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Patients after heart transplantation (HTX) present with sinus tachycardia due to graft denervation. As elevated heart rates negatively affect survival, the aim of this study was to analyze the effects of ivabradine vs metoprolol succinate on heart rate, left ventricular (LV) mass and survival following HTX. This observational retrospective single-center study assessed 84 patients continuously receiving either ivabradine (n = 40) or metoprolol succinate (n = 44) within 2 years after HTX. Patients with dual therapy (ivabradine and metoprolol succinate), other beta blockers, amiodarone, or digitalis were excluded. Patient characteristics, post-transplant medication, heart rates, LV mass, and survival were investigated. Analysis of patient characteristics, immunosuppressive drug regimen, and post-transplant medication showed no significant differences between groups except for ivabradine and metoprolol succinate. Baseline heart rates differed not significantly between patients treated with ivabradine [87.0 beats per minute (bpm)] and metoprolol succinate (86.2 bpm; P = 0.6395). At 2-year follow-up, patients with ivabradine (76.7 bpm) had a significantly lower heart rate compared to baseline (P

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease, which goes along with increased risk for sudden cardiac death (SCD). Despite the knowledge about the different causal genes, the relationship between individual genotypes and phenotypes is incomplete. We retrieved PubMed/Medline literatures on genotype–phenotype associations in patients with HCM and mutations in MYBPC3, MYH7, TNNT2, and TNNI3. Altogether, 51 studies with 7675 HCM patients were included in our meta-analysis. The average frequency of mutations in MYBPC3 (20%) and MYH7 (14%) was higher than TNNT2 and TNNI3 (2% each). The mean age of HCM onset for MYH7 mutation positive patients was the beginning of the fourth decade, significantly earlier than patients without sarcomeric mutations. A high male proportion was observed in TNNT2 (69%), MYBPC3 (62%) and mutation negative group (64%). Cardiac conduction disease, ventricular arrhythmia and heart transplantation (HTx) rate were higher in HCM patients with MYH7 mutations in comparison to MYBPC3 (p

Left ventricular noncompaction (LVNC) is a cardiomyopathy with hypertrabeculation of the LV, often complicated by heart failure, arrhythmia and thromboembolic events. The features of LVNC are still incompletely characterized due to its late recognition as clinically relevant condition. The aims of this study were to describe echocardiographic and electrophysiologic characteristics of LVNC patients and to assess the effects of chronic β-blocker treatment. Study patients (n = 20; 42.5 [36.3; 52.5] years; 12 men) exhibited reduced LV ejection fraction (median LVEF = 32 %) and an increased LV mass of 210 g. Sinus rhythm was present in 19 patients, whereas one patient was in atrial fibrillation. Baseline heart rate was 77.5 beats per minute. Left bundle branch block was detected in five cases. In a subgroup of patients receiving β-blocker therapy (n = 17), LV mass was reduced from 226 [178; 306] g to 220 [169; 254] g (p = 0.007) at 13 ± 6 months follow-up. By contrast, a subgroup of three patients that were not treated with an anti-β-adrenergic agent showed LV mass increase from 180 [169; 197] g to 199 [185; 213] g (p = 0.023). LVEF and electrocardiographic parameters were not significantly modulated during chronic β-blocker treatment. There was no sustained symptomatic ventricular tachyarrhythmia, thromboembolic event or death in either group. In conclusion, this study reveals reduction of LV mass among LVNC patients during β-blocker therapy. Effects of β-blocker treatment in LVNC require validation in prospective controlled studies.

Die dilatative Kardiomyopathie (DCM) ist in 20–50 % der Falle familiar gehauft und somit genetisch bedingt. Derzeit ist eine Vielzahl von Mutationen in mehr als 40 Genen bekannt, die etwa 20 % aller familiaren Falle erklaren. Die strukturierte Erhebung der Familienanamnese mit Erstellen eines Stammbaums ist obligater Bestandteil der Erstdiagnostik bei DCM. Uber eine Familienuntersuchung zur Fruherkennung konnen weitere Risikopersonen identifiziert werden. Mit Ausnahme des Lamin-A/C-Gens (LMNA) erlaubt die genetische Diagnostik bisher noch keine Risikostratifizierung. Eine DCM aufgrund einer LMNA-Mutation ist mit einem hohen Risiko fur den plotzlichen Herztod verbunden. Bei familiaren AV-Blockierungen, plotzlichem Herztod sowie einer begleitenden Muskelerkrankung sollte eine LMNA-Mutation ausgeschlossen werden. Eine ICD-Implantation ist unabhangig von der Atiologie bei einer chronisch eingeschrankten LVEF unter 35 % indiziert, wobei dies mit Einschrankungen fur symptomfreie Patienten im Stadium NYHA I gilt. Grundsatzlich sollte vor ICD-Implantation fur 3–12 Monate eine optimierte medikamentose Therapie durchgefuhrt werden.

Dilated cardiomyopathy (DCM) is a frequent form among the cardiomyopathies and displays a very heterogeneous etiology. It is a familial disease in about one-third of DCM cases [8, 14, 16]. More than 20 DCM candidate genes were already identified [2, 4], but the genetic defects in the large majority of familial cases are still unknown. LMNA is among the most common genes affected in familial DCM and is coding for lamin A/C, which is a ubiquitous component of the nuclear skeleton and involved in the regulation of gene expression. However, there are many other non-cardiac diseases like Emery-Dreifuss muscular dystrophy (EDMD2; OMIM 181350), Limb-girdle muscular dystrophy type 1B (LGMD1B; OMIM 159001), Dunnigantype familial partial lipodystrophy (OMIM 151660), Charcot-Marie-Tooth disease (CMT2B1; OMIM 605588), Hutchinson-Gilford progeria syndrome (HGPS; OMIM 176670) and restrictive dermopathy (OMIM 275210), which can result from defects in this gene and are summarized under the term laminopathies [5]. DCM caused by LMNA mutations is attributed to a characteristic phenotype showing atrial fibrillation, skeletal muscle involvement, cardiac conduction defects and a high incidence of sudden death [3, 9, 20, 25, 26]. Due to these complications, DCM patients with LMNA mutations are reported to have a worse prognosis compared to other DCM patients [23, 28] and a nearly complete disease penetrance with disease expression between 20 and 60 years of age [19]. It is estimated that up to 5% of all DCM cases are caused by LMNA mutations [24]. Here we report about a family with a gene mutation in the lamin A/C gene (LMNA) with the incidence of sudden cardiac death even before the manifestation of dilated cardiomyopathy. A 32-year-old woman presented at the outpatient department after a sudden loss of consciousness for seconds, while she was driving a car on a motorway. There were no prodromi before this event and no diseases in the medical history. However, she reported about a premature death of her father at the age of 42 years, which was interpreted as related to myocardial infarction. There were no abnormal clinical findings and the ECG was interpreted as normal. Echocardiography revealed regular findings, with the exception, that in the apex of the right ventricle a small sacculation was suspected. In regard to the clinical event and family history further thorough examination was initiated (Table 1)

Z-disks, the mechanical integration sites of heart and skeletal muscle cells, link anchorage of myofilaments to force reception and processing. The key molecules that enable the Z-disk to persistently withstand the extreme mechanical forces during muscle contraction have not yet been identified. Here we isolated nexilin (encoded by NEXN) as a novel Z-disk protein. Loss of nexilin in zebrafish led to perturbed Z-disk stability and heart failure. To evaluate the role of nexilin in human heart failure, we performed a genetic association study on individuals with dilated cardiomyopathy and found several mutations in NEXN associated with the disease. Nexilin mutation carriers showed the same cardiac Z-disk pathology as observed in nexilin-deficient zebrafish. Expression in zebrafish of nexilin proteins encoded by NEXN mutant alleles induced Z-disk damage and heart failure, demonstrating a dominant-negative effect and confirming the disease-causing nature of these mutations. Increasing mechanical strain aggravated Z-disk damage in nexilin-deficient skeletal muscle, implying a unique role of nexilin in protecting Z-disks from mechanical trauma.

Peripartum cardiomyopathy (PPCM) is a major cause of pregnancy-related maternal heart failure that develops towards the end of pregnancy or in the months following delivery. In small retrospective case series, autoimmune responses in the pathogenesis of PPCM have been proposed upon identification of autoantibodies (AABs) to cardiac antigens. However, their clinical and prognostic relevance still remain unclear. In this study, we evaluated the presence of circulating AABs against cardiac sarcomeric myosin (MHC) and troponin I (TnI) in the sera of PPCM patients and in relation to clinical presentation. In this case-control study, 70 patients diagnosed with PPCM and 50 pregnancy-matched healthy women with normal cardiac function were enrolled. Clinical assessment, echocardiography and blood tests were performed at baseline and at 6 ± 2 months follow-up. The presence of serum AABs against MHC (anti-MHC) and TnI (anti-TnI) was determined with a custom-made enzyme-linked immunosorbent assay (ELISA). The seropositivity for these AABs was correlated with the severity of LV dysfunction and the occurrence of pericardial effusion indicative of perimyocardial inflammation at baseline. Potential impact of these AABs on disease progression was evaluated with regard to functional (left ventricular ejection fraction) and clinical improvement at follow-up. Either anti-MHC or anti-TnI or both AABs were detected in the serum of 46 % of PPCM patients and in 8 % of healthy controls. In PPCM the presence of either one of these AABs was associated with significantly lower baseline LVEF and lower rate of full cardiac recovery at follow-up. Patients who were seropositive for anti-TnI AABs showed more frequently pericardial effusion indicative of a more pronounced immune response of the peri-/myocardium in these patients. Further studies are required to clarify cellular and molecular circuits leading to elevated levels of AABs and their pathophysiological relevance for disease initiation and progression in PPCM.

Cardiomyopathies are complex myocardial diseases characterized by inappropriate ventricular hypertrophy (HCM) or dilation (DCM). Both disorders may lead to sudden death or progressive heart failure and exhibit familial aggregation with marked genetic heterogeneity. Many candidate genes were identified by linkage analysis, experimental animal studies, and expression analysis. A systematic assessment of the prevalence of different mutations in these genes requires high-throughput analyses. In this paper, we present a simple and reliable protocol for mutation screening by heteroduplex analysis which reduced costs and workload of sequencing. Employing denaturing gradient gel electrophoresis (DGGE), 11 known and 14 potential candidate genes for HCM and DCM were analyzed. DGGE assays allowed analysis of 286 of the 312 protein coding exons, performing only four alternative polymerase chain reaction protocols and only two different DGGE analysis conditions. Sensitivity for the detection of heteroduplexes proved excellent, even for GC-rich DNA fragments, which were analyzed by a combination of DGGE and constant denaturant gel electrophoresis. To confirm DGGE sensitivity in cases where no variants in our human DNA samples could be observed, we generated heteroduplexes from homologous human and chimpanzee DNA. The platform proved a valuable contribution to elucidating the genetic causes of DCM and HCM as demonstrated by the identification of 17 different known and novel mutations and 98 different polymorphisms in our setting.

Systemic embolism is a frequent cause of stroke. At the beginning of the last decade by introduction of transesophageal echocardiography and other imaging techniques atheromatosis of the aortic arch has been recognized as an important source of embolism. Formerly in the pre-TEE era, this entity was included into cryptogenic strokes. Aortic atheromas are found in about one quarter of patients presenting with embolic events. The severity of atherosclerosis graded by TEE correlates with the risk for future embolism, especially if mobile lesions or superimposed thrombi are present. Independent of plaque extension, patients with unstable plaques characterized by echo-lucency, inhomogenity, lacking of calcifications, ulceration, mobile parts and concomitant spontaneous echo contrast within the aorta have a higher risk for embolic events. However, the diagnosis of aortic atheromatosis is mostly established if an embolic event has already occurred. Therefore, it is important to identify patients at risk, especially before they undergo interventions with manipulation at the aorta like coronary bypass surgery. Risk factors are age above 70, diabetes mellitus, hyperlipidemia, arterial hypertension, aortic calcifications on standard chest X-ray, elevated serum levels of C-reactive protein, other inflammatory markers, and an activated coagulation. Randomized studies for treatment of patients with severe aortic atheromatosis are not yet existing. Warfarin has been shown to prevent stroke in patients with mobile atheromas and superimposed thrombi, but there are case reports about aggravation of cholesterol embolism under warfarin treatment. It is concluded from other atherosclerotic manifestations that plaque stabilizing treatment with statins and ACE inhibitors is also beneficial.

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.