Cardiology

Use of systemic anticoagulation may improve the chance of survival in patients hospitalized with the COVID-19 virus, a large study from the epicenter of the U.S. outbreak suggests.

Among nearly 3,000 patients with COVID-19 admitted to New York City’s Mount Sinai Health System beginning in mid-March, median survival increased from 14 days to 21 days with the addition of anticoagulation.

The results were particularly striking among sicker patients who required mechanical ventilation, in whom in-hospital mortality fell from 62.7% to 29.1% and median survival jumped from 9 days to 21 days.

Interestingly, the association with anticoagulation and improved survival remained even after adjusting for mechanical ventilation, the authors reported May 6 in the Journal of the American College of Cardiology.

“It’s important for the community to know, first of all, how this should be approached and, second, it’s really opening a door to a new reality,” senior corresponding author Valentin Fuster, MD, PhD, director of Mount Sinai’s Zena and Michael A. Wiener Cardiovascular Institute and JACC editor-in-chief.

“I can tell you any family of mine who will have this disease absolutely will be on antithrombotic therapy and, actually, so are all of the patients at Mount Sinai now,” he said in an interview. COVID-19 is thought to promote thrombosis but the exact role of anticoagulation in the management of COVID-19 and optimal regimen are unknown.

In late March, the International Society on Thrombosis and Haemostasis recommended that all hospitalized COVID-19 patients, even those not in the ICU, should receive prophylactic-dose low-molecular-weight heparin (LMWH), unless they have contraindications.

Last month, international consensus-based recommendations were published for the diagnosis and management of thrombotic disease in patients with COVID-19.

In early March, however, data were scare and only a minimal number of patients were receiving anticoagulants at Mount Sinai.

“But after a few weeks, we reached an intuitive feeling that anticoagulation was of benefit and, at the same time, the literature was beginning to say clots were important in this disease,” Dr. Fuster said. “So we took a very straightforward approach and set up a policy in our institution that all COVID-19 patients should be on antithrombotic therapy. It was a decision made without data, but it was a feeling.”

For the present study, the researchers examined mortality and bleeding among 2,773 patients hospitalized at Mount Sinai with confirmed COVID-19 between March 14 and April 11.

Of these, 786 (28%) received systemic anticoagulation including subcutaneous heparin, LMWH, fractionated heparin, and the novel oral anticoagulants apixaban and dabigatran, for a median of 3 days (range, 2-7 days). Tissue plasminogen activator was also used in some ICU cases.

Major bleeding was defined as hemoglobin less than 7 g/dL and any red blood cell transfusion; at least two units of red blood cell transfusion within 48 hours; or a diagnosis code for major bleeding, notably including intracranial hemorrhage.

Patients treated with anticoagulation were more likely to require invasive mechanical ventilation (29.8% vs. 8.1%) and to have significantly increased prothrombin time, activated partial thromboplastin time, lactate dehydrogenase, ferritin, C-reactive protein, and d-dimer values. In-hospital mortality was 22.5% with anticoagulation and 22.8% without anticoagulation (median survival, 14 days vs. 21 days).

In multivariate analysis, longer anticoagulation duration was associated with a 14% lower adjusted risk of in-hospital death (hazard ratio, 0.86 per day; 95% confidence interval, 0.82-0.89; P < .001).

The model adjusted for several potential confounders such as age, ethnicity, body mass index, and prehospital anticoagulation use. To adjust for differential length of stay and anticoagulation initiation, anticoagulation duration was used as a covariate and intubation was treated as a time-dependent variable.

Bleeding events were similar in patients treated with and without anticoagulation (3% vs. 1.9%; P = .2) but were more common among the 375 intubated patients than among nonintubated patients (7.5% vs. 1.35%; P value not given). “The most important thing was there was no increase in bleeding,” said Dr. Fuster.

Additional support for a possible survival benefit was published April 27 and included 449 patients with severe COVID-19 treated with heparin (mostly LMWH) for at least 7 days in Hunan, China. Overall, 28-day mortality was similar between heparin users and nonusers (30.3% vs. 29.7%) but was significantly lower among heparin users who had a Sepsis-Induced Coagulopathy score of at least 4 (40% vs. 64.2%; P = .02) or d-dimer greater than sixfold the upper limit of normal (32.8% vs. 52.4%; P = .01).

In multivariate analysis, d-dimer, prothrombin time, and age were positively correlated with 28-day mortality, and platelet count was negatively correlated with 28-day mortality.

Victor F. Tapson, MD, who directs the pulmonary embolism response team at Cedars-Sinai Medical Center in Los Angeles and was not involved with the study, said, “The Chinese data were not enough for me to anticoagulate patients therapeutically” but the Mount Sinai data strengthen the case.

“They’re wise to call this a ‘suggestion of improved outcomes,’ but it’s pretty compelling that those patients who were on anticoagulation had improved survival after adjusting for mechanical ventilation,” he said in an interview. “These are sicker patients and sicker patients may get anticoagulated more, but they may bleed more. The bleed risks were a little different but they didn’t seem too concerning.”

“I think this helps move us forward some that we should consider anticoagulating with therapeutic anticoagulation certain patients that meet certain criteria,” Dr. Tapson said. “An easy example is a patient who comes to the hospital, has active cancer and is on a DOAC [direct oral anticoagulant], and comes up with COVID.”

At the same time, some clinicians want to increase prophylactic anticoagulation “using enoxaparin 40 mg once a day and maybe go to twice a day – not quite therapeutic doses but increased prophylaxis,” he observed. Anticoagulation was given at “relatively low doses” in the Mount Sinai study but that is evolving in light of the reassuring bleeding data, Dr. Fuster said. They now have three enoxaparin regimens and, for example, give patients who don’t require intensive care enoxaparin 30 mg twice a day, up from 40 mg a day initially.

Patients are also stratified by factors such as renal failure and obesity, creating an intermediate group between those not initially needing intensive care and ICU cases.

In the coming weeks, the researchers will evaluate anticoagulation regimens and a broader array of outcomes among 5,000 patients, two-thirds of whom received anticoagulation after Mount Sinai enacted its anticoagulation policy. “We’re now going to look at the difference between all these [regimens],” Dr. Fuster said. “My personal feeling and, for feasibility issues, I hope the winner is subcutaneous heparin.”

Three randomized trials are also planned. “Three questions we really want to ask are: what to give in the hospital, what to give those who go home after the hospital, and what to give those who are not hospitalized,” he said.

The work was supported by U54 TR001433-05, National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Fuster has disclosed no relevant financial relationships. Dr. Tapson reported consulting and clinical trial work for BMS, Janssen, Daiichi Medical, ECOS/BTG, Inari, and Penumbra.

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

Use of systemic anticoagulation may improve the chance of survival in patients hospitalized with the COVID-19 virus, a large study from the epicenter of the U.S. outbreak suggests.

Among nearly 3,000 patients with COVID-19 admitted to New York City’s Mount Sinai Health System beginning in mid-March, median survival increased from 14 days to 21 days with the addition of anticoagulation.

The results were particularly striking among sicker patients who required mechanical ventilation, in whom in-hospital mortality fell from 62.7% to 29.1% and median survival jumped from 9 days to 21 days.

Interestingly, the association with anticoagulation and improved survival remained even after adjusting for mechanical ventilation, the authors reported May 6 in the Journal of the American College of Cardiology.

“It’s important for the community to know, first of all, how this should be approached and, second, it’s really opening a door to a new reality,” senior corresponding author Valentin Fuster, MD, PhD, director of Mount Sinai’s Zena and Michael A. Wiener Cardiovascular Institute and JACC editor-in-chief.

“I can tell you any family of mine who will have this disease absolutely will be on antithrombotic therapy and, actually, so are all of the patients at Mount Sinai now,” he said in an interview. COVID-19 is thought to promote thrombosis but the exact role of anticoagulation in the management of COVID-19 and optimal regimen are unknown.

In late March, the International Society on Thrombosis and Haemostasis recommended that all hospitalized COVID-19 patients, even those not in the ICU, should receive prophylactic-dose low-molecular-weight heparin (LMWH), unless they have contraindications.

Last month, international consensus-based recommendations were published for the diagnosis and management of thrombotic disease in patients with COVID-19.

In early March, however, data were scare and only a minimal number of patients were receiving anticoagulants at Mount Sinai.

“But after a few weeks, we reached an intuitive feeling that anticoagulation was of benefit and, at the same time, the literature was beginning to say clots were important in this disease,” Dr. Fuster said. “So we took a very straightforward approach and set up a policy in our institution that all COVID-19 patients should be on antithrombotic therapy. It was a decision made without data, but it was a feeling.”

For the present study, the researchers examined mortality and bleeding among 2,773 patients hospitalized at Mount Sinai with confirmed COVID-19 between March 14 and April 11.

Of these, 786 (28%) received systemic anticoagulation including subcutaneous heparin, LMWH, fractionated heparin, and the novel oral anticoagulants apixaban and dabigatran, for a median of 3 days (range, 2-7 days). Tissue plasminogen activator was also used in some ICU cases.

Major bleeding was defined as hemoglobin less than 7 g/dL and any red blood cell transfusion; at least two units of red blood cell transfusion within 48 hours; or a diagnosis code for major bleeding, notably including intracranial hemorrhage.

Patients treated with anticoagulation were more likely to require invasive mechanical ventilation (29.8% vs. 8.1%) and to have significantly increased prothrombin time, activated partial thromboplastin time, lactate dehydrogenase, ferritin, C-reactive protein, and d-dimer values. In-hospital mortality was 22.5% with anticoagulation and 22.8% without anticoagulation (median survival, 14 days vs. 21 days).

In multivariate analysis, longer anticoagulation duration was associated with a 14% lower adjusted risk of in-hospital death (hazard ratio, 0.86 per day; 95% confidence interval, 0.82-0.89; P < .001).

The model adjusted for several potential confounders such as age, ethnicity, body mass index, and prehospital anticoagulation use. To adjust for differential length of stay and anticoagulation initiation, anticoagulation duration was used as a covariate and intubation was treated as a time-dependent variable.

Bleeding events were similar in patients treated with and without anticoagulation (3% vs. 1.9%; P = .2) but were more common among the 375 intubated patients than among nonintubated patients (7.5% vs. 1.35%; P value not given). “The most important thing was there was no increase in bleeding,” said Dr. Fuster.

Additional support for a possible survival benefit was published April 27 and included 449 patients with severe COVID-19 treated with heparin (mostly LMWH) for at least 7 days in Hunan, China. Overall, 28-day mortality was similar between heparin users and nonusers (30.3% vs. 29.7%) but was significantly lower among heparin users who had a Sepsis-Induced Coagulopathy score of at least 4 (40% vs. 64.2%; P = .02) or d-dimer greater than sixfold the upper limit of normal (32.8% vs. 52.4%; P = .01).

In multivariate analysis, d-dimer, prothrombin time, and age were positively correlated with 28-day mortality, and platelet count was negatively correlated with 28-day mortality.

Victor F. Tapson, MD, who directs the pulmonary embolism response team at Cedars-Sinai Medical Center in Los Angeles and was not involved with the study, said, “The Chinese data were not enough for me to anticoagulate patients therapeutically” but the Mount Sinai data strengthen the case.

“They’re wise to call this a ‘suggestion of improved outcomes,’ but it’s pretty compelling that those patients who were on anticoagulation had improved survival after adjusting for mechanical ventilation,” he said in an interview. “These are sicker patients and sicker patients may get anticoagulated more, but they may bleed more. The bleed risks were a little different but they didn’t seem too concerning.”

“I think this helps move us forward some that we should consider anticoagulating with therapeutic anticoagulation certain patients that meet certain criteria,” Dr. Tapson said. “An easy example is a patient who comes to the hospital, has active cancer and is on a DOAC [direct oral anticoagulant], and comes up with COVID.”

At the same time, some clinicians want to increase prophylactic anticoagulation “using enoxaparin 40 mg once a day and maybe go to twice a day – not quite therapeutic doses but increased prophylaxis,” he observed. Anticoagulation was given at “relatively low doses” in the Mount Sinai study but that is evolving in light of the reassuring bleeding data, Dr. Fuster said. They now have three enoxaparin regimens and, for example, give patients who don’t require intensive care enoxaparin 30 mg twice a day, up from 40 mg a day initially.

Patients are also stratified by factors such as renal failure and obesity, creating an intermediate group between those not initially needing intensive care and ICU cases.

In the coming weeks, the researchers will evaluate anticoagulation regimens and a broader array of outcomes among 5,000 patients, two-thirds of whom received anticoagulation after Mount Sinai enacted its anticoagulation policy. “We’re now going to look at the difference between all these [regimens],” Dr. Fuster said. “My personal feeling and, for feasibility issues, I hope the winner is subcutaneous heparin.”

Three randomized trials are also planned. “Three questions we really want to ask are: what to give in the hospital, what to give those who go home after the hospital, and what to give those who are not hospitalized,” he said.

The work was supported by U54 TR001433-05, National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Fuster has disclosed no relevant financial relationships. Dr. Tapson reported consulting and clinical trial work for BMS, Janssen, Daiichi Medical, ECOS/BTG, Inari, and Penumbra.

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

Use of systemic anticoagulation may improve the chance of survival in patients hospitalized with the COVID-19 virus, a large study from the epicenter of the U.S. outbreak suggests.

Among nearly 3,000 patients with COVID-19 admitted to New York City’s Mount Sinai Health System beginning in mid-March, median survival increased from 14 days to 21 days with the addition of anticoagulation.

The results were particularly striking among sicker patients who required mechanical ventilation, in whom in-hospital mortality fell from 62.7% to 29.1% and median survival jumped from 9 days to 21 days.

Interestingly, the association with anticoagulation and improved survival remained even after adjusting for mechanical ventilation, the authors reported May 6 in the Journal of the American College of Cardiology.

“It’s important for the community to know, first of all, how this should be approached and, second, it’s really opening a door to a new reality,” senior corresponding author Valentin Fuster, MD, PhD, director of Mount Sinai’s Zena and Michael A. Wiener Cardiovascular Institute and JACC editor-in-chief.

“I can tell you any family of mine who will have this disease absolutely will be on antithrombotic therapy and, actually, so are all of the patients at Mount Sinai now,” he said in an interview. COVID-19 is thought to promote thrombosis but the exact role of anticoagulation in the management of COVID-19 and optimal regimen are unknown.

In late March, the International Society on Thrombosis and Haemostasis recommended that all hospitalized COVID-19 patients, even those not in the ICU, should receive prophylactic-dose low-molecular-weight heparin (LMWH), unless they have contraindications.

Last month, international consensus-based recommendations were published for the diagnosis and management of thrombotic disease in patients with COVID-19.

In early March, however, data were scare and only a minimal number of patients were receiving anticoagulants at Mount Sinai.

“But after a few weeks, we reached an intuitive feeling that anticoagulation was of benefit and, at the same time, the literature was beginning to say clots were important in this disease,” Dr. Fuster said. “So we took a very straightforward approach and set up a policy in our institution that all COVID-19 patients should be on antithrombotic therapy. It was a decision made without data, but it was a feeling.”

For the present study, the researchers examined mortality and bleeding among 2,773 patients hospitalized at Mount Sinai with confirmed COVID-19 between March 14 and April 11.

Of these, 786 (28%) received systemic anticoagulation including subcutaneous heparin, LMWH, fractionated heparin, and the novel oral anticoagulants apixaban and dabigatran, for a median of 3 days (range, 2-7 days). Tissue plasminogen activator was also used in some ICU cases.

Major bleeding was defined as hemoglobin less than 7 g/dL and any red blood cell transfusion; at least two units of red blood cell transfusion within 48 hours; or a diagnosis code for major bleeding, notably including intracranial hemorrhage.

Patients treated with anticoagulation were more likely to require invasive mechanical ventilation (29.8% vs. 8.1%) and to have significantly increased prothrombin time, activated partial thromboplastin time, lactate dehydrogenase, ferritin, C-reactive protein, and d-dimer values. In-hospital mortality was 22.5% with anticoagulation and 22.8% without anticoagulation (median survival, 14 days vs. 21 days).

In multivariate analysis, longer anticoagulation duration was associated with a 14% lower adjusted risk of in-hospital death (hazard ratio, 0.86 per day; 95% confidence interval, 0.82-0.89; P < .001).

The model adjusted for several potential confounders such as age, ethnicity, body mass index, and prehospital anticoagulation use. To adjust for differential length of stay and anticoagulation initiation, anticoagulation duration was used as a covariate and intubation was treated as a time-dependent variable.

Bleeding events were similar in patients treated with and without anticoagulation (3% vs. 1.9%; P = .2) but were more common among the 375 intubated patients than among nonintubated patients (7.5% vs. 1.35%; P value not given). “The most important thing was there was no increase in bleeding,” said Dr. Fuster.

Additional support for a possible survival benefit was published April 27 and included 449 patients with severe COVID-19 treated with heparin (mostly LMWH) for at least 7 days in Hunan, China. Overall, 28-day mortality was similar between heparin users and nonusers (30.3% vs. 29.7%) but was significantly lower among heparin users who had a Sepsis-Induced Coagulopathy score of at least 4 (40% vs. 64.2%; P = .02) or d-dimer greater than sixfold the upper limit of normal (32.8% vs. 52.4%; P = .01).

In multivariate analysis, d-dimer, prothrombin time, and age were positively correlated with 28-day mortality, and platelet count was negatively correlated with 28-day mortality.

Victor F. Tapson, MD, who directs the pulmonary embolism response team at Cedars-Sinai Medical Center in Los Angeles and was not involved with the study, said, “The Chinese data were not enough for me to anticoagulate patients therapeutically” but the Mount Sinai data strengthen the case.

“They’re wise to call this a ‘suggestion of improved outcomes,’ but it’s pretty compelling that those patients who were on anticoagulation had improved survival after adjusting for mechanical ventilation,” he said in an interview. “These are sicker patients and sicker patients may get anticoagulated more, but they may bleed more. The bleed risks were a little different but they didn’t seem too concerning.”

“I think this helps move us forward some that we should consider anticoagulating with therapeutic anticoagulation certain patients that meet certain criteria,” Dr. Tapson said. “An easy example is a patient who comes to the hospital, has active cancer and is on a DOAC [direct oral anticoagulant], and comes up with COVID.”

At the same time, some clinicians want to increase prophylactic anticoagulation “using enoxaparin 40 mg once a day and maybe go to twice a day – not quite therapeutic doses but increased prophylaxis,” he observed. Anticoagulation was given at “relatively low doses” in the Mount Sinai study but that is evolving in light of the reassuring bleeding data, Dr. Fuster said. They now have three enoxaparin regimens and, for example, give patients who don’t require intensive care enoxaparin 30 mg twice a day, up from 40 mg a day initially.

Patients are also stratified by factors such as renal failure and obesity, creating an intermediate group between those not initially needing intensive care and ICU cases.

In the coming weeks, the researchers will evaluate anticoagulation regimens and a broader array of outcomes among 5,000 patients, two-thirds of whom received anticoagulation after Mount Sinai enacted its anticoagulation policy. “We’re now going to look at the difference between all these [regimens],” Dr. Fuster said. “My personal feeling and, for feasibility issues, I hope the winner is subcutaneous heparin.”

Three randomized trials are also planned. “Three questions we really want to ask are: what to give in the hospital, what to give those who go home after the hospital, and what to give those who are not hospitalized,” he said.

The work was supported by U54 TR001433-05, National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Fuster has disclosed no relevant financial relationships. Dr. Tapson reported consulting and clinical trial work for BMS, Janssen, Daiichi Medical, ECOS/BTG, Inari, and Penumbra.

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

In patients with stable chest pain, the burden of low-attenuation noncalcified plaque on coronary CT angiography is a better predictor of future myocardial infarction risk than a cardiovascular risk score, an Agatson coronary artery calcium score, or angiographic severity of coronary stenoses, Michelle C. Williams, MBChB, PhD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

These findings from a post hoc analysis of the large multicenter SCOT-HEART trial challenge current concepts regarding the supposed superiority of the classic tools for MI risk prediction, noted Dr. Williams, a senior clinical research fellow at the University of Edinburgh.

Indeed, it’s likely that the current established predictors of risk – that is, coronary artery calcium, severity of stenosis, and cardiovascular risk score – are associated with clinical events only indirectly through their correlation with low-attenuated calcified plaque burden, which is the real driver of future MI, she continued.

Histologically, low-attenuated noncalcified plaque on coronary CT angiography (CCTA) is defined by a thin fibrous cap, a large, inflamed, lipid-rich necrotic core, and microcalcification. Previously, Dr. Williams and her coinvestigators demonstrated that visual identification of this unstable plaque subtype is of benefit in predicting future risk of MI (J Am Coll Cardiol. 2019 Jan 29;73[3]:291-301).

But visual identification of plaque subtypes is a crude and laborious process. In her current study, she and her coworkers have taken things a giant step further, using commercially available CCTA software to semiautomatically quantify the burden of this highest-risk plaque subtype as well as all the other subtypes.

This post hoc analysis of the previously reported main SCOT-HEART trial (N Engl J Med. 2018 Sep 6;379[10]:924-933) included 1,769 patients with stable chest pain randomized to standard care with or without CCTA guidance and followed for a median of 4.7 years, during which 41 patients had a fatal or nonfatal MI. At enrollment, 37% of participants had normal coronary arteries, 38% had nonobstructive coronary artery disease (CAD), and the remainder had obstructive CAD.

In a multivariate analysis, low-attenuation noncalcified plaque burden was the strongest predictor of future MI, with an adjusted hazard ratio of 1.6 per doubling. This metric was strongly correlated with coronary artery calcium score, underscoring the limited value of doing noncontrast CT in order to determine a coronary artery calcium score when CCTA is performed.

Low-attenuation plaque burden correlated very strongly with angiographic severity of stenosis, and only weakly with cardiovascular risk score, perhaps explaining the poor prognostic performance of cardiovascular risk scores in SCOT-HEART and other studies, according to Dr. Williams.

Patients with a low-attenuation noncalcified plaque burden greater than 4% in their coronary tree were 4.7 times more likely to have a subsequent MI than were those with a lesser burden. The predictive power was even greater in patients with nonobstructive CAD, where a low-attenuation noncalcified plaque burden in excess of 4% conferred a 6.6-fold greater likelihood of fatal or nonfatal MI, she observed.

Two things need to happen before measurement of low-attenuation noncalcified plaque via CCTA to predict MI risk is ready to be adopted in routine clinical practice, according to Dr. Williams. These SCOT-HEART results need to be validated in other cohorts, a process now underway in the SCOT-HEART 2 trial and other studies. Also, improved software incorporating machine learning is needed in order to speed up the semiautomated analysis of plaque subtypes, which now takes 20-30 minutes.

Dr. Williams reported having no financial conflicts regarding her study, funded by the National Health Service.

In conjunction with her virtual presentation at ACC 2020, the SCOT-HEART study results were published online (Circulation. 2020 Mar 16. doi: 10.1161/CIRCULATIONAHA.119.044720. [Epub ahead of print]).

bjancin@mdedge.com

SOURCE: Williams MC et al. ACC 2020, Abstract 909-06.

In patients with stable chest pain, the burden of low-attenuation noncalcified plaque on coronary CT angiography is a better predictor of future myocardial infarction risk than a cardiovascular risk score, an Agatson coronary artery calcium score, or angiographic severity of coronary stenoses, Michelle C. Williams, MBChB, PhD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

These findings from a post hoc analysis of the large multicenter SCOT-HEART trial challenge current concepts regarding the supposed superiority of the classic tools for MI risk prediction, noted Dr. Williams, a senior clinical research fellow at the University of Edinburgh.

Indeed, it’s likely that the current established predictors of risk – that is, coronary artery calcium, severity of stenosis, and cardiovascular risk score – are associated with clinical events only indirectly through their correlation with low-attenuated calcified plaque burden, which is the real driver of future MI, she continued.

Histologically, low-attenuated noncalcified plaque on coronary CT angiography (CCTA) is defined by a thin fibrous cap, a large, inflamed, lipid-rich necrotic core, and microcalcification. Previously, Dr. Williams and her coinvestigators demonstrated that visual identification of this unstable plaque subtype is of benefit in predicting future risk of MI (J Am Coll Cardiol. 2019 Jan 29;73[3]:291-301).

But visual identification of plaque subtypes is a crude and laborious process. In her current study, she and her coworkers have taken things a giant step further, using commercially available CCTA software to semiautomatically quantify the burden of this highest-risk plaque subtype as well as all the other subtypes.

This post hoc analysis of the previously reported main SCOT-HEART trial (N Engl J Med. 2018 Sep 6;379[10]:924-933) included 1,769 patients with stable chest pain randomized to standard care with or without CCTA guidance and followed for a median of 4.7 years, during which 41 patients had a fatal or nonfatal MI. At enrollment, 37% of participants had normal coronary arteries, 38% had nonobstructive coronary artery disease (CAD), and the remainder had obstructive CAD.

In a multivariate analysis, low-attenuation noncalcified plaque burden was the strongest predictor of future MI, with an adjusted hazard ratio of 1.6 per doubling. This metric was strongly correlated with coronary artery calcium score, underscoring the limited value of doing noncontrast CT in order to determine a coronary artery calcium score when CCTA is performed.

Low-attenuation plaque burden correlated very strongly with angiographic severity of stenosis, and only weakly with cardiovascular risk score, perhaps explaining the poor prognostic performance of cardiovascular risk scores in SCOT-HEART and other studies, according to Dr. Williams.

Patients with a low-attenuation noncalcified plaque burden greater than 4% in their coronary tree were 4.7 times more likely to have a subsequent MI than were those with a lesser burden. The predictive power was even greater in patients with nonobstructive CAD, where a low-attenuation noncalcified plaque burden in excess of 4% conferred a 6.6-fold greater likelihood of fatal or nonfatal MI, she observed.

Two things need to happen before measurement of low-attenuation noncalcified plaque via CCTA to predict MI risk is ready to be adopted in routine clinical practice, according to Dr. Williams. These SCOT-HEART results need to be validated in other cohorts, a process now underway in the SCOT-HEART 2 trial and other studies. Also, improved software incorporating machine learning is needed in order to speed up the semiautomated analysis of plaque subtypes, which now takes 20-30 minutes.

Dr. Williams reported having no financial conflicts regarding her study, funded by the National Health Service.

In conjunction with her virtual presentation at ACC 2020, the SCOT-HEART study results were published online (Circulation. 2020 Mar 16. doi: 10.1161/CIRCULATIONAHA.119.044720. [Epub ahead of print]).

bjancin@mdedge.com

SOURCE: Williams MC et al. ACC 2020, Abstract 909-06.

In patients with stable chest pain, the burden of low-attenuation noncalcified plaque on coronary CT angiography is a better predictor of future myocardial infarction risk than a cardiovascular risk score, an Agatson coronary artery calcium score, or angiographic severity of coronary stenoses, Michelle C. Williams, MBChB, PhD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

These findings from a post hoc analysis of the large multicenter SCOT-HEART trial challenge current concepts regarding the supposed superiority of the classic tools for MI risk prediction, noted Dr. Williams, a senior clinical research fellow at the University of Edinburgh.

Indeed, it’s likely that the current established predictors of risk – that is, coronary artery calcium, severity of stenosis, and cardiovascular risk score – are associated with clinical events only indirectly through their correlation with low-attenuated calcified plaque burden, which is the real driver of future MI, she continued.

Histologically, low-attenuated noncalcified plaque on coronary CT angiography (CCTA) is defined by a thin fibrous cap, a large, inflamed, lipid-rich necrotic core, and microcalcification. Previously, Dr. Williams and her coinvestigators demonstrated that visual identification of this unstable plaque subtype is of benefit in predicting future risk of MI (J Am Coll Cardiol. 2019 Jan 29;73[3]:291-301).

But visual identification of plaque subtypes is a crude and laborious process. In her current study, she and her coworkers have taken things a giant step further, using commercially available CCTA software to semiautomatically quantify the burden of this highest-risk plaque subtype as well as all the other subtypes.

This post hoc analysis of the previously reported main SCOT-HEART trial (N Engl J Med. 2018 Sep 6;379[10]:924-933) included 1,769 patients with stable chest pain randomized to standard care with or without CCTA guidance and followed for a median of 4.7 years, during which 41 patients had a fatal or nonfatal MI. At enrollment, 37% of participants had normal coronary arteries, 38% had nonobstructive coronary artery disease (CAD), and the remainder had obstructive CAD.

In a multivariate analysis, low-attenuation noncalcified plaque burden was the strongest predictor of future MI, with an adjusted hazard ratio of 1.6 per doubling. This metric was strongly correlated with coronary artery calcium score, underscoring the limited value of doing noncontrast CT in order to determine a coronary artery calcium score when CCTA is performed.

Low-attenuation plaque burden correlated very strongly with angiographic severity of stenosis, and only weakly with cardiovascular risk score, perhaps explaining the poor prognostic performance of cardiovascular risk scores in SCOT-HEART and other studies, according to Dr. Williams.

Patients with a low-attenuation noncalcified plaque burden greater than 4% in their coronary tree were 4.7 times more likely to have a subsequent MI than were those with a lesser burden. The predictive power was even greater in patients with nonobstructive CAD, where a low-attenuation noncalcified plaque burden in excess of 4% conferred a 6.6-fold greater likelihood of fatal or nonfatal MI, she observed.

Two things need to happen before measurement of low-attenuation noncalcified plaque via CCTA to predict MI risk is ready to be adopted in routine clinical practice, according to Dr. Williams. These SCOT-HEART results need to be validated in other cohorts, a process now underway in the SCOT-HEART 2 trial and other studies. Also, improved software incorporating machine learning is needed in order to speed up the semiautomated analysis of plaque subtypes, which now takes 20-30 minutes.

Dr. Williams reported having no financial conflicts regarding her study, funded by the National Health Service.

In conjunction with her virtual presentation at ACC 2020, the SCOT-HEART study results were published online (Circulation. 2020 Mar 16. doi: 10.1161/CIRCULATIONAHA.119.044720. [Epub ahead of print]).

bjancin@mdedge.com

SOURCE: Williams MC et al. ACC 2020, Abstract 909-06.

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

mzoler@mdedge.com

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

mzoler@mdedge.com

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

mzoler@mdedge.com

Moderate, daily coffee consumption had no apparent adverse effect for triggering incident heart arrhythmias, and even linked with a small but statistically significant drop in arrhythmias in an analysis of prospectively collected data from nearly 300,000 U.K. residents.

“In this large, population-based, prospective study, moderate habitual coffee drinking was associated with a lower risk of arrhythmia,” EunJeong Kim, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

Her analysis found that on average each additional daily cup of coffee that people said they drank reduced the incidence of arrhythmic episodes by a statistically significant 3%, compared with those who drank fewer daily cups. The relationship held for people who reported drinking as many as five or six cups of coffee daily.

“The main message of our study is that it does not appear to be deleterious to continue with moderate amounts of habitual coffee intake regarding a risk of overall arrhythmia,” said Dr. Kim, a cardiac electrophysiologist at the University of California, San Francisco.

Evidence builds for coffee’s safety

The finding adds to a substantial existing evidence base documenting the safety of moderate, habitual coffee drinking when it comes to heart rhythms. For example, a recent report from the Physicians Health Study of nearly 19,000 American men showed a statistically significant decrease in the incidence of atrial fibrillation during an average follow-up of 9 years among men who reported drinking one to three cups of coffee daily (J Am Heart Assoc. 2019 Aug 6;8[15]:e011346). In addition, a recent review of several reports found that “mild-to-moderate habitual consumption of caffeinated beverages, particularly a daily intake of 2-3 cups of coffee or tea, appears to be safe across a broad range of cardiovascular conditions, and may even be beneficial with respect to diabetes mellitus, atherosclerosis, heart failure, arrhythmia and total mortality,” but also concluded that “acute consumption of high doses of caffeine, particularly in the form of energy drinks, is best avoided”(Trends Cardiovasc Med. 2019 Aug;29[6]:345-50). Specifically about cardiac arrhythmias, the review said “while caffeine is commonly considered a trigger for arrhythmias by physicians and patients alike there is minimal evidence to support this misconception. Rather caffeine is associated with a mild reduction in the incidence of atrial fibrillation in observational studies.”

“There has been a lot of public interest about a possible association of caffeine and arrhythmias,” but an adverse effect from daily consumption of a moderate amount of coffee “is more legend and anecdote than fact based,” commented Andrew D. Krahn, MD, an electrophysiologist, professor of medicine, and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. “Increasingly we’re finding that there really is nothing here” when the proarrhythmic effects of moderate coffee undergo detailed assessment, he said in an interview.
 

What the study did

The study run by Dr. Kim and her associates used prospectively collected data from 296,227 participants in the UK Biobank during 2006-2016 who had complete data on their coffee intake and for the other covariables used in the analysis. During an average 5.25 years of follow-up, these people had more than 13,000 incident arrhythmic events, including 4,748 episodes of atrial fibrillation or flutter and 798 supraventricular tachycardia events, as well as fewer numbers of ventricular arrhythmias and many episodes of less clinically relevant events like skipped beats.

The multivariate analysis the researchers ran controlled for more than 20 demographic, lifestyle, and clinical variables, including adjustment for tea intake but not for consumption of other caffeine-containing drinks.

The adjusted analysis showed an average, statistically significant 3% incremental drop in both all incident arrhythmias and in incident atrial fibrillation episodes for each additional cup of coffee drunk a day, for up to 6 daily cups.

A strength of this study is that it included a large number of people, Dr. Krahn noted, and “the UK Biobank includes a very diverse, community-based sample” of people, said Dr. Kim. The analysis excluded people with prevalent arrhythmia at baseline, so the study couldn’t address the impact of coffee consumption in this setting. A limitation of the study is that participants in the UK Biobank are all volunteers, which could result in a selection bias, Dr. Krahn said.
 

What it tells us

While the main message from the results is that moderate daily coffee drinking is not arrhythmogenic, “it is also possible that coffee is beneficial” based on the small but statistically significant decline in new-onset events, Dr. Kim added. “Multiple studies revealed that caffeine and potentially other constituents in coffee have antioxidant and anti-inflammatory properties. Multiple studies have reported the potential benefit of coffee in multiple chronic medical conditions such as cardiovascular disease, diabetes, and certain types of cancers, as well as for all-cause mortality.”

“It’s plausible that a moderate amount of coffee intake a day will not cause big physiologic changes, and moderate coffee intake may link with other characteristics” of moderate behavior that result in average or better than average outcomes, Dr. Krahn commented. “These results add to the existing data in a different and large population,” which strengthens the case that moderate coffee intake isn’t harmful, he said.

The study received no commercial funding. Dr. Kim and Dr. Krahn had no disclosures. The senior author on Dr. Kim’s study, Gregory M. Marcus, MD, has been a consultant to Johnson & Johnson and Incardia, has an equity interest in Incardia, and has received research funding from Baylis, Eight Sleep, and Medtronic.

mzoler@mdedge.com

SOURCE: Kim EJ et al. Heart Rhythm 2020, abstract D-PO01-032.

Moderate, daily coffee consumption had no apparent adverse effect for triggering incident heart arrhythmias, and even linked with a small but statistically significant drop in arrhythmias in an analysis of prospectively collected data from nearly 300,000 U.K. residents.

“In this large, population-based, prospective study, moderate habitual coffee drinking was associated with a lower risk of arrhythmia,” EunJeong Kim, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

Her analysis found that on average each additional daily cup of coffee that people said they drank reduced the incidence of arrhythmic episodes by a statistically significant 3%, compared with those who drank fewer daily cups. The relationship held for people who reported drinking as many as five or six cups of coffee daily.

“The main message of our study is that it does not appear to be deleterious to continue with moderate amounts of habitual coffee intake regarding a risk of overall arrhythmia,” said Dr. Kim, a cardiac electrophysiologist at the University of California, San Francisco.

Evidence builds for coffee’s safety

The finding adds to a substantial existing evidence base documenting the safety of moderate, habitual coffee drinking when it comes to heart rhythms. For example, a recent report from the Physicians Health Study of nearly 19,000 American men showed a statistically significant decrease in the incidence of atrial fibrillation during an average follow-up of 9 years among men who reported drinking one to three cups of coffee daily (J Am Heart Assoc. 2019 Aug 6;8[15]:e011346). In addition, a recent review of several reports found that “mild-to-moderate habitual consumption of caffeinated beverages, particularly a daily intake of 2-3 cups of coffee or tea, appears to be safe across a broad range of cardiovascular conditions, and may even be beneficial with respect to diabetes mellitus, atherosclerosis, heart failure, arrhythmia and total mortality,” but also concluded that “acute consumption of high doses of caffeine, particularly in the form of energy drinks, is best avoided”(Trends Cardiovasc Med. 2019 Aug;29[6]:345-50). Specifically about cardiac arrhythmias, the review said “while caffeine is commonly considered a trigger for arrhythmias by physicians and patients alike there is minimal evidence to support this misconception. Rather caffeine is associated with a mild reduction in the incidence of atrial fibrillation in observational studies.”

“There has been a lot of public interest about a possible association of caffeine and arrhythmias,” but an adverse effect from daily consumption of a moderate amount of coffee “is more legend and anecdote than fact based,” commented Andrew D. Krahn, MD, an electrophysiologist, professor of medicine, and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. “Increasingly we’re finding that there really is nothing here” when the proarrhythmic effects of moderate coffee undergo detailed assessment, he said in an interview.
 

What the study did

The study run by Dr. Kim and her associates used prospectively collected data from 296,227 participants in the UK Biobank during 2006-2016 who had complete data on their coffee intake and for the other covariables used in the analysis. During an average 5.25 years of follow-up, these people had more than 13,000 incident arrhythmic events, including 4,748 episodes of atrial fibrillation or flutter and 798 supraventricular tachycardia events, as well as fewer numbers of ventricular arrhythmias and many episodes of less clinically relevant events like skipped beats.

The multivariate analysis the researchers ran controlled for more than 20 demographic, lifestyle, and clinical variables, including adjustment for tea intake but not for consumption of other caffeine-containing drinks.

The adjusted analysis showed an average, statistically significant 3% incremental drop in both all incident arrhythmias and in incident atrial fibrillation episodes for each additional cup of coffee drunk a day, for up to 6 daily cups.

A strength of this study is that it included a large number of people, Dr. Krahn noted, and “the UK Biobank includes a very diverse, community-based sample” of people, said Dr. Kim. The analysis excluded people with prevalent arrhythmia at baseline, so the study couldn’t address the impact of coffee consumption in this setting. A limitation of the study is that participants in the UK Biobank are all volunteers, which could result in a selection bias, Dr. Krahn said.
 

What it tells us

While the main message from the results is that moderate daily coffee drinking is not arrhythmogenic, “it is also possible that coffee is beneficial” based on the small but statistically significant decline in new-onset events, Dr. Kim added. “Multiple studies revealed that caffeine and potentially other constituents in coffee have antioxidant and anti-inflammatory properties. Multiple studies have reported the potential benefit of coffee in multiple chronic medical conditions such as cardiovascular disease, diabetes, and certain types of cancers, as well as for all-cause mortality.”

“It’s plausible that a moderate amount of coffee intake a day will not cause big physiologic changes, and moderate coffee intake may link with other characteristics” of moderate behavior that result in average or better than average outcomes, Dr. Krahn commented. “These results add to the existing data in a different and large population,” which strengthens the case that moderate coffee intake isn’t harmful, he said.

The study received no commercial funding. Dr. Kim and Dr. Krahn had no disclosures. The senior author on Dr. Kim’s study, Gregory M. Marcus, MD, has been a consultant to Johnson & Johnson and Incardia, has an equity interest in Incardia, and has received research funding from Baylis, Eight Sleep, and Medtronic.

mzoler@mdedge.com

SOURCE: Kim EJ et al. Heart Rhythm 2020, abstract D-PO01-032.

Moderate, daily coffee consumption had no apparent adverse effect for triggering incident heart arrhythmias, and even linked with a small but statistically significant drop in arrhythmias in an analysis of prospectively collected data from nearly 300,000 U.K. residents.

“In this large, population-based, prospective study, moderate habitual coffee drinking was associated with a lower risk of arrhythmia,” EunJeong Kim, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

Her analysis found that on average each additional daily cup of coffee that people said they drank reduced the incidence of arrhythmic episodes by a statistically significant 3%, compared with those who drank fewer daily cups. The relationship held for people who reported drinking as many as five or six cups of coffee daily.

“The main message of our study is that it does not appear to be deleterious to continue with moderate amounts of habitual coffee intake regarding a risk of overall arrhythmia,” said Dr. Kim, a cardiac electrophysiologist at the University of California, San Francisco.

Evidence builds for coffee’s safety

The finding adds to a substantial existing evidence base documenting the safety of moderate, habitual coffee drinking when it comes to heart rhythms. For example, a recent report from the Physicians Health Study of nearly 19,000 American men showed a statistically significant decrease in the incidence of atrial fibrillation during an average follow-up of 9 years among men who reported drinking one to three cups of coffee daily (J Am Heart Assoc. 2019 Aug 6;8[15]:e011346). In addition, a recent review of several reports found that “mild-to-moderate habitual consumption of caffeinated beverages, particularly a daily intake of 2-3 cups of coffee or tea, appears to be safe across a broad range of cardiovascular conditions, and may even be beneficial with respect to diabetes mellitus, atherosclerosis, heart failure, arrhythmia and total mortality,” but also concluded that “acute consumption of high doses of caffeine, particularly in the form of energy drinks, is best avoided”(Trends Cardiovasc Med. 2019 Aug;29[6]:345-50). Specifically about cardiac arrhythmias, the review said “while caffeine is commonly considered a trigger for arrhythmias by physicians and patients alike there is minimal evidence to support this misconception. Rather caffeine is associated with a mild reduction in the incidence of atrial fibrillation in observational studies.”

“There has been a lot of public interest about a possible association of caffeine and arrhythmias,” but an adverse effect from daily consumption of a moderate amount of coffee “is more legend and anecdote than fact based,” commented Andrew D. Krahn, MD, an electrophysiologist, professor of medicine, and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. “Increasingly we’re finding that there really is nothing here” when the proarrhythmic effects of moderate coffee undergo detailed assessment, he said in an interview.
 

What the study did

The study run by Dr. Kim and her associates used prospectively collected data from 296,227 participants in the UK Biobank during 2006-2016 who had complete data on their coffee intake and for the other covariables used in the analysis. During an average 5.25 years of follow-up, these people had more than 13,000 incident arrhythmic events, including 4,748 episodes of atrial fibrillation or flutter and 798 supraventricular tachycardia events, as well as fewer numbers of ventricular arrhythmias and many episodes of less clinically relevant events like skipped beats.

The multivariate analysis the researchers ran controlled for more than 20 demographic, lifestyle, and clinical variables, including adjustment for tea intake but not for consumption of other caffeine-containing drinks.

The adjusted analysis showed an average, statistically significant 3% incremental drop in both all incident arrhythmias and in incident atrial fibrillation episodes for each additional cup of coffee drunk a day, for up to 6 daily cups.

A strength of this study is that it included a large number of people, Dr. Krahn noted, and “the UK Biobank includes a very diverse, community-based sample” of people, said Dr. Kim. The analysis excluded people with prevalent arrhythmia at baseline, so the study couldn’t address the impact of coffee consumption in this setting. A limitation of the study is that participants in the UK Biobank are all volunteers, which could result in a selection bias, Dr. Krahn said.
 

What it tells us

While the main message from the results is that moderate daily coffee drinking is not arrhythmogenic, “it is also possible that coffee is beneficial” based on the small but statistically significant decline in new-onset events, Dr. Kim added. “Multiple studies revealed that caffeine and potentially other constituents in coffee have antioxidant and anti-inflammatory properties. Multiple studies have reported the potential benefit of coffee in multiple chronic medical conditions such as cardiovascular disease, diabetes, and certain types of cancers, as well as for all-cause mortality.”

“It’s plausible that a moderate amount of coffee intake a day will not cause big physiologic changes, and moderate coffee intake may link with other characteristics” of moderate behavior that result in average or better than average outcomes, Dr. Krahn commented. “These results add to the existing data in a different and large population,” which strengthens the case that moderate coffee intake isn’t harmful, he said.

The study received no commercial funding. Dr. Kim and Dr. Krahn had no disclosures. The senior author on Dr. Kim’s study, Gregory M. Marcus, MD, has been a consultant to Johnson & Johnson and Incardia, has an equity interest in Incardia, and has received research funding from Baylis, Eight Sleep, and Medtronic.

mzoler@mdedge.com

SOURCE: Kim EJ et al. Heart Rhythm 2020, abstract D-PO01-032.

Adolescents with obesity, type 2 diabetes, and systolic hypertension show accelerated development of signs of atherosclerosis significantly greater than their normal-weight peers, according to a longitudinal study published online in the Journal of the American Heart Association.

The study evaluated 448 adolescents over 5 years for changes in a variety of metrics to determine changes in arterial structure, including carotid intima media thickness (cIMT), carotid-femoral pulse-wave velocity (PWV), and augmentation index (Aix). The average age of the study group was 17.6 years. The three study groups broke down accordingly: 141 with normal weight, 156 with obesity, and 151 with type 2 diabetes. Patients were evaluated at baseline and 5 years later.

“The presence of obesity and especially type 2 diabetes in adolescents accelerates the early vascular aging process associated with several key risk factors,” wrote Justin R. Ryder, PhD, an assistant professor of pediatrics at the University of Minnesota, Minneapolis, and colleagues.

The researchers also noted that systolic hypertension was associated with changes in cIMT and arterial stiffness comparable to obesity and diabetes. “These data add further evidence underscoring the importance of efforts targeting prevention and treatment of obesity, type 2 diabetes, and elevated blood pressure among youth, with a goal of delaying and/or preventing the progression of early vascular aging,” Dr. Ryder and colleagues wrote.

Obese patients, when compared with normal-weight participants, had the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.02 mm, internal cIMT by 0.03 mm, and PWV carotid-femoral by 0.38 m/sec, all statistically significant differences. Patients with diabetes, compared with normal-weight participants, registered the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.06 mm, internal cIMT by 0.04 mm, Aix by 4.67%, and PWV carotid-femoral by 0.74 m/sec. All differences were highly significant at P less than .001.

The results also showed that higher baseline systolic blood pressure was associated with significantly greater average increases in the following factors: common cIMT by 0.007 mm, bulb cIMT by 0.009 mm, internal cIMT by 0.008 mm, and PWV carotid-femoral by 0.66 m/sec.

Drilling down into the data, the study reported that males had greater increases in bulb cIMT and incremental elastic modulus as well as reduced Aix, compared with females. Nonwhites also had greater increases in bulb cIMT than did whites. Age was associated with greater increases in bulb and internal cIMT and Aix.

“Our data support the concept that male sex is an independent and primary risk factor for accelerated early vascular aging,” Dr. Ryder and colleagues wrote. The study also determined that type 2 diabetes is a more prominent risk factor than obesity for early vascular aging.

The size of the study population, specifically adolescents with diabetes, is a study strength, Dr. Ryder and colleagues noted. Other strengths they pointed to are the 5-year duration and the robust panel of noninvasive measures, although not using hard cardiovascular outcomes is an acknowledged limitation.

“It should also be noted that many of the youth with type 2 diabetes were on medications for glycemic control, lipids, and/or blood pressure regulation,” Dr. Ryder and colleagues wrote. “Despite this, the vascular profiles worsened over time.”

The study showed “a really significant change” in the carotid anatomy in adolescents with obesity and type 2 diabetes over 5 years, Robert Eckel, MD, professor at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Notably, the PWV is not just anatomy; now we’re talking about function. In other words, the augmentation index and PWV will assess the compliance of the artery.”

The findings suggest that atherosclerosis begins with thickening of the arterial walls. “The question is, is thickness reversible?” Dr. Eckel said. “It’s probably not very reversible, so these are early changes that ultimately in the middle years or latter years are associated with major cardiovascular disease.”

They key lesson from the study, Dr. Eckel noted, is to “prevent obesity. If you prevent obesity in the teenage years, you basically prevent diabetes.”

Dr. Ryder disclosed receiving support from Boehringer Ingelheim in the form of drug/placebo. The National Institutes of Health provided funding. Dr. Eckel has no relevant relationships to disclose.

SOURCE: Ryder JR et al. J Am Heart Assoc. 2020 May 6:e014891. doi: 10.1161/JAHA.119.014891.

Adolescents with obesity, type 2 diabetes, and systolic hypertension show accelerated development of signs of atherosclerosis significantly greater than their normal-weight peers, according to a longitudinal study published online in the Journal of the American Heart Association.

The study evaluated 448 adolescents over 5 years for changes in a variety of metrics to determine changes in arterial structure, including carotid intima media thickness (cIMT), carotid-femoral pulse-wave velocity (PWV), and augmentation index (Aix). The average age of the study group was 17.6 years. The three study groups broke down accordingly: 141 with normal weight, 156 with obesity, and 151 with type 2 diabetes. Patients were evaluated at baseline and 5 years later.

“The presence of obesity and especially type 2 diabetes in adolescents accelerates the early vascular aging process associated with several key risk factors,” wrote Justin R. Ryder, PhD, an assistant professor of pediatrics at the University of Minnesota, Minneapolis, and colleagues.

The researchers also noted that systolic hypertension was associated with changes in cIMT and arterial stiffness comparable to obesity and diabetes. “These data add further evidence underscoring the importance of efforts targeting prevention and treatment of obesity, type 2 diabetes, and elevated blood pressure among youth, with a goal of delaying and/or preventing the progression of early vascular aging,” Dr. Ryder and colleagues wrote.

Obese patients, when compared with normal-weight participants, had the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.02 mm, internal cIMT by 0.03 mm, and PWV carotid-femoral by 0.38 m/sec, all statistically significant differences. Patients with diabetes, compared with normal-weight participants, registered the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.06 mm, internal cIMT by 0.04 mm, Aix by 4.67%, and PWV carotid-femoral by 0.74 m/sec. All differences were highly significant at P less than .001.

The results also showed that higher baseline systolic blood pressure was associated with significantly greater average increases in the following factors: common cIMT by 0.007 mm, bulb cIMT by 0.009 mm, internal cIMT by 0.008 mm, and PWV carotid-femoral by 0.66 m/sec.

Drilling down into the data, the study reported that males had greater increases in bulb cIMT and incremental elastic modulus as well as reduced Aix, compared with females. Nonwhites also had greater increases in bulb cIMT than did whites. Age was associated with greater increases in bulb and internal cIMT and Aix.

“Our data support the concept that male sex is an independent and primary risk factor for accelerated early vascular aging,” Dr. Ryder and colleagues wrote. The study also determined that type 2 diabetes is a more prominent risk factor than obesity for early vascular aging.

The size of the study population, specifically adolescents with diabetes, is a study strength, Dr. Ryder and colleagues noted. Other strengths they pointed to are the 5-year duration and the robust panel of noninvasive measures, although not using hard cardiovascular outcomes is an acknowledged limitation.

“It should also be noted that many of the youth with type 2 diabetes were on medications for glycemic control, lipids, and/or blood pressure regulation,” Dr. Ryder and colleagues wrote. “Despite this, the vascular profiles worsened over time.”

The study showed “a really significant change” in the carotid anatomy in adolescents with obesity and type 2 diabetes over 5 years, Robert Eckel, MD, professor at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Notably, the PWV is not just anatomy; now we’re talking about function. In other words, the augmentation index and PWV will assess the compliance of the artery.”

The findings suggest that atherosclerosis begins with thickening of the arterial walls. “The question is, is thickness reversible?” Dr. Eckel said. “It’s probably not very reversible, so these are early changes that ultimately in the middle years or latter years are associated with major cardiovascular disease.”

They key lesson from the study, Dr. Eckel noted, is to “prevent obesity. If you prevent obesity in the teenage years, you basically prevent diabetes.”

Dr. Ryder disclosed receiving support from Boehringer Ingelheim in the form of drug/placebo. The National Institutes of Health provided funding. Dr. Eckel has no relevant relationships to disclose.

SOURCE: Ryder JR et al. J Am Heart Assoc. 2020 May 6:e014891. doi: 10.1161/JAHA.119.014891.

Adolescents with obesity, type 2 diabetes, and systolic hypertension show accelerated development of signs of atherosclerosis significantly greater than their normal-weight peers, according to a longitudinal study published online in the Journal of the American Heart Association.

The study evaluated 448 adolescents over 5 years for changes in a variety of metrics to determine changes in arterial structure, including carotid intima media thickness (cIMT), carotid-femoral pulse-wave velocity (PWV), and augmentation index (Aix). The average age of the study group was 17.6 years. The three study groups broke down accordingly: 141 with normal weight, 156 with obesity, and 151 with type 2 diabetes. Patients were evaluated at baseline and 5 years later.

“The presence of obesity and especially type 2 diabetes in adolescents accelerates the early vascular aging process associated with several key risk factors,” wrote Justin R. Ryder, PhD, an assistant professor of pediatrics at the University of Minnesota, Minneapolis, and colleagues.

The researchers also noted that systolic hypertension was associated with changes in cIMT and arterial stiffness comparable to obesity and diabetes. “These data add further evidence underscoring the importance of efforts targeting prevention and treatment of obesity, type 2 diabetes, and elevated blood pressure among youth, with a goal of delaying and/or preventing the progression of early vascular aging,” Dr. Ryder and colleagues wrote.

Obese patients, when compared with normal-weight participants, had the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.02 mm, internal cIMT by 0.03 mm, and PWV carotid-femoral by 0.38 m/sec, all statistically significant differences. Patients with diabetes, compared with normal-weight participants, registered the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.06 mm, internal cIMT by 0.04 mm, Aix by 4.67%, and PWV carotid-femoral by 0.74 m/sec. All differences were highly significant at P less than .001.

The results also showed that higher baseline systolic blood pressure was associated with significantly greater average increases in the following factors: common cIMT by 0.007 mm, bulb cIMT by 0.009 mm, internal cIMT by 0.008 mm, and PWV carotid-femoral by 0.66 m/sec.

Drilling down into the data, the study reported that males had greater increases in bulb cIMT and incremental elastic modulus as well as reduced Aix, compared with females. Nonwhites also had greater increases in bulb cIMT than did whites. Age was associated with greater increases in bulb and internal cIMT and Aix.

“Our data support the concept that male sex is an independent and primary risk factor for accelerated early vascular aging,” Dr. Ryder and colleagues wrote. The study also determined that type 2 diabetes is a more prominent risk factor than obesity for early vascular aging.

The size of the study population, specifically adolescents with diabetes, is a study strength, Dr. Ryder and colleagues noted. Other strengths they pointed to are the 5-year duration and the robust panel of noninvasive measures, although not using hard cardiovascular outcomes is an acknowledged limitation.

“It should also be noted that many of the youth with type 2 diabetes were on medications for glycemic control, lipids, and/or blood pressure regulation,” Dr. Ryder and colleagues wrote. “Despite this, the vascular profiles worsened over time.”

The study showed “a really significant change” in the carotid anatomy in adolescents with obesity and type 2 diabetes over 5 years, Robert Eckel, MD, professor at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Notably, the PWV is not just anatomy; now we’re talking about function. In other words, the augmentation index and PWV will assess the compliance of the artery.”

The findings suggest that atherosclerosis begins with thickening of the arterial walls. “The question is, is thickness reversible?” Dr. Eckel said. “It’s probably not very reversible, so these are early changes that ultimately in the middle years or latter years are associated with major cardiovascular disease.”

They key lesson from the study, Dr. Eckel noted, is to “prevent obesity. If you prevent obesity in the teenage years, you basically prevent diabetes.”

Dr. Ryder disclosed receiving support from Boehringer Ingelheim in the form of drug/placebo. The National Institutes of Health provided funding. Dr. Eckel has no relevant relationships to disclose.

SOURCE: Ryder JR et al. J Am Heart Assoc. 2020 May 6:e014891. doi: 10.1161/JAHA.119.014891.

The American Heart Association (AHA) has awarded $1.2 million in grants to teams at 11 institutions to study COVID-19 effects on the cardiovascular and cerebrovascular systems. Work is set to start in June, with findings reported in as few as 6 months. The Cleveland Clinic will coordinate the efforts, collecting and disseminating the findings.

There were more than 750 research proposals in less than a month after the association announced its COVID-19 and Its Cardiovascular Impact Rapid Response Grant initiative.

“We were just blown away and so impressed to see this level of interest and commitment from the teams submitting such thorough proposals so quickly,” AHA President Robert Harrington, MD, chair of the department of medicine at Stanford (Calif.) University, said in a press statement. “There’s so much we don’t know about this unique coronavirus, and we continue to see emerging complications affecting both heart and brain health for which we desperately need answers and we need them quickly.”

The projects include the following:

• A Comprehensive Assessment of Arterial and Venous Thrombotic Complications in Patients with COVID-19, led by Columbia University, New York City.
• Repurposing Drugs for Treatment of Cardiomyopathy Caused by Coronavirus-2 (SARS-CoV-2), led by Brigham and Women’s Hospital and Harvard Medical School, Boston.
• Risk of Severe Morbidity and Mortality of Coronavirus Disease 2019 (COVID-19) Among Patients Taking Antihypertensive Medications, led by Kaiser Permanente Southern California.
• Deep Learning Using Chest Radiographs to Predict COVID-19 Cardiopulmonary Risk, led by Massachusetts General Hospital, Boston.
• Cardiovascular Outcomes and Biomarker Titrated Corticosteroid Dosing for SARS COV-2 (COVID-19): A Randomized Controlled Trial, led by the Mayo Clinic, Rochester Minn.
• Outcomes for Patients With Hypertension, Diabetes, and Heart Disease in the Coronavirus Pandemic: Impact of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Treatment, led by Stanford University.
• Rapid COVID-19-on-A-Chip to Screen Competitive Targets for SARS-CoV-2 Spike Binding Sites, led by University of California, Los Angeles.
• COVID-19 Infection, African American Women and Cardiovascular Health, led by University of California, San Francisco.
• Myocardial Virus and Gene Expression in SARS CoV-2 Positive Patients with Clinically Important Myocardial Dysfunction, led by the University of Colorado, Aurora.
• The Role of the Platelet in Mediating Cardiovascular Disease in SARS-CoV-2 Infection, led by the University of Massachusetts, Worcester.
• Harnessing Glycomics to Understand Myocardial Injury in COVID-19, led by the University of Nebraska Medical Center, Omaha.

The AHA also awarded $800,000 for short-term projects to members of its new Health Technologies & Innovation Strategically Focused Research Network.

Cincinnati Children’s Hospital will assess the use of ejection fraction to triage COVID-19 patients; Johns Hopkins University, Baltimore, will assess smartphones for “virtual check-in” for stroke symptoms; Stanford will assess digital tracking of COVID-19 patients with cardiovascular complications; and the University of Michigan, Ann Arbor, will assess a system to track physiological and cardiovascular consequences of the infection.

aotto@mdedge.com

The American Heart Association (AHA) has awarded $1.2 million in grants to teams at 11 institutions to study COVID-19 effects on the cardiovascular and cerebrovascular systems. Work is set to start in June, with findings reported in as few as 6 months. The Cleveland Clinic will coordinate the efforts, collecting and disseminating the findings.

There were more than 750 research proposals in less than a month after the association announced its COVID-19 and Its Cardiovascular Impact Rapid Response Grant initiative.

“We were just blown away and so impressed to see this level of interest and commitment from the teams submitting such thorough proposals so quickly,” AHA President Robert Harrington, MD, chair of the department of medicine at Stanford (Calif.) University, said in a press statement. “There’s so much we don’t know about this unique coronavirus, and we continue to see emerging complications affecting both heart and brain health for which we desperately need answers and we need them quickly.”

The projects include the following:

• A Comprehensive Assessment of Arterial and Venous Thrombotic Complications in Patients with COVID-19, led by Columbia University, New York City.
• Repurposing Drugs for Treatment of Cardiomyopathy Caused by Coronavirus-2 (SARS-CoV-2), led by Brigham and Women’s Hospital and Harvard Medical School, Boston.
• Risk of Severe Morbidity and Mortality of Coronavirus Disease 2019 (COVID-19) Among Patients Taking Antihypertensive Medications, led by Kaiser Permanente Southern California.
• Deep Learning Using Chest Radiographs to Predict COVID-19 Cardiopulmonary Risk, led by Massachusetts General Hospital, Boston.
• Cardiovascular Outcomes and Biomarker Titrated Corticosteroid Dosing for SARS COV-2 (COVID-19): A Randomized Controlled Trial, led by the Mayo Clinic, Rochester Minn.
• Outcomes for Patients With Hypertension, Diabetes, and Heart Disease in the Coronavirus Pandemic: Impact of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Treatment, led by Stanford University.
• Rapid COVID-19-on-A-Chip to Screen Competitive Targets for SARS-CoV-2 Spike Binding Sites, led by University of California, Los Angeles.
• COVID-19 Infection, African American Women and Cardiovascular Health, led by University of California, San Francisco.
• Myocardial Virus and Gene Expression in SARS CoV-2 Positive Patients with Clinically Important Myocardial Dysfunction, led by the University of Colorado, Aurora.
• The Role of the Platelet in Mediating Cardiovascular Disease in SARS-CoV-2 Infection, led by the University of Massachusetts, Worcester.
• Harnessing Glycomics to Understand Myocardial Injury in COVID-19, led by the University of Nebraska Medical Center, Omaha.

The AHA also awarded $800,000 for short-term projects to members of its new Health Technologies & Innovation Strategically Focused Research Network.

Cincinnati Children’s Hospital will assess the use of ejection fraction to triage COVID-19 patients; Johns Hopkins University, Baltimore, will assess smartphones for “virtual check-in” for stroke symptoms; Stanford will assess digital tracking of COVID-19 patients with cardiovascular complications; and the University of Michigan, Ann Arbor, will assess a system to track physiological and cardiovascular consequences of the infection.

aotto@mdedge.com

The American Heart Association (AHA) has awarded $1.2 million in grants to teams at 11 institutions to study COVID-19 effects on the cardiovascular and cerebrovascular systems. Work is set to start in June, with findings reported in as few as 6 months. The Cleveland Clinic will coordinate the efforts, collecting and disseminating the findings.

There were more than 750 research proposals in less than a month after the association announced its COVID-19 and Its Cardiovascular Impact Rapid Response Grant initiative.

“We were just blown away and so impressed to see this level of interest and commitment from the teams submitting such thorough proposals so quickly,” AHA President Robert Harrington, MD, chair of the department of medicine at Stanford (Calif.) University, said in a press statement. “There’s so much we don’t know about this unique coronavirus, and we continue to see emerging complications affecting both heart and brain health for which we desperately need answers and we need them quickly.”

The projects include the following:

• A Comprehensive Assessment of Arterial and Venous Thrombotic Complications in Patients with COVID-19, led by Columbia University, New York City.
• Repurposing Drugs for Treatment of Cardiomyopathy Caused by Coronavirus-2 (SARS-CoV-2), led by Brigham and Women’s Hospital and Harvard Medical School, Boston.
• Risk of Severe Morbidity and Mortality of Coronavirus Disease 2019 (COVID-19) Among Patients Taking Antihypertensive Medications, led by Kaiser Permanente Southern California.
• Deep Learning Using Chest Radiographs to Predict COVID-19 Cardiopulmonary Risk, led by Massachusetts General Hospital, Boston.
• Cardiovascular Outcomes and Biomarker Titrated Corticosteroid Dosing for SARS COV-2 (COVID-19): A Randomized Controlled Trial, led by the Mayo Clinic, Rochester Minn.
• Outcomes for Patients With Hypertension, Diabetes, and Heart Disease in the Coronavirus Pandemic: Impact of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Treatment, led by Stanford University.
• Rapid COVID-19-on-A-Chip to Screen Competitive Targets for SARS-CoV-2 Spike Binding Sites, led by University of California, Los Angeles.
• COVID-19 Infection, African American Women and Cardiovascular Health, led by University of California, San Francisco.
• Myocardial Virus and Gene Expression in SARS CoV-2 Positive Patients with Clinically Important Myocardial Dysfunction, led by the University of Colorado, Aurora.
• The Role of the Platelet in Mediating Cardiovascular Disease in SARS-CoV-2 Infection, led by the University of Massachusetts, Worcester.
• Harnessing Glycomics to Understand Myocardial Injury in COVID-19, led by the University of Nebraska Medical Center, Omaha.

The AHA also awarded $800,000 for short-term projects to members of its new Health Technologies & Innovation Strategically Focused Research Network.

Cincinnati Children’s Hospital will assess the use of ejection fraction to triage COVID-19 patients; Johns Hopkins University, Baltimore, will assess smartphones for “virtual check-in” for stroke symptoms; Stanford will assess digital tracking of COVID-19 patients with cardiovascular complications; and the University of Michigan, Ann Arbor, will assess a system to track physiological and cardiovascular consequences of the infection.

aotto@mdedge.com

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

Four more studies of the relationship of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with COVID-19 have been published in the past few days in top-tier peer-reviewed journals, and on the whole, the data are reassuring.

Three of the new studies were published in the New England Journal of Medicine on May 1, and one study was published in JAMA Cardiology on May 5.

Although all the studies are observational in design and have some confounding factors, overall, the results do not suggest that continued use of ACE inhibitors and ARBs causes harm. However, there are some contradictory findings in secondary analyses regarding possible differences in the effects of the two drug classes.

Providing commentary, John McMurray, MD, professor of medical cardiology at the University of Glasgow, said: “The overall picture seems to suggest no increase in risk of adverse outcomes in patients taking renin-angiotensin system [RAS] blockers ― but with lots of caveats: These are all observational rather than randomized studies, and there may be residual or unmeasured confounding.”
 

Was it ‘Much ado about nothing’?

Franz Messerli, MD, professor of medicine at the University of Bern (Switzerland), added: “Given this state of the art, I am inclined to consider RAS blockade and COVID-19 – despite all the hype in the news media – as much ado about nothing.”

But both Dr. McMurray and Dr. Messerli said they were intrigued about possible differences in the effects of ACE inhibitors and ARBs that some of the new results suggest.

In one study, a team led by Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center, Boston, analyzed data from 8,910 patients with COVID-19 admitted to 169 hospitals in Asia, Europe, and North America who had either died in the hospital (5.8%) or survived to hospital discharge (94.2%).

In multivariate logistic-regression analysis, age greater than 65 years, coronary artery disease, congestive heart failure, history of cardiac arrhythmia, chronic obstructive pulmonary disease, and current smoking were associated with an increased risk for in-hospital death. Female sex was associated with a decreased risk. Neither ACE inhibitors nor ARBs were associated with an increased risk for in-hospital death.

In fact, ACE inhibitors were associated with a significant reduction in mortality (odds ratio, 0.33), as were statins (OR, 0.35).

The authors, however, stressed that these observations about reduced mortality with ACE inhibitors and statins “should be considered with extreme caution.”

“Because our study was not a randomized, controlled trial, we cannot exclude the possibility of confounding. In addition, we examined relationships between many variables and in-hospital death, and no primary hypothesis was prespecified; these factors increased the probability of chance associations being found. Therefore, a cause-and-effect relationship between drug therapy and survival should not be inferred,” they wrote.

A secondary analysis that was restricted to patients with hypertension (those for whom an ACE inhibitor or an ARB would be indicated) also did not show harm.

A second study published in the New England Journal of Medicine had a case-control design. The authors, led by Giuseppe Mancia, MD, of the University of Milano-Bicocca (Italy), compared 6,272 patients with confirmed COVID-19 (case patients) with 30,759 control persons who were matched according to age, sex, and municipality of residence.

In a conditional logistic-regression multivariate analysis, neither ACE inhibitors nor ARBs were associated with the likelihood of SARS-CoV-2 infection.

“Thus, our results do not provide evidence of an independent relationship between renin angiotensin aldosterone blockers and the susceptibility to COVID-19 in humans,” the authors concluded.

In addition, a second analysis that compared patients who had severe or fatal infections with matched control persons did not show an association between ACE inhibitors or ARBs and severe disease.

In the third study published in the New England Journal of Medicine, a group led by Harmony R. Reynolds, MD, of New York University, analyzed data from the health records of 12,594 patients in the NYU Langone Health system who had been tested for COVID-19. They found 5,894 patients whose test results were positive. Of these patients, 1,002 had severe illness, which was defined as illness requiring admission to the ICU, need for mechanical ventilation, or death.

Using Bayesian analysis and propensity score matching, the researchers assessed the relation between previous treatment with five different classes of antihypertensive drugs (ACE inhibitors, ARBs, beta blockers, calcium blockers, and thiazide diuretics) and the likelihood of a positive or negative result on COVID-19 testing, as well as the likelihood of severe illness among patients who tested positive.

Results showed no positive association between any of the analyzed drug classes and either a positive test result or severe illness.

In an accompanying editorial, a group led by John A. Jarcho, MD, of Harvard Medical School, Boston, and deputy editor of the New England Journal of Medicine, wrote: “Taken together, these three studies do not provide evidence to support the hypothesis that ACE inhibitor or ARB use is associated with the risk of SARS-CoV-2 infection, the risk of severe COVID-19 among those infected, or the risk of in-hospital death among those with a positive test.

“Each of these studies has weaknesses inherent in observational data, but we find it reassuring that three studies in different populations and with different designs arrive at the consistent message that the continued use of ACE inhibitors and ARBs is unlikely to be harmful in patients with COVID-19. Several other smaller studies from China and the United Kingdom have come to the same conclusion,” the authors of the editorial stated.

In the study published in JAMA Cardiology, a group led by Neil Mehta, MBBS, of the Cleveland Clinic, Ohio, analyzed data on 18,472 patients who had been tested for COVID-19 between March 8 and April 12 in the Cleveland Clinic Health System in Ohio and Florida. Of these patients, 9.4% tested positive.

After overlap propensity score weighting for both ACE inhibitors and ARBs to take into account relevant comorbidities, there was no difference in risk for testing positive among patients taking an ACE inhibitor or an ARB in comparison with those not taking such medication.
 

Are there different effects between ACE inhibitors and ARBs?

A secondary exploratory analysis showed a higher likelihood of hospital admission among patients who tested positive and who were taking either ACE inhibitors (OR, 1.84) or ARBs (OR, 1.61), and there was a higher likelihood of ICU admission among patients who tested positive and who were taking an ACE inhibitor (OR 1.77), but no such difference was observed among those taking ARBs.

Coauthor Ankur Kalra, MD, of the Cleveland Clinic, said in an interview that results of the exploratory analysis fit with the hypothesis that the two drugs classes may have different effects in patients with COVID-19.

“Angiotensin II promotes vasoconstriction, inflammation, and fibrosis in the lungs, and ARBs block the effects of angiotensin II more effectively than ACE inhibitors. In addition, ACE inhibitors (but not ARBs) increase levels of bradykinin, which may be one factor leading to acute respiratory distress syndrome,” he noted.

“However, these results should only be considered exploratory, as there is inherent bias in observational data,” Dr. Kalra stressed.

In an accompanying editorial in JAMA Cardiology, a group led by Laine E. Thomas, PhD, of Duke Clinical Research Institute, Durham, North Carolina, said that the results of this secondary exploratory analysis are limited by a small number of patients and “are likely explained by confounding and should not be inferred as causal.”

The New England Journal of Medicine editorialists reached a similar conclusion regarding the lower mortality in COVID-19 patients who took ACE inhibitors in the study by Dr. Mehra and colleagues. They say this unexpected result “may be due to unmeasured confounding and, in the absence of a randomized trial, should not be regarded as evidence to prescribe these drugs in patients with COVID-19.”

Providing further comment, Dr. McMurray said: “Normally, I would not read too much into the different effects of ACE inhibitors and ARBs suggested in the Cleveland study because of the small numbers (about 28 ACE inhibitor–treated patients admitted to ICU) and the limited information about matching and/or adjustment for potential differences between groups.

“I could also argue that the comparison that would best answer the question about risk related to type of RAS blocker would be the direct comparison of people taking an ACE inhibitor with those taking an ARB (and that doesn’t look very different). The only thing that makes me a little cautious about completely dismissing the possibility of a difference between ACE inhibitor and ARB here is the suggestion of a similar trend in another large study from the VA [Veterans Affairs] system,” he added.

He also noted that speculation about there being mechanisms that involve different effects of the two drug classes on bradykinin and angiotensin II was “plausible but unproven.”

Dr. Messerli added: “Before turning the page, I would like to see an analysis comparing ACE inhibitors and ARBs, since experimentally, their effect on ACE2 (the receptor to which the virus binds) seems to differ. The study of Mehta et al in JAMA Cardiology may be the first clinical hint indicating that ARBs are more protective than ACEIs. However even here, the looming possibility of confounding cannot be excluded.”

Dr. Messerli also pointed to a hypothesis that suggests that direct viral infection of endothelial cells expressing ACE2 receptors may explain worse outcomes in patients with cardiovascular comorbidities, which provides a rationale for therapies to stabilize the endothelium, particularly with anti-inflammatory anticytokine drugs, ACE inhibitors, and statins.

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

Four more studies of the relationship of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with COVID-19 have been published in the past few days in top-tier peer-reviewed journals, and on the whole, the data are reassuring.

Three of the new studies were published in the New England Journal of Medicine on May 1, and one study was published in JAMA Cardiology on May 5.

Although all the studies are observational in design and have some confounding factors, overall, the results do not suggest that continued use of ACE inhibitors and ARBs causes harm. However, there are some contradictory findings in secondary analyses regarding possible differences in the effects of the two drug classes.

Providing commentary, John McMurray, MD, professor of medical cardiology at the University of Glasgow, said: “The overall picture seems to suggest no increase in risk of adverse outcomes in patients taking renin-angiotensin system [RAS] blockers ― but with lots of caveats: These are all observational rather than randomized studies, and there may be residual or unmeasured confounding.”
 

Was it ‘Much ado about nothing’?

Franz Messerli, MD, professor of medicine at the University of Bern (Switzerland), added: “Given this state of the art, I am inclined to consider RAS blockade and COVID-19 – despite all the hype in the news media – as much ado about nothing.”

But both Dr. McMurray and Dr. Messerli said they were intrigued about possible differences in the effects of ACE inhibitors and ARBs that some of the new results suggest.

In one study, a team led by Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center, Boston, analyzed data from 8,910 patients with COVID-19 admitted to 169 hospitals in Asia, Europe, and North America who had either died in the hospital (5.8%) or survived to hospital discharge (94.2%).

In multivariate logistic-regression analysis, age greater than 65 years, coronary artery disease, congestive heart failure, history of cardiac arrhythmia, chronic obstructive pulmonary disease, and current smoking were associated with an increased risk for in-hospital death. Female sex was associated with a decreased risk. Neither ACE inhibitors nor ARBs were associated with an increased risk for in-hospital death.

In fact, ACE inhibitors were associated with a significant reduction in mortality (odds ratio, 0.33), as were statins (OR, 0.35).

The authors, however, stressed that these observations about reduced mortality with ACE inhibitors and statins “should be considered with extreme caution.”

“Because our study was not a randomized, controlled trial, we cannot exclude the possibility of confounding. In addition, we examined relationships between many variables and in-hospital death, and no primary hypothesis was prespecified; these factors increased the probability of chance associations being found. Therefore, a cause-and-effect relationship between drug therapy and survival should not be inferred,” they wrote.

A secondary analysis that was restricted to patients with hypertension (those for whom an ACE inhibitor or an ARB would be indicated) also did not show harm.

A second study published in the New England Journal of Medicine had a case-control design. The authors, led by Giuseppe Mancia, MD, of the University of Milano-Bicocca (Italy), compared 6,272 patients with confirmed COVID-19 (case patients) with 30,759 control persons who were matched according to age, sex, and municipality of residence.

In a conditional logistic-regression multivariate analysis, neither ACE inhibitors nor ARBs were associated with the likelihood of SARS-CoV-2 infection.

“Thus, our results do not provide evidence of an independent relationship between renin angiotensin aldosterone blockers and the susceptibility to COVID-19 in humans,” the authors concluded.

In addition, a second analysis that compared patients who had severe or fatal infections with matched control persons did not show an association between ACE inhibitors or ARBs and severe disease.

In the third study published in the New England Journal of Medicine, a group led by Harmony R. Reynolds, MD, of New York University, analyzed data from the health records of 12,594 patients in the NYU Langone Health system who had been tested for COVID-19. They found 5,894 patients whose test results were positive. Of these patients, 1,002 had severe illness, which was defined as illness requiring admission to the ICU, need for mechanical ventilation, or death.

Using Bayesian analysis and propensity score matching, the researchers assessed the relation between previous treatment with five different classes of antihypertensive drugs (ACE inhibitors, ARBs, beta blockers, calcium blockers, and thiazide diuretics) and the likelihood of a positive or negative result on COVID-19 testing, as well as the likelihood of severe illness among patients who tested positive.

Results showed no positive association between any of the analyzed drug classes and either a positive test result or severe illness.

In an accompanying editorial, a group led by John A. Jarcho, MD, of Harvard Medical School, Boston, and deputy editor of the New England Journal of Medicine, wrote: “Taken together, these three studies do not provide evidence to support the hypothesis that ACE inhibitor or ARB use is associated with the risk of SARS-CoV-2 infection, the risk of severe COVID-19 among those infected, or the risk of in-hospital death among those with a positive test.

“Each of these studies has weaknesses inherent in observational data, but we find it reassuring that three studies in different populations and with different designs arrive at the consistent message that the continued use of ACE inhibitors and ARBs is unlikely to be harmful in patients with COVID-19. Several other smaller studies from China and the United Kingdom have come to the same conclusion,” the authors of the editorial stated.

In the study published in JAMA Cardiology, a group led by Neil Mehta, MBBS, of the Cleveland Clinic, Ohio, analyzed data on 18,472 patients who had been tested for COVID-19 between March 8 and April 12 in the Cleveland Clinic Health System in Ohio and Florida. Of these patients, 9.4% tested positive.

After overlap propensity score weighting for both ACE inhibitors and ARBs to take into account relevant comorbidities, there was no difference in risk for testing positive among patients taking an ACE inhibitor or an ARB in comparison with those not taking such medication.
 

Are there different effects between ACE inhibitors and ARBs?

A secondary exploratory analysis showed a higher likelihood of hospital admission among patients who tested positive and who were taking either ACE inhibitors (OR, 1.84) or ARBs (OR, 1.61), and there was a higher likelihood of ICU admission among patients who tested positive and who were taking an ACE inhibitor (OR 1.77), but no such difference was observed among those taking ARBs.

Coauthor Ankur Kalra, MD, of the Cleveland Clinic, said in an interview that results of the exploratory analysis fit with the hypothesis that the two drugs classes may have different effects in patients with COVID-19.

“Angiotensin II promotes vasoconstriction, inflammation, and fibrosis in the lungs, and ARBs block the effects of angiotensin II more effectively than ACE inhibitors. In addition, ACE inhibitors (but not ARBs) increase levels of bradykinin, which may be one factor leading to acute respiratory distress syndrome,” he noted.

“However, these results should only be considered exploratory, as there is inherent bias in observational data,” Dr. Kalra stressed.

In an accompanying editorial in JAMA Cardiology, a group led by Laine E. Thomas, PhD, of Duke Clinical Research Institute, Durham, North Carolina, said that the results of this secondary exploratory analysis are limited by a small number of patients and “are likely explained by confounding and should not be inferred as causal.”

The New England Journal of Medicine editorialists reached a similar conclusion regarding the lower mortality in COVID-19 patients who took ACE inhibitors in the study by Dr. Mehra and colleagues. They say this unexpected result “may be due to unmeasured confounding and, in the absence of a randomized trial, should not be regarded as evidence to prescribe these drugs in patients with COVID-19.”

Providing further comment, Dr. McMurray said: “Normally, I would not read too much into the different effects of ACE inhibitors and ARBs suggested in the Cleveland study because of the small numbers (about 28 ACE inhibitor–treated patients admitted to ICU) and the limited information about matching and/or adjustment for potential differences between groups.

“I could also argue that the comparison that would best answer the question about risk related to type of RAS blocker would be the direct comparison of people taking an ACE inhibitor with those taking an ARB (and that doesn’t look very different). The only thing that makes me a little cautious about completely dismissing the possibility of a difference between ACE inhibitor and ARB here is the suggestion of a similar trend in another large study from the VA [Veterans Affairs] system,” he added.

He also noted that speculation about there being mechanisms that involve different effects of the two drug classes on bradykinin and angiotensin II was “plausible but unproven.”

Dr. Messerli added: “Before turning the page, I would like to see an analysis comparing ACE inhibitors and ARBs, since experimentally, their effect on ACE2 (the receptor to which the virus binds) seems to differ. The study of Mehta et al in JAMA Cardiology may be the first clinical hint indicating that ARBs are more protective than ACEIs. However even here, the looming possibility of confounding cannot be excluded.”

Dr. Messerli also pointed to a hypothesis that suggests that direct viral infection of endothelial cells expressing ACE2 receptors may explain worse outcomes in patients with cardiovascular comorbidities, which provides a rationale for therapies to stabilize the endothelium, particularly with anti-inflammatory anticytokine drugs, ACE inhibitors, and statins.

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

Four more studies of the relationship of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with COVID-19 have been published in the past few days in top-tier peer-reviewed journals, and on the whole, the data are reassuring.

Three of the new studies were published in the New England Journal of Medicine on May 1, and one study was published in JAMA Cardiology on May 5.

Although all the studies are observational in design and have some confounding factors, overall, the results do not suggest that continued use of ACE inhibitors and ARBs causes harm. However, there are some contradictory findings in secondary analyses regarding possible differences in the effects of the two drug classes.

Providing commentary, John McMurray, MD, professor of medical cardiology at the University of Glasgow, said: “The overall picture seems to suggest no increase in risk of adverse outcomes in patients taking renin-angiotensin system [RAS] blockers ― but with lots of caveats: These are all observational rather than randomized studies, and there may be residual or unmeasured confounding.”
 

Was it ‘Much ado about nothing’?

Franz Messerli, MD, professor of medicine at the University of Bern (Switzerland), added: “Given this state of the art, I am inclined to consider RAS blockade and COVID-19 – despite all the hype in the news media – as much ado about nothing.”

But both Dr. McMurray and Dr. Messerli said they were intrigued about possible differences in the effects of ACE inhibitors and ARBs that some of the new results suggest.

In one study, a team led by Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center, Boston, analyzed data from 8,910 patients with COVID-19 admitted to 169 hospitals in Asia, Europe, and North America who had either died in the hospital (5.8%) or survived to hospital discharge (94.2%).

In multivariate logistic-regression analysis, age greater than 65 years, coronary artery disease, congestive heart failure, history of cardiac arrhythmia, chronic obstructive pulmonary disease, and current smoking were associated with an increased risk for in-hospital death. Female sex was associated with a decreased risk. Neither ACE inhibitors nor ARBs were associated with an increased risk for in-hospital death.

In fact, ACE inhibitors were associated with a significant reduction in mortality (odds ratio, 0.33), as were statins (OR, 0.35).

The authors, however, stressed that these observations about reduced mortality with ACE inhibitors and statins “should be considered with extreme caution.”

“Because our study was not a randomized, controlled trial, we cannot exclude the possibility of confounding. In addition, we examined relationships between many variables and in-hospital death, and no primary hypothesis was prespecified; these factors increased the probability of chance associations being found. Therefore, a cause-and-effect relationship between drug therapy and survival should not be inferred,” they wrote.

A secondary analysis that was restricted to patients with hypertension (those for whom an ACE inhibitor or an ARB would be indicated) also did not show harm.

A second study published in the New England Journal of Medicine had a case-control design. The authors, led by Giuseppe Mancia, MD, of the University of Milano-Bicocca (Italy), compared 6,272 patients with confirmed COVID-19 (case patients) with 30,759 control persons who were matched according to age, sex, and municipality of residence.

In a conditional logistic-regression multivariate analysis, neither ACE inhibitors nor ARBs were associated with the likelihood of SARS-CoV-2 infection.

“Thus, our results do not provide evidence of an independent relationship between renin angiotensin aldosterone blockers and the susceptibility to COVID-19 in humans,” the authors concluded.

In addition, a second analysis that compared patients who had severe or fatal infections with matched control persons did not show an association between ACE inhibitors or ARBs and severe disease.

In the third study published in the New England Journal of Medicine, a group led by Harmony R. Reynolds, MD, of New York University, analyzed data from the health records of 12,594 patients in the NYU Langone Health system who had been tested for COVID-19. They found 5,894 patients whose test results were positive. Of these patients, 1,002 had severe illness, which was defined as illness requiring admission to the ICU, need for mechanical ventilation, or death.

Using Bayesian analysis and propensity score matching, the researchers assessed the relation between previous treatment with five different classes of antihypertensive drugs (ACE inhibitors, ARBs, beta blockers, calcium blockers, and thiazide diuretics) and the likelihood of a positive or negative result on COVID-19 testing, as well as the likelihood of severe illness among patients who tested positive.

Results showed no positive association between any of the analyzed drug classes and either a positive test result or severe illness.

In an accompanying editorial, a group led by John A. Jarcho, MD, of Harvard Medical School, Boston, and deputy editor of the New England Journal of Medicine, wrote: “Taken together, these three studies do not provide evidence to support the hypothesis that ACE inhibitor or ARB use is associated with the risk of SARS-CoV-2 infection, the risk of severe COVID-19 among those infected, or the risk of in-hospital death among those with a positive test.

“Each of these studies has weaknesses inherent in observational data, but we find it reassuring that three studies in different populations and with different designs arrive at the consistent message that the continued use of ACE inhibitors and ARBs is unlikely to be harmful in patients with COVID-19. Several other smaller studies from China and the United Kingdom have come to the same conclusion,” the authors of the editorial stated.

In the study published in JAMA Cardiology, a group led by Neil Mehta, MBBS, of the Cleveland Clinic, Ohio, analyzed data on 18,472 patients who had been tested for COVID-19 between March 8 and April 12 in the Cleveland Clinic Health System in Ohio and Florida. Of these patients, 9.4% tested positive.

After overlap propensity score weighting for both ACE inhibitors and ARBs to take into account relevant comorbidities, there was no difference in risk for testing positive among patients taking an ACE inhibitor or an ARB in comparison with those not taking such medication.
 

Are there different effects between ACE inhibitors and ARBs?

A secondary exploratory analysis showed a higher likelihood of hospital admission among patients who tested positive and who were taking either ACE inhibitors (OR, 1.84) or ARBs (OR, 1.61), and there was a higher likelihood of ICU admission among patients who tested positive and who were taking an ACE inhibitor (OR 1.77), but no such difference was observed among those taking ARBs.

Coauthor Ankur Kalra, MD, of the Cleveland Clinic, said in an interview that results of the exploratory analysis fit with the hypothesis that the two drugs classes may have different effects in patients with COVID-19.

“Angiotensin II promotes vasoconstriction, inflammation, and fibrosis in the lungs, and ARBs block the effects of angiotensin II more effectively than ACE inhibitors. In addition, ACE inhibitors (but not ARBs) increase levels of bradykinin, which may be one factor leading to acute respiratory distress syndrome,” he noted.

“However, these results should only be considered exploratory, as there is inherent bias in observational data,” Dr. Kalra stressed.

In an accompanying editorial in JAMA Cardiology, a group led by Laine E. Thomas, PhD, of Duke Clinical Research Institute, Durham, North Carolina, said that the results of this secondary exploratory analysis are limited by a small number of patients and “are likely explained by confounding and should not be inferred as causal.”

The New England Journal of Medicine editorialists reached a similar conclusion regarding the lower mortality in COVID-19 patients who took ACE inhibitors in the study by Dr. Mehra and colleagues. They say this unexpected result “may be due to unmeasured confounding and, in the absence of a randomized trial, should not be regarded as evidence to prescribe these drugs in patients with COVID-19.”

Providing further comment, Dr. McMurray said: “Normally, I would not read too much into the different effects of ACE inhibitors and ARBs suggested in the Cleveland study because of the small numbers (about 28 ACE inhibitor–treated patients admitted to ICU) and the limited information about matching and/or adjustment for potential differences between groups.

“I could also argue that the comparison that would best answer the question about risk related to type of RAS blocker would be the direct comparison of people taking an ACE inhibitor with those taking an ARB (and that doesn’t look very different). The only thing that makes me a little cautious about completely dismissing the possibility of a difference between ACE inhibitor and ARB here is the suggestion of a similar trend in another large study from the VA [Veterans Affairs] system,” he added.

He also noted that speculation about there being mechanisms that involve different effects of the two drug classes on bradykinin and angiotensin II was “plausible but unproven.”

Dr. Messerli added: “Before turning the page, I would like to see an analysis comparing ACE inhibitors and ARBs, since experimentally, their effect on ACE2 (the receptor to which the virus binds) seems to differ. The study of Mehta et al in JAMA Cardiology may be the first clinical hint indicating that ARBs are more protective than ACEIs. However even here, the looming possibility of confounding cannot be excluded.”

Dr. Messerli also pointed to a hypothesis that suggests that direct viral infection of endothelial cells expressing ACE2 receptors may explain worse outcomes in patients with cardiovascular comorbidities, which provides a rationale for therapies to stabilize the endothelium, particularly with anti-inflammatory anticytokine drugs, ACE inhibitors, and statins.

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

Women with cardiovascular conditions who are planning pregnancy should be assessed and managed by a multidisciplinary team to ensure the best outcomes, according to a statement from the American Heart Association.

©American Heart Association

Cardiovascular disease (CVD) remains the leading cause of pregnancy-related mortality in the United States, and accounted for approximately 17 deaths per 100,000 live births in 2015, wrote Laxmi S. Mehta, MD, of The Ohio State University, Columbus, and colleagues.

Ideally, a woman with CVD at the time of pregnancy should be managed by a multidisciplinary cardio-obstetrics team that can assess cardiovascular risk, obstetric risk, and fetal risk throughout pregnancy, delivery, and up to a year post partum. The team should develop a shared strategy to promote best outcomes, according to the statement. The cardio-obstetrics team may include obstetricians, cardiologists, anesthesiologists, maternal-fetal medicine specialists, geneticists, neurologists, nurses, and pharmacists, according to the statement.

Women with preexisting CVD should receive counseling about maternal and fetal risks before conception, if possible, to involve the women in shared decision-making and to develop strategies for each stage of pregnancy and delivery, Dr. Mehta and associates said. Such counseling should include a review of all medications and assessment of risk factors.

However, some women present already in the early stages of pregnancy even with severe conditions such as pulmonary arterial hypertension, severe ventricular dysfunction, severe left-sided heart obstruction, and significant aortic dilatation with underlying connective tissue disease. Women with these conditions often are counseled to avoid pregnancy, but if they already are pregnant, a high-risk cardio-obstetrics team will need to work together to discover the best strategies going forward to mitigate risk, Dr. Mehta and associates said.

Common CVD conditions that affect pregnancy include hypertensive disorders, notably preeclampsia, defined as systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg in women after 20 weeks of gestation whose blood pressure was normal prior to pregnancy. A management strategy to reduce the risk of pregnancy-related complications from hypertension includes healthy lifestyle behaviors such as exercise, nutrition, and smoking cessation, according to the statement. However, patients with severe hypertension may require intravenous labetalol or hydralazine. The statement gives more information about handling preeclampsia with pulmonary edema, and prevention of eclampsia and treatment of seizures.

It is important to recognize that severe hypertension or superimposed preeclampsia may occur for the first time post partum. Early ambulatory visits in the first 1-2 weeks are sensible. Medications may be needed to keep a systolic blood pressure not higher than 150 mm Hg and a diastolic blood pressure not higher than 100 mm Hg, Dr. Mehta and associates said.

According to the statement, severe hypertriglyceridemia and familial hypercholesterolemia are the two most common conditions in which lipids should be addressed during pregnancy, with consideration of the fetal risks associated with certain medications.

“Statins are contraindicated during pregnancy, and all women who are on any lipid-lowering agents should review with their physician the safety of treatment during pregnancy and whether to discontinue treatment before pregnancy,” according to the statement. A heart-healthy lifestyle can help improve lipid profiles in all pregnant patients, Dr. Mehta and associates said. Patients with extremely high triglycerides above 500 mg/dL are at risk of pancreatitis and “may benefit from pharmacological agents (omega-3 fatty acids with or without fenofibrate or gemfibrozil) during the second trimester,” they noted. Pregnant women with familial hypercholesterolemia might take bile acid sequestrants, or as a last resort, low-density lipoprotein apheresis.

Other conditions calling for a multidisciplinary cardio-obstetric approach include preexisting coronary artery disease, cardiomyopathies, arrhythmias, valvular heart disease, cerebrovascular disease, and deep venous thrombosis, according to the statement, which provides information about the risks, diagnosis, and management.

When it is time for delivery, spontaneous labor and vaginal birth are preferable for most women with heart disease, as cesarean delivery is associated with increased risk of infection, thrombotic complications, and blood loss, according to the statement.

Women with CVD and associated complications will require “specialized long-term cardiovascular follow-up,” Dr. Mehta and associates said. “In women with a high-risk pregnancy, a cardio-obstetrics team is essential to prevent maternal morbidity and mortality during the length of the pregnancy and post partum.”

“The release of this document demonstrates the AHA’s recognition of the importance of CVD in pregnancy-related death and their commitment to education and ensuring best practices in this field,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and chief medical officer at Texas Children’s Health Plan, Bellaire.

“I think one of the most important outcomes from the release of this scientific statement from AHA will be increased implementation of cardio-obstetrics teams,” she said in an interview.

“In the United States, cardiovascular disease and cardiomyopathy together are now the leading cause of death in pregnancy and the postpartum period, and constitute 26.5% of pregnancy-related deaths, with higher rates of mortality among women of color and women with lower incomes,” she said. “The rising trend in cardiovascular-related maternal deaths appears to be due to acquired, not congenital, heart disease.”

During her tenure as president of ACOG, Dr. Hollier convened a task force on cardiovascular disease in pregnancy that developed guidance that outlines screening, diagnosis, and management of CVD for women from prepregnancy through post partum.

Dr. Hollier noted that COVID-19 emphasizes racial disparities for maternal mortality.

“Pregnant patients with comorbidities, like heart conditions, may be at increased risk for severe illness from COVID-19 – consistent with the general population with similar comorbidities,” she said. “And as we know, black women’s risk of dying from CVD-related pregnancy complications is 3.4 times higher than that of white women. During the COVID-19 pandemic, we are seeing these racial health disparities exacerbated.”

However, any pregnant patients should not hesitate to communicate with their health care providers despite the pandemic situation, Dr. Hollier emphasized. “Communication between a patient and her ob.gyn., cardiologist, or other clinician is even more critical now during the COVID-19 pandemic. We’re hearing reports that patients who are experiencing symptoms or those with known cardiac conditions are avoiding the hospital and delaying or not seeking necessary treatment. This has the very real possibility of worsening the devastating maternal mortality crisis that we’re already experiencing in this country.”

To help overcome barriers to treatment, “collaboration between ob.gyns. and cardiologists, such as the cardio-obstetrics team or pregnancy heart team, is critical,” said Dr. Hollier. “These collaborative teams with a multidisciplinary approach can prospectively reduce the communication gaps across specialties when patients are seen separately. They can also improve the communication during care transitions such as between outpatient and inpatient care.


“In reviews of maternal deaths, we have found that there are often delays in diagnosis of heart conditions during and after pregnancy,” Dr. Hollier added. “Most maternal deaths from CVD are due to either undiagnosed cardiovascular disease or new-onset cardiomyopathy. ACOG recommends that all women be assessed for cardiovascular disease in the antepartum and postpartum periods using a recently developed algorithm,” she said. “Women who have known CVD and women who have concerning symptoms should have a consultation with this team. With increased awareness and screening, women can receive the additional care that they need.

“Because management of cardiac conditions in pregnancy is so complex, it is important to ensure that women receive care with teams and in facilities that have appropriate resources,” explained Dr. Hollier. “Women with known heart disease should see a cardiologist prior to pregnancy and receive prepregnancy counseling,” as noted in the AHA statement. “Patients determined to have moderate and high-risk CVD should be managed during pregnancy, delivery, and post partum in a medical center that is able to provide a higher level of care, including a cardio-obstetrics team.”

Early recognition of cardiovascular conditions is essential to help manage care and reduce risks to mother and baby, said Dr. Hollier. “Identification before a woman becomes pregnant means the patient’s care can be properly managed throughout the pregnancy and a detailed delivery plan can be developed through shared decision making between the patient and provider. We must think of heart disease as a possibility in every pregnant or postpartum patient we see to detect and treat at-risk mothers,” she said.

Additional research should focus on identifying risk factors prior to pregnancy, said Dr. Hollier. “There are often delays in recognizing symptoms during pregnancy and post partum, particularly for black women. We need data to understand which protocols are best to identify heart disease,”

Dr. Hollier had no financial conflicts to disclose. The authors of the AHA statement had no financial conflicts to disclose. The scientific statement was produced on behalf of the American Heart Association Council on Clinical Cardiology; Council on Atherosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

SOURCE: Mehta LS et al. Circulation. 2020 May 4. doi: 10.1161/CIR.0000000000000772.

Women with cardiovascular conditions who are planning pregnancy should be assessed and managed by a multidisciplinary team to ensure the best outcomes, according to a statement from the American Heart Association.

©American Heart Association

Cardiovascular disease (CVD) remains the leading cause of pregnancy-related mortality in the United States, and accounted for approximately 17 deaths per 100,000 live births in 2015, wrote Laxmi S. Mehta, MD, of The Ohio State University, Columbus, and colleagues.

Ideally, a woman with CVD at the time of pregnancy should be managed by a multidisciplinary cardio-obstetrics team that can assess cardiovascular risk, obstetric risk, and fetal risk throughout pregnancy, delivery, and up to a year post partum. The team should develop a shared strategy to promote best outcomes, according to the statement. The cardio-obstetrics team may include obstetricians, cardiologists, anesthesiologists, maternal-fetal medicine specialists, geneticists, neurologists, nurses, and pharmacists, according to the statement.

Women with preexisting CVD should receive counseling about maternal and fetal risks before conception, if possible, to involve the women in shared decision-making and to develop strategies for each stage of pregnancy and delivery, Dr. Mehta and associates said. Such counseling should include a review of all medications and assessment of risk factors.

However, some women present already in the early stages of pregnancy even with severe conditions such as pulmonary arterial hypertension, severe ventricular dysfunction, severe left-sided heart obstruction, and significant aortic dilatation with underlying connective tissue disease. Women with these conditions often are counseled to avoid pregnancy, but if they already are pregnant, a high-risk cardio-obstetrics team will need to work together to discover the best strategies going forward to mitigate risk, Dr. Mehta and associates said.

Common CVD conditions that affect pregnancy include hypertensive disorders, notably preeclampsia, defined as systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg in women after 20 weeks of gestation whose blood pressure was normal prior to pregnancy. A management strategy to reduce the risk of pregnancy-related complications from hypertension includes healthy lifestyle behaviors such as exercise, nutrition, and smoking cessation, according to the statement. However, patients with severe hypertension may require intravenous labetalol or hydralazine. The statement gives more information about handling preeclampsia with pulmonary edema, and prevention of eclampsia and treatment of seizures.

It is important to recognize that severe hypertension or superimposed preeclampsia may occur for the first time post partum. Early ambulatory visits in the first 1-2 weeks are sensible. Medications may be needed to keep a systolic blood pressure not higher than 150 mm Hg and a diastolic blood pressure not higher than 100 mm Hg, Dr. Mehta and associates said.

According to the statement, severe hypertriglyceridemia and familial hypercholesterolemia are the two most common conditions in which lipids should be addressed during pregnancy, with consideration of the fetal risks associated with certain medications.

“Statins are contraindicated during pregnancy, and all women who are on any lipid-lowering agents should review with their physician the safety of treatment during pregnancy and whether to discontinue treatment before pregnancy,” according to the statement. A heart-healthy lifestyle can help improve lipid profiles in all pregnant patients, Dr. Mehta and associates said. Patients with extremely high triglycerides above 500 mg/dL are at risk of pancreatitis and “may benefit from pharmacological agents (omega-3 fatty acids with or without fenofibrate or gemfibrozil) during the second trimester,” they noted. Pregnant women with familial hypercholesterolemia might take bile acid sequestrants, or as a last resort, low-density lipoprotein apheresis.

Other conditions calling for a multidisciplinary cardio-obstetric approach include preexisting coronary artery disease, cardiomyopathies, arrhythmias, valvular heart disease, cerebrovascular disease, and deep venous thrombosis, according to the statement, which provides information about the risks, diagnosis, and management.

When it is time for delivery, spontaneous labor and vaginal birth are preferable for most women with heart disease, as cesarean delivery is associated with increased risk of infection, thrombotic complications, and blood loss, according to the statement.

Women with CVD and associated complications will require “specialized long-term cardiovascular follow-up,” Dr. Mehta and associates said. “In women with a high-risk pregnancy, a cardio-obstetrics team is essential to prevent maternal morbidity and mortality during the length of the pregnancy and post partum.”

“The release of this document demonstrates the AHA’s recognition of the importance of CVD in pregnancy-related death and their commitment to education and ensuring best practices in this field,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and chief medical officer at Texas Children’s Health Plan, Bellaire.

“I think one of the most important outcomes from the release of this scientific statement from AHA will be increased implementation of cardio-obstetrics teams,” she said in an interview.

“In the United States, cardiovascular disease and cardiomyopathy together are now the leading cause of death in pregnancy and the postpartum period, and constitute 26.5% of pregnancy-related deaths, with higher rates of mortality among women of color and women with lower incomes,” she said. “The rising trend in cardiovascular-related maternal deaths appears to be due to acquired, not congenital, heart disease.”

During her tenure as president of ACOG, Dr. Hollier convened a task force on cardiovascular disease in pregnancy that developed guidance that outlines screening, diagnosis, and management of CVD for women from prepregnancy through post partum.

Dr. Hollier noted that COVID-19 emphasizes racial disparities for maternal mortality.

“Pregnant patients with comorbidities, like heart conditions, may be at increased risk for severe illness from COVID-19 – consistent with the general population with similar comorbidities,” she said. “And as we know, black women’s risk of dying from CVD-related pregnancy complications is 3.4 times higher than that of white women. During the COVID-19 pandemic, we are seeing these racial health disparities exacerbated.”

However, any pregnant patients should not hesitate to communicate with their health care providers despite the pandemic situation, Dr. Hollier emphasized. “Communication between a patient and her ob.gyn., cardiologist, or other clinician is even more critical now during the COVID-19 pandemic. We’re hearing reports that patients who are experiencing symptoms or those with known cardiac conditions are avoiding the hospital and delaying or not seeking necessary treatment. This has the very real possibility of worsening the devastating maternal mortality crisis that we’re already experiencing in this country.”

To help overcome barriers to treatment, “collaboration between ob.gyns. and cardiologists, such as the cardio-obstetrics team or pregnancy heart team, is critical,” said Dr. Hollier. “These collaborative teams with a multidisciplinary approach can prospectively reduce the communication gaps across specialties when patients are seen separately. They can also improve the communication during care transitions such as between outpatient and inpatient care.


“In reviews of maternal deaths, we have found that there are often delays in diagnosis of heart conditions during and after pregnancy,” Dr. Hollier added. “Most maternal deaths from CVD are due to either undiagnosed cardiovascular disease or new-onset cardiomyopathy. ACOG recommends that all women be assessed for cardiovascular disease in the antepartum and postpartum periods using a recently developed algorithm,” she said. “Women who have known CVD and women who have concerning symptoms should have a consultation with this team. With increased awareness and screening, women can receive the additional care that they need.

“Because management of cardiac conditions in pregnancy is so complex, it is important to ensure that women receive care with teams and in facilities that have appropriate resources,” explained Dr. Hollier. “Women with known heart disease should see a cardiologist prior to pregnancy and receive prepregnancy counseling,” as noted in the AHA statement. “Patients determined to have moderate and high-risk CVD should be managed during pregnancy, delivery, and post partum in a medical center that is able to provide a higher level of care, including a cardio-obstetrics team.”

Early recognition of cardiovascular conditions is essential to help manage care and reduce risks to mother and baby, said Dr. Hollier. “Identification before a woman becomes pregnant means the patient’s care can be properly managed throughout the pregnancy and a detailed delivery plan can be developed through shared decision making between the patient and provider. We must think of heart disease as a possibility in every pregnant or postpartum patient we see to detect and treat at-risk mothers,” she said.

Additional research should focus on identifying risk factors prior to pregnancy, said Dr. Hollier. “There are often delays in recognizing symptoms during pregnancy and post partum, particularly for black women. We need data to understand which protocols are best to identify heart disease,”

Dr. Hollier had no financial conflicts to disclose. The authors of the AHA statement had no financial conflicts to disclose. The scientific statement was produced on behalf of the American Heart Association Council on Clinical Cardiology; Council on Atherosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

SOURCE: Mehta LS et al. Circulation. 2020 May 4. doi: 10.1161/CIR.0000000000000772.

Women with cardiovascular conditions who are planning pregnancy should be assessed and managed by a multidisciplinary team to ensure the best outcomes, according to a statement from the American Heart Association.

©American Heart Association

Cardiovascular disease (CVD) remains the leading cause of pregnancy-related mortality in the United States, and accounted for approximately 17 deaths per 100,000 live births in 2015, wrote Laxmi S. Mehta, MD, of The Ohio State University, Columbus, and colleagues.

Ideally, a woman with CVD at the time of pregnancy should be managed by a multidisciplinary cardio-obstetrics team that can assess cardiovascular risk, obstetric risk, and fetal risk throughout pregnancy, delivery, and up to a year post partum. The team should develop a shared strategy to promote best outcomes, according to the statement. The cardio-obstetrics team may include obstetricians, cardiologists, anesthesiologists, maternal-fetal medicine specialists, geneticists, neurologists, nurses, and pharmacists, according to the statement.

Women with preexisting CVD should receive counseling about maternal and fetal risks before conception, if possible, to involve the women in shared decision-making and to develop strategies for each stage of pregnancy and delivery, Dr. Mehta and associates said. Such counseling should include a review of all medications and assessment of risk factors.

However, some women present already in the early stages of pregnancy even with severe conditions such as pulmonary arterial hypertension, severe ventricular dysfunction, severe left-sided heart obstruction, and significant aortic dilatation with underlying connective tissue disease. Women with these conditions often are counseled to avoid pregnancy, but if they already are pregnant, a high-risk cardio-obstetrics team will need to work together to discover the best strategies going forward to mitigate risk, Dr. Mehta and associates said.

Common CVD conditions that affect pregnancy include hypertensive disorders, notably preeclampsia, defined as systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg in women after 20 weeks of gestation whose blood pressure was normal prior to pregnancy. A management strategy to reduce the risk of pregnancy-related complications from hypertension includes healthy lifestyle behaviors such as exercise, nutrition, and smoking cessation, according to the statement. However, patients with severe hypertension may require intravenous labetalol or hydralazine. The statement gives more information about handling preeclampsia with pulmonary edema, and prevention of eclampsia and treatment of seizures.

It is important to recognize that severe hypertension or superimposed preeclampsia may occur for the first time post partum. Early ambulatory visits in the first 1-2 weeks are sensible. Medications may be needed to keep a systolic blood pressure not higher than 150 mm Hg and a diastolic blood pressure not higher than 100 mm Hg, Dr. Mehta and associates said.

According to the statement, severe hypertriglyceridemia and familial hypercholesterolemia are the two most common conditions in which lipids should be addressed during pregnancy, with consideration of the fetal risks associated with certain medications.

“Statins are contraindicated during pregnancy, and all women who are on any lipid-lowering agents should review with their physician the safety of treatment during pregnancy and whether to discontinue treatment before pregnancy,” according to the statement. A heart-healthy lifestyle can help improve lipid profiles in all pregnant patients, Dr. Mehta and associates said. Patients with extremely high triglycerides above 500 mg/dL are at risk of pancreatitis and “may benefit from pharmacological agents (omega-3 fatty acids with or without fenofibrate or gemfibrozil) during the second trimester,” they noted. Pregnant women with familial hypercholesterolemia might take bile acid sequestrants, or as a last resort, low-density lipoprotein apheresis.

Other conditions calling for a multidisciplinary cardio-obstetric approach include preexisting coronary artery disease, cardiomyopathies, arrhythmias, valvular heart disease, cerebrovascular disease, and deep venous thrombosis, according to the statement, which provides information about the risks, diagnosis, and management.

When it is time for delivery, spontaneous labor and vaginal birth are preferable for most women with heart disease, as cesarean delivery is associated with increased risk of infection, thrombotic complications, and blood loss, according to the statement.

Women with CVD and associated complications will require “specialized long-term cardiovascular follow-up,” Dr. Mehta and associates said. “In women with a high-risk pregnancy, a cardio-obstetrics team is essential to prevent maternal morbidity and mortality during the length of the pregnancy and post partum.”

“The release of this document demonstrates the AHA’s recognition of the importance of CVD in pregnancy-related death and their commitment to education and ensuring best practices in this field,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and chief medical officer at Texas Children’s Health Plan, Bellaire.

“I think one of the most important outcomes from the release of this scientific statement from AHA will be increased implementation of cardio-obstetrics teams,” she said in an interview.

“In the United States, cardiovascular disease and cardiomyopathy together are now the leading cause of death in pregnancy and the postpartum period, and constitute 26.5% of pregnancy-related deaths, with higher rates of mortality among women of color and women with lower incomes,” she said. “The rising trend in cardiovascular-related maternal deaths appears to be due to acquired, not congenital, heart disease.”

During her tenure as president of ACOG, Dr. Hollier convened a task force on cardiovascular disease in pregnancy that developed guidance that outlines screening, diagnosis, and management of CVD for women from prepregnancy through post partum.

Dr. Hollier noted that COVID-19 emphasizes racial disparities for maternal mortality.

“Pregnant patients with comorbidities, like heart conditions, may be at increased risk for severe illness from COVID-19 – consistent with the general population with similar comorbidities,” she said. “And as we know, black women’s risk of dying from CVD-related pregnancy complications is 3.4 times higher than that of white women. During the COVID-19 pandemic, we are seeing these racial health disparities exacerbated.”

However, any pregnant patients should not hesitate to communicate with their health care providers despite the pandemic situation, Dr. Hollier emphasized. “Communication between a patient and her ob.gyn., cardiologist, or other clinician is even more critical now during the COVID-19 pandemic. We’re hearing reports that patients who are experiencing symptoms or those with known cardiac conditions are avoiding the hospital and delaying or not seeking necessary treatment. This has the very real possibility of worsening the devastating maternal mortality crisis that we’re already experiencing in this country.”

To help overcome barriers to treatment, “collaboration between ob.gyns. and cardiologists, such as the cardio-obstetrics team or pregnancy heart team, is critical,” said Dr. Hollier. “These collaborative teams with a multidisciplinary approach can prospectively reduce the communication gaps across specialties when patients are seen separately. They can also improve the communication during care transitions such as between outpatient and inpatient care.


“In reviews of maternal deaths, we have found that there are often delays in diagnosis of heart conditions during and after pregnancy,” Dr. Hollier added. “Most maternal deaths from CVD are due to either undiagnosed cardiovascular disease or new-onset cardiomyopathy. ACOG recommends that all women be assessed for cardiovascular disease in the antepartum and postpartum periods using a recently developed algorithm,” she said. “Women who have known CVD and women who have concerning symptoms should have a consultation with this team. With increased awareness and screening, women can receive the additional care that they need.

“Because management of cardiac conditions in pregnancy is so complex, it is important to ensure that women receive care with teams and in facilities that have appropriate resources,” explained Dr. Hollier. “Women with known heart disease should see a cardiologist prior to pregnancy and receive prepregnancy counseling,” as noted in the AHA statement. “Patients determined to have moderate and high-risk CVD should be managed during pregnancy, delivery, and post partum in a medical center that is able to provide a higher level of care, including a cardio-obstetrics team.”

Early recognition of cardiovascular conditions is essential to help manage care and reduce risks to mother and baby, said Dr. Hollier. “Identification before a woman becomes pregnant means the patient’s care can be properly managed throughout the pregnancy and a detailed delivery plan can be developed through shared decision making between the patient and provider. We must think of heart disease as a possibility in every pregnant or postpartum patient we see to detect and treat at-risk mothers,” she said.

Additional research should focus on identifying risk factors prior to pregnancy, said Dr. Hollier. “There are often delays in recognizing symptoms during pregnancy and post partum, particularly for black women. We need data to understand which protocols are best to identify heart disease,”

Dr. Hollier had no financial conflicts to disclose. The authors of the AHA statement had no financial conflicts to disclose. The scientific statement was produced on behalf of the American Heart Association Council on Clinical Cardiology; Council on Atherosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

SOURCE: Mehta LS et al. Circulation. 2020 May 4. doi: 10.1161/CIR.0000000000000772.

As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.

The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.

“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.

The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.

The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.

“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”

The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.

“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”

The document also includes eight guiding principles such as:
 

• The expectation that response levels will be different between regions, and even within a given region.
• A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
• A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
• In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.

Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.

Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”

As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”

Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.

“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”

That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.

The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.

“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.

Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.

“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”

“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.

Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.

“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”

Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.

Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.

“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?

“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”

Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.

This article first appeared on Medscape.com.

As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.

The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.

“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.

The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.

The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.

“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”

The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.

“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”

The document also includes eight guiding principles such as:
 

• The expectation that response levels will be different between regions, and even within a given region.
• A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
• A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
• In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.

Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.

Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”

As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”

Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.

“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”

That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.

The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.

“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.

Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.

“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”

“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.

Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.

“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”

Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.

Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.

“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?

“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”

Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.

This article first appeared on Medscape.com.

As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.

The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.

“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.

The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.

The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.

“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”

The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.

“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”

The document also includes eight guiding principles such as:
 

• The expectation that response levels will be different between regions, and even within a given region.
• A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
• A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
• In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.

Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.

Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”

As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”

Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.

“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”

That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.

The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.

“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.

Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.

“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”

“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.

Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.

“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”

Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.

Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.

“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?

“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”

Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.

This article first appeared on Medscape.com.