Larger End-Diastolic Volume Associates With Response to Cell Therapy in Patients With Nonischemic Dilated Cardiomyopathy

Abstract

Objective: To investigate the association of left ventricular end-diastolic volume (LVEDV) and the response to cell therapy in patients with nonischemic dilated cardiomyopathy (NICM).Patients and Methods: Five-year registry data from 133 consecutive patients with NICM who underwent CD34 + cell treatment were analyzed. All patients received granulocyte-colony stimulating factor; CD34 + cells were collected by apheresis and delivered by transendocardial injections. Patients with baseline LVEDV less than 200 mL (group A; n=72) and patients with LVEDV 200 to 370 mL (group B; n=54) were included. Patients with LVEDV greater than 370 mL were excluded (n=7). Favorable ejection fraction response was pre-defined by improvement in left ventricular ejection fraction (LVEF) greater than or equal to 5% at 1 y post-cell therapy.Results: At baseline, groups A and B were comparable with regards to age (52±11 y in group A vs 53±10 y in group B; P=.95), sex (male: 79% vs 83%, respectively; P=.55), creatinine (1.07±0.28 mg/dL vs 1.03±0.21 mg/dL, respectively; P=.21), or N-terminal probrain natriuretic peptide (1454±1658 pg/mL vs 1589±1338 pg/mL, respectively; P=.80). Baseline LVEF was higher in group A (32.8±8.7%) than in group B (30.2±8.7%; P=.03). During follow-up, there were four deaths in group A (6%), and 2 in group B (4%, P=.63). At 1-y post-cell therapy, LVEDV decreased significantly in group B (−56±30 mL; P=.003), but not in group A (+12±97 mL; P=.13).On multivariate analysis, baseline LVEDV was an independent correlate of favorable response in LVEF to therapy (P=.02). Conclusion:Larger LVEDV was associated with more pronounced increase in LVEF after transendocardial CD34 + cell therapy in NICM patients, informing target individuals with the highest likelihood of regenerative response.Trial Registration: clinicaltrials.gov identifier: NCT02445534 Nonischemic dilated cardiomyopathy (NICM) is a leading cause of advanced heart failure accounting for more than half of all heart transplantations. 1 This evolving trend underscores

Ventricular remodeling in ischemic heart failure stratifies responders to stem cell therapy

“…Adjusted by body weight, moderate-, advanced-, and end-stage ischemic cardiomyopathy in mice corresponds to that of LVEDV <200, 200-370, >370 ml, respectively in humans. 17,21,22 Δ ejection fraction, change in ejection faction post-therapy vs pretherapy; blue solid lines, predetermined criteria of improvement (>4%) and worsening (<−4%) in Δ ejection fraction. B, Reverse remodeling (>15% reduction in LV end-systolic volume) occurred in the majority of advanced stage recipients, displaying a v-shaped relationship between Δ end-systolic volume and pretherapy LVEDV.…”

“…The significance of LV size in prioritizing best responders is potentially applicable in practice as supported by recent clinical subanalysis in both ischemic and non-ischemic cardiomyopathy using multiple cell types. 17,21,22,25 Further prospective investigation across the translational axis is now required to certify the utility of LV volumes in screening candidates for optimized regenerative biotherapy in heart failure.…”

Secretome Signature of Cardiopoietic Cells Echoed in Rescued infarcted Heart Proteome

“…19,20 While genetic and structural determinants intrinsic to recipient hearts are recognized, less is known regarding stem cell characteristics governing therapeutic effectiveness. 16,21,22 We explored here, at systems level, cardiopoietic cell imprints that segregate with benefit. Merging multiomics datasets provides inclusive, unbiased strategies enabling functional prioritization of complex multidimensional outputs.…”

Acute Kidney Injury Successfully Treated with Autologous Granulocyte Colony-Stimulating Factor-mobilized Peripheral Blood CD34-Positive Cell Transplantation: A first-in-Human Report

“…Not all patients would benefit from cell therapy, however. 16 Identifying individuals with a higher response to cell therapy would be of great interest in future trials.…”