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1. Progression of Tricuspid Regurgitation After Surgery for Ischemic Mitral Regurgitation

Author

Philippe B. Bertrand, Jessica R. Overbey, Xin Zeng, Robert A. Levine, Gorav Ailawadi, Michael A. Acker, Peter K. Smith, Vinod H. Thourani, Emilia Bagiella, Marissa A. Miller, Lopa Gupta, Michael J. Mack, A. Marc Gillinov, Gennaro Giustino, Alan J. Moskowitz, Annetine C. Gelijns, Michael E. Bowdish, Patrick T. O’Gara, James S. Gammie, Judy Hung, Wendy C. Taddei-Peters, Dennis Buxton, Ron Caulder, Nancy L. Geller, David Gordon, Neal O. Jeffries, Albert Lee, Claudia S. Moy, Ilana Kogan Gombos, Jennifer Ralph, Richard D. Weisel, Timothy J. Gardner, Eric A. Rose, Michael K. Parides, Deborah D. Ascheim, Ellen Moquete, Helena Chang, Melissa Chase, James Foo, Yingchun Chen, Seth Goldfarb, Katherine Kirkwood, Edlira Dobrev, Ron Levitan, Karen O’Sullivan, Jessica Overbey, Milerva Santos, Deborah Williams, Michael Weglinski, Paula Williams, Carrie Wood, Xia Ye, Sten Lyager Nielsen, Henrik Wiggers, Henning Malgaard, Michael Mack, Tracine Adame, Natalie Settele, Jenny Adams, William Ryan, Robert L. Smith, Paul Grayburn, Frederick Y. Chen, Anju Nohria, Lawrence Cohn, Prem Shekar, Sary Aranki, Gregory Couper, Michael Davidson, R. Morton Bolman, Anne Burgess, Debra Conboy, Rita Lawrence, Nicolas Noiseux, Louis-Mathieu Stevens, Ignacio Prieto, Fadi Basile, Joannie Dionne, Julie Fecteau, Eugene H. Blackstone, Pamela Lackner, Leoma Berroteran, Diana Dolney, Suzanne Fleming, Roberta Palumbo, Christine Whitman, Kathy Sankovic, Denise Kosty Sweeney, Carrie Geither, Kristen Doud, Gregory Pattakos, Pamela A. Clarke, Michael Argenziano, Mathew Williams, Lyn Goldsmith, Craig R. Smith, Yoshifumi Naka, Allan Stewart, Allan Schwartz, Daniel Bell, Danielle Van Patten, Sowmya Sreekanth, John H. Alexander, Carmelo A. Milano, Donald D. Glower, Joseph P. Mathew, J. Kevin Harrison, Stacey Welsh, Mark F. Berry, Cyrus J. Parsa, Betty C. Tong, Judson B. Williams, T. Bruce Ferguson, Alan P. Kypson, Evelio Rodriguez, Malissa Harris, Brenda Akers, Allison O'Neal, John D. Puskas, Robert Guyton, Jefferson Baer, Kim Baio, Alexis A. Neill, Pierre Voisine, Mario Senechal, François Dagenais, Kim O’Connor, Gladys Dussault, Tatiana Ballivian, Suzanne Keilani, Alan M. Speir, Patrick Magee, Niv Ad, Sally Keyte, Minh Dang, Mark Slaughter, Marsha Headlee, Heather Moody, Naresh Solankhi, Emma Birks, Mark A. Groh, Leslie E. Shell, Stephanie A. Shepard, Benjamin H. Trichon, Tracy Nanney, Lynne C. Hampton, Ralph Mangusan, Robert E. Michler, David A. D'Alessandro, Joseph J. DeRose, Daniel J. Goldstein, Ricardo Bello, William Jakobleff, Mario Garcia, Cynthia Taub, Daniel Spevak, Roger Swayze, Nadia Sookraj, Louis P. Perrault, Arsène-Joseph Basmadjian, Denis Bouchard, Michel Carrier, Raymond Cartier, Michel Pellerin, Jean François Tanguay, Ismail El-Hamamsy, André Denault, Philippe Demers, Sophie Robichaud Jonathan Lacharité, Keith A. Horvath, Philip C. Corcoran, Michael P. Siegenthaler, Mandy Murphy, Margaret Iraola, Ann Greenberg, Chittoor Sai-Sudhakar, Ayseha Hasan, Asia McDavid, Bradley Kinn, Pierre Pagé, Carole Sirois, David Latter, Howard Leong-Poi, Daniel Bonneau, Lee Errett, Mark D. Peterson, Subodh Verma, Randi Feder-Elituv, Gideon Cohen, Campbell Joyner, Stephen E. Fremes, Fuad Moussa, George Christakis, Reena Karkhanis, Terry Yau, Michael Farkouh, Anna Woo, Robert James Cusimano, Tirone David, Christopher Feindel, Lisa Garrard, Suzanne Fredericks, Amelia Mociornita, John C. Mullen, Jonathan Choy, Steven Meyer, Emily Kuurstra, Cindi A. Young, Dana Beach, Robert Villanueva, Pavan Atluri, Y. Joseph Woo, Mary Lou Mayer, Michael Bowdish, Vaughn A. Starnes, David Shavalle, Ray Matthews, Shadi Javadifar, Linda Romar, Irving L. Kron, Karen Johnston, John M. Dent, John Kern, Jessica Keim, Sandra Burks, Kim Gahring, David A. Bull, Patrice Desvigne-Nickens, Dennis O. Dixon, Mark Haigney, Richard Holubkov, Alice Jacobs, Frank Miller, John M. Murkin, John Spertus, Andrew S. Wechsler, Frank Sellke, Cheryl L. McDonald, Robert Byington, Neal Dickert, John S. Ikonomidis, David O. Williams, Clyde W. Yancy, James C. Fang, Nadia Giannetti, Wayne Richenbacher, Vivek Rao, Karen L. Furie, Rachel Miller, Sean Pinney, William C. Roberts, Mary N. Walsh, Niamh Kilcullen, David Hung, Stephen J. Keteyian, Clinton A. Brawner, Heather Aldred, Jeffrey Browndyke, and Yanne Toulgoat-Dubois

Subjects
Male, Pacemaker, Artificial, medicine.medical_specialty, medicine.medical_treatment, Myocardial Ischemia, 030204 cardiovascular system & hematology, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Recurrence, medicine, Humans, Clinical significance, Prospective Studies, 030212 general & internal medicine, Stroke, Aged, Heart Failure, Mitral valve repair, business.industry, Area under the curve, Mitral Valve Insufficiency, Atrial fibrillation, medicine.disease, Tricuspid Valve Insufficiency, Defibrillators, Implantable, Surgery, Hospitalization, Echocardiography, Heart failure, Disease Progression, Female, Tricuspid Valve, Tricuspid Valve Regurgitation, Cardiology and Cardiovascular Medicine, Mitral valve regurgitation, business, Follow-Up Studies
Abstract

Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain.The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery.Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years.Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04).After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

Published
2021
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2. The impact of perioperative stroke and delirium on outcomes after surgical aortic valve replacement

Author

Steven R. Messé, Jessica R. Overbey, Vinod H. Thourani, Alan J. Moskowitz, Annetine C. Gelijns, Mark A. Groh, Michael J. Mack, Gorav Ailawadi, Karen L. Furie, Andrew M. Southerland, Michael L. James, Claudia Scala Moy, Lopa Gupta, Pierre Voisine, Louis P. Perrault, Michael E. Bowdish, A. Marc Gillinov, Patrick T. O'Gara, Maral Ouzounian, Bryan A. Whitson, John C. Mullen, Marissa A. Miller, James S. Gammie, Stephanie Pan, Guray Erus, Jeffrey N. Browndyke, Wendy C. Taddei-Peters, Neal O. Jeffries, Dennis Buxton, Nancy L. Geller, David Gordon, Catherine Burke, Albert Lee, Tyrone Smith, Claudia S. Moy, Ilana Kogan Gombos, Richard Weisel, Timothy J. Gardner, Eric A. Rose, Michael K. Parides, Deborah D. Ascheim, Emilia Bagiella, Ellen Moquete, Kinjal Shah, Helena Chang, Melissa Chase, Seth Goldfarb, Katherine Kirkwood, Edlira Dobrev, Ron Levitan, Karen O'Sullivan, Milerva Santos, Xia Ye, Michael Mack, Rachelle Winkle, Haley Boswell, Amanda Fenlon, Melissa Johnson, Jessica Jones, Megan Kolb, Sarah Lam, Lucy Miranda, Jackie Ward, Renessa Whitman, Brittany Zingler, William Ryan, Robert L. Smith, Paul Grayburn, Pedro Nosnik, Eugene H. Blackstone, Nader Moazami, Randall C. Starling, Benico Barzilai, Richard A. Grimm, Edward G. Soltesz, Irene Katzan, Brian Strippy, Shoi Smith, Michelle Garcia, Mary Alice bowman, Carrie Geither, Robert Wang, Michael Argenziano, Michael Borger, Hiroo Takayama, Martin B. Leon, Lyn Goldsmith, Allan Schwartz, Nadia Sookraj, Talaya McCright-Gill, Sowmya Sreekanth, Jock N. McCullough, Alexander Iribarne, Joseph P. DeSimone, Anthony W. DiScipio, Henry Stokes, Amanda St. Ivany, Gaylin Petty, Peter K. Smith, John H. Alexander, Carmelo A. Milano, Donald D. Glower, Joel Huber, Joel Morganlander, Joseph P. Mathew, Stacey Welsh, Sarah Casalinova, Victoria Johnson, Kathleen Lane, Derek Smith, Greg Tipton, Mark F. Berry, Judson B. Williams, Brian Englum, Matthew Hartwig, Robert Guyton, Omar Lattouf, Edward Chen, J. David Vega, Jefferson Baer, Duc Nguyen, Michael Halkos, Kim Baio, Tamara Prince, Natascha Cook, Alexis A. Neill, Mario Senechal, François Dagenais, Robert Laforce, Kim O'Connor, Gladys Dussault, Manon Caouette, Hugo Tremblay, Nathalie Gagne, Julie Dumont, Patricia Landry, Benjamin H. Trichon, Oliver A. Binns, Stephen W. Ely, Alan M. Johnson, Todd H. Hansen, John G. Short, Reid D. Taylor, Ralph Mangusan, Tracy Nanney, Holly Aubart, Kristin Cross, Leslie McPeters, Christina Riggsbee, Lucy Rixey, Robert E. Michler, Joseph J. DeRose, Daniel J. Goldstein, Ricardo A. Bello, Cynthia Taub, Daniel Spevack, Kathryn Kirchoff, Rebecca Meli, Juan Garcia, Jon Goldenberg, Lauren Kealy, Denis Bouchard, Jean François Tanguay, Eileen O'Meara, Jonathan Lacharité, Sophie Robichaud, Keith A. Horvath, Philip C. Corcoran, Michael P. Siegenthaler, Mandy Murphy, Margaret Iraola, Ann Greenberg, Greg Kumkumian, Mark Milner, Zurab Nadareishvili, Ayesha Hasan, Asia McDavid, Denise Fadorsen, Terry Yau, Michael Farkouh, Anna Woo, Robert James Cusimano, Tirone David, Christopher Feindel, Nishit Fumakia, Shakira Christie, Asvina Bissonauth, Alexandra Hripko, Zahid Noor, Kristen Mackowick, Stephanie Deasey, Manal Al-Suqi, Julia Collins, Michael A. Acker, Steven Messé, James Kirkpatrick, Mary Lou Mayer, Caitlin McDonald, Holley Fok, Breanna Maffei, Stephen Cresse, Christine Gepty, Michael Bowdish, Vaughn A. Starnes, David Shavalle, Christi Heck, Amy Hackmann, Craig Baker, Fernando Fleischman, Mark Cunningham, Edward Lozano, Michelle Hernandez, Irving L. Kron, Karen Johnston, Ravi K. Ghanta, John M. Dent, John Kern, Leora Yarboro, Michael Ragosta, Brian Annex, Jim Bergin, Sandra Burks, Mike Cosner, China Green, Samantha Loya, Hye Ryun Kim, David A. Bull, Patrice Desvigne-Nickens, Dennis O. Dixon, Rebecca Gottesman, Mark Haigney, Richard Holubkov, Constantino Iadecola, Alice Jacobs, Eric M. Meslin, John M. Murkin, John A. Spertus, Frank Sellke, Cheryl L. McDonald, John Canty, Neal Dickert, John S. Ikonomidis, KyungMann Kim, David O. Williams, Clyde W. Yancy, Seemant Chaturvedi, Marc Chimowitz, James C. Fang, Wayne Richenbacher, Vivek Rao, Rachel Miller, Jennifer Cook, David D'Alessandro, Frederick Han, Sean Pinney, Mary N. Walsh, David Greer, Koto Ishida, Christian Stapf, Judy Hung, Xin Zeng, David Hung, Sudarat Satitthummanid, Michel Billelo, Christos Davatzikos, Lauren Karpf, Lisa Desiderio, Yanne Toulgoat-Dubois, Rachele Brassard, Renu Virmanu, Maria E. Romero, and Ryan Braumann

Subjects
Pulmonary and Respiratory Medicine, Surgery, Cardiology and Cardiovascular Medicine
Abstract

The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days.Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life.By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01).Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Published
2022
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3. Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators

Author

Wojciech Zareba, James P. Daubert, Christopher A. Beck, David T. Huang, Jeffrey D. Alexis, Mary W. Brown, Kathryn Pyykkonen, Scott McNitt, David Oakes, Changyong Feng, Mehmet K. Aktas, Felix Ayala-Parades, Adrian Baranchuk, Marc Dubuc, Mark Haigney, Alexander Mazur, Craig A. McPherson, L. Brent Mitchell, Andrea Natale, Jonathan P. Piccini, Merritt Raitt, Mayer Y. Rashtian, Claudio Schuger, Stephen Winters, Seth J. Worley, Ohad Ziv, Arthur J. Moss, W. Zareba, K. Pyykkonen, A. Buttaccio, E. Perkins, D. DeGrey, S. Robertson, A.J. Moss, M. Brown, R. Lansing, A. Oberer, B. Polonsky, V. Ross, A. Papernov, S. Schleede, C. Beck, D. Oakes, C. Feng, S. McNitt S, W.J. Hall, A. Moss, J. Daubert, D. Huang, S. Winters, C. Schuger, M. Haigney, J. Piccini, J. Alexis, L. Chen, A. Miller, J.F. Richeson, S. Rosero, V. Kutyifa, A. Shah, G. Lamas, F. Cohn, F. Harrell, I. Piña, J. Poole, M. Sullivan, D. Lathrop, N. Geller, R. Boineau, J. Trondell, L. Cooper, E. Itturiaga, C. Gottlieb, S. Greer, C. Perzanowski, C. McPherson, C. Hedgepeth, C. Assal, T. Salam, I. Woollett, G. Tomassoni, F. Ayala-Paredes, A. Russo, S. Punnam, R. Sangrigoli, S. Sloan, S. Kutalek, A. Sun, D. Lustgarten, G. Monir, D. Haithcock, R. Sorrentino, D. Cannom, J. Kluger, S. Varanasi, M. Rashtian, F. Philippon, R. Berger, M. Mazzella, T. Lessmeier, J. Silver, S. Worley, M. Bernabei, D. Esberg, M. Dixon, P. LeLorier, Y. Greenberg, V. Essebag, G. Venkataraman, T. Shinn, M. Dubuc, G. Turitto, C. Henrikson, M. Mirro, M. Raitt, A. Baranchuk, G. O'Neill, E. Lockwood, M. Vloka, J. Hurwitz, R.H. Mead, P. Somasundarum, E. Aziz, E. Rashba, A. Budzikowski, M. Cox, A. Natale, E. Chung, O. Ziv, F. McGrew, K. Tamirisa, A. Greenspon, M. Estes, S. Taylor, R. Janardhanan, L.B. Mitchell, M. Burke, M. Attari, B. Mikaelian, S. Hsu, J. Conti, A. Mazur, S. Shorofsky, L. Rosenthal, S. Sakaguchi, D. Wolfe, G. Flaker, S. Saba, M. Aktas, P. Mason, A. Shalaby, D. Musat, R. Abraham, K. Ellenbogen, C. Fellows, N. Kavesh, G. Thomas, D. Hemsworth, and B. Williamson

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Hazard ratio, Ranolazine, 030204 cardiovascular system & hematology, Implantable cardioverter-defibrillator, Lower risk, Ventricular tachycardia, medicine.disease, Placebo, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Ventricular fibrillation, medicine, Clinical endpoint, Cardiology, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs). Objectives This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD. Methods This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy. Results Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life. Conclusions In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253)

Published
2018
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4. Risk for non-home discharge following surgery for ischemic mitral valve disease

Author

Anuradha Lala, Helena L. Chang, Xiaoyu Liu, Eric J. Charles, Babatunde A. Yerokun, Michael E. Bowdish, Vinod H. Thourani, Michael J. Mack, Marissa A. Miller, Patrick T. O'Gara, Eugene H. Blackstone, Alan J. Moskowitz, Annetine C. Gelijns, John C. Mullen, Lynne W. Stevenson, Joseph J. DeRose, Alice Wang, Peter K. Smith, Michael A. Acker, Gorav Ailawadi, Wendy C. Taddei-Peters, Dennis Buxton, Ron Caulder, Nancy L. Geller, David Gordon, Neal O. Jeffries, Albert Lee, Ilana Kogan Gombos, Jennifer Ralph, Richard D. Weisel, Timothy J. Gardner, Eric A. Rose, Michael K. Parides, Deborah D. Ascheim, Emilia Bagiella, Ellen Moquete, Helena Chang, Melissa Chase, James Foo, Yingchun Chen, Seth Goldfarb, Lopa Gupta, Katherine Kirkwood, Edlira Dobrev, Ron Levitan, Karen O'Sullivan, Jessica Overbey, Milerva Santos, Deborah Williams, Michael Weglinski, Paula Williams, Carrie Wood, Xia Ye, Sten Lyager Nielsen, Henrik Wiggers, Henning Malgaard, Michael Mack, Tracine Adame, Natalie Settele, Jenny Adams, William Ryan, Robert L. Smith, Paul Grayburn, Frederick Y. Chen, Anju Nohria, Lawrence Cohn, Prem Shekar, Sary Aranki, Gregory Couper, Michael Davidson, R. Morton Bolman, Anne Burgess, Debra Conboy, Rita Lawrence, Nicolas Noiseux, Louis-Mathieu Stevens, Ignacio Prieto, Fadi Basile, Joannie Dionne, Julie Fecteau, A. Marc Gillinov, Pamela Lackner, Leoma Berroteran, Diana Dolney, Suzanne Fleming, Roberta Palumbo, Christine Whitman, Kathy Sankovic, Denise Kosty Sweeney, Carrie Geither, Kristen Doud, Gregory Pattakos, Pamela A. Clarke, Michael Argenziano, Mathew Williams, Lyn Goldsmith, Craig R. Smith, Yoshifumi Naka, Allan Stewart, Allan Schwartz, Daniel Bell, Danielle Van Patten, Sowmya Sreekanth, John H. Alexander, Carmelo A. Milano, Donald D. Glower, Joseph P. Mathew, J. Kevin Harrison, Stacey Welsh, Mark F. Berry, Cyrus J. Parsa, Betty C. Tong, Judson B. Williams, T. Bruce Ferguson, Alan P. Kypson, Evelio Rodriguez, Malissa Harris, Brenda Akers, Allison O'Neal, John D. Puskas, Robert Guyton, Jefferson Baer, Kim Baio, Alexis A. Neill, Pierre Voisine, Mario Senechal, François Dagenais, Kim O'Connor, Gladys Dussault, Tatiana Ballivian, Suzanne Keilani, Alan M. Speir, Patrick Magee, Niv Ad, Sally Keyte, Minh Dang, Mark Slaughter, Marsha Headlee, Heather Moody, Naresh Solankhi, Emma Birks, Mark A. Groh, Leslie E. Shell, Stephanie A. Shepard, Benjamin H. Trichon, Tracy Nanney, Lynne C. Hampton, Ralph Mangusan, Robert E. Michler, David A. D'Alessandro, Daniel J. Goldstein, Ricardo Bello, William Jakobleff, Mario Garcia, Cynthia Taub, Daniel Spevak, Roger Swayze, Nadia Sookraj, Louis P. Perrault, Arsène-Joseph Basmadjian, Denis Bouchard, Michel Carrier, Raymond Cartier, Michel Pellerin, Jean François Tanguay, Ismail El-Hamamsy, André Denault, Philippe Demers, Sophie Robichaud Jonathan Lacharité, Keith A. Horvath, Philip C. Corcoran, Michael P. Siegenthaler, Mandy Murphy, Margaret Iraola, Ann Greenberg, Chittoor Sai-Sudhakar, Ayseha Hasan, Asia McDavid, Bradley Kinn, Pierre Pagé, Carole Sirois, David Latter, Howard Leong-Poi, Daniel Bonneau, Lee Errett, Mark D. Peterson, Subodh Verma, Randi Feder-Elituv, Gideon Cohen, Campbell Joyner, Stephen E. Fremes, Fuad Moussa, George Christakis, Reena Karkhanis, Terry Yau, Michael Farkouh, Anna Woo, Robert James Cusimano, Tirone David, Christopher Feindel, Lisa Garrard, Suzanne Fredericks, Amelia Mociornita, Jonathan Choy, Steven Meyer, Emily Kuurstra, James S. Gammie, Cindi A. Young, Dana Beach, Robert Villanueva, Pavan Atluri, Y. Joseph Woo, Mary Lou Mayer, Michael Bowdish, Vaughn A. Starnes, David Shavalle, Ray Matthews, Shadi Javadifar, Linda Romar, Irving L. Kron, Karen Johnston, John M. Dent, John Kern, Jessica Keim, Sandra Burks, Kim Gahring, David A. Bull, Dennis O. Dixon, Mark Haigney, Richard Holubkov, Alice Jacobs, Frank Miller, John M. Murkin, John Spertus, Andrew S. Wechsler, Frank Sellke, Robert Byington, Neal Dickert, John S. Ikonomidis, David O. Williams, Clyde W. Yancy, James C. Fang, Nadia Giannetti, Wayne Richenbacher, Vivek Rao, Karen L. Furie, Rachel Miller, Sean Pinney, William C. Roberts, Mary N. Walsh, Judy Hung, Xin Zeng, Niamh Kilcullen, David Hung, Stephen J. Keteyian, Clinton A. Brawner, Heather Aldred, Jeffrey Browndyke, and Yanne Toulgoat-Dubois

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Myocardial Ischemia, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Risk Factors, Mitral valve, Humans, Medicine, Prospective Studies, Adverse effect, Aged, Mitral regurgitation, business.industry, Mitral Valve Insufficiency, Odds ratio, Middle Aged, medicine.disease, Patient Discharge, Confidence interval, 3. Good health, Cardiac surgery, Surgery, Treatment Outcome, medicine.anatomical_structure, 030228 respiratory system, Heart failure, Quality of Life, Female, Cardiology and Cardiovascular Medicine, business
Abstract

To determine the frequency and risk factors for non-home discharge (NHD) and its association with clinical outcomes and quality of life (QOL) at 1 year following cardiac surgery in patients with ischemic mitral regurgitation (IMR).Discharge disposition was evaluated in 552 patients enrolled in trials of severe or moderate IMR. Patient and in-hospital factors associated with NHD were identified using logistic regression. Subsequently, association of NHD with 1-year mortality, serious adverse events (SAEs), and QOL was assessed.NHD was observed in 30% (154/522) with 25% (n = 71/289) in moderate and 36% (n = 83/233) in patients with severe IMR (unadjusted P = .006), a difference not significant after including age (5-year change: adjusted odds ratio [adjOR], 1.52; 95% confidence interval [CI], 1.35-1.72; P .001), diabetes (adjOR, 1.94; 95% CI, 1.27-2.94; P = .002), and previous heart failure (adjOR, 1.64; 95% CI, 1.06-2.52; P = .03). Odds of NHD were increased for patients with postoperative SAEs (adjOR, 1.85; 95% CI, 1.19-2.86; P = .01) but not based on type of cardiac surgery. Greater rates of death and SAEs were observed in NHD patients at 1 year: adjusted hazard ratio, 4.29 (95% CI, 2.14-8.59; P .001) and adjusted rate ratio, 1.45 (95% CI, 1.03-2.02; P = .03), respectively. QOL did not differ significantly between groups.NHD is common following surgery for IMR, influenced by older age, diabetes, previous heart failure, and postoperative SAEs. These patients may be at greater risk of death and subsequent SAEs after discharge. Discussion of NHD with patients may have important implications for decision-making and guiding expectations following cardiac surgery.

Published
2021
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5. Potent Inhibition of hERG Channels by the Over-the-Counter Antidiarrheal Agent Loperamide

Author

Mark Haigney, Michael Klein, Philip S. Mehler, Naheed Fatima, Mori J. Krantz, and Thomas P. Flagg

Subjects
Agonist, medicine.medical_specialty, Loperamide, Swine, medicine.drug_class, Heart Ventricles, hERG, CHO Cells, 030204 cardiovascular system & hematology, Pharmacology, 03 medical and health sciences, Cricetulus, 0302 clinical medicine, Cricetinae, Internal medicine, medicine, Animals, Humans, Repolarization, Myocytes, Cardiac, Channel blocker, cardiovascular diseases, 030212 general & internal medicine, Antidiarrheals, IC50, Cells, Cultured, biology, Chemistry, Ether-A-Go-Go Potassium Channels, Potassium channel, Diarrhea, Endocrinology, biology.protein, medicine.symptom, medicine.drug
Abstract

The aim of this study was to determine the in vitro electrophysiological properties of loperamide. The authors' hypothesis was that loperamide is a potent blocker of the current carried by the human ether-à-go-go-related gene (hERG) potassium channel.Loperamide is a peripherally-acting μ-opioid agonist available worldwide as an over-the-counter treatment for diarrhea. Like most opioids, it is not currently known to be proarrhythmic. Recent cases of torsade de pointes in association with high-dose loperamide raise concern given its structural similarity to methadone, another synthetic opioid with an established arrhythmia risk.Effects of loperamide on blockade of the hERG potassium channel ion current were assessed in Chinese Hamster Ovary (CHO) cells stably expressing hERG to elucidate current amplitude and kinetics. The concentration required to produce 50% inhibition of hERG current was assessed from the amplitude of tail currents and the impact on action potential duration was assessed in isolated swine ventricular cardiomyocytes.The 50% inhibitory concentration for loperamide inhibition of hERG ionic tail currents was approximately 40 nmol/l. In current-voltage measurements, loperamide reduced steady and tail currents and shifted the current activation to more negative potentials. Loperamide (10 nmol/l) also increased the action potential duration, assessed at 90% of repolarization, in ventricular myocytes by 16.4 ± 1.7% (n = 6; p 0.004). The maximum rate of rise of phase 0 of the action potential, however, was not significantly altered at any tested concentration of loperamide.Loperamide is a potent hERG channel blocker. It significantly prolongs the action potential duration and suggests a causal association between loperamide and recent clinical cases of torsade de pointes.

Published
2016
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6. Multicenter Cardiovascular Studies and Trials

Author

Arthur J. Moss, Jesia Benhorin, Thomas Bigger, Poul Eric Block-Thomsen, Monty Bodenheimer, Mary Brown, Robert Case, Edward M. Dwyer, Shirley Eberly, Joseph Fleiss, Charles Francis, John Gillespie, Robert Goldstein, Henry Greenberg, Mark Haigney, Helmut Klein, Ronald Krone, Valentina Kutyifa, Edgar Lichstein, Emanuela Locati, Frank Marcus, David Oakes, Charles Odoroff, Daniel Ryan, Wojciech Zareba, Christopher Beck, David Cannom, James Daubert, Mark Estes, Ilan Goldenberg, Jack Hall, Stephen Hammes, David Huang, Reinoud Knops, Michael Kosiborod, Jeanne Poole, Claudio Schuger, Jagmeet Singh, Scott Solomon, and David Wilber

Subjects
Gerontology, medicine.medical_specialty, business.industry, MEDLINE, Alternative medicine, 030204 cardiovascular system & hematology, Executive committee, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Family medicine, Medicine, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business
Abstract

[Figure][1] The Heart Research Follow-up Program at the University of Rochester Medical Center has an ongoing record of successfully carrying out large-scale clinical cardiovascular studies and randomized clinical trials for >35 years, and nearly all of the original executive committee

Published
2016
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7. Assessing the interaction of respiration and heart rate in heart failure and controls using ambulatory Holter recordings

Author

Mark Haigney, Maria Teresa La Rovere, Ian Grasso, Wojceich Zareba, and David Mortara

Subjects
medicine.medical_specialty, Sensitivity and Specificity, Pattern Recognition, Automated, Respiratory Rate, Heart Rate, Internal medicine, Respiration, Heart rate, Humans, Medicine, Diagnosis, Computer-Assisted, Respiratory system, Heart Failure, business.industry, Reproducibility of Results, Sleep apnea, medicine.disease, Heart failure, Ambulatory, Electrocardiography, Ambulatory, Breathing, Cardiology, Analysis of variance, Cardiology and Cardiovascular Medicine, business, Algorithms
Abstract

Breathing is a critical component of cardiopulmonary function, but few tools exist to evaluate respiration in ambulatory patients. Holter monitoring allows accurate diagnosis of a host of cardiac issues, and several investigators have demonstrated the ability to detect respiratory effort on the electrocardiogram. In this study we introduce a myogram signal derived from 12-lead, high frequency Holter as a means of detecting respiratory effort. Using the combined myogram and ECG signal, four novel variables were created: total number of Cheyne-Stokes episodes; the BWRatio, the ratio of power (above baseline) measured one second after peak-to-peak respiratory power, an assessment of the "shape" of the respiratory effort; DRR, the change in RR interval centering around peak inspiration; and minutes of synchronized breathing, a fixed ratio of heart beats to respiratory cycles. These variables were assessed in 24-hour recordings from three cohorts: healthy volunteers (n=33), heart failure subjects from the GISSI HF trial (n=383), and subjects receiving implantable defibrillators with severely depressed left ventricular function enrolled in the M2Risk trial (n=470). We observed a statistically significant 6-fold increase in the number of Cheyne-Stokes episodes (p=0.01 by ANOVA), decreases in BWRatio (p0.001), as well as decrease in DRR in heart failure subjects; only minutes of synchronized breathing was not significantly decreased in heart failure. This study provides "proof of concept" that novel variables incorporating Holter-derived respiration can distinguish healthy subjects from heart failure. The utility of these variables for predicting heart failure, arrhythmia, and death risk in prospective studies needs to be assessed.

Published
2014
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8. Biatrial maze procedure versus pulmonary vein isolation for atrial fibrillation during mitral valve surgery: New analytical approaches and end points

Author

Eugene H. Blackstone, Helena L. Chang, Jeevanantham Rajeswaran, Michael K. Parides, Hemant Ishwaran, Liang Li, John Ehrlinger, Annetine C. Gelijns, Alan J. Moskowitz, Michael Argenziano, Joseph J. DeRose, Jean-Phillipe Couderc, Dan Balda, François Dagenais, Michael J. Mack, Gorav Ailawadi, Peter K. Smith, Michael A. Acker, Patrick T. O'Gara, A. Marc Gillinov, Marissa A. Miller, Wendy C. Taddei-Peters, Dennis Buxton, Amy Connolly, Nancy L. Geller, David Gordon, Neal O. Jeffries, Albert Lee, Claudia S. Moy, Ilana Kogan Gombos, Jennifer Ralph, Richard Weisel, Timothy J. Gardner, Eric A. Rose, Deborah D. Ascheim, Emilia Bagiella, Ellen Moquete, Helena Chang, Melissa Chase, Seth Goldfarb, Lopa Gupta, Katherine Kirkwood, Edlira Kumbarce, Ron Levitan, Karen O'Sullivan, Jessica Overbey, Milerva Santos, Michael Weglinski, Paula Williams, Carrie Wood, Xia Ye, Michael Mack, Tracine Adame, Natalie Settele, Jenny Adams, William Ryan, Robert L. Smith, Paul Grayburn, Frederick Y. Chen, Anju Nohria, Lawrence Cohn, Prem Shekar, Sary Aranki, Gregory Couper, Michael Davidson, R. Morton Bolman, Anne Burgess, Debra Conboy, Ray Blackwell, Roger Kerzner, Michael Banbury, Andrea M. Squire, Bruce Lytle, Tomislav Mihaljevic, Pamela Lackner, Leoma Berroteran, Diana Dolney, Suzanne Fleming, Roberta Palumbo, Christine Whitman, Kathy Sankovic, Denise Kosty Sweeney, Gregory Pattakos, Mathew Williams, Lyn Goldsmith, Craig R. Smith, Yoshifumi Naka, Allan Stewart, Allan Schwartz, Daniel Bell, Danielle Van Patten, Sowmya Sreekanth, John H. Alexander, Carmelo A. Milano, Donald D. Glower, Joseph P. Mathew, J. Kevin Harrison, Stacey Welsh, T. Bruce Ferguson, Alan P. Kypson, Evelio Rodriguez, Malissa Harris, Brenda Akers, Allison O'Neal, John D. Puskas, Vinod H. Thourani, Robert Guyton, Jefferson Baer, Kim Baio, Alexis A. Neill, Pierre Voisine, Mario Senechal, Kim O'Connor, Gladys Dussault, Tatiana Ballivian, Suzanne Keilani, Robert E. Michler, David A. D'Alessandro, Daniel J. Goldstein, Ricardo Bello, William Jakobleff, Mario Garcia, Cynthia Taub, Daniel Spevack, Roger Swayze, Nadia Sookraj, Louis P. Perrault, Arsène-Joseph Basmadjian, Denis Bouchard, Michel Carrier, Raymond Cartier, Michel Pellerin, Jean François Tanguay, Ismael El-Hamamsy, André Denault, Jonathan Lacharité, Sophie Robichaud, David H. Adams, Robin Varghese, Yael Mandel-Portnoy, Keith A. Horvath, Philip C. Corcoran, Michael P. Siegenthaler, Mandy Murphy, Margaret Iraola, Ann Greenberg, Chittoor Sai-Sudhakar, Ayseha Hasan, Asia McDavid, Bradley Kinn, John C. Mullen, Jonathan Choy, Steven Meyer, Emily Kuurstra, James S. Gammie, Christopher R. DeFilippi, Dino T. Gaetani, Cindi A. Young, Dana Beach, Julia Collins, Steven F. Bolling, Francis D. Pagani, Cathie Bloem, Y. Joseph Woo, Mary Lou Mayer, Joseph E. Bavaria, Wilson Y. Szeto, Kenneth Margulies, Martin Keane, Helene Glassberg, Dinesh Jagasia, James Kirkpatrick, Irving L. Kron, Karen Johnston, John M. Dent, John Kern, Jessica Keim, Sandra Burks, Kim Gahring, Abeel Mangi, Joseph Akar, David Yuh, Lynn Wilson, David A. Bull, Patrice Desvigne-Nickens, Dennis O. Dixon, Mark Haigney, Richard Holubkov, Alice Jacobs, Frank Miller, John M. Murkin, John Spertus, Andrew S. Wechsler, Frank Sellke, Cheryl L. McDonald, Robert Byington, Neal Dickert, John S. Ikonomidis, David O. Williams, Clyde W. Yancy, John M. Canty, James C. Fang, Nadia Giannetti, Wayne Richenbacher, Vivek Rao, Karen L. Furie, Rachel Miller, Sean Pinney, William C. Roberts, Mary N. Walsh, Judy Hung, Xin Zeng, Jean-Philippe Couderc, Wayne Bowen, Mauri Wilson, and Anne Schering

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, medicine.medical_treatment, Atrial fibrillation, Odds ratio, 030204 cardiovascular system & hematology, Ablation, medicine.disease, Confidence interval, 3. Good health, Confirmatory trial, Pulmonary vein, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, medicine, Cardiology, Surgery, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Atrial tachycardia, Atrial flutter
Abstract

Objective To use novel statistical methods for analyzing the effect of lesion set on (long-standing) persistent atrial fibrillation (AF) in the Cardiothoracic Surgical Trials Network trial of surgical ablation during mitral valve surgery (MVS). Methods Two hundred sixty such patients were randomized to MVS + surgical ablation or MVS alone. Ablation was randomized between pulmonary vein isolation and biatrial maze. During 12 months postsurgery, 228 patients (88%) submitted 7949 transtelephonic monitoring (TTM) recordings, analyzed for AF, atrial flutter (AFL), or atrial tachycardia (AT). As previously reported, more ablation than MVS-alone patients were free of AF or AF/AFL at 6 and 12 months (63% vs 29%; P Results Estimated freedom from AF/AFL/AT on any transmission trended higher after biatrial maze than pulmonary vein isolation (odds ratio, 2.31; 95% confidence interval, 0.95-5.65; P = .07) 3 to 12 months postsurgery; estimated AF/AFL/AT load (ie, proportion of TTM strips recording AF/AFL/AT) was similar (odds ratio, 0.90; 95% confidence interval, 0.57-1.43; P = .6). Within 12 months, estimated prevalence of AF/AFL/AT by TTM was 58% after MVS alone, and 36% versus 23% after pulmonary vein isolation versus biatrial maze (P Conclusions Statistical modeling using TTM recordings after MVS in patients with (long-standing) persistent AF suggests that a biatrial maze is associated with lower AF/AFL/AT prevalence, but not a lower load, compared with pulmonary vein isolation. The discrepancy between AF/AFL/AT prevalence assessed at 2 time points by Holter monitoring versus weekly TTM suggests the need for a confirmatory trial, reassessment of definitions for failure after ablation, and validation of statistical methods for assessing atrial rhythms longitudinally.

Published
2019
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