Circulating neuregulin during the transition from stage A to stage B/C heart failure in a breast cancer cohort.

BACKGROUND: Breast cancer (BC) treatments can cause heart failure (HF) in a subset of patients. ACC/AHA guidelines classify patients receiving cardiotoxic medications as stage A, a high-risk population for the development of HF. Circulating neuregulin (NRG) correlates with outcomes in stage C and D HF. We examined the levels of NRG in a BC cohort receiving cardiotoxic chemotherapy and its relationship with adverse cardiac effects during the transition from stage A to stage B or C HF. METHODS AND RESULTS: In an ongoing prospective study, a planned interim analysis of 78 BC women receiving either anthracycline (AC) or trastuzumab (Tsz) was performed. Biometric data, cardiac risk factors, and NRG levels, were collected before chemotherapy and after completion of AC therapy and/or 3 months into Tsz therapy. Cardiac function was measured by left ventricular ejection fraction (LVEF) by echocardiography at the above time points and longitudinally as standard of care. The interim cohort was predominately white with stage II BC and a median age of 50 years. A reduction of \u3e10 absolute percentage points in LVEF was observed in 21.4% of the cohort, representing a transition from stage A to stage B or C HF. A statistically significant drop in plasma NRG was observed in women treated with AC and/or Tsz (P \u3c .001). Additionally, baseline NRG correlated with the maximal change in LVEF. CONCLUSIONS: More than 20% of women experienced cardiac dysfunction, detected by decline in LVEF, and were reclassified as stage B or C HF. Plasma NRG levels were reduced after exposure to cardiotoxic chemotherapy, suggesting a loss in a cardioprotective growth factor. Higher baseline NRG levels were observed in those with the greatest decline in LVEF, supporting the continued investigation of NRG as a potential prognostic marker in early-stage HF

Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study

•Immune cell subsets were examined in healthy postpartum and peripartum cardiomyopathy (PPCM) women.•In the early postpartum, PPCM women had lower NK and higher CD3+CD4–CD8–CD38+ T cell levels.•Levels largely normalized by 6 months postpartum. The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non–pregnancy-associated recent-onset cardiomyopathy (ROCM). Entry NK cell levels (CD3–CD56+CD16+; reported as % of CD3– cells) were significantly (P < .0003) reduced in PPCM (6.6 ± 4.9% of CD3– cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4–CD8–CD38+ cells differed significantly (P < .004) between PPCM (24.5 ± 12.5% of CD3+CD4–CD8– cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4–CD8–CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4–CD8–CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and “double negative” (CD4–CD8–) T regulatory cells in PPCM requires further investigation