Udo Sechtem

Significance of Late Gadolinium Enhancement in Cardiovascular Magnetic Resonance Imaging (CMR)

Cardiovascular magnetic resonance imaging (CMR) permits optimal differentiation between normal and diseased myocardium with the use of gadoliniumbased contrast agents and special magnetic resonance pulse sequences. Imaging is performed 10–20 min after contrast agent application to produce so-called late gadolinium enhancement (LGE) images which depict diseased myocardium with excellent reproducibility. Areas showing LGE correspond to zones of myocyte necrosis or myocardial fibrosis as shown by comparison with histopathology. Typical patterns of hyperenhancement exist in ischemic heart disease but also in dilated cardiomyopathy, hypertrophic cardiomyopathy and other inflammatory or infiltrative myocardial disease and are described in this article. LGE-CMR is helpful to distinguish advanced ischemic heart disease from nonischemic dilated cardiomyopathy. In ischemic heart disease LGE can also predict the functional recovery after revascularization procedures by directly showing the remaining viable myocardium. LGE may also become useful to predict malignant arrhythmias in patients with ischemic heart disease or nonischemic cardiomyopathy. This may lead in future to an increased role of LGE-CMR as a prognostic tool.ZusammenfassungMit speziellen Magnetresonanzsequenzen (s. Abbildung 2) und Gadolinium-(Gd-)basierten Kontrastmitteln kann das sog. Late Gadolinium Enhancement (LGE) dargestellt werden (s. Abbildung 1). Eine relative Anreicherung von Gd und damit ein LGE entsteht, wenn im Rahmen einer akuten Nekrose myokardiale Zellmembranen rupturiert sind und damit das Verteilungsvolumen von Gd zunimmt. Zugrunde liegen kann aber auch bei chonischen Prozessen ein Rahmen des fibrotischen Umbaus vergrößerter extrazellulärer Raum im Myokard (s. Abbildung 3). Die verschiedenen myokardialen Erkrankungen führen zu unterschiedlicher, typischer Ausprägung von LGE (s. Abbildungen 5 bis 10). Aufgrund dieser krankheitstypischen Bilder kann LGE-CMR bei der Differentialdiagnose bei Patienten mit unklaren kardialen Krankheitsbildern, Herzinsuffizienz, Kardiomyopathien, Speichererkrankungen oder Myokarditis sehr nützlich sein. Zuverlässig kann z. B. eine fortgeschrittene ischämische Herzerkrankung von dilatativen Kardiomyopathien nichtischämischer Genese unterschieden werden. Die LGE-CMR bietet auch zunehmend Möglichkeiten zur individuellen Prognoseabschätzung. Anhand des transmuralen Ausmaßes von Infarkten lässt sich der von einer revaskularisierenden Maßnahme zu erwartende Gewinn abschätzen. Zunehmendes Interesse gilt der weiteren Charakterisierung des mit Ausmaß, Verteilung und Homogenität von LGE-Arealen (und damit von myokardialen Narben) verknüpften Risikos für das Auftreten maligner Rhythmusstörungen. Entsprechende Studien gibt es sowohl für ischämische als auch für dilatative und hypertrophe Kardiomyopathien. Eingang in die gültigen Leitlinien für entsprechende therapeutische Maßnahmen wie Implantation automatischer Kardioverter-Defibrillatoren haben diese Daten bisher noch nicht gefunden.

Transient left ventricular dysfunction with apical ballooning (tako-tsubo cardiomyopathy) in Germany.

SummaryAimsA peculiarntype of an acute coronarynsyndrome is characterised bynacute onset of chest pain, STsegmentnchanges, elevatedntroponin I levels and a transientnballoon–like apical leftnventricular dysfunction, butnwithout significant coronarynartery disease. We sought tonassess this syndrome in Germannpatients.Methods and resultsAntotal of 22 females and 1 male withnacute transient left ventricularndysfunction were identified duringnan interval of 2 years and wereninvestigated clinically and angiographically.nAll patients presentednwithout obstructive coronary arteryndisease. In 16 patients (70%)nST–segment elevations were observednmimicking acute myocardialninfarction, whereas the remainingnpatients (30%) revealednonly negative T waves. Deep negativenTwaves were characteristicallynseen during the course of recoverynin all patients. Elevated troponin Inlevels > 2.0 µg/l (upper level ofnnormal) were measured in all patientsn(mean 18 ± 26.5 µg/l, rangenfrom 2.2–135.7 µg/l). Creatinenkinase rose up to a mean ofn282 ± 236 IU/l (upper level of normaln180 U/l). Emotional or physicalnstress situations associatednwith the onset of the symptomsnwere observed in 16 patientsn(70%). Other suspected triggernfactors were gastrointestinal infectionnand in one case a surgicalnintervention. In four patients antrigger factor could not be identified.nLeft ventriculography showednan ejection fraction of 53 ± 15%.nAfter an interval of 7 ± 2 days afternthe first angiogram, ejection fractionnhad increased from 48 ± 11%nto 64 ± 11% in eight controllednpatients by repeated ventriculography.nCoronary spasm with anlumen reduction > 75% could benprovoked using acetylcholine in 10nof 17 tested patients (59%) withnreproduction of the symptoms.nWithin 14 days the LV dysfunctionnreturned to normal in all patients.nThe ECG abnormalities disappearedncompletely as early asn3 months (74%) and were not seennin any patient after 6 months.ConclusionTako–tsubo cardiomyopathynis not exclusively anJapanese or Northern Americannphenomenon. Despite increasednpatient reports the exact underlyingncause and pathophysiology ofnthis syndrome remain unclear.nHowever, despite the initial dramaticnpresentation of this diseasenthe prognosis is good.

ECG findings in comparison to cardiovascular MR imaging in viral myocarditis

OBJECTIVESnWe sought (1) to assess prevalence and type of ECG abnormalities in patients with biopsy proven myocarditis and signs of myocardial damage indicated by LGE, and (2) to evaluate whether ECG abnormalities are related to the pattern of myocardial damage.nnnBACKGROUNDnPrevalence and type of ECG abnormalities in patients presenting biopsy proven myocarditis, as well as any relation between ECG abnormalities and the in vivo pattern of myocardial damage are unknown.nnnMETHODSnEighty-four consecutive patients fulfilled the following criteria: (1) newly diagnosed biopsy proven viral myocarditis, and (2) non-ischemic LGE, and (3) standard 12-lead-ECG upon admission.nnnRESULTSnSixty-five patients with biopsy proven myocarditis had abnormal ECGs upon admission (77%). In this group, ST-abnormalities were detected most frequently (69%), followed by bundle-branch-block in 26%, and Q-waves in 8%. Atrial fibrillation was present in 6%, and AV-Block in two patients. In patients with septal LGE ST-abnormalities were more frequently located in anterolateral leads compared to patients with lateral LGE, in whom ST-abnormalities were most frequently observed in inferolateral leads. Bundle-branch-block occurred more often in patients with septal LGE (11/17). Four of five patients with Q-waves had severe and almost transmural LGE in the lateral wall.nnnCONCLUSIONnECG abnormalities can be found in most patients with biopsy proven viral myocarditis at initial presentation. However, similar to suspected acute myocardial infarction, a normal ECG does not rule out myocarditis. ECG findings are related to the amount and area of damage as indicated by LGE, which confirms the important clinical role of ECG.

Coronary microvascular dysfunction assessed by intracoronary acetylcholine provocation testing is a frequent cause of ischemia and angina in patients with exercise-induced electrocardiographic changes and unobstructed coronary arteries.

The exercise electrocardiogram (ECG) is a standard examination in patients with suspected coronary artery disease. However, despite a pathologic result, many patients undergoing diagnostic coronary angiography do not have any significant epicardial stenosis. In this study, we assessed the relation between a pathologic exercise ECG and coronary microvascular dysfunction in response to intracoronary acetylcholine (ACh) provocation in patients without any relevant epicardial stenosis.

Recurrent Aortic Dissection: Observations from the International Registry of Aortic Dissection (IRAD)

Background: Improved medical care after initial aortic dissection (AD) has led to increased survivorship and a population of individuals at risk for further cardiovascular events, including recurrent AD. Reports describing recurrent ADs have been restricted to small numbers of patients from single institutions. We used the IRAD (International Registry of Acute Aortic Dissection) database to examine the clinical profiles and outcomes of patients with recurrent AD. Methods: We identified 204 patients enrolled in IRAD with recurrent AD. For the primary analysis, patient characteristics, interventions, and outcomes were analyzed and compared with 3624 patients with initial AD. Iterative logistic modeling was performed to investigate variables associated with recurrent AD. Cox regression analyses were used to determine variables associated with 5-year survival. A subset of recurrent AD patients was analyzed for anatomic and demographic details of initial and recurrent ADs. Results: Patients with recurrent AD were more likely to have Marfan syndrome (21.5% versus 3.1%; P<0.001) but not bicuspid aortic valve (3.6% versus 3.2%; P=0.77). Descending aortic dimensions were greater in patients with recurrent AD than in patients with initial AD independently of sentinel dissection type (type A: 4.3 cm [3.5–5.6 cm] versus 3.3 cm [2.9–3.7 cm], P<0.001; type B: 5.0 cm [3.9–6.0 cm] versus 4.0 cm [3.5–4.8 cm], P<0.001), and this observation was accentuated among patients with Marfan syndrome. In multivariate analysis, the diagnosis of Marfan syndrome independently predicted recurrent AD (hazard ratio, 8.6; 95% confidence interval, 5.8–12.8; P<0.001). Patients with recurrent AD who presented with proximal followed by distal AD were younger than patients who experienced distal followed by proximal dissection AD (42.1±16.1 versus 54.3±14.8 years; P=0.004). Conclusions: Among those suffering acute aortic dissection, 5% have a history of a prior aortic dissection. Recurrent AD is strongly associated with Marfan syndrome.

Images in cardiovascular medicine. Cardiomyopathy in a Duchenne muscular dystrophy carrier and her diseased son: similar pattern revealed by cardiovascular MRI.

14-year-old boy with Duchenne muscular dystrophy(DMD; duplication of dystrophin gene exons 8 to 11),accompanied by his mother, was brought to our hospital toundergo a comprehensive cardiac study as a participant in ourongoing research project on patients with muscular dystrophy(to evaluate the presence and presentation pattern of cardio-myopathy). He had lost ambulation at the age of 9 and useda wheelchair. He had undergone annual cardiac examinationsbyechocardiography,whichtothatdatehadbeenwithoutanypathological finding. He described of minor dyspnea onexertion and transient palpitations occurring infrequently. Hisresting ECG (Figure 1A) demonstrated negative T waves inleads V1 through V3. Blood analysis revealed an elevatedtotal creatine kinase level of 2630 U/L (normal 190 U/L), aslightly elevated creatine kinase-MB fraction level of 80 U/L(normal 25 U/L), an elevated troponin T level of 0.09 ng/mL(normal 0.03 ng/mL), and a normal N-terminal pro-brainnatriuretic peptide level of 137 pg/mL (normal 450 pg/mL).Because of the patients’ scoliosis, the acoustic windowduring echocardiography was limited, and only parasternalviews with normal findings could be obtained with acceptableimage quality (Movies I and II in the online-only DataSupplement). Then, cardiovascular MRI (CMR) was per-formed on a clinical scanner (1.5 Tesla Sonata, Siemens,Germany). The CMR cine images demonstrated slightlyreduced left ventricular (LV) systolic function (ejectionfraction 52%) with regional hypokinesia in the inferolateralwall (Figure 2A, upper and middle panels; Movies III to IV,full-motion images in the online-only Data Supplement).Contrast imaging was performed after intravenous applica-

Identification of cardiomyopathy associated circulating miRNA biomarkers in patients with muscular dystrophy using a complementary cardiovascular magnetic resonance and plasma profiling approach

BackgroundDuchenne and Becker muscular dystrophy (DMD and BMD) are X-chromosomal recessive neuromuscular disorders that are caused by mutations in the dystrophin gene and characterized by cardiac involvement. Circulating microRNAs (miRNAs) have been proposed as diagnostic biomarkers for various cardiovascular diseases. However, circulating miRNAs reflecting the presence and/or disease severity of cardiac involvement in DMD/BMD patients have not been described so far.MethodsSixty-three male patients with known MD and 26 age-matched healthy male controls were prospectively enrolled. All MD patients and controls underwent comprehensive cardiovascular magnetic resonance (CMR) studies as well as venous blood sampling on the same day.ResultsAn impaired left ventricular (LV) systolic function (defined as LV-EF <55xa0%) was detected in 29 (46xa0%) and presence of late gadolinium enhancement (LGE) indicative of myocardial fibrosis in 48 (76xa0%) MD patients with an exclusively non-ischemic pattern. Whereas no significant differences were observed for the 27 selected circulating miRNAs in MD patients with abnormal CMR findings (comprising structural and/or functional impairments) compared to those with completely normal CMR studies, a significant up-regulation of three miRNAs was observed in LGE-positive MD patients compared to LGE-negative ones: miR-222 (1.8-fold, pu2009=u20090.035), miR-26a (2.1-fold, pu2009=u20090.03) and miR-378a-5p (2.4-fold, pu2009=u20090.026). A signature of these three miRNAs (miR-26a, miR-222 and miR-378a-5p) resulted in an area under the curve (AUC) value of 0.74 for the diagnosis of LGE-positive MD patients. In a multivariable model, three independent predictors for LGE presence were identified comprising not only clinical and laboratory markers (LV-EF: OR 0.47, 95xa0% CI 0.24-0.89, pu2009=u20090.021 and elevated hs-Trop: OR 2559, 95xa0% CI 2.97-22.04*105, pu2009=u20090.023) but also the circulating miR-222 (OR 938, 95xa0% CI 938.46, 3.56-24.73*104, pu2009=u20090.016).ConclusionsUp-regulation of circulating miRNAs miR-222, miR-26a and miR-378a-5p indicates the presence of myocardial scars in MD patients. Plasma miR-222 appears to be a promising novel biomarker reflecting structural – but not functional – cardiac alterations in MD patients.

Imaging and Intervention in Cardiology

Foreword. Introduction. Part One: Thrombolysis. Part Two: Coronary revascularization: assessment before intervention. Part Three: Coronary revascularization: assessment after intervention. Part Four: Imaging and valvular interventions. Part Five: Intervention in congenital heart disease. Colour illustrations. Index.

Epicardial coronary artery spasm as cause of capecitabine-induced tako tsubo cardiomyopathy

Cardiotoxicity of fluoropyrimidines like the orally administered capecitabine and the intravenous 5-fluorouracil (5-FU) is a well-known clinical challenge [1, 2]. The cardiotoxic effects of both agents seem to occur through the same mechanisms [3]. However, capecitabine-induced cardiotoxicity is less common because it obtains its pharmacological active form through a three-step enzymatic conversion, while the last step is catalyzed by the enzyme thymidine phosphorylase, which is more active in neoplastic tissues [4, 5]. But this enzyme is also actively expressed in arteriosclerotic plaques, which is thought to be one potential mechanism leading to coronary side effects, especially in patients with a history of coronary artery disease [3]. Until today, numerous reports have shown cardiac side effects of fluoropyrimidines. However, there is no explicit evidence of capecitabine as a direct trigger for tako tsubo cardiomyopathy (TTC). Amongst other causes, coronary artery spasm is discussed as a potential cause of TTC [6]. Epicardial vasospasm is a widely accepted hypothetical pathomechanism of 5-FU-associated cardiac side effects [7, 8]. Therefore, fluoropyrimidines could be plausible triggers for TTC and the following case will strengthen this possible connection. An 81-year-old female with metastatic breast cancer was admitted to our emergency unit with acute chest pain and severe dyspnoea. The symptoms began at about 4 p.m., shortly after a 1-h workout as part of a diabetes group training. On the same day, in the morning at about 9 a.m., the patient had received the first dose of capecitabine (1,500 mg). The patient did not report any extraordinary emotional stress, but had a history of obstructive coronary artery disease. Five years ago she had undergone percutaneous coronary intervention in the left anterior descending coronary artery (LAD). The patient further suffered from insulin-dependent diabetes mellitus type 2, hypercholesterolemia, hypertension and peripheral vascular disease. On admission the symptoms were relieved by sublingual nitroglycerin, but recurred after a few minutes. The electrocardiogram (ECG) showed sinus rhythm with ST-segment elevations, which had not been detected in a routine ECG 3 weeks ago (Fig. 1a). High sensitive cardiac troponin T concentration was 282 pg/ml (n 14 pg/ml). The patient was treated with acetylsalicylic acid (500 mg intravenous), clopidogrel (600 mg orally) and heparin (5,000 units intravenous) because of the suspicion of acute ST-elevation myocardial infarction. No abnormalities were discovered by physical examination. Blood pressure was 140/63 mm/Hg. Cardiac catheterization was performed immediately. Ventriculography showed apical dyskinesia Electronic supplementary material The online version of this article (doi:10.1007/s00392-013-0636-4) contains supplementary material, which is available to authorized users.

Differences in cardiac involvement between carriers of Duchenne and Becker muscular dystrophy - a cardiovascular magnetic resonance study

Background Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked recessive disorders associated with both skeletal myopathy and progressive cardiomyopathy in males. Although BMD patients present milder skeletal muscle involvement, they have been shown to present more advanced cardiomyopathy than DMD. Female DMD/BMD carriers are usually free of skeletal muscle symptoms but they may also develop cardiomyopathy. The present study aimed at characterizing the presence and pattern of cardiac abnormalities in a group of genetically-proven MD-carriers by means of comprehensive CMR studies. Moreover, we wanted to test whether DMD carriers (DMDc) and BMD carriers (BMDc) are differently affected.