Myocarditis is an inflammatory disease of myocardium with a wide range of clinical presentations. Myocarditis may mimic acute coronary syndrome (ACS) and adequate differential diagnosis is not possible by conventional tests. Cardiac magnetic resonance (CMR) has emerged as a leading imaging modality in the diagnosis of myocarditis in such patients. Here, we report three cases of myocarditis mimicking ACS with normal coronary arteries. CMR was used for confirming the diagnosis of myocarditis in all three patients presented here

Alkema, W. B. L.

de Vries, E.

Guranda, D. T.

Jamskova, O. V.

Janssen, D. B.

Shapovalova, I. V.

Svedas, V. K.

English

PubMed

Residue phenylalanine 71 of the beta-chain of penicillin acylase from E. coil is involved in substrate binding and chiral discrimination of its enantiomers. Different amino acid residues have been introduced at position beta F71, and the mutants were studied with respect to their enantioselectivity and substrate specificity. Some mutants demonstrated remarkably improved catalytic activity. Moreover, mutation of beta F71 residue allowed to enhance penicillin acylase enantioselectivity. The catalytic activity to the specific substrates was improved up to 36 times, most notably for K, R, and L mutants. Increased activity to a D-phenylglycine derivative - a valuable specificity improvement for biocatalytic synthesis of new penicillins and cephalosporins - was shown for beta F71R and beta F7IL mutants. The synthetic capacity of penicillin acylase with 6-aminopenicillanic acid as an external nucleophile was especially sensitive to mutation of the beta 71 residue in contrast to the synthesis with 7-aminodeacetoxycephalosporanic acid.</p

Proceedings - University of Groningen

Mutation of Residue βF71 of Escherichia coli Penicillin Acylase Results in Enhanced Enantioselectivity and Improved Catalytic Properties

Dissertations of the University of Groningen

ARTS repository - University of Groningen

University of Groningen

Residue phenylalanine 71 of the beta-chain of penicillin acylase from E. coil is involved in substrate binding and chiral discrimination of its enantiomers. Different amino acid residues have been introduced at position beta F71, and the mutants were studied with respect to their enantioselectivity and substrate specificity. Some mutants demonstrated remarkably improved catalytic activity. Moreover, mutation of beta F71 residue allowed to enhance penicillin acylase enantioselectivity. The catalytic activity to the specific substrates was improved up to 36 times, most notably for K, R, and L mutants. Increased activity to a D-phenylglycine derivative - a valuable specificity improvement for biocatalytic synthesis of new penicillins and cephalosporins - was shown for beta F71R and beta F7IL mutants. The synthetic capacity of penicillin acylase with 6-aminopenicillanic acid as an external nucleophile was especially sensitive to mutation of the beta 71 residue in contrast to the synthesis with 7-aminodeacetoxycephalosporanic acid

NARCIS 

Sultan, Fateh Ali Tipoo

Adnan, Ghurfan

eCommons@AKU

eCommons@AKUSection of Cardiology Department of MedicineMarch 2018Myocarditis mimicking acute coronary syndrome -the role of cardiac magnetic resonance imaging inthe diagnosisFateh Ali Tipoo SultanAga Khan University, fatehali.tipoo@aku.eduGhurfan AdnanAga Khan University, ghufran.adnan@aku.eduFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_med_cardiolPart of the Cardiology CommonsRecommended CitationSultan, F., Adnan, G. (2018). Myocarditis mimicking acute coronary syndrome - the role of cardiac magnetic resonance imaging in thediagnosis. JPMA. The Journal of the Pakistan Medical Association, 68(3), 477-479.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_med_cardiol/48AbstractMyocarditis is an inflammatory disease of myocardiumwith a wide range of clinical presentations. Myocarditismay mimic acute coronary syndrome (ACS) and adequatedifferential diagnosis is not possible by conventionaltests. Cardiac magnetic resonance (CMR) has emerged asa leading imaging modality in the diagnosis ofmyocarditis in such patients. Here, we report three casesof myocarditis mimicking ACS with normal coronaryarteries. CMR was used for confirming the diagnosis ofmyocarditis in all three patients presented here.Keywords: Myocarditis, Troponin levels, Cardiacmagnetic resonance imaging (CMR).IntroductionMyocarditis is defined as "inflammation of themyocardium." The clinical presentations of myocarditisrange from nonspecific symptoms to fulminant heartfailure.1 Myocarditis may resemble an ACS2 and should beconsidered as a differential, especially in younger patientspresenting with ACS. Endomyocardial biopsy is the goldstandard for the diagnosis of myocarditis.3 However, theinvasive character and poor sensitivity limit, the use ofendomyocardial biopsy is not very popular. CMR plays animportant role in the diagnosis of acute myocarditis andits differentiation from ACS. After obtaining written consent from patients to utilize theirfindings, we report three cases seen at Aga Khan UniversityHospital, Karachi, with myocarditis. The presentation wasmimicking ACS and the diagnosis of myocarditis wasconfirmed on CMR. CMR use is limited in countries likePakistan, due to lack of awareness on the importance of thisimaging modality and also less availability. This is the first caseseries of myocarditis from Pakistan in which the diagnosis wasconfirmed non-invasively with the help of CMR.Case PresentationCase-1A 31 years old previously healthy male, presented to theemergency department on 16th March 2017 withworsening shortness of breath and chest pain. There washistory of fever and cough for the last 3-4 days.Electrocardiogram (ECG) revealed complete atrio-ventricular block.  On presentation, he was severelyhypoxic and required intubation with ventilatory support.He developed cardiac arrest soon after intubation, butfortunately revived after two minutes of cardiopulmorayresuscitation (CPR). Temporary pace maker (TPM) wasinserted for complete A-V block. Transthoracicechocardiogram (TTE) revealed an ejection fraction (EF) of25-30%with global hypokinesia. Troponin I levels wereelevated. Coronary angiography was done whichrevealed normal coronary arteries. He was managed withanti-platelets, anti-failure medications and antibiotics.CMR was performed which confirmed the diagnosis ofmyocarditis by showing evidence of myocardial oedemaon T2 weighted images (Figure-1). His further hospitalcourse was uneventful with gradual recovery. Repeat TTEafter couple of weeks showed significant improvement inleft ventricular systolic function.Case-2A25 years old previously healthy female, presented to theVol. 68, No. 3, March 2018477CASE REPORTMyocarditis mimicking acute coronary syndrome — the role of cardiac magneticresonance imaging in the diagnosisFateh Ali Tipoo Sultan, Ghufran AdnanDepartment of Cardiology, Aga Khan University Hospital, Karachi.Correspondence: Fateh Ali Tipoo Sultan. Email:fatehali.tipoo@aku.eduFigure-1: Cardiac MRI T2 weighted image showing myocardial oedema.emergency department on 6th February 2015 with acutechest discomfort. Clinical examination was unremarkableand ECG showed non-specific ST-T changes. First troponinI was 5.7 which was increased to 27, on repeating aftercouple of hours. TTE revealed normal left ventricularsystolic function with no wall motion abnormality. In viewof acute symptoms and positive troponin I, cardiaccomputed tomographic angiography (CTA) wasperformed which showed normal coronary arteries. CMRwas done which confirmed the presence of myocarditis(Figure-2). Her further course was uneventful.Case-3A young male of 24 years age with no prior history of anysignificant illness, presented to the emergencydepartment on 10th February 2015 with acute chest pain.ECG revealed ST elevation in infero-lateral leads (Figure-3). Troponin I was 14.08. In view of chest pain, ECGchanges and positive troponin, invasive coronaryangiography was performed, which revealed normalcoronary arteries. CMR was done which confirmed thediagnosis of myocarditis (Figure-4). His further course wasfree of significant issues.DiscussionMyocarditis may mimic ACS. Establishing a correctdiagnosis is important for such patients, both fromprognostic and therapeutic point of view. Conventionaltests lack enough specificity for adequatedifferential diagnosis.ECG changes are neither specific norsensitive for diagnosing myocarditis. Theycan vary from non-specific ST-T changes toeven ST segment elevation. Two of ourpatients showed non-specific ST-T changeswhile one patient had ST elevation at thetime of presentation. Serum markers of myocardial damage mayor may not be elevated in patients withmyocarditis, depending on the extent ofdamage. All three patients presented herehad positive troponins, suggestingmyocardial necrosis. In the literature,around 10% of the patients, initiallyJ Pak Med Assoc478 Myocarditis mimicking acute coronary syndrome — the role of cardiac magnetic resonance imaging in the diagnosisFigure-2: Cardiac MRI late gadolinium image showing subepicardialhyperenhancement.Figure-3: ECG showing ST elevation in inferolateral leads.Figure-4: Cardiac MRI late gadolinium showing patchy subepicardialhyperenhancement.diagnosed as ACS show normal coronary arteries onangiography.4The role of echocardiography is also limited as thefindings are not specific for myocarditis and segmentalwall motion abnormalities similar to ACS may be seen.5Endomyocardial biopsy is considered the gold standardfor the diagnosis of myocarditis.6 However, the biopsy haslow sensitivity due to focal nature of the disease andbeing an invasive procedure it carries potential risk ofcomplications. Due to these limitations, we did notconsider the endomyocardial biopsy in our patientsCMR is especially useful in such settings.7 A number ofstudies,5,8,9 have demonstrated the ability of CMR todifferentiate ACS from acute myocarditis. T2 weightedimages can be used to detect the presence of myocardialoedema both in inflammatory and ischaemic diseases. Inthe case of ACS, oedema is localized to the culprit vesselterritory, while in myocarditis, it is either diffuse orsegmental.10There is strong evidence in the literature that contrastCMR with late gadolinium images, is a good diagnosticmodality to detect myocardial necrosis and fibrosis bothin ischaemic heart disease and in other types of non-ischaemic lesions.7 In myocarditis, the late gadoliniumenhancement (LGE) is patchy or multifocal in a sub-epicardial or intra-myocardial distribution, usuallyinvolving the lateral wall.  In patients with ischaemic heartdisease, LGE is either sub-endocardial or transmural in acoronary artery distribution.Due to these features, CMR is helpful in differentiatingmyocarditis from ACS in patients with acute chest pain, aswas the case in our patients.Disclaimer: None.Conflict of Interest: None.Funding Sources: None.References1. Dec GW. Introduction to clinical myocarditis. In: Cooper LT, ed.Myocarditis: From Bench to Bedside. Totowa, NJ: Humana Press,2003; pp- 257-81.2. Sarda L, Colin P, Boccara F, Daou D, Lebtahi R, Faraggi M, NguyenC, et al. Myocarditis in patients with clinical presentation ofmyocardial infarction and normal coronary angiograms. J Am CollCardiol. 2001; 37:786-92.3. Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J,Felix SB. Current state of knowledge on a etiology, diagnosis,management, and therapy of myocarditis: a position statement ofthe European Society of Cardiology Working Group on Myocardialand Pericardial Diseases. Eur Heart J. 2013; 34:2636-48.4. Larson DM, Menssen KM, Sharkey SW, Duval S, Schwartz RS, HarrisJ, et al. "False-positive" cardiac catheterization laboratoryactivation among patients with suspected ST segment elevationmyocardial infarction. JAMA. 2007; 298:2754-60.5. Gerbaud E, Harcaut E, Coste P. Cardiac magnetic resonanceimaging for the diagnosis of patients presenting with chest pain,raised troponin, and unobstructed coronary arteries. Int JCardiovasc Imaging. 2012; 28:783-94.6. Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT,Fenoglio JJ, et al. Myocarditis: a histopathologic definition andclassification. Am J Cardiovasc Pathol. 1987; 1:3-14.7. Isbell DC, Kramer CM. The evolving role of cardiovascularmagnetic resonance imaging in nonischemic cardiomyopathy.Semin Ultrasound CT MRI. 2006; 27:20-31. 8. Stensaeth KH, Fossum E, Hoffmann P. Clinical characteristics androle of early cardiac magnetic resonance imaging in patients withsuspected ST-elevation myocardial infarction and normalcoronary arteries. Int J Cardiovasc Imaging. 27:355-65.9. Monney PA, Sekhri N, Burchell T. Acute myocarditis presenting asacute coronary syndrome: role of early cardiac magneticresonance in its diagnosis. Heart. 2011; 97:1312-8.10. Abdel-Aty H, Boye P, Zagrosek A. Diagnostic performance ofcardiovascular magnetic resonance in patients with suspectedacute myocarditis: comparison of different approaches. J Am CollCardiol. 2005; 45:1815-22.Vol. 68, No. 3, March 2018F. A. T. Sultan, G. Adnan 479