title: Ranolazine and Microvascular Angina by PET in the Emergency Department: Results From a Pilot Randomized Controlled Trial.
abstract: Coronary microvascular dysfunction (CMD) is a common but underdiagnosed cause of chest pain. Literature is scant regarding effective treatments. We explored the effect of ranolazine on coronary flow reserve (CFR) among symptomatic patients with CMD.
  
  
  
  This pilot double-blinded randomized controlled trial included emergency department patients with chest pain and CMD admitted to an observation unit between June 2014 and November 2015. Participants were assessed by cardiac Rb-82 positron emission tomography and computed tomography imaging at baseline and 30 days. CMD was defined as CFR <2 corrected for rate pressure product or <2.5 uncorrected, with no evidence of obstructive or nonobstructive coronary artery disease or calcification. Patients with infarction, hypertensive urgency, heart failure, or prescribed QTc-prolonging drugs were excluded. Participants were assigned to ranolazine or placebo in a 2:1 ratio. Primary outcome was change in CFR at 30 days.
  
  
  
  We enrolled 31 patients (71% female, mean [SD] age 50 [6] years) with CMD (mean [SD] corrected CFR 1.6 [0.3]). Ranolazine improved CFR at 30 days by 17% (P = 0.005) compared with 0% with placebo (P = 0.67). However, there was no significant difference in the primary outcome as measured by mean change in CFR (0.27 ranolazine compared with 0.06 placebo; 95% CI, -0.08 to 0.62).
  
  
  
  The emergency department offers a unique venue to diagnose CMD with acute symptoms. In an exploratory randomized controlled trial of symptomatic patients with CMD and no coronary artery disease, promising results were seem with ranolazine and CFR improving at 30 days. Large robust clinical trials are needed to verify improvement of CMD in a sex-specific model. ClinicalTrials.gov identifier NCT02052011.
authors.affiliation: Department of Emergency Medicine, Yale University School of Medicine, New Haven, Connecticut. Electronic address: basmah.safdar@yale.edu.
authors.forename: Basmah
authors.initials: B
authors.lastname: Safdar
authors.affiliation: Department of Emergency Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Gail
authors.initials: G
authors.lastname: D'Onofrio
authors.affiliation: Department of Emergency Medicine, Yale University School of Medicine, New Haven, Connecticut; Yale Center for Analytical Sciences, New Haven, Connecticut.
authors.forename: James
authors.initials: J
authors.lastname: Dziura
authors.affiliation: Department of Internal Medicine, Section of Cardiovascular Medicine, Warren Alpert Medical School, Brown University, Providence, Rhode Island.
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Russell
authors.affiliation: Department of Emergency Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Sinusas
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D004636:Emergency Service, Hospital; D005260:Female; D006321:Heart / Q000503:physiopathology; D006801:Humans; D008297:Male; D017566:Microvascular Angina / Q000175:diagnosis*; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D000069458:Ranolazine / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000069458:Ranolazine
keywords: PET; chest pain; emergency department; microvascular angina; randomized controlled trial; ranolazine