title: Coronary microvascular spasm triggers transient ischemic left ventricular diastolic abnormalities in patients with chest pain and angiographically normal coronary arteries.
abstract: OBJECTIVE
  Impaired coronary microvascular dilatory function can lead to exercise induced myocardial ischemia and angina pectoris even in patients without significant (>50%) obstructive coronary atherosclerosis (APWOCA). Diffuse distal vessel epicardial spasm and microvascular spasm have been also proposed as a plausible explanation for angina at rest in these patients. However, objective systematic evidence for the latter i.e. echocardiographic wall motion abnormalities during angina, is lacking at present. Coronary epicardial and microvascular spasm can be triggered in susceptible patients by the administration of intracoronary acetylcholine (Ach). We sought to assess whether Ach induced diffuse distal epicardial coronary artery spasm (≥75% diameter reduction) and coronary microvascular spasm can cause transient ischemic left ventricular dysfunction, as assessed by echocardiography.
  
  
  METHODS
  50 patients (19 men aged 60.5 ± 8.9 years) with stable APWOCA were assessed for coronary spasm and myocardial ischemia with intracoronary Ach infusion, 2D transthoracic echocardiography (before and during Ach testing), continuous 12-lead ECG monitoring, and ultrasensitive cardiac troponin (US-cTn) measurement before and within 4 h after Ach testing.
  
  
  RESULTS
  14 patients (28%) had a "negative" Ach test, 14 (28%) developed coronary microvascular spasm and 17 (34%) had diffuse distal epicardial spasm. In 5 patients (10%) the test was inconclusive. Echocardiographic variables including deceleration time, EF slope and E/A, as well as ultrasensitive-cTn concentrations were abnormal during Ach induced ischemic ECG changes.
  
  
  CONCLUSIONS
  We have, for the first time, demonstrated that Ach induced coronary microvascular spasm is associated with echocardiographic changes and ultrasensitive-cTn elevations, indicative of myocardial ischemia.
authors: Unidad de Hemodinámica, Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain; Cardiovascular and Cell Sciences Research Institute, St. George's, University of London, London, UK.
authors: Antonio Luis
authors: AL
authors: Arrebola-Moreno
authors: Laboratorio de Investigaciones Médicas, Hospital Universitario San Cecilio, Universidad de Granada, Granada, Spain.
authors: Juan Pedro
authors: JP
authors: Arrebola
authors: Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors: Antonio
authors: A
authors: Moral-Ruiz
authors: Unidad de Hemodinámica, Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors: Jose Antonio
authors: JA
authors: Ramirez-Hernandez
authors: Unidad de Hemodinámica, Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors: Rafael
authors: R
authors: Melgares-Moreno
authors: Unidad de Hemodinámica, Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain. Electronic address: jkaski@sgul.ac.uk.
authors: Juan Carlos
authors: JC
authors: Kaski
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000368:Aged; D015415:Biomarkers; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D003329:Coronary Vasospasm / Q000503:physiopathology*; D003971:Diastole; D004562:Electrocardiography; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D017566:Microvascular Angina / Q000503:physiopathology*; D008875:Middle Aged; D012307:Risk Factors; D016037:Single-Blind Method; D020107:Troponin T / Q000097:blood; D014463:Ultrasonography; D014664:Vasodilation; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D020107:Troponin T; D000109:Acetylcholine
keywords: Coronary microvascular spasm; Echocardiographic diastolic changes; Epicardial coronary artery spasm; Stable angina; Ultrasensitive cardiac troponins; Unobstructed coronary arteries