Sabine Rösch

Left ventricular systolic function and the pattern of late-gadolinium-enhancement independently and additively predict adverse cardiac events in muscular dystrophy patients

BackgroundCardiac involvement is a frequent finding in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies. With this study, we aimed at elucidating the relationship between the phenotypic expression of cardiac involvement and the occurrence of adverse cardiac events in DMD/BMD patients.MethodsEighty-eight male DMD/BMD patients (age 29 ± 14 yrs) were prospectively enrolled. All patients underwent cardiovascular magnetic resonance (CMR) comprising cine- and late-gadolinium-enhancement (LGE)-CMR at study entry and were subsequently followed-up for adverse cardiac events. The primary endpoint was defined as all-cause/cardiac death or cardiac transplantation. Secondary endpoints were (1) hospitalization for heart failure and/or (2) occurrence of non-/sustained ventricular tachycardia (VT).ResultsDuring a mean follow-up time of 47 ± 18 months, the primary endpoint was observed in three (3%) and the secondary endpoint in 21 (24%) patients. On multivariable analysis, LV-EF (HR, 95% CI: 0.94, 0.89-0.97, p = 0.001) and the presence of “transmural” LGE (HR, 95% CI: 2.89, 1.09-7.68, p = 0.033) were the only independent predictors for secondary endpoints. A cut-off for LV-EF of 45% was associated with the highest hazard ratio (HR, 95% CI: 11.50, 4.49-29.43, p < 0.0001) in a Cox regression survival analysis. In the group of patients with a LV-EF (>45%), those patients already showing “transmural” LGE had a significantly lower event-free-survival (HR, 95% CI: 13.48, 1.89-96.12, p = 0.009) compared to those without.ConclusionsAn impaired LV systolic function (LV-EF ≤45%) and a “transmural” pattern of myocardial fibrosis independently predict the occurrence of adverse cardiac events in DMD/BMD patients. Even in DMD/BMD patients with relatively preserved LV-EF (>45%), the simple and visually assessable parameter “transmural LGE” is of additive prognostic value.

First Multiparametric Cardiovascular Magnetic Resonance Study Using Ultrasmall Superparamagnetic Iron Oxide Nanoparticles in a Patient With Acute Myocardial Infarction New Vistas for the Clinical Application of Ultrasmall Superparamagnetic Iron Oxide

A 50-year-old man presented with acute chest pain that had started about 6 hours prior to admission to our emergency department. His resting ECG revealed an ST-elevation myocardial infarction with typical ST-segment elevation in the leads V1 through V4 and reciprocal ST-segment depression. Consequently, immediate coronary angiography was performed and revealed a proximally occluded left anterior descending artery (Figure 1). The left anterior descending artery was recanalized and a bare-metal stent was implanted. Postinterventional blood analysis revealed a peak total creatine kinase level of 2962 U/L (normal, <190 U/L), a peak creatine kinase–muscle-brain type level of 231 U/L (normal, <25 U/L), a peak high-sensitivity troponin T level of 5705 pg/mL (normal, <14 pg/mL), and a slightly elevated N-terminal pro-brain natriuretic peptide level of 882 pg/mL (normal, <450 pg/mL). Figure 1. Coronary angiograms of the left coronary artery (LCA) and right coronary artery (RCA). A total occlusion of the left anterior descending artery ( left , red arrow) was observed and treated with a bare-metal stent ( middle , red arrow). PCI indicates percutaneous coronary intervention. After coronary angiography, the patient was enrolled in an ongoing clinical trial (Non-invasive myocardial inflammation imaging study 2 [NIMINI-2]) that is attempting to evaluate whether myocardial infarct imaging using ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) and multiparametric cardiovascular magnetic resonance (CMR) techniques allow an improved characterization of infarct as well as peri-infarct pathology (compared with conventional gadolinium-based necrosis/fibrosis imaging). Therefore, multiparametric CMR studies were performed before and after intravenous ferumoxytol (Feraheme, a USPIO; 17 mL IV=510 mg Fe) administration. The first CMR (pre-Feraheme) was performed 3 days after presentation with acute ST-elevation myocardial infarction. Serial CMR studies were then performed 6 hours, 24 hours, 48 hours, 96 hours, and 3 months after intravenous Feraheme administration (post-Feraheme). Only the first (pre-Feraheme) and last CMR study (3 months post-Feraheme) …

Cardiovascular magnetic resonance imaging (CMR) reveals characteristic pattern of myocardial damage in patients with mitochondrial myopathy

BackgroundMitochondrial myopathy comprises various clinical subforms of neuromuscular disorders that are characterised by impaired mitochondrial energy metabolism due to dysfunction of the mitochondrial respiratory chain. No comprehensive and targeted cardiovascular magnetic resonance (CMR) studies have been performed so far in patients with mitochondrial disorders. The present study aimed at characterising cardiac disease manifestations in patients with mitochondrial myopathy and elucidating the in vivo cardiac damage pattern of patients with different subforms of mitochondrial disease by CMR studies.Methods and resultsIn a prospective study, 37 patients with mitochondrial myopathy underwent comprehensive neurological and cardiac evaluations including physical examination, resting ECG and CMR. The CMR studies comprised cine-CMR, T2-weighted “edema” imaging and T1-weighted late-gadolinium-enhancement (LGE) imaging. Various patterns and degrees of skeletal myopathy were present in the participants of this study, whereas clinical symptoms such as chest pain symptoms (in eight (22%) patients) and various degrees of dyspnea (in 16 (43%) patients) were less frequent. Pathological ECG findings were documented in eight (22%) patients. T2-weighted “edema” imaging was positive in one (3%) patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) only. LGE imaging demonstrated the presence of non-ischemic LGE in 12 (32%) patients: 10 out of 24 (42%) patients with CPEO (chronic progressive external ophthalmoplegia) or KSS (Kearns-Sayre syndrome) and 2 of 3 (67%) patients with MELAS were LGE positive. All 10 LGE-positive patients with CPEO or KSS demonstrated a potentially typical pattern of diffuse intramural LGE in the left-ventricular (LV) inferolateral segments.ConclusionsCardiac involvement is a frequent finding in patients with mitochondrial myopathy. A potentially characteristic pattern of diffuse intramural LGE in the LV inferolateral segments was identified in patients suffering from the subforms CPEO or KSS.

The proteoglycan–dystrophin complex in genetic cardiomyopathies—lessons from three siblings with limb-girdle muscular dystrophy-2I (LGMD-2I)

The term limb-girdle muscular dystrophy (LGMD) is used to describe neuromuscular disorders that are characterized by muscle weakness and wasting predominantly affecting the extremities (proximal to a greater extent than distal). The LGMD family consists of seven autosomal-dominant and 13 autosomal-recessive forms, and a distinction between the different types on clinical criteria alone is difficult and requires protein analysis in muscle biopsies and genetic studies. LGMD has to be distinguished from the much more frequent X-linked dystrophinopathies (e.g. Duchenne muscular dystrophy, DMD) although the clinical picture may be quite similar. Former studies suggested that the prevalence rate of all forms of LGMD disorders is *7:100.000 [1]. However, since diagnostic capabilities have tremendously improved in the past years, a higher prevalence rate is likely. LGMD-2I is one of the autosomal recessive forms of the LGMD family and caused by mutations in the Fukutinrelated protein gene (FKRP) on chromosome 19q. The most common genetic finding in northern Europe is the homozygous mutation (C826A) in FKRP and is mostly associated with a milder phenotype of muscular dystrophy compared with those who are compound heterozygous. FKRP encodes a putative Golgi-based glycosyltransferase and is involved in posttranslational glycosylation of a-dystroglycan. Mutations in FKRP lead to a glycosylation defect and subsequently downregulation of a-dystroglycan which constitutes an essential component of the proteoglycan–dystrophin complex. The clinical picture of patients with LGMD-2I resembles DMD. Major causes of morbidity and mortality are cardiac and/or respiratory failure. Respiratory involvement with a forced vital capacity lower than 75% has been described in about 50% of affected individuals in one prior study [2]. Although previous studies suggested cardiac involvement to be a frequent finding (in up to 60%) in patients with LGMD-2I [2, 3], the morphological pattern of cardiomyopathy as well as the underlying pathophysiology has not been sufficiently evaluated so far. Currently, we are performing a cardiovascular magnetic resonance imaging (CMR) study on patients with neuromuscular disorders with special focus on the presence and presentation pattern of cardiomyopathy. The following three siblings with genetically proven LGMD-2I (homozygous C826A mutation on chromosome 19q3) participated in this ongoing research project and underwent a comprehensive CMR study on a clinical scanner (1.5-T Sonata, Siemens, Germany) after obtaining written informed consent. The first and youngest patient, a 38-year-old male suffered only from minor skeletal muscle weakness (predominantly in the lower extremities) with rapid exhaustion following exercise, and he was still able to walk and slowly climb stairs. Already 5 years previously, a biventricular dilation with impaired left ventricular (LV) systolic function was diagnosed and he was at that time taking an ACEinhibitor and a b-blocker. Apart from minor dyspnea on exertion, he had no cardiac complaints. In particular, there were no chest pain symptoms and no clinical signs suggestive of myocarditis. A. Yilmaz (&) S. Rosch U. Sechtem Division of Cardiology, Robert-Bosch-Krankenhaus, Auerbachstrasse 110, 70376 Stuttgart, Germany e-mail: ali.yilmaz@rbk.de

Magnetic resonance of the heart in a muscular dystrophy patient with an MR conditional ICD: Assessment of safety, diagnostic value and technical limitations

Cardiovascular magnetic resonance (CMR) studies in patients with pacemakers or implantable cardioverter/defibrillators (ICD) are increasingly required in daily clinical practice. Therefore, in the last years the manufacturers developed not only MR-conditional pacemakers, but also MR-conditional ICDs. However, the clinical experience regarding the feasibility and limitations of MR studies of the heart in patients with ICDs is still limited. In particular, there are hardly any CMR studies in the same patients performed prior to and post ICD implantation allowing a one-to-one comparison of the obtained CMR images. This is the first presentation of a CMR study in a patient with the world’s first and so far only MR-conditional ICD. In our case, a major problem related to the presence of the MR conditional ICD was an image artifact caused by the device’s generator which hampered the visualization of the midventricular and apical anterior and antero-lateral segments in all sequences performed. Considering previous studies, right chest implantation of the ICD could probably have helped in this setting and may be preferred in future ICD implantations. Our case report nicely illustrates the real clinical need for specially designed implantable devices that ensure safe and high-quality imaging in patients in whom serial CMR is required.

Diagnostic capability of CMR for the diagnosis of acute myocarditis in young patients is determined by the presence of elevated cardiac enzymes

Summary Only in patients with elevated levels of cardiac troponin CMR can reliably corroborate the clinical diagnosis of acute myocarditis Background Diagnosis of myocarditis remains a difficult clinical challenge, since the clinical spectrum of myocarditis is multifaceted. As clinical presentation and ECG-changes tend to be non-specific, cardiovascular magnetic resonance (CMR) has proven to be av aluable diagnostic tool regarding non-invasive diagnosis of myocarditis. However, CMR studies are time- and cost-intensive. Hence, further parameters are warranted to identify those individuals in whom a CMR study is likely to add crucial information regarding correct and timely diagnosis of acute myocarditis. The current study sought to elucidate the diagnostic yield of CMR in young patients aged ≤ 40 yrs with clinical diagnosis of myocarditis based on symptoms and ECG in relation to the presence or absence of elevated levels of cardiac troponin as an additional marker of acute myocardial injury. Methods Between 2009 and 2011, young patients aged ≤ 40 yrs presenting with acute or subacute chest pain and significant new-onset ST-segment changes suggestive of myocarditis, prospectively underwent CMR studies after obstructive coronary artery disease (CAD) was ruled out by coronary angiography if risk factors were present. Black-blood T2-weighted turbo-spin-echo (TSE) sequences were obtained to detect myocardial edema. Late gadolinium enhancement (LGE) imaging was performed in order to detect focal areas of contrast enhancement. Studies were performed on a 1.5 Tesla MR-Scanner (Siemens Sonata). Results During the recruitment period, 106 consecutive patients aged 17 to 40 yrs were included. Mean age was 29±7 yrs. In 19 patients additional cardiac catheterization was performed in order to definitely rule out obstructive CAD. LGE was successfully performed in all patients while in one patient T2-weighted edema images could not be obtained due to insufficient image quality. 13 (12%) patients showed significantly elevated levels of cardiac troponin. 15 (14%) patients showed focal late gadolinium enhancement (LGE) indicating myocarditis. All patients (100%) who presented with elevated levels of troponin showed presence of focal LGE. T2-weighted edema imaging showed correlating myocardial edema in 7 of these 13 individuals (54%). However, none of the 2 patients demonstrating LGE in the absence of elevated cardiac enzymes had signs of myocardial edema assessed by T2-weighted edema imaging but both turned out to have anamnestic evidence of subsided myocarditis in the past requiring exclusion of “acute” myocarditis. Moreover, the remaining 91 young patients with an unequivocal clinical diagnosis of myocarditis - but normal troponin levels - demonstrated normal findings by both T2-weighted edema and LGE imaging.

Molecular magnetic resonance imaging (MRI) of inflamed myocardium using ferucarbotran in patients with acute myocardial infarction

Superparamagnetic iron oxide nanoparticle (SPIO)-based molecular imaging agents targeting macrophages have been developed and successfully applied in animal models of myocardial infarction.