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1. Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy.

Author

Braunwald, Eugene, Saberi, Sara, Abraham, Theodore, Elliott, Perry, and Olivotto, Iacopo

Subjects
Ejection fraction, Myectomy, Myosin, Pressure gradient, Adult, Humans, Benzylamines, Cardiomyopathy, Hypertrophic, Heart, United States, Uracil
Abstract

Mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association Classes II and III obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten was developed to target the hyper-contractile phenotype, which plays a critical role in the pathophysiology of the disease. In Phase 2 and 3 clinical trials, mavacamten was well tolerated, reduced left ventricular outflow tract gradients, improved exercise capacity and symptoms, and was associated with improvements in other clinically relevant parameters, such as patient-reported outcomes and circulating biomarkers. In addition, treatment with mavacamten was associated with evidence of favourable cardiac remodelling in multi-modality imaging studies. Mavacamten substantially reduced guideline eligibility for septal reduction therapy candidates with oHCM and drug-refractory symptoms. In this article, the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM are reviewed. Longer term extension studies may help address questions related to the positioning of mavacamten in current oHCM management algorithms, interactions with background therapy, as well as the potential for disease modification beyond symptomatic relief of left ventricular outflow tract obstruction.

Published
2023

4. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines

Author

Ommen, Steve R., Ho, Carolyn Y., Asif, Irfan M., Balaji, Seshadri, Burke, Michael A., Day, Sharlene M., Dearani, Joseph A., Epps, Kelly C., Evanovich, Lauren, Ferrari, Victor A., Joglar, José A., Khan, Sadiya S., Kim, Jeffrey J., Kittleson, Michelle M., Krittanawong, Chayakrit, Martinez, Matthew W., Mital, Seema, Naidu, Srihari S., Saberi, Sara, Semsarian, Christopher, Times, Sabrina, and Waldman, Cynthia Burstein

Published
2024
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6. Hypertrophic Cardiomyopathy

Author

Saberi, Sara, Smith, Eric, Toth, Peter P., Series Editor, Sharma, Garima, editor, Scott, Nandita S., editor, Davis, Melinda B., editor, and Economy, Katherine E., editor

Published
2023
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9. Mavacamten-Associated Temporal Changes in Left Atrial Function in Obstructive HCM: Insights From the VALOR-HCM Trial

Author

Desai, M., Geske, J., Sherrid, M., Owens, A.T., Saberi, S., Wang, A., Tower-Rader, A., Fermin, D., Lakdawala, N., Masri, A., Zenker, M., Stendahl, J., Wheeler, M., Bach, R., Orford, J., Naidu, S., Rader, F., Bajona, P., Desai, Milind Y., Okushi, Yuichiro, Wolski, Kathy, Geske, Jeffrey B., Owens, Anjali, Saberi, Sara, Wang, Andrew, Cremer, Paul C., Sherrid, Mark, Lakdawala, Neal K., Tower-Rader, Albree, Fermin, David, Naidu, Srihari S., Lampl, Kathy L., Sehnert, Amy J., Nissen, Steven E., and Popovic, Zoran B.

Published
2024
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10. Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4

Author

MASRI, AHMAD, SHERRID, MARK V., ABRAHAM, THEODORE P., CHOUDHURY, LUBNA, GARCIA-PAVIA, PABLO, KRAMER, CHRISTOPHER M., BARRIALES-VILLA, ROBERTO, OWENS, ANJALI T., RADER, FLORIAN, NAGUEH, SHERIF F., OLIVOTTO, IACOPO, SABERI, SARA, TOWER-RADER, ALBREE, WONG, TIMOTHY C., COATS, CAROLINE J., WATKINS, HUGH, FIFER, MICHAEL A., SOLOMON, SCOTT D., HEITNER, STEPHEN B., JACOBY, DANIEL L., KUPFER, STUART, MALIK, FADY I., MENG, LISA, SOHN, REGINA L., WOHLTMAN, AMY, and MARON, MARTIN S.

Published
2024
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15. Abstract 17216: Limited Concordance of Core Lab Left Ventricular Ejection Fraction With Automated Assessments: A Sub-Study From VALOR-HCM

Author

Parizher, Gary, Jaber, Wael A, Owens, Anjali T, Wolski, Kathy E, Geske, Jeffrey B, Saberi, Sara, Wang, Andrew, Sherrid, Mark, Lakdawala, Neal K, Fifer, Michael A, Fermin, David R, Naidu, Srihari S, Smedira, Nicholas G, Schaff, Hartzell, McErlean, Ellen, Sewell, Christina M, Lampl, Kathy L, Sehnert, Amy J, Nissen, Steven E, Desai, Milind Y, and Cremer, Paul C

Published
2023
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16. Abstract 14249: Sex and Gene Based Differences in Age Related Penetrance of Dilated and Arrhythmogenic Cardiomyopathy

Author

Bart, Nicole K, Stroeks, Sophie, Khan, Sadiya S, Reza, Nosheen, Olivotto, Iacopo, Vissing, Christoffer, Sinnette, Corine, Owens, Anjali T, Fornaro, Alessandra, Mestroni, Luisa, Taylor, Matthew, Helms, Adam S, Prasad, Sanjay K, Saberi, Sara, Shore, Supriya, Verdonschot, Job, sinagra, Gianfranco, Merlo, Marco, Gigli, Marta, Wilsbacher, Lisa D, Heymans, Stephane, Wheeler, Matthew, Ashley, Euan A, Dal Ferro, Matteo, Paldino, Alessia, Day, Sharlene, de Feria, Alejandro, Stevenson, Lynne W, Ho, Carolyn, Claggett, Brian, Ware, James S, Parikh, Victoria N, Tayal, Upasana, and Lakdawala, Neal K

Published
2023
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19. Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry

Author

Abou Alaiwi, Sarah, Roston, Thomas M., Marstrand, Peter, Claggett, Brian Lee, Parikh, Victoria N., Helms, Adam S., Ingles, Jodie, Lampert, Rachel, Lakdawala, Neal K., Michels, Michelle, Owens, Anjali T., Rossano, Joseph W., Saberi, Sara, Abrams, Dominic J., Ashley, Euan A., Semsarian, Christopher, Stendahl, John C., Ware, James S., Miller, Erin, Ryan, Thomas D., Russell, Mark W., Day, Sharlene M., Olivotto, Iacopo, Vissing, Christoffer R., and Ho, Carolyn Y.

Published
2023
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20. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines

Author

Ommen, Steve R., primary, Ho, Carolyn Y., additional, Asif, Irfan M., additional, Balaji, Seshadri, additional, Burke, Michael A., additional, Day, Sharlene M., additional, Dearani, Joseph A., additional, Epps, Kelly C., additional, Evanovich, Lauren, additional, Ferrari, Victor A., additional, Joglar, José A., additional, Khan, Sadiya S., additional, Kim, Jeffrey J., additional, Kittleson, Michelle M., additional, Krittanawong, Chayakrit, additional, Martinez, Matthew W., additional, Mital, Seema, additional, Naidu, Srihari S., additional, Saberi, Sara, additional, Semsarian, Christopher, additional, Times, Sabrina, additional, and Waldman, Cynthia Burstein, additional

Published
2024
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21. Mitral Regurgitation in Obstructive Hypertrophic Cardiomyopathy

Author

Cremer, Paul C., primary, Geske, Jeffrey B., additional, Owens, Anjali, additional, Jaber, Wael A., additional, Harb, Serge C., additional, Saberi, Sara, additional, Wang, Andrew, additional, Sherrid, Mark, additional, Naidu, Srihari S., additional, Schaff, Hartzell V., additional, Smedira, Nicholas G., additional, Wang, Qiuqing, additional, Wolski, Kathy, additional, Lampl, Kathy L., additional, Sehnert, Amy J., additional, Nissen, Steven E., additional, and Desai, Milind Y., additional

Published
2024
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24. Genetic constraint at single amino acid resolution in protein domains improves missense variant prioritisation and gene discovery.

Author

Zhang, Xiaolei, Theotokis, Pantazis I., Li, Nicholas, Ashley, Euan, Colan, Steven D., Day, Sharlene M., Helms, Adam, Ho, Carolyn Y., Ingles, Jodie, Jacoby, Daniel, Lakdawala, Neal K., Michels, Michelle, Olivotto, Iacopo, Owens, Anjali, Parikh, Victoria N., Pereira, Alexandre C., Rossano, Joseph, Saberi, Sara, Semsarian, Chris, and Wittekind, Samuel

Subjects
AMINO acid separation, MISSENSE mutation, PROTEIN fractionation, PROTEIN domains, GENETIC variation
Abstract

Background: One of the major hurdles in clinical genetics is interpreting the clinical consequences associated with germline missense variants in humans. Recent significant advances have leveraged natural variation observed in large-scale human populations to uncover genes or genomic regions that show a depletion of natural variation, indicative of selection pressure. We refer to this as "genetic constraint". Although existing genetic constraint metrics have been demonstrated to be successful in prioritising genes or genomic regions associated with diseases, their spatial resolution is limited in distinguishing pathogenic variants from benign variants within genes. Methods: We aim to identify missense variants that are significantly depleted in the general human population. Given the size of currently available human populations with exome or genome sequencing data, it is not possible to directly detect depletion of individual missense variants, since the average expected number of observations of a variant at most positions is less than one. We instead focus on protein domains, grouping homologous variants with similar functional impacts to examine the depletion of natural variations within these comparable sets. To accomplish this, we develop the Homologous Missense Constraint (HMC) score. We utilise the Genome Aggregation Database (gnomAD) 125 K exome sequencing data and evaluate genetic constraint at quasi amino-acid resolution by combining signals across protein homologues. Results: We identify one million possible missense variants under strong negative selection within protein domains. Though our approach annotates only protein domains, it nonetheless allows us to assess 22% of the exome confidently. It precisely distinguishes pathogenic variants from benign variants for both early-onset and adult-onset disorders. It outperforms existing constraint metrics and pathogenicity meta-predictors in prioritising de novo mutations from probands with developmental disorders (DD). It is also methodologically independent of these, adding power to predict variant pathogenicity when used in combination. We demonstrate utility for gene discovery by identifying seven genes newly significantly associated with DD that could act through an altered-function mechanism. Conclusions: Grouping variants of comparable functional impacts is effective in evaluating their genetic constraint. HMC is a novel and accurate predictor of missense consequence for improved variant interpretation. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Design of DISCOVER-HCM: A Registry of Real-world Treatment Patterns and Outcomes of Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy

Author

Hernandez, Adrian, primary, Masoudi, Frederick, additional, Mazimba, Sula, additional, Saberi, Sara, additional, Setoguchi, Soko, additional, Spertus, John, additional, Shen, Sophie, additional, Balaratnam, Ganesh, additional, Chen, Yu-mao, additional, Afsari, Sonia, additional, Minton, Neil, additional, and Januzzi, James, additional

Published
2024
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26. Effect of Aficamten on Structure and Function in Patients with Obstructive Hypertrophic Cardiomyopathy: The FOREST-HCM CMR Sub-study

Author

Masri, Ahmad, primary, Cardoso, Rhanderson, additional, Abraham, Theodore, additional, Choudhury, Lubna, additional, Rader, Florian, additional, Saberi, Sara, additional, Tower-Rader, Albree, additional, Wang, Andrew, additional, Heitner, Stephen, additional, Kupfer, Stuart, additional, Malik, Fady, additional, Melloni, Chiara, additional, Wei, Jenny, additional, Wohltman, Amy, additional, and Kwong, Raymond, additional

Published
2024
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27. Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation

Author

Thompson, Andrea D., Helms, Adam S., Kannan, Anamika, Yob, Jaime, Lakdawala, Neal K., Wittekind, Samuel G., Pereira, Alexandre C., Jacoby, Daniel L., Colan, Steven D., Ashley, Euan A., Saberi, Sara, Ware, James S., Ingles, Jodie, Semsarian, Christopher, Michels, Michelle, Mazzarotto, Francesco, Olivotto, Iacopo, Ho, Carolyn Y., and Day, Sharlene M.

Published
2021
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28. Myosin Inhibition and Left Ventricular Diastolic Function in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy: Insights From the VALOR-HCM Study

Author

Cremer, Paul C., Geske, Jeffrey B., Owens, Anjali, Jaber, Wael A., Harb, Serge C., Saberi, Sara, Wang, Andrew, Sherrid, Mark, Naidu, Srihari S., Schaff, Hartzell, Smedira, Nicholas G., Wang, Qiuqing, Wolski, Kathy, Lampl, Kathy L., Sehnert, Amy J., Nissen, Steven E., and Desai, Milind Y.

Published
2022
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30. Abstract 12598: Effect of Mavacamten on Systolic Anterior Motion of the Mitral Valve and Mitral Regurgitation in Patients With Obstructive Hypertrophic Cardiomyopathy: Insights From the VALOR-HCM Study

Author

Cremer, Paul C, Geske, Jeffrey B, Owens, Anjali T, Jaber, Wael A, Harb, Serge C, Saberi, Sara, Wang, Andrew, Naidu, Srihari S, Schaff, Hartzell V, Smedira, Nicholas G, Wang, Quing, Lampl, Kathy, Sehnert, Amy J, Nissen, Steven E, and Desai, Milind Y

Published
2022
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32. Abstract 12104: Pediatric Hypertrophic Cardiomyopathy With Left Ventricular Systolic Dysfunction: Insights From the Sarcomeric Human Cardiomyopathy Registry (SHaRe)

Author

Abou Alaiwi, Sarah, Roston, Thomas M, Vissing, Christoffer, Marstrand, Peter, Claggett, Brian, Nauffal, Victor, Parikh, Victoria N, Helms, Adam S, Ingles, Jodie, Jacoby, Daniel L, Lakdawala, Neal K, Michels, Michelle, Owens, Anjali T, Ashley, Euan A, Pereira, Alexandre, Rossano, Joseph, Saberi, Sara, Semsarian, Christopher, Ware, James S, Miller, Erin, Wittekind, Samuel, Russell, Mark W, Day, Sharlene, olivotto, iacopo, and Ho, Carolyn

Published
2022
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39. Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction

Author

Desai, Milind Y., primary, Owens, Anjali, additional, Wolski, Kathy, additional, Geske, Jeffrey B., additional, Saberi, Sara, additional, Wang, Andrew, additional, Sherrid, Mark, additional, Cremer, Paul C., additional, Lakdawala, Neal K., additional, Tower-Rader, Albree, additional, Fermin, David, additional, Naidu, Srihari S., additional, Smedira, Nicholas G., additional, Schaff, Hartzell, additional, McErlean, Ellen, additional, Sewell, Christina, additional, Mudarris, Lana, additional, Gong, Zhiqun, additional, Lampl, Kathy, additional, Sehnert, Amy J., additional, and Nissen, Steven E., additional

Published
2023
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45. Impact of SARS‐Cov‐2 infection in patients with hypertrophic cardiomyopathy: results of an international multicentre registry

Author

Gimeno, Juan R., Olivotto, Iacopo, Isabel Rodriguez, Ana, Ho, Carolyn Y., Fernandez, Adrian, Quiroga, Alejandro, Angeles Espinosa, Mari, Gomez-Gonzalez, Cristina, Robledo, Maria, Tojal-Sierra, Lucas, Day, Sharlene M., Owens, Anjali, Barriales-Villa, Roberto, Maria Larranaga, Jose, Rodriguez-Palomares, Jose, Gonzalez-del-Hoyo, Maribel, Piqueras-Flores, Jesus, Reza, Nosheen, Chumakova, Olga, Ashley, Euan A., Parikh, Victoria, Wheeler, Matthew, Jacoby, Daniel, Pereira, Alexandre C., Saberi, Sara, Helms, Adam S., Villacorta, Eduardo, Gallego-Delgado, Maria, Castro, Daniel, Dominguez, Fernando, Ripoll-Vera, Tomas, Zorio-Grima, Esther, Carlos Sanchez-Martinez, Jose, Garcia-Alvarez, Ana, Arbelo, Elena, Victoria Mogollon, Maria, Eugenia Fuentes-Canamero, Maria, Grande, Elias, Pena, Carlos, Monserrat, Lorenzo, Lakdawala, Neal K., Dilema Int Cardiomyopathy Heart Fa, [Gimeno, Juan R.] Univ Murcia, Dept Med Interns, Ctra Finca Buenavista S-N,Campus Ciencias Salud, Murcia 30120, Spain, [Isabel Rodriguez, Ana] Univ Murcia, Dept Med Interns, Ctra Finca Buenavista S-N,Campus Ciencias Salud, Murcia 30120, Spain, [Gimeno, Juan R.] European Reference Networks Rare Low Prevalence &, Amsterdam, Netherlands, [Isabel Rodriguez, Ana] European Reference Networks Rare Low Prevalence &, Amsterdam, Netherlands, [Castro, Daniel] European Reference Networks Rare Low Prevalence &, Amsterdam, Netherlands, [Dominguez, Fernando] European Reference Networks Rare Low Prevalence &, Amsterdam, Netherlands, [Gimeno, Juan R.] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Angeles Espinosa, Mari] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Gomez-Gonzalez, Cristina] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Barriales-Villa, Roberto] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Maria Larranaga, Jose] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Rodriguez-Palomares, Jose] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Gonzalez-del-Hoyo, Maribel] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Villacorta, Eduardo] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Gallego-Delgado, Maria] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Castro, Daniel] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Dominguez, Fernando] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Zorio-Grima, Esther] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Carlos Sanchez-Martinez, Jose] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Garcia-Alvarez, Ana] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Arbelo, Elena] Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid, Spain, [Olivotto, Iacopo] Careggi Univ Hosp, Cardiomyopathy Unit, Florence, Italy, [Ho, Carolyn Y.] Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA, [Lakdawala, Neal K.] Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA, [Fernandez, Adrian] Favaloro Fdn Univ Hosp, Unidad Cardiopatias Familiares, Buenos Aires, DF, Argentina, [Quiroga, Alejandro] Favaloro Fdn Univ Hosp, Unidad Cardiopatias Familiares, Buenos Aires, DF, Argentina, [Angeles Espinosa, Mari] Hosp Gen Univ Gregorio Maranon, Unidad Cardiopatias Familiares, Madrid, Spain, [Gomez-Gonzalez, Cristina] Hosp Gen Univ Gregorio Maranon, Unidad Cardiopatias Familiares, Madrid, Spain, [Robledo, Maria] Hosp Univ Araba Txagorritxu, Alava, Spain, [Tojal-Sierra, Lucas] Hosp Univ Araba Txagorritxu, Alava, Spain, [Day, Sharlene M.] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA, [Owens, Anjali] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA, [Reza, Nosheen] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA, [Barriales-Villa, Roberto] Complexo Hosp Univ A Coruna, Unidad CSUR Cardiopatias Familiares, La Coruna, Spain, [Maria Larranaga, Jose] Complexo Hosp Univ A Coruna, Unidad CSUR Cardiopatias Familiares, La Coruna, Spain, [Rodriguez-Palomares, Jose] Hosp Univ Vall dHebron, Dept Cardiol, Barcelona, Spain, [Gonzalez-del-Hoyo, Maribel] Hosp Univ Vall dHebron, Dept Cardiol, Barcelona, Spain, [Rodriguez-Palomares, Jose] Univ Autonoma Barcelona, Vall dHebron Inst Recerca VHIR, Barcelona, Spain, [Gonzalez-del-Hoyo, Maribel] Univ Autonoma Barcelona, Vall dHebron Inst Recerca VHIR, Barcelona, Spain, [Piqueras-Flores, Jesus] Hosp Gen Univ Ciudad Real, Cardiac Dept, Ciudad Real, Spain, [Chumakova, Olga] Municipal Clin Hosp 17, Moscow, Russia, [Ashley, Euan A.] Stanford Univ, Med Ctr, Ctr Inherited Heart Dis, Stanford, CA 94305 USA, [Parikh, Victoria] Stanford Univ, Med Ctr, Ctr Inherited Heart Dis, Stanford, CA 94305 USA, [Wheeler, Matthew] Stanford Univ, Med Ctr, Ctr Inherited Heart Dis, Stanford, CA 94305 USA, [Jacoby, Daniel] Yale New Haven Hosp, New Haven, CT USA, [Pereira, Alexandre C.] Univ Sao Paulo, Hosp Clin, Sao Paulo, Brazil, [Saberi, Sara] Univ Michigan Hosp, Dept Internal Med, Ann Arbor, MI 48109 USA, [Helms, Adam S.] Univ Michigan Hosp, Dept Internal Med, Ann Arbor, MI 48109 USA, [Villacorta, Eduardo] Complejo Asistencial Univ Salamanca, Serv Cardiol, Unidad Cardiopatias Familiares, Salamanca, Spain, [Gallego-Delgado, Maria] Complejo Asistencial Univ Salamanca, Serv Cardiol, Unidad Cardiopatias Familiares, Salamanca, Spain, [Villacorta, Eduardo] Inst Invest Biomed Salamanca IBSAL, Gerencia Reg Salud Castilla & Leon SACYL, Salamanca, Spain, [Gallego-Delgado, Maria] Inst Invest Biomed Salamanca IBSAL, Gerencia Reg Salud Castilla & Leon SACYL, Salamanca, Spain, [Villacorta, Eduardo] Univ Salamanca, Dept Med, Salamanca, Spain, [Gallego-Delgado, Maria] Univ Salamanca, Dept Med, Salamanca, Spain, [Castro, Daniel] Hosp Univ Puerta Hierro Majadahonda, Unidad CSUR ERN Cardiopatias Familiares, Madrid, Spain, [Dominguez, Fernando] Hosp Univ Puerta Hierro Majadahonda, Unidad CSUR ERN Cardiopatias Familiares, Madrid, Spain, [Ripoll-Vera, Tomas] Hosp Univ Son Llatzer, Unidad Cardiopatias Familiares, Mallorca, Spain, [Zorio-Grima, Esther] Hosp Univ & Politecn La Fe, Unidad Cardiopatias Familiares, Valencia, Spain, [Carlos Sanchez-Martinez, Jose] Hosp Univ & Politecn La Fe, Unidad Cardiopatias Familiares, Valencia, Spain, [Garcia-Alvarez, Ana] Univ Barcelona, Hosp Clin, Cardiol Dept, Arrhythmia Sect, Barcelona, Spain, [Arbelo, Elena] Univ Barcelona, Hosp Clin, Cardiol Dept, Arrhythmia Sect, Barcelona, Spain, [Garcia-Alvarez, Ana] Inst Invest August Pi & Sunyer IDIBAPS, Barcelona, Spain, [Arbelo, Elena] Inst Invest August Pi & Sunyer IDIBAPS, Barcelona, Spain, [Victoria Mogollon, Maria] Hosp San Pedro Alcantara, Cardiac Dept, Caceres, Spain, [Eugenia Fuentes-Canamero, Maria] Badajoz Univ Hosp, Cardiac Dept, Badajoz, Spain, [Grande, Elias] Dilemma Solut SL, La Coruna, Spain, [Pena, Carlos] Dilemma Solut SL, La Coruna, Spain, [Monserrat, Lorenzo] Dilemma Solut SL, La Coruna, SpainHosp Univ Virgen de la Victoria, Unidad Insuficiencia Cardiaca & Cardiopatias Fami, Serv Cardiol, Malaga, SpainHosp Vega Baja, Cardiac Dept, Alicante, SpainHosp Univ Virgen del Rocio, Unidad Cardiopatias Familiares, Seville, SpainUniv Trieste, Azienda Sanitaria Univ Giuliano Isontina ASUGI, Cardiothoracovasc Dept, Trieste, ItalyHosp Univ Infanta Leonor, Cardiac Dept, Madrid, SpainHosp Gen Univ Alicante, Unidad Cardiopatias Familiares, Alicante, SpainHosp Arquitecto Morcide, Cardiac Dept, Ferrol, Spain, Instituto de Salud Carlos III (ICSIII), MyoKardia/Bristol Myers Squibb, Institut Català de la Salut, [Gimeno JR] Departamento de Medicina Interna, Universidad de Murcia, Murcia, Spain. European Reference Networks for rare, low prevalence and complex diseases of the heart (ERN GUARD-Heart), Amsterdam, The Netherlands. Center for Biomedical Network Research on Cardiovascular Diseases (CIBERCV), Madrid, Spain. [Olivotto I] Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy. [Rodríguez AI] Departamento de Medicina Interna, Universidad de Murcia, Murcia, Spain. European Reference Networks for rare, low prevalence and complex diseases of the heart (ERN GUARD-Heart), Amsterdam, The Netherlands. [Ho CY] Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA, USA. [Fernández A, Quiroga A] Unidad de Cardiopatías Familiares, Favaloro Foundation University Hospital, Buenos Aires, Argentina. [Rodríguez-Palomares J, González-del-Hoyo M] Center for Biomedical Network Research on Cardiovascular Diseases (CIBERCV), Madrid, Spain. Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Adult, Registry, Cardiology, Heart failure, Miocardi - Malalties - Factors de risc, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Ventricular Dysfunction, Left, Atrial Fibrillation, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Humans, Disease, Registries, Aged, COVID-19 (Malaltia) - Complicacions, SARS-CoV-2, SARS-CoV-2 infection, Cor - Hipertròfia, COVID-19, Cardiovascular Diseases::Heart Diseases::Cardiomyopathies::Cardiomyopathy, Hypertrophic [DISEASES], Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Middle Aged, Cardiomyopathy, Hypertrophic, Prognosis, Classification, Hypertrophic cardiomyopathy, enfermedades cardiovasculares::enfermedades cardíacas::miocardiopatías::miocardiopatía hipertrófica [ENFERMEDADES], Female, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Statement, Cardiology and Cardiovascular Medicine
Abstract

COVID-19; SARS-CoV-2 infection; Heart failure COVID-19; Infección por SARS-CoV-2; Insuficiencia cardiaca COVID-19; Infecció per SARS-CoV-2; Insuficiència cardíaca Aims To describe the natural history of SARS-CoV-2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. Methods and results Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS-Cov-2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS-CoV-2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty-nine (22.9%) HCM patients were hospitalized for non-ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS-CoV-2-related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12–4.51], P = 0.0229}, baseline New York Heart Association class [OR per one-unit increase 4.01 (95%CI: 1.75–9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16–26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20–49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community-based SARS-CoV-2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98–2.91, P = 0.0600). Conclusions Over one-fourth of HCM patients infected with SARS-Cov-2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality. The project was funded by a grant from the Instituto de Salud Carlos III (ICSIII, COV20 00420). We should state that the SHaRe registry has been supported by an unrestricted grant from MyoKardia/Bristol Myers Squibb.

Published
2022

49. Efficacy And Safety Of Aficamten In Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From The Randomized Evaluation Of Dosing With Ck-3773274 In Hypertrophic Cardiomyopathy Open Label Extension Study

Author

Masri, Ahmad, primary, Abraham, Theodore P., additional, Choudhury, Lubna, additional, Owens, Anjali T., additional, Tower-Rader, Albree, additional, Rader, Florian, additional, Garcia-Pavia, Pablo, additional, Olivotto, Iacopo, additional, Coats, Caroline, additional, Fifer, Michael A., additional, Solomon, Scott D., additional, Watkins, Hugh, additional, Heitner, Stephen B., additional, Jacoby, Daniel, additional, Kupfer, Stuart, additional, Malik, Fady I., additional, Meng, Lisa, additional, Paige, Sharon L., additional, Wohltman, Amy, additional, Maron, Martin S., additional, and Saberi, Sara, additional

Published
2023
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