Charles F McTiernan1, Penelope Morel2, Leslie T Cooper3, Navin Rajagopalan4, Vinay Thohan4, Mark Zucker5, John Boehmer6, Biykem Bozkurt7, Paul Mather8, John Thornton9, Jalal K Ghali10, Karen Hanley-Yanez11, James Fett11, Indrani Halder11, Dennis M McNamara11. 1. Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: mctiernanc@upmc.edu. 2. Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania. 3. Mayo Clinic, Jacksonville, Florida. 4. Gill Heart Institute, University of Kentucky, Lexington, Kentucky. 5. Cardiac Transplant Center, Beth Israel Newark Medical Center, New Jersey. 6. Division of Cardiology, Penn State Hershey Medical Center, Hershey, Pennsylvania. 7. Winters Center for Heart Failure Research, Baylor College of Medicine, Houston, Texas. 8. Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 9. Division of Cardiology, Georgia Regents University in Augusta, Augusta, Georgia. 10. Division of Cardiology, Mercer University School of Medicine, Macon, Georgia. 11. Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
Abstract
OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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 HPwomen and women with non-pregnancy-associated recent-onset cardiomyopathy (ROCM). RESULTS: 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. CONCLUSIONS: 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.
Authors: Martijn F Hoes; Zoltan Arany; Johann Bauersachs; Denise Hilfiker-Kleiner; Mark C Petrie; Karen Sliwa; Peter van der Meer Journal: Nat Rev Cardiol Date: 2022-01-11 Impact factor: 49.421
Authors: Natalia I Gokina; Rebecca I Fairchild; Kirtika Prakash; Nicole M DeLance; Elizabeth A Bonney Journal: Front Physiol Date: 2021-06-16 Impact factor: 4.566
Authors: Alagarraju Muthukumar; Madhusudhanan Narasimhan; Quan-Zhen Li; Lenin Mahimainathan; Imran Hitto; Franklin Fuda; Kiran Batra; Xuan Jiang; Chengsong Zhu; John Schoggins; James B Cutrell; Carol L Croft; Amit Khera; Mark H Drazner; Justin L Grodin; Benjamin M Greenberg; Pradeep P A Mammen; Sean J Morrison; James A de Lemos Journal: Circulation Date: 2021-06-16 Impact factor: 29.690