SAN DIEGO – Clinical outcomes were better when stent placement was guided by intravascular ultrasound rather than angiography, based on the results of a trial conducted in China. Unlike previous comparative studies, which focused on patients with more complex lesions, this trial included all patients undergoing drug-eluting stent (DES) placement.

In the ULTIMATE trial, 1,448 all-comer patients receiving DES were randomized to either intravascular ultrasound (IVUS)–guided or angiography-guided implantation, reported Junjie Zhang, PhD, of Nanjing Medical University in China, and colleagues. The study excluded patients who had a life expectancy shorter than 12 months, who were intolerant of dual antiplatelet therapy, and who had severe calcification needing rotational atherectomy.

At 30 days after stent placement, the incidence of target vessel failure was 0.8% in the IVUS group and 1.9% in the angiography group, a nonsignificant trend. However, outcomes were significantly different at 1 year, with target vessel failure occurring in 2.9% of IVUS patients and 5.4% of angiography patients (hazard ratio, 0.530; 95% confidence interval, 0.312-0.901; P = .019).

The work was simultaneously published in the Journal of the American College of Cardiology (2018 Sept. doi: 10.1016/j.jacc.2018.09.013) .

Despite good results in this and prior studies, uptake of the IVUS procedure is not high in the United States or Europe, according to members of a panel that reviewed the results at the Transcatheter Cardiovascular Therapeutics annual meeting.

“How can people continue to ignore the importance of imaging-guided stent optimization? Even with second-generation DES, the results are consistent across the studies. This is just another piece of irrefutable evidence,” said Gary S. Mintz, MD, chief medical officer at the Cardiovascular Research Foundation, and a discussant at the meeting, sponsored by the Cardiovascular Research Foundation.

Jim Kling/MDedge News

SAN DIEGO – Clinical outcomes were better when stent placement was guided by intravascular ultrasound rather than angiography, based on the results of a trial conducted in China. Unlike previous comparative studies, which focused on patients with more complex lesions, this trial included all patients undergoing drug-eluting stent (DES) placement.

In the ULTIMATE trial, 1,448 all-comer patients receiving DES were randomized to either intravascular ultrasound (IVUS)–guided or angiography-guided implantation, reported Junjie Zhang, PhD, of Nanjing Medical University in China, and colleagues. The study excluded patients who had a life expectancy shorter than 12 months, who were intolerant of dual antiplatelet therapy, and who had severe calcification needing rotational atherectomy.

At 30 days after stent placement, the incidence of target vessel failure was 0.8% in the IVUS group and 1.9% in the angiography group, a nonsignificant trend. However, outcomes were significantly different at 1 year, with target vessel failure occurring in 2.9% of IVUS patients and 5.4% of angiography patients (hazard ratio, 0.530; 95% confidence interval, 0.312-0.901; P = .019).

The work was simultaneously published in the Journal of the American College of Cardiology (2018 Sept. doi: 10.1016/j.jacc.2018.09.013) .

Despite good results in this and prior studies, uptake of the IVUS procedure is not high in the United States or Europe, according to members of a panel that reviewed the results at the Transcatheter Cardiovascular Therapeutics annual meeting.

“How can people continue to ignore the importance of imaging-guided stent optimization? Even with second-generation DES, the results are consistent across the studies. This is just another piece of irrefutable evidence,” said Gary S. Mintz, MD, chief medical officer at the Cardiovascular Research Foundation, and a discussant at the meeting, sponsored by the Cardiovascular Research Foundation.

Jim Kling/MDedge News

SAN DIEGO – Clinical outcomes were better when stent placement was guided by intravascular ultrasound rather than angiography, based on the results of a trial conducted in China. Unlike previous comparative studies, which focused on patients with more complex lesions, this trial included all patients undergoing drug-eluting stent (DES) placement.

In the ULTIMATE trial, 1,448 all-comer patients receiving DES were randomized to either intravascular ultrasound (IVUS)–guided or angiography-guided implantation, reported Junjie Zhang, PhD, of Nanjing Medical University in China, and colleagues. The study excluded patients who had a life expectancy shorter than 12 months, who were intolerant of dual antiplatelet therapy, and who had severe calcification needing rotational atherectomy.

At 30 days after stent placement, the incidence of target vessel failure was 0.8% in the IVUS group and 1.9% in the angiography group, a nonsignificant trend. However, outcomes were significantly different at 1 year, with target vessel failure occurring in 2.9% of IVUS patients and 5.4% of angiography patients (hazard ratio, 0.530; 95% confidence interval, 0.312-0.901; P = .019).

The work was simultaneously published in the Journal of the American College of Cardiology (2018 Sept. doi: 10.1016/j.jacc.2018.09.013) .

Despite good results in this and prior studies, uptake of the IVUS procedure is not high in the United States or Europe, according to members of a panel that reviewed the results at the Transcatheter Cardiovascular Therapeutics annual meeting.

“How can people continue to ignore the importance of imaging-guided stent optimization? Even with second-generation DES, the results are consistent across the studies. This is just another piece of irrefutable evidence,” said Gary S. Mintz, MD, chief medical officer at the Cardiovascular Research Foundation, and a discussant at the meeting, sponsored by the Cardiovascular Research Foundation.

Jim Kling/MDedge News

Interruptions of patients’ refills for combination inhaled corticosteroid medication caused by the Medicare Part D formulary switch may have resulted in increased exacerbations and hospitalizations, according to a study that will be presented at the CHEST 2018 annual meeting.

Katie Devane, PhD, and her colleagues examined pharmacy records of 44,832 patients aged 12 years and older who had received a combination inhaled corticosteroid (budesonide/formoterol) and a long-acting beta-agonist medication in 2016-2017. They were followed to track their refills, medication switches, and use of other medications such as oral corticosteroids, antibiotics, and rescue inhalers.

After the Medicare Part D formulary switch on Jan. 1, 2017, many of these patients experienced disruption of their refills. About half of the patients attempted to get a refill of their inhaled corticosteroid prescription but only 46% were approved. One-third of the patients studied did not replace their medication, 12% switched to monotherapy, and 17% had no inhaled medication, the study found.

The investigators concluded that the formulary block resulted in many patients going without optimal medication and potentially led to more exacerbations and ER visits.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31877-4/fulltext

The study will be presented in the session Improving Care in COPD, Monday, Oct. 8, 2:15 p.m., Convention Center Room 207A.

Interruptions of patients’ refills for combination inhaled corticosteroid medication caused by the Medicare Part D formulary switch may have resulted in increased exacerbations and hospitalizations, according to a study that will be presented at the CHEST 2018 annual meeting.

Katie Devane, PhD, and her colleagues examined pharmacy records of 44,832 patients aged 12 years and older who had received a combination inhaled corticosteroid (budesonide/formoterol) and a long-acting beta-agonist medication in 2016-2017. They were followed to track their refills, medication switches, and use of other medications such as oral corticosteroids, antibiotics, and rescue inhalers.

After the Medicare Part D formulary switch on Jan. 1, 2017, many of these patients experienced disruption of their refills. About half of the patients attempted to get a refill of their inhaled corticosteroid prescription but only 46% were approved. One-third of the patients studied did not replace their medication, 12% switched to monotherapy, and 17% had no inhaled medication, the study found.

The investigators concluded that the formulary block resulted in many patients going without optimal medication and potentially led to more exacerbations and ER visits.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31877-4/fulltext

The study will be presented in the session Improving Care in COPD, Monday, Oct. 8, 2:15 p.m., Convention Center Room 207A.

Interruptions of patients’ refills for combination inhaled corticosteroid medication caused by the Medicare Part D formulary switch may have resulted in increased exacerbations and hospitalizations, according to a study that will be presented at the CHEST 2018 annual meeting.

Katie Devane, PhD, and her colleagues examined pharmacy records of 44,832 patients aged 12 years and older who had received a combination inhaled corticosteroid (budesonide/formoterol) and a long-acting beta-agonist medication in 2016-2017. They were followed to track their refills, medication switches, and use of other medications such as oral corticosteroids, antibiotics, and rescue inhalers.

After the Medicare Part D formulary switch on Jan. 1, 2017, many of these patients experienced disruption of their refills. About half of the patients attempted to get a refill of their inhaled corticosteroid prescription but only 46% were approved. One-third of the patients studied did not replace their medication, 12% switched to monotherapy, and 17% had no inhaled medication, the study found.

The investigators concluded that the formulary block resulted in many patients going without optimal medication and potentially led to more exacerbations and ER visits.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31877-4/fulltext

The study will be presented in the session Improving Care in COPD, Monday, Oct. 8, 2:15 p.m., Convention Center Room 207A.

Children with asthma who are provided with care and medication per National Asthma Education and Prevention Program guidelines can improve over time, despite the presence of environmental factors such as second-hand tobacco smoke and domestic pets, according to a study presented at the CHEST 2018 annual meeting.

A study conducted at the Nationwide Children’s Hospital in Columbus, Ohio, included 395 children aged 2-17 years with a diagnosis of uncontrolled asthma. These children were then treated using the NAEPP guidelines for acute care needs and symptom control. In this sample of patients, 25% were exposed to second-hand smoke, and 55% had a cat or dog in the home.

The investigators followed these patients and observed improvement of symptoms. But in a comparison of those with and without the potentially problematic environmental factors, improvement was independent of the presence of these factors. The findings suggest that NAEPP-recommended treatment of asthma is more important than are some environmental factors.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31862-2/fulltext.

The findings will be presented in the session on Obstructive Lung Diseases, Wednesday, Oct. 10, at 1:00 p.m.
 

Children with asthma who are provided with care and medication per National Asthma Education and Prevention Program guidelines can improve over time, despite the presence of environmental factors such as second-hand tobacco smoke and domestic pets, according to a study presented at the CHEST 2018 annual meeting.

A study conducted at the Nationwide Children’s Hospital in Columbus, Ohio, included 395 children aged 2-17 years with a diagnosis of uncontrolled asthma. These children were then treated using the NAEPP guidelines for acute care needs and symptom control. In this sample of patients, 25% were exposed to second-hand smoke, and 55% had a cat or dog in the home.

The investigators followed these patients and observed improvement of symptoms. But in a comparison of those with and without the potentially problematic environmental factors, improvement was independent of the presence of these factors. The findings suggest that NAEPP-recommended treatment of asthma is more important than are some environmental factors.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31862-2/fulltext.

The findings will be presented in the session on Obstructive Lung Diseases, Wednesday, Oct. 10, at 1:00 p.m.
 

Children with asthma who are provided with care and medication per National Asthma Education and Prevention Program guidelines can improve over time, despite the presence of environmental factors such as second-hand tobacco smoke and domestic pets, according to a study presented at the CHEST 2018 annual meeting.

A study conducted at the Nationwide Children’s Hospital in Columbus, Ohio, included 395 children aged 2-17 years with a diagnosis of uncontrolled asthma. These children were then treated using the NAEPP guidelines for acute care needs and symptom control. In this sample of patients, 25% were exposed to second-hand smoke, and 55% had a cat or dog in the home.

The investigators followed these patients and observed improvement of symptoms. But in a comparison of those with and without the potentially problematic environmental factors, improvement was independent of the presence of these factors. The findings suggest that NAEPP-recommended treatment of asthma is more important than are some environmental factors.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31862-2/fulltext.

The findings will be presented in the session on Obstructive Lung Diseases, Wednesday, Oct. 10, at 1:00 p.m.
 

Former smokers’ adherence to annual follow-up screening for lung cancer was found to be less than optimal, according to a study to be presented at the CHEST 2018 annual meeting.

Paul B. Brasher, MD, and his colleagues from the Thoracic Oncology Research Group at the Medical University of South Carolina in Charleston studied adherence to recommended low-dose computed tomography (LDCT) among Veterans Affairs patients who were at high risk for lung cancer and whose baseline LDCTs were negative.

A total of 2,106 veterans aged 55-80 years who had at least a 30-pack year smoking history were initially screened within the Veterans Health Administration Lung Cancer Screening Demonstration Project. The study tracked 1,120 of these patients for 18 months to determine their adherence to annual LDCT screening; the rate of adherence was 77.6%.

View the abstract here: https://journal.chestnet.org/article/S0012-3692(18)31772-0/fulltext

The study will be presented in the session Lung Cancer Screening: New Questions and New Answers, Tuesday, Oct. 9, 8:45 a.m., Convention Center 207A.

Former smokers’ adherence to annual follow-up screening for lung cancer was found to be less than optimal, according to a study to be presented at the CHEST 2018 annual meeting.

Paul B. Brasher, MD, and his colleagues from the Thoracic Oncology Research Group at the Medical University of South Carolina in Charleston studied adherence to recommended low-dose computed tomography (LDCT) among Veterans Affairs patients who were at high risk for lung cancer and whose baseline LDCTs were negative.

A total of 2,106 veterans aged 55-80 years who had at least a 30-pack year smoking history were initially screened within the Veterans Health Administration Lung Cancer Screening Demonstration Project. The study tracked 1,120 of these patients for 18 months to determine their adherence to annual LDCT screening; the rate of adherence was 77.6%.

View the abstract here: https://journal.chestnet.org/article/S0012-3692(18)31772-0/fulltext

The study will be presented in the session Lung Cancer Screening: New Questions and New Answers, Tuesday, Oct. 9, 8:45 a.m., Convention Center 207A.

Former smokers’ adherence to annual follow-up screening for lung cancer was found to be less than optimal, according to a study to be presented at the CHEST 2018 annual meeting.

Paul B. Brasher, MD, and his colleagues from the Thoracic Oncology Research Group at the Medical University of South Carolina in Charleston studied adherence to recommended low-dose computed tomography (LDCT) among Veterans Affairs patients who were at high risk for lung cancer and whose baseline LDCTs were negative.

A total of 2,106 veterans aged 55-80 years who had at least a 30-pack year smoking history were initially screened within the Veterans Health Administration Lung Cancer Screening Demonstration Project. The study tracked 1,120 of these patients for 18 months to determine their adherence to annual LDCT screening; the rate of adherence was 77.6%.

View the abstract here: https://journal.chestnet.org/article/S0012-3692(18)31772-0/fulltext

The study will be presented in the session Lung Cancer Screening: New Questions and New Answers, Tuesday, Oct. 9, 8:45 a.m., Convention Center 207A.

SAN DIEGO – Don’t be satisfied with a diagnosis of angina with no obstructive coronary artery disease; push for acetylcholine testing, the findings from a trial in Scotland suggest.

M. Alexander Otto/MDedge News

Going a little further with an acetylcholine challenge in the cath lab will usually uncover microvascular or vasospastic heart problems, and this can lead to appropriate treatment. Patients will have less angina and a better quality of life at 6 months, according to investigators from the University of Glasgow (Scotland).

Invasive angiography usually ends on both sides of the Atlantic when no occlusions are found. There are concerns about the safety of going further with acetylcholine challenges, and until now, there had been no grade A evidence from a randomized trial that it improves outcomes. The Glasgow team filled the evidence gap with their presentation of the Coronary Microvascular Angina (CorMicA) trial at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting, and there wasn’t a single serious adverse event (J Am Coll Cardiol. 2018 Sep 25. doi: 10.1016/j.jacc.2018.09.006).

“This was a proof-of-concept study, which we believe [should] substantiate a large, multicenter trial,” said senior investigator Colin Berry, PhD, a professor of cardiology and imaging at the university.

Acetylcholine was infused down the pressure wire in 151 subjects diagnosed with angina with no obstructive coronary artery diseases before they left the catheter lab. Of these patients, 76 were randomized to have their results shared with their treating cardiologist, and 75 were randomized to not have their results shared. Coronary functional testing is hardly ever done, so the no-share group was considered the standard-of-care control arm. The idea was to see whether it made a difference when treating physicians knew what was causing chest pain when their patients didn’t have occlusive disease.

It turned out to make a huge difference. The diagnosis of “chest pain of noncardiac origin” almost fell off the map. Once cardiologists knew what was going on, they switched up treatment according to European Society of Cardiology guidelines for functional heart pain. Patients with microvascular angina were given beta-blockers and switched off nitrates because these drugs make angina worse in microvascular disease. Subjects with vasospasms were shifted to calcium channel blockers and long-acting nitrates and away from beta-blockers because beta-blockers make vasospasms worse.

Cardiologists who didn’t know the results kept muddling along with what patients came in on at baseline – beta-blockers in two-thirds, long-acting nitrates in half, and calcium channel blockers in a third.

Subjects who got the right treatment because of acetylcholine testing outpaced the standard care group by almost 12 points on the Seattle Angina Questionnaire at 6 months; they could walk farther and didn’t have crushing angina almost every day (P = .001). They reported a statistically significant improvement in quality of life, and they were much happier with their doctors.

“This is the first randomized, sham-controlled trial in this space”; functional testing “was routinely safe and feasible. Therapy guided by the results of physiologic testing improved outcomes” and “treatment satisfaction,” said University of Glasgow interventional cardiologist Tom Ford, MD.

Acetylcholine was infused down the pressure wire into the radial artery, with the left anterior descending coronary artery as the target vessel. A final bolus of less than 100 mcg checked for coronary artery spasms; a symptomatic constriction of greater than 90% was considered positive. Glyceryl trinitrate was used to reverse the effects.

Three-quarters of the subjects were women, which Dr. Ford noted is unusual in an angina study. The mean age was 61 years, and subjects had about a 20% chance of a heart attack within 10 years. The whole procedure, including the angiogram, randomization, and functional testing, took a median of about 60 minutes.

There were no differences in major adverse cardiac events at 6 months, at 2.6% in both groups.

One patient developed persistent atrial fibrillation with acetylcholine testing that was converted to sinus rhythm with intravenous amiodarone, without a night in the hospital.

The work was funded by the British Heart Foundation. No companies were involved. The investigators didn’t have any relevant disclosures. The TCT meeting is sponsored by the Cardiovascular Research Foundation.

aotto@mdedge.com

SOURCE: Ford TG et al. TCT 2018, Late-Breaking Trial.

SAN DIEGO – Don’t be satisfied with a diagnosis of angina with no obstructive coronary artery disease; push for acetylcholine testing, the findings from a trial in Scotland suggest.

M. Alexander Otto/MDedge News

Going a little further with an acetylcholine challenge in the cath lab will usually uncover microvascular or vasospastic heart problems, and this can lead to appropriate treatment. Patients will have less angina and a better quality of life at 6 months, according to investigators from the University of Glasgow (Scotland).

Invasive angiography usually ends on both sides of the Atlantic when no occlusions are found. There are concerns about the safety of going further with acetylcholine challenges, and until now, there had been no grade A evidence from a randomized trial that it improves outcomes. The Glasgow team filled the evidence gap with their presentation of the Coronary Microvascular Angina (CorMicA) trial at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting, and there wasn’t a single serious adverse event (J Am Coll Cardiol. 2018 Sep 25. doi: 10.1016/j.jacc.2018.09.006).

“This was a proof-of-concept study, which we believe [should] substantiate a large, multicenter trial,” said senior investigator Colin Berry, PhD, a professor of cardiology and imaging at the university.

Acetylcholine was infused down the pressure wire in 151 subjects diagnosed with angina with no obstructive coronary artery diseases before they left the catheter lab. Of these patients, 76 were randomized to have their results shared with their treating cardiologist, and 75 were randomized to not have their results shared. Coronary functional testing is hardly ever done, so the no-share group was considered the standard-of-care control arm. The idea was to see whether it made a difference when treating physicians knew what was causing chest pain when their patients didn’t have occlusive disease.

It turned out to make a huge difference. The diagnosis of “chest pain of noncardiac origin” almost fell off the map. Once cardiologists knew what was going on, they switched up treatment according to European Society of Cardiology guidelines for functional heart pain. Patients with microvascular angina were given beta-blockers and switched off nitrates because these drugs make angina worse in microvascular disease. Subjects with vasospasms were shifted to calcium channel blockers and long-acting nitrates and away from beta-blockers because beta-blockers make vasospasms worse.

Cardiologists who didn’t know the results kept muddling along with what patients came in on at baseline – beta-blockers in two-thirds, long-acting nitrates in half, and calcium channel blockers in a third.

Subjects who got the right treatment because of acetylcholine testing outpaced the standard care group by almost 12 points on the Seattle Angina Questionnaire at 6 months; they could walk farther and didn’t have crushing angina almost every day (P = .001). They reported a statistically significant improvement in quality of life, and they were much happier with their doctors.

“This is the first randomized, sham-controlled trial in this space”; functional testing “was routinely safe and feasible. Therapy guided by the results of physiologic testing improved outcomes” and “treatment satisfaction,” said University of Glasgow interventional cardiologist Tom Ford, MD.

Acetylcholine was infused down the pressure wire into the radial artery, with the left anterior descending coronary artery as the target vessel. A final bolus of less than 100 mcg checked for coronary artery spasms; a symptomatic constriction of greater than 90% was considered positive. Glyceryl trinitrate was used to reverse the effects.

Three-quarters of the subjects were women, which Dr. Ford noted is unusual in an angina study. The mean age was 61 years, and subjects had about a 20% chance of a heart attack within 10 years. The whole procedure, including the angiogram, randomization, and functional testing, took a median of about 60 minutes.

There were no differences in major adverse cardiac events at 6 months, at 2.6% in both groups.

One patient developed persistent atrial fibrillation with acetylcholine testing that was converted to sinus rhythm with intravenous amiodarone, without a night in the hospital.

The work was funded by the British Heart Foundation. No companies were involved. The investigators didn’t have any relevant disclosures. The TCT meeting is sponsored by the Cardiovascular Research Foundation.

aotto@mdedge.com

SOURCE: Ford TG et al. TCT 2018, Late-Breaking Trial.

SAN DIEGO – Don’t be satisfied with a diagnosis of angina with no obstructive coronary artery disease; push for acetylcholine testing, the findings from a trial in Scotland suggest.

M. Alexander Otto/MDedge News

Going a little further with an acetylcholine challenge in the cath lab will usually uncover microvascular or vasospastic heart problems, and this can lead to appropriate treatment. Patients will have less angina and a better quality of life at 6 months, according to investigators from the University of Glasgow (Scotland).

Invasive angiography usually ends on both sides of the Atlantic when no occlusions are found. There are concerns about the safety of going further with acetylcholine challenges, and until now, there had been no grade A evidence from a randomized trial that it improves outcomes. The Glasgow team filled the evidence gap with their presentation of the Coronary Microvascular Angina (CorMicA) trial at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting, and there wasn’t a single serious adverse event (J Am Coll Cardiol. 2018 Sep 25. doi: 10.1016/j.jacc.2018.09.006).

“This was a proof-of-concept study, which we believe [should] substantiate a large, multicenter trial,” said senior investigator Colin Berry, PhD, a professor of cardiology and imaging at the university.

Acetylcholine was infused down the pressure wire in 151 subjects diagnosed with angina with no obstructive coronary artery diseases before they left the catheter lab. Of these patients, 76 were randomized to have their results shared with their treating cardiologist, and 75 were randomized to not have their results shared. Coronary functional testing is hardly ever done, so the no-share group was considered the standard-of-care control arm. The idea was to see whether it made a difference when treating physicians knew what was causing chest pain when their patients didn’t have occlusive disease.

It turned out to make a huge difference. The diagnosis of “chest pain of noncardiac origin” almost fell off the map. Once cardiologists knew what was going on, they switched up treatment according to European Society of Cardiology guidelines for functional heart pain. Patients with microvascular angina were given beta-blockers and switched off nitrates because these drugs make angina worse in microvascular disease. Subjects with vasospasms were shifted to calcium channel blockers and long-acting nitrates and away from beta-blockers because beta-blockers make vasospasms worse.

Cardiologists who didn’t know the results kept muddling along with what patients came in on at baseline – beta-blockers in two-thirds, long-acting nitrates in half, and calcium channel blockers in a third.

Subjects who got the right treatment because of acetylcholine testing outpaced the standard care group by almost 12 points on the Seattle Angina Questionnaire at 6 months; they could walk farther and didn’t have crushing angina almost every day (P = .001). They reported a statistically significant improvement in quality of life, and they were much happier with their doctors.

“This is the first randomized, sham-controlled trial in this space”; functional testing “was routinely safe and feasible. Therapy guided by the results of physiologic testing improved outcomes” and “treatment satisfaction,” said University of Glasgow interventional cardiologist Tom Ford, MD.

Acetylcholine was infused down the pressure wire into the radial artery, with the left anterior descending coronary artery as the target vessel. A final bolus of less than 100 mcg checked for coronary artery spasms; a symptomatic constriction of greater than 90% was considered positive. Glyceryl trinitrate was used to reverse the effects.

Three-quarters of the subjects were women, which Dr. Ford noted is unusual in an angina study. The mean age was 61 years, and subjects had about a 20% chance of a heart attack within 10 years. The whole procedure, including the angiogram, randomization, and functional testing, took a median of about 60 minutes.

There were no differences in major adverse cardiac events at 6 months, at 2.6% in both groups.

One patient developed persistent atrial fibrillation with acetylcholine testing that was converted to sinus rhythm with intravenous amiodarone, without a night in the hospital.

The work was funded by the British Heart Foundation. No companies were involved. The investigators didn’t have any relevant disclosures. The TCT meeting is sponsored by the Cardiovascular Research Foundation.

aotto@mdedge.com

SOURCE: Ford TG et al. TCT 2018, Late-Breaking Trial.

Using aspirin across the board is not justified based on results of the ASPREE trial as well as on the equivocal results from other recent primary prevention trials. Also today, swings in four metabolic measures predicted death in healthy people, anticoagulation plus single antiplatelet fails noninferiority measure 1 year after stenting, and Behavioral checklist identifies children at risk of depressive and/or anxiety disorders.
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Using aspirin across the board is not justified based on results of the ASPREE trial as well as on the equivocal results from other recent primary prevention trials. Also today, swings in four metabolic measures predicted death in healthy people, anticoagulation plus single antiplatelet fails noninferiority measure 1 year after stenting, and Behavioral checklist identifies children at risk of depressive and/or anxiety disorders.
Amazon Alexa
Apple Podcasts
Spotify

Using aspirin across the board is not justified based on results of the ASPREE trial as well as on the equivocal results from other recent primary prevention trials. Also today, swings in four metabolic measures predicted death in healthy people, anticoagulation plus single antiplatelet fails noninferiority measure 1 year after stenting, and Behavioral checklist identifies children at risk of depressive and/or anxiety disorders.
Amazon Alexa
Apple Podcasts
Spotify

Photo courtesy of NCCN

NEW YORK—Two chimeric antigen receptor (CAR) T-cell therapies—axicabtagene ciloleucel (Yescarta ®) and tisagenlecleucel (Kymriah™)—are already approved in B-cell lymphoma by the U.S. Food and Drug Administration.

A third, lisocabtagene maraleucel, will most likely be approved before too long.

Despite differences in their costimulatory molecules, persistence, efficacy, and toxicity profiles, they all have high overall response rates and a fall-out of response during the first 3 to 6 months.

Longer-term follow-up is necessary to determine whether CAR T-cell therapy is actually curative.

“But based on the way things are looking,” said Reem Karmali, MD, of Robert H. Lurie Comprehensive Cancer Center of Northwestern University, “it seems this might be a realistic expectation.”

“CAR T-cell therapy is clearly effective and has been a ground-breaking form of therapy,” she said, “but there seems to be two sides to the coin. There are a number of challenges that we face with CAR T-cell therapy.”

Dr. Karmali outlined those challenges in a presentation at the NCCN 13^th Annual Congress: Hematologic Malignancies.

Patient selection

One of the biggest challenges, according to Dr. Karmali, is patient selection.

First, patients must have an adequate hematopoietic reserve to ensure successful CAR T-cell manufacture.

Dr. Karmali referred to the JULIET study, in which 7% of patients failed the manufacturing process due to insufficient apheresis.

Second, the patient’s disease must be stable enough to make it through the time it takes to manufacturing the CAR product, which is typically 2 to 4 weeks.

Third, the patient’s overall health must be good enough to tolerate CAR T toxicities. "The patient needs good major organ function as well as preserved neurologic function,” she explained, “to withstand the unique toxicities that come with CAR T-cell therapy, specifically CRS [cytokine release syndrome] and neurotoxicity.”

Toxicities

The major toxicities are CRS and CAR‑T‑cell‑related encephalopathy syndrome (CRES).

Dr. Karmali pointed out there is also a theoretical risk of insertional oncogenesis from viral transduction used in manufacturing the T cells, and an off-tumor on target-effect that can result in B-cell aplasia and hypogammaglobulinemia.

The profiles of inflammatory cytokines and inflammation markers differ for each CAR construct and are driven in different ways. However, IL-6 is an important mediator for CRS and IL-6 receptor blockade is effective in managing the toxicity.

The drug of choice is tocilizumab, Dr. Karmali said, and for patients who are refractory to tocilizumab, siltuximab can be used.

“Steroids are extremely useful for CRS,” she added, “because they hold down inflammation and prevent immune activation.”

Steroids are also the mainstay for managing the neurotoxicity of CAR T-cell therapy because they help stabilize the blood-brain barrier.

“It’s important to make a note,” she said, “that there actually have been a number of analyses that have looked at the impact of using IL-6 receptor blockade and steroids on CAR T-cell expansion and persistence and there really doesn’t seem to be an impact.”

“So we really ought to use these quite liberally for grade 2 or higher toxicity without worrying about dampening the effect of CAR T-cell therapy,” she emphasized.

The Lee grading criteria for the management of CRS and the CTCAE 4.03 and CARTOX-10 for CRES provide guidance in assessing and managing the toxicities.

Future directions

Dr. Karmali outlined a few new directions to address the challenges with CAR T-cell therapy, such as switchable CARs that can be turned on or off and potentially improve safety; development of new constructs that may improve homing; improvement in persistence; use of combination and sequencing strategies; and improved antigen selection that may be effective with other lymphoproliferative diseases.

“A provocative question is whether CAR T-cell therapy can actually replace autologous stem cell transplant as second-line therapy,” she said.  “This is actually being actively evaluated in a number of clinical trials including ZUMA-7 (NCT03391466).”

“I think another provocative question is whether CAR T-cell therapy can be used as consolidation in CR1 [first complete remission],” she added.

The rationale for using CAR Ts as either a replacement for autologous stem cell transplant or in CR1 is that there may be minimal residual disease present that would be enough to elicit a CAR T-cell effect, she explained.

“Ultimately, one envisions the following paradigm for the treatment of lymphomas across the board,” Dr. Karmali concluded.

“Specifically, chemotherapy with a targeted agent for rapid cytoreduction, followed by CAR T-cell consolidation in combination with either other cellular therapies or immunotherapy as a means of eradicating the minimal residual disease and ensuring a pathway to cure.” 

Photo courtesy of NCCN

NEW YORK—Two chimeric antigen receptor (CAR) T-cell therapies—axicabtagene ciloleucel (Yescarta ®) and tisagenlecleucel (Kymriah™)—are already approved in B-cell lymphoma by the U.S. Food and Drug Administration.

A third, lisocabtagene maraleucel, will most likely be approved before too long.

Despite differences in their costimulatory molecules, persistence, efficacy, and toxicity profiles, they all have high overall response rates and a fall-out of response during the first 3 to 6 months.

Longer-term follow-up is necessary to determine whether CAR T-cell therapy is actually curative.

“But based on the way things are looking,” said Reem Karmali, MD, of Robert H. Lurie Comprehensive Cancer Center of Northwestern University, “it seems this might be a realistic expectation.”

“CAR T-cell therapy is clearly effective and has been a ground-breaking form of therapy,” she said, “but there seems to be two sides to the coin. There are a number of challenges that we face with CAR T-cell therapy.”

Dr. Karmali outlined those challenges in a presentation at the NCCN 13^th Annual Congress: Hematologic Malignancies.

Patient selection

One of the biggest challenges, according to Dr. Karmali, is patient selection.

First, patients must have an adequate hematopoietic reserve to ensure successful CAR T-cell manufacture.

Dr. Karmali referred to the JULIET study, in which 7% of patients failed the manufacturing process due to insufficient apheresis.

Second, the patient’s disease must be stable enough to make it through the time it takes to manufacturing the CAR product, which is typically 2 to 4 weeks.

Third, the patient’s overall health must be good enough to tolerate CAR T toxicities. "The patient needs good major organ function as well as preserved neurologic function,” she explained, “to withstand the unique toxicities that come with CAR T-cell therapy, specifically CRS [cytokine release syndrome] and neurotoxicity.”

Toxicities

The major toxicities are CRS and CAR‑T‑cell‑related encephalopathy syndrome (CRES).

Dr. Karmali pointed out there is also a theoretical risk of insertional oncogenesis from viral transduction used in manufacturing the T cells, and an off-tumor on target-effect that can result in B-cell aplasia and hypogammaglobulinemia.

The profiles of inflammatory cytokines and inflammation markers differ for each CAR construct and are driven in different ways. However, IL-6 is an important mediator for CRS and IL-6 receptor blockade is effective in managing the toxicity.

The drug of choice is tocilizumab, Dr. Karmali said, and for patients who are refractory to tocilizumab, siltuximab can be used.

“Steroids are extremely useful for CRS,” she added, “because they hold down inflammation and prevent immune activation.”

Steroids are also the mainstay for managing the neurotoxicity of CAR T-cell therapy because they help stabilize the blood-brain barrier.

“It’s important to make a note,” she said, “that there actually have been a number of analyses that have looked at the impact of using IL-6 receptor blockade and steroids on CAR T-cell expansion and persistence and there really doesn’t seem to be an impact.”

“So we really ought to use these quite liberally for grade 2 or higher toxicity without worrying about dampening the effect of CAR T-cell therapy,” she emphasized.

The Lee grading criteria for the management of CRS and the CTCAE 4.03 and CARTOX-10 for CRES provide guidance in assessing and managing the toxicities.

Future directions

Dr. Karmali outlined a few new directions to address the challenges with CAR T-cell therapy, such as switchable CARs that can be turned on or off and potentially improve safety; development of new constructs that may improve homing; improvement in persistence; use of combination and sequencing strategies; and improved antigen selection that may be effective with other lymphoproliferative diseases.

“A provocative question is whether CAR T-cell therapy can actually replace autologous stem cell transplant as second-line therapy,” she said.  “This is actually being actively evaluated in a number of clinical trials including ZUMA-7 (NCT03391466).”

“I think another provocative question is whether CAR T-cell therapy can be used as consolidation in CR1 [first complete remission],” she added.

The rationale for using CAR Ts as either a replacement for autologous stem cell transplant or in CR1 is that there may be minimal residual disease present that would be enough to elicit a CAR T-cell effect, she explained.

“Ultimately, one envisions the following paradigm for the treatment of lymphomas across the board,” Dr. Karmali concluded.

“Specifically, chemotherapy with a targeted agent for rapid cytoreduction, followed by CAR T-cell consolidation in combination with either other cellular therapies or immunotherapy as a means of eradicating the minimal residual disease and ensuring a pathway to cure.” 

Photo courtesy of NCCN

NEW YORK—Two chimeric antigen receptor (CAR) T-cell therapies—axicabtagene ciloleucel (Yescarta ®) and tisagenlecleucel (Kymriah™)—are already approved in B-cell lymphoma by the U.S. Food and Drug Administration.

A third, lisocabtagene maraleucel, will most likely be approved before too long.

Despite differences in their costimulatory molecules, persistence, efficacy, and toxicity profiles, they all have high overall response rates and a fall-out of response during the first 3 to 6 months.

Longer-term follow-up is necessary to determine whether CAR T-cell therapy is actually curative.

“But based on the way things are looking,” said Reem Karmali, MD, of Robert H. Lurie Comprehensive Cancer Center of Northwestern University, “it seems this might be a realistic expectation.”

“CAR T-cell therapy is clearly effective and has been a ground-breaking form of therapy,” she said, “but there seems to be two sides to the coin. There are a number of challenges that we face with CAR T-cell therapy.”

Dr. Karmali outlined those challenges in a presentation at the NCCN 13^th Annual Congress: Hematologic Malignancies.

Patient selection

One of the biggest challenges, according to Dr. Karmali, is patient selection.

First, patients must have an adequate hematopoietic reserve to ensure successful CAR T-cell manufacture.

Dr. Karmali referred to the JULIET study, in which 7% of patients failed the manufacturing process due to insufficient apheresis.

Second, the patient’s disease must be stable enough to make it through the time it takes to manufacturing the CAR product, which is typically 2 to 4 weeks.

Third, the patient’s overall health must be good enough to tolerate CAR T toxicities. "The patient needs good major organ function as well as preserved neurologic function,” she explained, “to withstand the unique toxicities that come with CAR T-cell therapy, specifically CRS [cytokine release syndrome] and neurotoxicity.”

Toxicities

The major toxicities are CRS and CAR‑T‑cell‑related encephalopathy syndrome (CRES).

Dr. Karmali pointed out there is also a theoretical risk of insertional oncogenesis from viral transduction used in manufacturing the T cells, and an off-tumor on target-effect that can result in B-cell aplasia and hypogammaglobulinemia.

The profiles of inflammatory cytokines and inflammation markers differ for each CAR construct and are driven in different ways. However, IL-6 is an important mediator for CRS and IL-6 receptor blockade is effective in managing the toxicity.

The drug of choice is tocilizumab, Dr. Karmali said, and for patients who are refractory to tocilizumab, siltuximab can be used.

“Steroids are extremely useful for CRS,” she added, “because they hold down inflammation and prevent immune activation.”

Steroids are also the mainstay for managing the neurotoxicity of CAR T-cell therapy because they help stabilize the blood-brain barrier.

“It’s important to make a note,” she said, “that there actually have been a number of analyses that have looked at the impact of using IL-6 receptor blockade and steroids on CAR T-cell expansion and persistence and there really doesn’t seem to be an impact.”

“So we really ought to use these quite liberally for grade 2 or higher toxicity without worrying about dampening the effect of CAR T-cell therapy,” she emphasized.

The Lee grading criteria for the management of CRS and the CTCAE 4.03 and CARTOX-10 for CRES provide guidance in assessing and managing the toxicities.

Future directions

Dr. Karmali outlined a few new directions to address the challenges with CAR T-cell therapy, such as switchable CARs that can be turned on or off and potentially improve safety; development of new constructs that may improve homing; improvement in persistence; use of combination and sequencing strategies; and improved antigen selection that may be effective with other lymphoproliferative diseases.

“A provocative question is whether CAR T-cell therapy can actually replace autologous stem cell transplant as second-line therapy,” she said.  “This is actually being actively evaluated in a number of clinical trials including ZUMA-7 (NCT03391466).”

“I think another provocative question is whether CAR T-cell therapy can be used as consolidation in CR1 [first complete remission],” she added.

The rationale for using CAR Ts as either a replacement for autologous stem cell transplant or in CR1 is that there may be minimal residual disease present that would be enough to elicit a CAR T-cell effect, she explained.

“Ultimately, one envisions the following paradigm for the treatment of lymphomas across the board,” Dr. Karmali concluded.

“Specifically, chemotherapy with a targeted agent for rapid cytoreduction, followed by CAR T-cell consolidation in combination with either other cellular therapies or immunotherapy as a means of eradicating the minimal residual disease and ensuring a pathway to cure.” 

Credit: Penn Medicine

Investigators report that a single leukemic cell unintentionally engineered into the chimeric antigen receptor (CAR) T-cell product can mask it from recognition and confer resistance to CAR T-cell therapy.

They described the case of a 20-year-old male who received the anti-CD19 CAR tisagenlecleucel (Kymriah) and relapsed at day 252 after the infusion.

The transduction of a leukemic cell during manufacture of the CAR T-cell product “is a rare event,” they wrote, and indicated that “this is the only case out of 369 patients reported worldwide at the time of publication.”

Lead author Marco Ruella, MD, of the University of Pennsylvania, and colleagues described the case in a Brief Communication published in Nature Medicine.

"In this case,” Dr. Ruella said, “we found that 100 percent of relapsed leukemic cells carried the CAR that we use to genetically modify T cells."

The patient had B-cell acute lymphoblastic leukemia (B-ALL) and relapsed three times after chemotherapy and a cord blood transplant before enrolling in the phase 1 trial of CTL019 (NCT 01626495).

The investigators reported that the infused CAR cells “displayed the typical pattern of in vivo engraftment and expansion.” At day 28 after the infusion, the patient was in complete remission.

But by day 252, he experienced a second expansion of CAR cells that did not correspond to the re-expansion of CAR+ T cells.

At day 261, the patient relapsed with more than 90% CD10+CD19- leukemic cells in the bone marrow and circulating blasts. The cells were CAR-transduced B-cell leukemia (CARB) cells.

The CARB cells continued to expand, and the patient died of progressive leukemia.

The investigators tracked the origin of the CARB cells by analyzing the relapsed CAR19+ cells using next-generation sequencing.

They hypothesized that the CAR19+ leukemia relapse occurred through lentiviral transduction during the manufacturing process, since they detected no replication-competent lentivirus when testing the patient’s peripheral blood at numerous time points after CTL019 infusion.

Further analysis confirmed the CARB cells were a byproduct made during CTL019 cell manufacturing.

To confirm that the leukemia relapse originated from a single clone, the investigators expanded in mice blast cells detected in the patient at month 9. Nine of 71 cells analyzed were positive for vector-host junctions. This confirmed that the relapsed cells originated from a single blast clone.

The investigators also excluded other possible reasons for the loss of CD19, including mutations, splicing variants, and structural alteration of the B-cell receptor complex.

They found that expression of the CAR in cis on B-ALL blasts masked the CAR target epitope.

The investigators concluded that their results “provide a direct confirmation of the cancer stem cell hypothesis in humans, given that clonal analysis indicated that the relapse and subsequent death of the patient were attributed to the progeny of a single leukemic blast cell with extensive replicative capacity, both in culture and in vivo.”

They called for improved manufacturing technologies that can eliminate contamination by residual tumor cells from engineered T cells.

Interestingly, this case developed not long after a case that showed essentially the opposite situation—a patient with chronic lymphocytic leukemia went into remission because of a single CAR T cell that reproduced and fought off the disease. 

Credit: Penn Medicine

Investigators report that a single leukemic cell unintentionally engineered into the chimeric antigen receptor (CAR) T-cell product can mask it from recognition and confer resistance to CAR T-cell therapy.

They described the case of a 20-year-old male who received the anti-CD19 CAR tisagenlecleucel (Kymriah) and relapsed at day 252 after the infusion.

The transduction of a leukemic cell during manufacture of the CAR T-cell product “is a rare event,” they wrote, and indicated that “this is the only case out of 369 patients reported worldwide at the time of publication.”

Lead author Marco Ruella, MD, of the University of Pennsylvania, and colleagues described the case in a Brief Communication published in Nature Medicine.

"In this case,” Dr. Ruella said, “we found that 100 percent of relapsed leukemic cells carried the CAR that we use to genetically modify T cells."

The patient had B-cell acute lymphoblastic leukemia (B-ALL) and relapsed three times after chemotherapy and a cord blood transplant before enrolling in the phase 1 trial of CTL019 (NCT 01626495).

The investigators reported that the infused CAR cells “displayed the typical pattern of in vivo engraftment and expansion.” At day 28 after the infusion, the patient was in complete remission.

But by day 252, he experienced a second expansion of CAR cells that did not correspond to the re-expansion of CAR+ T cells.

At day 261, the patient relapsed with more than 90% CD10+CD19- leukemic cells in the bone marrow and circulating blasts. The cells were CAR-transduced B-cell leukemia (CARB) cells.

The CARB cells continued to expand, and the patient died of progressive leukemia.

The investigators tracked the origin of the CARB cells by analyzing the relapsed CAR19+ cells using next-generation sequencing.

They hypothesized that the CAR19+ leukemia relapse occurred through lentiviral transduction during the manufacturing process, since they detected no replication-competent lentivirus when testing the patient’s peripheral blood at numerous time points after CTL019 infusion.

Further analysis confirmed the CARB cells were a byproduct made during CTL019 cell manufacturing.

To confirm that the leukemia relapse originated from a single clone, the investigators expanded in mice blast cells detected in the patient at month 9. Nine of 71 cells analyzed were positive for vector-host junctions. This confirmed that the relapsed cells originated from a single blast clone.

The investigators also excluded other possible reasons for the loss of CD19, including mutations, splicing variants, and structural alteration of the B-cell receptor complex.

They found that expression of the CAR in cis on B-ALL blasts masked the CAR target epitope.

The investigators concluded that their results “provide a direct confirmation of the cancer stem cell hypothesis in humans, given that clonal analysis indicated that the relapse and subsequent death of the patient were attributed to the progeny of a single leukemic blast cell with extensive replicative capacity, both in culture and in vivo.”

They called for improved manufacturing technologies that can eliminate contamination by residual tumor cells from engineered T cells.

Interestingly, this case developed not long after a case that showed essentially the opposite situation—a patient with chronic lymphocytic leukemia went into remission because of a single CAR T cell that reproduced and fought off the disease. 

Credit: Penn Medicine

Investigators report that a single leukemic cell unintentionally engineered into the chimeric antigen receptor (CAR) T-cell product can mask it from recognition and confer resistance to CAR T-cell therapy.

They described the case of a 20-year-old male who received the anti-CD19 CAR tisagenlecleucel (Kymriah) and relapsed at day 252 after the infusion.

The transduction of a leukemic cell during manufacture of the CAR T-cell product “is a rare event,” they wrote, and indicated that “this is the only case out of 369 patients reported worldwide at the time of publication.”

Lead author Marco Ruella, MD, of the University of Pennsylvania, and colleagues described the case in a Brief Communication published in Nature Medicine.

"In this case,” Dr. Ruella said, “we found that 100 percent of relapsed leukemic cells carried the CAR that we use to genetically modify T cells."

The patient had B-cell acute lymphoblastic leukemia (B-ALL) and relapsed three times after chemotherapy and a cord blood transplant before enrolling in the phase 1 trial of CTL019 (NCT 01626495).

The investigators reported that the infused CAR cells “displayed the typical pattern of in vivo engraftment and expansion.” At day 28 after the infusion, the patient was in complete remission.

But by day 252, he experienced a second expansion of CAR cells that did not correspond to the re-expansion of CAR+ T cells.

At day 261, the patient relapsed with more than 90% CD10+CD19- leukemic cells in the bone marrow and circulating blasts. The cells were CAR-transduced B-cell leukemia (CARB) cells.

The CARB cells continued to expand, and the patient died of progressive leukemia.

The investigators tracked the origin of the CARB cells by analyzing the relapsed CAR19+ cells using next-generation sequencing.

They hypothesized that the CAR19+ leukemia relapse occurred through lentiviral transduction during the manufacturing process, since they detected no replication-competent lentivirus when testing the patient’s peripheral blood at numerous time points after CTL019 infusion.

Further analysis confirmed the CARB cells were a byproduct made during CTL019 cell manufacturing.

To confirm that the leukemia relapse originated from a single clone, the investigators expanded in mice blast cells detected in the patient at month 9. Nine of 71 cells analyzed were positive for vector-host junctions. This confirmed that the relapsed cells originated from a single blast clone.

The investigators also excluded other possible reasons for the loss of CD19, including mutations, splicing variants, and structural alteration of the B-cell receptor complex.

They found that expression of the CAR in cis on B-ALL blasts masked the CAR target epitope.

The investigators concluded that their results “provide a direct confirmation of the cancer stem cell hypothesis in humans, given that clonal analysis indicated that the relapse and subsequent death of the patient were attributed to the progeny of a single leukemic blast cell with extensive replicative capacity, both in culture and in vivo.”

They called for improved manufacturing technologies that can eliminate contamination by residual tumor cells from engineered T cells.

Interestingly, this case developed not long after a case that showed essentially the opposite situation—a patient with chronic lymphocytic leukemia went into remission because of a single CAR T cell that reproduced and fought off the disease. 

The other day, I saw my health care provider for a routine appointment—and indeed, it seemed that I saw him, rather than the other way around. After having my vital signs measured by the medical assistant, I was led into the exam room. To my surprise, the provider (I will not divulge whether he was a physician, PA, or NP) was already there, sitting in front of his computer. He glanced up to say hello, but did not stand up, shake my hand, or maintain any level of eye contact. He did swear under his breath several times—something about his hatred of electronic medical records (EMRs)—while he asked me questions, hammering away on his laptop in time with my responses. After confirming that I was there for a prescription refill, he picked up his laptop and walked out of the room. A few minutes later, he popped back in to say, “Gee, I guess I should listen to your heart.” He placed the stethoscope on my chest over my shirt for a fraction of a second and was gone again. When I got to the pharmacy, I discovered he had called in the wrong prescription.

When Harvard professor Clayton M. Christensen coined the phrase disruptive technology, I’m not sure he imagined quite this level of impact! The time focused on a computer or device, rather than on the patient, has become so disproportionate that Dr. Abraham Verghese coined the term iPatient—a result of what he calls the chart-as-surrogate-for-the-patient approach.¹

While I hope my experience is not a regular occurrence in health care today, I’m well aware that the addition of e-this and e-that (computers, tablets, smartphones) at the bedside has clinicians multitasking more and more. Sure, performing more than one task at a time can be time-saving. But it can also lead to preoccupation and medical errors—at a time when medical errors are the third leading cause of death in the United States.²

We, as clinicians and as a larger society, are fascinated by speed. We want information faster than ever: medical information, lab results, etc. Our devices, stimulating and exhilarating as they are, have created a new society. Tell me you have not noticed the zombie-like motions of our colleagues walking in an electronic trance, pecking away at their preferred device! (OK, I am guilty of this, as well.)

Furthermore—and counterintuitively—efficiency in the clinic has been decimated by technology. In the “old days,” we could see patients roughly every 15 minutes, and many were double-booked. No problem; we merely dictated a note while walking from room to room, turned in our tapes at the end of the day, and signed a stack of notes two days later. Now, documentation alone takes at least 15 minutes, because it’s not just the note; it’s also the charges and the visit summary that is supposed to (but never does) go home with the patient.

So, if you want to see patients, if you want to generate revenue, if you want to keep the corporate slave drivers at bay, you either skimp on patient care or you document on your own time. One colleague lamented to me that, by implementing cost-saving measures to eliminate medical transcription ($2-$3/h outsourced to India), administrators and EMRs have reduced clinicians to the role of “Doc-retary.”

The diversion of attention, coupled with pressure to “perform,” is at the heart of the problem. Lately, every clinician I have spoken to seems to feel burdened by an influx of demands to see more patients in abbreviated visits while maintaining detailed records and documenting everything. It is no wonder that more than 75% of respondents in a study on physician distress met the criteria for burnout.³ I worry that NPs and PAs are not far behind. In a 2018 study, more than half (55.6%) of PAs rated “spending too many hours at work” as an important contributor to stress, and about 29% had previously quit a job due to stress.⁴

Continue to: If my own editorials are anything to judge by...

If my own editorials are anything to judge by, the joys and (welcome) challenges of the job are increasingly rare. I’ve discussed the “lost art” of the physical examination (November 2010); lamented the “death of altruism” (April 2016); and listed the pros and cons (mostly cons) of social media use (December 2017). Is careful listening to the patient the next thing to go?

We know intuitively that careful listening leads to better diagnosis and fewer errors. In fact, Balogh and colleagues identified patient engagement as one of four major cultural movements in health care (the others are patient safety, professionalism, and collaboration) that health care organizations need to foster in order to improve diagnosis and reduce errors.⁵ To my mind, that means finding ways to bring back the interpersonal relationship between clinician and patient and finding ways to remove the barriers that electronics can build.

I know exam room computing and EMRs are here to stay—and even, I suspect, likely to increase. But it is still possible, in my opinion, to incorporate patients into the interaction between clinician and computer. It is also possible, with the use of scribes, to have a third party transcribe your thoughts and actions as you interact directly with the patient. The last clinic I worked at operated this way, and it was liberating to be able to spend my time doing what I love best: interacting with my patients.

For those of you saying, “Yes, but my practice won’t hire scribes,” there is good advice out there on how to improve your interaction with patients in the Digital Age. In 2016, Frankel introduced the mnemonic POISED to enhance patient encounters while incorporating technologic devices:

Prepare. Review the patient’s medical records before you enter the exam room.

Continue to: Prepare

Orient. Let the patient know what you are doing or plan to do, and explain the use of the computer or scribe.

Information gathering. Although clinician-centric, this process should involve a two-way conversation between the clinician and patient.

Share. Use audiovisual sources (ie, your computer screen) to share information—for example, test results—with the patient.

Educate. Similarly, the computer can be a useful tool for educating the patient, as can low-tech materials like pictures and/or models.

Continue to: Debrief

Debrief. Review what has been said and make sure the patient has a chance to ask questions.⁶

The use of computers, EMRs, and other gadgets carries many potential consequences—but when used appropriately, these devices can be valuable tools for clinicians to interact with patients, stimulate engagement, and enrich patient-centered relationships. Do you agree? Please share with me your ideas on how we can better use the technology being placed before us at PAeditor@mdedge.com.

The other day, I saw my health care provider for a routine appointment—and indeed, it seemed that I saw him, rather than the other way around. After having my vital signs measured by the medical assistant, I was led into the exam room. To my surprise, the provider (I will not divulge whether he was a physician, PA, or NP) was already there, sitting in front of his computer. He glanced up to say hello, but did not stand up, shake my hand, or maintain any level of eye contact. He did swear under his breath several times—something about his hatred of electronic medical records (EMRs)—while he asked me questions, hammering away on his laptop in time with my responses. After confirming that I was there for a prescription refill, he picked up his laptop and walked out of the room. A few minutes later, he popped back in to say, “Gee, I guess I should listen to your heart.” He placed the stethoscope on my chest over my shirt for a fraction of a second and was gone again. When I got to the pharmacy, I discovered he had called in the wrong prescription.

When Harvard professor Clayton M. Christensen coined the phrase disruptive technology, I’m not sure he imagined quite this level of impact! The time focused on a computer or device, rather than on the patient, has become so disproportionate that Dr. Abraham Verghese coined the term iPatient—a result of what he calls the chart-as-surrogate-for-the-patient approach.¹

While I hope my experience is not a regular occurrence in health care today, I’m well aware that the addition of e-this and e-that (computers, tablets, smartphones) at the bedside has clinicians multitasking more and more. Sure, performing more than one task at a time can be time-saving. But it can also lead to preoccupation and medical errors—at a time when medical errors are the third leading cause of death in the United States.²

We, as clinicians and as a larger society, are fascinated by speed. We want information faster than ever: medical information, lab results, etc. Our devices, stimulating and exhilarating as they are, have created a new society. Tell me you have not noticed the zombie-like motions of our colleagues walking in an electronic trance, pecking away at their preferred device! (OK, I am guilty of this, as well.)

Furthermore—and counterintuitively—efficiency in the clinic has been decimated by technology. In the “old days,” we could see patients roughly every 15 minutes, and many were double-booked. No problem; we merely dictated a note while walking from room to room, turned in our tapes at the end of the day, and signed a stack of notes two days later. Now, documentation alone takes at least 15 minutes, because it’s not just the note; it’s also the charges and the visit summary that is supposed to (but never does) go home with the patient.

So, if you want to see patients, if you want to generate revenue, if you want to keep the corporate slave drivers at bay, you either skimp on patient care or you document on your own time. One colleague lamented to me that, by implementing cost-saving measures to eliminate medical transcription ($2-$3/h outsourced to India), administrators and EMRs have reduced clinicians to the role of “Doc-retary.”

The diversion of attention, coupled with pressure to “perform,” is at the heart of the problem. Lately, every clinician I have spoken to seems to feel burdened by an influx of demands to see more patients in abbreviated visits while maintaining detailed records and documenting everything. It is no wonder that more than 75% of respondents in a study on physician distress met the criteria for burnout.³ I worry that NPs and PAs are not far behind. In a 2018 study, more than half (55.6%) of PAs rated “spending too many hours at work” as an important contributor to stress, and about 29% had previously quit a job due to stress.⁴

Continue to: If my own editorials are anything to judge by...

If my own editorials are anything to judge by, the joys and (welcome) challenges of the job are increasingly rare. I’ve discussed the “lost art” of the physical examination (November 2010); lamented the “death of altruism” (April 2016); and listed the pros and cons (mostly cons) of social media use (December 2017). Is careful listening to the patient the next thing to go?

We know intuitively that careful listening leads to better diagnosis and fewer errors. In fact, Balogh and colleagues identified patient engagement as one of four major cultural movements in health care (the others are patient safety, professionalism, and collaboration) that health care organizations need to foster in order to improve diagnosis and reduce errors.⁵ To my mind, that means finding ways to bring back the interpersonal relationship between clinician and patient and finding ways to remove the barriers that electronics can build.

I know exam room computing and EMRs are here to stay—and even, I suspect, likely to increase. But it is still possible, in my opinion, to incorporate patients into the interaction between clinician and computer. It is also possible, with the use of scribes, to have a third party transcribe your thoughts and actions as you interact directly with the patient. The last clinic I worked at operated this way, and it was liberating to be able to spend my time doing what I love best: interacting with my patients.

For those of you saying, “Yes, but my practice won’t hire scribes,” there is good advice out there on how to improve your interaction with patients in the Digital Age. In 2016, Frankel introduced the mnemonic POISED to enhance patient encounters while incorporating technologic devices:

Prepare. Review the patient’s medical records before you enter the exam room.

Continue to: Prepare

Orient. Let the patient know what you are doing or plan to do, and explain the use of the computer or scribe.

Information gathering. Although clinician-centric, this process should involve a two-way conversation between the clinician and patient.

Share. Use audiovisual sources (ie, your computer screen) to share information—for example, test results—with the patient.

Educate. Similarly, the computer can be a useful tool for educating the patient, as can low-tech materials like pictures and/or models.

Continue to: Debrief

Debrief. Review what has been said and make sure the patient has a chance to ask questions.⁶

The use of computers, EMRs, and other gadgets carries many potential consequences—but when used appropriately, these devices can be valuable tools for clinicians to interact with patients, stimulate engagement, and enrich patient-centered relationships. Do you agree? Please share with me your ideas on how we can better use the technology being placed before us at PAeditor@mdedge.com.

The other day, I saw my health care provider for a routine appointment—and indeed, it seemed that I saw him, rather than the other way around. After having my vital signs measured by the medical assistant, I was led into the exam room. To my surprise, the provider (I will not divulge whether he was a physician, PA, or NP) was already there, sitting in front of his computer. He glanced up to say hello, but did not stand up, shake my hand, or maintain any level of eye contact. He did swear under his breath several times—something about his hatred of electronic medical records (EMRs)—while he asked me questions, hammering away on his laptop in time with my responses. After confirming that I was there for a prescription refill, he picked up his laptop and walked out of the room. A few minutes later, he popped back in to say, “Gee, I guess I should listen to your heart.” He placed the stethoscope on my chest over my shirt for a fraction of a second and was gone again. When I got to the pharmacy, I discovered he had called in the wrong prescription.

When Harvard professor Clayton M. Christensen coined the phrase disruptive technology, I’m not sure he imagined quite this level of impact! The time focused on a computer or device, rather than on the patient, has become so disproportionate that Dr. Abraham Verghese coined the term iPatient—a result of what he calls the chart-as-surrogate-for-the-patient approach.¹

While I hope my experience is not a regular occurrence in health care today, I’m well aware that the addition of e-this and e-that (computers, tablets, smartphones) at the bedside has clinicians multitasking more and more. Sure, performing more than one task at a time can be time-saving. But it can also lead to preoccupation and medical errors—at a time when medical errors are the third leading cause of death in the United States.²

We, as clinicians and as a larger society, are fascinated by speed. We want information faster than ever: medical information, lab results, etc. Our devices, stimulating and exhilarating as they are, have created a new society. Tell me you have not noticed the zombie-like motions of our colleagues walking in an electronic trance, pecking away at their preferred device! (OK, I am guilty of this, as well.)

Furthermore—and counterintuitively—efficiency in the clinic has been decimated by technology. In the “old days,” we could see patients roughly every 15 minutes, and many were double-booked. No problem; we merely dictated a note while walking from room to room, turned in our tapes at the end of the day, and signed a stack of notes two days later. Now, documentation alone takes at least 15 minutes, because it’s not just the note; it’s also the charges and the visit summary that is supposed to (but never does) go home with the patient.

So, if you want to see patients, if you want to generate revenue, if you want to keep the corporate slave drivers at bay, you either skimp on patient care or you document on your own time. One colleague lamented to me that, by implementing cost-saving measures to eliminate medical transcription ($2-$3/h outsourced to India), administrators and EMRs have reduced clinicians to the role of “Doc-retary.”

The diversion of attention, coupled with pressure to “perform,” is at the heart of the problem. Lately, every clinician I have spoken to seems to feel burdened by an influx of demands to see more patients in abbreviated visits while maintaining detailed records and documenting everything. It is no wonder that more than 75% of respondents in a study on physician distress met the criteria for burnout.³ I worry that NPs and PAs are not far behind. In a 2018 study, more than half (55.6%) of PAs rated “spending too many hours at work” as an important contributor to stress, and about 29% had previously quit a job due to stress.⁴

Continue to: If my own editorials are anything to judge by...

If my own editorials are anything to judge by, the joys and (welcome) challenges of the job are increasingly rare. I’ve discussed the “lost art” of the physical examination (November 2010); lamented the “death of altruism” (April 2016); and listed the pros and cons (mostly cons) of social media use (December 2017). Is careful listening to the patient the next thing to go?

We know intuitively that careful listening leads to better diagnosis and fewer errors. In fact, Balogh and colleagues identified patient engagement as one of four major cultural movements in health care (the others are patient safety, professionalism, and collaboration) that health care organizations need to foster in order to improve diagnosis and reduce errors.⁵ To my mind, that means finding ways to bring back the interpersonal relationship between clinician and patient and finding ways to remove the barriers that electronics can build.

I know exam room computing and EMRs are here to stay—and even, I suspect, likely to increase. But it is still possible, in my opinion, to incorporate patients into the interaction between clinician and computer. It is also possible, with the use of scribes, to have a third party transcribe your thoughts and actions as you interact directly with the patient. The last clinic I worked at operated this way, and it was liberating to be able to spend my time doing what I love best: interacting with my patients.

For those of you saying, “Yes, but my practice won’t hire scribes,” there is good advice out there on how to improve your interaction with patients in the Digital Age. In 2016, Frankel introduced the mnemonic POISED to enhance patient encounters while incorporating technologic devices:

Prepare. Review the patient’s medical records before you enter the exam room.

Continue to: Prepare

Orient. Let the patient know what you are doing or plan to do, and explain the use of the computer or scribe.

Information gathering. Although clinician-centric, this process should involve a two-way conversation between the clinician and patient.

Share. Use audiovisual sources (ie, your computer screen) to share information—for example, test results—with the patient.

Educate. Similarly, the computer can be a useful tool for educating the patient, as can low-tech materials like pictures and/or models.

Continue to: Debrief

Debrief. Review what has been said and make sure the patient has a chance to ask questions.⁶

The use of computers, EMRs, and other gadgets carries many potential consequences—but when used appropriately, these devices can be valuable tools for clinicians to interact with patients, stimulate engagement, and enrich patient-centered relationships. Do you agree? Please share with me your ideas on how we can better use the technology being placed before us at PAeditor@mdedge.com.

Vaginal rejuvenation encompasses a group of procedures that alter the vaginal anatomy to improve cosmesis or achieve more pleasurable sexual intercourse. External vaginal procedures are defined as those performed on the female genitalia outside of the vaginal introitus, with major structures including the labia majora, mons pubis, labia minora, clitoral hood, clitoral glans, and vaginal vestibule. Internal vaginal procedures are defined as those performed within the vagina, extending from the vaginal introitus to the cervix.

The prevalence of elective vaginal rejuvenation procedures has increased in recent years, a trend that may be attributed to greater exposure through the media, including reality television and pornography. In a survey of 482 women undergoing labiaplasty, nearly all had heard about rejuvenation procedures within the last 2.2 years, and 78% had received their information through the media.¹ Additionally, genital self-image can have a considerable effect on a woman’s sexual behavior and relationships. Genital dissatisfaction has been associated with decreased sexual activity, whereas positive genital self-image correlates with increased sexual desire and less sexual distress or depression.^2,3

Currently, the 2 primary applications of noninvasive vaginal rejuvenation are vaginal laxity and genitourinary syndrome of menopause (GSM). Vaginal laxity occurs in premenopausal or postmenopausal women and is caused by aging, childbearing, or hormonal imbalances. These factors can lead to decreased friction within the vagina during intercourse, which in turn can decrease sexual pleasure. Genitourinary syndrome of menopause, previously known as vulvovaginal atrophy, encompasses genital (eg, dryness, burning, irritation), sexual (eg, lack of lubrication, discomfort or pain, impaired function), and urinary (eg, urgency, dysuria, recurrent urinary tract infections) symptoms of menopause.⁴

Noninvasive procedures are designed to apply ablative or nonablative energy to the vaginal mucosa to tighten a lax upper vagina, also known as a wide vagina.⁵ A wide vagina has been defined as a widened vaginal diameter that interferes with sexual function and sensation.⁶ Decreased sexual sensation also may result from fibrosis or scarring of the vaginal mucosa after prior vaginal surgery, episiotomy, or tears during childbirth.⁷ The objective of rejuvenation procedures to treat the vaginal mucosa is to create increased frictional forces that may lead to increased sexual sensation.⁸ Although there are numerous reports of heightened sexual satisfaction after reduction of the vaginal diameter, a formal link between sexual pleasure and vaginal laxity has yet to be established.^8,9 At present, there are no US Food and Drug Administration (FDA)–approved energy-based devices to treat urinary incontinence or sexual function, and the FDA recently issued an alert cautioning patients on the current lack of safety and efficacy regulations.¹⁰

In this article we review the safety and efficacy data behind lasers and radiofrequency (RF) devices used in noninvasive vaginal rejuvenation procedures.

Lasers

CO₂ Laser
The infrared CO₂ laser utilizes 10,600-nm energy to target and vaporize water molecules within the target tissue. This thermal heating extends to the dermal collagen, which stimulates inflammatory pathways and neocollagenesis.¹¹ The depth of penetration ranges from 20 to 125 μm.¹² Zerbinati et al¹³ demonstrated the histologic and ultrastructural effects of a fractional CO₂ laser on atrophic vaginal mucosa. Comparing pretreatment and posttreatment mucosal biopsies in 5 postmenopausal women, the investigators found that fractional CO₂ laser treatment caused increased epithelial thickness, vascularity, and fibroblast activity, which led to augmented synthesis of collagen and ground substance proteins.¹³

New devices seek to translate these histologic improvements to the aesthetic appearance and function of female genitalia. The MonaLisa Touch (Cynosure), a new fractional CO₂ laser specifically designed for treatment of the vaginal mucosa, uses dermal optical thermolysis (DOT) therapy to apply energy in a noncontinuous mode at 200-μm dots. Salvatore et al¹⁴ examined the use of this device in a noncontrolled study of 50 patients with GSM, with each patient undergoing 3 treatment sessions at monthly intervals. Intravaginal treatments were performed at the following settings: DOT (microablative zone) power of 30 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack parameter of 1 to 3. The investigators used the Vaginal Health Index (VHI) to objectively assess vaginal elasticity, secretions, pH, mucosa integrity, and moisture. Total VHI scores significantly improved between baseline and 1 month following the final treatment (mean score [SD], 13.1 [2.5] vs 23.1 [1.9]; P<.0001). There were no significant adverse events, and 84% of patients reported being satisfied with their outcome; however, the study lacked a comparison or control group, raising the possibility of placebo effect.¹⁴

Other noncontrolled series have corroborated the benefits of CO₂ laser in GSM patients.^15,16 In one of the largest studies to date, Filippini et al¹⁷ reviewed the outcomes of 386 menopausal women treated for GSM. Patients underwent 3 intravaginal laser sessions with the MonaLisa Touch. Intravaginal treatments were performed at a DOT power of 40 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack of 2. For the vulva, the DOT power was reduced to 30 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack of 1. Two months after the final treatment session, patients completed a nonvalidated questionnaire about their symptoms, with improved dryness reported in 60% of patients, improved burning in 56%, improved dyspareunia in 49%, improved itch in 56%, improved soreness in 73%, and improved vaginal introitus pain in 49%. Although most patients did not experience discomfort with the procedure, a minority noted a burning sensation (11%), bother with handpiece movement (6%), or vulvar pain (5%).¹⁷

Recently, Cruz et al¹⁸ performed one of the first randomized, double-blind, placebo-controlled trials comparing fractional CO₂ laser therapy, topical estrogen therapy, and the combination of both treatments in patients with GSM. Forty-five women were included in the study, and validated assessments were performed at baseline and weeks 8 and 20. Intravaginal treatments were performed at a DOT power of 30 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack of 2. Importantly, the study incorporated placebo laser treatments (with the power adjusted to 0.0 W) in the topical estrogen group, thereby decreasing result bias. There was a significant increase in VHI scores from baseline to week 8 (P<.05) and week 20 (P<.01) in all study arms. At week 20, the laser group and laser plus estrogen group showed significant improvements in reported dyspareunia, burning, and dryness, whereas the estrogen arm only reported improvements in dryness (all values P<.05).¹⁸

Erbium-Doped YAG Laser
The erbium-doped YAG (Er:YAG) laser is an ablative laser emitting light at 2940 nm. This wavelength provides an absorption coefficient for water 16 times greater than the CO₂ laser, leading to decreased penetration depth of 1 to 3 μm and reduced damage to the surrounding tissues.^19,20 As such, the Er:YAG laser results in milder postoperative discomfort and faster overall healing times.²¹

In a noncontrolled study of vaginal relaxation syndrome, Lee²² used an Er:YAG laser fitted with Petit Lady (Lutronic) 90° and 360° vaginal scanning scopes. Thirty patients were divided into 2 groups and were treated with 4 sessions at weekly intervals. In group A, the first 2 sessions were performed with the 360° scope, and the last 2 sessions with the 90° scope in multiple micropulse mode (3 multishots; pulse width of 250 μs; 1.7 J delivered per shot). Group B was treated with the 90° scope in all 4 sessions in multiple micropulse mode (same parameters as group A), and during the last 2 sessions patients were additionally treated with 2 passes per session with the 360° scope (long-pulsed mode; pulse width of 1000 μs; 3.7 J delivered per shot). Perineometer measurements taken 2 months after the final treatment showed that the combined patient population experienced significant increases in both maximal vaginal pressure (P<.01) and average vaginal pressure (P<.05). Roughly 76% of patients’ partners noted improved vaginal tightening, and 70% of patients reported being satisfied with their treatment outcome. Histologic specimens taken at baseline and 2 months postprocedure showed evidence of thicker and more cellular epithelia along with more compact lamina propria with denser connective tissue. The sessions were well tolerated, with patients reporting a nonpainful heating sensation in the vagina during treatment. Three patients from the combined patient population experienced a mild burning sensation and vaginal ecchymoses, which lasted 24 to 48 hours following treatment and resolved spontaneously. There was no control group and no reports of major or long-term adverse events.²²

Investigations also have shown the benefit of Er:YAG in the treatment of GSM.^23,24 In a study by Gambacciani et al,²⁴ patients treated with the Er:YAG laser FotonaSmooth (Fotona) every 30 days for 3 months reported significant improvements in vaginal dryness and dyspareunia (P<.01), which lasted up to 6 months posttreatment, though there was no placebo group comparator. Similar results were seen by Gaspar et al²³ using 3 treatments at 3-week intervals, with results sustained up to 18 months after the final session.

Radiofrequency Devices

Radiofrequency devices emit focused electromagnetic waves that heat underlying tissues without targeting melanin. The release of thermal energy induces collagen contraction, neocollagenesis, and neovascularization, all of which aid in restoring the elasticity and moisture of the vaginal mucosa.²⁵ Devices also may be equipped with cooling probes and reverse-heating gradients to protect the surface mucosa while deeper tissues are heated.

Millheiser et al²⁶ performed a noncontrolled pilot study in 24 women with vaginal laxity using the Viveve System (Viveve), a cryogen-cooled monopolar RF device. Participants underwent a single 30-minute session (energy ranging from 75–90 J/cm²) during which the mucosal surface of the vaginal introitus (excluding the urethra) was treated with pulses at 0.5-cm overlapping intervals. Follow-up assessments were completed at 1, 3, and 6 months posttreatment. Self-reported vaginal tightness improved in 67% of participants at 1-month posttreatment and in 87% of participants at 6 months posttreatment (P<.001). There were no adverse events reported.²⁶ Sekiguchi et al²⁷ reported similar benefits lasting up to 12 months after a single 26-minute session at 90 J/cm².

A prospective, randomized, placebo-controlled clinical trial using the Viveve system was recently completed by Krychman et al.²⁸ Participants (N=186) were randomized to receive a single session of active treatment (90 J/cm²) or placebo treatment (1 J/cm²). In both groups, the vaginal introitus was treated with pulses at 0.5 cm in overlapping intervals, with the entire area (excluding the urethra) treated 5 times up to a total of 110 pulses. The primary end point was the proportion of randomized participants reporting no vaginal laxity at 6 months postin-tervention, which was assessed using the Vaginal Laxity Questionnaire. A grade of no vaginal laxity was achieved by 43.5% of participants in the active treatment group and 19.6% of participants in the sham group (P=.002). Overall numbers of treatment-emergent adverse events were comparable between the 2 groups, with the most commonly reported being vaginal discharge (2.6% in the active treatment group vs 3.5% in the sham group). There were no serious adverse events reported in the active treatment group.²⁸

ThermiVa (ThermiGen, LLC), a unipolar RF device, was evaluated by Alinsod²⁹ in the treatment of orgasmic dysfunction. The noncontrolled study included 25 women with self-reported difficulty achieving orgasm during intercourse, each of whom underwent 3 treatment sessions at 1-month intervals. Of the 25 enrolled women, 19 (76%) reported an average reduction in time to orgasm of at least 50%. All anorgasmic patients (n=10) at baseline reported renewed ability to achieve orgasms. Two (8%) patients failed to achieve a significant benefit from the treatments. Of note, the study did not include a control group, and specific data on the durability of beneficial effects was lacking.²⁹

The Ultra Femme 360 (BLT Industries Inc), a monopolar RF device, was evaluated by Lalji and Lozanova³⁰ in a noncontrolled study of 27 women with mild to moderate vaginal laxity and urinary incontinence. Participants underwent 3 treatment sessions at weekly intervals. Vaginal laxity was assessed by a subjective vulvovaginal laxity questionnaire, and data were collected before the first treatment and at 1-month follow-up. All 27 participants reported improvements in vaginal laxity, with the average grade (SD) increasing from very loose (2.19 [1.08]) to moderately tight (5.74 [0.76]; P<.05) on the questionnaire’s 7-point scale. The trial did not include a control group.³⁰

Conclusion

With growing patient interest in vaginal rejuvenation, clinicians are increasingly incorporating a variety of procedures into their practice. Although long-term data on the safety and efficacy of these treatments has yet to be established, current evidence indicates that fractional ablative lasers and RF devices can improve vaginal laxity, sexual sensation, and symptoms of GSM.

To date, major complications have not been reported, but the FDA has advocated caution until regulatory approval is achieved.¹⁰ Concerns exist over the limited number of robust clinical trials as well as the prevalence of advertising campaigns that promise wide-ranging improvements without sufficient evidence. Definitive statements on medical or cosmetic indications will undoubtedly require more thorough investigation. At this time, the safety profile of these devices appears to be favorable, and high rates of patient satisfaction have been reported. As such, noninvasive vaginal rejuvenation procedures may represent a valuable addition to the cosmetic landscape.

Vaginal rejuvenation encompasses a group of procedures that alter the vaginal anatomy to improve cosmesis or achieve more pleasurable sexual intercourse. External vaginal procedures are defined as those performed on the female genitalia outside of the vaginal introitus, with major structures including the labia majora, mons pubis, labia minora, clitoral hood, clitoral glans, and vaginal vestibule. Internal vaginal procedures are defined as those performed within the vagina, extending from the vaginal introitus to the cervix.

The prevalence of elective vaginal rejuvenation procedures has increased in recent years, a trend that may be attributed to greater exposure through the media, including reality television and pornography. In a survey of 482 women undergoing labiaplasty, nearly all had heard about rejuvenation procedures within the last 2.2 years, and 78% had received their information through the media.¹ Additionally, genital self-image can have a considerable effect on a woman’s sexual behavior and relationships. Genital dissatisfaction has been associated with decreased sexual activity, whereas positive genital self-image correlates with increased sexual desire and less sexual distress or depression.^2,3

Currently, the 2 primary applications of noninvasive vaginal rejuvenation are vaginal laxity and genitourinary syndrome of menopause (GSM). Vaginal laxity occurs in premenopausal or postmenopausal women and is caused by aging, childbearing, or hormonal imbalances. These factors can lead to decreased friction within the vagina during intercourse, which in turn can decrease sexual pleasure. Genitourinary syndrome of menopause, previously known as vulvovaginal atrophy, encompasses genital (eg, dryness, burning, irritation), sexual (eg, lack of lubrication, discomfort or pain, impaired function), and urinary (eg, urgency, dysuria, recurrent urinary tract infections) symptoms of menopause.⁴

Noninvasive procedures are designed to apply ablative or nonablative energy to the vaginal mucosa to tighten a lax upper vagina, also known as a wide vagina.⁵ A wide vagina has been defined as a widened vaginal diameter that interferes with sexual function and sensation.⁶ Decreased sexual sensation also may result from fibrosis or scarring of the vaginal mucosa after prior vaginal surgery, episiotomy, or tears during childbirth.⁷ The objective of rejuvenation procedures to treat the vaginal mucosa is to create increased frictional forces that may lead to increased sexual sensation.⁸ Although there are numerous reports of heightened sexual satisfaction after reduction of the vaginal diameter, a formal link between sexual pleasure and vaginal laxity has yet to be established.^8,9 At present, there are no US Food and Drug Administration (FDA)–approved energy-based devices to treat urinary incontinence or sexual function, and the FDA recently issued an alert cautioning patients on the current lack of safety and efficacy regulations.¹⁰

In this article we review the safety and efficacy data behind lasers and radiofrequency (RF) devices used in noninvasive vaginal rejuvenation procedures.

Lasers

CO₂ Laser
The infrared CO₂ laser utilizes 10,600-nm energy to target and vaporize water molecules within the target tissue. This thermal heating extends to the dermal collagen, which stimulates inflammatory pathways and neocollagenesis.¹¹ The depth of penetration ranges from 20 to 125 μm.¹² Zerbinati et al¹³ demonstrated the histologic and ultrastructural effects of a fractional CO₂ laser on atrophic vaginal mucosa. Comparing pretreatment and posttreatment mucosal biopsies in 5 postmenopausal women, the investigators found that fractional CO₂ laser treatment caused increased epithelial thickness, vascularity, and fibroblast activity, which led to augmented synthesis of collagen and ground substance proteins.¹³

New devices seek to translate these histologic improvements to the aesthetic appearance and function of female genitalia. The MonaLisa Touch (Cynosure), a new fractional CO₂ laser specifically designed for treatment of the vaginal mucosa, uses dermal optical thermolysis (DOT) therapy to apply energy in a noncontinuous mode at 200-μm dots. Salvatore et al¹⁴ examined the use of this device in a noncontrolled study of 50 patients with GSM, with each patient undergoing 3 treatment sessions at monthly intervals. Intravaginal treatments were performed at the following settings: DOT (microablative zone) power of 30 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack parameter of 1 to 3. The investigators used the Vaginal Health Index (VHI) to objectively assess vaginal elasticity, secretions, pH, mucosa integrity, and moisture. Total VHI scores significantly improved between baseline and 1 month following the final treatment (mean score [SD], 13.1 [2.5] vs 23.1 [1.9]; P<.0001). There were no significant adverse events, and 84% of patients reported being satisfied with their outcome; however, the study lacked a comparison or control group, raising the possibility of placebo effect.¹⁴

Other noncontrolled series have corroborated the benefits of CO₂ laser in GSM patients.^15,16 In one of the largest studies to date, Filippini et al¹⁷ reviewed the outcomes of 386 menopausal women treated for GSM. Patients underwent 3 intravaginal laser sessions with the MonaLisa Touch. Intravaginal treatments were performed at a DOT power of 40 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack of 2. For the vulva, the DOT power was reduced to 30 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack of 1. Two months after the final treatment session, patients completed a nonvalidated questionnaire about their symptoms, with improved dryness reported in 60% of patients, improved burning in 56%, improved dyspareunia in 49%, improved itch in 56%, improved soreness in 73%, and improved vaginal introitus pain in 49%. Although most patients did not experience discomfort with the procedure, a minority noted a burning sensation (11%), bother with handpiece movement (6%), or vulvar pain (5%).¹⁷

Recently, Cruz et al¹⁸ performed one of the first randomized, double-blind, placebo-controlled trials comparing fractional CO₂ laser therapy, topical estrogen therapy, and the combination of both treatments in patients with GSM. Forty-five women were included in the study, and validated assessments were performed at baseline and weeks 8 and 20. Intravaginal treatments were performed at a DOT power of 30 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack of 2. Importantly, the study incorporated placebo laser treatments (with the power adjusted to 0.0 W) in the topical estrogen group, thereby decreasing result bias. There was a significant increase in VHI scores from baseline to week 8 (P<.05) and week 20 (P<.01) in all study arms. At week 20, the laser group and laser plus estrogen group showed significant improvements in reported dyspareunia, burning, and dryness, whereas the estrogen arm only reported improvements in dryness (all values P<.05).¹⁸

Erbium-Doped YAG Laser
The erbium-doped YAG (Er:YAG) laser is an ablative laser emitting light at 2940 nm. This wavelength provides an absorption coefficient for water 16 times greater than the CO₂ laser, leading to decreased penetration depth of 1 to 3 μm and reduced damage to the surrounding tissues.^19,20 As such, the Er:YAG laser results in milder postoperative discomfort and faster overall healing times.²¹

In a noncontrolled study of vaginal relaxation syndrome, Lee²² used an Er:YAG laser fitted with Petit Lady (Lutronic) 90° and 360° vaginal scanning scopes. Thirty patients were divided into 2 groups and were treated with 4 sessions at weekly intervals. In group A, the first 2 sessions were performed with the 360° scope, and the last 2 sessions with the 90° scope in multiple micropulse mode (3 multishots; pulse width of 250 μs; 1.7 J delivered per shot). Group B was treated with the 90° scope in all 4 sessions in multiple micropulse mode (same parameters as group A), and during the last 2 sessions patients were additionally treated with 2 passes per session with the 360° scope (long-pulsed mode; pulse width of 1000 μs; 3.7 J delivered per shot). Perineometer measurements taken 2 months after the final treatment showed that the combined patient population experienced significant increases in both maximal vaginal pressure (P<.01) and average vaginal pressure (P<.05). Roughly 76% of patients’ partners noted improved vaginal tightening, and 70% of patients reported being satisfied with their treatment outcome. Histologic specimens taken at baseline and 2 months postprocedure showed evidence of thicker and more cellular epithelia along with more compact lamina propria with denser connective tissue. The sessions were well tolerated, with patients reporting a nonpainful heating sensation in the vagina during treatment. Three patients from the combined patient population experienced a mild burning sensation and vaginal ecchymoses, which lasted 24 to 48 hours following treatment and resolved spontaneously. There was no control group and no reports of major or long-term adverse events.²²

Investigations also have shown the benefit of Er:YAG in the treatment of GSM.^23,24 In a study by Gambacciani et al,²⁴ patients treated with the Er:YAG laser FotonaSmooth (Fotona) every 30 days for 3 months reported significant improvements in vaginal dryness and dyspareunia (P<.01), which lasted up to 6 months posttreatment, though there was no placebo group comparator. Similar results were seen by Gaspar et al²³ using 3 treatments at 3-week intervals, with results sustained up to 18 months after the final session.

Radiofrequency Devices

Radiofrequency devices emit focused electromagnetic waves that heat underlying tissues without targeting melanin. The release of thermal energy induces collagen contraction, neocollagenesis, and neovascularization, all of which aid in restoring the elasticity and moisture of the vaginal mucosa.²⁵ Devices also may be equipped with cooling probes and reverse-heating gradients to protect the surface mucosa while deeper tissues are heated.

Millheiser et al²⁶ performed a noncontrolled pilot study in 24 women with vaginal laxity using the Viveve System (Viveve), a cryogen-cooled monopolar RF device. Participants underwent a single 30-minute session (energy ranging from 75–90 J/cm²) during which the mucosal surface of the vaginal introitus (excluding the urethra) was treated with pulses at 0.5-cm overlapping intervals. Follow-up assessments were completed at 1, 3, and 6 months posttreatment. Self-reported vaginal tightness improved in 67% of participants at 1-month posttreatment and in 87% of participants at 6 months posttreatment (P<.001). There were no adverse events reported.²⁶ Sekiguchi et al²⁷ reported similar benefits lasting up to 12 months after a single 26-minute session at 90 J/cm².

A prospective, randomized, placebo-controlled clinical trial using the Viveve system was recently completed by Krychman et al.²⁸ Participants (N=186) were randomized to receive a single session of active treatment (90 J/cm²) or placebo treatment (1 J/cm²). In both groups, the vaginal introitus was treated with pulses at 0.5 cm in overlapping intervals, with the entire area (excluding the urethra) treated 5 times up to a total of 110 pulses. The primary end point was the proportion of randomized participants reporting no vaginal laxity at 6 months postin-tervention, which was assessed using the Vaginal Laxity Questionnaire. A grade of no vaginal laxity was achieved by 43.5% of participants in the active treatment group and 19.6% of participants in the sham group (P=.002). Overall numbers of treatment-emergent adverse events were comparable between the 2 groups, with the most commonly reported being vaginal discharge (2.6% in the active treatment group vs 3.5% in the sham group). There were no serious adverse events reported in the active treatment group.²⁸

ThermiVa (ThermiGen, LLC), a unipolar RF device, was evaluated by Alinsod²⁹ in the treatment of orgasmic dysfunction. The noncontrolled study included 25 women with self-reported difficulty achieving orgasm during intercourse, each of whom underwent 3 treatment sessions at 1-month intervals. Of the 25 enrolled women, 19 (76%) reported an average reduction in time to orgasm of at least 50%. All anorgasmic patients (n=10) at baseline reported renewed ability to achieve orgasms. Two (8%) patients failed to achieve a significant benefit from the treatments. Of note, the study did not include a control group, and specific data on the durability of beneficial effects was lacking.²⁹

The Ultra Femme 360 (BLT Industries Inc), a monopolar RF device, was evaluated by Lalji and Lozanova³⁰ in a noncontrolled study of 27 women with mild to moderate vaginal laxity and urinary incontinence. Participants underwent 3 treatment sessions at weekly intervals. Vaginal laxity was assessed by a subjective vulvovaginal laxity questionnaire, and data were collected before the first treatment and at 1-month follow-up. All 27 participants reported improvements in vaginal laxity, with the average grade (SD) increasing from very loose (2.19 [1.08]) to moderately tight (5.74 [0.76]; P<.05) on the questionnaire’s 7-point scale. The trial did not include a control group.³⁰

Conclusion

With growing patient interest in vaginal rejuvenation, clinicians are increasingly incorporating a variety of procedures into their practice. Although long-term data on the safety and efficacy of these treatments has yet to be established, current evidence indicates that fractional ablative lasers and RF devices can improve vaginal laxity, sexual sensation, and symptoms of GSM.

To date, major complications have not been reported, but the FDA has advocated caution until regulatory approval is achieved.¹⁰ Concerns exist over the limited number of robust clinical trials as well as the prevalence of advertising campaigns that promise wide-ranging improvements without sufficient evidence. Definitive statements on medical or cosmetic indications will undoubtedly require more thorough investigation. At this time, the safety profile of these devices appears to be favorable, and high rates of patient satisfaction have been reported. As such, noninvasive vaginal rejuvenation procedures may represent a valuable addition to the cosmetic landscape.

Vaginal rejuvenation encompasses a group of procedures that alter the vaginal anatomy to improve cosmesis or achieve more pleasurable sexual intercourse. External vaginal procedures are defined as those performed on the female genitalia outside of the vaginal introitus, with major structures including the labia majora, mons pubis, labia minora, clitoral hood, clitoral glans, and vaginal vestibule. Internal vaginal procedures are defined as those performed within the vagina, extending from the vaginal introitus to the cervix.

The prevalence of elective vaginal rejuvenation procedures has increased in recent years, a trend that may be attributed to greater exposure through the media, including reality television and pornography. In a survey of 482 women undergoing labiaplasty, nearly all had heard about rejuvenation procedures within the last 2.2 years, and 78% had received their information through the media.¹ Additionally, genital self-image can have a considerable effect on a woman’s sexual behavior and relationships. Genital dissatisfaction has been associated with decreased sexual activity, whereas positive genital self-image correlates with increased sexual desire and less sexual distress or depression.^2,3

Currently, the 2 primary applications of noninvasive vaginal rejuvenation are vaginal laxity and genitourinary syndrome of menopause (GSM). Vaginal laxity occurs in premenopausal or postmenopausal women and is caused by aging, childbearing, or hormonal imbalances. These factors can lead to decreased friction within the vagina during intercourse, which in turn can decrease sexual pleasure. Genitourinary syndrome of menopause, previously known as vulvovaginal atrophy, encompasses genital (eg, dryness, burning, irritation), sexual (eg, lack of lubrication, discomfort or pain, impaired function), and urinary (eg, urgency, dysuria, recurrent urinary tract infections) symptoms of menopause.⁴

Noninvasive procedures are designed to apply ablative or nonablative energy to the vaginal mucosa to tighten a lax upper vagina, also known as a wide vagina.⁵ A wide vagina has been defined as a widened vaginal diameter that interferes with sexual function and sensation.⁶ Decreased sexual sensation also may result from fibrosis or scarring of the vaginal mucosa after prior vaginal surgery, episiotomy, or tears during childbirth.⁷ The objective of rejuvenation procedures to treat the vaginal mucosa is to create increased frictional forces that may lead to increased sexual sensation.⁸ Although there are numerous reports of heightened sexual satisfaction after reduction of the vaginal diameter, a formal link between sexual pleasure and vaginal laxity has yet to be established.^8,9 At present, there are no US Food and Drug Administration (FDA)–approved energy-based devices to treat urinary incontinence or sexual function, and the FDA recently issued an alert cautioning patients on the current lack of safety and efficacy regulations.¹⁰

In this article we review the safety and efficacy data behind lasers and radiofrequency (RF) devices used in noninvasive vaginal rejuvenation procedures.

Lasers

CO₂ Laser
The infrared CO₂ laser utilizes 10,600-nm energy to target and vaporize water molecules within the target tissue. This thermal heating extends to the dermal collagen, which stimulates inflammatory pathways and neocollagenesis.¹¹ The depth of penetration ranges from 20 to 125 μm.¹² Zerbinati et al¹³ demonstrated the histologic and ultrastructural effects of a fractional CO₂ laser on atrophic vaginal mucosa. Comparing pretreatment and posttreatment mucosal biopsies in 5 postmenopausal women, the investigators found that fractional CO₂ laser treatment caused increased epithelial thickness, vascularity, and fibroblast activity, which led to augmented synthesis of collagen and ground substance proteins.¹³

New devices seek to translate these histologic improvements to the aesthetic appearance and function of female genitalia. The MonaLisa Touch (Cynosure), a new fractional CO₂ laser specifically designed for treatment of the vaginal mucosa, uses dermal optical thermolysis (DOT) therapy to apply energy in a noncontinuous mode at 200-μm dots. Salvatore et al¹⁴ examined the use of this device in a noncontrolled study of 50 patients with GSM, with each patient undergoing 3 treatment sessions at monthly intervals. Intravaginal treatments were performed at the following settings: DOT (microablative zone) power of 30 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack parameter of 1 to 3. The investigators used the Vaginal Health Index (VHI) to objectively assess vaginal elasticity, secretions, pH, mucosa integrity, and moisture. Total VHI scores significantly improved between baseline and 1 month following the final treatment (mean score [SD], 13.1 [2.5] vs 23.1 [1.9]; P<.0001). There were no significant adverse events, and 84% of patients reported being satisfied with their outcome; however, the study lacked a comparison or control group, raising the possibility of placebo effect.¹⁴

Other noncontrolled series have corroborated the benefits of CO₂ laser in GSM patients.^15,16 In one of the largest studies to date, Filippini et al¹⁷ reviewed the outcomes of 386 menopausal women treated for GSM. Patients underwent 3 intravaginal laser sessions with the MonaLisa Touch. Intravaginal treatments were performed at a DOT power of 40 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack of 2. For the vulva, the DOT power was reduced to 30 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack of 1. Two months after the final treatment session, patients completed a nonvalidated questionnaire about their symptoms, with improved dryness reported in 60% of patients, improved burning in 56%, improved dyspareunia in 49%, improved itch in 56%, improved soreness in 73%, and improved vaginal introitus pain in 49%. Although most patients did not experience discomfort with the procedure, a minority noted a burning sensation (11%), bother with handpiece movement (6%), or vulvar pain (5%).¹⁷

Recently, Cruz et al¹⁸ performed one of the first randomized, double-blind, placebo-controlled trials comparing fractional CO₂ laser therapy, topical estrogen therapy, and the combination of both treatments in patients with GSM. Forty-five women were included in the study, and validated assessments were performed at baseline and weeks 8 and 20. Intravaginal treatments were performed at a DOT power of 30 W, dwell time of 1000 μs, DOT spacing of 1000 μm, and SmartStack of 2. Importantly, the study incorporated placebo laser treatments (with the power adjusted to 0.0 W) in the topical estrogen group, thereby decreasing result bias. There was a significant increase in VHI scores from baseline to week 8 (P<.05) and week 20 (P<.01) in all study arms. At week 20, the laser group and laser plus estrogen group showed significant improvements in reported dyspareunia, burning, and dryness, whereas the estrogen arm only reported improvements in dryness (all values P<.05).¹⁸

Erbium-Doped YAG Laser
The erbium-doped YAG (Er:YAG) laser is an ablative laser emitting light at 2940 nm. This wavelength provides an absorption coefficient for water 16 times greater than the CO₂ laser, leading to decreased penetration depth of 1 to 3 μm and reduced damage to the surrounding tissues.^19,20 As such, the Er:YAG laser results in milder postoperative discomfort and faster overall healing times.²¹

In a noncontrolled study of vaginal relaxation syndrome, Lee²² used an Er:YAG laser fitted with Petit Lady (Lutronic) 90° and 360° vaginal scanning scopes. Thirty patients were divided into 2 groups and were treated with 4 sessions at weekly intervals. In group A, the first 2 sessions were performed with the 360° scope, and the last 2 sessions with the 90° scope in multiple micropulse mode (3 multishots; pulse width of 250 μs; 1.7 J delivered per shot). Group B was treated with the 90° scope in all 4 sessions in multiple micropulse mode (same parameters as group A), and during the last 2 sessions patients were additionally treated with 2 passes per session with the 360° scope (long-pulsed mode; pulse width of 1000 μs; 3.7 J delivered per shot). Perineometer measurements taken 2 months after the final treatment showed that the combined patient population experienced significant increases in both maximal vaginal pressure (P<.01) and average vaginal pressure (P<.05). Roughly 76% of patients’ partners noted improved vaginal tightening, and 70% of patients reported being satisfied with their treatment outcome. Histologic specimens taken at baseline and 2 months postprocedure showed evidence of thicker and more cellular epithelia along with more compact lamina propria with denser connective tissue. The sessions were well tolerated, with patients reporting a nonpainful heating sensation in the vagina during treatment. Three patients from the combined patient population experienced a mild burning sensation and vaginal ecchymoses, which lasted 24 to 48 hours following treatment and resolved spontaneously. There was no control group and no reports of major or long-term adverse events.²²

Investigations also have shown the benefit of Er:YAG in the treatment of GSM.^23,24 In a study by Gambacciani et al,²⁴ patients treated with the Er:YAG laser FotonaSmooth (Fotona) every 30 days for 3 months reported significant improvements in vaginal dryness and dyspareunia (P<.01), which lasted up to 6 months posttreatment, though there was no placebo group comparator. Similar results were seen by Gaspar et al²³ using 3 treatments at 3-week intervals, with results sustained up to 18 months after the final session.

Radiofrequency Devices

Radiofrequency devices emit focused electromagnetic waves that heat underlying tissues without targeting melanin. The release of thermal energy induces collagen contraction, neocollagenesis, and neovascularization, all of which aid in restoring the elasticity and moisture of the vaginal mucosa.²⁵ Devices also may be equipped with cooling probes and reverse-heating gradients to protect the surface mucosa while deeper tissues are heated.

Millheiser et al²⁶ performed a noncontrolled pilot study in 24 women with vaginal laxity using the Viveve System (Viveve), a cryogen-cooled monopolar RF device. Participants underwent a single 30-minute session (energy ranging from 75–90 J/cm²) during which the mucosal surface of the vaginal introitus (excluding the urethra) was treated with pulses at 0.5-cm overlapping intervals. Follow-up assessments were completed at 1, 3, and 6 months posttreatment. Self-reported vaginal tightness improved in 67% of participants at 1-month posttreatment and in 87% of participants at 6 months posttreatment (P<.001). There were no adverse events reported.²⁶ Sekiguchi et al²⁷ reported similar benefits lasting up to 12 months after a single 26-minute session at 90 J/cm².

A prospective, randomized, placebo-controlled clinical trial using the Viveve system was recently completed by Krychman et al.²⁸ Participants (N=186) were randomized to receive a single session of active treatment (90 J/cm²) or placebo treatment (1 J/cm²). In both groups, the vaginal introitus was treated with pulses at 0.5 cm in overlapping intervals, with the entire area (excluding the urethra) treated 5 times up to a total of 110 pulses. The primary end point was the proportion of randomized participants reporting no vaginal laxity at 6 months postin-tervention, which was assessed using the Vaginal Laxity Questionnaire. A grade of no vaginal laxity was achieved by 43.5% of participants in the active treatment group and 19.6% of participants in the sham group (P=.002). Overall numbers of treatment-emergent adverse events were comparable between the 2 groups, with the most commonly reported being vaginal discharge (2.6% in the active treatment group vs 3.5% in the sham group). There were no serious adverse events reported in the active treatment group.²⁸

ThermiVa (ThermiGen, LLC), a unipolar RF device, was evaluated by Alinsod²⁹ in the treatment of orgasmic dysfunction. The noncontrolled study included 25 women with self-reported difficulty achieving orgasm during intercourse, each of whom underwent 3 treatment sessions at 1-month intervals. Of the 25 enrolled women, 19 (76%) reported an average reduction in time to orgasm of at least 50%. All anorgasmic patients (n=10) at baseline reported renewed ability to achieve orgasms. Two (8%) patients failed to achieve a significant benefit from the treatments. Of note, the study did not include a control group, and specific data on the durability of beneficial effects was lacking.²⁹

The Ultra Femme 360 (BLT Industries Inc), a monopolar RF device, was evaluated by Lalji and Lozanova³⁰ in a noncontrolled study of 27 women with mild to moderate vaginal laxity and urinary incontinence. Participants underwent 3 treatment sessions at weekly intervals. Vaginal laxity was assessed by a subjective vulvovaginal laxity questionnaire, and data were collected before the first treatment and at 1-month follow-up. All 27 participants reported improvements in vaginal laxity, with the average grade (SD) increasing from very loose (2.19 [1.08]) to moderately tight (5.74 [0.76]; P<.05) on the questionnaire’s 7-point scale. The trial did not include a control group.³⁰

Conclusion

With growing patient interest in vaginal rejuvenation, clinicians are increasingly incorporating a variety of procedures into their practice. Although long-term data on the safety and efficacy of these treatments has yet to be established, current evidence indicates that fractional ablative lasers and RF devices can improve vaginal laxity, sexual sensation, and symptoms of GSM.

To date, major complications have not been reported, but the FDA has advocated caution until regulatory approval is achieved.¹⁰ Concerns exist over the limited number of robust clinical trials as well as the prevalence of advertising campaigns that promise wide-ranging improvements without sufficient evidence. Definitive statements on medical or cosmetic indications will undoubtedly require more thorough investigation. At this time, the safety profile of these devices appears to be favorable, and high rates of patient satisfaction have been reported. As such, noninvasive vaginal rejuvenation procedures may represent a valuable addition to the cosmetic landscape.