Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction ancillary study

Cecil A. Rambarat; Islam Y. Elgendy; Eileen M. Handberg; C. Noel Bairey Merz; Janet Wei; Margo B. Minissian; Michael D. Nelson; Louise E.J. Thomson; Daniel S. Berman; Leslee J. Shaw; Galen Cook-Wiens; Carl J. Pepine

doi:10.1016/j.ijcard.2018.09.081

Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction ancillary study

Cecil A. Rambarat
, Islam Y. Elgendy
, Eileen M. Handberg
, C. Noel Bairey Merz
, Janet Wei
, Margo B. Minissian
, Michael D. Nelson
, Louise E.J. Thomson
, Daniel S. Berman
, Leslee J. Shaw
, Galen Cook-Wiens
, Carl J. Pepine

Producción científica: Article › revisión exhaustiva

47 Citas (Scopus)

Resumen

Background: In a prior trial of late sodium channel inhibition (ranolazine) among symptomatic subjects without obstructive coronary artery disease (CAD) and limited myocardial perfusion reserve index (MPRI), we observed no improvement in angina or MPRI, overall. Here we describe the clinical characteristics and myocardial perfusion responses of a pre-defined subgroup who had coronary flow reserve (CFR) assessed invasively. Methods: Symptomatic patients without obstructive CAD and limited MPRI in a randomized, double-blind, crossover trial of ranolazine vs. placebo were subjects of this prespecified substudy. Because we had previously observed that adverse outcomes and beneficial treatment responses occurred in those with lower CFR, patients were subgrouped by CFR <2.5 vs ≥2.5. Symptoms were assessed using the Seattle Angina Questionnaire and the SAQ-7, and left-ventricular volume and MPRI were assessed by magnetic resonance imaging (MRI). Coronary angiograms, CFR, and MRI data were analyzed by core labs masked to treatment and patient characteristics. Results: During qualifying coronary angiography, 81 patients (mean age 55 years, 98% women) had invasively determined CFR 2.69 ± 0.65 (mean ± SD; range 1.4–5.5); 43% (n = 35) had CFR <2.5. Demographic and symptomatic findings did not differ comparing CFR subgroups. Those with low CFR had improved angina (p = 0.04) and midventricular MPRI (p = 0.03) with ranolazine vs placebo. Among patients with low CFR, reduced left-ventricular end-diastolic volume predicted a beneficial angina response. Conclusions: Symptomatic patients with CFR <2.5 and no obstructive CAD had improved angina and myocardial perfusion with ranolazine, supporting the hypothesis that the late sodium channel is important in management of coronary microvascular dysfunction. Trial registration: clinicaltrials.gov

Idioma original	English
Páginas (desde-hasta)	8-13
Número de páginas	6
Publicación	International Journal of Cardiology
Volumen	276
DOI	https://doi.org/10.1016/j.ijcard.2018.09.081
Estado	Published - feb 1 2019

Nota bibliográfica

Publisher Copyright:
© 2018 Elsevier B.V.

Financiación

This work was supported by an unrestricted research grant from Gilead ; and by contracts from the National Heart, Lung, and Blood Institute [ N01-HV-68161 , N01-HV-68162 , N01-HV-68163 , N01-HV-68164 , R01 HL090957 , R01 HL089765 ]; GCRC grant from the National Center for Research Resources [ MO1-RR00425 ]; National Center for Research Resources [ UL1RR033176 ]; NIH/ National Center for Advancing Translational Sciences (NCATS) UCLA CTSI grant [ UL1TR000124 ] and UF CTSI grant [ UL1TR001427 ]; American Heart Association [ 16SDG27260115 ]; and grants from the Gustavus and Louis Pfeiffer Research Foundation , Denville, New Jersey; the Women's Guild of Cedars-Sinai Medical Center , Los Angeles, California; the Edythe L. Broad Women's Heart Research Fellowship, Cedars-Sinai Medical Center, Los Angeles, California; the Constance Austin Women's Heart Research Fellowship; the Barbra Streisand Women's Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles; and the Erika Glazer Women's Heart Health Project, Cedars-Sinai Medical Center, Los Angeles; the Gatorade Trust through funds distributed by the University of Florida Department of Medicine, and PCORnet-OneFlorida Clinical Research Consortium CDRN-1501-26692 , University of Florida, Gainesville, FL. The study was an investigator-initiated ancillary trial to the National Heart, Lung and Blood Institute (NHLBI)-sponsored WISE-CVD, funded in part by Gilead Sciences, with oversight by the WISE Data Safety Monitoring Committee. Statistical analysis was performed by investigators independent of NHLBI and Gilead. The decision to submit for publication was made by the investigators who had access to all data after the last subject completed the study.

Financiadores	Número del financiador
Barbra Streisand Women's Cardiovascular Research and Education Program
Constance Austin Women's Heart Research Fellowship
Edythe L. Broad Women's Heart Research Fellowship
Erika Glazer Women's Heart Health Project
GCRC
Gatorade Trust
UCLA CTSI
UF CTSI
University of Florida Department of Medicine
Women's Guild of Cedars-Sinai Medical Center
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)	R01 HL090957, N01-HV-68161, N01-HV-68163, N01-HV-68162, N01-HV-68164, R01 HL089765
National Center for Research Resources	MO1-RR00425, UL1RR033176
American the American Heart Association	16SDG27260115
Gustavus and Louise Pfeiffer Research Foundation
Gilead Sciences
National Center for Advancing Translational Sciences (NCATS)	UL1TR000124, UL1TR001427
Florida AandM University and Florida State University	CDRN-1501-26692
Cedars-Sinai Medical Center

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.ijcard.2018.09.081

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Rambarat, C. A., Elgendy, I. Y., Handberg, E. M., Bairey Merz, C. N., Wei, J., Minissian, M. B., Nelson, M. D., Thomson, L. E. J., Berman, D. S., Shaw, L. J., Cook-Wiens, G., & Pepine, C. J. (2019). Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction ancillary study. International Journal of Cardiology, 276, 8-13. https://doi.org/10.1016/j.ijcard.2018.09.081

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title = "Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction ancillary study",

abstract = "Background: In a prior trial of late sodium channel inhibition (ranolazine) among symptomatic subjects without obstructive coronary artery disease (CAD) and limited myocardial perfusion reserve index (MPRI), we observed no improvement in angina or MPRI, overall. Here we describe the clinical characteristics and myocardial perfusion responses of a pre-defined subgroup who had coronary flow reserve (CFR) assessed invasively. Methods: Symptomatic patients without obstructive CAD and limited MPRI in a randomized, double-blind, crossover trial of ranolazine vs. placebo were subjects of this prespecified substudy. Because we had previously observed that adverse outcomes and beneficial treatment responses occurred in those with lower CFR, patients were subgrouped by CFR <2.5 vs ≥2.5. Symptoms were assessed using the Seattle Angina Questionnaire and the SAQ-7, and left-ventricular volume and MPRI were assessed by magnetic resonance imaging (MRI). Coronary angiograms, CFR, and MRI data were analyzed by core labs masked to treatment and patient characteristics. Results: During qualifying coronary angiography, 81 patients (mean age 55 years, 98\% women) had invasively determined CFR 2.69 ± 0.65 (mean ± SD; range 1.4–5.5); 43\% (n = 35) had CFR <2.5. Demographic and symptomatic findings did not differ comparing CFR subgroups. Those with low CFR had improved angina (p = 0.04) and midventricular MPRI (p = 0.03) with ranolazine vs placebo. Among patients with low CFR, reduced left-ventricular end-diastolic volume predicted a beneficial angina response. Conclusions: Symptomatic patients with CFR <2.5 and no obstructive CAD had improved angina and myocardial perfusion with ranolazine, supporting the hypothesis that the late sodium channel is important in management of coronary microvascular dysfunction. Trial registration: clinicaltrials.gov",

keywords = "Angina, Coronary microvascular dysfunction, Late sodium channel inhibition",

author = "Rambarat, \{Cecil A.\} and Elgendy, \{Islam Y.\} and Handberg, \{Eileen M.\} and \{Bairey Merz\}, \{C. Noel\} and Janet Wei and Minissian, \{Margo B.\} and Nelson, \{Michael D.\} and Thomson, \{Louise E.J.\} and Berman, \{Daniel S.\} and Shaw, \{Leslee J.\} and Galen Cook-Wiens and Pepine, \{Carl J.\}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",

year = "2019",

month = feb,

day = "1",

doi = "10.1016/j.ijcard.2018.09.081",

language = "English",

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Rambarat, CA, Elgendy, IY, Handberg, EM, Bairey Merz, CN, Wei, J, Minissian, MB, Nelson, MD, Thomson, LEJ, Berman, DS, Shaw, LJ, Cook-Wiens, G & Pepine, CJ 2019, 'Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction ancillary study', International Journal of Cardiology, vol. 276, pp. 8-13. https://doi.org/10.1016/j.ijcard.2018.09.081

Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction ancillary study. / Rambarat, Cecil A.; Elgendy, Islam Y.; Handberg, Eileen M. et al.
En: International Journal of Cardiology, Vol. 276, 01.02.2019, p. 8-13.

Producción científica: Article › revisión exhaustiva

TY - JOUR

T1 - Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction

T2 - Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction ancillary study

AU - Rambarat, Cecil A.

AU - Elgendy, Islam Y.

AU - Handberg, Eileen M.

AU - Bairey Merz, C. Noel

AU - Wei, Janet

AU - Minissian, Margo B.

AU - Nelson, Michael D.

AU - Thomson, Louise E.J.

AU - Berman, Daniel S.

AU - Shaw, Leslee J.

AU - Cook-Wiens, Galen

AU - Pepine, Carl J.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Background: In a prior trial of late sodium channel inhibition (ranolazine) among symptomatic subjects without obstructive coronary artery disease (CAD) and limited myocardial perfusion reserve index (MPRI), we observed no improvement in angina or MPRI, overall. Here we describe the clinical characteristics and myocardial perfusion responses of a pre-defined subgroup who had coronary flow reserve (CFR) assessed invasively. Methods: Symptomatic patients without obstructive CAD and limited MPRI in a randomized, double-blind, crossover trial of ranolazine vs. placebo were subjects of this prespecified substudy. Because we had previously observed that adverse outcomes and beneficial treatment responses occurred in those with lower CFR, patients were subgrouped by CFR <2.5 vs ≥2.5. Symptoms were assessed using the Seattle Angina Questionnaire and the SAQ-7, and left-ventricular volume and MPRI were assessed by magnetic resonance imaging (MRI). Coronary angiograms, CFR, and MRI data were analyzed by core labs masked to treatment and patient characteristics. Results: During qualifying coronary angiography, 81 patients (mean age 55 years, 98% women) had invasively determined CFR 2.69 ± 0.65 (mean ± SD; range 1.4–5.5); 43% (n = 35) had CFR <2.5. Demographic and symptomatic findings did not differ comparing CFR subgroups. Those with low CFR had improved angina (p = 0.04) and midventricular MPRI (p = 0.03) with ranolazine vs placebo. Among patients with low CFR, reduced left-ventricular end-diastolic volume predicted a beneficial angina response. Conclusions: Symptomatic patients with CFR <2.5 and no obstructive CAD had improved angina and myocardial perfusion with ranolazine, supporting the hypothesis that the late sodium channel is important in management of coronary microvascular dysfunction. Trial registration: clinicaltrials.gov

AB - Background: In a prior trial of late sodium channel inhibition (ranolazine) among symptomatic subjects without obstructive coronary artery disease (CAD) and limited myocardial perfusion reserve index (MPRI), we observed no improvement in angina or MPRI, overall. Here we describe the clinical characteristics and myocardial perfusion responses of a pre-defined subgroup who had coronary flow reserve (CFR) assessed invasively. Methods: Symptomatic patients without obstructive CAD and limited MPRI in a randomized, double-blind, crossover trial of ranolazine vs. placebo were subjects of this prespecified substudy. Because we had previously observed that adverse outcomes and beneficial treatment responses occurred in those with lower CFR, patients were subgrouped by CFR <2.5 vs ≥2.5. Symptoms were assessed using the Seattle Angina Questionnaire and the SAQ-7, and left-ventricular volume and MPRI were assessed by magnetic resonance imaging (MRI). Coronary angiograms, CFR, and MRI data were analyzed by core labs masked to treatment and patient characteristics. Results: During qualifying coronary angiography, 81 patients (mean age 55 years, 98% women) had invasively determined CFR 2.69 ± 0.65 (mean ± SD; range 1.4–5.5); 43% (n = 35) had CFR <2.5. Demographic and symptomatic findings did not differ comparing CFR subgroups. Those with low CFR had improved angina (p = 0.04) and midventricular MPRI (p = 0.03) with ranolazine vs placebo. Among patients with low CFR, reduced left-ventricular end-diastolic volume predicted a beneficial angina response. Conclusions: Symptomatic patients with CFR <2.5 and no obstructive CAD had improved angina and myocardial perfusion with ranolazine, supporting the hypothesis that the late sodium channel is important in management of coronary microvascular dysfunction. Trial registration: clinicaltrials.gov

KW - Angina

KW - Coronary microvascular dysfunction

KW - Late sodium channel inhibition

UR - https://www.scopus.com/pages/publications/85054537929

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DO - 10.1016/j.ijcard.2018.09.081

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C2 - 30293664

AN - SCOPUS:85054537929

SN - 0167-5273

VL - 276

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JO - International Journal of Cardiology

JF - International Journal of Cardiology

ER -

Rambarat CA, Elgendy IY, Handberg EM, Bairey Merz CN, Wei J, Minissian MB et al. Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction ancillary study. International Journal of Cardiology. 2019 feb 1;276:8-13. doi: 10.1016/j.ijcard.2018.09.081