Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC
Objective: Evaluate the relationship of cathepsin-D (CD) on disease severity and clinical outcomes for women with peripartum cardiomyopathy. Background: Cathepsin-D is a protease released during oxidative stress that cleaves prolactin (PRL) generating a 16 kDa fragment that is pro-apoptotic, anti-an...
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Elsevier
2025-01-01
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| Series: | American Heart Journal Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666602224001320 |
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| author | Vincenzo B. Polsinelli Karen Hanley-Yanez Charles F. McTiernan Kalgi Modi Jennifer Haythe Hal Skopicki Uri Elkayam Leslie T. Cooper, Jr James D. Fett Dennis M. McNamara |
| author_facet | Vincenzo B. Polsinelli Karen Hanley-Yanez Charles F. McTiernan Kalgi Modi Jennifer Haythe Hal Skopicki Uri Elkayam Leslie T. Cooper, Jr James D. Fett Dennis M. McNamara |
| author_sort | Vincenzo B. Polsinelli |
| collection | DOAJ |
| description | Objective: Evaluate the relationship of cathepsin-D (CD) on disease severity and clinical outcomes for women with peripartum cardiomyopathy. Background: Cathepsin-D is a protease released during oxidative stress that cleaves prolactin (PRL) generating a 16 kDa fragment that is pro-apoptotic, anti-angiogenic, and has been implicated in the pathogenesis of peripartum cardiomyopathy (PPCM). Methods: In 99 women with newly diagnosed PPCM enrolled in the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study, CD levels were assessed by ELISA from serum obtained at study entry. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6, and 12-months. CD levels were compared to healthy PP and non-PP controls. Survival free from major cardiovascular events (death, transplantation, or left ventricular assist device) was determined up to 12 months post-partum (PP). Results: Mean age was 30 ± 6 years, with a baseline LVEF of 34 % ± 10. Cathepsin-D levels were higher in PPCM women (278 ± 114 ng/ml) than in healthy PP (190 ± 74, p = 0.02) and healthy non-PP controls (136 ± 79, p < 0.001). There was no association of CD with age, breastfeeding status, or time from delivery to the presentation. Cathepsin-D levels were higher in women with higher New York Heart Association (NYHA) functional class (p = 0.001). Higher tertiles of CD levels were associated with lower event-free survival (p = 0.008). Conclusions: In this prospective cohort of women with PPCM, higher CD levels at the time of diagnosis were associated with worse symptoms, less recovery of LVEF, and worse clinical outcomes. Circulating CD may contribute to the development of PPCM and influence disease severity, myocardial recovery, and clinical outcomes. |
| format | Article |
| id | doaj-art-82ed6b3b9e204b72acca326671583e86 |
| institution | Kabale University |
| issn | 2666-6022 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | American Heart Journal Plus |
| spelling | doaj-art-82ed6b3b9e204b72acca326671583e862025-01-07T04:17:34ZengElsevierAmerican Heart Journal Plus2666-60222025-01-0149100489Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPACVincenzo B. Polsinelli0Karen Hanley-Yanez1Charles F. McTiernan2Kalgi Modi3Jennifer Haythe4Hal Skopicki5Uri Elkayam6Leslie T. Cooper, Jr7James D. Fett8Dennis M. McNamara9University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America; Corresponding author at: Division of Cardiology, Department of Medicine, University of Colorado, 12631 E. 17th Avenue, Mailstop B130, Aurora, CO 80045, United States of America.University of Pittsburgh Medical Center, Pittsburgh, PA, United States of AmericaUniversity of Pittsburgh Medical Center, Pittsburgh, PA, United States of AmericaLouisiana State University Health Science Center, Shreveport, LA, United States of AmericaColumbia University, New York, NY, United States of AmericaStony Brook Medical Center, Stony Brook, NY, United States of AmericaUniversity of Southern California Los Angeles, CA, United States of AmericaMayo Clinic Foundation, Jacksonville, FL, United States of AmericaUniversity of Pittsburgh Medical Center, Pittsburgh, PA, United States of America; Albert Schweitzer Hospital, Deschapelles, HaitiUniversity of Pittsburgh Medical Center, Pittsburgh, PA, United States of AmericaObjective: Evaluate the relationship of cathepsin-D (CD) on disease severity and clinical outcomes for women with peripartum cardiomyopathy. Background: Cathepsin-D is a protease released during oxidative stress that cleaves prolactin (PRL) generating a 16 kDa fragment that is pro-apoptotic, anti-angiogenic, and has been implicated in the pathogenesis of peripartum cardiomyopathy (PPCM). Methods: In 99 women with newly diagnosed PPCM enrolled in the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study, CD levels were assessed by ELISA from serum obtained at study entry. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6, and 12-months. CD levels were compared to healthy PP and non-PP controls. Survival free from major cardiovascular events (death, transplantation, or left ventricular assist device) was determined up to 12 months post-partum (PP). Results: Mean age was 30 ± 6 years, with a baseline LVEF of 34 % ± 10. Cathepsin-D levels were higher in PPCM women (278 ± 114 ng/ml) than in healthy PP (190 ± 74, p = 0.02) and healthy non-PP controls (136 ± 79, p < 0.001). There was no association of CD with age, breastfeeding status, or time from delivery to the presentation. Cathepsin-D levels were higher in women with higher New York Heart Association (NYHA) functional class (p = 0.001). Higher tertiles of CD levels were associated with lower event-free survival (p = 0.008). Conclusions: In this prospective cohort of women with PPCM, higher CD levels at the time of diagnosis were associated with worse symptoms, less recovery of LVEF, and worse clinical outcomes. Circulating CD may contribute to the development of PPCM and influence disease severity, myocardial recovery, and clinical outcomes.http://www.sciencedirect.com/science/article/pii/S2666602224001320CardiomyopathiesHeart failurePeripartum cardiomyopathyPregnancy |
| spellingShingle | Vincenzo B. Polsinelli Karen Hanley-Yanez Charles F. McTiernan Kalgi Modi Jennifer Haythe Hal Skopicki Uri Elkayam Leslie T. Cooper, Jr James D. Fett Dennis M. McNamara Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC American Heart Journal Plus Cardiomyopathies Heart failure Peripartum cardiomyopathy Pregnancy |
| title | Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC |
| title_full | Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC |
| title_fullStr | Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC |
| title_full_unstemmed | Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC |
| title_short | Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC |
| title_sort | cathepsin d and outcomes in peripartum cardiomyopathy results from ipac |
| topic | Cardiomyopathies Heart failure Peripartum cardiomyopathy Pregnancy |
| url | http://www.sciencedirect.com/science/article/pii/S2666602224001320 |
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