2173
Titin gene mutations in PPCM/DCM families
38.
39. 40.
41.
42.
Exome Sequencing Project. Evaluating pathogenicity of rare variants from dilated cardiomyopathy in the exome era. Circ Cardiovasc Genet 2012;5:167 –174. Golbus JR, Puckelwartz MJ, Fahrenbach JP, Dellefave-Castillo LM, Wolfgeher D, McNally EM. Population-based variation in cardiomyopathy genes. Circ Cardiovasc Genet 2012;5:391–399. Hidalgo C, Granzier H. Tuning the molecular giant titin through phosphorylation: Role in health and disease. Trends Cardiovasc Med 2013;23:165 – 171. Makarenko I, Opitz CA, Leake MC, Kulke M, Gwathmey JK, del Monte F, Hajjar RJ, Linke WA. Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts. Circ Res 2004;95:708 –716. Nagueh SF, Shah G, Wu Y, Torre-Amione G, King NM, Lahmers S, Witt CC, Becker K, Labeit S, Granzier HL. Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy. Circulation 2004;110:155–162. van Heerebeek L, Hamdani N, Falca˜o-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG, van der Velden J, Stienen GJ, Laarman GJ, Somsen A, Verheugt FW,
Niessen HW, Paulus WJ. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation 2012;126:830 –839. 43. Horne BD, Rasmusson KD, Alharethi R, Budge D, Brunisholz KD Metz T, Carlquist JF, Connolly JJ, Porter TF, Lappe´ DL, Muhlestein JB, Silver R, Stehlik J, Park JJ, May HT, Bair TL, Anderson JL, Renlund DG, Kfoury AG. Genomewide significance and replication of the chromosome 12p11.22 locus near the PTHLH gene for peripartum cardiomyopathy. Circ Cardiovasc Genet 2011;4:359–366. 44. Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, Kawamura N, Ariga T, Pasic S, Stojkovic O, Metin A, Karasuyama H. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 2007;448:1058–1062. 45. Norton N, Li D, Rampersaud E, Morales A, Martin ER, Zuchner S, Guo S, Gonzalez M, Hedges DJ, Robertson PD, Krumm N, Nickerson DA, Hershberger RE. Exome sequencing and genome-wide linkage in 17 families illustrates the complex contribution of TTN truncating variants to dilated cardiomyopathy. Circ Cardiovasc Genet 2013;6:144–153.
doi:10.1093/eurheartj/ehu086 Online publish-ahead-of-print 26 February 2014
.............................................................................................................................................................................
Multiparametric assessment of myocarditis using simultaneous positron emission tomography/magnetic resonance imaging Felix Nensa1*, Thorsten D. Poeppel2, Peter Krings3, and Thomas Schlosser1 1 Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany; 2Department of Nuclear Medicine, University Hospital Essen, Essen, Germany; and 3Department of Cardiology, University Hospital Essen, Essen, Germany
* Corresponding author. Tel: +49 20172384595, Fax: +49 2017239471528, Email: [email protected]
A 19-year-old man presented with general malaise, retrosternal chest pain, and palpitations. ECG demonstrated a flattening of T-waves in pre-cordial leads. Laboratory measurements showed elevated troponin I (6.6 ng/mL) and creatine kinase (477 U/L). Histopathological analysis of three samples taken from the right ventricle (RV) via endomyocardial biopsy (EMB) was unsuspicious, but polymerase chain reaction revealed DNA of parvorvirus B19. Simultaneous PET/MRI with 18F-fluorodeoxyglucose (FDG) was performed (Biograph mMR, Siemens, Germany). Myocardial glucose uptake was suppressed with high-fat-low-carbohydrate diet and i.v. administration of unfractionated heparin (50 IU/kg) 15 min before the FDG injection. Cine imaging showed normal left ventricular (LV) function. No pericardial effusion was found. T2-weighted images revealed an oedema in the LV anterior wall (Panel C). Dynamic perfusion imaging revealed hyperaemia in the LV anterior wall (Panel D). Subepicardial late gadolinium-enhancement (LGE; Panel A) was found in the LV anterior wall that was in excellent agreement with increased FDG uptake (Panel B). An acute myocarditis, probably caused by parvovirus B19, was diagnosed. The negative histopathological results of EMB are most likely due to sampling errors, especially as the samples were taken from the RV, whereas imaging showed focal disease in the anterior wall of the LV. The present case demonstrates the potential of FDG-PET/MRI in the management of myocarditis. With MR one can rapidly detect the disease, evaluate its extent, and quantify the impairment of cardiac function. 18F-fluorodeoxyglucose uptake is not only a sensitive marker of inflammation, but also a quantifiably parameter for disease activity that could complement MR in the detection, differential diagnosis, and monitoring of myocarditis. Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected]
Downloaded from http://eurheartj.oxfordjournals.org/ at Fachbereichsbibliothek on August 25, 2014
CARDIOVASCULAR FLASHLIGHT
Titin gene mutations in PPCM/DCM families
38.
39. 40.
41.
42.
Exome Sequencing Project. Evaluating pathogenicity of rare variants from dilated cardiomyopathy in the exome era. Circ Cardiovasc Genet 2012;5:167 –174. Golbus JR, Puckelwartz MJ, Fahrenbach JP, Dellefave-Castillo LM, Wolfgeher D, McNally EM. Population-based variation in cardiomyopathy genes. Circ Cardiovasc Genet 2012;5:391–399. Hidalgo C, Granzier H. Tuning the molecular giant titin through phosphorylation: Role in health and disease. Trends Cardiovasc Med 2013;23:165 – 171. Makarenko I, Opitz CA, Leake MC, Kulke M, Gwathmey JK, del Monte F, Hajjar RJ, Linke WA. Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts. Circ Res 2004;95:708 –716. Nagueh SF, Shah G, Wu Y, Torre-Amione G, King NM, Lahmers S, Witt CC, Becker K, Labeit S, Granzier HL. Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy. Circulation 2004;110:155–162. van Heerebeek L, Hamdani N, Falca˜o-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG, van der Velden J, Stienen GJ, Laarman GJ, Somsen A, Verheugt FW,
Niessen HW, Paulus WJ. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation 2012;126:830 –839. 43. Horne BD, Rasmusson KD, Alharethi R, Budge D, Brunisholz KD Metz T, Carlquist JF, Connolly JJ, Porter TF, Lappe´ DL, Muhlestein JB, Silver R, Stehlik J, Park JJ, May HT, Bair TL, Anderson JL, Renlund DG, Kfoury AG. Genomewide significance and replication of the chromosome 12p11.22 locus near the PTHLH gene for peripartum cardiomyopathy. Circ Cardiovasc Genet 2011;4:359–366. 44. Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, Kawamura N, Ariga T, Pasic S, Stojkovic O, Metin A, Karasuyama H. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 2007;448:1058–1062. 45. Norton N, Li D, Rampersaud E, Morales A, Martin ER, Zuchner S, Guo S, Gonzalez M, Hedges DJ, Robertson PD, Krumm N, Nickerson DA, Hershberger RE. Exome sequencing and genome-wide linkage in 17 families illustrates the complex contribution of TTN truncating variants to dilated cardiomyopathy. Circ Cardiovasc Genet 2013;6:144–153.
doi:10.1093/eurheartj/ehu086 Online publish-ahead-of-print 26 February 2014
.............................................................................................................................................................................
Multiparametric assessment of myocarditis using simultaneous positron emission tomography/magnetic resonance imaging Felix Nensa1*, Thorsten D. Poeppel2, Peter Krings3, and Thomas Schlosser1 1 Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany; 2Department of Nuclear Medicine, University Hospital Essen, Essen, Germany; and 3Department of Cardiology, University Hospital Essen, Essen, Germany
* Corresponding author. Tel: +49 20172384595, Fax: +49 2017239471528, Email: [email protected]
A 19-year-old man presented with general malaise, retrosternal chest pain, and palpitations. ECG demonstrated a flattening of T-waves in pre-cordial leads. Laboratory measurements showed elevated troponin I (6.6 ng/mL) and creatine kinase (477 U/L). Histopathological analysis of three samples taken from the right ventricle (RV) via endomyocardial biopsy (EMB) was unsuspicious, but polymerase chain reaction revealed DNA of parvorvirus B19. Simultaneous PET/MRI with 18F-fluorodeoxyglucose (FDG) was performed (Biograph mMR, Siemens, Germany). Myocardial glucose uptake was suppressed with high-fat-low-carbohydrate diet and i.v. administration of unfractionated heparin (50 IU/kg) 15 min before the FDG injection. Cine imaging showed normal left ventricular (LV) function. No pericardial effusion was found. T2-weighted images revealed an oedema in the LV anterior wall (Panel C). Dynamic perfusion imaging revealed hyperaemia in the LV anterior wall (Panel D). Subepicardial late gadolinium-enhancement (LGE; Panel A) was found in the LV anterior wall that was in excellent agreement with increased FDG uptake (Panel B). An acute myocarditis, probably caused by parvovirus B19, was diagnosed. The negative histopathological results of EMB are most likely due to sampling errors, especially as the samples were taken from the RV, whereas imaging showed focal disease in the anterior wall of the LV. The present case demonstrates the potential of FDG-PET/MRI in the management of myocarditis. With MR one can rapidly detect the disease, evaluate its extent, and quantify the impairment of cardiac function. 18F-fluorodeoxyglucose uptake is not only a sensitive marker of inflammation, but also a quantifiably parameter for disease activity that could complement MR in the detection, differential diagnosis, and monitoring of myocarditis. Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected]
Downloaded from http://eurheartj.oxfordjournals.org/ at Fachbereichsbibliothek on August 25, 2014
CARDIOVASCULAR FLASHLIGHT
![[Magnetic resonance imaging].](/assets/img/hold.png)
