Meeting News

Cardiopoietic stem cells may confer reverse LV remodeling in HF

Intramyocardial administration of cardiopoietic stem cells in patients with advanced HF prompted significant reverse left ventricular remodeling, according to results presented at Heart Failure 2017.

In the CHART-1 trial, researchers analyzed data from 271 patients with chronic HF secondary to ischemic heart disease, with a LV ejection fraction less than 35%, John R. Teerlink, MD, FACC, FAHA, FESC, FHFA, FHFSA, FRCP (London), director of Heart Failure and of the Echocardiography Laboratory at the San Francisco Veterans Affairs Medical Center and a professor of medicine at the University of California, San Francisco, said in the presentation. Patients were assigned to receive up to a total of 600 x 106 lineage-directed cardiopoietic cell via 20 intramyocardial injections (C3BS-CQR-1; n = 120; mean age, 61 years; 89% men) or a sham procedure (n = 151; mean age, 62 years; 90% men).

Teerlink presented results from a post-hoc analysis, which demonstrated that administration of cardiopoietic stem cells was associated with significant reductions in both LV end diastolic volume (mean difference, –17 mL; P = .0057) and LV end systolic volume (mean difference, –12.8 mL; P = .0172) at 52 weeks after treatment. Adjustment for age, baseline LV end diastolic volume, prior MI, systolic BP and LV ejection fraction did not change the results. Teerlink said meta-analyses of multiple studies of patients with chronic HF have suggested that such improvements in LV remodeling are predictive of improved survival.

John R. Teerlink
John R. Teerlink

Interestingly, patients who received 16 or fewer cardiopoietic cell injections had the greatest change in LV end diastolic volume (P = .006) and LV end systolic volume (P = .008) compared with those with 17 or more injections or those in the control group.

Change in LV end diastolic volume was also associated with the number of injections compared with the control group (mean difference = –8.08; 95% CI, –19.66 to 3.49; P = .0207). These findings suggested that there may be an optimal number of injections for the administration of this cardiopoietic stem cell therapy, but do not give any insight into the mechanism explaining the decreased effectiveness of the maximal number of injections.

“Effects on remodeling appear most pronounced in patients who received a moderate number of injections,” Teerlink said in the presentation.

These analyses also confirmed findings from other studies that changed in LV end diastolic volume, LV end diastolic systolic volume, LVEF and LV mass impacted clinical outcomes regardless of treatment group, Teerlink said. Increased all-cause death, CV death, HF hospitalization and the combined endpoint of CV death and HF hospitalization at 52 weeks were all associated with increases in LV end diastolic volume and LV end systolic volume, as well as decreases in LVEF. Increases in LV mass were only associated with increased HF hospitalization and CV death/HF hospitalization, he said.

Primary results for CHART-1 were previously published in the European Heart Journal by Jozef Bartunek, MD, PhD, interventional cardiologist at the Cardiovascular Center Aalst in Belgium, and colleagues. The primary efficacy outcome was a hierarchical composite of the number of worsening HF events, mortality, Minnesota Living with HF Questionnaire score, 6-minute walk distance, LV end-systolic volume change and LVEF change, which was assessed 39 weeks after the procedure. The primary endpoint throughout the entire cohort was neutral at 39 weeks (Mann-Whitney estimator, 0.54; 95% CI, 0.47-0.61; P = .27), according to the researchers.

These emerging findings from CHART-1 support further research with this potentially promising stem cell therapy, Teerlink said. – by Darlene Dobkowski

References:

Teerlink JR, et al. Late-breaking trials III: Innovative and device therapies. Presented at: Heart Failure 2017 and the 4th World Congress on Acute Heart Failure; April 29-May 2, 2017; Paris.

Bartunek J, et al. Eur Heart J. 2017;doi:10.1093/eurheartj/ehw543.

Teerlink JR, et al. Eur J Heart Fail. 2017;doi:10.1002/ejhf.898.

Disclosure: The study was funded by Celyad. Bartunek reports employment with Cardiovascular Centre at OLV Hospital, which is a co-founder of Cardio3Biosciences (now Celyad), and receives consultant/speaker fees and research contracts that are directed to Cardiovascular Onderzoek and Cardiac Research Institute in Aalst, Belgium. Teerlink reports receiving research grants from Amgen, Bayer, Bristol-Myers Squibb, Celyad, Cytokinetics, Mast Therapeutics, Medtronic, Novartis and Trevena; personal fees and nonfinancial support from Amgen, Bayer, Bristol-Myers Squibb, Mast Therapeutics, Novartis, Relypsa, Trevena and ZS Pharma, and nonfinancial support from Medtronic.

Intramyocardial administration of cardiopoietic stem cells in patients with advanced HF prompted significant reverse left ventricular remodeling, according to results presented at Heart Failure 2017.

In the CHART-1 trial, researchers analyzed data from 271 patients with chronic HF secondary to ischemic heart disease, with a LV ejection fraction less than 35%, John R. Teerlink, MD, FACC, FAHA, FESC, FHFA, FHFSA, FRCP (London), director of Heart Failure and of the Echocardiography Laboratory at the San Francisco Veterans Affairs Medical Center and a professor of medicine at the University of California, San Francisco, said in the presentation. Patients were assigned to receive up to a total of 600 x 106 lineage-directed cardiopoietic cell via 20 intramyocardial injections (C3BS-CQR-1; n = 120; mean age, 61 years; 89% men) or a sham procedure (n = 151; mean age, 62 years; 90% men).

Teerlink presented results from a post-hoc analysis, which demonstrated that administration of cardiopoietic stem cells was associated with significant reductions in both LV end diastolic volume (mean difference, –17 mL; P = .0057) and LV end systolic volume (mean difference, –12.8 mL; P = .0172) at 52 weeks after treatment. Adjustment for age, baseline LV end diastolic volume, prior MI, systolic BP and LV ejection fraction did not change the results. Teerlink said meta-analyses of multiple studies of patients with chronic HF have suggested that such improvements in LV remodeling are predictive of improved survival.

John R. Teerlink
John R. Teerlink

Interestingly, patients who received 16 or fewer cardiopoietic cell injections had the greatest change in LV end diastolic volume (P = .006) and LV end systolic volume (P = .008) compared with those with 17 or more injections or those in the control group.

Change in LV end diastolic volume was also associated with the number of injections compared with the control group (mean difference = –8.08; 95% CI, –19.66 to 3.49; P = .0207). These findings suggested that there may be an optimal number of injections for the administration of this cardiopoietic stem cell therapy, but do not give any insight into the mechanism explaining the decreased effectiveness of the maximal number of injections.

“Effects on remodeling appear most pronounced in patients who received a moderate number of injections,” Teerlink said in the presentation.

These analyses also confirmed findings from other studies that changed in LV end diastolic volume, LV end diastolic systolic volume, LVEF and LV mass impacted clinical outcomes regardless of treatment group, Teerlink said. Increased all-cause death, CV death, HF hospitalization and the combined endpoint of CV death and HF hospitalization at 52 weeks were all associated with increases in LV end diastolic volume and LV end systolic volume, as well as decreases in LVEF. Increases in LV mass were only associated with increased HF hospitalization and CV death/HF hospitalization, he said.

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Primary results for CHART-1 were previously published in the European Heart Journal by Jozef Bartunek, MD, PhD, interventional cardiologist at the Cardiovascular Center Aalst in Belgium, and colleagues. The primary efficacy outcome was a hierarchical composite of the number of worsening HF events, mortality, Minnesota Living with HF Questionnaire score, 6-minute walk distance, LV end-systolic volume change and LVEF change, which was assessed 39 weeks after the procedure. The primary endpoint throughout the entire cohort was neutral at 39 weeks (Mann-Whitney estimator, 0.54; 95% CI, 0.47-0.61; P = .27), according to the researchers.

These emerging findings from CHART-1 support further research with this potentially promising stem cell therapy, Teerlink said. – by Darlene Dobkowski

References:

Teerlink JR, et al. Late-breaking trials III: Innovative and device therapies. Presented at: Heart Failure 2017 and the 4th World Congress on Acute Heart Failure; April 29-May 2, 2017; Paris.

Bartunek J, et al. Eur Heart J. 2017;doi:10.1093/eurheartj/ehw543.

Teerlink JR, et al. Eur J Heart Fail. 2017;doi:10.1002/ejhf.898.

Disclosure: The study was funded by Celyad. Bartunek reports employment with Cardiovascular Centre at OLV Hospital, which is a co-founder of Cardio3Biosciences (now Celyad), and receives consultant/speaker fees and research contracts that are directed to Cardiovascular Onderzoek and Cardiac Research Institute in Aalst, Belgium. Teerlink reports receiving research grants from Amgen, Bayer, Bristol-Myers Squibb, Celyad, Cytokinetics, Mast Therapeutics, Medtronic, Novartis and Trevena; personal fees and nonfinancial support from Amgen, Bayer, Bristol-Myers Squibb, Mast Therapeutics, Novartis, Relypsa, Trevena and ZS Pharma, and nonfinancial support from Medtronic.