PFOA) and 2-N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), with 47% (aHR, 1.47; 95% CI, 1.24-1.75; P trend = .01) and 42% (aHR, 1.42; 95% CI, 1.19-1.70; P trend = .01) higher risks of incident hypertension, comparing the highest to the lowest tertiles.
The risks persisted after adjusting for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.
In the PFAS “mixture” analysis, women in the highest tertile of overall PFAS concentrations were 71% more likely to develop hypertension during follow-up, compared with women in the lowest tertile (aHR, 1.71; 95% CI, 1.15-2.54; P trend = .008).
“These findings suggest that PFAS might be an underappreciated contributing factor to women’s cardiovascular disease risk,” the researchers write.
They caution that the study only included middle-aged women and that it is unclear whether the findings hold for middle-aged men.
“This is an important question, but the answer is that we do not know,” Dr. Park told this news organization.
“Women become more susceptible to metabolic changes and hypertension risk during the menopausal transition. Our findings suggest that PFAS may play a role in the development of hypertension in women during this critical life stage,” Dr. Park said.
The researchers say more research is needed to confirm and expand the findings and to find ways to reduce PFAS exposure.
“If confirmed in future studies, these findings suggest that understanding human exposure to PFAS and developing effective strategies to reduce PFAS exposure may help prevent the development of hypertension and thereby reduce the global burden of CVD,” the researchers write.
‘The more we learn, the worse it gets’
This is an “interesting” study and shows that “the more we learn about PFAS, the worse it seems to get,” Ankur Shah, MD, division of kidney disease and hypertension, Warren Alpert Medical School of Brown University, Providence, R.I., said in an interview.
“This multisite, multiracial and multiethnic, community-based longitudinal study establishes an association between PFAS and hypertension,” said Dr. Shah, who wasn’t involved in the study.
“This adds to a growing literature base of associations of PFAS with illnesses, including malignancy, thyroid disorders, diabetes, ulcerative colitis, hyperlipidemia, and pregnancy-induced hypertension,” he noted.
Dr. Shah also noted that the authors adjusted for race and ethnicity, study site, education, financial strain, smoking status, environmental tobacco smoke, alcohol consumption, total calorie intake, and menopausal status “and still found a strong association.”
“Still to be determined are both whether PFAS are the causative agent or if there is an unmeasured/unadjusted for entity which has resulted in both increased PFAS exposure and hypertension, as well as if PFAS are causative, if reduction in PFAS exposure would be result in blood pressure reduction,” Dr. Shah added.
The study had no sources of funding. Dr. Park and Dr. Shah have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk of hypertension in middle-aged women. Women in the highest tertile of overall PFAS concentrations had a 71% increased risk of developing hypertension.
“Our findings suggest that long-term cumulative exposure, even before midlife, may increase the risk of high blood pressure, and therefore, the benefit of reducing the population exposure to PFAS and potential prevention of high blood pressure and other health conditions would be enormous,” Sung Kyun Park, ScD, MPH, University of Michigan School of Public Health, Ann Arbor, said in an interview.
The study was published online in Hypertension.
Everywhere and forever
“PFAS are forever chemicals as well as everywhere chemicals,” Dr. Park noted.
Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and drinking water. They have been detected in the blood of most people and have been linked to a variety of health concerns.
“A few studies showed an association between PFAS and hypertension, but those were cross-sectional and examined prevalence of hypertension. It was unclear whether PFAS are associated with the development (incidence) of hypertension,” Dr. Park explained.
For their study, the researchers examined the association between serum concentrations of PFAS and risks of incident hypertension in 1,058 initially normotensive women participating in the Study of Women’s Health Across the Nation-Multi-Pollutant Study (SWAN-MPS). They were followed annually between 1999 and 2017.
During 11,722 person-years of follow-up, 470 of the women developed hypertension, at a rate of 40.1 cases per 1,000 person-years. Hypertension was defined as blood pressure of at least 140 mm Hg systolic or at least 90 mm Hg diastolic or receiving antihypertensive treatment.
Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension, compared with peers in the lowest tertile (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-1.68; P trend = .01).
Similar results were found for perfluorooctanoate (PFOA) and 2-N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), with 47% (aHR, 1.47; 95% CI, 1.24-1.75; P trend = .01) and 42% (aHR, 1.42; 95% CI, 1.19-1.70; P trend = .01) higher risks of incident hypertension, comparing the highest to the lowest tertiles.
The risks persisted after adjusting for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.
In the PFAS “mixture” analysis, women in the highest tertile of overall PFAS concentrations were 71% more likely to develop hypertension during follow-up, compared with women in the lowest tertile (aHR, 1.71; 95% CI, 1.15-2.54; P trend = .008).
“These findings suggest that PFAS might be an underappreciated contributing factor to women’s cardiovascular disease risk,” the researchers write.
They caution that the study only included middle-aged women and that it is unclear whether the findings hold for middle-aged men.
“This is an important question, but the answer is that we do not know,” Dr. Park told this news organization.
“Women become more susceptible to metabolic changes and hypertension risk during the menopausal transition. Our findings suggest that PFAS may play a role in the development of hypertension in women during this critical life stage,” Dr. Park said.
The researchers say more research is needed to confirm and expand the findings and to find ways to reduce PFAS exposure.
“If confirmed in future studies, these findings suggest that understanding human exposure to PFAS and developing effective strategies to reduce PFAS exposure may help prevent the development of hypertension and thereby reduce the global burden of CVD,” the researchers write.
‘The more we learn, the worse it gets’
This is an “interesting” study and shows that “the more we learn about PFAS, the worse it seems to get,” Ankur Shah, MD, division of kidney disease and hypertension, Warren Alpert Medical School of Brown University, Providence, R.I., said in an interview.
“This multisite, multiracial and multiethnic, community-based longitudinal study establishes an association between PFAS and hypertension,” said Dr. Shah, who wasn’t involved in the study.
“This adds to a growing literature base of associations of PFAS with illnesses, including malignancy, thyroid disorders, diabetes, ulcerative colitis, hyperlipidemia, and pregnancy-induced hypertension,” he noted.
Dr. Shah also noted that the authors adjusted for race and ethnicity, study site, education, financial strain, smoking status, environmental tobacco smoke, alcohol consumption, total calorie intake, and menopausal status “and still found a strong association.”
“Still to be determined are both whether PFAS are the causative agent or if there is an unmeasured/unadjusted for entity which has resulted in both increased PFAS exposure and hypertension, as well as if PFAS are causative, if reduction in PFAS exposure would be result in blood pressure reduction,” Dr. Shah added.
The study had no sources of funding. Dr. Park and Dr. Shah have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM HYPERTENSION
Cause of death in pig heart recipient: New clues
The underlying cause of David Bennett’s death on March 8, two months after he received the heart of a genetically altered pig, remains unknown and is only slightly less mysterious for what can likely be ruled out, suggests a progress report on the case from the director of the cardiac xenotransplantation program where the pioneering surgery took place.
Mr. Bennett died in “diastolic heart failure,” reported Muhammad M. Mohiuddin, MBBS, University of Maryland School of Medicine, Baltimore, “but the mechanism is still under investigation.”
Although the immediate cause could have been single or multiple, evidence so far does not point to immune rejection nor does it support a role for a recently proposed suspect, infection by porcine cytomegalovirus (PCMV), Dr. Mohiuddin observed in front of a standing-room-only audience June 6 at the American Transplant Congress (ATC) in Boston. The congress is a joint meeting of the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST).
Rocky clinical course
Early characterizations of the patient’s death focused more on his diminished, end-stage clinical condition at the time of the surgery than on immune rejection or other direct effects of the xenograft or on the first-of-its-kind procedure itself.
The 57-year-old Mr. Bennett had presented to the University of Maryland team with nonischemic cardiomyopathy, on multiple inotropes, and requiring an intra-aortic balloon pump, Dr. Mohiuddin said in his ATC presentation. The patient had suffered multiple arrests and resuscitations, and by the time of surgery had been hospitalized for almost 2 months, including 40 days on veno-arterial extracorporeal membrane oxygenation (ECMO).
The transplant procedure itself went as planned until removal of the aortic cross clamp, which triggered a type-A aortic dissection. “We put a graft in the ascending aorta and a stent in the descending aorta. Even after 2 days, we found the dissection extending to the renal artery, so we had to go back and also put a stent in the renal artery,” Dr. Mohiuddin said.
Mr. Bennett also underwent two exploratory laparotomies in the first 10 days after transplantation, after CT imaging revealed signs of possible bowel inflammation and ischemia.
Further, he had to fight back a series of infections that led to major changes to his experimental drug regimen, which included immunosuppressants methylprednisolone and mycophenolate mofetil (MMF), the investigational anti-CD40 antibody KPL-404 (Kiniksa Pharmaceuticals), and the anti-inflammatories etanercept (Enbrel) and tocilizumab (Actemra).
One episode of sepsis, in particular, forced temporary withdrawal of MMF and a reduction in methylprednisolone dosage. It’s unknown whether the 30-day MMF suspension played a role in Mr. Bennett’s ultimate clinical deterioration and death, but it’s “highly possible,” Dr. Mohiuddin said in an interview.
Realistically, Mr. Bennett’s death was likely “multifactorial,” Dr. Mohiuddin said. He was in such poor clinical condition going into the procedure, and afterward confronted so many clinical challenges, that “it’s very difficult to say that one thing caused it.”
That hasn’t lessened speculation that the patient’s heart failed secondary to immunologic rejection or PCMV infection, either in Mr. Bennett or the donor pig.
A role for PCMV?
Weeks after Mr. Bennett’s death, as previously reported, his surgeon announced at a public forum that PCMV had been identified in the transplanted heart and in tissues of the donor pig. Mr. Bennett’s circulation showed traces of the viral DNA but not of the virus itself.
The presence of PCMV in transplanted porcine hearts is a well-recognized potential hazard in animal models but is considered avoidable with proper screening. In Mr. Bennett’s case, preoperative screening of the pig donor missed signs of the virus.
Still, PCMV could potentially have contributed to Mr. Bennett’s death, acknowledged Bartley P. Griffith, MD, University of Maryland School of Medicine, who had announced the PCMV finding in an AST-sponsored April 20 webcast.
Preclinical evidence does suggest that PCMV can harm a xenograft organ, observed David H. Sachs, MD, Columbia University Medical Center, New York, from the audience during the comment period after Dr. Mohiuddin’s presentation.
“Each species has a CMV, and they’re quite species-specific,” observed the renowned surgeon and xenotransplantation immunologist. “We showed almost 10 years ago that if PCMV was in a pig kidney, it led to a much shortened survival of the pig kidney in a baboon. There was never any evidence, however, that the CMV infected the baboon or any baboon cells.”
Dr. Sachs asked Dr. Mohiuddin for confirmation that Mr. Bennett displayed no more than DNAemia, circulating cell-free PCMV DNA presumably shed from the porcine heart, but no sign of the virus itself outside of the heart’s porcine cells.
Cell-free DNA had shown up in Mr. Bennett’s circulation about 20 days after the surgery, with concentrations rising until at least day 50. Post-hoc polymerase chain reaction (PCR) testing disclosed PCMV only in the pig’s spleen and porcine cells of the transplanted heart, Dr. Mohiuddin noted.
“We have not found any evidence that the patient was infected by PCMV,” nor was there evidence of any disease related to PCMV, Dr. Mohiuddin replied.
Nor of ongoing rejection
Mr. Bennett’s new heart passed a critical test in the first post-implantation hours by avoiding acute rejection, a potentially disastrous outcome that three of the pig’s 10 gene edits had been designed to prevent.
Although chronic immune rejection was always a concern despite Mr. Bennett’s novel immunosuppressant regimen, myocardial biopsy on postoperative days 34, 50, and 56 and necropsy showed “no signs of typical xenograft rejection,” Dr. Mohiuddin said at the ATC presentation. But “there’s a chance of atypical rejection which we were not accustomed to.”
By day 50, his diastolic function showed echocardiographic signs of deterioration, and “we started seeing interstitial edema with some extravasation of red blood cells, which we thought would resolve over a period of time,” he said. Eventually, however, “we saw that turn into fibroblasts and scar tissue.”
Mr. Bennett once again went on veno-arterial ECMO but died 10 days later. Once they had seen histologic evidence of fibrosis, Dr. Mohiuddin told this news organization, the team believed the myocardial injury was irreversible. “That was the reason we gave up on recovery.”
Mr. Bennett’s xenotransplantation journey has taught the field a lot, he said. “By no means was this a failure; we consider this a huge success. You can do all the experiments in animal models, but you won’t find out the true mechanism of rejection unless you do these kinds of human experiments.”
Looking ahead to clinical trials
Research involving humans is always subject to vagaries of human nature, including degree of adherence to prescribed therapy and – in xenotransplantation – precautions in place to mitigate any risks to public health. Such risks theoretically include transfer of porcine viruses or other pathogens to the patient and subsequent release into the general population.
Looking ahead to the possibility of clinical trials after this successful xenotransplantation experience, transplant nephrologist and epidemiologist Peter P. Reese, MD, PhD, University of Pennsylvania, Philadelphia, raised the potentially controversial issue in discussion following Dr. Mohiuddin’s presentation.
It’s known that Mr. Bennett had been repeatedly turned down for a conventional allograft transplant primarily because of his history of treatment noncompliance. Should such a record, Dr. Reese asked, be a relative contraindication to enrollment in any future xenotransplantation trials? Or does the field need a standardized gauge of a patient’s readiness, once discharged, to adhere not only to all medications – including those that fight infection – but also with rules established for public safety, such as routine contact reporting?
“It makes me wonder about choosing a noncompliant patient for these trials,” Dr. Reese said. “If we discharge a patient from the hospital who is at risk for a zoonotic infection that could spread if they basically refuse to cooperate with us or with public health authorities, it really could have negative consequences for the reputation of the field.”
Dr. Mohiuddin agreed such concerns are valid. Mr. Bennett “and all his immediate contacts” signed consent forms acknowledging their willingness to be followed should he be discharged. Mr. Bennett himself “signed a consent to inform us if he has any other intimate contact with someone,” he said in an interview.
“But those are only on paper.” Had Mr. Bennett survived to be discharged, Dr. Mohuiddin said, “no one knows how he would have behaved.”
Dr. Mohiuddin said the research staff had prepared to monitor Mr. Bennett at his home if that’s what it took. “We were ready to follow him as long as we could. There was a surveillance plan in place.”
A version of this article first appeared on Medscape.com.
The underlying cause of David Bennett’s death on March 8, two months after he received the heart of a genetically altered pig, remains unknown and is only slightly less mysterious for what can likely be ruled out, suggests a progress report on the case from the director of the cardiac xenotransplantation program where the pioneering surgery took place.
Mr. Bennett died in “diastolic heart failure,” reported Muhammad M. Mohiuddin, MBBS, University of Maryland School of Medicine, Baltimore, “but the mechanism is still under investigation.”
Although the immediate cause could have been single or multiple, evidence so far does not point to immune rejection nor does it support a role for a recently proposed suspect, infection by porcine cytomegalovirus (PCMV), Dr. Mohiuddin observed in front of a standing-room-only audience June 6 at the American Transplant Congress (ATC) in Boston. The congress is a joint meeting of the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST).
Rocky clinical course
Early characterizations of the patient’s death focused more on his diminished, end-stage clinical condition at the time of the surgery than on immune rejection or other direct effects of the xenograft or on the first-of-its-kind procedure itself.
The 57-year-old Mr. Bennett had presented to the University of Maryland team with nonischemic cardiomyopathy, on multiple inotropes, and requiring an intra-aortic balloon pump, Dr. Mohiuddin said in his ATC presentation. The patient had suffered multiple arrests and resuscitations, and by the time of surgery had been hospitalized for almost 2 months, including 40 days on veno-arterial extracorporeal membrane oxygenation (ECMO).
The transplant procedure itself went as planned until removal of the aortic cross clamp, which triggered a type-A aortic dissection. “We put a graft in the ascending aorta and a stent in the descending aorta. Even after 2 days, we found the dissection extending to the renal artery, so we had to go back and also put a stent in the renal artery,” Dr. Mohiuddin said.
Mr. Bennett also underwent two exploratory laparotomies in the first 10 days after transplantation, after CT imaging revealed signs of possible bowel inflammation and ischemia.
Further, he had to fight back a series of infections that led to major changes to his experimental drug regimen, which included immunosuppressants methylprednisolone and mycophenolate mofetil (MMF), the investigational anti-CD40 antibody KPL-404 (Kiniksa Pharmaceuticals), and the anti-inflammatories etanercept (Enbrel) and tocilizumab (Actemra).
One episode of sepsis, in particular, forced temporary withdrawal of MMF and a reduction in methylprednisolone dosage. It’s unknown whether the 30-day MMF suspension played a role in Mr. Bennett’s ultimate clinical deterioration and death, but it’s “highly possible,” Dr. Mohiuddin said in an interview.
Realistically, Mr. Bennett’s death was likely “multifactorial,” Dr. Mohiuddin said. He was in such poor clinical condition going into the procedure, and afterward confronted so many clinical challenges, that “it’s very difficult to say that one thing caused it.”
That hasn’t lessened speculation that the patient’s heart failed secondary to immunologic rejection or PCMV infection, either in Mr. Bennett or the donor pig.
A role for PCMV?
Weeks after Mr. Bennett’s death, as previously reported, his surgeon announced at a public forum that PCMV had been identified in the transplanted heart and in tissues of the donor pig. Mr. Bennett’s circulation showed traces of the viral DNA but not of the virus itself.
The presence of PCMV in transplanted porcine hearts is a well-recognized potential hazard in animal models but is considered avoidable with proper screening. In Mr. Bennett’s case, preoperative screening of the pig donor missed signs of the virus.
Still, PCMV could potentially have contributed to Mr. Bennett’s death, acknowledged Bartley P. Griffith, MD, University of Maryland School of Medicine, who had announced the PCMV finding in an AST-sponsored April 20 webcast.
Preclinical evidence does suggest that PCMV can harm a xenograft organ, observed David H. Sachs, MD, Columbia University Medical Center, New York, from the audience during the comment period after Dr. Mohiuddin’s presentation.
“Each species has a CMV, and they’re quite species-specific,” observed the renowned surgeon and xenotransplantation immunologist. “We showed almost 10 years ago that if PCMV was in a pig kidney, it led to a much shortened survival of the pig kidney in a baboon. There was never any evidence, however, that the CMV infected the baboon or any baboon cells.”
Dr. Sachs asked Dr. Mohiuddin for confirmation that Mr. Bennett displayed no more than DNAemia, circulating cell-free PCMV DNA presumably shed from the porcine heart, but no sign of the virus itself outside of the heart’s porcine cells.
Cell-free DNA had shown up in Mr. Bennett’s circulation about 20 days after the surgery, with concentrations rising until at least day 50. Post-hoc polymerase chain reaction (PCR) testing disclosed PCMV only in the pig’s spleen and porcine cells of the transplanted heart, Dr. Mohiuddin noted.
“We have not found any evidence that the patient was infected by PCMV,” nor was there evidence of any disease related to PCMV, Dr. Mohiuddin replied.
Nor of ongoing rejection
Mr. Bennett’s new heart passed a critical test in the first post-implantation hours by avoiding acute rejection, a potentially disastrous outcome that three of the pig’s 10 gene edits had been designed to prevent.
Although chronic immune rejection was always a concern despite Mr. Bennett’s novel immunosuppressant regimen, myocardial biopsy on postoperative days 34, 50, and 56 and necropsy showed “no signs of typical xenograft rejection,” Dr. Mohiuddin said at the ATC presentation. But “there’s a chance of atypical rejection which we were not accustomed to.”
By day 50, his diastolic function showed echocardiographic signs of deterioration, and “we started seeing interstitial edema with some extravasation of red blood cells, which we thought would resolve over a period of time,” he said. Eventually, however, “we saw that turn into fibroblasts and scar tissue.”
Mr. Bennett once again went on veno-arterial ECMO but died 10 days later. Once they had seen histologic evidence of fibrosis, Dr. Mohiuddin told this news organization, the team believed the myocardial injury was irreversible. “That was the reason we gave up on recovery.”
Mr. Bennett’s xenotransplantation journey has taught the field a lot, he said. “By no means was this a failure; we consider this a huge success. You can do all the experiments in animal models, but you won’t find out the true mechanism of rejection unless you do these kinds of human experiments.”
Looking ahead to clinical trials
Research involving humans is always subject to vagaries of human nature, including degree of adherence to prescribed therapy and – in xenotransplantation – precautions in place to mitigate any risks to public health. Such risks theoretically include transfer of porcine viruses or other pathogens to the patient and subsequent release into the general population.
Looking ahead to the possibility of clinical trials after this successful xenotransplantation experience, transplant nephrologist and epidemiologist Peter P. Reese, MD, PhD, University of Pennsylvania, Philadelphia, raised the potentially controversial issue in discussion following Dr. Mohiuddin’s presentation.
It’s known that Mr. Bennett had been repeatedly turned down for a conventional allograft transplant primarily because of his history of treatment noncompliance. Should such a record, Dr. Reese asked, be a relative contraindication to enrollment in any future xenotransplantation trials? Or does the field need a standardized gauge of a patient’s readiness, once discharged, to adhere not only to all medications – including those that fight infection – but also with rules established for public safety, such as routine contact reporting?
“It makes me wonder about choosing a noncompliant patient for these trials,” Dr. Reese said. “If we discharge a patient from the hospital who is at risk for a zoonotic infection that could spread if they basically refuse to cooperate with us or with public health authorities, it really could have negative consequences for the reputation of the field.”
Dr. Mohiuddin agreed such concerns are valid. Mr. Bennett “and all his immediate contacts” signed consent forms acknowledging their willingness to be followed should he be discharged. Mr. Bennett himself “signed a consent to inform us if he has any other intimate contact with someone,” he said in an interview.
“But those are only on paper.” Had Mr. Bennett survived to be discharged, Dr. Mohuiddin said, “no one knows how he would have behaved.”
Dr. Mohiuddin said the research staff had prepared to monitor Mr. Bennett at his home if that’s what it took. “We were ready to follow him as long as we could. There was a surveillance plan in place.”
A version of this article first appeared on Medscape.com.
The underlying cause of David Bennett’s death on March 8, two months after he received the heart of a genetically altered pig, remains unknown and is only slightly less mysterious for what can likely be ruled out, suggests a progress report on the case from the director of the cardiac xenotransplantation program where the pioneering surgery took place.
Mr. Bennett died in “diastolic heart failure,” reported Muhammad M. Mohiuddin, MBBS, University of Maryland School of Medicine, Baltimore, “but the mechanism is still under investigation.”
Although the immediate cause could have been single or multiple, evidence so far does not point to immune rejection nor does it support a role for a recently proposed suspect, infection by porcine cytomegalovirus (PCMV), Dr. Mohiuddin observed in front of a standing-room-only audience June 6 at the American Transplant Congress (ATC) in Boston. The congress is a joint meeting of the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST).
Rocky clinical course
Early characterizations of the patient’s death focused more on his diminished, end-stage clinical condition at the time of the surgery than on immune rejection or other direct effects of the xenograft or on the first-of-its-kind procedure itself.
The 57-year-old Mr. Bennett had presented to the University of Maryland team with nonischemic cardiomyopathy, on multiple inotropes, and requiring an intra-aortic balloon pump, Dr. Mohiuddin said in his ATC presentation. The patient had suffered multiple arrests and resuscitations, and by the time of surgery had been hospitalized for almost 2 months, including 40 days on veno-arterial extracorporeal membrane oxygenation (ECMO).
The transplant procedure itself went as planned until removal of the aortic cross clamp, which triggered a type-A aortic dissection. “We put a graft in the ascending aorta and a stent in the descending aorta. Even after 2 days, we found the dissection extending to the renal artery, so we had to go back and also put a stent in the renal artery,” Dr. Mohiuddin said.
Mr. Bennett also underwent two exploratory laparotomies in the first 10 days after transplantation, after CT imaging revealed signs of possible bowel inflammation and ischemia.
Further, he had to fight back a series of infections that led to major changes to his experimental drug regimen, which included immunosuppressants methylprednisolone and mycophenolate mofetil (MMF), the investigational anti-CD40 antibody KPL-404 (Kiniksa Pharmaceuticals), and the anti-inflammatories etanercept (Enbrel) and tocilizumab (Actemra).
One episode of sepsis, in particular, forced temporary withdrawal of MMF and a reduction in methylprednisolone dosage. It’s unknown whether the 30-day MMF suspension played a role in Mr. Bennett’s ultimate clinical deterioration and death, but it’s “highly possible,” Dr. Mohiuddin said in an interview.
Realistically, Mr. Bennett’s death was likely “multifactorial,” Dr. Mohiuddin said. He was in such poor clinical condition going into the procedure, and afterward confronted so many clinical challenges, that “it’s very difficult to say that one thing caused it.”
That hasn’t lessened speculation that the patient’s heart failed secondary to immunologic rejection or PCMV infection, either in Mr. Bennett or the donor pig.
A role for PCMV?
Weeks after Mr. Bennett’s death, as previously reported, his surgeon announced at a public forum that PCMV had been identified in the transplanted heart and in tissues of the donor pig. Mr. Bennett’s circulation showed traces of the viral DNA but not of the virus itself.
The presence of PCMV in transplanted porcine hearts is a well-recognized potential hazard in animal models but is considered avoidable with proper screening. In Mr. Bennett’s case, preoperative screening of the pig donor missed signs of the virus.
Still, PCMV could potentially have contributed to Mr. Bennett’s death, acknowledged Bartley P. Griffith, MD, University of Maryland School of Medicine, who had announced the PCMV finding in an AST-sponsored April 20 webcast.
Preclinical evidence does suggest that PCMV can harm a xenograft organ, observed David H. Sachs, MD, Columbia University Medical Center, New York, from the audience during the comment period after Dr. Mohiuddin’s presentation.
“Each species has a CMV, and they’re quite species-specific,” observed the renowned surgeon and xenotransplantation immunologist. “We showed almost 10 years ago that if PCMV was in a pig kidney, it led to a much shortened survival of the pig kidney in a baboon. There was never any evidence, however, that the CMV infected the baboon or any baboon cells.”
Dr. Sachs asked Dr. Mohiuddin for confirmation that Mr. Bennett displayed no more than DNAemia, circulating cell-free PCMV DNA presumably shed from the porcine heart, but no sign of the virus itself outside of the heart’s porcine cells.
Cell-free DNA had shown up in Mr. Bennett’s circulation about 20 days after the surgery, with concentrations rising until at least day 50. Post-hoc polymerase chain reaction (PCR) testing disclosed PCMV only in the pig’s spleen and porcine cells of the transplanted heart, Dr. Mohiuddin noted.
“We have not found any evidence that the patient was infected by PCMV,” nor was there evidence of any disease related to PCMV, Dr. Mohiuddin replied.
Nor of ongoing rejection
Mr. Bennett’s new heart passed a critical test in the first post-implantation hours by avoiding acute rejection, a potentially disastrous outcome that three of the pig’s 10 gene edits had been designed to prevent.
Although chronic immune rejection was always a concern despite Mr. Bennett’s novel immunosuppressant regimen, myocardial biopsy on postoperative days 34, 50, and 56 and necropsy showed “no signs of typical xenograft rejection,” Dr. Mohiuddin said at the ATC presentation. But “there’s a chance of atypical rejection which we were not accustomed to.”
By day 50, his diastolic function showed echocardiographic signs of deterioration, and “we started seeing interstitial edema with some extravasation of red blood cells, which we thought would resolve over a period of time,” he said. Eventually, however, “we saw that turn into fibroblasts and scar tissue.”
Mr. Bennett once again went on veno-arterial ECMO but died 10 days later. Once they had seen histologic evidence of fibrosis, Dr. Mohiuddin told this news organization, the team believed the myocardial injury was irreversible. “That was the reason we gave up on recovery.”
Mr. Bennett’s xenotransplantation journey has taught the field a lot, he said. “By no means was this a failure; we consider this a huge success. You can do all the experiments in animal models, but you won’t find out the true mechanism of rejection unless you do these kinds of human experiments.”
Looking ahead to clinical trials
Research involving humans is always subject to vagaries of human nature, including degree of adherence to prescribed therapy and – in xenotransplantation – precautions in place to mitigate any risks to public health. Such risks theoretically include transfer of porcine viruses or other pathogens to the patient and subsequent release into the general population.
Looking ahead to the possibility of clinical trials after this successful xenotransplantation experience, transplant nephrologist and epidemiologist Peter P. Reese, MD, PhD, University of Pennsylvania, Philadelphia, raised the potentially controversial issue in discussion following Dr. Mohiuddin’s presentation.
It’s known that Mr. Bennett had been repeatedly turned down for a conventional allograft transplant primarily because of his history of treatment noncompliance. Should such a record, Dr. Reese asked, be a relative contraindication to enrollment in any future xenotransplantation trials? Or does the field need a standardized gauge of a patient’s readiness, once discharged, to adhere not only to all medications – including those that fight infection – but also with rules established for public safety, such as routine contact reporting?
“It makes me wonder about choosing a noncompliant patient for these trials,” Dr. Reese said. “If we discharge a patient from the hospital who is at risk for a zoonotic infection that could spread if they basically refuse to cooperate with us or with public health authorities, it really could have negative consequences for the reputation of the field.”
Dr. Mohiuddin agreed such concerns are valid. Mr. Bennett “and all his immediate contacts” signed consent forms acknowledging their willingness to be followed should he be discharged. Mr. Bennett himself “signed a consent to inform us if he has any other intimate contact with someone,” he said in an interview.
“But those are only on paper.” Had Mr. Bennett survived to be discharged, Dr. Mohuiddin said, “no one knows how he would have behaved.”
Dr. Mohiuddin said the research staff had prepared to monitor Mr. Bennett at his home if that’s what it took. “We were ready to follow him as long as we could. There was a surveillance plan in place.”
A version of this article first appeared on Medscape.com.
Prediabetes is linked independently to myocardial infarction
Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.
“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.
There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
Data drawn from 1.8 million patients
In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.
Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).
A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.
As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
Relevance seen for community care
Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.
Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.
“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.
Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.
Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
Worsening prediabetes should be addressed
“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.
“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.
These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.
“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.
“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.
Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.
“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.
Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.
Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.
“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.
There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
Data drawn from 1.8 million patients
In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.
Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).
A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.
As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
Relevance seen for community care
Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.
Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.
“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.
Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.
Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
Worsening prediabetes should be addressed
“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.
“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.
These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.
“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.
“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.
Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.
“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.
Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.
Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.
“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.
There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
Data drawn from 1.8 million patients
In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.
Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).
A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.
As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
Relevance seen for community care
Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.
Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.
“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.
Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.
Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
Worsening prediabetes should be addressed
“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.
“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.
These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.
“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.
“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.
Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.
“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.
Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.
FROM ENDO 2022
Omega-3 supplement sweet spot found for BP reduction
A meta-analysis of 71 randomized controlled trials has found the sweet spot for omega-3 fatty acid intake for lowering blood pressure: between 2 and 3 g/day. The investigators also reported that people at higher risk for cardiovascular disease may benefit from higher daily intake of omega-3.
The study analyzed data from randomized controlled trials involving 4,973 individuals and published from 1987 to 2020. Most of the trials used a combined supplementation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Outcomes analysis involved the impact of combined DHA-EPA at 1, 2, 3, 4, or 5 grams daily on average changes in both systolic and diastolic BP and compared them with the placebo or control groups who had a combined intake of 0 g/day.
“We found a significant nonlinear dose-response relationship for both SBP and DBP models,” wrote senior author Xinzhi Li, MD, PhD, and colleagues. Dr. Li is program director of the school of pharmacy at Macau University of Science and Technology in Taipa, China.
Most of the trials included in the meta-analysis evaluated fish oil supplements, but a number also included EPA and DHA omega-3 fatty acids consumed in food.
When the investigators analyzed studies that used an average baseline SBP of greater than 130 mm Hg, they found that increasing omega-3 supplementation resulted in strong reductions in SBP and DBP, but not so with people with baseline SBP below 130 mm Hg.
Across the entire cohort, average SBP and DBP changes averaged –2.61 (95% confidence interval, –3.57 to –1.65) and –1.64 (95% CI, –2.29 to –0.99) mm Hg for people taking 2 g/d omega-3 supplements, and –2.61 (95% CI, –3.52 to –1.69) and –1.80 (95% CI, –2.38 to –1.23) for those on 3 g/d. The changes weren’t as robust in higher and lower intake groups overall.
However, the higher the BP, the more robust the reductions. For those with SBP greater than 130 mm Hg, 3 g/d resulted in an average change of –3.22 mm Hg (95% CI, –5.21 to –1.23). In the greater than 80 mm Hg DBP group, 3 g/d of omega-3 resulted in an average –3.81 mm Hg reduction (95% CI, –4.48 to –1.87). In patients with BP greater than 140/90 and hypertension, the reductions were even more pronounced. And in patients with BP greater than 130/80, omega-3 intake of 4-5 g/d had a greater impact than 2-3 g/d, although that benefit didn’t carry over in the greater than 140/90 group.
High cholesterol was also a factor in determining the benefits of omega-3 supplementation on BP, as Dr. Li and colleagues wrote that they found “an approximately linear relationship” between hyperlipidemia and SBP, “suggesting that increasing supplementation was associated with greater reductions in SBP.” Likewise, the study found stronger effects on BP in studies with an average patient age greater than 45 years.
In 2019, the Food and Drug Administration issued an update that consuming combined EPA and DHA may lower BP in the general population and reduce the risk of hypertension, but that “the evidence is inconsistent and inconclusive.”
“However, while our study may add a layer of credible evidence, it does not meet the threshold to make an authorized health claim for omega-3 fatty acids in compliance with FDA regulations,” Dr. Li said.
The study addresses shortcomings of previous studies of omega-3 and BP and by identifying the optimal dose, Marc George, MRCP, PhD, of the Institute of Cardiovascular Science, University College, London, and Ajay Gupta, MD, PhD, of the William Harvey Research Institute at Queen Mary University, London, wrote in an accompanying editorial. “More importantly, they have demonstrated a significantly stronger and increased BP-lowering effect in higher cardiovascular risk groups, such as those with hypertension or hyperlipidemia.”
They also noted that the 2.61–mm Hg reduction in SBP the study reported is “likely to be significant” on a population level. “A 2–mm Hg reduction in SBP is estimated to reduce stroke mortality by 10% and deaths from ischemic heart disease by 7%,” they wrote. “Expressed another way, an analysis in the U.S. population using 2010 data estimates that a population-wide reduction in SBP of 2 mm Hg in those aged 45- 64 years would translate to 30,045 fewer cardiovascular events ([coronary heart disease], stroke, and heart failure).”
The investigators and editorialists have no disclosures.
A meta-analysis of 71 randomized controlled trials has found the sweet spot for omega-3 fatty acid intake for lowering blood pressure: between 2 and 3 g/day. The investigators also reported that people at higher risk for cardiovascular disease may benefit from higher daily intake of omega-3.
The study analyzed data from randomized controlled trials involving 4,973 individuals and published from 1987 to 2020. Most of the trials used a combined supplementation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Outcomes analysis involved the impact of combined DHA-EPA at 1, 2, 3, 4, or 5 grams daily on average changes in both systolic and diastolic BP and compared them with the placebo or control groups who had a combined intake of 0 g/day.
“We found a significant nonlinear dose-response relationship for both SBP and DBP models,” wrote senior author Xinzhi Li, MD, PhD, and colleagues. Dr. Li is program director of the school of pharmacy at Macau University of Science and Technology in Taipa, China.
Most of the trials included in the meta-analysis evaluated fish oil supplements, but a number also included EPA and DHA omega-3 fatty acids consumed in food.
When the investigators analyzed studies that used an average baseline SBP of greater than 130 mm Hg, they found that increasing omega-3 supplementation resulted in strong reductions in SBP and DBP, but not so with people with baseline SBP below 130 mm Hg.
Across the entire cohort, average SBP and DBP changes averaged –2.61 (95% confidence interval, –3.57 to –1.65) and –1.64 (95% CI, –2.29 to –0.99) mm Hg for people taking 2 g/d omega-3 supplements, and –2.61 (95% CI, –3.52 to –1.69) and –1.80 (95% CI, –2.38 to –1.23) for those on 3 g/d. The changes weren’t as robust in higher and lower intake groups overall.
However, the higher the BP, the more robust the reductions. For those with SBP greater than 130 mm Hg, 3 g/d resulted in an average change of –3.22 mm Hg (95% CI, –5.21 to –1.23). In the greater than 80 mm Hg DBP group, 3 g/d of omega-3 resulted in an average –3.81 mm Hg reduction (95% CI, –4.48 to –1.87). In patients with BP greater than 140/90 and hypertension, the reductions were even more pronounced. And in patients with BP greater than 130/80, omega-3 intake of 4-5 g/d had a greater impact than 2-3 g/d, although that benefit didn’t carry over in the greater than 140/90 group.
High cholesterol was also a factor in determining the benefits of omega-3 supplementation on BP, as Dr. Li and colleagues wrote that they found “an approximately linear relationship” between hyperlipidemia and SBP, “suggesting that increasing supplementation was associated with greater reductions in SBP.” Likewise, the study found stronger effects on BP in studies with an average patient age greater than 45 years.
In 2019, the Food and Drug Administration issued an update that consuming combined EPA and DHA may lower BP in the general population and reduce the risk of hypertension, but that “the evidence is inconsistent and inconclusive.”
“However, while our study may add a layer of credible evidence, it does not meet the threshold to make an authorized health claim for omega-3 fatty acids in compliance with FDA regulations,” Dr. Li said.
The study addresses shortcomings of previous studies of omega-3 and BP and by identifying the optimal dose, Marc George, MRCP, PhD, of the Institute of Cardiovascular Science, University College, London, and Ajay Gupta, MD, PhD, of the William Harvey Research Institute at Queen Mary University, London, wrote in an accompanying editorial. “More importantly, they have demonstrated a significantly stronger and increased BP-lowering effect in higher cardiovascular risk groups, such as those with hypertension or hyperlipidemia.”
They also noted that the 2.61–mm Hg reduction in SBP the study reported is “likely to be significant” on a population level. “A 2–mm Hg reduction in SBP is estimated to reduce stroke mortality by 10% and deaths from ischemic heart disease by 7%,” they wrote. “Expressed another way, an analysis in the U.S. population using 2010 data estimates that a population-wide reduction in SBP of 2 mm Hg in those aged 45- 64 years would translate to 30,045 fewer cardiovascular events ([coronary heart disease], stroke, and heart failure).”
The investigators and editorialists have no disclosures.
A meta-analysis of 71 randomized controlled trials has found the sweet spot for omega-3 fatty acid intake for lowering blood pressure: between 2 and 3 g/day. The investigators also reported that people at higher risk for cardiovascular disease may benefit from higher daily intake of omega-3.
The study analyzed data from randomized controlled trials involving 4,973 individuals and published from 1987 to 2020. Most of the trials used a combined supplementation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Outcomes analysis involved the impact of combined DHA-EPA at 1, 2, 3, 4, or 5 grams daily on average changes in both systolic and diastolic BP and compared them with the placebo or control groups who had a combined intake of 0 g/day.
“We found a significant nonlinear dose-response relationship for both SBP and DBP models,” wrote senior author Xinzhi Li, MD, PhD, and colleagues. Dr. Li is program director of the school of pharmacy at Macau University of Science and Technology in Taipa, China.
Most of the trials included in the meta-analysis evaluated fish oil supplements, but a number also included EPA and DHA omega-3 fatty acids consumed in food.
When the investigators analyzed studies that used an average baseline SBP of greater than 130 mm Hg, they found that increasing omega-3 supplementation resulted in strong reductions in SBP and DBP, but not so with people with baseline SBP below 130 mm Hg.
Across the entire cohort, average SBP and DBP changes averaged –2.61 (95% confidence interval, –3.57 to –1.65) and –1.64 (95% CI, –2.29 to –0.99) mm Hg for people taking 2 g/d omega-3 supplements, and –2.61 (95% CI, –3.52 to –1.69) and –1.80 (95% CI, –2.38 to –1.23) for those on 3 g/d. The changes weren’t as robust in higher and lower intake groups overall.
However, the higher the BP, the more robust the reductions. For those with SBP greater than 130 mm Hg, 3 g/d resulted in an average change of –3.22 mm Hg (95% CI, –5.21 to –1.23). In the greater than 80 mm Hg DBP group, 3 g/d of omega-3 resulted in an average –3.81 mm Hg reduction (95% CI, –4.48 to –1.87). In patients with BP greater than 140/90 and hypertension, the reductions were even more pronounced. And in patients with BP greater than 130/80, omega-3 intake of 4-5 g/d had a greater impact than 2-3 g/d, although that benefit didn’t carry over in the greater than 140/90 group.
High cholesterol was also a factor in determining the benefits of omega-3 supplementation on BP, as Dr. Li and colleagues wrote that they found “an approximately linear relationship” between hyperlipidemia and SBP, “suggesting that increasing supplementation was associated with greater reductions in SBP.” Likewise, the study found stronger effects on BP in studies with an average patient age greater than 45 years.
In 2019, the Food and Drug Administration issued an update that consuming combined EPA and DHA may lower BP in the general population and reduce the risk of hypertension, but that “the evidence is inconsistent and inconclusive.”
“However, while our study may add a layer of credible evidence, it does not meet the threshold to make an authorized health claim for omega-3 fatty acids in compliance with FDA regulations,” Dr. Li said.
The study addresses shortcomings of previous studies of omega-3 and BP and by identifying the optimal dose, Marc George, MRCP, PhD, of the Institute of Cardiovascular Science, University College, London, and Ajay Gupta, MD, PhD, of the William Harvey Research Institute at Queen Mary University, London, wrote in an accompanying editorial. “More importantly, they have demonstrated a significantly stronger and increased BP-lowering effect in higher cardiovascular risk groups, such as those with hypertension or hyperlipidemia.”
They also noted that the 2.61–mm Hg reduction in SBP the study reported is “likely to be significant” on a population level. “A 2–mm Hg reduction in SBP is estimated to reduce stroke mortality by 10% and deaths from ischemic heart disease by 7%,” they wrote. “Expressed another way, an analysis in the U.S. population using 2010 data estimates that a population-wide reduction in SBP of 2 mm Hg in those aged 45- 64 years would translate to 30,045 fewer cardiovascular events ([coronary heart disease], stroke, and heart failure).”
The investigators and editorialists have no disclosures.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
ESG’s cardiometabolic benefits last 5 years
SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.
Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week® (DDW).
Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.
He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.
“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.
The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.
Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).
In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.
The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.
Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.
Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).
Serious adverse events were rare, occurring in just two cases (< 1%).
The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.
Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.
SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.
Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week® (DDW).
Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.
He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.
“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.
The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.
Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).
In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.
The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.
Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.
Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).
Serious adverse events were rare, occurring in just two cases (< 1%).
The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.
Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.
SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.
Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week® (DDW).
Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.
He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.
“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.
The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.
Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).
In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.
The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.
Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.
Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).
Serious adverse events were rare, occurring in just two cases (< 1%).
The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.
Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.
At DDW 2022
Voice-analysis app promising as early warning system for heart failure decompensation
A voice can carry a long distance, but in patients with heart failure (HF) a voice can also carry otherwise hidden signs useful for predicting short-term risk for worsening disease, even acute decompensation. Potentially, it only has to reach a smartphone to do it, suggests a preliminary study of a mobile app designed to alert patients and clinicians to such looming HF events, if possible in time to avert them.
The proprietary app and analysis system (HearO, Cordio Medical), used daily at home by 180 patients with stable HF, demonstrated 82% accuracy in picking out vocal signals of early congestion that would soon be followed by a need for intensified therapy or acute decompensation.
In practice, clinicians receiving the system’s alerts about altered fluid status would intervene with medication adjustments before the patient deteriorates and possibly heads for the ED. That would be the plan; there were no interventions in the current study, which was designed only to explore the strategy’s feasibility and accuracy.
The system could emerge as “a useful tool in remote monitoring of heart failure patients, providing early warning of worsening heart failure,” said William Abraham, MD, from Ohio State University Wexner Medical Center, Columbus. “It has the potential to reduce acute decompensated heart failure hospitalizations and improve patient quality of life and economic outcomes. But, of course, we have to show that now in larger and randomized clinical studies.”
Abraham presented the Cordio HearO Community Study preliminary results at the Heart Failure Association of the European Society of Cardiology sessions. It follows a recent small study that showed the same app could identify vocal signals linked to altered fluid status in patients with HF hospitalized with acute decompensation.
In the current study, researchers prospectively tracked any worsening HF events that hit patients within a month after the system sent them an alert suggesting early changes in fluid status. Then, they retrospectively assessed the strategy’s predictive accuracy for an initial episode.
The system correctly predicted 32 of 39 first HF events, for an 82% sensitivity and a false-positive rate of 18%. On an annualized basis, Dr. Abraham said, the patients experienced an estimated two to three false alarms per year, alerts that were not followed by HF events. For context, the standard practice of monitoring the patient’s weight “has a sensitivity of about 10%-20%. So this performs very well as a noninvasive technology.”
On average, Dr. Abraham said, “we were able to detect future events about 18 days prior to the worsening heart failure event,” which in practice would provide “a pretty broad window for intervention.”
The false positives were not a surprise. Lung fluid status can change in conditions other than heart failure, he observed, and the HearO system alerts aren’t meant to be followed blindly.
“I don’t know that we clearly understand what those false-positives represent just yet,” Dr. Abraham said. “The bottom line is, as with any diagnostic tool, you have to use the totality of clinical information you have available. If you get an alert and the patient has a fever and a cough, you might think of pneumonia before worsening heart failure.”
“The false positives don’t appear to be alarming,” agreed Antoni Bayés-Genís, MD, PhD, Hospital Universitari Germans Trias i Pujol, Badalona, Spain, and Universitat Autònoma de Barcelona.
The study suggests that the HearO system, combined with sound clinical judgment, “has the potential to identify early congestion that may allow for treatment management, and then avoiding hospital admission,” Dr. Bayés-Genís, who isn’t connected with the study, said in an interview.
The entirely noninvasive, smartphone-based app would be more appealing than implanted devices that, for example, measure thoracic bioimpedance or pulmonary artery pressure and are also intended as congestion early-warning systems, he proposed. “Its scalability makes it very attractive as well.”
But all that “would have to be validated in a large clinical trial,” Dr. Bayés-Genís, who comoderated the conference session featuring Dr. Abraham’s presentation, said when interviewed.
The ongoing study has enrolled 430 clinically stable adult patients with HF in New York Heart Association functional class II or III, regardless of left ventricular ejection fraction, who were cared for by teams at eight centers in Israel. At the outset, during a period of stability, each patient spoke a few sentences into the app to establish a vocal-pattern baseline.
Once home, their assignment was to speak the same sentences into their phones once a day. The app, working through a cloud-based, artificial intelligence–derived processing system, compared each day’s vocal signature with the baseline and alerted researchers when it detected signs of altered fluid status.
About 460,000 recordings were collected from the 180 patients in the current analysis, of whom about 27% were women. They used the app for a mean of 512 days.
The system seems to work well regardless of language or dialect, Dr. Abraham said. About 70% of the current study’s patients spoke Hebrew, and most of the rest spoke either Russian or Arabic.
Most patients (almost 80%) used the app at least 70% of the prescribed time. Only 14 patients used the app less than 60% of the time, he reported.
Dr. Bayés-Genís proposed that, in practice, unfamiliarity with or resistance to smartphone technology would be unlikely to figure greatly in any nonadherence with the daily app regimen, except “maybe for the eldest of the eldest.” The current cohort’s mean age was 70 years. In his experience, he said, most older persons younger than age 80 use a smartphone, at least in more developed countries.
Dr. Abraham disclosed serving on an advisory board for and receiving consulting fees from Cordio Medical; receiving consulting fees from Abbott, Boehringer Ingelheim, CVRx, Edwards Lifesciences, and Respicardia; receiving salary from V-Wave Medical; and receiving research support from the National Heart, Lung, and Blood Institute. Dr. Bayés-Genís reported receiving personal fees from AstraZeneca, Vifor-Fresenius, Novartis, Boehringer Ingelheim, Abbott, Roche Diagnostics, and Critical Diagnostics.
A version of this article first appeared on Medscape.com.
A voice can carry a long distance, but in patients with heart failure (HF) a voice can also carry otherwise hidden signs useful for predicting short-term risk for worsening disease, even acute decompensation. Potentially, it only has to reach a smartphone to do it, suggests a preliminary study of a mobile app designed to alert patients and clinicians to such looming HF events, if possible in time to avert them.
The proprietary app and analysis system (HearO, Cordio Medical), used daily at home by 180 patients with stable HF, demonstrated 82% accuracy in picking out vocal signals of early congestion that would soon be followed by a need for intensified therapy or acute decompensation.
In practice, clinicians receiving the system’s alerts about altered fluid status would intervene with medication adjustments before the patient deteriorates and possibly heads for the ED. That would be the plan; there were no interventions in the current study, which was designed only to explore the strategy’s feasibility and accuracy.
The system could emerge as “a useful tool in remote monitoring of heart failure patients, providing early warning of worsening heart failure,” said William Abraham, MD, from Ohio State University Wexner Medical Center, Columbus. “It has the potential to reduce acute decompensated heart failure hospitalizations and improve patient quality of life and economic outcomes. But, of course, we have to show that now in larger and randomized clinical studies.”
Abraham presented the Cordio HearO Community Study preliminary results at the Heart Failure Association of the European Society of Cardiology sessions. It follows a recent small study that showed the same app could identify vocal signals linked to altered fluid status in patients with HF hospitalized with acute decompensation.
In the current study, researchers prospectively tracked any worsening HF events that hit patients within a month after the system sent them an alert suggesting early changes in fluid status. Then, they retrospectively assessed the strategy’s predictive accuracy for an initial episode.
The system correctly predicted 32 of 39 first HF events, for an 82% sensitivity and a false-positive rate of 18%. On an annualized basis, Dr. Abraham said, the patients experienced an estimated two to three false alarms per year, alerts that were not followed by HF events. For context, the standard practice of monitoring the patient’s weight “has a sensitivity of about 10%-20%. So this performs very well as a noninvasive technology.”
On average, Dr. Abraham said, “we were able to detect future events about 18 days prior to the worsening heart failure event,” which in practice would provide “a pretty broad window for intervention.”
The false positives were not a surprise. Lung fluid status can change in conditions other than heart failure, he observed, and the HearO system alerts aren’t meant to be followed blindly.
“I don’t know that we clearly understand what those false-positives represent just yet,” Dr. Abraham said. “The bottom line is, as with any diagnostic tool, you have to use the totality of clinical information you have available. If you get an alert and the patient has a fever and a cough, you might think of pneumonia before worsening heart failure.”
“The false positives don’t appear to be alarming,” agreed Antoni Bayés-Genís, MD, PhD, Hospital Universitari Germans Trias i Pujol, Badalona, Spain, and Universitat Autònoma de Barcelona.
The study suggests that the HearO system, combined with sound clinical judgment, “has the potential to identify early congestion that may allow for treatment management, and then avoiding hospital admission,” Dr. Bayés-Genís, who isn’t connected with the study, said in an interview.
The entirely noninvasive, smartphone-based app would be more appealing than implanted devices that, for example, measure thoracic bioimpedance or pulmonary artery pressure and are also intended as congestion early-warning systems, he proposed. “Its scalability makes it very attractive as well.”
But all that “would have to be validated in a large clinical trial,” Dr. Bayés-Genís, who comoderated the conference session featuring Dr. Abraham’s presentation, said when interviewed.
The ongoing study has enrolled 430 clinically stable adult patients with HF in New York Heart Association functional class II or III, regardless of left ventricular ejection fraction, who were cared for by teams at eight centers in Israel. At the outset, during a period of stability, each patient spoke a few sentences into the app to establish a vocal-pattern baseline.
Once home, their assignment was to speak the same sentences into their phones once a day. The app, working through a cloud-based, artificial intelligence–derived processing system, compared each day’s vocal signature with the baseline and alerted researchers when it detected signs of altered fluid status.
About 460,000 recordings were collected from the 180 patients in the current analysis, of whom about 27% were women. They used the app for a mean of 512 days.
The system seems to work well regardless of language or dialect, Dr. Abraham said. About 70% of the current study’s patients spoke Hebrew, and most of the rest spoke either Russian or Arabic.
Most patients (almost 80%) used the app at least 70% of the prescribed time. Only 14 patients used the app less than 60% of the time, he reported.
Dr. Bayés-Genís proposed that, in practice, unfamiliarity with or resistance to smartphone technology would be unlikely to figure greatly in any nonadherence with the daily app regimen, except “maybe for the eldest of the eldest.” The current cohort’s mean age was 70 years. In his experience, he said, most older persons younger than age 80 use a smartphone, at least in more developed countries.
Dr. Abraham disclosed serving on an advisory board for and receiving consulting fees from Cordio Medical; receiving consulting fees from Abbott, Boehringer Ingelheim, CVRx, Edwards Lifesciences, and Respicardia; receiving salary from V-Wave Medical; and receiving research support from the National Heart, Lung, and Blood Institute. Dr. Bayés-Genís reported receiving personal fees from AstraZeneca, Vifor-Fresenius, Novartis, Boehringer Ingelheim, Abbott, Roche Diagnostics, and Critical Diagnostics.
A version of this article first appeared on Medscape.com.
A voice can carry a long distance, but in patients with heart failure (HF) a voice can also carry otherwise hidden signs useful for predicting short-term risk for worsening disease, even acute decompensation. Potentially, it only has to reach a smartphone to do it, suggests a preliminary study of a mobile app designed to alert patients and clinicians to such looming HF events, if possible in time to avert them.
The proprietary app and analysis system (HearO, Cordio Medical), used daily at home by 180 patients with stable HF, demonstrated 82% accuracy in picking out vocal signals of early congestion that would soon be followed by a need for intensified therapy or acute decompensation.
In practice, clinicians receiving the system’s alerts about altered fluid status would intervene with medication adjustments before the patient deteriorates and possibly heads for the ED. That would be the plan; there were no interventions in the current study, which was designed only to explore the strategy’s feasibility and accuracy.
The system could emerge as “a useful tool in remote monitoring of heart failure patients, providing early warning of worsening heart failure,” said William Abraham, MD, from Ohio State University Wexner Medical Center, Columbus. “It has the potential to reduce acute decompensated heart failure hospitalizations and improve patient quality of life and economic outcomes. But, of course, we have to show that now in larger and randomized clinical studies.”
Abraham presented the Cordio HearO Community Study preliminary results at the Heart Failure Association of the European Society of Cardiology sessions. It follows a recent small study that showed the same app could identify vocal signals linked to altered fluid status in patients with HF hospitalized with acute decompensation.
In the current study, researchers prospectively tracked any worsening HF events that hit patients within a month after the system sent them an alert suggesting early changes in fluid status. Then, they retrospectively assessed the strategy’s predictive accuracy for an initial episode.
The system correctly predicted 32 of 39 first HF events, for an 82% sensitivity and a false-positive rate of 18%. On an annualized basis, Dr. Abraham said, the patients experienced an estimated two to three false alarms per year, alerts that were not followed by HF events. For context, the standard practice of monitoring the patient’s weight “has a sensitivity of about 10%-20%. So this performs very well as a noninvasive technology.”
On average, Dr. Abraham said, “we were able to detect future events about 18 days prior to the worsening heart failure event,” which in practice would provide “a pretty broad window for intervention.”
The false positives were not a surprise. Lung fluid status can change in conditions other than heart failure, he observed, and the HearO system alerts aren’t meant to be followed blindly.
“I don’t know that we clearly understand what those false-positives represent just yet,” Dr. Abraham said. “The bottom line is, as with any diagnostic tool, you have to use the totality of clinical information you have available. If you get an alert and the patient has a fever and a cough, you might think of pneumonia before worsening heart failure.”
“The false positives don’t appear to be alarming,” agreed Antoni Bayés-Genís, MD, PhD, Hospital Universitari Germans Trias i Pujol, Badalona, Spain, and Universitat Autònoma de Barcelona.
The study suggests that the HearO system, combined with sound clinical judgment, “has the potential to identify early congestion that may allow for treatment management, and then avoiding hospital admission,” Dr. Bayés-Genís, who isn’t connected with the study, said in an interview.
The entirely noninvasive, smartphone-based app would be more appealing than implanted devices that, for example, measure thoracic bioimpedance or pulmonary artery pressure and are also intended as congestion early-warning systems, he proposed. “Its scalability makes it very attractive as well.”
But all that “would have to be validated in a large clinical trial,” Dr. Bayés-Genís, who comoderated the conference session featuring Dr. Abraham’s presentation, said when interviewed.
The ongoing study has enrolled 430 clinically stable adult patients with HF in New York Heart Association functional class II or III, regardless of left ventricular ejection fraction, who were cared for by teams at eight centers in Israel. At the outset, during a period of stability, each patient spoke a few sentences into the app to establish a vocal-pattern baseline.
Once home, their assignment was to speak the same sentences into their phones once a day. The app, working through a cloud-based, artificial intelligence–derived processing system, compared each day’s vocal signature with the baseline and alerted researchers when it detected signs of altered fluid status.
About 460,000 recordings were collected from the 180 patients in the current analysis, of whom about 27% were women. They used the app for a mean of 512 days.
The system seems to work well regardless of language or dialect, Dr. Abraham said. About 70% of the current study’s patients spoke Hebrew, and most of the rest spoke either Russian or Arabic.
Most patients (almost 80%) used the app at least 70% of the prescribed time. Only 14 patients used the app less than 60% of the time, he reported.
Dr. Bayés-Genís proposed that, in practice, unfamiliarity with or resistance to smartphone technology would be unlikely to figure greatly in any nonadherence with the daily app regimen, except “maybe for the eldest of the eldest.” The current cohort’s mean age was 70 years. In his experience, he said, most older persons younger than age 80 use a smartphone, at least in more developed countries.
Dr. Abraham disclosed serving on an advisory board for and receiving consulting fees from Cordio Medical; receiving consulting fees from Abbott, Boehringer Ingelheim, CVRx, Edwards Lifesciences, and Respicardia; receiving salary from V-Wave Medical; and receiving research support from the National Heart, Lung, and Blood Institute. Dr. Bayés-Genís reported receiving personal fees from AstraZeneca, Vifor-Fresenius, Novartis, Boehringer Ingelheim, Abbott, Roche Diagnostics, and Critical Diagnostics.
A version of this article first appeared on Medscape.com.
FROM ESC HEART FAILURE 2022
Updated AHA/ASA guideline changes care for spontaneous intracerebral hemorrhage
Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).
Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.
The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.
“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.
“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.
“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.
Time-honored treatments no more?
Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.
For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.
Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.
“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.
The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.
In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.
The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.
For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.
It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.
For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.
However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
Multidisciplinary care
For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.
Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.
Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.
“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.
The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
Opportunity for prevention?
The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.
While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.
“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.
“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.
“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.
The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.
This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.
A version of this article first appeared on Medscape.com.
Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).
Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.
The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.
“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.
“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.
“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.
Time-honored treatments no more?
Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.
For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.
Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.
“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.
The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.
In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.
The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.
For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.
It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.
For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.
However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
Multidisciplinary care
For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.
Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.
Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.
“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.
The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
Opportunity for prevention?
The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.
While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.
“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.
“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.
“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.
The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.
This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.
A version of this article first appeared on Medscape.com.
Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).
Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.
The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.
“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.
“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.
“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.
Time-honored treatments no more?
Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.
For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.
Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.
“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.
The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.
In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.
The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.
For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.
It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.
For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.
However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
Multidisciplinary care
For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.
Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.
Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.
“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.
The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
Opportunity for prevention?
The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.
While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.
“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.
“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.
“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.
The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.
This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.
A version of this article first appeared on Medscape.com.
Combo of hypertension and advanced age linked to higher cesarean rates
Advanced maternal age and maternal hypertension are a one-two punch that boosts the risk of cesarean births, a new study reports.
While the findings presented at the 2022 annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists aren’t surprising, the insight they provide can be helpful in counseling women at risk about delivery options, lead author and Loma Linda (Calif.) University maternal-fetal medicine physician Sarah D. Smithson, DO, said in an interview.
The prospect of a cesarean birth “can be introduced early and often, which can be important in managing expectations,” she said, especially since women can feel depression and a sense of failure if it turns out they can’t give birth vaginally as they anticipated.
As Dr. Smithson noted, there’s a continuum of maternal hypertension conditions from less severe to more severe. The physicians need to hurry delivery along in the most severe cases. “The clock is clicking when you have preeclampsia, and you do not have time for an induction that could take 2-3 days if you’re having a hard time controlling blood pressure. You may consider cesarean to expedite delivery,” she said.
For the new study, Dr. Smithson and colleagues sought to understand how a combination of maternal hypertension and advanced maternal age affected cesarean delivery rates. They retrospectively tracked 1,625 women with maternal hypertension (chronic hypertension, gestational hypertension, preeclampsia without severe features, and preeclampsia with severe features) who were treated in the Oregon Health & Science University system from 2013 to 2018.
Of the women, 450 were older than 35, and they were more likely than younger women to have cesarean deliveries (46% vs. 34%; P < .001; adjusted OR, 1.7; 95% CI, 1.0-2.7; P = .03).
“We aim to get our cesarean section rates below 20%,” Dr. Smithson said. “These are high rates, and the fact that they’re significantly higher in the advanced maternal age group is compelling.”
The cesarean rates were higher at a statistically significant rate in patients with gestational hypertension (37% in older women vs. 26% in younger women; P = .021) and in those with preeclampsia with severe features (57% vs. 44%, respectively; P = .02). However, the differences were not statistically significant in the groups with chronic hypertension and preeclampsia without severe features.
In an interview, maternal-fetal medicine specialist Alex C. Vidaeff, MD, MPH, of Baylor College of Medicine, Houston, questioned the usefulness of the subgroup analysis, which he thinks may be statistically misleading. “How would one otherwise explain that the rate difference between advanced maternal-age and non–advanced maternal-age subjects is statistically significant for gestational hypertension but not for preeclampsia without severe features?”
He added: “With the very limited information provided by this study, important questions remained unanswered. What is causing the increased rate of cesarean delivery? Provider’s bias or preferences? It would have been useful to know if the cesarean deliveries were elective, without labor, or cesarean deliveries performed during labor or even emergency cesarean deliveries.”
No study funding or disclosures are reported.
Advanced maternal age and maternal hypertension are a one-two punch that boosts the risk of cesarean births, a new study reports.
While the findings presented at the 2022 annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists aren’t surprising, the insight they provide can be helpful in counseling women at risk about delivery options, lead author and Loma Linda (Calif.) University maternal-fetal medicine physician Sarah D. Smithson, DO, said in an interview.
The prospect of a cesarean birth “can be introduced early and often, which can be important in managing expectations,” she said, especially since women can feel depression and a sense of failure if it turns out they can’t give birth vaginally as they anticipated.
As Dr. Smithson noted, there’s a continuum of maternal hypertension conditions from less severe to more severe. The physicians need to hurry delivery along in the most severe cases. “The clock is clicking when you have preeclampsia, and you do not have time for an induction that could take 2-3 days if you’re having a hard time controlling blood pressure. You may consider cesarean to expedite delivery,” she said.
For the new study, Dr. Smithson and colleagues sought to understand how a combination of maternal hypertension and advanced maternal age affected cesarean delivery rates. They retrospectively tracked 1,625 women with maternal hypertension (chronic hypertension, gestational hypertension, preeclampsia without severe features, and preeclampsia with severe features) who were treated in the Oregon Health & Science University system from 2013 to 2018.
Of the women, 450 were older than 35, and they were more likely than younger women to have cesarean deliveries (46% vs. 34%; P < .001; adjusted OR, 1.7; 95% CI, 1.0-2.7; P = .03).
“We aim to get our cesarean section rates below 20%,” Dr. Smithson said. “These are high rates, and the fact that they’re significantly higher in the advanced maternal age group is compelling.”
The cesarean rates were higher at a statistically significant rate in patients with gestational hypertension (37% in older women vs. 26% in younger women; P = .021) and in those with preeclampsia with severe features (57% vs. 44%, respectively; P = .02). However, the differences were not statistically significant in the groups with chronic hypertension and preeclampsia without severe features.
In an interview, maternal-fetal medicine specialist Alex C. Vidaeff, MD, MPH, of Baylor College of Medicine, Houston, questioned the usefulness of the subgroup analysis, which he thinks may be statistically misleading. “How would one otherwise explain that the rate difference between advanced maternal-age and non–advanced maternal-age subjects is statistically significant for gestational hypertension but not for preeclampsia without severe features?”
He added: “With the very limited information provided by this study, important questions remained unanswered. What is causing the increased rate of cesarean delivery? Provider’s bias or preferences? It would have been useful to know if the cesarean deliveries were elective, without labor, or cesarean deliveries performed during labor or even emergency cesarean deliveries.”
No study funding or disclosures are reported.
Advanced maternal age and maternal hypertension are a one-two punch that boosts the risk of cesarean births, a new study reports.
While the findings presented at the 2022 annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists aren’t surprising, the insight they provide can be helpful in counseling women at risk about delivery options, lead author and Loma Linda (Calif.) University maternal-fetal medicine physician Sarah D. Smithson, DO, said in an interview.
The prospect of a cesarean birth “can be introduced early and often, which can be important in managing expectations,” she said, especially since women can feel depression and a sense of failure if it turns out they can’t give birth vaginally as they anticipated.
As Dr. Smithson noted, there’s a continuum of maternal hypertension conditions from less severe to more severe. The physicians need to hurry delivery along in the most severe cases. “The clock is clicking when you have preeclampsia, and you do not have time for an induction that could take 2-3 days if you’re having a hard time controlling blood pressure. You may consider cesarean to expedite delivery,” she said.
For the new study, Dr. Smithson and colleagues sought to understand how a combination of maternal hypertension and advanced maternal age affected cesarean delivery rates. They retrospectively tracked 1,625 women with maternal hypertension (chronic hypertension, gestational hypertension, preeclampsia without severe features, and preeclampsia with severe features) who were treated in the Oregon Health & Science University system from 2013 to 2018.
Of the women, 450 were older than 35, and they were more likely than younger women to have cesarean deliveries (46% vs. 34%; P < .001; adjusted OR, 1.7; 95% CI, 1.0-2.7; P = .03).
“We aim to get our cesarean section rates below 20%,” Dr. Smithson said. “These are high rates, and the fact that they’re significantly higher in the advanced maternal age group is compelling.”
The cesarean rates were higher at a statistically significant rate in patients with gestational hypertension (37% in older women vs. 26% in younger women; P = .021) and in those with preeclampsia with severe features (57% vs. 44%, respectively; P = .02). However, the differences were not statistically significant in the groups with chronic hypertension and preeclampsia without severe features.
In an interview, maternal-fetal medicine specialist Alex C. Vidaeff, MD, MPH, of Baylor College of Medicine, Houston, questioned the usefulness of the subgroup analysis, which he thinks may be statistically misleading. “How would one otherwise explain that the rate difference between advanced maternal-age and non–advanced maternal-age subjects is statistically significant for gestational hypertension but not for preeclampsia without severe features?”
He added: “With the very limited information provided by this study, important questions remained unanswered. What is causing the increased rate of cesarean delivery? Provider’s bias or preferences? It would have been useful to know if the cesarean deliveries were elective, without labor, or cesarean deliveries performed during labor or even emergency cesarean deliveries.”
No study funding or disclosures are reported.
FROM ACOG 2022
Mixing BP meds with NSAID may be ‘triple whammy’ for kidneys
The study also looked at risk factors associated with the effect of triple therapy with these agents, which has been called “triple whammy” AKI.
“It’s not that everyone who happens to take this combination of drugs is going to have problems,” Anita Layton, PhD, University of Waterloo, Ontario, said in a statement. “But the research shows it’s enough of a problem that you should exercise caution.”
The study was published online in Mathematical Biosciences.
In an earlier study, triple therapy with a diuretic, RAS inhibitor, and NSAID was associated with a 31% increased risk for AKI, relative to diuretic and RAS inhibitor therapy only.
However, the factors that predispose some patients to develop “triple whammy” AKI are unclear.
To better understand the mechanism by which triple therapy increases risk for AKI, Dr. Layton and colleagues used computational models to gauge interactions between concurrent use of a diuretic, a RAS inhibitor, and an NSAID.
They identified dehydration and high sensitivity to drug treatment as key contributing factors to the development of triple whammy AKI.
Their model simulations suggested that low water intake, the myogenic response (that is, the reflex response of arteries and arterioles to changes in blood pressure to maintain consistent blood flow), and drug sensitivity “may predispose patients with hypertension to develop triple whammy-induced AKI,” they wrote.
“We hypothesize that individuals with an impaired myogenic response may be particularly susceptible to triple whammy AKI. Additionally, increased drug sensitivity or low water intake can predispose patients to triple whammy AKI,” they added.
In the absence of additional risk factors, there was no indication of an elevated risk for AKI when an angiotensin-converting enzyme (ACE) inhibitor and NSAID are combined, the study team said.
In contrast, when an ACE inhibitor, diuretic, and NSAID are combined, critical blood pressure and glomerular filtration rate (GFR) regulatory mechanisms are simultaneously interrupted, they reported.
“Perhaps not unexpectedly, model simulations indicate that triple treatment reduces GFR more than single or double treatments in all individuals. However, under triple treatment, urine volume and GFR have not been predicted to fall sufficiently far to indicate AKI,” they wrote. “This result is consistent with the fact that only a fraction of individuals develop AKI following triple treatment.”
They expect, therefore, that hypertensive patients who are otherwise healthy will be able to withstand triple treatment, in the absence of these aggravating factors, the researchers concluded.
Nonetheless, it’s wise to “always be careful when mixing medications,” Dr. Layton told this news organization.
She noted that “triple whammy AKI is known among kidney researchers and nephrologists. To what extent nonspecialists are aware, it isn’t clear.
“More importantly,” Dr. Layton said, “NSAIDs can be obtained over the counter, and triple whammy AKI isn’t common knowledge outside of the medical community.”
This research was supported by the Canada 150 Research Chair program and by the Natural Sciences and Engineering Research Council of Canada. The authors have declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
The study also looked at risk factors associated with the effect of triple therapy with these agents, which has been called “triple whammy” AKI.
“It’s not that everyone who happens to take this combination of drugs is going to have problems,” Anita Layton, PhD, University of Waterloo, Ontario, said in a statement. “But the research shows it’s enough of a problem that you should exercise caution.”
The study was published online in Mathematical Biosciences.
In an earlier study, triple therapy with a diuretic, RAS inhibitor, and NSAID was associated with a 31% increased risk for AKI, relative to diuretic and RAS inhibitor therapy only.
However, the factors that predispose some patients to develop “triple whammy” AKI are unclear.
To better understand the mechanism by which triple therapy increases risk for AKI, Dr. Layton and colleagues used computational models to gauge interactions between concurrent use of a diuretic, a RAS inhibitor, and an NSAID.
They identified dehydration and high sensitivity to drug treatment as key contributing factors to the development of triple whammy AKI.
Their model simulations suggested that low water intake, the myogenic response (that is, the reflex response of arteries and arterioles to changes in blood pressure to maintain consistent blood flow), and drug sensitivity “may predispose patients with hypertension to develop triple whammy-induced AKI,” they wrote.
“We hypothesize that individuals with an impaired myogenic response may be particularly susceptible to triple whammy AKI. Additionally, increased drug sensitivity or low water intake can predispose patients to triple whammy AKI,” they added.
In the absence of additional risk factors, there was no indication of an elevated risk for AKI when an angiotensin-converting enzyme (ACE) inhibitor and NSAID are combined, the study team said.
In contrast, when an ACE inhibitor, diuretic, and NSAID are combined, critical blood pressure and glomerular filtration rate (GFR) regulatory mechanisms are simultaneously interrupted, they reported.
“Perhaps not unexpectedly, model simulations indicate that triple treatment reduces GFR more than single or double treatments in all individuals. However, under triple treatment, urine volume and GFR have not been predicted to fall sufficiently far to indicate AKI,” they wrote. “This result is consistent with the fact that only a fraction of individuals develop AKI following triple treatment.”
They expect, therefore, that hypertensive patients who are otherwise healthy will be able to withstand triple treatment, in the absence of these aggravating factors, the researchers concluded.
Nonetheless, it’s wise to “always be careful when mixing medications,” Dr. Layton told this news organization.
She noted that “triple whammy AKI is known among kidney researchers and nephrologists. To what extent nonspecialists are aware, it isn’t clear.
“More importantly,” Dr. Layton said, “NSAIDs can be obtained over the counter, and triple whammy AKI isn’t common knowledge outside of the medical community.”
This research was supported by the Canada 150 Research Chair program and by the Natural Sciences and Engineering Research Council of Canada. The authors have declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
The study also looked at risk factors associated with the effect of triple therapy with these agents, which has been called “triple whammy” AKI.
“It’s not that everyone who happens to take this combination of drugs is going to have problems,” Anita Layton, PhD, University of Waterloo, Ontario, said in a statement. “But the research shows it’s enough of a problem that you should exercise caution.”
The study was published online in Mathematical Biosciences.
In an earlier study, triple therapy with a diuretic, RAS inhibitor, and NSAID was associated with a 31% increased risk for AKI, relative to diuretic and RAS inhibitor therapy only.
However, the factors that predispose some patients to develop “triple whammy” AKI are unclear.
To better understand the mechanism by which triple therapy increases risk for AKI, Dr. Layton and colleagues used computational models to gauge interactions between concurrent use of a diuretic, a RAS inhibitor, and an NSAID.
They identified dehydration and high sensitivity to drug treatment as key contributing factors to the development of triple whammy AKI.
Their model simulations suggested that low water intake, the myogenic response (that is, the reflex response of arteries and arterioles to changes in blood pressure to maintain consistent blood flow), and drug sensitivity “may predispose patients with hypertension to develop triple whammy-induced AKI,” they wrote.
“We hypothesize that individuals with an impaired myogenic response may be particularly susceptible to triple whammy AKI. Additionally, increased drug sensitivity or low water intake can predispose patients to triple whammy AKI,” they added.
In the absence of additional risk factors, there was no indication of an elevated risk for AKI when an angiotensin-converting enzyme (ACE) inhibitor and NSAID are combined, the study team said.
In contrast, when an ACE inhibitor, diuretic, and NSAID are combined, critical blood pressure and glomerular filtration rate (GFR) regulatory mechanisms are simultaneously interrupted, they reported.
“Perhaps not unexpectedly, model simulations indicate that triple treatment reduces GFR more than single or double treatments in all individuals. However, under triple treatment, urine volume and GFR have not been predicted to fall sufficiently far to indicate AKI,” they wrote. “This result is consistent with the fact that only a fraction of individuals develop AKI following triple treatment.”
They expect, therefore, that hypertensive patients who are otherwise healthy will be able to withstand triple treatment, in the absence of these aggravating factors, the researchers concluded.
Nonetheless, it’s wise to “always be careful when mixing medications,” Dr. Layton told this news organization.
She noted that “triple whammy AKI is known among kidney researchers and nephrologists. To what extent nonspecialists are aware, it isn’t clear.
“More importantly,” Dr. Layton said, “NSAIDs can be obtained over the counter, and triple whammy AKI isn’t common knowledge outside of the medical community.”
This research was supported by the Canada 150 Research Chair program and by the Natural Sciences and Engineering Research Council of Canada. The authors have declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM MATHEMATICAL BIOSCIENCES
‘Goodie bag’ pill mill doctor sentenced to 2 decades in prison
A Pennsylvania-based internist was sentenced to 20 years in prison by a federal judge on May 10 for running a prescription “pill mill” from his medical practice.
Since May 2005, Andrew Berkowitz, MD, 62, of Huntington Valley, Pa., was president and CEO of A+ Pain Management, a clinic in the Philadelphia area, according to his LinkedIn profile.
Prosecutors said patients, no matter their complaint, would leave Dr. Berkowitz’s offices with “goodie bags” filled with a selection of drugs. A typical haul included topical analgesics, such as Relyyt and/or lidocaine; muscle relaxants, including chlorzoxazone and/or cyclobenzaprine; anti-inflammatories, such as celecoxib and/or fenoprofen; and schedule IV substances, including tramadol, eszopiclone, and quazepam.
The practice was registered in Pennsylvania as a nonpharmacy dispensing site, allowing Dr. Berkowitz to bill insurers for the drugs, according to The Pennsylvania Record, a journal covering Pennsylvania’s legal system. Dr. Berkowitz also prescribed oxycodone for “pill seeking” patients, who gave him their tacit approval of submitting claims to their insurance providers, which included Medicare, Aetna, and others, for the items in the goodie bag.
In addition, Dr. Berkowitz fraudulently billed insurers for medically unnecessary physical therapy, acupuncture, and chiropractic adjustments, as well as for treatments that were never provided, according to federal officials.
According to the Department of Justice, Dr. Berkowitz collected more than $4,000 per bag from insurers. From 2015 to 2018, prosecutors estimate that Dr. Berkowitz took in more than $4 million in fraudulent proceeds from his scheme.
The pill mill came to the attention of federal authorities after Blue Cross investigators forwarded to the FBI several complaints it had received about Dr. Berkowitz. In 2017, the FBI sent a cooperating witness to Dr. Berkowitz’s clinic. The undercover patient received a prescription for oxycodone, Motrin, and Flexeril and paid $185, according to The Record.
After being indicted in 2019, Dr. Berkowitz pleaded guilty in January 2020 to 19 counts of health care fraud and to 23 counts of distributing oxycodone outside the course of professional practice and without a legitimate medical purpose.
On May 10, he was sentenced to 20 years in prison, followed by 5 years of supervised release. In addition, he was ordered to pay a $40,000 fine and almost $4 million in restitution. As a result of civil False Claims Act liability for false claims submitted to Medicare, he is also obligated to pay approximately $1.8 million and is subject to a permanent prohibition on prescribing, distributing, or dispensing controlled substances.
Dr. Berkowitz’s actions were deemed especially egregious in light of the opioid epidemic.
“Doctors are supposed to treat illness, not feed it,” said Jacqueline Maguire, special agent in charge of the FBI’s Philadelphia division. “Andrew Berkowitz prescribed patients unnecessary pills and handed out opioids to addicts.” Jennifer Arbittier Williams, acting U.S. Attorney, added upon announcing the sentence, “Doctors who dare engage in health care fraud and drug diversion, two drivers of the opioid epidemic ravaging our communities, should heed this sentence as a warning that they will be held responsible, criminally and financially.”
A version of this article first appeared on Medscape.com.
A Pennsylvania-based internist was sentenced to 20 years in prison by a federal judge on May 10 for running a prescription “pill mill” from his medical practice.
Since May 2005, Andrew Berkowitz, MD, 62, of Huntington Valley, Pa., was president and CEO of A+ Pain Management, a clinic in the Philadelphia area, according to his LinkedIn profile.
Prosecutors said patients, no matter their complaint, would leave Dr. Berkowitz’s offices with “goodie bags” filled with a selection of drugs. A typical haul included topical analgesics, such as Relyyt and/or lidocaine; muscle relaxants, including chlorzoxazone and/or cyclobenzaprine; anti-inflammatories, such as celecoxib and/or fenoprofen; and schedule IV substances, including tramadol, eszopiclone, and quazepam.
The practice was registered in Pennsylvania as a nonpharmacy dispensing site, allowing Dr. Berkowitz to bill insurers for the drugs, according to The Pennsylvania Record, a journal covering Pennsylvania’s legal system. Dr. Berkowitz also prescribed oxycodone for “pill seeking” patients, who gave him their tacit approval of submitting claims to their insurance providers, which included Medicare, Aetna, and others, for the items in the goodie bag.
In addition, Dr. Berkowitz fraudulently billed insurers for medically unnecessary physical therapy, acupuncture, and chiropractic adjustments, as well as for treatments that were never provided, according to federal officials.
According to the Department of Justice, Dr. Berkowitz collected more than $4,000 per bag from insurers. From 2015 to 2018, prosecutors estimate that Dr. Berkowitz took in more than $4 million in fraudulent proceeds from his scheme.
The pill mill came to the attention of federal authorities after Blue Cross investigators forwarded to the FBI several complaints it had received about Dr. Berkowitz. In 2017, the FBI sent a cooperating witness to Dr. Berkowitz’s clinic. The undercover patient received a prescription for oxycodone, Motrin, and Flexeril and paid $185, according to The Record.
After being indicted in 2019, Dr. Berkowitz pleaded guilty in January 2020 to 19 counts of health care fraud and to 23 counts of distributing oxycodone outside the course of professional practice and without a legitimate medical purpose.
On May 10, he was sentenced to 20 years in prison, followed by 5 years of supervised release. In addition, he was ordered to pay a $40,000 fine and almost $4 million in restitution. As a result of civil False Claims Act liability for false claims submitted to Medicare, he is also obligated to pay approximately $1.8 million and is subject to a permanent prohibition on prescribing, distributing, or dispensing controlled substances.
Dr. Berkowitz’s actions were deemed especially egregious in light of the opioid epidemic.
“Doctors are supposed to treat illness, not feed it,” said Jacqueline Maguire, special agent in charge of the FBI’s Philadelphia division. “Andrew Berkowitz prescribed patients unnecessary pills and handed out opioids to addicts.” Jennifer Arbittier Williams, acting U.S. Attorney, added upon announcing the sentence, “Doctors who dare engage in health care fraud and drug diversion, two drivers of the opioid epidemic ravaging our communities, should heed this sentence as a warning that they will be held responsible, criminally and financially.”
A version of this article first appeared on Medscape.com.
A Pennsylvania-based internist was sentenced to 20 years in prison by a federal judge on May 10 for running a prescription “pill mill” from his medical practice.
Since May 2005, Andrew Berkowitz, MD, 62, of Huntington Valley, Pa., was president and CEO of A+ Pain Management, a clinic in the Philadelphia area, according to his LinkedIn profile.
Prosecutors said patients, no matter their complaint, would leave Dr. Berkowitz’s offices with “goodie bags” filled with a selection of drugs. A typical haul included topical analgesics, such as Relyyt and/or lidocaine; muscle relaxants, including chlorzoxazone and/or cyclobenzaprine; anti-inflammatories, such as celecoxib and/or fenoprofen; and schedule IV substances, including tramadol, eszopiclone, and quazepam.
The practice was registered in Pennsylvania as a nonpharmacy dispensing site, allowing Dr. Berkowitz to bill insurers for the drugs, according to The Pennsylvania Record, a journal covering Pennsylvania’s legal system. Dr. Berkowitz also prescribed oxycodone for “pill seeking” patients, who gave him their tacit approval of submitting claims to their insurance providers, which included Medicare, Aetna, and others, for the items in the goodie bag.
In addition, Dr. Berkowitz fraudulently billed insurers for medically unnecessary physical therapy, acupuncture, and chiropractic adjustments, as well as for treatments that were never provided, according to federal officials.
According to the Department of Justice, Dr. Berkowitz collected more than $4,000 per bag from insurers. From 2015 to 2018, prosecutors estimate that Dr. Berkowitz took in more than $4 million in fraudulent proceeds from his scheme.
The pill mill came to the attention of federal authorities after Blue Cross investigators forwarded to the FBI several complaints it had received about Dr. Berkowitz. In 2017, the FBI sent a cooperating witness to Dr. Berkowitz’s clinic. The undercover patient received a prescription for oxycodone, Motrin, and Flexeril and paid $185, according to The Record.
After being indicted in 2019, Dr. Berkowitz pleaded guilty in January 2020 to 19 counts of health care fraud and to 23 counts of distributing oxycodone outside the course of professional practice and without a legitimate medical purpose.
On May 10, he was sentenced to 20 years in prison, followed by 5 years of supervised release. In addition, he was ordered to pay a $40,000 fine and almost $4 million in restitution. As a result of civil False Claims Act liability for false claims submitted to Medicare, he is also obligated to pay approximately $1.8 million and is subject to a permanent prohibition on prescribing, distributing, or dispensing controlled substances.
Dr. Berkowitz’s actions were deemed especially egregious in light of the opioid epidemic.
“Doctors are supposed to treat illness, not feed it,” said Jacqueline Maguire, special agent in charge of the FBI’s Philadelphia division. “Andrew Berkowitz prescribed patients unnecessary pills and handed out opioids to addicts.” Jennifer Arbittier Williams, acting U.S. Attorney, added upon announcing the sentence, “Doctors who dare engage in health care fraud and drug diversion, two drivers of the opioid epidemic ravaging our communities, should heed this sentence as a warning that they will be held responsible, criminally and financially.”
A version of this article first appeared on Medscape.com.