Cardiac MRI findings to differentiate athlete's heart from hypertrophic (HCM), arrhythmogenic right ventricular (ARVC) and dilated (DCM) cardiomyopathy.

To provide clinically relevant criteria for differentiation between the athlete's heart and similar appearing hypertrophic (HCM), dilated (DCM), and arrhythmogenic right-ventricular cardiomyopathy (ARVC) in MRI. 40 top-level athletes were prospectively examined with cardiac MR (CMR) in two university centres and compared to retrospectively recruited patients diagnosed with HCM (n = 14), ARVC (n = 18), and DCM (n = 48). Analysed MR imaging parameters in the whole study cohort included morphology, functional parameters and late gadolinium enhancement (LGE). Mean left-ventricular enddiastolic volume index (LVEDVI) was high in athletes (105 ml/m2) but significantly lower compared to DCM (132 ml/m2; p = 0.001). Mean LV ejection fraction (EF) was 61% in athletes, below normal in 7 (18%) athletes vs. EF 29% in DCM, below normal in 46 (96%) patients (p < 0.0001). Mean RV-EF was 54% in athletes vs. 60% in HCM, 46% in ARVC, and 41% in DCM (p < 0.0001). Mean interventricular myocardial thickness was 10 mm in athletes vs. 12 mm in HCM (p = 0.0005), 9 mm in ARVC, and 9 mm in DCM. LGE was present in 1 (5%) athlete, 8 (57%) HCM, 10 (56%) ARVC, and 21 (44%) DCM patients (p < 0.0001). Healthy athletes' hearts are characterized by both hypertrophy and dilation, low EF of both ventricles at rest, and increased interventricular septal thickness with a low prevalence of LGE. Differentiation of athlete's heart from other non-ischemic cardiomyopathies in MRI can be challenging due to a significant overlap of characteristics also seen in HCM, ARVC, and DCM.

Diagnosis and treatment of cardiac amyloidosis: position statement of the German Cardiac Society (DGK).

Systemic forms of amyloidosis affecting the heart are mostly light-chain (AL) and transthyretin (ATTR) amyloidoses. The latter is caused by deposition of misfolded transthyretin, either in wild-type (ATTRwt) or mutant (ATTRv) conformation. For diagnostics, specific serum biomarkers and modern non-invasive imaging techniques, such as cardiovascular magnetic resonance imaging (CMR) and scintigraphic methods, are available today. These imaging techniques do not only complement conventional echocardiography, but also allow for accurate assessment of the extent of cardiac involvement, in addition to diagnosing cardiac amyloidosis. Endomyocardial biopsy still plays a major role in the histopathological diagnosis and subtyping of cardiac amyloidosis. The main objective of the diagnostic algorithm outlined in this position statement is to detect cardiac amyloidosis as reliably and early as possible, to accurately determine its extent, and to reliably identify the underlying subtype of amyloidosis, thereby enabling subsequent targeted treatment.

[Proximal myopathy and fulminant heart failure in a 57 year-old female patient with lupus erythematosus]. / Proximale Muskelschwäche und fulminante Herzinsuffizienz bei einer 57-jährigen Patientin mit Lupus erythematodes.

A case report is presented of fulminant hydroxychloroquine-induced cardiomyopathy in a 57 year-old female patient with a long history of systemic lupus erythematosus. Diagnosis was established based on clinical findings, imaging (echocardiography and cardiac magnetic resonance imaging) as well as endomyocardial biopsy. Despite immediate discontinuation of the medication, the patient died from heart failure within a few days. Since the rare adverse effect described here might be reversible, early diagnosis and discontinuation of hydroxychloroquine are crucial for the prognosis of these patients.

[Fatigue, breathlessness and chest pain in a 31-year-old man with schizoaffective disorder]. / Müdigkeit, Kurzatmigkeit und Brustschmerz bei einem 31-jährigen Mann mit schizoaffektiver Störung.

BACKGROUND: Clozapine is an alternative antipsychotic medication used to control symptoms of schizophrenia and to reduce risks of suicidal behavior in patients who did not adequately respond to standard medication. Due to severe side effects including cardiomyopathy and myocarditis its clinical use is limited. CASE REPORT: A 31-year-old man of east European descent presented to the emergency medical department with fatigue, shortness of breath and chest pain. Due to a schizoaffective disorder he was treated with clozapine and lithium. Echocardiography revealed severely impaired left ventricular systolic function. After exclusion of coronary artery disease by coronary angiography an endomyocardial biopsy was performed according to the guidelines. This confirmed the clinically suspected toxic cardiomyopathy. Therefore, antipsychotic treatment was immediately changed and state of the art heart failure medication was started resulting in a clear improvement of left ventricular function. CONCLUSION: In patients treated with clozapine or lithium and clinical signs of heart failure, toxic cardiomyopathy should be considered.

[Atrioventricular block and left ventricular wall mobility disorder in a 44-year-old female patient : A case report of a rarity with pitfalls]. / Atrioventrikuläre Blockierung und linksventrikuläre Wandbewegungsstörung bei einer 44-jährigen Patientin : Fallbericht über eine Rarität mit Tücken.

Eosinophilic myocarditis is a rare condition with good treatment options, which can be difficult to diagnose. The clinical presentation can vary from asymptomatic to life-threatening forms. This article describes the case of a 44-year-old woman who suffered from vertigo, chest pain and dyspnea. The woman presented with an intermittent atrioventricular (AV) block II Mobitz type II° and mild impairment of left ventricular ejection fraction. Hypereosinophilia in the peripheral blood, cardiac magnetic resonance imaging (MRI) and endomyocardial biopsy led to the diagnosis of eosinophilic myocarditis, most likely as a result of an allergic reaction to Aspergillus fumigatus. A general treatment recommendation cannot be made due to the lack of evidence-based guidelines; however, recent scientific studies confirmed timely, high-dose steroid administration over several months to be the mainstay of treatment of eosinophilic myocarditis. The following article may be helpful in the early diagnosis and treatment of this underdiagnosed and insidious disease.

Adaptive Mutations That Occurred during Circulation in Humans of H1N1 Influenza Virus in the 2009 Pandemic Enhance Virulence in Mice.

UNLABELLED: During the 2009 H1N1 influenza pandemic, infection attack rates were particularly high among young individuals who suffered from pneumonia with occasional death. Moreover, previously reported determinants of mammalian adaptation and pathogenicity were not present in 2009 pandemic H1N1 influenza A viruses. Thus, it was proposed that unknown viral factors might have contributed to disease severity in humans. In this study, we performed a comparative analysis of two clinical 2009 pandemic H1N1 strains that belong to the very early and later phases of the pandemic. We identified mutations in the viral hemagglutinin (HA) and the nucleoprotein (NP) that occurred during pandemic progression and mediate increased virulence in mice. Lethal disease outcome correlated with elevated viral replication in the alveolar epithelium, increased proinflammatory cytokine and chemokine responses, pneumonia, and lymphopenia in mice. These findings show that viral mutations that have occurred during pandemic circulation among humans are associated with severe disease in mice. IMPORTANCE: In this study, novel determinants of 2009 pandemic H1N1 influenza pathogenicity were identified in the viral hemagglutinin (HA) and the nucleoprotein (NP) genes. In contrast to highly pathogenic avian influenza viruses, increased virulence in mice did not correlate with enhanced polymerase activity but with reduced activity. Lethal 2009 pandemic H1N1 infection in mice correlated with lymphopenia and severe pneumonia. These studies suggest that molecular mechanisms that mediate 2009 pandemic H1N1 influenza pathogenicity are distinct from those that mediate avian influenza virus pathogenicity in mice.

Monocyte imaging after myocardial infarction with 19F MRI at 3 T: a pilot study in explanted porcine hearts.

AIM: Inflammation is a hallmark of cardiac healing after myocardial infarction and it determines subsequent cardiovascular morbidity and mortality. The aim of the present study was to explore whether inflammation imaging with two perfluorocarbon (PFC) nanoemulsions and fluorine magnetic resonance imaging ((19)F MRI) is feasible at 3.0 T with sufficient signal-to-noise ratio (SNR) using explanted hearts, an (19)F surface coil and dedicated MR sequences. METHODS AND RESULTS: Acute myocardial infarction (AMI) was induced by balloon angioplasty (50 min) of the distal left anterior descending artery in 12 pigs. One day thereafter, PFCs were injected intravenously to label circulating monocytes. Either emulsified perfluoro-15-crown-5 ether or already clinically applied perfluorooctyl bromide (PFOB) was applied. Four days after AMI and immediately after gadolinium administration, hearts were explanted and imaged with a 3.0 T Achieva MRI scanner. (19)F MRI could be acquired with an SNR of >15 using an in-plane resolution of 2 × 2 mm(2) within <20 min for both agents. Combined late gadolinium enhancement (LGE) and (19)F MRI revealed that (19)F signal was inhomogenously distributed across LGE myocardium reflecting patchy macrophage infiltration as confirmed by histology. In whole hearts, we found an apico-basal (19)F gradient within LGE-positive myocardium. The (19)F-positive volume was always smaller than LGE volume. Ex vivo experiments on isolated monocytes revealed that pig and human cells phagocytize PFCs even more avidly than mouse monocytes. CONCLUSION: This pilot study demonstrates that (19)F MRI at 3.0 T with clinically applicable PFOB is feasible, thus highlighting the potential of (19)F MRI to monitor the inflammatory response after AMI.

Adiponectin promotes coxsackievirus B3 myocarditis by suppression of acute anti-viral immune responses.

Adiponectin (APN) is an immunomodulatory adipocytokine that improves outcome in patients with virus-negative inflammatory cardiomyopathy and mice with autoimmune myocarditis. Here, we investigated whether APN modulates cardiac inflammation and injury in coxsackievirus B3 (CVB3) myocarditis. Myocarditis was induced by CVB3 infection of APN-KO and WT mice. APN reconstitution was performed by adenoviral gene transfer. Expression analyses were performed by qRT-PCR and immunoblot. Cardiac histology was analyzed by H&E-stain and immunohistochemistry. APN-KO mice exhibited diminished subacute myocarditis with reduced viral load, attenuated inflammatory infiltrates determined by NKp46, F4/80 and CD3/CD4/CD8 expression and reduced IFNß, IFNγ, TNFα, IL-1ß and IL-12 levels. Moreover, myocardial injury assessed by necrotic lesions and troponin I release was attenuated resulting in preserved left ventricular function. Those changes were reversed by APN reconstitution. APN had no influence on adhesion, uptake or replication of CVB3 in cardiac myocytes. In acute CVB3 myocarditis, cardiac viral load did not differ between APN-KO and WT mice. However, APN-KO mice displayed an enhanced acute immune response, i.e. increased expression of myocardial CD14, IFNß, IFNγ, IL-12, and TNFα resulting in increased cardiac infiltration with pro-inflammatory M1 macrophages and activated NK cells. Up-regulation of cardiac CD14 expression, type I and II IFNs and inflammatory cell accumulation in APN-KO mice was inhibited by APN reconstitution. Our observations indicate that APN promotes CVB3 myocarditis by suppression of toll-like receptor-dependent innate immune responses, polarization of anti-inflammatory M2 macrophages and reduction of number and activation of NK cells resulting in attenuated acute anti-viral immune responses.

["Catecholamine refractory" cardiogenic shock? "Bridging-to-recovery" by implantation of a percutaneous cardiac assist device]. / "Therapierefraktärer" kardiogener Schock? "Bridging-to-recovery" mittels Implantation eines perkutanen Assistdevices.

HISTORY AND ADMISSION FINDINGS: A 27-year-old man presented with acute dyspnea and a previous respiratory tract infection with progressive dyspnoea and chest pain over 2 weeks. Clinical findings revealed severe cardiac failure with development of cardiogenic shock and need for adrenergic drug therapy for circulatory support. INVESTIGATIONS: The electrocardiogram showed a sinus tachycardia with unspecific T-wave-inversions, the echocardiogram revealed a dilated left ventricle and severely reduced systolic LV-function. An acute coronary syndrome could be excluded by coronary angiogram. TREATMENT AND COURSE: A myocardial biopsy was taken to exclude giant cell myocarditis. The immediate initiation of a mechanical circulatory support by an Extracorporal Membrane Oxygenator (ECMO) facilitated rapid hemodynamic stabilization and recovery of organ function. CONCLUSIONS: A drug-only circulatory support very often does not enable stabilization of a patient in progressive cardiogenic shock and cannot prevent multiorgan dysfunction. Therefore implantation of an assist device facilitates a "bridging-to-recovery" or a "bridging-to transplant" concept in critically ill patients presenting with cardiogenic shock. The bridging also allows for reviewing etiology and evaluation of further treatment options. In case of recovery continuous care in a specialized Heart Failure Clinic can help to maintain the clinical status and offer frequent reevaluation of cardiac status and therapeutic concepts.

An unusual presentation of a common infection.

A 40-year-old Ghanaian woman presented with fever and exanthema. She had anemia, leukopenia, increased erythrocyte sedimentation rate (ESR), creatinin kinase, lactate dehydrogenase (LDH), and liver enzymes. She was diagnosed with schistosomiasis and was cured with praziquantel. During the following years, she developed polymyositis, chronic nephritis, and life-threatening perimyocarditis. High numbers of Epstein-Barr virus (EBV)-encoded RNA copies were demonstrated in CD8+ T-lymphocytes from endomyocardial biopsies. There was no evidence of any underlying immunosuppression or an EBV-related malignancy. Chronic active EBV infection was diagnosed, a clinical picture not described in an adult African previously. Interestingly, among all therapy attempts, only rituximab was effective at stabilizing the disease.

Initial white blood cell count is an independent risk factor for survival in patients with dilated cardiomyopathy.

BACKGROUND: The impact of white blood cell count (WBCc) on the outcome of patients with non-ischemic left ventricular (LV) dysfunction is unknown. In the present study we investigated the influence of WBCc on mortality and cardiac inflammation in patients with reduced LV systolic function in the absence of ischemic or valvular etiology. METHODS AND RESULTS: We included 381 patients with reduced left ventricular (LV) ejection fraction (LVEF ≤ 45%) quantified by two-dimensional echocardiography. Coronary artery disease and valvular diseases were excluded by angiography and echo, respectively, in all patients. WBCc was quantified routinely upon first hospital admission. In 291 patients, endomyocardial biopsies from the right ventricle were performed upon first hospital admission for assessment of cardiac inflammation. Follow-up was up to 5.5 years (median 2.93 [1.7;4.0]). Information on vital status of patients was obtained from official resident data files. WBCc >11 Gpt/l was associated with significantly increased mortality in patients with severe LV dilation (end-diastolic diameter (LVEDD) >70 mm quantified by echocardiography) in comparison to patients showing WBCc ≤ 11 Gpt/l (41.7% vs 13.6%, p=0.02). Multivariable Cox regression analysis showed that WBCc predicts mortality independently of other cardiovascular risk factors and LVEF (hazard ratio 1.14; p=0.04). Doses of heart failure medication did not differ significantly in patients with LVEDD >70 mm and WBCc >11 Gpt/l when compared to LVEDD >70 mm and WBCc ≤ 11 Gpt/l (percent of maximum doses: ß-blockers p=0.51, ACE inhibitors p=0.56, AT1 antagonists p=0.77, aldosterone antagonists p=0.35). WBCc including its subpopulations (monocytes, lymphocytes and granulocytes) did not show a significant correlation with cardiac amounts of CD3(+)-lymphocytes (r=0.02, p=0.78) or CD68(+)-macrophages (r=1.0, p=0.09) (n=291). CONCLUSION: WBCc at first hospital admission predicts long term-mortality in patients with dilated cardiomyopathy independently of cardiovascular risk factors.

Antibodies to cardiac receptors.

Inflammation of cardiac tissue is generally associated with an activation of the host's immune system. On the one hand, this activation is mandatory to protect the heart by fighting the invading microbial agents or toxins and by engaging myocardial reparation and healing processes. On the other hand, uncontrolled activation of the immune defense has the risk of an arousal of auto- or cross-reactive immune cells, which in some cases bring more harm than good. Dependent on the individual genetic predisposition, such heart-directed autoimmune reactions most likely occur as a result of myocyte apoptosis or necrosis and subsequent liberation of self-antigens previously hidden to the immune system. During the past two decades, evidence for a pathogenic relevance of autoimmunity in human heart disease has substantially increased. Conformational cardiac (auto)antibodies affecting cardiac function and, in particular, (auto)antibodies that target G protein-coupled cardiac membrane receptors are thought to play a key role in the development of heart failure. Clinical pilot studies even suggest that such antibodies negatively affect survival in heart failure patients. However, the true prevalence and clinical impact of many cardiac (auto)antibodies in human heart diseases are still unclear, as are the events triggering their formation, their titer course, and their patterns of clearance and/or persistence. The present article summarizes current knowledge in the field of cardiac receptor (auto)antibodies including recent efforts to address some of the aforementioned gaps of knowledge, thereby attempting to pave the way for novel, more specific therapeutic approaches.

No evidence of enteroviruses in the intestine of patients with type 1 diabetes.

AIMS/HYPOTHESIS: The purpose of this study was to investigate whether the gut mucosa is a reservoir for enterovirus persistence in patients with type 1 diabetes. METHODS: Small intestine biopsy samples from 25 individuals at different stages of type 1 diabetes, 21 control individuals and 27 individuals with coeliac disease were analysed for the presence of enterovirus RNA by using both radioactive in-situ hybridisation and real-time RT-PCR and for the presence of enterovirus proteins by immunostaining with antibodies against VP1 and VP4-2-3 capsid proteins and virus polymerase. Lymphocytic enteropathy and serum anti-VP1 antibodies were also evaluated at the time of biopsy. Moreover, high-throughput sequencing was performed to identify viral transcripts or genomes. RESULTS: Enterovirus was not detected by in-situ hybridisation or RT-PCR in any of the individuals tested. Immunohistology revealed a few stained cells in the intestinal epithelium in a low number of individuals, with no difference between diabetic and non-diabetic individuals. Levels of serum IgG against VP1 did not differ between control individuals and those with diabetes or coeliac disease and no evidence of diabetes-related lymphocytic enteropathy was detected. High-throughput sequencing did not reveal specific enterovirus sequences in the gut mucosa of individuals with type 1 diabetes. CONCLUSIONS/INTERPRETATION: Prolonged/persistent enterovirus infections in gut mucosa are not common in patients with type 1 diabetes.

Cell volume, the serum and glucocorticoid inducible kinase 1 and the liver.

In virtually all cells including hepatocytes cell volume regulation is accomplished during cell swelling by cellular ion release (activation of K (+) channels and/or anion channels, KCl-cotransport, parallel activation of K (+)/H (+) exchange and Cl (-)/HCO (3)(-) exchange) and following cell shrinkage by cellular ion uptake (activation of Na (+), K (+), 2Cl (-) cotransport, Na (+)/H (+) exchange in parallel to Cl (-)/HCO (3)(-) exchange and Na (+)-channels). Moreover, cell shrinkage triggers the cellular accumulation of organic osmolytes (e. g., myoinositol, betaine, phosphorylcholine, taurine). Cell volume is a powerful regulator of hepatic metabolism. Cell shrinkage stimulates and cell swelling inhibits proteolysis and glycogenolysis. Moreover, cell volume influences the generation of and sensitivity to oxidants. Cell volume regulatory mechanisms furthermore do play a role in fibrosing disease. Kinases stimulating cell volume regulatory mechanisms include the serum and glucocorticoid inducible kinase SGK1, which is expressed in the liver, is genomically up-regulated by cell shrinkage, stimulates a wide variety of channels and transporters including Na (+), K (+), 2Cl (-) cotransport and Na (+)/H (+) exchange and is known to participate in the stimulation of fibrosis. Accordingly, excessive SGK1 expression is observed in liver cirrhosis. The case is made that SGK1 participates in the regulation of liver cell volume and thus in the regulation of hepatic metabolism.

[Immunsuppressive therapy in virus-negative eosinophilic inflammatory cardiomyopathy]. / Immunsuppressive Therapie bei Virus-negativer eosinophiler inflammatorischer Kardiomyopathie.

HISTORY AND ADMISSION FINDINGS: A 52 year-old women presented with long-standing dyspnoea at exercise as a symptom of heart failure. A coronary heart disease had been excluded by coronary angiography a year before. The symptoms had persisted despite application of guideline-based anticongestive medication. INVESTIGATIONS: Electrocardiography showed sinus rhythm with decreased anterior wall amplitudes without acute ischemic signs. The white blood count revealed elevated leucocytes with high numbers of eosinophilic granulocytes. Echocardiography demonstrated severe left ventricular dysfunction with an ejection fraction of 30 % and a left ventricular end-diastolic diameter of 75 mm. Magnetic resonance imaging showed a pathologic late enhancement in the left ventricular wall. Six myocardial biopsies were obtained and revealed virus-negative eosinophilic inflammatory cardiomyopathy with focal fibrotic scarring. DIAGNOSIS, TREATMENT AND COURSE: The patient was treated according to a previously published study on virus-negative inflammatory heart disease with prednisone 1 mg/kg daily for 4 weeks followed by 0.33 mg/kg daily for 5 month and azathioprine 2 mg/kg daily for 6 month. The echocardiography of the left ventricular function showed an increase from 30 to 45 % and the clinical symptoms of the heart failure resolved to NYHA II. CONCLUSION: In patients with virus-negative eosinophilic inflammatory cardiomyopathy standardized therapy with prednisone and azathioprine can improve LV function and clinical symptoms.

Glycogen synthase kinase-3ß is a crucial mediator of signal-induced RelB degradation.

The immediate early transcription factor nuclear factor (IκBs) kappa B (NF-κB) is crucially involved in the regulation of numerous physiological or pathophysiological processes such as inflammation and tumourigenesis. Therefore, the control of NF-κB activity, which is mainly regulated by signal-induced degradation of cytoplasmic inhibitors of NF-κB (IκBs), is of high relevance. One known alternative pathway of NF-κB regulation is the stimulus-induced proteasomal degradation of RelB, a component of the NF-κB dimer. Here, we identified the serine/threonine protein kinase glycogen synthase kinase-3ß (GSK-3ß) as a critical signalling component leading to RelB degradation. In Jurkat leukaemic T cells as well as in primary human T cells, tetradecanoylphorbolacetate/ionomycin- and CD3/CD28-induced RelB degradation were impaired by a GSK-3ß-specific pharmacological inhibitor, an ectopically expressed dominant-negative GSK-3ß mutant and by small-interfering RNA-mediated silencing of GSK-3ß expression. Furthermore, a physical interaction between RelB and GSK-3ß was shown by co-immunoprecipitation, which was already notable in unstimulated cells. Most importantly, as demonstrated by in vitro kinase assays, human RelB is inducibly phosphorylated by GSK-3ß, indicating a direct substrate-enzyme relationship. The serine residue 552 is a target of GSK-3ß-mediated phosphorylation in vitro and in vivo. We conclude that GSK-3ß is a crucial regulator of RelB degradation, stressing the relevant linkage between the NF-κB system and GSK-3ß.

[Risk stratification in non ischemic cardiomyopathy: a case report--Case 5/2010]. / Risikostratifizierung bei nichtischämischer Kardiomyopathie: Eine Kasuistik - Fall 5/2010.

HISTORY AND ADMISSION FINDINGS: A 65-year-old male patient with rapid increasing shortness of breath and newly diagnosed atrial fibrillation was admitted to our hospital. INVESTIGATIONS: The ECG revealed atrial fibrillation. Echocardiography showed severe decreased left ventricular function. The magnetic resonance imaging (MRI) scan confirmed the severe reduced left ventricular function with a two graded mitral regurgitation as well as a pronounced late enhancement in the posterobasal area of the interventricular septum. Cardiac catheterisation showed mild diffuse atherosclerosis of the coronary arteries without stenotic lesions. Multiple myocardial biopsies of the right ventricle revealed extensive remodelling processes with focal fibrosis in presence of mononuclear cell infiltrates, T-wave alternans and the heart rate variability were positive. DIAGNOSIS, TREATMENT AND COURSE: Nonischaemic cardiomyopathy (NICM) with severe reduced left ventriucular function was diagnosed. After successful electrical cardioversion and initiation of a sufficient heart failure treatment, the clinical symptoms as well as left ventricular function improved significantly. CONCLUSION: Risk stratification of sudden cardiac death remains a clinical challenge especially in NICM. Significantly predictors in ischaemic cardiomyopathy, such as heart rate turbulance (HRT) and T-wave alternans, are not useful or have no importance in NICM. However, the prognosis does not correlate with restricted left ventricular function in NICM. Cardiac MRI or marker of autonomic dysfunction could be helpful in risk stratification. How far late enhancement is a surrogate parameter or the real substrate for life threatening arrhythmias is still unclear. Non-invasive risk stratification could be helpful in borderline decisions, however, it should not be taken mandatory. Close-meshed control intervals of the clinical status under optimal medication are recommended, followed by a implantation of an implantable cardioverter-defibrillator (ICD) if needed. ICD implantation is superior to medical treatment in persistent depressed left ventricular function. The ideal time for ICD implantation in newly diagnosed NICM remains unclear at the moment.

Fcgamma-receptor IIa polymorphism and the role of immunoadsorption in cardiac dysfunction in patients with dilated cardiomyopathy.

In patients with dilated cardiomyopathy (DCM), cardiac autoantibodies are able to bind with their Fab fragment to epitopes on cardiomyocytes, but thereafter they crosslink through their Fc fragment to cardiac Fc(gamma)-receptor IIa. Polymorphic variability of the Fc(gamma)-receptor IIa is associated with modified affinity of immunoglobin G (IgG) binding and may influence therapeutic effects. In this study, 103 consecutive DCM patients were treated with immunoadsorption (IA) therapy with subsequent IgG substitution (IA/IgG). Echocardiography was performed at baseline and again at 3 and 6 months after IA/IgG. Fc(gamma)-receptor IIa polymorphism R/H131 was genotyped using a nested sequence-specific primer polymerase chain reaction (PCR). Patients with the Fc(gamma)-receptor IIa genotype R/R131 showed significantly greater improvement in left ventricular (LV) function than patients with the R/H131 or H/H131 genotypes did. Irrespective of the Fc(gamma)-receptor polymorphism, patients with shorter disease duration and a more impaired LV function responded with a greater increase in LV ejection fraction (LVEF). Therefore, the Fc(gamma)-receptor polymorphism influences the efficacy of immunomodulatory therapy involving IA/IgG.