[Prognostic impact of heart failure with preserved versus reduced ejection fraction in patients with mild symptoms]. / Prognostische Bedeutung der diastolischen versus systolischen Herzinsuffizienz bei Patienten mit klinisch milder Symptomatik.

BACKGROUND AND AIM: Previous studies have found a similarly impaired prognosis in patients with heart failure with preserved ejection fraction (HFpEF) as in patients with systolic heart failure (HFrEF). This study examines the prognosis of HFpEF patients with only mild symptoms and compares two different methods of diagnosing HFpEF. METHODS: Of 670 consecutive patients presenting in our outpatient clinic (57.6 ± 16 years, 50.1 % male), 165 revealed a typical clinical presentation with heart failure NYHA class II-III. The following echocardiographic parameters were assessed: ejection fraction (EF), left atrial size (LA), early and late antegrade mitral flow (E and A), early mitral annular movement (E'). Criteria for HFrEF were typical symptoms (NYHA II-III) and an EF < 50 %, HFpEF was diagnosed in patients with typical presentation, NYHA ≥ 2 and EF ≥ 50 % using 2 different definitions: similarly to the criteria of the I-Preserve study or as recommended by the german association of cardiology (DGK) that imply prove of diastolic dysfunction. Patients were followed-up for up to 2.5 years (mean 1.7±0.7) and the following events were registered: death, hospitalisation (myocardial infarction/coronary intervention/cardiac decompensation), cardiac transplantation (HTX). RESULTS: The majority (93.3 %) of the 165 heart failure patients had mild symptoms NYHA II. Of the 165 patients with typical symptoms, systolic heart failure could be found in 51 (30.9 %) and HFpEF according to I-Preserve criteria in 114 (69.1 %) patients. 56 (33.9 %) patients fulfilled the DGK criteria for HFpEF. Patients with HFpEF were significantly older, more often obese, female and hypertensive. The event rate was higher in patients with systolic heart failure (32 events, 62.7 %) than in patients with HFpEF (I-PRESERVE criteria: 28 events, 24.6 %; DGK criteria: 16 events, 28.6 %; both p < 0,001, log-rank), whereby this difference was mainly caused by increased hospitalisations (43.1 vs. 14.9 and 21,4 %, p < 0.001 and p < 0.016). Significantly more patients with HFrEF reached the combined end point death/HTX (p = 0.019 [I-Preserve] and p = 0.022 [DGK]). Both HFpEF groups showed no significant difference in any of the event types. CONCLUSION: Patients with HFpEF and mild symptoms have a more benign prognosis than those with systolic heart failure. Whether additional echocardiographic measurements are valuable for the diagnosis of HFpEF has to be proved in larger studies.

Magnetic stents retain nanoparticle-bound antirestenotic drugs transported by lipid microbubbles.

PURPOSE: Coating coronary stents with antirestenotic drugs revolutionized interventional cardiology. We developed a system for post-hoc drug delivery to uncoated stents. METHODS: We coupled rapamycin or a chemically similar fluorescent dye to superparamagnetic nanoparticles. The antiproliferative activity of rapamycin coupled to nanoparticles was confirmed in vitro in primary porcine vascular cells. The particles were then incorporated into lipid based microbubbles. Commercially available stents were made magnetizable by nickel plating and used to induce strong field gradients in order to capture magnetic microbubbles from flowing liquids when placed in an external magnetic field. RESULTS: Nanoparticle bound Rapamycin dose dependently inhibited cell proliferation in vitro. Magnetic microcbubbles carrying coated nanoparticles were caught by magnets placed external to a flow-through tube. Plating commercial stents with nickel resulted in increased deposition at stent struts and allowed for widely increased distance of external magnets. Deposition depended on circulation time and velocity and distance of magnets. Deposited microbubbles were destroyed by ultrasound and delivered their cargo to targeted sites. CONCLUSIONS: Drugs can be incorporated into nanoparticle loaded microbubbles and thus be delivered to magnetizable stents from circulating fluids by applying external magnetic fields. This technology could allow for post-hoc drug coating of already implanted vascular stents.

Clinical management of clopidogrel inefficiency by point of care platelet function testing and individual adjustment of anti-platelet therapy--initial experiences.

Insufficient inhibition of ADP dependent platelet aggregation by clopidogrel is associated with an increased risk for adverse coronary events, such as stent thrombosis, after percutaneous coronary intervention. Here, we describe an approach to the clinical management of patients with insufficient inhibition of ADP dependent platelet aggregation by clopidogrel involving dose adjustment or switching of the thienoyridine. We put special emphasize on a patient who experienced recurrent acute myocardial infarction due to stent thrombosis associated with severe clopidogrel non response following elective coronary drug eluting stent implantation. In this patient, an inadequate clopidogrel effect at maintenance doses was confirmed by repeated platelet function assessment with a multiple electrode impedance point of care platelet function test. Subsequent dose adjustments still did not result in sufficient inhibition of ADP dependent platelet aggregation. Only after switching to the then shortly available new thienopyridine prasugrel could a sufficient platelet inhibition be obtained. However, our data from further patients show that although this may overcome inadequate clopidogrel efficiency in many cases, even under prasugrel suboptimal platelet inhibition may occur.

Prothrombotic effects of diclofenac on arteriolar platelet activation and thrombosis in vivo.

BACKGROUND: Diclofenac, like selective cyclooxygenase-2 inhibitors, which alter vascular levels of platelet active prostaglandins, has been reported to increase rates of acute myocardial infarction. OBJECTIVE: The study was performed to investigate, in an animal model of arterial thrombosis in vivo, whether diclofenac differentially influences platelet activation and thrombosis in vessels under non-stimulated conditions or during acute systemic inflammation, such as induced by tumor necrosis factor-alpha (TNF-alpha). METHODS: Platelet-vessel wall interaction (PVWI), firm platelet adhesion and arterial thrombosis following vessel injury were analyzed by intravital microscopy in arterioles of hamsters in the dorsal skinfold chamber model. Prostacyclin [prostaglandin I(2) (PGI(2))] and thromboxane A(2) (TxA(2)) metabolites were measured. In vitro, endothelial adhesion molecule expression in cultured human microvascular endothelial cells was analyzed. RESULTS: Under non-stimulated conditions, diclofenac (1 mg kg(-1)) enhanced PVWI, which was not mediated by increased adhesion molecule expression, but by decreased systemic PGI(2) levels. Following ferric chloride-induced endothelial injury, diclofenac accelerated thrombotic vessel occlusion time, an effect that was reversed by the stable PGI(2) analog iloprost. TNF-alpha, through induction of endothelial adhesion molecule expression, also enhanced PVWI, firm adhesion, and arterial thrombosis, but simultaneous treatment with TNF-alpha and diclofenac did not have an additive effect. CONCLUSIONS: By decreasing levels of PGI(2) without, at the same time, altering prothrombotic TxA(2) levels, diclofenac can exert prothrombotic effects. However, this is not the case when an inflammatory situation is created by TNF-alpha treatment. These data may explain the enhanced risk of acute myocardial infarction observed in patients taking diclofenac.

Early time course of neointima formation and vascular remodelling following percutaneous coronary intervention and vascular brachytherapy of in-stent restenotic lesions as assessed by intravascular ultrasound analysis.

In-stent restenosis (ISR) represents the major limitation of stent implantation. Treatment, although of relative technical ease, is unsatisfactory due to a high incidence of recurrent restenosis. Vascular brachytherapy (VBT) has emerged as a powerful adjunct therapeutic modality to treat ISR. Inhibition of neointima formation has been regarded as the relevant mechanism of action. Yet, positive remodelling has been suspected as another contributing factor. Since only very few precise analyses of the extent, distribution and time course of the respective mechanims exist, the goal of the present study was to describe the changes of the vessel geometry at the target lesion and at the reference site following angioplasty and VBT of ISR in 42 patients by means of quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) before and after the index procedure and at the 3 and 6 month follow-up. By QCA the acute lumen gain measured 2.2+/-0.8 mm, the late lumen loss at 3 months was 0.1+/-0.5 mm and at 6 months 0.4+/-0.7 mm. By IVUS luminal cross-sectional area increased from 1.5+/-1.2 mm(2) to 7.9+/-1.9 mm(2) (p<0.001). The intima hyperplasia cross-sectional area at 3 months was only 0.2+/-1.0 mm(2) (p=0.191), but increased to 0.7+/-0.6 mm(2) (p<0.001) at 6 months resulting in a lumen cross-sectional area of 7.1+/-1.7 mm(2). Stent dimensions did not show any significant changes over time. The external elastic membrane cross-sectional area at 3 months increased by 1.3+/-1.9 mm(2) (p<0.001), and showed a further increase by 0.7+/-2.9 mm(2) at 6 months. Positive remodelling could be demonstrated also at the reference segment. In conclusion the absolute amount of intima hyperplasia during a 6-month follow-up period after VBT of ISR is low and most pronounced between the third and sixth month. Besides this, predominantly within the first 3 months of follow-up, significant positive remodelling could be demonstrated at the target lesion and at the reference site. Both observed effects may contribute to the preservation of the vessel lumen.

[Hepatitis of unknown origin with protracted liver failure in a 48-year-old patient with significantly increased pANCA titer]. / Unklare Hepatitis mit protrahiertem Leberversagen bei einem 48-jährigen Patienten mit deutlich erhöhtem pANCA-Titer.

In spite of intense diagnostic testing, no cause for the chronically aggressive hepatitis of a 48-year old male patient was found. Evidence for an autoimmune process, however, could be derived from a high titer of pANCA. Only according to the revised criteria of the working group on autoimmune hepatitis, but not to the first version, it was possible to classify this as an autoimmune hepatitis. Despite of high-dose steroid treatment and accelerated preparation for liver transplantation the patient died of the complications of rapid liver failure. Thus, in case of unclear rapid progressive hepatitis, the revised criteria of autoimmune hepatitis should be reviewed early and with high priority and consequent high-dose steroid therapy and preparation for liver transplantation should be initiated. The prognostic impact of a high titer of pANCA in patients with autoimmune hepatitis remains to be established.