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VIDEO: Serial lung fluid measurement improved heart failure outcomes
CHICAGO – Regular assessment of a heart failure patient’s lung fluid volume using a device that measures electrical conduction through the chest – lung impedance – helped guide clinicians to make timely adjustments in a patient’s medications and thereby significantly reduce mortality and hospitalizations during an average 4 years of follow-up in a randomized, controlled study with 256 patients.
Monthly measurement of lung impedance and medication adjustments based on the information led to a 58% reduction in hospitalizations for acute heart failure during the first year of the study, compared with control patients, and a 56% reduction in heart failure hospitalizations, compared with controls, during the entire course of the study, the study’s two primary endpoints, Dr. Michael K. Shochat reported at the annual meeting of the American College of Cardiology.
The results also showed that performing regular lung impedance measurements and using the results to guide treatment led to a 43% reduction in all-cause mortality and a 62% drop in heart failure mortality during the average 4-year course of the study, said Dr. Shochat, a cardiologist at the Heart Institute of Hillel Yaffe Medical Center in Hadera, Israel. Concurrent with Dr. Shochat’s report at the meeting the results also appeared in an article published online (J Card Failure. 2016;doi:10.1016/j.cardfail.2016.03.015).
A key aspect of the study was that the clinicians who treated the enrolled patients who underwent lung impedance monitoring used this information to adjust medications the patients received. Overall, patients who underwent monitoring had more than twice the number of medication dose adjustments, compared with the control patients. These adjustments particularly focused on diuretic dosages, which changed three times as often in the monitored patients, compared with controls, Dr. Shochat reported. Changes in the dosages of beta-blockers and ACE inhibitors also showed marked increases in the monitored patients, compared with the controls.
The Non-Invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic Heart Failure Patients (IMPEDANCE-HF) trial enrolled 256 patients at two centers in Israel during 2005-2014. Patients had New York Heart Association class II-IV heart failure and a left ventricular ejection fraction of 35% or less. The enrolled patients averaged 67 years of age, and 80% were men.
Clinicians measured lung impedance using a proprietary device that places external electrodes on opposite sides of the patient’s chest. Calculation of impedance used a formula that eliminated the noise from chest wall impedance and focused exclusively on lung impedance. Once the electrodes are placed collection of the impedance data takes about 1 minute, Dr. Shochat said. The study protocol called for impedance data to be collected monthly, and in practice it occurred about 11 times a year during the study.
The investigators calculated for each patient in the active arm of the study a “basal” lung impedance level that reflected their level of lung conductivity when their lungs were clear of excess fluid. Participating clinicians were instructed to intervene by altering medications when the impedance level dropped more than 18% below the basal level. Their goal was to prevent impedance from dropping to more than 24% below the basal level, which correlated with when heart failure patients usually required hospitalization for acute decompensation. The specifics of how to adjust medications to manage patients who showed these signs of fluid overload were left to the discretion of each attending physician.
MPEDANCE-HF was sponsored by the RSMM Company, which is developing the lung impedance measurement device used in the study. Dr. Shochat is a cofounder of RSMM and is a member of the company’s board of directors.
On Twitter @mitchelzoler
The very exciting results reported by Dr. Shochat came from a small, positive trial that showed impedance monitoring was an effective way to detect an increased amount of fluid in a heart failure patient’s lungs. This resulted in improved outcomes, compared with patients managed using usual care, including fewer hospitalizations and reduced mortality.
These results suggest that when physicians had lung impedance information, they identified episodes of acute heart failure decompensation sooner and that they used this alert to change treatment and prevent patient worsening. Heart failure exacerbations and decompensation events are a recurring problem for heart failure patients, and the earlier they are identified and addressed with altered treatment, the better it is for the patient’s well being. The next step is to see if these positive results can be confirmed by other research groups and in larger numbers of patients.
These results contrast with the findings from a German study reported in 2015 that used lung impedance information collected by implantable cardioverter defibrillators in heart failure patients to identify episodes of fluid buildup and decompensation. That study failed to show a statistically significant impact on patient outcomes. The researchers speculated that this may have been because patients often did not go online to allow their information to get transmitted to their physician, and physicians often did not act on the information because the patients reported no coincident change in symptoms.
This problem with the German study highlights that collecting lung impedance information will only improve outcomes if physicians then act on the information and modify a patient’s treatment. In the new study reported by Dr. Shochat, patients consistently underwent evaluation for their lung impedance status every month, and when the results suggested a growing problem of fluid overload the physicians consistently acted on the information by adjusting medication dosages.
Use of lung impedance measurement is similar to another approach for monitoring patients with heart failure that recently entered routine U.S. practice, an implanted device to monitor pulmonary artery pressure and identify episodes of fluid overload and acute decompensation. In the future, it will be interesting to compare the efficacy and ease of use of managing heart failure patients with pulmonary artery pressure monitoring with an implanted device and monitoring fluid build up in the lungs with lung impedance.
Dr. John A. Jarcho is a cardiologist at Brigham and Women’s Hospital, Boston. He had no disclosures. He made these comments as a discussant of Dr. Shochat’s report and in an interview.
The very exciting results reported by Dr. Shochat came from a small, positive trial that showed impedance monitoring was an effective way to detect an increased amount of fluid in a heart failure patient’s lungs. This resulted in improved outcomes, compared with patients managed using usual care, including fewer hospitalizations and reduced mortality.
These results suggest that when physicians had lung impedance information, they identified episodes of acute heart failure decompensation sooner and that they used this alert to change treatment and prevent patient worsening. Heart failure exacerbations and decompensation events are a recurring problem for heart failure patients, and the earlier they are identified and addressed with altered treatment, the better it is for the patient’s well being. The next step is to see if these positive results can be confirmed by other research groups and in larger numbers of patients.
These results contrast with the findings from a German study reported in 2015 that used lung impedance information collected by implantable cardioverter defibrillators in heart failure patients to identify episodes of fluid buildup and decompensation. That study failed to show a statistically significant impact on patient outcomes. The researchers speculated that this may have been because patients often did not go online to allow their information to get transmitted to their physician, and physicians often did not act on the information because the patients reported no coincident change in symptoms.
This problem with the German study highlights that collecting lung impedance information will only improve outcomes if physicians then act on the information and modify a patient’s treatment. In the new study reported by Dr. Shochat, patients consistently underwent evaluation for their lung impedance status every month, and when the results suggested a growing problem of fluid overload the physicians consistently acted on the information by adjusting medication dosages.
Use of lung impedance measurement is similar to another approach for monitoring patients with heart failure that recently entered routine U.S. practice, an implanted device to monitor pulmonary artery pressure and identify episodes of fluid overload and acute decompensation. In the future, it will be interesting to compare the efficacy and ease of use of managing heart failure patients with pulmonary artery pressure monitoring with an implanted device and monitoring fluid build up in the lungs with lung impedance.
Dr. John A. Jarcho is a cardiologist at Brigham and Women’s Hospital, Boston. He had no disclosures. He made these comments as a discussant of Dr. Shochat’s report and in an interview.
The very exciting results reported by Dr. Shochat came from a small, positive trial that showed impedance monitoring was an effective way to detect an increased amount of fluid in a heart failure patient’s lungs. This resulted in improved outcomes, compared with patients managed using usual care, including fewer hospitalizations and reduced mortality.
These results suggest that when physicians had lung impedance information, they identified episodes of acute heart failure decompensation sooner and that they used this alert to change treatment and prevent patient worsening. Heart failure exacerbations and decompensation events are a recurring problem for heart failure patients, and the earlier they are identified and addressed with altered treatment, the better it is for the patient’s well being. The next step is to see if these positive results can be confirmed by other research groups and in larger numbers of patients.
These results contrast with the findings from a German study reported in 2015 that used lung impedance information collected by implantable cardioverter defibrillators in heart failure patients to identify episodes of fluid buildup and decompensation. That study failed to show a statistically significant impact on patient outcomes. The researchers speculated that this may have been because patients often did not go online to allow their information to get transmitted to their physician, and physicians often did not act on the information because the patients reported no coincident change in symptoms.
This problem with the German study highlights that collecting lung impedance information will only improve outcomes if physicians then act on the information and modify a patient’s treatment. In the new study reported by Dr. Shochat, patients consistently underwent evaluation for their lung impedance status every month, and when the results suggested a growing problem of fluid overload the physicians consistently acted on the information by adjusting medication dosages.
Use of lung impedance measurement is similar to another approach for monitoring patients with heart failure that recently entered routine U.S. practice, an implanted device to monitor pulmonary artery pressure and identify episodes of fluid overload and acute decompensation. In the future, it will be interesting to compare the efficacy and ease of use of managing heart failure patients with pulmonary artery pressure monitoring with an implanted device and monitoring fluid build up in the lungs with lung impedance.
Dr. John A. Jarcho is a cardiologist at Brigham and Women’s Hospital, Boston. He had no disclosures. He made these comments as a discussant of Dr. Shochat’s report and in an interview.
CHICAGO – Regular assessment of a heart failure patient’s lung fluid volume using a device that measures electrical conduction through the chest – lung impedance – helped guide clinicians to make timely adjustments in a patient’s medications and thereby significantly reduce mortality and hospitalizations during an average 4 years of follow-up in a randomized, controlled study with 256 patients.
Monthly measurement of lung impedance and medication adjustments based on the information led to a 58% reduction in hospitalizations for acute heart failure during the first year of the study, compared with control patients, and a 56% reduction in heart failure hospitalizations, compared with controls, during the entire course of the study, the study’s two primary endpoints, Dr. Michael K. Shochat reported at the annual meeting of the American College of Cardiology.
The results also showed that performing regular lung impedance measurements and using the results to guide treatment led to a 43% reduction in all-cause mortality and a 62% drop in heart failure mortality during the average 4-year course of the study, said Dr. Shochat, a cardiologist at the Heart Institute of Hillel Yaffe Medical Center in Hadera, Israel. Concurrent with Dr. Shochat’s report at the meeting the results also appeared in an article published online (J Card Failure. 2016;doi:10.1016/j.cardfail.2016.03.015).
A key aspect of the study was that the clinicians who treated the enrolled patients who underwent lung impedance monitoring used this information to adjust medications the patients received. Overall, patients who underwent monitoring had more than twice the number of medication dose adjustments, compared with the control patients. These adjustments particularly focused on diuretic dosages, which changed three times as often in the monitored patients, compared with controls, Dr. Shochat reported. Changes in the dosages of beta-blockers and ACE inhibitors also showed marked increases in the monitored patients, compared with the controls.
The Non-Invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic Heart Failure Patients (IMPEDANCE-HF) trial enrolled 256 patients at two centers in Israel during 2005-2014. Patients had New York Heart Association class II-IV heart failure and a left ventricular ejection fraction of 35% or less. The enrolled patients averaged 67 years of age, and 80% were men.
Clinicians measured lung impedance using a proprietary device that places external electrodes on opposite sides of the patient’s chest. Calculation of impedance used a formula that eliminated the noise from chest wall impedance and focused exclusively on lung impedance. Once the electrodes are placed collection of the impedance data takes about 1 minute, Dr. Shochat said. The study protocol called for impedance data to be collected monthly, and in practice it occurred about 11 times a year during the study.
The investigators calculated for each patient in the active arm of the study a “basal” lung impedance level that reflected their level of lung conductivity when their lungs were clear of excess fluid. Participating clinicians were instructed to intervene by altering medications when the impedance level dropped more than 18% below the basal level. Their goal was to prevent impedance from dropping to more than 24% below the basal level, which correlated with when heart failure patients usually required hospitalization for acute decompensation. The specifics of how to adjust medications to manage patients who showed these signs of fluid overload were left to the discretion of each attending physician.
MPEDANCE-HF was sponsored by the RSMM Company, which is developing the lung impedance measurement device used in the study. Dr. Shochat is a cofounder of RSMM and is a member of the company’s board of directors.
On Twitter @mitchelzoler
CHICAGO – Regular assessment of a heart failure patient’s lung fluid volume using a device that measures electrical conduction through the chest – lung impedance – helped guide clinicians to make timely adjustments in a patient’s medications and thereby significantly reduce mortality and hospitalizations during an average 4 years of follow-up in a randomized, controlled study with 256 patients.
Monthly measurement of lung impedance and medication adjustments based on the information led to a 58% reduction in hospitalizations for acute heart failure during the first year of the study, compared with control patients, and a 56% reduction in heart failure hospitalizations, compared with controls, during the entire course of the study, the study’s two primary endpoints, Dr. Michael K. Shochat reported at the annual meeting of the American College of Cardiology.
The results also showed that performing regular lung impedance measurements and using the results to guide treatment led to a 43% reduction in all-cause mortality and a 62% drop in heart failure mortality during the average 4-year course of the study, said Dr. Shochat, a cardiologist at the Heart Institute of Hillel Yaffe Medical Center in Hadera, Israel. Concurrent with Dr. Shochat’s report at the meeting the results also appeared in an article published online (J Card Failure. 2016;doi:10.1016/j.cardfail.2016.03.015).
A key aspect of the study was that the clinicians who treated the enrolled patients who underwent lung impedance monitoring used this information to adjust medications the patients received. Overall, patients who underwent monitoring had more than twice the number of medication dose adjustments, compared with the control patients. These adjustments particularly focused on diuretic dosages, which changed three times as often in the monitored patients, compared with controls, Dr. Shochat reported. Changes in the dosages of beta-blockers and ACE inhibitors also showed marked increases in the monitored patients, compared with the controls.
The Non-Invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic Heart Failure Patients (IMPEDANCE-HF) trial enrolled 256 patients at two centers in Israel during 2005-2014. Patients had New York Heart Association class II-IV heart failure and a left ventricular ejection fraction of 35% or less. The enrolled patients averaged 67 years of age, and 80% were men.
Clinicians measured lung impedance using a proprietary device that places external electrodes on opposite sides of the patient’s chest. Calculation of impedance used a formula that eliminated the noise from chest wall impedance and focused exclusively on lung impedance. Once the electrodes are placed collection of the impedance data takes about 1 minute, Dr. Shochat said. The study protocol called for impedance data to be collected monthly, and in practice it occurred about 11 times a year during the study.
The investigators calculated for each patient in the active arm of the study a “basal” lung impedance level that reflected their level of lung conductivity when their lungs were clear of excess fluid. Participating clinicians were instructed to intervene by altering medications when the impedance level dropped more than 18% below the basal level. Their goal was to prevent impedance from dropping to more than 24% below the basal level, which correlated with when heart failure patients usually required hospitalization for acute decompensation. The specifics of how to adjust medications to manage patients who showed these signs of fluid overload were left to the discretion of each attending physician.
MPEDANCE-HF was sponsored by the RSMM Company, which is developing the lung impedance measurement device used in the study. Dr. Shochat is a cofounder of RSMM and is a member of the company’s board of directors.
On Twitter @mitchelzoler
AT ACC 2016
Key clinical point: Monthly, noninvasive measurement of lung fluid levels using lung impedance produced better fluid control in heart failure patients and significantly fewer deaths and heart failure hospitalizations.
Major finding: Lung impedance–based management produced a 56% cut in heart failure hospitalizations, compared with standard care.
Data source: IMPEDANCE-HF, a randomized study with 256 heart failure patients at two Israeli centers.
Disclosures: IMPEDANCE-HF was sponsored by the RSMM Company, which is developing the lung impedance measurement device used in the study. Dr. Shochat is a cofounder of RSMM and is a member of the company’s board of directors.
DANAMI 3-iPOST: No significant benefit with ischemic postconditioning after STEMI
CHICAGO – Ischemic postconditioning in patients with ST-segment elevation myocardial infarction failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.
At a mean follow-up of 37.5 months, the primary composite endpoint of death from any cause and hospitalization for heart failure occurred in 69 of 617 patients with STEMI who received standard angioplasty and in 65 of 617 patients who received ischemic postconditioning in DANAMI 3-iPOST (the Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: iPOST conditioning during primary PCI). The 7% difference (hazard ratio, 0.93) was not statistically significant, Dr. Thomas Engstrøm reported at the annual meeting of the American College of Cardiology.
For the individual component of all-cause mortality, the reduction in the ischemic postconditioning group was 25%, occurring in 50 patients, compared with 38 in the conventionally treated group (hazard ratio, 0.75), but this difference also did not reach statistical significance, Dr. Engstrøm said.
Thirty patients in each group required hospitalization for heart failure.
However, an improvement in a secondary endpoint of left ventricular ejection fraction above 45% in patients with anterior infarcts was statistically significant, occurring in 72% of patients in the standard angioplasty group and 80% of those in the ischemic postconditioning group, said Dr. Engstrøm of Rigshospitalet University of Copenhagen.
This finding may translate into improved survival with longer follow-up, he noted.
Patients in the DANAMI-3 iPOST trial, who had a mean age of age 61 years, had acute STEMI (ST-segment elevation MI) symptoms of less than 12 hours’ duration at the time of randomization. They were followed for at least 2 years.
Ischemic postconditioning – a variation on angioplasty that involves using 30-second bursts of blood flow interspersed with 30-second pauses to restore blood flow to the heart – was shown in earlier studies to improve ST-segment resolution, reduce damage to heart muscle, and – in some patients – limit the extent of reperfusion injury.
Whether these factors would reduce hospitalizations or improve patient survival remained unclear, Dr. Engstrøm said.
Abrupt reperfusion by angioplasty may itself damage the heart muscle. In fact, up to 35% of patients may experience such injury during angioplasty.
“The thinking was that performing the reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury,” Dr. Engstrøm explained.
The findings of DANAMI 3-iPOST – the first large clinical trial designed to evaluate clinical outcomes in STEMI patients (as opposed to surrogate endpoints such as ST-segment resolution) were disappointing, but larger trials may be required to definitively establish whether ischemic postconditioning improves clinical outcomes, Dr. Engstrøm said.
The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.
CHICAGO – Ischemic postconditioning in patients with ST-segment elevation myocardial infarction failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.
At a mean follow-up of 37.5 months, the primary composite endpoint of death from any cause and hospitalization for heart failure occurred in 69 of 617 patients with STEMI who received standard angioplasty and in 65 of 617 patients who received ischemic postconditioning in DANAMI 3-iPOST (the Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: iPOST conditioning during primary PCI). The 7% difference (hazard ratio, 0.93) was not statistically significant, Dr. Thomas Engstrøm reported at the annual meeting of the American College of Cardiology.
For the individual component of all-cause mortality, the reduction in the ischemic postconditioning group was 25%, occurring in 50 patients, compared with 38 in the conventionally treated group (hazard ratio, 0.75), but this difference also did not reach statistical significance, Dr. Engstrøm said.
Thirty patients in each group required hospitalization for heart failure.
However, an improvement in a secondary endpoint of left ventricular ejection fraction above 45% in patients with anterior infarcts was statistically significant, occurring in 72% of patients in the standard angioplasty group and 80% of those in the ischemic postconditioning group, said Dr. Engstrøm of Rigshospitalet University of Copenhagen.
This finding may translate into improved survival with longer follow-up, he noted.
Patients in the DANAMI-3 iPOST trial, who had a mean age of age 61 years, had acute STEMI (ST-segment elevation MI) symptoms of less than 12 hours’ duration at the time of randomization. They were followed for at least 2 years.
Ischemic postconditioning – a variation on angioplasty that involves using 30-second bursts of blood flow interspersed with 30-second pauses to restore blood flow to the heart – was shown in earlier studies to improve ST-segment resolution, reduce damage to heart muscle, and – in some patients – limit the extent of reperfusion injury.
Whether these factors would reduce hospitalizations or improve patient survival remained unclear, Dr. Engstrøm said.
Abrupt reperfusion by angioplasty may itself damage the heart muscle. In fact, up to 35% of patients may experience such injury during angioplasty.
“The thinking was that performing the reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury,” Dr. Engstrøm explained.
The findings of DANAMI 3-iPOST – the first large clinical trial designed to evaluate clinical outcomes in STEMI patients (as opposed to surrogate endpoints such as ST-segment resolution) were disappointing, but larger trials may be required to definitively establish whether ischemic postconditioning improves clinical outcomes, Dr. Engstrøm said.
The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.
CHICAGO – Ischemic postconditioning in patients with ST-segment elevation myocardial infarction failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.
At a mean follow-up of 37.5 months, the primary composite endpoint of death from any cause and hospitalization for heart failure occurred in 69 of 617 patients with STEMI who received standard angioplasty and in 65 of 617 patients who received ischemic postconditioning in DANAMI 3-iPOST (the Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: iPOST conditioning during primary PCI). The 7% difference (hazard ratio, 0.93) was not statistically significant, Dr. Thomas Engstrøm reported at the annual meeting of the American College of Cardiology.
For the individual component of all-cause mortality, the reduction in the ischemic postconditioning group was 25%, occurring in 50 patients, compared with 38 in the conventionally treated group (hazard ratio, 0.75), but this difference also did not reach statistical significance, Dr. Engstrøm said.
Thirty patients in each group required hospitalization for heart failure.
However, an improvement in a secondary endpoint of left ventricular ejection fraction above 45% in patients with anterior infarcts was statistically significant, occurring in 72% of patients in the standard angioplasty group and 80% of those in the ischemic postconditioning group, said Dr. Engstrøm of Rigshospitalet University of Copenhagen.
This finding may translate into improved survival with longer follow-up, he noted.
Patients in the DANAMI-3 iPOST trial, who had a mean age of age 61 years, had acute STEMI (ST-segment elevation MI) symptoms of less than 12 hours’ duration at the time of randomization. They were followed for at least 2 years.
Ischemic postconditioning – a variation on angioplasty that involves using 30-second bursts of blood flow interspersed with 30-second pauses to restore blood flow to the heart – was shown in earlier studies to improve ST-segment resolution, reduce damage to heart muscle, and – in some patients – limit the extent of reperfusion injury.
Whether these factors would reduce hospitalizations or improve patient survival remained unclear, Dr. Engstrøm said.
Abrupt reperfusion by angioplasty may itself damage the heart muscle. In fact, up to 35% of patients may experience such injury during angioplasty.
“The thinking was that performing the reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury,” Dr. Engstrøm explained.
The findings of DANAMI 3-iPOST – the first large clinical trial designed to evaluate clinical outcomes in STEMI patients (as opposed to surrogate endpoints such as ST-segment resolution) were disappointing, but larger trials may be required to definitively establish whether ischemic postconditioning improves clinical outcomes, Dr. Engstrøm said.
The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.
AT ACC 16
Key clinical point: Ischemic postconditioning in patients with STEMI failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.
Major finding: No significant difference was seen in the primary composite endpoint of death from any cause and hospitalization for heart failure in standard angioplasty and ischemic postconditioning patients (HR, 0.93).
Data source: A randomized, controlled, open-label study of 1,234 patients from the DANAMI 3-iPOST trial.
Disclosures: The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.
Stem cells show heart failure benefits in phase II trial
CHICAGO – After rattling around in early-stage clinical studies for more than a decade, stem cell therapy for heart failure may have finally gained the efficacy evidence to send it to the next level: large-scale, phase III trials.
Patients with ischemic cardiomyopathy and severe heart failure showed a statistically significant 37% relative reduction in their combined rate of death and cardiovascular hospitalization during 1 year of follow-up after autologous stem cell injections to their left ventricular myocardium in a multicenter, fully blinded control, phase II trial with 109 North American patients.
The treatment used a technique in commercial development by Vericel that selectively expands ex vivo bone marrow cells taken from the heart failure patient. Clinicians inject 0.4 mL aliquots of the expanded cells – enriched for mesenchymal stem cells and M2 macrophages – via a transcatheter approach into the left ventricular myocardium using 12-17 injections per patient. The bone marrow preparation during ex vivo expansion is called ixmyelocel-T.
This treatment now needs testing in more patients, Dr. Timothy D. Henry said at the annual meeting of the American College of Cardiology. “We need a new generation of cell trials in larger studies with completely double-blind, placebo controls using a more uniform preparation of cells,” said Dr. Henry.
“To the best of our knowledge, ixCELL-DCM is the largest randomized, double-blind clinical trial to date for cell therapy use in congestive heart failure,” said Dr. Henry and his associates in their report. The concept of stem cell therapy to replace damaged myocardium “has been very attractive, but most clinical trials to date have been small and unblinded, and used unselected bone marrow cells,” explained Dr. Henry, director of cardiology at the Cedars-Sinai Heart Institute in Los Angeles.
The ixCELL-DCM study ran at 31 sites in the United States and Canada. About 90% of patients had New York Heart Association class III disease, the average left ventricular ejection fraction was about 25%, patients on average would cover about 310 m during a 6-minute walk test, and the average serum level of NT-ProBNP was about 1,900 pg/L. Patients in the control arm all underwent the same bone marrow retrieval and transcatheter injection into the left ventricle, but the injections only contained carrier material without active cells.
The primary endpoint of death or a cardiovascular event, primarily hospitalization, occurred at a rate of 110 events per 100 patient years during 1-year follow-up of 51 patients in the sham-treatment group. In the active-treatment arm, the endpoint occurred at a rate of 70 events per 100 patient years among 58 patients. The difference was primarily driven by a 3% death rate with cell therapy, compared with a 14% rate in the controls, and a 38% hospitalization rate, compared with a 47% rate among controls.
The study results appeared online concurrent with Dr. Henry’s report (Lancet. 2016 Apr 5. doi: 10.1016/S0140-6736[16]30137-4).
The results showed no significant differences between the active and sham groups for changes in left ventricular size, ejection fraction, and 6-minute walk distance.
“This trial was designed to look at events. It is not a cause for concern that we did not see effects on heart function,” Dr. Henry said. The current results were also generally consistent with results from two earlier, controlled, phase II studies with a total of 61 patients (Circ Res. 2014 Sep 26;115[8]:730-7).
In the safety analysis, done in 114 patients, the rates of all adverse events and major adverse cardiovascular events were similar in the two arms. The rate of serious adverse events was significantly reduced in the patients treated with expanded bone marrow cells, compared with the controls.
The high rate of death and hospitalization of patients with severe heart failure “is a very large, unmet need, so it’s a natural to go to a larger trial,” Dr. Henry said. “The cell preparation was very safe and easy to do.”
Another pressing research issue is to try to understand the mechanism by which the cell treatment improves clinical outcomes, with improved heart function or improved exercise capacity apparently excluded as mechanisms.
The trial was sponsored by Vericel, the company developing the ex vivo protocol for selective marrow cell expansion. Dr. Henry has been a consultant to or received honoraria from Abbott Vascular, Baxter, Capricor, Cytori, Eli Lilly, and the Medicines Company, and he has received research grants from Aastrom, Baxter International, Mesoblast, and Vericel.
On Twitter @mitchelzoler
The results reported by Dr. Henry come from one of the first trials of stem cell or bone marrow treatment of failing hearts that used clinical outcomes as the primary endpoint. In contrast, prior studies focused on changes in functional characteristics of patients, such as 6-minute walk distance or left ventricular ejection fraction or size. What makes Dr. Henry’s study distinctive is that it showed benefit for a clinical outcome: the rate of death or cardiovascular hospitalization.
Another distinct difference, compared with the vast majority of earlier trials, was the way the bone marrow was handled prior to placement in a heart. The bone marrow cells underwent a 12-day period of ex vivo treatment designed to expand the content of certain mesenchymal stem cells and macrophages.
The current study was also larger than most prior reported studies, with 114 randomized patients available for the safety analysis and 109 for the efficacy analysis. But by no means was this a large study; in fact, it is relatively small. Although it produced a statistically significant result for the primary endpoint, the efficacy needs expanded testing in larger numbers.
It’s currently unclear how the expanded bone marrow cell injections improve clinical status and lead to reduced deaths and hospitalization. The results show essentially no impact from the treatment on ejection fraction or 6-minute walk distance, raising the question of what alternative mechanisms link this treatment to improved clinical outcomes.
Until now, it has not been possible to move beyond early-stage trial designs for cell therapy of failing hearts. Now, for the first time, we have study results that suggest a phase III trial is indicated.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. John A. Jarcho is a deputy editor of the New England Journal of Medicine and a cardiologist at Brigham and Women’s Hospital, both in Boston. He had no disclosures. He made these comments as a discussant of Dr. Henry’s report and in an interview.
The results reported by Dr. Henry come from one of the first trials of stem cell or bone marrow treatment of failing hearts that used clinical outcomes as the primary endpoint. In contrast, prior studies focused on changes in functional characteristics of patients, such as 6-minute walk distance or left ventricular ejection fraction or size. What makes Dr. Henry’s study distinctive is that it showed benefit for a clinical outcome: the rate of death or cardiovascular hospitalization.
Another distinct difference, compared with the vast majority of earlier trials, was the way the bone marrow was handled prior to placement in a heart. The bone marrow cells underwent a 12-day period of ex vivo treatment designed to expand the content of certain mesenchymal stem cells and macrophages.
The current study was also larger than most prior reported studies, with 114 randomized patients available for the safety analysis and 109 for the efficacy analysis. But by no means was this a large study; in fact, it is relatively small. Although it produced a statistically significant result for the primary endpoint, the efficacy needs expanded testing in larger numbers.
It’s currently unclear how the expanded bone marrow cell injections improve clinical status and lead to reduced deaths and hospitalization. The results show essentially no impact from the treatment on ejection fraction or 6-minute walk distance, raising the question of what alternative mechanisms link this treatment to improved clinical outcomes.
Until now, it has not been possible to move beyond early-stage trial designs for cell therapy of failing hearts. Now, for the first time, we have study results that suggest a phase III trial is indicated.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. John A. Jarcho is a deputy editor of the New England Journal of Medicine and a cardiologist at Brigham and Women’s Hospital, both in Boston. He had no disclosures. He made these comments as a discussant of Dr. Henry’s report and in an interview.
The results reported by Dr. Henry come from one of the first trials of stem cell or bone marrow treatment of failing hearts that used clinical outcomes as the primary endpoint. In contrast, prior studies focused on changes in functional characteristics of patients, such as 6-minute walk distance or left ventricular ejection fraction or size. What makes Dr. Henry’s study distinctive is that it showed benefit for a clinical outcome: the rate of death or cardiovascular hospitalization.
Another distinct difference, compared with the vast majority of earlier trials, was the way the bone marrow was handled prior to placement in a heart. The bone marrow cells underwent a 12-day period of ex vivo treatment designed to expand the content of certain mesenchymal stem cells and macrophages.
The current study was also larger than most prior reported studies, with 114 randomized patients available for the safety analysis and 109 for the efficacy analysis. But by no means was this a large study; in fact, it is relatively small. Although it produced a statistically significant result for the primary endpoint, the efficacy needs expanded testing in larger numbers.
It’s currently unclear how the expanded bone marrow cell injections improve clinical status and lead to reduced deaths and hospitalization. The results show essentially no impact from the treatment on ejection fraction or 6-minute walk distance, raising the question of what alternative mechanisms link this treatment to improved clinical outcomes.
Until now, it has not been possible to move beyond early-stage trial designs for cell therapy of failing hearts. Now, for the first time, we have study results that suggest a phase III trial is indicated.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. John A. Jarcho is a deputy editor of the New England Journal of Medicine and a cardiologist at Brigham and Women’s Hospital, both in Boston. He had no disclosures. He made these comments as a discussant of Dr. Henry’s report and in an interview.
CHICAGO – After rattling around in early-stage clinical studies for more than a decade, stem cell therapy for heart failure may have finally gained the efficacy evidence to send it to the next level: large-scale, phase III trials.
Patients with ischemic cardiomyopathy and severe heart failure showed a statistically significant 37% relative reduction in their combined rate of death and cardiovascular hospitalization during 1 year of follow-up after autologous stem cell injections to their left ventricular myocardium in a multicenter, fully blinded control, phase II trial with 109 North American patients.
The treatment used a technique in commercial development by Vericel that selectively expands ex vivo bone marrow cells taken from the heart failure patient. Clinicians inject 0.4 mL aliquots of the expanded cells – enriched for mesenchymal stem cells and M2 macrophages – via a transcatheter approach into the left ventricular myocardium using 12-17 injections per patient. The bone marrow preparation during ex vivo expansion is called ixmyelocel-T.
This treatment now needs testing in more patients, Dr. Timothy D. Henry said at the annual meeting of the American College of Cardiology. “We need a new generation of cell trials in larger studies with completely double-blind, placebo controls using a more uniform preparation of cells,” said Dr. Henry.
“To the best of our knowledge, ixCELL-DCM is the largest randomized, double-blind clinical trial to date for cell therapy use in congestive heart failure,” said Dr. Henry and his associates in their report. The concept of stem cell therapy to replace damaged myocardium “has been very attractive, but most clinical trials to date have been small and unblinded, and used unselected bone marrow cells,” explained Dr. Henry, director of cardiology at the Cedars-Sinai Heart Institute in Los Angeles.
The ixCELL-DCM study ran at 31 sites in the United States and Canada. About 90% of patients had New York Heart Association class III disease, the average left ventricular ejection fraction was about 25%, patients on average would cover about 310 m during a 6-minute walk test, and the average serum level of NT-ProBNP was about 1,900 pg/L. Patients in the control arm all underwent the same bone marrow retrieval and transcatheter injection into the left ventricle, but the injections only contained carrier material without active cells.
The primary endpoint of death or a cardiovascular event, primarily hospitalization, occurred at a rate of 110 events per 100 patient years during 1-year follow-up of 51 patients in the sham-treatment group. In the active-treatment arm, the endpoint occurred at a rate of 70 events per 100 patient years among 58 patients. The difference was primarily driven by a 3% death rate with cell therapy, compared with a 14% rate in the controls, and a 38% hospitalization rate, compared with a 47% rate among controls.
The study results appeared online concurrent with Dr. Henry’s report (Lancet. 2016 Apr 5. doi: 10.1016/S0140-6736[16]30137-4).
The results showed no significant differences between the active and sham groups for changes in left ventricular size, ejection fraction, and 6-minute walk distance.
“This trial was designed to look at events. It is not a cause for concern that we did not see effects on heart function,” Dr. Henry said. The current results were also generally consistent with results from two earlier, controlled, phase II studies with a total of 61 patients (Circ Res. 2014 Sep 26;115[8]:730-7).
In the safety analysis, done in 114 patients, the rates of all adverse events and major adverse cardiovascular events were similar in the two arms. The rate of serious adverse events was significantly reduced in the patients treated with expanded bone marrow cells, compared with the controls.
The high rate of death and hospitalization of patients with severe heart failure “is a very large, unmet need, so it’s a natural to go to a larger trial,” Dr. Henry said. “The cell preparation was very safe and easy to do.”
Another pressing research issue is to try to understand the mechanism by which the cell treatment improves clinical outcomes, with improved heart function or improved exercise capacity apparently excluded as mechanisms.
The trial was sponsored by Vericel, the company developing the ex vivo protocol for selective marrow cell expansion. Dr. Henry has been a consultant to or received honoraria from Abbott Vascular, Baxter, Capricor, Cytori, Eli Lilly, and the Medicines Company, and he has received research grants from Aastrom, Baxter International, Mesoblast, and Vericel.
On Twitter @mitchelzoler
CHICAGO – After rattling around in early-stage clinical studies for more than a decade, stem cell therapy for heart failure may have finally gained the efficacy evidence to send it to the next level: large-scale, phase III trials.
Patients with ischemic cardiomyopathy and severe heart failure showed a statistically significant 37% relative reduction in their combined rate of death and cardiovascular hospitalization during 1 year of follow-up after autologous stem cell injections to their left ventricular myocardium in a multicenter, fully blinded control, phase II trial with 109 North American patients.
The treatment used a technique in commercial development by Vericel that selectively expands ex vivo bone marrow cells taken from the heart failure patient. Clinicians inject 0.4 mL aliquots of the expanded cells – enriched for mesenchymal stem cells and M2 macrophages – via a transcatheter approach into the left ventricular myocardium using 12-17 injections per patient. The bone marrow preparation during ex vivo expansion is called ixmyelocel-T.
This treatment now needs testing in more patients, Dr. Timothy D. Henry said at the annual meeting of the American College of Cardiology. “We need a new generation of cell trials in larger studies with completely double-blind, placebo controls using a more uniform preparation of cells,” said Dr. Henry.
“To the best of our knowledge, ixCELL-DCM is the largest randomized, double-blind clinical trial to date for cell therapy use in congestive heart failure,” said Dr. Henry and his associates in their report. The concept of stem cell therapy to replace damaged myocardium “has been very attractive, but most clinical trials to date have been small and unblinded, and used unselected bone marrow cells,” explained Dr. Henry, director of cardiology at the Cedars-Sinai Heart Institute in Los Angeles.
The ixCELL-DCM study ran at 31 sites in the United States and Canada. About 90% of patients had New York Heart Association class III disease, the average left ventricular ejection fraction was about 25%, patients on average would cover about 310 m during a 6-minute walk test, and the average serum level of NT-ProBNP was about 1,900 pg/L. Patients in the control arm all underwent the same bone marrow retrieval and transcatheter injection into the left ventricle, but the injections only contained carrier material without active cells.
The primary endpoint of death or a cardiovascular event, primarily hospitalization, occurred at a rate of 110 events per 100 patient years during 1-year follow-up of 51 patients in the sham-treatment group. In the active-treatment arm, the endpoint occurred at a rate of 70 events per 100 patient years among 58 patients. The difference was primarily driven by a 3% death rate with cell therapy, compared with a 14% rate in the controls, and a 38% hospitalization rate, compared with a 47% rate among controls.
The study results appeared online concurrent with Dr. Henry’s report (Lancet. 2016 Apr 5. doi: 10.1016/S0140-6736[16]30137-4).
The results showed no significant differences between the active and sham groups for changes in left ventricular size, ejection fraction, and 6-minute walk distance.
“This trial was designed to look at events. It is not a cause for concern that we did not see effects on heart function,” Dr. Henry said. The current results were also generally consistent with results from two earlier, controlled, phase II studies with a total of 61 patients (Circ Res. 2014 Sep 26;115[8]:730-7).
In the safety analysis, done in 114 patients, the rates of all adverse events and major adverse cardiovascular events were similar in the two arms. The rate of serious adverse events was significantly reduced in the patients treated with expanded bone marrow cells, compared with the controls.
The high rate of death and hospitalization of patients with severe heart failure “is a very large, unmet need, so it’s a natural to go to a larger trial,” Dr. Henry said. “The cell preparation was very safe and easy to do.”
Another pressing research issue is to try to understand the mechanism by which the cell treatment improves clinical outcomes, with improved heart function or improved exercise capacity apparently excluded as mechanisms.
The trial was sponsored by Vericel, the company developing the ex vivo protocol for selective marrow cell expansion. Dr. Henry has been a consultant to or received honoraria from Abbott Vascular, Baxter, Capricor, Cytori, Eli Lilly, and the Medicines Company, and he has received research grants from Aastrom, Baxter International, Mesoblast, and Vericel.
On Twitter @mitchelzoler
AT ACC 16
Key clinical point: Severe, ischemic heart failure patients had a significant cut in death and cardiovascular hospitalizations 1 year after endovascular myocardial injection with selectively expanded autologous bone marrow cells in a fully blinded, placebo-controlled phase II study.
Major finding: Cell-treated patients had a 37% drop in death and cardiovascular hospitalization relative to controls in 1-year follow-up.
Data source: A multicenter, fully blinded study with 109 patients for the per protocol efficacy analysis, and 114 patients for the safety analysis.
Disclosures: The trial was sponsored by Vericel, the company developing the ex vivo protocol for selective marrow cell expansion. Dr. Henry has been a consultant to or received honoraria from Abbott Vascular, Baxter, Capricor, Cytori, Eli Lilly, and the Medicines Company, and he has received research grants from Aastrom, Baxter International, Mesoblast, and Vericel.
FDA adds safety warnings to certain type 2 diabetes medications
Type 2 diabetes medicines that contain saxagliptin and alogliptin may increase the risk of heart failure, especially in patients who already have heart or kidney disease, according to results from an Food and Drug Administration safety review.
The development, which was announced by MedWatch on April 5, 2016, means that the FDA will add new warnings to the drug labels about this safety issue. “Health care professionals should consider discontinuing medications containing saxagliptin and alogliptin in patients who develop heart failure and monitor their diabetes control,” the communication states. “If a patient’s blood sugar level is not well-controlled with their current treatment, other diabetes medicines may be required.”
The medications of concern include Onglyza (saxagliptin); Kombiglyze XR (saxagliptin and metformin extended release); Nesina (alogliptin); Kazano (alogliptin and metformin), and Oseni (alogliptin and pioglitazone). The move comes after two clinical trials showed that more patients who received saxagliptin- or alogliptin-containing medicines were hospitalized for heart failure, compared with patients who received placebo (for specifics, see the data summary section in the FDA Drug Safety Communication).
The communication noted that patients taking these medicines should contact their health care clinician if they develop signs and symptoms of heart failure such as: unusual shortness of breath during daily activities; trouble breathing when lying down; tiredness, weakness, or fatigue; and weight gain with swelling in the ankles, feet, legs, or stomach.
Clinicians and patients can report adverse events or side effects related to the use of these products at www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home.
Type 2 diabetes medicines that contain saxagliptin and alogliptin may increase the risk of heart failure, especially in patients who already have heart or kidney disease, according to results from an Food and Drug Administration safety review.
The development, which was announced by MedWatch on April 5, 2016, means that the FDA will add new warnings to the drug labels about this safety issue. “Health care professionals should consider discontinuing medications containing saxagliptin and alogliptin in patients who develop heart failure and monitor their diabetes control,” the communication states. “If a patient’s blood sugar level is not well-controlled with their current treatment, other diabetes medicines may be required.”
The medications of concern include Onglyza (saxagliptin); Kombiglyze XR (saxagliptin and metformin extended release); Nesina (alogliptin); Kazano (alogliptin and metformin), and Oseni (alogliptin and pioglitazone). The move comes after two clinical trials showed that more patients who received saxagliptin- or alogliptin-containing medicines were hospitalized for heart failure, compared with patients who received placebo (for specifics, see the data summary section in the FDA Drug Safety Communication).
The communication noted that patients taking these medicines should contact their health care clinician if they develop signs and symptoms of heart failure such as: unusual shortness of breath during daily activities; trouble breathing when lying down; tiredness, weakness, or fatigue; and weight gain with swelling in the ankles, feet, legs, or stomach.
Clinicians and patients can report adverse events or side effects related to the use of these products at www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home.
Type 2 diabetes medicines that contain saxagliptin and alogliptin may increase the risk of heart failure, especially in patients who already have heart or kidney disease, according to results from an Food and Drug Administration safety review.
The development, which was announced by MedWatch on April 5, 2016, means that the FDA will add new warnings to the drug labels about this safety issue. “Health care professionals should consider discontinuing medications containing saxagliptin and alogliptin in patients who develop heart failure and monitor their diabetes control,” the communication states. “If a patient’s blood sugar level is not well-controlled with their current treatment, other diabetes medicines may be required.”
The medications of concern include Onglyza (saxagliptin); Kombiglyze XR (saxagliptin and metformin extended release); Nesina (alogliptin); Kazano (alogliptin and metformin), and Oseni (alogliptin and pioglitazone). The move comes after two clinical trials showed that more patients who received saxagliptin- or alogliptin-containing medicines were hospitalized for heart failure, compared with patients who received placebo (for specifics, see the data summary section in the FDA Drug Safety Communication).
The communication noted that patients taking these medicines should contact their health care clinician if they develop signs and symptoms of heart failure such as: unusual shortness of breath during daily activities; trouble breathing when lying down; tiredness, weakness, or fatigue; and weight gain with swelling in the ankles, feet, legs, or stomach.
Clinicians and patients can report adverse events or side effects related to the use of these products at www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home.
High-dose vitamin D improves heart structure, function in chronic heart failure
High-dose oral vitamin D supplements taken for 1 year significantly improved cardiac structure and function in patients with chronic heart failure secondary to left ventricular systolic dysfunction, according to results from a new study.
However, the same study. led by Dr. Klaus Witte of the University of Leeds (England), found that 6-minute walk distance – the study’s primary outcome measure – was not improved after a year’s supplementation with vitamin D.
It is unclear why vitamin D deficiency co-occurs in a majority of people with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) or to what degree reversing it can improve outcomes. However, vitamin D deficiency is thought to interfere with calcium transport in cardiac cells, and may contribute to cardiac fibrosis and inflammation, leading to faster progression to heart failure following damage to cardiac muscle.
The new VINDICATE study randomized 223 patients with CHF due to LVSD and vitamin D deficiency to 1 year’s treatment with 4,000 IU of 25(OH) vitamin D3 daily, or placebo, Dr. Witte and associates concluded at the annual meeting of the American College of Cardiology. The results were published online April 4 in JACC (doi: 10.1016/j.jacc.2016.03.508).
Of these patients, 163 completed follow-up at 12 months, and 6-minute walk distance (MWT) and echocardiography findings were recorded at baseline and follow-up.
Dr. Witte and colleagues found significant evidence of improved function in the vitamin D–treated patients as measured by left ventricular ejection fraction +6.07% (95% confidence interval 3.20, 8.95; P less than .0001); and a reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm (95% CI –4.09, –0.90; P equal to .002) and left ventricular end systolic diameter –2.09 mm (95% CI –4.11; –0.06; P equal to .043).
The researchers also drew blood at 3-month intervals to check for serum calcium concentration, renal function, and vitamin D levels. Treatment was well tolerated, and no patients suffered hypervitaminosis or required a dose adjustment.
“There was no effect of vitamin D supplementation on the primary endpoint of 6 MWT distance but there were statistically significant, and prognostically and clinically relevant improvements in the secondary outcomes of left ventricular ejection fraction, dimensions, and volumes, suggesting that vitamin D is leading to beneficial reverse remodeling,” the investigators wrote in their analysis.
The study’s failure to meet its primary endpoint despite significant results from its secondary endpoints led Dr. Witte and colleagues to say that its design led to underpowering.
“Variability in the walk distance measure at baseline was much greater than predicted from our pilot study such that our sample size only had 7% post hoc power to detect a difference between the groups,” meaning it was underpowered to detect a clinically relevant change in walk distance. The findings “have implications for future studies using 6-minute walk distance as an outcome measure,” they wrote.
The investigators championed the addition of vitamin D3 to CHF treatment regimens.
As new therapies for CHF are “often expensive, increasingly technical, and frequently fail to meet the rigorous demands of large phase III clinical trials,” Dr. Witte and colleagues wrote, vitamin D “might be a cheap and safe additional option for CHF patients and may have beneficial effects on multiple features of the syndrome.”
The U.K.’s National Institute for Health Research supported the study, and none of its authors declared conflicts of interest.
High-dose oral vitamin D supplements taken for 1 year significantly improved cardiac structure and function in patients with chronic heart failure secondary to left ventricular systolic dysfunction, according to results from a new study.
However, the same study. led by Dr. Klaus Witte of the University of Leeds (England), found that 6-minute walk distance – the study’s primary outcome measure – was not improved after a year’s supplementation with vitamin D.
It is unclear why vitamin D deficiency co-occurs in a majority of people with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) or to what degree reversing it can improve outcomes. However, vitamin D deficiency is thought to interfere with calcium transport in cardiac cells, and may contribute to cardiac fibrosis and inflammation, leading to faster progression to heart failure following damage to cardiac muscle.
The new VINDICATE study randomized 223 patients with CHF due to LVSD and vitamin D deficiency to 1 year’s treatment with 4,000 IU of 25(OH) vitamin D3 daily, or placebo, Dr. Witte and associates concluded at the annual meeting of the American College of Cardiology. The results were published online April 4 in JACC (doi: 10.1016/j.jacc.2016.03.508).
Of these patients, 163 completed follow-up at 12 months, and 6-minute walk distance (MWT) and echocardiography findings were recorded at baseline and follow-up.
Dr. Witte and colleagues found significant evidence of improved function in the vitamin D–treated patients as measured by left ventricular ejection fraction +6.07% (95% confidence interval 3.20, 8.95; P less than .0001); and a reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm (95% CI –4.09, –0.90; P equal to .002) and left ventricular end systolic diameter –2.09 mm (95% CI –4.11; –0.06; P equal to .043).
The researchers also drew blood at 3-month intervals to check for serum calcium concentration, renal function, and vitamin D levels. Treatment was well tolerated, and no patients suffered hypervitaminosis or required a dose adjustment.
“There was no effect of vitamin D supplementation on the primary endpoint of 6 MWT distance but there were statistically significant, and prognostically and clinically relevant improvements in the secondary outcomes of left ventricular ejection fraction, dimensions, and volumes, suggesting that vitamin D is leading to beneficial reverse remodeling,” the investigators wrote in their analysis.
The study’s failure to meet its primary endpoint despite significant results from its secondary endpoints led Dr. Witte and colleagues to say that its design led to underpowering.
“Variability in the walk distance measure at baseline was much greater than predicted from our pilot study such that our sample size only had 7% post hoc power to detect a difference between the groups,” meaning it was underpowered to detect a clinically relevant change in walk distance. The findings “have implications for future studies using 6-minute walk distance as an outcome measure,” they wrote.
The investigators championed the addition of vitamin D3 to CHF treatment regimens.
As new therapies for CHF are “often expensive, increasingly technical, and frequently fail to meet the rigorous demands of large phase III clinical trials,” Dr. Witte and colleagues wrote, vitamin D “might be a cheap and safe additional option for CHF patients and may have beneficial effects on multiple features of the syndrome.”
The U.K.’s National Institute for Health Research supported the study, and none of its authors declared conflicts of interest.
High-dose oral vitamin D supplements taken for 1 year significantly improved cardiac structure and function in patients with chronic heart failure secondary to left ventricular systolic dysfunction, according to results from a new study.
However, the same study. led by Dr. Klaus Witte of the University of Leeds (England), found that 6-minute walk distance – the study’s primary outcome measure – was not improved after a year’s supplementation with vitamin D.
It is unclear why vitamin D deficiency co-occurs in a majority of people with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) or to what degree reversing it can improve outcomes. However, vitamin D deficiency is thought to interfere with calcium transport in cardiac cells, and may contribute to cardiac fibrosis and inflammation, leading to faster progression to heart failure following damage to cardiac muscle.
The new VINDICATE study randomized 223 patients with CHF due to LVSD and vitamin D deficiency to 1 year’s treatment with 4,000 IU of 25(OH) vitamin D3 daily, or placebo, Dr. Witte and associates concluded at the annual meeting of the American College of Cardiology. The results were published online April 4 in JACC (doi: 10.1016/j.jacc.2016.03.508).
Of these patients, 163 completed follow-up at 12 months, and 6-minute walk distance (MWT) and echocardiography findings were recorded at baseline and follow-up.
Dr. Witte and colleagues found significant evidence of improved function in the vitamin D–treated patients as measured by left ventricular ejection fraction +6.07% (95% confidence interval 3.20, 8.95; P less than .0001); and a reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm (95% CI –4.09, –0.90; P equal to .002) and left ventricular end systolic diameter –2.09 mm (95% CI –4.11; –0.06; P equal to .043).
The researchers also drew blood at 3-month intervals to check for serum calcium concentration, renal function, and vitamin D levels. Treatment was well tolerated, and no patients suffered hypervitaminosis or required a dose adjustment.
“There was no effect of vitamin D supplementation on the primary endpoint of 6 MWT distance but there were statistically significant, and prognostically and clinically relevant improvements in the secondary outcomes of left ventricular ejection fraction, dimensions, and volumes, suggesting that vitamin D is leading to beneficial reverse remodeling,” the investigators wrote in their analysis.
The study’s failure to meet its primary endpoint despite significant results from its secondary endpoints led Dr. Witte and colleagues to say that its design led to underpowering.
“Variability in the walk distance measure at baseline was much greater than predicted from our pilot study such that our sample size only had 7% post hoc power to detect a difference between the groups,” meaning it was underpowered to detect a clinically relevant change in walk distance. The findings “have implications for future studies using 6-minute walk distance as an outcome measure,” they wrote.
The investigators championed the addition of vitamin D3 to CHF treatment regimens.
As new therapies for CHF are “often expensive, increasingly technical, and frequently fail to meet the rigorous demands of large phase III clinical trials,” Dr. Witte and colleagues wrote, vitamin D “might be a cheap and safe additional option for CHF patients and may have beneficial effects on multiple features of the syndrome.”
The U.K.’s National Institute for Health Research supported the study, and none of its authors declared conflicts of interest.
FROM ACC16
Key clinical point: Oral supplementation of high-dose vitamin D3 led to significantly improved left ventricular function and structure in a cohort of vitamin-deficient patients.
Major finding: Treated patients had significantly improved left ventricular ejection fraction of +6.07% vs. nontreated patients at 1 year, and significant reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm and left ventricular end systolic diameter –2.09 mm).
Data source: A single-site randomized trial in which 229 patients with LV CHF received high-dose vitamin D or placebo for 12 months.
Disclosures: The U.K.’s National Institute for Health Research supported the study, and none of its authors declared conflicts of interest.
VIDEO: STICHES trial update boosts CABG in ischemic cardiomyopathy
CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.
STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.
These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.
He reported having no financial conflicts regarding this National Institutes of Health–funded study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.
STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.
These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.
He reported having no financial conflicts regarding this National Institutes of Health–funded study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.
STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.
These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.
He reported having no financial conflicts regarding this National Institutes of Health–funded study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ACC 16
VIDEO: STICHES trial update boosts CABG in ischemic cardiomyopathy
CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.
STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.
These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.
He reported having no financial conflicts regarding this National Institutes of Health–funded study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.
STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.
These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.
He reported having no financial conflicts regarding this National Institutes of Health–funded study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.
STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.
These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.
He reported having no financial conflicts regarding this National Institutes of Health–funded study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ACC 16
Heart failure severity at AMI predicts long-term CV death risk
CHICAGO – The severity of heart failure in the setting of acute myocardial infarction predicts long-term cardiovascular death risk, according to a post hoc analysis of data from the IMPROVE IT Trial.
Among 11,185 individuals with MI and known Killip Classification who were part of that randomized, double-blind trial, those with Killip Class II or greater had more than double the risk of long-term cardiovascular death, compared with those with Killip Class I heart failure, Dr Michael G. Silverman, a cardiovascular medicine fellow at Brigham and Women’s Hospital, Boston and a research fellow at the Thrombolysis in MI (TIMI) Study Group reported in a poster at the annual meeting of the American College of Cardiology.
After adjusting for a number of factors, including age, gender, diabetes, hypertension, left ventricular ejection fraction (LVEF), beta blocker and ACE inhibitor/angiotensin receptor blocker use at randomization, and percutaneous coronary intervention at the index event, the 7-year event rate was 14.5% among those with Killip Class II or higher vs. 5.7% those with Killip Class I heart failure (adjusted hazard ratio, 1.9), Dr. Silverman reported on behalf of the TIMI Study Group.
The event rates from 30 days to 6 months were 4.85% and 1.25% in the groups, respectively (adjusted hazard ratio, 1.96), and from 6 months to 7 years they were 1.52% and 0.61%, in the groups, respectively, (adjusted hazard ratio, 1.85).
Further, the increased risk of cardiovascular death associated with Killip Class II or higher was also apparent among important subgroups, including those with ST Segment Elevation MI, those with non-STEMI, those with LVEF of 50 or greater, those with LVEF less than 50, those with diabetes, those without diabetes, men, and women (adjusted hazard ratios ranging from 1.6 to 2.1), Dr Silverman explained in an interview.
The severity of heart failure according to Killip Class is a strong independent predictor of mortality in the setting of acute MI, and the current findings demonstrate that it also predicts cardiovascular death for at least 7 years, suggesting a need for careful attention to the findings of the physical exam in AMI, as it can serve as an important biomarker of long-term cardiovascular death risk, he said.
“AMI patients with Killip Class II or greater warrant continued close medical follow-up and adherence to guideline -directed medial therapy beyond the acute hospitalization to prevent this potentially modifiable outcome,” he concluded.
Dr. Silverman reported having no disclosures.
CHICAGO – The severity of heart failure in the setting of acute myocardial infarction predicts long-term cardiovascular death risk, according to a post hoc analysis of data from the IMPROVE IT Trial.
Among 11,185 individuals with MI and known Killip Classification who were part of that randomized, double-blind trial, those with Killip Class II or greater had more than double the risk of long-term cardiovascular death, compared with those with Killip Class I heart failure, Dr Michael G. Silverman, a cardiovascular medicine fellow at Brigham and Women’s Hospital, Boston and a research fellow at the Thrombolysis in MI (TIMI) Study Group reported in a poster at the annual meeting of the American College of Cardiology.
After adjusting for a number of factors, including age, gender, diabetes, hypertension, left ventricular ejection fraction (LVEF), beta blocker and ACE inhibitor/angiotensin receptor blocker use at randomization, and percutaneous coronary intervention at the index event, the 7-year event rate was 14.5% among those with Killip Class II or higher vs. 5.7% those with Killip Class I heart failure (adjusted hazard ratio, 1.9), Dr. Silverman reported on behalf of the TIMI Study Group.
The event rates from 30 days to 6 months were 4.85% and 1.25% in the groups, respectively (adjusted hazard ratio, 1.96), and from 6 months to 7 years they were 1.52% and 0.61%, in the groups, respectively, (adjusted hazard ratio, 1.85).
Further, the increased risk of cardiovascular death associated with Killip Class II or higher was also apparent among important subgroups, including those with ST Segment Elevation MI, those with non-STEMI, those with LVEF of 50 or greater, those with LVEF less than 50, those with diabetes, those without diabetes, men, and women (adjusted hazard ratios ranging from 1.6 to 2.1), Dr Silverman explained in an interview.
The severity of heart failure according to Killip Class is a strong independent predictor of mortality in the setting of acute MI, and the current findings demonstrate that it also predicts cardiovascular death for at least 7 years, suggesting a need for careful attention to the findings of the physical exam in AMI, as it can serve as an important biomarker of long-term cardiovascular death risk, he said.
“AMI patients with Killip Class II or greater warrant continued close medical follow-up and adherence to guideline -directed medial therapy beyond the acute hospitalization to prevent this potentially modifiable outcome,” he concluded.
Dr. Silverman reported having no disclosures.
CHICAGO – The severity of heart failure in the setting of acute myocardial infarction predicts long-term cardiovascular death risk, according to a post hoc analysis of data from the IMPROVE IT Trial.
Among 11,185 individuals with MI and known Killip Classification who were part of that randomized, double-blind trial, those with Killip Class II or greater had more than double the risk of long-term cardiovascular death, compared with those with Killip Class I heart failure, Dr Michael G. Silverman, a cardiovascular medicine fellow at Brigham and Women’s Hospital, Boston and a research fellow at the Thrombolysis in MI (TIMI) Study Group reported in a poster at the annual meeting of the American College of Cardiology.
After adjusting for a number of factors, including age, gender, diabetes, hypertension, left ventricular ejection fraction (LVEF), beta blocker and ACE inhibitor/angiotensin receptor blocker use at randomization, and percutaneous coronary intervention at the index event, the 7-year event rate was 14.5% among those with Killip Class II or higher vs. 5.7% those with Killip Class I heart failure (adjusted hazard ratio, 1.9), Dr. Silverman reported on behalf of the TIMI Study Group.
The event rates from 30 days to 6 months were 4.85% and 1.25% in the groups, respectively (adjusted hazard ratio, 1.96), and from 6 months to 7 years they were 1.52% and 0.61%, in the groups, respectively, (adjusted hazard ratio, 1.85).
Further, the increased risk of cardiovascular death associated with Killip Class II or higher was also apparent among important subgroups, including those with ST Segment Elevation MI, those with non-STEMI, those with LVEF of 50 or greater, those with LVEF less than 50, those with diabetes, those without diabetes, men, and women (adjusted hazard ratios ranging from 1.6 to 2.1), Dr Silverman explained in an interview.
The severity of heart failure according to Killip Class is a strong independent predictor of mortality in the setting of acute MI, and the current findings demonstrate that it also predicts cardiovascular death for at least 7 years, suggesting a need for careful attention to the findings of the physical exam in AMI, as it can serve as an important biomarker of long-term cardiovascular death risk, he said.
“AMI patients with Killip Class II or greater warrant continued close medical follow-up and adherence to guideline -directed medial therapy beyond the acute hospitalization to prevent this potentially modifiable outcome,” he concluded.
Dr. Silverman reported having no disclosures.
AT ACC 16
Key clinical point: The severity of heart failure in the setting of acute myocardial infarction predicts long-term cardiovascular death risk, according to a post hoc analysis of data from the IMPROVE IT Trial.
Major finding: The 7-year event rate was 14.5% among those with Killip Class II or higher vs. 5.7% among those with Killip Class I heart failure (adjusted hazard ratio, 1.9).
Data source: A post-hoc analysis of data from 11,185 subjects from the IMPROVE IT trial.
Disclosures: Dr. Silverman reported having no disclosures.
Breast cancer treatment linked to mild systolic dysfunction
AMSTERDAM – Breast cancer patients who underwent chemotherapy or radiotherapy had about a two-fold increased prevalence of mild systolic cardiac dysfunction a median of 10 years after treatment, compared with age-matched controls in a study that included a total of 700 people.
But even longer follow-up of treated breast cancer patients is needed to determine whether the excess mild cardiac dysfunction seen in this analysis eventually progresses to more severe cardiac impairment, Liselotte M. Boerman said at the European Breast Cancer Conference.
Data from the Breast Cancer Long-term Outcome of Cardiac Dysfunction (BLOC) study showed that 175 breast cancer patients who received chemotherapy (and may have also received radiotherapy) had a 2.5-fold higher prevalence of a left ventricular ejection fraction (LVEF) below 54% (95% confidence interval, 1.2-5.4) when measured by echocardiography a median of 10 years after treatment, compared with an equal number of age-matched individuals from the general population.
A separate group of 175 patients treated with radiotherapy only and evaluated by echocardiography a median of 10 years later had a 2.3-fold increased prevalence (1.1-4.7) of a LVEF below 54% when compared with an equal number of age-matched individuals, said Ms. Boerman, an epidemiology researcher at the University of Groningen (the Netherlands).
This degree of left-ventricular dysfunction was found in 15% of the chemotherapy patients and 6% of their controls, and in 16% of the radiotherapy patients and 8% of their controls.
However, the treated breast cancer patients had no long-term increase in their prevalence of more significant systolic cardiac dysfunction, defined as a LVEF of less than 45%, compared with the controls, and the overall rate of systolic dysfunction of this severity was low, affecting fewer than 1% of patients.
Also, the chemotherapy and radiotherapy patients showed no significant increase in the prevalence of diastolic cardiac dysfunction, defined as delayed cardiac relaxation beyond the age-appropriate range. Treated patients did show, after 10 years, a suggestion of an increased prevalence of diagnosed cardiovascular disease, which was 2.3-fold higher (1.0-4.9) in the chemotherapy-receiving patients, compared with their controls; and 70% higher (0.9-3.4) among the patients treated with radiotherapy, compared with their controls, Ms. Boerman said.
The study used data collected from breast cancer patients younger than 80 years old treated after 1980 and controls seen by general practice Dutch physicians. The chemotherapy patients were diagnosed at an average age of 49 years old (range 26-66 years old). About 78% had received treatment with an anthracycline agent and 7% had received trastuzumab (Herceptin). Radiotherapy had also been administered to 70%, while 62% had also received hormonal therapy, and 7% either had a recurrence or developed a tumor in their contralateral breast.
None of the radiotherapy-only patients had received chemotherapy, but 21% had also received hormonal therapy. Their average age at diagnosis was 54 years old (range 32-79 years old), and 10% had a recurrence or a contralateral tumor.
Follow-up echocardiography occurred 5-34 years after the index treatment, at a median age of 60 years old. Echocardiography follow-up occurred in 70% of the chemotherapy breast cancer patients contacted, and in 63% of those who received radiotherapy only. Among controls, about half of those selected by age matching, and contacted, agreed to participate.
Rates of cardiovascular-disease risk factors – dyslipidemia, hypertension, and diabetes – were at roughly similar levels in the cases and controls at the time of breast cancer diagnosis. But the rate of current smoking at the time of diagnosis appeared higher in the cases (30% among those who received chemotherapy and 33% among those on radiotherapy), compared with their respective control groups (22% and 30%). Ms. Boerman said that a multivariate analysis had not yet been run on the data but should occur soon.
“The prevalence of cardiac dysfunction was higher [in treated patients] than I would have expected, but there is potential bias as only 70% of invited patients actually participated,” commented Dr. Robert Mansel, a professor at the Institute of Cancer & Genetics at Cardiff University (Wales). He also noted the very low rate of patients who developed severe cardiac dysfunction.
Ms. Boerman and Dr. Mansel reported having no financial disclosures.
On Twitter @mitchelzoler
AMSTERDAM – Breast cancer patients who underwent chemotherapy or radiotherapy had about a two-fold increased prevalence of mild systolic cardiac dysfunction a median of 10 years after treatment, compared with age-matched controls in a study that included a total of 700 people.
But even longer follow-up of treated breast cancer patients is needed to determine whether the excess mild cardiac dysfunction seen in this analysis eventually progresses to more severe cardiac impairment, Liselotte M. Boerman said at the European Breast Cancer Conference.
Data from the Breast Cancer Long-term Outcome of Cardiac Dysfunction (BLOC) study showed that 175 breast cancer patients who received chemotherapy (and may have also received radiotherapy) had a 2.5-fold higher prevalence of a left ventricular ejection fraction (LVEF) below 54% (95% confidence interval, 1.2-5.4) when measured by echocardiography a median of 10 years after treatment, compared with an equal number of age-matched individuals from the general population.
A separate group of 175 patients treated with radiotherapy only and evaluated by echocardiography a median of 10 years later had a 2.3-fold increased prevalence (1.1-4.7) of a LVEF below 54% when compared with an equal number of age-matched individuals, said Ms. Boerman, an epidemiology researcher at the University of Groningen (the Netherlands).
This degree of left-ventricular dysfunction was found in 15% of the chemotherapy patients and 6% of their controls, and in 16% of the radiotherapy patients and 8% of their controls.
However, the treated breast cancer patients had no long-term increase in their prevalence of more significant systolic cardiac dysfunction, defined as a LVEF of less than 45%, compared with the controls, and the overall rate of systolic dysfunction of this severity was low, affecting fewer than 1% of patients.
Also, the chemotherapy and radiotherapy patients showed no significant increase in the prevalence of diastolic cardiac dysfunction, defined as delayed cardiac relaxation beyond the age-appropriate range. Treated patients did show, after 10 years, a suggestion of an increased prevalence of diagnosed cardiovascular disease, which was 2.3-fold higher (1.0-4.9) in the chemotherapy-receiving patients, compared with their controls; and 70% higher (0.9-3.4) among the patients treated with radiotherapy, compared with their controls, Ms. Boerman said.
The study used data collected from breast cancer patients younger than 80 years old treated after 1980 and controls seen by general practice Dutch physicians. The chemotherapy patients were diagnosed at an average age of 49 years old (range 26-66 years old). About 78% had received treatment with an anthracycline agent and 7% had received trastuzumab (Herceptin). Radiotherapy had also been administered to 70%, while 62% had also received hormonal therapy, and 7% either had a recurrence or developed a tumor in their contralateral breast.
None of the radiotherapy-only patients had received chemotherapy, but 21% had also received hormonal therapy. Their average age at diagnosis was 54 years old (range 32-79 years old), and 10% had a recurrence or a contralateral tumor.
Follow-up echocardiography occurred 5-34 years after the index treatment, at a median age of 60 years old. Echocardiography follow-up occurred in 70% of the chemotherapy breast cancer patients contacted, and in 63% of those who received radiotherapy only. Among controls, about half of those selected by age matching, and contacted, agreed to participate.
Rates of cardiovascular-disease risk factors – dyslipidemia, hypertension, and diabetes – were at roughly similar levels in the cases and controls at the time of breast cancer diagnosis. But the rate of current smoking at the time of diagnosis appeared higher in the cases (30% among those who received chemotherapy and 33% among those on radiotherapy), compared with their respective control groups (22% and 30%). Ms. Boerman said that a multivariate analysis had not yet been run on the data but should occur soon.
“The prevalence of cardiac dysfunction was higher [in treated patients] than I would have expected, but there is potential bias as only 70% of invited patients actually participated,” commented Dr. Robert Mansel, a professor at the Institute of Cancer & Genetics at Cardiff University (Wales). He also noted the very low rate of patients who developed severe cardiac dysfunction.
Ms. Boerman and Dr. Mansel reported having no financial disclosures.
On Twitter @mitchelzoler
AMSTERDAM – Breast cancer patients who underwent chemotherapy or radiotherapy had about a two-fold increased prevalence of mild systolic cardiac dysfunction a median of 10 years after treatment, compared with age-matched controls in a study that included a total of 700 people.
But even longer follow-up of treated breast cancer patients is needed to determine whether the excess mild cardiac dysfunction seen in this analysis eventually progresses to more severe cardiac impairment, Liselotte M. Boerman said at the European Breast Cancer Conference.
Data from the Breast Cancer Long-term Outcome of Cardiac Dysfunction (BLOC) study showed that 175 breast cancer patients who received chemotherapy (and may have also received radiotherapy) had a 2.5-fold higher prevalence of a left ventricular ejection fraction (LVEF) below 54% (95% confidence interval, 1.2-5.4) when measured by echocardiography a median of 10 years after treatment, compared with an equal number of age-matched individuals from the general population.
A separate group of 175 patients treated with radiotherapy only and evaluated by echocardiography a median of 10 years later had a 2.3-fold increased prevalence (1.1-4.7) of a LVEF below 54% when compared with an equal number of age-matched individuals, said Ms. Boerman, an epidemiology researcher at the University of Groningen (the Netherlands).
This degree of left-ventricular dysfunction was found in 15% of the chemotherapy patients and 6% of their controls, and in 16% of the radiotherapy patients and 8% of their controls.
However, the treated breast cancer patients had no long-term increase in their prevalence of more significant systolic cardiac dysfunction, defined as a LVEF of less than 45%, compared with the controls, and the overall rate of systolic dysfunction of this severity was low, affecting fewer than 1% of patients.
Also, the chemotherapy and radiotherapy patients showed no significant increase in the prevalence of diastolic cardiac dysfunction, defined as delayed cardiac relaxation beyond the age-appropriate range. Treated patients did show, after 10 years, a suggestion of an increased prevalence of diagnosed cardiovascular disease, which was 2.3-fold higher (1.0-4.9) in the chemotherapy-receiving patients, compared with their controls; and 70% higher (0.9-3.4) among the patients treated with radiotherapy, compared with their controls, Ms. Boerman said.
The study used data collected from breast cancer patients younger than 80 years old treated after 1980 and controls seen by general practice Dutch physicians. The chemotherapy patients were diagnosed at an average age of 49 years old (range 26-66 years old). About 78% had received treatment with an anthracycline agent and 7% had received trastuzumab (Herceptin). Radiotherapy had also been administered to 70%, while 62% had also received hormonal therapy, and 7% either had a recurrence or developed a tumor in their contralateral breast.
None of the radiotherapy-only patients had received chemotherapy, but 21% had also received hormonal therapy. Their average age at diagnosis was 54 years old (range 32-79 years old), and 10% had a recurrence or a contralateral tumor.
Follow-up echocardiography occurred 5-34 years after the index treatment, at a median age of 60 years old. Echocardiography follow-up occurred in 70% of the chemotherapy breast cancer patients contacted, and in 63% of those who received radiotherapy only. Among controls, about half of those selected by age matching, and contacted, agreed to participate.
Rates of cardiovascular-disease risk factors – dyslipidemia, hypertension, and diabetes – were at roughly similar levels in the cases and controls at the time of breast cancer diagnosis. But the rate of current smoking at the time of diagnosis appeared higher in the cases (30% among those who received chemotherapy and 33% among those on radiotherapy), compared with their respective control groups (22% and 30%). Ms. Boerman said that a multivariate analysis had not yet been run on the data but should occur soon.
“The prevalence of cardiac dysfunction was higher [in treated patients] than I would have expected, but there is potential bias as only 70% of invited patients actually participated,” commented Dr. Robert Mansel, a professor at the Institute of Cancer & Genetics at Cardiff University (Wales). He also noted the very low rate of patients who developed severe cardiac dysfunction.
Ms. Boerman and Dr. Mansel reported having no financial disclosures.
On Twitter @mitchelzoler
AT EBCC10
Key clinical point: Breast cancer patients treated with chemotherapy or radiotherapy showed a doubled rate of mild left-ventricular dysfunction, compared with matched controls 10 years after treatment.
Major finding: Mildly reduced left-ventricular function occurred in 15% of post-chemotherapy patients, compared with 6% of controls.
Data source: Echocardiography examinations conducted on 350 Dutch breast cancer patients and an equal number of age-matched controls.
Disclosures: Ms. Boerman and Dr. Mansel reported having no financial disclosures.
Incretin-based diabetes drugs don’t raise heart failure risk
Incretin-based antidiabetic drugs didn’t raise the risk of hospitalization for heart failure in an international observational study involving 1.5 million patients reported online March 24 in the New England Journal of Medicine.
The safety of dipeptidyl peptidase 4 (DPP-4) inhibitors such as sitagliptin, saxagliptin, and linagliptin, and of glucagon-like peptide–1 (GLP-1) analogues such as exenatide and liraglutide is controversial. Some clinical trials have reported these agents raise the risk of heart failure (HF) while others have found no increase in risk, but all of the studies are underpowered to settle the question, said Kristian B. Filion, Ph.D., of McGill University and the Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, and his associates.
They examined this issue by analyzing data from several large cohorts of diabetes patients treated in routine clinical practice in the United States, Canada, and England. Their study population comprised 1,499,650 adults who began taking noninsulin antidiabetic drugs at or after the date that incretin-based agents entered the market. “With 3.2 million person-years of observations, we had the statistical power to robustly assess this important drug safety issue,” the investigators said.
Patients taking DPP-4 inhibitors and GLP-1 analogues were compared with those taking non–incretin-based drugs such as biguanides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, and sodium-glucose cotransporter-2 inhibitors. A total of 29,741 patients were hospitalized for HF, for an overall rate of 9.2 events per 1,000 person-years.
Incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs (hazard ratio, 0.82) among the roughly 1.4 million patients who had no history of HF at baseline. Individually, neither DPP-4 inhibitors (HR, 0.84) nor GLP-1 analogues (HR, 0.95) were associated with an increased risk of hospitalization for HF. These findings remained consistent through several subgroup and sensitivity analyses that categorized the data according to duration of exposure, presence or absence of a history of MI, and duration of diabetes, Dr. Filion and his associates said (N Engl J Med. 2016 Mar 24. doi: 10.1056/NEJMoa1506115).
Similarly, incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs among the approximately 80,000 patients who had a history of HF at baseline (HR, 0.86).
This study was supported by the Canadian Institutes of Health Research and the Quebec Foundation for Health Research. Dr. Filion reported having no relevant financial disclosures; some of his associates reported ties to numerous industry sources.
Incretin-based antidiabetic drugs didn’t raise the risk of hospitalization for heart failure in an international observational study involving 1.5 million patients reported online March 24 in the New England Journal of Medicine.
The safety of dipeptidyl peptidase 4 (DPP-4) inhibitors such as sitagliptin, saxagliptin, and linagliptin, and of glucagon-like peptide–1 (GLP-1) analogues such as exenatide and liraglutide is controversial. Some clinical trials have reported these agents raise the risk of heart failure (HF) while others have found no increase in risk, but all of the studies are underpowered to settle the question, said Kristian B. Filion, Ph.D., of McGill University and the Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, and his associates.
They examined this issue by analyzing data from several large cohorts of diabetes patients treated in routine clinical practice in the United States, Canada, and England. Their study population comprised 1,499,650 adults who began taking noninsulin antidiabetic drugs at or after the date that incretin-based agents entered the market. “With 3.2 million person-years of observations, we had the statistical power to robustly assess this important drug safety issue,” the investigators said.
Patients taking DPP-4 inhibitors and GLP-1 analogues were compared with those taking non–incretin-based drugs such as biguanides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, and sodium-glucose cotransporter-2 inhibitors. A total of 29,741 patients were hospitalized for HF, for an overall rate of 9.2 events per 1,000 person-years.
Incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs (hazard ratio, 0.82) among the roughly 1.4 million patients who had no history of HF at baseline. Individually, neither DPP-4 inhibitors (HR, 0.84) nor GLP-1 analogues (HR, 0.95) were associated with an increased risk of hospitalization for HF. These findings remained consistent through several subgroup and sensitivity analyses that categorized the data according to duration of exposure, presence or absence of a history of MI, and duration of diabetes, Dr. Filion and his associates said (N Engl J Med. 2016 Mar 24. doi: 10.1056/NEJMoa1506115).
Similarly, incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs among the approximately 80,000 patients who had a history of HF at baseline (HR, 0.86).
This study was supported by the Canadian Institutes of Health Research and the Quebec Foundation for Health Research. Dr. Filion reported having no relevant financial disclosures; some of his associates reported ties to numerous industry sources.
Incretin-based antidiabetic drugs didn’t raise the risk of hospitalization for heart failure in an international observational study involving 1.5 million patients reported online March 24 in the New England Journal of Medicine.
The safety of dipeptidyl peptidase 4 (DPP-4) inhibitors such as sitagliptin, saxagliptin, and linagliptin, and of glucagon-like peptide–1 (GLP-1) analogues such as exenatide and liraglutide is controversial. Some clinical trials have reported these agents raise the risk of heart failure (HF) while others have found no increase in risk, but all of the studies are underpowered to settle the question, said Kristian B. Filion, Ph.D., of McGill University and the Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, and his associates.
They examined this issue by analyzing data from several large cohorts of diabetes patients treated in routine clinical practice in the United States, Canada, and England. Their study population comprised 1,499,650 adults who began taking noninsulin antidiabetic drugs at or after the date that incretin-based agents entered the market. “With 3.2 million person-years of observations, we had the statistical power to robustly assess this important drug safety issue,” the investigators said.
Patients taking DPP-4 inhibitors and GLP-1 analogues were compared with those taking non–incretin-based drugs such as biguanides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, and sodium-glucose cotransporter-2 inhibitors. A total of 29,741 patients were hospitalized for HF, for an overall rate of 9.2 events per 1,000 person-years.
Incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs (hazard ratio, 0.82) among the roughly 1.4 million patients who had no history of HF at baseline. Individually, neither DPP-4 inhibitors (HR, 0.84) nor GLP-1 analogues (HR, 0.95) were associated with an increased risk of hospitalization for HF. These findings remained consistent through several subgroup and sensitivity analyses that categorized the data according to duration of exposure, presence or absence of a history of MI, and duration of diabetes, Dr. Filion and his associates said (N Engl J Med. 2016 Mar 24. doi: 10.1056/NEJMoa1506115).
Similarly, incretin-based drugs were not associated with an increased rate of hospitalization for HF when compared with other antidiabetic drugs among the approximately 80,000 patients who had a history of HF at baseline (HR, 0.86).
This study was supported by the Canadian Institutes of Health Research and the Quebec Foundation for Health Research. Dr. Filion reported having no relevant financial disclosures; some of his associates reported ties to numerous industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Incretin-based antidiabetic drugs did not raise the risk of hospitalization for heart failure in a large international observational study.
Major finding: Neither DPP-4 inhibitors (HR, 0.84) nor GLP-1 analogues (HR, 0.95) were associated with an increased risk of hospitalization for HF, compared with non–incretin-based antidiabetic drugs.
Data source: A retrospective international observational cohort study involving roughly 1.5 million diabetes patients, of whom 29,741 were hospitalized for HF.
Disclosures: This study was supported by the Canadian Institutes of Health Research and the Quebec Foundation for Health Research. Dr. Filion reported having no relevant financial disclosures; some of his associates reported ties to numerous industry sources.