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1. The Box—eHealth in the Outpatient Clinic Follow-up of Patients With Acute Myocardial Infarction: Cost-Utility Analysis

Author

Roderick Willem Treskes, M Elske van den Akker-van Marle, Louise van Winden, Nicole van Keulen, Enno Tjeerd van der Velde, Saskia Beeres, Douwe Atsma, and Martin Jan Schalij

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundSmartphone compatible wearables have been released on the consumers market, enabling remote monitoring. Remote monitoring is often named as a tool to reduce the cost of care. ObjectiveThe primary purpose of this paper is to describe a cost-utility analysis of an eHealth intervention compared to regular follow-up in patients with acute myocardial infarction (AMI). MethodsIn this trial, of which clinical results have been published previously, patients with an AMI were randomized in a 1:1 fashion between an eHealth intervention and regular follow-up. The remote monitoring intervention consisted of a blood pressure monitor, weight scale, electrocardiogram device, and step counter. Furthermore, two in-office outpatient clinic visits were replaced by e-visits. The control group received regular care. The differences in mean costs and quality of life per patient between both groups during one-year follow-up were calculated. ResultsMean costs per patient were €2417±2043 (US $2657±2246) for the intervention and €2888±2961 (US $3175±3255) for the control group. This yielded a cost reduction of €471 (US $518) per patient. This difference was not statistically significant (95% CI –€275 to €1217; P=.22, US $–302 to $1338). The average quality-adjusted life years in the first year of follow-up was 0.74 for the intervention group and 0.69 for the control (difference –0.05, 95% CI –0.09 to –0.01; P=.01). ConclusionseHealth in the outpatient clinic setting for patients who suffered from AMI is likely to be cost-effective compared to regular follow-up. Further research should be done to corroborate these findings in other patient populations and different care settings. Trial RegistrationClinicalTrials.gov NCT02976376; https://clinicaltrials.gov/ct2/show/NCT02976376 International Registered Report Identifier (IRRID)RR2-10.2196/resprot.8038

Published
2022
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2. Real-World Experience of mHealth Implementation in Clinical Practice (the Box): Design and Usability Study

Author

Tom Biersteker, Alexander Hilt, Enno van der Velde, Martin Jan Schalij, and Roderick Willem Treskes

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundMobile health (mHealth) is an emerging field of scientific interest worldwide. Potential benefits include increased patient engagement, improved clinical outcomes, and reduced health care costs. However, mHealth is often studied in projects or trials, and structural implantation in clinical practice is less common. ObjectiveThe purpose of this paper is to outline the design of the Box and its implementation and use in an outpatient clinic setting. The impact on logistical outcomes and patient and provider satisfaction is discussed. MethodsIn 2016, an mHealth care track including smartphone-compatible devices, named the Box, was implemented in the cardiology department of a tertiary medical center in the Netherlands. Patients with myocardial infarction, rhythm disorders, cardiac surgery, heart failure, and congenital heart disease received devices to measure daily weight, blood pressure, heart rate, temperature, and oxygen saturation. In addition, professional and patient user comments on the experience with the care track were obtained via structured interviews. ResultsFrom 2016 to April 2020, a total of 1140 patients were connected to the mHealth care track. On average, a Box cost €350 (US $375), not including extra staff costs. The median patient age was 60.8 (IQR 52.9-69.3) years, and 73.59% (839/1140) were male. A median of 260 (IQR 105-641) measurements was taken on a median of 189 (IQR 98-372) days. Patients praised the ease of use of the devices and felt more involved with their illness and care. Professionals reported more productive outpatient consultations as well as improved insight into health parameters such as blood pressure and weight. A feedback loop from the hospital to patient to focus on measurements was commented as an important improvement by both patients and professionals. ConclusionsIn this study, the design and implementation of an mHealth care track for outpatient follow-up of patients with various cardiovascular diseases is described. Data from these 4 years indicate that mHealth is feasible to incorporate in outpatient management and is generally well-accepted by patients and providers. Limitations include the need for manual measurement data checks and the risk of data overload. Moreover, the tertiary care setting in which the Box was introduced may limit the external validity of logistical and financial end points to other medical centers. More evidence is needed to show the effects of mHealth on clinical outcomes and on cost-effectiveness.

Published
2021
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3. Mobile health vs. standard care after cardiac surgery: results of The Box 2.0 study

Author

Tom E Biersteker, Mark J Boogers, Martin Jan Schalij, Bas B L Penning de Vries, Rolf H H Groenwold, Anouk P van Alem, Arend de Weger, Nicolette van Hof, and Roderick W Treskes

Subjects
Remote patient monitoring, mHealth, Physiology (medical), Coronary artery bypass grafting, eHealth, Cardiology and Cardiovascular Medicine, Postoperative atrial fibrillation, Cardiac surgical procedures
Abstract

Aims Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery, yet difficult to detect in ambulatory patients. The primary aim of this study is to investigate the effect of a mobile health (mHealth) intervention on POAF detection after cardiac surgery. Methods and results We performed an observational cohort study among 730 adult patients who underwent cardiac surgery at a tertiary care hospital in The Netherlands. Of these patients, 365 patients received standard care and were included as a historical control group, undergoing surgery between December 2017 and September 2018, and 365 patients were prospectively included from November 2018 and November 2020, undergoing an mHealth intervention which consisted of blood pressure, temperature, weight, and electrocardiogram (ECG) monitoring. One physical outpatient follow-up moment was replaced by an electronic visit. All patients were requested to fill out a satisfaction and quality of life questionnaire. Mean age in the intervention group was 62 years, 275 (70.4%) patients were males. A total of 4136 12-lead ECGs were registered. In the intervention group, 61 (16.7%) patients were diagnosed with POAF vs. 25 (6.8%) patients in the control group [adjusted risk ratio (RR) of POAF detection: 2.15; 95% confidence interval (CI): 1.55–3.97]. De novo atrial fibrillation was found in 13 patients using mHealth (6.5%) vs. 4 control group patients (1.8%; adjusted RR 3.94, 95% CI: 1.50–11.27). Conclusion Scheduled self-measurements with mHealth devices could increase the probability of detecting POAF within 3 months after cardiac surgery. The effect of an increase in POAF detection on clinical outcomes needs to be addressed in future research.

Published
2022

4. The Box—eHealth in the Outpatient Clinic Follow-up of Patients With Acute Myocardial Infarction: Cost-Utility Analysis (Preprint)

Author

Roderick Willem Treskes, M Elske van den Akker-van Marle, Louise van Winden, Nicole van Keulen, Enno Tjeerd van der Velde, Saskia Beeres, Douwe Atsma, and Martin Jan Schalij

Abstract

BACKGROUND Smartphone compatible wearables have been released on the consumers market, enabling remote monitoring. Remote monitoring is often named as a tool to reduce the cost of care. OBJECTIVE The primary purpose of this paper is to describe a cost-utility analysis of an eHealth intervention compared to regular follow-up in patients with acute myocardial infarction (AMI). METHODS In this trial, of which clinical results have been published previously, patients with an AMI were randomized in a 1:1 fashion between an eHealth intervention and regular follow-up. The remote monitoring intervention consisted of a blood pressure monitor, weight scale, electrocardiogram device, and step counter. Furthermore, two in-office outpatient clinic visits were replaced by e-visits. The control group received regular care. The differences in mean costs and quality of life per patient between both groups during one-year follow-up were calculated. RESULTS Mean costs per patient were €2417±2043 (US $2657±2246) for the intervention and €2888±2961 (US $3175±3255) for the control group. This yielded a cost reduction of €471 (US $518) per patient. This difference was not statistically significant (95% CI –€275 to €1217; P=.22, US $–302 to $1338). The average quality-adjusted life years in the first year of follow-up was 0.74 for the intervention group and 0.69 for the control (difference –0.05, 95% CI –0.09 to –0.01; P=.01). CONCLUSIONS eHealth in the outpatient clinic setting for patients who suffered from AMI is likely to be cost-effective compared to regular follow-up. Further research should be done to corroborate these findings in other patient populations and different care settings. CLINICALTRIAL ClinicalTrials.gov NCT02976376; https://clinicaltrials.gov/ct2/show/NCT02976376 INTERNATIONAL REGISTERED REPORT RR2-10.2196/resprot.8038

Published
2021
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5. Real-World Experience of mHealth Implementation in Clinical Practice (the Box): Design and Usability Study (Preprint)

Author

Tom Biersteker, Alexander Hilt, Enno van der Velde, Martin Jan Schalij, and Roderick Willem Treskes

Abstract

BACKGROUND Mobile health (mHealth) is an emerging field of scientific interest worldwide. Potential benefits include increased patient engagement, improved clinical outcomes, and reduced health care costs. However, mHealth is often studied in projects or trials, and structural implantation in clinical practice is less common. OBJECTIVE The purpose of this paper is to outline the design of the Box and its implementation and use in an outpatient clinic setting. The impact on logistical outcomes and patient and provider satisfaction is discussed. METHODS In 2016, an mHealth care track including smartphone-compatible devices, named the Box, was implemented in the cardiology department of a tertiary medical center in the Netherlands. Patients with myocardial infarction, rhythm disorders, cardiac surgery, heart failure, and congenital heart disease received devices to measure daily weight, blood pressure, heart rate, temperature, and oxygen saturation. In addition, professional and patient user comments on the experience with the care track were obtained via structured interviews. RESULTS From 2016 to April 2020, a total of 1140 patients were connected to the mHealth care track. On average, a Box cost €350 (US $375), not including extra staff costs. The median patient age was 60.8 (IQR 52.9-69.3) years, and 73.59% (839/1140) were male. A median of 260 (IQR 105-641) measurements was taken on a median of 189 (IQR 98-372) days. Patients praised the ease of use of the devices and felt more involved with their illness and care. Professionals reported more productive outpatient consultations as well as improved insight into health parameters such as blood pressure and weight. A feedback loop from the hospital to patient to focus on measurements was commented as an important improvement by both patients and professionals. CONCLUSIONS In this study, the design and implementation of an mHealth care track for outpatient follow-up of patients with various cardiovascular diseases is described. Data from these 4 years indicate that mHealth is feasible to incorporate in outpatient management and is generally well-accepted by patients and providers. Limitations include the need for manual measurement data checks and the risk of data overload. Moreover, the tertiary care setting in which the Box was introduced may limit the external validity of logistical and financial end points to other medical centers. More evidence is needed to show the effects of mHealth on clinical outcomes and on cost-effectiveness.

Published
2020
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6. Mobile Health for Central Sleep Apnea Screening Among Patients With Stable Heart Failure: Single-Cohort, Open, Prospective Trial (Preprint)

Author

Roderick Willem Treskes, Arie C Maan, Harriette Florence Verwey, Robert Schot, Saskia Lambertha Maria Anna Beeres, Laurens F Tops, Enno Tjeerd Van Der Velde, Martin Jan Schalij, and Annelies Margaretha Slats

Abstract

BACKGROUND Polysomnography is the gold standard for detection of central sleep apnea in patients with stable heart failure. However, this procedure is costly, time consuming, and a burden to the patient and therefore unsuitable as a screening method. An electronic health (eHealth) app to measure overnight oximetry may be an acceptable screening alternative, as it can be automatically analyzed and is less burdensome to patients. OBJECTIVE This study aimed to assess whether overnight pulse oximetry using a smartphone-compatible oximeter can be used to detect central sleep apnea in a population with stable heart failure. METHODS A total of 26 patients with stable heart failure underwent one night of both a polygraph examination and overnight saturation using a smartphone-compatible oximeter. The primary endpoint was agreement between the oxygen desaturation index (ODI) above or below 15 on the smartphone-compatible oximeter and the diagnosis of the polygraph. RESULTS The median age of patients was 66.4 (interquartile range, 62-71) years and 92% were men. The median body mass index was 27.1 (interquartile range, 24.4-30.8) kg/m2. Two patients were excluded due to incomplete data, and two other patients were excluded because they could not use a smartphone. Seven patients had central sleep apnea, and 6 patients had obstructive sleep apnea. Of the 7 (of 22, 32%) patients with central sleep apnea that were included in the analysis, 3 (13%) had an ODI≥15. Of all patients without central sleep apnea, 8 (36%) had an ODI CONCLUSIONS Oxygen desaturation measured by this smartphone-compatible oximeter is a weak predictor of central sleep apnea in patients with stable heart failure.

Published
2018
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7. Contributors

Author

Philip Aagaard, Dominic James Abrams, Hugues Abriel, Wayne O. Adkisson, Esperanza Agullo-Pascual, Francisco J. Alvarado, Ahmad S. Amin, Charles Antzelevitch, Justus M.B. Anumonwo, Luciana Armaganijan, Arash Arya, Samuel Asirvatham, Felipe Atienza, Peter H. Backx, Lisa M. Ballou, Elise Balse, Sujata Balulad, Andrea Barbuti, Gust H. Bardy, Guillaume Bassil, David G. Benditt, Omer Berenfeld, Donald M. Bers, Ofer Binah, Frank Bogun, Rossana Bongianino, Noel G. Boyle, Patrick M. Boyle, Günter Breithardt, Marisa Brini, Peter R. Brink, Pedro Brugada, Eric Buch, Feliksas F. Bukauskas, Hugh Calkins, David J. Callans, Sean M. Caples, Ernesto Carafoli, William A. Catterall, Marina Cerrone, Arnaud Chaumeil, Caressa Chen, Lan S. Chen, Peng-Sheng Chen, Jianding Cheng, Nipavan Chiamvimonvat, David J. Christini, Aman Chugh, Andreu M. Climent, Ira S. Cohen, Stuart J. Connolly, Lebron Cooper, Eric M. Crespo, Lia Crotti, Thomas A. Csepe, Frank Cuoco, Anne B. Curtis, Ralph J. Damiano, Dawood Darbar, Mithilesh K. Das, Andre d’Avila, Mario Delmar, Eva Delpón, Marco Denegri, Arnaud Denis, Nicolas Derval, Isabelle Deschênes, Abhishek Deshmukh, Luigi Di Biase, Timm M. Dickfeld, Hans Dierckx, Borislav Dinov, Sanjay Dixit, Dobromir Dobrev, Remi Dubois, Lars Eckardt, Andrew G. Edwards, Kenneth A. Ellenbogen, Patrick T. Ellinor, N.A. Mark Estes, Larissa Fabritz, Vadim V. Fedorov, Antonio B. Fernandez, Elvis Teijeira Fernández, David Filgueiras-Rama, Michael C. Fishbein, Glenn I. Fishman, David S. Frankel, Paul Friedman, Antonio Frontera, Apoor S. Gami, Paul Garabelli, Alfred L. George, Edward P. Gerstenfeld, Sigfus Gizurarson, Michael R. Gold, Jeffrey J. Goldberger, Andrew Grace, Guido Grassi, Ruth Ann Greenfield, Wendy L. Gross, Blair P. Grubb, María S. Guillem, Sándor Györke, Michel Haïssaguerre, Johan Hake, Henry R. Halperin, Brian J. Hansen, Stéphane Hatem, David L. Hayes, Jordi Heijman, Todd J. Herron, Gerhard Hindricks, Mélèze Hocini, Stefan H. Hohnloser, David R. Holmes, Masahiko Hoshijima, Thomas J. Hund, Mathew D. Hutchinson, Leonard Ilkhanoff, Jodie Ingles, James E. Ip, Warren M. Jackman, Nicholas Jackson, Pierre Jaïs, José Jalife, Bong Sook Jhun, Roy M. John, Monique Jongbloed, Luc Jordaens, Jonathan M. Kalman, Timothy J. Kamp, Mohamed H. Kanj, Suraj Kapa, Beverly Karabin, Ioannis Karakikes, Demosthenes G. Katritsis, Kuljeet Kaur, Paulus Kirchhof, André G. Kléber, George J. Klein, Peter Kohl, Jayanthi N. Koneru, Jacob S. Koruth, Andrew D. Krahn, Trine Krogh-Madsen, Karl Heinz Kuck, Saurabh Kumar, Alexander Kushnir, Neal K. Lakdawala, Zachary W.M. Laksman, Rakesh Latchamsetty, Dennis H. Lau, Bruce B. Lerman, Richard Z. Lin, Shien-Fong Lin, Mark S. Link, Bin Liu, Christopher F. Liu, Deborah J. Lockwood, Anatoli N. Lopatin, Steven A. Lubitz, Rajiv Mahajan, Jonathan C. Makielski, Marek Malik, Francis E. Marchlinski, Steven M. Markowitz, Barry J. Maron, Martin S. Maron, Steven O. Marx, Stéphane Massé, Andrew D. McCulloch, Pippa McKelvie-Sebileau, Spencer J. Melby, Andreas Metzner, Anushka P. Michailova, Gregory F. Michaud, John M. Miller, Jyotsna Mishra, Raul D. Mitrani, Peter J. Mohler, Fred Morady, Robert J. Myerburg, Hiroshi Nakagawa, Chrishan Joseph Nalliah, Kumaraswamy Nanthakumar, Carlo Napolitano, Sanjiv M. Narayan, Andrea Natale, Stanley Nattel, Saman Nazarian, Thao P. Nguyen, Akihiko Nogami, Sami F. Noujaim, Karine Nubret Le Coniat, Brian Olshansky, Jin O-Uchi, Gavin Y. Oudit, Feifan Ouyang, Cevher Ozcan, Douglas L. Packer, Sandeep V. Pandit, Alexander V. Panfilov, David S. Park, Bence Patocskai, Dainius H. Pauza, Neringa Pauziene, Jonathan P. Piccini, Geoffrey S. Pitt, Sunny S. Po, Abhiram Prasad, Silvia G. Priori, Przemysław B. Radwański, Wouter-Jan Rappel, Michelle Reiser, Alejandro Jimenez Restrepo, Richard B. Robinson, Dan M. Roden, Michael R. Rosen, Raphael Rosso, Yoram Rudy, Kristina Rysevaite-Kyguoliene, Hani N. Sabbah, Frederic Sacher, Frank B. Sachse, Ardan M. Saguner, Prashanthan Sanders, Michael C. Sanguinetti, Pasquale Santangeli, Mohammad Sarraf, Jonathan Satin, Martin Jan Schalij, Benjamin J. Scherlag, Matthew R. Schill, J. William Schleifer, Richard B. Schuessler, Peter J. Schwartz, Timon Seeger, Christopher Semsarian, Gino Seravalle, Ashok J. Shah, Robin M. Shaw, Mark J. Shen, Win–Kuang Shen, Shey-Shing Sheu, Kalyanam Shivkumar, Jennifer N.A. Silva, Allan C. Skanes, Kyoko Soejima, Virend K. Somers, Dan Sorajja, Stavros Stavrakis, Christian Steinberg, Lynne Warner Stevenson, William G. Stevenson, Michael O. Sweeney, Charles Swerdlow, Masateru Takigawa, Juan Tamargo, Harikrishna Tandri, Usha B. Tedrow, Nathaniel Thompson, Paul D. Thompson, Gordon F. Tomaselli, Jeffrey A. Towbin, Natalia A. Trayanova, Martin Tristani-Firouzi, Zian H. Tseng, Akiko Ueda, Héctor H. Valdivia, Virginijus Valiunas, Christian van der Werf, George F. Van Hare, David Vidmar, Sami Viskin, Niels Voigt, Edward P. Walsh, Paul J. Wang, Xander H.T. Wehrens, Mark S. Weiss, Arthur A.M. Wilde, Bruce L. Wilkoff, Y. Joseph Woo, Joseph C. Wu, Raymond Yee, Junaid A.B. Zaman, Manuel Zarzoso, Emily P. Zeitler, Katja Zeppenfeld, Tarek Zghaib, Xiao-Dong Zhang, and Douglas P. Zipes

Published
2018
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8. Comparison of four smartphone compatible blood pressure monitors

Author

Enno T. van der Velde, D.C. Eindhoven, Martin-Jan Schalij, and Roderick W Treskes

Subjects
Blood pressure, Bp monitors, Blood pressure monitors, business.industry, Computer science, Bp monitoring, ComputerSystemsOrganization_MISCELLANEOUS, Embedded system, business, Computer hardware
Abstract

Out-of-office blood pressure (BP) monitoring is advocated by the guidelines for various reasons. Recently developed smartphone compatible BP monitors are potentially very useful for out-of-office BP monitoring. This study is ought to compare performances of these BP monitors.

Published
2015
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9. Contributors

Author

Hugues Abriel, Wayne O. Adkisson, Esperanza Agullo-Pascual, Olujimi A. Ajijola, Amin Al-Ahmad, Oluseun Alli, Robert K. Altman, Elad Anter, Charles Antzelevitch, Justus M.B. Anumonwo, Luciana Armaganijan, Hiroshi Ashikaga, Felipe Atienza, Uma Mahesh R. Avula, Peter H. Backx, Elise Balse, Conor D. Barrett, David G. Benditt, Omer Berenfeld, Donald M. Bers, Charles I. Berul, A. Christian Blank, Raffaella Bloise, Frank Matthias Bogun, Martin Borggrefe, Noel G. Boyle, Günter Breithardt, Marisa Brini, Peter R. Brink, Josep Brugada, Pau Brugada, Pedro Brugada, Ramon Brugada, Victoria Brugada, Eric Buch, Feliksas F. Bukauskas, J. David Burkhardt, Nenad Bursac, Hugh Calkins, David J. Callans, Oscar Campuzano, Sean M. Caples, Ernesto Carafoli, Augustin Castellanos, William Catterall, Marina Cerrone, Lan S. Chen, Lei Chen, Peng-Sheng Chen, Ashley Chin, Aman Chugh, Ira S. Cohen, Stuart J. Connolly, Jason Constantino, Lia Crotti, Frank A. Cuoco, Anne B. Curtis, Ralph J. Damiano, Dawood Darbar, Mithilesh K. Das, Mario Delmar, Eva Delpón, Luigi Di Biase, Sanjay Dixit, Dobromir Dobrev, Derek J. Dosdall, John W. Dyer, Lars Eckardt, Andrew G. Edwards, Igor R. Efimov, Kenneth A. Ellenbogen, Patrick T. Ellinor, Emilia Entcheva, N.A. Mark Estes, Rodolphe Fischmeister, John D. Fisher, Glenn I. Fishman, David S. Frankel, Michael R. Franz, Paul A. Friedman, Victor F. Froelicher, Apoor S. Gami, Alfred L. George, Edward P. Gerstenfeld, Michael R. Gold, Jeffrey J. Goldberger, Eleonora Grandi, Richard A. Gray, William J. Groh, Blair P. Grubb, Michel Haissaguerre, Johan Hake, Henry R. Halperin, Louise Harris, Stéphane Hatem, David L. Hayes, Meleze Hocini, Stefan H. Hohnloser, David Richard Holmes, Masahiko Hoshijima, Yuxuan Hu, Thomas J. Hund, Mathew D. Hutchinson, Hye Jin Hwang, Raymond E. Ideker, Leonard Ilkhanoff, Jodie Ingles, Warren M. Jackman, Pierre Jais, José Jalife, Bong Sook Jhun, Roy M. John, Monique Jongbloed, Mark E. Josephson, Alan H. Kadish, Jérôme Kalifa, Jonathan M. Kalman, Timothy J. Kamp, Mohamed Hani Kanj, Beverly Karabin, Robert S. Kass, Demosthenes G. Katritsis, Kuljeet Kaur, Jong J. Kim, Paulus Kirchhof, André G. Kléber, George J. Klein, Peter Kohl, Aravindan Kolandaivelu, Andrew D. Krahn, Andrew Krumerman, Saurabh Kumar, Karl-Heinz Kuck, Edward G. Lakatta, Rakesh Latchamsetty, Dennis H. Lau, Bruce B. Lerman, Jérôme Leroy, William R. Lewis, Shien-Fong Lin, Mark S. Link, Christopher F. Liu, Deborah J. Lockwood, Peter Loh, Anatoli N. Lopatin, John C. Lopshire, Steven A. Lubitz, Christopher Madias, Aman Mahajan, Jonathan C. Makielski, Marek Malik, Victor A. Maltsev, Francis E. Marchlinski, Ariane J. Marelli, Steven M. Markowitz, Barry J. Maron, Jeffrey R. Martens, Steven O. Marx, Andrew D. McCulloch, Andreas Metzner, Anuska P. Michailova, John Michael Miller, Michelle Lynne Milstein, Peter Mohler, Fred Morady, Robert J. Myerburg, Hiroshi Nakagawa, Carlo Napolitano, Sanjiv M. Narayan, Andrea Natale, Stanley Nattel, Saman Nazarian, Jeanne M. Nerbonne, Fu Siong Ng, Akihiko Nogami, Sami F. Noujaim, Brian Olshansky, Hakan Oral, Jin O-Uchi, Feifan Ouyang, Cevher Ozcan, Douglas L. Packer, Olle Pahlm, Sandeep V. Pandit, David S. Park, Geoffrey S. Pitt, Sunny S. Po, Silvia G. Priori, Wouter-Jan Rappel, Vivek Y. Reddy, Jason O. Robertson, Richard B. Robinson, Dan M. Roden, Robert A. Rose, Michael R. Rosen, Raphael Rosso, Yoram Rudy, Jeremy N. Ruskin, Hani N. Sabbah, Frank B. Sachse, Lindsey L. Saint, Javier Saiz, José A. Sánchez-Chapula, Prashanthan Sanders, Michael C. Sanguinetti, Pasquale Santangeli, Georgia Sarquella-Brugada, Jonathan Satin, Martin Jan Schalij, Benjamin J. Scherlag, Rainer Schimpf, Georg Schmidt, Peter J. Schwartz, Christopher Semsarian, Ashok J. Shah, Robin Shaw, Shey Shing Sheu, Kalyanam Shivkumar, Allan C. Skanes, Virend K. Somers, Bruce S. Stambler, Adam B. Stein, Lynne Warner Stevenson, William G. Stevenson, Jian Sun, Richard Sutton, Michael O. Sweeney, Charles Swerdlow, Juan Tamargo, Harikrishna Tandri, Rabi Tawil, Usha Tedrow, Cecile Terrenoire, Catalina Tobón, Jeffrey A. Towbin, Natalia A. Trayanova, Martin Tristani-Firouzi, Richard G. Trohman, Zian H. Tseng, Mintu P. Turakhia, Ravi Vaidyanathan, Héctor H. Valdivia, Virginijus Valiunas, Marcel A.G. van der Heyden, Christian van der Werf, George F. Van, Marmar Vaseghi, Christian Veltmann, Victoria L. Vetter, Sami Viskin, Niels Voigt, Marc A. Vos, Galen S. Wagner, Paul J. Wang, Rukshen Weerasooriya, Arthur A.M. Wilde, Bruce L. Wilkoff, Erik Wissner, Y. Joseph Woo, Masatoshi Yamazaki, Felix Yang, Yael Yaniv, Sing-Chien Yap, Raymond Yee, Manuel Zarzoso, Katja Zeppenfeld, and Douglas P. Zipes

Published
2014
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10. Abstract 532: The RNA-binding Protein Quaking Critically Regulates Vascular Smooth Muscle Cell Phenotype

Author

Eric P van der Veer, Ruben G de Bruin, Adriaan O Kraaijeveld, Margreet R de Vries, Tonio Pera, Filip M Segers, Stella Trompet, Janine M van Gils, Marko K Roeten, Cora M Beckers, Peter J van Santbrink, Anique Janssen, Coen van Solingen, Jim Swildens, Hetty C de Boer, Ilze Bot, Erna A Peters, Mat Rousch, Merijn Doop, Martin Jan Schalij, Allard C van der Wal, Stehpane Richard, Theo J van Berkel, J. G Pickering, Pieter S Hiemstra, Marie Jose Goumans, Ton J Rabelink, Antoine A de Vries, Paul H Quax, J. W Jukema, Erik A Biessen, and Anton Jan van Zonneveld

Subjects
cardiovascular system, Cardiology and Cardiovascular Medicine
Abstract

In response to vascular injury, smooth muscle cells (VSMC) adopt a proliferative, synthetic hypocontractile phenotype. This phenotype switch is deemed instrumental in vascular remodeling in both health and disease. Here, we detail a decisive role for the RNA-binding protein Quaking (QKI) in regulating VSMC plasticity. We identified that the RNA-binding protein Quaking (QKI) is highly expressed by neointimal VSMCs of human coronary restenotic lesions, but not in healthy vessels. In a mouse model of vascular injury, we observed reduced neointima hyperplasia in Qk v mice, which have decreased QKI expression. Concordantly, abrogation of QKI attenuated fibroproliferative properties of VSMCs, while potently inducing contractile apparatus protein expression, rendering non-contractile VSMCs with the capacity to contract. We identified that QKI localizes to the spliceosome in proliferative VSMCs, where it interacts with and impacts myocardin (pre)-mRNA metabolism by mediating myocardin exon 2a exclusion. As such, in vitro and in vivo experiments indicate that the modulation of QKI expression directly influences the myocardin_v3 / myocardin_v1 mRNA balance, which could play a role in shifting the Myocardin-induced transcriptional coactivation profile following arterial damage. We propose that QKI is a central regulator of VSMC phenotypic plasticity and that intervention in QKI activity can ameliorate pathogenic, fibroproliferative responses to vascular injury.

Published
2013
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