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How Does Snoring Affect Cardiovascular Health?
Snoring is a common disorder that affects 20%-40% of the general population. The mechanism of snoring is the vibration of anatomical structures in the pharyngeal airways. The flutter of the soft palate explains the harsh aspect of the snoring sound, which occurs during natural sleep or drug-induced sleep. The presentation of snoring may vary throughout the night or between nights, with a subjective, and therefore inconsistent, assessment of its loudness.
Objective evaluation of snoring is important for clinical decision-making and predicting the effect of therapeutic interventions. It also provides information regarding the site and degree of upper airway obstruction. Snoring is one of the main features of sleep-disordered breathing, including hypopnea events, which reflect partial upper airway obstruction.
Obstructive sleep apnea (OSA) is characterized by episodes of complete (apnea) or partial (hypopnea) collapse of the upper airways with associated oxygen desaturation or awakening from sleep. Most patients with OSA snore loudly almost every night. However, in the Sleep Heart Health Study, one-third of participants with OSA reported no snoring, while one-third of snoring participants did not meet the criteria for OSA. Therefore, subjective assessments of snoring (self-reported) may not be sufficiently reliable to assess its potential impact on cardiovascular (CV) health outcomes.
CV Effects
OSA has been hypothesized as a modifiable risk factor for CV diseases (CVD), including hypertension, coronary artery disease (CAD), atrial fibrillation, heart failure, and stroke, primarily because of the results of traditional observational studies. Snoring is reported as a symptom of the early stage of OSA and has also been associated with a higher risk for CVD. However, establishing causality based on observational studies is difficult because of residual confounding from unknown or unmeasured factors and reverse causality (i.e., the scenario in which CVD increases the risk for OSA or snoring). A Mendelian randomization study, using the natural random allocation of genetic variants as instruments capable of producing results analogous to those of randomized controlled trials, suggested that OSA and snoring increase the risk for hypertension and CAD, with associations partly driven by body mass index (BMI). Conversely, no evidence was found that CVD causally influenced OSA or snoring.
Snoring has been associated with multiple subclinical markers of CV pathology, including high blood pressure, and loud snoring can interfere with restorative sleep and contribute to the risk for hypertension and other adverse outcomes in snorers. However, evidence on the associations between snoring and CV health outcomes remains limited and is primarily based on subjective assessments of snoring or small clinical samples with objective assessments of snoring for only 1 night.
Snoring and Hypertension
A study of 12,287 middle-aged patients (age, 50 years) who were predominantly males (88%) and generally overweight (BMI, 28 kg/m2) determined the prevalence of snoring and its association with the prevalence of hypertension using objective evaluation of snoring over multiple nights and multiple daytime blood pressure measurements. The findings included the following observations:
An increase in snoring duration was associated with a 3-mmHg increase in systolic (SBP) and a 4 mmHg increase in diastolic blood pressure (DBP) in patients with frequent and regular snoring, compared with those with infrequent snoring, regardless of age, BMI, sex, and estimated apnea/hypopnea index.
The association between severe OSA alone and blood pressure had an effect size similar to that of the association between snoring alone and blood pressure. In a model where OSA severity was classified and snoring duration was stratified into quartiles, severe OSA without snoring was associated with 3.6 mmHg higher SBP and 3.5 mmHg higher DBP, compared with the absence of snoring or OSA. Participants without OSA but with intense snoring (4th quartile) had 3.8 mmHg higher SBP and 4.5 mmHg higher DBP compared with participants without nighttime apnea or snoring.
Snoring was significantly associated with uncontrolled hypertension. There was a 20% increase in the probability of uncontrolled hypertension in subjects aged > 50 years with obesity and a 98% increase in subjects aged ≤ 50 years with normal BMI.
Duration of snoring was associated with an 87% increase in the likelihood of uncontrolled hypertension.
Implications for Practice
This study indicates that 15% of a predominantly overweight male population snore for > 20% of the night and about 10% of these subjects without nighttime apnea snore for > 12% of the night.
Regular nighttime snoring is associated with elevated blood pressure and uncontrolled hypertension, regardless of the presence or severity of OSA.
Physicians must be aware of the potential consequences of snoring on the risk for hypertension, and these results highlight the need to consider snoring in clinical care and in the management of sleep problems, especially in the context of managing arterial hypertension.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Snoring is a common disorder that affects 20%-40% of the general population. The mechanism of snoring is the vibration of anatomical structures in the pharyngeal airways. The flutter of the soft palate explains the harsh aspect of the snoring sound, which occurs during natural sleep or drug-induced sleep. The presentation of snoring may vary throughout the night or between nights, with a subjective, and therefore inconsistent, assessment of its loudness.
Objective evaluation of snoring is important for clinical decision-making and predicting the effect of therapeutic interventions. It also provides information regarding the site and degree of upper airway obstruction. Snoring is one of the main features of sleep-disordered breathing, including hypopnea events, which reflect partial upper airway obstruction.
Obstructive sleep apnea (OSA) is characterized by episodes of complete (apnea) or partial (hypopnea) collapse of the upper airways with associated oxygen desaturation or awakening from sleep. Most patients with OSA snore loudly almost every night. However, in the Sleep Heart Health Study, one-third of participants with OSA reported no snoring, while one-third of snoring participants did not meet the criteria for OSA. Therefore, subjective assessments of snoring (self-reported) may not be sufficiently reliable to assess its potential impact on cardiovascular (CV) health outcomes.
CV Effects
OSA has been hypothesized as a modifiable risk factor for CV diseases (CVD), including hypertension, coronary artery disease (CAD), atrial fibrillation, heart failure, and stroke, primarily because of the results of traditional observational studies. Snoring is reported as a symptom of the early stage of OSA and has also been associated with a higher risk for CVD. However, establishing causality based on observational studies is difficult because of residual confounding from unknown or unmeasured factors and reverse causality (i.e., the scenario in which CVD increases the risk for OSA or snoring). A Mendelian randomization study, using the natural random allocation of genetic variants as instruments capable of producing results analogous to those of randomized controlled trials, suggested that OSA and snoring increase the risk for hypertension and CAD, with associations partly driven by body mass index (BMI). Conversely, no evidence was found that CVD causally influenced OSA or snoring.
Snoring has been associated with multiple subclinical markers of CV pathology, including high blood pressure, and loud snoring can interfere with restorative sleep and contribute to the risk for hypertension and other adverse outcomes in snorers. However, evidence on the associations between snoring and CV health outcomes remains limited and is primarily based on subjective assessments of snoring or small clinical samples with objective assessments of snoring for only 1 night.
Snoring and Hypertension
A study of 12,287 middle-aged patients (age, 50 years) who were predominantly males (88%) and generally overweight (BMI, 28 kg/m2) determined the prevalence of snoring and its association with the prevalence of hypertension using objective evaluation of snoring over multiple nights and multiple daytime blood pressure measurements. The findings included the following observations:
An increase in snoring duration was associated with a 3-mmHg increase in systolic (SBP) and a 4 mmHg increase in diastolic blood pressure (DBP) in patients with frequent and regular snoring, compared with those with infrequent snoring, regardless of age, BMI, sex, and estimated apnea/hypopnea index.
The association between severe OSA alone and blood pressure had an effect size similar to that of the association between snoring alone and blood pressure. In a model where OSA severity was classified and snoring duration was stratified into quartiles, severe OSA without snoring was associated with 3.6 mmHg higher SBP and 3.5 mmHg higher DBP, compared with the absence of snoring or OSA. Participants without OSA but with intense snoring (4th quartile) had 3.8 mmHg higher SBP and 4.5 mmHg higher DBP compared with participants without nighttime apnea or snoring.
Snoring was significantly associated with uncontrolled hypertension. There was a 20% increase in the probability of uncontrolled hypertension in subjects aged > 50 years with obesity and a 98% increase in subjects aged ≤ 50 years with normal BMI.
Duration of snoring was associated with an 87% increase in the likelihood of uncontrolled hypertension.
Implications for Practice
This study indicates that 15% of a predominantly overweight male population snore for > 20% of the night and about 10% of these subjects without nighttime apnea snore for > 12% of the night.
Regular nighttime snoring is associated with elevated blood pressure and uncontrolled hypertension, regardless of the presence or severity of OSA.
Physicians must be aware of the potential consequences of snoring on the risk for hypertension, and these results highlight the need to consider snoring in clinical care and in the management of sleep problems, especially in the context of managing arterial hypertension.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Snoring is a common disorder that affects 20%-40% of the general population. The mechanism of snoring is the vibration of anatomical structures in the pharyngeal airways. The flutter of the soft palate explains the harsh aspect of the snoring sound, which occurs during natural sleep or drug-induced sleep. The presentation of snoring may vary throughout the night or between nights, with a subjective, and therefore inconsistent, assessment of its loudness.
Objective evaluation of snoring is important for clinical decision-making and predicting the effect of therapeutic interventions. It also provides information regarding the site and degree of upper airway obstruction. Snoring is one of the main features of sleep-disordered breathing, including hypopnea events, which reflect partial upper airway obstruction.
Obstructive sleep apnea (OSA) is characterized by episodes of complete (apnea) or partial (hypopnea) collapse of the upper airways with associated oxygen desaturation or awakening from sleep. Most patients with OSA snore loudly almost every night. However, in the Sleep Heart Health Study, one-third of participants with OSA reported no snoring, while one-third of snoring participants did not meet the criteria for OSA. Therefore, subjective assessments of snoring (self-reported) may not be sufficiently reliable to assess its potential impact on cardiovascular (CV) health outcomes.
CV Effects
OSA has been hypothesized as a modifiable risk factor for CV diseases (CVD), including hypertension, coronary artery disease (CAD), atrial fibrillation, heart failure, and stroke, primarily because of the results of traditional observational studies. Snoring is reported as a symptom of the early stage of OSA and has also been associated with a higher risk for CVD. However, establishing causality based on observational studies is difficult because of residual confounding from unknown or unmeasured factors and reverse causality (i.e., the scenario in which CVD increases the risk for OSA or snoring). A Mendelian randomization study, using the natural random allocation of genetic variants as instruments capable of producing results analogous to those of randomized controlled trials, suggested that OSA and snoring increase the risk for hypertension and CAD, with associations partly driven by body mass index (BMI). Conversely, no evidence was found that CVD causally influenced OSA or snoring.
Snoring has been associated with multiple subclinical markers of CV pathology, including high blood pressure, and loud snoring can interfere with restorative sleep and contribute to the risk for hypertension and other adverse outcomes in snorers. However, evidence on the associations between snoring and CV health outcomes remains limited and is primarily based on subjective assessments of snoring or small clinical samples with objective assessments of snoring for only 1 night.
Snoring and Hypertension
A study of 12,287 middle-aged patients (age, 50 years) who were predominantly males (88%) and generally overweight (BMI, 28 kg/m2) determined the prevalence of snoring and its association with the prevalence of hypertension using objective evaluation of snoring over multiple nights and multiple daytime blood pressure measurements. The findings included the following observations:
An increase in snoring duration was associated with a 3-mmHg increase in systolic (SBP) and a 4 mmHg increase in diastolic blood pressure (DBP) in patients with frequent and regular snoring, compared with those with infrequent snoring, regardless of age, BMI, sex, and estimated apnea/hypopnea index.
The association between severe OSA alone and blood pressure had an effect size similar to that of the association between snoring alone and blood pressure. In a model where OSA severity was classified and snoring duration was stratified into quartiles, severe OSA without snoring was associated with 3.6 mmHg higher SBP and 3.5 mmHg higher DBP, compared with the absence of snoring or OSA. Participants without OSA but with intense snoring (4th quartile) had 3.8 mmHg higher SBP and 4.5 mmHg higher DBP compared with participants without nighttime apnea or snoring.
Snoring was significantly associated with uncontrolled hypertension. There was a 20% increase in the probability of uncontrolled hypertension in subjects aged > 50 years with obesity and a 98% increase in subjects aged ≤ 50 years with normal BMI.
Duration of snoring was associated with an 87% increase in the likelihood of uncontrolled hypertension.
Implications for Practice
This study indicates that 15% of a predominantly overweight male population snore for > 20% of the night and about 10% of these subjects without nighttime apnea snore for > 12% of the night.
Regular nighttime snoring is associated with elevated blood pressure and uncontrolled hypertension, regardless of the presence or severity of OSA.
Physicians must be aware of the potential consequences of snoring on the risk for hypertension, and these results highlight the need to consider snoring in clinical care and in the management of sleep problems, especially in the context of managing arterial hypertension.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Artificially Sweetened Drinks Linked to Increased AF Risk
TOPLINE:
(AF) in a new observational study.
METHODOLOGY:
- The population-based cohort study looked at the associations of sugar-sweetened beverages, artificial sweetened beverages, and pure fruit juice consumption with the risk for incident AF and evaluated whether genetic susceptibility modifies these associations.
- The authors analyzed data from the UK Biobank on 201,856 participants who were free of baseline AF, had genetic data available, and completed a 24-hour diet questionnaire. The diagnosis of AF was obtained by linkage from primary care, hospital inpatient, and death register records.
- The results were adjusted for a wide range of potential confounders including age, sex, ethnicity, education level, socioeconomic status, smoking, alcohol consumption, physical activity level, sleep duration, body mass index, blood pressure, kidney function, sleep apnea, coronary heart disease, diabetes, and the use of lipid-lowering or antihypertensive medication.
TAKEAWAY:
- During a median follow-up of 9.9 years, 9362 incident AF cases were documented.
- Compared with nonconsumers, individuals who consumed more than 2 L per week of artificially sweetened beverages had a 20% increased risk of developing AF (hazard ratio [HR], 1.20; 95% CI, 1.10-1.31).
- Those who drank more than 2 L per week of sugar-sweetened beverages had a 10% increased risk for AF (HR, 1.10; 95% CI, 1.01-1.20).
- Consumption of 1 L or less per week of pure fruit juice was associated with an 8% lower risk of developing AF (HR, 0.92; 95% CI, 0.87-0.97).
- The associations persisted after adjustment for genetic susceptibility for AF.
IN PRACTICE:
The study authors concluded that this study does not demonstrate that consumption of sugar-sweetened or artificially sweetened beverages alters AF risk but rather that the consumption of these drinks may predict AF risk beyond traditional risk factors. They added that intervention studies and basic research are warranted to confirm whether the observed associations are causal. Commenting on the study, Duane Mellor, MD, registered dietitian at Aston University, Birmingham, England, said it is unclear if the observations in this study are a chance finding as there is a lack of a clear biological link. Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow, Glasgow, Scotland, added that although the authors tried to adjust for many factors, there is a strong chance that other behavioral aspects linked to beverage choice could be more relevant as a cause of AF rather than the drinks themselves. Tom Sanders, MD, professor emeritus of nutrition and dietetics, King’s College London, London, England, pointed out that as this is the first study that has reported such an effect with artificially sweetened drinks, the finding needs replication before any conclusions can be drawn. “It remains good dietary advice to recommend the consumption of low-calorie artificially sweetened drink in place of sugar-sweetened drinks and alcohol,” he added.
SOURCE:
The study, led by Ying Sun, MD, Shanghai Jiao Tong University School of Medicine, Shanghai, China, was published online in Circulation: Arrhythmia and Electrophysiology.
LIMITATIONS:
The consumption of beverages was self-reported and based on only five separate single-day food intake recalls which were taken over the first 3 years of the study, which was extrapolated to estimate weekly intake. The researchers could not tell whether the sugar-sweetened and artificially sweetened drinks were caffeinated and could not rule out residual confounding by other unmeasured or unknown factors.
DISCLOSURES:
This study was supported by the National Natural Science Foundation of China, Shanghai Municipal Health Commission, Shanghai Municipal Human Resources and Social Security Bureau, Clinical Research Plan of Shanghai Hospital Development Center, Postdoctoral Scientific Research Foundation of Shanghai Ninth People’s Hospital, and Shanghai Jiao Tong University School of Medicine.
A version of this article appeared on Medscape.com.
TOPLINE:
(AF) in a new observational study.
METHODOLOGY:
- The population-based cohort study looked at the associations of sugar-sweetened beverages, artificial sweetened beverages, and pure fruit juice consumption with the risk for incident AF and evaluated whether genetic susceptibility modifies these associations.
- The authors analyzed data from the UK Biobank on 201,856 participants who were free of baseline AF, had genetic data available, and completed a 24-hour diet questionnaire. The diagnosis of AF was obtained by linkage from primary care, hospital inpatient, and death register records.
- The results were adjusted for a wide range of potential confounders including age, sex, ethnicity, education level, socioeconomic status, smoking, alcohol consumption, physical activity level, sleep duration, body mass index, blood pressure, kidney function, sleep apnea, coronary heart disease, diabetes, and the use of lipid-lowering or antihypertensive medication.
TAKEAWAY:
- During a median follow-up of 9.9 years, 9362 incident AF cases were documented.
- Compared with nonconsumers, individuals who consumed more than 2 L per week of artificially sweetened beverages had a 20% increased risk of developing AF (hazard ratio [HR], 1.20; 95% CI, 1.10-1.31).
- Those who drank more than 2 L per week of sugar-sweetened beverages had a 10% increased risk for AF (HR, 1.10; 95% CI, 1.01-1.20).
- Consumption of 1 L or less per week of pure fruit juice was associated with an 8% lower risk of developing AF (HR, 0.92; 95% CI, 0.87-0.97).
- The associations persisted after adjustment for genetic susceptibility for AF.
IN PRACTICE:
The study authors concluded that this study does not demonstrate that consumption of sugar-sweetened or artificially sweetened beverages alters AF risk but rather that the consumption of these drinks may predict AF risk beyond traditional risk factors. They added that intervention studies and basic research are warranted to confirm whether the observed associations are causal. Commenting on the study, Duane Mellor, MD, registered dietitian at Aston University, Birmingham, England, said it is unclear if the observations in this study are a chance finding as there is a lack of a clear biological link. Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow, Glasgow, Scotland, added that although the authors tried to adjust for many factors, there is a strong chance that other behavioral aspects linked to beverage choice could be more relevant as a cause of AF rather than the drinks themselves. Tom Sanders, MD, professor emeritus of nutrition and dietetics, King’s College London, London, England, pointed out that as this is the first study that has reported such an effect with artificially sweetened drinks, the finding needs replication before any conclusions can be drawn. “It remains good dietary advice to recommend the consumption of low-calorie artificially sweetened drink in place of sugar-sweetened drinks and alcohol,” he added.
SOURCE:
The study, led by Ying Sun, MD, Shanghai Jiao Tong University School of Medicine, Shanghai, China, was published online in Circulation: Arrhythmia and Electrophysiology.
LIMITATIONS:
The consumption of beverages was self-reported and based on only five separate single-day food intake recalls which were taken over the first 3 years of the study, which was extrapolated to estimate weekly intake. The researchers could not tell whether the sugar-sweetened and artificially sweetened drinks were caffeinated and could not rule out residual confounding by other unmeasured or unknown factors.
DISCLOSURES:
This study was supported by the National Natural Science Foundation of China, Shanghai Municipal Health Commission, Shanghai Municipal Human Resources and Social Security Bureau, Clinical Research Plan of Shanghai Hospital Development Center, Postdoctoral Scientific Research Foundation of Shanghai Ninth People’s Hospital, and Shanghai Jiao Tong University School of Medicine.
A version of this article appeared on Medscape.com.
TOPLINE:
(AF) in a new observational study.
METHODOLOGY:
- The population-based cohort study looked at the associations of sugar-sweetened beverages, artificial sweetened beverages, and pure fruit juice consumption with the risk for incident AF and evaluated whether genetic susceptibility modifies these associations.
- The authors analyzed data from the UK Biobank on 201,856 participants who were free of baseline AF, had genetic data available, and completed a 24-hour diet questionnaire. The diagnosis of AF was obtained by linkage from primary care, hospital inpatient, and death register records.
- The results were adjusted for a wide range of potential confounders including age, sex, ethnicity, education level, socioeconomic status, smoking, alcohol consumption, physical activity level, sleep duration, body mass index, blood pressure, kidney function, sleep apnea, coronary heart disease, diabetes, and the use of lipid-lowering or antihypertensive medication.
TAKEAWAY:
- During a median follow-up of 9.9 years, 9362 incident AF cases were documented.
- Compared with nonconsumers, individuals who consumed more than 2 L per week of artificially sweetened beverages had a 20% increased risk of developing AF (hazard ratio [HR], 1.20; 95% CI, 1.10-1.31).
- Those who drank more than 2 L per week of sugar-sweetened beverages had a 10% increased risk for AF (HR, 1.10; 95% CI, 1.01-1.20).
- Consumption of 1 L or less per week of pure fruit juice was associated with an 8% lower risk of developing AF (HR, 0.92; 95% CI, 0.87-0.97).
- The associations persisted after adjustment for genetic susceptibility for AF.
IN PRACTICE:
The study authors concluded that this study does not demonstrate that consumption of sugar-sweetened or artificially sweetened beverages alters AF risk but rather that the consumption of these drinks may predict AF risk beyond traditional risk factors. They added that intervention studies and basic research are warranted to confirm whether the observed associations are causal. Commenting on the study, Duane Mellor, MD, registered dietitian at Aston University, Birmingham, England, said it is unclear if the observations in this study are a chance finding as there is a lack of a clear biological link. Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow, Glasgow, Scotland, added that although the authors tried to adjust for many factors, there is a strong chance that other behavioral aspects linked to beverage choice could be more relevant as a cause of AF rather than the drinks themselves. Tom Sanders, MD, professor emeritus of nutrition and dietetics, King’s College London, London, England, pointed out that as this is the first study that has reported such an effect with artificially sweetened drinks, the finding needs replication before any conclusions can be drawn. “It remains good dietary advice to recommend the consumption of low-calorie artificially sweetened drink in place of sugar-sweetened drinks and alcohol,” he added.
SOURCE:
The study, led by Ying Sun, MD, Shanghai Jiao Tong University School of Medicine, Shanghai, China, was published online in Circulation: Arrhythmia and Electrophysiology.
LIMITATIONS:
The consumption of beverages was self-reported and based on only five separate single-day food intake recalls which were taken over the first 3 years of the study, which was extrapolated to estimate weekly intake. The researchers could not tell whether the sugar-sweetened and artificially sweetened drinks were caffeinated and could not rule out residual confounding by other unmeasured or unknown factors.
DISCLOSURES:
This study was supported by the National Natural Science Foundation of China, Shanghai Municipal Health Commission, Shanghai Municipal Human Resources and Social Security Bureau, Clinical Research Plan of Shanghai Hospital Development Center, Postdoctoral Scientific Research Foundation of Shanghai Ninth People’s Hospital, and Shanghai Jiao Tong University School of Medicine.
A version of this article appeared on Medscape.com.
Lung Cancer Radiation May Up AF Risk
TOPLINE:
METHODOLOGY:
- Arrhythmia — with AF being the most common type — affects roughly 11% of patients following lung cancer RT.
- Given RT’s recognized impact on cardiac tissues over time, researchers hypothesized that the dosage affecting pulmonary veins might contribute to the observed increased rates of AF after RT.
- To investigate, researchers looked back at 420 patients with NSCLC (52% women, median age 70) undergoing definitive RT (± chemo) with modern planning techniques at 55 Gy in 20 once-daily fractions over 4 weeks.
- Most patients underwent treatment planning using volumetric modulated arc therapy (50%) or static gantry intensity-modulated RT (20%). Chemotherapy was administered in a minority of cases (33%).
- Pulmonary veins were contoured on planning CT scans, and dose metrics were calculated. The association between pulmonary veins dose and incidence of new AF was evaluated, with AF verified by a cardiologist.
TAKEAWAY:
- Out of the entire cohort, 26 patients (6%) developed AF a median of 13 months after treatment. All cases of AF were grade 3 except for two grade 4 events.
- Radiation dose to the left and right pulmonary veins was significantly associated with incident AF. Dose volumes most strongly associated with AF were ≥ 55 Gy (V55) on the left and ≥ 10 Gy (V10) on the right.
- The risk for AF increased by 2% per percentage point increase in the left pulmonary veins V55 and 1% in the right pulmonary veins V10. The associations were statistically significant after accounting for cardiovascular factors and risk for death risk.
- The area under the curve for prediction of AF events was 0.64 (P = .02) for the left pulmonary veins V55 and 0.61 (P = .03) for the right pulmonary veins V10. The optimal thresholds for predicting AF were 2% and 54%, respectively.
IN PRACTICE:
“The implications of these data are that actively sparing these structures could reduce the incidence of [AF], and where this is not possible, patients identified as being at high risk of AF could undergo active screening during follow-up,” the researchers said, adding that further validation of these findings should take place before implementation.
SOURCE:
The study, with first author Gerard M. Walls, MB, MRCP, Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, Northern Ireland, was published online on January 4 in Radiotherapy and Oncology .
LIMITATIONS:
This was a single-center, retrospective study with a small number of AF events. The study may have underestimated the relationship between pulmonary vein irradiation and new AF events. The findings needed validation in larger datasets.
DISCLOSURES:
The study had no commercial funding. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Arrhythmia — with AF being the most common type — affects roughly 11% of patients following lung cancer RT.
- Given RT’s recognized impact on cardiac tissues over time, researchers hypothesized that the dosage affecting pulmonary veins might contribute to the observed increased rates of AF after RT.
- To investigate, researchers looked back at 420 patients with NSCLC (52% women, median age 70) undergoing definitive RT (± chemo) with modern planning techniques at 55 Gy in 20 once-daily fractions over 4 weeks.
- Most patients underwent treatment planning using volumetric modulated arc therapy (50%) or static gantry intensity-modulated RT (20%). Chemotherapy was administered in a minority of cases (33%).
- Pulmonary veins were contoured on planning CT scans, and dose metrics were calculated. The association between pulmonary veins dose and incidence of new AF was evaluated, with AF verified by a cardiologist.
TAKEAWAY:
- Out of the entire cohort, 26 patients (6%) developed AF a median of 13 months after treatment. All cases of AF were grade 3 except for two grade 4 events.
- Radiation dose to the left and right pulmonary veins was significantly associated with incident AF. Dose volumes most strongly associated with AF were ≥ 55 Gy (V55) on the left and ≥ 10 Gy (V10) on the right.
- The risk for AF increased by 2% per percentage point increase in the left pulmonary veins V55 and 1% in the right pulmonary veins V10. The associations were statistically significant after accounting for cardiovascular factors and risk for death risk.
- The area under the curve for prediction of AF events was 0.64 (P = .02) for the left pulmonary veins V55 and 0.61 (P = .03) for the right pulmonary veins V10. The optimal thresholds for predicting AF were 2% and 54%, respectively.
IN PRACTICE:
“The implications of these data are that actively sparing these structures could reduce the incidence of [AF], and where this is not possible, patients identified as being at high risk of AF could undergo active screening during follow-up,” the researchers said, adding that further validation of these findings should take place before implementation.
SOURCE:
The study, with first author Gerard M. Walls, MB, MRCP, Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, Northern Ireland, was published online on January 4 in Radiotherapy and Oncology .
LIMITATIONS:
This was a single-center, retrospective study with a small number of AF events. The study may have underestimated the relationship between pulmonary vein irradiation and new AF events. The findings needed validation in larger datasets.
DISCLOSURES:
The study had no commercial funding. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Arrhythmia — with AF being the most common type — affects roughly 11% of patients following lung cancer RT.
- Given RT’s recognized impact on cardiac tissues over time, researchers hypothesized that the dosage affecting pulmonary veins might contribute to the observed increased rates of AF after RT.
- To investigate, researchers looked back at 420 patients with NSCLC (52% women, median age 70) undergoing definitive RT (± chemo) with modern planning techniques at 55 Gy in 20 once-daily fractions over 4 weeks.
- Most patients underwent treatment planning using volumetric modulated arc therapy (50%) or static gantry intensity-modulated RT (20%). Chemotherapy was administered in a minority of cases (33%).
- Pulmonary veins were contoured on planning CT scans, and dose metrics were calculated. The association between pulmonary veins dose and incidence of new AF was evaluated, with AF verified by a cardiologist.
TAKEAWAY:
- Out of the entire cohort, 26 patients (6%) developed AF a median of 13 months after treatment. All cases of AF were grade 3 except for two grade 4 events.
- Radiation dose to the left and right pulmonary veins was significantly associated with incident AF. Dose volumes most strongly associated with AF were ≥ 55 Gy (V55) on the left and ≥ 10 Gy (V10) on the right.
- The risk for AF increased by 2% per percentage point increase in the left pulmonary veins V55 and 1% in the right pulmonary veins V10. The associations were statistically significant after accounting for cardiovascular factors and risk for death risk.
- The area under the curve for prediction of AF events was 0.64 (P = .02) for the left pulmonary veins V55 and 0.61 (P = .03) for the right pulmonary veins V10. The optimal thresholds for predicting AF were 2% and 54%, respectively.
IN PRACTICE:
“The implications of these data are that actively sparing these structures could reduce the incidence of [AF], and where this is not possible, patients identified as being at high risk of AF could undergo active screening during follow-up,” the researchers said, adding that further validation of these findings should take place before implementation.
SOURCE:
The study, with first author Gerard M. Walls, MB, MRCP, Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, Northern Ireland, was published online on January 4 in Radiotherapy and Oncology .
LIMITATIONS:
This was a single-center, retrospective study with a small number of AF events. The study may have underestimated the relationship between pulmonary vein irradiation and new AF events. The findings needed validation in larger datasets.
DISCLOSURES:
The study had no commercial funding. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Guidelines Aren’t For Everybody
An 88-year-old man comes for clinic follow up. He has a medical history of type 2 diabetes, hypertension, heart failure with reduced ejection fraction, and chronic kidney disease. He recently had laboratory tests done: BUN, 32 mg/dL; creatinine, 2.3 mg/dL; potassium, 4.5 mmol/L; bicarbonate, 22 Eq/L; and A1c, 8.2%.
He checks his blood glucose daily (alternating between fasting blood glucose and before dinner) and his fasting blood glucose levels are around 130 mg/dL. His highest glucose reading was 240 mg/dL. He does not have polyuria or visual changes. Current medications: atorvastatin, irbesartan, empagliflozin, and amlodipine. On physical exam his blood pressure is 130/70 mm Hg, pulse is 80, and his BMI 20.
What medication adjustments would you recommend?
A. Begin insulin glargine at bedtime
B. Begin mealtime insulin aspart
C. Begin semaglutide
D. Begin metformin
E. No changes
I think the correct approach here would be no changes. Most physicians know guideline recommendations for A1c of less than 7% are used for patients with diabetes with few comorbid conditions, normal cognition, and functional status. Many of our elderly patients do not meet these criteria and the goal of intense medical treatment of diabetes is different in those patients. The American Diabetes Association has issued a thoughtful paper on treatment of diabetes in elderly people, stressing that patients should have very individualized goals, and that there is no one-size-fits all A1c goal.1
In this patient I would avoid adding insulin, given hypoglycemia risk. A GLP-1 agonist might appear attractive given his multiple cardiovascular risk factors, but his low BMI is a major concern for frailty that may well be worsened with reduced nutrient intake. Diabetes is the chronic condition that probably has the most guidance for management in elderly patients.
I recently saw a 92-year-old man with heart failure with reduced ejection fraction and atrial fibrillation who had been losing weight and becoming weaker. He had suffered several falls in the previous 2 weeks. His medication list included amiodarone, apixaban, sacubitril/valsartan, carvedilol, empagliflozin, spironolactone, and furosemide. He was extremely frail and had stopped eating. He was receiving all guideline-directed therapies, yet he was miserable and dying. Falls in this population are potentially as fatal as decompensated heart disease.
I stopped his amiodarone, furosemide, and spironolactone, and reduced his doses of sacubitril/valsartan and carvedilol. His appetite returned and his will to live returned. Heart failure guidelines do not include robust studies of very elderly patients because few studies exist in this population. Frailty assessment is crucial in decision making in your elderly patients.2,3 and frequent check-ins to make sure that they are not suffering from the effects of polypharmacy are crucial. Our goal in our very elderly patients is quality life-years. Polypharmacy has the potential to decrease the quality of life, as well as potentially shorten life.
The very elderly are at risk of the negative consequences of polypharmacy, especially if they have several diseases like diabetes, congestive heart failure, and hypertension that may require multiple medications. Gutierrez-Valencia and colleagues performed a systematic review of 25 articles on frailty and polypharmacy.4 Their findings demonstrated a significant association between an increased number of medications and frailty. They postulated that polypharmacy could actually be a contributor to frailty. There just isn’t enough evidence for the benefit of guidelines in the very aged and the risks of polypharmacy are real. We should use the lowest possible doses of medications in this population, frequently reassess goals, and monitor closely for side effects.
Pearl: Always consider the risks of polypharmacy when considering therapies for your elderly patients.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Older Adults: Standards of Medical Care in Diabetes — 2021. Diabetes Care 2021;44(Suppl 1):S168–S179.
2. Gaur A et al. Cardiogeriatrics: The current state of the art. Heart. 2024 Jan 11:heartjnl-2022-322117.
3. Denfeld QE et al. Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement. J Heart Lung Transplant. 2023 Nov 29:S1053-2498(23)02028-4.
4. Gutiérrez-Valencia M et al. The relationship between frailty and polypharmacy in older people: A systematic review. Br J Clin Pharmacol. 2018 Jul;84(7):1432-44.
An 88-year-old man comes for clinic follow up. He has a medical history of type 2 diabetes, hypertension, heart failure with reduced ejection fraction, and chronic kidney disease. He recently had laboratory tests done: BUN, 32 mg/dL; creatinine, 2.3 mg/dL; potassium, 4.5 mmol/L; bicarbonate, 22 Eq/L; and A1c, 8.2%.
He checks his blood glucose daily (alternating between fasting blood glucose and before dinner) and his fasting blood glucose levels are around 130 mg/dL. His highest glucose reading was 240 mg/dL. He does not have polyuria or visual changes. Current medications: atorvastatin, irbesartan, empagliflozin, and amlodipine. On physical exam his blood pressure is 130/70 mm Hg, pulse is 80, and his BMI 20.
What medication adjustments would you recommend?
A. Begin insulin glargine at bedtime
B. Begin mealtime insulin aspart
C. Begin semaglutide
D. Begin metformin
E. No changes
I think the correct approach here would be no changes. Most physicians know guideline recommendations for A1c of less than 7% are used for patients with diabetes with few comorbid conditions, normal cognition, and functional status. Many of our elderly patients do not meet these criteria and the goal of intense medical treatment of diabetes is different in those patients. The American Diabetes Association has issued a thoughtful paper on treatment of diabetes in elderly people, stressing that patients should have very individualized goals, and that there is no one-size-fits all A1c goal.1
In this patient I would avoid adding insulin, given hypoglycemia risk. A GLP-1 agonist might appear attractive given his multiple cardiovascular risk factors, but his low BMI is a major concern for frailty that may well be worsened with reduced nutrient intake. Diabetes is the chronic condition that probably has the most guidance for management in elderly patients.
I recently saw a 92-year-old man with heart failure with reduced ejection fraction and atrial fibrillation who had been losing weight and becoming weaker. He had suffered several falls in the previous 2 weeks. His medication list included amiodarone, apixaban, sacubitril/valsartan, carvedilol, empagliflozin, spironolactone, and furosemide. He was extremely frail and had stopped eating. He was receiving all guideline-directed therapies, yet he was miserable and dying. Falls in this population are potentially as fatal as decompensated heart disease.
I stopped his amiodarone, furosemide, and spironolactone, and reduced his doses of sacubitril/valsartan and carvedilol. His appetite returned and his will to live returned. Heart failure guidelines do not include robust studies of very elderly patients because few studies exist in this population. Frailty assessment is crucial in decision making in your elderly patients.2,3 and frequent check-ins to make sure that they are not suffering from the effects of polypharmacy are crucial. Our goal in our very elderly patients is quality life-years. Polypharmacy has the potential to decrease the quality of life, as well as potentially shorten life.
The very elderly are at risk of the negative consequences of polypharmacy, especially if they have several diseases like diabetes, congestive heart failure, and hypertension that may require multiple medications. Gutierrez-Valencia and colleagues performed a systematic review of 25 articles on frailty and polypharmacy.4 Their findings demonstrated a significant association between an increased number of medications and frailty. They postulated that polypharmacy could actually be a contributor to frailty. There just isn’t enough evidence for the benefit of guidelines in the very aged and the risks of polypharmacy are real. We should use the lowest possible doses of medications in this population, frequently reassess goals, and monitor closely for side effects.
Pearl: Always consider the risks of polypharmacy when considering therapies for your elderly patients.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Older Adults: Standards of Medical Care in Diabetes — 2021. Diabetes Care 2021;44(Suppl 1):S168–S179.
2. Gaur A et al. Cardiogeriatrics: The current state of the art. Heart. 2024 Jan 11:heartjnl-2022-322117.
3. Denfeld QE et al. Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement. J Heart Lung Transplant. 2023 Nov 29:S1053-2498(23)02028-4.
4. Gutiérrez-Valencia M et al. The relationship between frailty and polypharmacy in older people: A systematic review. Br J Clin Pharmacol. 2018 Jul;84(7):1432-44.
An 88-year-old man comes for clinic follow up. He has a medical history of type 2 diabetes, hypertension, heart failure with reduced ejection fraction, and chronic kidney disease. He recently had laboratory tests done: BUN, 32 mg/dL; creatinine, 2.3 mg/dL; potassium, 4.5 mmol/L; bicarbonate, 22 Eq/L; and A1c, 8.2%.
He checks his blood glucose daily (alternating between fasting blood glucose and before dinner) and his fasting blood glucose levels are around 130 mg/dL. His highest glucose reading was 240 mg/dL. He does not have polyuria or visual changes. Current medications: atorvastatin, irbesartan, empagliflozin, and amlodipine. On physical exam his blood pressure is 130/70 mm Hg, pulse is 80, and his BMI 20.
What medication adjustments would you recommend?
A. Begin insulin glargine at bedtime
B. Begin mealtime insulin aspart
C. Begin semaglutide
D. Begin metformin
E. No changes
I think the correct approach here would be no changes. Most physicians know guideline recommendations for A1c of less than 7% are used for patients with diabetes with few comorbid conditions, normal cognition, and functional status. Many of our elderly patients do not meet these criteria and the goal of intense medical treatment of diabetes is different in those patients. The American Diabetes Association has issued a thoughtful paper on treatment of diabetes in elderly people, stressing that patients should have very individualized goals, and that there is no one-size-fits all A1c goal.1
In this patient I would avoid adding insulin, given hypoglycemia risk. A GLP-1 agonist might appear attractive given his multiple cardiovascular risk factors, but his low BMI is a major concern for frailty that may well be worsened with reduced nutrient intake. Diabetes is the chronic condition that probably has the most guidance for management in elderly patients.
I recently saw a 92-year-old man with heart failure with reduced ejection fraction and atrial fibrillation who had been losing weight and becoming weaker. He had suffered several falls in the previous 2 weeks. His medication list included amiodarone, apixaban, sacubitril/valsartan, carvedilol, empagliflozin, spironolactone, and furosemide. He was extremely frail and had stopped eating. He was receiving all guideline-directed therapies, yet he was miserable and dying. Falls in this population are potentially as fatal as decompensated heart disease.
I stopped his amiodarone, furosemide, and spironolactone, and reduced his doses of sacubitril/valsartan and carvedilol. His appetite returned and his will to live returned. Heart failure guidelines do not include robust studies of very elderly patients because few studies exist in this population. Frailty assessment is crucial in decision making in your elderly patients.2,3 and frequent check-ins to make sure that they are not suffering from the effects of polypharmacy are crucial. Our goal in our very elderly patients is quality life-years. Polypharmacy has the potential to decrease the quality of life, as well as potentially shorten life.
The very elderly are at risk of the negative consequences of polypharmacy, especially if they have several diseases like diabetes, congestive heart failure, and hypertension that may require multiple medications. Gutierrez-Valencia and colleagues performed a systematic review of 25 articles on frailty and polypharmacy.4 Their findings demonstrated a significant association between an increased number of medications and frailty. They postulated that polypharmacy could actually be a contributor to frailty. There just isn’t enough evidence for the benefit of guidelines in the very aged and the risks of polypharmacy are real. We should use the lowest possible doses of medications in this population, frequently reassess goals, and monitor closely for side effects.
Pearl: Always consider the risks of polypharmacy when considering therapies for your elderly patients.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Older Adults: Standards of Medical Care in Diabetes — 2021. Diabetes Care 2021;44(Suppl 1):S168–S179.
2. Gaur A et al. Cardiogeriatrics: The current state of the art. Heart. 2024 Jan 11:heartjnl-2022-322117.
3. Denfeld QE et al. Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement. J Heart Lung Transplant. 2023 Nov 29:S1053-2498(23)02028-4.
4. Gutiérrez-Valencia M et al. The relationship between frailty and polypharmacy in older people: A systematic review. Br J Clin Pharmacol. 2018 Jul;84(7):1432-44.
Medical Cannabis for Chronic Pain Tied to Arrhythmia Risk
TOPLINE:
, mainly atrial fibrillation/flutter, a Danish registry study suggested. Cannabis use has been associated with increased cardiovascular (CV) risk, but data on CV side effects with use of medical cannabis for chronic pain are limited.
METHODOLOGY:
- To investigate, researchers identified 5391 patients with chronic pain (median age 59; 63% women) initiating first-time treatment with medical cannabis during 2018-2021 and matched them (1:5) to 26,941 control patients on age, sex, chronic pain diagnosis, and concomitant use of other noncannabis pain medication.
- They calculated and compared absolute risks for first-time arrhythmia (atrial fibrillation/flutter, conduction disorders, paroxysmal tachycardias, and ventricular arrhythmias) and acute coronary syndrome (ACS) between groups.
TAKEAWAY:
- Within 180 days, 42 medical cannabis users and 107 control participants developed arrhythmia, most commonly atrial fibrillation/flutter.
- Medical cannabis users had a slightly elevated risk for new-onset arrhythmia compared with nonusers (180-day absolute risk, 0.8% vs 0.4%).
- The 180-day risk ratio with cannabis use was 2.07 (95% CI, 1.34-2.80), and the 1-year risk ratio was 1.36 (95% CI, 1.00-1.73).
- Adults with cancer or cardiometabolic disease had the highest risk for arrhythmia with cannabis use (180-day absolute risk difference, 1.1% and 0.8%). There was no significant association between medical cannabis use and ACS risk.
IN PRACTICE:
“With the investigated cohort’s low age and low prevalence of comorbidity in mind, the notable relative risk increase of new-onset arrhythmia, mainly driven by atrial fibrillation/flutter, could be a reason for concern, albeit the absolute risks in this study population were modest,” the authors wrote.
“Medical cannabis may not be a ‘one-size-fits-all’ therapeutic option for certain medical conditions and should be contextualized based on patient comorbidities and potential vulnerability to side effects,” added the author of an editorial.
SOURCE:
The study, led by Anders Holt, MD, Copenhagen University and Herlev-Gentofte Hospital, Hellerup, Denmark, was published online on January 11, 2024, in the European Heart Journal, with an editorial by Robert Page II, PharmD, MSPH, University of Colorado, Aurora.
LIMITATIONS:
Residual confounding is possible. The registers lack information on disease severity, clinical measures, blood tests, and lifestyle factors. The route of cannabis administration was not known.
DISCLOSURES:
The study was funded by external and independent medical research grants. Holt had no relevant disclosures. Some coauthors reported research grants and speakers’ fees from various drug companies.
A version of this article appeared on Medscape.com.
TOPLINE:
, mainly atrial fibrillation/flutter, a Danish registry study suggested. Cannabis use has been associated with increased cardiovascular (CV) risk, but data on CV side effects with use of medical cannabis for chronic pain are limited.
METHODOLOGY:
- To investigate, researchers identified 5391 patients with chronic pain (median age 59; 63% women) initiating first-time treatment with medical cannabis during 2018-2021 and matched them (1:5) to 26,941 control patients on age, sex, chronic pain diagnosis, and concomitant use of other noncannabis pain medication.
- They calculated and compared absolute risks for first-time arrhythmia (atrial fibrillation/flutter, conduction disorders, paroxysmal tachycardias, and ventricular arrhythmias) and acute coronary syndrome (ACS) between groups.
TAKEAWAY:
- Within 180 days, 42 medical cannabis users and 107 control participants developed arrhythmia, most commonly atrial fibrillation/flutter.
- Medical cannabis users had a slightly elevated risk for new-onset arrhythmia compared with nonusers (180-day absolute risk, 0.8% vs 0.4%).
- The 180-day risk ratio with cannabis use was 2.07 (95% CI, 1.34-2.80), and the 1-year risk ratio was 1.36 (95% CI, 1.00-1.73).
- Adults with cancer or cardiometabolic disease had the highest risk for arrhythmia with cannabis use (180-day absolute risk difference, 1.1% and 0.8%). There was no significant association between medical cannabis use and ACS risk.
IN PRACTICE:
“With the investigated cohort’s low age and low prevalence of comorbidity in mind, the notable relative risk increase of new-onset arrhythmia, mainly driven by atrial fibrillation/flutter, could be a reason for concern, albeit the absolute risks in this study population were modest,” the authors wrote.
“Medical cannabis may not be a ‘one-size-fits-all’ therapeutic option for certain medical conditions and should be contextualized based on patient comorbidities and potential vulnerability to side effects,” added the author of an editorial.
SOURCE:
The study, led by Anders Holt, MD, Copenhagen University and Herlev-Gentofte Hospital, Hellerup, Denmark, was published online on January 11, 2024, in the European Heart Journal, with an editorial by Robert Page II, PharmD, MSPH, University of Colorado, Aurora.
LIMITATIONS:
Residual confounding is possible. The registers lack information on disease severity, clinical measures, blood tests, and lifestyle factors. The route of cannabis administration was not known.
DISCLOSURES:
The study was funded by external and independent medical research grants. Holt had no relevant disclosures. Some coauthors reported research grants and speakers’ fees from various drug companies.
A version of this article appeared on Medscape.com.
TOPLINE:
, mainly atrial fibrillation/flutter, a Danish registry study suggested. Cannabis use has been associated with increased cardiovascular (CV) risk, but data on CV side effects with use of medical cannabis for chronic pain are limited.
METHODOLOGY:
- To investigate, researchers identified 5391 patients with chronic pain (median age 59; 63% women) initiating first-time treatment with medical cannabis during 2018-2021 and matched them (1:5) to 26,941 control patients on age, sex, chronic pain diagnosis, and concomitant use of other noncannabis pain medication.
- They calculated and compared absolute risks for first-time arrhythmia (atrial fibrillation/flutter, conduction disorders, paroxysmal tachycardias, and ventricular arrhythmias) and acute coronary syndrome (ACS) between groups.
TAKEAWAY:
- Within 180 days, 42 medical cannabis users and 107 control participants developed arrhythmia, most commonly atrial fibrillation/flutter.
- Medical cannabis users had a slightly elevated risk for new-onset arrhythmia compared with nonusers (180-day absolute risk, 0.8% vs 0.4%).
- The 180-day risk ratio with cannabis use was 2.07 (95% CI, 1.34-2.80), and the 1-year risk ratio was 1.36 (95% CI, 1.00-1.73).
- Adults with cancer or cardiometabolic disease had the highest risk for arrhythmia with cannabis use (180-day absolute risk difference, 1.1% and 0.8%). There was no significant association between medical cannabis use and ACS risk.
IN PRACTICE:
“With the investigated cohort’s low age and low prevalence of comorbidity in mind, the notable relative risk increase of new-onset arrhythmia, mainly driven by atrial fibrillation/flutter, could be a reason for concern, albeit the absolute risks in this study population were modest,” the authors wrote.
“Medical cannabis may not be a ‘one-size-fits-all’ therapeutic option for certain medical conditions and should be contextualized based on patient comorbidities and potential vulnerability to side effects,” added the author of an editorial.
SOURCE:
The study, led by Anders Holt, MD, Copenhagen University and Herlev-Gentofte Hospital, Hellerup, Denmark, was published online on January 11, 2024, in the European Heart Journal, with an editorial by Robert Page II, PharmD, MSPH, University of Colorado, Aurora.
LIMITATIONS:
Residual confounding is possible. The registers lack information on disease severity, clinical measures, blood tests, and lifestyle factors. The route of cannabis administration was not known.
DISCLOSURES:
The study was funded by external and independent medical research grants. Holt had no relevant disclosures. Some coauthors reported research grants and speakers’ fees from various drug companies.
A version of this article appeared on Medscape.com.
Sudden Cardiac Deaths Down Among NCAA Athletes
TOPLINE:
A new study shows sudden cardiac deaths among collegiate athletes decreased over a recent 20-year period, but risks are still elevated among males, Black players, and basketball players, suggesting more intensive screening among these groups is needed.
METHODOLOGY:
- The study examined incidence and surrounding circumstances of sudden cardiac death (SCD) among student athletes who competed in at least one varsity sport at National Collegiate Athletic Association (NCAA) Division I, II, or III institutions in the 20 years from July 1, 2002, to June 30, 2022.
- Researchers determined causes of death and gathered demographic characteristics using multiple methods, including review of autopsy and other official documents, Internet searches, and contacts to next of kin, coaches, athletic trainers, coroners, medical examiners, scholarship foundations, and physicians involved in the case.
- SCD was defined as sudden unexpected death attributable to a cardiac cause, or a sudden death in a structurally normal heart with no other explanation for death and a history consistent with cardiac-related death that occurred within an hour of symptom onset, or an unwitnessed death occurring within 24 hours of the person being alive.
- Researchers calculated incidence rates over a typical 4-year collegiate career and reported these as athlete-years.
TAKEAWAY:
- The incidence of SCD, which accounted for 13% of the 1102 total deaths during the study period, decreased over time, with a 5-year incidence rate ratio (IRR) of 0.71 (95% CI, 0.61-0.82), while noncardiovascular deaths remained stable.
- IRR for males versus females was 3.79 (95% CI, 2.45-5.88) and for Black versus White athletes was 2.79 (95% CI, 1.98-3.94).
- Basketball and football players were at increased risk of SCD; for example, the incidence rate among Division I Black male basketball athletes was 1:1924 per 4-year athlete-years.
- The most common postmortem finding was autopsy-negative sudden unexplained death, at 19%, followed by idiopathic left ventricular hypertrophy/possible cardiomyopathy (17%) and hypertrophic cardiomyopathy (13%), with no cases of death attributable to COVID-19 myocarditis.
IN PRACTICE:
Although the reason for the decrease in SCD is unknown, “our data suggest that strategies to reduce SCD among competing athletes may be having a positive effect,” wrote the authors. More intensive screening strategies among groups with high SCD incidence may be warranted, they added.
SOURCE:
The study was conducted by Bradley J. Petek, MD, Sports Cardiology Program, Knight Cardiovascular Institute, Oregon Health & Science University, Portland. It was published online November 13 in Circulation and presented at the American Heart Association scientific sessions (abstract 479).
LIMITATIONS:
Some cases of SCD may have been missed as there is no mandatory reporting system in the United States. Approaches to cardiac autopsy and reporting varied significantly. The cause of death was unknown in 16 cases, and postmortem genetic testing was available for only 3% of athletes. As the study didn’t have data on resuscitated sudden cardiac arrest or preparticipation cardiovascular screening practices and findings, definitive conclusions couldn’t be drawn regarding causal factors underlying the decreased incidence of SCD.
DISCLOSURES:
There was no outside funding source. Dr. Petek has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article appeared on Medscape.com.
TOPLINE:
A new study shows sudden cardiac deaths among collegiate athletes decreased over a recent 20-year period, but risks are still elevated among males, Black players, and basketball players, suggesting more intensive screening among these groups is needed.
METHODOLOGY:
- The study examined incidence and surrounding circumstances of sudden cardiac death (SCD) among student athletes who competed in at least one varsity sport at National Collegiate Athletic Association (NCAA) Division I, II, or III institutions in the 20 years from July 1, 2002, to June 30, 2022.
- Researchers determined causes of death and gathered demographic characteristics using multiple methods, including review of autopsy and other official documents, Internet searches, and contacts to next of kin, coaches, athletic trainers, coroners, medical examiners, scholarship foundations, and physicians involved in the case.
- SCD was defined as sudden unexpected death attributable to a cardiac cause, or a sudden death in a structurally normal heart with no other explanation for death and a history consistent with cardiac-related death that occurred within an hour of symptom onset, or an unwitnessed death occurring within 24 hours of the person being alive.
- Researchers calculated incidence rates over a typical 4-year collegiate career and reported these as athlete-years.
TAKEAWAY:
- The incidence of SCD, which accounted for 13% of the 1102 total deaths during the study period, decreased over time, with a 5-year incidence rate ratio (IRR) of 0.71 (95% CI, 0.61-0.82), while noncardiovascular deaths remained stable.
- IRR for males versus females was 3.79 (95% CI, 2.45-5.88) and for Black versus White athletes was 2.79 (95% CI, 1.98-3.94).
- Basketball and football players were at increased risk of SCD; for example, the incidence rate among Division I Black male basketball athletes was 1:1924 per 4-year athlete-years.
- The most common postmortem finding was autopsy-negative sudden unexplained death, at 19%, followed by idiopathic left ventricular hypertrophy/possible cardiomyopathy (17%) and hypertrophic cardiomyopathy (13%), with no cases of death attributable to COVID-19 myocarditis.
IN PRACTICE:
Although the reason for the decrease in SCD is unknown, “our data suggest that strategies to reduce SCD among competing athletes may be having a positive effect,” wrote the authors. More intensive screening strategies among groups with high SCD incidence may be warranted, they added.
SOURCE:
The study was conducted by Bradley J. Petek, MD, Sports Cardiology Program, Knight Cardiovascular Institute, Oregon Health & Science University, Portland. It was published online November 13 in Circulation and presented at the American Heart Association scientific sessions (abstract 479).
LIMITATIONS:
Some cases of SCD may have been missed as there is no mandatory reporting system in the United States. Approaches to cardiac autopsy and reporting varied significantly. The cause of death was unknown in 16 cases, and postmortem genetic testing was available for only 3% of athletes. As the study didn’t have data on resuscitated sudden cardiac arrest or preparticipation cardiovascular screening practices and findings, definitive conclusions couldn’t be drawn regarding causal factors underlying the decreased incidence of SCD.
DISCLOSURES:
There was no outside funding source. Dr. Petek has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article appeared on Medscape.com.
TOPLINE:
A new study shows sudden cardiac deaths among collegiate athletes decreased over a recent 20-year period, but risks are still elevated among males, Black players, and basketball players, suggesting more intensive screening among these groups is needed.
METHODOLOGY:
- The study examined incidence and surrounding circumstances of sudden cardiac death (SCD) among student athletes who competed in at least one varsity sport at National Collegiate Athletic Association (NCAA) Division I, II, or III institutions in the 20 years from July 1, 2002, to June 30, 2022.
- Researchers determined causes of death and gathered demographic characteristics using multiple methods, including review of autopsy and other official documents, Internet searches, and contacts to next of kin, coaches, athletic trainers, coroners, medical examiners, scholarship foundations, and physicians involved in the case.
- SCD was defined as sudden unexpected death attributable to a cardiac cause, or a sudden death in a structurally normal heart with no other explanation for death and a history consistent with cardiac-related death that occurred within an hour of symptom onset, or an unwitnessed death occurring within 24 hours of the person being alive.
- Researchers calculated incidence rates over a typical 4-year collegiate career and reported these as athlete-years.
TAKEAWAY:
- The incidence of SCD, which accounted for 13% of the 1102 total deaths during the study period, decreased over time, with a 5-year incidence rate ratio (IRR) of 0.71 (95% CI, 0.61-0.82), while noncardiovascular deaths remained stable.
- IRR for males versus females was 3.79 (95% CI, 2.45-5.88) and for Black versus White athletes was 2.79 (95% CI, 1.98-3.94).
- Basketball and football players were at increased risk of SCD; for example, the incidence rate among Division I Black male basketball athletes was 1:1924 per 4-year athlete-years.
- The most common postmortem finding was autopsy-negative sudden unexplained death, at 19%, followed by idiopathic left ventricular hypertrophy/possible cardiomyopathy (17%) and hypertrophic cardiomyopathy (13%), with no cases of death attributable to COVID-19 myocarditis.
IN PRACTICE:
Although the reason for the decrease in SCD is unknown, “our data suggest that strategies to reduce SCD among competing athletes may be having a positive effect,” wrote the authors. More intensive screening strategies among groups with high SCD incidence may be warranted, they added.
SOURCE:
The study was conducted by Bradley J. Petek, MD, Sports Cardiology Program, Knight Cardiovascular Institute, Oregon Health & Science University, Portland. It was published online November 13 in Circulation and presented at the American Heart Association scientific sessions (abstract 479).
LIMITATIONS:
Some cases of SCD may have been missed as there is no mandatory reporting system in the United States. Approaches to cardiac autopsy and reporting varied significantly. The cause of death was unknown in 16 cases, and postmortem genetic testing was available for only 3% of athletes. As the study didn’t have data on resuscitated sudden cardiac arrest or preparticipation cardiovascular screening practices and findings, definitive conclusions couldn’t be drawn regarding causal factors underlying the decreased incidence of SCD.
DISCLOSURES:
There was no outside funding source. Dr. Petek has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article appeared on Medscape.com.
Anticoagulants Safe With Enzyme-Inducing Meds for Epilepsy
ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.
These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago.
The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.
The findings were presented at the American Epilepsy Society annual meeting.
Important Implications
Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”
This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”
Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.
“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.
The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton.
Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs.
They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.
Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.
The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
Reduced Risk of Major Bleeding
Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).
In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.
The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.
For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).
“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.
However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.
With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).
“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.
However, she cautioned that more research is needed.
As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
‘Really Great News’
Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.
“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.
The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.
While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.
However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.
He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.
Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”
The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.
Ms. Acton and Dr. Goldenholz report no relevant financial relationships.
A version of this article appeared on Medscape.com.
ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.
These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago.
The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.
The findings were presented at the American Epilepsy Society annual meeting.
Important Implications
Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”
This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”
Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.
“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.
The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton.
Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs.
They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.
Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.
The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
Reduced Risk of Major Bleeding
Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).
In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.
The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.
For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).
“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.
However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.
With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).
“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.
However, she cautioned that more research is needed.
As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
‘Really Great News’
Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.
“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.
The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.
While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.
However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.
He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.
Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”
The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.
Ms. Acton and Dr. Goldenholz report no relevant financial relationships.
A version of this article appeared on Medscape.com.
ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.
These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago.
The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.
The findings were presented at the American Epilepsy Society annual meeting.
Important Implications
Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”
This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”
Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.
“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.
The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton.
Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs.
They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.
Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.
The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
Reduced Risk of Major Bleeding
Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).
In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.
The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.
For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).
“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.
However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.
With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).
“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.
However, she cautioned that more research is needed.
As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
‘Really Great News’
Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.
“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.
The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.
While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.
However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.
He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.
Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”
The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.
Ms. Acton and Dr. Goldenholz report no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM AES 2023
Thyroidectomy Beneficial but Risky for Hashimoto Disease
TOPLINE:
In patients with Hashimoto disease and persistent symptoms despite adequate medical treatment, total thyroidectomy had a beneficial effect up to 5 years but with a substantially higher risk for complications than initially anticipated.
METHODOLOGY:
- The 5-year follow-up of 65 participants in a randomized, open-label trial of thyroidectomy plus medical management vs medical management alone aimed at testing the hypothesis that persistent symptoms despite adequate thyroxine replacement may be related to extrathyroidal autoimmune reactions and that complete removal of thyroid tissues may attenuate autoimmune responses and relieve symptoms.
- Patients in the control group were given the option of having surgery 18 months after enrollment, depending on trial results.
- The primary outcome was patient-reported health-related quality of life measured by the dimensional general health score in the generic Short Form-36 Health Survey questionnaire.
TAKEAWAY:
- The positive treatment effect seen after 18 months was maintained throughout the 3-year follow-up.
- In the intervention group, the improved general health score remained at the same level during the 5-year follow-up.
- Results were similar for the other Short Form-36 Health Survey domains and for total fatigue and chronic fatigue.
- Short-term (<12 months) or longer-lasting complications occurred in 23 patients, including 6 with recurrent laryngeal nerve paralysis (4 were long-term) and 12 with hypoparathyroidism (6 long-term, including 3 permanent).
- Five patients had postoperative hematoma and/or infection requiring intervention.
IN PRACTICE:
“The improvements in patient-reported outcome measures reported at 18 months after surgery were maintained at 5 years after surgery in the intervention group. In contrast, no spontaneous improvement was seen during 3 years in the control group.”
“Long-term complications in 10 of 73 (14%) patients despite use of meticulous dissection to achieve total thyroidectomy is unacceptably high. Medication and compensatory mechanisms for hypoparathyroidism and unilateral recurrent nerve injury, respectively, did alleviate symptoms.”
SOURCE:
This study was published in Annals of Internal Medicine, by Geir Hoff, MD, PhD, of the Department of Research, Telemark Hospital, Skien, and the Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and colleagues.
LIMITATIONS:
None listed.
DISCLOSURES:
None.
TOPLINE:
In patients with Hashimoto disease and persistent symptoms despite adequate medical treatment, total thyroidectomy had a beneficial effect up to 5 years but with a substantially higher risk for complications than initially anticipated.
METHODOLOGY:
- The 5-year follow-up of 65 participants in a randomized, open-label trial of thyroidectomy plus medical management vs medical management alone aimed at testing the hypothesis that persistent symptoms despite adequate thyroxine replacement may be related to extrathyroidal autoimmune reactions and that complete removal of thyroid tissues may attenuate autoimmune responses and relieve symptoms.
- Patients in the control group were given the option of having surgery 18 months after enrollment, depending on trial results.
- The primary outcome was patient-reported health-related quality of life measured by the dimensional general health score in the generic Short Form-36 Health Survey questionnaire.
TAKEAWAY:
- The positive treatment effect seen after 18 months was maintained throughout the 3-year follow-up.
- In the intervention group, the improved general health score remained at the same level during the 5-year follow-up.
- Results were similar for the other Short Form-36 Health Survey domains and for total fatigue and chronic fatigue.
- Short-term (<12 months) or longer-lasting complications occurred in 23 patients, including 6 with recurrent laryngeal nerve paralysis (4 were long-term) and 12 with hypoparathyroidism (6 long-term, including 3 permanent).
- Five patients had postoperative hematoma and/or infection requiring intervention.
IN PRACTICE:
“The improvements in patient-reported outcome measures reported at 18 months after surgery were maintained at 5 years after surgery in the intervention group. In contrast, no spontaneous improvement was seen during 3 years in the control group.”
“Long-term complications in 10 of 73 (14%) patients despite use of meticulous dissection to achieve total thyroidectomy is unacceptably high. Medication and compensatory mechanisms for hypoparathyroidism and unilateral recurrent nerve injury, respectively, did alleviate symptoms.”
SOURCE:
This study was published in Annals of Internal Medicine, by Geir Hoff, MD, PhD, of the Department of Research, Telemark Hospital, Skien, and the Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and colleagues.
LIMITATIONS:
None listed.
DISCLOSURES:
None.
TOPLINE:
In patients with Hashimoto disease and persistent symptoms despite adequate medical treatment, total thyroidectomy had a beneficial effect up to 5 years but with a substantially higher risk for complications than initially anticipated.
METHODOLOGY:
- The 5-year follow-up of 65 participants in a randomized, open-label trial of thyroidectomy plus medical management vs medical management alone aimed at testing the hypothesis that persistent symptoms despite adequate thyroxine replacement may be related to extrathyroidal autoimmune reactions and that complete removal of thyroid tissues may attenuate autoimmune responses and relieve symptoms.
- Patients in the control group were given the option of having surgery 18 months after enrollment, depending on trial results.
- The primary outcome was patient-reported health-related quality of life measured by the dimensional general health score in the generic Short Form-36 Health Survey questionnaire.
TAKEAWAY:
- The positive treatment effect seen after 18 months was maintained throughout the 3-year follow-up.
- In the intervention group, the improved general health score remained at the same level during the 5-year follow-up.
- Results were similar for the other Short Form-36 Health Survey domains and for total fatigue and chronic fatigue.
- Short-term (<12 months) or longer-lasting complications occurred in 23 patients, including 6 with recurrent laryngeal nerve paralysis (4 were long-term) and 12 with hypoparathyroidism (6 long-term, including 3 permanent).
- Five patients had postoperative hematoma and/or infection requiring intervention.
IN PRACTICE:
“The improvements in patient-reported outcome measures reported at 18 months after surgery were maintained at 5 years after surgery in the intervention group. In contrast, no spontaneous improvement was seen during 3 years in the control group.”
“Long-term complications in 10 of 73 (14%) patients despite use of meticulous dissection to achieve total thyroidectomy is unacceptably high. Medication and compensatory mechanisms for hypoparathyroidism and unilateral recurrent nerve injury, respectively, did alleviate symptoms.”
SOURCE:
This study was published in Annals of Internal Medicine, by Geir Hoff, MD, PhD, of the Department of Research, Telemark Hospital, Skien, and the Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and colleagues.
LIMITATIONS:
None listed.
DISCLOSURES:
None.
ACC/AHA issue updated atrial fibrillation guideline
The American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) have issued an updated guideline for preventing and optimally managing atrial fibrillation (AF).
The 2023 ACC/AHA/ACCP/HRS Guideline for Diagnosis and Management of Atrial Fibrillation was published online in the Journal of the American College of Cardiology and Circulation.
“The new guideline has important changes,” including a new way to classify AF, Jose Joglar, MD, professor of cardiac electrophysiology at UT Southwestern Medical Center in Dallas, Texas, and chair of the writing committee, said in an interview.
The previous classification was largely based only on arrhythmia duration and tended to emphasize specific therapeutic interventions rather than a more holistic and multidisciplinary management approach, Dr. Joglar explained.
, from prevention, lifestyle and risk factor modification, screening, and therapy.
Stage 1: At risk for AF due to the presence of risk factors
Stage 2: Pre-AF, with evidence of structural or electrical findings predisposing to AF
Stage 3: AF, including paroxysmal (3A), persistent (3B), long-standing persistent (3C), successful AF ablation (3D)
Stage 4: Permanent AF
The updated guideline recognizes lifestyle and risk factor modification as a “pillar” of AF management and offers “more prescriptive” recommendations, including management of obesity, weight loss, physical activity, smoking cessation, alcohol moderation, hypertension, and other comorbidities.
“We should not only be telling patients they need to be healthy, which doesn’t mean much to a patient, we need to tell them precisely what they need to do. For example, how much exercise to do or how much weight to lose to have a benefit,” Dr. Joglar said in an interview.
The good news for many people, he noted, is that coffee, which has had a “bad reputation,” is okay, as the latest data show it doesn’t seem to exacerbate AF.
The new guideline continues to endorse use of the CHA2DS2-VASc score as the predictor of choice to determine the risk of stroke, but it also allows for flexibility to use other calculators when uncertainty exists or when other risk factors, such as kidney disease, need to be included.
With the emergence of “new and consistent” evidence, the guideline also emphasizes the importance of early and continued management of patients with AF with a focus on maintaining sinus rhythm and minimizing AF burden.
Catheter ablation of AF is given a class 1 indication as first-line therapy in selected patients, including those with heart failure with reduced ejection fraction.
That’s based on recent randomized studies that have shown catheter ablation to be “superior to pharmacological therapy” for rhythm control in appropriately selected patients, Dr. Joglar told this news organization.
“There’s no need to try pharmacological therapies after a discussion between the patient and doctor and they decide that they want to proceed with the most effective intervention,” he added.
The new guideline also upgrades the class of recommendation for left atrial appendage occlusion devices to 2a, compared with the 2019 AF Focused Update, for use of these devices in patients with long-term contraindications to anticoagulation.
It also provides updated recommendations for AF detected via implantable devices and wearables as well as recommendations for patients with AF identified during medical illness or surgery.
Development of the guideline had no commercial funding. Disclosures for the writing group are available with the original articles.
A version of this article appeared on Medscape.com.
The American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) have issued an updated guideline for preventing and optimally managing atrial fibrillation (AF).
The 2023 ACC/AHA/ACCP/HRS Guideline for Diagnosis and Management of Atrial Fibrillation was published online in the Journal of the American College of Cardiology and Circulation.
“The new guideline has important changes,” including a new way to classify AF, Jose Joglar, MD, professor of cardiac electrophysiology at UT Southwestern Medical Center in Dallas, Texas, and chair of the writing committee, said in an interview.
The previous classification was largely based only on arrhythmia duration and tended to emphasize specific therapeutic interventions rather than a more holistic and multidisciplinary management approach, Dr. Joglar explained.
, from prevention, lifestyle and risk factor modification, screening, and therapy.
Stage 1: At risk for AF due to the presence of risk factors
Stage 2: Pre-AF, with evidence of structural or electrical findings predisposing to AF
Stage 3: AF, including paroxysmal (3A), persistent (3B), long-standing persistent (3C), successful AF ablation (3D)
Stage 4: Permanent AF
The updated guideline recognizes lifestyle and risk factor modification as a “pillar” of AF management and offers “more prescriptive” recommendations, including management of obesity, weight loss, physical activity, smoking cessation, alcohol moderation, hypertension, and other comorbidities.
“We should not only be telling patients they need to be healthy, which doesn’t mean much to a patient, we need to tell them precisely what they need to do. For example, how much exercise to do or how much weight to lose to have a benefit,” Dr. Joglar said in an interview.
The good news for many people, he noted, is that coffee, which has had a “bad reputation,” is okay, as the latest data show it doesn’t seem to exacerbate AF.
The new guideline continues to endorse use of the CHA2DS2-VASc score as the predictor of choice to determine the risk of stroke, but it also allows for flexibility to use other calculators when uncertainty exists or when other risk factors, such as kidney disease, need to be included.
With the emergence of “new and consistent” evidence, the guideline also emphasizes the importance of early and continued management of patients with AF with a focus on maintaining sinus rhythm and minimizing AF burden.
Catheter ablation of AF is given a class 1 indication as first-line therapy in selected patients, including those with heart failure with reduced ejection fraction.
That’s based on recent randomized studies that have shown catheter ablation to be “superior to pharmacological therapy” for rhythm control in appropriately selected patients, Dr. Joglar told this news organization.
“There’s no need to try pharmacological therapies after a discussion between the patient and doctor and they decide that they want to proceed with the most effective intervention,” he added.
The new guideline also upgrades the class of recommendation for left atrial appendage occlusion devices to 2a, compared with the 2019 AF Focused Update, for use of these devices in patients with long-term contraindications to anticoagulation.
It also provides updated recommendations for AF detected via implantable devices and wearables as well as recommendations for patients with AF identified during medical illness or surgery.
Development of the guideline had no commercial funding. Disclosures for the writing group are available with the original articles.
A version of this article appeared on Medscape.com.
The American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) have issued an updated guideline for preventing and optimally managing atrial fibrillation (AF).
The 2023 ACC/AHA/ACCP/HRS Guideline for Diagnosis and Management of Atrial Fibrillation was published online in the Journal of the American College of Cardiology and Circulation.
“The new guideline has important changes,” including a new way to classify AF, Jose Joglar, MD, professor of cardiac electrophysiology at UT Southwestern Medical Center in Dallas, Texas, and chair of the writing committee, said in an interview.
The previous classification was largely based only on arrhythmia duration and tended to emphasize specific therapeutic interventions rather than a more holistic and multidisciplinary management approach, Dr. Joglar explained.
, from prevention, lifestyle and risk factor modification, screening, and therapy.
Stage 1: At risk for AF due to the presence of risk factors
Stage 2: Pre-AF, with evidence of structural or electrical findings predisposing to AF
Stage 3: AF, including paroxysmal (3A), persistent (3B), long-standing persistent (3C), successful AF ablation (3D)
Stage 4: Permanent AF
The updated guideline recognizes lifestyle and risk factor modification as a “pillar” of AF management and offers “more prescriptive” recommendations, including management of obesity, weight loss, physical activity, smoking cessation, alcohol moderation, hypertension, and other comorbidities.
“We should not only be telling patients they need to be healthy, which doesn’t mean much to a patient, we need to tell them precisely what they need to do. For example, how much exercise to do or how much weight to lose to have a benefit,” Dr. Joglar said in an interview.
The good news for many people, he noted, is that coffee, which has had a “bad reputation,” is okay, as the latest data show it doesn’t seem to exacerbate AF.
The new guideline continues to endorse use of the CHA2DS2-VASc score as the predictor of choice to determine the risk of stroke, but it also allows for flexibility to use other calculators when uncertainty exists or when other risk factors, such as kidney disease, need to be included.
With the emergence of “new and consistent” evidence, the guideline also emphasizes the importance of early and continued management of patients with AF with a focus on maintaining sinus rhythm and minimizing AF burden.
Catheter ablation of AF is given a class 1 indication as first-line therapy in selected patients, including those with heart failure with reduced ejection fraction.
That’s based on recent randomized studies that have shown catheter ablation to be “superior to pharmacological therapy” for rhythm control in appropriately selected patients, Dr. Joglar told this news organization.
“There’s no need to try pharmacological therapies after a discussion between the patient and doctor and they decide that they want to proceed with the most effective intervention,” he added.
The new guideline also upgrades the class of recommendation for left atrial appendage occlusion devices to 2a, compared with the 2019 AF Focused Update, for use of these devices in patients with long-term contraindications to anticoagulation.
It also provides updated recommendations for AF detected via implantable devices and wearables as well as recommendations for patients with AF identified during medical illness or surgery.
Development of the guideline had no commercial funding. Disclosures for the writing group are available with the original articles.
A version of this article appeared on Medscape.com.
Vagus nerve stimulation promising in POTS
TOPLINE:
possibly through decreased antiadrenergic autoantibodies and inflammatory cytokines, and improved cardiac autonomic function, in a small proof-of-concept study.
METHODOLOGY:
The double-blind study included 25 female patients with POTS, a syndrome of orthostatic intolerance (mean age 31 years and 81% Caucasian), who were randomly assigned to transcutaneous vagus nerve stimulation (tVNS) to the right tragus or sham stimulation to the earlobe, a site devoid of vagal innervation.
After training, patients delivered the tVNS themselves at a frequency of 20 Hz and pulse width of 200 ms during 1-hour daily sessions over 2 months.
At baseline and 2 months, patients underwent a tilt test to determine postural tachycardia; they remained supine for 25 minutes, followed by 10 minutes of standing, as tolerated.
Researchers used electrocardiogram data to examine heart rate and blood samples to assess serum cytokines and antiautonomic autoantibodies.
The primary outcome was a comparison of orthostatic tachycardia (standing – supine) between the two arms at 2 months.
TAKEAWAY:
At 2 months, postural tachycardia was significantly less in the active vs sham arm (mean postural increase in heart rate 17.6 beats/min vs 31.7 beats/min; P = .01).
There was a significant decrease in beta 1-adrenergic receptor (beta 1-AR; P = .01) and alpha-1-AR (P = .04) autoantibody activity in the active vs sham group, which may account at least in part for the reduced orthostatic tachycardia, although the exact mechanisms for this effect have not been clearly defined, the authors said.
Serum tumor necrosis factor-alpha (TNF-alpha) levels were significantly decreased in the active group relative to the sham group (8.3 pg/mL vs 13.9 pg/mL; P = .01).
As for heart rate variability, change in low frequency (LF) and high frequency (HF) from supine to standing was significantly decreased, and postural change in LF/HF ratio, a surrogate for sympathovagal balance, was significantly lower in the active group compared with the sham group.
IN PRACTICE:
“Collectively, these data suggest that tVNS, a low-cost, low-risk intervention, applied for a short period of time in selected patients with POTS, may result in a significant amelioration of their disease,” the authors conclude.
SOURCE:
The study was led by Stavros Stavrakis, MD, PhD, University of Oklahoma Health Sciences Center, Oklahoma City. It was published online in JACC: Clinical Electrophysiology..
LIMITATIONS:
The study had a small sample size, included only females, and extended only up to 2 months. As there was no improvement on the overall score from the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire, researchers can’t conclude tVNS improved patient reported outcomes. The study used 1 hour of daily stimulation but the optimal duration and ideal timing of tVNS is yet to be determined.
DISCLOSURES:
The study was supported by the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute, NIH/National Institute of General Medical Sciences, and individual donations from Francie Fitzgerald and family through the OU Foundation Fund. The authors have no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
possibly through decreased antiadrenergic autoantibodies and inflammatory cytokines, and improved cardiac autonomic function, in a small proof-of-concept study.
METHODOLOGY:
The double-blind study included 25 female patients with POTS, a syndrome of orthostatic intolerance (mean age 31 years and 81% Caucasian), who were randomly assigned to transcutaneous vagus nerve stimulation (tVNS) to the right tragus or sham stimulation to the earlobe, a site devoid of vagal innervation.
After training, patients delivered the tVNS themselves at a frequency of 20 Hz and pulse width of 200 ms during 1-hour daily sessions over 2 months.
At baseline and 2 months, patients underwent a tilt test to determine postural tachycardia; they remained supine for 25 minutes, followed by 10 minutes of standing, as tolerated.
Researchers used electrocardiogram data to examine heart rate and blood samples to assess serum cytokines and antiautonomic autoantibodies.
The primary outcome was a comparison of orthostatic tachycardia (standing – supine) between the two arms at 2 months.
TAKEAWAY:
At 2 months, postural tachycardia was significantly less in the active vs sham arm (mean postural increase in heart rate 17.6 beats/min vs 31.7 beats/min; P = .01).
There was a significant decrease in beta 1-adrenergic receptor (beta 1-AR; P = .01) and alpha-1-AR (P = .04) autoantibody activity in the active vs sham group, which may account at least in part for the reduced orthostatic tachycardia, although the exact mechanisms for this effect have not been clearly defined, the authors said.
Serum tumor necrosis factor-alpha (TNF-alpha) levels were significantly decreased in the active group relative to the sham group (8.3 pg/mL vs 13.9 pg/mL; P = .01).
As for heart rate variability, change in low frequency (LF) and high frequency (HF) from supine to standing was significantly decreased, and postural change in LF/HF ratio, a surrogate for sympathovagal balance, was significantly lower in the active group compared with the sham group.
IN PRACTICE:
“Collectively, these data suggest that tVNS, a low-cost, low-risk intervention, applied for a short period of time in selected patients with POTS, may result in a significant amelioration of their disease,” the authors conclude.
SOURCE:
The study was led by Stavros Stavrakis, MD, PhD, University of Oklahoma Health Sciences Center, Oklahoma City. It was published online in JACC: Clinical Electrophysiology..
LIMITATIONS:
The study had a small sample size, included only females, and extended only up to 2 months. As there was no improvement on the overall score from the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire, researchers can’t conclude tVNS improved patient reported outcomes. The study used 1 hour of daily stimulation but the optimal duration and ideal timing of tVNS is yet to be determined.
DISCLOSURES:
The study was supported by the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute, NIH/National Institute of General Medical Sciences, and individual donations from Francie Fitzgerald and family through the OU Foundation Fund. The authors have no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
possibly through decreased antiadrenergic autoantibodies and inflammatory cytokines, and improved cardiac autonomic function, in a small proof-of-concept study.
METHODOLOGY:
The double-blind study included 25 female patients with POTS, a syndrome of orthostatic intolerance (mean age 31 years and 81% Caucasian), who were randomly assigned to transcutaneous vagus nerve stimulation (tVNS) to the right tragus or sham stimulation to the earlobe, a site devoid of vagal innervation.
After training, patients delivered the tVNS themselves at a frequency of 20 Hz and pulse width of 200 ms during 1-hour daily sessions over 2 months.
At baseline and 2 months, patients underwent a tilt test to determine postural tachycardia; they remained supine for 25 minutes, followed by 10 minutes of standing, as tolerated.
Researchers used electrocardiogram data to examine heart rate and blood samples to assess serum cytokines and antiautonomic autoantibodies.
The primary outcome was a comparison of orthostatic tachycardia (standing – supine) between the two arms at 2 months.
TAKEAWAY:
At 2 months, postural tachycardia was significantly less in the active vs sham arm (mean postural increase in heart rate 17.6 beats/min vs 31.7 beats/min; P = .01).
There was a significant decrease in beta 1-adrenergic receptor (beta 1-AR; P = .01) and alpha-1-AR (P = .04) autoantibody activity in the active vs sham group, which may account at least in part for the reduced orthostatic tachycardia, although the exact mechanisms for this effect have not been clearly defined, the authors said.
Serum tumor necrosis factor-alpha (TNF-alpha) levels were significantly decreased in the active group relative to the sham group (8.3 pg/mL vs 13.9 pg/mL; P = .01).
As for heart rate variability, change in low frequency (LF) and high frequency (HF) from supine to standing was significantly decreased, and postural change in LF/HF ratio, a surrogate for sympathovagal balance, was significantly lower in the active group compared with the sham group.
IN PRACTICE:
“Collectively, these data suggest that tVNS, a low-cost, low-risk intervention, applied for a short period of time in selected patients with POTS, may result in a significant amelioration of their disease,” the authors conclude.
SOURCE:
The study was led by Stavros Stavrakis, MD, PhD, University of Oklahoma Health Sciences Center, Oklahoma City. It was published online in JACC: Clinical Electrophysiology..
LIMITATIONS:
The study had a small sample size, included only females, and extended only up to 2 months. As there was no improvement on the overall score from the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire, researchers can’t conclude tVNS improved patient reported outcomes. The study used 1 hour of daily stimulation but the optimal duration and ideal timing of tVNS is yet to be determined.
DISCLOSURES:
The study was supported by the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute, NIH/National Institute of General Medical Sciences, and individual donations from Francie Fitzgerald and family through the OU Foundation Fund. The authors have no relevant conflicts of interest.
A version of this article appeared on Medscape.com.