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5. Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways

Author

aaaMcNamara, Dennis M., Fett, James D., Pisarcik, Jessica, McTiernan, Charles, Hanley-Yanez, Karen, Gorcsan, John, III, Schelbert, Erik, Alharethi, Rami, Rasmusson, Kismet, Brunisholz, Kim, Butler, Amy, Budge, Deborah, Kfoury, A.G., Horne, Benjamin, Tuinei, Joe, Brown, Heather, Damp, Julie, Naftilan, Allen J., Russell, Jill, Freehardt, Darla, Hsich, Eileen, Oblak, Cynthia, Ewald, Greg, Whitehead, Donna, Flanagan, Jean, Platts, Anne, Elkayam, Uri, Caro, Jorge, Mullin, Stephanie, Givertz, Michael M., Anello, M. Susan, Rajagopalan, Navin, Booth, David, Sandlin, Tiffany, Wijesiri, Wendy, Cooper, Leslie T., Blauwet, Lori A., Brunner, Joann, Phelps, Mary, Kempf, Ruth, Modi, Kalgi, Norwood, Tracy, Briller, Joan, Griza, Decebal Sorin, Felker, G. Michael, Kociol, Robb, Adams, Patricia, Wells, Gretchen, Thohan, Vinay, Wesley-Farrington, Deborah, Soots, Sandra, Sheppard, Richard, Michel, Caroline, Lapointe, Nathalie, Nathaniel, Heather, Kealey, Angela, Semigran, Marc, Daher, Maureen, Boehmer, John, Silber, David, Popjes, Eric, Frey, Patricia, Nicklas, Todd, Alexis, Jeffrey, Caufield, Lori, Thornton, John W., III, Gentry, Mindy, Robinson, Vincent J.B., Sharma, Gyanendra K., Holloway, Joan, Powell, Maria, Markham, David, Drazner, Mark, Fernandez, Lynn, Zucker, Mark, Baran, David A., Gimovsky, Martin L., Hochbaum, Natalia, Patel, Bharati, Adams, Laura, Ramani, Gautam, Gottlieb, Stephen, Robinson, Shawn, Fisher, Stacy, Marshall, Joanne, Haythe, Jennifer, Mancini, Donna, Bijou, Rachel, Farr, Maryjane, Marks, Marybeth, Arango, Henry, Bozkurt, Biykem, Bolos, Mariana, Mather, Paul, Rubin, Sharon, Bonita, Raphael, Eberwine, Susan, Skopicki, Hal, Stergiopoulos, Kathleen, McCathy-Santoro, Ellen, Intravaia, Jennifer, Maas, Elizabeth, Safirstein, Jordan, Kleet, Audrey, Martinez, Nancy, Corpoin, Christine, Hesari, Donna, Chaparro, Sandra, Hudson, Laura J., Ghali, Jalal K., Injic, Zora, Wittstein, Ilan S., McNamara, Dennis M., Janosko, Karen, London, Barry, Gorcsan, John, Tanaka, Hidekazu, Suffoletto, Mathew, Starling, Randall C., McNallan, Annette, Koenig, LuAnne, Pierson, Natalie, Bell, Yanique, Ervin, Alicia, Schrack, Janice, LaDuke, Pam, Torre-Amione, Guillermo, Arredondo, Jeannie, Pauly, Daniel F., Smith, Pamela C., Fuoco, Stephanie, Breton, Elayne, Wesley, Deborah, Dec, G. William, Cocca-Spofford, Diane, Markham, David W., Debes, Colleen, Zucker, Mark J., Liu, Peter, Renton, Judith, Narula, Jagat, Allen, Byron, Westberg, Elizabeth, Lovell, Jana P., Bermea, Kevin, Yu, Jinsheng, Rousseau, Sylvie, Cohen, Charles D., Bhalodia, Aashik, Zita, Marcelle Dina, Head, Richard D., Blumenthal, Roger S., Sharma, Garima, and Adamo, Luigi

Published
2023
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6. Abstract 16898: Myocardial Recovery Associated Gene Cdcp1 Expression Attenuates Cardiac Fibrosis in a Pressure Over-Load Mouse Model

Author

Wang, Min, Vyas, Hridyanshu, Roos, Carolyn, Huang, Runqing, Liu, Duan, Sahni, Jyotan, McNamara, Dennis M, Barlera, Simona, Pileggi, Silvana, Mestroni, Luisa, Merlo, Marco, Sinagra, Gianfranco, Pinet, Florence, Chaloupka, Anna, Krejci, Jan, de GROOTE, Pascal, Weinshilboum, Richard, Miller, Jordan D, and Pereira, Naveen L

Published
2023
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10. Impact of cannabidiol on myocardial recovery in patients with acute myocarditis: Rationale & design of the ARCHER trial.

Author

McNamara, Dennis M., Cooper, Leslie T., Arbel, Yaron, Bhimaraj, Arvind, Bocchi, Edimar, Friedrich, Matthias G., Kerneis, Matthieu, Liu, Peter, Parker, Andrea B., Smith, Eldon R., Tang, W. H. Wilson, Torre‐Amione, Guillermo, and Tschöpe, Carsten

Subjects
GLOBAL longitudinal strain, CARDIAC arrest, CARDIAC magnetic resonance imaging, VENTRICULAR ejection fraction, YOUNG adults, HEART failure
Abstract

Aims: Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti‐inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF). Methods and results: We present the rationale and design of the ARCHER Trial, an international multicentre, double‐blind, randomized, placebo‐controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow‐up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs‐troponin, NT‐proBNP, markers of inflammation and endothelial function during the 12‐week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper. Conclusions: The ongoing ARCHER Trial is an international, multicentre, double‐blind, randomized, placebo‐controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Breastfeeding, Cellular Immune Activation, and Myocardial Recovery in Peripartum Cardiomyopathy

Author

McNamara, Dennis M, Fett, James D., Pisarcik, Jessica, McTiernan, Charles, Hanley-Yanez, Karen, Gorcsan, John, III, Schelbert, Erik, Alharethi, Rami, Rasmusson, Kismet, Brunisholz, Kim, Butler, Amy, Budge, Deborah, Kfoury, A.G., Horne, Benjamin, Tuinei, Joe, Brown, Heather, Damp, Julie, Naftilan, Allen J., Russell, Jill, Freehardt, Darla, Hsich, Eileen, Oblak, Cynthia, Ewald, Greg, Whitehead, Donna, Flanagan, Jean, Platts, Anne, Elkayam, Uri, Caro, Jorge, Mullin, Stephanie, Givertz, Michael M., Anello, M. Susan, Rajagopalan, Navin, Booth, David, Sandlin, Tiffany, Wijesiri, Wendy, Cooper, Leslie T., Blauwet, Lori A., Brunner, Joann, Phelps, Mary, Kempf, Ruth, Modi, Kalgi, Norwood, Tracy, Briller, Joan, Griza, Decebal Sorin, Felker, G. Michael, Kociol, Robb, Adams, Patricia, Wells, Gretchen, Thohan, Vinay, Wesley-Farrington, Deborah, Soots, Sandra, Sheppard, Richard, Michel, Caroline, Lapointe, Nathalie, Nathaniel, Heather, Kealey, Angela, Semigran, Marc, Daher, Maureen, Boehmer, John, Silber, David, Popjes, Eric, Frey, Patricia, Nicklas, Todd, Alexis, Jeffrey, Caufield, Lori, Thornton, John W., III, Gentry, Mindy, Robinson, Vincent J.B., Sharma, Gyanendra K., Holloway, Joan, Powell, Maria, Markham, David, Drazner, Mark, Fernandez, Lynn, Zucker, Mark, Baran, David A., Gimovsky, Martin L., Hochbaum, Natalia, Patel, Bharati, Adams, Laura, Ramani, Gautam, Gottlieb, Stephen, Robinson, Shawn, Fisher, Stacy, Marshall, Joanne, Haythe, Jennifer, Mancini, Donna, Bijou, Rachel, Farr, Maryjane, Marks, Marybeth, Arango, Henry, Bozkurt, Biykem, Bolos, Mariana, Mather, Paul, Rubin, Sharon, Bonita, Raphael, Eberwine, Susan, Skopicki, Hal, Stergiopoulos, Kathleen, McCathy-Santoro, Ellen, Intravaia, Jennifer, Maas, Elizabeth, Safirstein, Jordan, Kleet, Audrey, Martinez, Nancy, Corpoin, Christine, Hesari, Donna, Chaparro, Sandra, Hudson, Laura J., Ghali, Jalal K., Injic, Zora, Wittstein, Ilan S., Koczo, Agnes, Marino, Amy, Jeyabalan, Arun, Fett, James, Blauwet, Lori, Morel, Penelope A., and McNamara, Dennis M.

Published
2019
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12. Heart Failure Association, Heart Failure Society of America, and Japanese Heart Failure Society Position Statement on Endomyocardial Biopsy

Author

Seferović, Petar M., Tsutsui, Hiroyuki, Mcnamara, Dennis M., Ristić, Arsen D., Basso, Cristina, Bozkurt, Biykem, Cooper, Leslie T., Filippatos, Gerasimos, Ide, Tomomi, Inomata, Takayuki, Klingel, Karin, Linhart, Aleš, lyon, Alexander R., Mehra, Mandeep R., Polovina, Marija, Milinković, Ivan, Nakamura, Kazufumi, Anker, Stefan D., Veljić, Ivana, Ohtani, Tomohito, Okumura, Takahiro, Thum, Thomas, Tschöpe, Carsten, Rosano, Giuseppe, Coats, Andrew J.S., and Starling, Randall C.

Published
2021
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14. Chemokine receptor patterns and right heart failure in mechanical circulatory support

Author

Nayak, Aditi, Neill, Colin, Kormos, Robert L, Lagazzi, Luigi, Halder, Indrani, McTiernan, Charles, Larsen, Jennifer, Inashvili, Ana, Teuteberg, Jeffrey, Bachman, Timothy N, Hanley-Yanez, Karen, McNamara, Dennis M, and Simon, Marc A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Cardiovascular, Heart Disease, Clinical Research, Biomarkers, Female, Follow-Up Studies, Heart Failure, Heart-Assist Devices, Humans, Male, Middle Aged, Pennsylvania, Receptors, Chemokine, Retrospective Studies, Risk Assessment, Risk Factors, Survival Rate, Time Factors, Ventricular Dysfunction, Right, chemokine receptor, inflammation, left ventricular assist device, prognostication, right ventricular failure, survival, Cardiorespiratory Medicine and Haematology, Surgery, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundRight ventricular failure (RVF) complicates 9% to 44% of left ventricular assist device (LVAD) implants post-operatively. Current prediction scores perform only modestly in validation studies, and do not include immune markers. Chemokines are inflammatory signaling molecules with a fundamental role in cardiac physiology and stress adaptation. In this study we investigated chemokine receptor regulation in LVAD recipients who develop RVF.MethodsExpression of chemokine receptor (CCR) genes 3 to 8 were examined in the peripheral blood of 111 LVAD patients, collected 24 hours before implant. RNA was isolated using a PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR Array; Qiagen). Results were expressed as polymerase chain reaction (PCR) cycles to threshold and normalized to the average of 3 control genes, glyceraldehyde phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and β2-microglobulin (B2M). Secondary outcomes studied were 1-year mortality and long-term RV failure (RVF-LT).ResultsCCR3, CCR4, CCR6, CCR7 and CCR8 were downregulated in LVAD recipients with RVF. Within this cohort of patients, CCR4, CCR7 and CCR8 were further downregulated in those who required RV mechanical support. In addition, under-expression of CCR3 to CCR8 was independently associated with an increased risk of mortality at 1 year, even after adjusting for RVF. CCR expression did not predict RVF-LT in our patient cohort.ConclusionsPre-LVAD CCR downregulation is associated with RVF and increased mortality after implant. Inflammatory signatures may play a major role in prognostication in this patient population.

Published
2017

17. Impact of Socioeconomic Factors on Patient Desire for Early LVAD Therapy Prior to Inotrope Dependence

Author

Tchoukina, Inna, Shah, Keyur B., Thibodeau, Jennifer T., Estep, Jerry D., Lala, Anuradha, Lanfear, David E., Gilotra, Nisha A., Pamboukian, Salpy V., Horstmanshof, Douglas A., Mcnamara, Dennis M., Haas, Donald C., Jorde, Ulrich P., Mclean, Rhondalyn C., Cascino, Thomas M., Khalatbari, Shokoufeh, Richards, Blair, Yosef, Matheos, Spino, Cathie, Baldwin, J. Timothy, Mann, Douglas L., Aaronson, Keith D., and Stewart, Garrick C.

Published
2020
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18. Registry Evaluation of Vital Information for VADs in Ambulatory Life (REVIVAL): Rationale, design, baseline characteristics, and inclusion criteria performance

Author

Aaronson, Keith D., Stewart, Garrick C., Pagani, Francis D., Stevenson, Lynne W., Palardy, Maryse, McNamara, Dennis M., Mancini, Donna M., Grady, Kathleen, Gorcsan, John, Kormos, Robert, Jeffries, Neal, Taddei-Peters, Wendy C., Richards, Blair, Khalatbari, Shokoufeh, Spino, Cathie, Baldwin, J. Timothy, and Mann, Douglas L.

Published
2020
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20. Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death

Author

Carew, Nolan T., Schmidt, Heidi M., Yuan, Shuai, Galley, Joseph C., Hall, Robert, Altmann, Helene M., Hahn, Scott A., Miller, Megan P., Wood, Katherine C., Gabris, Bethann, Stapleton, Margaret C., Hartwick, Sean, Fazzari, Marco, Wu, Yijen L., Trebak, Mohamed, Kaufman, Brett A., McTiernan, Charles F., Schopfer, Francisco J., Navas, Placido, Thibodeau, Patrick H., McNamara, Dennis M., Salama, Guy, and Straub, Adam C.

Subjects
Gene expression -- Research, Cardiovascular research, Heart cells -- Health aspects -- Genetic aspects, Enzymes -- Genetic aspects -- Health aspects, Cellular signal transduction -- Research, Cardiac arrest -- Causes of -- Genetic aspects -- Risk factors, Oxidation-reduction reaction -- Health aspects -- Genetic aspects, Health care industry
Abstract

Sudden cardiac death (SCD) in patients with heart failure (HF) is allied with an imbalance in reduction and oxidation (redox) signaling in cardiomyocytes; however, the basic pathways and mechanisms governing redox homeostasis in cardiomyocytes are not fully understood. Here, we show that cytochrome b5 reductase 3 (CYB5R3), an enzyme known to regulate redox signaling in erythrocytes and vascular cells, is essential for cardiomyocyte function. Using a conditional cardiomyocytespecific CYB5R3-knockout mouse, we discovered that deletion of CYB5R3 in male, but not female, adult cardiomyocytes causes cardiac hypertrophy, bradycardia, and SCD. The increase in SCD in CYB5R3-KO mice is associated with calcium mishandling, ventricular fibrillation, and cardiomyocyte hypertrophy. Molecular studies reveal that CYB5R3-KO hearts display decreased adenosine triphosphate (ATP), increased oxidative stress, suppressed coenzyme Q levels, and hemoprotein dysregulation. Finally, from a translational perspective, we reveal that the high-frequency missense genetic variant rs1800457, which translates into a CYB5R3 T117S partial loss-of-function protein, associates with decreased event-free survival (~20%) in Black persons with HF with reduced ejection fraction (HFrEF). Together, these studies reveal a crucial role for CYB5R3 in cardiomyocyte redox biology and identify a genetic biomarker for persons of African ancestry that may potentially increase the risk of death from HFrEF., Introduction The healthy heart requires a highly synchronized series of reduction and oxidation (redox) reactions to support the electrical and mechanical demands of beating cardiomyocytes (1). In the aging population, [...]

Published
2022
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23. Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis

Author

Liu, Duan, primary, Wang, Min, additional, Murthy, Vishakantha, additional, McNamara, Dennis M., additional, Nguyen, Thanh Thanh L., additional, Philips, Trudy J., additional, Vyas, Hridyanshu, additional, Gao, Huanyao, additional, Sahni, Jyotan, additional, Starling, Randall C., additional, Cooper, Leslie T., additional, Skime, Michelle K., additional, Batzler, Anthony, additional, Jenkins, Gregory D., additional, Barlera, Simona, additional, Pileggi, Silvana, additional, Mestroni, Luisa, additional, Merlo, Marco, additional, Sinagra, Gianfranco, additional, Pinet, Florence, additional, Krejčí, Jan, additional, Chaloupka, Anna, additional, Miller, Jordan D., additional, de Groote, Pascal, additional, Tschumperlin, Daniel J., additional, Weinshilboum, Richard M., additional, and Pereira, Naveen L., additional

Published
2023
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24. Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways

Author

Lovell, Jana P., primary, Bermea, Kevin, additional, Yu, Jinsheng, additional, Rousseau, Sylvie, additional, Cohen, Charles D., additional, Bhalodia, Aashik, additional, Zita, Marcelle Dina, additional, Head, Richard D., additional, Blumenthal, Roger S., additional, Alharethi, Rami, additional, Damp, Julie, additional, Boehmer, John, additional, Alexis, Jeffrey, additional, McNamara, Dennis M., additional, Sharma, Garima, additional, Adamo, Luigi, additional, aaaMcNamara, Dennis M., additional, Fett, James D., additional, Pisarcik, Jessica, additional, McTiernan, Charles, additional, Hanley-Yanez, Karen, additional, Gorcsan, John, additional, Schelbert, Erik, additional, Rasmusson, Kismet, additional, Brunisholz, Kim, additional, Butler, Amy, additional, Budge, Deborah, additional, Kfoury, A.G., additional, Horne, Benjamin, additional, Tuinei, Joe, additional, Brown, Heather, additional, Naftilan, Allen J., additional, Russell, Jill, additional, Freehardt, Darla, additional, Hsich, Eileen, additional, Oblak, Cynthia, additional, Ewald, Greg, additional, Whitehead, Donna, additional, Flanagan, Jean, additional, Platts, Anne, additional, Elkayam, Uri, additional, Caro, Jorge, additional, Mullin, Stephanie, additional, Givertz, Michael M., additional, Anello, M. Susan, additional, Rajagopalan, Navin, additional, Booth, David, additional, Sandlin, Tiffany, additional, Wijesiri, Wendy, additional, Cooper, Leslie T., additional, Blauwet, Lori A., additional, Brunner, Joann, additional, Phelps, Mary, additional, Kempf, Ruth, additional, Modi, Kalgi, additional, Norwood, Tracy, additional, Briller, Joan, additional, Griza, Decebal Sorin, additional, Felker, G. Michael, additional, Kociol, Robb, additional, Adams, Patricia, additional, Wells, Gretchen, additional, Thohan, Vinay, additional, Wesley-Farrington, Deborah, additional, Soots, Sandra, additional, Sheppard, Richard, additional, Michel, Caroline, additional, Lapointe, Nathalie, additional, Nathaniel, Heather, additional, Kealey, Angela, additional, Semigran, Marc, additional, Daher, Maureen, additional, Silber, David, additional, Popjes, Eric, additional, Frey, Patricia, additional, Nicklas, Todd, additional, Caufield, Lori, additional, Thornton, John W., additional, Gentry, Mindy, additional, Robinson, Vincent J.B., additional, Sharma, Gyanendra K., additional, Holloway, Joan, additional, Powell, Maria, additional, Markham, David, additional, Drazner, Mark, additional, Fernandez, Lynn, additional, Zucker, Mark, additional, Baran, David A., additional, Gimovsky, Martin L., additional, Hochbaum, Natalia, additional, Patel, Bharati, additional, Adams, Laura, additional, Ramani, Gautam, additional, Gottlieb, Stephen, additional, Robinson, Shawn, additional, Fisher, Stacy, additional, Marshall, Joanne, additional, Haythe, Jennifer, additional, Mancini, Donna, additional, Bijou, Rachel, additional, Farr, Maryjane, additional, Marks, Marybeth, additional, Arango, Henry, additional, Bozkurt, Biykem, additional, Bolos, Mariana, additional, Mather, Paul, additional, Rubin, Sharon, additional, Bonita, Raphael, additional, Eberwine, Susan, additional, Skopicki, Hal, additional, Stergiopoulos, Kathleen, additional, McCathy-Santoro, Ellen, additional, Intravaia, Jennifer, additional, Maas, Elizabeth, additional, Safirstein, Jordan, additional, Kleet, Audrey, additional, Martinez, Nancy, additional, Corpoin, Christine, additional, Hesari, Donna, additional, Chaparro, Sandra, additional, Hudson, Laura J., additional, Ghali, Jalal K., additional, Injic, Zora, additional, Wittstein, Ilan S., additional, Janosko, Karen, additional, London, Barry, additional, Tanaka, Hidekazu, additional, Suffoletto, Mathew, additional, Starling, Randall C., additional, McNallan, Annette, additional, Koenig, LuAnne, additional, Pierson, Natalie, additional, Bell, Yanique, additional, Ervin, Alicia, additional, Schrack, Janice, additional, LaDuke, Pam, additional, Torre-Amione, Guillermo, additional, Arredondo, Jeannie, additional, Pauly, Daniel F., additional, Smith, Pamela C., additional, Fuoco, Stephanie, additional, Breton, Elayne, additional, Wesley, Deborah, additional, Dec, G. William, additional, Cocca-Spofford, Diane, additional, Markham, David W., additional, Debes, Colleen, additional, Zucker, Mark J., additional, Liu, Peter, additional, Renton, Judith, additional, Narula, Jagat, additional, Allen, Byron, additional, and Westberg, Elizabeth, additional

Published
2023
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26. Contributors

Author

Abel, E. Dale, primary, Adamo, Luigi, additional, Ali, Shah R., additional, Allen, Larry A., additional, Bakris, George L., additional, Bloomfield, Gerald S., additional, Bonow, Robert O., additional, Bozkurt, Biykem, additional, Bristow, Michael R., additional, Brown, Angela L., additional, Bugger, Heiko, additional, Burnett, John C., additional, Butler, Javed, additional, Carroll, John D., additional, Castaño, Adam, additional, Chang, Anna Marie, additional, Cohn, Jay N., additional, Colucci, Wilson S., additional, Dell’Italia, Louis J., additional, Deswal, Anita, additional, DeVore, Adam D., additional, Diwan, Abhinav, additional, DuBrock, Hilary M., additional, Dunlay, Shannon M., additional, Dzhoyashvili, Nina, additional, Ewald, Gregory A., additional, Ezekowitz, Justin A., additional, Fang, James C., additional, Fedson, Savitri, additional, Feinstein, Matthew J., additional, Felker, G. Michael, additional, Ferguson, John D., additional, Ferrari, Victor A., additional, Ferrario, Carlos M., additional, Flaherty, James D., additional, Floras, John S., additional, Florea, Viorel G., additional, Gaggin, Hanna K., additional, Greenberg, Barry, additional, Hare, Joshua M., additional, Hernandez, Adrian F., additional, Hill, Joseph A., additional, Ibrahim, Nasrien E., additional, Januzzi, James L., additional, Joseph, Susan M., additional, Judge, Daniel P., additional, Kahn, Andrew M., additional, Kalogeropoulos, Andreas P., additional, Kass, David A., additional, Keaney, John, additional, Khan, Ahsan A., additional, Kim, Paul J., additional, Kobashigawa, Jon A., additional, Kransdorf, Evan P., additional, Krieger, Eric V., additional, Lam, Nicholas T., additional, Lenihan, Daniel J., additional, Lip, Gregory Y.H., additional, Longenecker, Chris T., additional, MacLellan, W. Robb, additional, Mann, Douglas L., additional, Marian, Ali J., additional, Matlock, Daniel D., additional, Maurer, Mathew S., additional, McNamara, Dennis M., additional, Mentz, Robert J., additional, Metra, Marco, additional, Milano, Carmelo A., additional, Misra, Arunima, additional, Mitchell, Joshua D., additional, Morrison, Alan R., additional, Nabeebaccus, Adam, additional, Nakamura, Kenta, additional, Nativi-Nicolau, Jose, additional, Ngo, Doan T.M., additional, Oatmen, Kelsie E., additional, Pang, Peter S., additional, Papadimitriou, Lampros, additional, Paulus, Walter J., additional, Polonsky, Tamar S., additional, Port, J. David, additional, Rader, Florian, additional, Ragupathi, Loheetha, additional, Redfield, Margaret M., additional, Rich, Michael W., additional, Rogers, Joseph G., additional, Ryan, John J., additional, Sadek, Hesham A., additional, Sag, Can Martin, additional, Sapp, Ashley A., additional, Sawyer, Douglas B., additional, Schulze, P. Christian, additional, Shah, Ajay M., additional, Shantsila, Eduard, additional, Singh, Jagmeet P., additional, Sinusas, Albert J., additional, Sliwa, Karen, additional, Spinale, Francis G., additional, Stewart, Simon, additional, Sucharov, Carmen, additional, John Sutton, Martin St., additional, Sverdlov, Aaron L., additional, Toth, Michael J., additional, Valente, Anne Marie, additional, van Heerebeek, Loek, additional, Varagic, Jasmina, additional, Victor, Ronald G., additional, Webb, Ian, additional, Wende, Adam R., additional, Whellan, David, additional, and Wiktor, Dominik M., additional

Published
2020
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28. Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study

Author

McNamara, Dennis M., Fett, James D., Pisarcik, Jessica, McTiernan, Charles, Hanley-Yanez, Karen, Gorcsan, John, III, Schelbert, Erik, Alharethi, Rami, Rasmusson, Kismet, Brunisholz, Kim, Butler, Amy, Budge, Deborah, Kfoury, A.G., Horne, Benjamin, Tuinei, Joe, Brown, Heather, Damp, Julie, Naftilan, Allen J., Russell, Jill, Freehardt, Darla, Hsich, Eileen, Oblak, Cynthia, Ewald, Greg, Whitehead, Donna, Flanagan, Jean, Platts, Anne, Elkayam, Uri, Caro, Jorge, Mullin, Stephanie, Givertz, Michael M., Anello, M. Susan, Rajagopalan, Navin, Booth, David, Sandlin, Tiffany, Wijesiri, Wendy, Cooper, Leslie T., Blauwet, Lori A., Brunner, Joann, Phelps, Mary, Kempf, Ruth, Modi, Kalgi, Norwood, Tracy, Briller, Joan, Griza, Decebal Sorin, Felker, G. Michael, Kociol, Robb, Adams, Patricia, Wells, Gretchen, Thohan, Vinay, Wesley-Farrington, Deborah, Soots, Sandra, Sheppard, Richard, Michel, Caroline, Lapointe, Nathalie, Nathaniel, Heather, Kealey, Angela, Semigran, Marc, Daher, Maureen, Boehmer, John, Silber, David, Popjes, Eric, Frey, Patricia, Nicklas, Todd, Alexis, Jeffrey, Caufield, Lori, Thornton, John W., III, Gentry, Mindy, Robinson, Vincent J.B., Sharma, Gyanendra K., Holloway, Joan, Powell, Maria, Markham, David, Drazner, Mark, Fernandez, Lynn, Zucker, Mark, Baran, David A., Gimovsky, Martin L., Hochbaum, Natalia, Patel, Bharati, Adams, Laura, Ramani, Gautam, Gottlieb, Stephen, Robinson, Shawn, Fisher, Stacy, Marshall, Joanne, Haythe, Jennifer, Mancini, Donna, Bijou, Rachel, Farr, Maryjane, Marks, Marybeth, Arango, Henry, Bozkurt, Biykem, Bolos, Mariana, Mather, Paul, Rubin, Sharon, Bonita, Raphael, Eberwine, Susan, Skopicki, Hal, Stergiopoulos, Kathleen, McCathy-Santoro, Ellen, Intravaia, Jennifer, Maas, Elizabeth, Safirstein, Jordan, Kleet, Audrey, Martinez, Nancy, Corpoin, Christine, Hesari, Donna, Chaparro, Sandra, Hudson, Laura J., Ghali, Jalal K., Injic, Zora, Wittstein, Ilan S., McTiernan, Charles F., Morel, Penelope, Thornton, John, Fett, James, and Halder, Indrani

Published
2018
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30. Improved Waitlist and Comparable Post-transplant Outcomes in Simultaneous Heart-Kidney Transplantation under the 2018 Heart Allocation System

Author

Hong, Yeahwa, primary, Hess, Nicholas R., additional, Ziegler, Luke A., additional, Hickey, Gavin W., additional, Huston, Jessica H., additional, Mathier, Michael A., additional, McNamara, Dennis M., additional, Keebler, Mary E., additional, Gómez, Hernando, additional, and Kaczorowski, David J., additional

Published
2023
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31. Serum proteomic analysis of peripartum cardiomyopathy reveals a unique disease with distinctive dysregulation of inflammatory and cholesterol metabolism pathways

Author

Lovell, Jana, primary, Bermea, Kevin, additional, Rousseau, Sylvie, additional, Cohen, Charles D., additional, Bhalodia, Aashik, additional, Zita, Marcelle Dina, additional, Yu, Jinsheng, additional, Head, Richard D., additional, Blumenthal, Roger S., additional, McNamara, Dennis M., additional, Sharma, Garima, additional, and Adamo, Luigi, additional

Published
2023
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33. Abstract 15826: SCUBE1 Controls BMPR2-relevant Pulmonary Endothelial Function: Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension

Author

Sun, Wei, Tang, Ying, Tai, Yi-Yin, Handen, Adam, Zhao, Jingsi, Speyer, Gil, Al Aaraj, Yassmin, Watson, Annie, Romanelli, Makenna, Sembrat, John C, Rojas, Mauricio, Simon, Marc A, Zhang, Yingze, Lee, Janet S, Xiong, Zeyu, Dutta, Partha, Vasamsetti, Sathish, McNamara, Dennis M, McVerry, Bryan, MCTIERNAN, Charles F, Sciurba, Frank, Kim, Seungchan, Smith, Akaya, Mazurek, Jeremy A, Han, Yuchi, Vaidya, Anjali, Nouraie, Mehdi, Kelly, Neil, and Chan, Stephen Y

Published
2020
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34. A common variant alters SCN5A-miR-24 interaction and associates with heart failure mortality

Author

Zhang, Xiaoming, Yoon, Jin-Young, Morley, Michael, McLendon, Jared M., Mapuskar, Kranti A., Gutmann, Rebecca, Mehdi, Haider, Bloom, Heather L., Dudley, Samuel C., Ellinor, Patrick T., Shalaby, Alaa A., Weiss, Raul, Tang, W.H. Wilson, Moravec, Christine S., Singh, Madhurmeet, Taylor, Anne L., Yancy, Clyde W., Feldman, Arthur M., McNamara, Dennis M., Irani, Kaikobad, Spitz, Douglas R., Breheny, Patrick, Margulies, Kenneth B., London, Barry, and Boudreau, Ryan L.

Subjects
Sodium channels -- Health aspects, MicroRNA -- Health aspects, Heart diseases -- Genetic aspects -- Development and progression -- Care and treatment, Genetic variation -- Health aspects, Health care industry
Abstract

SCN5A encodes the voltage-gated [Na.sup.+] channel [Na.sub.v]1.5 that is responsible for depolarization of the cardiac action potential and rapid intercellular conduction. Mutations disrupting the SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked to SCN5A splicing, localization, and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. We recently generated a transcriptome-wide map of microRNA (miR) binding sites in human heart, evaluated their overlap with common SNPs, and identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within the SCN5A coding sequence. This SNP was previously shown to reproducibly associate with cardiac electrophysiological parameters, but was not considered to be causal. Here, we show that miR-24 potently suppresses SCN5A expression and that rs1805126 modulates this regulation. We found that the rs1805126 minor allele associates with decreased cardiac SCN5A expression and that heart failure subjects homozygous for the minor allele have decreased ejection fraction and increased mortality, but not increased ventricular tachyarrhythmias. In mice, we identified a potential basis for this in discovering that decreased 5cn5a expression leads to accumulation of myocardial reactive oxygen species. Together, these data reiterate the importance of considering the mechanistic significance of synonymous SNPs as they relate to miRs and disease, and highlight a surprising link between SCN5A expression and nonarrhythmic death in heart failure., Introduction The onset and clinical course of heart failure is shaped by a complex interplay of environmental and genetic factors that influence a host of biological processes, including gene regulatory [...]

Published
2018
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38. Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis.

Author

Duan Liu, Min Wang, Murthy, Vishakantha, McNamara, Dennis M., Nguyen, Thanh Thanh L., Philips, Trudy J., Vyas, Hridyanshu, Huanyao Gao, Sahni, Jyotan, Starling, Randall C., Cooper, Leslie T., Skime, Michelle K., Batzler, Anthony, Jenkins, Gregory D., Barlera, Simona, Pileggi, Silvana, Mestroni, Luisa, Merlo, Marco, Sinagra, Gianfranco, and Pinet, Florence

Published
2023
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39. Sex and age differences in sST2 in cardiovascular disease

Author

Beetler, Danielle J., primary, Bruno, Katelyn A., additional, Di Florio, Damian N., additional, Douglass, Erika J., additional, Shrestha, Swikriti, additional, Tschöpe, Carsten, additional, Cunningham, Madeleine W., additional, Krejčí, Jan, additional, Bienertová-Vašků, Julie, additional, Pankuweit, Sabine, additional, McNamara, Dennis M., additional, Jeon, Eun-Seok, additional, van Linthout, Sophie, additional, Blauwet, Lori A., additional, Cooper, Leslie T., additional, and Fairweather, DeLisa, additional

Published
2023
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40. Effect of Angiotensin-Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock in Patients With Severe Systolic Heart Failure (from the GRADE Multicenter Study)

Author

AlJaroudi, Wael A., Refaat, Marwan M., Habib, Robert H., Al-Shaar, Laila, Singh, Madhurmeet, Gutmann, Rebecca, Bloom, Heather L., Dudley, Samuel C., Ellinor, Patrick T., Saba, Samir F., Shalaby, Alaa A., Weiss, Raul, McNamara, Dennis M., Halder, Indrani, and London, Barry

Published
2015
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48. Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death

Author

National Institutes of Health (US), American Heart Association, Ministerio de Sanidad (España), Junta de Andalucía, European Commission, Instituto de Salud Carlos III, University of Pittsburgh, Carew, Nolan T., Schmidt, Heidi M., Yuan, Shuai, Galley, Joseph C., Hall, Robert, Altmann, Helene M., Hahn, Scott A., Miller, Megan P., Wood, Katherine C., Gabris, Bethann, Stapleton, Margaret C., Hartwick, Sean, Fazzari, Marco, Wu, Yijen L., Trebak, Mohamed, Kaufman, Brett A., McTiernan, Charles F., Schopfer, Francisco J., Navas, Plácido, Thibodeau, Patrick H., McNamara, Dennis M., Salama, Guy, Straub, Adam C., National Institutes of Health (US), American Heart Association, Ministerio de Sanidad (España), Junta de Andalucía, European Commission, Instituto de Salud Carlos III, University of Pittsburgh, Carew, Nolan T., Schmidt, Heidi M., Yuan, Shuai, Galley, Joseph C., Hall, Robert, Altmann, Helene M., Hahn, Scott A., Miller, Megan P., Wood, Katherine C., Gabris, Bethann, Stapleton, Margaret C., Hartwick, Sean, Fazzari, Marco, Wu, Yijen L., Trebak, Mohamed, Kaufman, Brett A., McTiernan, Charles F., Schopfer, Francisco J., Navas, Plácido, Thibodeau, Patrick H., McNamara, Dennis M., Salama, Guy, and Straub, Adam C.

Abstract

Sudden cardiac death (SCD) in patients with heart failure (HF) is allied with an imbalance in reduction and oxidation (redox) signaling in cardiomyocytes; however, the basic pathways and mechanisms governing redox homeostasis in cardiomyocytes are not fully understood. Here, we show that cytochrome b5 reductase 3 (CYB5R3), an enzyme known to regulate redox signaling in erythrocytes and vascular cells, is essential for cardiomyocyte function. Using a conditional cardiomyocyte-specific CYB5R3-knockout mouse, we discovered that deletion of CYB5R3 in male, but not female, adult cardiomyocytes causes cardiac hypertrophy, bradycardia, and SCD. The increase in SCD in CYB5R3-KO mice is associated with calcium mishandling, ventricular fibrillation, and cardiomyocyte hypertrophy. Molecular studies reveal that CYB5R3-KO hearts display decreased adenosine triphosphate (ATP), increased oxidative stress, suppressed coenzyme Q levels, and hemoprotein dysregulation. Finally, from a translational perspective, we reveal that the high-frequency missense genetic variant rs1800457, which translates into a CYB5R3 T117S partial loss-of-function protein, associates with decreased event-free survival (~20%) in Black persons with HF with reduced ejection fraction (HFrEF). Together, these studies reveal a crucial role for CYB5R3 in cardiomyocyte redox biology and identify a genetic biomarker for persons of African ancestry that may potentially increase the risk of death from HFrEF.

Published
2022

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