1. Contribution of Cardiac Magnetic Resonance to Differential Diagnosis of Suspected Acute Coronary Syndromes with No Culprit Lesion Dr. Giuseppe Gibelli, Cardiology Department, San Carlo Clinic, Paderno Dugnano, Italy

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3. 26-year-old man chest pain begun 3 h prev. 5 days earlier sore throat, malaise and fever up to 398C; 2 days later, typical pericarditis pain. 26 year-old man; typical pericarditis pain since 3 h; 5 days earlier sore throat, malaise and fever up to 39°(a): admission nd day abrupt typical ischaemic pain, transmural IL ischemia (b); after ntg pain subsided (c), normal coronary angiogram; 10’ later asymtomatic; ECG similar to admission+ IL negative T waves (d).

4. Typical LGE epicardial pattern. Sudden ST elevation Acute myocarditis, simulating ACS. TpI peak 12 U (nv<0.01). VARIANT ANGINA DURING MYOCARDITS?

5. Gallagher, Heart 2012;98:974e981 Presumed acute coronary syndromes Reported frequencies of culprit-free angiography : ≈ 10%

6. . Gallagher, Heart 2012;98:974-981 cardiac MRI in presumed acute coronary syndromes and culprit free angiograms

7. ACS like simptoms, raised markers, no culprit lesion Monney et Al. Heart 2011;97:1312e1318

8. JACC White Paper: CMR in Myocarditis 2009:Vol. 53: 1475–87

9. T2-weighted CMR: “The principle of all things is water” Thales of Miletus (624 BC - 546 BC) In patients with acute chest pain, identify acute or recent myocardial ischemic injury …to distinguish acute coronary syndrome (ACS) from non-ACS… determine the area at risk in reperfused and non-reperfused infarction (1). T2 STIR (triple suppression: normal myocardium, blood, fat)… is accurate in detecting acute myocardial infarction distinguishing acute from chronic MI …T2 STIR should be regarded as an edema-weighted technique (2). (1) Eitel and Friedrich Journal of Cardiovascular Magnetic Resonance 2011, 13:13 (2) h-Ici et al. Journal of Cardiovascular Magnetic Resonance 2012, 14:22

10. gadolinium contrast agents are not specific markers for myocardial fibrosis Late gadolinium enhancement : contrast distribution space wash-in and wash-out kinetics of the contrast into interstitial space or extracellular matrix This… is increased in myocardial fibrosis but can also be increased in other pathological processes, such as inflammation and edema. Mewton, N et al JACC Vol. 57, No. 8, 2011

11. Post ischemic changes: ACS like, TPi +, T2 +, no LGE T2STIR admission No LGE T2STIR 2 months

12. LGE patterns in AMI and various myocarditis PVB19: epicardial LGE HHV6: mid wall LGE Endocardial LGE in AMI

13. Myocarditis PVB19 type T2STIR LGE LGE

14. Acute myocarditis, anterolateral foci T2STIRSAxisLGE LGE 4C

15. Acute myocarditis Multiple LGE foci

16. 2nd day: subepicardial LGE, wall swelling Myocarditis: common LGE evolution two months later: reduced LGE, normal width

17. Other: Tako-Tsubo, HCM, inconclusive findings, false negatives……..

18. HCM– various LGE

19. Apical HCM End diastole End systole

20. Tako Tsubo Cine end diastole end systole T2 STIR+LGE -

21. T2 STIRLGE Cine, end systole Mixed pattern : old myocarditis, inferolateral Acute MI, inferior Small pericardial effusion (!)

22. Everithing clear? 4 of 13 pts with myocarditis,viral presence and LGE had ischemic pattern of LGE Yilmaz et Al. Coronary vasospasm as the underlying cause for chest pain in patients with PVB19 myocarditis 2008;94:1456–1463.

23. “adventitial coronary stimulation with inflammatory cytokines induced spasmogenic changes of VSMCs in animal models”. Shimokawa et alJ Clin Invest. 1996;97:769 –776.36 Acute myocarditis, simulating ACS Tpi peak 12 U (nv<0.01). Typical LGE epicardial pattern. Coronary artery spasm in lymphocytic myocarditis: a rare cause of acute myocardial infarction R B McCully et Al. Heart. 2005 ; 91(2): 202. Coronary vasospasm as the underlying cause for chest pain in patients with PVB19 myocarditis. A Yilmaz et Al, Heart 2008;94:1456–1463. Sudden ST elevation with angina-like pain in myocarditis. G Gibelli et Al. J Cardiovasc Med 2009, 10:264–266

24. Yilmaz et Al. Coronary vasospasm as the underlying cause for chest pain in patients with PVB19 myocarditis 2008;94:1456–1463. Myocarditis patients with PVB19 infection, HHV6 infection and controls. Only patients with isolated PVB19 infection demonstrated a significantly higher incidence of coronary vasospasm

25. Causes of CRM false negatives Late enhancement: small patchy foci interspersed with healty muscle ie. pixels containing high signal and low signal areas (partial volume effect) or enhanced areas of few adjacent pixels T2 : inflammation with poor water content (importance of temporal window) Late enhancement: small patchy foci interspersed with healty muscle ie. pixels containing high signal and low signal areas (partial volume effect) or enhanced areas of few adjacent pixels T2 : inflammation with poor water content (importance of temporal window)

26. CMR accuracy in myocarditis Friedrich et Al. JACC White Paper: CMR in Myocarditis April 28, 2009:1475–87

27. Accuracy of CMR in myocarditis Clinical pattern variable Serum antibody titers and virus identification: poor accuracy Histology and immuno chemistry: biopsy only if HF, poor sensitivity due to focal patterns. Viral genoma : biopsy required, not widely available NO TRUE GOLD STANDARD

28. Conclusions CMR with cine, T2 W and Gd enhancement is a must in ACS like no culprit lesions Myocarditis is the most prevalent cause Interactions between inflammation and coronary vasomotricity may be common and generate mixed patterns ; prevalence unknown Diagnostic accuracy of CRM still imperfectly known (lack of gold standard for myocarditis) Ongoing studies and new sequences (T1 mapping post contrast, T2 new sequences and mapping) will add to knowledge

29. Thank you for your attention