Cardiology News

Patients with RA were at lower risk for developing incident type 2 diabetes mellitus (T2DM) in comparison with patients with hypertension, psoriatic arthritis (PsA), or osteoarthritis, as well as the general population without RA in a retrospective cohort study of a large, nationwide, commercial health insurance claims database.

This result goes against what the study researchers from the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, initially hypothesized: The “risk of incident T2DM in RA patients would be similar to or less than PsA and [hypertension] patients, but higher, compared to general non-RA and OA patients.”

Prior epidemiologic studies of the relationship between RA and incident diabetes have yielded inconclusive results suggesting a small increase or no increase in risk of T2DM in patients with RA, possibly because of differences in the risk of T2DM in comparison groups used by previous studies to calculate relative risk, first author Yinzhu Jin and colleagues noted in their report published in Arthritis Care & Research.

After mining a nationwide U.S. commercial health insurance claims database, the Optum Clinformatics Data Mart, for claims data from Jan. 1, 2005, to Dec. 31, 2017, the researchers matched a total of 108,568 patients in RA, general population non-RA, hypertension, and OA cohorts based on age, sex, and index date (the date of disease-specific medication dispensing). Overall, 77% of those patients were female and had a mean age of nearly 56 years, whereas 48% of patients with PsA were female and their mean age was nearly 49 years. (PsA patients were not matched because of smaller numbers.)

During a median follow-up period of 1.4-1.8 years across the comparison groups, the crude incidence rate for diabetes per 1,000 person-years in the cohorts was 7.0 for RA, 7.4 for general non-RA, 12.3 for hypertension, 7.8 for OA, and 9.9 for PsA. The hazard ratios and 95% confidence interval for risk of diabetes in patients with RA – after adjustment for more than 40 baseline covariates that included demographics, comorbidities, medication use, and health care utilization – was 0.72 (0.66-0.78) in comparison withh the general non-RA cohort, 0.65 (0.60-0.71) in comparison with the hypertension cohort, 0.75 (0.69-0.81) in comparison with the OA cohort, and 0.76 (0.67-0.86) in comparison with the PsA cohort. These values correspond to RA patients having a 24%-35% lower risk of incident diabetes versus the comparison groups, the researchers noted. They observed results consistent to these when they conducted a sensitivity analysis using a 1-year lag time from the index date before starting follow-up.

The lower risk of T2DM in patients with RA in comparison with patients in the non-RA cohort “may be, in part, due to the effect of biologic DMARD [disease-modifying antirheumatic drug] treatment in RA which likely modifies the risk of DM,” the researchers wrote. “Both the increasing use of biologic DMARDs for RA in the U.S. over the last decade and our cohort entry criteria for the RA cohort (i.e., at least one dispensing of a DMARD) may explain the finding of the lower risk of DM in RA.”

The results found with the other three cohorts did not surprise the researchers. The reduced risk of diabetes among RA patients versus those with OA jibes with “higher rates of obesity and other comorbidities in patients with OA” as well as findings from a recent study that found a higher incidence rate of diabetes in OA, compared with RA. Ms. Jin and colleagues also acknowledged it is well known that “hypertension and PsA are associated with metabolic dysregulation and increase the risk of diabetes.”

The researchers defined patients with RA as having at least twoinpatient or outpatient ICD-9 or ICD-10 diagnosis codes of RA, separated by 7-365 days and having at least one dispensing for DMARDs within 1 year from the first RA diagnosis date, and defined the primary outcome of incident T2DM as at least one inpatient or outpatient diagnosis of T2DM plus at least one dispensing of an antidiabetic drug. They set the general non-RA cohort by selecting patients with any inpatient or outpatient diagnosis codes and a dispensing of any medications, and the hypertension, PsA, and OA comparator groups as having at least two inpatient or outpatient disease-specific ICD-9/ICD-10 codes separated by 7-365 days and at least one dispensing of disease-specific medication within 1 year from the first diagnosis date. They excluded patients with RA, PsA, or psoriasis diagnosis or disease-specific medication dispensing any time prior to or on the index date (the date of disease-specific medication dispensing).

The researchers recognized that the conclusions that can be drawn from the study are limited by the “potential misclassification of cohorts and covariates” because they “mainly used diagnosis codes and pharmacy dispensing records in claims data,” and some “important covariates such as baseline obesity are likely underreported and not adequately captured in claims data.” The level of covariate misclassification also may have been different across the study cohorts on “unmeasured covariates such as body mass index, diet, and physical activity, as well as disease specific measures,” thus introducing residual confounding. They also could not “examine potential difference in the risk of T2DM in untreated or undertreated RA patients” because “RA and all the non-RA comparator cohorts were required to use a disease-specific drug,” they wrote.

“While systemic inflammation in RA is thought to increase the risk of [cardiovascular disease] and cardiovascular risk factors such as DM, our findings suggest having RA itself does not confer an increased risk of DM. Future study should determine whether untreated RA or undertreated RA is associated with a greater risk of developing DM,” the researchers concluded.

The study was supported by a research grant from Bristol-Myers Squibb, which “played no role in the study design, data analysis or interpretation of data or presentation of results,” the researchers said. The company was “given the opportunity to make nonbinding comments on a draft of the manuscript, but the authors retained the right of publication and to determine the final wording.” One author reported receiving research grants from Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche for unrelated topics.

[email protected]

SOURCE: Jin Y et al. Arthritis Care Res. 2020 Aug 4. doi: 10.1002/acr.24343.

Patients with RA were at lower risk for developing incident type 2 diabetes mellitus (T2DM) in comparison with patients with hypertension, psoriatic arthritis (PsA), or osteoarthritis, as well as the general population without RA in a retrospective cohort study of a large, nationwide, commercial health insurance claims database.

This result goes against what the study researchers from the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, initially hypothesized: The “risk of incident T2DM in RA patients would be similar to or less than PsA and [hypertension] patients, but higher, compared to general non-RA and OA patients.”

Prior epidemiologic studies of the relationship between RA and incident diabetes have yielded inconclusive results suggesting a small increase or no increase in risk of T2DM in patients with RA, possibly because of differences in the risk of T2DM in comparison groups used by previous studies to calculate relative risk, first author Yinzhu Jin and colleagues noted in their report published in Arthritis Care & Research.

After mining a nationwide U.S. commercial health insurance claims database, the Optum Clinformatics Data Mart, for claims data from Jan. 1, 2005, to Dec. 31, 2017, the researchers matched a total of 108,568 patients in RA, general population non-RA, hypertension, and OA cohorts based on age, sex, and index date (the date of disease-specific medication dispensing). Overall, 77% of those patients were female and had a mean age of nearly 56 years, whereas 48% of patients with PsA were female and their mean age was nearly 49 years. (PsA patients were not matched because of smaller numbers.)

During a median follow-up period of 1.4-1.8 years across the comparison groups, the crude incidence rate for diabetes per 1,000 person-years in the cohorts was 7.0 for RA, 7.4 for general non-RA, 12.3 for hypertension, 7.8 for OA, and 9.9 for PsA. The hazard ratios and 95% confidence interval for risk of diabetes in patients with RA – after adjustment for more than 40 baseline covariates that included demographics, comorbidities, medication use, and health care utilization – was 0.72 (0.66-0.78) in comparison withh the general non-RA cohort, 0.65 (0.60-0.71) in comparison with the hypertension cohort, 0.75 (0.69-0.81) in comparison with the OA cohort, and 0.76 (0.67-0.86) in comparison with the PsA cohort. These values correspond to RA patients having a 24%-35% lower risk of incident diabetes versus the comparison groups, the researchers noted. They observed results consistent to these when they conducted a sensitivity analysis using a 1-year lag time from the index date before starting follow-up.

The lower risk of T2DM in patients with RA in comparison with patients in the non-RA cohort “may be, in part, due to the effect of biologic DMARD [disease-modifying antirheumatic drug] treatment in RA which likely modifies the risk of DM,” the researchers wrote. “Both the increasing use of biologic DMARDs for RA in the U.S. over the last decade and our cohort entry criteria for the RA cohort (i.e., at least one dispensing of a DMARD) may explain the finding of the lower risk of DM in RA.”

The results found with the other three cohorts did not surprise the researchers. The reduced risk of diabetes among RA patients versus those with OA jibes with “higher rates of obesity and other comorbidities in patients with OA” as well as findings from a recent study that found a higher incidence rate of diabetes in OA, compared with RA. Ms. Jin and colleagues also acknowledged it is well known that “hypertension and PsA are associated with metabolic dysregulation and increase the risk of diabetes.”

The researchers defined patients with RA as having at least twoinpatient or outpatient ICD-9 or ICD-10 diagnosis codes of RA, separated by 7-365 days and having at least one dispensing for DMARDs within 1 year from the first RA diagnosis date, and defined the primary outcome of incident T2DM as at least one inpatient or outpatient diagnosis of T2DM plus at least one dispensing of an antidiabetic drug. They set the general non-RA cohort by selecting patients with any inpatient or outpatient diagnosis codes and a dispensing of any medications, and the hypertension, PsA, and OA comparator groups as having at least two inpatient or outpatient disease-specific ICD-9/ICD-10 codes separated by 7-365 days and at least one dispensing of disease-specific medication within 1 year from the first diagnosis date. They excluded patients with RA, PsA, or psoriasis diagnosis or disease-specific medication dispensing any time prior to or on the index date (the date of disease-specific medication dispensing).

The researchers recognized that the conclusions that can be drawn from the study are limited by the “potential misclassification of cohorts and covariates” because they “mainly used diagnosis codes and pharmacy dispensing records in claims data,” and some “important covariates such as baseline obesity are likely underreported and not adequately captured in claims data.” The level of covariate misclassification also may have been different across the study cohorts on “unmeasured covariates such as body mass index, diet, and physical activity, as well as disease specific measures,” thus introducing residual confounding. They also could not “examine potential difference in the risk of T2DM in untreated or undertreated RA patients” because “RA and all the non-RA comparator cohorts were required to use a disease-specific drug,” they wrote.

“While systemic inflammation in RA is thought to increase the risk of [cardiovascular disease] and cardiovascular risk factors such as DM, our findings suggest having RA itself does not confer an increased risk of DM. Future study should determine whether untreated RA or undertreated RA is associated with a greater risk of developing DM,” the researchers concluded.

The study was supported by a research grant from Bristol-Myers Squibb, which “played no role in the study design, data analysis or interpretation of data or presentation of results,” the researchers said. The company was “given the opportunity to make nonbinding comments on a draft of the manuscript, but the authors retained the right of publication and to determine the final wording.” One author reported receiving research grants from Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche for unrelated topics.

[email protected]

SOURCE: Jin Y et al. Arthritis Care Res. 2020 Aug 4. doi: 10.1002/acr.24343.

Patients with RA were at lower risk for developing incident type 2 diabetes mellitus (T2DM) in comparison with patients with hypertension, psoriatic arthritis (PsA), or osteoarthritis, as well as the general population without RA in a retrospective cohort study of a large, nationwide, commercial health insurance claims database.

This result goes against what the study researchers from the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, initially hypothesized: The “risk of incident T2DM in RA patients would be similar to or less than PsA and [hypertension] patients, but higher, compared to general non-RA and OA patients.”

Prior epidemiologic studies of the relationship between RA and incident diabetes have yielded inconclusive results suggesting a small increase or no increase in risk of T2DM in patients with RA, possibly because of differences in the risk of T2DM in comparison groups used by previous studies to calculate relative risk, first author Yinzhu Jin and colleagues noted in their report published in Arthritis Care & Research.

After mining a nationwide U.S. commercial health insurance claims database, the Optum Clinformatics Data Mart, for claims data from Jan. 1, 2005, to Dec. 31, 2017, the researchers matched a total of 108,568 patients in RA, general population non-RA, hypertension, and OA cohorts based on age, sex, and index date (the date of disease-specific medication dispensing). Overall, 77% of those patients were female and had a mean age of nearly 56 years, whereas 48% of patients with PsA were female and their mean age was nearly 49 years. (PsA patients were not matched because of smaller numbers.)

During a median follow-up period of 1.4-1.8 years across the comparison groups, the crude incidence rate for diabetes per 1,000 person-years in the cohorts was 7.0 for RA, 7.4 for general non-RA, 12.3 for hypertension, 7.8 for OA, and 9.9 for PsA. The hazard ratios and 95% confidence interval for risk of diabetes in patients with RA – after adjustment for more than 40 baseline covariates that included demographics, comorbidities, medication use, and health care utilization – was 0.72 (0.66-0.78) in comparison withh the general non-RA cohort, 0.65 (0.60-0.71) in comparison with the hypertension cohort, 0.75 (0.69-0.81) in comparison with the OA cohort, and 0.76 (0.67-0.86) in comparison with the PsA cohort. These values correspond to RA patients having a 24%-35% lower risk of incident diabetes versus the comparison groups, the researchers noted. They observed results consistent to these when they conducted a sensitivity analysis using a 1-year lag time from the index date before starting follow-up.

The lower risk of T2DM in patients with RA in comparison with patients in the non-RA cohort “may be, in part, due to the effect of biologic DMARD [disease-modifying antirheumatic drug] treatment in RA which likely modifies the risk of DM,” the researchers wrote. “Both the increasing use of biologic DMARDs for RA in the U.S. over the last decade and our cohort entry criteria for the RA cohort (i.e., at least one dispensing of a DMARD) may explain the finding of the lower risk of DM in RA.”

The results found with the other three cohorts did not surprise the researchers. The reduced risk of diabetes among RA patients versus those with OA jibes with “higher rates of obesity and other comorbidities in patients with OA” as well as findings from a recent study that found a higher incidence rate of diabetes in OA, compared with RA. Ms. Jin and colleagues also acknowledged it is well known that “hypertension and PsA are associated with metabolic dysregulation and increase the risk of diabetes.”

The researchers defined patients with RA as having at least twoinpatient or outpatient ICD-9 or ICD-10 diagnosis codes of RA, separated by 7-365 days and having at least one dispensing for DMARDs within 1 year from the first RA diagnosis date, and defined the primary outcome of incident T2DM as at least one inpatient or outpatient diagnosis of T2DM plus at least one dispensing of an antidiabetic drug. They set the general non-RA cohort by selecting patients with any inpatient or outpatient diagnosis codes and a dispensing of any medications, and the hypertension, PsA, and OA comparator groups as having at least two inpatient or outpatient disease-specific ICD-9/ICD-10 codes separated by 7-365 days and at least one dispensing of disease-specific medication within 1 year from the first diagnosis date. They excluded patients with RA, PsA, or psoriasis diagnosis or disease-specific medication dispensing any time prior to or on the index date (the date of disease-specific medication dispensing).

The researchers recognized that the conclusions that can be drawn from the study are limited by the “potential misclassification of cohorts and covariates” because they “mainly used diagnosis codes and pharmacy dispensing records in claims data,” and some “important covariates such as baseline obesity are likely underreported and not adequately captured in claims data.” The level of covariate misclassification also may have been different across the study cohorts on “unmeasured covariates such as body mass index, diet, and physical activity, as well as disease specific measures,” thus introducing residual confounding. They also could not “examine potential difference in the risk of T2DM in untreated or undertreated RA patients” because “RA and all the non-RA comparator cohorts were required to use a disease-specific drug,” they wrote.

“While systemic inflammation in RA is thought to increase the risk of [cardiovascular disease] and cardiovascular risk factors such as DM, our findings suggest having RA itself does not confer an increased risk of DM. Future study should determine whether untreated RA or undertreated RA is associated with a greater risk of developing DM,” the researchers concluded.

The study was supported by a research grant from Bristol-Myers Squibb, which “played no role in the study design, data analysis or interpretation of data or presentation of results,” the researchers said. The company was “given the opportunity to make nonbinding comments on a draft of the manuscript, but the authors retained the right of publication and to determine the final wording.” One author reported receiving research grants from Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche for unrelated topics.

[email protected]

SOURCE: Jin Y et al. Arthritis Care Res. 2020 Aug 4. doi: 10.1002/acr.24343.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

If people try telemedicine, they’ll like telemedicine. And if they want to avoid a doctor’s office, as most people do these days, they’ll try telemedicine. That is the message coming from 1,000 people surveyed for DocASAP, a provider of online patient access and engagement systems.

Here are a couple of numbers: 92% of those who made a telemedicine visit said they were satisfied with the overall appointment experience, and 91% said that they are more likely to schedule a telemedicine visit instead of an in-person appointment. All of the survey respondents had visited a health care provider in the past year, and 40% already had made a telemedicine visit, DocASAP reported.

“Telehealth has quickly emerged as the preferred care setting during the pandemic and will drive patient behavior in the future,” Puneet Maheshwari, DocASAP cofounder and CEO, said in a statement. “As providers continue to adopt innovative technology to power a more seamless, end-to-end digital consumer experience, I expect telehealth to become fully integrated into overall care management.”

For now, though, COVID-19 is an overriding concern and health care facilities are suspect. When respondents were asked to identify the types of public facilities where they felt safe, hospitals were named by 32%, doctors’ offices by 26%, and ED/urgent care by just 12%, the DocASAP report said. Even public transportation got 13%.

The safest place to be, according to 42% of the respondents? The grocery store.

Of those surveyed, 43% “indicated they will not feel safe entering any health care setting until at least the fall,” the company said. An even higher share of patients, 68%, canceled or postponed an in-person appointment during the pandemic.

“No longer are remote health services viewed as ‘nice to have’ – they are now a must-have care delivery option,” DocASAP said in their report.

Safety concerns involving COVID-19, named by 47% of the sample, were the leading factor that would influence patients’ decision to schedule a telemedicine visit. Insurance coverage was next at 43%, followed by “ease of accessing quality care” at 40%, the report said.

Among those who had made a telemedicine visit, scheduling the appointment was the most satisfying aspect of the experience, according to 54% of respondents, with day-of-appointment wait time next at 38% and quality of the video/audio technology tied with preappointment communication at almost 33%, the survey data show.

Conversely, scheduling the appointment also was declared the most frustrating aspect of the telemedicine experience, although the total in that category was a much lower 29%.

“The pandemic has thrust profound change on every aspect of life, particularly health care. … Innovations – like digital and telehealth solutions – designed to meet patient needs will likely become embedded into the health care delivery system,” DocASAP said.

The survey was commissioned by DocASAP and conducted by marketing research company OnePoll on June 29-30, 2020.
 

[email protected]

If people try telemedicine, they’ll like telemedicine. And if they want to avoid a doctor’s office, as most people do these days, they’ll try telemedicine. That is the message coming from 1,000 people surveyed for DocASAP, a provider of online patient access and engagement systems.

Here are a couple of numbers: 92% of those who made a telemedicine visit said they were satisfied with the overall appointment experience, and 91% said that they are more likely to schedule a telemedicine visit instead of an in-person appointment. All of the survey respondents had visited a health care provider in the past year, and 40% already had made a telemedicine visit, DocASAP reported.

“Telehealth has quickly emerged as the preferred care setting during the pandemic and will drive patient behavior in the future,” Puneet Maheshwari, DocASAP cofounder and CEO, said in a statement. “As providers continue to adopt innovative technology to power a more seamless, end-to-end digital consumer experience, I expect telehealth to become fully integrated into overall care management.”

For now, though, COVID-19 is an overriding concern and health care facilities are suspect. When respondents were asked to identify the types of public facilities where they felt safe, hospitals were named by 32%, doctors’ offices by 26%, and ED/urgent care by just 12%, the DocASAP report said. Even public transportation got 13%.

The safest place to be, according to 42% of the respondents? The grocery store.

Of those surveyed, 43% “indicated they will not feel safe entering any health care setting until at least the fall,” the company said. An even higher share of patients, 68%, canceled or postponed an in-person appointment during the pandemic.

“No longer are remote health services viewed as ‘nice to have’ – they are now a must-have care delivery option,” DocASAP said in their report.

Safety concerns involving COVID-19, named by 47% of the sample, were the leading factor that would influence patients’ decision to schedule a telemedicine visit. Insurance coverage was next at 43%, followed by “ease of accessing quality care” at 40%, the report said.

Among those who had made a telemedicine visit, scheduling the appointment was the most satisfying aspect of the experience, according to 54% of respondents, with day-of-appointment wait time next at 38% and quality of the video/audio technology tied with preappointment communication at almost 33%, the survey data show.

Conversely, scheduling the appointment also was declared the most frustrating aspect of the telemedicine experience, although the total in that category was a much lower 29%.

“The pandemic has thrust profound change on every aspect of life, particularly health care. … Innovations – like digital and telehealth solutions – designed to meet patient needs will likely become embedded into the health care delivery system,” DocASAP said.

The survey was commissioned by DocASAP and conducted by marketing research company OnePoll on June 29-30, 2020.
 

[email protected]

If people try telemedicine, they’ll like telemedicine. And if they want to avoid a doctor’s office, as most people do these days, they’ll try telemedicine. That is the message coming from 1,000 people surveyed for DocASAP, a provider of online patient access and engagement systems.

Here are a couple of numbers: 92% of those who made a telemedicine visit said they were satisfied with the overall appointment experience, and 91% said that they are more likely to schedule a telemedicine visit instead of an in-person appointment. All of the survey respondents had visited a health care provider in the past year, and 40% already had made a telemedicine visit, DocASAP reported.

“Telehealth has quickly emerged as the preferred care setting during the pandemic and will drive patient behavior in the future,” Puneet Maheshwari, DocASAP cofounder and CEO, said in a statement. “As providers continue to adopt innovative technology to power a more seamless, end-to-end digital consumer experience, I expect telehealth to become fully integrated into overall care management.”

For now, though, COVID-19 is an overriding concern and health care facilities are suspect. When respondents were asked to identify the types of public facilities where they felt safe, hospitals were named by 32%, doctors’ offices by 26%, and ED/urgent care by just 12%, the DocASAP report said. Even public transportation got 13%.

The safest place to be, according to 42% of the respondents? The grocery store.

Of those surveyed, 43% “indicated they will not feel safe entering any health care setting until at least the fall,” the company said. An even higher share of patients, 68%, canceled or postponed an in-person appointment during the pandemic.

“No longer are remote health services viewed as ‘nice to have’ – they are now a must-have care delivery option,” DocASAP said in their report.

Safety concerns involving COVID-19, named by 47% of the sample, were the leading factor that would influence patients’ decision to schedule a telemedicine visit. Insurance coverage was next at 43%, followed by “ease of accessing quality care” at 40%, the report said.

Among those who had made a telemedicine visit, scheduling the appointment was the most satisfying aspect of the experience, according to 54% of respondents, with day-of-appointment wait time next at 38% and quality of the video/audio technology tied with preappointment communication at almost 33%, the survey data show.

Conversely, scheduling the appointment also was declared the most frustrating aspect of the telemedicine experience, although the total in that category was a much lower 29%.

“The pandemic has thrust profound change on every aspect of life, particularly health care. … Innovations – like digital and telehealth solutions – designed to meet patient needs will likely become embedded into the health care delivery system,” DocASAP said.

The survey was commissioned by DocASAP and conducted by marketing research company OnePoll on June 29-30, 2020.
 

[email protected]

A new analysis from Michigan’s largest health system provides sobering verification of the risks for QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin (HCQ/AZM).

One in five patients (21%) had a corrected QT (QTc) interval of at least 500 msec, a value that increases the risk for torsade de pointes in the general population and at which cardiovascular leaders have suggested withholding HCQ/AZM in COVID-19 patients.

“One of the most striking findings was when we looked at the other drugs being administered to these patients; 61% were being administered drugs that had QT-prolonging effects concomitantly with the HCQ and AZM therapy. So they were inadvertently doubling down on the QT-prolonging effects of these drugs,” senior author David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital, Royal Oak, Mich., said in an interview.

A total of 34 medications overlapped with HCQ/AZM therapy are known or suspected to increase the risk for torsade de pointes, a potentially life-threatening ventricular tachycardia. The most common of these were propofol coadministered in 123 patients, ondansetron in 114, dexmedetomidine in 54, haloperidol in 44, amiodarone in 43, and tramadol in 26.

“This speaks to the medical complexity of this patient population, but also suggests inadequate awareness of the QT-prolonging effects of many common medications,” the researchers say.

The study was published Aug. 5 in JACC Clinical Electrophysiology.

Both hydroxychloroquine and azithromycin increase the risk for QTc-interval prolongation by blocking the KCHN2-encoded hERG potassium channel. Several reports have linked the drugs to a triggering of QT prolongation in patients with COVID-19.

For the present study, Dr. Haines and colleagues examined data from 586 consecutive patients admitted with COVID-19 to the Beaumont Hospitals in Royal Oak and Troy, Mich., between March 13 and April 6. A baseline QTc interval was measured with 12-lead ECG prior to treatment initiation with hydroxychloroquine 400 mg twice daily for two doses, then 200 mg twice daily for 4 days, and azithromycin 500 mg once followed by 250 mg daily for 4 days.

Because of limited availability at the time, lead II ECG telemetry monitoring over the 5-day course of HCQ/AZM was recommended only in patients with baseline QTc intervals of at least 440 msec.

Patients without an interpretable baseline ECG or available telemetry/ECG monitoring for at least 1 day were also excluded, leaving 415 patients (mean age, 64 years; 45% female) in the study population. More than half (52%) were Black, 52% had hypertension, 30% had diabetes, and 14% had cancer.

As seen in previous studies, the QTc interval increased progressively and significantly after the administration of HCQ/AZM, from 443 msec to 473 msec.

The average time to maximum QTc was 2.9 days in a subset of 135 patients with QTc measurements prior to starting therapy and on days 1 through 5.

In multivariate analysis, independent predictors of a potentially hazardous QTc interval of at least 500 msec were:

• Age older than 65 years (odds ratio, 3.0; 95% confidence interval, 1.62-5.54).
• History of  (OR, 4.65; 95% CI, 2.01-10.74).
• Admission  of at least 1.5 mg/dL (OR, 2.22; 95% CI, 1.28-3.84).
• Peak troponin I level above 0.04 mg/mL (OR, 3.89; 95% CI, 2.22-6.83).
• Body mass index below 30 kg/m² (OR for a BMI of 30 kg/m² or higher, 0.45; 95% CI, 0.26-0.78).

Concomitant use of drugs with known risk for torsade de pointes was a significant risk factor in univariate analysis (OR, 1.73; P = .036), but fell out in the multivariate model.

No patients experienced high-grade arrhythmias during the study. In all, 112 of the 586 patients died during hospitalization, including 85 (21%) of the 415 study patients.

The change in QTc interval from baseline was greater in patients who died. Despite this, the only independent predictor of mortality was older age. One possible explanation is that the decision to monitor patients with baseline QTc intervals of at least 440 msec may have skewed the study population toward people with moderate or slightly long QTc intervals prior to the initiation of HCQ/AZM, Dr. Haines suggested. Monitoring and treatment duration were short, and clinicians also likely adjusted medications when excess QTc prolongation was observed.

Although it’s been months since data collection was completed in April, and the paper was written in record-breaking time, the study “is still very relevant because the drug is still out there,” observed Dr. Haines. “Even though it may not be used in as widespread a fashion as it had been when we first submitted the paper, it is still being used routinely by many hospitals and many practitioners.”

The use of hydroxychloroquine is “going through the roof” because of COVID-19, commented Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, HCA Midwest Health, Overland Park, Kan., who was not involved in the study.

“This study is very relevant, and I’m glad they shared their experience, and it’s pretty consistent with the data presented by other people. The question of whether hydroxychloroquine helps people with COVID is up for debate, but there is more evidence today that it is not as helpful as it was 3 months ago,” said Dr. Lakkireddy, who is also chair of the American College of Cardiology Electrophysiology Council.

He expressed concern for patients who may be taking HCQ with other medications that have QT-prolonging effects, and for the lack of long-term protocols in place for the drug.

In the coming weeks, however, the ACC and rheumatology leaders will be publishing an expert consensus statement that addresses key issues, such as how to best to use HCQ, maintenance HCQ, electrolyte monitoring, the optimal timing of electrocardiography and cardiac magnetic imaging, and symptoms to look for if cardiac involvement is suspected, Dr. Lakkireddy said.

Asked whether HCQ and AZM should be used in COVID-19 patients, Dr. Haines said in an interview that the “QT-prolonging effects are real, the arrhythmogenic potential is real, and the benefit to patients is nil or marginal. So I think that use of these drugs is appropriate and reasonable if it is done in a setting of a controlled trial, and I support that. But the routine use of these drugs probably is not warranted based on the data that we have available.”

Still, hydroxychloroquine continues to be dragged into the spotlight in recent days as an effective treatment for COVID-19, despite discredited research and the U.S. Food and Drug Administration’s June 15 revocation of its emergency-use authorization to allow use of HCQ and chloroquine to treat certain hospitalized COVID-19 patients.

“The unfortunate politicization of this issue has really muddied the waters because the general public doesn’t know what to believe or who to believe. The fact that treatment for a disease as serious as COVID should be modulated by political affiliation is just crazy to me,” said Dr. Haines. “We should be using the best science and taking careful observations, and whatever the recommendations derived from that should be uniformly adopted by everybody, irrespective of your political affiliation.”

Dr. Haines has received honoraria from Biosense Webster, Farapulse, and Sagentia, and is a consultant for Affera, Boston Scientific, Integer, Medtronic, Philips Healthcare, and Zoll. Dr. Lakkireddy has served as a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. 

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

A new analysis from Michigan’s largest health system provides sobering verification of the risks for QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin (HCQ/AZM).

One in five patients (21%) had a corrected QT (QTc) interval of at least 500 msec, a value that increases the risk for torsade de pointes in the general population and at which cardiovascular leaders have suggested withholding HCQ/AZM in COVID-19 patients.

“One of the most striking findings was when we looked at the other drugs being administered to these patients; 61% were being administered drugs that had QT-prolonging effects concomitantly with the HCQ and AZM therapy. So they were inadvertently doubling down on the QT-prolonging effects of these drugs,” senior author David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital, Royal Oak, Mich., said in an interview.

A total of 34 medications overlapped with HCQ/AZM therapy are known or suspected to increase the risk for torsade de pointes, a potentially life-threatening ventricular tachycardia. The most common of these were propofol coadministered in 123 patients, ondansetron in 114, dexmedetomidine in 54, haloperidol in 44, amiodarone in 43, and tramadol in 26.

“This speaks to the medical complexity of this patient population, but also suggests inadequate awareness of the QT-prolonging effects of many common medications,” the researchers say.

The study was published Aug. 5 in JACC Clinical Electrophysiology.

Both hydroxychloroquine and azithromycin increase the risk for QTc-interval prolongation by blocking the KCHN2-encoded hERG potassium channel. Several reports have linked the drugs to a triggering of QT prolongation in patients with COVID-19.

For the present study, Dr. Haines and colleagues examined data from 586 consecutive patients admitted with COVID-19 to the Beaumont Hospitals in Royal Oak and Troy, Mich., between March 13 and April 6. A baseline QTc interval was measured with 12-lead ECG prior to treatment initiation with hydroxychloroquine 400 mg twice daily for two doses, then 200 mg twice daily for 4 days, and azithromycin 500 mg once followed by 250 mg daily for 4 days.

Because of limited availability at the time, lead II ECG telemetry monitoring over the 5-day course of HCQ/AZM was recommended only in patients with baseline QTc intervals of at least 440 msec.

Patients without an interpretable baseline ECG or available telemetry/ECG monitoring for at least 1 day were also excluded, leaving 415 patients (mean age, 64 years; 45% female) in the study population. More than half (52%) were Black, 52% had hypertension, 30% had diabetes, and 14% had cancer.

As seen in previous studies, the QTc interval increased progressively and significantly after the administration of HCQ/AZM, from 443 msec to 473 msec.

The average time to maximum QTc was 2.9 days in a subset of 135 patients with QTc measurements prior to starting therapy and on days 1 through 5.

In multivariate analysis, independent predictors of a potentially hazardous QTc interval of at least 500 msec were:

• Age older than 65 years (odds ratio, 3.0; 95% confidence interval, 1.62-5.54).
• History of  (OR, 4.65; 95% CI, 2.01-10.74).
• Admission  of at least 1.5 mg/dL (OR, 2.22; 95% CI, 1.28-3.84).
• Peak troponin I level above 0.04 mg/mL (OR, 3.89; 95% CI, 2.22-6.83).
• Body mass index below 30 kg/m² (OR for a BMI of 30 kg/m² or higher, 0.45; 95% CI, 0.26-0.78).

Concomitant use of drugs with known risk for torsade de pointes was a significant risk factor in univariate analysis (OR, 1.73; P = .036), but fell out in the multivariate model.

No patients experienced high-grade arrhythmias during the study. In all, 112 of the 586 patients died during hospitalization, including 85 (21%) of the 415 study patients.

The change in QTc interval from baseline was greater in patients who died. Despite this, the only independent predictor of mortality was older age. One possible explanation is that the decision to monitor patients with baseline QTc intervals of at least 440 msec may have skewed the study population toward people with moderate or slightly long QTc intervals prior to the initiation of HCQ/AZM, Dr. Haines suggested. Monitoring and treatment duration were short, and clinicians also likely adjusted medications when excess QTc prolongation was observed.

Although it’s been months since data collection was completed in April, and the paper was written in record-breaking time, the study “is still very relevant because the drug is still out there,” observed Dr. Haines. “Even though it may not be used in as widespread a fashion as it had been when we first submitted the paper, it is still being used routinely by many hospitals and many practitioners.”

The use of hydroxychloroquine is “going through the roof” because of COVID-19, commented Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, HCA Midwest Health, Overland Park, Kan., who was not involved in the study.

“This study is very relevant, and I’m glad they shared their experience, and it’s pretty consistent with the data presented by other people. The question of whether hydroxychloroquine helps people with COVID is up for debate, but there is more evidence today that it is not as helpful as it was 3 months ago,” said Dr. Lakkireddy, who is also chair of the American College of Cardiology Electrophysiology Council.

He expressed concern for patients who may be taking HCQ with other medications that have QT-prolonging effects, and for the lack of long-term protocols in place for the drug.

In the coming weeks, however, the ACC and rheumatology leaders will be publishing an expert consensus statement that addresses key issues, such as how to best to use HCQ, maintenance HCQ, electrolyte monitoring, the optimal timing of electrocardiography and cardiac magnetic imaging, and symptoms to look for if cardiac involvement is suspected, Dr. Lakkireddy said.

Asked whether HCQ and AZM should be used in COVID-19 patients, Dr. Haines said in an interview that the “QT-prolonging effects are real, the arrhythmogenic potential is real, and the benefit to patients is nil or marginal. So I think that use of these drugs is appropriate and reasonable if it is done in a setting of a controlled trial, and I support that. But the routine use of these drugs probably is not warranted based on the data that we have available.”

Still, hydroxychloroquine continues to be dragged into the spotlight in recent days as an effective treatment for COVID-19, despite discredited research and the U.S. Food and Drug Administration’s June 15 revocation of its emergency-use authorization to allow use of HCQ and chloroquine to treat certain hospitalized COVID-19 patients.

“The unfortunate politicization of this issue has really muddied the waters because the general public doesn’t know what to believe or who to believe. The fact that treatment for a disease as serious as COVID should be modulated by political affiliation is just crazy to me,” said Dr. Haines. “We should be using the best science and taking careful observations, and whatever the recommendations derived from that should be uniformly adopted by everybody, irrespective of your political affiliation.”

Dr. Haines has received honoraria from Biosense Webster, Farapulse, and Sagentia, and is a consultant for Affera, Boston Scientific, Integer, Medtronic, Philips Healthcare, and Zoll. Dr. Lakkireddy has served as a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. 

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

A new analysis from Michigan’s largest health system provides sobering verification of the risks for QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin (HCQ/AZM).

One in five patients (21%) had a corrected QT (QTc) interval of at least 500 msec, a value that increases the risk for torsade de pointes in the general population and at which cardiovascular leaders have suggested withholding HCQ/AZM in COVID-19 patients.

“One of the most striking findings was when we looked at the other drugs being administered to these patients; 61% were being administered drugs that had QT-prolonging effects concomitantly with the HCQ and AZM therapy. So they were inadvertently doubling down on the QT-prolonging effects of these drugs,” senior author David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital, Royal Oak, Mich., said in an interview.

A total of 34 medications overlapped with HCQ/AZM therapy are known or suspected to increase the risk for torsade de pointes, a potentially life-threatening ventricular tachycardia. The most common of these were propofol coadministered in 123 patients, ondansetron in 114, dexmedetomidine in 54, haloperidol in 44, amiodarone in 43, and tramadol in 26.

“This speaks to the medical complexity of this patient population, but also suggests inadequate awareness of the QT-prolonging effects of many common medications,” the researchers say.

The study was published Aug. 5 in JACC Clinical Electrophysiology.

Both hydroxychloroquine and azithromycin increase the risk for QTc-interval prolongation by blocking the KCHN2-encoded hERG potassium channel. Several reports have linked the drugs to a triggering of QT prolongation in patients with COVID-19.

For the present study, Dr. Haines and colleagues examined data from 586 consecutive patients admitted with COVID-19 to the Beaumont Hospitals in Royal Oak and Troy, Mich., between March 13 and April 6. A baseline QTc interval was measured with 12-lead ECG prior to treatment initiation with hydroxychloroquine 400 mg twice daily for two doses, then 200 mg twice daily for 4 days, and azithromycin 500 mg once followed by 250 mg daily for 4 days.

Because of limited availability at the time, lead II ECG telemetry monitoring over the 5-day course of HCQ/AZM was recommended only in patients with baseline QTc intervals of at least 440 msec.

Patients without an interpretable baseline ECG or available telemetry/ECG monitoring for at least 1 day were also excluded, leaving 415 patients (mean age, 64 years; 45% female) in the study population. More than half (52%) were Black, 52% had hypertension, 30% had diabetes, and 14% had cancer.

As seen in previous studies, the QTc interval increased progressively and significantly after the administration of HCQ/AZM, from 443 msec to 473 msec.

The average time to maximum QTc was 2.9 days in a subset of 135 patients with QTc measurements prior to starting therapy and on days 1 through 5.

In multivariate analysis, independent predictors of a potentially hazardous QTc interval of at least 500 msec were:

• Age older than 65 years (odds ratio, 3.0; 95% confidence interval, 1.62-5.54).
• History of  (OR, 4.65; 95% CI, 2.01-10.74).
• Admission  of at least 1.5 mg/dL (OR, 2.22; 95% CI, 1.28-3.84).
• Peak troponin I level above 0.04 mg/mL (OR, 3.89; 95% CI, 2.22-6.83).
• Body mass index below 30 kg/m² (OR for a BMI of 30 kg/m² or higher, 0.45; 95% CI, 0.26-0.78).

Concomitant use of drugs with known risk for torsade de pointes was a significant risk factor in univariate analysis (OR, 1.73; P = .036), but fell out in the multivariate model.

No patients experienced high-grade arrhythmias during the study. In all, 112 of the 586 patients died during hospitalization, including 85 (21%) of the 415 study patients.

The change in QTc interval from baseline was greater in patients who died. Despite this, the only independent predictor of mortality was older age. One possible explanation is that the decision to monitor patients with baseline QTc intervals of at least 440 msec may have skewed the study population toward people with moderate or slightly long QTc intervals prior to the initiation of HCQ/AZM, Dr. Haines suggested. Monitoring and treatment duration were short, and clinicians also likely adjusted medications when excess QTc prolongation was observed.

Although it’s been months since data collection was completed in April, and the paper was written in record-breaking time, the study “is still very relevant because the drug is still out there,” observed Dr. Haines. “Even though it may not be used in as widespread a fashion as it had been when we first submitted the paper, it is still being used routinely by many hospitals and many practitioners.”

The use of hydroxychloroquine is “going through the roof” because of COVID-19, commented Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, HCA Midwest Health, Overland Park, Kan., who was not involved in the study.

“This study is very relevant, and I’m glad they shared their experience, and it’s pretty consistent with the data presented by other people. The question of whether hydroxychloroquine helps people with COVID is up for debate, but there is more evidence today that it is not as helpful as it was 3 months ago,” said Dr. Lakkireddy, who is also chair of the American College of Cardiology Electrophysiology Council.

He expressed concern for patients who may be taking HCQ with other medications that have QT-prolonging effects, and for the lack of long-term protocols in place for the drug.

In the coming weeks, however, the ACC and rheumatology leaders will be publishing an expert consensus statement that addresses key issues, such as how to best to use HCQ, maintenance HCQ, electrolyte monitoring, the optimal timing of electrocardiography and cardiac magnetic imaging, and symptoms to look for if cardiac involvement is suspected, Dr. Lakkireddy said.

Asked whether HCQ and AZM should be used in COVID-19 patients, Dr. Haines said in an interview that the “QT-prolonging effects are real, the arrhythmogenic potential is real, and the benefit to patients is nil or marginal. So I think that use of these drugs is appropriate and reasonable if it is done in a setting of a controlled trial, and I support that. But the routine use of these drugs probably is not warranted based on the data that we have available.”

Still, hydroxychloroquine continues to be dragged into the spotlight in recent days as an effective treatment for COVID-19, despite discredited research and the U.S. Food and Drug Administration’s June 15 revocation of its emergency-use authorization to allow use of HCQ and chloroquine to treat certain hospitalized COVID-19 patients.

“The unfortunate politicization of this issue has really muddied the waters because the general public doesn’t know what to believe or who to believe. The fact that treatment for a disease as serious as COVID should be modulated by political affiliation is just crazy to me,” said Dr. Haines. “We should be using the best science and taking careful observations, and whatever the recommendations derived from that should be uniformly adopted by everybody, irrespective of your political affiliation.”

Dr. Haines has received honoraria from Biosense Webster, Farapulse, and Sagentia, and is a consultant for Affera, Boston Scientific, Integer, Medtronic, Philips Healthcare, and Zoll. Dr. Lakkireddy has served as a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. 

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

Fractional flow reserve derived noninvasively from coronary CT angiography is a safe and accurate method for assessing the significance of coronary artery disease in patients with severe aortic stenosis who are headed for transcatheter aortic valve replacement (TAVR), according to results of the CAST-FFR prospective study.

Indeed, utilization of coronary CT angiography–derived fractional flow reserve (CT-FFR) for this purpose offers the advantage of using a single noninvasive imaging method to replace two invasive procedures: coronary angiography to assess the anatomy of coronary lesions, and conventional FFR using a pressure wire to determine the functional significance of a given coronary stenosis as a cause of ischemia, Michael Michail, MBBS, explained in reporting the results at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“Because up to 50% of patients with severe aortic stenosis undergoing TAVR have coexisting coronary artery disease, it remains common practice to perform prior invasive coronary angiography. However, this is associated with inherent risks, particularly in an elderly cohort with comorbidities. Additionally, coronary angiography provides no information on the functional impact of coronary stenoses, which may be important in guiding revascularization decisions prior to TAVR,” noted Dr. Michail, a cardiologist at Monash University, Melbourne.
 

Simulating FFR: ‘A one-stop shop cardiac CT’

Dr. Michail presented the results of the prospective CAST-FFR study, the first evaluation of CT-FFR for assessment of coronary arteries in patients with severe symptomatic aortic stenosis. This method uses computational fluid dynamics to transform data obtained noninvasively from a standard coronary CT angiography acquisition into a simulated FFR. And it offers the potential to streamline patient care.

“In current practice we see elderly patients with a long pre-TAVR assessment period, with numerous appointments and invasive procedures. Our vision is a one-stop shop cardiac CT that will provide the cardiologist with a complete assessment of the annular measurements, peripheral vasculature, and the coronary arteries ahead of their procedure,” according to Dr. Michail.

“We believe the ability to perform the requisite coronary assessment using CT-FFR will translate to improved patient care in several ways,” he continued. “Firstly, this will shorten the number of tests and overall diagnostic journey for patients. It will reduce the risk from unnecessary invasive procedures, and this will also reduce discomfort for the patient. Based on emerging evidence on the adverse prognostic impact of functionally significant coronary disease in aortic stenosis, this data has the potential to improve procedural risk stratification. And finally, contingent on further data, this may improve lesion selection for upfront revascularization.”

The CAST-FFR study was a small, single-center, proof-of-concept study in which 42 patients with severe aortic stenosis underwent both coronary CT angiography and conventional FFR with a pressure wire. The CT data was sent to a core laboratory for conversion into CT-FFR by evaluators blinded to the conventional FFR values.

Of the 42 participants, 39 (93%) had usable CT-FFR data on 60 coronary vessels. Dr. Michail and coinvestigators found a strong correlation between the conventional pressure wire FFR and CT-FFR findings, with a receiver operating characteristic area under the curve of 0.83 per vessel. CT-FFR had a diagnostic sensitivity and specificity of 73.9% and 78.4%, respectively, with a positive predictive value of 68%, a negative predictive value of 82.9%, and a diagnostic accuracy of 76.7%.

He cited as study limitations the small size, the fact that patients with previous revascularization or significant left ventricular impairment were excluded, and the study cohort’s relative youth.

“With a mean age of 76.2 years, it’s unclear whether these results can be extrapolated to very elderly patients with more calcified arteries undergoing TAVR. Encouragingly, though, a subgroup analysis based on calcium score showed no effect on accuracy,” according to the cardiologist.

CT-FFR may ‘shorten the diagnostic journey’ for fragile patients

Discussant Daniele Andreini, MD, PhD, praised the investigators’ concept of integrating the functional assessment provided by CT-FFR into a one-stop shop examination by cardiac CT angiography for TAVR planning.

“I would like to underline one of Dr. Michail’s messages: It’s really important to shorten the diagnostic journey for these fragile, older patients with aortic stenosis in order to improve safety, use less contrast, and avoid complications,” said Dr. Andreini, a cardiologist at the University of Milan and director of the cardiovascular CT and radiology unit at Monzino Cardiology Center, also in Milan.

Both Dr. Michail and Dr. Andreini reported having no financial conflicts of interest.

[email protected]

Fractional flow reserve derived noninvasively from coronary CT angiography is a safe and accurate method for assessing the significance of coronary artery disease in patients with severe aortic stenosis who are headed for transcatheter aortic valve replacement (TAVR), according to results of the CAST-FFR prospective study.

Indeed, utilization of coronary CT angiography–derived fractional flow reserve (CT-FFR) for this purpose offers the advantage of using a single noninvasive imaging method to replace two invasive procedures: coronary angiography to assess the anatomy of coronary lesions, and conventional FFR using a pressure wire to determine the functional significance of a given coronary stenosis as a cause of ischemia, Michael Michail, MBBS, explained in reporting the results at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“Because up to 50% of patients with severe aortic stenosis undergoing TAVR have coexisting coronary artery disease, it remains common practice to perform prior invasive coronary angiography. However, this is associated with inherent risks, particularly in an elderly cohort with comorbidities. Additionally, coronary angiography provides no information on the functional impact of coronary stenoses, which may be important in guiding revascularization decisions prior to TAVR,” noted Dr. Michail, a cardiologist at Monash University, Melbourne.
 

Simulating FFR: ‘A one-stop shop cardiac CT’

Dr. Michail presented the results of the prospective CAST-FFR study, the first evaluation of CT-FFR for assessment of coronary arteries in patients with severe symptomatic aortic stenosis. This method uses computational fluid dynamics to transform data obtained noninvasively from a standard coronary CT angiography acquisition into a simulated FFR. And it offers the potential to streamline patient care.

“In current practice we see elderly patients with a long pre-TAVR assessment period, with numerous appointments and invasive procedures. Our vision is a one-stop shop cardiac CT that will provide the cardiologist with a complete assessment of the annular measurements, peripheral vasculature, and the coronary arteries ahead of their procedure,” according to Dr. Michail.

“We believe the ability to perform the requisite coronary assessment using CT-FFR will translate to improved patient care in several ways,” he continued. “Firstly, this will shorten the number of tests and overall diagnostic journey for patients. It will reduce the risk from unnecessary invasive procedures, and this will also reduce discomfort for the patient. Based on emerging evidence on the adverse prognostic impact of functionally significant coronary disease in aortic stenosis, this data has the potential to improve procedural risk stratification. And finally, contingent on further data, this may improve lesion selection for upfront revascularization.”

The CAST-FFR study was a small, single-center, proof-of-concept study in which 42 patients with severe aortic stenosis underwent both coronary CT angiography and conventional FFR with a pressure wire. The CT data was sent to a core laboratory for conversion into CT-FFR by evaluators blinded to the conventional FFR values.

Of the 42 participants, 39 (93%) had usable CT-FFR data on 60 coronary vessels. Dr. Michail and coinvestigators found a strong correlation between the conventional pressure wire FFR and CT-FFR findings, with a receiver operating characteristic area under the curve of 0.83 per vessel. CT-FFR had a diagnostic sensitivity and specificity of 73.9% and 78.4%, respectively, with a positive predictive value of 68%, a negative predictive value of 82.9%, and a diagnostic accuracy of 76.7%.

He cited as study limitations the small size, the fact that patients with previous revascularization or significant left ventricular impairment were excluded, and the study cohort’s relative youth.

“With a mean age of 76.2 years, it’s unclear whether these results can be extrapolated to very elderly patients with more calcified arteries undergoing TAVR. Encouragingly, though, a subgroup analysis based on calcium score showed no effect on accuracy,” according to the cardiologist.

CT-FFR may ‘shorten the diagnostic journey’ for fragile patients

Discussant Daniele Andreini, MD, PhD, praised the investigators’ concept of integrating the functional assessment provided by CT-FFR into a one-stop shop examination by cardiac CT angiography for TAVR planning.

“I would like to underline one of Dr. Michail’s messages: It’s really important to shorten the diagnostic journey for these fragile, older patients with aortic stenosis in order to improve safety, use less contrast, and avoid complications,” said Dr. Andreini, a cardiologist at the University of Milan and director of the cardiovascular CT and radiology unit at Monzino Cardiology Center, also in Milan.

Both Dr. Michail and Dr. Andreini reported having no financial conflicts of interest.

[email protected]

Fractional flow reserve derived noninvasively from coronary CT angiography is a safe and accurate method for assessing the significance of coronary artery disease in patients with severe aortic stenosis who are headed for transcatheter aortic valve replacement (TAVR), according to results of the CAST-FFR prospective study.

Indeed, utilization of coronary CT angiography–derived fractional flow reserve (CT-FFR) for this purpose offers the advantage of using a single noninvasive imaging method to replace two invasive procedures: coronary angiography to assess the anatomy of coronary lesions, and conventional FFR using a pressure wire to determine the functional significance of a given coronary stenosis as a cause of ischemia, Michael Michail, MBBS, explained in reporting the results at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“Because up to 50% of patients with severe aortic stenosis undergoing TAVR have coexisting coronary artery disease, it remains common practice to perform prior invasive coronary angiography. However, this is associated with inherent risks, particularly in an elderly cohort with comorbidities. Additionally, coronary angiography provides no information on the functional impact of coronary stenoses, which may be important in guiding revascularization decisions prior to TAVR,” noted Dr. Michail, a cardiologist at Monash University, Melbourne.
 

Simulating FFR: ‘A one-stop shop cardiac CT’

Dr. Michail presented the results of the prospective CAST-FFR study, the first evaluation of CT-FFR for assessment of coronary arteries in patients with severe symptomatic aortic stenosis. This method uses computational fluid dynamics to transform data obtained noninvasively from a standard coronary CT angiography acquisition into a simulated FFR. And it offers the potential to streamline patient care.

“In current practice we see elderly patients with a long pre-TAVR assessment period, with numerous appointments and invasive procedures. Our vision is a one-stop shop cardiac CT that will provide the cardiologist with a complete assessment of the annular measurements, peripheral vasculature, and the coronary arteries ahead of their procedure,” according to Dr. Michail.

“We believe the ability to perform the requisite coronary assessment using CT-FFR will translate to improved patient care in several ways,” he continued. “Firstly, this will shorten the number of tests and overall diagnostic journey for patients. It will reduce the risk from unnecessary invasive procedures, and this will also reduce discomfort for the patient. Based on emerging evidence on the adverse prognostic impact of functionally significant coronary disease in aortic stenosis, this data has the potential to improve procedural risk stratification. And finally, contingent on further data, this may improve lesion selection for upfront revascularization.”

The CAST-FFR study was a small, single-center, proof-of-concept study in which 42 patients with severe aortic stenosis underwent both coronary CT angiography and conventional FFR with a pressure wire. The CT data was sent to a core laboratory for conversion into CT-FFR by evaluators blinded to the conventional FFR values.

Of the 42 participants, 39 (93%) had usable CT-FFR data on 60 coronary vessels. Dr. Michail and coinvestigators found a strong correlation between the conventional pressure wire FFR and CT-FFR findings, with a receiver operating characteristic area under the curve of 0.83 per vessel. CT-FFR had a diagnostic sensitivity and specificity of 73.9% and 78.4%, respectively, with a positive predictive value of 68%, a negative predictive value of 82.9%, and a diagnostic accuracy of 76.7%.

He cited as study limitations the small size, the fact that patients with previous revascularization or significant left ventricular impairment were excluded, and the study cohort’s relative youth.

“With a mean age of 76.2 years, it’s unclear whether these results can be extrapolated to very elderly patients with more calcified arteries undergoing TAVR. Encouragingly, though, a subgroup analysis based on calcium score showed no effect on accuracy,” according to the cardiologist.

CT-FFR may ‘shorten the diagnostic journey’ for fragile patients

Discussant Daniele Andreini, MD, PhD, praised the investigators’ concept of integrating the functional assessment provided by CT-FFR into a one-stop shop examination by cardiac CT angiography for TAVR planning.

“I would like to underline one of Dr. Michail’s messages: It’s really important to shorten the diagnostic journey for these fragile, older patients with aortic stenosis in order to improve safety, use less contrast, and avoid complications,” said Dr. Andreini, a cardiologist at the University of Milan and director of the cardiovascular CT and radiology unit at Monzino Cardiology Center, also in Milan.

Both Dr. Michail and Dr. Andreini reported having no financial conflicts of interest.

[email protected]

The brain’s reaction to stress may be an important contributor to chest pain in patients with coronary artery disease (CAD), according to results of a cohort study.

Jana Blaková/Thinkstock

“Although more research is needed, these results may potentially shift the paradigm by which angina is evaluated by refocusing clinical evaluation and management of psychological stress as adjunct to traditional cardiac evaluations,” wrote Kasra Moazzami, MD, MPH, of Emory University in Atlanta, and his coauthors in Circulation: Cardiovascular Imaging.

To determine if an association exists between stress-induced frontal lobe activity and angina, the researchers launched a study of 148 patients with stable CAD. Their mean age was 62, 69% were male, and roughly 36% were Black. Angina symptoms were assessed at baseline and also after 2 years through the Seattle Angina Questionnaire’s angina frequency subscale.

As the patients underwent stress testing that included both speech and arithmetic stressors, they also received eight brain scans via high-resolution positron emission tomography (HR-PET) brain imaging. Two scans occurred during each of the two control and two stress conditions. Subsequent analysis of these images evaluated regional blood flow relative to total brain flow. Each patient also underwent myocardial perfusion imaging (MPI) at rest, under stress conditions, and during conventional stress testing.

At baseline, patients who reported experiencing angina monthly (35) or daily/weekly (19) had higher rates of mental stress–induced ischemia, more common symptoms of depression and anxiety, and more use of antidepressants and nitrates. Patients reporting angina during stress testing with MPI had higher inferior frontal lobe activation (1.43), compared with patients without active chest pain (1.19; P = 0.03). Patients reporting angina during stress testing also had fewer years of education, higher Beck Depression Inventory scores, and higher posttraumatic stress disorder (PTSD) checklist scores.
 

More angina correlates with more mental stress

At 2-year-follow-up, 28 (24%) of the 112 returning patients reported an increase in angina episodes. Those patients had a higher mean inferior frontal lobe activation with mental stress at baseline, compared with returning patients who reported a decrease in chest pain frequency (1.82 versus 0.92; P = .01).

After adjustment for sociodemographic and lifestyle variables, any doubling in inferior frontal lobe activation led to an increase in angina frequency by 13.7 units at baseline (95% confidence interval, 6.3-21.7; P = .008) and 11.6 units during follow-up (95% CI, 4.1-19.2; P = .01). After relative importance analysis, the most important correlate of angina was found to be inferior frontal lobe activation at 36.5%, followed by Beck Depression Inventory score and PTSD checklist score.
 

‘It shows that the heart and brain are connected’

“Previous studies have linked mental stress with ischemia using nuclear stress testing. This study is unique in that it looked at brain activity associated with mental stress and was able to correlate that activity with angina,” said cardiologist Nieca Goldberg, MD, of NYU Langone in New York City in an interview. “It shows that the heart and brain are connected.”

The authors acknowledged their study’s limitations, including using standard stress-inducing protocols that did not account for or reflect any real-life stressors. In addition, although their methods are still considered clinically relevant, retrospectively collecting angina symptoms via questionnaire rather than a prospective diary could have led to incomplete responses.

Dr. Goldberg noted that additional research should include a more diverse population – women in particular were underrepresented in this study – while focusing on how interventions for stress can play a role in angina symptoms and brain activity.

That said, she added, “until there are more studies, it is important to consider mental stress in assessing angina symptoms in patients.”

The study was supported by grants from the National Institutes of Health. The authors reported no potential conflicts of interest.

SOURCE: Moazzami K et al. Circ Cardiovasc Imaging. 2020 Aug 10. doi: 10.1161/circimaging.120.010710.

The brain’s reaction to stress may be an important contributor to chest pain in patients with coronary artery disease (CAD), according to results of a cohort study.

Jana Blaková/Thinkstock

“Although more research is needed, these results may potentially shift the paradigm by which angina is evaluated by refocusing clinical evaluation and management of psychological stress as adjunct to traditional cardiac evaluations,” wrote Kasra Moazzami, MD, MPH, of Emory University in Atlanta, and his coauthors in Circulation: Cardiovascular Imaging.

To determine if an association exists between stress-induced frontal lobe activity and angina, the researchers launched a study of 148 patients with stable CAD. Their mean age was 62, 69% were male, and roughly 36% were Black. Angina symptoms were assessed at baseline and also after 2 years through the Seattle Angina Questionnaire’s angina frequency subscale.

As the patients underwent stress testing that included both speech and arithmetic stressors, they also received eight brain scans via high-resolution positron emission tomography (HR-PET) brain imaging. Two scans occurred during each of the two control and two stress conditions. Subsequent analysis of these images evaluated regional blood flow relative to total brain flow. Each patient also underwent myocardial perfusion imaging (MPI) at rest, under stress conditions, and during conventional stress testing.

At baseline, patients who reported experiencing angina monthly (35) or daily/weekly (19) had higher rates of mental stress–induced ischemia, more common symptoms of depression and anxiety, and more use of antidepressants and nitrates. Patients reporting angina during stress testing with MPI had higher inferior frontal lobe activation (1.43), compared with patients without active chest pain (1.19; P = 0.03). Patients reporting angina during stress testing also had fewer years of education, higher Beck Depression Inventory scores, and higher posttraumatic stress disorder (PTSD) checklist scores.
 

More angina correlates with more mental stress

At 2-year-follow-up, 28 (24%) of the 112 returning patients reported an increase in angina episodes. Those patients had a higher mean inferior frontal lobe activation with mental stress at baseline, compared with returning patients who reported a decrease in chest pain frequency (1.82 versus 0.92; P = .01).

After adjustment for sociodemographic and lifestyle variables, any doubling in inferior frontal lobe activation led to an increase in angina frequency by 13.7 units at baseline (95% confidence interval, 6.3-21.7; P = .008) and 11.6 units during follow-up (95% CI, 4.1-19.2; P = .01). After relative importance analysis, the most important correlate of angina was found to be inferior frontal lobe activation at 36.5%, followed by Beck Depression Inventory score and PTSD checklist score.
 

‘It shows that the heart and brain are connected’

“Previous studies have linked mental stress with ischemia using nuclear stress testing. This study is unique in that it looked at brain activity associated with mental stress and was able to correlate that activity with angina,” said cardiologist Nieca Goldberg, MD, of NYU Langone in New York City in an interview. “It shows that the heart and brain are connected.”

The authors acknowledged their study’s limitations, including using standard stress-inducing protocols that did not account for or reflect any real-life stressors. In addition, although their methods are still considered clinically relevant, retrospectively collecting angina symptoms via questionnaire rather than a prospective diary could have led to incomplete responses.

Dr. Goldberg noted that additional research should include a more diverse population – women in particular were underrepresented in this study – while focusing on how interventions for stress can play a role in angina symptoms and brain activity.

That said, she added, “until there are more studies, it is important to consider mental stress in assessing angina symptoms in patients.”

The study was supported by grants from the National Institutes of Health. The authors reported no potential conflicts of interest.

SOURCE: Moazzami K et al. Circ Cardiovasc Imaging. 2020 Aug 10. doi: 10.1161/circimaging.120.010710.

The brain’s reaction to stress may be an important contributor to chest pain in patients with coronary artery disease (CAD), according to results of a cohort study.

Jana Blaková/Thinkstock

“Although more research is needed, these results may potentially shift the paradigm by which angina is evaluated by refocusing clinical evaluation and management of psychological stress as adjunct to traditional cardiac evaluations,” wrote Kasra Moazzami, MD, MPH, of Emory University in Atlanta, and his coauthors in Circulation: Cardiovascular Imaging.

To determine if an association exists between stress-induced frontal lobe activity and angina, the researchers launched a study of 148 patients with stable CAD. Their mean age was 62, 69% were male, and roughly 36% were Black. Angina symptoms were assessed at baseline and also after 2 years through the Seattle Angina Questionnaire’s angina frequency subscale.

As the patients underwent stress testing that included both speech and arithmetic stressors, they also received eight brain scans via high-resolution positron emission tomography (HR-PET) brain imaging. Two scans occurred during each of the two control and two stress conditions. Subsequent analysis of these images evaluated regional blood flow relative to total brain flow. Each patient also underwent myocardial perfusion imaging (MPI) at rest, under stress conditions, and during conventional stress testing.

At baseline, patients who reported experiencing angina monthly (35) or daily/weekly (19) had higher rates of mental stress–induced ischemia, more common symptoms of depression and anxiety, and more use of antidepressants and nitrates. Patients reporting angina during stress testing with MPI had higher inferior frontal lobe activation (1.43), compared with patients without active chest pain (1.19; P = 0.03). Patients reporting angina during stress testing also had fewer years of education, higher Beck Depression Inventory scores, and higher posttraumatic stress disorder (PTSD) checklist scores.
 

More angina correlates with more mental stress

At 2-year-follow-up, 28 (24%) of the 112 returning patients reported an increase in angina episodes. Those patients had a higher mean inferior frontal lobe activation with mental stress at baseline, compared with returning patients who reported a decrease in chest pain frequency (1.82 versus 0.92; P = .01).

After adjustment for sociodemographic and lifestyle variables, any doubling in inferior frontal lobe activation led to an increase in angina frequency by 13.7 units at baseline (95% confidence interval, 6.3-21.7; P = .008) and 11.6 units during follow-up (95% CI, 4.1-19.2; P = .01). After relative importance analysis, the most important correlate of angina was found to be inferior frontal lobe activation at 36.5%, followed by Beck Depression Inventory score and PTSD checklist score.
 

‘It shows that the heart and brain are connected’

“Previous studies have linked mental stress with ischemia using nuclear stress testing. This study is unique in that it looked at brain activity associated with mental stress and was able to correlate that activity with angina,” said cardiologist Nieca Goldberg, MD, of NYU Langone in New York City in an interview. “It shows that the heart and brain are connected.”

The authors acknowledged their study’s limitations, including using standard stress-inducing protocols that did not account for or reflect any real-life stressors. In addition, although their methods are still considered clinically relevant, retrospectively collecting angina symptoms via questionnaire rather than a prospective diary could have led to incomplete responses.

Dr. Goldberg noted that additional research should include a more diverse population – women in particular were underrepresented in this study – while focusing on how interventions for stress can play a role in angina symptoms and brain activity.

That said, she added, “until there are more studies, it is important to consider mental stress in assessing angina symptoms in patients.”

The study was supported by grants from the National Institutes of Health. The authors reported no potential conflicts of interest.

SOURCE: Moazzami K et al. Circ Cardiovasc Imaging. 2020 Aug 10. doi: 10.1161/circimaging.120.010710.

Monogenic disorders with heart and vascular effects are each pretty rare in clinical practice but collectively can make up a fair proportion of the patients cardiologists see. Still, the diagnosis is missed more often than not, even when the clinical signs are there, suggests an observational study, supporting broader genetic testing in cardiovascular patients.

In a cohort of more than 8,000 patients referred for cardiac catheterization, diagnosis of such a monogenic cardiovascular disease (MCVD) was made in only 35% of those with one related gene variant and signs of phenotypic expression in the electronic health record.

The findings are novel for measuring the field’s “burden of missed diagnoses” in patients with MCVD, which “represent a missed opportunity that could be addressed by genetic screening,” contended the study report, published in the Aug. 18 issue of the Journal of the American College of Cardiology.

“The underrecognition of these diseases underscores the importance of including monogenic diseases in the treating physician’s differential diagnosis,” say the authors, led by Jawan W. Abdulrahim, MD, Duke University, Durham, N.C.

Diagnosis of MCVDs can be important, the group wrote, because many, including familial transthyretin amyloidosis (TTR) and other disorders that pose an increased risk for sudden death, have evidence-based treatment modalities available or are clinically actionable. “Identification of patients with MCVD variants” is also “important for cascade screening of family members who are at risk of inheriting the pathogenic mutations.”

“We tend to ignore these monogenic diseases because they are so rare individually but, in aggregate, monogenic diseases are actually quite common,” senior author Svati H. Shah, MD, MHS, also of Duke University, said in an interview.

The results “support that the cardiology community over time adopt a genotype-forward approach,” one in which every patient presenting to a cardiovascular clinic is genotyped, she said.

One implication of such an approach, Dr. Shah agreed, is that “we would be able to pick these people up earlier in their disease, especially in the context of therapies that could improve certainly their progression, but even their survival.”

For now, she said, the study suggests that “these disorders are more frequent than perhaps all cardiologists are aware of, and we just need to keep our eyes open and know when to refer patients to a cardiovascular genetics clinic, which maybe has more time and can deal with all the nuances that go along with genetic testing.”

In the total cohort, 4.5% were found to carry a gene variant known or believed to cause such diseases. The most frequently represented conditions were familial TTR, hereditary hemochromatosis, heterozygous familial hypercholesterolemia, and various cardiomyopathies.

Of those patients, 52 received a clinical diagnosis of the monogenic disorder after an EHR review. Of the 290 without such a diagnosis, two-thirds showed no evidence in their EHR of the variant’s phenotypic signs. But the records of the other third featured at least some signs that the disease had manifested clinically.

“These data serve as a reminder that monogenic Mendelian disease, including heart and vascular disease, varies in penetrance from individual to individual and may not always present with clinically detectable phenotypes,” noted an editorial accompanying the report.

They also “provide a compelling basis for expanding the role of targeted genetic testing in patients with more traditional forms of heart and vascular disease,” wrote Scott M. Damrauer, MD, University of Pennsylvania, Philadelphia, and William S. Weintraub, MD, Medstar Washington Hospital Center and Georgetown University, Washington.

“Based on the current report, the number needed to screen in a complex cardiovascular patient population to detect 1 case of undiagnosed monogenic cardiovascular disease is 85,” they wrote. “This places targeted genetic testing well within what is considered to be efficacious for most screening programs and in the range of that of other common cardiovascular diseases and cancers.”

Among the 342 patients with a variant predicting a single MCVD – in addition to the 52 who received a diagnosis – 193 had records with no indication of phenotypic expression and so did not receive a diagnosis.

But the 97 patients without a diagnosis who nevertheless had documented signs of some phenotypic expression were deemed, on the basis of extent of expression, to represent a possibly, probably, or definitely missed diagnosis.

Familial TTR made up about 45% of such potentially missed diagnoses, the report noted.

Broader screening of patients with cardiovascular disease, Dr. Shah speculated, “might actually be not only a clinically useful endeavor, but – when we think about the aggregate burden of these monogenic disorders – potentially even cost-effective.”

As the price of genetic sequencing drops, she said, “I think we’ll start to see even more health systems wanting to incorporate the genotype-forward approach.”

Dr. Shah reports serving as primary investigator for research sponsored by Verily Life Sciences and AstraZeneca. Dr. Abdulrahim reports no relevant relationships. Disclosures for the other authors are in the report. Dr. Damrauer discloses receiving research support from RenalytixAI and consulting fees from Calico Labs. Dr. Weintraub had no relevant disclosures.

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

Monogenic disorders with heart and vascular effects are each pretty rare in clinical practice but collectively can make up a fair proportion of the patients cardiologists see. Still, the diagnosis is missed more often than not, even when the clinical signs are there, suggests an observational study, supporting broader genetic testing in cardiovascular patients.

In a cohort of more than 8,000 patients referred for cardiac catheterization, diagnosis of such a monogenic cardiovascular disease (MCVD) was made in only 35% of those with one related gene variant and signs of phenotypic expression in the electronic health record.

The findings are novel for measuring the field’s “burden of missed diagnoses” in patients with MCVD, which “represent a missed opportunity that could be addressed by genetic screening,” contended the study report, published in the Aug. 18 issue of the Journal of the American College of Cardiology.

“The underrecognition of these diseases underscores the importance of including monogenic diseases in the treating physician’s differential diagnosis,” say the authors, led by Jawan W. Abdulrahim, MD, Duke University, Durham, N.C.

Diagnosis of MCVDs can be important, the group wrote, because many, including familial transthyretin amyloidosis (TTR) and other disorders that pose an increased risk for sudden death, have evidence-based treatment modalities available or are clinically actionable. “Identification of patients with MCVD variants” is also “important for cascade screening of family members who are at risk of inheriting the pathogenic mutations.”

“We tend to ignore these monogenic diseases because they are so rare individually but, in aggregate, monogenic diseases are actually quite common,” senior author Svati H. Shah, MD, MHS, also of Duke University, said in an interview.

The results “support that the cardiology community over time adopt a genotype-forward approach,” one in which every patient presenting to a cardiovascular clinic is genotyped, she said.

One implication of such an approach, Dr. Shah agreed, is that “we would be able to pick these people up earlier in their disease, especially in the context of therapies that could improve certainly their progression, but even their survival.”

For now, she said, the study suggests that “these disorders are more frequent than perhaps all cardiologists are aware of, and we just need to keep our eyes open and know when to refer patients to a cardiovascular genetics clinic, which maybe has more time and can deal with all the nuances that go along with genetic testing.”

In the total cohort, 4.5% were found to carry a gene variant known or believed to cause such diseases. The most frequently represented conditions were familial TTR, hereditary hemochromatosis, heterozygous familial hypercholesterolemia, and various cardiomyopathies.

Of those patients, 52 received a clinical diagnosis of the monogenic disorder after an EHR review. Of the 290 without such a diagnosis, two-thirds showed no evidence in their EHR of the variant’s phenotypic signs. But the records of the other third featured at least some signs that the disease had manifested clinically.

“These data serve as a reminder that monogenic Mendelian disease, including heart and vascular disease, varies in penetrance from individual to individual and may not always present with clinically detectable phenotypes,” noted an editorial accompanying the report.

They also “provide a compelling basis for expanding the role of targeted genetic testing in patients with more traditional forms of heart and vascular disease,” wrote Scott M. Damrauer, MD, University of Pennsylvania, Philadelphia, and William S. Weintraub, MD, Medstar Washington Hospital Center and Georgetown University, Washington.

“Based on the current report, the number needed to screen in a complex cardiovascular patient population to detect 1 case of undiagnosed monogenic cardiovascular disease is 85,” they wrote. “This places targeted genetic testing well within what is considered to be efficacious for most screening programs and in the range of that of other common cardiovascular diseases and cancers.”

Among the 342 patients with a variant predicting a single MCVD – in addition to the 52 who received a diagnosis – 193 had records with no indication of phenotypic expression and so did not receive a diagnosis.

But the 97 patients without a diagnosis who nevertheless had documented signs of some phenotypic expression were deemed, on the basis of extent of expression, to represent a possibly, probably, or definitely missed diagnosis.

Familial TTR made up about 45% of such potentially missed diagnoses, the report noted.

Broader screening of patients with cardiovascular disease, Dr. Shah speculated, “might actually be not only a clinically useful endeavor, but – when we think about the aggregate burden of these monogenic disorders – potentially even cost-effective.”

As the price of genetic sequencing drops, she said, “I think we’ll start to see even more health systems wanting to incorporate the genotype-forward approach.”

Dr. Shah reports serving as primary investigator for research sponsored by Verily Life Sciences and AstraZeneca. Dr. Abdulrahim reports no relevant relationships. Disclosures for the other authors are in the report. Dr. Damrauer discloses receiving research support from RenalytixAI and consulting fees from Calico Labs. Dr. Weintraub had no relevant disclosures.

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

Monogenic disorders with heart and vascular effects are each pretty rare in clinical practice but collectively can make up a fair proportion of the patients cardiologists see. Still, the diagnosis is missed more often than not, even when the clinical signs are there, suggests an observational study, supporting broader genetic testing in cardiovascular patients.

In a cohort of more than 8,000 patients referred for cardiac catheterization, diagnosis of such a monogenic cardiovascular disease (MCVD) was made in only 35% of those with one related gene variant and signs of phenotypic expression in the electronic health record.

The findings are novel for measuring the field’s “burden of missed diagnoses” in patients with MCVD, which “represent a missed opportunity that could be addressed by genetic screening,” contended the study report, published in the Aug. 18 issue of the Journal of the American College of Cardiology.

“The underrecognition of these diseases underscores the importance of including monogenic diseases in the treating physician’s differential diagnosis,” say the authors, led by Jawan W. Abdulrahim, MD, Duke University, Durham, N.C.

Diagnosis of MCVDs can be important, the group wrote, because many, including familial transthyretin amyloidosis (TTR) and other disorders that pose an increased risk for sudden death, have evidence-based treatment modalities available or are clinically actionable. “Identification of patients with MCVD variants” is also “important for cascade screening of family members who are at risk of inheriting the pathogenic mutations.”

“We tend to ignore these monogenic diseases because they are so rare individually but, in aggregate, monogenic diseases are actually quite common,” senior author Svati H. Shah, MD, MHS, also of Duke University, said in an interview.

The results “support that the cardiology community over time adopt a genotype-forward approach,” one in which every patient presenting to a cardiovascular clinic is genotyped, she said.

One implication of such an approach, Dr. Shah agreed, is that “we would be able to pick these people up earlier in their disease, especially in the context of therapies that could improve certainly their progression, but even their survival.”

For now, she said, the study suggests that “these disorders are more frequent than perhaps all cardiologists are aware of, and we just need to keep our eyes open and know when to refer patients to a cardiovascular genetics clinic, which maybe has more time and can deal with all the nuances that go along with genetic testing.”

In the total cohort, 4.5% were found to carry a gene variant known or believed to cause such diseases. The most frequently represented conditions were familial TTR, hereditary hemochromatosis, heterozygous familial hypercholesterolemia, and various cardiomyopathies.

Of those patients, 52 received a clinical diagnosis of the monogenic disorder after an EHR review. Of the 290 without such a diagnosis, two-thirds showed no evidence in their EHR of the variant’s phenotypic signs. But the records of the other third featured at least some signs that the disease had manifested clinically.

“These data serve as a reminder that monogenic Mendelian disease, including heart and vascular disease, varies in penetrance from individual to individual and may not always present with clinically detectable phenotypes,” noted an editorial accompanying the report.

They also “provide a compelling basis for expanding the role of targeted genetic testing in patients with more traditional forms of heart and vascular disease,” wrote Scott M. Damrauer, MD, University of Pennsylvania, Philadelphia, and William S. Weintraub, MD, Medstar Washington Hospital Center and Georgetown University, Washington.

“Based on the current report, the number needed to screen in a complex cardiovascular patient population to detect 1 case of undiagnosed monogenic cardiovascular disease is 85,” they wrote. “This places targeted genetic testing well within what is considered to be efficacious for most screening programs and in the range of that of other common cardiovascular diseases and cancers.”

Among the 342 patients with a variant predicting a single MCVD – in addition to the 52 who received a diagnosis – 193 had records with no indication of phenotypic expression and so did not receive a diagnosis.

But the 97 patients without a diagnosis who nevertheless had documented signs of some phenotypic expression were deemed, on the basis of extent of expression, to represent a possibly, probably, or definitely missed diagnosis.

Familial TTR made up about 45% of such potentially missed diagnoses, the report noted.

Broader screening of patients with cardiovascular disease, Dr. Shah speculated, “might actually be not only a clinically useful endeavor, but – when we think about the aggregate burden of these monogenic disorders – potentially even cost-effective.”

As the price of genetic sequencing drops, she said, “I think we’ll start to see even more health systems wanting to incorporate the genotype-forward approach.”

Dr. Shah reports serving as primary investigator for research sponsored by Verily Life Sciences and AstraZeneca. Dr. Abdulrahim reports no relevant relationships. Disclosures for the other authors are in the report. Dr. Damrauer discloses receiving research support from RenalytixAI and consulting fees from Calico Labs. Dr. Weintraub had no relevant disclosures.

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

Patients with sarcoidosis have an increased risk of heart failure and other adverse outcomes, including all-cause mortality, according to a decade-long nationwide study of Danish patients with the inflammatory disease.

“Although these findings are suggestive of the need for regular monitoring of cardiac manifestations in patients with sarcoidosis, it is important to emphasize that no causal relationships can be established from an observational study. Further studies are therefore needed to confirm our findings,” said first author Adelina Yafasova, MB, of Copenhagen University Hospital in Denmark, in an interview. The study was published in the Journal of the American College of Cardiology.

To determine the long-term risk of cardiac outcomes, and beyond – including incident heart failure; a composite of implantable cardioverter-defibrillator (ICD) implantation, ventricular arrhythmias or cardiac arrest; and all-cause mortality – Dr. Yafasova and her colleagues analyzed data from all Danish residents 18 years or older who were diagnosed with sarcoidosis from 1996 to 2016. Patients with any history of cardiac events were excluded. Of the 12,883 diagnosed patients, 11,834 were matched with subjects from a nationwide background population of more than 47,000 based on age, sex, and comorbidity. The median age of both populations was 42.8 (33.1-55.8) and 54.3% were men.

Median follow-up was 8.2 years for the sarcoidosis population and 8.4 years for the background population. The absolute 10-year risk of heart failure was 3.18% (95% confidence interval, 2.83%-3.57%) for sarcoidosis patients and 1.72% (95% CI, 1.58%-1.86%) for their matched controls. The 10-year risk for the composite of ICD implantation, ventricular arrhythmias and cardiac arrest was 0.96% (95% CI, 0.77%-1.18%) for sarcoidosis patients and 0.45% (95% CI, 0.38%-0.53%) for the background population.

For all-cause mortality, the 10-year risk was 10.88% (95% CI, 10.23%-11.55%) for sarcoidosis patients and 7.43% (95% CI, 7.15%-7.72%) for the background population. In a secondary analysis that compared all-cause mortality between the 364 sarcoidosis patients who developed heart failure and the 1,456 patients with heart failure without a history of sarcoidosis, the sarcoidosis group had a 35% higher rate than the nonsarcoidosis group (adjusted hazard ratio 1.35; 95% CI, 1.10-1.64).

“It’s not necessarily surprising that sarcoidosis patients would have a higher rate of heart failure,” said Melissa A. Lyle, MD, of the Mayo Clinic in Jacksonville, Fla., in an interview. “But the key takeaway is that sarcoidosis was associated with a higher rate of all-cause mortality compared to patients with heart failure and no sarcoidosis. That was more of a surprise.”

“There’s been some discrepancy in previous studies describing the cardiovascular outcomes in sarcoidosis,” Dr. Lyle added, “so I think this study provides excellent information while also highlighting the need for additional large-scale studies. We need to have further data on cardiovascular outcomes, which will allow us to refine the consensus statements and guidelines for management and the diagnosis of cardiac sarcoidosis.”

Dr. Lyle and Leslie T. Cooper Jr., MD, also of the Mayo Clinic, extrapolated on those thoughts in an editorial that accompanied the study. In it, the two authors praised the size and lengthy follow-up of the study, while noting its limitations. Specifically, they stressed that the study’s Danish population “may not be representative of other general populations” because of notable differences in ethnicity, age, and comorbidities.

That said, they reinforced that the study did feature “important takeaways” and that its findings emphasize the “need for monitoring for cardiac manifestations in patients with systemic sarcoidosis.”

In addition to the limitations noted in the editorial, the study’s authors acknowledged that the observational nature limited its “assessment of cause-effect relationships” and that the diagnosis codes for sarcoidosis had not been validated in the Danish National Patient Registry.

The authors of both the study and the editorial reported no conflicts of interest.

SOURCE: Yafasova A et al. J Am Coll Cardiol. 2020 Aug 10. doi: 10.1016/j.jacc.2020.06.038.

Patients with sarcoidosis have an increased risk of heart failure and other adverse outcomes, including all-cause mortality, according to a decade-long nationwide study of Danish patients with the inflammatory disease.

“Although these findings are suggestive of the need for regular monitoring of cardiac manifestations in patients with sarcoidosis, it is important to emphasize that no causal relationships can be established from an observational study. Further studies are therefore needed to confirm our findings,” said first author Adelina Yafasova, MB, of Copenhagen University Hospital in Denmark, in an interview. The study was published in the Journal of the American College of Cardiology.

To determine the long-term risk of cardiac outcomes, and beyond – including incident heart failure; a composite of implantable cardioverter-defibrillator (ICD) implantation, ventricular arrhythmias or cardiac arrest; and all-cause mortality – Dr. Yafasova and her colleagues analyzed data from all Danish residents 18 years or older who were diagnosed with sarcoidosis from 1996 to 2016. Patients with any history of cardiac events were excluded. Of the 12,883 diagnosed patients, 11,834 were matched with subjects from a nationwide background population of more than 47,000 based on age, sex, and comorbidity. The median age of both populations was 42.8 (33.1-55.8) and 54.3% were men.

Median follow-up was 8.2 years for the sarcoidosis population and 8.4 years for the background population. The absolute 10-year risk of heart failure was 3.18% (95% confidence interval, 2.83%-3.57%) for sarcoidosis patients and 1.72% (95% CI, 1.58%-1.86%) for their matched controls. The 10-year risk for the composite of ICD implantation, ventricular arrhythmias and cardiac arrest was 0.96% (95% CI, 0.77%-1.18%) for sarcoidosis patients and 0.45% (95% CI, 0.38%-0.53%) for the background population.

For all-cause mortality, the 10-year risk was 10.88% (95% CI, 10.23%-11.55%) for sarcoidosis patients and 7.43% (95% CI, 7.15%-7.72%) for the background population. In a secondary analysis that compared all-cause mortality between the 364 sarcoidosis patients who developed heart failure and the 1,456 patients with heart failure without a history of sarcoidosis, the sarcoidosis group had a 35% higher rate than the nonsarcoidosis group (adjusted hazard ratio 1.35; 95% CI, 1.10-1.64).

“It’s not necessarily surprising that sarcoidosis patients would have a higher rate of heart failure,” said Melissa A. Lyle, MD, of the Mayo Clinic in Jacksonville, Fla., in an interview. “But the key takeaway is that sarcoidosis was associated with a higher rate of all-cause mortality compared to patients with heart failure and no sarcoidosis. That was more of a surprise.”

“There’s been some discrepancy in previous studies describing the cardiovascular outcomes in sarcoidosis,” Dr. Lyle added, “so I think this study provides excellent information while also highlighting the need for additional large-scale studies. We need to have further data on cardiovascular outcomes, which will allow us to refine the consensus statements and guidelines for management and the diagnosis of cardiac sarcoidosis.”

Dr. Lyle and Leslie T. Cooper Jr., MD, also of the Mayo Clinic, extrapolated on those thoughts in an editorial that accompanied the study. In it, the two authors praised the size and lengthy follow-up of the study, while noting its limitations. Specifically, they stressed that the study’s Danish population “may not be representative of other general populations” because of notable differences in ethnicity, age, and comorbidities.

That said, they reinforced that the study did feature “important takeaways” and that its findings emphasize the “need for monitoring for cardiac manifestations in patients with systemic sarcoidosis.”

In addition to the limitations noted in the editorial, the study’s authors acknowledged that the observational nature limited its “assessment of cause-effect relationships” and that the diagnosis codes for sarcoidosis had not been validated in the Danish National Patient Registry.

The authors of both the study and the editorial reported no conflicts of interest.

SOURCE: Yafasova A et al. J Am Coll Cardiol. 2020 Aug 10. doi: 10.1016/j.jacc.2020.06.038.

Patients with sarcoidosis have an increased risk of heart failure and other adverse outcomes, including all-cause mortality, according to a decade-long nationwide study of Danish patients with the inflammatory disease.

“Although these findings are suggestive of the need for regular monitoring of cardiac manifestations in patients with sarcoidosis, it is important to emphasize that no causal relationships can be established from an observational study. Further studies are therefore needed to confirm our findings,” said first author Adelina Yafasova, MB, of Copenhagen University Hospital in Denmark, in an interview. The study was published in the Journal of the American College of Cardiology.

To determine the long-term risk of cardiac outcomes, and beyond – including incident heart failure; a composite of implantable cardioverter-defibrillator (ICD) implantation, ventricular arrhythmias or cardiac arrest; and all-cause mortality – Dr. Yafasova and her colleagues analyzed data from all Danish residents 18 years or older who were diagnosed with sarcoidosis from 1996 to 2016. Patients with any history of cardiac events were excluded. Of the 12,883 diagnosed patients, 11,834 were matched with subjects from a nationwide background population of more than 47,000 based on age, sex, and comorbidity. The median age of both populations was 42.8 (33.1-55.8) and 54.3% were men.

Median follow-up was 8.2 years for the sarcoidosis population and 8.4 years for the background population. The absolute 10-year risk of heart failure was 3.18% (95% confidence interval, 2.83%-3.57%) for sarcoidosis patients and 1.72% (95% CI, 1.58%-1.86%) for their matched controls. The 10-year risk for the composite of ICD implantation, ventricular arrhythmias and cardiac arrest was 0.96% (95% CI, 0.77%-1.18%) for sarcoidosis patients and 0.45% (95% CI, 0.38%-0.53%) for the background population.

For all-cause mortality, the 10-year risk was 10.88% (95% CI, 10.23%-11.55%) for sarcoidosis patients and 7.43% (95% CI, 7.15%-7.72%) for the background population. In a secondary analysis that compared all-cause mortality between the 364 sarcoidosis patients who developed heart failure and the 1,456 patients with heart failure without a history of sarcoidosis, the sarcoidosis group had a 35% higher rate than the nonsarcoidosis group (adjusted hazard ratio 1.35; 95% CI, 1.10-1.64).

“It’s not necessarily surprising that sarcoidosis patients would have a higher rate of heart failure,” said Melissa A. Lyle, MD, of the Mayo Clinic in Jacksonville, Fla., in an interview. “But the key takeaway is that sarcoidosis was associated with a higher rate of all-cause mortality compared to patients with heart failure and no sarcoidosis. That was more of a surprise.”

“There’s been some discrepancy in previous studies describing the cardiovascular outcomes in sarcoidosis,” Dr. Lyle added, “so I think this study provides excellent information while also highlighting the need for additional large-scale studies. We need to have further data on cardiovascular outcomes, which will allow us to refine the consensus statements and guidelines for management and the diagnosis of cardiac sarcoidosis.”

Dr. Lyle and Leslie T. Cooper Jr., MD, also of the Mayo Clinic, extrapolated on those thoughts in an editorial that accompanied the study. In it, the two authors praised the size and lengthy follow-up of the study, while noting its limitations. Specifically, they stressed that the study’s Danish population “may not be representative of other general populations” because of notable differences in ethnicity, age, and comorbidities.

That said, they reinforced that the study did feature “important takeaways” and that its findings emphasize the “need for monitoring for cardiac manifestations in patients with systemic sarcoidosis.”

In addition to the limitations noted in the editorial, the study’s authors acknowledged that the observational nature limited its “assessment of cause-effect relationships” and that the diagnosis codes for sarcoidosis had not been validated in the Danish National Patient Registry.

The authors of both the study and the editorial reported no conflicts of interest.

SOURCE: Yafasova A et al. J Am Coll Cardiol. 2020 Aug 10. doi: 10.1016/j.jacc.2020.06.038.

For some patients, a bout of COVID-19 may not be over after hospital discharge, acute symptoms subside, or a couple of tests for SARS-CoV-2 come back negative. Those who have reached these milestones of conquering the disease may find that their recovery journey has only begun. Debilitating symptoms such as fatigue, headache, and dyspnea may linger for weeks or longer. Patients with persistent symptoms, often referred to as “long haulers” in reference to the duration of their recovery, are looking for answers about their condition and when their COVID-19 illness will finally resolve.

Long-haul patients organize

What started as an accumulation of anecdotal evidence in social media, blogs, and the mainstream press about slow recovery and long-lasting symptoms of COVID-19 is now the focus of clinical trials in the population of recovering patients. Projects such as the COVID Symptom Study, initiated by the Massachusetts General Hospital, Boston; the Harvard School of Public Health, Boston; King’s College London; and Stanford (Calif.) University, are collecting data on symptoms from millions of patients and will eventually contribute to a better understanding of prolonged recovery.

Patients looking for answers have created groups on social media such as Facebook to exchange information about their experiences (e.g., Survivor Corps, COVID-19 Support Group, COVID-19 Recovered Survivors). Recovering patients have created patient-led research organizations (Body Politic COVID-19 Support Group) to explore persistent symptoms and begin to create data for research.
 

Some data on lingering symptoms

A small study of 143 previously hospitalized, recovering patients in Italy found that 87.4% of the cohort had at least one persistent symptom 2 months or longer after initial onset and at more than a month after discharge. In this sample, only 5% had been intubated. (JAMA 2020 Jul 9. doi: 10.1001/jama.2020.12603).

One study found that even patients who have had relatively mild symptoms and were not hospitalized can have persistent symptoms. The Centers for Disease Control and Prevention conducted a survey of adults who tested positive for the positive reverse transcription–polymerase chain reaction test for SARS-CoV-2 and found that, among the 292 respondents, 35% were still feeling the impact of the disease 2-3 weeks after testing. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms. The survey found that delayed recovery was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization (MMWR. 2020 Jul 24. doi: 10.15585/mmwr.mm6930e1).

Sachin Gupta, MD, FCCP, ATSF, a pulmonologist and member of the CHEST Physician editorial advisory board, has treated patients with COVID-19 and shared some of his thoughts on the problem of prolonged symptoms of COVID-19.
 

Q: Should clinicians expect to see COVID-19 patients who have symptoms persisting weeks after they are diagnosed?

Dr. Gupta: I think clinicians, especially in primary care, are already seeing many patients with lingering symptoms, both respiratory and nonrespiratory related, and debility. A few patients here in the San Francisco Bay Area that I have spoken with 4-6 weeks out from their acute illness have complained of persisting, though improving, fatigue and cough. Early studies are confirming this as a topical issue. There may be other long-lasting sequelae of COVID-19 beyond the common mild lingering symptoms. It will also be important to consider (and get more data on) to what degree asymptomatic patients develop some degree of mild inflammatory and subsequent fibrotic changes in organs like the lungs and heart

Q: How does the recovery phase of COVID-19 compare with recovery from severe influenza or ARDS?

Dr. Gupta: Most prior influenza and acute respiratory distress syndrome (ARDS) studies have provided initial follow-up at 3 months and beyond, so technically speaking, it is a little difficult to compare the symptomatology patterns in the JAMA study of 2 months on follow-up. Nevertheless, the key takeaway is that, even though few patients in the study had ARDS requiring intubation (severe disease), many patients with milder disease had significant lingering symptoms (55% with three or more symptoms) at 2 months.

This fits logically with the premise, which we have some limited data on with ARDS (N Engl J Med. 2003;348:683-93. doi: 10.1056/NEJMoa022450) and severe influenza infection survivors (Nature Sci Rep. 2017;7:17275. doi: 10.1038/s41598-017-17497-6) that varying degrees of the inflammation cascade triggered by certain viruses can lead to changes in important patient-reported outcomes, and objective measures such as pulmonary function over the long term.

Q: What can you do for patients with lingering symptoms of COVID-19 or what can you tell them about their symptoms?

Dr. Gupta: For many patients, there is fear, given the novel nature of the virus/pandemic, that their symptoms may persist long term. Acknowledgment of their symptoms is validating and important for us to recognize as we learn more about the virus. As we are finding, many patients are going online to find answers, after sometimes feeling rushed or dismissed initially in the clinical setting.

In my experience, the bar is fairly high for most patients to reach out to their physicians with complaints of lingering symptoms after acute infection. For the ones who do reach out, they tend to have either a greater constellation of symptoms or higher severity of one or two key symptoms. After assessing and, when appropriate, ruling out secondary infections or newly developed conditions, I shift toward symptom management. I encourage such patients to build up slowly. I suggest they work first on their activities of daily living (bathing, grooming), then their instrumental activities of daily living (cooking, cleaning, checking the mail), and then to engage, based on their tolerance of symptoms, to light purposeful exercise. There are many online resources for at-home exercise activities that I recommend to patients who are more debilitated; some larger centers are beginning to offer some forms of telepulmonary rehab.

Based on what we know about other causes of viral pneumonitis and ARDS, I ask such symptomatic patients to expect a slow, gradual, and in most cases a complete recovery, and depending on the individual case, I recommend pulmonary function tests and imaging that may be helpful to track that progress.

I remind myself, and patients, that our understanding may change as we learn more over time. Checking in at set intervals, even if not in person but through a phone call, can go a long way in a setting where we do not have a specific therapy, other than gradual exercise training, to help these patients recover faster. Reassurance and encouragement are vital for patients who are struggling with the lingering burden of disease and who may find it difficult to return to work or function as usual at home. The final point is to be mindful of our patient’s mental health and, where our reassurance is not enough, to consider appropriate mental health referrals.

Q: Can you handle this kind of problem with telemedicine or which patients with lingering symptoms need to come into the office – or failing that, the ED?

Dr. Gupta: Telemedicine in the outpatient setting provides a helpful tool to assess and manage patients, in my experience, with limited and straightforward complaints. Its scope is limited diagnostically (assessing symptoms and signs) as is its reach (ability to connect with elderly, disabled, or patients without/limited telemedicine access). In many instances, telemedicine limits our ability to connect with patients emotionally and build trust. Many patients who have gone through the acute illness that we see in pulmonary clinic on follow-up are older in age, and for many, video visits are not a practical solution. Telemedicine visits can sometimes present challenges for me as well in terms of thoroughly conveying lifestyle and symptom management strategies. Health literacy is typically easier to gauge and address in person.

For patients with any degree of enduring dyspnea, more so in the acute phase, I recommend home pulse oximetry for monitoring their oxygen saturation if it is financially and technically feasible for them to obtain one. Sending a patient to the ED is an option of last resort, but one that is necessary in some cases. I expect patients with lingering symptoms to tell me that symptoms may be persisting, hopefully gradually improving, and not getting worse. If post–COVID-19 symptoms such as fever, dyspnea, fatigue, or lightheadedness are new or worsening, particularly rapidly, the safest and best option I advise patients is to go to the ED for further assessment and testing. Postviral bacterial pneumonia is something we should consider, and there is some potential for aspergillosis as well.

Q: Do you have any concerns about patients with asthma, chronic obstructive pulmonary disease, or other pulmonary issues having lingering symptoms that may mask exacerbations or may cause exacerbation of their disease?

Dr. Gupta: So far, patients with chronic lung conditions do not appear to have not been disproportionately affected by the pandemic in terms of absolute numbers or percentage wise compared to the general public. I think that sheltering in place has been readily followed by many of these patients, and in addition, I assume better adherence to their maintenance therapies has likely helped. The very few cases of patients with underlying chronic obstructive pulmonary disease and interstitial lung disease that I have seen have fared very poorly when they were diagnosed with COVID-19 in the hospital. There are emerging data about short-term outcomes from severe COVID-19 infection in patients with interstitial lung disease in Europe (medRxiv. 2020 Jul 17. doi: 10.1101/2020.07.15.20152967), and from physicians treating pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (Ann Am Thorac Soc. 2020 Jul 29. doi: 10.1513/AnnalsATS.202005-521OC). But so far, little has been published on the outcomes of mild disease in these patients with chronic lung disease.

Q: It’s still early days to know the significance of lingering symptoms. But at what point do you begin to consider the possibility of some kind of relapse? And what is your next move if the symptoms get worse?

Dr. Gupta: COVID-19 recurrence, whether because of reinfection or relapse, is a potential concern but not one that is very commonly seen so far in my purview. Generally, symptoms of post–COVID-19 infection that are lingering trend toward getting better, even if slowly. If post–COVID-19 infection symptoms are progressing (particularly if rapidly), that would be a strong indication to evaluate that patient in the ED (less likely in clinic), reswab them for SARS-CoV-2, and obtain further testing such as blood work and imaging. A significant challenge from a research perspective will be determining if coinfection with another virus is playing a role as we move closer to the fall season.

[email protected]

For some patients, a bout of COVID-19 may not be over after hospital discharge, acute symptoms subside, or a couple of tests for SARS-CoV-2 come back negative. Those who have reached these milestones of conquering the disease may find that their recovery journey has only begun. Debilitating symptoms such as fatigue, headache, and dyspnea may linger for weeks or longer. Patients with persistent symptoms, often referred to as “long haulers” in reference to the duration of their recovery, are looking for answers about their condition and when their COVID-19 illness will finally resolve.

Long-haul patients organize

What started as an accumulation of anecdotal evidence in social media, blogs, and the mainstream press about slow recovery and long-lasting symptoms of COVID-19 is now the focus of clinical trials in the population of recovering patients. Projects such as the COVID Symptom Study, initiated by the Massachusetts General Hospital, Boston; the Harvard School of Public Health, Boston; King’s College London; and Stanford (Calif.) University, are collecting data on symptoms from millions of patients and will eventually contribute to a better understanding of prolonged recovery.

Patients looking for answers have created groups on social media such as Facebook to exchange information about their experiences (e.g., Survivor Corps, COVID-19 Support Group, COVID-19 Recovered Survivors). Recovering patients have created patient-led research organizations (Body Politic COVID-19 Support Group) to explore persistent symptoms and begin to create data for research.
 

Some data on lingering symptoms

A small study of 143 previously hospitalized, recovering patients in Italy found that 87.4% of the cohort had at least one persistent symptom 2 months or longer after initial onset and at more than a month after discharge. In this sample, only 5% had been intubated. (JAMA 2020 Jul 9. doi: 10.1001/jama.2020.12603).

One study found that even patients who have had relatively mild symptoms and were not hospitalized can have persistent symptoms. The Centers for Disease Control and Prevention conducted a survey of adults who tested positive for the positive reverse transcription–polymerase chain reaction test for SARS-CoV-2 and found that, among the 292 respondents, 35% were still feeling the impact of the disease 2-3 weeks after testing. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms. The survey found that delayed recovery was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization (MMWR. 2020 Jul 24. doi: 10.15585/mmwr.mm6930e1).

Sachin Gupta, MD, FCCP, ATSF, a pulmonologist and member of the CHEST Physician editorial advisory board, has treated patients with COVID-19 and shared some of his thoughts on the problem of prolonged symptoms of COVID-19.
 

Q: Should clinicians expect to see COVID-19 patients who have symptoms persisting weeks after they are diagnosed?

Dr. Gupta: I think clinicians, especially in primary care, are already seeing many patients with lingering symptoms, both respiratory and nonrespiratory related, and debility. A few patients here in the San Francisco Bay Area that I have spoken with 4-6 weeks out from their acute illness have complained of persisting, though improving, fatigue and cough. Early studies are confirming this as a topical issue. There may be other long-lasting sequelae of COVID-19 beyond the common mild lingering symptoms. It will also be important to consider (and get more data on) to what degree asymptomatic patients develop some degree of mild inflammatory and subsequent fibrotic changes in organs like the lungs and heart

Q: How does the recovery phase of COVID-19 compare with recovery from severe influenza or ARDS?

Dr. Gupta: Most prior influenza and acute respiratory distress syndrome (ARDS) studies have provided initial follow-up at 3 months and beyond, so technically speaking, it is a little difficult to compare the symptomatology patterns in the JAMA study of 2 months on follow-up. Nevertheless, the key takeaway is that, even though few patients in the study had ARDS requiring intubation (severe disease), many patients with milder disease had significant lingering symptoms (55% with three or more symptoms) at 2 months.

This fits logically with the premise, which we have some limited data on with ARDS (N Engl J Med. 2003;348:683-93. doi: 10.1056/NEJMoa022450) and severe influenza infection survivors (Nature Sci Rep. 2017;7:17275. doi: 10.1038/s41598-017-17497-6) that varying degrees of the inflammation cascade triggered by certain viruses can lead to changes in important patient-reported outcomes, and objective measures such as pulmonary function over the long term.

Q: What can you do for patients with lingering symptoms of COVID-19 or what can you tell them about their symptoms?

Dr. Gupta: For many patients, there is fear, given the novel nature of the virus/pandemic, that their symptoms may persist long term. Acknowledgment of their symptoms is validating and important for us to recognize as we learn more about the virus. As we are finding, many patients are going online to find answers, after sometimes feeling rushed or dismissed initially in the clinical setting.

In my experience, the bar is fairly high for most patients to reach out to their physicians with complaints of lingering symptoms after acute infection. For the ones who do reach out, they tend to have either a greater constellation of symptoms or higher severity of one or two key symptoms. After assessing and, when appropriate, ruling out secondary infections or newly developed conditions, I shift toward symptom management. I encourage such patients to build up slowly. I suggest they work first on their activities of daily living (bathing, grooming), then their instrumental activities of daily living (cooking, cleaning, checking the mail), and then to engage, based on their tolerance of symptoms, to light purposeful exercise. There are many online resources for at-home exercise activities that I recommend to patients who are more debilitated; some larger centers are beginning to offer some forms of telepulmonary rehab.

Based on what we know about other causes of viral pneumonitis and ARDS, I ask such symptomatic patients to expect a slow, gradual, and in most cases a complete recovery, and depending on the individual case, I recommend pulmonary function tests and imaging that may be helpful to track that progress.

I remind myself, and patients, that our understanding may change as we learn more over time. Checking in at set intervals, even if not in person but through a phone call, can go a long way in a setting where we do not have a specific therapy, other than gradual exercise training, to help these patients recover faster. Reassurance and encouragement are vital for patients who are struggling with the lingering burden of disease and who may find it difficult to return to work or function as usual at home. The final point is to be mindful of our patient’s mental health and, where our reassurance is not enough, to consider appropriate mental health referrals.

Q: Can you handle this kind of problem with telemedicine or which patients with lingering symptoms need to come into the office – or failing that, the ED?

Dr. Gupta: Telemedicine in the outpatient setting provides a helpful tool to assess and manage patients, in my experience, with limited and straightforward complaints. Its scope is limited diagnostically (assessing symptoms and signs) as is its reach (ability to connect with elderly, disabled, or patients without/limited telemedicine access). In many instances, telemedicine limits our ability to connect with patients emotionally and build trust. Many patients who have gone through the acute illness that we see in pulmonary clinic on follow-up are older in age, and for many, video visits are not a practical solution. Telemedicine visits can sometimes present challenges for me as well in terms of thoroughly conveying lifestyle and symptom management strategies. Health literacy is typically easier to gauge and address in person.

For patients with any degree of enduring dyspnea, more so in the acute phase, I recommend home pulse oximetry for monitoring their oxygen saturation if it is financially and technically feasible for them to obtain one. Sending a patient to the ED is an option of last resort, but one that is necessary in some cases. I expect patients with lingering symptoms to tell me that symptoms may be persisting, hopefully gradually improving, and not getting worse. If post–COVID-19 symptoms such as fever, dyspnea, fatigue, or lightheadedness are new or worsening, particularly rapidly, the safest and best option I advise patients is to go to the ED for further assessment and testing. Postviral bacterial pneumonia is something we should consider, and there is some potential for aspergillosis as well.

Q: Do you have any concerns about patients with asthma, chronic obstructive pulmonary disease, or other pulmonary issues having lingering symptoms that may mask exacerbations or may cause exacerbation of their disease?

Dr. Gupta: So far, patients with chronic lung conditions do not appear to have not been disproportionately affected by the pandemic in terms of absolute numbers or percentage wise compared to the general public. I think that sheltering in place has been readily followed by many of these patients, and in addition, I assume better adherence to their maintenance therapies has likely helped. The very few cases of patients with underlying chronic obstructive pulmonary disease and interstitial lung disease that I have seen have fared very poorly when they were diagnosed with COVID-19 in the hospital. There are emerging data about short-term outcomes from severe COVID-19 infection in patients with interstitial lung disease in Europe (medRxiv. 2020 Jul 17. doi: 10.1101/2020.07.15.20152967), and from physicians treating pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (Ann Am Thorac Soc. 2020 Jul 29. doi: 10.1513/AnnalsATS.202005-521OC). But so far, little has been published on the outcomes of mild disease in these patients with chronic lung disease.

Q: It’s still early days to know the significance of lingering symptoms. But at what point do you begin to consider the possibility of some kind of relapse? And what is your next move if the symptoms get worse?

Dr. Gupta: COVID-19 recurrence, whether because of reinfection or relapse, is a potential concern but not one that is very commonly seen so far in my purview. Generally, symptoms of post–COVID-19 infection that are lingering trend toward getting better, even if slowly. If post–COVID-19 infection symptoms are progressing (particularly if rapidly), that would be a strong indication to evaluate that patient in the ED (less likely in clinic), reswab them for SARS-CoV-2, and obtain further testing such as blood work and imaging. A significant challenge from a research perspective will be determining if coinfection with another virus is playing a role as we move closer to the fall season.

[email protected]

For some patients, a bout of COVID-19 may not be over after hospital discharge, acute symptoms subside, or a couple of tests for SARS-CoV-2 come back negative. Those who have reached these milestones of conquering the disease may find that their recovery journey has only begun. Debilitating symptoms such as fatigue, headache, and dyspnea may linger for weeks or longer. Patients with persistent symptoms, often referred to as “long haulers” in reference to the duration of their recovery, are looking for answers about their condition and when their COVID-19 illness will finally resolve.

Long-haul patients organize

What started as an accumulation of anecdotal evidence in social media, blogs, and the mainstream press about slow recovery and long-lasting symptoms of COVID-19 is now the focus of clinical trials in the population of recovering patients. Projects such as the COVID Symptom Study, initiated by the Massachusetts General Hospital, Boston; the Harvard School of Public Health, Boston; King’s College London; and Stanford (Calif.) University, are collecting data on symptoms from millions of patients and will eventually contribute to a better understanding of prolonged recovery.

Patients looking for answers have created groups on social media such as Facebook to exchange information about their experiences (e.g., Survivor Corps, COVID-19 Support Group, COVID-19 Recovered Survivors). Recovering patients have created patient-led research organizations (Body Politic COVID-19 Support Group) to explore persistent symptoms and begin to create data for research.
 

Some data on lingering symptoms

A small study of 143 previously hospitalized, recovering patients in Italy found that 87.4% of the cohort had at least one persistent symptom 2 months or longer after initial onset and at more than a month after discharge. In this sample, only 5% had been intubated. (JAMA 2020 Jul 9. doi: 10.1001/jama.2020.12603).

One study found that even patients who have had relatively mild symptoms and were not hospitalized can have persistent symptoms. The Centers for Disease Control and Prevention conducted a survey of adults who tested positive for the positive reverse transcription–polymerase chain reaction test for SARS-CoV-2 and found that, among the 292 respondents, 35% were still feeling the impact of the disease 2-3 weeks after testing. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms. The survey found that delayed recovery was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization (MMWR. 2020 Jul 24. doi: 10.15585/mmwr.mm6930e1).

Sachin Gupta, MD, FCCP, ATSF, a pulmonologist and member of the CHEST Physician editorial advisory board, has treated patients with COVID-19 and shared some of his thoughts on the problem of prolonged symptoms of COVID-19.
 

Q: Should clinicians expect to see COVID-19 patients who have symptoms persisting weeks after they are diagnosed?

Dr. Gupta: I think clinicians, especially in primary care, are already seeing many patients with lingering symptoms, both respiratory and nonrespiratory related, and debility. A few patients here in the San Francisco Bay Area that I have spoken with 4-6 weeks out from their acute illness have complained of persisting, though improving, fatigue and cough. Early studies are confirming this as a topical issue. There may be other long-lasting sequelae of COVID-19 beyond the common mild lingering symptoms. It will also be important to consider (and get more data on) to what degree asymptomatic patients develop some degree of mild inflammatory and subsequent fibrotic changes in organs like the lungs and heart

Q: How does the recovery phase of COVID-19 compare with recovery from severe influenza or ARDS?

Dr. Gupta: Most prior influenza and acute respiratory distress syndrome (ARDS) studies have provided initial follow-up at 3 months and beyond, so technically speaking, it is a little difficult to compare the symptomatology patterns in the JAMA study of 2 months on follow-up. Nevertheless, the key takeaway is that, even though few patients in the study had ARDS requiring intubation (severe disease), many patients with milder disease had significant lingering symptoms (55% with three or more symptoms) at 2 months.

This fits logically with the premise, which we have some limited data on with ARDS (N Engl J Med. 2003;348:683-93. doi: 10.1056/NEJMoa022450) and severe influenza infection survivors (Nature Sci Rep. 2017;7:17275. doi: 10.1038/s41598-017-17497-6) that varying degrees of the inflammation cascade triggered by certain viruses can lead to changes in important patient-reported outcomes, and objective measures such as pulmonary function over the long term.

Q: What can you do for patients with lingering symptoms of COVID-19 or what can you tell them about their symptoms?

Dr. Gupta: For many patients, there is fear, given the novel nature of the virus/pandemic, that their symptoms may persist long term. Acknowledgment of their symptoms is validating and important for us to recognize as we learn more about the virus. As we are finding, many patients are going online to find answers, after sometimes feeling rushed or dismissed initially in the clinical setting.

In my experience, the bar is fairly high for most patients to reach out to their physicians with complaints of lingering symptoms after acute infection. For the ones who do reach out, they tend to have either a greater constellation of symptoms or higher severity of one or two key symptoms. After assessing and, when appropriate, ruling out secondary infections or newly developed conditions, I shift toward symptom management. I encourage such patients to build up slowly. I suggest they work first on their activities of daily living (bathing, grooming), then their instrumental activities of daily living (cooking, cleaning, checking the mail), and then to engage, based on their tolerance of symptoms, to light purposeful exercise. There are many online resources for at-home exercise activities that I recommend to patients who are more debilitated; some larger centers are beginning to offer some forms of telepulmonary rehab.

Based on what we know about other causes of viral pneumonitis and ARDS, I ask such symptomatic patients to expect a slow, gradual, and in most cases a complete recovery, and depending on the individual case, I recommend pulmonary function tests and imaging that may be helpful to track that progress.

I remind myself, and patients, that our understanding may change as we learn more over time. Checking in at set intervals, even if not in person but through a phone call, can go a long way in a setting where we do not have a specific therapy, other than gradual exercise training, to help these patients recover faster. Reassurance and encouragement are vital for patients who are struggling with the lingering burden of disease and who may find it difficult to return to work or function as usual at home. The final point is to be mindful of our patient’s mental health and, where our reassurance is not enough, to consider appropriate mental health referrals.

Q: Can you handle this kind of problem with telemedicine or which patients with lingering symptoms need to come into the office – or failing that, the ED?

Dr. Gupta: Telemedicine in the outpatient setting provides a helpful tool to assess and manage patients, in my experience, with limited and straightforward complaints. Its scope is limited diagnostically (assessing symptoms and signs) as is its reach (ability to connect with elderly, disabled, or patients without/limited telemedicine access). In many instances, telemedicine limits our ability to connect with patients emotionally and build trust. Many patients who have gone through the acute illness that we see in pulmonary clinic on follow-up are older in age, and for many, video visits are not a practical solution. Telemedicine visits can sometimes present challenges for me as well in terms of thoroughly conveying lifestyle and symptom management strategies. Health literacy is typically easier to gauge and address in person.

For patients with any degree of enduring dyspnea, more so in the acute phase, I recommend home pulse oximetry for monitoring their oxygen saturation if it is financially and technically feasible for them to obtain one. Sending a patient to the ED is an option of last resort, but one that is necessary in some cases. I expect patients with lingering symptoms to tell me that symptoms may be persisting, hopefully gradually improving, and not getting worse. If post–COVID-19 symptoms such as fever, dyspnea, fatigue, or lightheadedness are new or worsening, particularly rapidly, the safest and best option I advise patients is to go to the ED for further assessment and testing. Postviral bacterial pneumonia is something we should consider, and there is some potential for aspergillosis as well.

Q: Do you have any concerns about patients with asthma, chronic obstructive pulmonary disease, or other pulmonary issues having lingering symptoms that may mask exacerbations or may cause exacerbation of their disease?

Dr. Gupta: So far, patients with chronic lung conditions do not appear to have not been disproportionately affected by the pandemic in terms of absolute numbers or percentage wise compared to the general public. I think that sheltering in place has been readily followed by many of these patients, and in addition, I assume better adherence to their maintenance therapies has likely helped. The very few cases of patients with underlying chronic obstructive pulmonary disease and interstitial lung disease that I have seen have fared very poorly when they were diagnosed with COVID-19 in the hospital. There are emerging data about short-term outcomes from severe COVID-19 infection in patients with interstitial lung disease in Europe (medRxiv. 2020 Jul 17. doi: 10.1101/2020.07.15.20152967), and from physicians treating pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (Ann Am Thorac Soc. 2020 Jul 29. doi: 10.1513/AnnalsATS.202005-521OC). But so far, little has been published on the outcomes of mild disease in these patients with chronic lung disease.

Q: It’s still early days to know the significance of lingering symptoms. But at what point do you begin to consider the possibility of some kind of relapse? And what is your next move if the symptoms get worse?

Dr. Gupta: COVID-19 recurrence, whether because of reinfection or relapse, is a potential concern but not one that is very commonly seen so far in my purview. Generally, symptoms of post–COVID-19 infection that are lingering trend toward getting better, even if slowly. If post–COVID-19 infection symptoms are progressing (particularly if rapidly), that would be a strong indication to evaluate that patient in the ED (less likely in clinic), reswab them for SARS-CoV-2, and obtain further testing such as blood work and imaging. A significant challenge from a research perspective will be determining if coinfection with another virus is playing a role as we move closer to the fall season.

[email protected]

A new scientific statement from the American Heart Association recommends incorporating a rapid diet-screening tool into routine primary care visits to inform dietary counseling and integrating the tool into patients’ electronic health record platforms across all healthcare settings.

American Heart Association

The statement authors evaluated 15 existing screening tools and, although they did not recommend a specific tool, they did present advantages and disadvantages of some of the tools and encouraged “critical conversations” among clinicians and other specialists to arrive at a tool that would be most appropriate for use in a particular health care setting.

“The key takeaway is for clinicians to incorporate discussion of dietary patterns into routine preventive care appointments because a suboptimal diet is the No. 1 risk factor for cardiovascular disease,” Maya Vadiveloo, PhD, RD, chair of the statement group, said in an interview.

“We also wanted to touch on the fact the screening tool could be incorporated into the EHR and then used for clinical support and for tracking and monitoring the patient’s dietary patterns over time,” said Dr. Vadiveloo, assistant professor of nutrition and food sciences in the College of Health Science, University of Rhode Island, Kingston.

The statement was published online Aug. 7 in Circulation: Cardiovascular Quality and Outcomes.
 

Competing demands

Poor dietary quality has “surpassed all other mortality risk factors, accounting for 11 million deaths and about 50% of cardiovascular disease (CVD) deaths globally,” the authors wrote.

Diets deficient in fruits, vegetables, and whole grains and high in red and processed meat, added sugars, sodium, and total energy are the “leading determinants” of the risks for CVD and other conditions, so “strategies that promote holistically healthier dietary patterns to reduce chronic disease risk are of contemporary importance.”

Most clinicians and other members of health care teams “do not currently assess or counsel patients about their food and beverage intake during routine clinical care,” the authors observed.

Reasons for this may include lack of training and knowledge, insufficient time, insufficient integration of nutrition services into health care settings, insufficient reimbursement, and “competing demands during the visit,” they noted.

Dr. Vadiveloo said that an evidence-based rapid screening tool can go a long way toward helping to overcome these barriers.

“Research shows that when primary care practitioners discuss diet with patients, the patients are receptive, but we also know that clinical workloads are already very compressed, and adding another thing to a routine preventive care appointment is challenging,” she said. “So we wanted to look and see if there were already screening tools that showed promise as valid, reliable, reflective of the best science, and easy to incorporate into various types of practice settings.”
 

Top picks

The authors established “theoretical and practice-based criteria” for an optimal diet screening tool for use in the adult population (aged 20 to 75 years). The tool had to:

• Be developed or used within clinical practice in the past 10 years.
• Be evidence-based, reliable, and valid.
• Assess total dietary pattern rather than focusing on a single food or nutrient.
• Be able to be completed and scored at administration without special knowledge or software.
• Give actionable next steps and support to patients.
• Be able track and monitor dietary change over time.
• Be brief.
• Be useful for chronic disease management.

Of the 15 tools reviewed, the three that met the most theoretical and practice-based validity criteria were the Mediterranean Diet Adherence Screener (MEDAS) and its variations; the modified, shortened Rapid Eating Assessment for Participants (REAP), and the modified version of the Starting the Conversation Tool. However, the authors noted that the Powell and Greenberg Screening Tool was the “least time-intensive.”
 

One size does not fit all

No single tool will be appropriate for all practice settings, so “we would like clinicians to discuss what will work in their particular setting,” Dr. Vadiveloo emphasized.

For example, should the screening tool be completed by the clinician, a member of the health care team, or the patient? Advantages of a tool completed by clinicians or team members include collection of the information in real time, where it can be used in shared decision-making during the encounter and increased reliability because the screen has been completed by a clinician. On the other hand, the clinician might not be able to prioritize administering the screening tool during a short clinical encounter.

Advantages of a tool completed by the patient via an EHR portal is that the patient may feel less risk of judgment by the clinician or health care professional and patients can complete the screen at their convenience. Disadvantages are limited reach into underserved populations and, potentially, less reliability than clinician-administered tools.

“It is advantageous to have tools that can be administered by multiple members of health care teams to ease the demand on clinicians, if such staff is available, but in other settings, self-administration might be better, so we tried to leave it open-ended,” Dr. Vadiveloo explained.
 

‘Ideal platform’

“The EHR is the ideal platform to prompt clinicians and other members of the health care team to capture dietary data and deliver dietary advice to patients,” the authors observed.

EHRs allow secure storage of data and also enable access to these data when needed at the point of care. They are also important for documentation purposes.

The authors noted that the use of “myriad EHR platforms and versions of platforms” have created “technical challenges.” They recommended “standardized approaches” for transmitting health data that will “more seamlessly allow rapid diet screeners to be implemented in the EHR.”

They also recommended that the prototypes of rapid diet screeners be tested by end users prior to implementation within particular clinics. “Gathering these data ahead of time can improve the uptake of the application in the real world,” they stated.

Dr. Vadiveloo added that dietary counseling can be conducted by several members of a health care team, such as a dietitian, not just by the physician. Or the patient may need to be referred to a dietitian for counseling and follow-up.

The authors concluded by characterizing the AHA statement as “a call to action ... designed to accelerate efforts to make diet quality assessment an integral part of office-based care delivery by encouraging critical conversations among clinicians, individuals with diet/lifestyle expertise, and specialists in information technology.”

Dr. Vadiveloo has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

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

A new scientific statement from the American Heart Association recommends incorporating a rapid diet-screening tool into routine primary care visits to inform dietary counseling and integrating the tool into patients’ electronic health record platforms across all healthcare settings.

American Heart Association

The statement authors evaluated 15 existing screening tools and, although they did not recommend a specific tool, they did present advantages and disadvantages of some of the tools and encouraged “critical conversations” among clinicians and other specialists to arrive at a tool that would be most appropriate for use in a particular health care setting.

“The key takeaway is for clinicians to incorporate discussion of dietary patterns into routine preventive care appointments because a suboptimal diet is the No. 1 risk factor for cardiovascular disease,” Maya Vadiveloo, PhD, RD, chair of the statement group, said in an interview.

“We also wanted to touch on the fact the screening tool could be incorporated into the EHR and then used for clinical support and for tracking and monitoring the patient’s dietary patterns over time,” said Dr. Vadiveloo, assistant professor of nutrition and food sciences in the College of Health Science, University of Rhode Island, Kingston.

The statement was published online Aug. 7 in Circulation: Cardiovascular Quality and Outcomes.
 

Competing demands

Poor dietary quality has “surpassed all other mortality risk factors, accounting for 11 million deaths and about 50% of cardiovascular disease (CVD) deaths globally,” the authors wrote.

Diets deficient in fruits, vegetables, and whole grains and high in red and processed meat, added sugars, sodium, and total energy are the “leading determinants” of the risks for CVD and other conditions, so “strategies that promote holistically healthier dietary patterns to reduce chronic disease risk are of contemporary importance.”

Most clinicians and other members of health care teams “do not currently assess or counsel patients about their food and beverage intake during routine clinical care,” the authors observed.

Reasons for this may include lack of training and knowledge, insufficient time, insufficient integration of nutrition services into health care settings, insufficient reimbursement, and “competing demands during the visit,” they noted.

Dr. Vadiveloo said that an evidence-based rapid screening tool can go a long way toward helping to overcome these barriers.

“Research shows that when primary care practitioners discuss diet with patients, the patients are receptive, but we also know that clinical workloads are already very compressed, and adding another thing to a routine preventive care appointment is challenging,” she said. “So we wanted to look and see if there were already screening tools that showed promise as valid, reliable, reflective of the best science, and easy to incorporate into various types of practice settings.”
 

Top picks

The authors established “theoretical and practice-based criteria” for an optimal diet screening tool for use in the adult population (aged 20 to 75 years). The tool had to:

• Be developed or used within clinical practice in the past 10 years.
• Be evidence-based, reliable, and valid.
• Assess total dietary pattern rather than focusing on a single food or nutrient.
• Be able to be completed and scored at administration without special knowledge or software.
• Give actionable next steps and support to patients.
• Be able track and monitor dietary change over time.
• Be brief.
• Be useful for chronic disease management.

Of the 15 tools reviewed, the three that met the most theoretical and practice-based validity criteria were the Mediterranean Diet Adherence Screener (MEDAS) and its variations; the modified, shortened Rapid Eating Assessment for Participants (REAP), and the modified version of the Starting the Conversation Tool. However, the authors noted that the Powell and Greenberg Screening Tool was the “least time-intensive.”
 

One size does not fit all

No single tool will be appropriate for all practice settings, so “we would like clinicians to discuss what will work in their particular setting,” Dr. Vadiveloo emphasized.

For example, should the screening tool be completed by the clinician, a member of the health care team, or the patient? Advantages of a tool completed by clinicians or team members include collection of the information in real time, where it can be used in shared decision-making during the encounter and increased reliability because the screen has been completed by a clinician. On the other hand, the clinician might not be able to prioritize administering the screening tool during a short clinical encounter.

Advantages of a tool completed by the patient via an EHR portal is that the patient may feel less risk of judgment by the clinician or health care professional and patients can complete the screen at their convenience. Disadvantages are limited reach into underserved populations and, potentially, less reliability than clinician-administered tools.

“It is advantageous to have tools that can be administered by multiple members of health care teams to ease the demand on clinicians, if such staff is available, but in other settings, self-administration might be better, so we tried to leave it open-ended,” Dr. Vadiveloo explained.
 

‘Ideal platform’

“The EHR is the ideal platform to prompt clinicians and other members of the health care team to capture dietary data and deliver dietary advice to patients,” the authors observed.

EHRs allow secure storage of data and also enable access to these data when needed at the point of care. They are also important for documentation purposes.

The authors noted that the use of “myriad EHR platforms and versions of platforms” have created “technical challenges.” They recommended “standardized approaches” for transmitting health data that will “more seamlessly allow rapid diet screeners to be implemented in the EHR.”

They also recommended that the prototypes of rapid diet screeners be tested by end users prior to implementation within particular clinics. “Gathering these data ahead of time can improve the uptake of the application in the real world,” they stated.

Dr. Vadiveloo added that dietary counseling can be conducted by several members of a health care team, such as a dietitian, not just by the physician. Or the patient may need to be referred to a dietitian for counseling and follow-up.

The authors concluded by characterizing the AHA statement as “a call to action ... designed to accelerate efforts to make diet quality assessment an integral part of office-based care delivery by encouraging critical conversations among clinicians, individuals with diet/lifestyle expertise, and specialists in information technology.”

Dr. Vadiveloo has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

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

A new scientific statement from the American Heart Association recommends incorporating a rapid diet-screening tool into routine primary care visits to inform dietary counseling and integrating the tool into patients’ electronic health record platforms across all healthcare settings.

American Heart Association

The statement authors evaluated 15 existing screening tools and, although they did not recommend a specific tool, they did present advantages and disadvantages of some of the tools and encouraged “critical conversations” among clinicians and other specialists to arrive at a tool that would be most appropriate for use in a particular health care setting.

“The key takeaway is for clinicians to incorporate discussion of dietary patterns into routine preventive care appointments because a suboptimal diet is the No. 1 risk factor for cardiovascular disease,” Maya Vadiveloo, PhD, RD, chair of the statement group, said in an interview.

“We also wanted to touch on the fact the screening tool could be incorporated into the EHR and then used for clinical support and for tracking and monitoring the patient’s dietary patterns over time,” said Dr. Vadiveloo, assistant professor of nutrition and food sciences in the College of Health Science, University of Rhode Island, Kingston.

The statement was published online Aug. 7 in Circulation: Cardiovascular Quality and Outcomes.
 

Competing demands

Poor dietary quality has “surpassed all other mortality risk factors, accounting for 11 million deaths and about 50% of cardiovascular disease (CVD) deaths globally,” the authors wrote.

Diets deficient in fruits, vegetables, and whole grains and high in red and processed meat, added sugars, sodium, and total energy are the “leading determinants” of the risks for CVD and other conditions, so “strategies that promote holistically healthier dietary patterns to reduce chronic disease risk are of contemporary importance.”

Most clinicians and other members of health care teams “do not currently assess or counsel patients about their food and beverage intake during routine clinical care,” the authors observed.

Reasons for this may include lack of training and knowledge, insufficient time, insufficient integration of nutrition services into health care settings, insufficient reimbursement, and “competing demands during the visit,” they noted.

Dr. Vadiveloo said that an evidence-based rapid screening tool can go a long way toward helping to overcome these barriers.

“Research shows that when primary care practitioners discuss diet with patients, the patients are receptive, but we also know that clinical workloads are already very compressed, and adding another thing to a routine preventive care appointment is challenging,” she said. “So we wanted to look and see if there were already screening tools that showed promise as valid, reliable, reflective of the best science, and easy to incorporate into various types of practice settings.”
 

Top picks

The authors established “theoretical and practice-based criteria” for an optimal diet screening tool for use in the adult population (aged 20 to 75 years). The tool had to:

• Be developed or used within clinical practice in the past 10 years.
• Be evidence-based, reliable, and valid.
• Assess total dietary pattern rather than focusing on a single food or nutrient.
• Be able to be completed and scored at administration without special knowledge or software.
• Give actionable next steps and support to patients.
• Be able track and monitor dietary change over time.
• Be brief.
• Be useful for chronic disease management.

Of the 15 tools reviewed, the three that met the most theoretical and practice-based validity criteria were the Mediterranean Diet Adherence Screener (MEDAS) and its variations; the modified, shortened Rapid Eating Assessment for Participants (REAP), and the modified version of the Starting the Conversation Tool. However, the authors noted that the Powell and Greenberg Screening Tool was the “least time-intensive.”
 

One size does not fit all

No single tool will be appropriate for all practice settings, so “we would like clinicians to discuss what will work in their particular setting,” Dr. Vadiveloo emphasized.

For example, should the screening tool be completed by the clinician, a member of the health care team, or the patient? Advantages of a tool completed by clinicians or team members include collection of the information in real time, where it can be used in shared decision-making during the encounter and increased reliability because the screen has been completed by a clinician. On the other hand, the clinician might not be able to prioritize administering the screening tool during a short clinical encounter.

Advantages of a tool completed by the patient via an EHR portal is that the patient may feel less risk of judgment by the clinician or health care professional and patients can complete the screen at their convenience. Disadvantages are limited reach into underserved populations and, potentially, less reliability than clinician-administered tools.

“It is advantageous to have tools that can be administered by multiple members of health care teams to ease the demand on clinicians, if such staff is available, but in other settings, self-administration might be better, so we tried to leave it open-ended,” Dr. Vadiveloo explained.
 

‘Ideal platform’

“The EHR is the ideal platform to prompt clinicians and other members of the health care team to capture dietary data and deliver dietary advice to patients,” the authors observed.

EHRs allow secure storage of data and also enable access to these data when needed at the point of care. They are also important for documentation purposes.

The authors noted that the use of “myriad EHR platforms and versions of platforms” have created “technical challenges.” They recommended “standardized approaches” for transmitting health data that will “more seamlessly allow rapid diet screeners to be implemented in the EHR.”

They also recommended that the prototypes of rapid diet screeners be tested by end users prior to implementation within particular clinics. “Gathering these data ahead of time can improve the uptake of the application in the real world,” they stated.

Dr. Vadiveloo added that dietary counseling can be conducted by several members of a health care team, such as a dietitian, not just by the physician. Or the patient may need to be referred to a dietitian for counseling and follow-up.

The authors concluded by characterizing the AHA statement as “a call to action ... designed to accelerate efforts to make diet quality assessment an integral part of office-based care delivery by encouraging critical conversations among clinicians, individuals with diet/lifestyle expertise, and specialists in information technology.”

Dr. Vadiveloo has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

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