ESC Congress 2015

LONDON – The positive findings of the Biomarkers in Acute Cardiovascular Care (BACC) study reinforce a key change contained in the brand-new European Society of Cardiology guidelines for management of patients with acute coronary syndrome without ST-segment elevation: namely, that it’s appropriate to assess such patients using two measurements of a validated high-sensitivity cardiac troponin assay taken just 1 hour apart, according to Dr. Kurt Huber.

The BACC results are the evidence-based icing on the cake in support of the new recommendation in the guidelines, released at the annual congress of the European Society of Cardiology. The BACC study, which included 1,045 patients who presented to a university emergency department with acute chest pain suggestive of an acute coronary syndrome without ST-segment elevation, was the latest of several studies to show that most such patients can either be safely sent home from the ED or ruled-in for acute MI in just 1 hour when evaluated using a high-sensitivity troponin assay backed by a validated patient-management algorithm. The result means reduced pressure on overcrowded EDs and less patient anxiety because of delayed diagnosis, Dr. Huber, director of cardiology and emergency medicine at Wilhelminen Hospital in Vienna, observed during an interview at the meeting.

The BACC study, presented by Dr. Dirk Westermann of the University Heart Center Hamburg (Germany), utilized a high-sensitivity cardiac troponin I assay. The 1-hour algorithm had a 99.7% negative predictive value for acute MI. A total of 53% of patients were ruled out or in for MI at the 1-hour mark; the rest required further evaluation.

bjancin@frontlinemedcom.com

LONDON – The positive findings of the Biomarkers in Acute Cardiovascular Care (BACC) study reinforce a key change contained in the brand-new European Society of Cardiology guidelines for management of patients with acute coronary syndrome without ST-segment elevation: namely, that it’s appropriate to assess such patients using two measurements of a validated high-sensitivity cardiac troponin assay taken just 1 hour apart, according to Dr. Kurt Huber.

The BACC results are the evidence-based icing on the cake in support of the new recommendation in the guidelines, released at the annual congress of the European Society of Cardiology. The BACC study, which included 1,045 patients who presented to a university emergency department with acute chest pain suggestive of an acute coronary syndrome without ST-segment elevation, was the latest of several studies to show that most such patients can either be safely sent home from the ED or ruled-in for acute MI in just 1 hour when evaluated using a high-sensitivity troponin assay backed by a validated patient-management algorithm. The result means reduced pressure on overcrowded EDs and less patient anxiety because of delayed diagnosis, Dr. Huber, director of cardiology and emergency medicine at Wilhelminen Hospital in Vienna, observed during an interview at the meeting.

The BACC study, presented by Dr. Dirk Westermann of the University Heart Center Hamburg (Germany), utilized a high-sensitivity cardiac troponin I assay. The 1-hour algorithm had a 99.7% negative predictive value for acute MI. A total of 53% of patients were ruled out or in for MI at the 1-hour mark; the rest required further evaluation.

bjancin@frontlinemedcom.com

LONDON – The positive findings of the Biomarkers in Acute Cardiovascular Care (BACC) study reinforce a key change contained in the brand-new European Society of Cardiology guidelines for management of patients with acute coronary syndrome without ST-segment elevation: namely, that it’s appropriate to assess such patients using two measurements of a validated high-sensitivity cardiac troponin assay taken just 1 hour apart, according to Dr. Kurt Huber.

The BACC results are the evidence-based icing on the cake in support of the new recommendation in the guidelines, released at the annual congress of the European Society of Cardiology. The BACC study, which included 1,045 patients who presented to a university emergency department with acute chest pain suggestive of an acute coronary syndrome without ST-segment elevation, was the latest of several studies to show that most such patients can either be safely sent home from the ED or ruled-in for acute MI in just 1 hour when evaluated using a high-sensitivity troponin assay backed by a validated patient-management algorithm. The result means reduced pressure on overcrowded EDs and less patient anxiety because of delayed diagnosis, Dr. Huber, director of cardiology and emergency medicine at Wilhelminen Hospital in Vienna, observed during an interview at the meeting.

The BACC study, presented by Dr. Dirk Westermann of the University Heart Center Hamburg (Germany), utilized a high-sensitivity cardiac troponin I assay. The 1-hour algorithm had a 99.7% negative predictive value for acute MI. A total of 53% of patients were ruled out or in for MI at the 1-hour mark; the rest required further evaluation.

bjancin@frontlinemedcom.com

LONDON – A wireless pacemaker that is secured within the right ventricle of the heart proved both effective and safe in a prospective, nonrandomized, multicenter study.

Interim results obtained for 300 patients at 6 months’ follow-up in the LEADLESS II study showed that the primary efficacy endpoint of both an acceptable pacing threshold and an acceptable sensing amplitude was achieved in 90% of patients, and the primary safety endpoint of freedom from device-related serious adverse events was achieved in 93.3%.

Both of these findings exceeded the performance goal of 85% set in the study, said principal study investigator Dr. Vivek Reddy at the annual congress of the European Society of Cardiology.

“Regular pacemakers are very reliable devices; they’ve been around for half a century,” said Dr. Reddy, who is professor of medicine at Mount Sinai Hospital in New York. “Having said that, they are not perfect,” he observed.

Conventional pacemakers require surgical implantation in the chest, and the wires or leads that go from the device need to be embedded in the vasculature of the heart itself. While the risk of complications is low (around 4% of all implanted devices), when they do happen they usually occur around the site where the pacemaker is implanted or involve placement of the leads in veins.

In contrast, the small cylindrical Nanostim device used in the study is a fully self-contained leadless pacemaker that can be nonsurgically implanted and removed via a catheter threaded through the femoral vein and into the patient’s right ventricle. It is about the size of an AAA battery and, based on the study’s findings, has a potential battery life of 15 years. This is comparable to similar standard single-chamber ventricular pacemakers, according to the manufacturer, St. Jude Medical.

The feasibility of using the device was first shown in the LEADLESS study (Circulation 2014;129:1466-71) and are now confirmed in the LEADLESS II study, which has enrolled 526 patients to date, with successful implantation of the device in 504 patients.

The mean age of the mostly male (61.8%) study cohort was 76 years, with the primary indication for pacemaker placement being atrial fibrillation with atrioventricular block in 55.9%.

The study was performed in 56 centers in the United States, Canada, and Australia and involved 100 operators, only one of whom had prior experience with leadless pacing, Dr. Reddy observed. On average the leadless device was placed within a half hour, and the majority (70.2%) did not require repositioning of the device during the original procedure.

The rate of serious device-related adverse events, such as dislodgement warranting percutaneous retrieval or cardiac perforation, was low, at a rate of 6.7% overall and 1.7% and 1.3%, respectively, with just 1.3% of patients needing to have the device removed because of an increased pacing threshold. There were no device-related deaths, but two deaths occurred that were thought to be procedure related. This is comparable to traditional pacemakers, Dr. Reddy said, although he noted that he was referring to historical controls as this was not a randomized trial.

“The device was shown to be retrievable in a subgroup of seven patients who needed a replacement at a mean of 160 days after implantation,” he noted. Due to the relatively short duration of follow-up, however, “we really can’t talk about what happens with extended follow-up and what happens 5, 10, or 15 years down the line whether we retrieve the devices or simply abandon them and put in a second device.”

The study included patients who had an indication for a single-chamber pacemaker only. Dr. Reddy noted that one of the study limitations is that the device is not suitable for patients needing dual-chamber pacing. The observational nature of the trial also limits the conclusions that can be drawn, and the device does not provide electrocardiogram data.

The Nanostim device is one of two self-contained, miniature wireless pacemakers given marketing authorization in Europe, but both have yet to be approved by the Food and Drug Administration. The other device, Medtronic’s Micra Transcatheter Pacing System, is also placed in the right ventricle and is being studied in the Micra Transcatheter Pacing Study, with promising first-in-human results presented recently at Heart Rhythm 2015.

St. Jude Medical funded the study. Dr. Reddy has received grant support, acted as a consultant to, and received stock options in Nanostim from the company.

LONDON – A wireless pacemaker that is secured within the right ventricle of the heart proved both effective and safe in a prospective, nonrandomized, multicenter study.

Interim results obtained for 300 patients at 6 months’ follow-up in the LEADLESS II study showed that the primary efficacy endpoint of both an acceptable pacing threshold and an acceptable sensing amplitude was achieved in 90% of patients, and the primary safety endpoint of freedom from device-related serious adverse events was achieved in 93.3%.

Both of these findings exceeded the performance goal of 85% set in the study, said principal study investigator Dr. Vivek Reddy at the annual congress of the European Society of Cardiology.

“Regular pacemakers are very reliable devices; they’ve been around for half a century,” said Dr. Reddy, who is professor of medicine at Mount Sinai Hospital in New York. “Having said that, they are not perfect,” he observed.

Conventional pacemakers require surgical implantation in the chest, and the wires or leads that go from the device need to be embedded in the vasculature of the heart itself. While the risk of complications is low (around 4% of all implanted devices), when they do happen they usually occur around the site where the pacemaker is implanted or involve placement of the leads in veins.

In contrast, the small cylindrical Nanostim device used in the study is a fully self-contained leadless pacemaker that can be nonsurgically implanted and removed via a catheter threaded through the femoral vein and into the patient’s right ventricle. It is about the size of an AAA battery and, based on the study’s findings, has a potential battery life of 15 years. This is comparable to similar standard single-chamber ventricular pacemakers, according to the manufacturer, St. Jude Medical.

The feasibility of using the device was first shown in the LEADLESS study (Circulation 2014;129:1466-71) and are now confirmed in the LEADLESS II study, which has enrolled 526 patients to date, with successful implantation of the device in 504 patients.

The mean age of the mostly male (61.8%) study cohort was 76 years, with the primary indication for pacemaker placement being atrial fibrillation with atrioventricular block in 55.9%.

The study was performed in 56 centers in the United States, Canada, and Australia and involved 100 operators, only one of whom had prior experience with leadless pacing, Dr. Reddy observed. On average the leadless device was placed within a half hour, and the majority (70.2%) did not require repositioning of the device during the original procedure.

The rate of serious device-related adverse events, such as dislodgement warranting percutaneous retrieval or cardiac perforation, was low, at a rate of 6.7% overall and 1.7% and 1.3%, respectively, with just 1.3% of patients needing to have the device removed because of an increased pacing threshold. There were no device-related deaths, but two deaths occurred that were thought to be procedure related. This is comparable to traditional pacemakers, Dr. Reddy said, although he noted that he was referring to historical controls as this was not a randomized trial.

“The device was shown to be retrievable in a subgroup of seven patients who needed a replacement at a mean of 160 days after implantation,” he noted. Due to the relatively short duration of follow-up, however, “we really can’t talk about what happens with extended follow-up and what happens 5, 10, or 15 years down the line whether we retrieve the devices or simply abandon them and put in a second device.”

The study included patients who had an indication for a single-chamber pacemaker only. Dr. Reddy noted that one of the study limitations is that the device is not suitable for patients needing dual-chamber pacing. The observational nature of the trial also limits the conclusions that can be drawn, and the device does not provide electrocardiogram data.

The Nanostim device is one of two self-contained, miniature wireless pacemakers given marketing authorization in Europe, but both have yet to be approved by the Food and Drug Administration. The other device, Medtronic’s Micra Transcatheter Pacing System, is also placed in the right ventricle and is being studied in the Micra Transcatheter Pacing Study, with promising first-in-human results presented recently at Heart Rhythm 2015.

St. Jude Medical funded the study. Dr. Reddy has received grant support, acted as a consultant to, and received stock options in Nanostim from the company.

LONDON – A wireless pacemaker that is secured within the right ventricle of the heart proved both effective and safe in a prospective, nonrandomized, multicenter study.

Interim results obtained for 300 patients at 6 months’ follow-up in the LEADLESS II study showed that the primary efficacy endpoint of both an acceptable pacing threshold and an acceptable sensing amplitude was achieved in 90% of patients, and the primary safety endpoint of freedom from device-related serious adverse events was achieved in 93.3%.

Both of these findings exceeded the performance goal of 85% set in the study, said principal study investigator Dr. Vivek Reddy at the annual congress of the European Society of Cardiology.

“Regular pacemakers are very reliable devices; they’ve been around for half a century,” said Dr. Reddy, who is professor of medicine at Mount Sinai Hospital in New York. “Having said that, they are not perfect,” he observed.

Conventional pacemakers require surgical implantation in the chest, and the wires or leads that go from the device need to be embedded in the vasculature of the heart itself. While the risk of complications is low (around 4% of all implanted devices), when they do happen they usually occur around the site where the pacemaker is implanted or involve placement of the leads in veins.

In contrast, the small cylindrical Nanostim device used in the study is a fully self-contained leadless pacemaker that can be nonsurgically implanted and removed via a catheter threaded through the femoral vein and into the patient’s right ventricle. It is about the size of an AAA battery and, based on the study’s findings, has a potential battery life of 15 years. This is comparable to similar standard single-chamber ventricular pacemakers, according to the manufacturer, St. Jude Medical.

The feasibility of using the device was first shown in the LEADLESS study (Circulation 2014;129:1466-71) and are now confirmed in the LEADLESS II study, which has enrolled 526 patients to date, with successful implantation of the device in 504 patients.

The mean age of the mostly male (61.8%) study cohort was 76 years, with the primary indication for pacemaker placement being atrial fibrillation with atrioventricular block in 55.9%.

The study was performed in 56 centers in the United States, Canada, and Australia and involved 100 operators, only one of whom had prior experience with leadless pacing, Dr. Reddy observed. On average the leadless device was placed within a half hour, and the majority (70.2%) did not require repositioning of the device during the original procedure.

The rate of serious device-related adverse events, such as dislodgement warranting percutaneous retrieval or cardiac perforation, was low, at a rate of 6.7% overall and 1.7% and 1.3%, respectively, with just 1.3% of patients needing to have the device removed because of an increased pacing threshold. There were no device-related deaths, but two deaths occurred that were thought to be procedure related. This is comparable to traditional pacemakers, Dr. Reddy said, although he noted that he was referring to historical controls as this was not a randomized trial.

“The device was shown to be retrievable in a subgroup of seven patients who needed a replacement at a mean of 160 days after implantation,” he noted. Due to the relatively short duration of follow-up, however, “we really can’t talk about what happens with extended follow-up and what happens 5, 10, or 15 years down the line whether we retrieve the devices or simply abandon them and put in a second device.”

The study included patients who had an indication for a single-chamber pacemaker only. Dr. Reddy noted that one of the study limitations is that the device is not suitable for patients needing dual-chamber pacing. The observational nature of the trial also limits the conclusions that can be drawn, and the device does not provide electrocardiogram data.

The Nanostim device is one of two self-contained, miniature wireless pacemakers given marketing authorization in Europe, but both have yet to be approved by the Food and Drug Administration. The other device, Medtronic’s Micra Transcatheter Pacing System, is also placed in the right ventricle and is being studied in the Micra Transcatheter Pacing Study, with promising first-in-human results presented recently at Heart Rhythm 2015.

St. Jude Medical funded the study. Dr. Reddy has received grant support, acted as a consultant to, and received stock options in Nanostim from the company.

LONDON – U.S. patients hospitalized for heart failure and treated with antibiotics during their hospital stay had an increased rate both for developing Clostridium difficile infection and dying from it, based on nationwide data collected from nearly six million patients.

“Heart failure was an independent risk factor” in multivariate analyses that controlled for demographic factors as well as for several comorbidities of heart failure, Dr. Petra Mamic said in a video interview at the annual congress of the European Society of Cardiology.

She and her associates used data collected by the National Inpatient Sample during 2012 in more than 5.8 million U.S. hospitalized patients who received antibiotic treatment for a urinary tract infection, pneumonia, or sepsis. They compared the rate of subsequent infection with C. difficile in the roughly 1.4 million of these patients who had heart failure and the nearly 4.5 million without heart failure. In a multivariate analysis heart failure patients were 13% more likely to develop C. difficile infection compared with patients without heart failure. In a second multivariate analysis that focused just on patients with heart failure those who had become infected by C. difficile were 81% more likely to die in hospital compared with heart failure patients without this type of infection.

“Heart failure patients are frequently hospitalized and have a lot of bacterial infections, and so receive treatment with a lot of antibiotics,” said Dr. Mamic, an internal medicine physician at Stanford (Calif.) University. “What is important is that C. difficile infection is preventable. Our ultimate goal is to prevent C. difficile in these patients who have such high morbidity and mortality,”

Dr. Mamic had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LONDON – U.S. patients hospitalized for heart failure and treated with antibiotics during their hospital stay had an increased rate both for developing Clostridium difficile infection and dying from it, based on nationwide data collected from nearly six million patients.

“Heart failure was an independent risk factor” in multivariate analyses that controlled for demographic factors as well as for several comorbidities of heart failure, Dr. Petra Mamic said in a video interview at the annual congress of the European Society of Cardiology.

She and her associates used data collected by the National Inpatient Sample during 2012 in more than 5.8 million U.S. hospitalized patients who received antibiotic treatment for a urinary tract infection, pneumonia, or sepsis. They compared the rate of subsequent infection with C. difficile in the roughly 1.4 million of these patients who had heart failure and the nearly 4.5 million without heart failure. In a multivariate analysis heart failure patients were 13% more likely to develop C. difficile infection compared with patients without heart failure. In a second multivariate analysis that focused just on patients with heart failure those who had become infected by C. difficile were 81% more likely to die in hospital compared with heart failure patients without this type of infection.

“Heart failure patients are frequently hospitalized and have a lot of bacterial infections, and so receive treatment with a lot of antibiotics,” said Dr. Mamic, an internal medicine physician at Stanford (Calif.) University. “What is important is that C. difficile infection is preventable. Our ultimate goal is to prevent C. difficile in these patients who have such high morbidity and mortality,”

Dr. Mamic had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LONDON – U.S. patients hospitalized for heart failure and treated with antibiotics during their hospital stay had an increased rate both for developing Clostridium difficile infection and dying from it, based on nationwide data collected from nearly six million patients.

“Heart failure was an independent risk factor” in multivariate analyses that controlled for demographic factors as well as for several comorbidities of heart failure, Dr. Petra Mamic said in a video interview at the annual congress of the European Society of Cardiology.

She and her associates used data collected by the National Inpatient Sample during 2012 in more than 5.8 million U.S. hospitalized patients who received antibiotic treatment for a urinary tract infection, pneumonia, or sepsis. They compared the rate of subsequent infection with C. difficile in the roughly 1.4 million of these patients who had heart failure and the nearly 4.5 million without heart failure. In a multivariate analysis heart failure patients were 13% more likely to develop C. difficile infection compared with patients without heart failure. In a second multivariate analysis that focused just on patients with heart failure those who had become infected by C. difficile were 81% more likely to die in hospital compared with heart failure patients without this type of infection.

“Heart failure patients are frequently hospitalized and have a lot of bacterial infections, and so receive treatment with a lot of antibiotics,” said Dr. Mamic, an internal medicine physician at Stanford (Calif.) University. “What is important is that C. difficile infection is preventable. Our ultimate goal is to prevent C. difficile in these patients who have such high morbidity and mortality,”

Dr. Mamic had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LONDON – Drinking more than three cups of coffee daily increased the risk of a cardiovascular event by 50% in a study of more than 1,000 adults aged 45 years or younger with mild, untreated hypertension.

The results of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) also showed that even moderate coffee intake, defined as between one and three cups per day, could up the risk of a cardiovascular event when compared with non–coffee drinkers.

“Don’t drink a lot of coffee; reduce your intake,” Dr. Lucio Mos advised young to middle-aged hypertensive adults in a video interview at the annual congress of the European Society of Cardiology.

Heavy coffee drinking is a strong predictor of increasing blood pressure and rising blood glucose, said Dr. Mos of Hospital San Daniele del Friuli in Udine, Italy. In this study, which had a mean of 12.5 years of follow-up, there was a linear relationship between coffee intake and cardiovascular events such as heart attacks, with the risk increasing with higher coffee intake.

LONDON – Drinking more than three cups of coffee daily increased the risk of a cardiovascular event by 50% in a study of more than 1,000 adults aged 45 years or younger with mild, untreated hypertension.

The results of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) also showed that even moderate coffee intake, defined as between one and three cups per day, could up the risk of a cardiovascular event when compared with non–coffee drinkers.

“Don’t drink a lot of coffee; reduce your intake,” Dr. Lucio Mos advised young to middle-aged hypertensive adults in a video interview at the annual congress of the European Society of Cardiology.

Heavy coffee drinking is a strong predictor of increasing blood pressure and rising blood glucose, said Dr. Mos of Hospital San Daniele del Friuli in Udine, Italy. In this study, which had a mean of 12.5 years of follow-up, there was a linear relationship between coffee intake and cardiovascular events such as heart attacks, with the risk increasing with higher coffee intake.

LONDON – Drinking more than three cups of coffee daily increased the risk of a cardiovascular event by 50% in a study of more than 1,000 adults aged 45 years or younger with mild, untreated hypertension.

The results of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) also showed that even moderate coffee intake, defined as between one and three cups per day, could up the risk of a cardiovascular event when compared with non–coffee drinkers.

“Don’t drink a lot of coffee; reduce your intake,” Dr. Lucio Mos advised young to middle-aged hypertensive adults in a video interview at the annual congress of the European Society of Cardiology.

Heavy coffee drinking is a strong predictor of increasing blood pressure and rising blood glucose, said Dr. Mos of Hospital San Daniele del Friuli in Udine, Italy. In this study, which had a mean of 12.5 years of follow-up, there was a linear relationship between coffee intake and cardiovascular events such as heart attacks, with the risk increasing with higher coffee intake.

Intravenous administration of cyclosporine just before percutaneous coronary intervention was not associated with a reduced risk of adverse outcomes at 1 year in a study of patients who underwent the procedure after experiencing an acute anterior ST-segment elevation myocardial infarction.

Findings from the multicenter, randomized study, known as the Does Cyclosporine Improve Clinical Outcome in ST Elevation Myocardial Infarction Patients (CIRCUS) trial, were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine (doi: 10.1056/NEJMoa1505489).

For the phase 3 trial, Dr. Michel Ovize and associates investigated whether a single intravenous dose of cyclosporine, administered just before PCI, would improve clinical outcomes and prevent left adverse left ventricular modeling at 1 year in patients with anterior STEMI.

“Growing evidence from experimental studies and small-size proof-of-concept clinical trials shows that reperfusion injury contributes greatly to the final infarct size,” the researchers wrote. “Preclinical studies indicate that the opening of the mitochondrial permeability transition pore (PTP) in the inner mitochondrial membrane plays a major role in reperfusion injury. Either genetic or pharmacologic inhibition of cyclophilin D, a major component of the PTP, reduces the severity of myocardial reperfusion injury.”

Dr. Ovize of the Clinical Investigation Center of Lyon, France, and his associates chose to test cyclosporine, a pharmacologic inhibitor of cyclophilin D, after a phase 2 trial conducted by the same researchers found that administration of cyclosporine immediately before PCI reduced the myocardial infarct size in patients with STEMI. In CIRCUS, which was conducted from April 2011 through February 2014 at 42 hospitals in three countries, 475 patients with an acute anterior STEMI who were undergoing PCI within 12 hours of symptom onset received IV cyclosporine at a dose of 2.5 mg/kg of body weight, while 495 patients received placebo. The primary outcome was a composite of death from any cause, worsening of heart failure during initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year.

At baseline, the mean age of patients was 60 years, 82% were men, and their mean body mass index was 27 kg/m². One year of follow-up data was available for 395 patients in the cyclosporine group and 396 in the placebo group. The researchers found no significant differences between the two groups in the proportion who experienced a primary outcome event (59% in the cyclosporine group vs. 58% in the control group) or in the rate of all-cause mortality (7.1% vs. 6.6%).

There were also no differences between groups in the rate of initial worsening of heart failure or rehospitalization for heart failure at 1 year (22.8% vs. 22.7%). In addition, a similar proportion of patients in both groups experienced adverse left ventricular remodeling (42.8% vs. 40.7%).

“One important limitation of this trial is that we included in the primary outcome the nonclinical outcome of adverse left ventricular remodeling, which accounted for a substantial proportion of the primary outcome rate,” the researchers wrote. “Left ventricular remodeling is a surrogate outcome – one that was not successfully measured in 17.4% of the trial participants. However, in secondary analyses, no beneficial effect of cyclosporine was detected on any of the hard clinical outcomes.”

They went on to note that nearly one of four patients in CIRCUS died or was hospitalized for heart failure, “a reminder of the substantial residual risk in this population and the persistent room for improvement in the medical treatment of high-risk patients with STEMI. The results of this trial do not challenge the concept that reperfusion injury is clinically important. Recent phase 2 trials that have used either ischemic or pharmacologic postconditioning suggest that interventions applied at the time of reperfusion can limit infarct size and improve functional recovery. Their effect on clinical outcome remains to be determined in phase 3 studies.”

The study was supported by grants from the French Ministry of Health and Research National Program and NeuroVive Pharmaceutical. Dr. Ovize disclosed that he is a consultant for NueroVive Pharmaceutical.

dbrunk@frontlinemedcom.com

Intravenous administration of cyclosporine just before percutaneous coronary intervention was not associated with a reduced risk of adverse outcomes at 1 year in a study of patients who underwent the procedure after experiencing an acute anterior ST-segment elevation myocardial infarction.

Findings from the multicenter, randomized study, known as the Does Cyclosporine Improve Clinical Outcome in ST Elevation Myocardial Infarction Patients (CIRCUS) trial, were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine (doi: 10.1056/NEJMoa1505489).

For the phase 3 trial, Dr. Michel Ovize and associates investigated whether a single intravenous dose of cyclosporine, administered just before PCI, would improve clinical outcomes and prevent left adverse left ventricular modeling at 1 year in patients with anterior STEMI.

“Growing evidence from experimental studies and small-size proof-of-concept clinical trials shows that reperfusion injury contributes greatly to the final infarct size,” the researchers wrote. “Preclinical studies indicate that the opening of the mitochondrial permeability transition pore (PTP) in the inner mitochondrial membrane plays a major role in reperfusion injury. Either genetic or pharmacologic inhibition of cyclophilin D, a major component of the PTP, reduces the severity of myocardial reperfusion injury.”

Dr. Ovize of the Clinical Investigation Center of Lyon, France, and his associates chose to test cyclosporine, a pharmacologic inhibitor of cyclophilin D, after a phase 2 trial conducted by the same researchers found that administration of cyclosporine immediately before PCI reduced the myocardial infarct size in patients with STEMI. In CIRCUS, which was conducted from April 2011 through February 2014 at 42 hospitals in three countries, 475 patients with an acute anterior STEMI who were undergoing PCI within 12 hours of symptom onset received IV cyclosporine at a dose of 2.5 mg/kg of body weight, while 495 patients received placebo. The primary outcome was a composite of death from any cause, worsening of heart failure during initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year.

At baseline, the mean age of patients was 60 years, 82% were men, and their mean body mass index was 27 kg/m². One year of follow-up data was available for 395 patients in the cyclosporine group and 396 in the placebo group. The researchers found no significant differences between the two groups in the proportion who experienced a primary outcome event (59% in the cyclosporine group vs. 58% in the control group) or in the rate of all-cause mortality (7.1% vs. 6.6%).

There were also no differences between groups in the rate of initial worsening of heart failure or rehospitalization for heart failure at 1 year (22.8% vs. 22.7%). In addition, a similar proportion of patients in both groups experienced adverse left ventricular remodeling (42.8% vs. 40.7%).

“One important limitation of this trial is that we included in the primary outcome the nonclinical outcome of adverse left ventricular remodeling, which accounted for a substantial proportion of the primary outcome rate,” the researchers wrote. “Left ventricular remodeling is a surrogate outcome – one that was not successfully measured in 17.4% of the trial participants. However, in secondary analyses, no beneficial effect of cyclosporine was detected on any of the hard clinical outcomes.”

They went on to note that nearly one of four patients in CIRCUS died or was hospitalized for heart failure, “a reminder of the substantial residual risk in this population and the persistent room for improvement in the medical treatment of high-risk patients with STEMI. The results of this trial do not challenge the concept that reperfusion injury is clinically important. Recent phase 2 trials that have used either ischemic or pharmacologic postconditioning suggest that interventions applied at the time of reperfusion can limit infarct size and improve functional recovery. Their effect on clinical outcome remains to be determined in phase 3 studies.”

The study was supported by grants from the French Ministry of Health and Research National Program and NeuroVive Pharmaceutical. Dr. Ovize disclosed that he is a consultant for NueroVive Pharmaceutical.

dbrunk@frontlinemedcom.com

Intravenous administration of cyclosporine just before percutaneous coronary intervention was not associated with a reduced risk of adverse outcomes at 1 year in a study of patients who underwent the procedure after experiencing an acute anterior ST-segment elevation myocardial infarction.

Findings from the multicenter, randomized study, known as the Does Cyclosporine Improve Clinical Outcome in ST Elevation Myocardial Infarction Patients (CIRCUS) trial, were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine (doi: 10.1056/NEJMoa1505489).

For the phase 3 trial, Dr. Michel Ovize and associates investigated whether a single intravenous dose of cyclosporine, administered just before PCI, would improve clinical outcomes and prevent left adverse left ventricular modeling at 1 year in patients with anterior STEMI.

“Growing evidence from experimental studies and small-size proof-of-concept clinical trials shows that reperfusion injury contributes greatly to the final infarct size,” the researchers wrote. “Preclinical studies indicate that the opening of the mitochondrial permeability transition pore (PTP) in the inner mitochondrial membrane plays a major role in reperfusion injury. Either genetic or pharmacologic inhibition of cyclophilin D, a major component of the PTP, reduces the severity of myocardial reperfusion injury.”

Dr. Ovize of the Clinical Investigation Center of Lyon, France, and his associates chose to test cyclosporine, a pharmacologic inhibitor of cyclophilin D, after a phase 2 trial conducted by the same researchers found that administration of cyclosporine immediately before PCI reduced the myocardial infarct size in patients with STEMI. In CIRCUS, which was conducted from April 2011 through February 2014 at 42 hospitals in three countries, 475 patients with an acute anterior STEMI who were undergoing PCI within 12 hours of symptom onset received IV cyclosporine at a dose of 2.5 mg/kg of body weight, while 495 patients received placebo. The primary outcome was a composite of death from any cause, worsening of heart failure during initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year.

At baseline, the mean age of patients was 60 years, 82% were men, and their mean body mass index was 27 kg/m². One year of follow-up data was available for 395 patients in the cyclosporine group and 396 in the placebo group. The researchers found no significant differences between the two groups in the proportion who experienced a primary outcome event (59% in the cyclosporine group vs. 58% in the control group) or in the rate of all-cause mortality (7.1% vs. 6.6%).

There were also no differences between groups in the rate of initial worsening of heart failure or rehospitalization for heart failure at 1 year (22.8% vs. 22.7%). In addition, a similar proportion of patients in both groups experienced adverse left ventricular remodeling (42.8% vs. 40.7%).

“One important limitation of this trial is that we included in the primary outcome the nonclinical outcome of adverse left ventricular remodeling, which accounted for a substantial proportion of the primary outcome rate,” the researchers wrote. “Left ventricular remodeling is a surrogate outcome – one that was not successfully measured in 17.4% of the trial participants. However, in secondary analyses, no beneficial effect of cyclosporine was detected on any of the hard clinical outcomes.”

They went on to note that nearly one of four patients in CIRCUS died or was hospitalized for heart failure, “a reminder of the substantial residual risk in this population and the persistent room for improvement in the medical treatment of high-risk patients with STEMI. The results of this trial do not challenge the concept that reperfusion injury is clinically important. Recent phase 2 trials that have used either ischemic or pharmacologic postconditioning suggest that interventions applied at the time of reperfusion can limit infarct size and improve functional recovery. Their effect on clinical outcome remains to be determined in phase 3 studies.”

The study was supported by grants from the French Ministry of Health and Research National Program and NeuroVive Pharmaceutical. Dr. Ovize disclosed that he is a consultant for NueroVive Pharmaceutical.

dbrunk@frontlinemedcom.com

LONDON – A regular midday nap is associated with clinically meaningful reductions in blood pressure in hypertensive patients, according to a prospective observational study presented at the annual congress of the European Society of Cardiology.

The midday nappers in the 386-patient study averaged 5 mm Hg lower daytime and 8 mm Hg lower nighttime systolic blood pressure, compared with non-nappers, Dr. Manolis Kallistratos said in a video interview.

Sleep during nap time was associated with bigger blood pressure reductions than simply resting. Sawing logs for 60 minutes or more brought the most benefits, according to Dr. Kallistratos, head of the hypertension division at Asklepieion Voula General Hospital in Athens.

Nappers also had significantly less arterial stiffness as reflected in a lower pulse wave velocity, as well as a smaller average left atrial diameter indicative of less structural heart damage, the cardiologist noted.

bjancin@frontlinemedcom.com

LONDON – A regular midday nap is associated with clinically meaningful reductions in blood pressure in hypertensive patients, according to a prospective observational study presented at the annual congress of the European Society of Cardiology.

The midday nappers in the 386-patient study averaged 5 mm Hg lower daytime and 8 mm Hg lower nighttime systolic blood pressure, compared with non-nappers, Dr. Manolis Kallistratos said in a video interview.

Sleep during nap time was associated with bigger blood pressure reductions than simply resting. Sawing logs for 60 minutes or more brought the most benefits, according to Dr. Kallistratos, head of the hypertension division at Asklepieion Voula General Hospital in Athens.

Nappers also had significantly less arterial stiffness as reflected in a lower pulse wave velocity, as well as a smaller average left atrial diameter indicative of less structural heart damage, the cardiologist noted.

bjancin@frontlinemedcom.com

LONDON – A regular midday nap is associated with clinically meaningful reductions in blood pressure in hypertensive patients, according to a prospective observational study presented at the annual congress of the European Society of Cardiology.

The midday nappers in the 386-patient study averaged 5 mm Hg lower daytime and 8 mm Hg lower nighttime systolic blood pressure, compared with non-nappers, Dr. Manolis Kallistratos said in a video interview.

Sleep during nap time was associated with bigger blood pressure reductions than simply resting. Sawing logs for 60 minutes or more brought the most benefits, according to Dr. Kallistratos, head of the hypertension division at Asklepieion Voula General Hospital in Athens.

Nappers also had significantly less arterial stiffness as reflected in a lower pulse wave velocity, as well as a smaller average left atrial diameter indicative of less structural heart damage, the cardiologist noted.

bjancin@frontlinemedcom.com