Vasospastic angina: Diagnostic and therapeutic challenge. Hakim BENAMER Hôpital FOCH Suresnes ICPS Massy et ICV-GVM La Roseraie Aubervilliers FRANCE

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1 Vasospastic angina: Diagnostic and therapeutic challenge Hakim BENAMER Hôpital FOCH Suresnes ICPS Massy et ICV-GVM La Roseraie Aubervilliers FRANCE

2 Conflicts of interests: No conflict of interest

3 Variant Angina: 1959!

Mutations prot of ion channels Inflammation Ach Cathecholamines

4 PHYSIOPATHOLOGY Endothelial dysfunction Endotheliale lesion Gene mutation NO synthetase SMC Hyperactivity Rho-kinase Gene Mutations prot of ion channels Inflammation Ach Cathecholamines Serotonine Histamine VC Stimuli Tabacco Cocaine THC 5 FU sumatripan

5 PREVALENCE «Rare disease» NIH (USA) SA diagnosed: 1,5 % of isch. disease Lanza (Italie) Int J Cardiol

6 cardiac death following an acute myocardial infarction. 44 G.A. Lanza et al. / International Jour Diagnostic: > 3 months for diagnostic in more than 40 % of cases Frequent initial mistake for the diagnostic MACE: 56 % in the 3 months after onset of symptoms ECG=electrocardiogram; Fig. 1. Determinant diagnostic method for final diagnosis of variant angina AECG=ambulatory ECG; in theett=exercise whole population treadmill of patients test; and in the subgroups of patients enrolled during CA=coronary the first half angiography. and the second half of the study period. ECG=electrocardiogram; AECG= ambulatory ECG; ETT =exercise treadmill test; CA =coronary angiography.

Clinical Characteristics 1 - Characterized by vague pain that cannot be indicated by a single finger, with a sensation of compression, a pressing sensation, and a sensation of tightness in the

7 Clinical Characteristics 1 - Characterized by vague pain that cannot be indicated by a single finger, with a sensation of compression, a pressing sensation, and a sensation of tightness in the precordium, especially in the center of the substernal region. 2 - Appears at rest, with pain persisting for several to about 15 minutes. The pain often radiates to the neck, jaws, left shoulder, and elsewhere 3 - Anginal attacks due to coronary spasm often persist longer than effort anginal attacks due to organic stenotic lesions, and are sometimes accompanied by cold sweats and disturbance of consciousness including syncope. 4 - Can be induced by hyperpnea and drinking of alcohol. (Circ J 2010; 74: )

Clinical Characteristics 5 - Fast-acting nitrates are remarkably effective against attacks of coronary spasm. 6 - Calcium channel blockers suppress attacks of coronary spasm.

8 Clinical Characteristics 5 - Fast-acting nitrates are remarkably effective against attacks of coronary spasm. 6 - Calcium channel blockers suppress attacks of coronary spasm. 7 - Attacks are often accompanied by arrhythmias; if they are complicated by complete atrioventricular block, ventricular tachycardia, or ventricular fibrillation, disturbance of consciousness or syncope is observed. 8 - Attacks of coronary spasm typically occur at rest between night and early morning. They are usually not induced by daytime exercise. Diurnal variation with a peak between night and early morning is observed 9 - Attacks of coronary spasm may occur frequently, ie, several times every day. (Circ J 2010; 74: )

9 ECG and Holter recording during spontaneus attacks : classe I Provocative tests during angiogram, Ach or ergonovine : classe I

PROVOCATIVE TEST 2 Invasive Evaluation (Cardiac Catheterization) A drug-induced coronary spasm provocation test is performed by intracoronary administration of acetylcholine or ergonovine.

10 PROVOCATIVE TEST 2 Invasive Evaluation (Cardiac Catheterization) A drug-induced coronary spasm provocation test is performed by intracoronary administration of acetylcholine or ergonovine. If increased diagnostic accuracy is desired, a washout period of 2 days or longer for any calcium channel blockers and nitrates should be included whenever possible. For patients undergoing this examination, adequate informed consent must be obtained before invasive evaluation is performed. (Circ J 2010; 74: )

12 Pendant la coronarographie

Standard Method of Provocation Test: Ergonovine Intracoronary Administration (1) Control angiography of left and right coronary arteries: Perform angiography an appropriate projection that ensures

(2) Injection of ergonovine into the left coronary artery: Inject 20 to 60 μg of ergonovine in solution in physiological saline into the left coronary artery over a period of several minutes (about 2

13 Standard Method of Provocation Test: Ergonovine Intracoronary Administration (1) Control angiography of left and right coronary arteries: Perform angiography an appropriate projection that ensures the best separation of the branches of each coronary artery. After injection of ergonovine, perform angiography in the same projection again. (2) Injection of ergonovine into the left coronary artery: Inject 20 to 60 μg of ergonovine in solution in physiological saline into the left coronary artery over a period of several minutes (about 2 to 5 minutes). Perform coronary angiography 1 to 2 minutes after completion of the injection. In the event of an ischemic change on the ECG or chest symptom, perform angiography at the time of its onset. In case of a negative result in the provocation test, proceed to the right coronary provocation test 5 minutes later. (3) Injection of ergonovine into the right coronary artery: Inject 20 to 60 μg of ergonovine in solution in physiological saline into the right coronary artery over a period of several minutes (about 2 to 5 minutes). The timing of angiography is the same as for the left coronary artery. (4) Left and right coronary angiography after administration of nitrate: Administer a sufficient dose of nitrate into each coronary artery, and perform angiography (Circ J 2010; 74: )

14 Un test de provocation positif est défini par : une occlusion ou une sub occlusion (>90%) d une artère coronaire avec des signes/symptômes d ischémie myocardique ( douleur thoracique et modification ECG (sus décalage de ST - onde U dans 2 dérivations)

15 Diagnostic Definitive or Suspected

16 Dr X Halna du Fretay et al Ann Cardiol Angeiol 2014;63(6):465-70

17 ECG Angio Holter Prov. IC Ach, ergonovine jusqu à 60 micro g (voie IC), critères de positivité non précisés

(en fonction de l opérateur, de la suspicion clinique et l existence de lésion significative).

18 On a utilisé une dose plus importante de 200 μg en injection unique pour une dose maximale de 120 μg dans la littérature. Notre protocole IC : 1 - Dose : une injection lente sur 2 minutes de la méthylergométrine de 200 μg (une ampoule) soit dans la coronaire gauche ou la coronaire droite (en fonction de l opérateur, de la suspicion clinique et l existence de lésion significative). 2 - Recueil des données : clinique (douleur), ECG (à l état basal, à 3mins et a 5mins), opacification coronaire (à 3mins et à 5mins) 3 - Traitement post procédure : Injection IC de Isosorbide Dinitrate dans chaque coronaire et un patch de 10mg de Trinitrine. Dr Dana MOHAMMED SAEED et al

19 Angiology Volume 55, Number 4,

20 No adverse cardiac event despite high dose: 200 μg Dr X Halna du Fretay et al Ann Cardiol Angeiol 2014;63(6):465-70

21 Smoker Rest Rest or stress ST + Ryth. Disea.

22 Nle Coro MultiVx

23 Prognostic factors

Traitement 1. Management of Daily Life Class I: 1. Smoking cessation 2. Blood pressure control 3. Maintenance of ideal body weight 4. Correction of impaired glucose tolerance 5.

26 Traitement 1. Management of Daily Life Class I: 1. Smoking cessation 2. Blood pressure control 3. Maintenance of ideal body weight 4. Correction of impaired glucose tolerance 5. Correction of lipid abnormalities 6. Avoidance of excessive fatigue and mental stress 7. No or moderate drinking Class Iia: None Class Iib: None Class III: None (Circ J 2010; 74: )

Traitement 1 Nitrates Class I: Sublingual administration, spraying in the oral cavity, or intravenous administration during an attack Class Iia: Administration of long-acting

27 Traitement 1 Nitrates Class I: Sublingual administration, spraying in the oral cavity, or intravenous administration during an attack Class Iia: Administration of long-acting nitrates for prevention of coronary spasm Class Iib: None Class III: Administration of nitrates within 24hours after taking an agent to treat erectile dysfunction (Circ J 2010; 74: )

28 Traitement 2 Calcium Channel Blockers Class I: Administration of calcium channel blockers for vasospastic angina Class Iia: None Class Iib: None Class III: None (Circ J 2010; 74: )

Traitement 4 β-blockers Class I: None Class Iia: Concomitant use of β-blockers for vasospastic angina with significant stenosis of coronary artery Class Iib: Concomitant use of β-blockers

29 Traitement 4 β-blockers Class I: None Class Iia: Concomitant use of β-blockers for vasospastic angina with significant stenosis of coronary artery Class Iib: Concomitant use of β-blockers for vasospastic angina without significant stenosis of coronary artery Class III: Monotherapy for vasospastic angina without significant stenosis of coronary artery (Circ J 2010; 74: )

30 CONCLUSIONS Spastic angina is an underestimated disease (chest pain at rest ) Worst prognosis if not treated Provocative tests are underused Provocative tests must be done by IC injections to improve sensibility Nitrates and Ca Channels blockers efficient for the treatment

Guidelines for Diagnosis and Treatment of Patients With Vasospastic Angina (Coronary Spastic Angina) (JCS 2013)

Circulation Journal Official Journal of the Japanese Circulation Society http://www.j-circ.or.jp JCS GUIDELINES Guidelines for Diagnosis and Treatment of Patients With Vasospastic Angina (Coronary Spastic