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Frequent Limb Movement in Restless Legs Syndrome Linked to LVH
NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.
Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.
"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.
Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.
Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.
The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.
At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.
The presence of severe LVH [defined as left ventricular mass index >116g/m2] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.
Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.
"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.
NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.
Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.
"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.
Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.
Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.
The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.
At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.
The presence of severe LVH [defined as left ventricular mass index >116g/m2] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.
Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.
"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.
NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.
Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.
"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.
Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.
Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.
The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.
At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.
The presence of severe LVH [defined as left ventricular mass index >116g/m2] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.
Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.
"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.
FROM THE ANNUAL MEETING OF THE AMERICAN COLLEGE OF CARDIOLOGY
Major Finding: Despite having a left ventricular ejection fraction of around 60% at baseline, restless legs syndrome patients with over 35 periodic limb movements per hour during sleep had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of left ventricular hypertrophy.
Data Source: Retrospective study of 584 restless legs syndrome patients who underwent overnight polysomnography studies.
Disclosures: The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic, Scottsdale.
Frequent Limb Movement in Restless Legs Syndrome Linked to LVH
NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.
Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.
"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.
Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.
Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.
The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.
At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.
The presence of severe LVH [defined as left ventricular mass index >116g/m2] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.
Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.
"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.
NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.
Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.
"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.
Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.
Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.
The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.
At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.
The presence of severe LVH [defined as left ventricular mass index >116g/m2] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.
Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.
"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.
NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.
Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.
"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.
Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.
Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.
The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.
At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.
The presence of severe LVH [defined as left ventricular mass index >116g/m2] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.
Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.
"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.
FROM THE ANNUAL MEETING OF THE AMERICAN COLLEGE OF CARDIOLOGY
Frequent Limb Movement in Restless Legs Syndrome Linked to LVH
NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.
Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.
"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.
Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.
Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.
The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.
At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.
The presence of severe LVH [defined as left ventricular mass index >116g/m2] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.
Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.
"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.
NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.
Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.
"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.
Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.
Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.
The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.
At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.
The presence of severe LVH [defined as left ventricular mass index >116g/m2] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.
Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.
"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.
NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.
Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.
"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.
Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.
Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.
The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.
At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.
The presence of severe LVH [defined as left ventricular mass index >116g/m2] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.
Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.
"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.
FROM THE ANNUAL MEETING OF THE AMERICAN COLLEGE OF CARDIOLOGY
Major Finding: Despite having a left ventricular ejection fraction of around 60% at baseline, restless legs syndrome patients with over 35 periodic limb movements per hour during sleep had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of left ventricular hypertrophy.
Data Source: Retrospective study of 584 restless legs syndrome patients who underwent overnight polysomnography studies.
Disclosures: The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic, Scottsdale.
Pulse Pressure May Help Distinguish White Coat From True Hypertension
NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.
About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.
Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.
Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.
The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.
Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.
Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).
No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.
Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.
NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.
About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.
Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.
Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.
The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.
Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.
Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).
No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.
Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.
NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.
About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.
Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.
Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.
The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.
Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.
Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).
No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.
Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN COLLEGE OF CARDIOLOGY
Major Finding: Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).
Data Source: The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings.
Disclosures: The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.
Pulse Pressure May Help Distinguish White Coat From True Hypertension
NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.
About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.
Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.
Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.
The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.
Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.
Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).
No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.
Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.
NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.
About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.
Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.
Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.
The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.
Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.
Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).
No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.
Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.
NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.
About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.
Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.
Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.
The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.
Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.
Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).
No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.
Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.
The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN COLLEGE OF CARDIOLOGY
Major Finding: Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).
Data Source: The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings.
Disclosures: The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.
Vorinostat demonstrates consistent safety
Berlin, Germany—Vorinostat demonstrates safety and tolerability alone and in combination with other systemic treatments for a wide range of solid and hematologic malignancies, according to a study of collated data from the vorinostat clinical trial program.
Investigators presented the safety data in a poster at the ECCO 15 - 34th ESMO Multidisciplinary Congress. The data suggest that a supratherapeutic single dose (800 mg) of this orally active histone deacetylase inhibitor does not prolong ventricular repolarization to a significant degree. This is reassuring, since cardiac rhythm and EEG changes are thought to be a class effect of HDACs.
Lead author David Siegel, MD, from Hackensack University Medical Center, Hackensack, New Jersey, and his fellow researchers observed that the study data support the overall safety profile of vorinostat use in cancer patients.
They based their analysis on 18 phase 1 and phase 2 vorinostat trials that included 498 patients, 341 who received the agent as monotherapy and 157 treated with the drug in combination with other therapies.
Vorinostat is approved by the US Food and Drug Administration to treat relapsed or refractory cutaneous T-cell lymphoma and was dosed at the approved level of 400 mg/day for 156 of the 341 patients in the monotherapy cohort. In the combination group, vorinostat was given on weekly or 2-weekly schedules instead of continuous dosing.
In the monotherapy group, the most commonly reported treatment-related adverse events were fatigue (61.9%), nausea (55.7%), diarrhea (49.3%), and anorexia (48.1%). The most common grade 3/4 adverse events were fatigue (12.0%), thrombocytopenia (10.6%), dehydration (7.0%), decreased platelet count (5.3%), and anorexia (5.0%).
Seventy-one (20.8%) patients required dose modifications for toxicity and 38 (11.1%) discontinued study medication due to drug-related adverse events. Three drug-related adverse events led to death.
In the combination treatment cohort, nausea (48.4%), diarrhea (40.8%), fatigue (34.4%), and vomiting (31.2%) were the most commonly reported adverse events. The most common grade 3/4 adverse events were fatigue (13.4%), thrombocytopenia (9.6%), neutropenia (8.3%), diarrhea (5.7%), and nausea.
Dose modifications were required in 27 patients (17.2%). Discontinuation due to adverse events was necessary in 31 patients (19.7%), and 1 death was attributed to vorinostat combination treatment.
The QTc phase 1 substudy was randomized, partially blind, and placebo-controlled. None of the 22 evaluable patients included in the analysis experienced a QtcF change greater than 30 msec from their baseline scores.
Berlin, Germany—Vorinostat demonstrates safety and tolerability alone and in combination with other systemic treatments for a wide range of solid and hematologic malignancies, according to a study of collated data from the vorinostat clinical trial program.
Investigators presented the safety data in a poster at the ECCO 15 - 34th ESMO Multidisciplinary Congress. The data suggest that a supratherapeutic single dose (800 mg) of this orally active histone deacetylase inhibitor does not prolong ventricular repolarization to a significant degree. This is reassuring, since cardiac rhythm and EEG changes are thought to be a class effect of HDACs.
Lead author David Siegel, MD, from Hackensack University Medical Center, Hackensack, New Jersey, and his fellow researchers observed that the study data support the overall safety profile of vorinostat use in cancer patients.
They based their analysis on 18 phase 1 and phase 2 vorinostat trials that included 498 patients, 341 who received the agent as monotherapy and 157 treated with the drug in combination with other therapies.
Vorinostat is approved by the US Food and Drug Administration to treat relapsed or refractory cutaneous T-cell lymphoma and was dosed at the approved level of 400 mg/day for 156 of the 341 patients in the monotherapy cohort. In the combination group, vorinostat was given on weekly or 2-weekly schedules instead of continuous dosing.
In the monotherapy group, the most commonly reported treatment-related adverse events were fatigue (61.9%), nausea (55.7%), diarrhea (49.3%), and anorexia (48.1%). The most common grade 3/4 adverse events were fatigue (12.0%), thrombocytopenia (10.6%), dehydration (7.0%), decreased platelet count (5.3%), and anorexia (5.0%).
Seventy-one (20.8%) patients required dose modifications for toxicity and 38 (11.1%) discontinued study medication due to drug-related adverse events. Three drug-related adverse events led to death.
In the combination treatment cohort, nausea (48.4%), diarrhea (40.8%), fatigue (34.4%), and vomiting (31.2%) were the most commonly reported adverse events. The most common grade 3/4 adverse events were fatigue (13.4%), thrombocytopenia (9.6%), neutropenia (8.3%), diarrhea (5.7%), and nausea.
Dose modifications were required in 27 patients (17.2%). Discontinuation due to adverse events was necessary in 31 patients (19.7%), and 1 death was attributed to vorinostat combination treatment.
The QTc phase 1 substudy was randomized, partially blind, and placebo-controlled. None of the 22 evaluable patients included in the analysis experienced a QtcF change greater than 30 msec from their baseline scores.
Berlin, Germany—Vorinostat demonstrates safety and tolerability alone and in combination with other systemic treatments for a wide range of solid and hematologic malignancies, according to a study of collated data from the vorinostat clinical trial program.
Investigators presented the safety data in a poster at the ECCO 15 - 34th ESMO Multidisciplinary Congress. The data suggest that a supratherapeutic single dose (800 mg) of this orally active histone deacetylase inhibitor does not prolong ventricular repolarization to a significant degree. This is reassuring, since cardiac rhythm and EEG changes are thought to be a class effect of HDACs.
Lead author David Siegel, MD, from Hackensack University Medical Center, Hackensack, New Jersey, and his fellow researchers observed that the study data support the overall safety profile of vorinostat use in cancer patients.
They based their analysis on 18 phase 1 and phase 2 vorinostat trials that included 498 patients, 341 who received the agent as monotherapy and 157 treated with the drug in combination with other therapies.
Vorinostat is approved by the US Food and Drug Administration to treat relapsed or refractory cutaneous T-cell lymphoma and was dosed at the approved level of 400 mg/day for 156 of the 341 patients in the monotherapy cohort. In the combination group, vorinostat was given on weekly or 2-weekly schedules instead of continuous dosing.
In the monotherapy group, the most commonly reported treatment-related adverse events were fatigue (61.9%), nausea (55.7%), diarrhea (49.3%), and anorexia (48.1%). The most common grade 3/4 adverse events were fatigue (12.0%), thrombocytopenia (10.6%), dehydration (7.0%), decreased platelet count (5.3%), and anorexia (5.0%).
Seventy-one (20.8%) patients required dose modifications for toxicity and 38 (11.1%) discontinued study medication due to drug-related adverse events. Three drug-related adverse events led to death.
In the combination treatment cohort, nausea (48.4%), diarrhea (40.8%), fatigue (34.4%), and vomiting (31.2%) were the most commonly reported adverse events. The most common grade 3/4 adverse events were fatigue (13.4%), thrombocytopenia (9.6%), neutropenia (8.3%), diarrhea (5.7%), and nausea.
Dose modifications were required in 27 patients (17.2%). Discontinuation due to adverse events was necessary in 31 patients (19.7%), and 1 death was attributed to vorinostat combination treatment.
The QTc phase 1 substudy was randomized, partially blind, and placebo-controlled. None of the 22 evaluable patients included in the analysis experienced a QtcF change greater than 30 msec from their baseline scores.