Cardiology

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

 

 

Commentary

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

 

 

Commentary

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

 

 

Commentary

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

The first international survey of parental benefits and policies among cardiovascular training programs shows wide variability among institutions.

Although a majority of cardiology fellows became parents during training, the survey found that family benefits and policies were not uniformly available and that knowledge about the existence of such policies was low across all institutions.

The findings are published in the Journal of the American College of Cardiology.

Such variability highlights disparities in real-world experiences, say Estefania Oliveros, MD, Temple University Hospital, Philadelphia, and colleagues.

“There are no policies to protect cardiology trainees when they become parents that are uniform across the United States or even internationally, even though, according to our survey, 61.7% become parents during training,” Dr. Oliveros told this news organization.

Dr. Oliveros said she wanted to learn more about the status of institutional practices surrounding pregnant trainees during cardiovascular fellowship, not only in the U.S., but internationally: “I wanted to study this because of my own experience.”

“I was probably the first pregnant trainee at my institution, and there were no specific policies in place, so I had to find out on my own what to do about radiation safety, where I would breastfeed, schedule changes, how that would impact my graduation time, things like that,” Dr. Oliveros said. “It would be nice if you had the resources and your institution could accommodate your needs, instead of every time you have a pregnant person on your staff, you have to reinvent the wheel.”

Dr. Oliveros and colleagues conducted an online survey during August 2020-October 2020 that was distributed via social media. Responses were made anonymous to encourage unbiased feedback.

Among the 417 completed responses, 47 (11.3%) were from training program directors, 146 (35%) from current or former pregnant trainees, and 224 (53.7%) from current or former trainees who were not pregnant during cardiology training. Two-thirds of the respondents (67.1%) were parents.

Most survey respondents said they became pregnant during the third year of general cardiology (29.1%), followed by the first year of general cardiology (26.3%), and the second year of general cardiology (23.5%).

Only 13 of the 47 training program directors (27.7%) received guidance or training on how to accommodate pregnant trainees during fellowship.

Additionally, 26% of the trainees reported their institution had readily available breastfeeding and pumping policies, 39% responded that their institution had no such policies, and 34.9% said they did not know.

Nearly one-half of the programs offered rearrangement of schedules because of radiation concerns, 27.5% did not.

The amount of parental leave varied greatly worldwide. For Europe, Central and South America, Africa, and Australia, the average parental leave was more than 4 months; for Canada, it was more than 3 months; for the United States, it was 1 to 2 months; and for Asia, it was 3 to 4 weeks.

“There is no uniformity, no policies for things like breastfeeding or places where you can pump. None of that is installed, even though by law we’re supposed to have these things,” Dr. Oliveros said.

In all countries, paternity leave was uncommon (2.6% of respondents), even though 48.5% of the programs had paternity leave.

“I would like to see associations, program directors, even trainees helping each other in finding ways to accommodate parents to promote wellness and assure that trainees can have both good training and life balance,” she added.

In an accompanying editorial, Ileana L. Piña, MD, MPH, Thomas Jefferson Institute, Philadelphia, writes: “Enough has been said about our need for a greater percentage of women cardiologists. There is no need to further debate that fact. However, it is puzzling that despite > 50% of medical students being women, the cardiology specialty is fraught with recent survey reports of hostility in the workplace, concerns of long hours, exposure to radiation, and poor work-life balance that can compel trainees to choose delaying pregnancy or taking unpaid leave, which will, in turn, delay training. Therefore, it is not surprising that only 14.9% of cardiologist specialists and 21.9% of cardiology fellows are women.”

Dr. Piña notes that while the authors understand that it’s difficult to change national policies, they issue a “call to action” for organizations and program directors to demonstrate leadership by developing fair and balanced decisions regarding parental policies.

“Those decisions are so impactful that they can change career trajectories for the better or worse ... the current status is unacceptable and must change for the benefit of all trainees, their families, and the program directors. The problem is too important and pervasive,” she adds.

Dr. Piña concludes: “Perhaps if the women who are the subjects of, and often the unwitting party to, administrative decisions about their lives, choices, and welfare were invited to contribute to the changes, we would finally see an increase in the number of women in cardiology careers. After all, aren’t we about diversity and belonging?”

“We need to normalize pregnancy and parental leave across the globe,” Laxmi S. Mehta, MD, Ohio State University Weiner Medical Center, Columbus, said in an interview.

As previously reported, Dr. Mehta recently led a study that surveyed 323 women cardiologists who were working while they were pregnant. Her study found that 75% of these women experienced discriminatory maternity leave practices, some of which were likely violations of the federal Family and Medical Leave Act.

“If we want more women to pursue a career in cardiology, then employers and health systems need to adequately support parenthood, including allowing people to spend uninterrupted time with their newborns without the fear of discrimination, retaliation, or financial burden,” Dr. Mehta said.

Limitations of the study are the small sample size, potential for bias associated with social media distribution, and the fact that 75% of respondents were women, Dr. Oliveros and colleagues write.

Dr. Oliveros, Dr. Piña, and Dr. Mehta report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The first international survey of parental benefits and policies among cardiovascular training programs shows wide variability among institutions.

Although a majority of cardiology fellows became parents during training, the survey found that family benefits and policies were not uniformly available and that knowledge about the existence of such policies was low across all institutions.

The findings are published in the Journal of the American College of Cardiology.

Such variability highlights disparities in real-world experiences, say Estefania Oliveros, MD, Temple University Hospital, Philadelphia, and colleagues.

“There are no policies to protect cardiology trainees when they become parents that are uniform across the United States or even internationally, even though, according to our survey, 61.7% become parents during training,” Dr. Oliveros told this news organization.

Dr. Oliveros said she wanted to learn more about the status of institutional practices surrounding pregnant trainees during cardiovascular fellowship, not only in the U.S., but internationally: “I wanted to study this because of my own experience.”

“I was probably the first pregnant trainee at my institution, and there were no specific policies in place, so I had to find out on my own what to do about radiation safety, where I would breastfeed, schedule changes, how that would impact my graduation time, things like that,” Dr. Oliveros said. “It would be nice if you had the resources and your institution could accommodate your needs, instead of every time you have a pregnant person on your staff, you have to reinvent the wheel.”

Dr. Oliveros and colleagues conducted an online survey during August 2020-October 2020 that was distributed via social media. Responses were made anonymous to encourage unbiased feedback.

Among the 417 completed responses, 47 (11.3%) were from training program directors, 146 (35%) from current or former pregnant trainees, and 224 (53.7%) from current or former trainees who were not pregnant during cardiology training. Two-thirds of the respondents (67.1%) were parents.

Most survey respondents said they became pregnant during the third year of general cardiology (29.1%), followed by the first year of general cardiology (26.3%), and the second year of general cardiology (23.5%).

Only 13 of the 47 training program directors (27.7%) received guidance or training on how to accommodate pregnant trainees during fellowship.

Additionally, 26% of the trainees reported their institution had readily available breastfeeding and pumping policies, 39% responded that their institution had no such policies, and 34.9% said they did not know.

Nearly one-half of the programs offered rearrangement of schedules because of radiation concerns, 27.5% did not.

The amount of parental leave varied greatly worldwide. For Europe, Central and South America, Africa, and Australia, the average parental leave was more than 4 months; for Canada, it was more than 3 months; for the United States, it was 1 to 2 months; and for Asia, it was 3 to 4 weeks.

“There is no uniformity, no policies for things like breastfeeding or places where you can pump. None of that is installed, even though by law we’re supposed to have these things,” Dr. Oliveros said.

In all countries, paternity leave was uncommon (2.6% of respondents), even though 48.5% of the programs had paternity leave.

“I would like to see associations, program directors, even trainees helping each other in finding ways to accommodate parents to promote wellness and assure that trainees can have both good training and life balance,” she added.

In an accompanying editorial, Ileana L. Piña, MD, MPH, Thomas Jefferson Institute, Philadelphia, writes: “Enough has been said about our need for a greater percentage of women cardiologists. There is no need to further debate that fact. However, it is puzzling that despite > 50% of medical students being women, the cardiology specialty is fraught with recent survey reports of hostility in the workplace, concerns of long hours, exposure to radiation, and poor work-life balance that can compel trainees to choose delaying pregnancy or taking unpaid leave, which will, in turn, delay training. Therefore, it is not surprising that only 14.9% of cardiologist specialists and 21.9% of cardiology fellows are women.”

Dr. Piña notes that while the authors understand that it’s difficult to change national policies, they issue a “call to action” for organizations and program directors to demonstrate leadership by developing fair and balanced decisions regarding parental policies.

“Those decisions are so impactful that they can change career trajectories for the better or worse ... the current status is unacceptable and must change for the benefit of all trainees, their families, and the program directors. The problem is too important and pervasive,” she adds.

Dr. Piña concludes: “Perhaps if the women who are the subjects of, and often the unwitting party to, administrative decisions about their lives, choices, and welfare were invited to contribute to the changes, we would finally see an increase in the number of women in cardiology careers. After all, aren’t we about diversity and belonging?”

“We need to normalize pregnancy and parental leave across the globe,” Laxmi S. Mehta, MD, Ohio State University Weiner Medical Center, Columbus, said in an interview.

As previously reported, Dr. Mehta recently led a study that surveyed 323 women cardiologists who were working while they were pregnant. Her study found that 75% of these women experienced discriminatory maternity leave practices, some of which were likely violations of the federal Family and Medical Leave Act.

“If we want more women to pursue a career in cardiology, then employers and health systems need to adequately support parenthood, including allowing people to spend uninterrupted time with their newborns without the fear of discrimination, retaliation, or financial burden,” Dr. Mehta said.

Limitations of the study are the small sample size, potential for bias associated with social media distribution, and the fact that 75% of respondents were women, Dr. Oliveros and colleagues write.

Dr. Oliveros, Dr. Piña, and Dr. Mehta report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The first international survey of parental benefits and policies among cardiovascular training programs shows wide variability among institutions.

Although a majority of cardiology fellows became parents during training, the survey found that family benefits and policies were not uniformly available and that knowledge about the existence of such policies was low across all institutions.

The findings are published in the Journal of the American College of Cardiology.

Such variability highlights disparities in real-world experiences, say Estefania Oliveros, MD, Temple University Hospital, Philadelphia, and colleagues.

“There are no policies to protect cardiology trainees when they become parents that are uniform across the United States or even internationally, even though, according to our survey, 61.7% become parents during training,” Dr. Oliveros told this news organization.

Dr. Oliveros said she wanted to learn more about the status of institutional practices surrounding pregnant trainees during cardiovascular fellowship, not only in the U.S., but internationally: “I wanted to study this because of my own experience.”

“I was probably the first pregnant trainee at my institution, and there were no specific policies in place, so I had to find out on my own what to do about radiation safety, where I would breastfeed, schedule changes, how that would impact my graduation time, things like that,” Dr. Oliveros said. “It would be nice if you had the resources and your institution could accommodate your needs, instead of every time you have a pregnant person on your staff, you have to reinvent the wheel.”

Dr. Oliveros and colleagues conducted an online survey during August 2020-October 2020 that was distributed via social media. Responses were made anonymous to encourage unbiased feedback.

Among the 417 completed responses, 47 (11.3%) were from training program directors, 146 (35%) from current or former pregnant trainees, and 224 (53.7%) from current or former trainees who were not pregnant during cardiology training. Two-thirds of the respondents (67.1%) were parents.

Most survey respondents said they became pregnant during the third year of general cardiology (29.1%), followed by the first year of general cardiology (26.3%), and the second year of general cardiology (23.5%).

Only 13 of the 47 training program directors (27.7%) received guidance or training on how to accommodate pregnant trainees during fellowship.

Additionally, 26% of the trainees reported their institution had readily available breastfeeding and pumping policies, 39% responded that their institution had no such policies, and 34.9% said they did not know.

Nearly one-half of the programs offered rearrangement of schedules because of radiation concerns, 27.5% did not.

The amount of parental leave varied greatly worldwide. For Europe, Central and South America, Africa, and Australia, the average parental leave was more than 4 months; for Canada, it was more than 3 months; for the United States, it was 1 to 2 months; and for Asia, it was 3 to 4 weeks.

“There is no uniformity, no policies for things like breastfeeding or places where you can pump. None of that is installed, even though by law we’re supposed to have these things,” Dr. Oliveros said.

In all countries, paternity leave was uncommon (2.6% of respondents), even though 48.5% of the programs had paternity leave.

“I would like to see associations, program directors, even trainees helping each other in finding ways to accommodate parents to promote wellness and assure that trainees can have both good training and life balance,” she added.

In an accompanying editorial, Ileana L. Piña, MD, MPH, Thomas Jefferson Institute, Philadelphia, writes: “Enough has been said about our need for a greater percentage of women cardiologists. There is no need to further debate that fact. However, it is puzzling that despite > 50% of medical students being women, the cardiology specialty is fraught with recent survey reports of hostility in the workplace, concerns of long hours, exposure to radiation, and poor work-life balance that can compel trainees to choose delaying pregnancy or taking unpaid leave, which will, in turn, delay training. Therefore, it is not surprising that only 14.9% of cardiologist specialists and 21.9% of cardiology fellows are women.”

Dr. Piña notes that while the authors understand that it’s difficult to change national policies, they issue a “call to action” for organizations and program directors to demonstrate leadership by developing fair and balanced decisions regarding parental policies.

“Those decisions are so impactful that they can change career trajectories for the better or worse ... the current status is unacceptable and must change for the benefit of all trainees, their families, and the program directors. The problem is too important and pervasive,” she adds.

Dr. Piña concludes: “Perhaps if the women who are the subjects of, and often the unwitting party to, administrative decisions about their lives, choices, and welfare were invited to contribute to the changes, we would finally see an increase in the number of women in cardiology careers. After all, aren’t we about diversity and belonging?”

“We need to normalize pregnancy and parental leave across the globe,” Laxmi S. Mehta, MD, Ohio State University Weiner Medical Center, Columbus, said in an interview.

As previously reported, Dr. Mehta recently led a study that surveyed 323 women cardiologists who were working while they were pregnant. Her study found that 75% of these women experienced discriminatory maternity leave practices, some of which were likely violations of the federal Family and Medical Leave Act.

“If we want more women to pursue a career in cardiology, then employers and health systems need to adequately support parenthood, including allowing people to spend uninterrupted time with their newborns without the fear of discrimination, retaliation, or financial burden,” Dr. Mehta said.

Limitations of the study are the small sample size, potential for bias associated with social media distribution, and the fact that 75% of respondents were women, Dr. Oliveros and colleagues write.

Dr. Oliveros, Dr. Piña, and Dr. Mehta report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A small group of patients with heart failure (HF) who underwent a novel transcatheter nerve-ablation procedure seemed to benefit with improved hemodynamics, symptoms, and quality of life in an admittedly limited observational series.

All had HF with preserved ejection fraction (HFpEF) and remained on guideline-directed medical therapy during the study.

The open-label experience has launched a randomized trial, featuring a sham control group, that could ultimately challenge dogma about volume overload in patients with chronic and acute HF and the perceived essential role of diuretics.

Researchers see transvenous ablation of the right greater splanchnic nerve (GSN) as potentially appropriate for patients with HF, regardless of ventricular function or acuity. But the ongoing REBALANCE-HF trial aims to enroll up to 80 patients with chronic HFpEF.

Meanwhile, the current 18 patients with elevated resting or exertional pulmonary capillary wedge pressure (PCWP), given the procedure as part of the main trial’s “roll-in” phase, showed declines in exercise PCWP after 1 month (P = .007) and improved quality-of-life scores at both 1 and 3 months (P < .01). Also at 1 month, a third of the patients improved by at least one step in NYHA functional class.

The procedure, called splanchnic ablation for volume management (SAVM), could potentially be used “across the spectrum of acute and chronic heart failure, maybe even with reduced ejection fraction (HFrEF) and preserved ejection fraction,” Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., told this news organization.

However, “for outcomes, we’ve really only looked in the ambulatory setting,” and only at symptomatic and functional responses. To that extent, based on the current experience and a few small previous studies, Dr. Fudim said, SAVM seems to benefit patients with HF in general who have dyspnea at exercise. Beyond that, the kind of patient who may be most suitable for it “is something I hope we will be able answer once the randomized dataset is in.”

Dr. Fudim reported the REBALANCE-HF roll-in results at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022 sessions, held virtually and live in Madrid. He is also lead author on the same-day publication in the European Journal of Heart Failure.

A different treatment paradigm

Splanchnic-nerve blockade as a possible HF treatment is based on growing evidence that volume overload in patients with HF is not always the cause, at least not a main cause, of congestion and dyspnea. Rather, those classic HF signs and symptoms may often be triggered by adverse redistribution of stable fluid volume from primarily the splanchnic vascular compartment to the intrathoracic space.

In other words, what might seem like classic volume overload calling for diuresis often might actually be euvolemic redistribution of fluid from the abdomen to the chest, raising intracardiac pressures and causing dyspnea.

In that scenario, loop diuretics might only dehydrate the patient and potentially put the kidneys at risk, Dr. Fudim proposed. His recent experience with HF patients implanted with a pulmonary-artery pressure monitor, he said, suggests many who received standard volume-overload therapy had actually been normo- or hypovolemic.

More then half the patients “did not have high volume, they just had high pressures,” he said. “So there is a significant portion of the population that has pathological processes leading to high pressures, but it’s not volume overload. Diuresing those patients would probably not be the right decision.”

The unilateral SAVM procedure appears to attenuate sympathetically mediated splanchnic volume redistribution to the heart and lungs, but as it doesn’t affect the left GSN, preserves some normal sympathetic response.

Sometimes in studies of surgical or catheter-based SAVM, Dr. Fudim said, “we have observationally seen that people discontinued diuretics or decreased doses in the treatment arm.”
 

‘Beyond our classical thinking’

It’s “impressive” that such right-GSN ablation seemed to reduce exercise-filling pressures, but one should be circumspect because “it’s way beyond our classical thinking,” Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, said as a panelist after Dr. Fudim’s presentation.

“These are invasive procedures,” he noted, “and our physiological understanding does not always match up with what we’re doing in real life, if you look at other interventional procedures, like renal denervation, which showed neutral effects, or if you look at even interatrial shunt devices, which might even be dangerous.”

The field should be “very prudent” before using SAVM in practice, which shouldn’t be “before we have sufficient data to support the efficacy and safety,” Dr. Mullens said. “It remains to be seen how treatment success will be defined. Is it during exercise? How long does the treatment last? What is the effect of the treatment over time; is it not harmful? These are things that we don’t know yet.”

The procedure was considered successful in all 18 patients, 14 of whom were women and 16 of whom were in NYHA class 3. Their average age was 75, and their mean left ventricular ejection fraction (LVEF) at baseline was 61%. The primary efficacy endpoints were a reduction in PCWP at rest, with legs raised, and at 20W exercise at 1 month. Their baseline invasively measured peak exercise PCWP was at least 25 mm Hg.

At 1 month, mean PCWP at 20W exercise fell from 36.4 mm Hg to 28.9 mm Hg (P = .007) and peak PCWP declined from 39.5 mm Hg to 31.9 mm Hg (P = .013); resting PCWP wasn’t significantly affected. Twelve patients improved by at least one NYHA functional class (P = .02).

Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which assesses quality of life, improved by 22 points at 1 month and 18.3 points at 3 months (P < .01 for both differences).

No significant effects on 6-minute walk distance or natriuretic peptide levels were observed, nor were any observed on LVEF or echocardiographic measures of diastolic function, left ventricular (LV) atrial volume, or LV mass at 3 months.

Three “nonserious” device-related adverse events were observed, including one case of acute decompensation early in the experience, ostensibly due to excessive saline administration, Dr. Fudim reported. There was also one case of transient periprocedural hypertension and one instance of postprocedure back pain.

The SAVM procedure is performed transvenously and in general is technically “really not that challenging,” Dr. Fudim said. In most cases, the necessary skills would be accessible not only to interventional cardiologists but also heart failure specialists. “I have performed this procedure myself, and I’m a heart failure guy.”

The REBALANCE-HF roll-in phase and main trial are supported by Axon Therapies. Dr. Fudim discloses receiving support from Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and consulting fees from Abbott, Audicor, Axon Therapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. Dr. Mullens discloses receiving fees for speaking from Medtronic, Abbott, Novartis, Boston Scientific, AstraZeneca, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

A small group of patients with heart failure (HF) who underwent a novel transcatheter nerve-ablation procedure seemed to benefit with improved hemodynamics, symptoms, and quality of life in an admittedly limited observational series.

All had HF with preserved ejection fraction (HFpEF) and remained on guideline-directed medical therapy during the study.

The open-label experience has launched a randomized trial, featuring a sham control group, that could ultimately challenge dogma about volume overload in patients with chronic and acute HF and the perceived essential role of diuretics.

Researchers see transvenous ablation of the right greater splanchnic nerve (GSN) as potentially appropriate for patients with HF, regardless of ventricular function or acuity. But the ongoing REBALANCE-HF trial aims to enroll up to 80 patients with chronic HFpEF.

Meanwhile, the current 18 patients with elevated resting or exertional pulmonary capillary wedge pressure (PCWP), given the procedure as part of the main trial’s “roll-in” phase, showed declines in exercise PCWP after 1 month (P = .007) and improved quality-of-life scores at both 1 and 3 months (P < .01). Also at 1 month, a third of the patients improved by at least one step in NYHA functional class.

The procedure, called splanchnic ablation for volume management (SAVM), could potentially be used “across the spectrum of acute and chronic heart failure, maybe even with reduced ejection fraction (HFrEF) and preserved ejection fraction,” Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., told this news organization.

However, “for outcomes, we’ve really only looked in the ambulatory setting,” and only at symptomatic and functional responses. To that extent, based on the current experience and a few small previous studies, Dr. Fudim said, SAVM seems to benefit patients with HF in general who have dyspnea at exercise. Beyond that, the kind of patient who may be most suitable for it “is something I hope we will be able answer once the randomized dataset is in.”

Dr. Fudim reported the REBALANCE-HF roll-in results at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022 sessions, held virtually and live in Madrid. He is also lead author on the same-day publication in the European Journal of Heart Failure.

A different treatment paradigm

Splanchnic-nerve blockade as a possible HF treatment is based on growing evidence that volume overload in patients with HF is not always the cause, at least not a main cause, of congestion and dyspnea. Rather, those classic HF signs and symptoms may often be triggered by adverse redistribution of stable fluid volume from primarily the splanchnic vascular compartment to the intrathoracic space.

In other words, what might seem like classic volume overload calling for diuresis often might actually be euvolemic redistribution of fluid from the abdomen to the chest, raising intracardiac pressures and causing dyspnea.

In that scenario, loop diuretics might only dehydrate the patient and potentially put the kidneys at risk, Dr. Fudim proposed. His recent experience with HF patients implanted with a pulmonary-artery pressure monitor, he said, suggests many who received standard volume-overload therapy had actually been normo- or hypovolemic.

More then half the patients “did not have high volume, they just had high pressures,” he said. “So there is a significant portion of the population that has pathological processes leading to high pressures, but it’s not volume overload. Diuresing those patients would probably not be the right decision.”

The unilateral SAVM procedure appears to attenuate sympathetically mediated splanchnic volume redistribution to the heart and lungs, but as it doesn’t affect the left GSN, preserves some normal sympathetic response.

Sometimes in studies of surgical or catheter-based SAVM, Dr. Fudim said, “we have observationally seen that people discontinued diuretics or decreased doses in the treatment arm.”
 

‘Beyond our classical thinking’

It’s “impressive” that such right-GSN ablation seemed to reduce exercise-filling pressures, but one should be circumspect because “it’s way beyond our classical thinking,” Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, said as a panelist after Dr. Fudim’s presentation.

“These are invasive procedures,” he noted, “and our physiological understanding does not always match up with what we’re doing in real life, if you look at other interventional procedures, like renal denervation, which showed neutral effects, or if you look at even interatrial shunt devices, which might even be dangerous.”

The field should be “very prudent” before using SAVM in practice, which shouldn’t be “before we have sufficient data to support the efficacy and safety,” Dr. Mullens said. “It remains to be seen how treatment success will be defined. Is it during exercise? How long does the treatment last? What is the effect of the treatment over time; is it not harmful? These are things that we don’t know yet.”

The procedure was considered successful in all 18 patients, 14 of whom were women and 16 of whom were in NYHA class 3. Their average age was 75, and their mean left ventricular ejection fraction (LVEF) at baseline was 61%. The primary efficacy endpoints were a reduction in PCWP at rest, with legs raised, and at 20W exercise at 1 month. Their baseline invasively measured peak exercise PCWP was at least 25 mm Hg.

At 1 month, mean PCWP at 20W exercise fell from 36.4 mm Hg to 28.9 mm Hg (P = .007) and peak PCWP declined from 39.5 mm Hg to 31.9 mm Hg (P = .013); resting PCWP wasn’t significantly affected. Twelve patients improved by at least one NYHA functional class (P = .02).

Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which assesses quality of life, improved by 22 points at 1 month and 18.3 points at 3 months (P < .01 for both differences).

No significant effects on 6-minute walk distance or natriuretic peptide levels were observed, nor were any observed on LVEF or echocardiographic measures of diastolic function, left ventricular (LV) atrial volume, or LV mass at 3 months.

Three “nonserious” device-related adverse events were observed, including one case of acute decompensation early in the experience, ostensibly due to excessive saline administration, Dr. Fudim reported. There was also one case of transient periprocedural hypertension and one instance of postprocedure back pain.

The SAVM procedure is performed transvenously and in general is technically “really not that challenging,” Dr. Fudim said. In most cases, the necessary skills would be accessible not only to interventional cardiologists but also heart failure specialists. “I have performed this procedure myself, and I’m a heart failure guy.”

The REBALANCE-HF roll-in phase and main trial are supported by Axon Therapies. Dr. Fudim discloses receiving support from Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and consulting fees from Abbott, Audicor, Axon Therapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. Dr. Mullens discloses receiving fees for speaking from Medtronic, Abbott, Novartis, Boston Scientific, AstraZeneca, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

A small group of patients with heart failure (HF) who underwent a novel transcatheter nerve-ablation procedure seemed to benefit with improved hemodynamics, symptoms, and quality of life in an admittedly limited observational series.

All had HF with preserved ejection fraction (HFpEF) and remained on guideline-directed medical therapy during the study.

The open-label experience has launched a randomized trial, featuring a sham control group, that could ultimately challenge dogma about volume overload in patients with chronic and acute HF and the perceived essential role of diuretics.

Researchers see transvenous ablation of the right greater splanchnic nerve (GSN) as potentially appropriate for patients with HF, regardless of ventricular function or acuity. But the ongoing REBALANCE-HF trial aims to enroll up to 80 patients with chronic HFpEF.

Meanwhile, the current 18 patients with elevated resting or exertional pulmonary capillary wedge pressure (PCWP), given the procedure as part of the main trial’s “roll-in” phase, showed declines in exercise PCWP after 1 month (P = .007) and improved quality-of-life scores at both 1 and 3 months (P < .01). Also at 1 month, a third of the patients improved by at least one step in NYHA functional class.

The procedure, called splanchnic ablation for volume management (SAVM), could potentially be used “across the spectrum of acute and chronic heart failure, maybe even with reduced ejection fraction (HFrEF) and preserved ejection fraction,” Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., told this news organization.

However, “for outcomes, we’ve really only looked in the ambulatory setting,” and only at symptomatic and functional responses. To that extent, based on the current experience and a few small previous studies, Dr. Fudim said, SAVM seems to benefit patients with HF in general who have dyspnea at exercise. Beyond that, the kind of patient who may be most suitable for it “is something I hope we will be able answer once the randomized dataset is in.”

Dr. Fudim reported the REBALANCE-HF roll-in results at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022 sessions, held virtually and live in Madrid. He is also lead author on the same-day publication in the European Journal of Heart Failure.

A different treatment paradigm

Splanchnic-nerve blockade as a possible HF treatment is based on growing evidence that volume overload in patients with HF is not always the cause, at least not a main cause, of congestion and dyspnea. Rather, those classic HF signs and symptoms may often be triggered by adverse redistribution of stable fluid volume from primarily the splanchnic vascular compartment to the intrathoracic space.

In other words, what might seem like classic volume overload calling for diuresis often might actually be euvolemic redistribution of fluid from the abdomen to the chest, raising intracardiac pressures and causing dyspnea.

In that scenario, loop diuretics might only dehydrate the patient and potentially put the kidneys at risk, Dr. Fudim proposed. His recent experience with HF patients implanted with a pulmonary-artery pressure monitor, he said, suggests many who received standard volume-overload therapy had actually been normo- or hypovolemic.

More then half the patients “did not have high volume, they just had high pressures,” he said. “So there is a significant portion of the population that has pathological processes leading to high pressures, but it’s not volume overload. Diuresing those patients would probably not be the right decision.”

The unilateral SAVM procedure appears to attenuate sympathetically mediated splanchnic volume redistribution to the heart and lungs, but as it doesn’t affect the left GSN, preserves some normal sympathetic response.

Sometimes in studies of surgical or catheter-based SAVM, Dr. Fudim said, “we have observationally seen that people discontinued diuretics or decreased doses in the treatment arm.”
 

‘Beyond our classical thinking’

It’s “impressive” that such right-GSN ablation seemed to reduce exercise-filling pressures, but one should be circumspect because “it’s way beyond our classical thinking,” Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, said as a panelist after Dr. Fudim’s presentation.

“These are invasive procedures,” he noted, “and our physiological understanding does not always match up with what we’re doing in real life, if you look at other interventional procedures, like renal denervation, which showed neutral effects, or if you look at even interatrial shunt devices, which might even be dangerous.”

The field should be “very prudent” before using SAVM in practice, which shouldn’t be “before we have sufficient data to support the efficacy and safety,” Dr. Mullens said. “It remains to be seen how treatment success will be defined. Is it during exercise? How long does the treatment last? What is the effect of the treatment over time; is it not harmful? These are things that we don’t know yet.”

The procedure was considered successful in all 18 patients, 14 of whom were women and 16 of whom were in NYHA class 3. Their average age was 75, and their mean left ventricular ejection fraction (LVEF) at baseline was 61%. The primary efficacy endpoints were a reduction in PCWP at rest, with legs raised, and at 20W exercise at 1 month. Their baseline invasively measured peak exercise PCWP was at least 25 mm Hg.

At 1 month, mean PCWP at 20W exercise fell from 36.4 mm Hg to 28.9 mm Hg (P = .007) and peak PCWP declined from 39.5 mm Hg to 31.9 mm Hg (P = .013); resting PCWP wasn’t significantly affected. Twelve patients improved by at least one NYHA functional class (P = .02).

Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which assesses quality of life, improved by 22 points at 1 month and 18.3 points at 3 months (P < .01 for both differences).

No significant effects on 6-minute walk distance or natriuretic peptide levels were observed, nor were any observed on LVEF or echocardiographic measures of diastolic function, left ventricular (LV) atrial volume, or LV mass at 3 months.

Three “nonserious” device-related adverse events were observed, including one case of acute decompensation early in the experience, ostensibly due to excessive saline administration, Dr. Fudim reported. There was also one case of transient periprocedural hypertension and one instance of postprocedure back pain.

The SAVM procedure is performed transvenously and in general is technically “really not that challenging,” Dr. Fudim said. In most cases, the necessary skills would be accessible not only to interventional cardiologists but also heart failure specialists. “I have performed this procedure myself, and I’m a heart failure guy.”

The REBALANCE-HF roll-in phase and main trial are supported by Axon Therapies. Dr. Fudim discloses receiving support from Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and consulting fees from Abbott, Audicor, Axon Therapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. Dr. Mullens discloses receiving fees for speaking from Medtronic, Abbott, Novartis, Boston Scientific, AstraZeneca, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

A version of this article first appeared on Medscape.com.

SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.

Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week^® (DDW).

Jim Kling/MDedge News

Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.

He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.

“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.

The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.

Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).

In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.

The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.

Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.

Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).

Serious adverse events were rare, occurring in just two cases (< 1%).

The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.

Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.

SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.

Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week^® (DDW).

Jim Kling/MDedge News

Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.

He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.

“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.

The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.

Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).

In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.

The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.

Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.

Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).

Serious adverse events were rare, occurring in just two cases (< 1%).

The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.

Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.

SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.

Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week^® (DDW).

Jim Kling/MDedge News

Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.

He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.

“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.

The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.

Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).

In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.

The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.

Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.

Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).

Serious adverse events were rare, occurring in just two cases (< 1%).

The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.

Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.

Takotsubo syndrome occurs much more frequently in women than it does in men, but men are much more likely to die from it, according to the results of a new study.

In an analysis of almost 2,500 patients with Takotsubo syndrome (TSS) who were enrolled in an international registry, men, who made up just 11% of the sample, had significantly higher rates of cardiogenic shock and were more than twice as likely to die in the hospital than their female counterparts.

The authors concluded that TSS in males requires close in-hospital monitoring and long-term follow-up. Their study was published in the Journal of the American College of Cardiology.

Takotsubo syndrome is a condition characterized by acute heart failure and transient ventricular contractile dysfunction that can be precipitated by acute emotional or physical stress. It affects mostly women, particularly postmenopausal women, although the reasons for this are still not fully clear, Luca Arcari, MD, from the Institute of Cardiology, Madre Giuseppina Vannini Hospital, Rome, and colleagues wrote.

The syndrome also affects men, and recent data have identified that male sex is associated with worse outcomes. But, because it occurs relatively uncommonly in men, information about outcomes in men is limited.

To shed more light on the influence of gender on TTS, the investigators looked at 2,492 TTS patients (286 men, 2,206 women) who were participants in the GEIST (German Italian Spanish Takotsubo) registry and compared the clinical features and short- and long-term outcomes between the two.

Male patients were significantly younger (69 years) than women (71 years; P = .005) and had a higher prevalence of comorbid conditions, including diabetes (25% vs. 19%; P = .01); pulmonary diseases (21% vs. 15%; P = .006); malignancies (25% vs. 13%; P < .001).

In addition, TTS in men was more likely to be caused by physical triggers (55% vs. 32%; P < .01), whereas emotional triggers were more common in females (39% vs. 19%; P < 0.001).

The investigators then performed a propensity score analysis by matching men and women 1:1; this yielded 207 patients from each group.

After propensity matching, male patients had higher rates of cardiogenic shock (16% vs 6%), and in-hospital mortality (8% vs. 3%; both P < .05).

Men also had a higher mortality rate during the acute and long-term follow up. Male sex remained independently associated with both in-hospital mortality (odds ratio, 2.26; 95% confidence interval, 1.16-4.40) and long-term mortality (hazard ratio, 1.83; 95% CI, 1.32-2.52).

The study by Dr. Arcari and colleagues “shows convincingly that although men are far less likely to develop TTS than women, they have more serious complications and are more likely to die than women presenting with the syndrome, Ilan S. Wittstein, MD, of Johns Hopkins University, Baltimore, wrote in an accompanying editorial.

In an interview, Dr. Wittstein said one of the strengths of the study was its size.

“Over the years, there have been a lot of smaller, single center studies. This large registry had over 2,000 patients. So when the researchers say the rate of TTS is 10% in men and 90% in women, this is not necessarily surprising because that’s about the breakdown we’ve had since the very beginning, but it certainly validates that in a cohort that is large,” he said.

“I think what was novel about the paper is that the size of the cohort allowed the researchers to do propensity matching, so they were able not only to compare men versus women, they could do a 1:1 comparison. And they found even when you match men and women for various comorbidities, the men were much sicker

“What makes this a fascinating syndrome and different from most types of heart muscle problems is that, in the majority of patients, the condition is precipitated by an acute stressor,” said Dr. Wittstein.

“It can either be an emotional trigger, so for instance, getting some bad news that a loved one just died. That’s why we nicknamed the syndrome ‘broken heart syndrome’ many years ago. Or it can be a physical trigger, which can be a wide variety of things, such infection, a stroke, bad pneumonia, anything that stresses the body and causes a stress response. Regular heart attacks are not triggered in this way,” he said.

Dr. Arcari and Dr. Wittstein reported no relevant financial relationships.

 

Takotsubo syndrome occurs much more frequently in women than it does in men, but men are much more likely to die from it, according to the results of a new study.

In an analysis of almost 2,500 patients with Takotsubo syndrome (TSS) who were enrolled in an international registry, men, who made up just 11% of the sample, had significantly higher rates of cardiogenic shock and were more than twice as likely to die in the hospital than their female counterparts.

The authors concluded that TSS in males requires close in-hospital monitoring and long-term follow-up. Their study was published in the Journal of the American College of Cardiology.

Takotsubo syndrome is a condition characterized by acute heart failure and transient ventricular contractile dysfunction that can be precipitated by acute emotional or physical stress. It affects mostly women, particularly postmenopausal women, although the reasons for this are still not fully clear, Luca Arcari, MD, from the Institute of Cardiology, Madre Giuseppina Vannini Hospital, Rome, and colleagues wrote.

The syndrome also affects men, and recent data have identified that male sex is associated with worse outcomes. But, because it occurs relatively uncommonly in men, information about outcomes in men is limited.

To shed more light on the influence of gender on TTS, the investigators looked at 2,492 TTS patients (286 men, 2,206 women) who were participants in the GEIST (German Italian Spanish Takotsubo) registry and compared the clinical features and short- and long-term outcomes between the two.

Male patients were significantly younger (69 years) than women (71 years; P = .005) and had a higher prevalence of comorbid conditions, including diabetes (25% vs. 19%; P = .01); pulmonary diseases (21% vs. 15%; P = .006); malignancies (25% vs. 13%; P < .001).

In addition, TTS in men was more likely to be caused by physical triggers (55% vs. 32%; P < .01), whereas emotional triggers were more common in females (39% vs. 19%; P < 0.001).

The investigators then performed a propensity score analysis by matching men and women 1:1; this yielded 207 patients from each group.

After propensity matching, male patients had higher rates of cardiogenic shock (16% vs 6%), and in-hospital mortality (8% vs. 3%; both P < .05).

Men also had a higher mortality rate during the acute and long-term follow up. Male sex remained independently associated with both in-hospital mortality (odds ratio, 2.26; 95% confidence interval, 1.16-4.40) and long-term mortality (hazard ratio, 1.83; 95% CI, 1.32-2.52).

The study by Dr. Arcari and colleagues “shows convincingly that although men are far less likely to develop TTS than women, they have more serious complications and are more likely to die than women presenting with the syndrome, Ilan S. Wittstein, MD, of Johns Hopkins University, Baltimore, wrote in an accompanying editorial.

In an interview, Dr. Wittstein said one of the strengths of the study was its size.

“Over the years, there have been a lot of smaller, single center studies. This large registry had over 2,000 patients. So when the researchers say the rate of TTS is 10% in men and 90% in women, this is not necessarily surprising because that’s about the breakdown we’ve had since the very beginning, but it certainly validates that in a cohort that is large,” he said.

“I think what was novel about the paper is that the size of the cohort allowed the researchers to do propensity matching, so they were able not only to compare men versus women, they could do a 1:1 comparison. And they found even when you match men and women for various comorbidities, the men were much sicker

“What makes this a fascinating syndrome and different from most types of heart muscle problems is that, in the majority of patients, the condition is precipitated by an acute stressor,” said Dr. Wittstein.

“It can either be an emotional trigger, so for instance, getting some bad news that a loved one just died. That’s why we nicknamed the syndrome ‘broken heart syndrome’ many years ago. Or it can be a physical trigger, which can be a wide variety of things, such infection, a stroke, bad pneumonia, anything that stresses the body and causes a stress response. Regular heart attacks are not triggered in this way,” he said.

Dr. Arcari and Dr. Wittstein reported no relevant financial relationships.

 

Takotsubo syndrome occurs much more frequently in women than it does in men, but men are much more likely to die from it, according to the results of a new study.

In an analysis of almost 2,500 patients with Takotsubo syndrome (TSS) who were enrolled in an international registry, men, who made up just 11% of the sample, had significantly higher rates of cardiogenic shock and were more than twice as likely to die in the hospital than their female counterparts.

The authors concluded that TSS in males requires close in-hospital monitoring and long-term follow-up. Their study was published in the Journal of the American College of Cardiology.

Takotsubo syndrome is a condition characterized by acute heart failure and transient ventricular contractile dysfunction that can be precipitated by acute emotional or physical stress. It affects mostly women, particularly postmenopausal women, although the reasons for this are still not fully clear, Luca Arcari, MD, from the Institute of Cardiology, Madre Giuseppina Vannini Hospital, Rome, and colleagues wrote.

The syndrome also affects men, and recent data have identified that male sex is associated with worse outcomes. But, because it occurs relatively uncommonly in men, information about outcomes in men is limited.

To shed more light on the influence of gender on TTS, the investigators looked at 2,492 TTS patients (286 men, 2,206 women) who were participants in the GEIST (German Italian Spanish Takotsubo) registry and compared the clinical features and short- and long-term outcomes between the two.

Male patients were significantly younger (69 years) than women (71 years; P = .005) and had a higher prevalence of comorbid conditions, including diabetes (25% vs. 19%; P = .01); pulmonary diseases (21% vs. 15%; P = .006); malignancies (25% vs. 13%; P < .001).

In addition, TTS in men was more likely to be caused by physical triggers (55% vs. 32%; P < .01), whereas emotional triggers were more common in females (39% vs. 19%; P < 0.001).

The investigators then performed a propensity score analysis by matching men and women 1:1; this yielded 207 patients from each group.

After propensity matching, male patients had higher rates of cardiogenic shock (16% vs 6%), and in-hospital mortality (8% vs. 3%; both P < .05).

Men also had a higher mortality rate during the acute and long-term follow up. Male sex remained independently associated with both in-hospital mortality (odds ratio, 2.26; 95% confidence interval, 1.16-4.40) and long-term mortality (hazard ratio, 1.83; 95% CI, 1.32-2.52).

The study by Dr. Arcari and colleagues “shows convincingly that although men are far less likely to develop TTS than women, they have more serious complications and are more likely to die than women presenting with the syndrome, Ilan S. Wittstein, MD, of Johns Hopkins University, Baltimore, wrote in an accompanying editorial.

In an interview, Dr. Wittstein said one of the strengths of the study was its size.

“Over the years, there have been a lot of smaller, single center studies. This large registry had over 2,000 patients. So when the researchers say the rate of TTS is 10% in men and 90% in women, this is not necessarily surprising because that’s about the breakdown we’ve had since the very beginning, but it certainly validates that in a cohort that is large,” he said.

“I think what was novel about the paper is that the size of the cohort allowed the researchers to do propensity matching, so they were able not only to compare men versus women, they could do a 1:1 comparison. And they found even when you match men and women for various comorbidities, the men were much sicker

“What makes this a fascinating syndrome and different from most types of heart muscle problems is that, in the majority of patients, the condition is precipitated by an acute stressor,” said Dr. Wittstein.

“It can either be an emotional trigger, so for instance, getting some bad news that a loved one just died. That’s why we nicknamed the syndrome ‘broken heart syndrome’ many years ago. Or it can be a physical trigger, which can be a wide variety of things, such infection, a stroke, bad pneumonia, anything that stresses the body and causes a stress response. Regular heart attacks are not triggered in this way,” he said.

Dr. Arcari and Dr. Wittstein reported no relevant financial relationships.

 

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

Intravenous thrombolysis (IVT) for acute stroke appears safe for patients who have recently received direct oral anticoagulant (DOAC) therapy, a new observational study suggests, prompting researchers to ask whether guidelines that restrict its use should be updated.

Researchers found that DOAC users were significantly less likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT, and there was no difference in functional independence at 3 months, compared with patients who received IVT but who did not receive DOAC.

“At the moment, the guidelines really pose a barrier and stop sign in front of the most important medical reperfusion therapy, which is thrombolysis,” said principal investigator Jan Purrucker, MD, professor of neurology at Heidelberg University Hospital.

“The main question we have to answer is, is IVT safe in patients with acute ischemic stroke who were pretreated with direct oral anticoagulants or not?”

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022, Lyon, France.
 

A ‘daily clinical problem’

As many as 20% of patients with atrial fibrillation experience ischemic stroke while receiving DOAC therapy. Reperfusion therapy with intravenous alteplase is considered standard of care for acute ischemic stroke, but current guidelines recommend against the use of IVT for patients who have recently received a DOAC, owing to safety concerns that researchers say are not backed by strong clinical evidence.

A recent study found no significant difference in sICH among patients who received IV alteplase for acute ischemic stroke within 7 days of receiving therapy with non–vitamin K antagonist oral anticoagulants.

“In our daily clinical practice, we face a lot of patients who have received oral anticoagulation, many with atrial fibrillation, but a lot of other indicators as well, and they suffer from ischemic stroke,” Dr. Purrucker said. “They usually are ineligible for medical reperfusion therapy because of quite strict guideline recommendations at the moment. This is a daily clinical problem.”

Dr. Purrucker and colleagues in New Zealand and Switzerland launched an international, observational, multicenter cohort study to examine the issue.

Researchers collected data on patients with ischemic stroke who had last received DOAC therapy 48 hours or less before the event or whose last intake was unknown and who had received IVT. They included 20,448 patients, 830 of whom were receiving DOAC therapy at the time of stroke onset.

Among the DOAC users, 30% received DOAC reversal prior to IVT, 27% had their DOAC level measured, and 42% received IVT without reversal treatment or knowledge of DOAC levels.

Overall, 4.5% of patients developed sICH. Compared with the control group, DOAC users were half as likely to develop sICH (adjusted odds ratio, 0.47; P = .003).

There was no significant difference between groups in independent outcome at 3 months, defined as a Modified Rankin Scale score of 1 to 3 (aOR, 1.21; 95% confidence interval, 0.99-1.49).

This finding held across patient subgroups, including patients for whom selection methods differed and patients with very recent intake of less than 12 hours.

“The question is whether we are so confident in these data that we would change our clinical practice now,” Dr. Purrucker said.
 

Infrastructure needed

While the findings are promising, more data are needed to strengthen the argument for revising current IVT guidelines, said Ho-Yan Yvonne Chun, PhD, honorary senior clinical lecturer with the Centre for Clinical Brain Sciences at the University of Edinburgh and a consultant in stroke medicine for NHS Lothian and Borders General Hospital, who commented on the findings.

“The study sample are a highly selected group of patients from selected centers that have the infrastructure to offer DOAC level checking and DOAC reversal,” Dr. Chun said. “The selected centers are not representative of the majority of hospitals that offer IVT to stroke patients with acute stroke.”

Most hospitals lack the equipment necessary to test DOAC levels and don’t have immediate access to DOAC reversal agents, Dr. Chun said. In those centers, she added, the administration of IVT could be delayed, which might affect clinical outcomes.

“Infrastructure needs to be in place to ensure timely delivery of IVT to these patients,” Dr. Chun added. “This means that in real-world practice, hospitals need to have right logistical pathway in place in order to provide timely DOAC level checking and DOAC reversal agents.”

Dr. Chun added that “large pragmatic clinical trials, preferably multicentered, are needed to provide the definitive evidence on the safety and effectiveness of using these approaches to select patients with prior DOAC use for IVT.”

But such a study may not be feasible, Dr. Purrucker said. Among the hurdles he noted are the large sample size needed for such a trial, uncertainty regarding funding, and patient selection bias, resulting from the fact that such studies would likely exclude patients eligible for mechanical thrombectomy or those eligible for reversal treatment.

In light of earlier studies, including preclinical data that support the safety of DOACs in IVT, and these new data, Dr. Purrucker said he hopes a change in guidelines might be taken up in the future.

“But it should be good academic practice to first let the results be externally evaluated, for example, during the manuscript submission process,” he said. “But once published, guideline working groups will have to evaluate the recent and new evidence and might reconsider previous recommendations.”

The study received no commercial funding. Dr. Purrucker and Dr. Chun reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Intravenous thrombolysis (IVT) for acute stroke appears safe for patients who have recently received direct oral anticoagulant (DOAC) therapy, a new observational study suggests, prompting researchers to ask whether guidelines that restrict its use should be updated.

Researchers found that DOAC users were significantly less likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT, and there was no difference in functional independence at 3 months, compared with patients who received IVT but who did not receive DOAC.

“At the moment, the guidelines really pose a barrier and stop sign in front of the most important medical reperfusion therapy, which is thrombolysis,” said principal investigator Jan Purrucker, MD, professor of neurology at Heidelberg University Hospital.

“The main question we have to answer is, is IVT safe in patients with acute ischemic stroke who were pretreated with direct oral anticoagulants or not?”

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022, Lyon, France.
 

A ‘daily clinical problem’

As many as 20% of patients with atrial fibrillation experience ischemic stroke while receiving DOAC therapy. Reperfusion therapy with intravenous alteplase is considered standard of care for acute ischemic stroke, but current guidelines recommend against the use of IVT for patients who have recently received a DOAC, owing to safety concerns that researchers say are not backed by strong clinical evidence.

A recent study found no significant difference in sICH among patients who received IV alteplase for acute ischemic stroke within 7 days of receiving therapy with non–vitamin K antagonist oral anticoagulants.

“In our daily clinical practice, we face a lot of patients who have received oral anticoagulation, many with atrial fibrillation, but a lot of other indicators as well, and they suffer from ischemic stroke,” Dr. Purrucker said. “They usually are ineligible for medical reperfusion therapy because of quite strict guideline recommendations at the moment. This is a daily clinical problem.”

Dr. Purrucker and colleagues in New Zealand and Switzerland launched an international, observational, multicenter cohort study to examine the issue.

Researchers collected data on patients with ischemic stroke who had last received DOAC therapy 48 hours or less before the event or whose last intake was unknown and who had received IVT. They included 20,448 patients, 830 of whom were receiving DOAC therapy at the time of stroke onset.

Among the DOAC users, 30% received DOAC reversal prior to IVT, 27% had their DOAC level measured, and 42% received IVT without reversal treatment or knowledge of DOAC levels.

Overall, 4.5% of patients developed sICH. Compared with the control group, DOAC users were half as likely to develop sICH (adjusted odds ratio, 0.47; P = .003).

There was no significant difference between groups in independent outcome at 3 months, defined as a Modified Rankin Scale score of 1 to 3 (aOR, 1.21; 95% confidence interval, 0.99-1.49).

This finding held across patient subgroups, including patients for whom selection methods differed and patients with very recent intake of less than 12 hours.

“The question is whether we are so confident in these data that we would change our clinical practice now,” Dr. Purrucker said.
 

Infrastructure needed

While the findings are promising, more data are needed to strengthen the argument for revising current IVT guidelines, said Ho-Yan Yvonne Chun, PhD, honorary senior clinical lecturer with the Centre for Clinical Brain Sciences at the University of Edinburgh and a consultant in stroke medicine for NHS Lothian and Borders General Hospital, who commented on the findings.

“The study sample are a highly selected group of patients from selected centers that have the infrastructure to offer DOAC level checking and DOAC reversal,” Dr. Chun said. “The selected centers are not representative of the majority of hospitals that offer IVT to stroke patients with acute stroke.”

Most hospitals lack the equipment necessary to test DOAC levels and don’t have immediate access to DOAC reversal agents, Dr. Chun said. In those centers, she added, the administration of IVT could be delayed, which might affect clinical outcomes.

“Infrastructure needs to be in place to ensure timely delivery of IVT to these patients,” Dr. Chun added. “This means that in real-world practice, hospitals need to have right logistical pathway in place in order to provide timely DOAC level checking and DOAC reversal agents.”

Dr. Chun added that “large pragmatic clinical trials, preferably multicentered, are needed to provide the definitive evidence on the safety and effectiveness of using these approaches to select patients with prior DOAC use for IVT.”

But such a study may not be feasible, Dr. Purrucker said. Among the hurdles he noted are the large sample size needed for such a trial, uncertainty regarding funding, and patient selection bias, resulting from the fact that such studies would likely exclude patients eligible for mechanical thrombectomy or those eligible for reversal treatment.

In light of earlier studies, including preclinical data that support the safety of DOACs in IVT, and these new data, Dr. Purrucker said he hopes a change in guidelines might be taken up in the future.

“But it should be good academic practice to first let the results be externally evaluated, for example, during the manuscript submission process,” he said. “But once published, guideline working groups will have to evaluate the recent and new evidence and might reconsider previous recommendations.”

The study received no commercial funding. Dr. Purrucker and Dr. Chun reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Intravenous thrombolysis (IVT) for acute stroke appears safe for patients who have recently received direct oral anticoagulant (DOAC) therapy, a new observational study suggests, prompting researchers to ask whether guidelines that restrict its use should be updated.

Researchers found that DOAC users were significantly less likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT, and there was no difference in functional independence at 3 months, compared with patients who received IVT but who did not receive DOAC.

“At the moment, the guidelines really pose a barrier and stop sign in front of the most important medical reperfusion therapy, which is thrombolysis,” said principal investigator Jan Purrucker, MD, professor of neurology at Heidelberg University Hospital.

“The main question we have to answer is, is IVT safe in patients with acute ischemic stroke who were pretreated with direct oral anticoagulants or not?”

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022, Lyon, France.
 

A ‘daily clinical problem’

As many as 20% of patients with atrial fibrillation experience ischemic stroke while receiving DOAC therapy. Reperfusion therapy with intravenous alteplase is considered standard of care for acute ischemic stroke, but current guidelines recommend against the use of IVT for patients who have recently received a DOAC, owing to safety concerns that researchers say are not backed by strong clinical evidence.

A recent study found no significant difference in sICH among patients who received IV alteplase for acute ischemic stroke within 7 days of receiving therapy with non–vitamin K antagonist oral anticoagulants.

“In our daily clinical practice, we face a lot of patients who have received oral anticoagulation, many with atrial fibrillation, but a lot of other indicators as well, and they suffer from ischemic stroke,” Dr. Purrucker said. “They usually are ineligible for medical reperfusion therapy because of quite strict guideline recommendations at the moment. This is a daily clinical problem.”

Dr. Purrucker and colleagues in New Zealand and Switzerland launched an international, observational, multicenter cohort study to examine the issue.

Researchers collected data on patients with ischemic stroke who had last received DOAC therapy 48 hours or less before the event or whose last intake was unknown and who had received IVT. They included 20,448 patients, 830 of whom were receiving DOAC therapy at the time of stroke onset.

Among the DOAC users, 30% received DOAC reversal prior to IVT, 27% had their DOAC level measured, and 42% received IVT without reversal treatment or knowledge of DOAC levels.

Overall, 4.5% of patients developed sICH. Compared with the control group, DOAC users were half as likely to develop sICH (adjusted odds ratio, 0.47; P = .003).

There was no significant difference between groups in independent outcome at 3 months, defined as a Modified Rankin Scale score of 1 to 3 (aOR, 1.21; 95% confidence interval, 0.99-1.49).

This finding held across patient subgroups, including patients for whom selection methods differed and patients with very recent intake of less than 12 hours.

“The question is whether we are so confident in these data that we would change our clinical practice now,” Dr. Purrucker said.
 

Infrastructure needed

While the findings are promising, more data are needed to strengthen the argument for revising current IVT guidelines, said Ho-Yan Yvonne Chun, PhD, honorary senior clinical lecturer with the Centre for Clinical Brain Sciences at the University of Edinburgh and a consultant in stroke medicine for NHS Lothian and Borders General Hospital, who commented on the findings.

“The study sample are a highly selected group of patients from selected centers that have the infrastructure to offer DOAC level checking and DOAC reversal,” Dr. Chun said. “The selected centers are not representative of the majority of hospitals that offer IVT to stroke patients with acute stroke.”

Most hospitals lack the equipment necessary to test DOAC levels and don’t have immediate access to DOAC reversal agents, Dr. Chun said. In those centers, she added, the administration of IVT could be delayed, which might affect clinical outcomes.

“Infrastructure needs to be in place to ensure timely delivery of IVT to these patients,” Dr. Chun added. “This means that in real-world practice, hospitals need to have right logistical pathway in place in order to provide timely DOAC level checking and DOAC reversal agents.”

Dr. Chun added that “large pragmatic clinical trials, preferably multicentered, are needed to provide the definitive evidence on the safety and effectiveness of using these approaches to select patients with prior DOAC use for IVT.”

But such a study may not be feasible, Dr. Purrucker said. Among the hurdles he noted are the large sample size needed for such a trial, uncertainty regarding funding, and patient selection bias, resulting from the fact that such studies would likely exclude patients eligible for mechanical thrombectomy or those eligible for reversal treatment.

In light of earlier studies, including preclinical data that support the safety of DOACs in IVT, and these new data, Dr. Purrucker said he hopes a change in guidelines might be taken up in the future.

“But it should be good academic practice to first let the results be externally evaluated, for example, during the manuscript submission process,” he said. “But once published, guideline working groups will have to evaluate the recent and new evidence and might reconsider previous recommendations.”

The study received no commercial funding. Dr. Purrucker and Dr. Chun reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A voice can carry a long distance, but in patients with heart failure (HF) a voice can also carry otherwise hidden signs useful for predicting short-term risk for worsening disease, even acute decompensation. Potentially, it only has to reach a smartphone to do it, suggests a preliminary study of a mobile app designed to alert patients and clinicians to such looming HF events, if possible in time to avert them.

The proprietary app and analysis system (HearO, Cordio Medical), used daily at home by 180 patients with stable HF, demonstrated 82% accuracy in picking out vocal signals of early congestion that would soon be followed by a need for intensified therapy or acute decompensation.

Andrew D. Bowser/MDedge News

In practice, clinicians receiving the system’s alerts about altered fluid status would intervene with medication adjustments before the patient deteriorates and possibly heads for the ED. That would be the plan; there were no interventions in the current study, which was designed only to explore the strategy’s feasibility and accuracy.

The system could emerge as “a useful tool in remote monitoring of heart failure patients, providing early warning of worsening heart failure,” said William Abraham, MD, from Ohio State University Wexner Medical Center, Columbus. “It has the potential to reduce acute decompensated heart failure hospitalizations and improve patient quality of life and economic outcomes. But, of course, we have to show that now in larger and randomized clinical studies.”

Abraham presented the Cordio HearO Community Study preliminary results at the Heart Failure Association of the European Society of Cardiology sessions. It follows a recent small study that showed the same app could identify vocal signals linked to altered fluid status in patients with HF hospitalized with acute decompensation.

In the current study, researchers prospectively tracked any worsening HF events that hit patients within a month after the system sent them an alert suggesting early changes in fluid status. Then, they retrospectively assessed the strategy’s predictive accuracy for an initial episode.

The system correctly predicted 32 of 39 first HF events, for an 82% sensitivity and a false-positive rate of 18%. On an annualized basis, Dr. Abraham said, the patients experienced an estimated two to three false alarms per year, alerts that were not followed by HF events. For context, the standard practice of monitoring the patient’s weight “has a sensitivity of about 10%-20%. So this performs very well as a noninvasive technology.”

On average, Dr. Abraham said, “we were able to detect future events about 18 days prior to the worsening heart failure event,” which in practice would provide “a pretty broad window for intervention.”

The false positives were not a surprise. Lung fluid status can change in conditions other than heart failure, he observed, and the HearO system alerts aren’t meant to be followed blindly.

“I don’t know that we clearly understand what those false-positives represent just yet,” Dr. Abraham said. “The bottom line is, as with any diagnostic tool, you have to use the totality of clinical information you have available. If you get an alert and the patient has a fever and a cough, you might think of pneumonia before worsening heart failure.”

“The false positives don’t appear to be alarming,” agreed Antoni Bayés-Genís, MD, PhD, Hospital Universitari Germans Trias i Pujol, Badalona, Spain, and Universitat Autònoma de Barcelona.

The study suggests that the HearO system, combined with sound clinical judgment, “has the potential to identify early congestion that may allow for treatment management, and then avoiding hospital admission,” Dr. Bayés-Genís, who isn’t connected with the study, said in an interview.

The entirely noninvasive, smartphone-based app would be more appealing than implanted devices that, for example, measure thoracic bioimpedance or pulmonary artery pressure and are also intended as congestion early-warning systems, he proposed. “Its scalability makes it very attractive as well.”

But all that “would have to be validated in a large clinical trial,” Dr. Bayés-Genís, who comoderated the conference session featuring Dr. Abraham’s presentation, said when interviewed.

The ongoing study has enrolled 430 clinically stable adult patients with HF in New York Heart Association functional class II or III, regardless of left ventricular ejection fraction, who were cared for by teams at eight centers in Israel. At the outset, during a period of stability, each patient spoke a few sentences into the app to establish a vocal-pattern baseline.

Once home, their assignment was to speak the same sentences into their phones once a day. The app, working through a cloud-based, artificial intelligence–derived processing system, compared each day’s vocal signature with the baseline and alerted researchers when it detected signs of altered fluid status.

About 460,000 recordings were collected from the 180 patients in the current analysis, of whom about 27% were women. They used the app for a mean of 512 days.

The system seems to work well regardless of language or dialect, Dr. Abraham said. About 70% of the current study’s patients spoke Hebrew, and most of the rest spoke either Russian or Arabic.

Most patients (almost 80%) used the app at least 70% of the prescribed time. Only 14 patients used the app less than 60% of the time, he reported.

Dr. Bayés-Genís proposed that, in practice, unfamiliarity with or resistance to smartphone technology would be unlikely to figure greatly in any nonadherence with the daily app regimen, except “maybe for the eldest of the eldest.” The current cohort’s mean age was 70 years. In his experience, he said, most older persons younger than age 80 use a smartphone, at least in more developed countries.

Dr. Abraham disclosed serving on an advisory board for and receiving consulting fees from Cordio Medical; receiving consulting fees from Abbott, Boehringer Ingelheim, CVRx, Edwards Lifesciences, and Respicardia; receiving salary from V-Wave Medical; and receiving research support from the National Heart, Lung, and Blood Institute. Dr. Bayés-Genís reported receiving personal fees from AstraZeneca, Vifor-Fresenius, Novartis, Boehringer Ingelheim, Abbott, Roche Diagnostics, and Critical Diagnostics.

A version of this article first appeared on Medscape.com.

A voice can carry a long distance, but in patients with heart failure (HF) a voice can also carry otherwise hidden signs useful for predicting short-term risk for worsening disease, even acute decompensation. Potentially, it only has to reach a smartphone to do it, suggests a preliminary study of a mobile app designed to alert patients and clinicians to such looming HF events, if possible in time to avert them.

The proprietary app and analysis system (HearO, Cordio Medical), used daily at home by 180 patients with stable HF, demonstrated 82% accuracy in picking out vocal signals of early congestion that would soon be followed by a need for intensified therapy or acute decompensation.

Andrew D. Bowser/MDedge News

In practice, clinicians receiving the system’s alerts about altered fluid status would intervene with medication adjustments before the patient deteriorates and possibly heads for the ED. That would be the plan; there were no interventions in the current study, which was designed only to explore the strategy’s feasibility and accuracy.

The system could emerge as “a useful tool in remote monitoring of heart failure patients, providing early warning of worsening heart failure,” said William Abraham, MD, from Ohio State University Wexner Medical Center, Columbus. “It has the potential to reduce acute decompensated heart failure hospitalizations and improve patient quality of life and economic outcomes. But, of course, we have to show that now in larger and randomized clinical studies.”

Abraham presented the Cordio HearO Community Study preliminary results at the Heart Failure Association of the European Society of Cardiology sessions. It follows a recent small study that showed the same app could identify vocal signals linked to altered fluid status in patients with HF hospitalized with acute decompensation.

In the current study, researchers prospectively tracked any worsening HF events that hit patients within a month after the system sent them an alert suggesting early changes in fluid status. Then, they retrospectively assessed the strategy’s predictive accuracy for an initial episode.

The system correctly predicted 32 of 39 first HF events, for an 82% sensitivity and a false-positive rate of 18%. On an annualized basis, Dr. Abraham said, the patients experienced an estimated two to three false alarms per year, alerts that were not followed by HF events. For context, the standard practice of monitoring the patient’s weight “has a sensitivity of about 10%-20%. So this performs very well as a noninvasive technology.”

On average, Dr. Abraham said, “we were able to detect future events about 18 days prior to the worsening heart failure event,” which in practice would provide “a pretty broad window for intervention.”

The false positives were not a surprise. Lung fluid status can change in conditions other than heart failure, he observed, and the HearO system alerts aren’t meant to be followed blindly.

“I don’t know that we clearly understand what those false-positives represent just yet,” Dr. Abraham said. “The bottom line is, as with any diagnostic tool, you have to use the totality of clinical information you have available. If you get an alert and the patient has a fever and a cough, you might think of pneumonia before worsening heart failure.”

“The false positives don’t appear to be alarming,” agreed Antoni Bayés-Genís, MD, PhD, Hospital Universitari Germans Trias i Pujol, Badalona, Spain, and Universitat Autònoma de Barcelona.

The study suggests that the HearO system, combined with sound clinical judgment, “has the potential to identify early congestion that may allow for treatment management, and then avoiding hospital admission,” Dr. Bayés-Genís, who isn’t connected with the study, said in an interview.

The entirely noninvasive, smartphone-based app would be more appealing than implanted devices that, for example, measure thoracic bioimpedance or pulmonary artery pressure and are also intended as congestion early-warning systems, he proposed. “Its scalability makes it very attractive as well.”

But all that “would have to be validated in a large clinical trial,” Dr. Bayés-Genís, who comoderated the conference session featuring Dr. Abraham’s presentation, said when interviewed.

The ongoing study has enrolled 430 clinically stable adult patients with HF in New York Heart Association functional class II or III, regardless of left ventricular ejection fraction, who were cared for by teams at eight centers in Israel. At the outset, during a period of stability, each patient spoke a few sentences into the app to establish a vocal-pattern baseline.

Once home, their assignment was to speak the same sentences into their phones once a day. The app, working through a cloud-based, artificial intelligence–derived processing system, compared each day’s vocal signature with the baseline and alerted researchers when it detected signs of altered fluid status.

About 460,000 recordings were collected from the 180 patients in the current analysis, of whom about 27% were women. They used the app for a mean of 512 days.

The system seems to work well regardless of language or dialect, Dr. Abraham said. About 70% of the current study’s patients spoke Hebrew, and most of the rest spoke either Russian or Arabic.

Most patients (almost 80%) used the app at least 70% of the prescribed time. Only 14 patients used the app less than 60% of the time, he reported.

Dr. Bayés-Genís proposed that, in practice, unfamiliarity with or resistance to smartphone technology would be unlikely to figure greatly in any nonadherence with the daily app regimen, except “maybe for the eldest of the eldest.” The current cohort’s mean age was 70 years. In his experience, he said, most older persons younger than age 80 use a smartphone, at least in more developed countries.

Dr. Abraham disclosed serving on an advisory board for and receiving consulting fees from Cordio Medical; receiving consulting fees from Abbott, Boehringer Ingelheim, CVRx, Edwards Lifesciences, and Respicardia; receiving salary from V-Wave Medical; and receiving research support from the National Heart, Lung, and Blood Institute. Dr. Bayés-Genís reported receiving personal fees from AstraZeneca, Vifor-Fresenius, Novartis, Boehringer Ingelheim, Abbott, Roche Diagnostics, and Critical Diagnostics.

A version of this article first appeared on Medscape.com.

A voice can carry a long distance, but in patients with heart failure (HF) a voice can also carry otherwise hidden signs useful for predicting short-term risk for worsening disease, even acute decompensation. Potentially, it only has to reach a smartphone to do it, suggests a preliminary study of a mobile app designed to alert patients and clinicians to such looming HF events, if possible in time to avert them.

The proprietary app and analysis system (HearO, Cordio Medical), used daily at home by 180 patients with stable HF, demonstrated 82% accuracy in picking out vocal signals of early congestion that would soon be followed by a need for intensified therapy or acute decompensation.

Andrew D. Bowser/MDedge News

In practice, clinicians receiving the system’s alerts about altered fluid status would intervene with medication adjustments before the patient deteriorates and possibly heads for the ED. That would be the plan; there were no interventions in the current study, which was designed only to explore the strategy’s feasibility and accuracy.

The system could emerge as “a useful tool in remote monitoring of heart failure patients, providing early warning of worsening heart failure,” said William Abraham, MD, from Ohio State University Wexner Medical Center, Columbus. “It has the potential to reduce acute decompensated heart failure hospitalizations and improve patient quality of life and economic outcomes. But, of course, we have to show that now in larger and randomized clinical studies.”

Abraham presented the Cordio HearO Community Study preliminary results at the Heart Failure Association of the European Society of Cardiology sessions. It follows a recent small study that showed the same app could identify vocal signals linked to altered fluid status in patients with HF hospitalized with acute decompensation.

In the current study, researchers prospectively tracked any worsening HF events that hit patients within a month after the system sent them an alert suggesting early changes in fluid status. Then, they retrospectively assessed the strategy’s predictive accuracy for an initial episode.

The system correctly predicted 32 of 39 first HF events, for an 82% sensitivity and a false-positive rate of 18%. On an annualized basis, Dr. Abraham said, the patients experienced an estimated two to three false alarms per year, alerts that were not followed by HF events. For context, the standard practice of monitoring the patient’s weight “has a sensitivity of about 10%-20%. So this performs very well as a noninvasive technology.”

On average, Dr. Abraham said, “we were able to detect future events about 18 days prior to the worsening heart failure event,” which in practice would provide “a pretty broad window for intervention.”

The false positives were not a surprise. Lung fluid status can change in conditions other than heart failure, he observed, and the HearO system alerts aren’t meant to be followed blindly.

“I don’t know that we clearly understand what those false-positives represent just yet,” Dr. Abraham said. “The bottom line is, as with any diagnostic tool, you have to use the totality of clinical information you have available. If you get an alert and the patient has a fever and a cough, you might think of pneumonia before worsening heart failure.”

“The false positives don’t appear to be alarming,” agreed Antoni Bayés-Genís, MD, PhD, Hospital Universitari Germans Trias i Pujol, Badalona, Spain, and Universitat Autònoma de Barcelona.

The study suggests that the HearO system, combined with sound clinical judgment, “has the potential to identify early congestion that may allow for treatment management, and then avoiding hospital admission,” Dr. Bayés-Genís, who isn’t connected with the study, said in an interview.

The entirely noninvasive, smartphone-based app would be more appealing than implanted devices that, for example, measure thoracic bioimpedance or pulmonary artery pressure and are also intended as congestion early-warning systems, he proposed. “Its scalability makes it very attractive as well.”

But all that “would have to be validated in a large clinical trial,” Dr. Bayés-Genís, who comoderated the conference session featuring Dr. Abraham’s presentation, said when interviewed.

The ongoing study has enrolled 430 clinically stable adult patients with HF in New York Heart Association functional class II or III, regardless of left ventricular ejection fraction, who were cared for by teams at eight centers in Israel. At the outset, during a period of stability, each patient spoke a few sentences into the app to establish a vocal-pattern baseline.

Once home, their assignment was to speak the same sentences into their phones once a day. The app, working through a cloud-based, artificial intelligence–derived processing system, compared each day’s vocal signature with the baseline and alerted researchers when it detected signs of altered fluid status.

About 460,000 recordings were collected from the 180 patients in the current analysis, of whom about 27% were women. They used the app for a mean of 512 days.

The system seems to work well regardless of language or dialect, Dr. Abraham said. About 70% of the current study’s patients spoke Hebrew, and most of the rest spoke either Russian or Arabic.

Most patients (almost 80%) used the app at least 70% of the prescribed time. Only 14 patients used the app less than 60% of the time, he reported.

Dr. Bayés-Genís proposed that, in practice, unfamiliarity with or resistance to smartphone technology would be unlikely to figure greatly in any nonadherence with the daily app regimen, except “maybe for the eldest of the eldest.” The current cohort’s mean age was 70 years. In his experience, he said, most older persons younger than age 80 use a smartphone, at least in more developed countries.

Dr. Abraham disclosed serving on an advisory board for and receiving consulting fees from Cordio Medical; receiving consulting fees from Abbott, Boehringer Ingelheim, CVRx, Edwards Lifesciences, and Respicardia; receiving salary from V-Wave Medical; and receiving research support from the National Heart, Lung, and Blood Institute. Dr. Bayés-Genís reported receiving personal fees from AstraZeneca, Vifor-Fresenius, Novartis, Boehringer Ingelheim, Abbott, Roche Diagnostics, and Critical Diagnostics.

A version of this article first appeared on Medscape.com.

The first-ever guidelines for interventional cardiologists using percutaneous patent foramen ovale closure recommend expanding the use of the procedure beyond the Food and Drug Administration–approved indication following PFO-associated ischemic stroke, adding clarification about the use of PFO with anticoagulation and hedging against abuse and overuse of the procedure, said the chair of the guideline writing committee.

“The most important things surrounding these guidelines are to help clinicians and policymakers – third-party payers – to address PFO in patient subsets that were not included in the large randomized clinical trials that led to FDA approval,” said writing group chair Clifford J. Kavinsky, MD, PhD, chief of structural and interventional cardiology at Rush University Medical Center, Chicago.

The Society for Cardiovascular Angiography & Interventions issued the guidelines at its annual scientific sessions meeting in Atlanta and published them simultaneously in the society’s journal.

The guidelines issue strong and conditional recommendations. The former means clinicians should order the intervention for most patients; the latter means decisionmaking is more nuanced and should consider contributing factors.

The guidelines clarify patient selection for PFO closure outside the “pretty narrow” indication the FDA approved, Dr. Kavinsky said, which is for PFO-associated ischemic stroke in patients aged 18-60 years.

“So what about patients who are older than 60? What about patients who had their stroke 10 years ago?” Dr. Kavinsky asked. “Those are issues that were unanswered in the randomized clinical trials.”

The guidelines also refine recommendations about anticoagulation in these patients, including its use after PFO closure in selected patients, Dr. Kavinsky noted. “It’s the opinion of the panel that although anticoagulants may be effective, because of issues of noncompliance, because of issues of interruption of therapy by physicians for a variety of reasons, including surgery or noncompliance, that it is preferable to do a PFO device closure to giving anticoagulant therapy.”

Many of the recommendations cover PFO closure alongside antiplatelet or anticoagulation therapy. Key conditional recommendations for patients who haven’t had a PFO-related stroke are:

• Avoiding its routine use in patients with chronic migraines, prior decompression illness (DCI), thrombophilia, atrial septal aneurysm, transient ischemic attack (TIA), or deep vein thrombosis (DVT).
• Considering PFO closure in patients with platypnea-orthodeoxia syndrome (POS) with no other discernible cause of hypoxia or systemic embolism in whom other embolic causes have been ruled out.

In patients who’ve had a PFO-related stroke, the guidelines strongly recommend PFO closure versus antiplatelet therapy alone, but conditionally, not in patients with atrial fibrillation who’ve had an ischemic stroke. They also conditionally suggest PFO closure rather than long-term antiplatelet therapy alone in PFO stroke patients aged 60 and older, as well as those with thrombophilia already on antiplatelet therapy but not anticoagulation. However, the guidelines make no recommendation on PFO closure based on how much time has passed since the previous stroke.

“Furthermore,” Dr. Kavinsky said, “in patients who require lifelong anticoagulation because of recurrent DVT or recurrent pulmonary emboli or thrombopenia, if they’ve had a PFO-mediated stroke, then it’s our opinion that they should have their PFO closed in addition to taking lifelong anticoagulation because of the same issues of noncompliance and interruption of therapy.” Those are conditional recommendations.

The guideline also checks a box in the FDA labeling that mandated agreement between cardiology and neurology in patient selection. The American Academy of Neurology (AAN) issued its own guideline in 2020 for patients with stroke and PFO. In Europe, the European Society of Cardiology issued two position papers on expanded applications of PFO closure.

The recommendations on when PFO closure shouldn’t be done are noteworthy, Dr. Kavinsky said. “PFOs are present in 25% of the adult population, so the number of patients with PFO is huge and the indication for the FDA is really narrow: to reduce the risk of recurrent stroke in patients with PFO-mediated stroke. So, there’s the tremendous potential for abuse out there, of excessive procedures, of doing unnecessary procedures.”

The guidelines are a follow-up to the operator institutional requirements document SCAI issued in 2019 that set requirements for hospital offering and physicians performing PFO closure, Dr. Kavinsky added.

In an editorial accompanying the published guideline, Robert J. Sommer, MD, and Jamil A. Aboulhosn, MD, wrote that they support the recommendations “which help spotlight and clarify the growing list of potential indications for PFO closure.” They noted that the guidelines panel’s “strong” recommendations were for indications validated by randomized trials and that “conditional” recommendations were based on panelists’ experience and observational data.

“It is critical to recognize that most of these guidelines represent consensus opinion only,” wrote Dr. Sommer, who specializes in adult congenital and pediatric cardiology at Columbia University Irving Medical Center, New York, and Dr. Aboulhosn, an interventional cardiologist at Ronald Reagan University of California, Los Angeles, Medical Center. They emphasized the guidelines’ “heavy emphasis” on shared decisionmaking with patients.

Dr. Kavinsky is a principal investigator for Edwards Lifesciences, W.L. Gore and Associates, Medtronic, and Abbott. Dr. Sommer is a principal investigator and investigator in studies sponsored by W.L. Gore & Associates. Dr. Aboulhosn is a consultant to Abbott Medical.
 

The first-ever guidelines for interventional cardiologists using percutaneous patent foramen ovale closure recommend expanding the use of the procedure beyond the Food and Drug Administration–approved indication following PFO-associated ischemic stroke, adding clarification about the use of PFO with anticoagulation and hedging against abuse and overuse of the procedure, said the chair of the guideline writing committee.

“The most important things surrounding these guidelines are to help clinicians and policymakers – third-party payers – to address PFO in patient subsets that were not included in the large randomized clinical trials that led to FDA approval,” said writing group chair Clifford J. Kavinsky, MD, PhD, chief of structural and interventional cardiology at Rush University Medical Center, Chicago.

The Society for Cardiovascular Angiography & Interventions issued the guidelines at its annual scientific sessions meeting in Atlanta and published them simultaneously in the society’s journal.

The guidelines issue strong and conditional recommendations. The former means clinicians should order the intervention for most patients; the latter means decisionmaking is more nuanced and should consider contributing factors.

The guidelines clarify patient selection for PFO closure outside the “pretty narrow” indication the FDA approved, Dr. Kavinsky said, which is for PFO-associated ischemic stroke in patients aged 18-60 years.

“So what about patients who are older than 60? What about patients who had their stroke 10 years ago?” Dr. Kavinsky asked. “Those are issues that were unanswered in the randomized clinical trials.”

The guidelines also refine recommendations about anticoagulation in these patients, including its use after PFO closure in selected patients, Dr. Kavinsky noted. “It’s the opinion of the panel that although anticoagulants may be effective, because of issues of noncompliance, because of issues of interruption of therapy by physicians for a variety of reasons, including surgery or noncompliance, that it is preferable to do a PFO device closure to giving anticoagulant therapy.”

Many of the recommendations cover PFO closure alongside antiplatelet or anticoagulation therapy. Key conditional recommendations for patients who haven’t had a PFO-related stroke are:

• Avoiding its routine use in patients with chronic migraines, prior decompression illness (DCI), thrombophilia, atrial septal aneurysm, transient ischemic attack (TIA), or deep vein thrombosis (DVT).
• Considering PFO closure in patients with platypnea-orthodeoxia syndrome (POS) with no other discernible cause of hypoxia or systemic embolism in whom other embolic causes have been ruled out.

In patients who’ve had a PFO-related stroke, the guidelines strongly recommend PFO closure versus antiplatelet therapy alone, but conditionally, not in patients with atrial fibrillation who’ve had an ischemic stroke. They also conditionally suggest PFO closure rather than long-term antiplatelet therapy alone in PFO stroke patients aged 60 and older, as well as those with thrombophilia already on antiplatelet therapy but not anticoagulation. However, the guidelines make no recommendation on PFO closure based on how much time has passed since the previous stroke.

“Furthermore,” Dr. Kavinsky said, “in patients who require lifelong anticoagulation because of recurrent DVT or recurrent pulmonary emboli or thrombopenia, if they’ve had a PFO-mediated stroke, then it’s our opinion that they should have their PFO closed in addition to taking lifelong anticoagulation because of the same issues of noncompliance and interruption of therapy.” Those are conditional recommendations.

The guideline also checks a box in the FDA labeling that mandated agreement between cardiology and neurology in patient selection. The American Academy of Neurology (AAN) issued its own guideline in 2020 for patients with stroke and PFO. In Europe, the European Society of Cardiology issued two position papers on expanded applications of PFO closure.

The recommendations on when PFO closure shouldn’t be done are noteworthy, Dr. Kavinsky said. “PFOs are present in 25% of the adult population, so the number of patients with PFO is huge and the indication for the FDA is really narrow: to reduce the risk of recurrent stroke in patients with PFO-mediated stroke. So, there’s the tremendous potential for abuse out there, of excessive procedures, of doing unnecessary procedures.”

The guidelines are a follow-up to the operator institutional requirements document SCAI issued in 2019 that set requirements for hospital offering and physicians performing PFO closure, Dr. Kavinsky added.

In an editorial accompanying the published guideline, Robert J. Sommer, MD, and Jamil A. Aboulhosn, MD, wrote that they support the recommendations “which help spotlight and clarify the growing list of potential indications for PFO closure.” They noted that the guidelines panel’s “strong” recommendations were for indications validated by randomized trials and that “conditional” recommendations were based on panelists’ experience and observational data.

“It is critical to recognize that most of these guidelines represent consensus opinion only,” wrote Dr. Sommer, who specializes in adult congenital and pediatric cardiology at Columbia University Irving Medical Center, New York, and Dr. Aboulhosn, an interventional cardiologist at Ronald Reagan University of California, Los Angeles, Medical Center. They emphasized the guidelines’ “heavy emphasis” on shared decisionmaking with patients.

Dr. Kavinsky is a principal investigator for Edwards Lifesciences, W.L. Gore and Associates, Medtronic, and Abbott. Dr. Sommer is a principal investigator and investigator in studies sponsored by W.L. Gore & Associates. Dr. Aboulhosn is a consultant to Abbott Medical.
 

The first-ever guidelines for interventional cardiologists using percutaneous patent foramen ovale closure recommend expanding the use of the procedure beyond the Food and Drug Administration–approved indication following PFO-associated ischemic stroke, adding clarification about the use of PFO with anticoagulation and hedging against abuse and overuse of the procedure, said the chair of the guideline writing committee.

“The most important things surrounding these guidelines are to help clinicians and policymakers – third-party payers – to address PFO in patient subsets that were not included in the large randomized clinical trials that led to FDA approval,” said writing group chair Clifford J. Kavinsky, MD, PhD, chief of structural and interventional cardiology at Rush University Medical Center, Chicago.

The Society for Cardiovascular Angiography & Interventions issued the guidelines at its annual scientific sessions meeting in Atlanta and published them simultaneously in the society’s journal.

The guidelines issue strong and conditional recommendations. The former means clinicians should order the intervention for most patients; the latter means decisionmaking is more nuanced and should consider contributing factors.

The guidelines clarify patient selection for PFO closure outside the “pretty narrow” indication the FDA approved, Dr. Kavinsky said, which is for PFO-associated ischemic stroke in patients aged 18-60 years.

“So what about patients who are older than 60? What about patients who had their stroke 10 years ago?” Dr. Kavinsky asked. “Those are issues that were unanswered in the randomized clinical trials.”

The guidelines also refine recommendations about anticoagulation in these patients, including its use after PFO closure in selected patients, Dr. Kavinsky noted. “It’s the opinion of the panel that although anticoagulants may be effective, because of issues of noncompliance, because of issues of interruption of therapy by physicians for a variety of reasons, including surgery or noncompliance, that it is preferable to do a PFO device closure to giving anticoagulant therapy.”

Many of the recommendations cover PFO closure alongside antiplatelet or anticoagulation therapy. Key conditional recommendations for patients who haven’t had a PFO-related stroke are:

• Avoiding its routine use in patients with chronic migraines, prior decompression illness (DCI), thrombophilia, atrial septal aneurysm, transient ischemic attack (TIA), or deep vein thrombosis (DVT).
• Considering PFO closure in patients with platypnea-orthodeoxia syndrome (POS) with no other discernible cause of hypoxia or systemic embolism in whom other embolic causes have been ruled out.

In patients who’ve had a PFO-related stroke, the guidelines strongly recommend PFO closure versus antiplatelet therapy alone, but conditionally, not in patients with atrial fibrillation who’ve had an ischemic stroke. They also conditionally suggest PFO closure rather than long-term antiplatelet therapy alone in PFO stroke patients aged 60 and older, as well as those with thrombophilia already on antiplatelet therapy but not anticoagulation. However, the guidelines make no recommendation on PFO closure based on how much time has passed since the previous stroke.

“Furthermore,” Dr. Kavinsky said, “in patients who require lifelong anticoagulation because of recurrent DVT or recurrent pulmonary emboli or thrombopenia, if they’ve had a PFO-mediated stroke, then it’s our opinion that they should have their PFO closed in addition to taking lifelong anticoagulation because of the same issues of noncompliance and interruption of therapy.” Those are conditional recommendations.

The guideline also checks a box in the FDA labeling that mandated agreement between cardiology and neurology in patient selection. The American Academy of Neurology (AAN) issued its own guideline in 2020 for patients with stroke and PFO. In Europe, the European Society of Cardiology issued two position papers on expanded applications of PFO closure.

The recommendations on when PFO closure shouldn’t be done are noteworthy, Dr. Kavinsky said. “PFOs are present in 25% of the adult population, so the number of patients with PFO is huge and the indication for the FDA is really narrow: to reduce the risk of recurrent stroke in patients with PFO-mediated stroke. So, there’s the tremendous potential for abuse out there, of excessive procedures, of doing unnecessary procedures.”

The guidelines are a follow-up to the operator institutional requirements document SCAI issued in 2019 that set requirements for hospital offering and physicians performing PFO closure, Dr. Kavinsky added.

In an editorial accompanying the published guideline, Robert J. Sommer, MD, and Jamil A. Aboulhosn, MD, wrote that they support the recommendations “which help spotlight and clarify the growing list of potential indications for PFO closure.” They noted that the guidelines panel’s “strong” recommendations were for indications validated by randomized trials and that “conditional” recommendations were based on panelists’ experience and observational data.

“It is critical to recognize that most of these guidelines represent consensus opinion only,” wrote Dr. Sommer, who specializes in adult congenital and pediatric cardiology at Columbia University Irving Medical Center, New York, and Dr. Aboulhosn, an interventional cardiologist at Ronald Reagan University of California, Los Angeles, Medical Center. They emphasized the guidelines’ “heavy emphasis” on shared decisionmaking with patients.

Dr. Kavinsky is a principal investigator for Edwards Lifesciences, W.L. Gore and Associates, Medtronic, and Abbott. Dr. Sommer is a principal investigator and investigator in studies sponsored by W.L. Gore & Associates. Dr. Aboulhosn is a consultant to Abbott Medical.