Refractory Angina: Investigation And Treatment Α-Δ. ΜΑΥΡΟΓΙΑΝΝΗ ΚΑΡΔΙΟΛΟΓΟΣ AIMOΔΥΝΑΜIΚΟ ΕΡΓΑΣΤΗΡΙΟ Γ.Ν.Θ. «Γ.ΠΑΠΑΝΙΚΟΛΑΟΥ» ΘΕΣΣΑΛΟΝΙΚΗ

Transcription

1 Refractory Angina: Investigation And Treatment Α-Δ. ΜΑΥΡΟΓΙΑΝΝΗ ΚΑΡΔΙΟΛΟΓΟΣ AIMOΔΥΝΑΜIΚΟ ΕΡΓΑΣΤΗΡΙΟ Γ.Ν.Θ. «Γ.ΠΑΠΑΝΙΚΟΛΑΟΥ» ΘΕΣΣΑΛΟΝΙΚΗ

2 Disclosure Statement of Financial Interest none whatsoever

3 Refractory Angina: Definition of a Problem Refractory angina: a chronic condition Angina caused by coronary insufficiency in the presence of coronary artery disease which cannot be controlled by a combination of OMT+/ PCI+/ CABG Reversible myocardial ischaemia should be clinically established to be the cause of symptoms. Chronic: duration of more than 3 months Joint Study Group on the Treatment of Refractory Angina (European Society of Cardiology) Mannheimer C. et al. The problem of chronic refractory angina; report from the ESC Joint Study Group on the Treatment of Refractory Angina. Eur Heart J Mar;23(5):355-70

4 Refractory Angina: Burden REFRACTORY ANGINA CHEST PAIN SCAD Europe: 30-50,000 new case per year ~10-15% of patients undergoing C.A unsuitable for revasc. Severe diffuse atherosclerosis Lack of suitable graft conduits Comorbidities - LV function, DM, PAD, CKD Advanced age Increasing prevalence Ageing population Good prognosis in SCAD Henry TD. et al. Long-term survival in patients with refractory angina. Eur Heart J Sep;34(34): Williams B. et al. Patients with coronary artery disease not amenable to traditional revascularization: prevalence and 3-year mortality. Catheter Cardiovasc Interv May 1;75(6):886-91

5 Incidence of Angina Pectoris By Age And Sex (Framingham Heart Study ) *Angina pectoris deemed uncomplicated on the basis of physician interview of patient. Mozaffarian D. et al. Heart disease and stroke statistics update: a report from the American Heart Association. Circulation Jan 27;131(4):e29-322

6 Refractory Angina: Long-term Survival of Patients On the basis of 14 16% of 1.1 million angiograms performed per year in the United States, 154, ,000 patients have CAD, which is not amenable to revascularization Williams B. et al. Patients with coronary artery disease not amenable to traditional revascularization: prevalence and 3-year mortality. Catheter Cardiovasc Interv May 1;75(6):886-91

7 Secular Trends in Age-and Sex-standardized Prevalence Rates of Angina For Adults Aged 40 Years (US./ by Race/ Rose Questionnaire) Mozaffarian D. et al. Heart disease and stroke statistics update: a report from the American Heart Association. Circulation Jan 27;131(4):e29-322

8 Incidence of Angina: the Rose Questionnaire Study Country Years Age Definition Male Female Wales Rose 17.8% 9 Comm Italy Rose 2.3% 3.1% SHS Scotland Rose 6.3% 8.5% BRHS For every patient admitted with the diagnosis of UK Rose 4.8% MI there are 30 patients living with angina EPES USA >65 Rose 3-4% 4-6% CVHS USA >65 Confirmed 16% 10% NHANES USA self report Rose 5.2% 6.2% PANES Spain 1990s Rose 7.3% 7.8% Rose GA. ISCHEMIC HEART DISEASE. CHEST PAIN QUESTIONNAIRE. Milbank Mem Fund Q Apr;43:32-9

9 Quantification of Angina: the Rose Questionnaire Responses required to define a case in brackets 1. Have you ever had any pain or discomfort in your chest? (yes) 2. Do you get it when you walk uphill or hurry? 3. Do you get it when you walk at an ordinary pace on the level? If the answer to question Q 2 or Q 3 is yes, then proceed to Q4 4. What do you do if you get it while walking? (stop or slow down) 5. If you stand still what happens? (relieved) 6. How soon? (10 minutes or less) 7. Location? (central chest or left arm) Rose GA. ISCHEMIC HEART DISEASE. CHEST PAIN QUESTIONNAIRE. Milbank Mem Fund Q Apr;43:32-9

10 Refractory Angina: Clinical Features Mind Racing? Dizzy, disoriented, lightheaded? Possible sleep disturbance? Vision strange, blurry? Poor health status Feeling breathless, Limited quality of life fear, misconception Difficulty in swallowing? breathing Significant hard and disability (physical and psychological) shallow? Recurrent and sustained pain Polypharmacy Heart racing palpitations? High utilisation of healthcare resources Nausea, lack of Symptom burden often disproportionate to ischaemic appetite? Sweating burden or shivering? Restless, jelly like legs? Trembling? Wanting to run? De Jongste MJ., Tio RA., Foreman RD. Chronic therapeutically refractory angina pectoris. Heart Feb;90(2):225-30

11 COURAGE: Freedom from Angina with OMT 100 PCI + OMT OMT *due to severe / progressive angina ; remain OMT by ITT P=NS 72 40% P<0.001 Angina free (%) CCS Class 0 / 1 P=NS <10% crossovers* prespecified! Angina free at 5 years Revascularization after discharge Boden WE. et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med Apr 12;356(15):

12 Angina: Importance in Patients with CAD/ HF, and LVsD Jolicœur EM. et al. Importance of angina in patients with coronary disease, heart failure, and left ventricular systolic dysfunction: insights from STICH. J Am Coll Cardiol Nov 10;66(19):

13 Refractory Angina: Long-term Survival of Patients Registry of ~1,200 patients >70% survive 9 years from time of diagnosis Henry TD. et al. Long-term survival in patients with refractory angina. Eur Heart J Sep;34(34):2683-8

14 Suspected angina Clinical Assessment Non angina symptoms NURSE SPECIALIST Reassure, Educate, Exercise Angina Plan, Cardiac Rehabilitation Questionnaires (HADS, EQ5, SAQ) Reassure Ix/Rx non-cardiac conditions Review and optimise CV medical therapy Non-invasive/invasive investigations: Anatomy, Ischaemia, LV function Multidisciplinary Team Discussion Mod/Sev ischaemia PCI (CTO) Redo CABG CS Reducer LIMITING SYMPTOMS PERSIST EECP Biologics Mild/No ischaemia Specialist pain management: CBT (1:1 or group) Drugs Stellate Ganglion Block TENS, Spinal Cord Stimulator Nurse specialist follow-up (face to face/telephone) Review, Refine, Reinforce Questionnaires (HADS, EQ5, SAQ), Audit

15 Identify Ischemia I. Cardiological and cardiothoracic surgical assessment: angina of ischaemic origin + revasc. is unfeasible. II. Assessment of current reversible myocardial ischaemia III. Outpatient assessment to include: review of pain history, drug history and a physical examination IV. Exclude non-cardiac causes V. Multidisciplinary cognitive behavioural pain management programme. HADS Score VI. Rehabilitation programme including secondary prevention through active risk factor management Mannheimer C. et al. The problem of chronic refractory angina; report from the ESC Joint Study Group on the Treatment of Refractory Angina. Eur Heart J Mar;23(5):355-70

16 Treatment Approaches to Relieve Myocardial Ischaemia Intermittent thrombolytics Blood rheology FIo2 Hb O2 carrying capacity allopurinol Oxidative stress O2 sparing Trimetazidine 3KAT inhibition Perhexiline CP1/2 inhibition Metabolic modulation Coronary flow redistribution Coronary flow redistribution SUPPLY DEMAND Ranolazine Coronary Coronary sinus sinus reduction reduction I Na inhibition Coronary blood flow EECP PCI CABG Angiogenesis Gene therapy Cell therapy Nitrates Nicorandil Heart rate/ Contractility/ Wall tension B blockers Ivabradine CCBs Henry TD. et al. Treatment of refractory angina in patients not suitable for revascularization. Nat Rev Cardiol Feb;11(2):78-95

17 Refractory Angina: Stairway to Heaven Narcotics Transplantation Angiogenesis ESWT, sinus reduction O2 sparing: allopurinol Self management training Nonpharmacological: EECP, SCS, TMLR Metabolic modulation: trimetazidine, perhexiline (?) Late Na current inhibition: ranolazine Coronary vasodilation:nitrates, nicorandil,molsidonine (?) Heart rate and contractility reduction: b blockers, CCBs, ivabradine Treat hypertension, diabetes mellitus, dyslipidaemia Smoking cessation, regular exercise and rehabilitation, healthy lifestyle Experimental and palliative options Therapies for refractory angina Evidence based therapies for stable angina Risk factor reduction Henry TD. et al. Treatment of refractory angina in patients not suitable for revascularization. Nat Rev Cardiol Feb;11(2):78-95

18 Metabolic Factors Influencing Angina Henry TD. et al. Treatment of refractory angina in patients not suitable for revascularization. Nat Rev Cardiol Feb;11(2):78-95

19 Refractory Angina and Ranolazine: the RIVER PCI Trial Weisz G. et al. Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Jan 9;387(10014):136-45

20 Refractory Angina and Ivabradine: the BEAUTIFUL Trial Substudy Fox K. et al. Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J Oct;30(19):

21 Non Invasive Treatment: Extracorporeal Shockwave Therapy VEGF.07 P < CNTRL mj/mm² P <0.05 Flt-1 CNTRL Nishida T. et al. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation Nov 9;110(19):

22 CSWT Improves Myocardial Ischemia First Clinical Study Before Longitudinal Horizontal Washout ratio After Fukumoto Y. et al. Extracorporeal cardiac shock wave therapy ameliorates myocardial ischemia in patients with severe coronary artery disease. Coron Artery Dis Feb;17(1):63-70

23 Non Invasive Treatment: Enhanced External Counterpulsation Qin X. et al. Does Enhanced External Counterpulsation (EECP) Significantly Affect Myocardial Perfusion?: A Systematic Review & Meta-Analysis. PLoS One Apr 5;11(4):e

24 Biologics: Gene and Cell Therapy Fisher SA. Et al. Bone Marrow Stem Cell Treatment for Ischemic Heart Disease in Patients with No Option of Revascularization: A Systematic Review and Meta-Analysis. PLoS One Jun 19;8(6):e64669

25 Intramyocardial Bone Marrow Cell Injection Mann I. et al. Repeated Intramyocardial Bone Marrow Cell Injection in Previously Responding Patients With Refractory Angina Again Improves Myocardial Perfusion, Anginal Complaints, and Quality of Life.

26 Invasive Treatment: CTO The Good ~70% success rate Improves Symptoms QOL LV function Ischaemic burden Arrhythmic risk? The Bad No RCT s (EURO-CTO) Operator experience Procedure duration Adverse effect of failed procedure? George S. et al. Long-term follow-up of elective chronic total coronary occlusion angioplasty: analysis from the U.K. Central Cardiac Audit Database. J Am Coll Cardiol Jul 22;64(3):235-43

27 CS Reducer Implantation

28 Efficacy of a Device to Narrow the Coronary Sinus in Refractory Angina Verheye S. et al. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med Feb 5;372(6):519-27

29 Real World Experience Abawi M. et al. Safety and efficacy of a device to narrow the coronary sinus for the treatment of refractory angina: A single-centre real-world experience. Neth Heart J Sep;24(9):544-51

30 How Does Angina Become Refractory? Ranil de Silva FRCP PhD ESC 2015

31 Pregabalin Tricyclics, SSRI CBT Opiates CBT CBT Spinal Cord Stimulator Stellate Ganglion Block TENS SENS Pregabalin Tricyclics SSRI Henry TD. et al. Treatment of refractory angina in patients not suitable for revascularization. Nat Rev Cardiol Feb;11(2):78-95

32 Why is the Stenocentric Approach Soooo Disappointing? Inflammation Platelets and Coagulation Critical Coronary Artery Stenosis Myocardial Ischemia Vasospasm Endothelial Dysfunction Microv/lar Dysfunction

33 Treatment Approaches to Relieve Myocardial Ischaemia Intermittent thrombolytics Blood rheology FIo2 Hb O2 carrying capacity allopurinol Oxidative stress O2 sparing Trimetazidine 3KAT inhibition Perhexiline CP1/2 inhibition Metabolic modulation Coronary flow redistribution Coronary flow redistribution ENERGY SUPPLY SUPPLY ENERGY DEMAND DEMAND Ranolazine Coronary Coronary sinus sinus reduction reduction I Na inhibition Coronary blood flow EECP PCI CABG Angiogenesis Gene therapy Cell therapy Nitrates Nicorandil Heart rate/ Contractility/ Wall tension B blockers Ivabradine CCBs Henry TD. et al. Treatment of refractory angina in patients not suitable for revascularization. Nat Rev Cardiol Feb;11(2):78-95

34 Editing the Future? ary 2016, British scientists were given permission by regulators to genetically modify human embryos by using CRISPR-Cas9 and related techniques. The embryos were to be destroyed after seven days.