Strauer Be

Cardiac Troponin T in Patients With Clinically Suspected Myocarditis

OBJECTIVES The present study investigated whether myocyte injury can be assessed sensitively by measurement of serum levels of cardiac troponin T (cTnT) in patients with clinically suspected myocarditis and whether cTnT levels may predict the results of histologic and immunohistologic analysis of endomyocardial biopsy specimens. BACKGROUND Conventionally used laboratory variables often fail to show myocyte injury in patients with clinically suspected myocarditis, possibly because of a low extent of myocardial injury in these patients. Sensitive variables for myocyte injury have not yet been investigated. METHODS Eighty patients with clinically suspected myocarditis were screened for creatine kinase (CK) activity, MB isoform of CK (CK-MB) activity and cTnT. Endomyocardial biopsy specimens were examined histologically and immunohistologically. RESULTS cTnT was elevated in 28 of 80 patients with clinically suspected myocarditis, CK in 4 and CK-MB in 1. Histologic analysis alone of the endomyocardial biopsy specimen revealed evidence of myocarditis in only five patients, all with elevated cTnT levels. Twenty-three of 28 patients with elevated cTnT levels had histologically negative findings for myocarditis. Additional immunohistologic analysis revealed evidence of myocarditis in 26 (93%) of 28 patients with elevated cTnT levels and in 23 (44%) of 52 patients with normal cTnT levels. Mean cTnT levels were higher in patients with myocarditis proved histologically or immunohistologically, or both, than in patients without myocarditis (0.59 +/- 1.68 vs. 0.04 +/- 0.05, p < 0.001). CONCLUSIONS Measurement of serum levels of cTnT provides evidence of myocyte injury in patients with clinically suspected myocarditis more sensitively than does conventional determination of cardiac enzyme levels. Myocardial cell damage may be present even in the absence of histologic signs of myocarditis. Additional immunohistologic analysis often shows lymphocytic infiltrates in these patients. Elevated levels of cTnT are highly predictive for myocarditis in this group.

Left Ventricular Diastolic Dysfunction as an Early Manifestation of Diabetic Cardiomyopathy

Aims/Hypothesis: Early determination of myocardial manifestations of diabetes mellitus is of major importance, since myocardial involvement considerably influences the prognosis of diabetic patients. The aim of this study was to investigate whether young patients with insulin-dependent diabetes mellitus and normal systolic left ventricular (LV) function already show a diastolic LV dysfunction and an increased risk of arrhythmias. Methods: Echocardiography was performed in 87 patients suffering from type I diabetes mellitus, without known cardiac disease and in 87 controls. Patients with a known manifest cardiac disease or a long-term diabetic syndrome were excluded. Morphological parameters were determined using M-mode echocardiography. Doppler echocardiography was used to evaluate parameters of LV diastolic function. The risk of arrhythmia was assessed by means of electrocardiography, heart rate variability, and late potential analysis. Results: The left atrial and ventricular dimensions and systolic functional parameters of all patients were normal. A diastolic dysfunction with a reduction in early diastolic filling, an increase in atrial filling, an extension of isovolumetric relaxation and deceleration time was documented in diabetic patients, as well as an increased number of supraventricular and ventricular premature beats. Conclusion: Even young patients with diabetes mellitus suffer from a diastolic dysfunction while systolic ventricular function is normal. Therefore, echocardiography with measurements of diastolic functional parameters appears to be a sensitive method for evaluating the manifestation and course of early diabetic cardiomyopathy.

Autoantibodies in against human ventricular myosin in sera of patients with acute and chronic myocarditis

OBJECTIVES The present study investigated the presence of antimyosin autoantibodies in sera of patients with myocarditis and in three control groups: healthy blood donors, patients with alcoholic cardiomyopathy and patients with other cardiac diseases. BACKGROUND An increasing body of evidence indicates that in the course of myocarditis, autoimmunologic mechanisms may play a pathogenetic role. Animal studies with Coxsackie B3 virus-induced murine myocarditis could demonstrate the appearance of circulating autoantibodies against cardiac myosin. METHODS Sera were analyzed by enzyme-linked immunosorbent assay (ELISA) and Western blot with human left ventricular myosin as antigen. RESULTS Seventeen (42%) of 40 serum samples from patients with myocarditis showed antibody-binding against myosin, whereas only 1 (2.5%) of 39 samples from healthy blood donors and 9 (21%) of 43 samples from patients with other cardiac diseases showed autoantibodies against myosin (p < 0.05 vs. myocarditis). In sera from patients with alcoholic cardiomyopathy (n = 12), no antibodies against human ventricular myosin could be detected. In Western blots, the antimyosin antibodies in patients with myocarditis bound to the myosin heavy chain. Using protein-A sepharose chromatography, it could be shown that the antimyosin autoantibodies are of the immunoglobulin G (IgG) type. In ELISA, the antimyosin autoantibodies bind equally to myosin prepared from either cardiac or skeletal muscle, respectively. CONCLUSIONS These results demonstrate the presence of autoantibodies against human ventricular myosin in patients with myocarditis. The prevalence of these autoantibodies is significantly higher in patients with myocarditis than in patients with other cardiac diseases. No organ specificity of the autoantibodies could be detected.

Frequency and quantity of the parvovirus B19 genome in endomyocardial biopsies from patients with suspected myocarditis or idiopathic left ventricular dysfunction

n Zusammenfassung Parvovirus B19 (PB19) gilt als Erreger der Myokarditis und als möglicher Auslöser einer Herzinsuffizienz im Kindes- und Erwachsenenalter. In der vorliegenden Studie wurde mittels quantitativer PCR-Analyse (real time PCR) die Häufigkeit und Quantität von PB19-Genom in Endomyokardbiopsien von 80 Patienten mit Verdacht auf Myokarditis oder idiopathischer linksventrikulärer Funktionsstörung und 36 Kontrollenpersonen ermittelt. Das Vorliegen einer Entzündung des Myokards wurde durch histologische (Dallas-Klassifikation) und immunhistologische Untersuchungen der Myokardbiopsien erfasst. PB19-Virusgenom konnte bei 9 von 80 Patienten (11,2%) bioptisch nachgewiesen werden. Bei 4 von 31 (12,9%) Patienten mit immunhistologisch nachgewiesenen entzündlichen Infiltraten im Myokard und bei 5 von 49 (10,2%) Patienten mit linksventrikulärer Dysfunktion ohne Entzündungszeichen in der Myokardbiopsie. Die Menge viraler PB19-DNA in der Endomyokardbiopsie lag zwischen 30 und 3900 Kopien pro μg zellulärer DNA. Vier Patienten mit dem klinischen Verdacht auf Myokarditis hatten Kopienzahlen für PB19 DNA von 70, 740, 3400 und 3900 pro μg zellulärer DNA in der Endomyokardbiopsie. Fünf Patienten mit idiopathischer linksventrikulärer Dysfunktion ohne entzündliche Infiltrate im Myokard wiesen bioptisch Kopienzahlen für PB19-DNA von 30, 38, 52, 58 und 90 pro μg zellulärer DNA auf. Die Sequenzierung eines der neun positiven PCR-Fragmente zeigte eine identische Sequenz zu den publizierten PB19-VP1/VP2-Genen (NCBI-Genbank). Bei allen Patienten konnte eine akute Myokarditis histologisch nach den Dallas-Kriterien ausgeschlossen werden. Alle Biopsien der 36 Kontrollpersonen, die weder bioptisch eine Myokarditis noch eine positive Anamnese für eine kürzlich durchgemachte Virusinfektion aufwiesen, waren für PB19-DNA negativ. Zusammengefasst zeigen die vorliegenden Ergebnisse, dass PB19-Virusgenom in Endomyokardbiopsien von Patienten mit Verdacht auf Myokarditis und idiopathischer linksventrikulärer Funktionsstörung mittels real time PCR erfasst und quantifiziert werden kann. Parvovirus B19 (PB19) has been identified as a possible cause of myocarditis and heart failure in both children and adult patients. This study used real time PCR analysis, to determine the frequency and to quantify PB19 viral genomes in endomyocardial tissue samples from 80 adult patients with clinically suspected myocarditis or idiopathic left ventricular dysfunction and from 36 controls. Histological (Dallas classification) and immunohistological analyses were performed to detect myocardial inflammation in the endomyocardial biopsies. PB19 genomic DNA was found in nine of 80 patients (11.2%), 4 out of 31 (12.9%) patients with inflammatory infiltrates detected via immunohistological methods and 5 out of 49 (10.2%) patients with left ventricular dysfunction without myocardial inflammation. The copy numbers for PB19 DNA ranged between 30 and 3900 per μg of cellular DNA. Four patients with clinically suspected myocarditis had copy numbers for PB19 DNA of 70, 740, 3400 and 3900, respectively, per μg of cellular DNA in the endomyocardial biopsy. Five patients with idiopathic left ventricular dysfunction had copy numbers for PB19 DNA of 30, 38, 52, 58 and 90, respectively, per μg of cellular DNA in the endomyocardial biopsy. The amplicon of one of the nine positive PCR fragment was sequenced and was found to be fully identical in the highly conserved sequence of published Parvovirus B19 VP1/VP2 genes (NCBI gene bank). In all patients, acute myocarditis was excluded according to the Dallas classification. All biopsies of 36 controls with no history of myocarditis or recent viral infection were negative for myocardial inflammation and parvovirus B19 genomes. In summary, Parvovirus B19 DNA is present within the myocardium of patients with suspected myocarditis and idiopathic left ventricular dysfunction and can be detected and quantified in endomyocardial specimens via real time PCR.

Factors influencing spontaneous mobilization of CD34+ and CD133+ progenitor cells after myocardial infarction.

Background  Bone marrow‐derived circulating progenitor cells (BM‐CPCs) are mobilized into adult peripheral blood (PB) during acute myocardial infarction (AMI) and may contribute to the regeneration of infarcted myocardium. The purpose of the present study is to determine whether mobilization of BM‐CPCs into PB depends on cardiovascular risk factors (CVRFs), age of patients, infarct associated inflammatory markers, and left ventricular function after AMI.

The therapeutic potential of stem cells in heart disease.

Abstract.  Coronary heart disease and chronic heart failure are common and have an increasing frequency. Although interventional and conventional drug therapy may delay ventricular remodelling, there is no basic therapeutic regime available for preventing or even reversing this process. Chronic coronary artery disease and heart failure impairs quality of life and are associated with subsequent worsening of the cardiac pump function. Numerous studies within the past few years have been demonstrated, that the intracoronary stem cell therapy has to be considered as a safe therapeutic procedure in heart disease, when destroyed and/or compromised heart muscle must be regenerated. This kind of cell therapy with autologous bone marrow cells is completely justified ethically, except for the small numbers of patients with direct or indirect bone marrow disease (e.g. myeloma, leukaemic infiltration) in whom there would be lesions of mononuclear cells. Several preclinical as well as clinical trials have shown that transplantation of autologous bone marrow cells or precursor cells improved cardiac function after myocardial infarction and in chronic coronary heart disease. The age of infarction seems to be irrelevant to regenerative potency of stem cells, since stem cells therapy in old infarctions (many years old) is almost equally effective in comparison to previous infarcts. Further indications are non‐ischemic cardiomyopathy (dilative cardiomyopathy) and heart failure due to hypertensive heart disease.

EFFECTS OF EXERCISE TRAINING ON MOBILIZATION AND FUNCTIONAL ACTIVITY OF BLOOD-DERIVED PROGENITOR CELLS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

BackgroundThe aim of the present study was to determine whether regular exercise training (ET) is effective at promoting the mobilization of CPCs and improving their functional activity in patients with recently acquired myocardial infarction(STEMI). Regular physical training has been shown to improve myocardial perfusion and cardiovascular function. This mayberelatedin part to a mobilization of bonemarrow-derived circulating progenitor cells (CPCs) as well as an enhanced vascularisation.Methods37 patients with STEMI were randomly assigned to an ET group or a non-ET group(controls). Two weeks after STEMI, three weeks after regular ET and three months after ET, BNP levels, exercise echocardiography and exercise spiroergometry were evaluated. The number of CD34+/CD45+ and CD133+/CD45+CPCs was measured by flow cytometry analysis. The migration capacity of the CPCs was determined with a boyden chamber and the clonogenic capacity by CFU-assay.ResultsIn the ET-group the number and migration capacity of CPCs increased significantly after regular exercise training. The BNP level decreased significantly from 121 ± 94 to 75 ± 47 pg/ml (p < 0.001) after the ET period, the left ventricular rejection fraction raised in parallel at peak exercise, and the cardiorespiratory condition improved as demonstrated by an increase of VO2max (from 1641 ± 522 to 1842 ± 724 ml/min, p < 0.02). These three effects persist till three months after the ET period.ConclusionsRegular physical activity appears to predispose the mobilization and enhanced functional activity of CPCs, a phenomenon which might lead to an improved cardiac function in patients with recently acquired acute myocardial infarction.

In vitro Bleeding Test with PFA-100TM—Aspects of Controlling Individual Acetylsalicylic Acid Induced Platelet Inhibition in Patients with Cardiovascular Disease

AbstractObjectives: This study investigated the usefulness and practicability of a platelet function analyzer (PFA-100TM, DADE-Behring, Germany) to determine individual platelet inhibition in patients treated with acetylsalicylic acid (ASA). Background: Patients with coronary artery disease (CAD) routinely and during angioplasty (PTCA) receive standard doses of ASA to avoid acute coronary syndromes and abrupt vessel closures without information of the individual efficacy of platelet inhibition. Methods: With the PFA-100TM a standardized bleeding time is measured. Whole-blood anticoagulated with 3.2% sodium citrate is aspirated through a capillary (⊘ 200μm) and through an aperture (⊘ 147μm). The time until occlusion of the aperture (closure time, CT) by a stable platelet plug induced by shear stress, collagen and epinephrine (COLL/EPI-CT) or shear stress, collagen and adenosine 5′-diphosphate (COLL/ADP-CT) is determined. To examine the usefulness of the PFA-100TM as a rapid bedside test and the individual effect of ASA, closure time was measured in healthy individuals (n=17), in patients with stable CAD (n=19) and in patients undergoing PTCA (n=8). Results: Patients with stable CAD and regular medication with 100mg ASA per day for at least 3 month showed shorter COLL/ADP-CT in comparison to healthy individuals who took only one single dose of 100mg ASA. Of the patients with CAD 63% had a COLL/EPI-CT within normal range suggesting a low or no response to ASA. Also only 50% of the patients undergoing PTCA reached the expected COLL/EPI-CT>300s after an additive single dose of 500mg ASA intravenously. Neither heparin, phenprocoumon, sex nor different blood sampling methods seem to influence the measurements relevantly. Conclusions: This pilot study indicates that with the PFA-100TM test device a simple and quick measurement of an in vitro bleeding time is possible. It is able to detect an increase in the bleeding time after a single dose of ASA 100mg in healthy subjects, reflecting a sensitive detection of ASA induced changes in platelet inhibition respective activation. Differences in the individual response to ASA could be observed in healthy subjects, patients with stable CAD and patients undergoing PTCA. Further studies should validate the PFA-100TM with standard methods to determine ASA response in patients with cardiovascular disease and investigate implications for treatment and outcome in this patient group.

[Rapid healing of a therapy-refractory diabetic foot after transplantation of autologous bone marrow stem cells].

ZusammenfassungHintergrund:Der diabetische Fuß entsteht meist durch schmerzlose Druckläsionen, wozu die diabetische Polyneuropathie und Mikroangiopathie wesentlich beitragen. Das regenerative Potential adulter, autologer mononukleärer Knochenmarkstammzellen könnte zur Therapie beitragen.Anamnese und klinischer Befund:Ein 63-jähriger Patient mit langjährigem Diabetes mellitus Typ 2 leidet unter einer Gehstreckenlimitierung auf 200 m sowie einem therapierefraktären Ulkus am rechten Großzehenballen. Die Autoren haben bei dieser Erkrankung erstmals die Indikation zur kombinierten intraarteriellen und intramuskulären Stammzelltransplantation in das rechte Bein gestellt.Therapie und Ergebnisse:Aus Knochenmarkpunktat des Patienten wurde die mononukleäre Zellfraktion (157 × 106 Zellen) separiert. Anschließend erfolgte fraktioniert die intraarterielle und intramuskuläre Transplantation der Stammzellsuspension (jeweils 10 ml). Bereits 8 Wochen später kam es zu einem kompletten Abheilen des seit 3 Jahren therapierefraktären Ulkus, nach 6 Monaten verbesserte sich die Gehstrecke auf mehr als das Doppelte, in der Venenverschlussplethysmographie stiegen die arterielle Ruhedurchblutung um 23% und die reaktive Hyperämie um 56%.Folgerung:Die kombinierte intraarterielle und intramuskuläre Transplantation von adulten, autologen Knochenmarkstammzellen könnte eine neuartige, klinisch einfach und sicher durchzuführende Therapieoption bei Patienten mit diabetischem Fußsyndrom darstellen. Als Ursache für den Therapieerfolg ist eine Mikroangioneogenese und möglicherweise auch antiinflammatorische Wirkung durch die transplantierten Stammzellen zu diskutieren.AbstractBackground:The diabetic foot mainly depends on painless pressure lesions, which are based on diabetic polyneuropathy and microangiopathy. In these cases the regenerative potential of adult autologous mononuclear stem cells could serve as causal therapy.History and Clinical Findings:A 63-year-old patient with long-lasting type 2 diabetes mellitus suffers from a reduced walking distance of 200 m and a therapy-refractory ulcer at the right ball of the great toe. Therefore, the authors have decided to perform a combined intraarterial and intramuscular transplantation of stem cells into the right limb for the first time on this disease.Therapy and Results:After harvesting of bone marrow the mononuclear cell fraction was separated (157 × 106 cells). Thereafter, the fractional intraarterial and intramuscular transplantation of the cell suspension was performed (10 ml each). Already 8 weeks later, the ulcer healed completely, after 6 months the walking distance increased by > 100%, on venous occlusion plethysmography the arterial blood circulation at rest increased by 23% and the reactive hyperemia by 56%.Conclusion:The combined intraarterial and intramuscular transplantation of autologous bone marrow stem cells could constitute a novel, clinically feasible and safe therapy for patients with diabetic foot syndrome. The success of this approach may be ascribed to microangiogenesis and to an anti-inflammatory effect of the transplanted stem cells.

Akutes Cor pulmonale bei Lungenarterienembolie

Zum ThemaRechnet man die Zahlen aus den USA auf die deutsche Bevölkerungszahl um, so kommt man auf etwa 60.000–80.000 diagnostizierte Fälle von Lungenembolien hierzulande, wobei noch eine beachtliche Dunkelziffer hinzuzurechnen wäre. Die Tendenz ist allerdings im Vergleich zu Zahlen vor 1990 deutlich rückläufig, was vermutlich auf verbesserte prophylaktische Maßnahmen zurückzuführen ist.Die vorliegende Arbeit befaßt sich mit der Epidemiologie, Pathophysiologie, Klinik, Diagnostik, Differentialdiagnostik sowie – ausführlich – den verschiedenen Therapiemaßnahmen bei akuter Lungenembolie. Dabei müssen wegen der lebensbedrohlichen Schwere der akuten arteriellen Lungenembolie teilweise gravierende Nebenwirkungen in Kauf genommen werden. Die günstige Beeinflußung der Letalität rechtfertigt in jedem Fall den Einsatz aggressiver therapeutischer Strategien.