• Je něco špatně v tomto záznamu ?

Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy

SM. Hegde, SJ. Lester, SD. Solomon, M. Michels, PM. Elliott, SF. Nagueh, L. Choudhury, D. Zemanek, DR. Zwas, D. Jacoby, A. Wang, CY. Ho, W. Li, AJ. Sehnert, I. Olivotto, TP. Abraham

. 2021 ; 78 (25) : 2518-2532. [pub] 20211221

Jazyk angličtina Země Spojené státy americké

Typ dokumentu klinické zkoušky, fáze III, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22011666

BACKGROUND: EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy) demonstrated that mavacamten, a cardiac myosin inhibitor, improves symptoms, exercise capacity, and left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM). OBJECTIVES: The purpose of this study was to evaluate mavacamten's effect on measures of cardiac structure and function and its association with changes in other clinical measures. METHODS: Key echocardiographic parameters from serial echocardiograms over 30 weeks from 251 symptomatic oHCM patients (mavacamten [n = 123], placebo [n = 128]) were assessed in a core laboratory. RESULTS: More patients on mavacamten (80.9%; n = 76 of 94) vs placebo (34.0%; n = 33 of 97) showed complete resolution of mitral valve systolic anterior motion after 30 weeks (difference, 46.8%; P < 0.0001). Mavacamten also improved measures of diastolic function vs placebo, including left atrial volume index (LAVI) (mean ± SD baseline: 40 ± 12 mL/m2 vs 41 ± 14 mL/m2; mean change from baseline of -7.5 mL/m2 [95% CI: -9.0 to -6.1 mL/m2] vs -0.09 mL/m2 [95% CI: -1.6 to 1.5 mL/m2]; P < 0.0001) and lateral E/e' (baseline, 15 ± 6 vs 15 ± 8; change of -3.8 [95% CI: -4.7 to -2.8] vs 0.04 [95% CI: -0.9 to 1.0]; P < 0.0001). Among mavacamten-treated patients, improvement in resting, Valsalva, and post-exercise LVOT gradients, LAVI, and lateral E/e' was associated with reduction in N-terminal pro-B-type natriuretic peptide (P ≤ 0.03 for all). Reduction in LAVI was associated with improved peak exercise oxygen consumption (P = 0.04). CONCLUSIONS: Mavacamten significantly improved measures of left ventricular diastolic function and systolic anterior motion. Improvement in LVOT obstruction, LAVI, and E/e' was associated with reduction in a biomarker of myocardial wall stress (N-terminal pro-B-type natriuretic peptide). These findings demonstrate improvement in important markers of the pathophysiology of oHCM with mavacamten. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545).

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22011666
003      
CZ-PrNML
005      
20220506130049.0
007      
ta
008      
220425s2021 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.jacc.2021.09.1381 $2 doi
035    __
$a (PubMed)34915982
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Hegde, Sheila M $u Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address: shegde@bwh.harvard.edu
245    10
$a Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy / $c SM. Hegde, SJ. Lester, SD. Solomon, M. Michels, PM. Elliott, SF. Nagueh, L. Choudhury, D. Zemanek, DR. Zwas, D. Jacoby, A. Wang, CY. Ho, W. Li, AJ. Sehnert, I. Olivotto, TP. Abraham
520    9_
$a BACKGROUND: EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy) demonstrated that mavacamten, a cardiac myosin inhibitor, improves symptoms, exercise capacity, and left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM). OBJECTIVES: The purpose of this study was to evaluate mavacamten's effect on measures of cardiac structure and function and its association with changes in other clinical measures. METHODS: Key echocardiographic parameters from serial echocardiograms over 30 weeks from 251 symptomatic oHCM patients (mavacamten [n = 123], placebo [n = 128]) were assessed in a core laboratory. RESULTS: More patients on mavacamten (80.9%; n = 76 of 94) vs placebo (34.0%; n = 33 of 97) showed complete resolution of mitral valve systolic anterior motion after 30 weeks (difference, 46.8%; P < 0.0001). Mavacamten also improved measures of diastolic function vs placebo, including left atrial volume index (LAVI) (mean ± SD baseline: 40 ± 12 mL/m2 vs 41 ± 14 mL/m2; mean change from baseline of -7.5 mL/m2 [95% CI: -9.0 to -6.1 mL/m2] vs -0.09 mL/m2 [95% CI: -1.6 to 1.5 mL/m2]; P < 0.0001) and lateral E/e' (baseline, 15 ± 6 vs 15 ± 8; change of -3.8 [95% CI: -4.7 to -2.8] vs 0.04 [95% CI: -0.9 to 1.0]; P < 0.0001). Among mavacamten-treated patients, improvement in resting, Valsalva, and post-exercise LVOT gradients, LAVI, and lateral E/e' was associated with reduction in N-terminal pro-B-type natriuretic peptide (P ≤ 0.03 for all). Reduction in LAVI was associated with improved peak exercise oxygen consumption (P = 0.04). CONCLUSIONS: Mavacamten significantly improved measures of left ventricular diastolic function and systolic anterior motion. Improvement in LVOT obstruction, LAVI, and E/e' was associated with reduction in a biomarker of myocardial wall stress (N-terminal pro-B-type natriuretic peptide). These findings demonstrate improvement in important markers of the pathophysiology of oHCM with mavacamten. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545).
650    _2
$a senioři $7 D000368
650    _2
$a benzylaminy $x farmakologie $x terapeutické užití $7 D001596
650    _2
$a biologické markery $x krev $7 D015415
650    _2
$a srdeční myosiny $x antagonisté a inhibitory $7 D024722
650    _2
$a hypertrofická kardiomyopatie $x krev $x diagnostické zobrazování $x farmakoterapie $7 D002312
650    _2
$a dvojitá slepá metoda $7 D004311
650    _2
$a echokardiografie $7 D004452
650    _2
$a tolerance zátěže $x účinky léků $7 D017079
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a srdce $x účinky léků $7 D006321
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a uracil $x analogy a deriváty $x farmakologie $x terapeutické užití $7 D014498
655    _2
$a klinické zkoušky, fáze III $7 D017428
655    _2
$a časopisecké články $7 D016428
655    _2
$a multicentrická studie $7 D016448
655    _2
$a randomizované kontrolované studie $7 D016449
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Lester, Steven J $u Department of Cardiovascular Diseases, Mayo Clinic, Phoenix, Arizona, USA
700    1_
$a Solomon, Scott D $u Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
700    1_
$a Michels, Michelle $u Department of Cardiology, Thoraxcenter, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
700    1_
$a Elliott, Perry M $u Institute of Cardiovascular Science, University College London, London, United Kingdom
700    1_
$a Nagueh, Sherif F $u Methodist DeBakey Heart and Vascular Center, Houston, Texas, USA
700    1_
$a Choudhury, Lubna $u Bluhm Cardiovascular Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA
700    1_
$a Zemanek, David $u 2nd Department of Internal Medicine-Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
700    1_
$a Zwas, Donna R $u Heart Institute, Hadassah University Medical Center, Jerusalem, Israel
700    1_
$a Jacoby, Daniel $u Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University, New Haven, Connecticut, USA
700    1_
$a Wang, Andrew $u Duke University School of Medicine, Durham, North Carolina, USA
700    1_
$a Ho, Carolyn Y $u Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
700    1_
$a Li, Wanying $u MyoKardia, Inc, a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, California, USA
700    1_
$a Sehnert, Amy J $u MyoKardia, Inc, a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, California, USA
700    1_
$a Olivotto, Iacopo $u Cardiomyopathy Unit, Azienda Ospedaliera Universitaria Careggi and the University of Florence, Florence, Italy
700    1_
$a Abraham, Theodore P $u UCSF HCM Center of Excellence, University of California San Francisco, San Francisco, California, USA
773    0_
$w MED00002964 $t Journal of the American College of Cardiology $x 1558-3597 $g Roč. 78, č. 25 (2021), s. 2518-2532
856    41
$u https://pubmed.ncbi.nlm.nih.gov/34915982 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220425 $b ABA008
991    __
$a 20220506130041 $b ABA008
999    __
$a ok $b bmc $g 1789327 $s 1162864
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 78 $c 25 $d 2518-2532 $e 20211221 $i 1558-3597 $m Journal of the American College of Cardiology $n J. Am. Coll. Cardiol. $x MED00002964
LZP    __
$a Pubmed-20220425

Najít záznam

Citační ukazatele

Možnosti archivace