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2. Safety and Efficacy of CYP2C19 Genotype-Guided Escalation of P2Y12 Inhibitor Therapy After Percutaneous Coronary Intervention in Chronic Kidney Disease: a Post Hoc Analysis of the TAILOR-PCI Study

Author

Mathew, Roy O., Sidhu, Mandeep S., Rihal, Charanjit S., Lennon, Ryan, El-Hajjar, Mohammed, Yager, Neil, Lyubarova, Radmila, Abdul-Nour, Khaled, Weitz, Steven, O’Cochlain, D. Fearghas, Murthy, Vishakantha, Levisay, Justin, Marzo, Kevin, Graham, John, Dzavik, Vlad, So, Derek, Goodman, Shaun, Rosenberg, Yves D., Pereira, Naveen, and Farkouh, Michael E.

Published
2024
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3. Myocardial Fibrosis and Cardiomyopathy Risk: A Genetic Link in the MESA

Author

Shabani, Mahsima, Wang, Min, Jenkins, Gregory D, Rotter, Jerome I, Rich, Stephen S, Batzler, Anthony, Taylor, Kent D, Mychaleckyj, Josyf C, Liu, Duan, Lima, Joao AC, and Pereira, Naveen L

Subjects
Biomedical and Clinical Sciences, Medical Physiology, Cardiovascular Medicine and Haematology, Genetics, Cardiovascular, Clinical Research, Heart Disease, Minority Health, Rare Diseases, Health Disparities, 2.1 Biological and endogenous factors, Humans, Cardiomyopathy, Dilated, Magnetic Resonance Imaging, Cine, Heart Failure, Cardiomyopathies, Myocardium, Cardiomyopathy, Hypertrophic, Fibrosis, Contrast Media, Ventricular Function, Left, cardiomyopathy, fibroblasts, fibrosis, genetics, heart failure, magnetic resonance imaging, risk, Biochemistry and Cell Biology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Medical physiology
Abstract

BackgroundCommon genetic variants are associated with risk for hypertrophic cardiomyopathy and dilated cardiomyopathy and with left ventricular (LV) traits. Whether these variants are associated with myocardial fibrosis, an important pathophysiological mediator of cardiomyopathy, is unknown.MethodsMulti-Ethnic Study of Atherosclerosis participants with T1-mapping cardiac magnetic resonance imaging in-whom extracellular volume was assessed, and genotyping information was available were included (N=1255). Log extracellular volume (%) was regressed on 50 candidate single nucleotide polymorphisms (previously identified to be associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and LV traits) adjusting for age, sex, diabetes, blood pressure, and principal components of ancestry. Ancestry-specific results were pooled by fixed-effect meta-analyses. Gene knockdown experiments were performed in human cardiac fibroblasts.ResultsThe SMARCB1 rs2186370 intronic variant (minor allele frequency: 0.18 in White and 0.50 in Black participants), previously identified as a risk variant for dilated cardiomyopathy and hypertrophic cardiomyopathy, was significantly associated with increased extracellular volume (P=0.0002) after adjusting for confounding clinical variables. The SMARCB1 rs2070458 locus previously associated with increased LV wall thickness and mass was similarly significantly associated with increased extracellular volume (P=0.0002). The direction of effect was similar in all 4 ancestry groups, but the effect was strongest in Black participants. The variants are strong expression quantitative loci in human LV tissue and associated with genotype-dependent decreased expression of SMARCB1 (P=7.3×10-22). SMARCB1 knockdown in human cardiac fibroblasts resulted in increased TGF (transforming growth factor)-β1-mediated α-smooth muscle actin and collagen expression.ConclusionsCommon genetic variation in SMARCB1 previously associated with risk for cardiomyopathies and increased LV wall thickness is associated with increased cardiac magnetic resonance imaging-based myocardial fibrosis and increased TGF-β1 mediated myocardial fibrosis in vitro. Whether these findings suggest a pathophysiologic link between myocardial fibrosis and cardiomyopathy risk remains to be proven.

Published
2023

5. Point of care CYP2C19 genotyping after percutaneous coronary intervention

Author

Baudhuin, Linnea M, Train, Laura J, Goodman, Shaun G, Lane, Gary E, Lennon, Ryan J, Mathew, Verghese, Murthy, Vishakantha, Nazif, Tamim M, So, Derek YF, Sweeney, John P, Wu, Alan HB, Rihal, Charanjit S, Farkouh, Michael E, and Pereira, Naveen L

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Clinical Trials and Supportive Activities, Good Health and Well Being, Humans, Cytochrome P-450 CYP2C19, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Point-of-Care Systems, Prospective Studies, Genotype, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

Loss-of-function CYP2C19 variants are associated with increased cumulative ischemic outcomes warranting CYP2C19 genotyping prior to clopidogrel administration. TAILOR-PCI was an international, multicenter (40 sites), prospective, randomized trial comparing rapid point of care (POC) genotype-guided vs. conventional anti-platelet therapy. The performance of buccal-based rapid CYP2C19 genotyping performed by non-laboratory-trained staff in TAILOR-PCI was assessed. Pre-trial training and evaluation involved rapid genotyping of 373 oral samples, with 99.5% (371/373) concordance with Sanger sequencing. During TAILOR-PCI, 5302 patients undergoing PCI were randomized to POC rapid CYP2C19 *2, *3, and *17 genotyping versus no genotyping. At 12 months post-PCI, TaqMan genotyping determined 99.1% (2,364/2,385) concordance with the POC results, with 90.7-98.8% sensitivity and 99.2-99.6% specificity. In conclusion, non-laboratory personnel can be successfully trained for on-site instrument operation and POC rapid genotyping with analytical accuracy and precision across multiple international centers, thereby supporting POC genotyping in patient-care settings, such as the cardiac catheterization laboratory.Clinical Trial Registration: https://www.clinicalTrials.gov (Identifier: NCT01742117).

Published
2022

9. Magnetic Resonance Imaging Characterization and Clinical Outcomes of Dilated and Arrhythmogenic Left Ventricular Cardiomyopathies

Author

Castrichini, Matteo, De Luca, Antonio, De Angelis, Giulia, Neves, Raquel, Paldino, Alessia, Dal Ferro, Matteo, Barbati, Giulia, Medo, Kristen, Barison, Andrea, Grigoratos, Chrysanthos, Gigli, Marta, Stolfo, Davide, Brun, Francesca, Groves, Daniel W., Quaife, Robert, Eldemire, Ramone, Graw, Sharon, Addison, Jeffrey, Todiere, Giancarlo, Gueli, Ignazio Alessio, Botto, Nicoletta, Emdin, Michele, Aquaro, Giovanni Donato, Garmany, Ramin, Pereira, Naveen L., Taylor, Matthew R.G., Ackerman, Michael J., Sinagra, Gianfranco, Mestroni, Luisa, Giudicessi, John R., and Merlo, Marco

Published
2024
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10. Summary of a consensus conference on heart-liver transplantation

Author

Kobashigawa, Jon, VanWagner, Lisa B., Hall, Shelley, Ardehali, Abbas, Baran, David, Bhimaraj, Arvind, Bonham, Clark Andrew, Breda, Joao Roberto, Chen, Sharon, Czer, Lawrence, Alessandro, David D', Daugherty, Tami, De Marco, Teresa, Emamaullee, Juliet, Emerson, Dominic, Entwistle, John W., Esmailian, Fardad, Estep, Jerry, Gaber, Osama, Ganger, Daniel, Gebel, Howard, Ebel, Noelle Hanako, Harmath, Carla, Heimbach, Julie, Izzy, Manhal, Jackson, Annette, Jeevanandam, Val, Kahn, Jeffrey, Kaldas, Fady, Kamath, Patrick, Kilic, Ahmet, Kittleson, Michelle, Kuo, Alex, Kushwaha, Sudhir, Kwong, Allison, Lewis, Matthew, Loebe, Matthias, Lui, George, Madsen, Joren, McLean, Rhondalyn, Menachem, Jonathan, Mobley, Constance, Mufti, Arji, Patel, Jignesh, Pereira, Naveen, Pinney, Sean, Potter, Lisa, Sack, Jordan, Sahota, Amandeep, Schiano, Thomas D., Schlendorf, Kelly, Shingina, Alexandra, Takeda, Koji, Taner, Timucin, Te, Helen, Teuteberg, Jeffrey, Tompkins, Rose, Verna, Betsy, Wall, Anji, Jeevanandam, Valluvan, Lui, George K., Motayagheni, Negar, Patel, Nikhil, and Sani, Maryam

Published
2024
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11. Rare Genetic Variants Associated With Myocardial Fibrosis: Multi-Ethnic Study of Atherosclerosis

Author

Shabani, Mahsima, Dutta, Diptavo, Ambale-Venkatesh, Bharath, Post, Wendy S, Taylor, Kent D, Rich, Stephen S, Wu, Colin O, Pereira, Naveen L, Shah, Sanjiv J, Chatterjee, Nilanjan, Rotter, Jerome I, Arking, Dan E, and Lima, Joao AC

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Atherosclerosis, Clinical Research, Heart Disease, Genetics, Biomedical Imaging, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, cardiomyopathy, genetics, fibrosis, magnetic resonance imaging, T1, interstitial, rare, Cardiovascular medicine and haematology
Abstract

BackgroundRare pathogenic variants in cardiomyopathy (CM) genes can predispose to cardiac remodeling or fibrosis. We studied the carrier status for such variants in adults without clinical cardiovascular disease (CVD) in whom cardiac MRI (CMR)-derived measures of myocardial fibrosis were obtained in the Multi-Ethnic Study of Atherosclerosis (MESA).ObjectivesTo identify CM-associated pathogenic variants and assess their relative prevalence in participants with extensive myocardial fibrosis by CMR.MethodsMESA whole-genome sequencing data was evaluated to capture variants in CM-associated genes (n = 82). Coding variants with a frequency of

Published
2022

12. RApid Throughput Screening for Asymptomatic COVID-19 Infection With an Electrocardiogram: A Prospective Observational Study

Author

Adedinsewo, Demilade, Dugan, Jennifer, Johnson, Patrick W., Douglass, Erika J., Morales-Lara, Andrea Carolina, Parkulo, Mark A., Ting, Henry H., Cooper, Leslie T., Scott, Luis R., Valverde, Arturo M., Padmanabhan, Deepak, Peters, Nicholas S., Bachtiger, Patrik, Kelshiker, Mihir, Fernandez-Aviles, Francisco, Atienza, Felipe, Glotzer, Taya V., Lahiri, Marc K., Dominic, Paari, Attia, Zachi I., Kapa, Suraj, Noseworthy, Peter A., Pereira, Naveen L., Cruz, Jessica, Berbari, Elie F., Carter, Rickey E., and Friedman, Paul A.

Published
2023
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13. Rationale and design of the TAILOR-PCI digital study: Transitioning a randomized controlled trial to a digital registry

Author

Pereira, Naveen L, Avram, Robert, So, Derek Y, Iturriaga, Erin, Byrne, Julia, Lennon, Ryan J, Murthy, Vishakantha, Geller, Nancy, Goodman, Shaun G, Rihal, Charanjit, Rosenberg, Yves, Bailey, Kent, Pletcher, Mark J, Marcus, Gregory M, Farkouh, Michael E, and Olgin, Jeffrey E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Clinical Trials and Supportive Activities, Patient Safety, Cardiovascular, Good Health and Well Being, COVID-19, Clopidogrel, Continuity of Patient Care, Feasibility Studies, Follow-Up Studies, Genotype, Geographic Information Systems, Health Surveys, Humans, Internet-Based Intervention, Ischemia, Mobile Applications, Multicenter Studies as Topic, Patient Compliance, Patient Generated Health Data, Patient Participation, Percutaneous Coronary Intervention, Postoperative Complications, Pragmatic Clinical Trials as Topic, Purinergic P2Y Receptor Antagonists, Randomized Controlled Trials as Topic, Registries, Research Design, SARS-CoV-2, Telephone, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundTailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention (TAILOR-PCI) is the largest cardiovascular genotype-based randomized pragmatic trial (NCT#01742117) to evaluate the role of genotype-guided selection of oral P2Y12 inhibitor therapy in improving ischemic outcomes after PCI. The trial has been extended from the original 12- to 24-month follow-up, using study coordinator-initiated telephone visits. TAILOR-PCI Digital Study tests the feasibility of extending the trial follow-up in a subset of patients for up to 24 months using state-of-the-art digital solutions. The rationale, design, and approach of extended digital study of patients recruited into a large, international, multi-center clinical trial has not been previously described.MethodsA total of 930 patients from U.S. and Canadian sites previously enrolled in the 5,302 patient TAILOR-PCI trial within 23 months of randomization are invited by mail to the Digital Study website (http://tailorpci.eurekaplatform.org) and by up to 2 recruiting telephone calls. Eureka, a direct-to-participant digital research platform, is used to consent and collect prospective data on patients for the digital study. Patients are asked to answer health-related surveys at fixed intervals using the Eureka mobile app and or desktop platform. The likelihood of patients enrolled in a randomized clinical trial transitioning to a registry using digital technology, the reasons for nonparticipation and engagement rates are evaluated. To capture hospitalizations, patients may optionally enable geofencing, a process that allows background location tracking and triggering of surveys if a hospital visit greater than 4 hours is detected. In addition, patients answer digital hospitalization surveys every month. Hospitalization data received from the Digital Study will be compared to data collected from study coordinator telephone visits during the same time frame.ConclusionsThe TAILOR-PCI Digital Study evaluates the feasibility of transitioning a large multicenter randomized clinical trial to a digital registry. The study could provide evidence for the ability of digital technology to follow clinical trial patients and to ascertain trial-related events thus also building the foundation for conducting digital clinical trials. Such a digital approach may be especially pertinent in the era of COVID-19.

Published
2021

14. Genetic-Guided Oral P2Y12 Inhibitor Selection and Cumulative Ischemic Events After Percutaneous Coronary Intervention

Author

Ingraham, Brenden S., Farkouh, Michael E., Lennon, Ryan J., So, Derek, Goodman, Shaun G., Geller, Nancy, Bae, Jang-Ho, Jeong, Myung Ho, Baudhuin, Linnea M., Mathew, Verghese, Bell, Malcolm R., Lerman, Amir, Fu, Yi-Ping, Hasan, Ahmed, Iturriaga, Erin, Tanguay, Jean-Francois, Welsh, Robert C., Rosenberg, Yves, Bailey, Kent, Rihal, Charanjit, and Pereira, Naveen L.

Published
2023
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19. 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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21. Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease: A Consensus Document from the Academic Research Consortium

Author

Capodanno, Davide, Mehran, Roxana, Krucoff, Mitchell W., Baber, Usman, Bhatt, Deepak L., Capranzano, Piera, Collet, Jean-Philippe, Cuisset, Thomas, De Luca, Giuseppe, De Luca, Leonardo, Farb, Andrew, Franchi, Francesco, Gibson, C. Michael, Hahn, Joo-Yong, Hong, Myeong-Ki, James, Stefan, Kastrati, Adnan, Kimura, Takeshi, Lemos, Pedro A., Lopes, Renato D., Magee, Adrian, Matsumura, Ryosuke, Mochizuki, Shuichi, O’Donoghue, Michelle L., Pereira, Naveen L., Rao, Sunil V., Rollini, Fabiana, Shirai, Yuko, Sibbing, Dirk, Smits, Peter C., Steg, P. Gabriel, Storey, Robert F., ten Berg, Jurrien, Valgimigli, Marco, Vranckx, Pascal, Watanabe, Hirotoshi, Windecker, Stephan, Serruys, Patrick W., Yeh, Robert W., Morice, Marie-Claude, and Angiolillo, Dominick J.

Published
2023
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22. Implementation of preemptive DNA sequence–based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study

Author

Wang, Liewei, Scherer, Steven E., Bielinski, Suzette J., Muzny, Donna M., Jones, Leila A., Black, John Logan, III, Moyer, Ann M., Giri, Jyothsna, Sharp, Richard R., Matey, Eric T., Wright, Jessica A., Oyen, Lance J., Nicholson, Wayne T., Wiepert, Mathieu, Sullard, Terri, Curry, Timothy B., Rohrer Vitek, Carolyn R., McAllister, Tammy M., St. Sauver, Jennifer L., Caraballo, Pedro J., Lazaridis, Konstantinos N., Venner, Eric, Qin, Xiang, Hu, Jianhong, Kovar, Christie L., Korchina, Viktoriya, Walker, Kimberly, Doddapaneni, HarshaVardhan, Wu, Tsung-Jung, Raj, Ritika, Denson, Shawn, Liu, Wen, Chandanavelli, Gauthami, Zhang, Lan, Wang, Qiaoyan, Kalra, Divya, Karow, Mary Beth, Harris, Kimberley J., Sicotte, Hugues, Peterson, Sandra E., Barthel, Amy E., Moore, Brenda E., Skierka, Jennifer M., Kluge, Michelle L., Kotzer, Katrina E., Kloke, Karen, Vander Pol, Jessica M., Marker, Heather, Sutton, Joseph A., Kekic, Adrijana, Ebenhoh, Ashley, Bierle, Dennis M., Schuh, Michael J., Grilli, Christopher, Erickson, Sara, Umbreit, Audrey, Ward, Leah, Crosby, Sheena, Nelson, Eric A., Levey, Sharon, Elliott, Michelle, Peters, Steve G., Pereira, Naveen, Frye, Mark, Shamoun, Fadi, Goetz, Matthew P., Kullo, Iftikhar J., Wermers, Robert, Anderson, Jan A., Formea, Christine M., El Melik, Razan M., Zeuli, John D., Herges, Joseph R., Krieger, Carrie A., Hoel, Robert W., Taraba, Jodi L., St. Thomas, Scott R., Absah, Imad, Bernard, Matthew E., Fink, Stephanie R., Gossard, Andrea, Grubbs, Pamela L., Jacobson, Therese M., Takahashi, Paul, Zehe, Sharon C., Buckles, Susan, Bumgardner, Michelle, Gallagher, Colette, Fee-Schroeder, Kelliann, Nicholas, Nichole R., Powers, Melody L., Ragab, Ahmed K., Richardson, Darcy M., Stai, Anthony, Wilson, Jaymi, Pacyna, Joel E., Olson, Janet E., Sutton, Erica J., Beck, Annika T., Horrow, Caroline, Kalari, Krishna R., Larson, Nicholas B., Liu, Hongfang, Wang, Liwei, Lopes, Guilherme S., Borah, Bijan J., Freimuth, Robert R., Zhu, Ye, Jacobson, Debra J., Hathcock, Matthew A., Armasu, Sebastian M., McGree, Michaela E., Jiang, Ruoxiang, Koep, Tyler H., Ross, Jason L., Hilden, Matthew G., Bosse, Kathleen, Ramey, Bronwyn, Searcy, Isabelle, Boerwinkle, Eric, Gibbs, Richard A., and Weinshilboum, Richard M.

Published
2022
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33. Next-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics

Author

Morales-Rosado, Joel A., Goel, Kashish, Zhang, Lingxin, Åkerblom, Axel, Baheti, Saurabh, Black, John L., Eriksson, Niclas, Wallentin, Lars, James, Stefan, Storey, Robert F., Goodman, Shaun G., Jenkins, Gregory D., Eckloff, Bruce W., Bielinski, Suzette J., Sicotte, Hugues, Johnson, Stephen, Roger, Veronique L., Wang, Liewei, Weinshilboum, Richard, Klee, Eric W., Rihal, Charanjit S., and Pereira, Naveen L.

Published
2021
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38. CYP2C19 Genetic Testing for Oral P2Y12 Inhibitor Therapy: A Scientific Statement From the American Heart Association.

Author

Pereira, Naveen L., Cresci, Sharon, Angiolillo, Dominick J., Batchelor, Wayne, Capers IV, Quinn, Cavallari, Larisa H., Leifer, Dana, Luzum, Jasmine A., Roden, Dan M., Stellos, Konstantinos, Turrise, Stephanie L., and Tuteja, Sony

Subjects
*PERIPHERAL vascular diseases, *PERCUTANEOUS coronary intervention, *ACUTE coronary syndrome, *PLATELET aggregation inhibitors, *GENETIC testing
Abstract

There is significant variability in the efficacy and safety of oral P2Y12 inhibitors, which are used to prevent ischemic outcomes in common diseases such as coronary and peripheral arterial disease and stroke. Clopidogrel, a prodrug, is the most used oral P2Y12 inhibitor and is activated primarily after being metabolized by a highly polymorphic hepatic cytochrome CYP2C219 enzyme. Loss-of-function genetic variants in CYP2C219 are common, can result in decreased active metabolite levels and increased on-treatment platelet aggregation, and are associated with increased ischemic events on clopidogrel therapy. Such patients can be identified by CYP2C19 genetic testing and can be treated with alternative therapy. Conversely, universal use of potent oral P2Y12 inhibitors such as ticagrelor or prasugrel, which are not dependent on CYP2C19 for activation, has been recommended but can result in increased bleeding. Recent clinical trials and meta-analyses have demonstrated that a precision medicine approach in which loss-of-function carriers are prescribed ticagrelor or prasugrel and noncarriers are prescribed clopidogrel results in reducing ischemic events without increasing bleeding risk. The evidence to date supports CYP2C19 genetic testing before oral P2Y12 inhibitors are prescribed in patients with acute coronary syndromes or percutaneous coronary intervention. Clinical implementation of such genetic testing will depend on among multiple factors: rapid availability of results or adoption of the concept of performing preemptive genetic testing, provision of easy-to-understand results with therapeutic recommendations, and seamless integration in the electronic health record. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Cardiac magnetic resonance imaging in heart transplant recipients with biopsy‐negative graft dysfunction.

Author

Anand, Senthil, Alnsasra, Hilmi, LeMond, Lisa M., Shrivastava, Sanskriti, Asleh, Rabea, Rosenbaum, Andrew, Kobrossi, Semaan, Mohananey, Akanksha, Murphy, Katie, Smith, Byron H., Kushwaha, Sudhir, Steidley, David E., Clavell, Alfredo, Young, Phillip, and Pereira, Naveen L.

Subjects
CARDIAC magnetic resonance imaging, HEART transplant recipients, CARDIAC imaging, KIDNEY transplantation, HOMOGRAFTS, HEART transplantation, GRAFT rejection
Abstract

Aims: Graft dysfunction (GD) after heart transplantation (HTx) can develop without evidence of cell‐ or antibody‐mediated rejection. Cardiac magnetic resonance imaging (CMR) has an evolving role in detecting rejection; however, its role in biopsy‐negative GD has not been described. This study examines CMR findings, evaluates outcomes based on CMR results, and seeks to identify the possibility of rejection missed through endomyocardial biopsy by using CMR in HTx recipients with biopsy‐negative GD. Methods and results: HTx recipients with GD [defined as a decrease in left ventricular ejection fraction (LVEF) by >5% and LVEF < 50%] in the absence of rejection by biopsy or allograft vasculopathy and who underwent CMR were included in the study. The primary outcome was a composite of all‐cause mortality, re‐transplantation, or persistent LVEF < 50%. Overall, 34 HTx recipients developed biopsy‐negative GD and underwent CMR. Left ventricular late gadolinium enhancement (LGE) on CMR was observed in 16 patients with two distinct patterns: diffuse epicardial (n = 13) and patchy (n = 3) patterns. Patients with LGE developed GD later after HTx [4 (1.4–6.8) vs. 0.8 (0.3–1.2) years, P < 0.001], were more often symptomatic (88% vs. 56%, P = 0.06), and had greater haemodynamic derangement (pulmonary capillary wedge pressure: 19 ± 7 vs. 13 ± 3 mmHg, P = 0.002) as compared with those without LGE. No significant difference was observed in the primary composite outcome between patients with LGE and those without LGE (50% vs. 38% of patients with events, P = 0.515). During a median follow‐up of 3.8 years, mean LVEF improved similarly in the LGE‐negative (37–55%) and LGE‐positive groups (32–55%) (P = 0.16). Conclusions: Biopsy‐negative GD occurs with and without LGE when assessed by CMR, indicative of possible rejection/inflammation occurring only in a subset of patients. Irrespective of LGE, LVEF improvement occurs in most GD patients, suggesting that other neurohormonal or immunomodulatory mechanisms may also contribute to GD development. [ABSTRACT FROM AUTHOR]

Published
2024
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40. Safety and Efficacy of CYP2C19 Genotype-Guided Escalation of P2Y12 Inhibitor Therapy After Percutaneous Coronary Intervention in Chronic Kidney Disease: a Post Hoc Analysis of the TAILOR-PCI Study.

Author

Mathew, Roy O., Sidhu, Mandeep S., Rihal, Charanjit S., Lennon, Ryan, El-Hajjar, Mohammed, Yager, Neil, Lyubarova, Radmila, Abdul-Nour, Khaled, Weitz, Steven, O'Cochlain, D. Fearghas, Murthy, Vishakantha, Levisay, Justin, Marzo, Kevin, Graham, John, Dzavik, Vlad, So, Derek, Goodman, Shaun, Rosenberg, Yves D., Pereira, Naveen, and Farkouh, Michael E.

Abstract

Purpose: Chronic kidney disease (CKD) is a risk factor for ischemic and bleeding events with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Whether the presence of CYP2C19 loss of function (LOF) alleles modifies this risk, and whether a genotype-guided (GG) escalation of P2Y12 inhibitor therapy post PCI is safe in this population is unclear. Methods: This was a post hoc analysis of randomized patients in TAILOR PCI. Patients were divided into two groups based on estimated glomerular filtration rate (eGFR) threshold of < 60 ml/min/1.73 m2 for CKD (n = 539) and non-CKD (n = 4276). The aggregate of cardiovascular death, stroke, myocardial infarction, stent thrombosis, and severe recurrent coronary ischemia at 12-months post-PCI was assessed as the primary endpoint. Secondary endpoint was major or minor bleeding. Results: Mean (standard deviation) eGFR among patients with CKD was 49.5 (8.4) ml/min/1.72 m2. Among all patients, there was no significant interaction between randomized strategy and CKD status for any endpoint. Among LOF carriers, the interaction between randomized strategy and CKD status on composite ischemic outcome was not significant (p = 0.2). GG strategy was not associated with an increased risk of bleeding in either CKD group. Conclusions: In this exploratory analysis, escalation of P2Y12 inhibitor therapy following a GG strategy did not reduce the primary outcome in CKD. However, P2Y12 inhibitor escalation following a GG strategy was not associated with increased bleeding risk in CKD. Larger studies in CKD are needed. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01742117?term=TAILOR-PCI&draw=2&rank=1. NCT01742117. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Updated Expert Consensus Statement on Platelet Function and Genetic Testing for Guiding P2Y12 Receptor Inhibitor Treatment in Percutaneous Coronary Intervention

Author

Sibbing, Dirk, Aradi, Daniel, Alexopoulos, Dimitrios, ten Berg, Jurrien, Bhatt, Deepak L., Bonello, Laurent, Collet, Jean-Philippe, Cuisset, Thomas, Franchi, Francesco, Gross, Lisa, Gurbel, Paul, Jeong, Young-Hoon, Mehran, Roxana, Moliterno, David J., Neumann, Franz-Josef, Pereira, Naveen L., Price, Matthew J., Sabatine, Marc S., So, Derek Y.F., Stone, Gregg W., Storey, Robert F., Tantry, Udaya, Trenk, Dietmar, Valgimigli, Marco, Waksman, Ron, and Angiolillo, Dominick J.

Published
2019
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46. 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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