Adjuvant Use of Ivabradine in Acute Heart Failure due to Myocarditis

We report two cases of young men in whom acute heart failure due to myocarditis was diagnosed. The patients had been transferred to the intensive care unit (ICU) with commencing symptoms of acute heart failure and consecutive multiorgan failure for further treatment and to evaluate the indication for implantation of a ventricular assist device or for high urgent orthotopic heart transplantation. In both patients, the If-channel inhibitor ivabradine was administered off-label to provide selective heart rate reduction, and thus support hemodynamic stabilization. Though currently considered off-label use in patients suffering from severe hypotension and acute heart failure, the use of ivabradine may beneficially influence outcome by allowing optimization of the patient's heart rate concomitant to initial measures of clinical stabilization

Increased proinflammatory endothelial response to S100A8/A9 after preactivation through advanced glycation end products

BACKGROUND: Atherosclerosis is an inflammatory disease in which a perpetuated activation of NFkappaB via the RAGE (receptor for advanced glycation end products)-MAPK signalling pathway may play an important pathogenetic role. As recently S100 proteins have been identified as ligands of RAGE, we sought to determine the effects of the proinflammatory heterodimer of S100A8/S100A9 on the RAGE-NFkappaB mediated induction of proinflammatory gene expression. METHODS: Human umbilical vein endothelial cells (HUVEC) were preincubated for 72 h with AGE-albumin or unmodified albumin for control, whereas AGE-albumin induction resulted in an upregulation of RAGE. Following this preactivation, cells were stimulated for 48 h with heterodimeric human recombinant S100A8/S100A9. RESULTS: Heterodimeric S100A8/S100A9 enhanced secretion of IL-6, ICAM-1, VCAM-1 and MCP1 in AGE-albumin pretreated HUVEC in a dose dependent manner. These effects could not be detected after stimulation with the homodimeric proteins S100A8, S100A9, S100A1 and S100B. The effects of heterodimeric S100A8/S100A9 were reduced by inhibition of the MAP-kinase pathways ERK1/2 and p38 by PD 98059 and SB 203580, respectively. CONCLUSION: The heterodimeric S100A8/S100A9 might therefore play a hitherto unknown role in triggering atherosclerosis in diabetes and renal failure, pathophysiological entities associated with a high AGE burden. Thus, blocking heterodimeric S100A8/S100A9 might represent a novel therapeutic modality in treating atherosclerosis

Heart transplantation as salvage therapy for progressive prosthetic valve endocarditis due to methicillin-resistant Staphylococcus epidermidis (MRSE)

Background: Prosthetic valve endocarditis (PVE) has the highest in-hospital mortality among all cases of infective endocarditis (IE), it is estimated at about 40 %. Orthotopic heart transplantation (OHT) as a measure of last resort, may be considered in selected cases where repeated surgical procedures and conservative efforts have failed to eradicate persistent or recurrent IE. Only few clinical data are available regarding this rare indication for OHT, since active IE has traditionally been considered as a contraindication for OHT. Case presentation: We report on a 55 year old male patient who underwent prosthetic valve replacement with a mechanical valved conduit ten years ago and developed now persistent PVE with severe complications due to methicillin-resistant Staphylococcus epidermidis (MRSE). Repeated surgical procedures and conservative efforts have failed to eradicate the pathogen. Regarding the lack of curative options, salvage OHT was discussed as a measure of last resort. 28 months after the first diagnosis of PVE, the patient was successfully transplanted and is now doing well under close follow-up (6 months post-OHT). Conclusions: PVE remains a challenging condition regarding diagnosis and treatment. The presented case underscores the urgent need for an integrated and multidisciplinary approach to patients with suspected and definitive IE - especially in PVE. OHT might be a feasible measure of last resort in selected patients with IE. Our case report adds published clinical experience to this rarely performed procedure and consolidates previous findings

Left ventricular long axis strain: a new prognosticator in non-ischemic dilated cardiomyopathy?

Background: Long axis strain (LAS) has been shown to be a fast assessable parameter representing global left ventricular (LV) longitudinal function in cardiovascular magnetic resonance (CMR). However, the prognostic value of LAS in cardiomyopathies with reduced left ventricular ejection fraction (LVEF) has not been evaluated yet. Methods and results: In 146 subjects with non-ischemic dilated cardiomyopathy (NIDCM, LVEF ≤45 %) LAS was assessed retrospectively from standard non-contrast SSFP cine sequences by measuring the distance between the epicardial border of the left ventricular apex and the midpoint of a line connecting the origins of the mitral valve leaflets in end-systole and end-diastole. The final values were calculated according to the strain formula. The primary endpoint of the study was defined as a combination of cardiac death, heart transplantation or aborted sudden cardiac death and occurred in 24 subjects during follow-up. Patients with LAS values > −5 % showed a significant higher rate of cardiac events independent of the presence of late gadolinium enhancement (LGE). The multivariate Cox regression analysis revealed that LVEDV/BSA (HR: 1.01, p  −10 % and the presence of LGE, patients with 3 points had a significantly higher risk for cardiac events than those with 2 or less points. Conclusion: Assessment of long axis function with LAS offers significant incremental information for the prediction of cardiac events in NIDCM and improves risk stratification beyond established CMR parameters

Adverse events in families with hypertrophic or dilated cardiomyopathy and mutations in the MYBPC3 gene

<p>Abstract</p> <p>Background</p> <p>Mutations in <it>MYBPC3 </it>encoding myosin binding protein C belong to the most frequent causes of hypertrophic cardiomyopathy (HCM) and may also lead to dilated cardiomyopathy (DCM). <it>MYBPC3 </it>mutations initially were considered to cause a benign form of HCM. The aim of this study was to examine the clinical outcome of patients and their relatives with 18 different <it>MYBPC3 </it>mutations.</p> <p>Methods</p> <p>87 patients with HCM and 71 patients with DCM were screened for <it>MYBPC3 </it>mutations by denaturing gradient gel electrophoresis and sequencing. Close relatives of mutation carriers were genotyped for the respective mutation. Relatives with mutation were then evaluated by echocardiography and magnetic resonance imaging. A detailed family history regarding adverse clinical events was recorded.</p> <p>Results</p> <p>In 16 HCM (18.4%) and two DCM (2.8%) index patients a mutation was detected. Seven mutations were novel. Mutation carriers exhibited no additional mutations in genes <it>MYH7</it>, <it>TNNT2</it>, <it>TNNI3</it>, <it>ACTC </it>and <it>TPM1</it>. Including relatives of twelve families, a total number of 42 mutation carriers was identified of which eleven (26.2%) had at least one adverse event. Considering the twelve families and six single patients with mutations, 45 individuals with cardiomyopathy and nine with borderline phenotype were identified. Among the 45 patients, 23 (51.1%) suffered from an adverse event. In eleven patients of seven families an unexplained sudden death was reported at the age between 13 and 67 years. Stroke or a transient ischemic attack occurred in six patients of five families. At least one adverse event occurred in eleven of twelve families.</p> <p>Conclusion</p> <p><it>MYBPC3 </it>mutations can be associated with cardiac events such as progressive heart failure, stroke and sudden death even at younger age. Therefore, patients with <it>MYBPC3 </it>mutations require thorough clinical risk assessment.</p

Atlas of the clinical genetics of human dilated cardiomyopathy

[Abstract] Aim. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results. In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion. This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.Hôpitaux de Paris; PHRC AOM0414